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Varshney P, Baghmar S, Sirohi B, Abou-Alfa GK, Cao HT, Sharma LM, Javle M, Goetze T, Kapoor VK. Neoadjuvant treatment for incidental gallbladder cancer: A systematic review. Ann Hepatobiliary Pancreat Surg 2025; 29:113-120. [PMID: 40064481 PMCID: PMC12093237 DOI: 10.14701/ahbps.24-223] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/25/2024] [Revised: 01/09/2025] [Accepted: 01/22/2025] [Indexed: 05/15/2025] Open
Abstract
Incidental gallbladder cancer (iGBC) diagnosed post-histopathological examination of gallbladders removed assuming benign gallstone disease constitutes a significant proportion of GBC patients. Most iGBC patients present with early-stage disease. The standard care for localized (non-metastatic) iGBC includes a reoperation for complete extended (radical) cholecystectomy involving liver resection and lymphadenectomy, followed by postoperative adjuvant systemic therapy. However, a major drawback of this approach is the high recurrence rate within six months post-radical surgery, which undermines the benefits of the extensive procedure; notably, most recurrences are distant, highlighting the efficacy of systemic therapy. Similar to other gastrointestinal cancers, there appears to be a potential for neoadjuvant systemic therapy (chemotherapy) before reoperative surgery in iGBC cases. The premise that neoadjuvant systemic therapy aids in selecting diseases with more favorable biological characteristics and addresses micro-metastatic disease appears applicable to iGBC as well. This systematic review examines the current evidence supporting or refuting neoadjuvant therapy and discusses criteria for selecting patients who would derive significant benefit, along with proposing an optimal chemotherapy regimen for iGBC patients. Improved outcomes have been reported in patients undergoing reoperation after 4 to 14 weeks following the initial cholecystectomy compared to immediate reoperation. Limited, yet promising, evidence supports the use of 3 to 4 cycles of gemcitabine-based neoadjuvant chemotherapy prior to reoperative surgery in select high-risk iGBC cases.
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Affiliation(s)
- Peeyush Varshney
- Department of Surgical Gastroenterology, All India Institute of Medical Sciences, Jodhpur, India
| | - Saphalta Baghmar
- Department of Medical Oncology, Amrita Institute of Medical Sciences, Faridabad, India
| | - Bhawna Sirohi
- Department of Medical Oncology, Vedanta Medical Research Foundation, Balco Medical Center, Raipur, India
| | - Ghassan K Abou-Alfa
- Department of Medical Oncology, Memorial Sloan Kettering Cancer Center, New York, NY, United States
- Department of Medical Oncology, Weill Cornell College at Cornell University, New York, NY, United States
- Department of Medical Oncology, Trinity College Dublin, Dublin, Ireland
| | - Hop Tran Cao
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, United States
| | - Lalit Mohan Sharma
- Department of Medical Oncology, Mahatma Gandhi Medical College and Hospital, Jaipur, India
| | - Milind Javle
- Department of Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, United States
| | - Thorsten Goetze
- Department of Visceral Surgery, Krankenhaus Nordwest, Frankfurt, Germany
- Department of Visceral Surgery, University Cancer Center Frankfurt, Frankfurt, Germany
| | - Vinay K Kapoor
- Department of Surgical Gastroenterology, Mahatma Gandhi Medical College and Hospital, Jaipur, India
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Tsilimigras DI, Kurzrock R, Pawlik TM. Molecular Testing and Targeted Therapies in Hepatobiliary Cancers: A Review. JAMA Surg 2025; 160:576-585. [PMID: 40105823 DOI: 10.1001/jamasurg.2025.0242] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/20/2025]
Abstract
Importance Hepatobiliary cancers are heterogeneous and molecularly complex. Recent advances in next-generation sequencing (NGS) have enhanced the understanding of their molecular landscape and enabled deployment of biomarker-based gene- and immune-targeted therapies. This review examines the role of molecular testing and targeted therapies in these malignant neoplasms. Observations Patients with hepatobiliary cancers have poor outcomes. Precision oncology studies have shown that while many common molecular alterations are not currently targetable in hepatocellular carcinoma (HCC), a large number of actionable alterations characterize biliary tract cancers (BTCs), with several therapies now approved by the US Food and Drug Administration. Immunotherapy is increasingly adopted in clinical practice, either as monotherapy or combined with cytotoxic chemotherapy, for both HCC and BTCs. Moreover, multiple solid cancer tumor-agnostic therapies are approved (larotrectinib, entrectinib, and repotrectinib for NTRK fusions; selpercatinib for RET fusions; dabrafenib and trametinib combination for BRAF V600E mutations; dostarlimab or pembrolizumab for tumors with high microsatellite instability and pembrolizumab for tumor mutation burden ≥10 mutations/megabase), highlighting the need for NGS as well as ERBB2 (formerly HER2) immunohistochemistry (IHC) (with the recent approval of solid tissue-agnostic deruxtecan trastuzumab for ERBB2-positive [IHC 3+] cancer) across cancers. N-of-1 clinical trials using customized drug combinations matched to the tumor's molecular profile have yielded encouraging results and provide a promising framework for future clinical trial design. Conclusions and Relevance Molecular testing and gene- and immune-targeted therapies are transforming hepatobiliary cancer treatment. Tumor-agnostic and N-of-1 clinical trials have challenged traditional clinical trial paradigms and provide the foundation for truly personalized oncology for patients with these aggressive cancers. Further work is needed to determine how to leverage these novel approaches into the management of operable disease.
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Affiliation(s)
- Diamantis I Tsilimigras
- Department of Surgery, Division of Surgical Oncology, The Ohio State University Wexner Medical Center and James Comprehensive Cancer Center, Columbus
| | - Razelle Kurzrock
- Medical College of Wisconsin Cancer Center and Linda T. and John A. Mellowes Center for Genomic Sciences and Precision Medicine, Milwaukee
| | - Timothy M Pawlik
- Department of Surgery, Division of Surgical Oncology, The Ohio State University Wexner Medical Center and James Comprehensive Cancer Center, Columbus
- Deputy Editor, JAMA Surgery
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Soliman N, Maqsood A, Connor AA. Role of genomics in liver transplantation for cholangiocarcinoma. Curr Opin Organ Transplant 2025; 30:158-170. [PMID: 39917813 DOI: 10.1097/mot.0000000000001209] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/06/2025]
Abstract
PURPOSE OF REVIEW The purpose of this review is to summarize the current knowledge of cholangiocarcinoma molecular biology and to suggest a framework for implementation of next-generation sequencing in all stages of liver transplantation. This is timely as recent guidelines recommend increased use of these technologies with promising results. RECENT FINDINGS The main themes covered here address germline and somatic genetic alterations recently discovered in cholangiocarcinoma, particularly those associated with prognosis and treatment responses, and nascent efforts to translate these into contemporary practice in the peri-liver transplantation period. SUMMARY Early efforts to translate molecular profiling to cholangiocarcinoma care demonstrate a growing number of potentially actionable alterations. Still lacking is a consensus on what biomarkers and technologies to adopt, at what scale and cost, and how to integrate them most effectively into care with the ambition of increasing the number of patients eligible for liver transplantation and improving their long-term outcomes.
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Affiliation(s)
- Nadine Soliman
- Department of Surgery
- J. C. Walter Jr. Transplant Center, Houston Methodist Hospital
- Houston Methodist Academic Institute
| | - Anaum Maqsood
- Department of Medicine
- Neill Cancer Center, Houston Methodist Hospital, Houston, Texas
| | - Ashton A Connor
- Department of Surgery
- J. C. Walter Jr. Transplant Center, Houston Methodist Hospital
- Houston Methodist Academic Institute
- Neill Cancer Center, Houston Methodist Hospital, Houston, Texas
- Department of Surgery, Weill Cornell Medicine, Cornell University, New York, New York, USA
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4
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Sharib J, Rhodin KE, Liu A, McIntyre S, Bartholomew A, Masoud S, DeLaura I, Kemeny NE, Cercek A, Harding JJ, O'Reilly EM, Abou-Alfa GK, Reidy-Lagunes D, Connell LC, Dika IE, Balachandran VP, Drebin J, Soares KC, Wei AC, Kingham TP, D'Angelica MI, Uronis H, Strickler J, Hsu SD, Morse M, Zani S, Allen PJ, Jarnagin WR, Lidsky ME. Adjuvant Cytotoxic Chemotherapy may not be Associated with a Survival Advantage for Resected Intrahepatic Cholangiocarcinoma. Ann Surg Oncol 2025; 32:2456-2466. [PMID: 39827317 DOI: 10.1245/s10434-024-16799-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/18/2024] [Accepted: 12/14/2024] [Indexed: 01/22/2025]
Abstract
BACKGROUND Randomized data suggest improved survival with adjuvant chemotherapy for biliary tract cancers; however, subset analyses of intrahepatic cholangiocarcinoma (IHC) show limited survival benefit. This study evaluated the impact of adjuvant chemotherapy on recurrence patterns and overall survival (OS) in patients with resected IHC. METHODS Patients who underwent curative-intent resection for IHC were identified within a bi-institutional dataset and the National Cancer Database (NCDB). Patients were stratified by receipt of adjuvant chemotherapy. Site of first recurrence was categorized as liver only, regional, distant, or multifocal. Survival outcomes within each dataset were compared using Kaplan-Meier methods. RESULTS In the bi-institutional dataset, 347 patients underwent resection for IHC, and 149 (43%) patients received adjuvant cytotoxic chemotherapy. Recurrence was observed in 222 (64.0%) patients. OS was similar between groups (adjuvant vs. observation: 42 vs. 49 months; p = 0.13), and did not differ in patients who received capecitabine specifically (p = 0.09) or in a risk-adjusted multivariable analysis. Recurrence-free survival was worse in those who received adjuvant chemotherapy (p = 0.04), although the liver was the most common site of recurrence in both groups (0.63). A similar analysis of 1159 resected IHCs from the NCDB also demonstrated no association between adjuvant chemotherapy and OS (49 vs. 57 months; p = 0.1). CONCLUSION Adjuvant chemotherapy may not be associated with improved OS in IHC and did not have an impact on hepatic recurrence in this retrospective analysis. Future investigation to identify more effective adjuvant systemic regimens and/or explore the potential role of adjuvant liver-directed therapies to reduce hepatic recurrence that may improve OS for IHC is warranted.
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Affiliation(s)
- Jeremy Sharib
- Department of Surgery, Duke University Medical Center, Durham, NC, USA.
| | - Kristen E Rhodin
- Department of Surgery, Duke University Medical Center, Durham, NC, USA
| | - Annie Liu
- Department of Surgery, Duke University Medical Center, Durham, NC, USA
| | - Sarah McIntyre
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Alex Bartholomew
- Department of Surgery, Duke University Medical Center, Durham, NC, USA
| | - Sabran Masoud
- Department of Surgery, Duke University Medical Center, Durham, NC, USA
| | - Isabel DeLaura
- Department of Surgery, Duke University Medical Center, Durham, NC, USA
| | - Nancy E Kemeny
- Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Andrea Cercek
- Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - James J Harding
- Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Eileen M O'Reilly
- Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Ghassan K Abou-Alfa
- Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Diane Reidy-Lagunes
- Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | | | - Imane El Dika
- Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Vinod P Balachandran
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Jeffrey Drebin
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Kevin C Soares
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Alice C Wei
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - T Peter Kingham
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Michael I D'Angelica
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Hope Uronis
- Department of Medicine, Duke University Medical Center, Durham, NC, USA
| | - John Strickler
- Department of Medicine, Duke University Medical Center, Durham, NC, USA
| | - S David Hsu
- Department of Medicine, Duke University Medical Center, Durham, NC, USA
| | - Michael Morse
- Department of Medicine, Duke University Medical Center, Durham, NC, USA
| | - Sabino Zani
- Department of Surgery, Duke University Medical Center, Durham, NC, USA
| | - Peter J Allen
- Department of Surgery, Duke University Medical Center, Durham, NC, USA
| | - William R Jarnagin
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Michael E Lidsky
- Department of Surgery, Duke University Medical Center, Durham, NC, USA
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5
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Aljehani MJ, Mukhtar RM, AlFallaj R, Alhusayni RA, Alraddadi RM, Alhussaini R. A spot review on relations between socioeconomic aspect and clinical recurrence of cholesteatoma. Eur Arch Otorhinolaryngol 2025; 282:895-905. [PMID: 39692803 DOI: 10.1007/s00405-024-09101-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/09/2024] [Accepted: 11/16/2024] [Indexed: 12/19/2024]
Abstract
BACKGROUND This study investigates the relationship between the recurrence of Chronic Otitis Media with Otorrhea (ChOLE) and patient-related factors, surgical procedures, and elements. It involved 190 patients and aimed to identify significant relationships between demographics, condition severity, surgical approaches, comorbidities, problem classification, hygiene practices, and education level. Statistical analyses, including Chi-Square tests, were used to determine these connections. METHODOLOGY Data from 190 patients were meticulously reviewed, leading to significant discoveries. Statistical techniques, particularly Chi-Square tests, were employed to comprehend the links between ChOLE recurrence and diverse patient-related factors. RESULTS The examination yielded crucial insights, revealing significant correlations between ChOLE recurrence and comorbidities, education level, complications, problem classification, and hygiene habits. These findings were confirmed with a confidence level of 95%. Moreover, specific relationships were observed between recurrence and surgical procedures, geographic location, and condition severity. CONCLUSION This study highlights the significance of factors like comorbidities, education level, complications, problem classification, and hygiene practices in predicting ChOLE recurrence. It also reveals notable associations with surgical techniques, patient location, and condition severity. Understanding these factors is vital for assessing recurrence risk, improving patient care, and developing personalized treatments. These findings advance our understanding of ChOLE recurrence, enabling more targeted interventions for this common ear condition.
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Affiliation(s)
| | | | | | | | | | - Rayan Alhussaini
- Otologist consultant cochlear implant surgeon, NGHM, Madinah, Saudi Arabia
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Dayyani F, Stirnadel-Farrant HA, Hu J, Lin Y, Kebede N, Valerio SJ, Ahn DH. Treatment Patterns and Outcomes in Patients with Advanced Biliary Tract Cancers Treated with Gemcitabine-Based Chemotherapy: A Retrospective Study. Cancers (Basel) 2025; 17:305. [PMID: 39858087 PMCID: PMC11764298 DOI: 10.3390/cancers17020305] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/09/2024] [Revised: 01/06/2025] [Accepted: 01/15/2025] [Indexed: 01/27/2025] Open
Abstract
Background: Historically, the standard of care for advanced biliary tract cancers (aBTCs) was gemcitabine plus cisplatin (GemCis). Immunotherapy plus GemCis is now recommended as a first-line treatment for aBTCs. Whether patients can tolerate eight cycles of GemCis in clinical practice, as per the Advanced Biliary Cancer (ABC)-02 study, remains to be assessed. We performed a retrospective observational cohort study to assess real-world treatment patterns and overall survival (OS) in patients with de novo or recurrent aBTCs treated with first-line gemcitabine-based chemotherapy in the United States. Methods: This retrospective observational cohort study used Optum's de-identified Market Clarity Data (Market Clarity). Adults diagnosed with de novo or recurrent aBTCs in the United States who began first-line gemcitabine-based chemotherapy from January 2016-March 2022 were identified and followed from index until death, the end of continuous enrolment, or the end of study period. Treatment patterns and OS were assessed. Results: Overall, 559 patients were included (de novo, n = 462; recurrent, n = 97). GemCis was the most common first-line therapy received (de novo: 73.8%; recurrent: 57.7%). Most patients received approximately five cycles of GemCis; median (95% CI) time to discontinuation was 4.6 (4.3-5.1) months. Most patients died over the follow-up period (de novo: 70.3%; recurrent: 62.9%). Median OS (95% CI) was 14.2 (12.1-16.1) months (de novo) and 18.5 (15.6-26.9) months (recurrent). Conclusions: GemCis was the most common first-line therapy received during the study period; most patients were unable to receive eight cycles of GemCis. Survival was limited over the follow-up period, highlighting the need for new treatments for aBTCs. Future studies are warranted to understand the real-world impact of first-line immunotherapy plus GemCis for patients with aBTCs.
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Affiliation(s)
- Farshid Dayyani
- Division of Hematology/Oncology and Chao Family Comprehensive Cancer Center, University of California, Irvine, 200 S Manchester Avenue, Orange, CA 92868, USA
| | | | - Jenny Hu
- Oncology Data & Analytics, AstraZeneca, Gaithersburg, MD 20878, USA; (J.H.); (N.K.)
| | - Yian Lin
- Oncology Biometrics, Oncology Research & Development, AstraZeneca, South San Francisco, CA 94080, USA;
| | - Nehemiah Kebede
- Oncology Data & Analytics, AstraZeneca, Gaithersburg, MD 20878, USA; (J.H.); (N.K.)
| | - Stephen J. Valerio
- United States Medical Affairs, AstraZeneca, Gaithersburg, MD 20878, USA;
| | - Daniel H. Ahn
- Division of Medical Oncology, Mayo Clinic, Phoenix, AZ 85054, USA;
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7
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Zhan T, Betge J, Schulte N, Dreikhausen L, Hirth M, Li M, Weidner P, Leipertz A, Teufel A, Ebert MP. Digestive cancers: mechanisms, therapeutics and management. Signal Transduct Target Ther 2025; 10:24. [PMID: 39809756 PMCID: PMC11733248 DOI: 10.1038/s41392-024-02097-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/29/2024] [Revised: 10/20/2024] [Accepted: 11/29/2024] [Indexed: 01/16/2025] Open
Abstract
Cancers of the digestive system are major contributors to global cancer-associated morbidity and mortality, accounting for 35% of annual cases of cancer deaths. The etiologies, molecular features, and therapeutic management of these cancer entities are highly heterogeneous and complex. Over the last decade, genomic and functional studies have provided unprecedented insights into the biology of digestive cancers, identifying genetic drivers of tumor progression and key interaction points of tumor cells with the immune system. This knowledge is continuously translated into novel treatment concepts and targets, which are dynamically reshaping the therapeutic landscape of these tumors. In this review, we provide a concise overview of the etiology and molecular pathology of the six most common cancers of the digestive system, including esophageal, gastric, biliary tract, pancreatic, hepatocellular, and colorectal cancers. We comprehensively describe the current stage-dependent pharmacological management of these malignancies, including chemo-, targeted, and immunotherapy. For each cancer entity, we provide an overview of recent therapeutic advancements and research progress. Finally, we describe how novel insights into tumor heterogeneity and immune evasion deepen our understanding of therapy resistance and provide an outlook on innovative therapeutic strategies that will shape the future management of digestive cancers, including CAR-T cell therapy, novel antibody-drug conjugates and targeted therapies.
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Affiliation(s)
- Tianzuo Zhan
- Department of Medicine II, University Medical Center Mannheim, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany
- DKFZ Hector Cancer Institute at University Medical Center Mannheim, Mannheim, Germany
- Mannheim Cancer Center, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany
- Molecular Medicine Partnership Unit, European Molecular Biology Laboratory, Heidelberg, Germany
| | - Johannes Betge
- Department of Medicine II, University Medical Center Mannheim, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany
- DKFZ Hector Cancer Institute at University Medical Center Mannheim, Mannheim, Germany
- Mannheim Cancer Center, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany
- Junior Clinical Cooperation Unit Translational Gastrointestinal Oncology and Preclinical Models, German Cancer Research Center (DKFZ), Heidelberg, Germany
| | - Nadine Schulte
- Department of Medicine II, University Medical Center Mannheim, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany
- Mannheim Cancer Center, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany
| | - Lena Dreikhausen
- Department of Medicine II, University Medical Center Mannheim, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany
- Molecular Medicine Partnership Unit, European Molecular Biology Laboratory, Heidelberg, Germany
| | - Michael Hirth
- Department of Medicine II, University Medical Center Mannheim, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany
| | - Moying Li
- Department of Medicine II, University Medical Center Mannheim, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany
| | - Philip Weidner
- Department of Medicine II, University Medical Center Mannheim, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany
| | - Antonia Leipertz
- Department of Medicine II, University Medical Center Mannheim, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany
| | - Andreas Teufel
- Department of Medicine II, University Medical Center Mannheim, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany
| | - Matthias P Ebert
- Department of Medicine II, University Medical Center Mannheim, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
- DKFZ Hector Cancer Institute at University Medical Center Mannheim, Mannheim, Germany.
