tbuckley/cabot-search huggingface dataset:
Abstract AP25: INHIBITION OF HDAC ACTIVITY SELECTIVELY INHIBITS ARID1A–MUTATED OVARIAN CLEAR CELL CARCINOMA THROUGH A NOVEL P53 REGULATORY MECHANISM
Authors: Benjamin G. Bitler, Pyoung Hwa Park, Yang Hai, Katherine M. Aird, Yemin Wang, David G. Huntsman, Kathleen R. Cho, David W. Christianson, Rugang Zhang
Journal: Clinical Cancer Research (2017)

Abstract PURPOSE OF THE STUDY: ARID1A is mutated ~50% and 30% of clear cell (OCCC) and endometrioid (OEC) ovarian cancers, respectively. Over 90% of the ARID1A mutations observed in ovarian cancer are frame-shift or nonsense mutations that result in loss of ARID1A protein expression. In several cancers including OCCC, ARID1A and p53 mutations are often mutually exclusive. OCCC carries a worse prognosis compared to the other histosubtypes of ovarian cancer. Thus, there is an urgent clinical need for improved therapeutic strategies. EXPERIMENTAL PROCEDURE: To investigate the role of specific HDACs in the context of ARID1A expression, we examined the effect of knocking down HDACs in an isogenic OCCC cell line with and without ARID1A expression. Utilizing a panel of ARID1A-mutated and wildtype OCCC cell lines, we evaluated the effect of HDAC knockdown and inhibition through a variety of 2D and 3D assays. We also examined the consequence of HDAC inhibition on tumor growth, survival, and dissemination in an in vivo mouse model of ovarian cancer. SUMMARY OF THE DATA: We have discovered that ARID1A is involved in the repression of HDACs, and ARID1A-inactivation promotes aberrant transcriptional regulation of HDACs. Importantly, we uncovered a novel HDAC-dependent regulatory mechanism of p53. Several HDAC inhibitors are currently in clinical trials. We found HDAC inhibitors were more selective in ARID1A-mutated OCCC cell lines compared to ARID1A-wildtype cells. We observed that HDAC inhibition led to a significant increase in apoptosis in ARID1A-mutated cells. In an orthotopic intra-bursal xenograft model using ARID1A wildtype and deficient cells, the HDAC inhibitor suppressed primary tumor growth and inhibited tumor cell dissemination only in the ARID1A-mutated tumors. Significantly, HDAC inhibition significantly improved the survival of mice bearing ARID1A-mutated tumors. CONCLUSIONS: These findings imply that HDAC inhibition represents a novel therapeutic strategy for ARID1A-deficient cancers. This study further elucidates the observed mutual exclusivity of ARID1A and p53. Importantly, we have uncovered a novel regulatory mechanism of p53 mediated through ARID1A and HDACs. Clinically, this study describes a precision medicine approach to the treatment of ARID1A-mutated OCCC. Citation Format: Benjamin G. Bitler, Pyoung Hwa Park, Yang Hai, Katherine M. Aird, Yemin Wang, David G. Huntsman, Kathleen R. Cho, David W. Christianson, Rugang Zhang. INHIBITION OF HDAC ACTIVITY SELECTIVELY INHIBITS ARID1A–MUTATED OVARIAN CLEAR CELL CARCINOMA THROUGH A NOVEL P53 REGULATORY MECHANISM [abstract]. In: Proceedings of the 11th Biennial Ovarian Cancer Research Symposium; Sep 12-13, 2016; Seattle, WA. Philadelphia (PA): AACR; Clin Cancer Res 2017;23(11 Suppl):Abstract nr AP25.
Refined estimates of local recurrence risks and the impact of the DCIS score adjusting for clinico-pathological features: Meta-analysis of E5194 and Ontario DCIS cohort studies.
