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Trin K, Dalleau C, Mathoulin-Pelissier S, Le Tourneau C, Dinart D, Bellera C. The Growth Modulation Index (GMI) as an Efficacy Outcome in Cancer Clinical Trials: A Scoping Review with Suggested Reporting Guidelines. Curr Oncol Rep 2025; 27:516-532. [PMID: 40156702 DOI: 10.1007/s11912-025-01667-1] [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] [Accepted: 03/10/2025] [Indexed: 04/01/2025]
Abstract
PURPOSE OF REVIEW The growth modulation index (GMI) is defined as the ratio between the time to progression of a new line of treatment and the previous line. This ratio can be used to determine whether the new line of treatment brings a clinical benefit. It has been proposed as an outcome in trials evaluating non-cytotoxic drugs. Its interest lies in the intra-patient comparison. The terminology employed to refer to the GMI, as well as its definitions, are highly variable in the literature. Some uses of the GMI are arbitrary and not based on any scientific rationale. Our aim is to describe how the GMI is reported in the scientific literature. RECENT FINDINGS We carried out a scoping review using PubMed, Scopus, Web of Science and BASE (Bielefeld Academic Search Engine). The algorithm was composed of the terms "growth modulation index", "time to progression ratio" and "progression-free survival ratio". Documents in English, with full-text available, published up to 2023, were included. Among 227 included documents, 166 of which discussed GMI specifically. On these 166 documents, 76 reported on observational studies, 62 on interventional studies and 17 on methodological or statistical developments pertaining to the GMI. All were about oncology. Our review highlights significant variability in the reporting and use of the GMI. To address this, we propose standardized reporting guidelines. Additionally, we emphasize the need for methodological and statistical developments to improve the use of the GMI and to develop novel GMI-based trial designs.
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Affiliation(s)
- Kilian Trin
- INSERM CIC-1401, Clinical and Epidemiological Research Unit, Institut Bergonié, Comprehensive Cancer Center, Bordeaux, France.
- Medical Science Faculty, University of Bordeaux, Bordeaux, France.
| | - Cynthia Dalleau
- INSERM CIC-1401, Clinical and Epidemiological Research Unit, Institut Bergonié, Comprehensive Cancer Center, Bordeaux, France
- ISPED, Centre INSERM U1219 Bordeaux Population Health, Epicene Team, University of Bordeaux, Bordeaux, France
| | - Simone Mathoulin-Pelissier
- INSERM CIC-1401, Clinical and Epidemiological Research Unit, Institut Bergonié, Comprehensive Cancer Center, Bordeaux, France
- ISPED, Centre INSERM U1219 Bordeaux Population Health, Epicene Team, University of Bordeaux, Bordeaux, France
| | - Christophe Le Tourneau
- Department of Drug Development and Innovation (D3i), Institut Curie, Paris, France
- INSERM U900 Research Unit, Institut Curie, Paris, France
- Paris-Saclay University, Paris, France
| | - Derek Dinart
- INSERM CIC-1401, Clinical and Epidemiological Research Unit, Institut Bergonié, Comprehensive Cancer Center, Bordeaux, France
- ISPED, Centre INSERM U1219 Bordeaux Population Health, Epicene Team, University of Bordeaux, Bordeaux, France
| | - Carine Bellera
- INSERM CIC-1401, Clinical and Epidemiological Research Unit, Institut Bergonié, Comprehensive Cancer Center, Bordeaux, France
- ISPED, Centre INSERM U1219 Bordeaux Population Health, Epicene Team, University of Bordeaux, Bordeaux, France
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Yasinzai AQK, Iqbal A, Olavarria-Bernal D, Ballur K, Wali A, Ballur S, Tareen B, Khan M, Jain H, Khan I, Fadhil N, Sohail AH, Ullah A. Pancreatic Acinar Cell Carcinoma: Demographics, Treatment, and Survival Outcomes, A Retrospective Population-Based Study. J Gastrointest Cancer 2025; 56:106. [PMID: 40266404 DOI: 10.1007/s12029-025-01233-9] [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] [Accepted: 04/12/2025] [Indexed: 04/24/2025]
Abstract
PURPOSE Pancreatic acinar cell carcinoma accounts for 1-2% of pancreatic tumors, with increasing frequency in recent years, and still represents a poor prognosis. This study aims to expand and update existing literature by analyzing national data gathered over almost two decades. METHODS Data from 488 patients diagnosed with PACC in the Surveillance, Epidemiology, and End Results database were analyzed. This study employed the Cox regression method to compute hazard ratios and identify independent factors influencing survival. Additionally, Kaplan-Meier survival curves were utilized alongside the log-rank test. RESULTS The median age was 64.7 years with male predilection (70.5%). "Poorly differentiated carcinoma" was the most common subtype (45.8%). The liver was the most common site of metastases (31.3%). The 5-year observed overall survival (OS) rate was 19.2% (95% CI, 14.9-23.8). The 5-year cause-specific survival (CSS) rate was 22.4% (95% CI, 17.7-27.5). Male gender has a 5-year OS of 19.2% (95% CI, 14.0-25.1) compared to female OS of 30.2% (95% CI, 20.7-40.1). Patients treated with multimodal therapy (surgery with chemoradiation) over only surgery or chemotherapy had better 5-year OS, 53.5% (95% CI, 31.8-71.0). Age > 60 and distant stage were independent factors associated with increased mortality. CONCLUSION Pancreatic acinar cell carcinoma is a rare, aggressive form of pancreatic cancer that primarily affects older adults. Our findings offer valuable insights to guide future clinical guidelines and tailored treatment strategies.
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Affiliation(s)
| | - Asif Iqbal
- Department of Hematology Oncology, University of Toledo, Toledo, OH, USA
| | - Diego Olavarria-Bernal
- Department of Internal Medicine, Texas Tech University Health Sciences Center, 3601 4 Th Street, MS 9410, Lubbock, TX, 79430, USA.
| | | | - Agha Wali
- Banner University Medical Center, Phoenix, AZ, USA
| | | | - Bisma Tareen
- Department of Medicine, Bolan Medical College, Quetta, Pakistan
| | - Marjan Khan
- Department of Medicine, Marshfield Clinic, Wisconsin, WI, USA
| | - Hritvik Jain
- All India Institute of Medical Sciences, Jodhpur, India
| | - Israr Khan
- Department of Medicine, Insight Hospital and Medical Center, Chicago, IL, USA
| | - Nooran Fadhil
- Texas Tech University Health Sciences Center, Lubbock, TX, USA
| | - Amir Humza Sohail
- Department of Surgery, University of New Mexico, Albuquerque, NM, USA
| | - Asad Ullah
- Department of Pathology, Texas Tech University Health Sciences Center, Lubbock, TX, USA
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Blair AB, Radomski SN, Chou J, Liu M, Howell TC, Park W, O'Reilly EM, Zheng L, Balachandran VP, Wei AC, Kingham TP, D'Angelica MI, Drebin J, Zani S, Blazer DG, Burkhart RA, Burns WR, Lafaro KJ, Allen PJ, Jarnagin WR, Lidsky ME, He J, Soares KC. Survival Outcomes and Genetic Characteristics of Resected Pancreatic Acinar Cell Carcinoma. Ann Surg Oncol 2025; 32:1869-1878. [PMID: 39576455 PMCID: PMC11811437 DOI: 10.1245/s10434-024-16331-4] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/16/2024] [Accepted: 09/23/2024] [Indexed: 02/12/2025]
Abstract
BACKGROUND Pancreatic acinar cell carcinoma (pACC) is a rare neoplasm of the exocrine pancreas. There is a dearth of information about tumor characteristics and patient outcomes. This study describes the clinical characteristics, genetic alterations, and survival outcomes of resected pACC. PATIENTS AND METHODS Consecutive patients undergoing pancreatectomy for pathologically confirmed pACC from 1999 to 2022 across three high-volume pancreas surgery centers were analyzed. Patient demographics, tumor characteristics, treatment data, and genetic sequencing were obtained through retrospective abstraction. RESULTS A total of 61 patients with resected pACC were identified. Median overall survival (OS) was 73 months and median recurrence free survival was 22 months. Nine patients underwent resection for oligometastatic disease; median OS was not reached after a median follow-up of 31 months from date of metastasectomy. Adjuvant chemotherapy was administered in 67% of patients with FOLFOX/FOLFIRINOX (5-fluorouracil, leucovorin, oxaliplatin, ± irinotecan) the most common regimen (58%). Sequencing data were obtained in 47 (77%) patients. A mutation in at least one of three core genes associated with the homologous recombination repair (HRR) pathway (BRCA1, BRCA2, or PALB2) occurred in 26% (n = 12) with BRCA2 the most frequently identified. A mutation in any other "non-core" gene associated with DNA damage repair or the HRR pathway was identified in 45% (n = 21) with a high tumor mutational burden of > 10 mutations per megabase in 13%. CONCLUSIONS Resection of pACC is associated with favorable survival outcomes, even in the setting of oligometastatic disease. Mutations in the HRR pathway are common, providing opportunities for potential targeted therapeutic options.
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Affiliation(s)
- Alex B Blair
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA
- Department of Surgery, The Ohio State University Wexner Medical Center, Columbus, OH, USA
| | - Shannon N Radomski
- Department of Surgery, Johns Hopkins Hospital, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Joanne Chou
- Department of Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Mengyuan Liu
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | | | - Wungki Park
- Department of Gastrointestinal Oncology, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Eileen M O'Reilly
- Department of Gastrointestinal Oncology, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Lei Zheng
- Department of Oncology, Johns Hopkins Hospital, Baltimore, MD, USA
| | - Vinod P Balachandran
- 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
| | - Jeffrey Drebin
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Sabino Zani
- Department of Surgery, Duke University Hospital, Durham, NC, USA
| | - Dan G Blazer
- Department of Surgery, Duke University Hospital, Durham, NC, USA
| | - Richard A Burkhart
- Department of Surgery, Johns Hopkins Hospital, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - William R Burns
- Department of Surgery, Johns Hopkins Hospital, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Kelly J Lafaro
- Department of Surgery, Johns Hopkins Hospital, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Peter J Allen
- Department of Surgery, Duke University Hospital, 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 Hospital, Durham, NC, USA
| | - Jin He
- Department of Surgery, Johns Hopkins Hospital, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
| | - Kevin C Soares
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
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Wang Y, Zhang J, Nie D, Zhang A, Hu Q, Liu A. Pediatric pancreatic acinar cell carcinoma with a non-canonical BRAF-KMT2C fusion and a classic SND1-BRAF fusion: a case report and literature review. BMC Pediatr 2025; 25:57. [PMID: 39856649 PMCID: PMC11760658 DOI: 10.1186/s12887-024-05378-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/22/2024] [Accepted: 12/30/2024] [Indexed: 01/27/2025] Open
Abstract
BACKGROUND Pediatric pancreatic acinar cell carcinoma (PACC) is an exceptionally rare and poorly understood malignancy with a challenging prognosis. Its clinical presentation is often atypical, and standardized treatment guidelines are currently unavailable. While genetic alterations in adult PACC have been studied to some extent, knowledge of genetic abnormalities in pediatric cases remains limited. CASE PRESENTATION We report a case of pediatric PACC in a 7-year-old male presenting with a large, non-tender abdominal mass (11 cm x 11 cm) on the right side. Pathological and imaging evidence confirmed the diagnosis of PACC, with no lymph node infiltration or distant metastasis. Comprehensive genomic profiling by next-generation sequencing identified a non-canonical BRAF fusion with KMT2C at the DNA level and a classic SND1-BRAF fusion at the RNA level. The patient underwent surgical resection through a Whipple operation followed by six cycles of mFOLIRINOX chemotherapy and radiation therapy, achieving a favorable outcome up to now. CONCLUSIONS Next-generation sequencing has demonstrated significant value in identifying genetic fusions in pediatric PACC. In our case report, we identified both the classical SND1-BRAF fusion, commonly associated with PACC, and a previously unreported nonclassical BRAF-KMT2C fusion. These findings underscore the critical role of BRAF alterations as key drivers of oncogenesis in PACC. A multidisciplinary treatment strategy integrating surgery, chemotherapy, and radiation therapy offers a promising precedent for improving therapeutic outcomes and prolonging survival in pediatric PACC cases.
