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Chen J, Ma Z, Xu Y, Ge J, Yao H, Li C, Hu X, Pu Y, Li M, Jiang C. CT-based machine learning radiomics predicts Ki-67 expression level and its relationship with overall survival in resectable pancreatic ductal adenocarcinoma. Abdom Radiol (NY) 2025:10.1007/s00261-025-04798-y. [PMID: 39841230 DOI: 10.1007/s00261-025-04798-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/13/2024] [Revised: 01/02/2025] [Accepted: 01/03/2025] [Indexed: 01/23/2025]
Abstract
BACKGROUND The prognostic prediction of pancreatic ductal adenocarcinoma (PDAC) remains challenging. This study aimed to develop a radiomics model to predict Ki-67 expression status in PDAC patients using radiomics features from dual-phase enhanced CT, and integrated clinical characteristics to create a radiomics-clinical nomogram for prognostic prediction. METHODS In this retrospective study, data were collected from 124 PDAC patients treated surgically at a single center, from January 2017 to March 2023. Patients were categorized according to the Ki-67 expression rate. Radiomics features were extracted from arterial and portal venous phase CT images using 3D Slicer v5.0.3. A radiomics model was formulated and validated to predict the Ki-67 expression, and a nomogram combining clinical indicators and the radiomics model was developed to predict 1, 2 and 3 year overall survival (OS). RESULTS The optimal Ki-67 expression rate cutoff was identified as 50%, with significant OS differences. The developed radiomics model showed good predictive ability with area under the curves of 0.806 and 0.801 in the training and validation groups, respectively. High radiomics score, elevated carbohydrate antigen 19-9 (CA19-9), and receipt of adjuvant chemotherapy were identified as independent prognostic factors for OS. The radiomics-clinical nomogram accurately predicted 1, 2 and 3 year OS in PDAC patients. CONCLUSIONS The radiomics-clinical nomogram provides a non-invasive and efficient method for predicting Ki-67 expression and overall survival in PDAC patients, which could potentially guide clinical decision-making and improve patient outcomes.
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Affiliation(s)
- Jiahao Chen
- Department of Hepato-Biliary-Pancreatic Surgery, Huadong Hospital affiliated to Fudan University, Shanghai, China
| | - Zhuangxuan Ma
- Department of Radiology, Huadong Hospital Affiliated to Fudan University, Shanghai, China
| | - Yamin Xu
- Department of Hepato-Biliary-Pancreatic Surgery, Huadong Hospital affiliated to Fudan University, Shanghai, China
| | - Jieqiong Ge
- Department of Hepato-Biliary-Pancreatic Surgery, Huadong Hospital affiliated to Fudan University, Shanghai, China
| | - Hongfei Yao
- Department of Hepato-Biliary-Pancreatic Surgery, Huadong Hospital affiliated to Fudan University, Shanghai, China
| | - Chunjing Li
- Department of Hepato-Biliary-Pancreatic Surgery, Huadong Hospital affiliated to Fudan University, Shanghai, China
| | - Xiao Hu
- Department of Hepato-Biliary-Pancreatic Surgery, Huadong Hospital affiliated to Fudan University, Shanghai, China
| | - Yunlong Pu
- Department of Hepato-Biliary-Pancreatic Surgery, Huadong Hospital affiliated to Fudan University, Shanghai, China
| | - Ming Li
- Department of Radiology, Huadong Hospital Affiliated to Fudan University, Shanghai, China.
| | - Chongyi Jiang
- Department of Hepato-Biliary-Pancreatic Surgery, Huadong Hospital affiliated to Fudan University, Shanghai, China.
