|
1
|
Yamane K, Anazawa T, Nagai K, Kasai Y, Masui T, Izuwa A, Kurahashi K, Ishida S, Ogiso S, Yoshimura M, Iwai T, Matsubara J, Fukuda A, Isoda H, Hidaka Y, Ibi Y, Hatano E. Neoadjuvant Chemoradiotherapy Using Moderately Hypofractionated Intensity-Modulated Radiotherapy Versus Upfront Surgery for Resectable Pancreatic Cancer: A Retrospective Cohort Study. Ann Surg Oncol 2025:10.1245/s10434-025-16956-z. [PMID: 39893341 DOI: 10.1245/s10434-025-16956-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/05/2024] [Accepted: 01/16/2025] [Indexed: 02/04/2025]
Abstract
BACKGROUND The efficacy of neoadjuvant chemoradiotherapy for resectable pancreatic ductal adenocarcinoma (R-PDAC) remains unclear. This study was designed to evaluate neoadjuvant chemoradiotherapy by using intensity-modulated radiotherapy (NAC-IMRT) for R-PDAC compared with upfront surgery (UpS). METHODS Among 198 patients with R-PDAC who were indicated for resection between 2013 and 2021, 130 were included in this study after excluding patients who underwent neoadjuvant chemotherapy and did not meet the NAC-IMRT criteria (Eligible set). NAC-IMRT was planned for 58 patients, and UpS was planned for 72 patients. Additionally, in 105 patients who could undergo the planned treatment (As-treated set), the surgical, pathological, and oncological outcomes were evaluated. RESULTS In the Eligible set, median overall survival (OS) was 50.5 months with NAC-IMRT and 34.7 months with UpS and progression-free survival was 20.4 months with NAC-IMRT and 13.9 months with UpS. In the As-treated set, OS was longer in the NAC-IMRT group (66.7 months vs. 34.7 months, p = 0.007). On multivariate analysis, NAC-IMRT was identified as an independent factor for better OS (hazard ratio 0.617, 95% confidence interval 0.382-0.995, p = 0.047, in the Eligible set). The incidence of postoperative complications did not show a difference between the two groups, and NAC-IMRT suppressed local tumor invasion, including lymphatic, venous, perineural invasion, and lymph node metastases. CONCLUSIONS NAC-IMRT may offer superior survival outcomes and manageable toxicity in R-PDAC patients compared with upfront surgery. This study supports the efficacy and safety of NAC-IMRT and recommends its consideration in R-PDAC treatment protocols.
Collapse
Affiliation(s)
- Kei Yamane
- Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - Takayuki Anazawa
- Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
| | - Kazuyuki Nagai
- Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - Yosuke Kasai
- Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - Toshihiko Masui
- Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan
- Department of Surgery, Kurashiki Central Hospital, Okayama, Japan
| | - Aya Izuwa
- Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - Koki Kurahashi
- Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - Satoshi Ishida
- Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - Satoshi Ogiso
- Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - Michio Yoshimura
- Department of Radiation Oncology and Image-Applied Therapy, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - Takahiro Iwai
- Department of Radiation Oncology and Image-Applied Therapy, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - Junichi Matsubara
- Department of Medical Oncology, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - Akihisa Fukuda
- Department of Gastroenterology and Hepatology, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - Hiroyoshi Isoda
- Department of Diagnostic Imaging and Nuclear Medicine, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - Yu Hidaka
- Department of Biomedical Statistics and Bioinformatics, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - Yumiko Ibi
- Department of Biomedical Statistics and Bioinformatics, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - Etsuro Hatano
- Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| |
Collapse
|
|
2
|
Hays SB, Kuchta K, Abreu AA, Chopra A, Farah E, Kannan A, Mehdi SA, Radi I, Ranson K, Rieser C, Rojas AE, Tcharni A, Boone BA, Paniccia A, Polanco PM, Schmidt CR, Talamonti MS, Zeh HJ, Zureikat AH, Hogg ME. Multimodal Therapy May be Key to Improving Survival for Octogenarians Undergoing Pancreaticoduodenectomy for Pancreatic Ductal Adenocarcinoma: An American Multicenter Analysis. Ann Surg Oncol 2025:10.1245/s10434-025-16916-7. [PMID: 39871074 DOI: 10.1245/s10434-025-16916-7] [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: 09/25/2024] [Accepted: 01/07/2025] [Indexed: 01/29/2025]
Abstract
BACKGROUND As the population ages, the number of octogenarians with pancreatic ductal adenocarcinoma (PDAC) continues to rise. Morbidity and mortality following pancreatectomy have improved owing to safer surgery and better chemoradiation regimens. This study compares the outcomes and multimodality utilization in octogenarians (≥80 years) who underwent pancreaticoduodenectomy (PD) for PDAC, with a younger cohort. METHODS This is a multi-institutional retrospective review from 2007 to 2023 of patients who underwent PD for PDAC. Preoperative, perioperative, and oncologic outcomes were analyzed, and multivariable analysis (MVA) was performed. RESULTS A total of 1,051 patients underwent PD for PDAC ( ≥ 80 = 125, < 80 = 926). Octogenarians had a higher age unadjusted Charlson Comorbidity Index (p = 0.0146) and were more likely to have prior abdominal surgery (p = 0.0019). Patients <80 years received chemotherapy (p < 0.0001) or radiation (p < 0.0001), including neoadjuvant chemotherapy (p < 0.0001), more frequently than octogenarians, who more commonly underwent upfront surgery (p < 0.0001). There were no significant differences in complications. Octogenarians had a higher 90 day mortality rate (7.2% versus 3.5%, p = 0.0424); however, this was not significant on MVA. The <80 cohort had longer overall survival (OS) (p = 0.0004). Receiving any chemotherapy was associated with longer OS (hazard ratio [HR] 0.59 [0.46-0.75], p < 0.0001). In survival analysis of octogenarians only, receiving multimodal therapy significantly prolonged OS compared with surgery alone (p = 0.0349). CONCLUSIONS Octogenarian status does not increase morbidity or mortality but is associated with decreased survival in PDAC patients undergoing PD. Chemotherapy had a protective effect on OS; however, octogenarians received less multimodal therapy compared with the younger cohort.
Collapse
Affiliation(s)
- Sarah B Hays
- Department of Surgery, NorthShore University Health System, Evanston, IL, USA.
- Department of Surgery, University of Chicago, Chicago, IL, USA.
| | - Kristine Kuchta
- Department of Surgery, NorthShore University Health System, Evanston, IL, USA
| | - Andres A Abreu
- Department of Surgery, University of Texas at Southwestern, Dallas, TX, USA
| | - Asmita Chopra
- Department of Surgery, University of Pittsburgh Medical Center, Pittsburgh, PA, USA
| | - Emile Farah
- Department of Surgery, University of Texas at Southwestern, Dallas, TX, USA
| | - Amudhan Kannan
- Department of Surgery, University of Texas at Southwestern, Dallas, TX, USA
| | - Syed Abbas Mehdi
- Department of Surgery, NorthShore University Health System, Evanston, IL, USA
| | - Imad Radi
- Department of Surgery, University of Texas at Southwestern, Dallas, TX, USA
| | - Kristen Ranson
- Department of Surgery, West Virginia University, Morgantown, WV, USA
| | - Caroline Rieser
- Department of Surgery, NorthShore University Health System, Evanston, IL, USA
- Department of Surgery, University of Chicago, Chicago, IL, USA
| | - Aram E Rojas
- Department of Surgery, NorthShore University Health System, Evanston, IL, USA
| | - Adam Tcharni
- Department of Surgery, University of Pittsburgh Medical Center, Pittsburgh, PA, USA
| | - Brian A Boone
- Department of Surgery, West Virginia University, Morgantown, WV, USA
| | - Alessandro Paniccia
- Department of Surgery, University of Pittsburgh Medical Center, Pittsburgh, PA, USA
| | - Patricio M Polanco
- Department of Surgery, University of Texas at Southwestern, Dallas, TX, USA
| | - Carl R Schmidt
- Department of Surgery, West Virginia University, Morgantown, WV, USA
| | - Mark S Talamonti
- Department of Surgery, NorthShore University Health System, Evanston, IL, USA
| | - Herbert J Zeh
- Department of Surgery, University of Texas at Southwestern, Dallas, TX, USA
| | - Amer H Zureikat
- Department of Surgery, University of Pittsburgh Medical Center, Pittsburgh, PA, USA
| | - Melissa E Hogg
- Department of Surgery, NorthShore University Health System, Evanston, IL, USA
| |
Collapse
|
|
3
|
Hajibandeh S, Hajibandeh S, Evans D, Athwal TS. Meta-analysis of pancreatic re-resection for locally recurrent pancreatic cancer following index pancreatectomy. Ann Hepatobiliary Pancreat Surg 2024; 28:315-324. [PMID: 38802115 PMCID: PMC11341876 DOI: 10.14701/ahbps.24-041] [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: 02/16/2024] [Revised: 04/12/2024] [Accepted: 04/18/2024] [Indexed: 05/29/2024] Open
Abstract
The role of surgical resection in patients with recurrent pancreatic cancer is unclear. We aimed to evaluate the survival outcomes of pancreatic re-resection for locally recurrent pancreatic cancer following index pancreatectomy. A literature search was carried out in CENTRAL, EMBASE, MEDLINE, CINAHL, and Web of Science. Proportion meta-analysis model was constructed to quantify 1 to 5-year survival after pancreatic re-resection for locally recurrent pancreatic cancer. Random-effects modelling was applied to calculate pooled outcome data. Fifteen retrospective studies were included, reporting a total of 250 patients who underwent pancreatic re-resection for locally recurrent pancreatic cancer following their index pancreatectomy. Pancreatic re-resection was associated with 1-year survival 70.6% (95% confidence interval [CI], 65.0-76.2), 2-year survival 38.8% (95% CI, 28.6-49.0), 3-year survival 20.2% (95% CI, 13.8-26.7), and 5-year survival 9.2% (95% CI, 5.5-12.8). The between-study heterogeneity was insignificant in all outcome syntheses. Repeat pancreatectomy for local recurrence of pancreatic cancer in the remnant pancreas following the index pancreatectomy is associated with acceptable overall patient survival. We recommend selective re-resection of such recurrences in younger patients with favorable tumor size and location. Our findings may encourage more robust studies to be conducted in this context to provide stronger evidence.
Collapse
Affiliation(s)
- Shahin Hajibandeh
- Department of Hepatobiliary and Pancreatic Surgery, Royal Stoke University Hospital, University Hospitals of North Midlands NHS Trust, Stoke-on-Trent, UK
| | - Shahab Hajibandeh
- Department of Hepatobiliary and Pancreatic Surgery, Swansea Bay University Health Board, Swansea, UK
| | - Daisy Evans
- Department of Hepatobiliary and Pancreatic Surgery, Royal Stoke University Hospital, University Hospitals of North Midlands NHS Trust, Stoke-on-Trent, UK
| | - Tejinderjit S. Athwal
- Department of Hepatobiliary and Pancreatic Surgery, Royal Stoke University Hospital, University Hospitals of North Midlands NHS Trust, Stoke-on-Trent, UK
| |
Collapse
|
|
4
|
Yoon H, Shin Y, Ryoo BY, Jeong H, Park I, Seo DW, Lee SS, Park DH, Song TJ, Oh D, Hwang DW, Lee JH, Song KB, Park Y, Kwak BJ, Hong SM, Park JH, Kim SC, Kim KP, Yoo C. Clinical outcomes of second-line therapy following disease progression on first-line modified FOLFIRINOX for borderline resectable and locally advanced pancreatic adenocarcinoma. Pancreatology 2024; 24:424-430. [PMID: 38395676 DOI: 10.1016/j.pan.2024.02.004] [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: 11/18/2023] [Revised: 01/21/2024] [Accepted: 02/09/2024] [Indexed: 02/25/2024]
Abstract
BACKGROUND Modified FOLFIRINOX (mFOLFIRINOX) is one of the standard first-line therapies in borderline resectable pancreatic cancer (BRPC) and locally advanced unresectable pancreatic cancer (LAPC). However, there is no globally accepted second-line therapy following progression on mFOLFIRINOX. METHODS Patients with BRPC and LAPC (n = 647) treated with first-line mFOLFIRINOX between January 2017 and December 2020 were included in this retrospective analysis. The details of the treatment outcomes and patterns of subsequent therapy after mFOLFIRINOX were reviewed. RESULTS With a median follow-up duration of 44.2 months (95% confidence interval [CI], 42.3-47.6), 322 patients exhibited disease progression on mFOLFIRINOX-locoregional progression only in 177 patients (55.0%) and distant metastasis in 145 patients (45.0%). The locoregional progression group demonstrated significantly longer post-progression survival (PPS) than that of the distant metastasis group (10.1 vs. 7.3 months, p = 0.002). In the locoregional progression group, survival outcomes did not differ between second-line chemoradiation/radiotherapy and systemic chemotherapy (progression-free survival with second-line therapy [PFS-2], 3.2 vs. 4.3 months; p = 0.649; PPS, 10.7 vs. 10.2 months; p = 0.791). In patients who received second-line systemic chemotherapy following progression on mFOLFIRINOX (n = 211), gemcitabine plus nab-paclitaxel was associated with better disease control rates (69.2% vs. 42.3%, p = 0.005) and PFS-2 (3.8 vs. 1.7 months, p = 0.035) than gemcitabine monotherapy. CONCLUSIONS The current study showed the real-world practice pattern of subsequent therapy and clinical outcomes following progression on first-line mFOLFIRINOX in BRPC and LAPC. Further investigation is necessary to establish the optimal therapy after failure of mFOLFIRINOX.
Collapse
Affiliation(s)
- Hyunseok Yoon
- Departments of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea
| | - Yeokyeong Shin
- Departments of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea
| | - Baek-Yeol Ryoo
- Departments of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea
| | - Hyehyun Jeong
- Departments of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea
| | - Inkeun Park
- Departments of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea
| | - Dong-Wan Seo
- Departments of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea
| | - Sang Soo Lee
- Departments of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea
| | - Do Hyun Park
- Departments of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea
| | - Tae Jun Song
- Departments of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea
| | - Dongwook Oh
- Departments of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea
| | - Dae Wook Hwang
- Departments of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea
| | - Jae Hoon Lee
- Departments of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea
| | - Ki Byung Song
- Departments of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea
| | - Yejong Park
- Departments of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea
| | - Bong Jun Kwak
- Departments of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea
| | - Seung-Mo Hong
- Departments of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea
| | - Jin-Hong Park
- Departments of Radiation Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea
| | - Song Cheol Kim
- Departments of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea
| | - Kyu-Pyo Kim
- Departments of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea
| | - Changhoon Yoo
- Departments of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea.
| |
Collapse
|
|
5
|
Endo Y, Kitago M, Kitagawa Y. Evidence and Future Perspectives for Neoadjuvant Therapy for Resectable and Borderline Resectable Pancreatic Cancer: A Scoping Review. Cancers (Basel) 2024; 16:1632. [PMID: 38730584 PMCID: PMC11083108 DOI: 10.3390/cancers16091632] [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: 02/24/2024] [Revised: 04/18/2024] [Accepted: 04/22/2024] [Indexed: 05/13/2024] Open
Abstract
Pancreatic cancer (PC) is a lethal disease that requires innovative therapeutic approaches to enhance the survival outcomes. Neoadjuvant treatment (NAT) has gained attention for resectable and borderline resectable PC, offering improved resection rates and enabling early intervention and patient selection. Several retrospective studies have validated its efficacy. However, previous studies have lacked intention-to-treat analyses and appropriate resectability classifications. Randomized comparative trials may help to enhance the clinical applicability of evidence. Therefore, after searching the MEDLINE database, this scoping review presents a comprehensive summary of the evidence from published (n = 14) and ongoing (n = 12) randomized Phase II and III trials. Diverse regimens and their outcomes were explored for both resectable and borderline resectable PC. While some trials have supported the efficacy of NAT, others have demonstrated no clear survival benefits for patients with resectable PC. The utility of NAT has been confirmed in patients with borderline resectable PC, but the optimal regimens remain debatable. Ongoing trials are investigating novel regimens, including immunotherapy, thereby highlighting the dynamic landscape of PC treatment. Studies should focus on biomarker identification, which may enable precision in oncology. Future endeavors aim to refine treatment strategies, guided by precision oncology.
Collapse
Affiliation(s)
| | - Minoru Kitago
- Department of Surgery, Keio University School of Medicine, Shinanomachi 35, Shinjuku, Tokyo 160-8582, Japan; (Y.E.); (Y.K.)
| | | |
Collapse
|
|
6
|
Kim K, Park HC, Yu JI, Park JO, Hong JY, Lee KT, Lee KH, Lee JK, Park JK, Heo JS, Shin SH, Min JH, Kim K, Han IW. Impact and optimal timing of local therapy addition in borderline resectable or locally advanced pancreatic cancer after FOLFIRINOX chemotherapy. Clin Transl Radiat Oncol 2024; 45:100732. [PMID: 38317678 PMCID: PMC10840322 DOI: 10.1016/j.ctro.2024.100732] [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: 04/04/2023] [Revised: 01/05/2024] [Accepted: 01/18/2024] [Indexed: 02/07/2024] Open
Abstract
Background To evaluate the efficacy and optimal timing of local treatment in patients with borderline resectable (BR) or locally advanced pancreatic cancer (LAPC) treated with upfront FOLFIRINOX. Method Between 2015 and 2020, 258 patients with pancreatic ductal adenocarcinoma (PDAC) were analysed. Treatment outcomes were compared between systemic treatment group (ST) and multimodality treatment groups (MT) using Kaplan-Meier curves and log-rank test. The MT were stratified as follows: FOLFIRINOX + radiation therapy (RT) (MT1), FOLFIRINOX + surgical resection (MT2), and FOLFIRINOX + RT + surgical resection (MT3). Results With median follow-up period of 18 months, the 2-year overall survival (OS) for the ST was 22.0%, and it was significantly worse than MT (MT1, 46.3%; MT2, 65.7% and MT3; 90.2%; P < .001). The 2-year locoregional progression free survival (LRPFS) and overall PFS in ST were 10.7% and 7.0%, which were also significantly lower than those of MT (2-year LRPFS: MT1, 31.8%; MT2, 45.3%; MT3, 81.0%; 2-year overall PFS: MT1, 23.3%; MT2, 35.0%; MT3, 66.3%; P < .001). In time-varying multivariate Cox proportional hazard model, local treatment contributed to better treatment outcomes, with adjusted hazard ratios of 0.568 (95% confidence interval [CI], 0.398-0.811), 0.490 (95% CI, 0.331-0.726), and 0.656 (95% CI, 0.458-0.940) for OS, LRPFS, and overall PFS, respectively. The time window of 11-17 months after FOLFIRINOX appeared to demonstrate the maximal efficacy of local treatments in OS. Conclusions Adding local treatment in BR/LAPC patients treated with upfront FOLFIRINOX seemed to contribute in improved treatment outcomes, and it showed maximal efficacy in OS when applied 11-17 months after the initiation of FOLFIRINOX. We suggest that administration of sufficient period of upfront FOLFIRINOX may intensify the efficacy of local treatments, and well controlled prospective trials are expected.