- Mannheim Cancer Center, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
- Molecular Medicine Partnership Unit, European Molecular Biology Laboratory, Heidelberg, Germany.
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8
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Palepu J, Endo I, Chaudhari VA, Murthy GVS, Chaudhuri S, Adam R, Smith M, de Reuver PR, Lendoire J, Shrikhande SV, De Aretxabala X, Sirohi B, Kokudo N, Kwon W, Pal S, Bouzid C, Dixon E, Shah SR, Maroni R, Nervi B, Mengoa C, Patil S, Ebata T, Maithel SK, Lang H, Primrose J, Hirano S, Guevara OA, Ohtsuka M, Valle JW, Sharma A, Nagarajan G, Núñez Ju JJ, Arroyo GF, Torrez SL, Erdmann JI, Butte JM, Furuse J, Lee SE, Gomes AP, Park SJ, Jang JY, Oddi R, Barreto SG, Kijima H, Ciacio O, Gowda NS, Jarnagin W. 'IHPBA-APHPBA clinical practice guidelines': international Delphi consensus recommendations for gallbladder cancer. HPB (Oxford) 2024; 26:1311-1326. [PMID: 39191539 DOI: 10.1016/j.hpb.2024.07.411] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/25/2024] [Revised: 07/12/2024] [Accepted: 07/16/2024] [Indexed: 08/29/2024]
Abstract
BACKGROUND The Delphi consensus study was carried out under the auspices of the International and Asia-Pacific Hepato-Pancreato-Biliary Associations (IHPBA-APHPBA) to develop practice guidelines for management of gallbladder cancer (GBC) globally. METHOD GBC experts from 17 countries, spanning 6 continents, participated in a hybrid four-round Delphi consensus development process. The methodology involved email, online consultations, and in-person discussions. Sixty eight clinical questions (CQs) covering various domains related to GBC, were administered to the experts. A consensus recommendation was accepted only when endorsed by more than 75% of the participating experts. RESULTS Out of the sixty experts invited initially to participate in the consensus process 45 (75%) responded to the invitation. The consensus was achieved in 92.6% (63/68) of the CQs. Consensus covers epidemiological aspects of GBC, early, incidental and advanced GBC management, definitions for radical GBC resections, the extent of liver resection, lymph node dissection, and definitions of borderline resectable and locally advanced GBC. CONCLUSIONS This is the first international Delphi consensus on GBC. These recommendations provide uniform terminology and practical clinical guidelines on the current management of GBC. Unresolved contentious issues like borderline resectable/locally advanced GBC need to be addressed by future clinical studies.
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Affiliation(s)
- Jagannath Palepu
- Continental Cancer Centre, Continental Hospitals, Hyderabad, India; Dept. of Surgical Oncology Lilavati Hospital & Research Centre and SL Raheja Hospital, Mumbai, India.
| | - Itaru Endo
- Department of Gastroenterological Surgery, Yokohama City University, Yokohama, Japan
| | - Vikram Anil Chaudhari
- GI and HPB Surgical Oncology, Tata Memorial Centre, Homi Bhabha National Institute, Mumbai, India
| | - G V S Murthy
- PRASHO Foundation, Hyderabad, India; London School of Hygiene and Tropical Medicine, London, UK
| | | | - Rene Adam
- Department of Hepatobiliary Surgery, Cancer and Transplantation, AP-HP Hôpital Paul Brousse / Univ Paris-Saclay, Centre Hépato-Biliaire, Villejuif, France
| | - Martin Smith
- Surgery, University of the Witwatersrand Johannesburg, Johannesburg, South Africa
| | | | - Javier Lendoire
- HPB & Liver Transplantation, Instituto de Trasplantes y Alta Complejidad (ITAC), Buenos Aires, Argentina
| | - Shailesh V Shrikhande
- GI and HPB Surgical Oncology, Tata Memorial Centre, Homi Bhabha National Institute, Mumbai, India
| | | | - Bhawna Sirohi
- Medical Oncology, Vedanta Medical Research foundation (Balco Medical Centre), Raipur, India
| | - Norihiro Kokudo
- Hepato-Biliary-Pancreatic Surgery Division, Department of Surgery, National Center for Global Health and Medicine, Tokyo, Japan
| | - Wooil Kwon
- Department of Surgery and Cancer Research Institute, Seoul National University College of Medicine, Seoul, South Korea
| | - Sujoy Pal
- Deptt of GI Surgery and Liver transplantation, All India Institute of Medical Sciences, New Delhi, India
| | - Chafik Bouzid
- HPB and Digestive Oncology Surgery, Dept. of Surgical Oncology, DBK anti cancer center, Mouloud Mammeri University, Tizi Ouzou, Algeria
| | - Elijah Dixon
- Department of Surgery, University of Calgary, Calgary, Canada
| | | | - Rodrigo Maroni
- Head of Program of Surgery, Hospital Papa Francisco, Salta, Argentina
| | - Bruno Nervi
- Chief Department, Department of Hematology and Oncology, Pontificia Universidad Católica de Chile, Santiago, Chile
| | - Claudio Mengoa
- Surgery, Instituto Regional de Enfermedades Neoplasicas, Arequipa, Peru
| | | | - Tomoki Ebata
- Surgical Oncology, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Shishir K Maithel
- Professor of Surgery, Department of Surgery, Emory University, Atlanta, USA
| | - Hauke Lang
- Visceral- and Transplantation Surgery, Universitätsmedizin Mainz, Mainz, Germany
| | - John Primrose
- Department of Surgery, University of Southampton, Southampton, UK
| | - Satoshi Hirano
- Gastroenterological Surgery II, Hokkaido University Faculty of Medicine, Sapporo, Japan
| | - Oscar A Guevara
- Surgery, Universidad Nacional de Colombia / Instituto Nacional de Cancerologia, Bogota, Colombia
| | - Masayuki Ohtsuka
- Department of General Surgery, Graduate School of Medicine, Chiba University, Chiba, Japan
| | - Juan W Valle
- Chief Medical Officer, Research Department, Cholangiocarcinoma Foundation, Herriman, UT, USA
| | - Atul Sharma
- Medical Oncology, Max Institute Of Cancer Care, New Delhi, India
| | - Ganesh Nagarajan
- Surgical oncology ( GI and HPB), Nanavati Max hospital mumbai, Mumbai, India
| | - Juan Jose Núñez Ju
- HPB General Surgery Service, Hospital Nacional Guillermo Almenara, Lima, Peru
| | | | | | | | - Jean M Butte
- Surgery, Instituto Oncologico FALP, Santiago, Chile
| | - Junji Furuse
- Gastroenterology, Kanagawa Cancer Center, Yokohama, Japan
| | - Seung Eun Lee
- Department of surgery, Chung-Ang University College of Medicine, Seoul, South Korea
| | - António Pedro Gomes
- Surgery Department, Hospital Vila Franca de Xira, Vila Franca de Xira, Portugal
| | - Sang-Jae Park
- Center for Liver and Pancreatobiliary Cancer, National Cancer Center, Goyang-si, South Korea
| | - Jin-Young Jang
- Department of Surgery and Cancer Research Institute, Seoul National University College of Medicine, Seoul, South Korea
| | - Ricardo Oddi
- Center for Clinical Medical Education and Research (CEMIC), Buenos Aires, Argentina
| | - Savio George Barreto
- HPB and Liver Transplant Unit, Flinders Medical Centre, Flinders University, Austraila
| | - Hiroshi Kijima
- Department of Pathology and Bioscience, Hirosaki University Graduate School of Medicine, Hirosaki, Aomori, Japan
| | - Oriana Ciacio
- Centre Hépato-Biliaire, AP-HP - Hôpital Paul Brousse / Paris-Saclay University, Villejuif, France
| | - Nagesh S Gowda
- Institute of Gastroenterology and Organ Transplantation, Bengaluru, India
| | - William Jarnagin
- Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, USA
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9
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Dominguez DA, Wong P, Chen YJ, Singh GP, Fong Y, Li D, Ituarte PHG, Melstrom LG. Adjuvant Chemoradiation in Resected Biliary Adenocarcinoma: Evaluation of SWOG S0809 with a Large National Database. Ann Surg Oncol 2024; 31:4896-4904. [PMID: 38443700 PMCID: PMC11236922 DOI: 10.1245/s10434-024-15117-y] [Citation(s) in RCA: 3] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/22/2023] [Accepted: 02/14/2024] [Indexed: 03/07/2024]
Abstract
BACKGROUND There is a paucity of evidence supporting the use of adjuvant radiation therapy in resected biliary cancer. Supporting evidence for use comes mainly from the small SWOG S0809 trial, which demonstrated an overall median survival of 35 months. We aimed to use a large national database to evaluate the use of adjuvant chemoradiation in resected extrahepatic bile duct and gallbladder cancer. METHODS Using the National Cancer Database, we selected patients from 2004 to 2017 with pT2-4, pN0-1, M0 extrahepatic bile duct or gallbladder adenocarcinoma with either R0 or R1 resection margins, and examined factors associated with overall survival (OS). We examined OS in a cohort of patients mimicking the SWOG S0809 protocol as a large validation cohort. Lastly, we compared patients who received chemotherapy only with patients who received adjuvant chemotherapy and radiation using entropy balancing propensity score matching. RESULTS Overall, 4997 patients with gallbladder or extrahepatic bile duct adenocarcinoma with available survival information meeting the SWOG S0809 criteria were selected, 469 of whom received both adjuvant chemotherapy and radiotherapy. Median OS in patients undergoing chemoradiation was 36.9 months, and was not different between primary sites (p = 0.841). In a propensity score matched cohort, receipt of adjuvant chemoradiation had a survival benefit compared with adjuvant chemotherapy only (hazard ratio 0.86, 95% confidence interval 0.77-0.95; p = 0.004). CONCLUSION Using a large national database, we support the findings of SWOG S0809 with a similar median OS in patients receiving chemoradiation. These data further support the consideration of adjuvant multimodal therapy in resected biliary cancers.
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Affiliation(s)
- Dana A Dominguez
- Department of Surgical Oncology, City of Hope National Medical Center, Duarte, CA, USA
| | - Paul Wong
- Department of Surgical Oncology, City of Hope National Medical Center, Duarte, CA, USA
- School of Medicine, University of California, San Francisco, San Francisco, CA, USA
| | - Yi-Jen Chen
- Department of Radiation Oncology, City of Hope National Medical Center, Duarte, CA, USA
| | - Gagandeep P Singh
- Department of Surgical Oncology, City of Hope National Medical Center, Duarte, CA, USA
| | - Yuman Fong
- Department of Surgical Oncology, City of Hope National Medical Center, Duarte, CA, USA
| | - Daneng Li
- Department of Medical Oncology, City of Hope National Medical Center, Duarte, CA, USA
| | - Philip H G Ituarte
- Department of Surgical Oncology, City of Hope National Medical Center, Duarte, CA, USA
| | - Laleh G Melstrom
- Department of Surgical Oncology, City of Hope National Medical Center, Duarte, CA, USA.
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10
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Esmail A, Badheeb M, Alnahar BW, Almiqlash B, Sakr Y, Al-Najjar E, Awas A, Alsayed M, Khasawneh B, Alkhulaifawi M, Alsaleh A, Abudayyeh A, Rayyan Y, Abdelrahim M. The Recent Trends of Systemic Treatments and Locoregional Therapies for Cholangiocarcinoma. Pharmaceuticals (Basel) 2024; 17:910. [PMID: 39065760 PMCID: PMC11279608 DOI: 10.3390/ph17070910] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/14/2024] [Revised: 07/03/2024] [Accepted: 07/05/2024] [Indexed: 07/28/2024] Open
Abstract
Cholangiocarcinoma (CCA) is a hepatic malignancy that has a rapidly increasing incidence. CCA is anatomically classified into intrahepatic (iCCA) and extrahepatic (eCCA), which is further divided into perihilar (pCCA) and distal (dCCA) subtypes, with higher incidence rates in Asia. Despite its rarity, CCA has a low 5-year survival rate and remains the leading cause of primary liver tumor-related death over the past 10-20 years. The systemic therapy section discusses gemcitabine-based regimens as primary treatments, along with oxaliplatin-based options. Second-line therapy is limited but may include short-term infusional fluorouracil (FU) plus leucovorin (LV) and oxaliplatin. The adjuvant therapy section discusses approaches to improve overall survival (OS) post-surgery. However, only a minority of CCA patients qualify for surgical resection. In comparison to adjuvant therapies, neoadjuvant therapy for unresectable cases shows promise. Gemcitabine and cisplatin indicate potential benefits for patients awaiting liver transplantation. The addition of immunotherapies to chemotherapy in combination is discussed. Nivolumab and innovative approaches like CAR-T cells, TRBAs, and oncolytic viruses are explored. We aim in this review to provide a comprehensive report on the systemic and locoregional therapies for CCA.
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Affiliation(s)
- Abdullah Esmail
- Section of GI Oncology, Houston Methodist Neal Cancer Center, Houston Methodist Hospital, Houston, TX 77030, USA
| | - Mohamed Badheeb
- Department of Internal Medicine, Yale New Haven Health, Bridgeport Hospital, Bridgeport, CT 06610, USA
| | | | - Bushray Almiqlash
- Zuckerman College of Public Health, Arizona State University, Tempe, AZ 85287, USA;
| | - Yara Sakr
- Department of GI Medical Oncology, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
| | - Ebtesam Al-Najjar
- Section of GI Oncology, Houston Methodist Neal Cancer Center, Houston Methodist Hospital, Houston, TX 77030, USA
| | - Ali Awas
- Faculty of Medicine and Health Sciences, University of Science and Technology, Sanaa P.O. Box 15201-13064, Yemen
| | | | - Bayan Khasawneh
- Section of GI Oncology, Houston Methodist Neal Cancer Center, Houston Methodist Hospital, Houston, TX 77030, USA
| | | | - Amneh Alsaleh
- Department of Medicine, Desert Regional Medical Center, Palm Springs, CA 92262, USA
| | - Ala Abudayyeh
- Division of Internal Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
| | - Yaser Rayyan
- Department of Gastroenterology & Hepatology, Faculty of Medicine, The University of Jordan, Amman 11942, Jordan
| | - Maen Abdelrahim
- Section of GI Oncology, Houston Methodist Neal Cancer Center, Houston Methodist Hospital, Houston, TX 77030, USA
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11
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Newhook TE, Tsai S, Meric-Bernstam F. Precision Oncology in Hepatopancreatobiliary Cancer Surgery. Surg Oncol Clin N Am 2024; 33:343-367. [PMID: 38401914 DOI: 10.1016/j.soc.2023.12.016] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/26/2024]
Abstract
Advances in technology have allowed for the characterization of tumors at the genomic, transcriptomic, and proteomic levels. There are well-established targets for biliary tract cancers, with exciting new targets emerging in pancreatic ductal adenocarcinoma and potential targets in hepatocellular carcinoma. Taken together, these data suggest an important role for molecular profiling for personalizing cancer therapy in advanced disease and need for design of novel neoadjuvant studies to leverage these novel therapeutics perioperatively in the surgical patient.
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Affiliation(s)
- Timothy E Newhook
- Department of Surgical Oncology, Division of Surgery, University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA
| | - Susan Tsai
- Division of Surgical Oncology, Department of Surgery, Ohio State University Comprehensive Cancer Center, N924 Doan Hall, 410 West 10th Avenue, Columbus, OH 43210, USA
| | - Funda Meric-Bernstam
- Department of Investigational Cancer Therapeutics, Division of Cancer Medicine, University of Texas MD Anderson Cancer Center, 1400 Holcombe Boulevard, FC8.3044, Houston, TX 77030, USA.
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12
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Khosla D, Misra S, Chu PL, Guan P, Nada R, Gupta R, Kaewnarin K, Ko TK, Heng HL, Srinivasalu VK, Kapoor R, Singh D, Klanrit P, Sampattavanich S, Tan J, Kongpetch S, Jusakul A, Teh BT, Chan JY, Hong JH. Cholangiocarcinoma: Recent Advances in Molecular Pathobiology and Therapeutic Approaches. Cancers (Basel) 2024; 16:801. [PMID: 38398194 PMCID: PMC10887007 DOI: 10.3390/cancers16040801] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/11/2024] [Revised: 02/05/2024] [Accepted: 02/12/2024] [Indexed: 02/25/2024] Open
Abstract
Cholangiocarcinomas (CCA) pose a complex challenge in oncology due to diverse etiologies, necessitating tailored therapeutic approaches. This review discusses the risk factors, molecular pathology, and current therapeutic options for CCA and explores the emerging strategies encompassing targeted therapies, immunotherapy, novel compounds from natural sources, and modulation of gut microbiota. CCA are driven by an intricate landscape of genetic mutations, epigenetic dysregulation, and post-transcriptional modification, which differs based on geography (e.g., for liver fluke versus non-liver fluke-driven CCA) and exposure to environmental carcinogens (e.g., exposure to aristolochic acid). Liquid biopsy, including circulating cell-free DNA, is a potential diagnostic tool for CCA, which warrants further investigations. Currently, surgical resection is the primary curative treatment for CCA despite the technical challenges. Adjuvant chemotherapy, including cisplatin and gemcitabine, is standard for advanced, unresectable, or recurrent CCA. Second-line therapy options, such as FOLFOX (oxaliplatin and 5-FU), and the significance of radiation therapy in adjuvant, neoadjuvant, and palliative settings are also discussed. This review underscores the need for personalized therapies and demonstrates the shift towards precision medicine in CCA treatment. The development of targeted therapies, including FDA-approved drugs inhibiting FGFR2 gene fusions and IDH1 mutations, is of major research focus. Investigations into immune checkpoint inhibitors have also revealed potential clinical benefits, although improvements in survival remain elusive, especially across patient demographics. Novel compounds from natural sources exhibit anti-CCA activity, while microbiota dysbiosis emerges as a potential contributor to CCA progression, necessitating further exploration of their direct impact and mechanisms through in-depth research and clinical studies. In the future, extensive translational research efforts are imperative to bridge existing gaps and optimize therapeutic strategies to improve therapeutic outcomes for this complex malignancy.