Authors: Eileen Rakovitch, Robert James Gray, Frederick L. Baehner, Dave P. Miller, Rinku Sutradhar, Michael Crager, Sumei Gu, Sharon Nofech-Mozes, Sunil S. Badve, Wedad Hanna, Lorie L. Hughes, William C. Wood, Lawrence Frank Paszat, Steven Shak, Joseph A. Sparano, Lawrence J. Solin
Journal: Journal of Clinical Oncology (2017)

528 Background: Better tools are needed to estimate the risk of local recurrence (LR; DCIS or invasive) after breast-conserving surgery (BCS) for DCIS to inform treatment decisions. The DCIS Score (DS) was validated as a predictor of LR in E5194 and Ontario DCIS Cohort (ODC) after BCS without radiation (Solin,2013; Rakovitch,2015). We performed a meta-analysis (MA) combining data from E5194 and ODC with additional follow-up from E5194 adjusting for pertinent clinico-pathologic factors to provide refined prediction estimates of LR risk after BCS alone. Methods: The MA used data from E5194 and ODC. Patients with positive margins and multifocality were excluded. Identical Cox regression models were fit including age at diagnosis ( &lt; 50, ≥50 yr), tumor size (1cm, &gt; 1cm), DCIS Score and year of surgery (before vs after 2000). Grade was not significant. MA was used to calculate precision-weighted estimates of 10 year LR risk by DS. Results: Combined cohort includes 773 pts (tamoxifen used in 20% E5194, 17% of ODC &gt; 65 yr). The DS and the clinico-pathologic variables age, tumor size and year provided independent prognostic information on 10 yr LR risk (p≤.009). Hazard ratios from E5194 and ODC cohorts were similar for tumor size ≤1 vs. &gt; 1cm (1.45, 1.47), age ≥50 vs. &lt; 50 yr (0.61, 0.84) and surgery year after 2000 (0.67, 0.49). 10 yr LR risks by combinations of age, tumor size, and DS are detailed in Table. For patients ≥50 yr with tumors ≤1cm and low risk DS, the 10 yr LR risks range from 5.3-10.0%. A high risk DS is associated with a higher 10 yr predicted risk of LR in all subsets. 10 yr risk of contralateral BC was 5.4%. Conclusions: This MA provides refined estimates of 10 yr LR risk after BCS alone for DCIS. Adding clinico-pathologic factors to the DCIS Score provides enhanced prognostic LR risk estimates to guide individualized treatment decision-making. [Table: see text]
Are There Differences in Disruptions of Reward Processing Between Substance Use Disorder and Gambling Disorder?
Authors: Ruth J. van Holst, Tim van Timmeren, Anneke E. Goudriaan
Journal: JAMA Psychiatry (2017)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Psychiatry HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Psychiatry journal
A phase II, randomized, open-label 3-arm clinical trial of fulvestrant (F) plus goserelin (G) versus anastrozole (A) plus goserelin (G) versus goserelin (G) alone for hormone receptor (HR) positive, tamoxifen (T) pretreated premenopausal women with recurrent or metastatic breast cance r(MBC) (KCSG BR10-04).