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Zhou L, Zhang L. Effect of postsurgical adjuvant chemotherapy timing on outcomes in patients with pancreatic cancer - a systematic review and meta-analysis. J Chemother 2024:1-11. [PMID: 39289876 DOI: 10.1080/1120009x.2024.2402175] [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: 06/07/2024] [Revised: 08/12/2024] [Accepted: 09/03/2024] [Indexed: 09/19/2024]
Abstract
To assess the association between the timing of postsurgical adjuvant chemotherapy and overall survival (OS) and disease-free survival (DFS) in patients with pancreatic cancer (PC). Literature search of PubMed, EMBASE, and Scopus databases was done for randomized controlled trials (RCTs) or observational studies (cohort studies, case-control studies), reporting outcomes of adult PC patients (aged 18 and above) who underwent surgery and received adjuvant chemotherapy at different time points after the operation. Pooled effect sizes were quantified and reported as hazard ratio (HR). The primary outcomes were OS and DFS. A random effects model to was used account for potential variability across studies. Sixteen studies were included. There was no significant difference between early and delayed initiation of adjuvant chemotherapy in terms of OS (HR 1.03, 95% CI: 0.98, 1.08) and DFS (HR 1.09, 95% CI: 0.91, 1.31). Subgroup analyses based on tumour stage, sample size, and the number of chemotherapeutic agents used did not reveal significant associations. Delayed initiation was associated with reduced OS in patients with well- to moderately differentiated tumours, with the confidence intervals approaching statistical significance (HR 1.12, 95% CI: 1.00,1.25). There was no significant association between the timing of postoperative adjuvant chemotherapy initiation and OS and DFS in patients with pancreatic cancer. These findings underscore the importance of optimizing treatment strategies and suggest that clinicians need to focus on other critical aspects such as drug selection, dosage, and patient-specific factors that might substantially impact treatment efficacy.
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Affiliation(s)
- Longlan Zhou
- Department of Oncology, Affiliated Banan Hospital of Chongqing Medical University, Chongqing, China
| | - Lin Zhang
- Department of Anesthesiology, Affiliated Banan Hospital of Chongqing Medical University, Chongqing, China
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Chen JH, Zhu LY, Cai ZW, Hu X, Ahmed AA, Ge JQ, Tang XY, Li CJ, Pu YL, Jiang CY. TRIANGLE operation, combined with adequate adjuvant chemotherapy, can improve the prognosis of pancreatic head cancer: A retrospective study. World J Gastrointest Oncol 2024; 16:1773-1786. [PMID: 38764839 PMCID: PMC11099462 DOI: 10.4251/wjgo.v16.i5.1773] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/07/2024] [Revised: 02/04/2024] [Accepted: 03/05/2024] [Indexed: 05/09/2024] Open
Abstract
BACKGROUND The TRIANGLE operation involves the removal of all tissues within the triangle bounded by the portal vein-superior mesenteric vein, celiac axis-common hepatic artery, and superior mesenteric artery to improve patient prognosis. Although previously promising in patients with locally advanced pancreatic ductal adenocarcinoma (PDAC), data are limited regarding the long-term oncological outcomes of the TRIANGLE operation among resectable PDAC patients undergoing pancreaticoduodenectomy (PD). AIM To evaluate the safety of the TRIANGLE operation during PD and the prognosis in patients with resectable PDAC. METHODS This retrospective cohort study included patients who underwent PD for pancreatic head cancer between January 2017 and April 2023, with or without the TRIANGLE operation. Patients were divided into the PDTRIANGLE and PDnon-TRIANGLE groups. Surgical and survival outcomes were compared between the two groups. Adequate adjuvant chemotherapy was defined as adjuvant chemotherapy ≥ 6 months. RESULTS The PDTRIANGLE and PDnon-TRIANGLE groups included 52 and 55 patients, respectively. There were no significant differences in the baseline characteristics or perioperative indexes between the two groups. Furthermore, the recurrence rate was lower in the PDTRIANGLE group than in the PDnon-TRIANGLE group (48.1% vs 81.8%, P < 0.001), and the local recurrence rate of PDAC decreased from 37.8% to 16.0%. Multivariate Cox regression analysis revealed that PDTRIANGLE (HR = 0.424; 95%CI: 0.256-0.702; P = 0.001), adequate adjuvant chemotherapy ≥ 6 months (HR = 0.370; 95%CI: 0.222-0.618; P < 0.001) and margin status (HR = 2.255; 95%CI: 1.252-4.064; P = 0.007) were found to be independent factors for the recurrence rate. CONCLUSION The TRIANGLE operation is safe for PDAC patients undergoing PD. Moreover, it reduces the local recurrence rate of PDAC and may improve survival in patients who receive adequate adjuvant chemotherapy.
