tbuckley/cabot-search huggingface dataset:
LGG-03. LONG-TERM FOLLOW UP OF TARGETED THERAPY IN PEDIATRIC LOW-GRADE GLIOMAS: THE DANA-FARBER/BOSTON CHILDREN’S EXPERIENCE
Authors: Jessica Tsai, Jayne Vogelzang, Cecilia Sousa, Kee Kiat Yeo, Keith Ligon, Pratiti Bandopadhayay, Tabitha Cooney
Journal: Neuro-Oncology (2021)

Abstract Background Pediatric low grade gliomas (pLGGs) are the most common central nervous system (CNS) tumor in children and characterized by alterations in the MAPK pathway. Standard of care is not well defined, and treatment has evolved over the last decade to include molecular targeted therapies. The impact of targeted agents on the natural history of pLGGs remains unknown. We present a retrospective review of patients receiving targeted agents integrated with molecular profiling. Methods We performed an IRB-approved, retrospective chart review of pLGGs treated with off-label use of dabrafenib, vemurafenib, everolimus, and trametinib at Dana-Farber/Boston Children’s Cancer and Blood Disorders Center from 2010 to 2020. Results Forty-nine patients were identified (dabrafenib n=9, everolimus n=27, trametinib n=10, and vemurafenib n=3). All patients receiving BRAF inhibitors harbored BRAF V600E mutation. Targeted agent was used as first-line therapy for 25% of patients, while for 31% of patients, targeted agent was second-line therapy. The median time from diagnosis to targeted therapy initiation was 4.76 years (0.10 – 23.77), median duration of targeted therapy was 0.79 years (0.01 – 4.87), median time to subsequent therapy post first-line targeted therapy was 0.2 years (0.01 – 3.33), and overall median follow-up for the entire cohort was 3.09 years (0.36 – 11.87). The 1-year, 3-year, and 5-year EFS from targeted therapy initiation was 58.0%, 32.2%, and 26.9%, respectively. Survival analyses by molecular subgroup and agent were performed. Reasons for cessation of targeted therapy included toxicities, progression, and/or planned end of therapy. Conclusions Further efforts are ongoing to perform volumetric analysis of growth rates before, during, and after treatment. While targeted molecular therapies show great promise, it will be critical to understand how these agents alter the natural history of pLGGs, particularly in the context of genomic profiling.
Continuous unobtrusive assessment of meaningful change in older adults with cancer: The Pacific Aging &amp; Cancer Study Collaborative—PACS collaborative.
Authors: Chao-Yi Wu, Deanne Tibbitts, Zachary Beattie, Hiroko H. Dodge, Tomasz M. Beer, Daniel Marks, Jackilen Shannon, Jeffrey Kaye, Kerri M. Winters-Stone
Journal: Journal of Clinical Oncology (2021)

1569 Background: Knowledge of changes in health that precede a cancer diagnosis is challenging because of a lack of longitudinal, objective measurement techniques. Current approaches rely on periodic assessment via self-report which may miss when and how health changes, particularly when changes may appear subtly over time. Remote-monitoring technologies provide a mechanism to continuously, passively, and unobtrusively monitor changes in health so that trajectories of change in relation to a life event (i.e., cancer diagnosis, treatment) can be detected and described. We examined the changes in digital indicators of health and life events 1 year before and after a self-reported cancer diagnosis in community-dwelling adults aged 65 and older. Methods: This is a secondary, retrospective data analysis of older adults who self-reported a new cancer diagnosis in the Oregon Center for Aging &amp; Technology (ORCATECH) cohort. Ten older adults (age = 71.8±4.9 years, 30% women) were included with various cancer types (esophageal, prostate, uterine, pancreatic, b-cell follicular lymphoma, multiple myeloma, basal cell melanoma, basal and/or squamous cell carcinoma). Daily physical activity was measured using step counts derived from an actigraph watch. Weekly health and life events (pain severity, loneliness, hospitalization/emergency room (ER) visits, days away from home overnight) were self-reported from weekly online surveys. Results: A total of 3,624 days of actigraphy data (210 ± 88 days pre-cancer; 153 ± 81 days post-cancer) and 750 weeks of self-reported online survey data (36 ± 12 weeks pre-cancer; 39 ± 14 weeks post-cancer) were collected. Longitudinal linear mixed-effects models revealed that the trajectory of step counts was different pre- and post-cancer (β = -1.52, p &lt;.001), with a gradual decrease in step counts before a cancer diagnosis. The trajectory of pain severity was different pre- and post-cancer (β = 0.01, p &lt;.001), with a gradual increase in pain severity before a cancer diagnosis. There was a gradual increase in the occurrence of hospitalization/ER visits (OR = 1.07, p = 0.02) and days away from home overnight (OR = 1.04, p = 0.01) before a cancer diagnosis. Feelings of loneliness increased over time, regardless of pre- or post-cancer (OR = 1.04, p &lt;.001). Conclusions: Changes in health and life events 1-year before a cancer diagnosis in older adults with varying cancer types and severity were unobtrusively observed. This study suggests that a remote-monitoring technology platform deployed in homes can detect meaningful intra-individual changes before and after a cancer diagnosis. Future studies can employ this technology as a pathway for improving the timeliness of detection and more effective therapeutic follow-up for older adults.
Determination of clinical benefit among patients with radiological stable disease to immune checkpoint inhibitors.
Authors: Jia Luo, Song Wu, Hira Rizvi, Qu Zhang, Jacklynn V. Egger, Juan C. Osorio, Adam Jacob Schoenfeld, Andrew J. Plodkowski, Michelle S. Ginsberg, Ashok Kumar Gupta, Rajiv Raja, Mark G. Kris, Matthew D. Hellmann
Journal: Journal of Clinical Oncology (2021)

