Dataset Information

Opinions and use of neoadjuvant therapy for resectable, borderline resectable, and locally advanced pancreatic cancer: international survey and case-vignette study.

ABSTRACT:

Background

Several new treatment options have become available for pancreatic ductal adenocarcinoma (PDAC), but the support for their use for resectable, borderline resectable and locally advanced PDAC is unclear.

Methods

A survey was distributed to the members of the European-African Hepato-Pancreato Biliary Association (E-AHPBA) and the pancreas group of the European Organization for Research and Treatment of Cancer (EORTC) regarding 1) definitions of local resectability, 2) indications for neoadjuvant therapy and 3) case-vignettes regarding the resectability and treatment of PDAC.

Results

In total, 114 participants from 37 countries were registered. About 35% of respondents, each, were of the opinion that borderline resectability is defined by any venous tumor contact and venous involvement < 180° or > 180°, respectively. The majority (75.4%) of participants believed that borderline resectable PDAC has a high risk for R1 resection and that neoadjuvant therapy might increase the R0-resection rate (79.8%) and improve oncological patient selection (84.2%). Chemotherapy was regarded useful to convert locally advanced to resectable PDAC by 55.7% of respondents. In the cases with resectable, borderline resectable, and locally advanced PDAC, 10 (8.8%), 78 (68.4%), 55 (48.2%) of participants would start with chemotherapy, respectively.

Conclusions

Although definitions for borderline resectability differ among European surgeons, there seems to be a rather strong support for preoperative chemotherapy in PDAC aiming at minimizing R1 resections while increasing resection rates.

SUBMITTER: Heinrich S

PROVIDER: S-EPMC6617881 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature

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Publications

Opinions and use of neoadjuvant therapy for resectable, borderline resectable, and locally advanced pancreatic cancer: international survey and case-vignette study.

Heinrich Stefan S Besselink Marc M Moehler Markus M van Laethem Jean-Luc JL Ducreux Michel M Grimminger Peter P Mittler Jens J Lang Hauke H Lutz Manfred P MP Lesurtel Mickael M

BMC cancer 20190709 1

<h4>Background</h4>Several new treatment options have become available for pancreatic ductal adenocarcinoma (PDAC), but the support for their use for resectable, borderline resectable and locally advanced PDAC is unclear.<h4>Methods</h4>A survey was distributed to the members of the European-African Hepato-Pancreato Biliary Association (E-AHPBA) and the pancreas group of the European Organization for Research and Treatment of Cancer (EORTC) regarding 1) definitions of local resectability, 2) ind ...[more]

PMID: 31288786

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Project description:Pancreatic ductal adenocarcinoma (PDAC) is currently ranked fourth place of cancer related mortality. Only a minority of 10-20% of patients with PDAC have a primarily resectable disease, while 50-60% of the patients are diagnosed with irresectable disease. A certain group of patients is defined as "borderline resectable", which is mainly relied to contact of the tumor to major abdominal vessels. For preoperative evaluation of resectability CT and MRI is commonly used. Although CT-scanning, which is the standard preoperative imaging modality, has striking limitations concerning evaluation of lymph node status as well as vessel involvement and approximately 20% of the patients are staged incorrectly. A central part of modern therapy of locally advanced or not primarily resectable PDAC is neoadjuvant therapy. Especially neoadjuvant chemotherapy according to the FOLFIRINOX protocol resulted in high resection rates of initially not resectable patients. Furthermore, treatment with FOLFIRINOX was shown to be an independent predictor of improved prognosis and resection after neoadjuvant treatment with FOLFIRINOX was associated with improved survival. Neoadjuvant treatment was able to increases the rates of R0 resection, which depicts an independent prognostic factor and FOLFIRINOX outmatched other treatment regimes (e.g., gemcitabine-based radio-chemotherapy) concerning achievement of a R0 resection. While most evidence of neoadjuvant treatment of PDAC is conferred by retrospective analysis, there is growing data from randomized controlled trials, confirming the beneficial effects of neoadjuvant therapy on the prognosis of PDAC. Thus, patients with borderline resectable and locally advanced PDAC should be evaluated for neoadjuvant treatment. If there is no progression of the disease during neoadjuvant treatment exploration with the goal of R0 resection should be performed. If possible, patients should be included in well-designed randomized controlled trials at specialized pancreatic centers.

