bluuebunny/crossref_metadata_2025_split huggingface dataset:
Selection of patients for surveillance imaging after radiotherapy for squamous cell carcinoma of oral cavity and oropharynx.
Authors: Zeng Johnathan , Fleming Christopher W , Lee Maxwell , Parikh Rujul H , Rybicki Lisa A. , Joshi Nikhil , Woody Neil McIver , Ku Jamie , Prendes Brandon , Lamarre Eric , Lorenz Robert R , Scharpf Joseph , Burkey Brian B. , Chute Deborah , Schwartzman Larisa , Geiger Jessica Lyn , Adelstein David J. , Koyfman Shlomo A. 
Published: May 2020

6533 Background: NCCN guidelines do not recommend routine surveillance imaging for distant failure (DF) after definitive treatment of head & neck squamous cell carcinoma (SCC). We hypothesized that there exists a subset of patients with sufficiently high enough risk for DF to benefit from surveillance imaging. This study attempts to define high risk cohorts of oropharynx (OP) and oral cavity (OC) patients. Methods: A retrospective review was conducted of patients with SCC of the OP or OC at a single tertiary care institution from 1994-2019. Patients were staged according to AJCC 7th edition and included in this study if they completed definitive-intent treatment and received 60 Gray or higher of radiotherapy (RT). Local, regional, and distant failure were estimated with cumulative incidence. Univariable & multivariable risk factors for DF were identified with Fine & Gray competing risk regression. Significant variables were compiled to calculate a risk score. Results: 863 patients were included (676 OP/187 OC). OC patients were 60.4% male, median age 61, with median follow up of 77.5 months. Smoking status was 27.3% current, 44.4% former, 28.3% never, with 30 median pack years. Disease was 57.3% T1-2, 42.7% T3-4, 55.6% N0-2a, 44.4% N2b-3. 94.1% had surgery & 34.3% had concurrent systemic therapy. OP patients were 87.9% male, median age 58, 96.3% HPV+, with median follow up of 60.8 months. Smoking status was 20.9% current, 44.5% former, 34.6% never, with 20 median pack years. Disease was 67.9% T1-2, 32.1% T3-4, 29.9% N0-2a, 70.1% N2b-3. 11.5% had surgery & 87.3% had concurrent systemic therapy. Specifically, 52.2% of OP patients received concurrent cisplatin, 10.6% concurrent cetuximab, and 24.5% other systemic therapies. 11.7% of patients experienced DF, of which 77% failed in the lung. Within the OC cohort, nodal stage 2b or higher was the only predictive factor (HR 3.26, p < 0.001), conferring a 3 year risk of DF of 34% vs 10%. Within the OP cohort, a high risk cohort of 87 patients (12.9%) was identified with a 3 year incidence DF of 22%, compared to 10% or less in lower risk cohorts. This high risk cohort consisted of active smokers treated with definitive RT and either concurrent cisplatin or no concurrent therapy, with at least T3 and N2b disease, as well as any patients treated with definitive RT and concurrent cetuximab. Conclusions: We identified groups of OC & OP patients with greater than 20% risk of developing DF at 3 years, the majority of which occurred in the lung. Surveillance imaging of the chest should be considered for patients meeting these criteria.
Cisplatin every three weeks versus weekly cisplatin or carboplatin with definitive radiotherapy for squamous cell carcinoma of the head and neck is associated with improved overall survival in a representative national population.
Authors: McCusker Michael Gerard , Mehra Ranee , Molitoris Jason K. , Taylor Rodney , Cullen Kevin J. , Goloubeva Olga G. 
Published: May 2020

6536 Background: For patients with primary untreated locally advanced head and neck squamous cell carcinoma (PULA-HNSCC), high dose once every 3 weeks cisplatin (HDC; 100 mg/m2) added to curative radiotherapy (RT) prolongs survival, but is associated with severe toxicities. Concurrent chemoradiation (CRT) with low dose weekly cisplatin (LDC; 30-40 mg/m2), carboplatin (C), or RT alone is often substituted for HDC. We estimated and compared overall survival (OS) and acquired toxicities among Medicare beneficiaries treated with CRT using HDC, LDC, C, or RT. Methods: Patients diagnosed from 2004-2011 with PULA-HNSCC (stages III-IVB AJCC 6th and 7th editions) of the oropharynx (OPC), hypopharynx (HP), or larynx (L) who received definitive RT or CRT were identified using the linked SEER-Medicare database. An analytic cohort of patients receiving CRT with HDC, LDC, or C was constructed using well-established eligibility criteria. OS was estimated and compared between patients grouped by treatment received utilizing a multivariable stratified propensity scores weighted Cox regression model, including demographic and disease characteristics. Toxicities were compared using exact common odds-ratio and Fisher’s tests. Results: We identified 1,335 patients that received RT: OPC (n = 731), HP (n = 174), or L (n = 430). Out of those, patients were treated with HDC (n = 264), LDC (n = 259), C (n = 353), or RT alone (n = 459). Median OS (years) was 5.61 (95% CI = 4.58-7.69) for HDC, 3.7 (95% CI = 3.1-4.79) for LDC, 3.1 (95% CI = 2.48-3.86) for C, and 1.36 (95% CI = 1.19-1.58) for RT, respectively. OS was significantly greater for HDC than for LDC (HR = 1.35, 95% CI = 1.06-1.72, p= 0.02), C (HR = 1.41, 95% CI = 1.12-1.76, p= 0.003), or RT (HR = 2.1, 95% CI = 1.68-2.61, p= < 0.001). Treatment with HDC compared to LDC was not associated with increased prevalence of dysphagia or neutropenia. HDC was associated with hearing loss when assessed at 9-12 months post-diagnosis ( p =0.03). Conclusions: In SEER-Medicare beneficiaries with PULA-HNSCC of the OPC, HP, or L, OS was significantly better for HDC than LDC when accounting for baseline clinical and demographic characteristics and propensity score weights. Toxicities were similar between regimens, except for an increased incidence of the late acute toxicity of hearing loss in HDC. A regimen of HDC improves OS, but needs to be carefully assessed against increased toxicity risk, with hearing loss in particular.
Combination of tumor multinucleation and spatial arrangement of tumor-infiltrating lymphocytes to predict overall survival in oropharyngeal squamous cell carcinoma: A multisite study.
Authors: Koyuncu Can , Corredor Germán , Lu Cheng , Toro Paula , Bera Kaustav , Fu Pingfu , Koyfman Shlomo A. , Chute Deborah , Adelstein David J. , Thorstad Wade , Bishop Justin A. , Faraji Farhoud , Lewis James S. , Madabhushi Anant 
Published: May 2020

