The US Cancer Moonshot initiative

Correspondence avoid surgery in rapidly progressive or chemo-insensitive disease. 4 Genotyping of pancreatic tumours via fine needle aspiration could influence the clinical management of pancreatic cancer. Fine-needle aspiration sequencing was used to identify subgroups of patients with specific actionable mutations related to resectable or locally advanced tumours. 5 In patients with radiologically resectable or borderline resectable tumours, preoperative fine-needle aspiration sequencing could distinguish between patients with a genetic pattern associated with micrometastatic tumours, who should undergo neoadjuvant therapy, and those with a truly localised disease that would be amenable to a surgery-first strategy. Michele Reni has served as a consultant for or on the advisory boards of Celgene, Boehringer-Ingelheim, Lilly, Genentech, Baxalta, Novocure, Astra-Zeneca, Pfizer, and Merck-Serono, and has received honoraria from Celgene. Massimo Falconi has received honoraria from Celgene, Ipsen and Novartis. The other authors declare no competing interests. *Stefano Crippa, Michele Reni, Gianpaolo Balzano, Claudio Doglioni, Massimo Falconi crippa1.stefano@hsr.it Division of Pancreatic Surgery, IRCCS San Raffaele Hospital, Milan, Italy (SC, GB, MF); Medical Oncology Department, IRCCS San Raffaele Hospital , Milan, Italy (MR); Department of Pathology, IRCCS San Raffaele Hospital , Milan, Italy (CD); Clinical and Translational Research Program on Pancreatic Cancer, IRCCS San Raffaele Hospital, Milan, Italy (SC, MR, GB, CD, MF) e178 Barreto SG, Windsor JA. Justifying vein resection with pancreatoduodenectomy. Lancet Oncol 2016; 17: e118–24 Giovinazzo F, Turri G, Katz MH, Heaton N, Ahmed I. Meta-analysis of benefit of portal-superior mesenteric vein resection in pancreatic resection for ductal adenocarcinoma. Br J Surg 2016; 103: 179–91. Bapat AA, Hostetter G, Von Hoff DD, Han H. Perineural invasion and associated pain in pancreatic cancer. Nat Rev Cancer 2011; Sohal DP, Walsh RM, Ramanathan RK, Khorana AA. Pancreatic adenocarcinoma: treating a systemic disease with systemic therapy. J Natl Cancer Inst 2014; 106: dju011 Valero V, Saunders TJ, He J, et al. Reliable detection of somatic mutations in fine needle aspirates of pancreatic cancer with next-generation sequencing: implications for surgical management. Ann Surg 2016; Author’s reply Stefano Crippa and colleagues, in responding to our manuscript, 1 agree that increasing the radicality of surgery for pancreatic ductal adenocarcinoma, including synchronous vein resection, is suspect. Indeed, a recent meta-analysis 2 indicates that synchronous vein resection, as reported, increases mortality and decreases survival. Crippa and colleagues put forward two interesting ideas that warrant further discussion. The first is that the surgery-first approach for pancreatic ductal adenocarcinoma might ultimately be retired, given that pancreatic ductal adenocarcinoma is usually systemic at presentation, local treatments have little effect, and neoadjuvant therapy has possible benefits. For now, the absence of high-level evidence for neoadjuvant therapy leaves largely theoretical benefits; namely that neoadjuvant therapy will reveal the biology (ie, those patients that can progress on neoadjuvant therapy will avoid futile surgery), or alter the biology (ie, those patients that are downstaged will become resectable). The preliminary results of the ALLIANCE trial 3 damages the lustre of these purported benefits with no improvement in the number of resections (10 [50%] of 20 patients who completed all preoperative therapy), and no rescue of aggressive tumour biology. This leads to the second idea, in which Crippa and colleagues suggest a biological (rather than radiological) basis for selecting patients for neoadjuvant therapy with a view to reduce the number of synchronous vein resections. Endoscopic ultrasonography- guided genotyping is a possible way to select subgroups of patients with heterogenous pancreatic ductal adenocarcinoma 4 who will benefit from neoadjuvant therapy. In support of this method, Hruban and colleagues 5 suggested that an intact SMAD4/DPC4 gene might be used to select surgery because there is lesser risk of distant metastases for this genotype. 6 In the future, we hope to more accurately select a subgroup of patients in whom a surgery-first approach, and even synchronous vein resection, is justified, but it is much more likely that precision neoadjuvant therapy will ultimately result in less radical surgery and the introduction of non-surgical techniques to support the response to neoadjuvant therapy. We declare no competing interests. Savio G Barreto, *John A Windsor j.windsor@auckland.ac.nz Department of Gastrointestinal Surgery, Gastrointestinal Oncology, and Bariatric Surgery, Medanta Institute of Digestive and Hepatobiliary Sciences, Medanta, The Medicity, Gurgaon, India (SGB); Hepatobiliary Pancreatic and Upper GI Unit, Department of General Surgery, Auckland City Hospital, Auckland, New Zealand (JAW) Barreto S, Windsor J. Justifying vein resection with pancreatoduodenectomy. Lancet Oncol 2016; 17: e118–24. Giovinazzo F, Turri G, Katz MH, Heaton N, Ahmed I. Meta-analysis of benefits of portal-superior mesenteric vein resection in pancreatic resection for ductal adenocarcinoma. Br J Surg 2016; Varadhachary G, Fleming J, Crane C, et al. Phase II study of preoperation mFOLFIRINOX and chemoradiation for high-risk resectable and borderline resectable pancreatic adenocarcinoma. Proc Am Soc Clin Oncol 2015; 33 (suppl 3): abstr 362. Killock D. Pancreatic cancer: a problem quartered—new subtypes, new solutions? Nat Rev Clin Oncol 2016; 13: 201. Hruban RH, Adsay NV. Molecular classification of neoplasms of the pancreas. Hum Pathol Iacobuzio-Donahue CA, Fu B, Yachida S, et al. DPC4 gene status of the primary carcinoma correlates with patterns of failure in patients with pancreatic cancer. J Clin Oncol 2009; The US Cancer Moonshot initiative We recently sent the following letter to Vice President of the USA, Joe Biden, to state that we, as Deans and Directors of Public Health schools and programmes around the USA, strongly support the goals of the Cancer Moonshot initiative to www.thelancet.com/oncology Vol 17 May 2016