Intention to treat outcomes among patients with pancreatic cancer treated using International Study Group on Pancreatic Surgery recommended pathways for resectable and borderline resectable disease.

The International Study Group on Pancreatic Surgery recommends upfront surgery for resectable pancreatic cancer or borderline resectable-venous (BR-V) disease and neoadjuvant therapy (NAT) among those with arterial involvement (BR-A or locally advanced, LA). Though neoadjuvant therapy (NAT) is a promising strategy, outcomes are rarely reported on intention-to-treat (ITT) basis. This study presents ITT outcomes where pathways to surgery were in line with International Study Group on Pancreatic Surgery guidelines. Patients recommended for potentially curative treatment with PDAC between 2012 and 2017 (n = 345) were classified as resectable, BR-A/BR-V or LA, according to NCCN criteria. The primary outcome was overall survival. Secondary outcomes were resection rates, positive margins and toxicity among patients receiving NAT. At surgery, the resection rates were 78% (172/221), 65% (35/54) and 54% (21/39) for those with resectable, BR-V and BR-A/LA disease, respectively (P < 0.0001). The median survival of those resected in the BR-A/LA cohort was 31 months. However, on an ITT basis, there was no significant difference in survival between resectable, BR-V and BR-A/LA disease (median: 19 versus 15 versus 19 months; P = 0.585). On review, some 31 (44%) patients of the BR-A/LA cohort either did not receive or did not complete NAT. To realize benefits of NAT, more patients need to complete NAT and to undergo resection. Upfront resection for BR-V disease is associated with equivalent outcomes to upfront surgery for resectable disease or NAT for BR-A/LA disease. Strategies to increase the proportion of patients who complete NAT and undergo resection are needed.

Kamarajah SK ，Chatzizacharias N ，Hodson J ，Marcon F ，Kalisvaart M ，Punia P ，Ting Ma Y ，Dasari B ，Marudanayagam R ，Sutcliffe RP ，Muiesan P ，Mirza DF ，Isaac J ，Roberts KJ ... -  《-》

Survival equivalence in patients treated for borderline resectable and unresectable locally advanced pancreatic ductal adenocarcinoma: a systematic review and network meta-analysis.

The clinical relevance of subdivision of non-metastatic pancreatic ductal adenocarcinoma (PDAC) into locally advanced borderline resectable (LA-BR) and locally advanced unresectable (LA-UR) has been questioned. We assessed equivalence of overall survival (OS) in patients with LA-BR and LA-UR PDAC. A systematic review was performed of studies published January 1, 2009 to August 21, 2019, reporting OS for LA-BR and LA-UR patients treated with or without neoadjuvant therapy (NAT), with or without surgical resection. A frequentist network meta-analysis was used to assess the primary outcome (hazard ratio for OS) and secondary outcomes (OS in LA-BR, LA-UR, and upfront resectable (UFR) PDAC). Thirty-nine studies, comprising 14,065 patients in a network of eight unique treatment subgroups were analysed. Overall survival was better for LA-BR than LA-UR patients following surgery both with and without NAT. Neoadjuvant therapy prior to surgery was associated with longer OS for UFR, LA-BR, and LA-UR tumours, compared to upfront surgery. Survival between the LA-BR and LA-UR subgroups was not equivalent. This subdivision is useful for prognostication, but likely unhelpful in treatment decision making. Our data supports NAT regardless of initial disease extent. Individual patient data assessment is needed to accurately estimate the benefit of NAT.

Lindemann J ，du Toit L ，Kotze U ，Bernon M ，Krige J ，Jonas E ... -  《-》

Meta-analysis comparing upfront surgery with neoadjuvant treatment in patients with resectable or borderline resectable pancreatic cancer.

Studies comparing upfront surgery with neoadjuvant treatment in pancreatic cancer may report only patients who underwent resection and so survival will be skewed. The aim of this study was to report survival by intention to treat in a comparison of upfront surgery versus neoadjuvant treatment in resectable or borderline resectable pancreatic cancer. MEDLINE, Embase and the Cochrane Library were searched for studies reporting median overall survival by intention to treat in patients with resectable or borderline resectable pancreatic cancer treated with or without neoadjuvant treatment. Secondary outcomes included overall and R0 resection rate, pathological lymph node rate, reasons for unresectability and toxicity of neoadjuvant treatment. In total, 38 studies were included with 3484 patients, of whom 1738 (49·9 per cent) had neoadjuvant treatment. The weighted median overall survival by intention to treat was 18·8 months for neoadjuvant treatment and 14·8 months for upfront surgery; the difference was larger among patients whose tumours were resected (26·1 versus 15·0 months respectively). The overall resection rate was lower with neoadjuvant treatment than with upfront surgery (66·0 versus 81·3 per cent; P < 0·001), but the R0 rate was higher (86·8 (95 per cent c.i. 84·6 to 88·7) versus 66·9 (64·2 to 69·6) per cent; P < 0·001). Reported by intention to treat, the R0 rates were 58·0 and 54·9 per cent respectively (P = 0·088). The pathological lymph node rate was 43·8 per cent after neoadjuvant therapy and 64·8 per cent in the upfront surgery group (P < 0·001). Toxicity of at least grade III was reported in up to 64 per cent of the patients. Neoadjuvant treatment appears to improve overall survival by intention to treat, despite lower overall resection rates for resectable or borderline resectable pancreatic cancer. PROSPERO registration number: CRD42016049374.

Versteijne E ，Vogel JA ，Besselink MG ，Busch ORC ，Wilmink JW ，Daams JG ，van Eijck CHJ ，Groot Koerkamp B ，Rasch CRN ，van Tienhoven G ，Dutch Pancreatic Cancer Group ... -  《-》

Intraoperative Radiation Therapy (IORT) for Borderline Resectable and Locally Advanced Pancreatic Ductal Adenocarcinoma (BR/LA PDAC) in the Era of Modern Neoadjuvant Treatment: Short-Term and Long-Term Outcomes.

Harrison JM ，Wo JY ，Ferrone CR ，Horick NK ，Keane FK ，Qadan M ，Lillemoe KD ，Hong TS ，Clark JW ，Blaszkowsky LS ，Allen JN ，Castillo CF ... -  《-》

The Oncological Stress Test of Neoadjuvant Therapy: A Systematic Review in Outcomes of Neoadjuvant Therapy Compared to Upfront Resection Approach for Borderline Resectable Pancreatic Adenocarcinoma.

Ross SB ，Popover J ，Sucandy I ，Christodoulou M ，Pattilachan TM ，Rosemurgy AS ... -  《-》