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Affiliation(s)
- Yaqin Wang
- Department of Pediatric, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China
| | - Jiasi Zhang
- Department of Pediatric, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China
| | - Dimin Nie
- Department of Pediatric, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China
| | - Ai Zhang
- Department of Pediatric, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China
| | - Qun Hu
- Department of Pediatric, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China
| | - Aiguo Liu
- Department of Pediatric, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
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Eslinger C, Seddighzadeh B, Yee C, Elsabbagh Z, Pai R, Hartley C, Starr J, Bekaii-Saab T, Halfdanarson TR, Sonbol MB. Clinical Outcomes and Molecular Profiling of Pancreatic Acinar Cell Carcinoma: A Retrospective Study. JCO Precis Oncol 2025; 9:e2400450. [PMID: 39772831 PMCID: PMC11706351 DOI: 10.1200/po-24-00450] [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: 07/01/2024] [Revised: 10/16/2024] [Accepted: 12/05/2024] [Indexed: 01/11/2025] Open
Abstract
PURPOSE Pancreatic acinar cell carcinoma (PACC) is a rare and aggressive form of pancreatic cancer that originates in the acinar cells of the exocrine pancreas. In this study, we aimed to investigate the clinical and molecular characteristics of patients with PACC at our institution. METHODS This was a retrospective study of patients with PACC seen at Mayo Clinic between 2002 and 2023. Baseline patient characteristics, tumor pathology, treatment strategies used, and survival outcomes were analyzed. Kaplan-Meier curves were estimated using newsurv macros in SAS. RESULTS The study included a total of 65 patients with PACC. The median age at diagnosis was 66 years. Almost half of the patients (48%) presented with resectable/borderline-resectable disease (n = 28). Five-year overall survival (OS) for resectable/borderline-resectable, locally advanced/unresectable, and metastatic disease were 72.0%, 21.6%, and 20.9%, respectively. Somatic and germline next-generation sequencing identified numerous potentially actionable targets including homologous recombination (43% somatic, 33% germline), RAF alterations (29% somatic), and mismatch repair (14% somatic). CONCLUSION Our findings underscore the heterogeneity and aggressive nature of PACC. Despite the improved prognosis for patients with resectable/borderline-resectable disease, OS remains poor, particularly for those with locally advanced or metastatic disease. The identification of actionable molecular targets in a significant proportion of patients highlights the potential for personalized therapeutic approaches. Future research should focus on tailored treatment strategies to exploit these molecular vulnerabilities, which may offer new options for improving outcomes in this rare malignancy.
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Affiliation(s)
- Cody Eslinger
- Department of Hematology and Oncology, Mayo Clinic, Phoenix, AZ
| | | | - Claire Yee
- Department of Clinical Trials and Biostatistics, Mayo Clinic, Phoenix, AZ
| | - Zaid Elsabbagh
- Department of Hematology and Oncology, Mayo Clinic, Phoenix, AZ
| | - Rish Pai
- Department of Laboratory Medicine and Pathology, Mayo Clinic, Phoenix, AZ
| | - Chris Hartley
- Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN
| | - Jason Starr
- Department of Hematology and Oncology, Mayo Clinic, Jacksonville, FL
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Teramatsu K, Fujimori N, Murakami M, Yasumori S, Matsumoto K, Nakata K, Nakamura M, Koga Y, Oda Y, Ogawa Y. Pathological complete response with FOLFIRINOX therapy for recurrence of pancreatic acinar cell carcinoma. Clin J Gastroenterol 2024; 17:776-781. [PMID: 38761340 DOI: 10.1007/s12328-024-01983-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/05/2024] [Accepted: 05/06/2024] [Indexed: 05/20/2024]
Abstract
Pancreatic acinar cell carcinoma (PACC) is a very rare subtype of pancreatic cancer. Due to small number of patients, no standard chemotherapy protocol has been established. We experienced an extremely rare case of PACC with liver metastasis that showed a pathological complete response after modified FOLFIRINOX (mFFX) therapy. A 42-year-old man who underwent distal pancreatectomy for an 80 mm tumor at the pancreatic tail 3 years ago was referred to our hospital in September 2017 for the treatment of a recurrent liver tumor. Percutaneous biopsy revealed an acinar-neuroendocrine carcinoma, similar to the surgical specimen. He received eight cycles of irinotecan plus cisplatin chemotherapy. However, the tumor increased in size, and treatment was switched to mFFX therapy. The tumor in the liver shrank remarkably after nine cycles of mFFX therapy. Conversion surgery was selected, and the patient underwent hepatic left and caudate lobectomy 8 months after administration of mFFX. The resected specimen showed no viable tumor cells, indicating a pathological complete response. The histological diagnosis was reconsidered, and PACC was finally diagnosed via an additional immunohistological review. The patient has remained well with no recurrence for 6 years after surgery. This study is the first to report a case of pathological complete response with mFFX therapy for the recurrence of PACC.
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Affiliation(s)
- Katsuhito Teramatsu
- Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1, Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan
| | - Nao Fujimori
- Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1, Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan.
| | - Masatoshi Murakami
- Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1, Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan
| | - Sho Yasumori
- Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1, Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan
| | - Kazuhide Matsumoto
- Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1, Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan
| | - Kohei Nakata
- Department of Surgery and Oncology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Masafumi Nakamura
- Department of Surgery and Oncology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Yutaka Koga
- Department of Pathology, National Hospital Organization Kyushu Cancer Center, Fukuoka, Japan
| | - Yoshinao Oda
- Department of Anatomic Pathology, Graduate School of Medical Sciences, Kyushu University Hospital, Fukuoka, Japan
| | - Yoshihiro Ogawa
- Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1, Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan
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de Jesus VHF, Donadio MDS, de Brito ÂBC, Gentilli AC. A narrative review on rare types of pancreatic cancer: should they be treated as pancreatic ductal adenocarcinomas? Ther Adv Med Oncol 2024; 16:17588359241265213. [PMID: 39072242 PMCID: PMC11282540 DOI: 10.1177/17588359241265213] [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: 02/17/2024] [Accepted: 06/13/2024] [Indexed: 07/30/2024] Open
Abstract
Pancreatic cancer is one of the deadliest malignancies in humans and it is expected to play a bigger part in cancer burden in the years to come. Pancreatic ductal adenocarcinoma (PDAC) represents 85% of all primary pancreatic malignancies. Recently, much attention has been given to PDAC, with significant advances in the understanding of the mechanisms underpinning disease initiation and progression, along with noticeable improvements in overall survival in both localized and metastatic settings. However, given their rarity, rare histological subtypes of pancreatic cancer have been underappreciated and are frequently treated as PDAC, even though they might present non-overlapping molecular alterations and clinical behavior. While some of these rare histological subtypes are true variants of PDAC that should be treated likewise, others represent separate clinicopathological entities, warranting a different therapeutic approach. In this review, we highlight clinical, pathological, and molecular aspects of rare histological types of pancreatic cancer, along with the currently available data to guide treatment decisions.
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Affiliation(s)
- Victor Hugo Fonseca de Jesus
- Oncoclínicas, Department of Gastrointestinal Medical Oncology, Santos Dumont St. 182, 4 floor, Florianópolis, Santa Catarina 88015-020, Brazil
- Department of Medical Oncology, Centro de Pesquisas Oncológicas, Florianópolis, Santa Catarina, Brazil
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Merz V, Maines F, Marcucci S, Sartori C, Frisinghelli M, Trentin C, Kadrija D, Carbone FG, Michielan A, Gabbrielli A, Melisi D, Barbareschi M, Brolese A, Caffo O. Complete pathological response to pembrolizumab in pretreated pancreatic acinar cell carcinoma. J Cancer Res Clin Oncol 2024; 150:347. [PMID: 38990367 PMCID: PMC11239721 DOI: 10.1007/s00432-024-05841-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/10/2024] [Accepted: 06/06/2024] [Indexed: 07/12/2024]
Abstract
BACKGROUND Therapeutic approach used for pancreatic ductal adenocarcinoma is usually translated also for the rarer acinar counterpart, which shows a different mutational landscape nevertheless. While dMMR/MSI-H status is rare in the ductal histotype, it appears to be more prevalent in pancreatic acinar cell carcinoma (PACC). CASE PRESENTATION We report the case of a patient with locally advanced MSI-H PACC in whom the treatment with the anti-PD-1 pembrolizumab, administered as third line, made possible surgical resection, achieving even an exceptional pathological complete response. CONCLUSIONS Treatment of PACC should be tailored based on the peculiar molecular features that distinguish PACC from ductal adenocarcinoma. Evaluation of potentially therapeutically targetable alterations should be mandatory in case of PACC diagnosis.
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Affiliation(s)
- Valeria Merz
- Department of Medical Oncology, Santa Chiara Hospital, APSS, L.Go Medaglie d'Oro,9, 38122, Trento, Italy.
- Digestive Molecular Clinical Oncology Research Unit, Università degli Studi di Verona, Verona, Italy.
| | - Francesca Maines
- Department of Medical Oncology, Santa Chiara Hospital, APSS, L.Go Medaglie d'Oro,9, 38122, Trento, Italy
| | - Stefano Marcucci
- Department of General Surgery and HPB Unit, Santa Chiara Hospital, APSS, Trento, Italy
| | - Chiara Sartori
- Department of Laboratory Medicine - Pathology Unit, Santa Chiara Hospital, APSS, Trento, Italy
| | - Michela Frisinghelli
- Department of Medical Oncology, Santa Chiara Hospital, APSS, L.Go Medaglie d'Oro,9, 38122, Trento, Italy
| | - Chiara Trentin
- Department of Medical Oncology, Santa Chiara Hospital, APSS, L.Go Medaglie d'Oro,9, 38122, Trento, Italy
| | - Dzenete Kadrija
- Department of Medical Oncology, Santa Chiara Hospital, APSS, L.Go Medaglie d'Oro,9, 38122, Trento, Italy
| | | | - Andrea Michielan
- Gastroenterology and Digestive Endoscopy Unit, Santa Chiara Hospital, APSS, Trento, Italy
| | - Armando Gabbrielli
- Gastroenterology and Digestive Endoscopy Unit, Santa Chiara Hospital, APSS, Trento, Italy
- Center for Medical Sciences (CISMed), University of Trento, Trento, Italy
| | - Davide Melisi
- Digestive Molecular Clinical Oncology Research Unit, Università degli Studi di Verona, Verona, Italy
| | - Mattia Barbareschi
- Department of Laboratory Medicine - Pathology Unit, Santa Chiara Hospital, APSS, Trento, Italy
- Center for Medical Sciences (CISMed), University of Trento, Trento, Italy
| | - Alberto Brolese
- Department of General Surgery and HPB Unit, Santa Chiara Hospital, APSS, Trento, Italy
| | - Orazio Caffo
- Department of Medical Oncology, Santa Chiara Hospital, APSS, L.Go Medaglie d'Oro,9, 38122, Trento, Italy
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9
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Ikezawa K, Urabe M, Kai Y, Takada R, Akita H, Nagata S, Ohkawa K. Comprehensive review of pancreatic acinar cell carcinoma: epidemiology, diagnosis, molecular features and treatment. Jpn J Clin Oncol 2024; 54:271-281. [PMID: 38109477 PMCID: PMC10925851 DOI: 10.1093/jjco/hyad176] [Citation(s) in RCA: 7] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/26/2023] [Accepted: 11/29/2023] [Indexed: 12/20/2023] Open
Abstract
Pancreatic acinar cell carcinoma is a rare form (0.2-4.3%) of pancreatic neoplasm with unique clinical and molecular characteristics, which largely differ from pancreatic ductal adenocarcinoma. Pancreatic acinar cell carcinoma occurs more frequently in males and can occur in children. Serum lipase is elevated in 24-58% of patients with pancreatic acinar cell carcinoma. Pancreatic acinar cell carcinomas tend to be large at diagnosis (median tumour size: ~5 cm) and are frequently located in the pancreas head. Radiologically, pancreatic acinar cell carcinoma generally exhibits a solid appearance; however, necrosis, cystic changes and intratumoral haemorrhage can occur in larger lesions. Immunostaining is essential for the definitive diagnosis of pancreatic acinar cell carcinoma. Compared with pancreatic ductal adenocarcinoma, pancreatic acinar cell carcinoma has a more favourable prognosis. Although radical surgery is recommended for patients with pancreatic acinar cell carcinoma who do not have distant metastases, the recurrence rate is high. The effectiveness of adjuvant therapy for pancreatic acinar cell carcinoma is unclear. The response to FOLFIRINOX is generally favourable, and some patients achieve a complete response. Pancreatic acinar cell carcinoma has a different genomic profile compared with pancreatic ductal adenocarcinoma. Although genomic analyses have shown that pancreatic acinar cell carcinoma rarely has KRAS, TP53 and CDKN2A mutations, it has a higher prevalence of homologous recombination-related genes, including BRCA1/2 and ATM, than pancreatic ductal adenocarcinoma, suggesting high sensitivity to platinum-containing regimens and PARP inhibitors. Targeted therapies for genomic alternations are beneficial. Therefore, genetic testing is important for patients with pancreatic acinar cell carcinoma to choose the optimal therapeutic strategy.
