tbuckley/cabot-search huggingface dataset:
Everolimus (EVE) in advanced, nonfunctional, well-differentiated neuroendocrine tumors (NET) of gastrointestinal (GI) or lung origin: Second interim overall survival (OS) results from the RADIANT-4 study.
Authors: James C. Yao, Nicola Fazio, Simron Singh, Roberto Buzzoni, Carlo Carnaghi, Edward M. Wolin, Jiri Tomasek, Markus Raderer, Harald Lahner, Maurizio Voi, Lida Bubuteishvili-Pacaud, Jeremie Lincy, Juan W. Valle, Gianfranco Delle Fave, Eric Van Cutsem, Do-Youn Oh, Jonathan R. Strosberg, Matthew H. Kulke, Marianne E. Pavel
Journal: Journal of Clinical Oncology (2016)

4090 Background: TheRADIANT-4 study met its primary end point with a median progression-free survival (PFS) of 11.0 months (mo) for EVE vs 3.9 mo for placebo (PBO; HR = 0.48 [95% CI 0.35-0.67]; P < .00001) in patients (pts) with advanced, progressive, well-differentiated NET of lung or GI origin. A planned first interim OS analysis favored EVE but did not cross the boundary for significance (HR = 0.64; 95% CI 0.40-1.05; P= .037). We report survival results from preplanned second interim OS analysis. Methods: 302 pts with advanced, progressive, well-differentiated, nonfunctional lung/GI NET were randomized (2:1) to EVE (10 mg/d) or PBO, each with best supportive care. Pts were stratified by tumor origin, WHO performance status, and prior somatostatin analogue use. Primary end point was PFS; OS was the key secondary end point. OS was estimated using the Kaplan–Meier method and the treatment groups were compared using a one-sided log-rank test. The Lan-DeMets method with O’Brien-Fleming type stopping boundary was used to control the cumulative type I error rate. HR was estimated by a stratified Cox proportional hazards model. Results: By data cutoff (Nov 30, 2015), 101 pts died; 66 of 205 (32%) in the EVE group and 35 of 97 (36%) in the PBO group. Median duration of study follow-up was 33.4 mo. EVE was associated with a 27% reduction in the estimated risk of death compared to PBO (HR = 0.73; 95% CI 0.48-1.11; P = .071 [the P-value threshold to claim significance for OS was 0.001982]). Estimated survival rate at 2 years was 77% with EVE and 62% with PBO (Table). Conclusions: The findings from this second interim OS analysis also suggested a trend for survival benefit with EVE, although statistical significance was not achieved. The final OS analysis will be performed when approximately 191 deaths have occurred. Clinical trial information: NCT01524783.Estimated OS rates. Kaplan-Meier Estimates (95% CI) at EVE 10 mg/d (n = 207) PBO (n = 97) 6 mo 94.9 (90.7-97.2) 90.3 (82.2-94.8) 12 mo 88.9 (83.5-92.6) 82.2 (72.6-88.7) 18 mo 81.5 (75.1-86.4) 73.5 (62.7-81.6) 24 mo 76.9 (70.0-82.4) 61.5 (50.0-71.1) 30 mo 67.4 (59.8-73.8) 58.8 (47.2-68.7)
A flourescence based assay for secreted PLA2 activity reveals diversity in the intestinal tract of inbred mouse strains
Authors: Marina Markova, Revati Koratkar, Karen Silverman, Melina Macphee-Pellini, Rhonda Walters, Juan Palazzo, Arthur M. Buchberg, Linda D. Siracusa, Steven A. Farber
Journal: Cancer Research (2004)

