How Does Chemoradiotherapy Following Induction FOLFIRINOX Improve the Results in Resected Borderline or Locally Advanced Pancreatic Adenocarcinoma? An AGEO-FRENCH Multicentric Cohort

Pietrasz, Daniel; Turrini, Olivıer; Vendrely, V.; Simon, Jean‐Marc; Hentic, Olivia; Coriat, Romain; Portales, Fabienne; Roy, Bertrand Le; Taieb, Julien; Régenet, Nicolas; Goèré, Diane; Artru, Pascal; Vaillant, Jean‐Christophe; Huguet, F.; Laurent, Alexis; Sauvanet, Alain; Delpero, Jean‐Robert; Bachet, Jean Baptiste; Cunha, Antonio Sa

doi:10.1245/s10434-018-6931-6

Cited by 69 publications

(72 citation statements)

References 27 publications

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“…Significant differences were demonstrated in favour of neoadjuvant treatment with FOLFIRINOX+CRT, both in BR and LAPC populations with greatly improved median OS (57.8 versus 35.5 months; p = 0.007), R0 resection rates (89.2% versus 76.3%, p = 0.017), and ypN0 rates (76.2% versus 48.5%, p < 0.001). 62 This neoadjuvant approach, providing true R0 resection, tumour downstaging and downsizing and major pathological response in a selected number of “good” patients with better outcomes suggests that this represents a multi-step selective process for patient selection that could offer a way to improve the prognosis of pancreatic cancer.…”

Section: Rt For Primary Pancreatic Cancermentioning

confidence: 99%

Novel strategies using modern radiotherapy to improve pancreatic cancer outcomes: toward a new standard?

et al. 2020

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Pancreatic ductal adenocarcinoma (PDAC) remains one of the most aggressive solid tumours with an estimated 5-year overall survival rate of 7% for all stages combined. In this highly resistant disease that is located in the vicinity of many radiosensitive organs, the role of radiotherapy (RT) and indications for its use in this setting have been debated for a long time and are still under investigation. Although a survival benefit has yet to be clearly demonstrated for RT, it is the only technique, other than surgery, that has been demonstrated to lead to local control improvement. The adjuvant approach is now strongly challenged by neoadjuvant treatments that could spare patients with rapidly progressive systemic disease from unnecessary surgery and may increase free margin (R0) resection rates for those eligible for surgery. Recently developed dose-escalated RT treatments, designed either to maintain full-dose chemotherapy or to deliver a high biologically effective dose, particularly to areas of contact between the tumour and blood vessels, such as hypofractionated ablative RT (HFA-RT) or stereotactic body RT (SBRT), are progressively changing the treatment landscape. These modern strategies are currently being tested in prospective clinical trials with encouraging preliminary results, paving the way for more effective treatment combinations using novel targeted therapies. This review summarizes the current literature regarding the use of RT for the treatment of primary PDAC, describes the limitations of conventional RT, and discusses the emerging role of dose-escalated RT and heavy-particle RT.

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Section: Rt For Primary Pancreatic Cancermentioning

confidence: 99%

Novel strategies using modern radiotherapy to improve pancreatic cancer outcomes: toward a new standard?

et al. 2020

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“…[12][13][14] Furthermore, a limitation of most studies is the inability to determine how many patients receiving primary chemotherapy never qualified for surgery because of treatment discontinuation, disease progression, or death. [15][16][17][18][19][20][21][22] This prospective cohort study enrolled consecutive patients with new diagnoses of BR and LA PDAC. The analysis is limited to a recent 3-year period, with the aim to evaluate pragmatically the rate of chemotherapy receipt, the treatment compliance, the rate of surgery, and survival outcomes.…”

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confidence: 99%

Outcomes of Primary Chemotherapy for Borderline Resectable and Locally Advanced Pancreatic Ductal Adenocarcinoma

et al. 2019

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IMPORTANCE Chemotherapy 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. OBJECTIVE To 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 PARTICIPANTS This 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. EXPOSURES The 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 MEASURES Rates of receipt and completion of chemotherapy, rates of conversion to surgery, and disease-specific survival. RESULTS Of 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 RELEVANCE This 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.

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“…3 Without progression after induction therapy, preoperative chemoradiotherapy seems to improve pathological results (R0 resection, ypN0 and major response rates), locoregional relapse-free survival and OS though these results need to be confirmed. 4 Adjuvant chemotherapy can be administered, but its modalities are not well defined and trials are ongoing, with generally continuing the preoperative regimen for a total of 6 months. When the tumour is not resectable after induction chemotherapy, chemoradiotherapy (intensity modulated radiation therapy or stereotactic body radiation therapy), though not standard, may allow tumour shrinkage and secondary resection in a small percentage of patients.…”

Section: Resectable Pamentioning

confidence: 99%

How I treat pancreatic cancer

Taı̈eb

Abdallah

2019

ESMO Open

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Pancreatic adenocarcinoma (PA) represents 90% of solid pancreatic malignant tumours. With one of the worst prognoses in oncology (all stages 5-year overall survival (OS) of 9%), PA was the seventh-leading cause of cancer-related deaths worldwide in 2018, and during the last 20 years, there have been unexplained increases in its incidence and mortality.This article summarises how to manage, to our opinion, PA in everyday practice according to tumour staging into resectable, unresectable or metastatic disease. Surgery followed by consensual adjuvant chemotherapy is the first-intention treatment for resectable patients. Unresectable but non-metastatic PA should be treated with induction chemotherapy and optionally with chemoradiotherapy to enable when possible secondary surgical resection. First-line and second-line chemotherapy does improve quality of life and OS in the metastatic setting, FOLFIRINOX and gemcitabine + nab-paclitaxel being the two current standard first-line options. Molecular profiling of metastatic patients is emerging, as some personalised therapies are possible for rare subtypes such as MSI high, BRCA1-2 mutated and NRG1/NTRK fusion gene PA.

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How Does Chemoradiotherapy Following Induction FOLFIRINOX Improve the Results in Resected Borderline or Locally Advanced Pancreatic Adenocarcinoma? An AGEO-FRENCH Multicentric Cohort

Cited by 69 publications

References 27 publications

Novel strategies using modern radiotherapy to improve pancreatic cancer outcomes: toward a new standard?

Novel strategies using modern radiotherapy to improve pancreatic cancer outcomes: toward a new standard?

Outcomes of Primary Chemotherapy for Borderline Resectable and Locally Advanced Pancreatic Ductal Adenocarcinoma

How I treat pancreatic cancer

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