Collapse
Affiliation(s)
- Kangpyo Kim
- Department of Radiation Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-Gu, 06351 Seoul, South Korea
| | - Hee Chul Park
- Department of Radiation Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-Gu, 06351 Seoul, South Korea
| | - Jeong Il Yu
- Department of Radiation Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-Gu, 06351 Seoul, South Korea
| | - Joon Oh Park
- Divisions of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea
| | - Jung Yong Hong
- Divisions of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea
| | - Kyu Taek Lee
- Divisions of Gastroenterology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea
| | - Kwang Hyuck Lee
- Divisions of Gastroenterology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea
| | - Jong Kyun Lee
- Divisions of Gastroenterology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea
| | - Joo Kyung Park
- Divisions of Gastroenterology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea
| | - Jin Seok Heo
- Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-Gu, 06351 Seoul, South Korea
| | - Sang Hyun Shin
- Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-Gu, 06351 Seoul, South Korea
| | - Ji Hye Min
- Department of Radiology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea
| | - Kyunga Kim
- Biomedical Statistics Center, Research Institute for Future Medicine, Samsung Medical Center, Seoul, South Korea
- Department of Digital Health, Samsung Advanced Institute for Health Sciences and Technology, Sungkyunkwan University, Seoul, South Korea
- Department of Data Convergence & Future Medicine, Sungkyunkwan University School of Medicine, Seoul, South Korea
| | - In Woong Han
- Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-Gu, 06351 Seoul, South Korea
| |
Collapse
|
|
7
|
Stoop TF, Theijse RT, Seelen LWF, Groot Koerkamp B, van Eijck CHJ, Wolfgang CL, van Tienhoven G, van Santvoort HC, Molenaar IQ, Wilmink JW, Del Chiaro M, Katz MHG, Hackert T, Besselink MG. Preoperative chemotherapy, radiotherapy and surgical decision-making in patients with borderline resectable and locally advanced pancreatic cancer. Nat Rev Gastroenterol Hepatol 2024; 21:101-124. [PMID: 38036745 DOI: 10.1038/s41575-023-00856-2] [Citation(s) in RCA: 21] [Impact Index Per Article: 21.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 10/05/2023] [Indexed: 12/02/2023]
Abstract
Surgical resection combined with systemic chemotherapy is the cornerstone of treatment for patients with localized pancreatic cancer. Upfront surgery is considered suboptimal in cases with extensive vascular involvement, which can be classified as either borderline resectable pancreatic cancer or locally advanced pancreatic cancer. In these patients, FOLFIRINOX or gemcitabine plus nab-paclitaxel chemotherapy is currently used as preoperative chemotherapy and is eventually combined with radiotherapy. Thus, more patients might reach 5-year overall survival. Patient selection for chemotherapy, radiotherapy and subsequent surgery is based on anatomical, biological and conditional parameters. Current guidelines and clinical practices vary considerably regarding preoperative chemotherapy and radiotherapy, response evaluation, and indications for surgery. In this Review, we provide an overview of the clinical evidence regarding disease staging, preoperative therapy, response evaluation and surgery in patients with borderline resectable pancreatic cancer or locally advanced pancreatic cancer. In addition, a clinical work-up is proposed based on the available evidence and guidelines. We identify knowledge gaps and outline a proposed research agenda.
Collapse
Affiliation(s)
- Thomas F Stoop
- Amsterdam UMC, location University of Amsterdam, Department of Surgery, Amsterdam, Netherlands
- Cancer Center Amsterdam, Amsterdam, Netherlands
- Division of Surgical Oncology, Department of Surgery, University of Colorado, Anschutz Medical Campus, Aurora, CO, USA
| | - Rutger T Theijse
- Amsterdam UMC, location University of Amsterdam, Department of Surgery, Amsterdam, Netherlands
- Cancer Center Amsterdam, Amsterdam, Netherlands
| | - Leonard W F Seelen
- Department of Surgery, Regional Academic Cancer Center Utrecht, University Medical Center Utrecht and St. Antonius Hospital Nieuwegein, Utrecht, Netherlands
| | - Bas Groot Koerkamp
- Department of Surgery, Erasmus MC Cancer Institute, Erasmus Medical Center, Rotterdam, Netherlands
| | - Casper H J van Eijck
- Department of Surgery, Erasmus MC Cancer Institute, Erasmus Medical Center, Rotterdam, Netherlands
| | - Christopher L Wolfgang
- Division of Surgical Oncology, Department of Surgery, New York University Medical Center, New York City, NY, USA
| | - Geertjan van Tienhoven
- Cancer Center Amsterdam, Amsterdam, Netherlands
- Amsterdam UMC, location University of Amsterdam, Department of Radiation Oncology, Amsterdam, Netherlands
| | - Hjalmar C van Santvoort
- Department of Surgery, Regional Academic Cancer Center Utrecht, University Medical Center Utrecht and St. Antonius Hospital Nieuwegein, Utrecht, Netherlands
| | - I Quintus Molenaar
- Department of Surgery, Regional Academic Cancer Center Utrecht, University Medical Center Utrecht and St. Antonius Hospital Nieuwegein, Utrecht, Netherlands
| | - Johanna W Wilmink
- Cancer Center Amsterdam, Amsterdam, Netherlands
- Amsterdam UMC, location University of Amsterdam, Department of Medical Oncology, Amsterdam, Netherlands
| | - Marco Del Chiaro
- Division of Surgical Oncology, Department of Surgery, University of Colorado, Anschutz Medical Campus, Aurora, CO, USA
| | - Matthew H G Katz
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Thilo Hackert
- Department of General, Visceral and Transplantation Surgery, University of Heidelberg, Heidelberg, Germany
- Department of General, Visceral and Thoracic Surgery, University Hospital Hamburg-Eppendorf, Hamburg, Germany
| | - Marc G Besselink
- Amsterdam UMC, location University of Amsterdam, Department of Surgery, Amsterdam, Netherlands.
- Cancer Center Amsterdam, Amsterdam, Netherlands.
| |
Collapse
|
|
8
|
Sugawara T, Rodriguez Franco S, Sherman S, Torphy RJ, Colborn K, Franklin O, Ishida J, Grandi S, Al-Musawi MH, Gleisner A, Schulick RD, Del Chiaro M. Neoadjuvant Chemotherapy Versus Upfront Surgery for Resectable Pancreatic Adenocarcinoma: An Updated Nationwide Study. Ann Surg 2024; 279:331-339. [PMID: 37226812 DOI: 10.1097/sla.0000000000005925] [Citation(s) in RCA: 5] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/26/2023]
Abstract
OBJECTIVE The objective of this study was to assess the association of survival with neoadjuvant chemotherapy (NAC) in resectable pancreatic adenocarcinoma (PDAC). BACKGROUND The early control of potential micrometastases and patient selection using NAC has been advocated for patients with PDAC. However, the role of NAC for resectable PDAC remains unclear. METHODS Patients with clinical T1 and T2 PDAC were identified in the National Cancer Database from 2010 to 2017. Kaplan-Meier estimates, and Cox regression models were used to compare survival. To address immortal time bias, landmark analysis was performed. Interactions between preoperative factors and NAC were investigated in subgroup analyses. A propensity score analysis was performed to compare survival between multiagent NAC and upfront surgery. RESULTS In total, 4041 patients were treated with upfront surgery and 1,175 patients were treated with NAC (79.4% multiagent NAC, 20.6% single-agent NAC). Using a landmark time of 6 months after diagnosis, patients treated with multiagent NAC had longer median overall survival compared with upfront surgery and single-agent NAC. (35.8 vs 27.1 vs 27.4 mo). Multiagent NAC was associated with lower mortality rates compared with upfront surgery (adjusted hazard ratio, 0.77; 95% CI, 0.70-0.85), whereas single-agent NAC was not. The association of survival with multiagent NAC were consistent in analyses using the matched data sets. Interaction analysis revealed that the association between multiagent NAC and a lower mortality rate did not significantly differ across age, facility type, tumor location, CA 19-9 levels, and clinical T/N stages. CONCLUSIONS The findings suggest that multiagent NAC followed by resection is associated with improved survival compared with upfront surgery.
Collapse
Affiliation(s)
- Toshitaka Sugawara
- Division of Surgical Oncology, Department of Surgery, University of Colorado School of Medicine, Aurora, CO
- Department of Hepatobiliary and Pancreatic Surgery, Graduate School of Medicine, Tokyo Medical and Dental University, Tokyo, Japan
| | - Salvador Rodriguez Franco
- Division of Surgical Oncology, Department of Surgery, University of Colorado School of Medicine, Aurora, CO
| | - Samantha Sherman
- Department of Surgery, Parkview Hospital Randallia, Fort Wayne, IN
| | - Robert J Torphy
- Department of Surgery, University of Colorado School of Medicine, Aurora, CO
| | - Kathryn Colborn
- Division of Surgical Oncology, Department of Surgery, University of Colorado School of Medicine, Aurora, CO
- Department of Biostatistics and Informatics, University of Colorado School of Medicine, Aurora, CO
- Surgical Outcomes and Applied Research Program, University of Colorado School of Medicine, Anschutz Medical Campus, Aurora, CO
| | - Oskar Franklin
- Division of Surgical Oncology, Department of Surgery, University of Colorado School of Medicine, Aurora, CO
- Department of Surgical and Perioperative Sciences, Surgery, Umeå University, Umeå, Sweden
| | - Jun Ishida
- Division of Surgical Oncology, Department of Surgery, University of Colorado School of Medicine, Aurora, CO
| | - Samuele Grandi
- Division of Surgical Oncology, Department of Surgery, University of Colorado School of Medicine, Aurora, CO
| | | | - Ana Gleisner
- Division of Surgical Oncology, Department of Surgery, University of Colorado School of Medicine, Aurora, CO
- University of Colorado Cancer Center, University of Colorado School of Medicine, Aurora, CO
| | - Richard D Schulick
- Surgical Outcomes and Applied Research Program, University of Colorado School of Medicine, Anschutz Medical Campus, Aurora, CO
- University of Colorado Cancer Center, University of Colorado School of Medicine, Aurora, CO
| | - Marco Del Chiaro
- Division of Surgical Oncology, Department of Surgery, University of Colorado School of Medicine, Aurora, CO
- University of Colorado Cancer Center, University of Colorado School of Medicine, Aurora, CO
| |
Collapse
|
|
9
|
Leonhardt CS, Hank T, Pils D, Gustorff C, Sahora K, Schindl M, Verbeke CS, Strobel O, Klaiber U. Prognostic impact of resection margin status on survival after neoadjuvant treatment for pancreatic cancer: systematic review and meta-analysis. Int J Surg 2024; 110:453-463. [PMID: 38315795 PMCID: PMC10793837 DOI: 10.1097/js9.0000000000000792] [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: 07/04/2023] [Accepted: 09/10/2023] [Indexed: 02/07/2024]
Abstract
BACKGROUND A greater than 1 mm tumour-free resection margin (R0 >1 mm) is a prognostic factor in upfront-resected pancreatic ductal adenocarcinoma. After neoadjuvant treatment (NAT); however, the prognostic impact of resection margin (R) status remains controversial. METHODS Randomised and non-randomised studies assessing the association of R status and survival in resected pancreatic ductal adenocarcinoma after NAT were sought by systematic searches of MEDLINE, Web of Science and CENTRAL. Hazard ratios (HR) and their corresponding 95% CI were collected to generate log HR using the inverse-variance method. Random-effects meta-analyses were performed and the results presented as weighted HR. Sensitivity and meta-regression analyses were conducted to account for different surgical procedures and varying length of follow-up, respectively. RESULTS Twenty-two studies with a total of 4929 patients were included. Based on univariable data, R0 greater than 1 mm was significantly associated with prolonged overall survival (OS) (HR 1.76, 95% CI 1.57-1.97; P<0.00001) and disease-free survival (DFS) (HR 1.66, 95% CI 1.39-1.97; P<0.00001). Using adjusted data, R0 greater than 1 mm was significantly associated with prolonged OS (HR 1.65, 95% CI 1.39-1.97; P<0.00001) and DFS (HR 1.76, 95% CI 1.30-2.39; P=0.0003). Results for R1 direct were comparable in the entire cohort; however, no prognostic impact was detected in sensitivity analysis including only partial pancreatoduodenectomies. CONCLUSION After NAT, a tumour-free margin greater than 1 mm is independently associated with improved OS as well as DFS in patients undergoing surgical resection for pancreatic cancer.
Collapse
Affiliation(s)
- Carl-Stephan Leonhardt
- Department of General Surgery, Division of Visceral Surgery, Medical University of Vienna, Vienna, Austria
| | - Thomas Hank
- Department of General Surgery, Division of Visceral Surgery, Medical University of Vienna, Vienna, Austria
| | - Dietmar Pils
- Department of General Surgery, Division of Visceral Surgery, Medical University of Vienna, Vienna, Austria
| | - Charlotte Gustorff
- Department of General Surgery, Division of Visceral Surgery, Medical University of Vienna, Vienna, Austria
| | - Klaus Sahora
- Department of General Surgery, Division of Visceral Surgery, Medical University of Vienna, Vienna, Austria
| | - Martin Schindl
- Department of General Surgery, Division of Visceral Surgery, Medical University of Vienna, Vienna, Austria
| | - Caroline S. Verbeke
- Department of Pathology, Institute of Clinical Medicine, University of Oslo, Oslo, Norway
| | - Oliver Strobel
- Department of General Surgery, Division of Visceral Surgery, Medical University of Vienna, Vienna, Austria
| | - Ulla Klaiber
- Department of General Surgery, Division of Visceral Surgery, Medical University of Vienna, Vienna, Austria
| |
Collapse
|
|
10
|
Aitken GL, Motta M, Samuels S, Reynolds PT, Gannon CJ, Llaguna OH. Impact of Palliative Interventions on Survival of Patients with Unresected Pancreatic Cancer: Review of the 2010-2016 National Cancer Database. Am J Hosp Palliat Care 2023; 40:1357-1364. [PMID: 37132387 DOI: 10.1177/10499091231174620] [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: 05/04/2023] Open
Abstract
INTRODUCTION Palliative interventions (PI) are offered to patients with pancreatic cancer with the aim of enhancing quality of life and improving overall survival (OS). The purpose of this study was to determine the impact of PI on survival amongst patients with unresected pancreatic cancer. METHODS Patients with stage I-IV unresected pancreatic adenocarcinoma were identified using the 2010-2016 National Cancer Database. The cohort was stratified by PI received: palliative surgery (PS), radiation therapy (RT), chemotherapy (CT), pain management (PM), or a combination (COM) of the preceding. Kaplan-Meier method with log-rank test was used to compare and estimate OS based on the PI received. A multivariate proportional hazards model was utilized to identify predictors of survival. RESULTS 25,995 patients were identified, of which 24.3% received PS, 7.7% RT, 40.8% CT, 16.6% PM, and 10.6% COM. The median OS was 4.9 months, with stage III patients having the highest and stage IV the lowest OS (7.8 vs 4.0 months). Across all stages, PM yielded the lowest median OS and CT the highest (P < .001). Despite this, the stage IV cohort was the only group in which CT (81%) accounted for the largest proportion of PI received (P < .001). Although all PI were identified as positive predictors of survival on multivariate analysis, CT had the strongest association (HR .43; 95% CI, .55-.60, P = .001). CONCLUSION PI offers a survival advantage to patients with pancreatic adenocarcinoma. Further studies to examine the observed limited use of CT in earlier disease stages are warranted.
Collapse
Affiliation(s)
- Gabriela L Aitken
- Department of Surgery, Memorial Healthcare System, Hollywood, FL, USA
| | - Monique Motta
- Department of Surgery, Memorial Healthcare System, Hollywood, FL, USA
| | - Shenae Samuels
- Office of Human Research, Memorial Healthcare System, Hollywood, FL, USA
| | - Patrick T Reynolds
- Oncology Supportive Care Services, Memorial Healthcare System, Hollywood, FL, USA
| | | | - Omar H Llaguna
- Division of Surgical Oncology, Memorial Healthcare System, Hollywood, FL, USA
| |
Collapse
|
|
11
|
Jayaraman S, Montagne JM, Nirschl TR, Marcisak E, Johnson J, Huff A, Hsiao MH, Nauroth J, Heumann T, Zarif JC, Jaffee EM, Azad N, Fertig EJ, Zaidi N, Larman HB. Barcoding intracellular reverse transcription enables high-throughput phenotype-coupled T cell receptor analyses. CELL REPORTS METHODS 2023; 3:100600. [PMID: 37776855 PMCID: PMC10626196 DOI: 10.1016/j.crmeth.2023.100600] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/01/2022] [Revised: 03/23/2023] [Accepted: 09/07/2023] [Indexed: 10/02/2023]
Abstract
Assays linking cellular phenotypes with T cell or B cell antigen receptor sequences are crucial for characterizing adaptive immune responses. Existing methodologies are limited by low sample throughput and high cost. Here, we present INtraCEllular Reverse Transcription with Sorting and sequencing (INCERTS), an approach that combines molecular indexing of receptor repertoires within intact cells and fluorescence-activated cell sorting (FACS). We demonstrate that INCERTS enables efficient processing of millions of cells from pooled human peripheral blood mononuclear cell (PBMC) samples while retaining robust association between T cell receptor (TCR) sequences and cellular phenotypes. We used INCERTS to discover antigen-specific TCRs from patients with cancer immunized with a novel mutant KRAS peptide vaccine. After ex vivo stimulation, 28 uniquely barcoded samples were pooled prior to FACS into peptide-reactive and non-reactive CD4+ and CD8+ populations. Combining complementary patient-matched single-cell RNA sequencing (scRNA-seq) data enabled retrieval of full-length, paired TCR alpha and beta chain sequences for future validation of therapeutic utility.