5125   The secreted type II nonpancreatic phospholipase A2  (Pla2g2a)  gene was previously identified as a modifier of intestinal adenoma multiplicity in  Apc Min/+   mice. To determine if intestinal secreted phospholipase A2 (sPLA 2 ) activity was also attenuated in susceptible strains, we developed a sensitive assay to characterize sPLA 2  activity utilizing a fluorescent BODIPY-labeled phospholipid substrate. Here we report assay conditions that can distinguish between secreted and cytosolic PLA 2  enzyme activities in extract of intestinal tissue. The small intestine of wildtype mice exhibited higher activity levels than the large intestine. Consistent with predictions from the  Pla2g2a  gene sequence from inbred strains, we detected low levels of enzyme activity in inbred strains containing  Pla2g2a  mutations; these strains were also associated with greater numbers of intestinal polyps. In contrast, the assay was able to distinguish differences in levels of secretory PLA 2  activity between neoplasia-resistant strains which carry wildtype  Pla2g2a  alleles. Immunohistochemical analyses of intestinal tissues were consistent with activity levels. This studies will further our understanding of the role of Pla2g2a in the development of intestinal and colorectal tumorigenesis in both mice and humans. Research supported in part by NIH grant RO1 DK60369 to SAF and NCI grant PO1 CA72027 and CA89560 to LDS and AMB.
Genome‐Wide Association Meta‐Analysis Reveals Novel Juvenile Idiopathic Arthritis Susceptibility Loci
Authors: Laura A. McIntosh, Miranda C. Marion, Marc Sudman, Mary E. Comeau, Mara L. Becker, John F. Bohnsack, Tasha E. Fingerlin, Thomas A. Griffin, J. Peter Haas, Daniel J. Lovell, Lisa A. Maier, Peter A. Nigrovic, Sampath Prahalad, Marilynn Punaro, Carlos D. Rosé, Carol A. Wallace, Carol A. Wise, Halima Moncrieffe, Timothy D. Howard, Carl D. Langefeld, Susan D. Thompson
Journal: Arthritis & Rheumatology (2017)

Objective Juvenile idiopathic arthritis (JIA) is the most common childhood rheumatic disease and has a strong genomic component. To date, JIA genetic association studies have had limited sample sizes, used heterogeneous patient populations, or included only candidate regions. The aim of this study was to identify new associations between JIA patients with oligoarticular disease and those with IgM rheumatoid factor (RF)−negative polyarticular disease, which are clinically similar and the most prevalent JIA disease subtypes. Methods Three cohorts comprising 2,751 patients with oligoarticular or RF‐negative polyarticular JIA were genotyped using the Affymetrix Genome‐Wide SNP Array 6.0 or the Illumina HumanCoreExome‐12+ Array. Overall, 15,886 local and out‐of‐study controls, typed on these platforms or the Illumina HumanOmni2.5, were used for association analyses. High‐quality single‐nucleotide polymorphisms (SNPs) were used for imputation to 1000 Genomes prior to SNP association analysis. Results Meta‐analysis showed evidence of association ( P &lt; 1 × 10 −6 ) at 9 regions: PRR9 _ LOR ( P = 5.12 × 10 −8 ), ILDR1 _ CD86 ( P = 6.73 × 10 −8 ), WDFY4 ( P = 1.79 × 10 −7 ), PTH1R ( P = 1.87 × 10 −7 ), RNF215 ( P = 3.09 × 10 −7 ), AHI1 _ LINC00271 ( P = 3.48 × 10 −7 ), JAK1 ( P = 4.18 × 10 −7 ), LINC00951 ( P = 5.80 × 10 −7 ), and HBP1 ( P = 7.29 × 10 −7 ). Of these, PRR9_LOR, ILDR1_CD86, RNF215, LINC00951, and HBP1 were shown, for the first time, to be autoimmune disease susceptibility loci. Furthermore, associated SNPs included cis expression quantitative trait loci for WDFY4 , CCDC12 , MTP18 , SF3A1 , AHI1 , COG5 , HBP1 , and GPR22 . Conclusion This study provides evidence of both unique JIA risk loci and risk loci overlapping between JIA and other autoimmune diseases. These newly associated SNPs are shown to influence gene expression, and their bounding regions tie into molecular pathways of immunologic relevance. Thus, they likely represent regions that contribute to the pathology of oligoarticular JIA and RF‐negative polyarticular JIA.
Scapular dyskinesis increases the risk of future shoulder pain by 43% in asymptomatic athletes: a systematic review and meta-analysis
Authors: Darren Hickey, Veronica Solvig, Vinicius Cavalheri, Meg Harrold, Leanda Mckenna
Journal: British Journal of Sports Medicine (2017)