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Affiliation(s)
- Kenji Ikezawa
- Department of Hepatobiliary and Pancreatic Oncology, Osaka International Cancer Institute, Osaka, Japan
| | - Makiko Urabe
- Department of Hepatobiliary and Pancreatic Oncology, Osaka International Cancer Institute, Osaka, Japan
| | - Yugo Kai
- Department of Hepatobiliary and Pancreatic Oncology, Osaka International Cancer Institute, Osaka, Japan
| | - Ryoji Takada
- Department of Hepatobiliary and Pancreatic Oncology, Osaka International Cancer Institute, Osaka, Japan
| | - Hirofumi Akita
- Department of Gastroenterological Surgery, Osaka International Cancer Institute, Osaka, Japan
| | - Shigenori Nagata
- Department of Diagnostic Pathology and Cytology, Osaka International Cancer Institute, Osaka, Japan
| | - Kazuyoshi Ohkawa
- Department of Hepatobiliary and Pancreatic Oncology, Osaka International Cancer Institute, Osaka, Japan
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10
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Garajová I, Peroni M, Gelsomino F, Leonardi F. A Simple Overview of Pancreatic Cancer Treatment for Clinical Oncologists. Curr Oncol 2023; 30:9587-9601. [PMID: 37999114 PMCID: PMC10669959 DOI: 10.3390/curroncol30110694] [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: 09/19/2023] [Revised: 10/13/2023] [Accepted: 10/24/2023] [Indexed: 11/25/2023] Open
Abstract
Pancreatic cancer (PDAC) is one of the most aggressive solid tumors and is showing increasing incidence. The aim of our review is to provide practical help for all clinical oncologists and to summarize the current management of PDAC using a simple "ABC method" (A-anatomical resectability, B-biological resectability and C-clinical conditions). For anatomically resectable PDAC without any high-risk factors (biological or conditional), the actual standard of care is represented by surgery followed by adjuvant chemotherapy. The remaining PDAC patients should all be treated with initial systemic therapy, though the intent for each is different: for borderline resectable patients, the intent is neoadjuvant; for locally advanced patients, the intent is conversion; and for metastatic PDAC patients, the intent remains just palliative. The actual standard of care in first-line therapy is represented by two regimens: FOLFIRINOX and gemcitabine/nab-paclitaxel. Recently, NALIRIFOX showed positive results over gemcitabine/nab-paclitaxel. There are limited data for maintenance therapy after first-line treatment, though 5-FU or FOLFIRI after initial FOLFIRINOX, and gemcitabine, after initial gemcitabine/nab-paclitaxel, might be considered. We also dedicate space to special rare conditions, such as PDAC with germline BRCA mutations, pancreatic acinar cell carcinoma and adenosquamous carcinoma of the pancreas, with few clinically relevant remarks.
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Affiliation(s)
- Ingrid Garajová
- Medical Oncology Unit, University Hospital of Parma, 43125 Parma, Italy; (M.P.)
| | - Marianna Peroni
- Medical Oncology Unit, University Hospital of Parma, 43125 Parma, Italy; (M.P.)
| | - Fabio Gelsomino
- Department of Oncology and Hematology, University Hospital of Modena, 41124 Modena, Italy
| | - Francesco Leonardi
- Medical Oncology Unit, University Hospital of Parma, 43125 Parma, Italy; (M.P.)
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11
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Yamada S, Motegi H, Kurihara Y, Shimbo T, Kikuchi I, Wakabayashi T, Sato T. A resected case of acinar cell carcinoma of the pancreas with liver metastasis following chemotherapy using modified FOLFIRINOX. Surg Case Rep 2023; 9:147. [PMID: 37610633 PMCID: PMC10447704 DOI: 10.1186/s40792-023-01729-1] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/19/2023] [Accepted: 08/08/2023] [Indexed: 08/24/2023] Open
Abstract
BACKGROUND Acinar cell carcinoma of the pancreas is a rare exocrine malignancy representing less than 1% of all pancreatic neoplasms. It has been reported that it responds to treatment differently from pancreatic ductal adenocarcinoma and the treatment algorithm for acinar cell carcinoma usually depends on the stage of the respective tumor and the patient's current status. CASE PRESENTATION A 60-year-old man presented with upper abdominal pain and anorexia. Abdominal ultrasonography showed a large-sized hepatic mass and he was referred to our hospital. Contrast-enhanced computed tomography demonstrated a 110-mm low-density area occupying the right hemi-liver and an enhanced mass of 70 × 56 mm in the tail of the pancreas, which seemed to directly infiltrate into the spleen. The case was diagnosed as acinar cell carcinoma with a simultaneous liver metastasis identified by liver biopsy. Upfront resection of pancreatic cancer with distant metastasis might not be considered as an optimal choice, and in this case chemotherapy was administered prior to curative resection. Chemotherapy using the modified FOLFIRINOX regimen was undertaken, resulting in a partial remission; the liver tumor reduced in size from 110 to 47 mm and the pancreatic tumor from 70 to 40 mm. The patient then safely underwent curative hepatic resection with distal pancreato-splenectomy. Histological examinations revealed small-sized atypical cells with large nuclei that had formed acinar patterns, and immunostaining with trypsin was positive in tumor cells, which was in accordance with acinar cell carcinoma. More than 3 years later, the patient is doing well without any recurrence. CONCLUSION Aggressive and curative surgery in combination with chemotherapy such as FOLFIRINOX could be a treatment option to achieve long-term survival in cases of acinar cell carcinoma with liver metastases.
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Affiliation(s)
- Shuhei Yamada
- Department of Gastroenterological Surgery, Akita City Hospital, 4-30 Kawamoto Matsuoka-machi, Akita-city, Akita, Japan.
| | - Haruka Motegi
- Department of Gastroenterological Surgery, Akita City Hospital, 4-30 Kawamoto Matsuoka-machi, Akita-city, Akita, Japan
| | - Yoshiki Kurihara
- Department of Gastroenterological Surgery, Akita City Hospital, 4-30 Kawamoto Matsuoka-machi, Akita-city, Akita, Japan
| | - Tomonori Shimbo
- Department of Gastroenterological Surgery, Akita City Hospital, 4-30 Kawamoto Matsuoka-machi, Akita-city, Akita, Japan
| | - Isao Kikuchi
- Department of Gastroenterological Surgery, Akita City Hospital, 4-30 Kawamoto Matsuoka-machi, Akita-city, Akita, Japan
| | - Toshiki Wakabayashi
- Department of Gastroenterological Surgery, Akita City Hospital, 4-30 Kawamoto Matsuoka-machi, Akita-city, Akita, Japan
| | - Tsutomu Sato
- Department of Gastroenterological Surgery, Akita City Hospital, 4-30 Kawamoto Matsuoka-machi, Akita-city, Akita, Japan
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12
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Zhao F, Yang D, Xu T, He J, Guo J, Li X. New treatment insights into pancreatic acinar cell carcinoma: case report and literature review. Front Oncol 2023; 13:1210064. [PMID: 37465113 PMCID: PMC10351044 DOI: 10.3389/fonc.2023.1210064] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/21/2023] [Accepted: 06/20/2023] [Indexed: 07/20/2023] Open
Abstract
Pancreatic acinar cell carcinoma (PACC) is a rare pancreatic malignancy with unique clinical, molecular, and morphologic features. The long-term survival of patients with PACC is substantially better than that of patients with ductal adenocarcinoma of the pancreas. Surgical resection is considered the first choice for treatment; however, there is no standard treatment option for patients with inoperable disease. The patient with metastatic PACC reported herein survived for more than 5 years with various treatments including chemotherapy, radiotherapy, antiangiogenic therapy and combined immunotherapy.
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Affiliation(s)
- Fangrui Zhao
- Department of Oncology, Renmin Hospital of Wuhan University, Wuhan, Hubei, China
| | - Dashuai Yang
- Department of Hepatobiliary Surgery, Renmin Hospital of Wuhan University, Wuhan, Hubei, China
| | - Tangpeng Xu
- Department of Oncology, Renmin Hospital of Wuhan University, Wuhan, Hubei, China
| | - Jiahui He
- Department of Oncology, Renmin Hospital of Wuhan University, Wuhan, Hubei, China
| | - Jin Guo
- Department of Oncology, Renmin Hospital of Wuhan University, Wuhan, Hubei, China
| | - Xiangpan Li
- Department of Oncology, Renmin Hospital of Wuhan University, Wuhan, Hubei, China
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13
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Nakayama S, Fukuda A, Kou T, Muto M, Seno H. A case of unresectable ectopic acinar cell carcinoma developed in the portal vein in complete response to FOLFIRINOX therapy. Clin J Gastroenterol 2023:10.1007/s12328-023-01793-y. [PMID: 37060504 DOI: 10.1007/s12328-023-01793-y] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/14/2023] [Accepted: 03/27/2023] [Indexed: 04/16/2023]
Abstract
A 56-year-old man presented to our hospital for close examination of a mass in the portal vein. CT showed a homogeneously enhanced mass occupying the portal vein. No other lesions suggestive of a primary tumor were detected. Endoscopic ultrasound-guided fine-needle aspiration revealed that the tumor was pathologically acinar cell carcinoma (ACC) based on the positive staining for both BCL-10 and trypsin. He was diagnosed with an ectopic ACC developed in the portal vein. Because the tumor invaded secondary branches of the right intrahepatic portal vein and the superior mesenteric vein, it was considered surgically un-resectable. Therefore, chemotherapy with gemcitabine plus nab-paclitaxel (GEM + nab-PTX) was started. After 2 courses, CT showed progressive disease, so the regimen was switched to FOLFIRINOX. After starting treatment with FOLFIRINOX, the tumor shrank gradually. After 29 courses, CT scan eventually showed disappearance of the tumor and complete response was achieved. After 34 courses, the chemotherapy was discontinued. Since then, the patient has been recurrence-free for 5 years. Our English literature review yielded 6 cases, including this case, of un-resectable ACC in which complete response was achieved by chemotherapy. Our case suggest that platinum-based regimen might be an effective therapy for un-resectable ACC, including ectopic ACC.
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Affiliation(s)
- Shinnosuke Nakayama
- Department of Gastroenterology and Hepatology, Kyoto University Graduate School of Medicine, 54 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto, 606-8507, Japan.
| | - Akihisa Fukuda
- Department of Gastroenterology and Hepatology, Kyoto University Graduate School of Medicine, 54 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto, 606-8507, Japan
| | - Tadayuki Kou
- Department of Gastroenterology and Hepatology, Tazuke Kofukai Medical Research Institute, Kitano Hospital, Osaka, Japan
| | - Manabu Muto
- Department of Oncology, Kyoto University Graduate School of Medicine, 54 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto, 606-8507, Japan
| | - Hiroshi Seno
- Department of Gastroenterology and Hepatology, Kyoto University Graduate School of Medicine, 54 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto, 606-8507, Japan
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14
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Yang FA, Cheng KS, Chou JW. Progressive nodule-like lesions on bilateral lower limbs. J Postgrad Med 2023; 69:50-52. [PMID: 36537394 PMCID: PMC9997608 DOI: 10.4103/jpgm.jpgm_136_22] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022] Open
Abstract
Pancreatic panniculitis is a rare disease characterized by subcutaneous fat necrosis. It could be the result of an associated pancreatic tumor. Herein, we reported a 63-year-old man who presented with progressive bilateral lower limb edema accompanied with nodule-like lesions for 1 month. His serum lipase was 3,927 U/L (normal, 0-160 U/L). Histopathology of the skin specimen revealed lobular panniculitis, favoring a diagnosis of pancreatic panniculitis. Abdominal computed tomography (CT) scan with contrast showed a huge mass in his left upper quadrant. Endoscopic ultrasound showed a mixed echoic tumor, measuring 11.9 × 7.8 cm in dimensions, originating from the pancreatic tail. Biopsy performed via an endoscopic ultrasound showed a poorly differentiated acinar cell carcinoma. Because of the unresectable status of the tumor, the patient underwent chemotherapy with paclitaxel and gemcitabine. After chemotherapy, his skin lesions improved progressively. It is important to treat pancreatic panniculitis with its underlying pancreatic disease.
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Affiliation(s)
- F A Yang
- China Medical University Hospital, China Medical University, Taichung, Taiwan
| | - K S Cheng
- China Medical University Hospital, China Medical University, Taichung, Taiwan
| | - J W Chou
- China Medical University Hospital, China Medical University, Taichung, Taiwan
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15
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Lelong M, Raoul J, Touchefeu Y, Berthelot J, Arnolfo P, Matysiak‐Budnik T, Senellart H. Prolonged response on olaparib maintenance in metastatic pancreatic acinar cell carcinoma associated with a germline BRCA 2 mutation, revealed by severe panniculitis. Clin Case Rep 2022; 10:e6718. [PMID: 36523391 PMCID: PMC9744715 DOI: 10.1002/ccr3.6718] [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: 07/05/2022] [Revised: 11/21/2022] [Accepted: 11/26/2022] [Indexed: 12/15/2022] Open
Abstract
This 38-year-old man has a familial BRCA2 mutation. He presented with skin erythema, polyarthritis, dactylitis, and febrile erythema nodosum; a biopsy of a liver metastase revealed acinar cell carcinoma of the pancreas. After FOLFIRINOX, olaparib was initiated, and 24 months after, the patient was PS 0 and asymptomatic.
