Surgery for pancreatic cancer: current controversies and challenges

2021 ◽  
Author(s):  
Monish Karunakaran ◽  
Savio George Barreto
Keyword(s):  
Pancreatic Cancer ◽  
Minimally Invasive ◽  
Neoadjuvant Therapy ◽  
Disease Free Survival ◽  
Current Status ◽  
Preoperative Imaging ◽  
R0 Resection ◽  
Term Survival ◽  
Strict Adherence ◽  
Operative Morbidity

Two areas that remain the focus of improvement in pancreatic cancer include high post-operative morbidity and inability to uniformly translate surgical success into long-term survival. This narrative review addresses specific aspects of pancreatic cancer surgery, including neoadjuvant therapy, vascular resections, extended pancreatectomy, extent of lymphadenectomy and current status of minimally invasive surgery. R0 resection confers longer disease-free survival and overall survival. Vascular and adjacent organ resections should be undertaken after neoadjuvant therapy, only if R0 resection can be ensured based on high-quality preoperative imaging, and that too, with acceptable post-operative morbidity. Extended lymphadenectomy does not offer any advantage over standard lymphadenectomy. Although minimally invasive distal pancreatectomies offers some short-term benefits over open distal pancreatectomy, safety remains a concern with minimally invasive pancreatoduodenectomy. Strict adherence to principles and judicious utilization of surgery within a multimodality framework is the way forward.

scholarly journals Liquid Biopsy in Pancreatic Cancer: Are We Ready to Apply It in the Clinical Practice?

Cancers ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 1986
Author(s):  
Victoria Heredia-Soto ◽  
Nuria Rodríguez-Salas ◽  
Jaime Feliu
Keyword(s):  
Pancreatic Cancer ◽  
Clinical Practice ◽  
Early Diagnosis ◽  
Minimally Invasive ◽  
Liquid Biopsy ◽  
Genetic Material ◽  
Current Status ◽  
Ductal Adenocarcinoma ◽  
Disease Monitoring ◽  
Global Status

Pancreatic ductal adenocarcinoma (PDAC) exhibits the poorest prognosis of all solid tumors, with a 5-year survival of less than 10%. To improve the prognosis, it is necessary to advance in the development of tools that help us in the early diagnosis, treatment selection, disease monitoring, evaluation of the response and prognosis. Liquid biopsy (LB), in its different modalities, represents a particularly interesting tool for these purposes, since it is a minimally invasive and risk-free procedure that can detect both the presence of genetic material from the tumor and circulating tumor cells (CTCs) in the blood and therefore distantly reflect the global status of the disease. In this work we review the current status of the main LB modalities (ctDNA, exosomes, CTCs and cfRNAs) for detecting and monitoring PDAC.

Dose-dense pemetrexed (P) and gemcitabine (G) as neoadjuvant therapy in resectable non-small cell lung cancer (NSCLC)

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 7129-7129
Author(s):  
G. Bepler ◽  
L. Robinson ◽  
E. Sommers ◽  
A. Sharma ◽  
C. Williams ◽  
...  
Keyword(s):  
Neoadjuvant Therapy ◽  
Response Rate ◽  
Brain Mri ◽  
Disease Free Survival ◽  
Response Rates ◽  
R0 Resection ◽  
Incomplete Resection ◽  
Imaging Studies ◽  
Disease Response ◽  
Dose Dense