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Affiliation(s)
- Jia-Hao Chen
- Department of Hepato-Biliary-Pancreatic Surgery, Huadong Hospital Affiliated to Fudan University, Shanghai 200040, China
| | - Li-Yong Zhu
- Department of Hepato-Biliary-Pancreatic Surgery, Huadong Hospital Affiliated to Fudan University, Shanghai 200040, China
| | - Zhi-Wei Cai
- Department of Hepato-Biliary-Pancreatic Surgery, Huadong Hospital Affiliated to Fudan University, Shanghai 200040, China
- Shanghai Key Laboratory of Clinical Geriatric Medicine, Fudan University, Shanghai 200040, China
| | - Xiao Hu
- Department of Hepato-Biliary-Pancreatic Surgery, Huadong Hospital Affiliated to Fudan University, Shanghai 200040, China
| | - Abousalam Abdoulkader Ahmed
- Department of Hepato-Biliary-Pancreatic Surgery, Huadong Hospital Affiliated to Fudan University, Shanghai 200040, China
| | - Jie-Qiong Ge
- Department of Nursing, Huadong Hospital Affiliated to Fudan University, Shanghai 200040, China
| | - Xiao-Yan Tang
- Department of Hepato-Biliary-Pancreatic Surgery, Huadong Hospital Affiliated to Fudan University, Shanghai 200040, China
| | - Chun-Jing Li
- Department of Hepato-Biliary-Pancreatic Surgery, Huadong Hospital Affiliated to Fudan University, Shanghai 200040, China
| | - Yun-Long Pu
- Department of Hepato-Biliary-Pancreatic Surgery, Huadong Hospital Affiliated to Fudan University, Shanghai 200040, China
| | - Chong-Yi Jiang
- Department of Hepato-Biliary-Pancreatic Surgery, Huadong Hospital Affiliated to Fudan University, Shanghai 200040, China
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Zhukova LG, Bordin DS, Dubtsova EA, Ilin MA, Kiriukova MA, Feoktistova PS, Egorov VI. How a significant increase in survival in pancreatic cancer is achieved. The role of nutritional status and supportive care: A review. JOURNAL OF MODERN ONCOLOGY 2024; 25. [DOI: 10.26442/18151434.2023.4.202541] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
Abstract
Pancreatic cancer (PC) is a serious public health problem. The mortality rate of patients with PC remains one of the highest among cancers. Early diagnosis of PC is challenging, so it is often diagnosed in the later stages. Current treatment approaches, including surgery, neoadjuvant and adjuvant chemotherapy, chemoradiotherapy, and supportive care, have demonstrated improved outcomes. A significant problem remains exocrine pancreatic insufficiency (EPI) in patients with PC, which requires enzyme replacement therapy. However, this is not given due attention in the Russian literature. This review addresses the survival trends of patients with PC, current therapies, and enzyme replacement therapy as an integral part of supportive care and improvement of nutritional status; also, the issues of routing patients with PC are addressed. It is emphasized that the diagnosis and treatment of EPI are mandatory to improve and maintain the nutritional status and quality of life; failure to treat EPI renders antitumor treatment ineffective.
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Kirkegård J, Ladekarl M, Lund A, Mortensen F. Impact on Survival of Early Versus Late Initiation of Adjuvant Chemotherapy After Pancreatic Adenocarcinoma Surgery: A Target Trial Emulation. Ann Surg Oncol 2024; 31:1310-1318. [PMID: 37914923 PMCID: PMC10761389 DOI: 10.1245/s10434-023-14497-x] [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: 08/04/2023] [Accepted: 10/10/2023] [Indexed: 11/03/2023]
Abstract
BACKGROUND We examined the impact of early (0-4 weeks after discharge) versus late (> 4-8 weeks after discharge) initiation of adjuvant chemotherapy on pancreatic adenocarcinoma survival. METHODS We used Danish population-based healthcare registries to emulate a hypothetical target trial using the clone-censor-weight approach. All eligible patients were cloned with one clone assigned to 'early initiation' and one clone assigned to 'late initiation'. Clones were censored when the assigned treatment was no longer compatible with the actual treatment. Informative censoring was addressed using inverse probability of censoring weighting. RESULTS We included 1491 patients in a hypothetical target trial, of whom 32.3% initiated chemotherapy within 0-4 weeks and 38.3% between > 4 and 8 weeks after discharge for pancreatic adenocarcinoma surgery; 206 (13.8%) initiated chemotherapy after > 8 weeks, and 232 (15.6%) did not initiate chemotherapy. Median overall survival was 30.4 and 29.9 months in late and early initiators, respectively. The absolute differences in OS, comparing late with early initiators, were 3.2% (95% confidence interval [CI] - 1.5%, 7.9%), - 0.7% (95% CI - 7.2%, 5.8%), and 3.2% (95% CI - 2.8%, 9.3%) at 1, 3, and 5 years, respectively. Late initiators had a higher increase in albumin levels as well as higher pretreatment albumin values. CONCLUSIONS Postponement of adjuvant chemotherapy up to 8 weeks after discharge from pancreatic adenocarcinoma surgery is safe and may allow more patients to receive adjuvant therapy due to better recovery.