Authors: Ji-Yeon Kim, Seock-Ah Im, Kyung Hae Jung, Jungsil Ro, Joohyuk Sohn, Jee Hyun Kim, Yeon Hee Park, Tae Yong Kim, Sung-Bae Kim, Keun-Seok Lee, Gun Min Kim, Se Hyun Kim, Jin Seok Ahn, Kyung-Hun Lee, Jin-Hee Ahn, In Hae Park, Young-Hyuck Im
Journal: Journal of Clinical Oncology (2017)

1041 Background: Endocrine therapy(ET) is the preferred treatment for HR(+) MBC. For premenopausal patients who were pretreated with T, ovarian function suppression with G ± aromatase inhibitor(A.I.) is a reasonable option. Fulvestrant yields favorable outcomes in postmenopausal women with MBC. We investigated the efficacy and safety of F+G and A+G in comparison with G alone in premenopausal women with HR(+), T-pretreated MBC. Methods: In this multicenter, open-label, randomized phase 2 study, women &gt; 18 years with HR(+), T-pretreated MBC were stratified by presence of visceral metastasis and recurrence within or after 1 year of completion of adjuvant T. Premenopausal women with T-pretreated MBC eligible for ET were randomly assigned (1:1:1) to F+G (F 500 mg IM + G 3.6 mg SC Q 4 wks), or A +G (A 1 mg P.O. qd + G 3.6 mg SC Q 4 wks) or G (G 3.6 mg SC Q 4 wks). The primary endpoint was time to progression(TTP), analyzed by intention to treat with log-rank test. Secondary endpoints included overall survival, overall response rate, clinical benefit rate and toxicities according to NCI CTCAE v3.0 (ClinicalTrials.gov, No. NCT01266213). Results: Of 138 eligible pts, 44 were randomly assigned to F+G, 47 to A+G, 47 to G. The median duration of follow-up was 28.8 months(mo) and median age was 43 (range; 23.0-55.0). The median TTP was 16.3 mo(95% C.I. 7.5-25.1) for F+G, 14.5 mo(95% C.I. 11.0-18.0) for A+G, and 13.5 mo(95% C.I. 10.3-16.8) for G alone, respectively. For the comparison of each experimental arm to control arm, 24-mo TTP were analyzed: F+G vs G(%±SE): 40.5±7.5 vs. 25.3±7.0, one-sided P = 0.048, A+G vs G(%±SE): 23.9±7.2 vs. 25.3±7.0, one-sided P = 0.304. Grade 3/4 toxicities were rarely observed. Most common adverse events were grade 1 joint stiffness and arthralgia which were more frequently observed in F+G compared to A+G and G (P = 0.018 and 0.015, respectively). Conclusions: The combination of F+G as well as G ±A.I. might be a valid option for HR(+) premenopausal women with T-pretreated MBC and further investigation is warranted. Clinical trial information: NCT01266213.
Abstract NTOC-106: FAK INHIBITION RE–SENSITIZES PLATINUM–RESISTANT SEROUS OVARIAN CANCER
Authors: Lisa M. Bean, Florian J. Sulzmaier, Kristen M. Anderson, Isabelle Tancioni, Cheyenne R. Butcher, Sean Uryu, Christine Jean, Christine Lawson, Xiao Lei Chen, Elizabeth G. Kleinschmidt, Vihren N. Kolev, Jonathan A. Pachter, Dwayne G. Stupack, David D. Schlaepfer
Journal: Clinical Cancer Research (2017)

Abstract Most ovarian cancer patients respond well to surgical debulking and platinum-taxol chemotherapy. However, ~80% of patients with a complete response to therapy will exhibit tumor recurrence, and in time develop platinum and chemotherapy-resistant disease. It is hypothesized that recurrent disease emanates from the regrowth of microscopic clusters of chemotherapy-resistant tumor cells - also termed cancer stem cells (CSCs). Here, we find that cisplatin chemotherapy elevates focal adhesion (FAK) tyrosine kinase phosphorylation (Y397 FAK) in 3D ovarian tumor spheroids. Notably, FAK is not known as a DNA-damage sensing kinase. Instead, FAK is linked to integrin adhesion-, migration-, and CSC-promoting signaling pathways. In mouse tumors, CP-taxol chemotherapy increases FAK Y397 phosphorylation and aldehyde dehydrogenase (ALDH-1A1, a known markers of CSCs) in tumor areas not associated with necrosis. FAK Y397 phosphorylation is constitutively-elevated in CP-resistant ovarian cancer cells and nanomolar levels of FAK inhibitor (VS-4718) block 3D colony cell growth. Oral VS-4718 administration to mice reduces CP-resistant orthotopic tumor burden with a concomitant decrease in tumor-associated ALDH activity and secondary tumor-initiating capacity. CRISPR-mediated FAK knockout or VS-4718 treated ovarian carcinoma cells exhibit diminished ALDH-1A1 expression. Importantly, co-administration of VS-4718 enhances the anti-tumor effectiveness of CP-taxol chemotherapy in an orthotopic CP-resistant mouse tumor model. As CP activates FAK and FAK signaling sustains ovarian carcinoma CSC phenotypes, our results support the future testing of FAK inhibitors in combination with CP to prevent recurrent and chemo-resistant ovarian cancer. Citation Format: Lisa M. Bean, Florian J. Sulzmaier, Kristen M. Anderson, Isabelle Tancioni, Cheyenne R. Butcher, Sean Uryu, Christine Jean, Christine Lawson, Xiao Lei Chen, Elizabeth G. Kleinschmidt, Vihren N. Kolev, Jonathan A. Pachter, Dwayne G. Stupack, and David D. Schlaepfer. FAK INHIBITION RE–SENSITIZES PLATINUM–RESISTANT SEROUS OVARIAN CANCER [abstract]. In: Proceedings of the 11th Biennial Ovarian Cancer Research Symposium; Sep 12-13, 2016; Seattle, WA. Philadelphia (PA): AACR; Clin Cancer Res 2017;23(11 Suppl):Abstract nr NTOC-106.