7129 Background: Adjuvant chemotherapy is standard of care for NSCLC stage IB-III after complete resection. Neoadjuvant therapy has potential advantages. P and G are efficacious in NSCLC with low toxicity. In combination, they can be given dose-dense, which may result in better efficacy, lower toxicity, and higher patient acceptability than traditional platinum-based therapy. Methods: Patients with resectable IB-IIIA and selected IIIB, PS 0–1, w/o prior therapy were eligible. CT, PET, brain MRI, and mediastinoscopy were used for staging. P (500 mg/m2) and G (1,500 mg/m2) were given on d1, 15, 29, and 43. Imaging studies were repeated 7–14 days after treatment and response determined by RECIST. Patients had surgery 3–4 weeks after the last treatment. F/U was every 3 months for 2 years with imaging studies. The primary clinical endpoint is radiographic disease response rate. The secondary endpoints are overall and disease-free survival, pathologic response rate, treatment-related toxicity, and surgical respectability and outcome Results: From 4/04 to 12/05, 45 eligible patients were enrolled. The disease stages were IB in 17, IIA in 3, IIB in 10, IIIA in 12, and IIIB in 3 patient. 8 had adeno, 15 squamous, and 22 large cell or unspecified NSCLC on initial diagnosis. 27 had a PS of 0 and 18 PS 1. 3/45 had weight loss. 22 were women. The median age was 67 (range 42–83 years). 2 were never-smokers, 24 had quit, and 19 were active smokers. Disease response rates to PG were 3% CR, 34% PR, 55% SD, and 8% PD. An R0 resection was performed in 75% of patients, 15% had an incomplete resection, and 10% did not have a thoracotomy. There have been no deaths or unexpected morbidities related to surgery or chemotherapy. Conclusions: Dose-dense PG is well tolerated with acceptable side effects. It appears to be equally as efficacious as platinum-containing chemotherapy doublets in terms of radiographic response rates. Survival rates and the median survival time are forthcoming to allow for a better comparison of this regimen with platinum-containing doublets. No significant financial relationships to disclose.

Multimodality therapy for borderline resectable pancreatic cancer: A single-institution experience.

2012 ◽  
Vol 30 (4_suppl) ◽  
pp. 280-280
Author(s):  
Jose Mario Pimiento ◽  
Tai Hutchinson ◽  
Jill M. Weber ◽  
Manish R. Patel ◽  
Pamela Joy Hodul ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Overall Survival ◽  
Disease Free Survival ◽  
Multimodality Therapy ◽  
Cancer Center ◽  
R0 Resection ◽  
Resection Rate ◽  
Resectable Pancreatic Cancer ◽  
Borderline Resectable ◽  
Borderline Resectable Pancreatic Cancer

280 Background: Multimodality therapy has been advocated for borderline resectable pancreatic cancer (BRCP); however, specific regimens vary widely by institution. Outcomes of these interventions need to be examined to inform future investigation of the optimal therapy for these patients. This study represents the experience of multimodality therapy for BRPC at an NCI designated cancer center. Methods: We identified all patients (pts) with operable pancreatic ductal adenocarcinoma (PDA) from 2006 to 2011. Patients were divided into two groups: resectable group and BRPC group as per the NCCN and AHPBA consensus guidelines. Primary outcomes were resection rate, microscopic negative margin (R0) resection rate, overall survival (OS), and disease free survival (DFS). Fisher's exact and chi-square were used for group comparison while Kaplan-Meier estimates was used for survival analysis. Results: 160pts were identified with operable PDA. 100 (63%) pts had resectable tumors, and 60 (37%) pts had borderline resectable tumors. Neoadjuvant therapy (NT) was administered to 0% in the group with resectable tumors, and 100% in the group with borderline resectable tumors. The resection rate was 100% in pts with resectable tumors and 58% in pts with borderline resectable tumors. R0 resection rates were 80% in the resectable tumors and 97% in the borderline resectable tumors following NT. Perioperative mortality was <1% (1/125) for resectable tumors and 0% in borderline resectable tumors. Median OS was 22.6 months (m) for pts that had resectable tumors and 13.9m for all pts with borderline resectable tumors (p=0.017); however, the median OS for resected pts with borderline resectable tumors was 21.5m (p=0.6). Improved DFS was seen in patients with resectable tumors when compared with resected borderline resectable tumors (15 vs. 9.5m; p=0.04). Conclusions: Multimodality therapy leads to high rates of R0 resections in borderline resectable pancreatic cancer; however 42% of patients progressed during NT. The overall survival for patients with resected borderline resectable pancreatic cancer following NT is similar to patients who undergo resection for resectable pancreatic cancer.