Project description:BackgroundThere is no agreed upon standard of care for borderline-resectable pancreatic cancer (BRPC) or locally-advanced pancreatic cancer (LAPC) patients regarding the benefit of chemotherapy or radiation alone or in combination.Patients and methodsWe completed a retrospective cohort analysis of BRPC and LAPC patients at a cancer center with expertise in multi-disciplinary pancreatic ductal adenocarcinoma (PDAC) treatment over a 5-year period from 03/01/2014 to 03/01/2019 (cut-off date). The total evaluable newly diagnosed, treatment naïve, BRPC, and LAPC patients with adequate organ function and ability to obtain treatment after multidisciplinary review was 52 patients. After analysis, patients were evaluated for rates of resection, extent of resection (R0 or R1), median progression-free survival (mPFS), and median overall survival (mOS).ResultsPatients were treated with chemotherapy alone (gemcitabine and nab-paclitaxel = 77% (20/26); FOLFIRINOX = 19% (5/26); single agent gemcitabine 3.8% (1/26)), or chemotherapy followed by chemoradiation (gemcitabine +5 Gy × 5 weeks), or chemoradiation alone prior to re-staging and potential resection. Of the 29% (15/52) of patients who went on to surgical resection, 73% (11/15) achieved R0 resection. An R0 resection was achieved in 35% (9/26) of patients treated with chemotherapy alone, 7.6% (1/13) in a patient treated with chemotherapy followed by radiation, and 7.6% (1/13) with concurrent chemoradiotherapy alone. Chemotherapy alone achieved a mPFS of 16.4 months (p < 0.0025) and mOS of 26.2 months (p < 0.0001), chemotherapy followed by chemoradiation was 13.0 months and 14.9 months respectively, while concurrent chemoradiotherapy was 6.9 months and 7.3 months.Conclusions and relevanceBRPC and LAPC patients capable of surgery after only receiving neoadjuvant treatment with chemotherapy had higher rates of R0 resection with prolonged median PFS and OS compared with any patient needing combination chemotherapy with radiotherapy.

Project description:Background The complete resection rate of pancreatic cancer has increased because of the advent of efficacious first-line treatments for unresectable pancreatic cancer. Still, strategies regarding adjuvant therapy after neoadjuvant FOLFIRINOX treatment remain to be established. Methods Data on 144 patients with borderline resectable and locally advanced pancreatic cancer who underwent resection after neoadjuvant FOLFIRINOX between January 2013 and April 2021 were retrospectively reviewed. Results Among the study patients, 113 patients (78.5%) were diagnosed with borderline resectable pancreatic cancer and 31 patients (21.5%) were diagnosed with locally advanced pancreatic cancer. Seventy-five patients (52.1%) received radiotherapy before surgery. After radical resection, 84 patients (58.3%) received 5-fluorouracil-based adjuvant therapy and 60 patients (41.7%) received non-5-fluorouracil-based adjuvant therapy. Adjuvant therapy with 5-fluorouracil-based regimen [hazard ratio (HR), 0.43 (95% CI, 0.21–0.87); p = 0.019], preoperative assessment as locally advanced pancreatic cancer [HR, 2.87 (95% CI, 1.08–7.64); p = 0.035], positive resection margin [HR, 3.91 (95% CI, 1.71–8.94); p = 0.001], and presence of pathologic lymph node involvement [HR, 2.31 (95% CI, 1.00–5.33), p = 0.050] were associated with decreased recurrence-free survival. Adjuvant therapy with 5-fluorouracil-based regimen [HR, 0.35 (95% CI, 0.15–0.84); p = 0.018], positive resection margin [HR, 4.14 (95% CI, 1.75–9.78); p = 0.001], presence of pathologic lymph node involvement [HR, 3.36 (95% CI, 1.23–9.15); p = 0.018], poor differentiation [HR, 5.69 (95% CI, 1.76–18.36); p = 0.004], and dose reduction during adjuvant therapy [HR, 1.78 (95% CI, 1.24–24.37); p = 0.025] were associated with decreased overall survival. Conclusions The 5-fluorouracil-based adjuvant therapy seems to be the proper adjuvant therapy for patients who received neoadjuvant FOLFIRINOX for borderline resectable and locally advanced pancreatic cancer.