9041 Background: SD is a common but ambiguous outcome in patients receiving immune checkpoint inhibitors (ICIs) and likely represents a heterogenous mix of responders and non-responders. This study aimed to characterize SD and identify the subset of patients with SD who are benefiting from treatment. The ability to distinguish whom among patients with SD is actually benefiting from treatment would facilitate drug development and improve precision in correlative research. Methods: A systematic review was performed to characterize SD in ICI trials. SD and objective response was compared to proliferation index using TCGA gene expression data. To identify a subgroup of SD with outcomes mirroring responders, we examined a discovery cohort of NSCLC treated with ICIs and had RECIST assessment. In patients with best overall response (BOR) of SD, serial cutpoints of two variables, % BOR and PFS, were tested to define a subgroup with similar survival as PR-minor (patients with partial response [PR] and % shrinkage &lt; median among responders). Results were then tested in two external validation cohorts (n = 326, n = 381). Results: Among trials of ICIs (59 studies, 14,280 patients), SD ranged from 16-42% in different tumor types and was associated with disease-specific proliferation index (Spearman rho = -0.75, p = 0.03), a proxy of tumor kinetics, rather than relative response to ICIs. In a discovery cohort of 1220 patients with NSCLC who were treated with ICIs, 26% had SD, 19% had PR/CR, and 55% had PD. Outcomes among those with SD ranged widely (OS range 0.5-76 months, PFS range 0.2-49 months). The subset of SD with PFS &gt; 6 months and no tumor growth mirrored PR-minor (OS HR 1.0) and was proposed as the definition of “SD-responder”. SD-responders (n = 87) represented 7% (95% CI 6-9%) of the overall population and 28% (95% CI 23-33%) of the SD population. This definition was confirmed in two validation cohorts from trials of NSCLC treated with durvalumab. Conclusions: RECIST-defined SD to immunotherapy is common, heterogenous, and may largely reflect tumor growth rate rather than ICI response. In patients with NSCLC and SD to ICIs, PFS &gt; 6 months and no tumor growth (̃1/3 of SD) may be considered “SD responders.” This definition may improve the efficiency of and insight derivable from clinical and translational research.
Cancer-specific mortality associated with germline genetic testing results among women with breast cancer or ovarian cancer treated with chemotherapy.
Authors: Allison W. Kurian, Paul Abrahamse, Ann S. Hamilton, Dennis Deapen, Scarlett Lin Gomez, Monica Morrow, Jonathan S. Berek, Steven J. Katz, Kevin C. Ward
Journal: Journal of Clinical Oncology (2021)