scholarly journals Analysis of the Curative Effect of Neoadjuvant Therapy on Pancreatic Cancer

2021 ◽  
Vol 11 ◽  
Author(s):  
Liqiong Yang ◽  
Yun Bai ◽  
Qing Li ◽  
Jie Chen ◽  
Fangfang Liu ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Neoadjuvant Therapy ◽  
Adverse Reactions ◽  
Neoadjuvant Chemoradiotherapy ◽  
Primary Treatment ◽  
R0 Resection ◽  
Resectable Pancreatic Cancer ◽  
Recurrence Rates ◽  
Borderline Resectable

The prevalence of pancreatic cancer is sharply increasing recently, which significantly increases the economic burden of the population. At present, the primary treatment of resectable pancreatic cancer is surgical resection, followed by chemotherapy with or without radiation. However, the recurrence rates remain high even after R0 resection. This treatment strategy does not distinguish undetected metastatic disease, and it is prone to postoperative complications. Neoadjuvant therapies, including neoadjuvant chemotherapy and radiotherapy, is being increasingly utilized in borderline resectable as well as resectable pancreatic cancer. This review summarized and discussed clinical trials of neoadjuvant therapy for pancreatic cancer, comparing resection rates, outcome measures, and adverse reactions between neoadjuvant chemotherapy and neoadjuvant chemoradiotherapy.

CONKO-005: Adjuvant Chemotherapy With Gemcitabine Plus Erlotinib Versus Gemcitabine Alone in Patients After R0 Resection of Pancreatic Cancer: A Multicenter Randomized Phase III Trial

2017 ◽  
Vol 35 (29) ◽  
pp. 3330-3337 ◽  
Author(s):  
Marianne Sinn ◽  
Marcus Bahra ◽  
Torsten Liersch ◽  
Klaus Gellert ◽  
Helmut Messmann ◽  
...  
Keyword(s):  
Overall Survival ◽  
Adjuvant Treatment ◽  
Kinase Inhibitor ◽  
Growth Factor Receptor ◽  
Disease Free Survival ◽  
Phase Iii ◽  
Ductal Adenocarcinoma ◽  
R0 Resection ◽  
Open Label ◽  
Term Survival

Purpose Gemcitabine is standard of care in the adjuvant treatment of resectable pancreatic ductal adenocarcinoma (PDAC). The epidermal growth factor receptor tyrosine kinase inhibitor erlotinib in combination with gemcitabine has shown efficacy in the treatment of advanced PDAC and was considered to improve survival in patients with primarily resectable PDAC after R0 resection. Patients and Methods In an open-label, multicenter trial, patients were randomly assigned to one of two study arms: gemcitabine 1,000 mg/m2 days 1, 8, 15, every 4 weeks plus erlotinib 100 mg once per day (GemErlo) or gemcitabine (Gem) alone for six cycles. The primary end point of the study was to improve disease-free survival (DFS) from 14 to 18 months by adding erlotinib to gemcitabine. Results In all, 436 patients were randomly assigned at 57 study centers between April 2008 and July 2013. A total of 361 instances (83%) of disease recurrence were observed after a median follow-up of 54 months. Median treatment duration was 22 weeks in both arms. There was no difference in median DFS (GemErlo 11.4 months; Gem 11.4 months) or median overall survival (GemErlo 24.5 months; Gem 26.5 months). There was a trend toward long-term survival in favor of GemErlo (estimated survival after 1, 2, and 5 years for GemErlo was 77%, 53%, and 25% v 79%, 54%, and 20% for Gem, respectively). The occurrence or the grade of rash was not associated with a better survival in the GemErlo arm. Conclusion To the best of our knowledge, CONKO-005 is the first study to investigate the combination of chemotherapy and a targeted therapy in the adjuvant treatment of PDAC. GemErlo for 24 weeks did not improve DFS or overall survival over Gem.

Current status of chemotherapy for advanced pancreatic and gastric cancer.

