Competing Interests Statement RMS, TAC and LGTM are inventors on a provisional patent application (62/569,053) filed by MSK, relating to the use of TMB in cancer immunotherapy.MDH, NAR and TAC are inventors on a PCT patent application (PCT/US2015/062208) filed by MSK, relating to the use of TMB in lung cancer immunotherapy.MSK and the inventors may receive a share of commercialization revenue from license agreements relating to these patent applications. CHL received research funding from Eisai, BMS, Exelixis, Pfizer, Calithera and consulting fees from Exelixis and Eisai. ANS has received research support from Bristol Myers Squibb, Immunocore, Astra-Zeneca, Xcovery and serves on the advisory board for Bristol Myers Squibb, Immunocore, Castle Biosciences; he also receives royalties from UpToDate. MDH receives research funding from Bristol-Myers Squibb; is paid consultant to Merck

Summary Nomograms are commonly used tools to estimate prognosis in oncology and medicine. With the ability to generate an individual numerical probability of a clinical event by integrating diverse prognostic and determinant variables, nomograms fulfill our desire for biologically and clinically integrated models and our drive towards personalized medicine. Rapid computation through user friendly digital interfaces, together with increased accuracy, and more easily understood prognoses compared to conventional staging, allow for seamless incorporation of nomogram derived prognosis to aid in clinical decision making. This has lead to the ubiquitous appearance of nomograms on the internet and in medical journals, and increasing nomogram use by patients and physicians alike. However, the statistical foundations of nomogram construction, their precise interpretation, and evidence supporting their use is commonly misunderstood, leading to an under appreciation of the inherent uncertainties regarding nomogram use. We provide a systematic, practical approach to evaluating and comprehending nomogram derived prognoses, with particular emphasis on clarifying common misconceptions and highlighting limitations.

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The standard of care for managing patients with gastrointestinal stromal tumors (GISTs) rapidly changed after the introduction of effective molecularly targeted therapies involving tyrosine kinase inhibitors (TKIs), such as imatinib mesylate and sunitinib malate. A better understanding of the molecular characteristics of GISTs have improved the diagnostic accuracy and led to the discovery of novel immunomarkers and new mechanisms of resistance to TKI therapy, which in turn have resulted in the development of novel treatment strategies. To address these issues, the NCCN organized a task force consisting of a multidisciplinary panel of experts in the fields of medical oncology, surgical oncology, molecular diagnostics, and pathology to discuss the recent advances, identify areas of future research, and recommend an optimal approach to care for patients with GIST at all stages of disease. The task force met for the first time in October 2003 and again in December 2006 and October 2009. This supplement describes the recent developments in the field of GIST as discussed at the October 2009 meeting.

ObjectiveTo analyze resectability and survival in patients with hilar cholangiocarcinoma according to a proposed preoperative staging scheme that fully integrates local, tumor-related factors. Summary Background DataIn patients with hilar cholangiocarcinoma, long-term survival depends critically on complete tumor resection. The current staging systems ignore factors related to local tumor extent, preclude accurate preoperative disease assessment, and correlate poorly with resectability and survival. MethodsDemographics, results of imaging studies, surgical findings, pathology, and survival were analyzed prospectively in consecutive patients. Using data from imaging studies, all patients were placed into one of three stages based on the extent of ductal involvement by tumor, the presence or absence of portal vein compromise, and the presence or absence of hepatic lobar atrophy. ResultsFrom March 1991 through December 2000, 225 patients were evaluated, 77% of whom were seen and treated within the last 6 years. Sixty-five patients had unresectable disease; 160 patients underwent exploration with curative intent. Eighty patients underwent resection: 62 (78%) had a concomitant hepatic resection and 62 (78%) had an R0 resection (negative histologic margins). Negative histologic margins, concomitant partial hepatectomy, and well-differentiated tumor histology were associated with improved outcome after all resections. However, in patients who underwent an R0 resection, concomitant partial hepatectomy was the only independent predictor of long-term survival. Of the 9 actual 5-year survivors (of 30 at risk), all had a concomitant hepatic resection and none had tumor-involved margins; 3 of these 9 patients remained free of disease at a median follow-up of 88 months. The rates of complications and death after resection were 64% and 10%, respectively. In the 219 patients whose disease could be staged, the proposed system predicted resectability and the likelihood of an R0 resection and correlated with metastatic disease and survival. ConclusionBy taking full account of local tumor extent, the proposed staging system for hilar cholangiocarcinoma accurately predicts resectability, the likelihood of metastatic disease, and survival. Complete resection remains the only therapy that offers the possibility of long-term survival, and hepatic resection is a critical component of the surgical approach.Cholangiocarcinoma is a rare disease, accounting for less than 2% of all human malignancies.1 Although the entire biliary tree is potentially at risk, tumors involving the biliary confluence or the right or left hepatic ducts (hilar cholangiocarcinoma) are most common and account for 40% to 60% of all cases. [2][3][4][5][6] Meaningful clinical experience in managing hilar cholangiocarcinomas has been limited to a few referral centers because of the infrequency with which they are encountered.Although resection has long been recognized as the most effective therapy for hilar cholangiocarcinoma, 7 the importance of partial hepatectomy an...

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Background-Gastrointestinal stromal tumor (GIST) is the most common sarcoma of the intestinal tract. The standard treatment of localized, primary GIST has been surgical resection alone. Most GISTs have a mutation in the KIT proto-oncogene, or less commonly in platelet-

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