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Affiliation(s)
- Divya Khosla
- Department of Radiotherapy and Oncology, Post Graduate Institute of Medical Education and Research, Chandigarh 160012, India
| | - Shagun Misra
- Department of Radiotherapy and Oncology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow 226014, India
| | - Pek Lim Chu
- Cancer and Stem Cell Biology Programme, Duke-NUS Medical School, Singapore 169857, Singapore
| | - Peiyong Guan
- Genome Institute of Singapore, Agency for Science, Technology and Research (A*STAR), Singapore 138672, Singapore
| | - Ritambhra Nada
- Department of Histopathology, Post Graduate Institute of Medical Education and Research, Chandigarh 160012, India
| | - Rajesh Gupta
- Department of GI Surgery, HPB, and Liver Transplantation, Post Graduate Institute of Medical Education and Research, Chandigarh 160012, India
| | - Khwanta Kaewnarin
- SingHealth Duke-NUS Institute of Biodiversity Medicine, Singapore 168583, Singapore
| | - Tun Kiat Ko
- Cancer Discovery Hub, National Cancer Center Singapore, Singapore 168583, Singapore
| | - Hong Lee Heng
- Laboratory of Cancer Epigenome, Division of Medical Science, National Cancer Center Singapore, Singapore 168583, Singapore
| | - Vijay Kumar Srinivasalu
- Department of Medical Oncology, Mazumdar Shaw Medical Center, NH Health City Campus, Bommasandra, Bangalore 560099, India
| | - Rakesh Kapoor
- Department of Radiotherapy and Oncology, Post Graduate Institute of Medical Education and Research, Chandigarh 160012, India
| | - Deepika Singh
- SingHealth Duke-NUS Institute of Biodiversity Medicine, Singapore 168583, Singapore
| | - Poramate Klanrit
- Cholangiocarcinoma Screening and Care Program (CASCAP), Khon Kaen University, Khon Kaen 40002, Thailand
- Department of Biochemistry, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand
| | - Somponnat Sampattavanich
- Siriraj Center of Research Excellence for Systems Pharmacology, Department of Pharmacology, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok 73170, Thailand
| | - Jing Tan
- Laboratory of Cancer Epigenome, Division of Medical Science, National Cancer Center Singapore, Singapore 168583, Singapore
- State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou 510060, China
| | - Sarinya Kongpetch
- Cholangiocarcinoma Research Institute, Khon Kaen University, Khon Kaen 40002, Thailand
- Department of Pharmacology, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand
| | - Apinya Jusakul
- Cholangiocarcinoma Research Institute, Khon Kaen University, Khon Kaen 40002, Thailand
- Centre for Research and Development of Medical Diagnostic Laboratories, Faculty of Associated Medical Sciences, Khon Kaen University, Khon Kaen 40002, Thailand
| | - Bin Tean Teh
- Cancer and Stem Cell Biology Programme, Duke-NUS Medical School, Singapore 169857, Singapore
- Genome Institute of Singapore, Agency for Science, Technology and Research (A*STAR), Singapore 138672, Singapore
- Laboratory of Cancer Epigenome, Division of Medical Science, National Cancer Center Singapore, Singapore 168583, Singapore
- Institute of Molecular and Cell Biology, Agency for Science, Technology and Research (A*STAR), Singapore 138673, Singapore
| | - Jason Yongsheng Chan
- Cancer Discovery Hub, National Cancer Center Singapore, Singapore 168583, Singapore
- Oncology Academic Clinical Program, Duke-NUS Medical School, Singapore 169857, Singapore
- Division of Medical Oncology, National Cancer Center, Singapore 168583, Singapore
| | - Jing Han Hong
- Cancer and Stem Cell Biology Programme, Duke-NUS Medical School, Singapore 169857, Singapore
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13
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Crum AE, Sestito M, Garland-Kledzik M, Boone BA. Prophylactic Hyperthermic Intraperitoneal Chemotherapy for Patients at High Risk of Developing Gallbladder Cancer Peritoneal Metastases: Case Report and Rationale for a Prospective Clinical Trial. J Clin Med 2024; 13:768. [PMID: 38337462 PMCID: PMC10856521 DOI: 10.3390/jcm13030768] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/25/2023] [Revised: 01/23/2024] [Accepted: 01/26/2024] [Indexed: 02/12/2024] Open
Abstract
Gallbladder cancer is a devastating disease with a 5-year survival of only 18%. The majority of gallbladder cancers are discovered incidentally in patients undergoing cholecystectomy. During non-oncologic laparoscopic cholecystectomy for gallbladder disease, gallbladder perforation occurs in 29% of cases and spillage of gallstones occurs in 9% of cases. Patients with gallbladder cancer frequently develop peritoneal recurrence, particularly after intra-operative bile spillage during cholecystectomy for incidental gallbladder cancer. The high likelihood of spillage and peritoneal seeding during cholecystectomy for incidental gallbladder cancer suggests the need for prophylactic strategies to prevent peritoneal carcinomatosis. Hyperthermic intraperitoneal chemotherapy (HIPEC) has efficacy in gallbladder cancer patients with macroscopic peritoneal disease undergoing cytoreductive surgery and has been associated with a survival advantage in a multi-institutional retrospective case series. However, the utilization of HIPEC with a prophylactic intent against the development of peritoneal disease following resection of gallbladder cancer has not yet been prospectively studied. Here, we review the literature surrounding gallbladder cancer and HIPEC, report an institutional experience utilizing prophylactic HIPEC, and discuss a recently proposed prospective clinical trial evaluating the efficacy of prophylactic HIPEC in the prevention of gallbladder peritoneal metastasis.
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Affiliation(s)
- Alexander E. Crum
- School of Medicine, West Virginia University, Morgantown, WV 26506, USA;
| | - Michael Sestito
- Department of Surgery, West Virginia University, Morgantown, WV 26506, USA; (M.S.); (M.G.-K.)
| | - Mary Garland-Kledzik
- Department of Surgery, West Virginia University, Morgantown, WV 26506, USA; (M.S.); (M.G.-K.)
| | - Brian A. Boone
- Department of Surgery, West Virginia University, Morgantown, WV 26506, USA; (M.S.); (M.G.-K.)
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14
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Wilbur HC, Soares HP, Azad NS. Neoadjuvant and adjuvant therapy for biliary tract cancer: Advances and limitations. Hepatology 2024:01515467-990000000-00725. [PMID: 38266282 DOI: 10.1097/hep.0000000000000760] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/06/2023] [Accepted: 12/31/2023] [Indexed: 01/26/2024]
Abstract
Biliary tract cancers (BTC) are a rare and aggressive consortium of malignancies, consisting of intrahepatic cholangiocarcinoma, extrahepatic cholangiocarcinoma, and gallbladder carcinoma. While most patients present with metastatic disease, a minority of patients with BTC are eligible for curative surgical resection at the time of presentation. However, these patients have poor 5-year overall survival rates and high rates of recurrence, necessitating the improvement of the neoadjuvant and adjuvant treatment of BTC. In this review, we assess the neoadjuvant and adjuvant clinical trials for the treatment of BTC and discuss the challenges and limitations of clinical trials, as well as future directions for the treatment of BTC.
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Affiliation(s)
- H Catherine Wilbur
- Department of Oncology, The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, Maryland, USA
| | - Heloisa P Soares
- Division of Oncology, Department of Internal Medicine Huntsman Cancer Institute, University of Utah, Salt Lake City, Utah, USA
| | - Nilofer S Azad
- Department of Oncology, The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, Maryland, USA
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15
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Iseki M, Mizuma M, Unno M, Maruyama H, Akagi S, Shimoda M, Uemura K, Inoue T, Shiomi H, Watanabe M, Kobayashi M, Matsuda A, Mizuuchi Y, Aoki T, Shinkawa H, Takahata R, Makino K, Arai H, Yokoyama Y, Takeda S, Yaguchi Y, Kitagawa Y. Prognostic impact of postoperative infection after resection of biliary malignancy: A multicenter retrospective cohort study. Surgery 2023; 174:1145-1152. [PMID: 37599194 DOI: 10.1016/j.surg.2023.05.019] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/05/2023] [Revised: 05/05/2023] [Accepted: 05/24/2023] [Indexed: 08/22/2023]
Abstract
BACKGROUND The aim of this study was to investigate the prognostic impact of postoperative infections in patients who underwent resection for biliary malignancy, including intrahepatic cholangiocarcinoma, perihilar cholangiocarcinoma, distal cholangiocarcinoma, gallbladder carcinoma, and carcinoma of the ampulla of Vater. METHODS This study was conducted in an 11-center retrospective cohort study. Patients with biliary tract cancer who underwent curative resection between April 2013 and March 2015 at 11 institutions in Japan were enrolled. We analyzed the prevalence of postoperative infection, infection-related factors, and prognostic factors. RESULTS Of the total 290 cases, 33 were intrahepatic cholangiocarcinoma, 60 were perihilar cholangiocarcinoma, 120 were distal cholangiocarcinoma, 55 were gallbladder carcinoma, and 22 were carcinoma of the ampulla of Vater. Postoperative infectious complications, including remote infection, were observed in 146 patients (50.3%), and Clavien-Dindo ≥III in 115 patients (39.7%). Postoperative infections occurred more commonly in the patients who received pancreaticoduodenectomy and bile duct resection. Patients with infectious complications had a significantly poorer prognosis than those without (median overall survival 38 months vs 62 months, P = .046). In a diagnosis-specific analysis, although there was no correlation between infectious complications and overall survival in intrahepatic cholangiocarcinoma, perihilar cholangiocarcinoma, distal cholangiocarcinoma, and carcinoma of the ampulla of Vater, infectious complications were a significantly poor prognostic factor in gallbladder carcinoma (P = .031). CONCLUSION Postoperative infection after surgery for biliary tract cancer commonly occurred, especially in patients who underwent pancreaticoduodenectomy and bile duct resection. Postoperative infection is relatively associated with the prognosis of patients with biliary malignancy, especially gallbladder carcinoma.
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Affiliation(s)
- Masahiro Iseki
- Department of Surgery, Tohoku University Graduate School of Medicine, Sendai, Japan.
| | - Masamichi Mizuma
- Department of Surgery, Tohoku University Graduate School of Medicine, Sendai, Japan
| | - Michiaki Unno
- Department of Surgery, Tohoku University Graduate School of Medicine, Sendai, Japan
| | - Hiroshi Maruyama
- Department of Surgery, Nippon Medical School, Tama-Nagayama Hospital, Tokyo, Japan; Clinical Research Support Committee, Japan Society for Surgical Infection, Tokyo, Japan
| | - Shinji Akagi
- Clinical Research Support Committee, Japan Society for Surgical Infection, Tokyo, Japan; Department of Surgery, Mazda Hospital, Hiroshima, Japan
| | - Mitsugi Shimoda
- Clinical Research Support Committee, Japan Society for Surgical Infection, Tokyo, Japan; Department of Gastroenterological Surgery, Ibaraki Medical Center, Tokyo Medical University, Ibaraki, Japan
| | - Kenichiro Uemura
- Clinical Research Support Committee, Japan Society for Surgical Infection, Tokyo, Japan; Department of Surgery, Graduate School of Biomedical and Health Sciences, Hiroshima University, Japan
| | - Toru Inoue
- Clinical Research Support Committee, Japan Society for Surgical Infection, Tokyo, Japan; Department of Gastrointestinal Surgery, Osaka City General Hospital, Japan
| | - Hisanori Shiomi
- Clinical Research Support Committee, Japan Society for Surgical Infection, Tokyo, Japan; Department of Surgery, Nagahama Red Cross Hospital, Shiga, Japan
| | - Manabu Watanabe
- Clinical Research Support Committee, Japan Society for Surgical Infection, Tokyo, Japan; Department of Surgery, Toho University Ohashi Medical Center, Tokyo, Japan
| | - Minako Kobayashi
- Clinical Research Support Committee, Japan Society for Surgical Infection, Tokyo, Japan; Department of Infection Control and Prevention, Nippon Medical School, Musashikosugi Hospital, Kanagawa, Japan
| | - Akihisa Matsuda
- Clinical Research Support Committee, Japan Society for Surgical Infection, Tokyo, Japan; Department of Gastrointestinal and Hepato-Biliary-Pancreatic Surgery, Nippon Medical School, Tokyo, Japan
| | - Yusuke Mizuuchi
- Clinical Research Support Committee, Japan Society for Surgical Infection, Tokyo, Japan; Department of Surgery and Oncology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Taku Aoki
- Clinical Research Support Committee, Japan Society for Surgical Infection, Tokyo, Japan; Department of Hepato-Biliary-Pancreatic Surgery, Dokkyo Medical University, Tochigi, Japan
| | - Hiroji Shinkawa
- Clinical Research Support Committee, Japan Society for Surgical Infection, Tokyo, Japan; Department of Hepatobiliary-Pancreatic Surgery, Osaka Metropolitan University Graduate School of Medicine, Japan
| | - Risa Takahata
- Clinical Research Support Committee, Japan Society for Surgical Infection, Tokyo, Japan; Department of Medical Risk Management and Infection Control, National Defense Medical Collage, Saitama, Japan
| | - Kenta Makino
- Clinical Research Support Committee, Japan Society for Surgical Infection, Tokyo, Japan; Department of Surgery, Graduate School of Medicine, Kyoto University, Japan
| | - Hiroki Arai
- Clinical Research Support Committee, Japan Society for Surgical Infection, Tokyo, Japan; Department of Surgery, Nippon Medical School Chiba Hokusoh Hospital, Japan
| | - Yasuyuki Yokoyama
- Clinical Research Support Committee, Japan Society for Surgical Infection, Tokyo, Japan; Department of Digestive Surgery, Nippon Medical School Musashikosugi Hospital, Kanagawa, Japan
| | - Shigeru Takeda
- Clinical Research Support Committee, Japan Society for Surgical Infection, Tokyo, Japan; Department of Gastroenterological, Breast, and Endocrine Surgery, Yamaguchi University Graduate School of Medicine, Japan
| | - Yoshihisa Yaguchi
- Clinical Research Support Committee, Japan Society for Surgical Infection, Tokyo, Japan; Department of Surgery, Sassa General Hospital, Tokyo, Japan
| | - Yuko Kitagawa
- Department of Surgery, Keio University School of Medicine, Tokyo, Japan; The Japan Society of Surgical Infection, Tokyo, Japan
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16
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Kashyap L, Singh A, Tomar S, Gupta A, Sansar B, Chaudhary AK, Mishra BK, Sambasivaiah K, Kapoor A. Pattern of Care and Outcomes of Gallbladder Cancer Patients: Retrospective Study from a High Incidence Region in India. South Asian J Cancer 2023; 12:245-249. [PMID: 38047044 PMCID: PMC10691906 DOI: 10.1055/s-0043-1761440] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/05/2023] Open
Abstract
Lakhan KasyapIntroduction Gallbladder cancer (GBC) is the 20th most common cancer in India with a crude incidence rate of 2.3 per 100,000 persons. Of note, it is relatively common in states which fall in the Gangetic plains. Patients often present in the advanced stage and have an unfavorable prognosis. Materials and Methods From January to June 2021, 170 treatment-naive GBC (adenocarcinoma) patients who were registered at a tertiary care cancer center in North India, were included. Data were extracted from electronic medical records and was analyzed with SPSS. Results Median age was 56 years (range 32-77 years) and 65.5% ( n = 112) were female. Incidental GBC was found in 20% patient ( n = 34). Majority of patients (79.4%, n = 135) had preserved performance status. Advanced GBC was present in 85.8% ( n = 146) patients (locally advanced = 37.0% and metastatic = 48.8%). Biliary drainage procedure was performed in 24% of patients (68% of patients with obstructive jaundice). More than half of patients (53.5%) were lost to follow-up without any treatment. There were 33 patients (19.4%) who underwent surgery and 20 of them received neoadjuvant chemotherapy. Adjuvant chemotherapy and adjuvant radiotherapy were received by 13 and 2 patients, respectively. Palliative chemotherapy was administered to 46 patients. The most common chemotherapy regimen was gemcitabine-cisplatin. At a median follow-up of 1.7 months (95% confidence interval, 1-2.4 months), 42 patients (24%) progressed and 24 patients (14%) died, with 6 months estimated progression-free survival and overall survival being 60.2 and 79%, respectively. Conclusion GBC is an aggressive and lethal malignancy predominantly affecting females in the fifth decade with dismal outcomes. Improved access to health care, an aggressive approach in operable cases, and optimization of systemic and adjuvant therapy are the need of the hour.
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Affiliation(s)
- Lakhan Kashyap
- Department of Medical Oncology, Mahamana Pandit Madan Mohan Malviya Cancer Centre and Homi Bhabha Cancer Hospital, Tata Memorial Centre, Varanasi, Uttar Pradesh, India
| | - Arpita Singh
- Department of Medical Oncology, Mahamana Pandit Madan Mohan Malviya Cancer Centre and Homi Bhabha Cancer Hospital, Tata Memorial Centre, Varanasi, Uttar Pradesh, India
| | - Subham Tomar
- Department of Medical Oncology, Mahamana Pandit Madan Mohan Malviya Cancer Centre and Homi Bhabha Cancer Hospital, Tata Memorial Centre, Varanasi, Uttar Pradesh, India
| | - Anuj Gupta
- Department of Medical Oncology, Mahamana Pandit Madan Mohan Malviya Cancer Centre and Homi Bhabha Cancer Hospital, Tata Memorial Centre, Varanasi, Uttar Pradesh, India
| | - Bipinesh Sansar
- Department of Medical Oncology, Mahamana Pandit Madan Mohan Malviya Cancer Centre and Homi Bhabha Cancer Hospital, Tata Memorial Centre, Varanasi, Uttar Pradesh, India
| | - Amit Kumar Chaudhary
- Department of Medical Oncology, Mahamana Pandit Madan Mohan Malviya Cancer Centre and Homi Bhabha Cancer Hospital, Tata Memorial Centre, Varanasi, Uttar Pradesh, India
| | - Bal Krishna Mishra
- Department of Medical Oncology, Mahamana Pandit Madan Mohan Malviya Cancer Centre and Homi Bhabha Cancer Hospital, Tata Memorial Centre, Varanasi, Uttar Pradesh, India
| | - Kuraparthy Sambasivaiah
- Department of Medical Oncology, Mahamana Pandit Madan Mohan Malviya Cancer Centre and Homi Bhabha Cancer Hospital, Tata Memorial Centre, Varanasi, Uttar Pradesh, India
| | - Akhil Kapoor
- Department of Medical Oncology, Mahamana Pandit Madan Mohan Malviya Cancer Centre and Homi Bhabha Cancer Hospital, Tata Memorial Centre, Varanasi, Uttar Pradesh, India
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17
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Park Y, Jung W, Kim K, Chang AR, Park HJ, Koh HK, Kim BH. Patterns of locoregional recurrences and suggestion of the clinical target volume in resected perihilar extrahepatic cholangiocarcinoma. Clin Transl Radiat Oncol 2023; 41:100646. [PMID: 37441542 PMCID: PMC10334123 DOI: 10.1016/j.ctro.2023.100646] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/16/2023] [Revised: 05/25/2023] [Accepted: 05/29/2023] [Indexed: 07/15/2023] Open
Abstract
Purpose To evaluate the patterns of locoregional recurrence (LRR) in patients with perihilar extrahepatic cholangiocarcinoma (PEHC) treated with radical resection and to suggest the optimal target volume for elective nodal irradiation. Methods Medical records of PEHC patients who underwent radical resection between January 2000 and September 2021 at five institutions were reviewed. Patients who were confirmed with LRR in the follow-up imaging study were included. The LRR sites were mapped onto the corresponding sites in template computed tomography images. The margin around the vascular structure was investigated to generate the clinical target volume (CTV) covering the common sites of regional recurrences. Results A total of 87 LRRs in 46 patients were identified, 29 (33.3%) of which were local recurrences and 58 (66.7%) were regional recurrences. The most common site of local recurrence was the liver resection margin (n = 16), followed by the anastomosis site (n = 8). Regional recurrences were observed most commonly in the para-aortic area (n = 13), followed by in the aortocaval space (n = 11), portal vein area (n = 11), and portocaval area (n = 9). Nodal CTV was generated by adding an individualized margin around the portal vein, aorta, common hepatic artery, celiac artery, and left gastric artery. Conclusions The LRR patterns in the resected PEHC were evaluated and specific guidelines for nodal CTV delineation were provided, which may help physicians delineating the target volume in postoperative radiotherapy for PEHC. These findings need further validation in a lager cohort.