1985 ◽  
Vol 3 (7) ◽  
pp. 1032-1039 ◽  
Author(s):  
M J O'Connell
Keyword(s):  
Gastric Cancer ◽  
Survival Benefit ◽  
Advanced Pancreatic Cancer ◽  
Treatment Strategies ◽  
Disease Free Survival ◽  
Current Status ◽  
Term Survival ◽  
Clinical Investigator ◽  
New Treatment

There is currently no effective systemic therapy for advanced pancreatic cancer. No definitive controlled data exist that demonstrate a survival benefit for any particular regimen yet developed. A statistically significant short-term survival benefit has been seen in three consecutive GITSG trials using the FAMe regimen in patients with advanced gastric cancer. Occasional long-term responders have been seen with a variety of regimens, but there is no evidence of improved long-term (more than two years) disease-free survival with any regimen reported to date. Continuing research with emphasis on new drug development, innovative alterations in chemotherapy combinations and administration schedules, or entirely new treatment strategies, are clearly required to allow the clinical investigator and the clinical practitioner to achieve their common goal--improved long-term survival for patients with advanced pancreatic and gastric cancer.

Long-term survival of patients receiving multimodality neoadjuvant therapy for resectable or borderline resectable pancreatic ductal adenocarcinoma.

2014 ◽  
Vol 32 (3_suppl) ◽  
pp. 309-309
Author(s):  
Kinsey McCormick ◽  
Samuel H. Whiting ◽  
Grace Gyurkey ◽  
Wui-Jin Koh ◽  
Mika Sinanan ◽  
...  
Keyword(s):  
Neoadjuvant Therapy ◽  
Survival Rates ◽  
Ductal Adenocarcinoma ◽  
Wound Complications ◽  
R0 Resection ◽  
Surgical Morbidity ◽  
Borderline Resectable ◽  
Term Survival

309 Background: While surgery offers the only chance for cure in localized PDA, outcomes remain poor for those who have undergone surgical resection (SR). Neoadjuvant therapy (NATx) has several advantages, including early treatment of micrometastatic disease, the potential for tumor downstaging, and improved selection of patients (pts) for surgery by excluding those with chemotherapy-refractory disease. Methods: We report long-term follow-up on consecutive pts with resectable or borderline resectable (R/BR) PDA treated at our institution with an off-protocol, but defined regimen of multi-modality NATx. Demographic, clinical and outcomes data were extracted from medical records. Overall survival (OS) and progression-free survival (PFS) were calculated by Kaplan-Meier analysis. Results: 16 pts with R/BR PDA were treated with NATx; median follow-up is now 41 months (mo) (7.9-91.5). The median age was 57, 50% were female, and all had an ECOG PS <2. Fourteen (88%) had BR disease, and 9 (56%) had radiographic evidence of nodal involvement. All pts received NA gemcitabine, docetaxel and capecitabine and 13 (81%) also received NA chemoradiotherapy with capecitabine +/- oxaliplatin. 14 pts (88%) underwent SR; of those, 11 (79%) received adjuvant chemotherapy. The median decline in CA19-9 over the course of NATx was 80%. An R0 resection was achieved in 11 pts (79%), and there were 2 pCR. To date, 12 pts have died, 4 are alive (including 2 with CA19-9 >1000 at dx), and 3 are without recurrence. The mPFS and mOS were 27.4 and 41 mo, respectively. 1- and 3-year survival rates were 94% and 56%, respectively. When analyses were restricted to pts who underwent SR, the mPFS and mOS were 29 mo and 47.8 mo, respectively. There were no surgery-related deaths. 3 pts had postoperative wound complications. Conclusions: In this series of mostly BR pancreatic cancer pts, treatment with multi-modality NATx resulted in an almost doubling of mOS when compared to historical controls. NATx was also safe, and did not increase surgical morbidity or mortality. Based on these encouraging results, a phase II protocol of multi-modality NATx for R/BR PDA was initiated and has now completed accrual.

Ten-year survival data following resection of locally recurrent rectal cancer (LRRC).