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Affiliation(s)
- Margaux Lelong
- Department of Medical OncologyInstitut de Cancérologie de l'OuestSaint‐HerblainFrance
| | - Jean‐Luc Raoul
- Department of Medical OncologyInstitut de Cancérologie de l'OuestSaint‐HerblainFrance
| | - Yann Touchefeu
- Department of Gastroenterology, (IMAD)University HospitalNantesFrance
| | | | - Paul Arnolfo
- Department of RhumatologyUniversity HospitalNantesFrance
| | | | - Hélène Senellart
- Department of Medical OncologyInstitut de Cancérologie de l'OuestSaint‐HerblainFrance
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16
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Uemura S, Maeda H, Tanioka N, Yamaguchi S, Munekage M, Kitagawa H, Namikawa T, Yamamoto S, Kohsaki T, Iguchi M, Uchida K, Hanazaki K. Successful conversion surgery after FOLFIRINOX therapy in a patient with advanced pancreatic acinar cell carcinoma with a solitary peritoneal dissemination: A case report. Cancer Rep (Hoboken) 2022; 5:e1648. [PMID: 35668046 PMCID: PMC9458499 DOI: 10.1002/cnr2.1648] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/16/2022] [Revised: 05/02/2022] [Accepted: 05/26/2022] [Indexed: 11/05/2022] Open
Abstract
BACKGROUND Pancreatic acinar cell carcinoma is rare; it accounts for 1% of all malignant pancreatic exocrine tumors. Although surgical resection is an option for curative treatment, the safety and efficacy of conversion surgery in patients with pancreatic acinar cell carcinoma with metastasis remain unknown. CASE A 67-year-old man with epigastric pain and a pancreatic tumor was referred to our hospital. Computed tomography revealed a large tumor with a maximum diameter of 67 mm at the pancreatic head and a 23-mm mass in the left upper abdominal cavity. Because a definitive diagnosis could not be made based on endoscopic ultrasonography-guided fine needle aspiration biopsy findings, a diagnostic laparoscopy was performed. The tumor in the greater omentum at the left upper abdomen, resected under laparoscopy, was histopathologically diagnosed as pancreatic acinar cell carcinoma. Therefore, the pancreatic tumor was diagnosed as an unresectable pancreatic acinar cell carcinoma with a solitary peritoneal dissemination. The size of the main pancreatic tumor decreased to 15 mm after 18 courses of FOLFIRINOX (5-fluorouracil, leucovorin, irinotecan, and oxaliplatin). Subsequently, the patient underwent conversion surgery, and the initial diagnosis of pancreatic acinar cell carcinoma was confirmed on pathological examination. The patient was discharged 31 days postoperatively, following which he received adjuvant chemotherapy with S-1. No sign of recurrence has been observed for 32 months after surgical resection. CONCLUSION FOLFIRINOX may be effective in patients with pancreatic acinar cell carcinoma, and conversion surgery after FOLFIRINOX may be applicable to selective patients.
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Affiliation(s)
- Sunao Uemura
- Department of SurgeryKochi Medical SchoolNankokuJapan
| | | | | | | | | | | | | | - Shota Yamamoto
- Department of Gastroenterology and HepatologyKochi Medical SchoolNankokuJapan
| | | | | | - Kazushige Uchida
- Department of Gastroenterology and HepatologyKochi Medical SchoolNankokuJapan
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17
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Xu JY, Guan WL, Lu SX, Wei XL, Shi WJ, Ren C, Li YH, Li SP, Qiu MZ, Wang FH. Optimizing Chemotherapy of Pancreatic Acinar Cell Carcinoma: Our Experiences and Pooled Analysis of Literature. Clin Med Insights Oncol 2022; 16:11795549221090186. [PMID: 35509769 PMCID: PMC9058357 DOI: 10.1177/11795549221090186] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/25/2021] [Accepted: 03/09/2022] [Indexed: 12/24/2022] Open
Abstract
BACKGROUND Pancreatic acinar cell carcinoma (PACC) is rare, and its appropriate treatment remains unknown. We aim to explore the characteristics and optimal treatment of it. METHODS The data on clinicopathologic characteristics, molecular alteration, treatment, and survival of patients diagnosed with PACC at the Sun Yat-sen University Cancer Center from 2005 to 2020 were collected. The optimal treatment was explored by co-analyzing our results and published literatures. RESULTS Twenty-two PACC patients were enrolled. Eight of 17 non-metastatic patients received adjuvant chemotherapy. The patients receiving fluoropyrimidine-based regimen (n = 3) had a better median disease-free survival (mDFS) than those with gemcitabine-based regimen (n = 5) (unreached vs 27 months). Eight metastatic patients received first-line chemotherapy. Four patients received second-line chemotherapy. The objective response rate (ORR) of the fluoropyrimidine-based regimen was 85.7% (6/7), much better than that of the gemcitabine-based regimen (0/5). One patient who had responded to the first-line FOLFIRINOX (5-fluorouracil + oxaliplatin + leucovorin + irinotecan) regimen received olaparib as maintenance treatment for 5 months with good tolerance. Thirty-one published literatures, with a total of 86 cases, were included in the co-analysis. The ORR of the first-line fluoropyrimidine-based regimen (n = 47) was higher than that of gemcitabine-based regimen (n = 39) (59.6% vs 15.3%, P < .001). Eight of 11 patients treated with the FOLFIRINOX regimen achieved partial response (PR). CONCLUSIONS For patients with metastasis, a fluorouracil-based regimen such as FOLFIRINOX may be preferred, and maintenance treatment of poly ADP-ribose polymerase (PARP) inhibitors after effective platinum-containing treatment for breast cancer susceptibility gene (BRCA) mutation patients must be assessed.
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Affiliation(s)
- Jian-Ying Xu
- Department of Medical Oncology, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China
| | - Wen-Long Guan
- Department of Medical Oncology, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China
| | - Shi-Xun Lu
- Department of Pathology, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China
| | - Xiao-Li Wei
- Department of Medical Oncology, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China
| | - Wen-Jie Shi
- University Hospital for Gynecology, Pius-Hospital, University Medicine Oldenburg, Oldenburg, Germany
| | - Chao Ren
- Department of Medical Oncology, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China
| | - Yu-Hong Li
- Department of Medical Oncology, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China
| | - Sheng-Ping Li
- Department of Hepatobiliary and Pancreatic Surgery, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China
| | - Miao-Zhen Qiu
- Department of Medical Oncology, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China
| | - Feng-Hua Wang
- Department of Medical Oncology, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China
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18
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Nasser A, Forse CL, Walsh C, Moyana T, Goel R. Mixed pancreatic acinar cell-ductal adenocarcinoma: Complexities in diagnosis and treatment. CURRENT PROBLEMS IN CANCER: CASE REPORTS 2022; 5:100144. [DOI: 10.1016/j.cpccr.2022.100144] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022] Open
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19
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Survival Outcome and Prognostic Factors for Pancreatic Acinar Cell Carcinoma: Retrospective Analysis from the German Cancer Registry Group. Cancers (Basel) 2021; 13:cancers13236121. [PMID: 34885230 PMCID: PMC8656891 DOI: 10.3390/cancers13236121] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/30/2021] [Revised: 11/29/2021] [Accepted: 12/01/2021] [Indexed: 12/18/2022] Open
Abstract
Simple Summary Less than 1% of all pancreatic malignancies are acinar cell carcinomas. Based on data from the German Cancer Registry Group, we performed a comparative analysis of characteristics and prognostic factors of pancreatic acinar cell carcinoma and the most common type of pancreatic cancer—pancreatic ductal adenocarcinoma. Compared to pancreatic ductal adenocarcinoma, patients with pancreatic acinar cell carcinoma were younger at the time of diagnosis and the percentage of males was higher. The prognosis of patients with pancreatic acinar carcinoma was better than that of patients with pancreatic ductal adenocarcinoma. Surgical resection was the strongest positive prognostic factor for pancreatic acinar cell carcinoma. The study shows that pancreatic acinar cell carcinoma has features distinct from pancreatic ductal adenocarcinoma. Radical resection should be advocated, whenever feasible. Abstract Background: Pancreatic acinar cell carcinoma (PACC) is a distinct type of pancreatic cancer with low prevalence. We aimed to analyze prognostic factors and survival outcome for PACC in comparison to pancreatic ductal adenocarcinoma (PDAC), based on data from the German Cancer Registry Group. Methods: Patients with PACC and PDAC were extracted from pooled data of the German clinical cancer registries (years 2000 to 2019). The distribution of demographic parameters, tumor stage and therapy modes were compared between PACC and PDAC. The Kaplan–Meier method and Cox regression analysis were used to delineate prognostic factors for PACC. Propensity score matching was used to compare survival between PACC and PDAC. Results: There were 233 (0.44%) patients with PACC out of 52,518 patients with pancreatic malignancy. Compared to PDAC, patients with PACC were younger (median age 66 versus 70, respectively, p < 0.001) and the percentage of males was higher (66.1% versus 53.3%, respectively, p < 0.001). More patients were resected with PACC than with PDAC (56.2% versus 38.9%, respectively, p < 0.001). The estimated overall median survival in PACC was 22 months (95% confidence interval 15 to 27), compared to 12 months (95% confidence interval 10 to 13) in the matched PDAC cohort (p < 0.001). Surgical resection was the strongest positive prognostic factor for PACC after adjusting for sex, age, and distant metastases (hazard ratio 0.34, 95% confidence interval 0.22 to 0.51, p < 0.001). There was no survival benefit for adjuvant therapy in PACC. Conclusions: PACC has overall better prognosis than PDAC. Surgical resection is the best therapeutic strategy for PACC and should be advocated even in advanced tumor stages.
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20
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Xu H, Wang X, Zhou S, Hu Q, Cao D. Efficacy of chemotherapy combined with toripalimab in PD-L1-positive and high tumor mutation burden pancreatic acinar cell carcinoma: case report. TUMORI JOURNAL 2021; 107:NP24-NP27. [PMID: 33345750 DOI: 10.1177/0300891620980792] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/05/2023]
Abstract
BACKGROUND Pancreatic acinar cell carcinoma (PACC) is a rare tumor, accounting for about 1% of all pancreatic exocrine cancers. Consensus on the management of metastatic PACC remains unclear. CASE PRESENTATION Starting from April 2019, a patient first received chemotherapy with two cycles of gemcitabine and nab-paclitaxel and two cycles of SOX regimen. After progression of disease evaluated based on RECIST 1.1, toripalimab and SOX regimen was administered because of PD-L1-positive expression, high tumor mutation burden (TMB), and somatic FANCA deletion in the tumor. Both the primary and metastatic tumor mass shrank significantly after two courses. The patient exhibited sustained partial response for at least six courses with well-controlled toxic effects. Then the treatment had to be stopped for 2 months because of the coronavirus disease 2019 pandemic. Computed tomography scan in March 2020 showed disease progression. Time from initiating treatment to tumor progression on toripalimab and SOX regimen treatment took up to at least 8 months. CONCLUSIONS We present the first case report where a PD-L1 positive, high TMB, and FANCA-deleted pancreatic acinar cell carcinoma was treated using chemotherapy combined with immunotherapy, in which the patient exhibited satisfactory response and tolerance.
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Affiliation(s)
- Huanji Xu
- Department of Abdominal Oncology, Cancer Center of West China Hospital, Sichuan University, Chengdu, Sichuan Province, China
| | - Xin Wang
- Department of Abdominal Oncology, Cancer Center of West China Hospital, Sichuan University, Chengdu, Sichuan Province, China
| | - Sheng Zhou
- Department of Abdominal Oncology, Cancer Center of West China Hospital, Sichuan University, Chengdu, Sichuan Province, China
| | - Qiancheng Hu
- Department of Abdominal Oncology, Cancer Center of West China Hospital, Sichuan University, Chengdu, Sichuan Province, China
| | - Dan Cao
- Department of Abdominal Oncology, Cancer Center of West China Hospital, Sichuan University, Chengdu, Sichuan Province, China
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21
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Gardi N, Ketkar M, McKinnon RA, Pandol SJ, Dutt S, Barreto SG. Down-regulation of metabolic pathways could offset the poor prognosis conferred by co-existent diabetes mellitus in pancreatic (head) adenocarcinoma. ANZ J Surg 2021; 91:2466-2474. [PMID: 34514690 DOI: 10.1111/ans.17194] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/26/2021] [Revised: 08/23/2021] [Accepted: 08/24/2021] [Indexed: 12/12/2022]
Abstract
BACKGROUND Pancreatic ductal adenocarcinoma (PDAC) patients with diabetes mellitus (DM) have poor overall survival. Underlying mechanisms have not been fully clarified. This presents an opportunity for precision-oncology for which we systematically analysed publicly-available PDAC transcriptome data. METHODS PDAC TCGA RNASeq data were used. Analyses were restricted to only 'high purity' and 'head' as anatomical site. Patients were characterised by: (1) Gene expression classification, and (2) Weighted gene correlation network analysis (WGCNA) to identify co-expression patterns of genes. Newly identified gene signature subclasses of pancreatic head PDAC were associated with clinical and functional characteristics of patients. RESULTS Consensus clustering identified two patient subclasses within PDAC involving pancreatic head. WGCNA identified 11 distinct networks of gene expression patterns across two sub-classes. Class 1 patients demonstrated a significant upregulation of Module 5 and Module 6 gene expression compared to Class 2. Class 1 predominantly expressed the acinar, ductal and islet cell gene signatures. There were significantly less patients with DM in Class 1 subclass compared to Class 2 (p < 0.037). Patients with DM had significant downregulation of pathways involved in cellular metabolism, hormone secretion and paucity of islet cell markers with no reduced survival compared with non-diabetics. CONCLUSIONS A significant proportion of patients with PDAC of pancreatic head and DM exhibit downregulation of pathways involved in cellular metabolism, hormone secretion and signalling accompanied by a paucity of islet expression. Investigating the relationship between DM and gene expression profiles in patients with PDAC presents opportunities to improve overall survival in diabetics with PDAC.