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Affiliation(s)
- Jakob Kirkegård
- HPB Section, Department of Surgery, Aarhus University Hospital, Aarhus, Denmark.
- Department of Clinical Medicine, Aarhus University, Aarhus, Denmark.
| | - Morten Ladekarl
- Department of Oncology and Clinical Cancer Research Center, Aalborg University Hospital, Aalborg, Denmark
- Department of Clinical Medicine, Aalborg University, Aalborg, Denmark
| | - Andrea Lund
- HPB Section, Department of Surgery, Aarhus University Hospital, Aarhus, Denmark
- Department of Clinical Medicine, Aarhus University, Aarhus, Denmark
| | - Frank Mortensen
- HPB Section, Department of Surgery, Aarhus University Hospital, Aarhus, Denmark
- Department of Clinical Medicine, Aarhus University, Aarhus, Denmark
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Sugumar K, Hue JJ, Gupta S, Elshami M, Rothermel LD, Ocuin LM, Ammori JB, Hardacre JM, Winter JM. Trends in and Prognostic Significance of Time to Treatment in Pancreatic Cancer: A Population-Based Study. Ann Surg Oncol 2023; 30:8610-8620. [PMID: 37624518 DOI: 10.1245/s10434-023-14221-9] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/22/2023] [Accepted: 08/08/2023] [Indexed: 08/26/2023]
Abstract
INTRODUCTION The association of time to treatment (TTT) with survival remains unclear in pancreatic adenocarcinoma (PDAC). In this study, we evaluate the recent trends in TTT, causes for delay, and its effect on survival. METHODS We included patients with PDAC of all stages from the National Cancer Database (2004-2020) who underwent either surgery or chemotherapy/radiotherapy (CT/RT). TTT was defined as the duration between tissue diagnosis and first treatment. Linear regression (β) was used to study the temporal trends in time delay. RESULTS A total of 239,638 patients were included. The median TTT was 25 days. Using multivariable analysis, we found that increasing age (OR 1.48), female gender (OR 1.04), Black race (OR 1.3), lower educational status (OR 1.2), Medicaid, Medicare insurance, and uninsured (OR 1.2, 1.5, and 1.2, respectively), treatment at academic centers (OR 1.3), higher Charlson-Deyo comorbidity index (OR 1.2), and CT/RT (OR 1.5) were associated with increased TTT. There was a steady rise in median TTT from 21 to 28 days between 2004 and 2020 (β = 0.3), suggestive of a worsening trend. Concurrently, there was an increasing trend in utilization of neoadjuvant CT/RT between 2004 and 2020 in early-stage PDAC. On Cox regression, TTT delay was associated with poor overall survival in stage I-IV patients (HR 1.1, 1.1, 1.09, and 1.53, respectively). CONCLUSIONS Delayed treatment approaching 2 months was observed in 10% of the population. The rising temporal trend in TTT may be attributed to the increasing shift toward neoadjuvant CT/RT in early-stage PDAC and/or the increasing use of tissue biopsy prior to surgery.