It is unclear whether the presence of scapular dyskinesis increases the risk of developing shoulder pain in asymptomatic athletes.To determine whether the presence of scapular dyskinesis in asymptomatic athletes increases the risk of developing shoulder pain by systematic review and meta-analysis.A systematic search was conducted in the Cochrane Library, Embase, PubMed, Cumulative Index to Nursing and Allied Health Literature, Allied and Complementary Medicine Database and SPORTDiscus. Prospective studies that assessed athletes for scapular dyskinesis and recorded incidents of shoulder pain were included. Study quality was assessed using the Downs and Black checklist. Meta-analysis was conducted to derive a pooled risk ratio (RR) for the development of shoulder pain in athletes with scapular dyskinesis compared with those without scapular dyskinesis.Five studies were included with a total of 419 athletes. Of the athletes with scapular dyskinesis, 35% (56/160) experienced shoulder pain during the follow-up, whereas 25% (65/259) of athletes without scapular dyskinesis experienced symptoms. The presence of scapular dyskinesis at baseline indicated a 43% increased risk of a shoulder pain event over a 9 to 24 months follow-up (RR=1.43, 95% CI 1.05 to 1.93).Athletes with scapular dyskinesis have 43% greater risk of developing shoulder pain than those without scapular dyskinesis.
A phase lb, open-label, multicenter, dose-escalation study of the oral pan-PI3K inhibitor BKM120 in combination with the oral MEK1/2 inhibitor GSK1120212 in patients (pts) with selected advanced solid tumors.
Authors: Philippe Bedard, Josep Tabernero, Razelle Kurzrock, Carolyn D. Britten, Anastasios Stathis, Jose Manuel Perez-Garcia, Angela Zubel, Ngocdiep T. Le, Kirsten Carter, Kevin M. Bellew, Chiara Gallarati, Faiz Niazi, David Demanse, Stefan S. De Buck, Cristiana Sessa
Journal: Journal of Clinical Oncology (2012)

3003 Background: MAPK and PI3K/AKT signaling pathways regulate proliferation, differentiation and cell death in human cancers. Known interaction between the 2 pathways provides the rationale for combining both inhibitors in a phase I study. Methods: The objective is to determine the maximum tolerated dose (MTD) and/or recommended phase II dose (RP2D) for oral, daily administered, BKM120 + GSK1120212, mainly in pts with tumors with RAS/RAF mutations (mt). A Bayesian logistic regression model with overdose control guides the dose escalation of the treatment. Secondary objectives include safety, tolerability, PK and efficacy. Results: As of 22.09.11, 49 pts were treated with BKM120 + GSK1120212 as follows: 30mg + 0.5mg, 60mg + 0.5mg, 60mg + 1.0mg, 60mg + 1.5mg, 60mg + 2.0mg, 70mg + 1.5mg, 80mg + 1.0mg, 80mg + 1.5mg. 6 pts had dose-limiting toxicities (DLTs); all were reversible. Grade 3 DLTs were: 3 x stomatitis, 1 x dysphagia, 1 x LVEF decrease, 1 x CK increase, 1 x nausea, 1 x anorexia, 1 x decreased oral intake. MTD and/or RP2D for the combination have not been reached. Most common adverse events (AEs) (&gt;25%), all grades and causality, were dermatitis acneiform, diarrhea (51% each); nausea (41%); vomiting (37%); rash (33%); asthenia (31%); CK increase, decreased appetite, pyrexia or stomatitis (29% each) and hyperglycemia (27%). There were 4 on-treatment deaths unrelated to treatment. AEs led to treatment discontinuation, 17 pts (35%) and interruptions/dose reductions, 25 pts (51%). Apparent steady-states of BKM120 and GSK1120212 were reached by day 28. Plasma concentrations of BKM120 in combination with GSK1120212 were lower than for monotherapy. Exposure to GSK1120212 with BKM120 was similar to that observed in monotherapy studies. 3 confirmed partial responses have been observed in pts with KRAS mt ovarian cancer; 2 lasting &gt;9 months. 2 patients with BRAF mt melanoma, who had previously progressed on BRAF inhibitors, had stable disease, for 1 of whom treatment is still ongoing in cycle 6. Conclusions: BKM120 and GSK1120212 can be safely combined. Signs of clinical activity have been seen in pts with RAS/RAF mt tumors.
Healthcare Costs Related to Treatment of Hepatocellular Carcinoma Among Veterans With Cirrhosis in the United States
Authors: David E. Kaplan, Michael K. Chapko, Rajni Mehta, Feng Dai, Melissa Skanderson, Ayse Aytaman, Michelle Baytarian, Kathryn D’Addeo, Rena Fox, Kristel Hunt, Christine Pocha, Adriana Valderrama, Tamar H. Taddei
Journal: Clinical Gastroenterology and Hepatology (2017)
Rifampicin-resistant tuberculosis: what is the best initial empiric regimen in Mumbai, India?
Authors: Jai Bharat Mullerpattan, Chaitali Nikam, Ujjwal Sharma, Camilla Rodrigues, Lancelot Mark Pinto
Journal: European Respiratory Journal (2017)