Project description:ImportanceChemotherapy is the recommended induction strategy in borderline resectable and locally advanced pancreatic ductal adenocarcinoma. However, the associated results on an intention-to-treat basis are poorly understood.ObjectiveTo investigate pragmatically the treatment compliance, conversion to surgery, and survival outcomes of patients with borderline resectable and locally advanced pancreatic ductal adenocarcinoma undergoing primary chemotherapy.Design, setting, and participantsThis prospective study took place in a national referral center for pancreatic diseases in Italy. Consecutive patients with borderline resectable and locally advanced pancreatic ductal adenocarcinoma were enrolled at the time of diagnosis (January 2013 through December 2015) and followed up to June 2018.ExposuresThe chemotherapy regimen, assigned based on multidisciplinary evaluation, was delivered either at a hub center or at spoke centers. By convention, primary chemotherapy was considered completed after 6 months. After restaging, surgical candidates were selected based on radiologic and biochemical response. All surgeries were carried out at the hub center.Main outcomes and measuresRates of receipt and completion of chemotherapy, rates of conversion to surgery, and disease-specific survival.ResultsOf 680 patients, 267 (39.3%) had borderline resectable and 413 (60.7%) had locally advanced pancreatic ductal adenocarcinoma. Overall, 66 patients (9.7%) were lost to follow-up. The rate of chemotherapy receipt was 92.9% (n = 570). The chemotherapeutic regimens most commonly used included FOLFIRINOX (fluorouracil, leucovorin, oxaliplatin, and irinotecan) (260 [45.6%]) and gemcitabine plus nanoparticle albumin-bound-paclitaxel (123 [21.6%]). Nineteen patients (3.3%) receiving chemotherapy died within 6 months, mainly for disease progression. The treatment completion rate was 71.6% (408 of 570). The overall rate of resection was 15.1% (93 of 614) (borderline resectable, 60 of 249 [24.1%]; locally advanced, 33 of 365 [9%]; resection:exploration ratio, 63.3%). Independent predictors of resection were age, borderline resectable disease, chemotherapy completion, radiologic response, and biochemical response. The median survival for the whole cohort was 12.8 (95% CI, 11.7-13.9) months. Factors independently associated with survival were completion of chemotherapy, receipt of complementary radiation therapy, and resection. In patients who underwent resection, the median survival was 35.4 (95% CI, 27.0-43.7) months for initially borderline resectable and 41.8 (95% CI, 27.5-56.1) months for initially locally advanced disease. No pretreatment and posttreatment factors were associated with survival after pancreatectomy.Conclusions and relevanceThis pragmatic observational cohort study with an intention-to-treat design provides real-world evidence of outcomes associated with the most current primary chemotherapy regimens used for borderline resectable and locally advanced pancreatic ductal adenocarcinoma.

Project description:Approximately 20% of pancreatic ductal adenocarcinoma (PDAC) patients have (borderline) resectable pancreatic cancer [(B)RPC] at diagnosis. Upfront resection with adjuvant chemotherapy has long been the standard of care for these patients. However, although surgical quality has improved, still about 50% of patients never receive adjuvant treatment. Therefore, recent developments have focused on a neoadjuvant approach. Directly comparing results from neoadjuvant and adjuvant regimens is challenging due to differences in patient populations that influence outcomes. Neoadjuvant trials include all patients who have (B)RPC on imaging, while adjuvant-only trials include patients who underwent a complete resection and recovered to a good performance status without any evidence of residual disease. Guidelines recommend neoadjuvant treatment for BRPC patients mainly to improve negative resection margin (R0) rates. For resectable PDAC, upfront resection is still considered the standard of care. However, theoretical advantages of neoadjuvant treatment, including the increased R0 resection rate, early delivery of systemic therapy to all patients, directly addressing occult metastatic disease, and improved patient selection for resection, may also apply to these patients. A systematic review by intention-to-treat showed a superior median overall survival (OS) for any neoadjuvant approach (19 months) compared to upfront surgery (15 months) in (B)RPC patients. A neoadjuvant approach was recently supported by three randomized controlled trials (RCTs). For resectable PDAC, neoadjuvant treatment was superior in a Japanese RCT of neoadjuvant gemcitabine with S-1 vs. upfront surgery, with adjuvant S-1 in both arms (median OS: 37 vs. 27 months, p = 0.015). A Korean trial of neoadjuvant gemcitabine-based chemoradiotherapy vs. upfront resection in BRPC patients was terminated early due to superiority of the neoadjuvant group (median OS: 21 vs. 12 months, p = 0.028; R0 resection: 52 vs. 26%, p = 0.004). The PREOPANC-1 trial for (B)RPC patients also showed favorable outcome for neoadjuvant gemcitabine-based chemoradiotherapy vs. upfront surgery (median OS: 17 vs. 14 months, p = 0.07; R0 resection: 63 vs. 31%, p < 0.001). FOLFIRINOX is likely a better neoadjuvant regimen, because of superiority compared to gemcitabine in both the metastatic and adjuvant setting. Currently, five RCTs evaluating neoadjuvant modified or fulldose FOLFIRINOX are accruing patients.

Dataset Information

Opinions and use of neoadjuvant therapy for resectable, borderline resectable, and locally advanced pancreatic cancer: international survey and case-vignette study.

Background

Methods

Results

Conclusions

Publications

Opinions and use of neoadjuvant therapy for resectable, borderline resectable, and locally advanced pancreatic cancer: international survey and case-vignette study.

Similar Datasets

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