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Affiliation(s)
- Younghee Park
- Department of Radiation Oncology, Ewha Womans University College of Medicine, Seoul, South Korea
| | - Wonguen Jung
- Department of Radiation Oncology, Ewha Womans University College of Medicine, Seoul, South Korea
| | - Kyubo Kim
- Department of Radiation Oncology, Ewha Womans University College of Medicine, Seoul, South Korea
| | - Ah Ram Chang
- Department of Radiation Oncology, Soonchunhyang University College of Medicine, Seoul, South Korea
| | - Hae Jin Park
- Department of Radiation Oncology, Hanyang University College of Medicine, Seoul, South Korea
| | - Hyeon Kang Koh
- Department of Radiation Oncology, Konkuk University School of Medicine, Seoul, South Korea
| | - Byoung Hyuck Kim
- Department of Radiation Oncology, Seoul Metropolitan Government-Seoul National University Boramae Medical Center, Seoul, South Korea
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18
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Palloni A, Bisello S, Maggio I, Massucci M, Galuppi A, Di Federico A, Rizzo A, Ricci AD, Siepe G, Morganti AG, Brandi G, Frega G. The Potential Role of Adjuvant Chemoradiotherapy in Patients with Microscopically Positive (R1) Surgical Margins after Resection of Cholangiocarcinoma. Curr Oncol 2023; 30:4754-4766. [PMID: 37232816 PMCID: PMC10217181 DOI: 10.3390/curroncol30050358] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/14/2023] [Revised: 04/27/2023] [Accepted: 05/02/2023] [Indexed: 05/27/2023] Open
Abstract
(1) Background: Biliary tract cancers (BTCs) are a heterogeneous group of neoplasms with dismal prognosis and the role of adjuvant chemoradiotherapy in high-risk resected patients is unclear. (2) Methods: We retrospectively analyzed the outcomes of BTC patients who received curative intent surgery with microscopically positive resection margins (R1) and adjuvant chemoradioradiotherapy (CCRT) or chemotherapy (CHT) from January 2001 to December 201. (3) Results: Out of 65 patients who underwent R1 resection, 26 received adjuvant CHT and 39 adjuvant CCRT. The median recurrence-free survival (RFS) in the CHT and CHRT groups was 13.2 and 26.8 months, respectively (p = 0.41). Median overall survival (OS) was higher in the CHRT group (41.9 months) as compared to the CHT group (32.2 months), but the difference was not statistically significant (HR 0.88; p = 0.7). A promising trend in favor of CHRT was observed in N0 patients. Finally, no statistically significant differences were observed between patients undergoing adjuvant CHRT after R1 resection and patients treated with chemotherapy alone after R0 surgery. (4) Conclusions: Our study did not show a significant survival benefit with adjuvant CHRT over CHT alone in BTC patients with positive resection margins, while a promising trend was observed.
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Affiliation(s)
- Andrea Palloni
- Medical Oncology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy; (A.P.)
| | - Silvia Bisello
- Radiation Oncology Center, Department of Experimental, Diagnostic and Specialty Medicine—DIMES, University of Bologna, S. Orsola-Malpighi Hospital, via Giuseppe Massarenti 9, 40138 Bologna, Italy
| | - Ilaria Maggio
- Department of Medical Oncology, Azienda USL, 40139 Bologna, Italy
| | - Maria Massucci
- Medical Oncology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy; (A.P.)
| | - Andrea Galuppi
- Radiation Oncology Center, Department of Experimental, Diagnostic and Specialty Medicine—DIMES, University of Bologna, S. Orsola-Malpighi Hospital, via Giuseppe Massarenti 9, 40138 Bologna, Italy
| | - Alessandro Di Federico
- Medical Oncology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy; (A.P.)
- Department of Experimental, Diagnostic and Speciality Medicine, Sant’Orsola-Malpighi Hospital, University of Bologna, via Giuseppe Massarenti 9, 40138 Bologna, Italy
| | - Alessandro Rizzo
- Struttura Semplice Dipartimentale di Oncologia Medica per la Presa in Carico Globale del Paziente Oncologico “Don Tonino Bello”, I.R.C.C.S. Istituto Tumori “Giovanni Paolo II”, Viale Orazio Flacco 65, 70124 Bari, Italy
| | - Angela Dalia Ricci
- Medical Oncology Unit, National Institute of Gastroenterology, “Saverio de Bellis” Research Hospital, 70013 Castellana Grotte, Italy
| | - Giambattista Siepe
- Radiation Oncology Center, Department of Experimental, Diagnostic and Specialty Medicine—DIMES, University of Bologna, S. Orsola-Malpighi Hospital, via Giuseppe Massarenti 9, 40138 Bologna, Italy
| | - Alessio Giuseppe Morganti
- Radiation Oncology Center, Department of Experimental, Diagnostic and Specialty Medicine—DIMES, University of Bologna, S. Orsola-Malpighi Hospital, via Giuseppe Massarenti 9, 40138 Bologna, Italy
| | - Giovanni Brandi
- Medical Oncology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy; (A.P.)
- Department of Experimental, Diagnostic and Speciality Medicine, Sant’Orsola-Malpighi Hospital, University of Bologna, via Giuseppe Massarenti 9, 40138 Bologna, Italy
| | - Giorgio Frega
- Osteoncology, Soft Tissue and Bone Sarcomas, Innovative Therapy Unit, IRCCS Istituto Ortopedico Rizzoli, 40136 Bologna, Italy;
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19
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Jeong H, Kim KP, Jeong JH, Hwang DW, Lee JH, Kim KH, Moon DB, Lee MA, Park SJ, Chon HJ, Park JH, Lee JS, Ryoo BY, Yoo C. Adjuvant gemcitabine plus cisplatin versus capecitabine in node-positive extrahepatic cholangiocarcinoma: the STAMP randomized trial. Hepatology 2023; 77:1540-1549. [PMID: 37070950 DOI: 10.1097/hep.0000000000000046] [Citation(s) in RCA: 19] [Impact Index Per Article: 9.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/16/2022] [Accepted: 11/11/2022] [Indexed: 04/19/2023]
Abstract
BACKGROUND AND AIMS The effectiveness of gemcitabine-based adjuvant chemotherapy is unclear in cholangiocarcinoma. We investigated the role of adjuvant gemcitabine plus cisplatin (GemCis) in a homogeneous group of high-risk patients with resected, lymph node-positive extrahepatic cholangiocarcinoma. APPROACH AND RESULTS Adenocarcinoma of perihilar or distal bile duct with regional lymph node metastasis who underwent curative-intent surgery (R0/R1) was eligible. Patients were randomized to receive GemCis (gemcitabine 1000 mg/m2, cisplatin 25 mg/m2 on days 1 and 8) or capecitabine (1250 mg/m2 twice daily on days 1-14) every 3 weeks for 8 cycles. Primary endpoint was disease-free survival. Secondary endpoints were overall survival and safety. All p values are 1 sided and were considered significant if <0.1. Between July 2017 and November 2020, 101 patients (50 in the GemCis and 51 in the capecitabine group) were included in the intention-to-treat population. Perihilar and distal bile ducts were the primary sites in 45 (44.6%) and 56 (55.4%) patients, respectively, and 32 (31.7%) had R1 resections. Median (1-sided 90% CI) follow-up duration was 33.4 (30.5-35.8) months. In the GemCis and capecitabine group, 2-year disease-free survival rates were 38.5% (29.5%-47.4%) and 25.1% (17.4%-33.5%) [HR=0.96 (CI, 0.71-1.30), p=0.430], and median overall survival was 35.7 months (29.5-not estimated) and 35.7 months (30.9-not estimated) [HR=1.08 (CI, 0.71-1.64), 1-sided p=0.404], respectively. Grade 3-4 adverse events occurred in 42 (84.0%) and 8 patients (16.0%) in the GemCis and capecitabine groups, respectively. No treatment-related deaths were reported. CONCLUSIONS In resected lymph node-positive extrahepatic cholangiocarcinoma, adjuvant GemCis did not improve survival outcomes compared with capecitabine.
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Affiliation(s)
- Hyehyun Jeong
- Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Kyu-Pyo Kim
- Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Jae Ho Jeong
- Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Dae Wook Hwang
- Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Jae Hoon Lee
- Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Ki-Hun Kim
- Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Deok-Bog Moon
- Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Myung Ah Lee
- Department of Internal Medicine, College of Medicine, Seoul St. Mary's Hospital, The Catholic University of Korea, Seoul, Republic of Korea
| | - Se Jun Park
- Department of Internal Medicine, College of Medicine, Seoul St. Mary's Hospital, The Catholic University of Korea, Seoul, Republic of Korea
| | - Hong Jae Chon
- Department of Medical Oncology, CHA Bundang Medical Center, CHA University, Seongnam, Republic of Korea
| | - Jin-Hong Park
- Department of Radiation Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Ji Sung Lee
- Department of Clinical Research Center, Asan Institute for Life Sciences, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Baek-Yeol Ryoo
- Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Changhoon Yoo
- Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
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20
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Zhu J, Wu Y, Xiao W, Li Y. Survival Predictors of Resectable Gallbladder Carcinoma: An Analysis of the Surveillance, Epidemiology, and End Results Database. Am Surg 2023; 89:1629-1637. [PMID: 35061561 DOI: 10.1177/00031348221074238] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/29/2022]
Abstract
BACKGROUND To analyze population-level data for resectable gallbladder carcinoma (GBC) according to the eighth edition of the American Joint Committee on Cancer staging system. METHODS We queried the Surveillance, Epidemiology, and End Results database to identify all patients aged 18 years or older with T1-3 M0 GBC diagnosed between 2004 and 2015. Multivariate cox hazard regression analysis was used to identify prognostic factors of cancer-specific survival (CSS). RESULTS Of the 1601 eligible patients, 1310 (81.8%) underwent cholecystectomy only and 291 (18.2%) underwent an en bloc resection. Overall, 219 (13.7%) patients were in stage I, 400 (25%) were in stage II, 260 (16.2%) were in stage IIIA, 653 (40.8%) were in stage IIIB, and 69 (4.3%) were in stage IVB. The 5-year survival rates for patients were 82.7% for stage I, 73.4% for stage II, 31.9% for stage IIIA, 24.1% for stage IIIB, and 10% for stage IVB. Multivariate cox analysis indicated that predictors of decreased CSS included age at diagnosis >65 years, tumor size >3.2 cm, adenocarcinoma, increasing tumor spread, and lymph node involvement. Besides, chemotherapy and radiation were predictors of increased CSS. CONCLUSIONS Older age, increasing tumor size, adenocarcinoma, and advanced tumor/node stage were associated with a poorer prognosis after resection for GBC. Furthermore, patients with resectable GBC can benefit from adjuvant therapy.
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Affiliation(s)
- Jisheng Zhu
- Department of General Surgery, The First Affiliated Hospital of Nanchang University, Nanchang, China
| | - Yunxiang Wu
- Department of Cardiovascular Medicine, The Second Affiliated Hospital of Nanchang University, Nanchang, China
| | - Weidong Xiao
- Department of General Surgery, The First Affiliated Hospital of Nanchang University, Nanchang, China
| | - Yong Li
- Department of General Surgery, The First Affiliated Hospital of Nanchang University, Nanchang, China
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21
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Gholami S, Colby S, Horowitz DP, Guthrie KA, Ben-Josef E, El-Khoueiry AB, Blanke CD, Philip PA, Kachnic LA, Ahmad SA, Rocha FG. Adjuvant Chemoradiation in Patients with Lymph Node-Positive Biliary Tract Cancers: Secondary Analysis of a Single-Arm Clinical Trial (SWOG 0809). Ann Surg Oncol 2023; 30:1354-1363. [PMID: 36622529 PMCID: PMC10695673 DOI: 10.1245/s10434-022-12863-9] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/04/2022] [Accepted: 10/10/2022] [Indexed: 01/10/2023]
Abstract
BACKGROUND SWOG 0809 is the only prospective study of adjuvant chemotherapy followed by chemoradiation focusing on margin status in patients with extrahepatic cholangiocarcinoma (EHCC) and gallbladder cancer (GBCA); however, the effects of adjuvant therapy by nodal status have never been reported in this population. METHODS Patients with resected EHCC and GBCA, stage pT2-4, node-positive (N+) or margin-positive (R1) who completed four cycles of chemotherapy followed by radiotherapy were included. Cox regression was used to compare overall survival (OS), disease-free survival (DFS), local recurrence, and distant metastasis by nodal status. DFS rates were compared with historical data via a one-sample t-test. RESULTS Sixty-nine patients [EHCC, n = 46 (66%); GBCA, n = 23 (33%)] were evaluated, with a median age of 61.7 years and an R0 rate of 66.7% and R1 rate of 33.3%. EHCC versus GBCA was more likely to be N+ (73.9% vs. 47.8%, p = 0.03). Nodal status did not significantly impact OS (hazard ratio [HR] 1.98, 95% confidence interval [CI] 0.86-4.54, p = 0.11) or DFS (HR 1.63, 95% CI 0.77-3.44, p = 0.20). Two-year OS was 70.6% for node-negative (N0) disease and 60.9% for N+ disease, while 2-year DFS was 62.5% for N0 tumors and 49.8% for N+ tumors. N+ versus N0 tumors showed higher rates of distant failure (42.2% vs. 25.0%, p = 0.04). The 2-year DFS rate in N+ tumors was significantly higher than in historical controls (49.8% vs. 29.7%, p = 0.004). CONCLUSIONS Adjuvant therapy is associated with favorable outcome independent of nodal status and may impact local control in N+ patients. These data could serve as a benchmark for future adjuvant trials, including molecular-targeted agents.
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Affiliation(s)
- Sepideh Gholami
- Department of Surgery, University of California, Davis, CA, USA.
| | - Sarah Colby
- SWOG Statistics and Data Management Center, Fred Hutchinson Cancer Center, Seattle, WA, USA
| | - David P Horowitz
- Department of Radiation Oncology, Columbia University Irving Medical Center, New York City, NY, USA
- Herbert Irving Comprehensive Cancer Center, New York City, NY, USA
| | - Katherine A Guthrie
- SWOG Statistics and Data Management Center, Fred Hutchinson Cancer Center, Seattle, WA, USA
| | - Edgar Ben-Josef
- Department of Radiation Oncology, University of Pennsylvania, Philadelphia, PA, USA
| | - Anthony B El-Khoueiry
- Department of Clinical Medicine, University of Southern California, Los Angeles, CA, USA
| | - Charles D Blanke
- SWOG Group Chair's Office, Oregon Health Sciences University, Knight Cancer Institute, Portland, OR, USA
| | - Philip A Philip
- Department of Oncology and Department of Pharmacology, School of Medicine, Wayne State University, Karmanos Cancer Center, Detroit, MI, USA
| | - Lisa A Kachnic
- Department of Radiation Oncology, Columbia University Irving Medical Center, New York City, NY, USA
- Herbert Irving Comprehensive Cancer Center, New York City, NY, USA
| | - Syed A Ahmad
- Department of Surgery, University of Cincinnati Medical Center, Cincinnati, OH, USA
| | - Flavio G Rocha
- Division of Surgical Oncology, Oregon Health Sciences University, Knight Cancer Institute, Portland, OR, USA
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22
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Bedmutha AS, Agrawal A, Rangarajan V, Goel M, Patkar S, Puranik AD, Ramadwar M, Purandare NC, Shah S, Choudhury S. Diagnostic performance of F-18 FDG PET/CT in recurrent adenocarcinoma gallbladder and its impact on post-recurrence survival. Jpn J Radiol 2023; 41:201-208. [PMID: 36121626 DOI: 10.1007/s11604-022-01340-8] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/19/2022] [Accepted: 09/12/2022] [Indexed: 02/03/2023]
Abstract
PURPOSE To analyze diagnostic performance of F-18 FDG PET/CT in recurrent adenocarcinoma gallbladder (GBC) and to establish its possible impact on post-recurrence survival. METHOD FDG PET/CT studies of suspected recurrent GBC were retrospectively analyzed alongside tumor markers serum CEA and CA 19-9. Abnormal FDG-avid lesions and abnormal morphological lesions were considered positive for recurrence, and were categorized as isolated abdominal wall recurrence, loco-regional recurrence, and distant metastatic disease. Histopathology, definite progression on imaging and positive response to treatment was considered as reference standard. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and accuracy were used as diagnostic performance parameters. Post-recurrence survival was calculated whenever appropriate follow-up was available, based on the abovementioned categories of sites of recurrence using survival curves and log-rank test. RESULTS Out of 117 PET/CT studies, 93 (79.5%) were positive and 24 (20.5%) were negative for recurrence. 86 out of 93 were true positive and 23 of 24 were true negative. PET/CT demonstrated sensitivity, specificity, PPV, NPV and accuracy of 98.8%, 76.7%, 92.5%, 95.8% and 93.1%, respectively. Diagnostic performance of PET/CT was significantly better than combination tumor markers. Of 66 cases with available follow-up, isolated abdominal wall (port/scar site) recurrence and loco-regional recurrence demonstrated significantly higher post-recurrence survival as compared to distant metastasis; median survival being 39, 25 and 12 months, respectively. CONCLUSION F-18 FDG PET/CT has better diagnostic performance than tumor markers combination. Isolated abdominal wall (port/scar site) recurrence and loco-regional recurrence on PET/CT demonstrated better survival than non-regional metastatic disease. These results suggest a possible role of PET/CT as a surveillance modality, as well as a guide to therapeutic decision-making in cases of recurrent GBC.
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Affiliation(s)
- Akshay S Bedmutha
- Department of Nuclear Medicine and Molecular Imaging, Tata Memorial Hospital, Homi Bhabha National Institute, E. Borges road, Parel, Mumbai, 400012, India
| | - Archi Agrawal
- Department of Nuclear Medicine and Molecular Imaging, Tata Memorial Hospital, Homi Bhabha National Institute, E. Borges road, Parel, Mumbai, 400012, India.
| | - Venkatesh Rangarajan
- Department of Nuclear Medicine and Molecular Imaging, Tata Memorial Hospital, Homi Bhabha National Institute, E. Borges road, Parel, Mumbai, 400012, India
| | - Mahesh Goel
- Gastro-intestinal and Hepato-pancreato-biliary surgical service, Department of Surgery, Tata Memorial Hospital, Homi Bhabha National Institute, E. Borges road, Parel, Mumbai, 400012, India
| | - Shraddha Patkar
- Gastro-intestinal and Hepato-pancreato-biliary surgical service, Department of Surgery, Tata Memorial Hospital, Homi Bhabha National Institute, E. Borges road, Parel, Mumbai, 400012, India
| | - Ameya D Puranik
- Department of Nuclear Medicine and Molecular Imaging, Tata Memorial Hospital, Homi Bhabha National Institute, E. Borges road, Parel, Mumbai, 400012, India
| | - Mukta Ramadwar
- Department of Pathology, Tata Memorial Hospital, Homi Bhabha National Institute, E. Borges road, Parel, Mumbai, 400012, India
| | - Nilendu C Purandare
- Department of Nuclear Medicine and Molecular Imaging, Tata Memorial Hospital, Homi Bhabha National Institute, E. Borges road, Parel, Mumbai, 400012, India
| | - Sneha Shah
- Department of Nuclear Medicine and Molecular Imaging, Tata Memorial Hospital, Homi Bhabha National Institute, E. Borges road, Parel, Mumbai, 400012, India
| | - Sayak Choudhury
- Department of Nuclear Medicine and Molecular Imaging, Tata Memorial Hospital, Homi Bhabha National Institute, E. Borges road, Parel, Mumbai, 400012, India
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23
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Li J, Rocha FG, Mayo SC. Past, Present, and Future Management of Localized Biliary Tract Malignancies. Surg Oncol Clin N Am 2023; 32:83-99. [PMID: 36410923 DOI: 10.1016/j.soc.2022.07.007] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/06/2022]
Abstract
Most of the patients with gallbladder cancer (GBC), intrahepatic cholangiocarcinoma (iCCA), and peri-hilar cholangiocarcinoma (pCCA) present with advanced disease. Complete staging with multiphasic liver imaging is essential to determine the extent of disease. Operative goals should include a margin-negative resection, portal lymphadenectomy for staging, and sufficient remnant liver volume. Biliary tract malignancies have distinct mutational drivers (GBC and pCCA = ERBB2 in 20%; iCCA = fibroblast growth factor receptor 2 or isocitrate dehydrogenase 1 in 20%) amenable to therapy with inhibitors. Clinical trials assessing neoadjuvant, peri-operative, and adjuvant treatments continue to evolve and now include targeted inhibitors and the integration of hepatic arterial infusion.