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Affiliation(s)
- Kavin Sugumar
- Department of Surgery, University Hospitals Seidman Cancer Center and Case Comprehensive Cancer Center, University Hospitals Cleveland Medical, Cleveland, OH, USA.
| | - Jonathan J Hue
- Department of Surgery, University Hospitals Seidman Cancer Center and Case Comprehensive Cancer Center, University Hospitals Cleveland Medical, Cleveland, OH, USA
| | - Shreya Gupta
- Department of Surgery, University Hospitals Seidman Cancer Center and Case Comprehensive Cancer Center, University Hospitals Cleveland Medical, Cleveland, OH, USA
| | - Mohamedraed Elshami
- Department of Surgery, University Hospitals Seidman Cancer Center and Case Comprehensive Cancer Center, University Hospitals Cleveland Medical, Cleveland, OH, USA
| | - Luke D Rothermel
- Department of Surgery, University Hospitals Seidman Cancer Center and Case Comprehensive Cancer Center, University Hospitals Cleveland Medical, Cleveland, OH, USA
| | - Lee M Ocuin
- Department of Surgery, University Hospitals Seidman Cancer Center and Case Comprehensive Cancer Center, University Hospitals Cleveland Medical, Cleveland, OH, USA
| | - John B Ammori
- Department of Surgery, University Hospitals Seidman Cancer Center and Case Comprehensive Cancer Center, University Hospitals Cleveland Medical, Cleveland, OH, USA
| | - Jeffrey M Hardacre
- Department of Surgery, University Hospitals Seidman Cancer Center and Case Comprehensive Cancer Center, University Hospitals Cleveland Medical, Cleveland, OH, USA
| | - Jordan M Winter
- Department of Surgery, University Hospitals Seidman Cancer Center and Case Comprehensive Cancer Center, University Hospitals Cleveland Medical, Cleveland, OH, USA
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Lee W, Song KB, Hong S, Park Y, Kwak BJ, Jun E, Hwang DW, Kim S, Lee JH, Kim SC. Minimally invasive versus open pancreaticoduodenectomy for distal bile duct cancer: an inverse probability of treatment weighting analysis of outcomes. Surg Endosc 2023; 37:881-890. [PMID: 36018360 DOI: 10.1007/s00464-022-09533-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] [Received: 05/18/2022] [Accepted: 07/31/2022] [Indexed: 10/15/2022]
Abstract
BACKGROUND Minimally invasive pancreaticoduodenectomy (MIPD) has been extended to periampullary cancers, but the oncologic outcome of MIPD for distal bile duct cancer (DBDC) has not been confirmed yet. METHODS Patients who underwent pancreaticoduodenectomy (PD) for DBDC of stage I-IIb from 2015 to 2019 at a tertiary referral center were identified and divided into open PD (OPD) and MIPD groups, the latter including laparoscopic and robotic procedures. Survival was compared between the two groups after inverse probability of treatment weighting (IPTW) using predetermined factors, and exploratory mediation analysis was performed using surgery-derived outcomes. RESULTS MIPD (n = 81) group had more female patients (46.9% vs 31.6%, p = 0.011) and longer operation time (366.2 min vs. 279.1 min, p < 0.001) than the OPD (n = 288) group before IPTW. Otherwise, intraoperative and immediate postoperative outcomes were comparable between the two groups. In oncologic outcomes, MIPD group showed comparable 3-year overall survival (78.2% vs 75.0%, p = 0.062) and recurrence-free survival (51.2% vs 53.4%, p = 0.871) rates with OPD group before IPTW, and MIPD was not related with survival (hazard ratio [HR] 0.61, 95% confidence interval [CI] 0.29-1.26, p = 0.18) and recurrence (HR 1.01, 95% CI 0.67-1.53, p = 0.949) after IPTW with consideration of potential mediators. Sensitivity analysis using propensity score matching also showed similar results for survival (HR 0.68, 95% CI 0.32-1.44, p = 0.312) and recurrence (HR 1.12, 95% CI 0.67-1.88, p = 0.653). CONCLUSION MIPD and OPD groups showed similar postoperative and oncologic outcomes. MIPD could be a considerable treatment option without oncological compromise in high-volume centers.