Multidrug-resistant tuberculosis (MDR-TB), defined as tuberculosis caused by strains of Mycobacterium tuberculosis (MTB) resistant to the two most important antituberculous drugs – isoniazid and rifampicin – carries a poor prognosis, a high mortality rate and treatment success rates as low as 65% [1]. India has the largest burden of MDR-TB worldwide, with an annual incidence of 130 000 patients [2]. Mumbai, a city populated by over 12 million people, is a hotspot for MDR-TB, with reports indicating the proportion of MDR-TB to be as high as 24% in newly diagnosed patients and 41% in previously treated patients with tuberculosis [3]. Time is tissue: an effective empiric regimen for multidrug-resistant TB tailored to local epidemiology <http://ow.ly/Tzw530c2uoI>
Parallel Evolution of Multiple PSMB5 mutations in a Myeloma Patient Treated with Bortezomib
Authors: Santiago Barrio, Thorsten Stühmer, Eva Teufel, Clara Barrio-Garcia, Manik Chatterjee, Martin Schreder, Mithun Das Gupta, Andreas Rosenwald, Raoul Tibes, Esteban Braggio, A. Keith Stewart, Ralf C Bargou, Hermann Einsele, K Martin Kortüm
Journal: Blood (2016)
A randomized, double-blind, placebo-controlled phase II study of prophylactic dexamethasone (dex) therapy for fatigue and malaise due to regorafenib in patient (pts) with metastatic colorectal cancer (mCRC): (KSCC1402/HGCSG1402).
Authors: Yuji Miyamoto, Satoshi Yuki, Mototsugu Shimokawa, Hiroaki Tanioka, Akihito Tsuji, Masako Asayama, Takeshi Shiraishi, Masahito Kotaka, Akitaka Makiyama, Yoshito Komatsu, Satohiro Masuda, Takuhiro Yamaguchi, Hiroshi Saeki, Eiji Oki, Yasunori Emi, Hideo Baba, Yoshihiko Maehara
Journal: Journal of Clinical Oncology (2016)

10127Background: Regorafenib (REG) is an oral multikinase inhibitor with survival benefit in salvage line therapy for metastatic colorectal cancer (mCRC); fatigue and malaise which are common adver...
Cell-targeted inhibition of constitutively activated NF-κB using IkBα/scFvMEL fusion construct radiosensitizes human melanoma cells.
Authors: Yuying Liu, Gautam Sethi, Weihe Zhang, Lawrence H. Cheung, Anupama Munshi, Raymond E. Meyn, Michael G. Rosenblum
Journal: Cancer Research (2006)

