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Article: Adjuvant radiation therapy for pancreatic cancer: a review of the old and the new.

Boyle, John / Czito, Brian / Willett, Christopher / Palta, Manisha

2015 Volume 6, Issue 4, Page(s) 436–444

Abstract: ... therapies (ATs) including chemotherapy and chemoradiation therapy (CRT) have been explored ... While adjuvant chemotherapy has been shown to consistently improve outcomes, the data regarding adjuvant radiation therapy (RT ... with pancreatic adenocarcinoma. Despite aggressive surgical management for patients deemed to be resectable, rates ...

Abstract	Surgery represents the only potential curative treatment option for patients diagnosed with pancreatic adenocarcinoma. Despite aggressive surgical management for patients deemed to be resectable, rates of local recurrence and/or distant metastases remain high, resulting in poor long-term outcomes. In an effort to reduce recurrence rates and improve survival for patients having undergone resection, adjuvant therapies (ATs) including chemotherapy and chemoradiation therapy (CRT) have been explored. While adjuvant chemotherapy has been shown to consistently improve outcomes, the data regarding adjuvant radiation therapy (RT) is mixed. Although the ability of radiation to improve local control has been demonstrated, it has not always led to improved survival outcomes for patients. Early trials are flawed in their utilization of sub-optimal radiation techniques, limiting their generalizability. Recent and ongoing trials incorporate more optimized RT approaches and seek to clarify its role in treatment strategies. At the same time novel radiation techniques such as intensity modulated RT (IMRT) and stereotactic body RT (SBRT) are under active investigation. It is hoped that these efforts will lead to improved disease-related outcomes while reducing toxicity rates.
Language	English
Publishing date	2015-08-11
Publishing country	China
Document type	Journal Article ; Review
ZDB-ID	2594644-4
ISSN	2219-679X ; 2078-6891
ISSN (online)	2219-679X
ISSN	2078-6891
DOI	10.3978/j.issn.2078-6891.2015.014
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Article: Adjuvant therapy for pancreatic cancer: a review.

Zuckerman, Dan S / Ryan, David P

Cancer

2008 Volume 112, Issue 2, Page(s) 243–249

Abstract: ... For this review, the evidence for adjuvant therapy in pancreatic cancer was examined, and the significant practice ... by the Gastrointestinal Tumor Study Group was the first to demonstrate a survival benefit from adjuvant therapy in the form ... of adjuvant chemotherapy or chemoradiation in pancreatic cancer, and the results have stirred great controversy ...

Abstract	Pancreatic cancer is uniformly fatal unless it can be surgically resected. Survival rates for the 15% to 20% of patients who have resectable disease, however, are a disappointing 10% to 30%, depending on the status of margins and surrounding lymph nodes. In the mid-1980s, a landmark study by the Gastrointestinal Tumor Study Group was the first to demonstrate a survival benefit from adjuvant therapy in the form of chemoradiation. Since then, several studies in both North America and Europe have tested the role of adjuvant chemotherapy or chemoradiation in pancreatic cancer, and the results have stirred great controversy. For this review, the evidence for adjuvant therapy in pancreatic cancer was examined, and the significant practice differences that exist between North American and European oncologists were highlighted. The authors investigated the results from the European Study Group for Pancreatic Cancer-1 trial and the reasons why that study has served to reinforce rather than resolve these trans-Atlantic differences. They also reviewed preliminary data from more recent adjuvant trials and explored the possible benefits of a neoadjuvant approach.
MeSH term(s)	Clinical Trials as Topic ; Combined Modality Therapy ; Humans ; Neoadjuvant Therapy ; Pancreatic Neoplasms/mortality ; Pancreatic Neoplasms/therapy ; Survival Rate
Language	English
Publishing date	2008-01-15
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	1429-1
ISSN	1097-0142 ; 0008-543X ; 1934-662X
ISSN (online)	1097-0142
ISSN	0008-543X ; 1934-662X
DOI	10.1002/cncr.23174
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Article ; Online: Adjuvant and neoadjuvant approaches in pancreatic cancer.