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Affiliation(s)
- Nilesh Gardi
- Department of Medical Oncology, Tata Memorial Hospital, Tata Memorial Centre, Mumbai, India
- Homi Bhabha National Institute, Mumbai, India
| | - Madhura Ketkar
- Homi Bhabha National Institute, Mumbai, India
- Shilpee Dutt Laboratory, Advanced Centre for Treatment, Research and Education in Cancer (ACTREC), Tata Memorial Centre, Mumbai, India
| | - Ross A McKinnon
- Flinders Health and Medical Research Institute, College of Medicine and Public Health, Flinders University, Adelaide, South Australia, Australia
| | - Stephen J Pandol
- Division of Digestive and Liver Diseases, Cedars-Sinai Medical Center, Los Angeles, California, USA
| | - Shilpee Dutt
- Homi Bhabha National Institute, Mumbai, India
- Shilpee Dutt Laboratory, Advanced Centre for Treatment, Research and Education in Cancer (ACTREC), Tata Memorial Centre, Mumbai, India
| | - Savio G Barreto
- Flinders Health and Medical Research Institute, College of Medicine and Public Health, Flinders University, Adelaide, South Australia, Australia
- Division of Surgery and Perioperative Medicine, Flinders Medical Centre, Adelaide, South Australia, Australia
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22
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Maehira H, Iida H, Mori H, Nitta N, Tokuda A, Takebayashi K, Kaida S, Miyake T, Matsubara A, Tani M. Pathological complete response in a patient with metastatic pancreatic acinar cell carcinoma who received a chemotherapy regimen containing cisplatin and irinotecan. Clin J Gastroenterol 2021; 14:1772-1778. [PMID: 34596871 DOI: 10.1007/s12328-021-01518-z] [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: 08/16/2021] [Accepted: 09/07/2021] [Indexed: 11/27/2022]
Abstract
Pancreatic acinar cell carcinoma is a rare tumor of the pancreas, and patients with such tumors rarely have a pathological complete response to treatment. Herein, we present a case involving a 48-year-old woman with a pancreatic tail mass. The pancreatic mass was connected to splenic and portal vein thrombosis. Distal pancreatectomy and removal of portal vein tumor thrombosis were performed. Ten months after surgery, multiple liver metastases and local recurrence in the pancreatic bed were detected, and chemotherapy was administered through the administration of a regimen containing both cisplatin and irinotecan. After seven courses of the cisplatin-plus-irinotecan regimen had been administered, computed tomography revealed that the patient had a partial response to treatment. Radical resection of multiple liver metastases and the locally recurrent tumor was performed. Pathological examination did not reveal the presence of carcinoma in any of the resected specimens. Thus, this case involves a pathological complete response in a patient with metastatic pancreatic acinar cell carcinoma who received a regimen containing both cisplatin and irinotecan. Our findings reveal that the administration of the cisplatin-plus-irinotecan regimen may be an option for the management of such tumors.
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Affiliation(s)
- Hiromitsu Maehira
- Department of Surgery, Shiga University of Medical Science, Seta-tsukinowacho, Otsu, Shiga, 520-2192, Japan.
| | - Hiroya Iida
- Department of Surgery, Shiga University of Medical Science, Seta-tsukinowacho, Otsu, Shiga, 520-2192, Japan
| | - Haruki Mori
- Department of Surgery, Shiga University of Medical Science, Seta-tsukinowacho, Otsu, Shiga, 520-2192, Japan
| | - Nobuhito Nitta
- Department of Surgery, Shiga University of Medical Science, Seta-tsukinowacho, Otsu, Shiga, 520-2192, Japan
| | - Aya Tokuda
- Cancer Center, Shiga University of Medical Science Hospital, Shiga, Japan
| | - Katsushi Takebayashi
- Department of Surgery, Shiga University of Medical Science, Seta-tsukinowacho, Otsu, Shiga, 520-2192, Japan
| | - Sachiko Kaida
- Department of Surgery, Shiga University of Medical Science, Seta-tsukinowacho, Otsu, Shiga, 520-2192, Japan
| | - Toru Miyake
- Department of Surgery, Shiga University of Medical Science, Seta-tsukinowacho, Otsu, Shiga, 520-2192, Japan
| | - Akiko Matsubara
- Division of Diagnostic Pathology, Shiga University of Medical Science Hospital, Shiga, Japan
| | - Masaji Tani
- Department of Surgery, Shiga University of Medical Science, Seta-tsukinowacho, Otsu, Shiga, 520-2192, Japan
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23
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Sridharan V, Mino-Kenudson M, Cleary JM, Rahma OE, Perez K, Clark JW, Clancy TE, Rubinson DA, Goyal L, Bazerbachi F, Visrodia KH, Qadan M, Parikh A, Ferrone CR, Casey BW, Fernandez-Del Castillo C, Ryan DP, Lillemoe KD, Warshaw AL, Krishnan K, Hernandez-Barco YG. Pancreatic acinar cell carcinoma: A multi-center series on clinical characteristics and treatment outcomes. Pancreatology 2021; 21:S1424-3903(21)00162-9. [PMID: 34023183 DOI: 10.1016/j.pan.2021.05.011] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/23/2021] [Revised: 05/03/2021] [Accepted: 05/10/2021] [Indexed: 02/07/2023]
Abstract
BACKGROUND Acinar cell carcinoma (ACC) is a very rare tumor of the exocrine pancreas, representing less than 1% of all pancreatic malignancies. The majority of data regarding ACC are limited to small case series. METHODS This is a retrospective study conducted at a large healthcare system from 1996 to 2019. Patients with pathologically confirmed ACC were included, and demographic data, tumor characteristics, and treatment outcomes were abstracted by chart review. Survival curves were obtained by using the Kaplan-Meier method and compared using the log-rank test. RESULTS Sixty-six patients with ACC were identified. The median patient age at diagnosis was 64, and 42% presented with metastatic disease. The majority presented with abdominal pain or pancreatitis (69%), and laboratory parameters did not correlate with tumor size, metastatic disease, or survival. Several somatic abnormalities were noted in tumors (BRCA2, TP53, and mismatch-repair genes). In patients with localized disease that underwent resection, the median time to develop metastatic lesions was 13 months. The median overall survival (OS) was 24.7 months from diagnosis, with a survival difference based on metastatic disease at diagnosis (median 15 vs 38 mos). Surgery was associated with improved survival in non-metastatic cases (p = 0.006) but not metastatic cases (p = 0.22), and chemotherapy showed OS benefit in metastatic disease (p < 0.01). Patients with metastatic ACC treated after 2010 utilized more platinum-based agents, and there was a OS benefit to FOLFOX or FOLFIRINOX chemotherapy compared to gemcitabine or capecitabine-based regimens (p = 0.006). CONCLUSION Pancreatic ACC patients often present with advanced disease. Surgery was associated with survival benefit among patients presenting with localized disease. The use of FOLFOX or FOLFIRINOX chemotherapy regimens was associated with improved OS in metastatic patients. These data add to our knowledge in this rare malignancy, and improves understanding about the genomic underpinnings, prognosis and treatment for acinar cancers.
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Affiliation(s)
- Vishwajith Sridharan
- Division of Gastroenterology, Massachusetts General Hospital, Harvard School of Medicine, Boston, MA, USA
| | - Mari Mino-Kenudson
- Division of Pathology, Massachusetts General Hospital, Harvard School of Medicine, Boston, MA, USA
| | - James M Cleary
- Dana Farber Cancer Institute and Brigham Women's Hospital, Harvard School of Medicine, Boston, MA, USA
| | - Osama E Rahma
- Dana Farber Cancer Institute and Brigham Women's Hospital, Harvard School of Medicine, Boston, MA, USA
| | - Kimberly Perez
- Dana Farber Cancer Institute and Brigham Women's Hospital, Harvard School of Medicine, Boston, MA, USA
| | - Jeffrey W Clark
- Division of Medical Oncology, Massachusetts General Hospital, Harvard School of Medicine, Boston, MA, USA
| | - Thomas E Clancy
- Dana Farber Cancer Institute and Brigham Women's Hospital, Harvard School of Medicine, Boston, MA, USA
| | - Douglas A Rubinson
- Dana Farber Cancer Institute and Brigham Women's Hospital, Harvard School of Medicine, Boston, MA, USA
| | - Lipika Goyal
- Division of Medical Oncology, Massachusetts General Hospital, Harvard School of Medicine, Boston, MA, USA
| | - Fateh Bazerbachi
- Division of Gastroenterology, Massachusetts General Hospital, Harvard School of Medicine, Boston, MA, USA
| | - Kavel H Visrodia
- Division of Gastroenterology, Massachusetts General Hospital, Harvard School of Medicine, Boston, MA, USA
| | - Motaz Qadan
- Division of Surgical Oncology, Massachusetts General Hospital, Harvard School of Medicine, Boston, MA, USA
| | - Aparna Parikh
- Division of Medical Oncology, Massachusetts General Hospital, Harvard School of Medicine, Boston, MA, USA
| | - Cristina R Ferrone
- Division of Surgical Oncology, Massachusetts General Hospital, Harvard School of Medicine, Boston, MA, USA
| | - Brenna W Casey
- Division of Gastroenterology, Massachusetts General Hospital, Harvard School of Medicine, Boston, MA, USA
| | | | - David Patrick Ryan
- Division of Medical Oncology, Massachusetts General Hospital, Harvard School of Medicine, Boston, MA, USA
| | - Keith D Lillemoe
- Division of Surgical Oncology, Massachusetts General Hospital, Harvard School of Medicine, Boston, MA, USA
| | - Andrew L Warshaw
- Division of Surgical Oncology, Massachusetts General Hospital, Harvard School of Medicine, Boston, MA, USA
| | - Kumar Krishnan
- Division of Gastroenterology, Massachusetts General Hospital, Harvard School of Medicine, Boston, MA, USA
| | - Yasmin G Hernandez-Barco
- Division of Gastroenterology, Massachusetts General Hospital, Harvard School of Medicine, Boston, MA, USA.
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24
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Busch E, Werft W, Bougatf N, Hackert T, Jäger D, Springfeld C, Berger AK. Metastatic Acinar Cell Carcinoma of the Pancreas: A Retrospective Cohort Study on Systemic Chemotherapy and Review of the Literature. Pancreas 2021; 50:300-305. [PMID: 33835959 DOI: 10.1097/mpa.0000000000001765] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
OBJECTIVES Acinar cell carcinoma of the pancreas (pACC) forms a rare subgroup of pancreatic tumors. We report on our institutional experience with systemic first- and further-line therapy in patients with metastatic pACC and embed our findings in a review of the literature. METHODS Patients with stage IV pACC who started systemic treatment between 2008 and 2019 at our institution were identified via our institutional database. Clinical data were extracted from the patients' electronic data records. Survival times were calculated by the Kaplan-Meier method. RESULTS Six patients received a fluoropyrimidine- and oxaliplatin-containing first-line treatment, and 4 patients were started on gemcitabine-based protocols. Median progression-free survival was 4.8 months [95% confidence interval (CI), 3.3 to not available (n.a.)], and median overall survival was 15.3 months (95% CI, 10.1 to n.a.). Residual survival for second-line treatment was 2.1 months (95% CI, 1.3 to n.a.), although 1 patient experienced almost complete remission under targeted therapy. CONCLUSIONS The most encouraging and deep responses result from poly-chemotherapy with leucovorin, 5-fluorouracil, irinotecan, and oxaliplatin (FOLFIRINOX), which seems to be the appropriate choice in fit patients. Gemcitabine monotherapy seems without substantial activity in pACC. Whenever possible, patients with pACC should be screened for targetable mutations.
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Affiliation(s)
- Elena Busch
- From the National Center for Tumor Diseases (NCT), Department of Medical Oncology, University Hospital Heidelberg, Heidelberg
| | - Wiebke Werft
- Hochschule Mannheim, University of Applied Sciences, Mannheim
| | | | - Thilo Hackert
- Department of Surgery, University Hospital Heidelberg, Heidelberg, Germany
| | - Dirk Jäger
- From the National Center for Tumor Diseases (NCT), Department of Medical Oncology, University Hospital Heidelberg, Heidelberg
| | - Christoph Springfeld
- From the National Center for Tumor Diseases (NCT), Department of Medical Oncology, University Hospital Heidelberg, Heidelberg
| | - Anne Katrin Berger
- From the National Center for Tumor Diseases (NCT), Department of Medical Oncology, University Hospital Heidelberg, Heidelberg
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25
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Takahashi H, Ikeda M, Shiba S, Imaoka H, Todaka A, Shioji K, Yane K, Kojima Y, Kobayashi S, Asagi A, Ozaka M, Takada R, Nagashio Y, Horiguchi S, Kasuga A, Suzuki E, Terashima T, Ueno M, Morizane C, Furuse J. Multicenter Retrospective Analysis of Chemotherapy for Advanced Pancreatic Acinar Cell Carcinoma: Potential Efficacy of Platinum- and Irinotecan-Containing Regimens. Pancreas 2021; 50:77-82. [PMID: 33370026 PMCID: PMC7748047 DOI: 10.1097/mpa.0000000000001718] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/07/2020] [Accepted: 11/02/2020] [Indexed: 02/06/2023]
Abstract
OBJECTIVES The aim of this multicenter retrospective study was to identify the optimal chemotherapeutic regimen for advanced pancreatic acinar cell carcinoma (PACC). METHODS Fifty-eight patients with histopathologically confirmed advanced PACC who had received chemotherapy between 1996 and 2013 were enrolled. The clinical characteristics of the patients and the treatment efficacy data were collected from the medical records at 16 Japanese institutions, using standardized data collection instrument. RESULTS The most commonly selected treatment regimens were gemcitabine-, fluoropyrimidine-, platinum-, and irinotecan-containing regimens. The overall response rate in the patients who received first-line chemotherapy were 7% and 38%, respectively, and the median overall survival was 13.2 months. When the data for all the treatment lines were aggregated, the response rates to gemcitabine-, fluoropyrimidine-, platinum-, and irinotecan-containing regimens were 7%, 18%, 40%, and 29%, respectively. The overall survival tended to be better in patients who had received a platinum-containing regimen (hazard ratio, 0.50; 95% confidence interval, 0.23-1.11; P = 0.08) or irinotecan-containing regimen (hazard ratio, 0.42; 95% confidence interval, 0.15-1.19; P = 0.09) at least once in the treatment course as compared with those who had not. CONCLUSIONS Our findings suggested that platinum- and irinotecan-containing regimens exhibited some potential efficacy in patients with advanced PACC.