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Affiliation(s)
- Janet Li
- Division of Surgical Oncology, Department of Surgery, Oregon Health & Science University, 3181 Southwest. Sam Jackson Park Road, Mail Code L-619, Portland, OR 97239, USA. https://twitter.com/JanetLiMD
| | - Flavio G Rocha
- Department of Surgery, Knight Cancer Institute at Oregon Health & Science University, 3181 Southwest Sam Jackson Park Road, Mail Code L-619, Portland, OR 97239, USA. https://twitter.com/FlavioRochaMD
| | - Skye C Mayo
- Division of Surgical Oncology, Department of Surgery, Knight Cancer Institute at Oregon Health & Science University, 3181 Southwest Sam Jackson Park Road, Mail Code L-619, Portland, OR 97239, USA.
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24
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Song J, Kang X, Di Y, Ren G, Wang Y. Associations between external beam radiotherapy and overall survival in patients with gallbladder cancer: A population-based study. Front Public Health 2022; 10:1012142. [PMID: 36311614 PMCID: PMC9614712 DOI: 10.3389/fpubh.2022.1012142] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/05/2022] [Accepted: 09/20/2022] [Indexed: 01/27/2023] Open
Abstract
Background There is a lack of studies regarding radiotherapy (RT) in patients with gallbladder cancer (GBC) on the survival benefit after surgery and nonsurgical treatment. Therefore, this study evaluated the impact of external beam RT on the overall survival (OS) of patients with GBC in a real-world setting. Methods Patients with GBC enrolled from the Surveillance, Epidemiology, and End Results (SEER) database were examined through Kaplan-Meier survival curves and multivariable Cox regression analyses. Results A total of 7,866 patients with GBC were screened for the current analysis, of whom 2,130 (27.1%) did not undergo RT or surgery, 209 (2.7%) underwent RT, 4,511 (57.3%) underwent surgery, and 1,016 (12.9%) underwent both RT and surgery. The median OS times were 4 months, 8 months, 16 months, and 22 months (p < 0.0001). OS was significantly different between adjuvant RT (p = 0.0002) and palliative RT (p < 0.0001). Multifactorial analysis (controlling for age, sex, year of diagnosis, marital status, race, grade, and stage) showed that both adjuvant RT (surgery and adjuvant RT vs. surgery alone; HR, 0.75; 95% CI, 0.69-0.82, p < 0.001) and palliative RT (RT alone vs. no treatment; HR, 0.80; 95% CI, 0.69-0.92, p = 0.003) had a significant impact on patient OS. The results remained stable following sensitivity analyses. Conclusion The study results indicate that adjuvant and palliative radiation treatment was associated with a survival benefit. GBC patients can derive a survival benefit from external beam RT.
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Affiliation(s)
- Jiazhao Song
- Graduate School of Hebei North University, Zhangjiakou, China,Department of Radiotherapy, Air Force Medical Center PLA, Beijing, China
| | - Xiaoli Kang
- Department of Radiotherapy, Air Force Medical Center PLA, Beijing, China
| | - Yupeng Di
- Department of Radiotherapy, Air Force Medical Center PLA, Beijing, China
| | - Gang Ren
- Department of Radiotherapy, Air Force Medical Center PLA, Beijing, China
| | - Yingjie Wang
- Department of Radiotherapy, Air Force Medical Center PLA, Beijing, China,*Correspondence: Yingjie Wang
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25
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Agrawal V, Lamture Y, Totade S. A Typical Case of an Atypical Disease: Klatskin Tumor. Cureus 2022; 14:e28782. [PMID: 36225470 PMCID: PMC9532961 DOI: 10.7759/cureus.28782] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/28/2022] [Accepted: 09/04/2022] [Indexed: 11/15/2022] Open
Abstract
Cholangiocarcinoma is a rare type of cancer disorder. The case report is of a 55-years-old male patient who came to the output patient department (OPD) with complaints of abdominal pain and weight loss for 15 days and later was diagnosed with Klatskin tumor after mandatory investigations. After the approval of the tumor board committee, he is under chemotherapy, to which he is responding positively. Klatskin tumor is a type of cholangiocarcinoma occurring at the convergence of the right and left lobes of hepatic bile ducts, forming the common bile duct. The source of cholangiocarcinoma is idiopathic, and most cholangiocarcinoma is treated with the help of either surgical resection or chemotherapy. Surgical resection is performed in initial cases, but most patients present with the advanced stage of Klatskin tumor. CA-19-9 is a tumor marker that indicates the presence of a Klatskin tumor.
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26
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Variation in clinical target volume delineation in postoperative radiotherapy for biliary tract cancer. PLoS One 2022; 17:e0273395. [PMID: 36048817 PMCID: PMC9436049 DOI: 10.1371/journal.pone.0273395] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/15/2022] [Accepted: 08/09/2022] [Indexed: 11/19/2022] Open
Abstract
We aimed to evaluate the inter-clinician variability in the clinical target volume (CTV) for postoperative radiotherapy (PORT) for biliary tract cancer (BTC) including extrahepatic bile duct cancer (EBDC) and gallbladder cancer (GBC). Nine experienced radiation oncologists delineated PORT CTVs for distal EBDC (pT2N1), proximal EBDC (pT2bN1) and GBC (pT2bN1) patients. The expectation maximization algorithm for Simultaneous Truth and Performance Level Estimation (STAPLE) was used to quantify expert agreements. We generated volumes with a confidence level of 80% to compare the maximum distance to each CTV in six directions. The degree of agreement was moderate; overall kappa values were 0.573 for distal EBDC, 0.513 for proximal EBDC, and 0.511 for GBC. In the distal EBDC, a larger variation was noted in the right, post, and inferior direction. In the proximal EBDC, all borders except the right and left direction showed a larger variation. In the GBC, a larger variation was found in the anterior, posterior, and inferior direction. The posterior and inferior borders were the common area having discrepancies, associated with the insufficient coverage of the paraaortic node. A consensus guideline is needed to reduce inter-clinician variability in the CTVs and adequate coverage of regional lymph node area.
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Liu S, Zhang L, Guan XE, Zhang L, Wang R. Target nursing care on anxiety and depression in patients with gallbladder cancer during perioperative period. Medicine (Baltimore) 2022; 101:e29883. [PMID: 35945715 PMCID: PMC9351855 DOI: 10.1097/md.0000000000029883] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/09/2023] Open
Abstract
BACKGROUND This study retrospectively investigated the effects of target nursing care (TNC) on anxiety and depression in patients with gallbladder cancer (GBC) during the perioperative period. METHODS This retrospective study analyzed the data of 80 patients with GBC during perioperative period. These records were divided into an intervention group (n = 40) or a control group (n = 40). All 80 patient records in both groups were administered routine nursing care (RNC). The patients in the intervention group also underwent TNC. The primary outcomes were depression (measured using the Hamilton Depression Scale, HAMD) and anxiety (assessed using the Hamilton Anxiety Scale, HAMA). The secondary outcomes were quality of life (assessed using the 36-Item Short Form Health Survey, SF-36) and adverse events. We collected and analyzed the outcome data before and after treatment. RESULTS After treatment, patients in the intervention group showed more promising effects on depression (HAMD, P < .01) and anxiety (HAMA, P < .01) than those in the control group did. However, there were no significant differences in the quality of life before and after treatment. No TNC- or RNC-associated adverse events were reported in patient records. CONCLUSION This study found that TNC was more effective than RNC in relieving depression and anxiety. Future studies should be conducted to validate the present findings.
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Affiliation(s)
- Shuang Liu
- Cardiac Intensive Care Unit, Hongqi Hospital Affiliated to Mudanjiang Medical University, Mudanjiang, China
| | - Li Zhang
- Department of Scientific Research, Hongqi Hospital Affiliated to Mudanjiang Medical University, Mudanjiang, China
| | - Xiu-e Guan
- Department of Oncology, Hongqi Hospital Affiliated to Mudanjiang Medical University, Mudanjiang, China
| | - Lei Zhang
- Dialysis Unit, Hongqi Hospital Affiliated to Mudanjiang Medical University, Mudanjiang, China
| | - Rui Wang
- First Ward of General Surgery Department, Hongqi Hospital Affiliated to Mudanjiang Medical University, Mudanjiang, China
- *Correspondence: Rui Wang, MB, First Ward of General Surgery Department, Hongqi Hospital Affiliated to Mudanjiang Medical University, No.5 Tongxiang Street, Aimin District, Mudanjiang, 157011, China (e-mail: )
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Yuan Z, Shui Y, Liu L, Guo Y, Wei Q. Postoperative recurrent patterns of gallbladder cancer: possible implications for adjuvant therapy. Radiat Oncol 2022; 17:118. [PMID: 35799270 PMCID: PMC9264693 DOI: 10.1186/s13014-022-02091-6] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/17/2022] [Accepted: 06/27/2022] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND Gallbladder cancer (GBC) is an uncommon malignancy with high recurrent rate and poor prognosis. This study investigates the recurrent patterns of postoperative GBC, with the aim to guide the adjuvant treatments, including the radiotherapy. METHODS Retrospectively analyzed the 109 GBC patients who underwent surgery in our institution from January 2013 to 2018. Clinical follow-up revealed 54 recurrent cases, of which 40 had detailed locations of recurrence. The sites of recurrence were recorded and divided into the tumor bed, corresponding lymphatic drainage area, intrahepatic recurrence, and the other distant metastasis. RESULTS The median follow-up time is 34 months (IQR: 11-64). The median disease-free survival (DFS) and overall survival (OS) were 48.8 months and 53.7 months, respectively. Through univariate analysis, risk factors for DFS and OS include tumor markers (CA199 and CEA), hepatic invasion, perineural invasion, lymphovascular invasion, TNM staging and tumor differentiation. Through multivariate analysis, risk factors for DFS include hepatic invasion and TNM staging, and for OS is TNM staging only. Of the 40 cases with specific recurrent sites, 29 patients (29/40, 72.5%) had recurrence in the potential target volume of postoperative radiotherapy (PORT), which include tumor bed and corresponding lymphatic drainage area. The common recurrent lymph node groups included abdominal para-aortic lymph node (No.16, 15/29), hepatoduodenal ligament lymph node (No.12, 8/29), retro-pancreatic head lymph node (No.13, 7/29) and celiac axis lymph node (No.9, 4/29). Twenty cases with recurrences inside the potential PORT target volume were accompanied by distant metastasis. Another 11 cases had distant metastasis alone, so totally 31 cases developed distant metastasis (31/40, 77.5%), including 18 cases with hepatic metastasis. CONCLUSION The recurrence and metastasis rates are high in GBC and adjuvant therapy is needed. Up to 75% of the recurrent cases occurred in the potential target volume of postoperative radiotherapy, suggesting that postoperative radiotherapy has the possible value of improving local-regional control. The potential target volume of radiotherapy should include the tumor bed, No.8, No.9, No.11, No.12, No.13, No.14, No. 16a2, No. 16b1 lymph node groups.
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Affiliation(s)
- Zhijun Yuan
- Department of Radiation Oncology, Ministry of Education Key Laboratory of Cancer Prevention and Intervention, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China
| | - Yongjie Shui
- Department of Radiation Oncology, Ministry of Education Key Laboratory of Cancer Prevention and Intervention, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China
| | - Lihong Liu
- Department of Radiation Oncology, Ministry of Education Key Laboratory of Cancer Prevention and Intervention, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China
| | - Yinglu Guo
- Department of Radiation Oncology, Ministry of Education Key Laboratory of Cancer Prevention and Intervention, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China
| | - Qichun Wei
- Department of Radiation Oncology, Ministry of Education Key Laboratory of Cancer Prevention and Intervention, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.
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Sinnamon AJ, Wood AC, Satyadi MA, Levitt CV, Hardy O, Haider M, Kim RD, Anaya DA, Denbo JW. Anatomic patterns of recurrence in biliary tract cancers: does primary tumor site matter? J Gastrointest Oncol 2022; 13:1413-1422. [PMID: 35837169 DOI: 10.21037/jgo-21-868] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/10/2021] [Accepted: 04/07/2022] [Indexed: 11/06/2022] Open
Abstract
Background Recommendations for postoperative surveillance and adjuvant therapy following curative-intent resection for biliary tract cancers-including intrahepatic and extrahepatic cholangiocarcinoma (IHCCA and EHCCA) and primary gallbladder cancer (GBC)-are uniform across primary tumor site. However, these tumors may have distinct patterns of recurrence. Methods A retrospective observational cohort study was performed at a specialty cancer center. Patients undergoing resection of IHCCA, EHCCA, and GBC were identified (2005-2020). Recurrence-free survival (RFS) was estimated using Kaplan-Meier and Cox proportional hazard methods. Anatomic patterns of initial site of recurrence were described and compared. Results There were 142 patients included; 50 IHCCA, 32 EHCCA, and 60 GBC. Median RFS was 30.8 months, which was not significantly different between IHCCA, EHCCA, or GBC in univariate analysis or after adjustment. Nodal positivity was significantly associated with poor RFS (HR 3.92, P≤0.001). The most common initial site of recurrence overall was intrahepatic (n=49/64, 77%), in isolation (n=32) or synchronous with other site of recurrence (n=17). Significant differences in anatomic pattern of recurrence were observed (P=0.049) with IHCCAs more commonly recurring with simultaneous hepatic-pulmonary disease (n=5/22, 23%; EHCCA n=2/19, 10%; GBC n=1/23, 4%), GBC more commonly recurring within the porta (n=7/23, 30%; IHCCA n=0; EHCCA n=1/19, 5%), and EHCCA more commonly recurring within the peritoneum (n=5/19, 26%; IHCCA n=2/22, 9%, GBC n=2/23, 9%). Conclusions Patterns of initial recurrence appear to differ between primary tumor site, likely reflecting underlying differences in anatomy and biology. These data could help inform future studies for adjuvant therapy as well as timing and anatomic focus for surveillance imaging.
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Affiliation(s)
- Andrew J Sinnamon
- Department of Gastrointestinal Oncology, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL, USA.,University of South Florida Morsani College of Medicine, Tampa, FL, USA
| | - Anthony C Wood
- Department of Gastrointestinal Oncology, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL, USA
| | - Megan A Satyadi
- University of South Florida Morsani College of Medicine, Tampa, FL, USA
| | | | - Olivia Hardy
- University of South Florida Morsani College of Medicine, Tampa, FL, USA
| | - Mintallah Haider
- Department of Gastrointestinal Oncology, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL, USA
| | - Richard D Kim
- Department of Gastrointestinal Oncology, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL, USA
| | - Daniel A Anaya
- Department of Gastrointestinal Oncology, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL, USA
| | - Jason W Denbo
- Department of Gastrointestinal Oncology, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL, USA
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Kamarajah SK, Al-Rawashdeh W, Parente A, Atherton P, Salti GI, Dahdaleh FS, Manas D, Hilal MA, White SA. Adjuvant chemotherapy for perihilar cholangiocarcinoma: A population-based comparative cohort study. EUROPEAN JOURNAL OF SURGICAL ONCOLOGY 2022; 48:1300-1308. [PMID: 34916085 DOI: 10.1016/j.ejso.2021.12.002] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/24/2021] [Revised: 11/24/2021] [Accepted: 12/02/2021] [Indexed: 11/30/2022]
Abstract
BACKGROUND Data supporting routine use of adjuvant chemotherapy (AC) compared to no AC (noAC) for perihilar cholangiocarcinoma (hCCA) is unclear. This study aimed to determine whether AC improves long-term survival following resection for hCCA. METHODS Patients receiving resection for hCCA followed by AC or no AC from 2010 to 2016 were identified from the National Cancer Database (NCDB). Propensity score matching (PSM) and Cox regression was performed to account for selection bias and analyze impact of AC on overall survival. RESULTS Of 924 (56%) noAC and 719 (44%) AC, 320 noAC and 320 AC patients remained after PSM. After matching, AC was associated with improved survival (median: 28.2 vs 19.9 months, p < 0.001), which remained after multivariable adjustment (HR: 0.61, CI95%: 0.50-0.75, p < 0.001). On multivariable interaction analyses, the benefit of AC over no AC persisted irrespective of nodal status: N0 (HR: 0.62, CI95%: 0.41-0.92, p = 0.019), N1 (HR: 0.52, CI95%: 0.36-0.75, p = 0.001), N2 (HR: 0.31, CI95%: 0.11-0.90, p = 0.032), Nx (HR: 0.22, CI95%: 0.09-0.55, p = 0.001) and margin status: R0 (HR: 0.74, CI95%: 0.57-0.97, p = 0.026), R1 (HR: 0.31, CI95%: 0.21-0.47, p < 0.001). Stratified analysis by nodal, margin and AC status demonstrated consistent results. CONCLUSION AC following resection for hCCA was associated with improved survival in this study, even in margin-negative and node-negative disease. These findings suggest incorporation of AC into multimodality therapy for hCCA in all cases, where appropriate.
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Affiliation(s)
- Sivesh K Kamarajah
- Department of Surgery, Queen Elizabeth Hospital Birmingham, University Hospital Birmingham NHS Trust, Birmingham, United Kingdom; Department of HPB and Transplant Surgery, The Freeman Hospital, Newcastle Upon Tyne Hospitals NHS Foundation Trust, Newcastle Upon Tyne, UK; Institute of Cancer and Genomic Sciences, College of Medical and Dental Sciences, University of Birmingham, Birmingham, United Kingdom
| | - Wasfi Al-Rawashdeh
- Department of HPB and Transplant Surgery, The Freeman Hospital, Newcastle Upon Tyne Hospitals NHS Foundation Trust, Newcastle Upon Tyne, UK
| | - Alessandro Parente
- Department of Hepatobiliary and Transplant Surgery, Queen Elizabeth Hospital Birmingham, University Hospital Birmingham NHS Trust, Birmingham, United Kingdom
| | - Phil Atherton
- Department of Clinical Oncology, Northern Centre for Cancer Care, Newcastle Upon Tyne Hospitals NHS Foundation Trust, Newcastle Upon Tyne, UK
| | - George I Salti
- Department of General Surgery, University of Illinois Hospital and Health Sciences System, Chicago, IL, USA; Edward-Elmhurst Health, Department of Surgical Oncology, Naperville, IL, USA
| | - Fadi S Dahdaleh
- Edward-Elmhurst Health, Department of Surgical Oncology, Naperville, IL, USA
| | - Derek Manas
- Department of HPB and Transplant Surgery, The Freeman Hospital, Newcastle Upon Tyne Hospitals NHS Foundation Trust, Newcastle Upon Tyne, UK; Newcastle University, Newcastle Upon Tyne, Newcastle, United Kingdom
| | - Mohammed Abu Hilal
- Department of Surgery, Southampton University Hospital NHS Foundation Trust, Southampton, UK; Department of Surgery, Fondazione Poliambulanza - Istituto Ospedaliero, Brescia, Italy
| | - Steven A White
- Department of HPB and Transplant Surgery, The Freeman Hospital, Newcastle Upon Tyne Hospitals NHS Foundation Trust, Newcastle Upon Tyne, UK; Newcastle University, Newcastle Upon Tyne, Newcastle, United Kingdom.