Conroy, Thierry / Lambert, Aurélien / Ducreux, Michel

Current opinion in oncology

2023 Volume 35, Issue 4, Page(s) 326–333

Abstract: Purpose of review: Pancreatic cancer treatment remains a challenging problem for surgeons and ... with resected pancreatic cancer, and limited high-level evidence support the use of neoadjuvant therapy ... of adjuvant therapy showed improvement of overall survival in both experimental and control groups ...

Abstract	Purpose of review: Pancreatic cancer treatment remains a challenging problem for surgeons and oncologists. This review aims to summarize the current advances on adjuvant and neoadjuvant treatment approaches for resectable pancreatic cancer. Recent findings: Recent phase III randomized trials of adjuvant therapy showed improvement of overall survival in both experimental and control groups. Effectiveness of adjuvant therapy in specific subgroups as elderly patients, intraductal papillary mucinous neoplasms, stage I, and DNA damage repair gene germline variants has been reported. Completion of all cycles of planned adjuvant chemotherapy is confirmed as an independent prognostic factor. Adjuvant chemotherapy remains underutilized, mainly because of early recurrence, prolonged recovery, or older age older than 75 years. So, neoadjuvant treatment is a logical approach to administer systemic treatment to more patients. Meta-analysis did not demonstrate an overall survival benefit of neoadjuvant treatments in resectable pancreatic cancer, and definitive conclusions cannot be drawn from available randomized controlled trials. Upfront surgery and adjuvant chemotherapy should still be considered a standard approach in resectable pancreatic cancer. Summary: Adjuvant chemotherapy with mFOLFIRINOX remains the standard of care in fit patients with resected pancreatic cancer, and limited high-level evidence support the use of neoadjuvant therapy in upfront resectable pancreatic cancer.
MeSH term(s)	Humans ; Aged ; Neoadjuvant Therapy ; Pancreatic Neoplasms/drug therapy ; Pancreatic Neoplasms/surgery ; Combined Modality Therapy ; Chemotherapy, Adjuvant ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Pancreatic Neoplasms
Language	English
Publishing date	2023-05-12
Publishing country	United States
Document type	Review ; Meta-Analysis ; Journal Article
ZDB-ID	1049384-0
ISSN	1531-703X ; 1040-8746
ISSN (online)	1531-703X
ISSN	1040-8746
DOI	10.1097/CCO.0000000000000962
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Article ; Online: Adjuvant Pancreatic Cancer Management

Anthony Turpin / Mehdi el Amrani / Jean-Baptiste Bachet / Daniel Pietrasz / Lilian Schwarz / Pascal Hammel

Cancers, Vol 12, Iss 3866, p

Towards New Perspectives in 2021

2020 Volume 3866

Abstract: ... resectability, promoting research in adjuvant therapy. In particular, should oncologists prescribe adjuvant ... Adjuvant chemotherapy is currently used in all patients with resected pancreatic cancer who are ... of induction treatment? The aim of this review is to summarize adjuvant management of resected ...