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Affiliation(s)
- Hideaki Takahashi
- From the Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital East, Kashiwa
| | - Masafumi Ikeda
- From the Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital East, Kashiwa
| | - Satoshi Shiba
- Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital, Tokyo
| | - Hiroshi Imaoka
- Department of Gastroenterology, Aichi Cancer Center Hospital, Nagoya
| | - Akiko Todaka
- Division of Gastrointestinal Oncology, Shizuoka Cancer Center, Shizuoka
| | - Kazuhiko Shioji
- Department of Internal Medicine, Niigata Cancer Center Hospital, Niigata
| | - Kei Yane
- Center for Gastroenterology, Teine-Keijinkai Hospital, Sapporo
| | - Yasushi Kojima
- Department of Gastroenterology, National Center for Global Health and Medicine, Tokyo
| | - Satoshi Kobayashi
- Department of Gastroenterology, Hepatobiliary and Pancreatic Medical Oncology Division, Kanagawa Cancer Center, Yokohama
| | - Akinori Asagi
- Department of Gastrointestinal Medical Oncology, National Hospital Organization Shikoku Cancer Center, Matsuyama
| | - Masato Ozaka
- Department of Gastroenterology, Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo
| | - Ryoji Takada
- Department of Hepatobiliary and Pancreatic Oncology, Osaka International Cancer Institute, Osaka
| | - Yoshikuni Nagashio
- Department of Hepato-Biliary-Pancreatology, National Kyushu Cancer Center, Fukuoka
| | - Shigeru Horiguchi
- Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Okayama
| | - Akiyoshi Kasuga
- Department of Gastroenterology, Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo
- Department of Medical Oncology, Kyorin University Faculty of Medicine, Tokyo
| | - Eiichiro Suzuki
- Department of Gastroenterology, Graduate School of Medicine, Chiba University, Chiba
| | - Takeshi Terashima
- Department of Gastroenterology, Kanazawa University Hospital, Kanazawa, Ishikawa, Japan
| | - Makoto Ueno
- Department of Gastroenterology, Hepatobiliary and Pancreatic Medical Oncology Division, Kanagawa Cancer Center, Yokohama
| | - Chigusa Morizane
- Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital, Tokyo
| | - Junji Furuse
- Department of Medical Oncology, Kyorin University Faculty of Medicine, Tokyo
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26
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Duorui N, Shi B, Zhang T, Chen C, Fang C, Yue Z, Wu P, Wu Z, Huang X, Li M. The contemporary trend in worsening prognosis of pancreatic acinar cell carcinoma: A population-based study. PLoS One 2020; 15:e0243164. [PMID: 33332471 PMCID: PMC7746196 DOI: 10.1371/journal.pone.0243164] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/23/2020] [Accepted: 11/14/2020] [Indexed: 12/13/2022] Open
Abstract
BACKGROUND Primary acinar cell carcinoma (ACC) is a rare exocrine tumor of the pancreas with unclear clinical characteristics. Our goal was to determine the incidence and update the clinical characteristics and outcomes of ACC. METHODS Through the Surveillance, Epidemiology, and End Results (SEER) database, we identified 252 patients with the latest diagnosis of ACC (2004-2016). The age-adjusted incidence (AAI) was calculated using the SEER*Stat Software version 8.3.6. The Kaplan-Meier method was used to draw survival curves and differences among them were compared by the log-rank test. Cox proportional hazards models were used to evaluate factors that had independent predictive effects on the overall survival. RESULTS The AAI of pancreatic ACC was on the rise with the mean age at diagnosis of 63.79±14.79 years. Most patients (15.9%) had poorer differentiated tumors. The patients presented with distant stage were 54.4% compared with 53.1% between 1988 and 2003. The 1-, 2-, and 5-years survival rates for pancreatic ACC patients were 53.5%, 34.6%,17.5%, respectively (compared with 78.5%, 67.0%, and 42.8%, between 1988 and 2003). The multivariate COX analysis showed that the patient's age, surgery, chemotherapy, and summary stage, but not marital status were independent prognosis factors for ACC. CONCLUSIONS Pancreatic ACC is a highly malignant tumor with an increasing incidence in recent years. The rate of distant metastasis is increasing and the survival rate is worse than in the past, suggesting that it may require more aggressive treatment and follow-up. Surgery, radiotherapy, and chemotherapy are all effective treatments, but prospective studies are still needed to verify them.
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Affiliation(s)
- Nie Duorui
- First Clinical Medical College, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, China
| | - Bin Shi
- First Clinical Medical College, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, China
| | - Tao Zhang
- First Clinical Medical College, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, China
| | - Chuyao Chen
- First Clinical Medical College, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, China
| | - Chongkai Fang
- First Clinical Medical College, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, China
| | - Zhijun Yue
- First Clinical Medical College, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, China
| | - Peng Wu
- First Clinical Medical College, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, China
| | - Zhiming Wu
- First Clinical Medical College, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, China
| | - Xuewu Huang
- Cancer center, Guangzhou University of Traditional Chinese Medicine First Affiliated Hospital, Guangzhou, Guangdong, China
| | - Meng Li
- Department of Oncology, Shenzhen Hospital (Futian) of Guangzhou University of Chinese Medicine, Shenzhen, Guangdong, China
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27
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Miksch RC, Schiergens TS, Weniger M, Ilmer M, Kazmierczak PM, Guba MO, Angele MK, Werner J, D'Haese JG. Pancreatic panniculitis and elevated serum lipase in metastasized acinar cell carcinoma of the pancreas: A case report and review of literature. World J Clin Cases 2020; 8:5304-5312. [PMID: 33269263 PMCID: PMC7674712 DOI: 10.12998/wjcc.v8.i21.5304] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/28/2020] [Revised: 07/28/2020] [Accepted: 09/28/2020] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Pancreatic panniculitis is an extremely rare condition associated with different underlying pancreatic disorders and characterized by subcutaneous fat necrosis induced by elevated serum lipase levels. These lesions usually affect the lower extremities and may precede abdominal symptoms of pancreatic disease. Acinar cell carcinoma (ACC) of the pancreas is a rare pancreatic neoplasm, accounting for only 1%-2% of pancreatic tumors in adults.
CASE SUMMARY We present the case of a 72-year-old man with ACC of the pancreatic head and synchronous liver metastases. Both the primary tumor and liver metastases were resected. Serum lipase was elevated before surgery and decreased to normal postoperatively. Rising serum lipase levels at follow-up led to the diagnosis of hepatic recurrence. This disease progression was then accompanied by pancreatic panniculitis, with subcutaneous fat necrosis and acute arthritis. To the best of our knowledge, only 4 cases have been reported in the literature and each showed a similar association of serum lipase levels with pancreatic panniculitis and progression of ACC.
CONCLUSION Clinical symptoms and progression of ACC may correlate with serum lipase levels, suggesting potential usefulness as a follow-up biomarker.
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Affiliation(s)
- Rainer Christoph Miksch
- Department of General, Visceral, and Transplantation Surgery, Ludwig-Maximilians-University Munich, Munich 81377, Bavaria, Germany
| | - Tobias S Schiergens
- Department of General, Visceral, and Transplantation Surgery, Ludwig-Maximilians-University Munich, Munich 81377, Bavaria, Germany
| | - Maximilian Weniger
- Department of General, Visceral, and Transplantation Surgery, Ludwig-Maximilians-University Munich, Munich 81377, Bavaria, Germany
| | - Matthias Ilmer
- Department of General, Visceral, and Transplantation Surgery, Ludwig-Maximilians-University Munich, Munich 81377, Bavaria, Germany
| | - Philipp M Kazmierczak
- Department of Radiology, Ludwig-Maximilians-University Munich, Munich 81377, Germany
| | - Markus O Guba
- Department of General, Visceral, and Transplantation Surgery, Ludwig-Maximilians-University Munich, Munich 81377, Bavaria, Germany
| | - Martin K Angele
- Department of General, Visceral, and Transplantation Surgery, Ludwig-Maximilians-University Munich, Munich 81377, Bavaria, Germany
| | - Jens Werner
- Department of General, Visceral, and Transplantation Surgery, Ludwig-Maximilians-University Munich, Munich 81377, Bavaria, Germany
| | - Jan G D'Haese
- Department of General, Visceral, and Transplantation Surgery, Ludwig-Maximilians-University Munich, Munich 81377, Bavaria, Germany
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28
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Busch E, Kreutzfeldt S, Agaimy A, Mechtersheimer G, Horak P, Brors B, Hutter B, Fröhlich M, Uhrig S, Mayer P, Schröck E, Stenzinger A, Glimm H, Jäger D, Springfeld C, Fröhling S, Zschäbitz S. Successful BRAF/MEK inhibition in a patient with BRAF V600E-mutated extrapancreatic acinar cell carcinoma. Cold Spring Harb Mol Case Stud 2020; 6:mcs.a005553. [PMID: 32843432 PMCID: PMC7476408 DOI: 10.1101/mcs.a005553] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/10/2020] [Accepted: 06/09/2020] [Indexed: 12/14/2022] Open
Abstract
Pancreatic acinar cell carcinoma (PAC) is a rare disease with a poor prognosis. Treatment options for metastatic PAC are limited and often follow chemotherapeutic regimens for pancreatic ductal adenocarcinoma. Although recurrent genomic alterations, such as BRAF fusions and defects in genes involved in homologous recombination DNA repair, have been described in PAC, data on the clinical efficacy of molecularly guided, targeted treatment are scarce. Here we describe the case of a 27-yr-old patient with BRAFV600E-mutated PAC who was successfully treated with a combination of BRAF and MEK inhibitors. The patient presented to our clinic with abdominal pain and weight loss. Imaging showed extensive retroperitoneal disease as well as mediastinal lymphadenopathy. Because of elevated α-fetoprotein (AFP) levels and inconclusive histologic findings, a germ cell tumor was suspected; however, PEI chemotherapy was unsuccessful. A repeat biopsy yielded the diagnosis of PAC and treatment with FOLFIRINOX was initiated. Comprehensive molecular profiling within the MASTER (Molecularly Aided Stratification for Tumor Eradication Research) precision oncology program revealed a somatic BRAFV600E mutation and a germline PALB2 stop-gain mutation. Therapy was therefore switched to BRAF/MEK inhibition, resulting in almost complete remission and disease control for 12 mo and a remarkable improvement in the patient's general condition. These results indicate that BRAF alterations are a valid therapeutic target in PAC that should be routinely assessed in this patient population.