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Choi SH, Rim CH, Shin IS, Yoon WS, Koom WS, Seong J. Benefit of adjuvant radiotherapy for gallbladder cancer: a comparability-based meta-analysis. Hepatol Int 2022; 16:712-727. [PMID: 35532861 DOI: 10.1007/s12072-022-10343-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/07/2022] [Accepted: 04/13/2022] [Indexed: 11/30/2022]
Abstract
BACKGROUND AND PURPOSE The benefits of adjuvant radiotherapy (ART) in gallbladder cancer (GBC) treatment remain inconclusive owing to the rarity of GBC and lack of randomized studies. METHODS PubMed, Medline, Embase, and Cochrane Library were systematically searched until March 2021. The primary endpoint was overall survival (OS). Comparative clinical studies that reported survival outcomes in GBC patients treated with or without ART were included. The comparability of each study was assessed by considering all possible clinical indicators (group 2: ART arm with poor clinical profile; group 1: ART arm with statistically similar profile or no evidence of having inferior clinical factors compared to non-ART arm). RESULTS Twenty-one studies involving 6876 GBC patients were reviewed. In pooled analyses of OS, the odds ratio (OR) was 1.26 (p = 0.111) neither favoring ART or non-ART arms. In subgroup analyses considering comparability, the OR significantly favored the ART arm (1.92, p = 0.008) among comparability group 1 studies, whereas it was 1.03 (p = 0.865) in comparability group 2 studies. The pooled rate of 5-year OS in the ART vs. non-ART arms was 44.9% vs. 20.9% in group 1 and 34.1% vs. 40.0% in group 2. With ART, significant reduction in locoregional recurrence (OR 0.21, p = 0.001) but not in distant metastasis (OR 1.32, p = 0.332) was noted. CONCLUSION ART not only showed benefits in patients with a similar clinical profile to those treated without ART but also yielded comparable survival in patients with an inferior clinical profile. Our results suggest the more active application of ART in GBC treatment. PROTOCOL REGISTRATION This study is registered in PROSPERO (CRD42021240624, available at: https://www.crd.york.ac.uk/ ).
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Affiliation(s)
- Seo Hee Choi
- Department of Radiation Oncology, Yongin Severance Hospital, Yonsei University College of Medicine, Yongin, Gyeonggi-do, Korea
| | - Chai Hong Rim
- Department of Radiation Oncology, Korea University Ansan Hospital, Korea University Medical College, 123 Jeokgeum-ro, Danwon-gu, Ansan, Gyeonggi-do, 15355, Republic of Korea.
| | - In-Soo Shin
- Graduate School of Education, AI Convergence Education, Dongguk University, Seoul, Korea
| | - Won Sup Yoon
- Department of Radiation Oncology, Korea University Ansan Hospital, Korea University Medical College, 123 Jeokgeum-ro, Danwon-gu, Ansan, Gyeonggi-do, 15355, Republic of Korea
| | - Woong Sub Koom
- Department of Radiation Oncology, Yonsei Cancer Center, Yonsei University Medical College, Seoul, Korea
| | - Jinsil Seong
- Department of Radiation Oncology, Yonsei Cancer Center, Yonsei University Medical College, Seoul, Korea
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Contrast-enhanced CT radiomics for prediction of recurrence-free survival in gallbladder carcinoma after surgical resection. Eur Radiol 2022; 32:7087-7097. [PMID: 35612664 DOI: 10.1007/s00330-022-08858-5] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/17/2022] [Revised: 04/11/2022] [Accepted: 04/30/2022] [Indexed: 11/04/2022]
Abstract
OBJECTIVES Gallbladder carcinoma (GBC) is the most common and aggressive biliary tract malignancy with high postoperative recurrence rates. This single-center study aimed to develop and validate a radiomics signature to estimate GBC recurrence-free survival (RFS). METHODS This study retrospectively included 204 consecutive patients with pathologically diagnosed GBC and were randomly divided into development (n = 142) and validation (n = 62) cohorts (7:3). The radiomics features of tumor were extracted from preoperative contrast-enhanced CT imaging for each patient. In the development cohort, the least absolute shrinkage and selection operator (LASSO) Cox regression was employed to develop a radiomics signature for RFS prediction. The patients were stratified into high-score or low-score groups according to their median value of radiomics score. A nomogram was established using multivariable Cox regression by incorporating significant pathological predictors and radiomics signatures. RESULTS The radiomics signature based on 12 features could discriminate high-risk patients with poor RFS. Multivariate Cox analysis revealed that pT3/4 stage (hazard ratio, [HR] = 2.691), pN2 stage (HR = 3.60), poor differentiation grade (HR = 2.651), and high radiomics score (HR = 1.482) were independent risk variables associated with worse RFS and were incorporated to construct a nomogram. The nomogram displayed good prediction performance in estimating RFS with AUC values of 0.895, 0.935, and 0.907 at 1, 3, and 5 years, respectively. CONCLUSIONS The radiomics signature and combined nomogram may assist in predicting RFS in GBC patients. KEY POINTS • A radiomics signature extracted from preoperative contrast-enhanced CT can be a useful tool to preoperatively predict RFS of GBC. • T3/T4 stage, N2, poor tumor differentiation, and high radiomics score were positively associated with postoperative recurrence.
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Yin C, Kulasekaran M, Roy T, Decker B, Alexander S, Margolis M, Jha RC, Kupfer GM, He AR. Homologous Recombination Repair in Biliary Tract Cancers: A Prime Target for PARP Inhibition? Cancers (Basel) 2022; 14:2561. [PMID: 35626165 PMCID: PMC9140037 DOI: 10.3390/cancers14102561] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/05/2022] [Revised: 05/10/2022] [Accepted: 05/14/2022] [Indexed: 01/27/2023] Open
Abstract
Biliary tract cancers (BTCs) are a heterogeneous group of malignancies that make up ~7% of all gastrointestinal tumors. It is notably aggressive and difficult to treat; in fact, >70% of patients with BTC are diagnosed at an advanced, unresectable stage and are not amenable to curative therapy. For these patients, chemotherapy has been the mainstay treatment, providing an inadequate overall survival of less than one year. Despite the boom in targeted therapies over the past decade, only a few targeted agents have been approved in BTCs (i.e., IDH1 and FGFR inhibitors), perhaps in part due to its relatively low incidence. This review will explore current data on PARP inhibitors (PARPi) used in homologous recombination deficiency (HRD), particularly with respect to BTCs. Greater than 28% of BTC cases harbor mutations in genes involved in homologous recombination repair (HRR). We will summarize the mechanisms for PARPi and its role in synthetic lethality and describe select genes in the HRR pathway contributing to HRD. We will provide our rationale for expanding patient eligibility for PARPi use based on literature and anecdotal evidence pertaining to mutations in HRR genes, such as RAD51C, and the potential use of reliable surrogate markers of HRD.
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Affiliation(s)
- Chao Yin
- Ruesch Center for the Cure of Gastrointestinal Cancers, Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC 20007, USA; (C.Y.); (M.K.); (T.R.)
| | - Monika Kulasekaran
- Ruesch Center for the Cure of Gastrointestinal Cancers, Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC 20007, USA; (C.Y.); (M.K.); (T.R.)
| | - Tina Roy
- Ruesch Center for the Cure of Gastrointestinal Cancers, Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC 20007, USA; (C.Y.); (M.K.); (T.R.)
| | - Brennan Decker
- Foundation Medicine, Cambridge, MA 20007, USA; (B.D.); (S.A.); (M.M.)
| | - Sonja Alexander
- Foundation Medicine, Cambridge, MA 20007, USA; (B.D.); (S.A.); (M.M.)
| | - Mathew Margolis
- Foundation Medicine, Cambridge, MA 20007, USA; (B.D.); (S.A.); (M.M.)
| | - Reena C. Jha
- Department of Radiology, Georgetown University Medical Center, Washington, DC 20007, USA;
| | - Gary M. Kupfer
- Departments of Oncology and Pediatrics, Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC 20007, USA;
| | - Aiwu R. He
- Ruesch Center for the Cure of Gastrointestinal Cancers, Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC 20007, USA; (C.Y.); (M.K.); (T.R.)
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Khosla D, Zaheer S, Gupta R, Madan R, Goyal S, Kumar N, Kapoor R. Role of intraluminal brachytherapy in palliation of biliary obstruction in cholangiocarcinoma: A brief review. World J Gastrointest Endosc 2022; 14:106-112. [PMID: 35432743 PMCID: PMC8984530 DOI: 10.4253/wjge.v14.i3.106] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/30/2021] [Revised: 11/24/2021] [Accepted: 02/25/2022] [Indexed: 02/06/2023] Open
Abstract
Surgery is the only curative treatment for cholangiocarcinoma. However, most patients present with advanced disease, and hence are unresectable. Thus, the intent of treatment shifts from curative to palliative in the majority of cases. Biliary drainage with intraluminal brachytherapy is an effective means of relieving the malignant biliary obstruction. In this review, we discuss the role of brachytherapy in the palliation of obstructive symptoms in extrahepatic cholangiocarcinoma.
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Affiliation(s)
- Divya Khosla
- Department of Radiotherapy and Oncology, Postgraduate Institute of Medical Education and Research, Chandigarh 160012, U.T., India
| | - Samreen Zaheer
- Department of Radiotherapy and Oncology, Postgraduate Institute of Medical Education and Research, Chandigarh 160012, U.T., India
| | - Rahul Gupta
- Department of Gastroenterology and Hepatology, Shalby Multispeciality Hospital, Mohali 160062, Punjab, India
| | - Renu Madan
- Department of Radiotherapy and Oncology, Postgraduate Institute of Medical Education and Research, Chandigarh 160012, U.T., India
| | - Shikha Goyal
- Department of Radiotherapy and Oncology, Postgraduate Institute of Medical Education and Research, Chandigarh 160012, U.T., India
| | - Narendra Kumar
- Department of Radiotherapy and Oncology, Postgraduate Institute of Medical Education and Research, Chandigarh 160012, U.T., India
| | - Rakesh Kapoor
- Department of Radiotherapy and Oncology, Postgraduate Institute of Medical Education and Research, Chandigarh 160012, U.T., India
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Kumar D, Kiran NM, Khosla D. Reviewing the potential role of radiation therapy in gallbladder cancer: an update. Radiat Oncol J 2022; 40:1-8. [PMID: 35368195 PMCID: PMC8984131 DOI: 10.3857/roj.2021.00717] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/28/2021] [Revised: 10/15/2021] [Accepted: 10/26/2021] [Indexed: 11/16/2022] Open
Abstract
Gallbladder cancer is a highly malignant disease with a poor prognosis. It is the most common cancer of the biliary tract pathway. Although surgery remains the treatment of choice for early-stage disease, majority of the patients presents in locally advanced, unresectable and metastatic stage of the disease. Radiotherapy and chemotherapy thus form an integral part of management for these locally advanced staged patients. The role of radiation though has been advocated in gallbladder cancer, majorly in the adjuvant setting, its role in neoadjuvant and palliative settings remains in an evolving phase. The article thus aims to review and update the existing literature regarding the role of radiation therapy in gallbladder cancer.
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Affiliation(s)
- Divyesh Kumar
- Department of Radiotherapy and Oncology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Nali Muni Kiran
- Department of Radiotherapy and Oncology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Divya Khosla
- Department of Radiotherapy and Oncology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
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Hu ZI, Lim KH. Evolving Paradigms in the Systemic Treatment of Advanced Gallbladder Cancer: Updates in Year 2022. Cancers (Basel) 2022; 14:1249. [PMID: 35267556 PMCID: PMC8909874 DOI: 10.3390/cancers14051249] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/23/2022] [Revised: 02/15/2022] [Accepted: 02/25/2022] [Indexed: 02/01/2023] Open
Abstract
Gallbladder cancer (GBC) is a biological, anatomical, and clinically distinct subset of biliary tract cancers (BTC), which also include extra- and intra-hepatic cholangiocarcinoma. The advent of next-generation sequencing (NGS) clearly shows that GBC is genetically different from cholangiocarcinoma. Although GBC is a relatively rare cancer, it is highly aggressive and carries a grave prognosis. To date, complete surgical resection remains the only path for cure but is limited to patients with early-stage disease. The majority of the patients are diagnosed at an advanced, inoperable stage when systemic treatment is administered as an attempt to enable surgery or for palliation. Gemcitabine and platinum-based chemotherapies have been the main treatment modality for unresectable, locally advanced, and metastatic gallbladder cancer. However, over the past decade, the treatment paradigm has evolved. These include the introduction of newer chemotherapeutic strategies after progression on frontline chemotherapy, incorporation of targeted therapeutics towards driver mutations of genes including HER2, FGFR, BRAF, as well as approaches to unleash host anti-tumor immunity using immune checkpoint inhibitors. Notably, due to the rarity of BTC in general, most clinical trials included both GBC and cholangiocarcinomas. Here, we provide a review on the pathogenesis of GBC, past and current systemic treatment options focusing specifically on GBC, clinical trials tailored towards its genetic mutations, and emerging treatment strategies based on promising recent clinical studies.
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Affiliation(s)
| | - Kian-Huat Lim
- Division of Oncology, Department of Internal Medicine, Barnes-Jewish Hospital and The Alvin J. Siteman Comprehensive Cancer Center, Washington University School of Medicine, St. Louis, MO 63110, USA;
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Trout RM, Gnanatheepam E, Gado A, Reik C, Ramella-Roman JC, Hunter M, Schnelldorfer T, Georgakoudi I. Polarization enhanced laparoscope for improved visualization of tissue structural changes associated with peritoneal cancer metastasis. BIOMEDICAL OPTICS EXPRESS 2022; 13:571-589. [PMID: 35284190 PMCID: PMC8884200 DOI: 10.1364/boe.443926] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/21/2021] [Revised: 12/17/2021] [Accepted: 12/20/2021] [Indexed: 06/03/2023]
Abstract
A polarization enhanced laparoscopy (PEL) imaging system was developed to examine the feasibility of utilizing PEL to augment conventional white light laparoscopy (WLL) in the visualization of peritoneal cancer metastases. The system includes a modified tip to illuminate tissue with linearly polarized light and elements in the detection path enabling recording of corresponding images linearly co- and cross-polarized relative to the incident light. WLL and PEL images from optical tissue phantoms with features of distinct scattering cross-section confirm the enhanced sensitivity of PEL to such characteristics. Additional comparisons based on images acquired from collagen gels with different levels of fiber alignment highlight another source of PEL contrast. Finally, PEL and WLL images of ex vivo human tissue illustrate the potential of PEL to improve visualization of cancerous tissue surrounded by healthy peritoneum. Given the simplicity of the approach and its potential for seamless integration with current clinical practice, our results provide motivation for clinical translation.
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Affiliation(s)
- Robert M. Trout
- Department of Biomedical Engineering, Tufts University, 200 College Ave, Medford, MA 01255, USA
| | - Einstein Gnanatheepam
- Department of Biomedical Engineering, Tufts University, 200 College Ave, Medford, MA 01255, USA
| | - Ahmed Gado
- Department of Biomedical Engineering, Tufts University, 200 College Ave, Medford, MA 01255, USA
| | - Christopher Reik
- Department of Biomedical Engineering, Tufts University, 200 College Ave, Medford, MA 01255, USA
| | | | - Martin Hunter
- Department of Biomedical Engineering, University of Massachusetts at Amherst, Amherst, MA, USA
| | - Thomas Schnelldorfer
- Department of Biomedical Engineering, Tufts University, 200 College Ave, Medford, MA 01255, USA
- Division of Surgical Oncology, Tufts Medical Center, 800 Washington St, Boston, MA 02111, USA
- Contributed equally
| | - Irene Georgakoudi
- Department of Biomedical Engineering, Tufts University, 200 College Ave, Medford, MA 01255, USA
- Contributed equally
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Peng DZ, Nie GL, Li B, Cai YL, Lu J, Xiong XZ, Cheng NS. Prediction of Early Recurrence After R0 Resection for Gallbladder Carcinoma of Stage T1b-T3. Cancer Manag Res 2022; 14:37-47. [PMID: 35018120 PMCID: PMC8740626 DOI: 10.2147/cmar.s342674] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/06/2021] [Accepted: 12/07/2021] [Indexed: 02/05/2023] Open
Abstract
Purpose The time-to-tumor recurrence can predict the prognosis of hepatobiliary cancers following curative-intent resection. Therefore, for patients with gallbladder carcinoma (GBC) of stage T1b–T3 who had undergone R0 resection, we investigated the risk factors for early recurrence of GBC and their prognosis. Patients and Methods A total of 260 patients with GBC with T1b–T3 disease and an R0 margin were identified. Their clinicopathologic characteristics, perioperative details and prognostic data were reviewed. Survival analyses were carried out using the Kaplan–Meier method. Logistic regression models were used to identify the risk factors for early recurrence. Results The optimal cutoff for early recurrence was 29 months. Early recurrence tended to result in relapse far from the primary tumor, and such patients tended to have significantly worse overall survival. Multivariate analysis revealed that T3 disease, N1/N2 stage, poor differentiation of tumor, and lymphovascular invasion (LI) were associated with a greater risk of early recurrence. Patients diagnosed as having GBC incidentally and who had the risk factors of early recurrence were more likely to benefit from re-resection 2–4 weeks after a cholecystectomy. Conclusion T3 stage, N1–N2 stage, poor differentiation, and LI were independent risk factors associated with early recurrence for patients with GBC with stage T1b–T3 disease after R0 resection.
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Affiliation(s)
- Ding-Zhong Peng
- Department of Biliary Surgery, West China Hospital of Sichuan University, Chengdu, Sichuan Province, People's Republic of China
| | - Gui-Lin Nie
- Department of Biliary Surgery, West China Hospital of Sichuan University, Chengdu, Sichuan Province, People's Republic of China
| | - Bei Li
- Department of Biliary Surgery, West China Hospital of Sichuan University, Chengdu, Sichuan Province, People's Republic of China
| | - Yu-Long Cai
- Department of Biliary Surgery, West China Hospital of Sichuan University, Chengdu, Sichuan Province, People's Republic of China
| | - Jiong Lu
- Department of Biliary Surgery, West China Hospital of Sichuan University, Chengdu, Sichuan Province, People's Republic of China
| | - Xian-Ze Xiong
- Department of Biliary Surgery, West China Hospital of Sichuan University, Chengdu, Sichuan Province, People's Republic of China
| | - Nan-Sheng Cheng
- Department of Biliary Surgery, West China Hospital of Sichuan University, Chengdu, Sichuan Province, People's Republic of China
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Goel S, Aggarwal A, Iqbal A, Talwar V, Mitra S, Singh S. Multimodality management of gallbladder cancer can lead to a better outcome: Experience from a tertiary care oncology centre in North India. World J Gastroenterol 2021; 27:7813-7830. [PMID: 34963744 PMCID: PMC8661382 DOI: 10.3748/wjg.v27.i45.7813] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/26/2021] [Revised: 06/23/2021] [Accepted: 09/02/2021] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Surgical resection is a treatment of choice for gallbladder cancer (GBC) patients but only 10% of patients have a resectable disease at presentation. Even after surgical resection, overall survival (OS) has been poor due to high rates of recurrence. Combination of surgery and systemic therapy can improve outcomes in this aggressive disease.