Abstract	Adjuvant chemotherapy is currently used in all patients with resected pancreatic cancer who are able to begin treatment within 3 months after surgery. Since the recent publication of the PRODIGE 24 trial results, modified FOLFIRINOX has become the standard-of-care in the non-Asian population with localized pancreatic adenocarcinoma following surgery. Nevertheless, there is still a risk of toxicity, and feasibility may be limited in heavily pre-treated patients. In more frail patients, gemcitabine-based chemotherapy remains a suitable option, for example gemcitabine or 5FU in monotherapy. In Asia, although S1-based chemotherapy is the standard of care it is not readily available outside Asia and data are lacking in non-Asiatic patients. In patients in whom resection is not initially possible, intensified schemes such as FOLFIRINOX or gemcitabine-nabpaclitaxel have been confirmed as options to enhance the response rate and resectability, promoting research in adjuvant therapy. In particular, should oncologists prescribe adjuvant treatment after a long sequence of chemotherapy +/– chemoradiotherapy and surgery? Should oncologists consider the response rate, the R0 resection rate alone, or the initial chemotherapy regimen? And finally, should they take into consideration the duration of the entire sequence, or the presence of limited toxicities of induction treatment? The aim of this review is to summarize adjuvant management of resected pancreatic cancer and to raise current and future concerns, especially the need for biomarkers and the best holistic care for patients.
Keywords	pancreatic cancer ; adjuvant therapy ; neoadjuvant therapy ; biomarkers ; precision medicine ; timing ; Neoplasms. Tumors. Oncology. Including cancer and carcinogens ; RC254-282
Subject code	610
Language	English
Publishing date	2020-12-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
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Article ; Online: Landscape of Health-Related Quality of Life in Patients With Early-Stage Pancreatic Cancer Receiving Adjuvant or Neoadjuvant Chemotherapy: A Systematic Literature Review.

Macarulla, Teresa / Hendifar, Andrew E / Li, Chung-Pin / Reni, Michele / Riess, Hanno / Tempero, Margaret A / Dueck, Amylou C / Botteman, Marc F / Deshpande, Chinmay G / Lucas, Eleanor J / Oh, Do-Youn

Pancreas

2020 Volume 49, Issue 3, Page(s) 393–407

Abstract: ... of life (QoL). A systematic literature review was conducted to understand the patient-reported ... outcome measure (PROM) landscape in early-stage pancreatic cancer (PC).: Methods: Databases/registries ... of Cancer QoL Questionnaire [QLQ] - Pancreatic Cancer [PAN26]).: Results: Of 750 studies identified, 39 ...

Abstract	Objectives: Pancreatic resection is associated with postoperative morbidity and reduced quality of life (QoL). A systematic literature review was conducted to understand the patient-reported outcome measure (PROM) landscape in early-stage pancreatic cancer (PC). Methods: Databases/registries (through January 24, 2019) and conference abstracts (2014-2017) were searched. Study quality was assessed using the Newcastle-Ottawa Scale/Cochrane risk-of-bias tool. Searches were for general (resectable PC, adjuvant/neoadjuvant, QoL) and supplemental studies (resectable PC, European Organisation for Research and Treatment of Cancer QoL Questionnaire [QLQ] - Pancreatic Cancer [PAN26]). Results: Of 750 studies identified, 39 (general, 22; supplemental, 17) were eligible: 32 used QLQ Core 30 (C30) and/or QLQ-PAN26, and 15 used other PROMs. Baseline QLQ-C30 global health status/QoL scores in early-stage PC were similar to all-stage PC reference values but lower than all-stage-all-cancer values. The QoL declined after surgery, recovered to baseline in 3 to 6 months, and then generally stabilized. A minimally important difference (MID) of 10 was commonly used for QLQ-C30 but was not established for QLQ-PAN26. Conclusions: In early-stage PC, QLQ-C30 and QLQ-PAN26 are the most commonly used PROMs. Baseline QLQ-C30 global health status/QoL scores suggested a high humanistic burden. Immediately after surgery, QoL declined but seemed stable over the longer term. The QLQ-C30 MID may elucidate the clinical impact of treatment on QoL; MID for QLQ-PAN26 needs to be established.
MeSH term(s)	Aged ; Chemotherapy, Adjuvant ; Female ; Health Status Indicators ; Humans ; Male ; Middle Aged ; Minimal Clinically Important Difference ; Neoadjuvant Therapy/adverse effects ; Neoplasm Staging ; Pancreatectomy/adverse effects ; Pancreatic Neoplasms/diagnosis ; Pancreatic Neoplasms/therapy ; Patient Reported Outcome Measures ; Predictive Value of Tests ; Quality of Life ; Time Factors ; Treatment Outcome
Language	English
Publishing date	2020-03-31
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Systematic Review
ZDB-ID	632831-3
ISSN	1536-4828 ; 0885-3177
ISSN (online)	1536-4828
ISSN	0885-3177
DOI	10.1097/MPA.0000000000001507
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Article: Adjuvant treatment for pancreatic cancer.