Proc Amer Assoc Cancer Res, Volume 47, 2006

5176 

Melanoma tumors and cell lines are relatively resistant to the cytotoxic effects of ionizing radiation, thereby limiting the use of radiotherapy as a treatment modality. The activated nuclear factor-κB (NF-κB) is one of the pathways responsible for the radioresistance of melanoma cells. New strategies for inhibiting NFκB may be useful in restoring the radioresponse of melanoma. Regulation of NF-κB is mainly controlled by the inhibitory IκB proteins, which include IκBα. Targeted delivery of IκBα protein using a melanoma- specific single-chain Fv antibody may specifically inhibit the nuclear translocation or function of NF-κB and sensitize cells to ionizing radiation. We generated a novel fusion construct composed of human IκBα fused to the single-chain anti-melanoma antibody scFvMEL (anti-gp240) via a short, flexible tether (G4S) using PCR construction. The fused gene was cloned into the pET32 vector and expressed in E. coli and purified by metal affinity chromatography. The His-tag was removed after digestion with thrombin. Two human metastatic melanoma cell lines, A375M (gp240-positive) and TXM-1 (gp240-negative), were used to examine the radiosensitizing effects of the fusion construct. Nuclear extracts from these cell lines were tested for active NF-κB using the electrophoretic mobility shift assay. The data demonstrated that NF-κB nuclear DNA binding is constitutively active in human melanoma cells and is enhanced by ionizing radiation. Cells treated with IkBα/scFvMEL at a concentration 0.3 μM for 2 hours prior to irradiation showed inhibition of both constitutive and radiation-induced NF-κB activity on gp240 antigen positive A375-M cells but not on gp240 antigen negative TXM-1 cells. Constitutive activation of NF-κB induces overexpression of its downstream targets such as bcl-2 and bcl-XL which may in turn mediate resistance to apoptosis induced by radiation. IkBα/scFvMEL fusion construct decreased the levels of bcl-2, bcl-XL only A375-M cells but not in TXM-1 cells. Clonogenic cell survival assays showed that pretreatment with IκBα/scFvMEL enhanced tumor cell radiosensitivity on antigen positive A375-M cells with the survival factor being reduced from 50.2 ± 1.06 % in vehicle-treated cells to 35.4 ± 2.75 % in the fusion protein-treated cells at 2 Gy (p < 0.05) and from 19.8 ± 2.50 % in vehicle-treated cells to 7.4 ± 0.74 % in the fusion protein-treated cells at 4 Gy (p< 0.05). These studies demonstrate for the first time that tumor-cell targeted delivery of IκBα may be beneficial for the treatment of melanoma when combined with standard anticancer therapies such as radiation. In addition, this approach may also be utilized to specifically suppress NF-κB activity in other tumor models or in other disease states. Research conducted, in part, by the Clayton Foundation for Research.
BRAF Inhibitors Amplify the Proapoptotic Activity of MEK Inhibitors by Inducing ER Stress in NRAS-Mutant Melanoma
Authors: Heike Niessner, Tobias Sinnberg, Corinna Kosnopfel, Keiran S.M. Smalley, Daniela Beck, Christian Praetorius, Marion Mai, Stefan Beissert, Dagmar Kulms, Martin Schaller, Claus Garbe, Keith T. Flaherty, Dana Westphal, Ines Wanke, Friedegund Meier
Journal: Clinical Cancer Research (2017)

Purpose: NRAS mutations in malignant melanoma are associated with aggressive disease requiring rapid antitumor intervention, but there is no approved targeted therapy for this subset of patients. In clinical trials, the MEK inhibitor (MEKi) binimetinib displayed modest antitumor activity, making combinations a requisite. In a previous study, the BRAF inhibitor (BRAFi) vemurafenib was shown to induce endoplasmic reticulum (ER) stress that together with inhibition of the RAF-MEK-ERK (MAPK) pathway amplified its proapoptotic activity in BRAF-mutant melanoma. The present study investigated whether this effect might extent to NRAS-mutant melanoma, in which MAPK activation would be expected.Experimental Design and Results: BRAFi increased pERK, but also significantly increased growth inhibition and apoptosis induced by the MEKi in monolayer, spheroids, organotypic, and patient-derived tissue slice cultures of NRAS-mutant melanoma. BRAFi such as encorafenib induced an ER stress response via the PERK pathway, as detected by phosphorylation of eIF2α and upregulation of the ER stress-related factors ATF4, CHOP, and NUPR1 and the proapoptotic protein PUMA. MEKi such as binimetinib induced the expression of the proapoptotic protein BIM and activation of the mitochondrial pathway of apoptosis, the latter of which was enhanced by combination with encorafenib. The increased apoptotic rates caused by the combination treatment were significantly reduced through siRNA knockdown of ATF4 and BIM, confirming its critical roles in this process.Conclusions: The data presented herein encourage further advanced in vivo and clinical studies to evaluate MEKi in combination with ER stress inducing BRAFi as a strategy to treat rapidly progressing NRAS-mutant melanoma. Clin Cancer Res; 23(20); 6203-14. ©2017 AACR.
Case-control study of PD-1, PD-L1, and B7-H3 expression in human immunodeficiency virus infected (HIV+) and uninfected patients with head and neck cancers.
Authors: Candace Barette Mainor, Katherine Ann Scilla, Jonathon Heath, Olga B. Ioffe, Ashley L Cellini, David Riedel, Soren Bentzen, Josephine Louella Feliciano, Dan Paul Zandberg
Journal: Journal of Clinical Oncology (2017)