AIM To summarize our single-center experience with multimodality management of resectable GBC patients.
METHODS Data of all patients undergoing surgery for suspected GBC from January 2012 to December 2018 was retrieved from a prospectively maintained electronic database. Information extracted included demographics, operative and perioperative details, histopathology, neoadjuvant/adjuvant therapy, follow-up, and recurrence. To know the factors associated with recurrence and OS, univariate and multivariate analysis was done using log rank test and cox proportional hazard analysis for categorical and continuous variables, respectively. Multivariate analysis was done using multiple regression analysis.
RESULTS Of 274 patients with GBC taken up for surgical resection, 172 (62.7%) were female and the median age was 56 years. On exploration, 102 patients were found to have a metastatic or unresectable disease (distant metastasis in 66 and locally unresectable in 34). Of 172 patients who finally underwent surgery, 93 (54%) underwent wedge resection followed by anatomical segment IVb/V resection in 66 (38.4%) and modified extended right hepatectomy in 12 (7%) patients. The postoperative mortality at 90 d was 4.6%. During a median follow-up period of 20 mo, 71 (41.2%) patients developed recurrence. Estimated 1-, 3-, and 5-years OS rates were 86.5%, 56%, and 43.5%, respectively. Estimated 1- and 3-year disease free survival (DFS) rates were 75% and 49.2%, respectively. On multivariate analysis, inferior OS was seen with pT3/T4 tumor (P = 0.0001), perineural invasion (P = 0.0096), and R+ resection (P = 0.0125). However, only pT3/T4 tumors were associated with a poor DFS (P < 0.0001).
CONCLUSION Multimodality treatment significantly improves the 5-year survival rate of patients with GBC up to 43%. R+ resection, higher T stage, and perineural invasion adversely affect the outcome and should be considered for systemic therapy in addition to surgery to optimize the outcomes. Multimodality treatment of GBC has potential to improve the survival of GBC patients.
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Affiliation(s)
- Shaifali Goel
- Department of GI and HPB Oncosurgery, Rajiv Gandhi Cancer Institute and Research Center, Delhi 110085, Delhi, India
| | - Abhishek Aggarwal
- Department of GI and HPB Oncosurgery, Rajiv Gandhi Cancer Institute and Research Center, Delhi 110085, Delhi, India
| | - Assif Iqbal
- Department of GI and HPB Oncosurgery, Rajiv Gandhi Cancer Institute and Research Center, Delhi 110085, Delhi, India
| | - Vineet Talwar
- Department of Medical Oncology, Rajiv Gandhi Cancer Institute and Research Center, Delhi 110085, Delhi, India
| | - Swarupa Mitra
- Department of Radiation Oncology, Rajiv Gandhi Cancer Institute and Research Center, Delhi 110085, Delhi, India
| | - Shivendra Singh
- Department of GI and HPB Oncosurgery, Rajiv Gandhi Cancer Institute and Research Center, Delhi 110085, Delhi, India
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Okumura K, Gogna S, Gachabayov M, Felsenreich DM, McGuirk M, Rojas A, Quintero L, Seshadri R, Gu K, Dong XD. Gallbladder cancer: Historical treatment and new management options. World J Gastrointest Oncol 2021; 13:1317-1335. [PMID: 34721769 PMCID: PMC8529935 DOI: 10.4251/wjgo.v13.i10.1317] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/06/2021] [Revised: 06/19/2021] [Accepted: 09/03/2021] [Indexed: 02/06/2023] Open
Abstract
Gallbladder cancer is a rare, aggressive malignancy that has a poor overall prognosis. Effective treatment consists of early detection and surgical treatment. With the wide spread treatment of gallbladder disease with minimally invasive techniques, the rate of incidental gallbladder cancer has seen an equitable rise along with stage migration towards earlier disease. Although the treatment remains mostly surgical, newer modalities such as regional therapy as well as directed therapy based on molecular medicine has led to improved outcomes in patients with advanced disease. We aim to summarize the management of gallbladder cancer along with the newer developments in this formidable disease process.
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Affiliation(s)
- Kenji Okumura
- Department of Surgery, Westchester Medical Center, Valhalla, NY 10595, United States
| | - Shekhar Gogna
- Department of Surgery, Westchester Medical Center, Valhalla, NY 10595, United States
| | - Mahir Gachabayov
- Department of Surgery, Westchester Medical Center, Valhalla, NY 10595, United States
| | | | - Matthew McGuirk
- Department of Surgery, Westchester Medical Center, Valhalla, NY 10595, United States
| | - Aram Rojas
- Department of Surgery, Westchester Medical Center, Valhalla, NY 10595, United States
| | - Luis Quintero
- Department of Surgery, New York Medical College, Valhalla, NY 10595, United States
| | - Ramanathan Seshadri
- Division of Surgical Oncology, Nuvance Health, Norwalk, CT 06856, United States
| | - Katie Gu
- Division of Surgical Oncology, Nuvance Health, Norwalk, CT 06856, United States
| | - Xiang Da Dong
- Division of Surgical Oncology, Nuvance Health, Norwalk, CT 06856, United States
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Transplant Oncology: An Evolving Field in Cancer Care. Cancers (Basel) 2021; 13:cancers13194911. [PMID: 34638395 PMCID: PMC8508383 DOI: 10.3390/cancers13194911] [Citation(s) in RCA: 30] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/19/2021] [Revised: 09/24/2021] [Accepted: 09/25/2021] [Indexed: 12/12/2022] Open
Abstract
Transplant oncology is an emerging concept of cancer treatment with a promising prospective outcome. The application of oncology, transplant medicine, and surgery to improve patients' survival and quality of life is the core of transplant oncology. Hepatobiliary malignancies have been treated by liver transplantation (LT) with significant improved outcome. In addition, as the liver is the most common site of metastasis for colorectal cancer (CRC), patients with CRC who have stable unresectable liver metastases are good candidates for LT, and initial studies have shown improved survival compared to palliative systemic therapy. The indications of LT for hepatobiliary malignancies have been slowly expanded over the years in a stepwise manner; however, they have only been shown to improve patient survival in the setting of limited systemic therapy options. This review illustrates the concept and history of transplant oncology as an evolving field for the management of hepatocellular carcinoma, intrahepatic biliary cancer, and liver-only metastasis of non-hepatobiliary carcinoma. The utility of immunotherapy in the transplant setting is discussed as well as the feasibility of using circulating tumor DNA for surveillance post-transplantation.
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Hau HM, Devantier M, Jahn N, Sucher E, Rademacher S, Seehofer D, Sucher R. Impact of Body Mass Index on Tumor Recurrence in Patients Undergoing Liver Resection for Perihilar Cholangiocarcinoma (pCCA). Cancers (Basel) 2021; 13:cancers13194772. [PMID: 34638257 PMCID: PMC8507532 DOI: 10.3390/cancers13194772] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/27/2021] [Accepted: 09/21/2021] [Indexed: 11/16/2022] Open
Abstract
Simple Summary Perihilar cholangiocarcinoma (pCCA) is a relatively rare and aggressive hepatobiliary tumor with a general poor prognosis. Surgical therapy remains the only curative treatment option with the best prospects for long-term survival. However, tumor recurrence is frequent, and is associated with a poor prognosis. The identification of risk factors as well as appropriate selection of surgical candidates is essential to accurately predict prognosis and to maximize survival while decreasing tumor recurrence rates. Previous studies have already established a link between an increased BMI and the occurrence of various tumors. At present, data on BMI-associated long-term outcome following curative liver resection in pCCA patients are warranted. This study aims to investigate the impact of increased BMI on patient’s outcome, especially on tumor recurrence, following liver resection in patients with pCCA as well as to evaluate prognostic and risk factors for accurate prediction of outcome in this selective group of patients. Abstract Background: The association of body mass index (BMI) and long-term prognosis and outcome of patients with perihilar cholangiocarcinoma (pCCA) has not been well defined. The aim of this study was to evaluate clinicopathologic and oncologic outcomes with pCCA undergoing resection, according to their BMI. Methods: Patients undergoing liver resection in curative intention for pCCA at a tertiary German hepatobiliary (HPB) center were identified from a prospective database. Patients were classified as normal weight (BMI 18.5–24.9 kg/m2), overweight (BMI 25.0–29.9 kg/m2) and obese (>30 kg/m2) according to their BMI. Impact of clinical and histo-pathological characteristics on recurrence-free survival (RFS) were assessed using Cox proportional hazard regression analysis among patients of all BMI groups. Results: Among a total of 95 patients undergoing liver resection in curative intention for pCCA in the analytic cohort, 48 patients (50.5%) had normal weight, 33 (34.7%) were overweight and 14 patients (14.7%) were obese. After a median follow-up of 4.3 ± 2.9 years, recurrence was observed in totally 53 patients (56%). The cumulative recurrence probability was higher in obese and overweight patients than normal weight patients (5-year recurrence rate: obese: 82% versus overweight: 81% versus normal weight: 58% at 5 years; p = 0.02). Totally, 1-, 3-, 5- and 10-year recurrence-free survival rates were 68.5%, 44.6%, 28.9% and 13%, respectively. On multivariable analysis, increased BMI (HR 1.08, 95% CI: 1.01–1.16; p = 0.021), poor/moderate tumor differentiation (HR 2.49, 95% CI: 1.2–5.2; p = 0.014), positive lymph node status (HR 2.01, 95% CI: 1.11–3.65; p = 0.021), positive resection margins (HR 1.89, 95% CI:1.02–3.4; p = 0.019) and positive perineural invasion (HR 2.92, 95% CI: 1.02–8.3; p = 0.045) were independent prognostic risk factors for inferior RFS. Conclusion: Our study shows that a high BMI is significantly associated with an increased risk of recurrence after liver resection in curative intention for pCCA. This factor should be considered in future studies to better predict patient’s individual prognosis and outcome based on their BMI.
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Affiliation(s)
- Hans-Michael Hau
- Department of Visceral, Transplantation, Vascular and Thoracic Surgery, University Hospital of Leipzig, 04103 Leipzig, Germany; (H.-M.H.); (M.D.); (S.R.); (D.S.)
- Department of Visceral, Thoracic and Vascular Surgery, University Hospital Carl Gustav Carus, Technische Universität Dresden, 01307 Dresden, Germany
| | - Mareen Devantier
- Department of Visceral, Transplantation, Vascular and Thoracic Surgery, University Hospital of Leipzig, 04103 Leipzig, Germany; (H.-M.H.); (M.D.); (S.R.); (D.S.)
| | - Nora Jahn
- Department of Anesthesiology and Intensive Care Medicine, University Hospital of Leipzig, 04103 Leipzig, Germany;
| | - Elisabeth Sucher
- Department of Oncology, Gastroenterology, Hepatology, Pneumology, Infectiology, and Nutritional Medicine, University Hospital of Leipzig, 04103 Leipzig, Germany;
| | - Sebastian Rademacher
- Department of Visceral, Transplantation, Vascular and Thoracic Surgery, University Hospital of Leipzig, 04103 Leipzig, Germany; (H.-M.H.); (M.D.); (S.R.); (D.S.)
| | - Daniel Seehofer
- Department of Visceral, Transplantation, Vascular and Thoracic Surgery, University Hospital of Leipzig, 04103 Leipzig, Germany; (H.-M.H.); (M.D.); (S.R.); (D.S.)
| | - Robert Sucher
- Department of Visceral, Transplantation, Vascular and Thoracic Surgery, University Hospital of Leipzig, 04103 Leipzig, Germany; (H.-M.H.); (M.D.); (S.R.); (D.S.)
- Correspondence: ; Tel.: +49-(0)341-9720-860; Fax: +49-(0)341-9717-209
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Kamarajah SK, Al-Rawashdeh W, White SA, Abu Hilal M, Salti GI, Dahdaleh FS. Adjuvant radiotherapy improves long-term survival after resection for gallbladder cancer A population-based cohort study. Eur J Surg Oncol 2021; 48:425-434. [PMID: 34518052 DOI: 10.1016/j.ejso.2021.09.002] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/16/2021] [Revised: 08/28/2021] [Accepted: 09/01/2021] [Indexed: 10/20/2022] Open
Abstract
BACKGROUND Data supporting routine use of adjuvant radiotherapy (RT) compared to without RT (noRT) for gallbladder cancer (GBC) is unclear. This study aimed to determine whether RT improves long-term survival following resection for GBC. METHODS Patients receiving resection for GBC followed by RT from 2004 to 2016 were identified from the National Cancer Database (NCDB). Patients with survival <6 months were excluded to account for immortal time bias. Propensity score matching (PSM) and Cox regression was performed to account for selection bias and analyze impact of RT on overall survival. RESULTS Of 7514 (77%) noRT and 2261 (23%) RT, 2067 noRT and 2067 RT patients remained after PSM. After matching, RT was associated with improved survival (median: 26.2 vs 21.5 months, p < 0.001), which remained after multivariable adjustment (HR: 0.82, CI95%: 0.76-0.89, p < 0.001). On multivariable interaction analyses, this benefit persisted irrespective of nodal status: N0 (HR: 0.84, CI95%: 0.77-0.93), N1 (HR: 0.77, CI95%: 0.68-0.88), N2/N3 (HR: 0.56, CI95%: 0.35-0.91), margin status: R0 (HR: 0.85, CI95%: 0.78-0.93), R1 (HR: 0.78, CI95%: 0.68-0.88) and use of adjuvant chemotherapy (AC) (HR: 0.67, CI95%: 0.57-0.79). Benefit with RT were also seen in patients with T2 - T4 disease and in patients undergoing simple and extended cholecystectomy. CONCLUSION RT following resection was associated with improved survival in this study, even in margin-negative and node-negative disease. These findings may suggest addition of RT into multimodality therapy for GBC.
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Affiliation(s)
- Sivesh K Kamarajah
- Department of Surgery, Queen Elizabeth Hospital Birmingham, University Hospital Birmingham NHS Trust, Birmingham, United Kingdom; Institute of Cancer and Genomic Sciences, University of Birmingham, Birmingham, United Kingdom.
| | - Wasfi Al-Rawashdeh
- Department of HPB and Transplant Surgery, The Freeman Hospital, Newcastle Upon Tyne, Tyne and Wear, United Kingdom
| | - Steven A White
- Department of HPB and Transplant Surgery, The Freeman Hospital, Newcastle Upon Tyne, Tyne and Wear, United Kingdom; Newcastle University, Newcastle Upon Tyne, Newcastle, United Kingdom
| | - Mohammed Abu Hilal
- Department of Surgery, Southampton University Hospital NHS Foundation Trust, Southampton, United Kingdom
| | - George I Salti
- Department of General Surgery, University of Illinois Hospital and Health Sciences System, Chicago, IL, USA; Edward-Elmhurst Health, Department of Surgical Oncology, Naperville, IL, USA
| | - Fadi S Dahdaleh
- Department of General Surgery, University of Illinois Hospital and Health Sciences System, Chicago, IL, USA
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Kim K, Yu JI, Jung W, Kim TH, Seong J, Kim WC, Choi JH, Park Y, Jeong BK, Kim BH, Kim TG, Kim JH, Park HJ, Shin HS, Im JH, Heo JS, Park JO, Jang JY, Oh DY, Woo SM, Lee WJ, Chie EK. Role of adjuvant radiotherapy in extrahepatic bile duct cancer: A multicenter retrospective study (Korean Radiation Oncology Group 18-14). Eur J Cancer 2021; 157:31-39. [PMID: 34474218 DOI: 10.1016/j.ejca.2021.07.045] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/02/2021] [Revised: 07/17/2021] [Accepted: 07/29/2021] [Indexed: 11/19/2022]
Abstract
PURPOSE To evaluate the role of adjuvant radiotherapy (RT) after curative resection in patients with extrahepatic bile duct (EHBD) cancer. METHODS Between January 2000 and December 2015, 1475 patients with EHBD cancer who underwent curative resection were accrued from 14 institutions in Korea. Among these, 959 patients did not receive any adjuvant therapy (RT(-) group), while 516 underwent postoperative RT with or without chemotherapy (RT(+) group). RESULTS The median age was 67 years. Nodal involvement was present in 482 patients (32.7%), and resection margin was involved in 293 patients (19.9%). RT(+) group had more patients with proximal tumours, advanced tumours, nodal involvement, perineural invasion, and involved resection margin than RT(-) group (all p < 0.001). With a median follow-up of 36 months, there were 211 locoregional recurrences, 307 distant metastases and 322 combined locoregional and distant failures. On multivariate analysis incorporating age, tumour location, differentiation, pT classification, pN classification, perineural invasion and resection margin, adjuvant RT was associated with improved overall survival (hazard ratio, 0.74; 95% confidence interval, 0.63-0.86; p < 0.001). When RT(+) group was separated into RT alone, concurrent chemoradiotherapy (CCRT) and CCRT followed by chemotherapy, the greatest benefit was observed in patients treated with CCRT followed by chemotherapy (hazard ratio, 0.52; 95% confidence interval, 0.41-0.68). CONCLUSIONS Adjuvant RT combined with chemotherapy improved survival outcomes of resected EHBD cancer patients. Considering the greatest benefit observed in patients receiving CCRT followed by chemotherapy, a randomised controlled trial comparing chemotherapy alone and CCRT followed by chemotherapy is urgently needed.
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Affiliation(s)
- Kyubo Kim
- Department of Radiation Oncology, Ewha Womans University College of Medicine, Seoul, South Korea
| | - Jeong Il Yu
- Department of Radiation Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea
| | - Wonguen Jung
- Department of Radiation Oncology, Ewha Womans University College of Medicine, Seoul, South Korea
| | - Tae Hyun Kim
- Center for Proton Therapy, National Cancer Center, Goyang, South Korea
| | - Jinsil Seong
- Department of Radiation Oncology, Yonsei University College of Medicine, Seoul, South Korea
| | - Woo Chul Kim
- Department of Radiation Oncology, Inha University School of Medicine, Incheon, South Korea
| | - Jin Hwa Choi
- Department of Radiation Oncology, Chung-Ang University College of Medicine, Seoul, South Korea
| | - Younghee Park
- Department of Radiation Oncology, Soonchunhyang University College of Medicine, Seoul, South Korea
| | - Bae Kwon Jeong
- Department of Radiation Oncology, Gyeongsang National University College of Medicine, Jinju, South Korea
| | - Byoung Hyuck Kim
- Department of Radiation Oncology, Seoul Metropolitan Government-Seoul National University Boramae Medical Center, Seoul, South Korea
| | - Tae Gyu Kim
- Department of Radiation Oncology, Samsung Changwon Hospital, Sungkyunkwan University School of Medicine, Changwon, South Korea
| | - Jin Hee Kim
- Department of Radiation Oncology, Keimyung University School of Medicine, Daegu, South Korea
| | - Hae Jin Park
- Department of Radiation Oncology, Hanyang University College of Medicine, Seoul, South Korea
| | - Hyun Soo Shin
- Department of Radiation Oncology, CHA University School of Medicine, Seongnam, South Korea
| | - Jung Ho Im
- Department of Radiation Oncology, Yonsei University College of Medicine, Seoul, South Korea; Department of Radiation Oncology, CHA University School of Medicine, Seongnam, South Korea
| | - Jin Seok Heo
- Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea
| | - Joon Oh Park
- Department of Internal Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea
| | - Jin-Young Jang
- Department of Surgery, Seoul National University College of Medicine, Seoul, South Korea
| | - Do-Youn Oh
- Department of Internal Medicine, Seoul National University College of Medicine, Seoul, South Korea
| | - Sang Myung Woo
- Center for Liver and Pancreatobiliary Cancer, National Cancer Center, Goyang, South Korea
| | - Woo Jin Lee
- Center for Liver and Pancreatobiliary Cancer, National Cancer Center, Goyang, South Korea
| | - Eui Kyu Chie
- Department of Radiation Oncology, Seoul National University College of Medicine, Seoul, South Korea.