Klaiber, Ulla / Hackert, Thilo / Neoptolemos, John P

Translational gastroenterology and hepatology

2019 Volume 4, Page(s) 27

Abstract: ... therapies. This review article summarizes the body of evidence on adjuvant treatment for pancreatic cancer ... the chance for cure. Until the 1990s, adjuvant therapy was not routinely used after resection ... Pancreatic cancer is the third leading cause of cancer-associated mortality in Western countries ...

Abstract	Pancreatic cancer is the third leading cause of cancer-associated mortality in Western countries. Upfront resection with adjuvant chemotherapy is the treatment of choice in resectable tumors, offering the chance for cure. Until the 1990s, adjuvant therapy was not routinely used after resection for pancreatic cancer. During the last three decades however, enormous progress has been made in evidence-based onco-surgical management of resectable pancreatic cancer. Based on the results from multicenter randomized controlled trials, primarily initiated by the European Study Group of Pancreatic Cancer (ESPAC), adjuvant chemotherapy has become the gold standard after upfront resection, while adjuvant chemoradiotherapy is not recommended. Combination chemotherapy with gemcitabine and capecitabine was shown to significantly prolong median overall survival after resection compared to monotherapy with either gemcitabine or 5-fluorouracil/folinic acid. Recent data from the French-Canadian Uni-Cancer GI PRODIGE 24/CCTG PA.6 trial showed that adjuvant poly-agent chemotherapy with modified FOLFIRINOX achieved median survival times of 54.4 months in selected patients. Despite improved survival times after resection followed by adjuvant chemotherapy, however, recurrence occurs still in more than 75% of patients within the first 2 years after resection. Further efforts are therefore to be made in early detection tools, the evaluation of neoadjuvant strategies, the development of new drug targets, and stratification strategies to better select patients for the available therapies. This review article summarizes the body of evidence on adjuvant treatment for pancreatic cancer, identifies evidence gaps and provides future perspectives.
Language	English
Publishing date	2019-04-29
Publishing country	China
Document type	Journal Article ; Review
ISSN	2415-1289
ISSN	2415-1289
DOI	10.21037/tgh.2019.04.04
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Article ; Online: Adjuvant treatment of pancreatic cancer.

Conroy, Thierry / Ducreux, Michel

Current opinion in oncology

2019 Volume 31, Issue 4, Page(s) 346–353

Abstract: Purpose of review: Pancreatic cancer will soon become one of the most common causes of cancer ... death. Early detection of pancreatic cancer remains impossible and only 20% of patients are suitable ... for resected pancreatic cancer and demonstrated better outcomes with a gemcitabine and capecitabine combination ...

Abstract	Purpose of review: Pancreatic cancer will soon become one of the most common causes of cancer death. Early detection of pancreatic cancer remains impossible and only 20% of patients are suitable for surgery once diagnosed. Even in this specific subgroup of patients, and despite improvements in surgery, overall survival remains poor, with an 80% recurrence rate. Consequently, many attempts have been made to prevent recurrence by adding chemotherapy, radiotherapy, or both. Recent findings: Here, we will focus on results of randomized trials evaluating the role of different postoperative treatments. Over 15 years ago, a trial demonstrated that chemoradiotherapy has a deleterious effect on survival. The same trial recommended adjuvant chemotherapy with fluorouracil as standard of care. Subsequent trials sought to identify better chemotherapy regimens. Two recently published trials evaluated the role of combination therapies for resected pancreatic cancer and demonstrated better outcomes with a gemcitabine and capecitabine combination and a fluorouracil, oxaliplatin, and irinotecan combination (FOLFIRINOX) versus gemcitabine alone. Summary: Results from recent trials suggest that FOLFIRINOX should be considered standard of care for fit patients.
MeSH term(s)	Antineoplastic Combined Chemotherapy Protocols/administration & dosage ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Chemotherapy, Adjuvant ; Deoxycytidine/analogs & derivatives ; Deoxycytidine/therapeutic use ; Fluorouracil/administration & dosage ; Humans ; Irinotecan/administration & dosage ; Leucovorin/administration & dosage ; Oxaliplatin/administration & dosage ; Pancreatic Neoplasms/drug therapy ; Pancreatic Neoplasms/surgery ; Randomized Controlled Trials as Topic
Chemical Substances	folfirinox ; Oxaliplatin (04ZR38536J) ; Deoxycytidine (0W860991D6) ; Irinotecan (7673326042) ; gemcitabine (B76N6SBZ8R) ; Leucovorin (Q573I9DVLP) ; Fluorouracil (U3P01618RT)
Language	English
Publishing date	2019-04-16
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	1049384-0
ISSN	1531-703X ; 1040-8746
ISSN (online)	1531-703X
ISSN	1040-8746
DOI	10.1097/CCO.0000000000000546
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Article: Timing of Adjuvant Chemotherapy and Survival in Colorectal, Gastric, and Pancreatic Cancer. A Systematic Review and Meta-Analysis.