2017 ◽  
Vol 35 (4_suppl) ◽  
pp. 730-730
Author(s):  
David Patrick Cyr ◽  
Francis Si Wai Zih ◽  
Jossie Swett-Cosentino ◽  
Shelly Luu ◽  
Bryan J Wells ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Survival Data ◽  
Univariate Analysis ◽  
Disease Free Survival ◽  
Oncologic Outcomes ◽  
R0 Resection ◽  
Study Cohort ◽  
Prognostic Variables ◽  
En Bloc ◽  
Term Survival

730 Background: The ‘Beyond TME’ Collaborative identified LRRC as a complex problem requiring multidisciplinary consultation and specialized surgical care. Aggressive en bloc resection of LRRC at specialized cancer centers is associated with 5y survival rates of 25-50%. However, skepticism persists that LRRC can be cured given the lack of published longer-term survival data. We investigated the oncologic outcomes at 10y following resection of LRRC and sought relevant clinicopathologic prognostic variables. Methods: The study cohort consists of 52 consecutive patients (31M, 21F) who underwent LRRC resection at our center between 09/1997 and 08/2005. En bloc sacrectomy was performed in 30 patients (58%) with the goal of achieving complete margin negative (R0) resection. At the time of LRRC resection, 46 of 52 patients had isolated LRRC (M0), and 6 had potentially resectable distant metastasis (M1). Patients were followed with H&P, CT-CAP q4mos X2y, q6mos X3y, then annually. Results: At last follow-up (f/u), 32 patients had died of rectal cancer, 1 died of other causes, 4 were alive with rectal cancer, and 15 (30%) were alive cancer-free. For the entire cohort of 52 patients, median f/u time was 44mos (4-162) and overall survival (OS) was 42% at 5y, 37% at 10y, median 43mos. In the group who were alive at last f/u (N = 19), median f/u time was 123mos (45-162). Prognostic variables for OS in univariate analysis included: m status, resection margin status, receipt of systemic Rx, and receipt of radiotherapy. All patients who had M1 disease at the time of LRRC resection died of recurrent cancer at a median of 21mos (4-46). In the 46 M0 patients, OS was 47% at 5y, 42% at 10y, median 50mos; furthermore, disease-free survival (DFS) was 38% at 5y, 38% at 10y, median 39mos. In patients who had R0 resection (n = 41), OS was 51% at 5y, 45% at 10y, median 72mos. Preoperative chemotherapy at the time of primary presentation (n = 26) or before resection of LRRC (n = 20) was associated with significantly improved prognosis ( p= 0.004, p= 0.03, respectively). Conclusions: Complete resection of LRRC was associated with durable survival in approximately 40% of patients, with plateauing of survival curves after 5y. Preoperative therapy of LRRC may improve survival.

Camrelizumab combined with albumin paclitaxel and cisplatin as neoadjuvant therapy for locally advanced esophageal squamous cell carcinoma (ESCC).

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e16021-e16021
Author(s):  
Huilai Lv ◽  
Yang Tian ◽  
Chao Huang ◽  
Zhenhua Li ◽  
Ziqiang Tian
Keyword(s):  
Surgical Treatment ◽  
Neoadjuvant Therapy ◽  
Clinical Stage ◽  
Objective Response ◽  
Locally Advanced ◽  
Pathologic Complete Response ◽  
Disease Free Survival ◽  
Complete Response ◽  
R0 Resection ◽  
Resection Rate