Splenomegaly Negatively Affects Patients with Acute Myeloid Leukemia and Myelodysplastic Syndrome after Allogeneic Stem Cell Transplantation
Authors: Yoshimitsu Shimomura, Yuichiro Ono, Satoshi Yoshioka, Nobuhiro Hiramoto, Noboru Yonetani, Akiko Matsushita, Hisako Hashimoto, Takayuki Ishikawa
Journal: Blood (2016)
Autoimmune antibody decline in Parkinson’s disease and Multiple System Atrophy; a step towards immunotherapeutic strategies
Authors: Tomasz Brudek, Kristian Winge, Jonas Folke, Søren Christensen, Karina Fog, Bente Pakkenberg, Lars Østergaard Pedersen
Journal: Molecular Neurodegeneration (2017)

Parkinson's' disease (PD) and Multiple System Atrophy (MSA) are progressive brain disorders characterized by intracellular accumulations of α-synuclein and nerve cell loss in specific brain areas. This loss causes problems with movement, balance and/or autonomic functions. Naturally occurring autoantibodies (NAbs) play potentially an important role in clearing or/and blocking circulating pathological proteins. Little is known about the functional properties of anti-α-synuclein NAbs in PD and MSA, and there have been opposing reports regarding their plasma concentrations in these disorders. We have investigated the apparent affinity of anti-α-synuclein NAbs in plasma samples from 46 PD patients, 18 MSA patients and 41 controls using competitive enzyme-linked immunosorbent assay (ELISA) and Meso Scale Discovery (MSD) set-ups. We found that the occurrence of high affinity anti-α-synuclein NAbs in plasma from PD patients is reduced compared to healthy controls, and nearly absent in plasma from MSA patients. Also, levels of α-synuclein/NAbs immunocomplexes is substantially reduced in plasma from both patient groups. Further, cross binding of anti-α-synuclein NAbs with β- and γ-synuclein monomers suggest, the high affinity anti-α-synuclein plasma component, seen in healthy individuals, is directed mainly against C-terminal epitopes. Furthermore, we also observed reduced occurrence of high affinity anti-phosphorylated-α-synuclein NAbs in plasma from PD and MSA patients. One interpretation implies that these patients may have impaired ability to clear and/or block the effects of pathological α-synuclein due to insufficient/absent concentration of NAbs and as such provides a rationale for testing immune-based therapeutic strategies directed against pathological α-synuclein. Following this interpretation, we can hypothesize that high affinity autoantibodies efficiently bind and clear potentially pathological species of α-synuclein in healthy brain, and that this mechanism is impaired or absent in PD and MSA patients.