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Sakata J, Nomura T, Aono T, Kitami C, Yokoyama N, Minagawa M, Takizawa K, Miura K, Hirose Y, Ichikawa H, Nagahashi M, Shimada Y, Kobayashi T, Wakai T. Oncological outcomes of surgery for recurrent biliary tract cancer: who are the best candidates? HPB (Oxford) 2021; 23:1371-1382. [PMID: 33558069 DOI: 10.1016/j.hpb.2021.01.007] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/18/2020] [Revised: 12/05/2020] [Accepted: 01/18/2021] [Indexed: 12/12/2022]
Abstract
BACKGROUND This study aimed to investigate the impact of surgery on outcomes in patients with recurrent biliary tract cancer (BTC) and elucidate factors affecting survival after surgery for this disease. METHODS A single-center study was undertaken in 178 patients with recurrent BTC, of whom 24 underwent surgery for recurrence, 85 received chemotherapy, and 69 received best supportive care. Then, we carried out a multicenter study in 52 patients undergoing surgery for recurrent BTC (gallbladder cancer, 39%; distal cholangiocarcinoma, 27%; perihilar cholangiocarcinoma, 21%; intrahepatic cholangiocarcinoma, 13%). RESULTS In the single-center study, 3-year survival after recurrence was 53% in patients who underwent surgery, 4% in those who received chemotherapy, and 0% in those who received best supportive care (p < 0.001). Surgery was an independently prognostic factor (p < 0.001). In the multicenter series, the respective 3-year and 5-year survival after surgery for recurrence was 50% and 29% in the 52 patients. Initial site of recurrence was the only independent prognostic factor (p = 0.019). Five-year survival after surgery for recurrence in patients with single distant, multifocal distant, and locoregional recurrence was 51%, 0%, and 0%, respectively (p = 0.002). Sites of single distant recurrence included the liver (n = 13, 54%), distant lymph nodes (all from gallbladder cancer, n = 7, 29%), lung (n = 2, 9%), peritoneum (n = 1, 4%), and abdominal wall (n = 1, 4%). CONCLUSION Surgery may be an effective option for patients with less aggressive tumor biology characterized by single distant recurrence in recurrent BTC.
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Affiliation(s)
- Jun Sakata
- Division of Digestive and General Surgery, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.
| | - Tatsuya Nomura
- Department of Gastrointestinal Surgery, Niigata Cancer Center Hospital, Niigata, Japan.
| | - Takashi Aono
- Department of Surgery, Niigata Prefectural Central Hospital, Joetsu, Japan.
| | - Chie Kitami
- Department of Surgery, Nagaoka Chuo General Hospital, Nagaoka, Japan.
| | - Naoyuki Yokoyama
- Department of Gastrointestinal Surgery, Niigata City General Hospital, Niigata, Japan.
| | | | - Kazuyasu Takizawa
- Division of Digestive and General Surgery, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.
| | - Kohei Miura
- Division of Digestive and General Surgery, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.
| | - Yuki Hirose
- Division of Digestive and General Surgery, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.
| | - Hiroshi Ichikawa
- Division of Digestive and General Surgery, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.
| | - Masayuki Nagahashi
- Division of Digestive and General Surgery, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.
| | - Yoshifumi Shimada
- Division of Digestive and General Surgery, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.
| | - Takashi Kobayashi
- Division of Digestive and General Surgery, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.
| | - Toshifumi Wakai
- Division of Digestive and General Surgery, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.
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A pilot study of Pan-FGFR inhibitor ponatinib in patients with FGFR-altered advanced cholangiocarcinoma. Invest New Drugs 2021; 40:134-141. [PMID: 34463891 DOI: 10.1007/s10637-021-01170-x] [Citation(s) in RCA: 18] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/21/2021] [Accepted: 08/26/2021] [Indexed: 12/15/2022]
Abstract
Background Biliary tract cancers (BTC) are rare, chemo resistant and are associated with a poor prognosis. Preclinical and early clinical work had demonstrated interesting anti-tumor activity from targeting fibroblast growth factor receptor (FGFR) pathway. We hypothesized that ponatinib, a multi-targeted tyrosine kinase inhibitor with activity against FGFR, would be active in BTC patients with FGFR alterations. Methods This was a multi-center, single institution pilot study of ponatinib in patients with advanced, refractory BTC with FGFR alterations. The primary end point was overall response rate, with secondary points of overall survival (OS), progression-free survival (PFS) and Health Related Quality of Life (HRQoL) assessment. Results Twelve patients were enrolled prior to early termination of the trial. Partial responses were observed in 1 from 12 patients. Median PFS was 2.4 months and median OS was 15.7 months. All observed toxicities were manageable and reversible. Toxicities were mild, with lymphopenia (75%), rash (63%) and fatigue (50%) being the most frequent. No significant detriment in global QoL was observed. Conclusions Ponatinib as a single agent in FGFR altered BTC is tolerable with limited clinical activity. This is the first report of prospective assessment of FGFR inhibition in BTC using ponatinib, and the first study to report its effect on HRQoL. Further development of ponatinib will involve correlative studies to better refine patient selection, focus on combinations with other molecular targeted agents, conventional cytotoxic chemotherapy, and studies to better understand mechanisms of treatment resistance.
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Xue R, Li R, Wang J, Tong W, Hao J. Horizons on the Therapy of Biliary Tract Cancers: A State-of-the-art Review. J Clin Transl Hepatol 2021; 9:559-567. [PMID: 34447686 PMCID: PMC8369023 DOI: 10.14218/jcth.2021.00007] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/02/2021] [Revised: 03/24/2021] [Accepted: 04/14/2021] [Indexed: 12/14/2022] Open
Abstract
Biliary tract cancers (BTCs) comprise a group of heterogeneous poor prognosis cancers with increasing incidence recent years. The combination chemotherapy with cisplatin and gemcitabine is the first-line therapy for advanced BTC. There remains no accepted standard treatment in the second-line setting. Nowadays, more and more novel treatment strategies have entered development, with some encouraging results being seen. Here, we review the current treatment status and clinical characteristics of BTC, the role of immunotherapy in BTC as well as the design of clinical trials for oncology drugs for BTC which aim to focus on the future profiles of clinical care and resolution of BTC.
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Affiliation(s)
- Ran Xue
- Key Laboratory of Carcinogenesis & Translational Research (Ministry of Education/Beijing), Early Drug Development Center, Peking University Cancer Hospital & Institute, Beijing, China
| | - Rong Li
- Department of Gastroenterology, Beijing Shuang-Qiao Hospital, Beijing, China
| | - Jianxin Wang
- Department of Gastroenterology, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, China
| | - Weiping Tong
- Department of Gastroenterology, Beijing Shuang-Qiao Hospital, Beijing, China
| | - Jianyu Hao
- Department of Gastroenterology, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, China
- Correspondence to: Jianyu Hao, Department of Gastroenterology, Beijing Chao-yang Hospital, Capital Medical University, Chao yang Area, Beijing 100020, China. Tel: +86-10-85231000, E-mail:
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Choi SH, Rim CH, Shin IS, Yoon WS, Koom WS, Seong J. Adjuvant Radiotherapy for Extrahepatic Cholangiocarcinoma: A Quality Assessment-Based Meta-Analysis. Liver Cancer 2021; 10:419-432. [PMID: 34721505 PMCID: PMC8527906 DOI: 10.1159/000518298] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/28/2021] [Accepted: 07/05/2021] [Indexed: 02/04/2023] Open
Abstract
INTRODUCTION The benefits of adjuvant radiotherapy (ART) for extrahepatic cholangiocarcinoma are uncertain largely because existing publications lack clear comparisons between ART and non-ART arms. METHODS PubMed, Medline, Embase, and the Cochrane library were systematically searched until December 2020. The primary endpoint was overall survival (OS). Sensitivity analysis was performed for studies with reliable comparability (i.e., no favorable prognosticators in the ART arm that could skew the data). RESULTS Twenty-three studies involving 1,731 patients with extrahepatic cholangiocarcinoma were reviewed. The overall median of all median prescribed doses was 50.4 Gy; brachytherapy or an intraoperative boost of 10-21 Gy was applied in 5 studies. The pooled 1-, 3-, and 5-year OS rates in the non-ART and ART arms were 69.2% versus 81.0%, p = 0.035; 34.3% versus 44.7%, p = 0.025; 25.6% versus 31.7%, p = 0.115, respectively. The corresponding pooled locoregional recurrence rates were 52.1% versus 34.9% (p = 0.014). The pooled rate of grade ≥3 gastrointestinal complications was 9.8%. Sensitivity analysis performed on 14 eligible studies showed that the ART arms had a lower pooled R0 rate (36.8% vs. 63.2%, p = 0.02) and a higher rate of positive lymph nodes (47.4% vs. 34.9%, p = 0.08). The pooled 1-, 3-, and 5-year OS rates in the non-ART versus ART arms of the selected studies were 78.2% versus 84.9%, p = 0.143; 38.5% versus 49.2%, p = 0.026; and 27.8% versus 34.5%, p = 0.11, respectively. CONCLUSIONS ART was shown to improve OS in all studies and in those selected for their reliable comparability.
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Affiliation(s)
- Seo Hee Choi
- Department of Radiation Oncology, Yongin Severance Hospital, Yonsei University College of Medicine, Yongin, Republic of Korea
| | - Chai Hong Rim
- Department of Radiation Oncology, Korea University Ansan Hospital, Korea University Medical College, Seoul, Republic of Korea,*Chai Hong Rim,
| | - In-Soo Shin
- Graduate School of Education, AI Convergence Education, Dongguk University, Seoul, Republic of Korea
| | - Won Sup Yoon
- Department of Radiation Oncology, Korea University Ansan Hospital, Korea University Medical College, Seoul, Republic of Korea
| | - Woong Sub Koom
- Department of Radiation Oncology, Yonsei Cancer Center, Yonsei University Medical College, Seoul, Republic of Korea
| | - Jinsil Seong
- Department of Radiation Oncology, Yonsei Cancer Center, Yonsei University Medical College, Seoul, Republic of Korea
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Wan W, Zheng B, Sun W, Wang J, Shen S, Huang L, Liu H, Ni X, Liu H. Adjuvant Therapy in Resected Nonmetastatic Stage II-IV Gallbladder Cancer: A Generalized Propensity Score Analysis. Oncol Res Treat 2021; 44:390-399. [PMID: 34218220 DOI: 10.1159/000517113] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/07/2020] [Accepted: 05/08/2021] [Indexed: 11/19/2022]
Abstract
BACKGROUND The clinical benefits and efficacies of adjuvant therapies for gallbladder cancer (GBC) have not been verified due to insufficient clinical evidence. METHODS Patients with resected nonmetastatic stage II-IV GBC were selected from the Surveillance, Epidemiology, and End Results database and distributed into nonchemotherapy and chemoradiotherapy (NCRT), chemotherapy (CT), and chemoradiotherapy (CRT) groups. Generalized propensity score and inverse probability of treatment weighting (IPTW) were used to reduce the imbalances between groups. RESULTS A total of 2,689 patients were enrolled, among whom 1,193 (44.4%) were classified as stage II, 1,371 (51.0%) as stage III, and 125 (4.6%) as stage IV GBC. A total of 1,703, 444, and 542 patients were placed in the NCRT, CT, and CRT groups, respectively. After the IPTW, there were no significant differences in overall survival (OS) between the 3 treatment groups (p > 0.05) in stage II GBC patients. In patients with stage III-IV GBC, the CT group exhibited a superior OS compared to the NCRT group (p < 0.001). In addition, the CRT group exhibited a superior OS compared to the CT (p < 0.001) and NCRT (p < 0.001) groups. For patients with stage III-IV tumors, a nomogram was constructed to predict the survival benefits of adjuvant therapies. CONCLUSION Patients with stage II GBC may not benefit from adjuvant therapy, while patients with stage III-IV GBC were shown to benefit from chemotherapy and chemoradiotherapy. Furthermore, chemoradiotherapy exhibited a superior OS. Nevertheless, the results need to be explained in the context of retrospective studies.
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Affiliation(s)
- Wenze Wan
- Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, China,
- Cancer Center, Zhongshan Hospital, Fudan University, Shanghai, China,
| | - Bohao Zheng
- Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, China
- Cancer Center, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Wentao Sun
- Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, China
- Cancer Center, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Jiwen Wang
- Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, China
- Cancer Center, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Sheng Shen
- Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, China
- Cancer Center, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Lihong Huang
- Cancer Center, Zhongshan Hospital, Fudan University, Shanghai, China
- Department of Biostatistics, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Han Liu
- Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, China
- Cancer Center, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Xiaojian Ni
- Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, China
- Cancer Center, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Houbao Liu
- Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, China
- Cancer Center, Zhongshan Hospital, Fudan University, Shanghai, China
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Li L, Ren T, Liu K, Li ML, Geng YJ, Yang Y, Li HF, Li XC, Bao RF, Shu YJ, Weng H, Gong W, Lau WY, Wu XS, Liu YB. Development and Validation of a Prognostic Nomogram Based on the Systemic Immune-Inflammation Index for Resectable Gallbladder Cancer to Predict Survival and Chemotherapy Benefit. Front Oncol 2021; 11:692647. [PMID: 34268122 PMCID: PMC8276054 DOI: 10.3389/fonc.2021.692647] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/08/2021] [Accepted: 06/07/2021] [Indexed: 02/05/2023] Open
Abstract
OBJECTIVES To investigate the prognostic significance of the systemic immune-inflammation index (SII) in patients after radical cholecystectomy for gallbladder cancer (GBC) using overall survival (OS) as the primary outcome measure. METHODS Based on data from a multi-institutional registry of patients with GBC, significant prognostic factors after radical cholecystectomy were identified by multivariate Cox proportional hazards model. A novel staging system was established, visualized as a nomogram. The response to adjuvant chemotherapy was compared between patients in different subgroups according to the novel staging system. RESULTS Of the 1072 GBC patients enrolled, 691 was randomly selected in the discovery cohort and 381 in the validation cohort. SII>510 was found to be an independent predictor of OS (hazard ratio [HR] 1.90, 95% confidence interval [CI] 1.42-2.54). Carbohydrate antigen 199(CA19-9), tumor differentiation, T stage, N stage, margin status and SII were involved in the nomogram. The nomogram showed a superior prediction compared with models without SII (1-, 3-, 5-year integrated discrimination improvement (IDI):2.4%, 4.1%, 5.4%, P<0.001), and compared to TNM staging system (1-, 3-, 5-year integrated discrimination improvement (IDI):5.9%, 10.4%, 12.2%, P<0.001). The C-index of the nomogram in predicting OS was 0.735 (95% CI 0.683-0.766). The novel staging system based on the nomogram showed good discriminative ability for patients with T2 or T3 staging and with negative lymph nodes after R0 resection. Adjuvant chemotherapy offered significant survival benefits to these patients with poor prognosis. CONCLUSIONS SII was an independent predictor of OS in patients after radical cholecystectomy for GBC. The new staging system identified subgroups of patients with T2 or T3 GBC with negative lymph nodes who benefited from adjuvant chemotherapy. CLINICAL TRIAL REGISTRATION ClinicalTrials.gov, identifier (NCT04140552).
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Affiliation(s)
- Lin Li
- Department of Biliary-Pancreatic Surgery, Renji Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
- Shanghai Key Laboratory of Biliary Tract Disease, Renji Hospital, Shanghai, China
- Shanghai Research Center of Biliary Tract Disease, Renji Hospital, Shanghai, China
- Department of General Surgery, Xinhua Hospital, Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Tai Ren
- Department of Biliary-Pancreatic Surgery, Renji Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
- Shanghai Key Laboratory of Biliary Tract Disease, Renji Hospital, Shanghai, China
- Shanghai Research Center of Biliary Tract Disease, Renji Hospital, Shanghai, China
| | - Ke Liu
- Department of Biliary-Pancreatic Surgery, Renji Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
- Shanghai Key Laboratory of Biliary Tract Disease, Renji Hospital, Shanghai, China
- Shanghai Research Center of Biliary Tract Disease, Renji Hospital, Shanghai, China
- Department of General Surgery, Xinhua Hospital, Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Mao-Lan Li
- Shanghai Key Laboratory of Biliary Tract Disease, Renji Hospital, Shanghai, China
- Shanghai Research Center of Biliary Tract Disease, Renji Hospital, Shanghai, China
- Department of General Surgery, Xinhua Hospital, Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Ya-Jun Geng
- Department of Biliary-Pancreatic Surgery, Renji Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
- Shanghai Key Laboratory of Biliary Tract Disease, Renji Hospital, Shanghai, China
- Shanghai Research Center of Biliary Tract Disease, Renji Hospital, Shanghai, China
- Department of General Surgery, Xinhua Hospital, Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Yang Yang
- Department of Biliary-Pancreatic Surgery, Renji Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
- Shanghai Key Laboratory of Biliary Tract Disease, Renji Hospital, Shanghai, China
- Shanghai Research Center of Biliary Tract Disease, Renji Hospital, Shanghai, China
- Department of General Surgery, Xinhua Hospital, Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Huai-Feng Li
- Shanghai Key Laboratory of Biliary Tract Disease, Renji Hospital, Shanghai, China
- Shanghai Research Center of Biliary Tract Disease, Renji Hospital, Shanghai, China
- Department of General Surgery, Xinhua Hospital, Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Xue-Chuan Li
- Department of Biliary-Pancreatic Surgery, Renji Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
- Shanghai Key Laboratory of Biliary Tract Disease, Renji Hospital, Shanghai, China
- Shanghai Research Center of Biliary Tract Disease, Renji Hospital, Shanghai, China
- Department of General Surgery, Xinhua Hospital, Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Run-Fa Bao
- Shanghai Key Laboratory of Biliary Tract Disease, Renji Hospital, Shanghai, China
- Shanghai Research Center of Biliary Tract Disease, Renji Hospital, Shanghai, China
- Department of General Surgery, Xinhua Hospital, Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Yi-Jun Shu
- Shanghai Key Laboratory of Biliary Tract Disease, Renji Hospital, Shanghai, China
- Shanghai Research Center of Biliary Tract Disease, Renji Hospital, Shanghai, China
- Department of General Surgery, Xinhua Hospital, Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Hao Weng
- Shanghai Key Laboratory of Biliary Tract Disease, Renji Hospital, Shanghai, China
- Shanghai Research Center of Biliary Tract Disease, Renji Hospital, Shanghai, China
- Department of General Surgery, Xinhua Hospital, Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Wei Gong
- Shanghai Key Laboratory of Biliary Tract Disease, Renji Hospital, Shanghai, China
- Shanghai Research Center of Biliary Tract Disease, Renji Hospital, Shanghai, China
- Department of General Surgery, Xinhua Hospital, Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Wan Yee Lau
- Faculty of Medicine, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong, Hong Kong
| | - Xiang-Song Wu
- Shanghai Key Laboratory of Biliary Tract Disease, Renji Hospital, Shanghai, China
- Shanghai Research Center of Biliary Tract Disease, Renji Hospital, Shanghai, China
- Department of General Surgery, Xinhua Hospital, Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Ying-Bin Liu
- Department of Biliary-Pancreatic Surgery, Renji Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
- Shanghai Key Laboratory of Biliary Tract Disease, Renji Hospital, Shanghai, China
- Shanghai Research Center of Biliary Tract Disease, Renji Hospital, Shanghai, China
- Shanghai Cancer Institute, State Key Laboratory of Oncogenes and Related Genes, Shanghai, China
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