10517 Background: Breast and ovarian cancer patients increasingly undergo germline genetic testing. While studies suggest a greater chemotherapy benefit for carriers of BRCA1/2 pathogenic variants, little is known about whether pathogenic variants in other genes are associated with cancer mortality. Methods: Georgia and California Surveillance, Epidemiology and End Results (SEER) registry records of women diagnosed with breast cancer or ovarian cancer from 2013-2017 were linked to results of clinical germline genetic testing from four participating laboratories. Patients were included if they linked to a genetic result, had stages I-III breast cancer or I-IV epithelial ovarian cancer and received chemotherapy. Multivariable Cox proportional hazard models were used to examine the association of genetic results, demographic and clinical factors with cancer-specific mortality. Results: 21,348 breast and 4,320 ovarian cancer patients were analyzed with median follow-up of 41 months. Pathogenic variants were present in 12% of patients with estrogen and progesterone receptor-positive, HER2-negative breast cancer, 9% with HER2-positive breast cancer, 17% with triple-negative breast cancer and 18% with ovarian cancer. Pathogenic variants were most common in BRCA1/2, CHEK2, PALB2, ATM and BRIP1. Among triple-negative breast cancer patients, mortality was lower with pathogenic variants in BRCA1 (hazard ratio (HR) 0.27, 95% confidence interval (CI) 0.17-0.45) and genes other than BRCA1/2 (HR 0.33, CI 0.13-0.81) versus no pathogenic variant. Genetic results were not associated with mortality in other breast cancer subtypes. Among ovarian cancer patients, mortality was lower with pathogenic variants in BRCA2 (HR 0.36, CI 0.26-0.49) and in genes other than BRCA1/2 (HR 0.48, CI 0.33-0.70). Conclusions: Among breast and ovarian cancer patients treated with chemotherapy, those with germline pathogenic variants in several cancer-associated genes had equivalent or lower short-term mortality than those testing negative. These results may guide patient counseling and clinical trial design.
Association of cancer treatment with excess heart age among young breast cancer survivors.
Authors: Jacqueline B Vo, Shoshana M. Rosenberg, Philip Daniel Poorvu, Kathryn Jean Ruddy, Rulla Tamimi, Jeffrey M. Peppercorn, Lidia Schapira, Virginia F. Borges, Steven E. Come, Anju Nohria, Ann H. Partridge
Journal: Journal of Clinical Oncology (2021)

12081 Background: Young women with breast cancer may be at increased risk for premature development of cardiovascular disease (CVD) in part due to their cancer treatment. Limited data are available on CVD risk among young breast cancer survivors. Methods: Women aged 30-40 years at diagnosis with stage 0-III breast cancer enrolled in a prospective cohort study of women diagnosed with breast cancer at ≤40 were eligible for inclusion in this analysis. Data were obtained from serial surveys and electronic medical records at breast cancer diagnosis and 5-year follow-up. We calculated “excess heart age,” which incorporates a CVD risk-based score (calculated using age, systolic blood pressure, blood pressure medication, diabetes, smoking, body mass index) to estimate the difference in years between an individual’s chronological age and their CVD-risk adjusted age. Multivariable logistic regression models (adjusting for age at diagnosis, stage, and race) were fitted to evaluate associations between treatment (radiation, endocrine therapy, anthracyclines, and trastuzumab) and having a change in excess heart age ≥2 years from baseline to 5 years. Results: Among 372 young breast cancer survivors, mean age at diagnosis was 36.6 (SD 2.89), 93% were white, and 79% were diagnosed with stage I or II breast cancer. Mean excess heart age was.32 (SD: 6.16) years at baseline, which declined to -.07 (SD 6.64) at 5-year follow-up (p=.17). At 5 years, 31% (n=114) of women experienced an increase of at least 2 years in their excess heart age since diagnosis, and their mean excess heart age was 4.34 years (range -9 to 30). In multivariable analyses, receipt of trastuzumab was associated with higher odds (OR: 1.68, 95% CI: 1.02-2.77) of experiencing an increase of ≥2 years in excess heart age between diagnosis and 5 years of follow-up. Endocrine therapy, anthracyclines, and radiation were not significantly associated with a change in excess heart age of ≥2 years at 5 years post-diagnosis. Conclusions: At 5 years post-diagnosis, approximately 1/3 of young breast cancer survivors experienced a change from baseline in their excess heart age of ≥2 years. Further research is warranted to confirm findings regarding trastuzumab and excess heart age, and potential effects on longer-term cardiac outcomes in this population. Extended follow-up of this cohort may further quantify CVD risk over time.[Table: see text]
Kaposi sarcoma among adults enrolling for HIV care in a large HIV clinic in Nigeria: 2006-2017.
Authors: Maxwell Oluwole Akanbi, Lucy Bilaver, Chad Achenbach, Lisa Hirschhorn, Oche Agbaji, Robert Murphy, Samuel O Adekolujo
Journal: Journal of Clinical Oncology (2021)