Abstract 158: Assessing the Paracrine Hypothesis in Cardiac Regeneration Through Endogenous c-Kit+ Cells
Authors: Ronald J Vagnozzi, Marjorie Maillet, Michelle A Sargent, Jeffery D Molkentin
Journal: Circulation Research (2015)

Multiple studies have shown an innate capacity of the adult mammalian heart to partially regenerate following stress or injuries such as myocardial infarction (MI). However, this modest capacity is insufficient to resolve the significant damage that occurs post-MI, thus efforts have centered on bolstering this regenerative potential by delivery of various stem or progenitor cell types. To-date, over fifty clinical trials have evaluated cell-based therapeutics to induce regeneration in the setting of ischemic heart disease - mostly using bone marrow mononuclear cells (BM-MNCs) although c-Kit + cardiac progenitor cells (CPCs) and mesenchymal stromal cells (MSCs) from bone were also evaluated. Collectively, cell therapy has demonstrated clinical safety; yet overall effectiveness has been questioned, as evidence that transplanted cells differentiate into cardiomyocytes is lacking. Hence, studies showing some functional benefit have ascribed it to enhanced endogenous regeneration via paracrine factors secreted by the implanted cells. One hypothesis is that these factors stimulate resident c-Kit + progenitors to generate new myocardium. We recently developed an inducible genetic system to trace endogenous c-Kit + cells in the murine heart. We now use this system to evaluate whether delivery of different progenitor-like cell types can enhance c-Kit + -derived myocyte or vessel formation in the uninjured heart; using a dual-reporter strategy to differentially fate map transplanted cells versus endogenous c-Kit + cells. We observed that BM-MNCs induced a modest increase in c-Kit + -derived, CD31 + vessels proximal to the site of injection, although no new myocytes were observed. There was no evidence for fusion between BM-MNCs and host myocardium, or for prolonged engraftment, as by 6 weeks virtually all injected cells were cleared. Taken together, this suggests that BM-MNCs are capable of inducing an acute c-Kit + -mediated vascular response in the uninjured heart. We are also currently evaluating CPCs, bone marrow or adipose-derived MSCs, and bone stromal cells for their capacity to stimulate c-Kit + cells, either without injury or after MI. Our goal is to better define the paracrine hypothesis, improving cell-based therapies for application in humans.
Clinical outcomes in very early breast cancer (≤ 1cm): A national population based analysis.
Authors: Mahvish Muzaffar, Abdul Rafeh Naqash, Nasreen A. Vohra, Darla K. Liles, Jan H. Wong
Journal: Journal of Clinical Oncology (2017)

e12034 Background: The utilization of screening mammogram has resulted in increased diagnosis of very small breast cancers including T1a (≤5 mm), T1b ( &gt; 0.5 but ≤1 cm). These small tumors have excellent prognosis with cancer-specific survival rates as high as 90% to 95%.This study evaluates outcomes in very early breast cancer in a national database. Methods: Patients with stage I breast cancer, tumor ≤ 1cm (T1aN0, T1bN0) diagnosed between 2006 and 2011 were selected from the SEER database. We excluded patients with missing biomarker information. Treatment outcome and prognostic factors for disease-specific survival (DSS) and overall survival (OS) were evaluated. Results: We identified 70,543 cases and included 54,796 patients with stageT1aN0M0 and T1bN0M0 in the final analysis.The mean age was 62.09 yrs(CI 95% 62.2-61.99),84% are white,7% black and 7% Other.89% were ER positive,11% ER negative and 3% had Her 2 positive tumors.71% of patients had T1b. ≤ 1cm breast cancer cases increased from 15% in 2006 to 18% in 2011.The 5-year disease specific survival (DSS) and overall survival (OS) for patients with stage T1aN0T1b N0 was 98.7% and 93.7%, respectively. Estrogen receptor(ER) positive tumors were associated with improved 5-yr DSS 99% vs 96% in ER negative (p &lt; 0.0001) and OS in ER positive 94% vs 92%( p &lt; 0.0001).Among white patients 5-yr DSS was 98.8% and OS was 93.7% while 5yr-DSS was 94%,OS 91.5% among black vs 5-yr DSS 99% and OS 96.3% in others( Asian or Pacific Islanders,AI), (p &lt; 0.0001).Tumor subtype was not associated with significant difference in outcome but T1a tumor was associated with OS 94.5% vs 93.4% with T1b tumors(p &lt; 0.0001) On cox model analysis factors which correlated with prolonged DSS and OS are race (p &lt; 0.0001),older age (p &lt; 0.0001), ER positivity (p &lt; 0.0001) and tumor less than 5mm (p = 0.0006). Conclusions: Very early breast cancer is associated with excellent outcome but has some heterogeneity. Nonwhite/Non Black race was associated with better survival compared to white and black patients.ER positive tumors, older age were also associated with better outcome. This data while reassuring also brings into question of overtreatment of this disease subset.