e23194 Background: HIV+patients are typically excluded from immunotherapy trials but there are limited data on co-signaling molecule expression in these patients, including in head and neck squamous cell carcinoma (HNSCC). Methods: A case control study was conducted to evaluate tumor tissue sections for PD-L1, PD-1, and B7-H3 expression in HIV+HNSCC patients (n = 12) and HNSCC controls (n = 12). Cases and controls were matched for age at diagnosis, race, gender, TNM stage, and primary site. Smoking status, HIV RNA viral load (VL), and CD4 count were also recorded. Immunostained tumor sections were analyzed for percent of tumor cells expressing PD-L1 (PD-L1%) and B7-H3(B7-H3%) (Abcam), and percent of tumor infiltrating lymphocytes (TIL) expressing PD-1 (TIL-PD-1%) and PD-L1 (TIL-PD-L1%) (Abcam). Statistical analysis used the non-parametric Mann-Whitney test, chi-square test and Spearman’s rank correlation, Rs. Results: The 12 HIV+ HNSCC cases were predominantly male (67%), black race (67%) and cigarette smokers (100%), with a median age of 50.4 years, median viral load (VL) of 52399 copies/mL, median CD4 count (CD4) of 236cells/uL, predominantly locally advanced (75% Stage III/IVa/IVb), and oropharyngeal primary site (42%). Defining positive expression as &gt; 5%, 42% of HIV+ HNSCC patients tumors were positive for PD-L1, 100% for B7-H3, and 92% had TILs that expressed PD-1 and PD-L1. HIV+ patients had significantly higher B7-H3% (Median 60% vs. 20%, p = 0.03) and TIL-PD-L1% (Median 15% vs. 10%, p = 0.045) compared to controls. There were no differences in PD-L1% or TIL-PD-1%. In HIV+ cases, increased VL correlated with increased TIL-PD-1% (Rs = 0.73, p = 0.011) and increased CD4 count correlated with increased tumor PD-L1% (Rs = 0.62, p = 0.04). There were no other significant correlations between CD4 count or VL and co-signaling molecule expression. Conclusions: HIV+ HNSCC patients had significantly higher tumor B7-H3 and TIL PD-L1 expression, with similar tumor PD-L1 and TIL PD-1 expression, compared to HIV negative HNSCC control patients. These findings support inclusion of HIV+ HNSCC patients in immunotherapy trials with checkpoint inhibitors.
Identifying an Optimal Adjuvant Radiotherapy Dose for Extremity and Trunk Merkel Cell Carcinoma Following Resection
Authors: Sagar A. Patel, Muhammad M. Qureshi, Debjani Sahni, Minh Tam Truong
Journal: JAMA Dermatology (2017)

Merkel cell carcinoma (MCC) is a rare and aggressive cutaneous neuroendocrine neoplasm with a high risk of recurrence following resection. Despite a rising incidence over the past 3 decades, there is a paucity of prospective data owing to the rarity of this disease.To determine the optimal adjuvant radiation therapy (RT) dose following resection of localized MCC of the extremities or trunk.Using the National Cancer Database, a large national database consisting of a heterogeneous population and treatment settings, we retrospectively analyzed a cohort of 2093 patients 18 years or older with stage I to III MCC of the extremities and/or trunk treated with definitive surgery and adjuvant RT between 1998 and 2011. Exclusion criteria included receiving treatment with palliative intent, preoperative RT, non-external-beam RT, and radiation dose of 30 Gy or lower or 70 Gy or higher. Cox proportional hazards regression model was used to compare overall survival (OS) between RT dose groups, accounting for age, sex, race, stage, surgery type, margin status, comorbidities, and use of chemotherapy.Radiation therapy dose was categorized into 4 groups: group 1 received the lowest dose (>30 to <40 Gy); group 2, the next lowest (40 to <50 Gy); group 3, the second highest dose (50 to 55 Gy); and group 4, the highest dose (>55 to 70 Gy).Overall survival.Data from 2093 patients were analyzed; there were 1293 men (61.8%) and 800 women (38.2%) (median age, 73 years). After a median follow-up of 37 months for the entire cohort, 904 deaths were reported. The 3-year OS rates for groups 1, 2, 3, and 4 were 41.8%, 69%, 69.2%, and 66%, respectively (omnibus P < .001). Compared with group 3 (50 to 55 Gy), equivalent OS was seen in group 2 (40 to <50 Gy; adjusted hazard ratio [AHR], 0.89; 95% CI, 0.63-1.27; P = .52) and group 4 (>55 to 70 Gy; AHR, 1.18; 95% CI, 0.93-1.48; P = .17), but worse OS was found in group 1 (>30 to <40 Gy; AHR, 2.63; 95% CI, 1.44-4.80; P < .001).Adjuvant RT dose from 40 to lower than 50 Gy appears adequate for extremities and/or trunk stage I to III MCC, with OS equivalent to that found at higher-dose regimens (>50 to 70 Gy).