Petrelli, Fausto / Zaniboni, Alberto / Ghidini, Antonio / Ghidini, Michele / Turati, Luca / Pizzo, Claudio / Ratti, Margherita / Libertini, Michela / Tomasello, Gianluca

Cancers

2019 Volume 11, Issue 4

Abstract: ... adjuvant CT within or after 6-8 weeks post-surgery in colorectal, gastric, and pancreatic cancer. (2 ... surgery for colorectal, gastric, and pancreatic cancer were identified. The primary endpoint was overall survival (OS ... is still a matter of debate. For colorectal cancer, it is recommended to start post-operative ...

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;
Language	English
Publishing date	2019-04-17
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2527080-1
ISSN	2072-6694
ISSN	2072-6694
DOI	10.3390/cancers11040550
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Article ; Online: Clinical and pathological factors associated with survival in patients with pancreatic cancer who receive adjuvant therapy after neoadjuvant therapy: A retrospective multi-institutional analysis.

Shimizu, Takayuki / Maeda, Shimpei / Link, Jason / Deranteriassian, Aletta / Premji, Alykhan / Verma, Arjun / Chervu, Nikhil / Park, Joon / Girgis, Mark / Benharash, Peyman / Hines, Joe / Wainberg, Zev / Wolfgang, Christopher / Burns, William / Yu, Jun / Fernandez-Del Castillo, Carlos / Lillemoe, Keith / Ferrone, Cristina / Donahue, Timothy

Surgery

2024 Volume 175, Issue 5, Page(s) 1377–1385

Abstract: ... with pancreatic cancer who receive adjuvant therapy after neoadjuvant therapy.: Methods: This study was conducted ... In the present study, 529 patients with resected pancreatic cancer after neoadjuvant therapy were reviewed ... Background: Neoadjuvant therapy is being increasingly used for patients with pancreatic cancer ...