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Affiliation(s)
- Elena Busch
- Department of Medical Oncology, University Hospital Heidelberg, National Center for Tumor Diseases (NCT) Heidelberg, Heidelberg, 69120, Germany
| | - Simon Kreutzfeldt
- Department of Translational Medical Oncology, NCT Heidelberg and German Cancer Research Center (DKFZ), Heidelberg, 69120, Germany
| | - Abbas Agaimy
- Institute of Pathology, University Hospital Erlangen, Erlangen, 91054, Germany
| | | | - Peter Horak
- Department of Translational Medical Oncology, NCT Heidelberg and German Cancer Research Center (DKFZ), Heidelberg, 69120, Germany
| | - Benedikt Brors
- Division of Applied Bioinformatics, DKFZ and NCT Heidelberg, Heidelberg, 69120, Germany.,German Cancer Consortium
| | - Barbara Hutter
- Division of Applied Bioinformatics, DKFZ and NCT Heidelberg, Heidelberg, 69120, Germany.,Molecular Diagnostics Program, NCT Heidelberg and DKFZ, Heidelberg, 69120, Germany
| | - Martina Fröhlich
- Division of Applied Bioinformatics, DKFZ and NCT Heidelberg, Heidelberg, 69120, Germany.,Molecular Diagnostics Program, NCT Heidelberg and DKFZ, Heidelberg, 69120, Germany
| | - Sebastian Uhrig
- Division of Applied Bioinformatics, DKFZ and NCT Heidelberg, Heidelberg, 69120, Germany.,Molecular Diagnostics Program, NCT Heidelberg and DKFZ, Heidelberg, 69120, Germany
| | - Philipp Mayer
- Department of Diagnostic and Interventional Radiology, University Hospital Heidelberg, Heidelberg, 69120, Germany
| | - Evelin Schröck
- NCT Partner Site Dresden, University Cancer Center (UCC) Dresden, Dresden, 01307, Germany.,Institute of Clinical Genetics, Technical University of Dresden, Dresden, 01307, Germany
| | - Albrecht Stenzinger
- Institute of Pathology, University Hospital Heidelberg, Heidelberg, 69120, Germany
| | - Hanno Glimm
- NCT Partner Site Dresden, University Cancer Center (UCC) Dresden, Dresden, 01307, Germany
| | - Dirk Jäger
- Department of Medical Oncology, University Hospital Heidelberg, National Center for Tumor Diseases (NCT) Heidelberg, Heidelberg, 69120, Germany
| | - Christoph Springfeld
- Department of Medical Oncology, University Hospital Heidelberg, National Center for Tumor Diseases (NCT) Heidelberg, Heidelberg, 69120, Germany
| | - Stefan Fröhling
- Department of Translational Medical Oncology, NCT Heidelberg and German Cancer Research Center (DKFZ), Heidelberg, 69120, Germany.,German Cancer Consortium
| | - Stefanie Zschäbitz
- Department of Medical Oncology, University Hospital Heidelberg, National Center for Tumor Diseases (NCT) Heidelberg, Heidelberg, 69120, Germany
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29
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Niger M, Prisciandaro M, Antista M, Monica MAT, Cattaneo L, Prinzi N, Manglaviti S, Nichetti F, Brambilla M, Torchio M, Corti F, Pusceddu S, Coppa J, Mazzaferro V, de Braud F, Di Bartolomeo M. One size does not fit all for pancreatic cancers: A review on rare histologies and therapeutic approaches. World J Gastrointest Oncol 2020; 12:833-849. [PMID: 32879662 PMCID: PMC7443847 DOI: 10.4251/wjgo.v12.i8.833] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/31/2020] [Revised: 05/01/2020] [Accepted: 05/20/2020] [Indexed: 02/05/2023] Open
Abstract
Exocrine pancreatic neoplasms represent up to 95% of pancreatic cancers (PCs) and are widely recognized among the most lethal solid cancers, with a very poor 5-year survival rate of 5%-10%. The remaining < 5% of PCs are neuroendocrine tumors that are usually characterized by a better prognosis, with a median overall survival of 3.6 years. The most common type of PC is pancreatic ductal adenocarcinoma (PDAC), which accounts for roughly 85% of all exocrine PCs. However up to 10% of exocrine PCs have rare histotypes, which are still poorly understood. These subtypes can be distinguished from PDAC in terms of pathology, imaging, clinical presentation and prognosis. Additionally, due to their rarity, any knowledge regarding these specific histotypes is mostly based on case reports and a small series of retrospective analyses. Therefore, treatment strategies are generally deduced from those used for PDAC, even if these patients are often excluded or not clearly represented in clinical trials for PDAC. For these reasons, it is essential to collect as much information as possible on the management of PC, as assimilating it with PDAC may lead to the potential mistreatment of these patients. Here, we report the most significant literature regarding the epidemiology, typical presentation, possible treatment strategies, and prognosis of the most relevant histotypes among rare PCs.
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Affiliation(s)
- Monica Niger
- Medical Oncology Department, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan 20133, Italy
| | - Michele Prisciandaro
- Medical Oncology Department, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan 20133, Italy
| | - Maria Antista
- Medical Oncology Department, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan 20133, Italy
| | - Melissa Anna Teresa Monica
- First Pathology Division, Department of Pathology and Laboratory Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan 20133, Italy
| | - Laura Cattaneo
- First Pathology Division, Department of Pathology and Laboratory Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan 20133, Italy
| | - Natalie Prinzi
- Medical Oncology Department, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan 20133, Italy
| | - Sara Manglaviti
- Medical Oncology Department, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan 20133, Italy
| | - Federico Nichetti
- Medical Oncology Department, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan 20133, Italy
| | - Marta Brambilla
- Medical Oncology Department, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan 20133, Italy
| | - Martina Torchio
- Medical Oncology Department, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan 20133, Italy
| | - Francesca Corti
- Medical Oncology Department, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan 20133, Italy
| | - Sara Pusceddu
- Medical Oncology Department, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan 20133, Italy
| | - Jorgelina Coppa
- Hepato-biliary-pancreatic Surgery and Liver Transplantation Department, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan 20133, Italy
| | - Vincenzo Mazzaferro
- Hepato-biliary-pancreatic Surgery and Liver Transplantation Department, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan 20133, Italy
- Università degli studi di Milano, Milan 20133, Italy
| | - Filippo de Braud
- Medical Oncology Department, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan 20133, Italy
- Università degli studi di Milano, Milan 20133, Italy
| | - Maria Di Bartolomeo
- Medical Oncology Department, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan 20133, Italy
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Abstract
OBJECTIVES Acinar cell carcinoma of the pancreas is a rare tumor with limited data. We aim to evaluate the characteristics, treatments, and outcomes of pancreatic acinar cell carcinoma after 2005. METHODS We retrospectively reviewed patients with pancreatic acinar cell carcinoma treated in Peking University Cancer Hospital and Institute (2005-2018) and identified cases from Surveillance, Epidemiology, and End Results database (2005-2015). RESULTS A total of 306 cases in our institute (n = 11) and Surveillance, Epidemiology, and End Results database (n = 295) were identified. The median age was 67 years, and 73.5% were male. The 5-year survival was 36.8% for all patients (median, 27 months). About 37% underwent surgical resection. The 5-year survival was 65.6% for resected patients as compared with 16.9% for unresected ones (P < 0.0001). Among locoregional and metastatic diseases, surgery significantly prolonged survival as well (P = 0.0003). Stage IV patients who received chemotherapy had a better survival than those without it (median, 16 vs 3 months; P = 0.0019). Aging, stage IV, and no surgery were independent predictors of poor overall survival. CONCLUSIONS For pancreatic acinar cell carcinoma, surgery is a potentially curative treatment contributing to long-term survival and suggested even in advanced diseases. Chemotherapy improved survival for metastatic patients.
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Robot-assisted combined pancreatectomy/hepatectomy for metastatic pancreatic acinar cell carcinoma: case report and review of the literature. Clin J Gastroenterol 2020; 13:973-980. [PMID: 32583372 DOI: 10.1007/s12328-020-01146-z] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/30/2020] [Accepted: 06/01/2020] [Indexed: 12/14/2022]
Abstract
Acinar cell carcinoma (ACC) of the pancreas is a rare neoplasm with less aggressive behavior than ductal carcinoma. As a result, surgical resection for metastatic ACC is a therapeutic option which can result in long-term survival. There is a paucity of data describing institutional approaches to these challenging patients, and therefore, we herein describe our institution's approach to a patient with a distal pancreatic ACC and isolated liver metastasis. The patient underwent neoadjuvant chemotherapy (FOLFIRINOX), followed by a robot-assisted distal pancreatectomy/splenectomy and non-anatomic segment 6 resection. He was discharged to home post-operative day 2. Final pathology revealed complete tumor response of the liver metastasis and a margin negative resection of the primary tumor. He remains disease free and without complications at 3 months. We highlight that combined modality therapy for metastatic ACC can yield long-term survival in selected patients. Similarly, the robotic platform enables performance of complex multivisceral resections with rapid recovery. Future research investigating precision medicine for metastatic ACC is warranted given widely variable tumor biology in this disease.
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Di Marco M, Carloni R, De Lorenzo S, Grassi E, Palloni A, Formica F, Brocchi S, Filippini DM, Golfieri R, Brandi G. Long-term survival of two patients with recurrent pancreatic acinar cell carcinoma treated with radiofrequency ablation: A case report. World J Clin Cases 2020; 8:1241-1250. [PMID: 32337198 PMCID: PMC7176612 DOI: 10.12998/wjcc.v8.i7.1241] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/19/2019] [Revised: 01/08/2020] [Accepted: 03/11/2020] [Indexed: 02/05/2023] Open
Abstract
BACKGROUND Pancreatic acinar cell carcinoma (PACC) is a rare type of malignant pancreatic cancer that represents approximately 1% of all pancreatic neoplasms. Due to its very low incidence, only a few retrospective studies are available. Although surgery is the first choice for treatment, most patients experience recurrence (mainly in the liver) and there are no clear recommendations for patients with advanced disease.
CASE SUMMARY We report two patients with PACC treated with surgery who experienced tumour recurrence in the liver. Patient 1 carried a germline mutation in the APC gene. Both patients were treated with gemcitabine plus oxaliplatin and gemcitabine plus capecitabine as first- and second-line therapies, respectively. After a favourable response to chemotherapy, the patients underwent radiofrequency ablation of the remaining liver metastases. For patient 1, we documented a relapse in the liver after a disease-free period of 9 mo, and treatment with gemcitabine plus capecitabine was restarted. The patient achieved a complete response, and he remains alive without evidence of disease recurrence after six years. After radiofrequency ablation, patient 2 experienced disease-free survival for 21 mo, when peritoneal relapse was diagnosed and treated with chemotherapy. The patient achieved a stable disease state for nearly two years; nevertheless, further progressive disease was documented, and he died seven years after the first relapse.
CONCLUSION PACC presents different biological behaviours than pancreatic adenocarcinoma. Multidisciplinary treatment involving local ablative therapies may be considered for PACC.
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Affiliation(s)
- Mariacristina Di Marco
- Department of Experimental, Diagnostic, and Specialty Medicine - DIMES, Sant'Orsola-Malpighi Hospital, University of Bologna, Bologna 40138, Italy
| | - Riccardo Carloni
- Department of Experimental, Diagnostic, and Specialty Medicine - DIMES, Sant'Orsola-Malpighi Hospital, University of Bologna, Bologna 40138, Italy
| | - Stefania De Lorenzo
- Department of Experimental, Diagnostic, and Specialty Medicine - DIMES, Sant'Orsola-Malpighi Hospital, University of Bologna, Bologna 40138, Italy
| | - Elisa Grassi
- Medical Oncology, Ospedale degli Infermi, Faenza 48018, Italy
| | - Andrea Palloni
- Department of Experimental, Diagnostic, and Specialty Medicine - DIMES, Sant'Orsola-Malpighi Hospital, University of Bologna, Bologna 40138, Italy
| | - Francesca Formica
- Department of Experimental, Diagnostic, and Specialty Medicine - DIMES, Sant'Orsola-Malpighi Hospital, University of Bologna, Bologna 40138, Italy
| | - Stefano Brocchi
- Radiology Unit, Department of Diagnostic Medicine and Prevention, Sant'Orsola-Malpighi Hospital, University of Bologna, Bologna 40138, Italy
| | - Daria Maria Filippini
- Department of Experimental, Diagnostic, and Specialty Medicine - DIMES, Sant'Orsola-Malpighi Hospital, University of Bologna, Bologna 40138, Italy
| | - Rita Golfieri
- Radiology Unit, Department of Diagnostic Medicine and Prevention, Sant'Orsola-Malpighi Hospital, University of Bologna, Bologna 40138, Italy
| | - Giovanni Brandi
- Department of Experimental, Diagnostic, and Specialty Medicine - DIMES, Sant'Orsola-Malpighi Hospital, University of Bologna, Bologna 40138, Italy
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Luu AM, Fahlbusch T, Munding J, Uhl W, Braumann C. The Unusual Suspects of the Pancreas-Understanding Pancreatic Acinar Cell Carcinomas and Adenomas. J Gastrointest Cancer 2020; 51:172-178. [PMID: 30953241 DOI: 10.1007/s12029-019-00231-y] [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: 10/27/2022]
Abstract
PURPOSE Acinar cell carcinomas (ACC) and adenomas (ACA) of the pancreas are rare entities. Sufficient knowledge about occurrence and prognosis is scarce. METHODS A retrospective chart review of our database was performed for all patients who had undergone pancreatic surgery between 2006 and 2018. Results were compared to recent literature findings. RESULTS Nine patients were diagnosed with ACC and four patients with ACA of the pancreas in the study period. ACC patients were older and more often male than patients of the ACA group. ACC were mainly localized in the pancreatic head, whereas ACA were more often found in the distal pancreas. Tumor markers are not necessarily elevated, even in case of malignancy. CONCLUSIONS ACC and ACA are very rare pancreatic tumors. Both entities account for less than 1% of all pancreatic neoplasms. Diagnosis is challenging due to unspecific radiologic features and clinical symptoms. Nevertheless, a patient complaining of abdominal discomfort and an unclear hypodense pancreatic lesion should undergo surgical exploration.