Collapse
Affiliation(s)
- Sahana Jayaraman
- Institute for Cell Engineering, Division of Immunology, Department of Pathology, Johns Hopkins School of Medicine, Baltimore, MD 21205, USA; Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
| | - Janelle M Montagne
- Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Convergence Institute, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Bloomberg Kimmel Immunology Institute, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Division of Quantitative Sciences, Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
| | - Thomas R Nirschl
- Pathobiology Graduate Program, Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Bloomberg∼Kimmel Institute for Cancer Immunotherapy, Johns Hopkins Medicine Sidney Kimmel Comprehensive Cancer Center, Baltimore, MD 21205, USA
| | - Emily Marcisak
- Convergence Institute, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Department of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Jeanette Johnson
- Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Department of Immunology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
| | - Amanda Huff
- Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Convergence Institute, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Bloomberg Kimmel Immunology Institute, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
| | - Meng-Hsuan Hsiao
- Institute for Cell Engineering, Division of Immunology, Department of Pathology, Johns Hopkins School of Medicine, Baltimore, MD 21205, USA
| | - Julie Nauroth
- Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
| | - Thatcher Heumann
- Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Division of Hematology Oncology, Vanderbilt-Ingram Comprehensive Cancer Center, Vanderbilt University Medical Center, Nashville, TN, USA
| | - Jelani C Zarif
- Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Bloomberg∼Kimmel Institute for Cancer Immunotherapy, Johns Hopkins Medicine Sidney Kimmel Comprehensive Cancer Center, Baltimore, MD 21205, USA
| | - Elizabeth M Jaffee
- Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Convergence Institute, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Bloomberg Kimmel Immunology Institute, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
| | - Nilo Azad
- Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Convergence Institute, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Bloomberg Kimmel Immunology Institute, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
| | - Elana J Fertig
- Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Convergence Institute, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Division of Quantitative Sciences, Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Department of Applied Mathematics and Statistics, Johns Hopkins University, Baltimore, MD 21218, USA; Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
| | - Neeha Zaidi
- Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Convergence Institute, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Bloomberg Kimmel Immunology Institute, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
| | - H Benjamin Larman
- Institute for Cell Engineering, Division of Immunology, Department of Pathology, Johns Hopkins School of Medicine, Baltimore, MD 21205, USA.
| |
Collapse
|
|
12
|
Su YY, Chao YJ, Wang CJ, Liao TK, Su PJ, Huang CJ, Chiang NJ, Yu YT, Tsai HM, Chen LT, Shan YS. The experience of neoadjuvant chemotherapy versus upfront surgery in resectable pancreatic cancer: a cross sectional study. Int J Surg 2023; 109:2614-2623. [PMID: 37300888 PMCID: PMC10498854 DOI: 10.1097/js9.0000000000000495] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/08/2023] [Accepted: 05/11/2023] [Indexed: 06/12/2023]
Abstract
BACKGROUND Upfront resection (UR) followed by adjuvant chemotherapy remains the standard treatment for resectable pancreatic cancer. There is increasing evidence suggesting favourable outcomes toward neoadjuvant chemotherapy (NAC) followed by surgery. METHODS All clinical staging with resectable pancreatic cancer patients treated at a tertiary medical centre from 2013 to 2020 were identified. The baseline characteristics, treatment course, surgery outcome and survival results of UR or NAC were compared. RESULTS Finally, in 159 resectable patients, 46 patients (29%) underwent NAC and 113 patients (71%) received UR. In NAC, 11 patients (24%) did not receive resection, 4 (36.4%) for comorbidity, 2 (18.2%) for patient refusal and 2 (18.2%) for disease progression. In UR, 13 patients (12%) were unresectable intraoperatively; 6 (46.2%) for locally advanced and 5 (38.5%) for distant metastasis. Overall, 97% of patients in NAC and 58% of patients in UR completed adjuvant chemotherapy. As of data cut-off, 24 patients (69%) in NAC and 42 patients (29%) in UR were still tumour free. The median recurrence-free survival in NAC, UR with adjuvant chemotherapy and without adjuvant chemotherapy were 31.3 months (95% CI, 14.4-not estimable), 10.6 months (95% CI, 9.0-14.3) and 8.5 months (95% CI, 5.8-11.8), P =0.036; and the median overall survival in each group were not reached (95% CI, 29.7-not estimable), 25.9 months (95% CI, 21.1-40.5) and 21.7 months (12.0-32.8), P =0.0053. Based on initial clinical staging, the median overall survival of NAC was not significantly different from UR with a tumour less than or equal to 2 cm, P =0.29. NAC patients had a higher R0 resection rate (83% versus 53%), lower recurrence rate (31% versus 71%) and harvested median number lymph node (23 versus 15). CONCLUSION This study demonstrates that NAC is superior to UR in resectable pancreatic cancer with better survival.
Collapse
Affiliation(s)
- Yung-Yeh Su
- Departments of Oncology
- Institute of Clinical Medicine, College of Medicine, National Cheng Kung University
- National Institute of Cancer Research, National Health Research Institute, Tainan
- Center for Cancer Research, Kaohsiung Medical University, Kaohsiung, Taiwan
| | | | - Chih-Jung Wang
- Surgery
- Institute of Clinical Medicine, College of Medicine, National Cheng Kung University
| | - Ting-Kai Liao
- Surgery
- Institute of Clinical Medicine, College of Medicine, National Cheng Kung University
| | | | - Chien-Jui Huang
- Internal Medicine
- Institute of Clinical Medicine, College of Medicine, National Cheng Kung University
| | - Nai-Jung Chiang
- National Institute of Cancer Research, National Health Research Institute, Tainan
- Department of Oncology, Taipei Veterans General Hospital, Taipei
- School of Medicine, College of Medicine, National Yang Ming Chiao Tung University, Taipei
| | | | - Hong-Ming Tsai
- Medical Imaging, National Cheng-Kung University Hospital
| | - Li-Tzong Chen
- Departments of Oncology
- National Institute of Cancer Research, National Health Research Institute, Tainan
- Department of Internal Medicine, Kaohsiung Medical University Hospital
- Center for Cancer Research, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Yan-Shen Shan
- Surgery
- Institute of Clinical Medicine, College of Medicine, National Cheng Kung University
| |
Collapse
|
|
13
|
Chen EY, Kardosh A, Nabavizadeh N, Foster B, Mayo SC, Billingsley KG, Gilbert EW, Lanciault C, Grossberg A, Bensch KG, Maynard E, Anderson EC, Sheppard BC, Thomas CR, Lopez CD, Vaccaro GM. Phase 2 study of preoperative chemotherapy with nab-paclitaxel and gemcitabine followed by chemoradiation for borderline resectable or node-positive pancreatic ductal adenocarcinoma. Cancer Med 2023; 12:12986-12995. [PMID: 37132281 PMCID: PMC10315770 DOI: 10.1002/cam4.5971] [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: 12/28/2022] [Revised: 03/30/2023] [Accepted: 04/10/2023] [Indexed: 05/04/2023] Open
Abstract
BACKGROUND Neoadjuvant treatment with nab-paclitaxel and gemcitabine for potentially operable pancreatic adenocarcinoma has not been well studied in a prospective interventional trial and could down-stage tumors to achieve negative surgical margins. METHODS A single-arm, open-label phase 2 trial (NCT02427841) enrolled patients with pancreatic adenocarcinoma deemed to be borderline resectable or clinically node-positive from March 17, 2016 to October 5, 2019. Patients received preoperative gemcitabine 1000 mg/m2 and nab-paclitaxel 125 mg/m2 on Days 1, 8, 15, every 28 days for two cycles followed by chemoradiation with 50.4 Gy intensity-modulated radiation over 28 fractions with concurrent fluoropyrimidine chemotherapy. After definitive resection, patients received four additional cycles of gemcitabine and nab-paclitaxel. The primary endpoint was R0 resection rate. Other endpoints included treatment completion rate, resection rate, radiographic response rate, survival, and adverse events. RESULTS Nineteen patients were enrolled, with the majority having head of pancreas primary tumors, both arterial and venous vasculature involvement, and clinically positive nodes on imaging. Among them, 11 (58%) underwent definitive resection and eight of 19 (42%) achieved R0 resection. Disease progression and functional decline were primary reasons for deferring surgical resection after neoadjuvant treatment. Pathologic near-complete response was observed in two of 11 (18%) resection specimens. Among the 19 patients, the 12-month progression-free survival was 58%, and 12-month overall survival was 79%. Common adverse events were alopecia, nausea, vomiting, fatigue, myalgia, peripheral neuropathy, rash, and neutropenia. CONCLUSION Gemcitabine and nab-paclitaxel followed by long-course chemoradiation represents a feasible neoadjuvant treatment strategy for borderline resectable or node-positive pancreatic cancer.
Collapse
Affiliation(s)
- Emerson Y. Chen
- Division of Hematology and Medical OncologyOregon Health & Science University, Knight Cancer InstitutePortlandOregonUSA
| | - Adel Kardosh
- Division of Hematology and Medical OncologyOregon Health & Science University, Knight Cancer InstitutePortlandOregonUSA
| | - Nima Nabavizadeh
- Department of Radiation MedicineOregon Health & Science UniversityPortlandOregonUSA
| | - Bryan Foster
- Department of Diagnostic RadiologyOregon Health & Science UniversityPortlandOregonUSA
| | - Skye C. Mayo
- Division of Surgical OncologyOregon Health & Science University, Knight Cancer InstitutePortlandOregonUSA
| | | | - Erin W. Gilbert
- Division of Gastrointestinal and General SurgeryOregon Health & Science UniversityPortlandOregonUSA
| | | | - Aaron Grossberg
- Department of Radiation MedicineOregon Health & Science UniversityPortlandOregonUSA
| | | | | | - Eric C. Anderson
- Division of Hematology and Medical OncologyOregon Health & Science University, Knight Cancer InstitutePortlandOregonUSA
| | - Brett C. Sheppard
- Division of Gastrointestinal and General SurgeryOregon Health & Science UniversityPortlandOregonUSA
| | - Charles R. Thomas
- Department of Radiation MedicineOregon Health & Science UniversityPortlandOregonUSA
- Radiation OncologyGeisel School of Medicine at Dartmouth and Dartmouth Cancer CenterNew HampshireLebanonUSA
| | - Charles D. Lopez
- Division of Hematology and Medical OncologyOregon Health & Science University, Knight Cancer InstitutePortlandOregonUSA
| | - Gina M. Vaccaro
- Division of Hematology and Medical OncologyOregon Health & Science University, Knight Cancer InstitutePortlandOregonUSA
- Providence Cancer InstitutePortlandOregonUSA
| | | |
Collapse
|
|
14
|
Mercanti L, Sindaco M, Mazzone M, Di Marcantonio MC, Piscione M, Muraro R, Mincione G. PDAC, the Influencer Cancer: Cross-Talk with Tumor Microenvironment and Connected Potential Therapy Strategies. Cancers (Basel) 2023; 15:2923. [PMID: 37296886 PMCID: PMC10251917 DOI: 10.3390/cancers15112923] [Citation(s) in RCA: 13] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/08/2023] [Revised: 05/18/2023] [Accepted: 05/24/2023] [Indexed: 06/12/2023] Open
Abstract
Pancreatic ductal adenocarcinoma (PDAC) is among the leading causes of death by cancer in the world. What makes this pathological condition particularly lethal is a combination of clinical and molecular heterogeneity, lack of early diagnostic indexes, and underwhelming results from current therapeutic protocols. A major cause of PDAC chemoresistance seems to lie in the ability of cancer cells to spread out and fill the pancreatic parenchyma, exchanging nutrients, substrates, and even genetic material with cells from the surrounding tumor microenvironment (TME). Several components can be found in the TME ultrastructure, including collagen fibers, cancer-associated fibroblasts, macrophages, neutrophils, mast cells, and lymphocytes. Cross-talk between PDAC and TME cells results in the latter being converted into cancer-favoring phenotypes; this behavior could be compared to an influencer guiding followers into supporting his activity. Moreover, TME could be a potential target for some of the newest therapeutic strategies; these include the use of pegvorhyaluronidase-α and CAR-T lymphocytes against HER2, FAP, CEA, MLSN, PSCA, and CD133. Other experimental therapy options are being currently studied, aiming to interfere with the KRAS pathway, DNA-repairing proteins, and apoptosis resistance in PDAC cells. Hopefully these new approaches will grant better clinical outcomes in future patients.
Collapse
Affiliation(s)
- Leonardo Mercanti
- Department of Innovative Technologies in Medicine & Dentistry, University “G. d’Annunzio” of Chieti–Pescara, 66100 Chieti, Italy; (L.M.); (M.S.); (M.M.)
| | - Maria Sindaco
- Department of Innovative Technologies in Medicine & Dentistry, University “G. d’Annunzio” of Chieti–Pescara, 66100 Chieti, Italy; (L.M.); (M.S.); (M.M.)
| | - Mariangela Mazzone
- Department of Innovative Technologies in Medicine & Dentistry, University “G. d’Annunzio” of Chieti–Pescara, 66100 Chieti, Italy; (L.M.); (M.S.); (M.M.)
| | - Maria Carmela Di Marcantonio
- Department of Innovative Technologies in Medicine & Dentistry, University “G. d’Annunzio” of Chieti–Pescara, 66100 Chieti, Italy; (L.M.); (M.S.); (M.M.)
| | | | - Raffaella Muraro
- Department of Innovative Technologies in Medicine & Dentistry, University “G. d’Annunzio” of Chieti–Pescara, 66100 Chieti, Italy; (L.M.); (M.S.); (M.M.)
| | - Gabriella Mincione
- Department of Innovative Technologies in Medicine & Dentistry, University “G. d’Annunzio” of Chieti–Pescara, 66100 Chieti, Italy; (L.M.); (M.S.); (M.M.)
| |
Collapse
|
|
15
|
Liu H, D'Alesio M, AlMasri S, Hammad A, Desilva A, Lebowitz S, Rieser C, Ashwat E, Hampton E, Khachfe H, Laffey M, Singhi A, Bahary N, Lee K, Zureikat A, Paniccia A. No survival benefit with suboptimal CA19-9 response: defining effective neoadjuvant chemotherapy in resectable or borderline resectable pancreatic cancer. HPB (Oxford) 2023; 25:521-532. [PMID: 36804826 PMCID: PMC11232030 DOI: 10.1016/j.hpb.2023.01.016] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/24/2022] [Revised: 11/14/2022] [Accepted: 01/30/2023] [Indexed: 02/23/2023]
Abstract
BACKGROUND/PURPOSE Neoadjuvant chemotherapy (NAC) is gaining popularity over a surgery-first (SF) approach in treating resectable and borderline resectable pancreatic ductal adenocarcinoma (PDAC). However, what constitutes effective neoadjuvant chemotherapy is unknown. METHODS We retrospectively analyzed resectable and borderline resectable PDAC patients who underwent pancreaticoduodenectomy (2010-2019) at a single institution. Optimal CA19-9 response was defined as normalization AND >50% reduction. We utilized Kaplan-Meier and multivariable-adjusted Cox models and competing risk subdistribution methods for statistical analysis. RESULTS 586 patients were included in this study. The multivariable-adjusted analysis demonstrated OS benefit in the NAC group only when OS was calculated from diagnosis (HR = 0.72, p = 0.02), but not from surgery (HR = 0.81, p = 0.1). However, in 59 patients who achieved optimal CA19-9 response, OS is significantly longer than the 134 patients with suboptimal CA19-9 response (39.3 m vs. 21.5 m, p = 0.005) or the 117 SF patients (39.3 m vs. 19.5 m, p < 0.001). Notably, a suboptimal CA19-9 response conferred no OS advantage compared to SF patients. The accumulative incidence of liver metastases (but not other metastases) was significantly reduced only in patients with optimal CA19-9 response to NAC (multivariable-adjusted subdistribution HR = 0.26, p = 0.03). CONCLUSION CA19-9 response to NAC may serve as the marker for effective NAC. These findings warrant validation in a multi-institutional study.
Collapse
Affiliation(s)
- Hao Liu
- Department of Surgery, University of Pittsburgh Medical Center (UPMC), United States
| | - Mark D'Alesio
- School of Medicine, University of Pittsburgh, United States
| | - Samer AlMasri
- Department of Surgery, University of Pittsburgh Medical Center (UPMC), United States
| | - Abdulrahman Hammad
- Department of Surgery, University of Pittsburgh Medical Center (UPMC), United States
| | - Annissa Desilva
- Department of Surgery, University of Pittsburgh Medical Center (UPMC), United States
| | | | - Caroline Rieser
- Department of Surgery, University of Pittsburgh Medical Center (UPMC), United States
| | - Eishan Ashwat
- School of Medicine, University of Pittsburgh, United States
| | - Erica Hampton
- School of Medicine, University of Pittsburgh, United States
| | - Hussein Khachfe
- Department of Surgery, University of Pittsburgh Medical Center (UPMC), United States
| | - Mckenna Laffey
- School of Medicine, University of Pittsburgh, United States
| | - Aatur Singhi
- Department of Pathology, University of Pittsburgh Medical Center, United States
| | - Nathan Bahary
- Department of Medicine, University of Pittsburgh Medical Center, United States
| | - Kenneth Lee
- Department of Surgery, University of Pittsburgh Medical Center (UPMC), United States
| | - Amer Zureikat
- Department of Surgery, University of Pittsburgh Medical Center (UPMC), United States
| | - Alessandro Paniccia
- Department of Surgery, University of Pittsburgh Medical Center (UPMC), United States.
| |
Collapse
|
|
16
|
Park J, Kim HY, Na HY, Lee JS, Lee JC, Kim JW, Yoon YS, Hwang JH, Han HS, Kim J. Continued adjuvant FOLFIRINOX for BRPC or LAPC after neoadjuvant FOLFIRINOX. J Cancer Res Clin Oncol 2023; 149:1765-1775. [PMID: 35723728 DOI: 10.1007/s00432-022-04108-9] [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] [Received: 03/31/2022] [Accepted: 05/31/2022] [Indexed: 10/18/2022]
Abstract
PURPOSE We aimed to assess the role of adjuvant FOLFIRINOX, in comparison with other adjuvant therapy, in patients who received neoadjuvant FOLFIRINOX and surgery for borderline resectable or locally advanced pancreatic cancer (BRPC or LAPC). METHODS Our target population was patients with BRPC or LAPC, who received adjuvant therapy following neoadjuvant FOLFIRINOX and surgery between June 2013 and October 2020. Multivariable Cox proportional-hazard model was used to identify factors associated with overall survival (OS) and recurrence free survival (RFS). RESULTS Among 244 patients with BRPC or LAPC who received neoadjuvant FOLFIRINOX, 79 patients underwent subsequent surgery. Among them, 58 who received adjuvant therapy [median age, 63 years; 33 females (56.9%)] were included. Thirty patients received adjuvant modified FOLFIRINOX (mFOLFIRINOX), while 28 received adjuvant therapy other than FOLFIRINOX. In multivariable analysis, mFOLFIRINOX and post-treatment carbohydrate antigen 19-9 (CA 19-9) were significantly associated with OS and RFS. According to mFOLFIRINOX vs. other adjuvant therapy, median OS was not reached at 37.5 months of follow-up vs. 29.7 months (P = .012); and median RFS was 30.5 vs. 11.0 months (P = .028). According to post-treatment CA 19-9 (< 37 vs. ≥ 37 U/mL), median OS was 46.0 vs. 25.5 months (P = .022); and median RFS was 25.9 vs. 7.6 months (P = .012). CONCLUSION Continued adjuvant mFOLFIRINOX and post-treatment CA 19-9 level were associated with survival in patients with BRPC or LAPC who received neoadjuvant FOLFIRINOX and surgery. Continued adjuvant mFOLFIRINOX after neoadjuvant FOLFIRINOX could be considered for patients with good performance.
Collapse
Affiliation(s)
- Jaewoo Park
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Songnam, Korea
| | - Hae Young Kim
- Department of Radiology, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Songnam, Korea
| | - Hee Young Na
- Department of Pathology, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Songnam, Korea
| | - Jun Suh Lee
- Department of Surgery, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Songnam, Korea
| | - Jong-Chan Lee
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Songnam, Korea
| | - Jin Won Kim
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Songnam, Korea
| | - Yoo-Seok Yoon
- Department of Surgery, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Songnam, Korea
| | - Jin-Hyeok Hwang
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Songnam, Korea
| | - Ho-Seong Han
- Department of Surgery, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Songnam, Korea
| | - Jaihwan Kim
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Songnam, Korea.
| |
Collapse
|
|
17
|
Anteby R, Blaszkowsky LS, Hong TS, Qadan M. Disparities in Receipt of Adjuvant Therapy After Upfront Surgical Resection for Pancreatic Ductal Adenocarcinoma. Ann Surg Oncol 2023; 30:2473-2481. [PMID: 36585536 DOI: 10.1245/s10434-022-12976-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/18/2022] [Accepted: 12/05/2022] [Indexed: 12/31/2022]
Abstract
BACKGROUND A multimodal approach of surgery and chemotherapy, with or without radiation, is the mainstay of therapy with curative-intent for resectable pancreatic ductal adenocarcinoma (PDAC). This study compared utilization trends and outcomes of upfront surgery with and without adjuvant therapy. METHODS The National Cancer Database was queried for patients with a diagnosis of stage 1 or 2 PDAC who underwent upfront resection. Multivariable regression was applied to identify factors associated with initiation of adjuvant therapy. RESULTS Of the 39,128 patients in the study, 67% initiated adjuvant therapy after resection, whereas 33% received upfront surgery alone. Receipt of adjuvant multimodal therapy increased from 59% in 2006 to 69% in 2017 (P < 0.0001). Non-white race was associated with lower odds of receiving adjuvant therapy after adjustment for income status, education attainment, and other variables (Hispanic/Spanish [odds ratio {OR}, 0.77; 95% confidence interval {CI}, 0.69-0.86] and non-Hispanic black [OR 0.84; 95% CI 0.78-0.91 vs non-Hispanic white; P < 0.001). The variables that contributed to receipt of adjuvant therapy were place of residence in high versus low education attainment area (OR 1.30; 95% CI 1.18-1.44; P < 0.0001) and lower odds for initiation of adjuvant therapy with increasing distance from the treating facility (> 50 miles [OR 0.51; 95% CI 0.47-0.54] vs <12.5 miles; P < 0.0001). The median unadjusted overall survival (OS) time was 18.2 months (95% CI 17.7-18.8 months) for upfront surgery alone and 25.3 months (95% CI 24.9-25.8 months) for surgery with adjuvant therapy. CONCLUSIONS The patients who underwent upfront surgical resection for PDAC showed wide socioeconomic disparities in the use of adjuvant therapy independent of insurance status, facility type, or travel distance.