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Affiliation(s)
- Woohyung Lee
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, 88, Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, Republic of Korea
| | - Ki Byung Song
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, 88, Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, Republic of Korea
| | - Sarang Hong
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, 88, Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, Republic of Korea
| | - Yejong Park
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, 88, Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, Republic of Korea
| | - Bong Jun Kwak
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, 88, Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, Republic of Korea
| | - Eunsung Jun
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, 88, Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, Republic of Korea
| | - Dae Wook Hwang
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, 88, Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, Republic of Korea
| | - Sehee Kim
- Department of Clinical Epidemiology and Biostatistics, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Jae Hoon Lee
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, 88, Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, Republic of Korea
| | - Song Cheol Kim
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, 88, Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, Republic of Korea.
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Sugumar K, Hue JJ, De La Serna S, Rothermel LD, Ocuin LM, Hardacre JM, Ammori JB, Winter JM. The importance of time-to-adjuvant treatment on survival with pancreatic cancer: A systematic review and meta-analysis. Cancer Rep (Hoboken) 2021; 4:e1390. [PMID: 34245139 PMCID: PMC8552002 DOI: 10.1002/cnr2.1390] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/27/2020] [Revised: 03/04/2021] [Accepted: 03/15/2021] [Indexed: 11/08/2022] Open
Abstract
BACKGROUND While adjuvant chemotherapy benefits patients with pancreatic ductal adenocarcinoma (PDAC), the importance of the time to initiation of adjuvant therapy remains unclear. AIM This study seeks to better understand whether the timing of postoperative chemotherapy initiation affects long-term outcomes in PDAC. METHODS AND RESULTS A systematic literature search was performed in Medline, Embase, and Cochrane Library in March 2020. Studies focused on the association between the timing of adjuvant therapy on long-term outcomes in resected PDAC patients were included. The impact of early and delayed therapy as defined by the respective studies was evaluated using forest plot analysis. Overall survival (OS) and disease-free survival (DFS) served as primary endpoints. Out of 3099 published articles, 10 retrospective studies met inclusion criteria. Combined, these studies included clinical data of 13 344 patients. The cut off used to define "early" and "delayed" treatment groups varied in the included studies ranging from 3 to 12 weeks. Due to this heterogeneity, a sub-group analysis of three time cut offs was performed: 3 to 5 weeks, 6 to 8 weeks, and 9 to 12 weeks. There was a significant decrease in OS and DFS when adjuvant therapy was delayed by 3 to 5 weeks after surgery (OS, pooled hazard ratio [HR] = 1.86, 95% confidence interval [CI] = 1.25-2.78; DFS, pooled HR = 1.62, 95% CI = 1.12-2.34). However, due to small sample size and limited studies in this subgroup analysis, the results may be indeterminate. There was no significant decrease in OS with delayed initiation of adjuvant therapy by 6 to 8 weeks and 9 to 12 weeks. Similarly, delay in adjuvant therapy beyond 3-5 weeks. CONCLUSIONS There was no conclusive evidence suggesting improved survival in patients starting treatment at various time cut offs. Studies investigating the extreme ends of the time-to-treatment spectrum may prove more informative.
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Affiliation(s)
- Kavin Sugumar
- Department of SurgeryUniversity Hospitals Seidman Cancer CenterClevelandOhioUSA
| | - Jonathan J. Hue
- Department of SurgeryUniversity Hospitals Seidman Cancer CenterClevelandOhioUSA
| | - Solanus De La Serna
- Case Comprehensive Cancer CenterCase Western Reserve University School of MedicineClevelandOhioUSA
| | - Luke D. Rothermel
- Department of SurgeryUniversity Hospitals Seidman Cancer CenterClevelandOhioUSA