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Affiliation(s)
- Andreas Minh Luu
- Department of General and Visceral Surgery, St. Josef-Hospital, University Hospital, Ruhr-University Bochum, Gudrunstrasse 56, 44791, Bochum, Germany
| | - Tim Fahlbusch
- Department of General and Visceral Surgery, St. Josef-Hospital, University Hospital, Ruhr-University Bochum, Gudrunstrasse 56, 44791, Bochum, Germany.
| | - Johanna Munding
- Department of Pathology, Berufsgenossenschaftliches Universitätsklinikum Bergmannsheil, Ruhr-University Bochum, Bürkle de la Camp Platz 1, 44789, Bochum, Germany
| | - Waldemar Uhl
- Department of General and Visceral Surgery, St. Josef-Hospital, University Hospital, Ruhr-University Bochum, Gudrunstrasse 56, 44791, Bochum, Germany
| | - Chris Braumann
- Department of General and Visceral Surgery, St. Josef-Hospital, University Hospital, Ruhr-University Bochum, Gudrunstrasse 56, 44791, Bochum, Germany
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Abstract
OBJECTIVES Acinar cell carcinoma is a rare tumor of the pancreas. Our current series aimed to assess the clinical and morphological features of pancreatic acinar cell carcinoma and to evaluate the treatment strategies and prognosis. METHODS This retrospective study was conducted in 3 French referral centers. Clinical data were obtained from medical records, and data about survival were then calculated and compared using statistical analysis. RESULTS Forty-four patients were included (men, 81.8%; median age, 65.5 years; range, 21-85). Tumors were localized, locally advanced, or metastatic in 48.8%, 14.0%, and 37.2% of cases, respectively. Twenty-nine patients (65.9%) underwent a curative-intent resection (R0, 79.2%). First-line chemotherapy in metastatic patients was heterogeneous but mainly consisted in 5-fluorouracil-based or gemcitabine plus oxaliplatin combinations. Median disease-free survival was 12 months (range, 0-82 months). Median overall survival was 55.5 months; it was 40 months in patients with metastatic tumor compared with 106.5 months (P = 0.1058) in those with a nonmetastatic one. Age older than 60 years and a proliferation index greater than 30% were poor prognostic factors. CONCLUSIONS In this large series of patients with pancreatic acinar cell carcinoma, the rate of R0 resection and the prognosis of patients appeared to be much better than that of classic ductal adenocarcinomas.
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35
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Xing-Mao Z, Hong-Juan Z, Qing L, Qiang H. Pancreatic acinar cell carcinoma-case report and literature review. BMC Cancer 2018; 18:1083. [PMID: 30409114 PMCID: PMC6225569 DOI: 10.1186/s12885-018-5008-z] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/19/2018] [Accepted: 10/29/2018] [Indexed: 02/07/2023] Open
Abstract
Background Pancreatic acinar cell carcinoma (ACC) is a rare tumor that constitutes 1% of all pancreatic neoplasms. Pancreatic ACC has unique characteristics in terms of biological behavior, imaging and prognosis. Case presentation The present study reported two cases of pancreatic ACC confirmed by postoperative pathology and both cases exhibited several different imaging features and laboratory test results. Both cases had approximately 4 cm mass located in uncinate process of pancreas. Dilated intra- and extra-hepatic bile ducts was observed in one case, along with calcification. Heterogeneous enhancement of the tumor was exhibited in both patients with different intensities. Obstructive jaundice, elevated α-fetoprotein and CA 19–9 was found in one case, while the other case had normal liver function and tumor markers. Conclusions It was difficult to accurately diagnose pancreatic ACC before the operation despite its unique characteristics. Radical resection was the best treatment modality for resectable pancreatic ACC.
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Affiliation(s)
- Zhang Xing-Mao
- Department of hepatobiliary surgery, Beijing Chaoyang Hospital, Capital Medical University, 8 Gongti South Street, Chaoyang District, 100021, Beijing, China
| | - Zhang Hong-Juan
- Department of general surgery, The 2nd Hospital of Chengde Medical College, Chengde Central Hospital, Chengde, Hebei province, China
| | - Li Qing
- Department of pathology, Beijing Chaoyang Hospital, Capital Medical University, Beijing, China
| | - He Qiang
- Department of hepatobiliary surgery, Beijing Chaoyang Hospital, Capital Medical University, 8 Gongti South Street, Chaoyang District, 100021, Beijing, China.
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Brunetti O, Aprile G, Marchetti P, Vasile E, Casadei Gardini A, Scartozzi M, Barni S, Delfanti S, De Vita F, Di Costanzo F, Milella M, Cella CA, Berardi R, Cataldo I, Scarpa A, Basile D, Mazzuca F, Graziano G, Argentiero A, Santini D, Reni M, Cascinu S, Silvestris N. Systemic Chemotherapy for Advanced Rare Pancreatic Histotype Tumors: A Retrospective Multicenter Analysis. Pancreas 2018; 47:759-771. [PMID: 29771769 DOI: 10.1097/mpa.0000000000001063] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
OBJECTIVES Two issues were put forth by clinicians in the management of the advanced stages of rare variants of pancreatic ductal adenocarcinoma and other exocrine histotypes with peculiar clinical and pathological features: Do chemotherapy regimens recommended in pancreatic ductal adenocarcinoma patients have a clinical activity in rare pancreatic tumors? Or should other chemotherapy combinations be considered in this subset of patients? METHODS We conducted a multicenter retrospective study that collected data from 2005 to 2016 at 14 Italian cancer centers with the aim to evaluate tumor response and time to progression for first- and second-line and overall survival. RESULTS Of approximately 4300 exocrine pancreatic cancer patients, 79 advanced cases affected by rare histological types were identified, with pancreatic acinar cell cancer (n = 23), pancreatic adenosquamous cancer (n = 16), and mucinous cystic neoplasm with an associated invasive mucinous cystadenocarcinoma (n = 15) most represented. Survival analyses for each subgroup in relation with the different chemotherapy regimens showed the lack of statistical significance correlations. CONCLUSIONS Because of the lack of clinical trials in patients affected by these rare pancreatic histotypes, only their molecular classification would help clinicians in future therapeutic choice.
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MESH Headings
- Adenocarcinoma, Mucinous/drug therapy
- Adenocarcinoma, Mucinous/pathology
- Aged
- Antineoplastic Combined Chemotherapy Protocols/therapeutic use
- Carcinoma, Acinar Cell/drug therapy
- Carcinoma, Acinar Cell/pathology
- Carcinoma, Adenosquamous/drug therapy
- Carcinoma, Adenosquamous/pathology
- Carcinoma, Pancreatic Ductal/drug therapy
- Carcinoma, Pancreatic Ductal/pathology
- Cystadenocarcinoma, Mucinous/drug therapy
- Cystadenocarcinoma, Mucinous/pathology
- Humans
- Kaplan-Meier Estimate
- Middle Aged
- Pancreatic Neoplasms/drug therapy
- Pancreatic Neoplasms/pathology
- Prognosis
- Retrospective Studies
- Treatment Outcome
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Affiliation(s)
| | | | - Paolo Marchetti
- Medical Oncology Unit, Sant'Andrea Hospital, University of Rome La Sapienza, Rome
| | - Enrico Vasile
- Medical Oncology Unit, Azienda Ospedaliero-Universitaria Pisana, Pisa
| | - Andrea Casadei Gardini
- Department of MedicalOncology, Istituto Scientifico Romagnolo per lo Studio e Cura dei Tumori (IRST) IRCCS, Meldola
| | | | - Sandro Barni
- Medical Oncology Unit, ASST Bergamo Ovest, Treviglio
| | - Sara Delfanti
- Medical Oncology Unit, Fondazione IRCCS Policlinico San Matteo, Pavia
| | | | | | - Michele Milella
- Medical Oncology 1, IRCCS Regina Elena National Cancer Institute, Rome
| | | | - Rossana Berardi
- Medical Oncology Unit, Università Politecnica Marche - Ospedali Riuniti Ancona, Ancona
| | - Ivana Cataldo
- Department of Pathology and Diagnostics, University of Verona, ARCNET, Verona
| | - Aldo Scarpa
- Department of Pathology and Diagnostics, University of Verona, ARCNET, Verona
| | - Debora Basile
- Department of Medical Oncology, University and General Hospital, Udine
| | - Federica Mazzuca
- Medical Oncology Unit, Sant'Andrea Hospital, University of Rome La Sapienza, Rome
| | - Giusi Graziano
- Scientific Direction, Cancer Institute "Giovanni Paolo II," Bari
| | | | | | - Michele Reni
- Department of Medical Oncology, IRCCS San Raffaele Scientific Institute, Milan
| | - Stefano Cascinu
- Modena Cancer Center, University of Modena and Reggio Emilia, Azienda Ospedaliera-Universitaria di Modena, Modena, Italy
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Richard C, Niogret J, Boidot R, Ghiringhelli F. EGFR amplification induces sensitivity to anti EGFR therapy in pancreatic acinar cell carcinoma. World J Gastrointest Oncol 2018; 10:103-107. [PMID: 29666669 PMCID: PMC5900454 DOI: 10.4251/wjgo.v10.i4.103] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/22/2017] [Revised: 02/28/2018] [Accepted: 03/06/2018] [Indexed: 02/05/2023] Open
Abstract
Pancreatic acinar cell carcinoma (PACC) is a rare cancer. When the tumor is metastatic, few therapeutic options are available. Precision medicine using next-generation sequencing is defined by the administration of drugs based on the tumor genetic mutations. The usage of precision medicine for finding new therapeutic options for rare cancers is an emerging field. We have reported here the case of a patient bearing a multitreated metastatic PACC. This patient underwent somatic and constitutional exome analyses. The analyses revealed in the liver metastasis an amplification of the EGFR gene. Accordingly, the patient was treated with off-label usage of panitumumab. We observed rapid response with necrosis of the liver metastasis, while no efficacy was observed in the primary tumor. An exome analysis of the primary tumor revealed amplification of HER2 and MET with EGFR amplification. Such amplifications are known as a resistance mechanism to antiEGFR therapy. Our results suggest that exome analysis may be helpful to highlight targets in rare cancers, such as PACC. EGFR amplification in this pathology should be determined and could be used as a biomarker to propose antiEGFR therapy.
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Affiliation(s)
- Corentin Richard
- Platform of Transfer in Oncology, Center GF Leclerc, Dijon 21000, France
- INSERM U1231, Dijon 21000, France
- University of Bourgogne Franche Comte, Dijon 21000, France
| | - Julie Niogret
- Department of Medical Oncology, Georges Francois Leclerc Cancer Center, Dijon 21000, France
| | - Romain Boidot
- Platform of Transfer in Oncology, Center GF Leclerc, Dijon 21000, France
- INSERM U1231, Dijon 21000, France
| | - Francois Ghiringhelli
- Platform of Transfer in Oncology, Center GF Leclerc, Dijon 21000, France
- INSERM U1231, Dijon 21000, France
- University of Bourgogne Franche Comte, Dijon 21000, France
- Department of Medical Oncology, Georges Francois Leclerc Cancer Center, Dijon 21000, France
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Hashimoto M, Hikichi T, Suzuki T, Tai M, Ichii O, Matsuhashi N, Kita E, Takahashi S, Okubo Y, Hakozaki H, Ejiri Y, Ohira H. Successful chemotherapy with modified FOLFIRINOX for pancreatic acinar cell carcinoma. Clin J Gastroenterol 2017; 10:564-569. [PMID: 29052123 DOI: 10.1007/s12328-017-0785-5] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/29/2017] [Accepted: 10/05/2017] [Indexed: 02/07/2023]
Abstract
Abdominal ultrasonography revealed a pancreatic mass in a 67-year-old man with diabetes mellitus. Endoscopic ultrasound-guided fine needle aspiration led to the histological diagnosis of acinar cell carcinoma. The clinical stage was determined to be IVb based on findings of multiple metastatic lesions in the liver and lymph nodes, as well as splenic vein infiltration. Because the patient was not a surgical candidate, he underwent chemotherapy with modified FOLFIRINOX. In the absence of any severe adverse events, 12 courses of chemotherapy were delivered, resulting in marked shrinkage of both the primary and metastatic lesions. The outcome was judged to be a partial response, which was maintained even 9 months from the introduction of the chemotherapy. The results of this case suggest that modified FOLFIRINOX is safe and effective in the treatment of pancreatic acinar cell carcinoma.
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Affiliation(s)
- Minami Hashimoto
- Department of Gastroenterology, Fukushima Rosai Hospital, Iwaki, Japan
- Department of Gastroenterology, Fukushima Medical University School of Medicine, Fukushima, Japan
| | - Takuto Hikichi
- Department of Endoscopy, Fukushima Medical University Hospital, 1 Hikarigaoka, Fukushima, 960-1295, Japan.
| | - Tomohiro Suzuki
- Department of Gastroenterology, Fukushima Rosai Hospital, Iwaki, Japan
| | - Mayumi Tai
- Department of Gastroenterology, Fukushima Rosai Hospital, Iwaki, Japan
| | - Osamu Ichii
- Department of Gastroenterology, Fukushima Rosai Hospital, Iwaki, Japan
| | - Nobuo Matsuhashi
- Department of Gastroenterology, Fukushima Rosai Hospital, Iwaki, Japan
| | - Eisaku Kita
- Department of Gastroenterology, Fukushima Rosai Hospital, Iwaki, Japan
| | | | - Yoshinori Okubo
- Department of Gastroenterology, Fukushima Rosai Hospital, Iwaki, Japan
| | - Hando Hakozaki
- Department of Pathology, Fukushima Rosai Hospital, Iwaki, Japan
| | - Yutaka Ejiri
- Department of Gastroenterology, Fukushima Rosai Hospital, Iwaki, Japan
| | - Hiromasa Ohira
- Department of Gastroenterology, Fukushima Medical University School of Medicine, Fukushima, Japan
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