Collapse
Affiliation(s)
- Roi Anteby
- School of Public Health, Harvard University, Boston, MA, USA
- Department of Surgery, Massachusetts General Hospital and Newton-Wellesley Hospital, Boston, MA, USA
| | - Lawrence S Blaszkowsky
- Division of Hematology-Oncology, Department of Medicine, Massachusetts General Hospital and Newton-Wellesley Hospital, Boston, Massachusetts, USA
| | - Theodore S Hong
- Department of Radiation Oncology, Massachusetts General Hospital and Newton-Wellesley Hospital, Harvard Medical School, Boston, MA, USA
| | - Motaz Qadan
- Department of Surgery, Massachusetts General Hospital and Newton-Wellesley Hospital, Boston, MA, USA.
| |
Collapse
|
|
18
|
de Geus SWL, Sachs TE. A Paradigm Shifts: Neoadjuvant Therapy for Clearly Resectable Pancreatic Cancer. Ann Surg Oncol 2023; 30:3427-3436. [PMID: 36869916 DOI: 10.1245/s10434-023-13281-1] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2022] [Accepted: 02/12/2023] [Indexed: 03/05/2023]
Abstract
Over the past decade, neoadjuvant therapy has become the standard of care for patients with borderline resectable and locally advanced pancreatic cancer. The surgical community remains divided regarding the value of neoadjuvant therapy for patients who present with clearly resectable disease. Thus far, randomized controlled trials comparing neoadjuvant therapy with conventional upfront surgical strategies for patients with clearly resectable pancreatic cancer have been plagued by poor accrual, and are often underpowered. Nonetheless, meta-analyses of the results of these trials suggest that neoadjuvant therapy can be offered as an acceptable standard of care for patients with clearly resectable pancreatic cancer. Previous trials used neoadjuvant gemcitabine, but more recent studies have demonstrated superior survival for patients who were able to tolerate neoadjuvant FOLFIRINOX (leucovorin, 5-fluorouracil, irinotecan hydrochloride, and oxaliplatin). The increased utilization of FOLFIRINOX may be shifting the treatment paradigm in favor of neoadjuvant therapy among patients with clearly resectable disease. Randomized controlled trials assessing the value of neoadjuvant FOLFIRINOX in clearly resectable pancreatic cancer, which are expected to provide more conclusive recommendations, are still ongoing. This review outlines the rationale, considerations, and current level of evidence for the use of neoadjuvant therapy in patients with clearly resectable pancreatic cancer.
Collapse
Affiliation(s)
- Susanna W L de Geus
- Department of Surgical Oncology, Boston Medical Center, Boston University Chobanian and Avedisian School of Medicine, Boston, MA, USA
| | - Teviah E Sachs
- Department of Surgical Oncology, Boston Medical Center, Boston University Chobanian and Avedisian School of Medicine, Boston, MA, USA.
| |
Collapse
|
|
19
|
Sugawara T, Rodriguez Franco S, Sherman S, Kirsch MJ, Colborn K, Ishida J, Grandi S, Al-Musawi MH, Gleisner A, Schulick RD, Del Chiaro M. Association of Adjuvant Chemotherapy in Patients With Resected Pancreatic Adenocarcinoma After Multiagent Neoadjuvant Chemotherapy. JAMA Oncol 2023; 9:316-323. [PMID: 36480190 PMCID: PMC9857517 DOI: 10.1001/jamaoncol.2022.5808] [Citation(s) in RCA: 21] [Impact Index Per Article: 10.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/16/2022] [Accepted: 09/13/2022] [Indexed: 12/13/2022]
Abstract
Importance The total number of patients with pancreatic ductal adenocarcinoma (PDAC) who receive neoadjuvant chemotherapy (NAC) is increasing. However, the added role of adjuvant chemotherapy (AC) in these patients remains unknown. Objective To evaluate the association of AC with overall survival (OS) in patients with PDAC who received multiagent NAC followed by curative-intent surgery. Design, Setting, and Participants This retrospective, matched-cohort study used data from the National Cancer Database and included patients with PDAC diagnosed between 2010 and 2018. The study included patients at least 18 years of age who received multiagent NAC followed by surgical resection and had available records of the pathological findings. Patients were excluded if they had clinical or pathological stage IV disease or died within 90 days of their operation. Exposures All included patients received NAC and underwent resection for primary PDAC. Some patients received adjuvant chemotherapy. Main Outcomes and Measures The main outcome was the OS of patients who received AC (AC group) vs those who did not (non-AC group). Interactions between pathological findings and AC were investigated in separate multivariable Cox regression models. Results In total, 1132 patients (mean [SD] age, 63.5 [9.4] years; 577 [50.1%] male; 970 [85.7%] White) were included, 640 patients in the non-AC group and 492 patients in the AC group. After being matched by propensity score according to demographic and pathological characteristics, 444 patients remained in each group. The multivariable Cox regression model adjusted for all covariates revealed an association between AC and improved survival (hazard ratio, 0.71; 95% CI, 0.59-0.85; P < .001). Subgroup interaction analysis revealed that AC was significantly associated with better OS (26.6 vs 21.2 months; P = .002), but the benefit varied by age, pathological T category, and tumor differentiation. Of note, AC was associated with better survival in patients with any pathological N category and positive margin status. Conclusions and Relevance In this cohort study, AC following multiagent NAC and resection in patients with PDAC was associated with significant survival benefit compared with that in patients who did not receive AC. These findings suggest that patients with aggressive tumors may benefit from AC to achieve prolonged survival, even after multiagent NAC and curative-intent resection.
Collapse
Affiliation(s)
- Toshitaka Sugawara
- Division of Surgical Oncology, Department of Surgery, University of Colorado School of Medicine, Aurora
- Department of Hepatobiliary and Pancreatic Surgery, Graduate School of Medicine, Tokyo Medical and Dental University, Tokyo, Japan
| | - Salvador Rodriguez Franco
- Division of Surgical Oncology, Department of Surgery, University of Colorado School of Medicine, Aurora
| | - Samantha Sherman
- Department of Surgery, Parkview Hospital Randallia, Fort Wayne, Indiana
| | - Michael J. Kirsch
- Department of Surgery, University of Colorado School of Medicine, Aurora
| | - Kathryn Colborn
- Department of Biostatistics and Informatics, University of Colorado School of Medicine, Aurora
- Surgical Outcomes and Applied Research Program, University of Colorado School of Medicine, Aurora
| | - Jun Ishida
- Division of Surgical Oncology, Department of Surgery, University of Colorado School of Medicine, Aurora
| | - Samuele Grandi
- Division of Surgical Oncology, Department of Surgery, University of Colorado School of Medicine, Aurora
| | - Mohammed H. Al-Musawi
- Clinical Trials Office, Department of Surgery, University of Colorado School of Medicine, Aurora
| | - Ana Gleisner
- Division of Surgical Oncology, Department of Surgery, University of Colorado School of Medicine, Aurora
- University of Colorado Cancer Center, University of Colorado School of Medicine, Aurora
| | - Richard D. Schulick
- Department of Surgery, University of Colorado School of Medicine, Aurora
- University of Colorado Cancer Center, University of Colorado School of Medicine, Aurora
| | - Marco Del Chiaro
- Division of Surgical Oncology, Department of Surgery, University of Colorado School of Medicine, Aurora
- University of Colorado Cancer Center, University of Colorado School of Medicine, Aurora
| |
Collapse
|
|
20
|
Ogobuiro I, Collier AL, Khan K, de Castro Silva I, Kwon D, Wilson GC, Schwartz PB, Parikh AA, Hammill C, Kim HJ, Kooby DA, Abbott D, Maithel SK, Snyder RA, Ahmad SA, Merchant NB, Datta J. Racial Disparity in Pathologic Response following Neoadjuvant Chemotherapy in Resected Pancreatic Cancer: A Multi-Institutional Analysis from the Central Pancreatic Consortium. Ann Surg Oncol 2023; 30:1485-1494. [PMID: 36316508 DOI: 10.1245/s10434-022-12741-4] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/10/2022] [Accepted: 10/10/2022] [Indexed: 11/18/2022]
Abstract
BACKGROUND Major pathologic response (MPR) following neoadjuvant therapy (NAT) in pancreatic ductal adenocarcinoma (PDAC) patients undergoing resection is associated with improved survival. We sought to determine whether racial disparities exist in MPR rates following NAT in patients with PDAC undergoing resection. METHODS Patients with potentially operable PDAC receiving at least 2 cycles of neoadjuvant FOLFIRINOX or gemcitabine/nab-paclitaxel ± radiation followed by pancreatectomy (2010-2019) at 7 high-volume centers were reviewed. Self-reported race was dichotomized as Black and non-Black, and multivariable models evaluated the association between race and MPR (i.e., pathologic complete response [pCR] or near-pCR). Cox regression evaluated the association between race and disease-free (DFS) and overall survival (OS). RESULTS Results of 486 patients who underwent resection following NAT (mFOLFIRINOX 56%, gemcitabine/nab-paclitaxel 25%, radiation 29%), 67 (13.8%) patients were Black. Black patients had lower CA19-9 at diagnosis (median 67 vs. 204 U/mL; P = 0.003) and were more likely to undergo mild/moderate chemotherapy dose modification (40 vs. 20%; P = 0.005) versus non-Black patients. Black patients had significantly lower rates of MPR compared with non-Black patients (13.4 vs. 25.8%; P = 0.039). Black race was independently associated with worse MPR (OR 0.26, 95% confidence interval [CI] 0.10-0.69) while controlling for NAT duration, CA19-9 dynamics, and chemotherapy modifications. There was no significant difference in DFS or OS between Black and non-Black cohorts. CONCLUSIONS Black patients undergoing pancreatectomy appear less likely to experience MPR following NAT. The contribution of biologic and nonbiologic factors to reduced chemosensitivity in Black patients warrants further investigation.
Collapse
Affiliation(s)
- Ifeanyichukwu Ogobuiro
- Department of Surgery, Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, 1120 NW 14th Street, Suite 410, Miami, FL, 33136, USA
| | - Amber L Collier
- Department of Surgery, Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, 1120 NW 14th Street, Suite 410, Miami, FL, 33136, USA
| | - Khadeja Khan
- Department of Surgery, Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, 1120 NW 14th Street, Suite 410, Miami, FL, 33136, USA
| | - Iago de Castro Silva
- Department of Surgery, Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, 1120 NW 14th Street, Suite 410, Miami, FL, 33136, USA
| | - Deukwoo Kwon
- Department of Surgery, Icahn School of Medicine at Mount Sinai Department of Population Health Science and Policy, New York, NY, USA
| | - Gregory C Wilson
- Department of Surgery, University of Cincinnati School of Medicine, Cincinnati, OH, USA
| | - Patrick B Schwartz
- Department of Surgery, Carbone Cancer Center, University of Wisconsin School of Medicine, Madison, WI, USA
| | - Alexander A Parikh
- Department of Surgery, East Carolina University Brody School of Medicine, Greenville, NC, USA
| | - Chet Hammill
- Department of Surgery, Washington University School of Medicine, St. Louis, MO, USA
| | - Hong J Kim
- Department of Surgery, Lineberger Cancer Center, University of North Carolina School of Medicine, Chapel Hill, NC, USA
| | - David A Kooby
- Department of Surgery, Emory University School of Medicine, Winship Cancer Institute, Atlanta, GA, USA
| | - Daniel Abbott
- Department of Surgery, Carbone Cancer Center, University of Wisconsin School of Medicine, Madison, WI, USA
| | - Shishir K Maithel
- Department of Surgery, Emory University School of Medicine, Winship Cancer Institute, Atlanta, GA, USA
| | - Rebecca A Snyder
- Department of Surgery, East Carolina University Brody School of Medicine, Greenville, NC, USA
| | - Syed A Ahmad
- Department of Surgery, University of Cincinnati School of Medicine, Cincinnati, OH, USA
| | - Nipun B Merchant
- Department of Surgery, Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, 1120 NW 14th Street, Suite 410, Miami, FL, 33136, USA
| | - Jashodeep Datta
- Department of Surgery, Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, 1120 NW 14th Street, Suite 410, Miami, FL, 33136, USA.
| |
Collapse
|
|
21
|
Bastin DJ, Montroy J, Kennedy MA, Martel AB, Shorr R, Ghiasi M, Boucher DM, Wong B, Gresham L, Diallo JS, Fergusson DA, Lalu MM, Kekre N, Auer RC. Safety and efficacy of autologous cell vaccines in solid tumors: a systematic review and meta-analysis of randomized control trials. Sci Rep 2023; 13:3347. [PMID: 36849805 PMCID: PMC9971202 DOI: 10.1038/s41598-023-29630-9] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/22/2022] [Accepted: 02/08/2023] [Indexed: 03/01/2023] Open
Abstract
We conducted a systematic review and meta-analysis of randomized control trials to formally assess the safety and efficacy of autologous whole cell vaccines as immunotherapies for solid tumors. Our primary safety outcome was number, and grade of adverse events. Our primary efficacy outcome was clinical responses. Secondary outcomes included survival metrics and correlative immune assays. We searched MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials for studies published between 1946 and August 2020 using any autologous whole cell product in the treatment of any solid tumor. The Cochrane Randomized Controlled Trial risk of bias tool was used to assess risk of bias. Eighteen manuscripts were identified with a total of 714 patients enrolled in control and 808 in vaccine arms. In 698 patients receiving at least one dose of vaccine, treatment was well tolerated with a total of 5 grade III or higher adverse events. Clinical response was reported in a minority (n = 2, 14%) of studies. Autologous cell vaccines were associated with improved overall (HR 1.28, 95% CI 1.01-1.63) and disease-free survival (HR 1.33, 95% CI 1.05-1.67) over thirteen and ten trials respectively. Where reported, immune assays correlated well with clinical outcomes. Our results suggest that autologous whole cell vaccination is safe and efficacious in increasing survival in patients undergoing treatment for solid tumors.Registration: PROSPERO CRD42019140187.
Collapse
Affiliation(s)
- Donald J Bastin
- Cancer Therapeutics Program, The Ottawa Hospital Research Institute, General Campus, 501 Smyth Road, Ottawa, ON, K1H 8L6, Canada
- Schulich School of Medicine, Western University, London, ON, Canada
| | - Joshua Montroy
- Clinical Epidemiology Program, Blueprint Translational Research Group, Ottawa Hospital Research Institute, Ottawa, ON, Canada
| | - Michael A Kennedy
- Cancer Therapeutics Program, The Ottawa Hospital Research Institute, General Campus, 501 Smyth Road, Ottawa, ON, K1H 8L6, Canada
| | - Andre B Martel
- Cancer Therapeutics Program, The Ottawa Hospital Research Institute, General Campus, 501 Smyth Road, Ottawa, ON, K1H 8L6, Canada
- Department of Surgery, University of Ottawa, Ottawa, ON, Canada
- Faculty of Medicine, University of Ottawa, Ottawa, ON, Canada
- Department of Biochemistry, Microbiology, and Immunology, University of Ottawa, Ottawa, ON, Canada
| | - Risa Shorr
- Learning Services, The Ottawa Hospital, Ottawa, ON, Canada
| | - Maryam Ghiasi
- Clinical Epidemiology Program, Blueprint Translational Research Group, Ottawa Hospital Research Institute, Ottawa, ON, Canada
| | - Dominique M Boucher
- Cancer Therapeutics Program, The Ottawa Hospital Research Institute, General Campus, 501 Smyth Road, Ottawa, ON, K1H 8L6, Canada
- Faculty of Medicine, University of Ottawa, Ottawa, ON, Canada
- Department of Biochemistry, Microbiology, and Immunology, University of Ottawa, Ottawa, ON, Canada
| | - Boaz Wong
- Cancer Therapeutics Program, The Ottawa Hospital Research Institute, General Campus, 501 Smyth Road, Ottawa, ON, K1H 8L6, Canada
- Faculty of Medicine, University of Ottawa, Ottawa, ON, Canada
- Department of Biochemistry, Microbiology, and Immunology, University of Ottawa, Ottawa, ON, Canada
| | - Louise Gresham
- Department of Surgery, University of Ottawa, Ottawa, ON, Canada
| | - Jean-Simon Diallo
- Cancer Therapeutics Program, The Ottawa Hospital Research Institute, General Campus, 501 Smyth Road, Ottawa, ON, K1H 8L6, Canada
- Faculty of Medicine, University of Ottawa, Ottawa, ON, Canada
- Department of Biochemistry, Microbiology, and Immunology, University of Ottawa, Ottawa, ON, Canada
| | - Dean A Fergusson
- Clinical Epidemiology Program, Blueprint Translational Research Group, Ottawa Hospital Research Institute, Ottawa, ON, Canada
- Faculty of Medicine, University of Ottawa, Ottawa, ON, Canada
- School of Epidemiology and Public Health, University of Ottawa, Ottawa, ON, Canada
| | - Manoj M Lalu
- Clinical Epidemiology Program, Blueprint Translational Research Group, Ottawa Hospital Research Institute, Ottawa, ON, Canada
- Faculty of Medicine, University of Ottawa, Ottawa, ON, Canada
- Department of Anesthesiology and Pain Medicine, The Ottawa Hospital, University of Ottawa, Ottawa, ON, Canada
- Regenerative Medicine Program, The Ottawa Health Research Institute, Ottawa, ON, Canada
| | - Natasha Kekre
- Cancer Therapeutics Program, The Ottawa Hospital Research Institute, General Campus, 501 Smyth Road, Ottawa, ON, K1H 8L6, Canada
- Faculty of Medicine, University of Ottawa, Ottawa, ON, Canada
| | - Rebecca C Auer
- Cancer Therapeutics Program, The Ottawa Hospital Research Institute, General Campus, 501 Smyth Road, Ottawa, ON, K1H 8L6, Canada.
- Department of Surgery, University of Ottawa, Ottawa, ON, Canada.
- Faculty of Medicine, University of Ottawa, Ottawa, ON, Canada.