e18539 Background: Expanded access to antiretroviral therapy (ART) has led to a dramatic decline in Kaposi sarcoma (KS) among people initiating HIV care globally. In Nigeria, the country with the second-largest global HIV population, ART coverage increased from 11% in 2006 to 57% by 2017. The impact of Nigeria’s ART expansion of KS risk is unclear. We examined trends in KS risk among patients enrolled for HIV care in a large clinic in Nigeria from 2006-2017. Methods: We analyzed data of 16,431 adults (age ≥18 years) enrolled for HIV care from January 1, 2006, to December 31, 2017, in a large clinic in Jos, Nigeria. KS at enrollment was defined as KS recorded in the electronic health record within 30 days of clinic enrollment. Time trends were compared among three periods: 2006-2009, 2010-2013, and 2014-2017 (Mean national ART coverage 16%, 33%, and 50% respectively), using the Chi-test trend test and logistic regression models to identify factors independently associated with KS. The study was approved by the local institutional Institutional Review Board (IRB) and ruled exempt by the IRBs of Northwestern University and Harvard School of Public Health. Results: The study population had a mean age 35.1 (standard deviation, SD 9.5) years, and were 65.7% female (n= 10,788). The median first CD4 cell count was 192 (IQR 84-320), 215 (IQR 98-344), and 222 (IQR 94-353) in 2006-2009, 2010-2013, and 2014-2017, respectively. The overall KS prevalence at entry was 0.59 % (95% CI 0.48-0.72). KS prevalence was lowest for patient entering care during 2006-2009 (0.39%, 95% CI 0.29-0.53), increased to 1.12% (95% CI 0.82-1.52) in 2010-2013 and declined to 0.72% (95% CI 0.42-1.20) from 2014-2017 (Chi2 for trend, 12.14, p&lt;0.01). Adjusting for age, sex, and CD4 T-cell count KS prevalence was significantly higher in 2010-2013 compared to 2006-2009 (Table). Conclusions: Despite ART expansion, KS at enrollment showed no significant decline. The low CD4+ cell count, across all periods, indicates delay in enrollment for HIV care, which increases KS risk. Interventions aimed at early HIV diagnosis and linkage to ART are critical to KS risk reduction in this population. Factors associated with Kaposi sarcoma at HIV care enrollment in Jos, Nigeria (2006-2017).[Table: see text]
FeNO testing in severe asthma: A clinical argument or an access constraint?
Authors: Pedro Carreiro-Martins, Frederico S. Regateiro, Jorge Ferreira, José Luís Plácido, Rita Gerardo, Cláudia Loureiro
Journal: Pulmonology (2021)

Funding Information: In the preparation of this article, the authors received collaboration from the medical writer Duarte Oliveira (W4Research) financially supported by Sanofi. Sanofi had no role in the preparation of the manuscript or in the decision to submit the manuscript for publication. All authors declare collaborating and receiving fees from Sanofi and other pharmaceutical companies either through participation in advisory boards or consultancy, congress symposia, conducting clinical trials, investigator-initiated trials or grants. Copyright: Copyright 2021 Elsevier B.V., All rights reserved.
Large cell neuroendocrine carcinoma of the urothelial tract (LNEC): The MSKCC experience.
Authors: Brendan John Guercio, Jatin Gandhi, Min Yuen Teo, Michael Lattanzi, Samuel Aaron Funt, David Henry Aggen, Ying-Bei Chen, Samson Fine, Eugene J. Pietzak, Bernard H. Bochner, Guido Dalbagni, Michael F. Berger, David B. Solit, Satish Tickoo, Victor E. Reuter, Dean F. Bajorin, Jonathan E. Rosenberg, Hikmat A. Al-Ahmadie, Gopa Iyer
Journal: Journal of Clinical Oncology (2021)