e16021 Background: The pathologic complete response (pCR) rate is improved by neoadjuvant therapy in locally advanced ESCC, but occurs less than 10% of patients(pts) with neoadjuvant chemotherapy agents. Immunotherapy has become a new promising treatment. Camrelizumab (anti-PD-1) is standard of care as second-line therapy for advanced ESCC in China. Therefore, we intended to evaluate the efficacy and safety of Camrelizumab combined with albumin paclitaxel and cisplatin as neoadjuvant therapy for pts with locally advanced ESCC. Methods: We retrospectively analysed locally advanced ESCC pts with clinical stage Ⅱ-ⅣA. Eligible pts were aged 18–75 years with no prior any therapy. Pts received 2-4 cycles neoadjuvant therapy which including Camrelizumab (200mg IV q3w), albumin paclitaxel (260 mg/m2 IV q3w) and cisplatin (75 mg/m2 IV q3w). Surgery was performed 4-6 weeks after neoadjuvant therapy. The primary endpoint was pCR, the secondary endpoints were major pathologic response (MPR), R0 resection rate, objective response rate (ORR), disease-free survival (DFS) and safety. Results: From Jul 27 2019 to Sep 26 2020,16 pts were enrolled and available evaluated. 8 pts (50%) had clinical complete response (cCR), and the ORR was 87.5% (14/16). All pts underwent surgery and surgical treatment was not delayed. The pCR was 43.8% (7/16), MPR was 75% (12/16). Notably, R0 resection rate was 100% (16/16). None of 16 pts progressed, the DFS was not yet achieved. The average intraoperative blood loss was 131ml (100-200ml) and the average hospitalization time after operation was 14 days (11-21 days). No patient developed anastomotic leak and other surgical treatment-related toxicity. The grade 1-2 treatment-related AEs were reactive cutaneous capillary endothelial proliferation (RCCEP) (n = 3,18.8%), weakness (n = 2, 12.5%), Myelosuppression (n = 1, 6.2%) and hypothyroidism (n = 1, 6.2%). No serious AEs resulted in termination of treatment, and treatment-related death was not observed. Conclusions: The addition of camrelizumab to albumin paclitaxel and carboplatin was demonstrated encouraging clinical efficacy and acceptable safety as neoadjuvant therapy, and might be a favorable option for pts with locally advanced ESCC. Further registered clinical trials are expected.

scholarly journals Adjuvant Gemcitabine Alone Versus Gemcitabine-Based Chemoradiotherapy After Curative Resection for Pancreatic Cancer: A Randomized EORTC-40013-22012/FFCD-9203/GERCOR Phase II Study

2010 ◽  
Vol 28 (29) ◽  
pp. 4450-4456 ◽  
Author(s):  
Jean-Luc Van Laethem ◽  
Pascal Hammel ◽  
Françoise Mornex ◽  
David Azria ◽  
Geertjan Van Tienhoven ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Phase Ii ◽  
Pancreatic Head ◽  
Disease Free Survival ◽  
Late Toxicity ◽  
Phase Iii ◽  
Adjuvant Chemoradiotherapy ◽  
R0 Resection ◽  
Type I ◽  
Pancreatic Head Cancer

Purpose The role of adjuvant chemoradiotherapy (CRT) in resectable pancreatic cancer is still debated. This randomized phase II intergroup study explores the feasibility and tolerability of a gemcitabine-based CRT regimen after R0 resection of pancreatic head cancer. Patients and Methods Within 8 weeks after surgery, patients were randomly assigned to receive either four cycles of gemcitabine (control arm) or gemcitabine for two cycles followed by weekly gemcitabine with concurrent radiation (50.4 Gy; CRT arm). The primary objective was to exclude a < 60% treatment completion and a > 40% rate of grade 4 hematologic or GI toxicity in the CRT arm with type I and II errors of 10%. Secondary end points were late toxicity, disease-free survival (DFS), and overall survival (OS). Results Between September 2004 and January 2007, 90 patients were randomly assigned (45:45). Patient characteristics were similar in both arms. Treatment was completed per protocol by 86.7% and 73.3% (80% CI, 63.1% to 81.9%; 95% CI, 58.1% to 85.4%) in the control and CRT arms, respectively, and grade 4 toxicity was 0% and 4.7% (two of 43; 80% CI, 1.2% to 11.9%), respectively. In the CRT arm, three patients experienced grade 3–related late toxicity. Median DFS was 12 months in the CRT arm and 11 months in the control arm. Median OS was 24 months in both arms. First local recurrence was less frequent in the CRT arm (11% v 24%). Conclusion Adjuvant gemcitabine-based CRT is feasible, well-tolerated, and not deleterious; adding this treatment to full-dose adjuvant gemcitabine after resection of pancreatic cancer should be evaluated in a phase III trial.

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