- Department of Biochemistry, Microbiology, and Immunology, University of Ottawa, Ottawa, ON, Canada.
| |
Collapse
|
|
22
|
Konno Y, Sugai Y, Kanoto M, Suzuki K, Hiraka T, Toyoguchi Y, Niino K. A retrospective preliminary study of intrapancreatic late enhancement as a noteworthy imaging finding in the early stages of pancreatic adenocarcinoma. Eur Radiol 2023:10.1007/s00330-022-09388-w. [PMID: 36648551 DOI: 10.1007/s00330-022-09388-w] [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: 04/02/2022] [Revised: 11/10/2022] [Accepted: 12/23/2022] [Indexed: 01/18/2023]
Abstract
OBJECTIVE To characterize intrapancreatic late enhancement (ILE) observed in the early stages of pancreatic adenocarcinoma (PAC). METHODS Among 203 patients pathologically diagnosed with PAC between October 2011 and February 2021, 32 patients with pre-diagnostic abdominal contrast-enhanced CT performed from 6 months to 5 years before the diagnosis were enrolled in this study. Indirect findings (IFs) on pre-diagnostic CT, including ILE, were evaluated and examined for various clinical data and time intervals to diagnosis (TIDs). The detected ILE was quantitatively evaluated, and the effect of ILE awareness on lesion detection by two radiologists and their interobserver agreement were assessed. RESULTS Among the 32 patients, 23 showed IFs. ILE was observed in 14 patients (63%), with a median TID of 17 months (interquartile ratio [IQR]: 9.3-42.3). ILE alone was observed in eight patients (35%), ILE with focal pancreatic parenchymal atrophy (FPPA) was observed in five patients (22%), and ILE with main pancreatic duct abnormalities (MPDA) was observed in one patient (4%). Pancreatic head lesions were significantly more frequent in patients with ILE alone than in patients with FPPA or MPDA (p = 0.026). The median long-axis diameters of the region with ILE and ILE-to-pancreas contrast were 10 (IQR: 5-11) mm and 24 (IQR: 17-33) HU, respectively. Awareness of ILE led observers to detect two or three more pancreatic head lesions, and interobserver agreement increased from poor agreement (k = 0.17) to moderate agreement (k = 0.55). CONCLUSION ILE is a significant IF for early PAC detection. KEY POINTS • Intrapancreatic late enhancement (ILE) is a significant indirect finding in the early detection of pancreatic adenocarcinoma. • ILE without other indirect findings is expected to help detect pancreatic head lesions. • Image evaluation focusing on ILE can increase lesion detection and improve the interobserver agreement.
Collapse
Affiliation(s)
- Yoshihiro Konno
- Department of Diagnostic Radiology, Faculty of Medicine, Yamagata University, 2-2-2 Iida-Nishi, Yamagata-Shi, Yamagata, 990-9585, Japan.
| | - Yasuhiro Sugai
- Department of Diagnostic Radiology, Faculty of Medicine, Yamagata University, 2-2-2 Iida-Nishi, Yamagata-Shi, Yamagata, 990-9585, Japan
| | - Masafumi Kanoto
- Department of Diagnostic Radiology, Faculty of Medicine, Yamagata University, 2-2-2 Iida-Nishi, Yamagata-Shi, Yamagata, 990-9585, Japan
| | - Keisuke Suzuki
- Department of Diagnostic Radiology, Faculty of Medicine, Yamagata University, 2-2-2 Iida-Nishi, Yamagata-Shi, Yamagata, 990-9585, Japan
| | - Toshitada Hiraka
- Department of Diagnostic Radiology, Faculty of Medicine, Yamagata University, 2-2-2 Iida-Nishi, Yamagata-Shi, Yamagata, 990-9585, Japan
| | - Yuki Toyoguchi
- Department of Diagnostic Radiology, Faculty of Medicine, Yamagata University, 2-2-2 Iida-Nishi, Yamagata-Shi, Yamagata, 990-9585, Japan
| | - Kazuho Niino
- Department of Radiology, Nihonkai General Hospital, 30 Akiho, Sakata-Shi, Yamagata, 998-8501, Japan
| |
Collapse
|
|
23
|
Tezuka R, Iwashita T, Uemura S, Senju A, Yoshida K, Maruta A, Iwata K, Shimizu M. The efficacy and safety of modified FOLFIRINOX for unresectable advanced pancreatic cancer in elderly versus young patients: A multicenter retrospective cohort study. Pancreatology 2022; 22:1134-1140. [PMID: 36404200 DOI: 10.1016/j.pan.2022.11.005] [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: 07/02/2022] [Revised: 10/16/2022] [Accepted: 11/07/2022] [Indexed: 11/13/2022]
Abstract
UNLABELLED In the treatment of advanced pancreatic cancer (APC), FOLFIRINOX (FX), including its dose-modified regimen (mFX), is considered an effective regimen; however, FX is also known to be associated with a high incidence of adverse events due to its multi-agent combination regimen. The efficacy and safety in elderly patients with APC have not been well studied. AIM To compare the safety and efficacy of first-line mFX for unresectable APC in elderly and young patients. METHODS This was a multicenter retrospective cohort study included patients who received first-line mFX for unresectable APC. A total of 151 patients were included and divided into the elderly (≥65 years old; 76 patients) and young (<65 years old; 75 patients) groups. The primary endpoint was overall survival (OS). The secondary endpoints were progression-free survival (PFS) and adverse events (AEs). RESULTS The median OS and PFS were similar between the two groups (OS: 14.4 months versus 13.9 months, p = 0.42; PFS: 7.4 months versus 6.6 months, p = 0.65). Although severe AEs (≥ grade 3) were observed frequently in both groups (80% versus 84.2%, p = 0.53), there was no significant difference in any of the events between the groups. In the multivariate analysis evaluating the factors affecting OS and febrile neutropenia, age was not significant factors in both analyses. CONCLUSION First-line mFX for APC in elderly patients was as safe and effective as in younger patients if performance status was good. Further evaluation in a larger cohort is required to confirm our findings.
Collapse
Affiliation(s)
- Ryuichi Tezuka
- First Department of Internal Medicine, Gifu University Hospital, Gifu, Japan
| | - Takuji Iwashita
- First Department of Internal Medicine, Gifu University Hospital, Gifu, Japan.
| | - Shinya Uemura
- First Department of Internal Medicine, Gifu University Hospital, Gifu, Japan
| | - Akihiko Senju
- First Department of Internal Medicine, Gifu University Hospital, Gifu, Japan
| | - Kensaku Yoshida
- Department of Gastroenterology, Gifu Prefectural General Medical Center, Gifu, Japan
| | - Akinori Maruta
- Department of Gastroenterology, Gifu Prefectural General Medical Center, Gifu, Japan
| | - Keisuke Iwata
- Department of Gastroenterology, Gifu Municipal Hospital, Gifu, Japan
| | - Masahito Shimizu
- First Department of Internal Medicine, Gifu University Hospital, Gifu, Japan
| |
Collapse
|
|
24
|
Possibility of Neoadjuvant Treatment for Radiologically Judged Resectable Pancreatic Cancer. J Clin Med 2022; 11:jcm11226792. [PMID: 36431269 PMCID: PMC9698623 DOI: 10.3390/jcm11226792] [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: 10/24/2022] [Revised: 11/07/2022] [Accepted: 11/11/2022] [Indexed: 11/19/2022] Open
Abstract
Survival remains poor even after resection of pancreatic cancer and the postoperative recurrence rate is extremely high. Thus, neoadjuvant treatment may improve outcomes for resectable pancreatic cancer (RPC). This study evaluated the efficacy of neoadjuvant therapy for radiologically judged RPC. A prospectively maintained institutional database was reviewed to identify patients who underwent potentially curative resection of radiologically judged RPC. Patient characteristics and intermediate-term outcomes were compared between groups that received neoadjuvant treatment or upfront surgery (UFS). We identified 353 eligible patients, including 55 patients who received neoadjuvant chemoradiotherapy (CRT group), 53 patients who received neoadjuvant gemcitabine plus nab-paclitaxel (GnP group), and 245 patients who underwent UFS (UFS group). The cumulative rates of pancreatic cancer recurrence at 2 years after pancreatic surgery were 49.5% in the UFS, 48.1% in the CRT group, and 52.7% in the GnP group. The recurrence rate tended to be improved after neoadjuvant treatment, although the difference was not significant at this follow-up point. While the clinical TNM classifications were noticeably different from the final pathological findings, the clinical and pathological TNM classifications were more similar in the groups that underwent neoadjuvant treatment. Neoadjuvant treatment can help identify good surgical candidates and avoid unnecessary laparotomy. Our results also suggest that neoadjuvant therapy might help improve the preoperative diagnostic accuracy for patients with RPC.
Collapse
|
|
25
|
Ivey GD, Shoucair S, Delitto DJ, Habib JR, Kinny-Köster B, Shubert CR, Lafaro KJ, Cameron JL, Burns WR, Burkhart RA, Thompson EL, Narang A, Zheng L, Wolfgang CL, He J. Postoperative Chemotherapy is Associated with Improved Survival in Patients with Node-Positive Pancreatic Ductal Adenocarcinoma After Neoadjuvant Therapy. World J Surg 2022; 46:2751-2759. [PMID: 35861852 PMCID: PMC9532378 DOI: 10.1007/s00268-022-06667-x] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 06/30/2022] [Indexed: 10/17/2022]
Abstract
BACKGROUND Postoperative chemotherapy following pancreatic cancer resection is the standard of care. The utility of postoperative chemotherapy for patients who receive neoadjuvant therapy (NAT) is unclear. METHODS Patients who underwent pancreatectomy after NAT with FOLFIRINOX or gemcitabine-based chemotherapy for non-metastatic pancreatic adenocarcinoma (2015-2019) were identified. Patients who received less than 2 months of neoadjuvant chemotherapy or died within 90 days from surgery were excluded. RESULTS A total of 427 patients (resectable, 22.2%; borderline resectable, 37.9%; locally advanced, 39.8%) were identified with the majority (69.3%) receiving neoadjuvant FOLFIRINOX. Median duration of NAT was 4.1 months. Following resection, postoperative chemotherapy was associated with an improved median overall survival (OS) (28.7 vs. 20.4 months, P = 0.006). Risk-adjusted multivariable modeling showed negative nodal status (N0), favorable pathologic response (College of American Pathologists score 0 & 1), and receipt of postoperative chemotherapy to be independent predictors of improved OS. Regimen, duration, and number of cycles of NAT were not significant predictors. Thirty-four percent (60/176) of node-positive and 50.1% (126/251) of node-negative patients did not receive postoperative chemotherapy due to poor functional status, postoperative complications, and patient preference. Among patients with node-positive disease, postoperative chemotherapy was associated with improved median OS (27.2 vs. 10.5 months, P < 0.001). Among node-negative patients, postoperative chemotherapy was not associated with a survival benefit (median OS, 30.9 vs. 36.9 months; P = 0.406). CONCLUSION Although there is no standard NAT regimen for patients with pancreatic cancer, postoperative chemotherapy following NAT and resection appears to be associated with improved OS for patients with node-positive disease.
Collapse
Affiliation(s)
- Gabriel D Ivey
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Sami Shoucair
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Daniel J Delitto
- Department of Surgery, Stanford University School of Medicine, Stanford, CA, USA
| | - Joseph R Habib
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | | | - Christopher R Shubert
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Kelly J Lafaro
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - John L Cameron
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - William R Burns
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Richard A Burkhart
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Elizabeth L Thompson
- Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Amol Narang
- Department of Radiation Oncology, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Lei Zheng
- Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | | | - Jin He
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
| |
Collapse
|
|
26
|
Novel Considerations in Surgical Management of Individuals with Pancreatic Adenocarcinoma. Hematol Oncol Clin North Am 2022; 36:979-994. [DOI: 10.1016/j.hoc.2022.07.004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022]
|
|
27
|
Drake JA, Fleming AM, Behrman SW, Glazer ES, Deneve JL, Yakoub D, Tsao MW, Dickson PV. Tumor Location in the Pancreatic Tail Is Associated with Decreased Likelihood of Receiving Chemotherapy for Pancreatic Adenocarcinoma. J Gastrointest Surg 2022; 26:2136-2147. [PMID: 35768717 DOI: 10.1007/s11605-022-05381-2] [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: 01/18/2022] [Accepted: 04/02/2022] [Indexed: 01/31/2023]
Abstract
BACKGROUND Chemotherapy (CTX) is associated with improved survival for patients undergoing resection for pancreatic ductal adenocarcinoma (PDAC). The current study evaluated the influence of tumor location on receipt of CTX. METHODS The NCDB (2006-2017) was queried to identify patients with clinical stage I-III PDAC. Predictors of receipt of CTX, sequencing of CTX, and overall survival (OS) were analyzed. RESULTS Among 14,557 patients who underwent resection for PDAC 3,453 (24%) did not receive CTX. On multivariable analysis, patients with tail tumors were 15% less likely to receive CTX (OR 0.85, 95% CI 0.747-0.968) and 58% less likely to receive neoadjuvant CTX (OR 0.42, 95% CI 0.351-0.509) relative to patients with head/neck tumors. For patients with body tumors, there was no difference in rates of administration or sequence of CTX. For patients with resected tail tumors, median OS was 29.9 vs 18.9 months (p < 0.001) between those who did and did not receive CTX. For patients with tail tumors, independent predictors of not receiving CTX, regardless of sequence, were increasing age (OR 0.95, 95% CI 0.935-0.965), increasing post-op length of stay (OR 0.95, 95% CI 0.932-0.968), and 30-day post-op readmission (OR 0.46, 95% CI 0.315-0.670). CONCLUSIONS In patients with clinical stage I-III PDAC, tumor location within the tail was independently associated with not receiving CTX. Given the marked improvement in OS when CTX is administered, strategies aimed at increasing the number of these patients who receive CTX are necessary.
Collapse
Affiliation(s)
- Justin A Drake
- Department of Surgery, Division of Surgical Oncology, University of Tennessee Health Science Center, 910 Madison Ave., 3rdFloor, Memphis, TN, 38163, USA
| | - Andrew M Fleming
- Department of Surgery, Division of Surgical Oncology, University of Tennessee Health Science Center, 910 Madison Ave., 3rdFloor, Memphis, TN, 38163, USA
| | - Stephen W Behrman
- Department of Surgery, Division of Surgical Oncology, University of Tennessee Health Science Center, 910 Madison Ave., 3rdFloor, Memphis, TN, 38163, USA
| | - Evan S Glazer
- Department of Surgery, Division of Surgical Oncology, University of Tennessee Health Science Center, 910 Madison Ave., 3rdFloor, Memphis, TN, 38163, USA
| | - Jeremiah L Deneve
- Department of Surgery, Division of Surgical Oncology, University of Tennessee Health Science Center, 910 Madison Ave., 3rdFloor, Memphis, TN, 38163, USA
| | - Danny Yakoub
- Department of Surgery, Division of Surgical Oncology, University of Tennessee Health Science Center, 910 Madison Ave., 3rdFloor, Memphis, TN, 38163, USA
| | - Miriam W Tsao
- Department of Surgery, Division of Surgical Oncology, University of Tennessee Health Science Center, 910 Madison Ave., 3rdFloor, Memphis, TN, 38163, USA
| | - Paxton V Dickson
- Department of Surgery, Division of Surgical Oncology, University of Tennessee Health Science Center, 910 Madison Ave., 3rdFloor, Memphis, TN, 38163, USA.
| |
Collapse
|
|
28
|
Gorbudhun R, Patel PH, Hopping E, Doyle J, Geropoulos G, Mavroeidis VK, Kumar S, Bhogal RH. Neoadjuvant Chemotherapy-Chemoradiation for Borderline-Resectable Pancreatic Adenocarcinoma: A UK Tertiary Surgical Oncology Centre Series. Cancers (Basel) 2022; 14:cancers14194678. [PMID: 36230600 PMCID: PMC9563387 DOI: 10.3390/cancers14194678] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/25/2022] [Revised: 09/13/2022] [Accepted: 09/19/2022] [Indexed: 11/16/2022] Open
Abstract
Background: Patients with borderline-resectable pancreatic ductal adenocarcinoma (BR-PDAC) have historically poor survival, even after curative pancreatic resection and adjuvant chemotherapy. Emerging evidence suggests that neoadjuvant chemoradiation (NCR) improves R0 resection rates in BR-PDAC patients. We evaluated the R0 resection rate, disease-free survival (DFS) and overall survival (OS) in our patients who underwent NCR for BR-PDAC at our institution. Methods: All patients who underwent NCR for BR-PDAC from January 2010 to March 2020 were included in the study. The patients received a variety of NCR regimens during the study period, and in patients with radiological evidence of tumour stability or regression, pancreatic resection was performed. The primary endpoint was the OS, and the secondary endpoints included patient morbidity, the R0 resection rate, histological parameters and the DFS. Results: The study included 29 patients (16 men and 13 women), with a median age of 65 years (range 46–74 years). Of these 29 patients, 17 received FOLFIRINOX and 12 received gemcitabine (GEM)-based NCR regimens. All patients received chemoradiation at the end of chemotherapy (range 45–56 Gy). R0 resection was achieved in 75% of the patients, with a higher rate noted in the FOLFIRINOX group. The median DFS was 22 months for the whole cohort but higher in the FOLFIRINOX group (34 months). The median OS for the cohort was 29 months, with a higher median OS noted for the FOLFIRINOX cohort versus the GEM cohort (42 versus 28 months). Conclusion: NCR, particularly FOLFIRINOX-based treatment, for BR-PDAC results in higher rates of R0 resection and an increased median DFS and OS, supporting its continued use in this patient group.
Collapse
Affiliation(s)
- Rachna Gorbudhun
- Department of Surgery, The Royal Marsden Hospital, Fulham Road, London SW3 6JJ, UK
| | - Pranav H. Patel
- Department of Surgery, The Royal Marsden Hospital, Fulham Road, London SW3 6JJ, UK
| | - Eve Hopping
- Department of Surgery, The Royal Marsden Hospital, Fulham Road, London SW3 6JJ, UK
| | - Joseph Doyle
- Department of Surgery, The Royal Marsden Hospital, Fulham Road, London SW3 6JJ, UK
| | - Georgios Geropoulos
- Department of Surgery, The Royal Marsden Hospital, Fulham Road, London SW3 6JJ, UK
| | | | - Sacheen Kumar
- Department of Surgery, The Royal Marsden Hospital, Fulham Road, London SW3 6JJ, UK
- Upper Gastrointestinal Research Group, Department of Radiotherapy, Institute of Cancer Research, 123 Old Brompton Road, London SW7 3RP, UK
| | - Ricky H. Bhogal
- Department of Surgery, The Royal Marsden Hospital, Fulham Road, London SW3 6JJ, UK
- Upper Gastrointestinal Research Group, Department of Radiotherapy, Institute of Cancer Research, 123 Old Brompton Road, London SW7 3RP, UK
- Correspondence: ; Tel.: +44-0208-7808-2781
| |
Collapse
|
|
29
|
Oncologic Benefits of Neoadjuvant Treatment versus Upfront Surgery in Borderline Resectable Pancreatic Cancer: A Systematic Review and Meta-Analysis. Cancers (Basel) 2022; 14:cancers14184360. [PMID: 36139520 PMCID: PMC9497278 DOI: 10.3390/cancers14184360] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/07/2022] [Revised: 08/31/2022] [Accepted: 09/03/2022] [Indexed: 11/17/2022] Open
Abstract
Simple Summary Borderline resectable pancreatic cancer (BRPC) has been primarily indicated for neoadjuvant treatment (NAT) in the last decade. This study is the updated meta-analysis for only patients with BRPC including recent NAT regimens such as FOLFIRINOX. The OS, R0 resection rate, and node-negativity rate was improved in NAT group compared with upfront surgery. Providing high-quality evidence is important to standardize the treatment protocol and help physicians decide the appropriate pancreatic cancer treatment. Abstract Neoadjuvant treatment (NAT) followed by surgery is the primary treatment for borderline resectable pancreatic cancer (BRPC). However, there is limited high-level evidence supporting the efficacy of NAT in BRPC. PubMed was searched to identify studies that compared the survival between BRPC patients who underwent NAT and those who underwent upfront surgery (UFS). The overall survival (OS) was compared using intention-to-treat (ITT) analysis. A total of 1204 publications were identified, and 19 publications with 21 data sets (2906 patients; NAT, 1516; UFS, 1390) were analyzed. Two randomized controlled trials and two prospective studies were included. Thirteen studies performed an ITT analysis, while six presented the data of resected patients. The NAT group had significantly better OS than the UFS group in the ITT analyses (HR: 0.63, 95% CI = 0.53–0.76) and resected patients (HR: 0.68, 95% CI = 0.60–0.78). Neoadjuvant chemotherapy with gemcitabine or S-1 and FOLFIRINOX improved the survival outcomes. Among the resected patients, the R0 resection and node-negativity rates were significantly higher in the NAT group. NAT improved the OS, R0 resection rate, and node-negativity rate compared with UFS. Standardizing treatment regimens based on high-quality evidence is fundamental for developing an optimal protocol.
