Dataset Information

Impact and optimal timing of local therapy addition in borderline resectable or locally advanced pancreatic cancer after FOLFIRINOX chemotherapy.

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.

SUBMITTER: Kim K

PROVIDER: S-EPMC10840322 | biostudies-literature | 2024 Mar

REPOSITORIES: biostudies-literature

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Publications

Impact and optimal timing of local therapy addition in borderline resectable or locally advanced pancreatic cancer after FOLFIRINOX chemotherapy.

Kim Kangpyo K Park Hee Chul HC Yu Jeong Il JI Park Joon Oh JO Hong Jung Yong JY Lee Kyu Taek KT Lee Kwang Hyuck KH Lee Jong Kyun JK Park Joo Kyung JK Heo Jin Seok JS Shin Sang Hyun SH Min Ji Hye JH Kim Kyunga K Han In Woong IW

Clinical and translational radiation oncology 20240124

<h4>Background</h4>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.<h4>Method</h4>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 foll ...[more]

PMID: 38317678

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Project description:BackgroundPancreatic cancer often presents as locally advanced (LAPC) or borderline resectable (BRPC). Neoadjuvant systemic therapy is recommended as initial treatment. It is currently unclear what chemotherapy should be preferred for patients with BRPC or LAPC.MethodsWe performed a systematic review and multi-institutional meta-analysis of patient-level data regarding the use of initial systemic therapy for BRPC and LAPC. Outcomes were reported separately for tumor entity and by chemotherapy regimen including FOLFIRINOX (FIO) or gemcitabine-based.ResultsA total of 23 studies comprising 2930 patients were analyzed for overall survival (OS) calculated from the beginning of systemic treatment. OS for patients with BRPC was 22.0 months with FIO, 16.9 months with gemcitabine/nab-paclitaxel (Gem/nab), 21.6 months with gemcitabine/cisplatin or oxaliplatin or docetaxel or capecitabine (GemX), and 10 months with gemcitabine monotherapy (Gem-mono) (p < 0.0001). In patients with LAPC, OS also was higher with FIO (17.1 months) compared with Gem/nab (12.5 months), GemX (12.3 months), and Gem-mono (9.4 months; p < 0.0001). This difference was driven by the patients who did not undergo surgery, where FIO was superior to other regimens. The resection rates for patients with BRPC were 0.55 for gemcitabine-based chemotherapy and 0.53 with FIO. In patients with LAPC, resection rates were 0.19 with Gemcitabine and 0.28 with FIO. In resected patients, OS for patients with BRPC was 32.9 months with FIO and not different compared to Gem/nab, (28.6 months, p = 0.285), GemX (38.8 months, p = 0.1), or Gem-mono (23.1 months, p = 0.083). A similar trend was observed in resected patients converted from LAPC.ConclusionsIn patients with BRPC or LAPC, primary treatment with FOLFIRINOX compared with Gemcitabine-based chemotherapy appears to provide a survival benefit for patients that are ultimately unresectable. For patients that undergo surgical resection, outcomes are similar between GEM+ and FOLFIRINOX when delivered in the neoadjuvant setting.

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:BackgroundThe 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.MethodsData 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.ResultsAmong 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.ConclusionsThe 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: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.

Dataset Information

Impact and optimal timing of local therapy addition in borderline resectable or locally advanced pancreatic cancer after FOLFIRINOX chemotherapy.

Background

Method

Results

Conclusions

Publications

Impact and optimal timing of local therapy addition in borderline resectable or locally advanced pancreatic cancer after FOLFIRINOX chemotherapy.

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