4526 Background: LNEC is a rare, poorly characterized entity morphologically resembling small cell NEC of the urothelial tract (SNEC). Methods: Pure and partial LNEC and SNEC cases were identified by histopathologic re-review; clinical outcomes were compared. A subset was sequenced with MSK-IMPACT (279-505 genes). Results: Between 1992-2020, 43 patients (pts) with LNEC were identified (42 bladder, 1 upper tract); 19 (44%) had concomitant SNEC. LNEC cases were compared to 192 SNEC without LNEC (SNEC-only) (Table 1). Compared to SNEC-only pts, LNEC pts experienced longer overall survival (OS), adjusting for age and M0 vs M1 (median OS not reached vs 22.4 months [mos]; HR 0.34, 95% CI 0.16-0.74, p =.006). Neoadjuvant chemo (NAC) use increased over time. Pathologic response rate (&lt;ypT2N0) after NAC was 25% for LNEC and 50% for SNEC-only (p =.13); the ypT0N0 rate was 25% for LNEC and 40% for SNEC-only (p =.52). Perioperative chemo did not improve OS compared to surgery alone in LNEC, adjusting for age and concurrent SNEC (HR 1.46, 95% CI 0.12-17.5, p =.76), but was associated with longer OS among SNEC-only pts (n = 98; HR 0.39, 95% CI 0.22-0.69, p =.001). Two M1 LNEC pts received immunotherapy (IO) in the first-line: 1 atezolizumab, 1 atezolizumab + chemo. Both remained free of progression on IO at a follow-up of 20 and 12 mos, respectively. Of 18 sequenced LNEC tumors, 89% had TERT promoter alterations (alts), similar to 85% seen in 52 SNEC tumors. All LNEC tumors had alts of TP53 or RB1, and 10 (56%) had both. Median tumor mutational burden (TMB) was 14 (IQR 8-38) in LNEC and 30 (IQR 15-55) in SNEC. Epigenetic modifiers were altered in 78% LNEC and 79% SNEC. Two LNEC pts had ERCC2 alts and received platinum chemo; both were alive at last follow-up from NEC diagnosis of 30.7-39.1 mos. Conclusions: LNEC pts experienced longer OS compared to pts with SNEC-only in this cohort, but did not appear more chemo-sensitive. Genomic profiles of LNEC and SNEC-only tumors were similar; TERT promoter mutations suggest a potential urothelial precursor. Further investigation of IO for LNEC is warranted.[Table: see text]
Effect of excess weight on immune-related adverse events from immune checkpoint inhibitor in lung cancer.
Authors: Soravis Osataphan, Yu Jen Jan, Katherine A. Stafford, Prudence B. Lam
Journal: Journal of Clinical Oncology (2021)

e21183 Background: Immune checkpoint inhibitors (ICIs) are effective therapies for advanced lung cancer however they are also associated with immune-related adverse events (irAEs). Obesity has been shown to be correlated with both ICIs’ anti-tumor efficacy particularly in melanoma and non-small cell lung cancer (NSCLC). However, there have been conflicting reports between the relationship between BMI and the incidence of irAEs. Methods: We conducted a retrospective cohort study on the use of immune checkpoint inhibitor in advance lung cancer from Mount Auburn Hospital, a community-based teaching hospital in the United States, between 2016 to 2020. We studied the association between overweight (BMI of more than 25 kg/m 2 ) versus normal weight patients (BMI 18.5 - 24.99 kg/m 2 ) and incidence of irAEs or progression free survival. Results: A total of 51 patients with advanced lung cancer were treated with either Pembrolizumab, Nivolumab, Durvalumab or Atezolizumab. NSCLC accounted for 90.2% of the histological findings and adenocarcinoma represented 45.0% of the cohort. Among these patients 61.0% were classified as. There was a trend to increase in the incidence of irAEs in overweight compared to normal weight patients (48.3% vs. 25.0%, OR 1.91, 95% CI 0.56-6.99, p = 0.308). The most common irAEs in this cohort was thyroid dysfunction. The overweight group also had a higher baseline blood glucose level (120.5 ± 39.9 mg/dL vs. 92.9 ± 13.8 mg/dL, p &lt; 0.01). However, no difference in progression free survival was found between the two groups (HR 1.19, 95%CI 0.58-2.42, p = 0.6). Conclusions: Although limited by sample size, here we reported a real-world experience where excessive weight may be an important predictor of irAEs development in patients with lung cancer.