Collapse
|
|
30
|
Hospital Surgical Volume Is Poorly Correlated With Delivery of Multimodal Treatment for Localized Pancreatic Cancer. ANNALS OF SURGERY OPEN 2022; 3:e197. [PMID: 36199487 PMCID: PMC9508964 DOI: 10.1097/as9.0000000000000197] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/06/2022] [Accepted: 07/12/2022] [Indexed: 11/26/2022] Open
Abstract
Using Donabedian’s quality of care model, this study assessed process (hospital multimodal treatment) and structure (hospital surgical case volume) measures to evaluate localized pancreatic cancer outcomes.
Collapse
|
|
31
|
Miura Y, Ohgi K, Sugiura T, Okamura Y, Ashida R, Yamada M, Otsuka S, Yasunaga Y, Nakagawa M, Uesaka K. Resectability Status of Pancreatic Cancer Having Tumor Contact with an Aberrant Right Hepatic Artery: Is Upfront Surgery Justified? Ann Surg Oncol 2022; 29:4979-4988. [PMID: 35362841 DOI: 10.1245/s10434-022-11624-y] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/11/2021] [Accepted: 02/27/2022] [Indexed: 11/18/2022]
Abstract
BACKGROUND The NCCN guidelines define pancreatic cancer that has contact with an aberrant right hepatic artery (A-RHA) as a borderline-resectable tumor. However, the impact of tumor contact with an A-RHA on surgical and survival outcomes has not been well discussed. METHODS A total of 541 patients who underwent pancreatoduodenectomy for resectable and borderline-resectable pancreatic cancer between 2002 and 2019 were retrospectively analyzed. The presence of an A-RHA and tumor contact with an A-RHA were evaluated based on the preoperative computed tomography findings. Patients with resectable tumors and tumors with A-RHA-contact (having contact with an A-RHA without involvement of the major arteries) were generally treated by upfront surgery, whereas those with borderline-resectable tumors generally underwent neoadjuvant therapy and subsequent resection. RESULTS Among the 541 patients, 116 (21.4%) had an A-RHA and 15 (2.8%) had tumor with A-RHA-contact. The A-RHA was resected in 12, and arterial reconstruction was performed in 8. The rates of morbidity and R1 resection in patients with an A-RHA (32.8 and 10.3%, respectively) were comparable to those without an A-RHA (27.3 and 11.3%, respectively). The overall survival in patients with A-RHA-contact was significantly worse than that in patients with borderline-resectable tumors (median survival time, 14.6 vs. 35.3 months, p = 0.048). CONCLUSIONS Although upfront resection was safely performed and led to a high R0 resection rate in patients with A-RHA-contact, the survival outcome was dismal. A tumor with A-RHA-contact should be regarded as technically resectable but oncologically borderline-resectable. Upfront surgery may not be appropriate for patients with A-RHA-contact.
Collapse
Affiliation(s)
- Yuya Miura
- Division of Hepato-Biliary-Pancreatic Surgery, Shizuoka Cancer Center, Shizuoka, Japan
| | - Katsuhisa Ohgi
- Division of Hepato-Biliary-Pancreatic Surgery, Shizuoka Cancer Center, Shizuoka, Japan.
| | - Teiichi Sugiura
- Division of Hepato-Biliary-Pancreatic Surgery, Shizuoka Cancer Center, Shizuoka, Japan
| | - Yukiyasu Okamura
- Division of Hepato-Biliary-Pancreatic Surgery, Shizuoka Cancer Center, Shizuoka, Japan
| | - Ryo Ashida
- Division of Hepato-Biliary-Pancreatic Surgery, Shizuoka Cancer Center, Shizuoka, Japan
| | - Mihoko Yamada
- Division of Hepato-Biliary-Pancreatic Surgery, Shizuoka Cancer Center, Shizuoka, Japan
| | - Shimpei Otsuka
- Division of Hepato-Biliary-Pancreatic Surgery, Shizuoka Cancer Center, Shizuoka, Japan
| | - Yoshichika Yasunaga
- Division of Plastic and Reconstructive Surgery, Shizuoka Cancer Center, Shizuoka, Japan
| | - Masahiro Nakagawa
- Division of Plastic and Reconstructive Surgery, Shizuoka Cancer Center, Shizuoka, Japan
| | - Katsuhiko Uesaka
- Division of Hepato-Biliary-Pancreatic Surgery, Shizuoka Cancer Center, Shizuoka, Japan
| |
Collapse
|
|
32
|
Vivarelli M, Mocchegiani F, Nicolini D, Vecchi A, Conte G, Dalla Bona E, Rossi R, Benedetti Cacciaguerra A. Neoadjuvant Treatment in Resectable Pancreatic Cancer. Is It Time for Pushing on It? Front Oncol 2022; 12:914203. [PMID: 35712487 PMCID: PMC9195424 DOI: 10.3389/fonc.2022.914203] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/06/2022] [Accepted: 04/28/2022] [Indexed: 11/13/2022] Open
Abstract
Pancreatic resection still represents the only curative option for patients affected by pancreatic ductal adenocarcinoma (PDAC). However, the association with modern chemotherapy regimens is a key factor in improving the inauspicious oncological outcome. The benefit of neoadjuvant treatment (NAT) for borderline resectable/locally advanced PDAC has been demonstrated; this evidence raises the question of whether even resectable PDAC should undergo NAT rather than upfront surgery. NAT may avoid futile surgery because of undetected distant metastases or aggressive tumor biology, providing more effective systemic control of the disease, which is hampered when adjuvant chemotherapy is delayed or precluded. However, recent data show controversial results regarding the efficacy and safety of NAT in resectable PDAC compared to upfront surgery. Although several prospective studies and meta-analyses indicate better oncologic outcomes after NAT, there are some biases, such as the methodological approaches used to capture the events of interest, which could make these results hardly reproducible. For instance, per-protocol studies, considering only the postoperative outcomes, tend to overestimate the performance of NAT by excluding patients who will never be suitable for surgery due to the development of chemotoxicity or tumor progression. To draw reliable conclusions, the studies should capture the events of interest of both strategies (NAT/upfront surgery) from the time of allocation to a specific treatment in an intention-to-treat fashion. This critical review highlights the current literature data concerning the use of NAT in resectable PDAC, summarizing the results of high-quality studies and focusing on the methodological issues of the most recent pieces of evidence.
Collapse
|
|
33
|
Janssen QP, van Dam JL, Doppenberg D, Prakash LR, van Eijck CHJ, Jarnagin WR, O’ Reilly EM, Paniccia A, Besselink MG, Katz MHG, Tzeng CWD, Wei AC, Zureikat AH, Groot Koerkamp B. FOLFIRINOX as Initial Treatment for Localized Pancreatic Adenocarcinoma: A Retrospective Analysis by the Trans-Atlantic Pancreatic Surgery Consortium. J Natl Cancer Inst 2022; 114:695-703. [PMID: 35157075 PMCID: PMC9086789 DOI: 10.1093/jnci/djac018] [Citation(s) in RCA: 28] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/21/2021] [Revised: 10/27/2021] [Accepted: 01/14/2022] [Indexed: 01/19/2023] Open
Abstract
BACKGROUND Large pragmatic studies of patients who received 5-fluorouracil with leucovorin, irinotecan, and oxaliplatin ([m]FOLFIRINOX) as initial treatment for localized pancreatic ductal adenocarcinoma (PDAC) are lacking. This study aimed to provide realistic estimates of oncologic outcomes in these patients. METHODS This international retrospective cohort study included all consecutive patients presenting with localized PDAC who received at least 1 cycle of (m)FOLFIRINOX as initial treatment in 5 referral centers from the United States and the Netherlands (2012-2019). Primary outcome was median overall survival (OS), calculated from the date of tissue diagnosis, assessed using Kaplan-Meier estimates. Log-rank test was used to compare OS between groups. A Cox proportional hazards regression model was used to assess prognostic baseline factors for OS. All statistical tests were 2-sided. RESULTS Overall, 1835 patients were included, of whom 958 (52.2%) had locally advanced (LA), 531 (28.9%) had borderline resectable (BR), and 346 (18.9%) had potentially resectable (PR) PDAC. The median number of (m)FOLFIRINOX cycles was 6 (interquartile range = 4-8). Subsequent treatment included second chemotherapy (12.9%), radiotherapy (49.0%), and resection (37.9%). The resection rate was 17.6% for LA, 53.1% for BR, and 70.5% for PR PDAC (P < .001). The margin-negative resection rate (>1 mm) was 55.2% for LA, 62.6% for BR, and 79.2% for PR PDAC (P < .001). The median OS was 18.7 months (95% confidence interval [CI] = 17.7 to 19.9 months) for LA, 23.2 months (95% CI = 21.0 to 25.7 months) for BR, and 31.2 months (95% CI = 26.2 to 36.6 months) for PR PDAC (P < .001). The median OS for 695 patients who underwent a resection was 38.3 months (95% CI = 36.1 to 42.0 months). Independent prognostic factors at baseline for worse OS were more advanced stage, worse performance status, baseline carbohydrate antigen (CA) 19-9 > 500 U/mL, and body mass index ≤18.5 kg/m2. CONCLUSIONS This large international cohort study provides realistic estimates of resection rates and survival in patients with LA, BR, and PR PDAC who started (m)FOLFIRINOX treatment in PDAC referral centers.
Collapse
Affiliation(s)
- Quisette P Janssen
- Department of Surgery, Erasmus MC Cancer Institute, University Medical Center Rotterdam, Rotterdam, the Netherlands
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Jacob L van Dam
- Department of Surgery, Erasmus MC Cancer Institute, University Medical Center Rotterdam, Rotterdam, the Netherlands
| | - Deesje Doppenberg
- Department of Surgery, Amsterdam UMC, University of Amsterdam, Cancer Center Amsterdam, Amsterdam, the Netherlands
| | - Laura R Prakash
- Department of Surgical Oncology, Division of Surgery, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Casper H J van Eijck
- Department of Surgery, Erasmus MC Cancer Institute, University Medical Center Rotterdam, Rotterdam, the Netherlands
| | - William R Jarnagin
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Eileen M O’ Reilly
- Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Alessandro Paniccia
- Department of Surgery, Division of Surgical Oncology, University of Pittsburgh Medical Center, Pittsburgh, PA, USA
| | - Marc G Besselink
- Department of Surgery, Amsterdam UMC, University of Amsterdam, Cancer Center Amsterdam, Amsterdam, the Netherlands
| | - Matthew H G Katz
- Department of Surgical Oncology, Division of Surgery, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Ching-Wei D Tzeng
- Department of Surgical Oncology, Division of Surgery, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Alice C Wei
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Amer H Zureikat
- Department of Surgery, Division of Surgical Oncology, University of Pittsburgh Medical Center, Pittsburgh, PA, USA
| | - Bas Groot Koerkamp
- Department of Surgery, Erasmus MC Cancer Institute, University Medical Center Rotterdam, Rotterdam, the Netherlands
| | | |
Collapse
|
|
34
|
Guenther M, Gil L, Surendran SA, Palm MA, Heinemann V, von Bergwelt-Baildon M, Mayerle J, Engel J, Werner J, Boeck S, Ormanns S. Bacterial Lipopolysaccharide as a Negative Predictor of Adjuvant Gemcitabine Efficacy in Pancreatic Cancer. JNCI Cancer Spectr 2022; 6:pkac039. [PMID: 35587155 PMCID: PMC9219162 DOI: 10.1093/jncics/pkac039] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/10/2022] [Revised: 05/01/2022] [Accepted: 05/02/2022] [Indexed: 11/21/2022] Open
Abstract
Adjuvant gemcitabine (aGC) is one standard of care after pancreatic ductal adenocarcinoma (PDAC) resection. No biomarker for its efficacy is established. As bacteria mediate gemcitabine resistance, we analyzed whether lipopolysaccharide (LPS) as surrogate for bacterial colonization is prognostic in PDAC patients treated with aGC or without aGC adjuvant gemcitabine. We detected LPS in 86 tumors from 376 patients, which defined a specific microbiome as revealed by 16 s-rRNA-sequencing. In the 230 aGC patients, LPS conferred worse disease-free survival (8.3 vs 13.7 months; hazard ratio = 1.75, 95% confidence interval = 1.22 to 2.49; log-rank P = .002) and overall survival (21.7 vs 28.5 months; hazard ratio = 1.80, 95% confidence interval = 1.23 to 2.57; log-rank P = .001) but not in the 146 naGC patients, which was confirmed in an independent validation cohort (n = 178). LPS may serve as a negative predictor for aGC efficacy in PDAC, which suggests a role for microbiome modification to overcome bacteria-mediated chemotherapy resistance.
Collapse
Affiliation(s)
- Michael Guenther
- Institute of Pathology, Faculty of Medicine, Ludwig-Maximilians-University, Munich, Germany
| | - Lina Gil
- Institute of Pathology, Faculty of Medicine, Ludwig-Maximilians-University, Munich, Germany
| | - Sai Agash Surendran
- Institute of Pathology, Faculty of Medicine, Ludwig-Maximilians-University, Munich, Germany
| | - Melanie Alexandra Palm
- Institute of Pathology, Faculty of Medicine, Ludwig-Maximilians-University, Munich, Germany
| | - Volker Heinemann
- Department of Internal Medicine III, Grosshadern University Hospital, Ludwig- Maximilians-University, Munich, Germany
- German Cancer Consortium (DKTK), partner site, Munich, Germany
| | - Michael von Bergwelt-Baildon
- Department of Internal Medicine III, Grosshadern University Hospital, Ludwig- Maximilians-University, Munich, Germany
- German Cancer Consortium (DKTK), partner site, Munich, Germany
| | - Julia Mayerle
- Department of Internal Medicine II, Grosshadern University Hospital, Ludwig-Maximilians-University, Munich, Germany
| | - Jutta Engel
- Munich Cancer Registry (MCR), Munich Tumor Centre (TZM), Institute for Medical Information Processing, Biometry and Epidemiology, Ludwig-Maximilians-University, Munich, Germany
| | - Jens Werner
- Department of General, Visceral and Transplant Surgery, Ludwig-Maximilians-University, Munich, Germany
| | - Stefan Boeck
- Department of Internal Medicine III, Grosshadern University Hospital, Ludwig- Maximilians-University, Munich, Germany
- German Cancer Consortium (DKTK), partner site, Munich, Germany
| | - Steffen Ormanns
- Institute of Pathology, Faculty of Medicine, Ludwig-Maximilians-University, Munich, Germany
- German Cancer Consortium (DKTK), partner site, Munich, Germany
| |
Collapse
|
|
35
|
Turner KM, Delman AM, Ammann AM, Sohal D, Olowokure O, Choe KA, Smith MT, Kharofa JR, Ahmad SA, Wilson GC, Patel SH. Is There a Benefit to Adjuvant Chemotherapy in Resected, Early Stage Pancreatic Ductal Adenocarcinoma? Ann Surg Oncol 2022; 29:10.1245/s10434-022-11580-7. [PMID: 35357614 DOI: 10.1245/s10434-022-11580-7] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/08/2021] [Accepted: 02/21/2022] [Indexed: 12/12/2022]
Abstract
BACKGROUND The role of systemic therapy for Stage IA pancreatic ductal adenocarcinoma (PDAC) is unclear. The aim of our study was to evaluate the impact of adjuvant chemotherapy (AC) on survival in patients with early stage disease. METHODS The National Cancer Database was queried from 2006 to 2017 for resected pT1N0M0 (Stage 1A) PDAC. Exclusion criteria included neoadjuvant therapy, radiation, or those who suffered a 90-day mortality. RESULTS Of the 1526 patients included in the study, 42.2% received AC and 57.8% underwent surgery alone. Patients who received AC were younger, had fewer comorbidities, and were more likely to have private insurance, compared with those treated with surgery alone. Patients who received AC had longer median overall survival (OS) compared with those who underwent surgery alone (105.7 months vs 72.0 months, p < 0.01). Subset analyses based on individual "good" prognostic features (size ≤ 1.0 cm, lymphovascular invasion negative, well/moderately differentiated, margin negative resection) demonstrated improved OS with AC. Following propensity score matching based on key clinicopathologic features, AC remained associated with improved median OS (83.7 months vs 59.8 months, p < 0.01). However, in the cohort with body/tail tumors (101.2 months vs 95.0 months, p = 0.19) and those with all "good" prognostic features (95.9 months vs 90.6 months, p = 0.15), AC was not associated with improved survival. CONCLUSIONS In resected, Stage IA PDAC, AC is associated with improved overall survival in the vast majority of patients; however, in select cohorts the role of AC is unclear. Further study is needed to tailor treatment to individual patients with PDAC.
Collapse
Affiliation(s)
- Kevin M Turner
- Cincinnati Research in Outcomes and Safety in Surgery (CROSS), Department of Surgery, University of Cincinnati College of Medicine, Cincinnati, OH, USA
| | - Aaron M Delman
- Cincinnati Research in Outcomes and Safety in Surgery (CROSS), Department of Surgery, University of Cincinnati College of Medicine, Cincinnati, OH, USA
| | - Allison M Ammann
- Cincinnati Research in Outcomes and Safety in Surgery (CROSS), Department of Surgery, University of Cincinnati College of Medicine, Cincinnati, OH, USA
| | - Davendra Sohal
- Department of Internal Medicine, Division of Hematology & Oncology, University of Cincinnati College of Medicine, Cincinnati, OH, USA
| | - Olugbenga Olowokure
- Department of Internal Medicine, Division of Hematology & Oncology, University of Cincinnati College of Medicine, Cincinnati, OH, USA
| | - Kyuran A Choe
- Department of Radiology, University of Cincinnati College of Medicine, Cincinnati, OH, USA
| | - Milton T Smith
- Department of Internal Medicine, Division of Digestive Diseases, University of Cincinnati College of Medicine, Cincinnati, OH, USA
| | - Jordan R Kharofa
- Department of Radiation Oncology, University of Cincinnati College of Medicine, Cincinnati, OH, USA
| | - Syed A Ahmad
- Department of Surgery, Division of Surgical Oncology, University of Cincinnati College of Medicine, Cincinnati, OH, USA
| | - Gregory C Wilson
- Department of Surgery, Division of Surgical Oncology, University of Cincinnati College of Medicine, Cincinnati, OH, USA
| | - Sameer H Patel
- Department of Surgery, Division of Surgical Oncology, University of Cincinnati College of Medicine, Cincinnati, OH, USA.
| |
Collapse
|
|
36
|
Ramaswamy A, Srinivas S, Chaudhari V, Bhargava P, Bhandare M, Shrikhande SV, Ostwal V. Systemic therapy in pancreatic ductal adenocarcinomas (PDACs)-basis and current status. Ecancermedicalscience 2022; 16:1367. [PMID: 35685956 PMCID: PMC9085164 DOI: 10.3332/ecancer.2022.1367] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/11/2021] [Indexed: 11/06/2022] Open
Abstract
A major shift in the approach to the management of pancreatic ductal adenocarcinomas (PDACs) has been the recognition of the systemic nature of the disease even in clinically and radiologically limited disease stages. The recalcitrant nature of PDAC is intrinsically related to the lack of therapeutic targets and dense surrounding stroma that limits the activity of currently available chemotherapeutic options. However, research is increasingly focusing on intensifying systemic management options in PDAC, resulting in gradual improvements in survival. Currently effective chemotherapeutic regimens like modified 5-fluorouracil-leucovorin-irinotecan-oxaliplatin and gemcitabine-nab-paclitaxel have improved outcomes in resectable and advanced PDAC. An increasing use of these regimens has also resulted in greater conversion of borderline resectable and locally advanced cancers to resection, though the most effective approach in this subgroup is yet to be identified. The current review presents an outline of the basic systemic nature of PDAC and current options of systemic therapy, predominantly chemotherapy .