| | - Lee M. Ocuin
- Department of Surgery, Division of HepatobiliaryPancreatic Surgery, Atrium HealthCharlotteNorth CarolinaUSA
| | - Jeffrey M. Hardacre
- Department of SurgeryUniversity Hospitals Seidman Cancer CenterClevelandOhioUSA
| | - John B. Ammori
- Department of SurgeryUniversity Hospitals Seidman Cancer CenterClevelandOhioUSA
| | - Jordan M. Winter
- Department of SurgeryUniversity Hospitals Seidman Cancer CenterClevelandOhioUSA
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Gasteiger S, Primavesi F, Göbel G, Braunwarth E, Cardini B, Maglione M, Sopper S, Öfner D, Stättner S. Early Post-Operative Pancreatitis and Systemic Inflammatory Response Assessed by Serum Lipase and IL-6 Predict Pancreatic Fistula. World J Surg 2020; 44:4236-4244. [PMID: 32901324 PMCID: PMC7599180 DOI: 10.1007/s00268-020-05768-9] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 08/16/2020] [Indexed: 02/06/2023]
Abstract
Background Post-operative pancreatic fistula (POPF) remains a critical complication after pancreatic resection. This prospective pilot study evaluates perioperative markers of pancreatitis and systemic inflammation to predict clinically relevant grade B/C-POPF (CR-POPF). Methods All patients undergoing pancreatic resection from December 2017 to April 2019 were prospectively enrolled. Surgical procedures and outcomes were correlated with perioperative blood markers. ROC analysis was performed to assess their predictive value for CR-POPF. Cut-offs were calculated with the Youden index. Results In total, 70 patients were analysed (43 pancreatoduodenectomies and 27 distal pancreatectomies). In-hospital/90-d mortality and morbidity were 5.7/7.1% (n = 4/n = 5) and 75.7% (n = 53). Major complications (Clavien–Dindo ≥ 3a) occurred in 28 (40.0%) patients, CR-POPF in 20 (28.6%) patients. Serum lipase (cut-off > 51U/L) and IL-6 (> 56.5 ng/l) on POD3 were significant predictors for CR-POPF (AUC = 0.799, 95%-CI 0.686–0.912 and AUC = 0.784, 95%-CI 0.668–0.900; combined AUC = 0.858, 95%-CI 0.758–0.958; all p < 0.001). Patients with both or one factor(s) above cut-off more frequently developed CR-POPF than cases without (100 vs. 50% vs. 7.5%, p < 0.001). This also applied for overall and severe complications (p = 0.013 and p = 0.009). Conclusions Post-operative pancreatitis and inflammatory response are major determinants for development of POPF. A combination of serum lipase and IL-6 on POD3 is a highly significant early predictor of CR-POPF and overall complications, potentially guiding patient management. Clinical trial registration The study protocol was registered at clinicaltrials.gov (NCT04294797) Electronic supplementary material The online version of this article (10.1007/s00268-020-05768-9) contains supplementary material, which is available to authorized users.
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Affiliation(s)
- S Gasteiger
- Department of Visceral, Transplant and Thoracic Surgery, Medical University of Innsbruck, Anichstrasse 35, 6020, Innsbruck, Austria
| | - F Primavesi
- Department of Visceral, Transplant and Thoracic Surgery, Medical University of Innsbruck, Anichstrasse 35, 6020, Innsbruck, Austria. .,Department of General, Vascular and Visceral Surgery, Salzkammergut Klinikum, Dr.-Wilhelm-Bock-Straße 1, 4840, Vöcklabruck, Austria.
| | - G Göbel
- Department of Medical Statistics, Informatics and Health Economics, Medical University of Innsbruck, Schoepfstrasse 41, 6020, Innsbruck, Austria
| | - E Braunwarth
- Department of Visceral, Transplant and Thoracic Surgery, Medical University of Innsbruck, Anichstrasse 35, 6020, Innsbruck, Austria
| | - B Cardini
- Department of Visceral, Transplant and Thoracic Surgery, Medical University of Innsbruck, Anichstrasse 35, 6020, Innsbruck, Austria
| | - M Maglione
- Department of Visceral, Transplant and Thoracic Surgery, Medical University of Innsbruck, Anichstrasse 35, 6020, Innsbruck, Austria
| | - S Sopper
- Department of Haematology and Oncology, Medical University of Innsbruck, Anichstrasse 35, 6020, Innsbruck, Austria
| | - D Öfner
- Department of Visceral, Transplant and Thoracic Surgery, Medical University of Innsbruck, Anichstrasse 35, 6020, Innsbruck, Austria
| | - S Stättner
- Department of Visceral, Transplant and Thoracic Surgery, Medical University of Innsbruck, Anichstrasse 35, 6020, Innsbruck, Austria.,Department of General, Vascular and Visceral Surgery, Salzkammergut Klinikum, Dr.-Wilhelm-Bock-Straße 1, 4840, Vöcklabruck, Austria