UGT1A1 gene polymorphism and irinotecan-induced toxicity in chemotherapy (CT) for colorectal cancer (CRC).
Authors: Natalya A Abramova, Liubov Yu Vladimirova, Dmitry I. Vodolazhsky, Oleg Ivanovich Kit, Konstantin Vladimirovich Dvadnenko, Irina L Popova, Irina S Mitashok
Journal: Journal of Clinical Oncology (2015)

e14577 Background: Topoisomerase I inhibitor Irinotecan (IT) is applied in CT for CRC. However, its toxicity associated with polymorphism of TATA box (T-thymine, A-adenine) of the UGT1А1 gene limits its use. Polymorphism of UGT1A1*28 allele induces an increase in TA sequence in gene promoter from 6 to 7. It is associated with inhibition of transcriptional activity and expression of the gene which results in reduction of enzyme activity, increase in time of SN-38 excretion and increase in IT toxicity. Methods: The study included pts with histologically verified CRC, ECOG ≤ 2, normal function of bone marrow, liver and kidneys, without brain metastases, who received IT in the 1st line of CT. Molecular and genetic study of polymorphism of allelic variants 6 and 28 of the UGT1A1 gene was performed with pyrosequencing method. FOLFIRI was used. IT dose was reduced by 25% for patients with high-risk (HR) toxicity. Association between CT toxicity and the UGT1А1 gene polymorphism was assessed. Results: 36 pts (18 male, 18 female) with CRC T2-4N0-1M0-1 G2-3, mean age 54±2.4, were recruited. *1/*28 and *6/*6 variants were the most frequent, *28/*28 and *1/*6 – the least frequent. Low-risk toxicity (LR) was in 36.1%(13), moderate-risk (MR) – in 50.0%(18), high-risk (HR) – in 13.9%(5). IT toxicity of 87 CT cycles (CTCAE 3.0) (35 LR, 39 MR, 13 HR) were analyzed with association UGT1A1 polymorphism. Differences in toxicitiy were: neutropenia 2/4 gr. MR 40.9%(16), HR 61.5%(2) and LR 28.6%(10), thrombocytopenia 2/3 gr. HR 15.4%(16) and LR (0), vomiting 1/2 gr. HR 61.5%(8) and MR 28.2%(11), LR 28.6%(10), diarrhea 1/3 gr. HR 69.2%(9) and MR 43.6%(17), LR 40.0%(14), increased transaminase 1 gr. HR 0.8%(4),LR 17.2%(15), hyperbilirubinemia 1 gr. in MR 17.9%(7),HR 38.4%(5), LR 2.9%(1). Differences in HR and LR thrombocytopenia (p = 0.0275), hyperbilirubinemia in MR and LR (p = 0.0442), in HR and LR (p = 0.0439) are statisticaly valid. Conclusions: The results confirm necessity of personalized approach in treatment with IT. Molecular and genetic analysis of the mutant UGT1A1 gene in CRC patients together with other clinical and laboratory parameters, prior to IT treatment, is necessary for toxicity prognosis.
Prognostic and Predictive Ability of Tumor Sidedness
Authors: George J. Chang, Mithat Gonen
Journal: JAMA Oncology (2017)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Oncology HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Oncology journal