Collapse
Affiliation(s)
- Anant Ramaswamy
- Department of Medical Oncology, Tata Memorial Hospital, Dr E Borges Road, Parel, Mumbai 400012, India
| | - Sujay Srinivas
- Department of Medical Oncology, Tata Memorial Hospital, Dr E Borges Road, Parel, Mumbai 400012, India
| | - Vikram Chaudhari
- GI and HPB Services, Tata Memorial Hospital, Homi Bhabha National Institute, Dr E Borges Road, Parel, Mumbai 400012, India
| | - Prabhat Bhargava
- Department of Medical Oncology, Tata Memorial Hospital, Dr E Borges Road, Parel, Mumbai 400012, India
| | - Manish Bhandare
- GI and HPB Services, Tata Memorial Hospital, Homi Bhabha National Institute, Dr E Borges Road, Parel, Mumbai 400012, India
| | - Shailesh V Shrikhande
- GI and HPB Services, Tata Memorial Hospital, Homi Bhabha National Institute, Dr E Borges Road, Parel, Mumbai 400012, India
| | - Vikas Ostwal
- Department of Medical Oncology, Tata Memorial Hospital, Dr E Borges Road, Parel, Mumbai 400012, India
| |
Collapse
|
|
37
|
Wang J, Zhang H, Shao P, Zhang X, Zhou B. Bioinformatic Analysis of Prognostic Value of Pyroptosis-Related Genes and Its Effect on Immune Cell Infiltration in Pancreatic Adenocarcinoma. Int J Gen Med 2022; 15:2311-2319. [PMID: 35256857 PMCID: PMC8898045 DOI: 10.2147/ijgm.s350959] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/14/2021] [Accepted: 02/08/2022] [Indexed: 12/12/2022] Open
Abstract
Purpose Pancreatic adenocarcinoma has a poor prognosis and chemotherapy has its limitation due to tumor heterogeneity. It is essential to find novel targets involving in tumorigenesis of pancreatic adenocarcinoma. Growing evidences indicated that pyroptosis is involved in tumorigenesis of many cancers, but the relationship between pyroptosis and pancreatic adenocarcinoma still remains to be elucidated. Our object is to explore whether pyroptosis-related different expression genes have association with survivals of pancreatic adenocarcinoma patients and the mechanism they may participate in. Besides, we also analyzed their effect on immune cell infiltration in tumor microenvironment. Patients and Methods We used the bioinformatic analysis tool including GEPIA, cBioPortal, STRING, GeneMANIA, R software 4.03 and TIMER2.0 to investigate the different expression, prognostic value, protein-protein interaction, gene ontology, pathway and effect of immune cell infiltration of pyroptosis-related genes in PAAD. Results Many pyroptosis-related genes express differently between pancreatic adenocarcinoma and normal tissues and they are associated with survival of PAAD. GABARAP and IL18 may play a key role in tumorigenesis of PAAD, for they are connected with overall survival, disease free survival and pathological stages at the same time. The function of pyroptosis-related genes includes cytokine production, endopeptidase activity, regulation of inflammation and inflammasome complex and pyroptosis-related genes have effect on immune cells infiltration in PAAD microenvironment. Conclusion Lots of pyroptosis-related DEGs may get involved in pathogenesis of PAAD and their high expression have an effect on survival. GABARAP and IL18 could be valuable research targets of PAAD.
Collapse
Affiliation(s)
- Jian Wang
- Department of General Surgery, Jiangsu Cancer Hospital & Jiangsu Institute of Cancer Research, The Affiliated Cancer Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, People’s Republic of China
| | - Hui Zhang
- Department of General Surgery, Jiangsu Cancer Hospital & Jiangsu Institute of Cancer Research, The Affiliated Cancer Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, People’s Republic of China
| | - Peng Shao
- Department of General Surgery, Jiangsu Cancer Hospital & Jiangsu Institute of Cancer Research, The Affiliated Cancer Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, People’s Republic of China
| | - Xu Zhang
- Department of General Surgery, Jiangsu Cancer Hospital & Jiangsu Institute of Cancer Research, The Affiliated Cancer Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, People’s Republic of China
- Correspondence: Xu Zhang; Bin Zhou, Tel/Fax +86-25-83284735, Email ;
| | - Bin Zhou
- Department of General Surgery, Jiangsu Cancer Hospital & Jiangsu Institute of Cancer Research, The Affiliated Cancer Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, People’s Republic of China
| |
Collapse
|
|
38
|
Mangieri CW, Valenzuela CD, Erali RA, Shen P, Howerton R, Clark CJ. Prognostic Effect of Aberrant Right Hepatic Artery with Pancreaticoduodenectomy: Focus on Hepatic Recurrence. Ann Surg Oncol 2022; 29:3219-3228. [DOI: 10.1245/s10434-022-11341-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/22/2021] [Accepted: 12/31/2021] [Indexed: 11/18/2022]
|
|
39
|
Wang R, Nissen NN, Zhang Y, Shao C, Chu CY, Huynh C, Posadas EM, Tomlinson JS, Lewis MS, Pandol SJ. Circulating Fatty Objects and Their Preferential Presence in Pancreatic Cancer Patient Blood Samples. Front Physiol 2022; 13:827531. [PMID: 35237181 PMCID: PMC8883044 DOI: 10.3389/fphys.2022.827531] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/02/2021] [Accepted: 01/10/2022] [Indexed: 01/28/2023] Open
Abstract
Human cancers are often complicated with increased incidences of blood vessel occlusion, which are mostly insensitive to anticoagulation therapy. We searched for causal factors of cancer-associated embolism. A total of 2,017 blood samples was examined for visible abnormalities. Examined were peripheral blood samples from cancer patients who were about to undergo surgical treatment for genitourinary, breast, gastrointestinal or abdominal tumors. Samples from ambulatory patients being treated for recurrent or castration-resistant prostate cancers were included in the study. The lipid-rich nature was studied with lipophilic stains and lipid panel analysis, while surface membrane was assessed with specific staining and antibody detection. We identified a new entity, lipid droplet-like objects or circulating fatty objects (CFOs), visible in the blood samples of many cancer patients, with the potential of causing embolism. CFOs were defined as lipid-rich objects with a membrane, capable of gaining in volume through interaction with peripheral blood mononuclear cells in ex vivo culture. Blood samples from pancreatic cancer patients were found to have the highest CFO incidence and largest CFO numbers. Most noticeably, CFOs from many pancreatic cancer samples presented as large clusters entangled in insoluble fiber networks, suggestive of intravascular clotting. This study identifies CFO as an abnormal entity in cancer patient blood, and a contributory factor to intravascular embolism during cancer development and progression.
Collapse
Affiliation(s)
- Ruoxiang Wang
- Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, CA, United States
| | - Nicholas N. Nissen
- Department of Surgery, Cedars-Sinai Medical Center, Los Angeles, CA, United States
| | - Yi Zhang
- Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA, United States
| | - Chen Shao
- Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, CA, United States
| | - Chia-Yi Chu
- Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, CA, United States
| | - Carissa Huynh
- Biobank and Translational Research Core, Cedars-Sinai Medical Center, Los Angeles, CA, United States
| | - Edwin M. Posadas
- Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, CA, United States
| | - James S. Tomlinson
- Department of Surgery, VA Greater Los Angeles Healthcare System, Los Angeles, CA, United States
| | - Michael S. Lewis
- Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, CA, United States
- Department of Pathology, VA Greater Los Angeles Healthcare System, Los Angeles, CA, United States
| | - Stephen J. Pandol
- Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, CA, United States
| |
Collapse
|
|
40
|
Irfan A, Rose JB, Wang TN, Vickers SM, Dudeja V, Gbolahan O, Reddy S. The Fate of Resectable Pancreatic Adenocarcinoma After Neoadjuvant Chemotherapy. Pancreas 2022; 51:100-105. [PMID: 35195602 DOI: 10.1097/mpa.0000000000001972] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/10/2022]
Abstract
OBJECTIVES Pancreatic cancer continues to be a major cause of cancer-related mortality. There has been a greater implementation of up-front chemotherapy for pancreatic adenocarcinoma patients. Although there are many theoretical benefits to neoadjuvant chemotherapy, its clinical impact is uncertain. We sought to understand the outcomes of patients with resectable and borderline-resectable pancreatic adenocarcinoma who underwent neoadjuvant chemotherapy. METHODS Patients were collected in a secure database from September 2018 to May 2020. Patients were excluded if they presented with locally advanced or metastatic disease, inability to complete chemotherapy, or if they were not a surgical candidate. RESULTS Sixty-six patients with resectable disease underwent chemotherapy. Folinic acid/5-fluorouracil/irinotecan/oxaliplatin was used in 41 patients (62.1%) and gemcitabine-based regimens in 28 patients (42.4%, greater than 100% as some patients underwent both regimens). After restaging, 47 patients (71.2%) were thought to have resectable disease. Of these patients, 36 have been successfully resected to date. Metastatic disease was found in 12 patients (18.2%) and 6 patients (9.1%) had locally advanced disease. CONCLUSIONS Most patients with resectable pancreatic cancer are resected after neoadjuvant chemotherapy, but a subset will develop local or distant progression. Further studies will be needed to determine which patients will progress locally and may benefit from an up-front surgical approach.
Collapse
Affiliation(s)
| | | | | | | | | | - Olumide Gbolahan
- Division of Hematology Oncology, Department of Medicine, University of Alabama at Birmingham, Birmingham, AL
| | | |
Collapse
|
|
41
|
Brendel K, Bekaii‐Saab T, Boland PM, Dayyani F, Dean A, Macarulla T, Maxwell F, Mody K, Pedret‐Dunn A, Wainberg ZA, Zhang B. Population pharmacokinetics of liposomal irinotecan in patients with cancer and exposure–safety analyses in patients with metastatic pancreatic cancer. CPT Pharmacometrics Syst Pharmacol 2021; 10:1550-1563. [PMID: 34750990 PMCID: PMC8674005 DOI: 10.1002/psp4.12725] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/15/2021] [Revised: 06/23/2021] [Accepted: 08/16/2021] [Indexed: 12/24/2022] Open
Abstract
Liposomal irinotecan is a liposomal formulation of irinotecan, which prolongs circulation of irinotecan and its active metabolite SN‐38. A population pharmacokinetic (PK) model was developed based on data from seven studies (N = 440). Adequacy of the model was assessed using multiple methods, including visual predictive check. Associations between PK exposure and the incidence of diarrhea (grade ≥3) and neutropenia adverse events (AEs) (grade ≥3) at first event in patients with metastatic pancreatic ductal adenocarcinoma (mPDAC) were investigated using logistic regression based on data from two studies (the phase III NAPOLI‐1 [N = 260] and phase I/II NCT02551991 [N = 56] trials). The PKs of total irinotecan was described by a two‐compartment model with first‐order elimination, with SN‐38 formed directly by a first‐order constant from the central compartment of irinotecan or after using a transit compartment. Clearance was 17.9 L/week (0.107 L/h) and 19,800 L/week (118 L/h) for total irinotecan and SN‐38, respectively. The UGT1A1*28 7/7 homozygous genotype had no significant impact on SN‐38 clearance. Model evaluation was satisfactory for both irinotecan and SN‐38. The incidence of diarrhea (grade ≥3) at first event was significantly higher with increasing average concentrations of total irinotecan and SN‐38; there was no significant association between an increased risk of neutropenia AEs (grade ≥3) at first event and average SN‐38 concentrations. In summary, the PKs of total irinotecan and SN‐38 after administration of liposomal irinotecan were well‐described by the model. The UGT1A1*28 status had no significant impact on the PKs of liposomal irinotecan.
Collapse
Affiliation(s)
| | | | | | | | - Andrew Dean
- St John of God Hospital Subiaco Perth Western Australia Australia
| | - Teresa Macarulla
- Vall d´Hebrón University Hospital Vall d´Hebrón Institute of Oncology Barcelona Spain
| | | | | | | | - Zev A Wainberg
- Ronald Regan UCLA Medical Center Los Angeles California USA
| | | |
Collapse
|
|
42
|
Ward EP, Zeh Iii HJ, Tsai S. Current Controversies in Neoadjuvant Therapy for Pancreatic Cancer. Surg Oncol Clin N Am 2021; 30:657-671. [PMID: 34511188 DOI: 10.1016/j.soc.2021.06.010] [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: 10/20/2022]
Abstract
Over the last two decades, there have been significant changes in the management of patients with localized pancreatic cancer. The rationale for an evolution toward a neoadjuvant approach and summary of relevant clinical trials is reviewed. Controversies in identifying optimal neoadjuvant therapeutic approaches are discussed.
Collapse
Affiliation(s)
- Erin P Ward
- Surgical Oncology Division, Department of Surgery, Medical College of Wisconsin, 8701 W Watertown Plank Road, Milwaukee, WI 53226, USA
| | - Herbert J Zeh Iii
- Division of Surgical Oncology, Department of Surgery, UT Southwestern (University of Texas), 5323 Harry Hines Blvd. Dallas, TX 75390, USA
| | - Susan Tsai
- Surgical Oncology Division, Department of Surgery, Medical College of Wisconsin, 8701 W Watertown Plank Road, Milwaukee, WI 53226, USA.
| |
Collapse
|
|
43
|
Taboada AGM, Lominchar PL, Roman LM, García-Alfonso P, Martin AJM, Rodriguez JAB, Pascual JMA. Advances in neoadjuvant therapy for resectable pancreatic cancer over the past two decades. Ann Hepatobiliary Pancreat Surg 2021; 25:179-191. [PMID: 34053920 PMCID: PMC8180394 DOI: 10.14701/ahbps.2021.25.2.179] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/01/2020] [Accepted: 12/31/2020] [Indexed: 02/06/2023] Open
Abstract
In the last two decades, pancreatic cancer has been undergoing important changes in its perioperative management due to the great interest in multidisciplinary management and preoperative multimodal therapy, which in numerous studies have shown promising clinical results. Although the standard of treatment for resectable pancreatic ductal adenocarcinoma (PDAC) today is surgery followed by adjuvant therapy, as it is a biologically aggressive disease, even with complete resection, it has high rates of local and distant relapse. Several retrospective and prospective phase I/II studies have opened the window for neoadjuvant therapy with chemotherapy (CT), chemoradiotherapy (CRT), or both, as an alternative treatment for resectable pancreatic cancer, with promising results. Neoadjuvant therapy could has some advantages, including early administration of systemic treatment, in vivo assessment of response to treatment, increase resectability rate in borderline patients, increase resection rate with negative margin and survival benefit. While it seems clear that even potentially resectable disease would benefit from preoperative multimodal therapy, the optimal neoadjuvant therapeutic strategy is still controversial and currently there are only recommendations for neoadjuvant treatment, in clinical guidelines such as the NCCN and ESMO, for borderline and/or locally advanced PDAC. This review provides an overview of recent studies available and how they relate to systemic treatment of resectable PDAC in the neoadjuvant setting.
Collapse
Affiliation(s)
- Alvaro Gregorio Morales Taboada
- Department of General and Digestive Surgery, Hospital General Universitario Gregorio Marañon, Complutense University of Madrid, Madrid, Spain.,Transplant and Hepatobiliopancreatic Surgery Unit, Department of General and Digestive Surgery, Hospital General Universitario Gregorio Marañón, Madrid, Spain
| | - Pablo Lozano Lominchar
- Department of General and Digestive Surgery, Hospital General Universitario Gregorio Marañon, Complutense University of Madrid, Madrid, Spain
| | - Lorena Martin Roman
- Department of General and Digestive Surgery, Hospital General Universitario Gregorio Marañon, Complutense University of Madrid, Madrid, Spain
| | - Pilar García-Alfonso
- Department of Medical Oncology, Department of Oncology, Hospital general Universitario Gregorio Marañon, Complutense University of Madrid, Madrid, Spain
| | - Andres Jesús Muñoz Martin
- Department of Medical Oncology, Department of Oncology, Hospital general Universitario Gregorio Marañon, Complutense University of Madrid, Madrid, Spain
| | - Jose Antonio Blanco Rodriguez
- Department of Radiation Oncology, Department of Oncology, Hospital general Universitario Gregorio Marañon, Complutense University of Madrid, Madrid, Spain
| | - Jose Manuel Asencio Pascual
- Department of General and Digestive Surgery, Hospital General Universitario Gregorio Marañon, Complutense University of Madrid, Madrid, Spain.,Transplant and Hepatobiliopancreatic Surgery Unit, Department of General and Digestive Surgery, Hospital General Universitario Gregorio Marañón, Madrid, Spain
| |
Collapse
|
|
44
|
Attiyeh MA, Amini A, Chung V, Melstrom LG. Multidisciplinary management of locally advanced pancreatic adenocarcinoma: Biology is King. J Surg Oncol 2021; 123:1395-1404. [PMID: 33831247 DOI: 10.1002/jso.26415] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/14/2020] [Revised: 01/18/2021] [Accepted: 01/27/2021] [Indexed: 12/21/2022]
Abstract
The annual incidence of pancreatic cancer is nearly 50,000 patients. The 5-year overall survival is only 9%, and there remains a great need for better therapy. A subset of these patients presents with locally advanced disease. Multidisciplinary therapy has evolved to include some combination of systemic chemotherapy, locoregional radiation, and surgery in select patients with excellent biology. This review will address the thoughtful evidence-based and individualized approach to these patients.
Collapse
Affiliation(s)
- Marc A Attiyeh
- Department of Surgical Oncology, City of Hope National Medical Center, Duarte, California, USA
| | - Arya Amini
- Department of Radiation Oncology, City of Hope National Medical Center, Duarte, California, USA
| | - Vincent Chung
- Department of Medical Oncology, City of Hope National Medical Center, Duarte, California, USA
| | - Laleh G Melstrom
- Department of Surgical Oncology, City of Hope National Medical Center, Duarte, California, USA
| |
Collapse
|
|
45
|
Liu D, Song T. Changes in and challenges regarding the surgical treatment of hepatocellular carcinoma in China. Biosci Trends 2021; 15:142-147. [PMID: 33716267 DOI: 10.5582/bst.2021.01083] [Citation(s) in RCA: 50] [Impact Index Per Article: 12.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022]
Abstract
Hepatocellular carcinoma (HCC) is a common malignant tumor with a high morbidity and mortality in China and elsewhere in the world. Due to its tumor heterogeneity and distant metastasis, patients with HCC often have a poor prognosis. A surgical treatment such as a radical hepatectomy is still the treatment of choice for patients with HCC in current clinical practice. However, the high rate of recurrence and rate of metastasis after surgery diminishes the survival of and prognosis for these patients. In an era of targeted therapy and immunotherapy, the surgical treatment of HCC must change. This review focuses on the definition, feasibility, and criteria with which to evaluate neoadjuvant therapy for HCC in order to provide a new perspective on surgical treatment of HCC.