Abstract	Background: Neoadjuvant therapy is being increasingly used for patients with pancreatic cancer. The role of adjuvant therapy in these patients is unclear. The purpose of this study was to identify clinical and pathologic characteristics that are associated with longer overall survival in patients with pancreatic cancer who receive adjuvant therapy after neoadjuvant therapy. Methods: This study was conducted using multi-institutional data. All patients underwent surgery after at least 1 cycle of neoadjuvant therapy for pancreatic cancer. Patients who died within 3 months after surgery and were known to have distant metastasis or macroscopic residual disease were excluded. Mann-Whitney U test, χ Results: In the present study, 529 patients with resected pancreatic cancer after neoadjuvant therapy were reviewed. For neoadjuvant therapy, 177 (33.5%) patients received neoadjuvant chemotherapy, and 352 (66.5%) patients received neoadjuvant chemoradiotherapy. The median duration of neoadjuvant therapy was 7.0 months (interquartile range, 5.0-8.7). Patients were followed for a median of 23.0 months after surgery. Adjuvant therapy was administered to 297 (56.1%) patients and was not associated with longer overall survival for the entire cohort (24 vs 22 months, P = .31). Interaction analysis showed that adjuvant therapy was associated with longer overall survival in patients who received less than 4 months neoadjuvant therapy (hazard ratio 0.40; 95% confidence interval 0.17-0.95; P = .03) or who had microscopic margin positive surgical resections (hazard ratio 0.56; 95% confidence interval 0.33-0.93; P = .03). Conclusion: In this retrospective study, there was a survival benefit associated with adjuvant therapy for patients who received less than 4 months of neoadjuvant therapy or had microscopic positive margins.
MeSH term(s)	Humans ; Neoadjuvant Therapy ; Retrospective Studies ; Neoplasm Staging ; Combined Modality Therapy ; Pancreatic Neoplasms/pathology ; Chemotherapy, Adjuvant
Language	English
Publishing date	2024-02-16
Publishing country	United States
Document type	Journal Article
ZDB-ID	202467-6
ISSN	1532-7361 ; 0039-6060
ISSN (online)	1532-7361
ISSN	0039-6060
DOI	10.1016/j.surg.2024.01.008
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Article ; Online: Adjuvant Chemotherapy and Radiotherapy in Resected Pancreatic Ductal Adenocarcinoma: A Systematic Review and Clinical Practice Guideline.

Biagi, James J / Cosby, Roxanne / Bahl, Mala / Elfiki, Tarek / Goodwin, Rachel / Hallet, Julie / Hirmiz, Khalid / Mahmud, Aamer

Current oncology (Toronto, Ont.)

2023 Volume 30, Issue 7, Page(s) 6575–6586

Abstract: ... of this systematic review and guidance document was to synthesize the evidence surrounding the role of adjuvant ... Pancreatic cancer is the seventh leading cause of cancer deaths worldwide, accounting for 4.7 ... treatment (chemotherapy and chemoradiation therapy [CRT], and stereotactic body radiation therapy [SBRT ...

Abstract	Pancreatic cancer is the seventh leading cause of cancer deaths worldwide, accounting for 4.7% of all cancer deaths, and is expected to climb significantly over the next decade. The purpose of this systematic review and guidance document was to synthesize the evidence surrounding the role of adjuvant treatment (chemotherapy and chemoradiation therapy [CRT], and stereotactic body radiation therapy [SBRT]) in resected pancreatic ductal adenocarcinoma (PDAC). Systematic literature searches of MEDLINE, EMBASE, and 11 guideline databases were conducted. Both direct and indirect comparisons indicate adjuvant chemotherapy offers a survival advantage over surgery alone. The optimal regimens recommended are mFOLFIRINOX with alternative options of gemcitabine plus capecitabine, gemcitabine alone, or S-1 (which is not available in North America). Trials comparing a CRT strategy to modern chemotherapy regimens are lacking. However, current evidence demonstrates that the addition of CRT to chemotherapy does not result in a survival advantage over chemotherapy alone and is therefore not recommended. Trials evaluating SBRT in PDAC are also lacking. SBRT should only be used within a clinical trial or multi-institutional registry.
MeSH term(s)	Humans ; Deoxycytidine/therapeutic use ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Carcinoma, Pancreatic Ductal/drug therapy ; Carcinoma, Pancreatic Ductal/surgery ; Pancreatic Neoplasms/drug therapy ; Pancreatic Neoplasms/surgery ; Chemotherapy, Adjuvant ; Pancreatic Neoplasms
Chemical Substances	Deoxycytidine (0W860991D6)
Language	English
Publishing date	2023-07-08
Publishing country	Switzerland
Document type	Systematic Review ; Journal Article ; Review ; Research Support, Non-U.S. Gov't
ZDB-ID	1236972-x
ISSN	1718-7729 ; 1198-0052
ISSN (online)	1718-7729
ISSN	1198-0052
DOI	10.3390/curroncol30070482
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