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Influence of the Retrocolic Versus Antecolic Route for Alimentary Tract Reconstruction on Delayed Gastric Emptying After Pancreatoduodenectomy: A Multicenter, Noninferiority Randomized Controlled Trial. Ann Surg 2020; 274:935-944. [PMID: 32773628 DOI: 10.1097/sla.0000000000004072] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
OBJECTIVE This study aimed to determine whether retrocolic alimentary tract reconstruction is noninferior to antecolic reconstruction in terms of DGE incidence after pancreatoduodenectomy (PD) and investigated patients' postoperative nutritional status. SUMMARY OF BACKGROUND DATA The influence of the route of alimentary tract reconstruction on DGE after PD is controversial. METHODS Patients from 9 participating institutions scheduled for PD were randomly allocated to the retrocolic or antecolic reconstruction groups. The primary outcome was incidence of DGE, defined according to the 2007 version of the International Study Group for Pancreatic Surgery definition. Noninferiority would be indicated if the incidence of DGE in the retrocolic group did not exceed that in the antecolic group by a margin of 10%. Patients' postoperative nutrition data were compared as secondary outcomes. RESULTS Total, 109 and 103 patients were allocated to the retrocolic and antecolic reconstruction group, respectively (n = 212). Baseline characteristics were similar between both groups. DGE occurred in 17 (15.6%) and 13 (12.6%) patients in the retrocolic and antecolic group, respectively (risk difference; 2.97%, 95% confidence interval; -6.3% to 12.6%, which exceeded the specified margin of 10%). There were no differences in the incidence of other postoperative complications and in the duration of hospitalization. Postoperative nutritional indices were similar between both groups. CONCLUSIONS This trial could not demonstrate the noninferiority of retrocolic to antecolic alimentary tract reconstruction in terms of DGE incidence. The alimentary tract should not be reconstructed via the retrocolic route after PD, to prevent DGE.
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Petrelli F, Zaniboni A, Ghidini A, Ghidini M, Turati L, Pizzo C, Ratti M, Libertini M, Tomasello G. Timing of Adjuvant Chemotherapy and Survival in Colorectal, Gastric, and Pancreatic Cancer. A Systematic Review and Meta-Analysis. Cancers (Basel) 2019; 11:cancers11040550. [PMID: 30999653 PMCID: PMC6520704 DOI: 10.3390/cancers11040550] [Citation(s) in RCA: 49] [Impact Index Per Article: 8.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/02/2019] [Revised: 04/13/2019] [Accepted: 04/15/2019] [Indexed: 12/18/2022] Open
Abstract
(1) Background: The optimal timing of adjuvant chemotherapy (CT) in gastrointestinal malignancies is still a matter of debate. For colorectal cancer, it is recommended to start post-operative treatment within eight weeks. The objective of this study was to assess the clinical effects of starting adjuvant CT within or after 6–8 weeks post-surgery in colorectal, gastric, and pancreatic cancer. (2) Methods: MEDLINE, EMBASE, and the Cochrane Library were searched in December 2018. Publications comparing the outcomes of patients treated with adjuvant CT administered before (early) or after (delayed) 6–8 weeks post-surgery for colorectal, gastric, and pancreatic cancer were identified. The primary endpoint was overall survival (OS). (3) Results: Out of 8752 publications identified, 34 comparative studies assessing a total of 141,853 patients were included. Meta-analysis indicated a statistically significant increased risk of death with delayed CT (>6–8 weeks post-surgery) in colorectal cancer (hazard ratio (HR) = 1.27, 95% confidence interval (CI) 1.21–1.33; p <0.001). Similarly, for gastric cancer, delaying adjuvant CT was associated with inferior overall survival (HR = 1.2, 95% CI 1.04–1.38; p = 0.01). Conversely, the benefit of earlier CT was not evident in pancreatic cancer (HR = 1, 95% CI 1–1.01; p = 0.37). Conclusions: Starting adjuvant CT within 6–8 weeks post-surgery is associated with a significant survival benefit for colorectal and gastric cancer, but not for pancreatic cancer.
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Affiliation(s)
| | | | | | | | - Luca Turati
- Surgical Oncology Unit, ASST of Bergamo, 24100 Bergamo Ovest, Italy.
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