Collapse
Affiliation(s)
- Dongming Liu
- Department of Hepatobiliary, HCC Research Center for Prevention and Therapy, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin, China
| | - Tianqiang Song
- Department of Hepatobiliary, HCC Research Center for Prevention and Therapy, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin, China
| |
Collapse
|
|
46
|
Sohal DPS, Duong M, Ahmad SA, Gandhi NS, Beg MS, Wang-Gillam A, Wade JL, Chiorean EG, Guthrie KA, Lowy AM, Philip PA, Hochster HS. Efficacy of Perioperative Chemotherapy for Resectable Pancreatic Adenocarcinoma: A Phase 2 Randomized Clinical Trial. JAMA Oncol 2021; 7:421-427. [PMID: 33475684 PMCID: PMC7821078 DOI: 10.1001/jamaoncol.2020.7328] [Citation(s) in RCA: 172] [Impact Index Per Article: 43.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
Importance Clinical outcomes after curative treatment of resectable pancreatic ductal adenocarcinoma (PDA) remain suboptimal. To assess the potential of early control of systemic disease with multiagent perioperative chemotherapy, we conducted a prospective trial. Objective To determine 2-year overall survival (OS) using perioperative chemotherapy for resectable PDA. Design, Setting, and Participants This was a randomized phase 2 trial of perioperative chemotherapy with a pick-the-winner design. It was conducted across the National Clinical Trials Network, including academic and community centers all across the US. Eligibility required patients with Zubrod Performance Score of 0 or 1, confirmed tissue diagnosis of PDA, and resectable disease per Intergroup criteria. Interventions Perioperative (12 weeks preoperative, 12 weeks postoperative) chemotherapy with either fluorouracil, irinotecan, and oxaliplatin (mFOLFIRINOX, arm 1) or gemcitabine/nab-paclitaxel (arm 2). Main Outcomes and Measures The primary outcome was 2-year overall survival (OS), using a pick-the-winner design; for 100 eligible patients, accrual up to 150 patients was planned to account for cases deemed ineligible at central radiology review. Results From 2015 to 2018, 147 patients were enrolled; 43 patients (29%) had ineligible disease, beyond resectability criteria, at central radiology review. There were 102 eligible and evaluable patients, 55 in arm 1 and 47 in arm 2, of whom the median (range) age was 66 (44-76) and 64 (46-76) years, respectively; 36 patients (65%) in arm 1 and 24 (51%) in arm 2 were men. In arm 1, 34 (62%) had Zubrod Performance Score of 0, while in arm 2, 31 (66%) did; and 44 (80%) in arm 1 and 39 (83%) in arm 2 had head tumors. Of 102 patients, 84% and 85% completed preoperative chemotherapy, 73% and 70% underwent resection, and 49% and 40% completed all treatment. Adverse events were expected hematologic toxic effects, fatigue, and gastrointestinal toxicities. Two-year OS was 47% (95% CI, 31%-61%) for arm 1 and 48% (95% CI, 31%-63%) for arm 2; median OS was 23.2 months (95% CI, 17.6-45.9 months) and 23.6 months (95% CI, 17.8-31.7 months). Neither arm's 2-year OS estimate was significantly higher than the a priori threshold of 40%. Median disease-free survival after resection was 10.9 months in arm 1 and 14.2 months in arm 2. Conclusions and Relevance This phase 2 randomized clinical trial did not demonstrate an improved OS with perioperative chemotherapy, compared with historical data from adjuvant trials in resectable pancreatic cancer. Two-year OS was 47% with mFOLFIRINOX and 48% with gemcitabine/nab-paclitaxel for all eligible patients starting treatment for resectable PDA. The trial also demonstrated adequate safety and high resectability rates with perioperative chemotherapy, and challenges in quality control for resectability criteria. Trial Registration ClinicalTrials.gov Identifier: NCT02562716.
Collapse
Affiliation(s)
- Davendra P S Sohal
- Division of Hematology and Oncology, University of Cincinnati, Cincinnati, Ohio
| | - Mai Duong
- SWOG Statistical and Data Management Center, Fred Hutchinson Cancer Research Center, Seattle, Washington
| | - Syed A Ahmad
- Division of Hematology and Oncology, University of Cincinnati, Cincinnati, Ohio
| | | | - M Shaalan Beg
- University of Texas Southwestern Medical Center, Dallas
| | - Andrea Wang-Gillam
- Division of Oncology, Washington University in St Louis, St Louis, Missouri
| | | | - E Gabriela Chiorean
- University of Washington School of Medicine, Fred Hutchinson Cancer Research Center, Seattle
| | - Katherine A Guthrie
- SWOG Statistical and Data Management Center, Fred Hutchinson Cancer Research Center, Seattle, Washington
| | - Andrew M Lowy
- Department of Surgery, University of California, San Diego, La Jolla
| | - Philip A Philip
- Medical Oncology, Karmanos Cancer Institute, Detroit, Michigan
| | - Howard S Hochster
- Gastrointestinal Oncology, Rutgers Cancer Institute of New Jersey, New Brunswick
| |
Collapse
|
|
47
|
Watson MD, Baimas-George MR, Murphy KJ, Pickens RC, Iannitti DA, Martinie JB, Baker EH, Vrochides D, Ocuin LM. Pure and Hybrid Deep Learning Models can Predict Pathologic Tumor Response to Neoadjuvant Therapy in Pancreatic Adenocarcinoma: A Pilot Study. Am Surg 2020; 87:1901-1909. [PMID: 33381979 DOI: 10.1177/0003134820982557] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
BACKGROUND Neoadjuvant therapy may improve survival of patients with pancreatic adenocarcinoma; however, determining response to therapy is difficult. Artificial intelligence allows for novel analysis of images. We hypothesized that a deep learning model can predict tumor response to NAC. METHODS Patients with pancreatic cancer receiving neoadjuvant therapy prior to pancreatoduodenectomy were identified between November 2009 and January 2018. The College of American Pathologists Tumor Regression Grades 0-2 were defined as pathologic response (PR) and grade 3 as no response (NR). Axial images from preoperative computed tomography scans were used to create a 5-layer convolutional neural network and LeNet deep learning model to predict PRs. The hybrid model incorporated decrease in carbohydrate antigen 19-9 (CA19-9) of 10%. Accuracy was determined by area under the curve. RESULTS A total of 81 patients were included in the study. Patients were divided between PR (333 images) and NR (443 images). The pure model had an area under the curve (AUC) of .738 (P < .001), whereas the hybrid model had an AUC of .785 (P < .001). CA19-9 decrease alone was a poor predictor of response with an AUC of .564 (P = .096). CONCLUSIONS A deep learning model can predict pathologic tumor response to neoadjuvant therapy for patients with pancreatic adenocarcinoma and the model is improved with the incorporation of decreases in serum CA19-9. Further model development is needed before clinical application.
Collapse
Affiliation(s)
- Michael D Watson
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, 2351Atrium Health, Charlotte, NC, USA
| | - Maria R Baimas-George
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, 2351Atrium Health, Charlotte, NC, USA
| | - Keith J Murphy
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, 2351Atrium Health, Charlotte, NC, USA
| | - Ryan C Pickens
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, 2351Atrium Health, Charlotte, NC, USA
| | - David A Iannitti
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, 2351Atrium Health, Charlotte, NC, USA
| | - John B Martinie
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, 2351Atrium Health, Charlotte, NC, USA
| | - Erin H Baker
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, 2351Atrium Health, Charlotte, NC, USA
| | - Dionisios Vrochides
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, 2351Atrium Health, Charlotte, NC, USA
| | - Lee M Ocuin
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, 2351Atrium Health, Charlotte, NC, USA
| |
Collapse
|
|
48
|
Salinas-Miranda E, Khalvati F, Namdar K, Deniffel D, Dong X, Abbas E, Wilson JM, O'Kane GM, Knox J, Gallinger S, Haider MA. Validation of Prognostic Radiomic Features From Resectable Pancreatic Ductal Adenocarcinoma in Patients With Advanced Disease Undergoing Chemotherapy. Can Assoc Radiol J 2020; 72:605-613. [PMID: 33151087 DOI: 10.1177/0846537120968782] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
BACKGROUND Radiomic features in pancreatic ductal adenocarcinoma (PDAC) often lack validation in independent test sets or are limited to early or late stage disease. Given the lethal nature of PDAC it is possible that there are similarities in radiomic features of both early and advanced disease reflective of aggressive biology. PURPOSE To assess the performance of prognostic radiomic features previously published in patients with resectable PDAC in a test set of patients with unresectable PDAC undergoing chemotherapy. METHODS The pre-treatment CT of 108 patients enrolled in a prospective chemotherapy trial were used as a test cohort for 2 previously published prognostic radiomic features in resectable PDAC (Sum Entropy and Cluster Tendency with square-root filter[Sqrt]). We assessed the performance of these 2 radiomic features for the prediction of overall survival (OS) and time to progression (TTP) using Cox proportional-hazard models. RESULTS Sqrt Cluster Tendency was significantly associated with outcome with a hazard ratio (HR) of 1.27(for primary pancreatic tumor plus local nodes), (Confidence Interval(CI):1.01 -1.6, P-value = 0.039) for OS and a HR of 1.25(CI:1.00 -1.55, P-value = 0.047) for TTP. Sum entropy was not associated with outcomes. Sqrt Cluster Tendency remained significant in multivariate analysis. CONCLUSION The CT radiomic feature Sqrt Cluster Tendency, previously demonstrated to be prognostic in resectable PDAC, remained a significant prognostic factor for OS and TTP in a test set of unresectable PDAC patients. This radiomic feature warrants further investigation to understand its biologic correlates and CT applicability in PDAC patients.
Collapse
Affiliation(s)
- Emmanuel Salinas-Miranda
- 90755Lunenfeld-Tanenbaum Research Institute, Sinai Health System, Mount Sinai Hospital, Joseph & Wolf Lebovic Health Complex, Toronto, Ontario, Canada.,PanCuRx Translational Research Initiative, 90755Ontario Institute for Cancer Research, Toronto, Ontario, Canada
| | - Farzad Khalvati
- 90755Lunenfeld-Tanenbaum Research Institute, Sinai Health System, Mount Sinai Hospital, Joseph & Wolf Lebovic Health Complex, Toronto, Ontario, Canada.,Joint Department of Medical Imaging, University Health Network/Sinai Health System, Toronto, Ontario, Canada
| | - Kashayar Namdar
- 90755Lunenfeld-Tanenbaum Research Institute, Sinai Health System, Mount Sinai Hospital, Joseph & Wolf Lebovic Health Complex, Toronto, Ontario, Canada
| | - Dominik Deniffel
- 90755Lunenfeld-Tanenbaum Research Institute, Sinai Health System, Mount Sinai Hospital, Joseph & Wolf Lebovic Health Complex, Toronto, Ontario, Canada
| | - Xin Dong
- 90755Lunenfeld-Tanenbaum Research Institute, Sinai Health System, Mount Sinai Hospital, Joseph & Wolf Lebovic Health Complex, Toronto, Ontario, Canada
| | - Engy Abbas
- Joint Department of Medical Imaging, University Health Network/Sinai Health System, Toronto, Ontario, Canada
| | - Julie M Wilson
- PanCuRx Translational Research Initiative, 90755Ontario Institute for Cancer Research, Toronto, Ontario, Canada
| | - Grainne M O'Kane
- PanCuRx Translational Research Initiative, 90755Ontario Institute for Cancer Research, Toronto, Ontario, Canada.,Department of Medical Oncology and Hematology, Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada
| | - Jennifer Knox
- PanCuRx Translational Research Initiative, 90755Ontario Institute for Cancer Research, Toronto, Ontario, Canada.,Department of Medical Oncology and Hematology, Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada
| | - Steven Gallinger
- PanCuRx Translational Research Initiative, 90755Ontario Institute for Cancer Research, Toronto, Ontario, Canada.,Hepatobiliary Pancreatic Surgical Oncology Program, University Health Network, Toronto, Ontario, Canada
| | - Masoom A Haider
- 90755Lunenfeld-Tanenbaum Research Institute, Sinai Health System, Mount Sinai Hospital, Joseph & Wolf Lebovic Health Complex, Toronto, Ontario, Canada.,PanCuRx Translational Research Initiative, 90755Ontario Institute for Cancer Research, Toronto, Ontario, Canada.,Joint Department of Medical Imaging, University Health Network/Sinai Health System, Toronto, Ontario, Canada
| |
Collapse
|
|
49
|
Drake JA, Stiles ZE, Behrman SW, Glazer ES, Deneve JL, Somer BG, Vanderwalde NA, Dickson PV. The utilization and impact of adjuvant therapy following neoadjuvant therapy and resection of pancreatic adenocarcinoma: does more really matter? HPB (Oxford) 2020; 22:1530-1541. [PMID: 32209323 DOI: 10.1016/j.hpb.2020.02.011] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/05/2019] [Revised: 01/13/2020] [Accepted: 02/26/2020] [Indexed: 12/12/2022]
Abstract
BACKGROUND Although neoadjuvant therapy is increasingly administered to patients with pancreatic ductal adenocarcinoma (PDAC), the impact of additional adjuvant therapy (AT) following resection is not well defined. METHODS The National Cancer Database (NCDB) was queried for patients who received neoadjuvant therapy followed by R0 or R1 resection for PDAC. Factors influencing survival, including the receipt of AT were evaluated. RESULTS Of patients receiving neoadjuvant therapy and resection 680 (33.8%) received AT and 1331 (66.2%) did not. For R0 resected patients (n = 1800), lymphovascular invasion (HR 1.24, p = 0.034) and increasing N classification (N1: HR 1.27, p = 0.019; N2: HR 1.51, p = 0.004) were associated with increased risk of death while AT was not associated with improved overall survival (OS) (HR 0.88, p = 0.179). Following R1 resection (n = 211), AT was associated with reduced risk of death (HR 0.57, p = 0.038). Within propensity matched cohorts, median OS for patients receiving and not receiving AT was 32.1 and 30.0 months after R0 resection (p = 0.184), and 23.6 and 20.5 months after R1 resection (p = 0.005). CONCLUSION This analysis demonstrated that AT did not yield OS benefit for patients who had neoadjuvant therapy and R0 resection and a statistically significant, although relatively short, improvement in OS for patients who underwent R1 resection.
Collapse
Affiliation(s)
- Justin A Drake
- Department of Surgery, Division of Surgical Oncology, University of Tennessee Health Science Center, 910 Madison Ave., 3rd Floor, Memphis, TN 38163, USA
| | - Zachary E Stiles
- Department of Surgery, Division of Surgical Oncology, University of Tennessee Health Science Center, 910 Madison Ave., 3rd Floor, Memphis, TN 38163, USA
| | - Stephen W Behrman
- Department of Surgery, Division of Surgical Oncology, University of Tennessee Health Science Center, 910 Madison Ave., 3rd Floor, Memphis, TN 38163, USA
| | - Evan S Glazer
- Department of Surgery, Division of Surgical Oncology, University of Tennessee Health Science Center, 910 Madison Ave., 3rd Floor, Memphis, TN 38163, USA
| | - Jeremiah L Deneve
- Department of Surgery, Division of Surgical Oncology, University of Tennessee Health Science Center, 910 Madison Ave., 3rd Floor, Memphis, TN 38163, USA
| | - Bradley G Somer
- Medical Oncology, West Cancer Center and Research Institute, 7945 Wolf River Blvd, Germanton, TN 38138, USA
| | - Noam A Vanderwalde
- Radiation Oncology, West Cancer Center and Research Institute, 7945 Wolf River Blvd, Germanton, TN 38138, USA
| | - Paxton V Dickson
- Department of Surgery, Division of Surgical Oncology, University of Tennessee Health Science Center, 910 Madison Ave., 3rd Floor, Memphis, TN 38163, USA.
| |
Collapse
|
|
50
|
Liu H, Zenati MS, Rieser CJ, Al-Abbas A, Lee KK, Singhi AD, Bahary N, Hogg ME, Zeh HJ, Zureikat AH. CA19-9 Change During Neoadjuvant Therapy May Guide the Need for Additional Adjuvant Therapy Following Resected Pancreatic Cancer. Ann Surg Oncol 2020; 27:3950-3960. [PMID: 32318949 PMCID: PMC7931260 DOI: 10.1245/s10434-020-08468-9] [Citation(s) in RCA: 29] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/02/2019] [Indexed: 02/06/2023]
Abstract
BACKGROUND Neoadjuvant therapy (NAT) is increasingly utilized for pancreatic cancer, however the added benefit of adjuvant therapy (AT) in this setting is unknown. We hypothesized that the magnitude of CA19-9 response to NAT can guide the need for further AT in resected pancreatic cancer. METHODS CA19-9 secretors who received NAT for pancreatic cancer during 2008-2016 at a single institution were analyzed and CA19-9 response (difference between pre- and post-NAT values) was measured. Kaplan-Meier estimators and Cox proportional hazard ratio models were used to determine the optimal CA19-9 response at which AT ceases to confer any additional survival benefit after NAT. RESULTS A total of 241 patients (mean age 65.4 years, 50% female) with complete CA19-9 data who underwent NAT followed by resection were analyzed. In a cohort of patients (n = 78) in whom CA19-9 normalized with a decrease > 50% after NAT (optimal responders), AT was not associated with additional survival benefit (40.6 vs. 39.0 months, p = 0.815). Conversely, in the cohort of patients (n = 163) in whom NAT was not associated with normalization and a decrease of ≤ 50% in CA19-9 (suboptimal responders), receipt of AT was associated with a survival benefit (34.5 vs. 19.1 months, p < 0.001) following NAT. A Cox proportional hazards model confirmed CA19-9 normalization and decrease > 50% during NAT to predict no additional survival benefit from AT. CONCLUSIONS The magnitude of CA19-9 response to NAT may predict the need for further AT in resected pancreatic cancer. Prospective studies are needed to elucidate the optimal interplay of NAT and AT in pancreatic cancer.
Collapse
Affiliation(s)
- Hao Liu
- Division of Gastrointestinal Surgical Oncology, Department of Surgery, University of Pittsburgh Medical Center, Pittsburgh, PA, USA
| | - Mazen S Zenati
- Department of Surgery and Epidemiology, University of Pittsburgh Medical Center, Pittsburgh, PA, USA
| | - Caroline J Rieser
- Division of Gastrointestinal Surgical Oncology, Department of Surgery, University of Pittsburgh Medical Center, Pittsburgh, PA, USA
| | - Amr Al-Abbas
- Division of Gastrointestinal Surgical Oncology, Department of Surgery, University of Pittsburgh Medical Center, Pittsburgh, PA, USA
| | - Kenneth K Lee
- Division of Gastrointestinal Surgical Oncology, Department of Surgery, University of Pittsburgh Medical Center, Pittsburgh, PA, USA
| | - Aatur D Singhi
- Department of Pathology, University of Pittsburgh Medical Center, Pittsburgh, PA, USA
| | - Nathan Bahary
- Department of Medicine, University of Pittsburgh Medical Center, Pittsburgh, PA, USA
| | - Melissa E Hogg
- Department of Surgery, NorthShore University Health System, Chicago, IL, USA
| | - Herbert J Zeh
- Department of Surgery, University of Texas Southwestern, Dallas, TX, USA
| | - Amer H Zureikat
- Division of Gastrointestinal Surgical Oncology, Department of Surgery, University of Pittsburgh Medical Center, Pittsburgh, PA, USA.
| |
Collapse
|