6566 Background: Oropharyngeal squamous cell carcinoma patients can have major morbidity from current treatment regimens, necessitating accurate identification of patients with aggressive versus indolent tumors. In this study, we sought to evaluate whether the combination of computer extracted features of tumor cell multinucleation (MN) and spatial interplay of tumor-infiltrating lymphocytes (TILs) is prognostic of overall survival (OS) in OPSCC patients. Methods: OPSCC specimens from 688 patients were retrospectively collected from 3 different sites. 141 patients from site 1 formed the training set (D1) and 322 patients from site 2 and 225 patients from site 3 formed the independent validation cohort (D2, n = 547). A machine learning (ML) model was employed to automatically calculate a Multi-nucleation risk index (MNI), which is the ratio of the number of MN to the number of epithelial cells, to each patient. A separate ML model was also used to capture measurements related to the interplay between TILs and tumor cells (SpaTIL), which were then used to compute a risk score using a Cox regression model. The median value of both the MNIs and the SpaTIL risk scores in D2 were used to identify patients as either low- or high-risk. A definitive label was assigned to each patient by combining the class labels obtained from the MNI and SpaTIL models using a logical AND operation. Results: In D2, the patients with high-risk scores had statistically significantly worse survival in univariate analysis. The univariate analysis yielded an HR = 1.91 (95% CI: 1.25-2.93, p = 0.0027) for D. Multivariate analysis controlling the effect of different clinical variables is shown in the table. Conclusions: We presented a computational pathology approach to prognosticate disease outcome in OPSCC by combining features relating to density of multinucleation and spatial arrangement of TILs and validated the approach on a large multi-site dataset. With additional validation the approach could potentially help identify OPSCC patients who could benefit from de-escalation of therapy. [Table: see text]
Machine learning guided adjuvant treatment of head and neck cancer.
Authors: Howard Frederick , Kochanny Sara , Koshy Matthew , Spiotto Michael T. , Pearson Alexander T. 
Published: May 2020

6567 Background: A combined analysis of the EORTC 22931 and RTOG 95-01 trials confirmed that patients (pts) with head and neck squamous cell carcinoma (HNSCC) and positive margins or extracapsular extension (ECE) benefit from adjuvant chemoradiotherapy (CRT), but the best treatment of pts with other risk factors is unclear. We hypothesized that deep learning models could identify the margin/ECE negative pts who benefit from CRT. Methods: We abstracted pts from the NCDB diagnosed from 2004-2016 with resected HNSCC who received radiotherapy (RT). We reserved 20% of pts for validation and used the remaining 80% for feature selection and model training. Features were chosen based on independent significance in a Cox proportional hazards model, and included demographics, tumor stage, site, grade, RT dose, and receipt of chemotherapy. HPV status was included, and imputed when unknown. We generated survival predictions with DeepSurv (DS), random survival forest (RSF), and neural network multitask (NNM) models. We consider CRT to be recommended by a model if predicted survival is longer with CRT than RT. We calculated the median overall survival (mOS) difference and hazard ratio (HR) for receipt of treatment in line with model recommendations. This was repeated with inverse probability of treatment weighting (IPTW) to account for confounding. As a comparator, we used the intermediate risk factors in the EORTC (T3-4 except T3N0 larynx, N2-3, LVI, deep nodes with oral / oropharynx cancer) and RTOG (2 involved nodes) trials as decision rules. Results: 36,831 pts from the NCDB met the inclusion criteria. 92% had T3-4 or node positive disease, and 40% received CRT. RTOG, EORTC, DS, NNM, and RSF models recommend CRT for 32%, 74%, 63%, 61%, and 35% of pts. The concordance index in the validation set was 0.696, 0.692, and 0.699 for DS, NNM, and RSF. Treatment according to model recommendations in the validation cohort was associated with a mOS benefit of 18.4 months (7.6 to 29.3, 95% CI) for DS, 20.5 months (8.8 to 32.2, 95% CI) for NNM, and 5.8 months (-6.6 to 18.3, 95% CI) for RSF. Similar results were seen with IPTW. Conclusions: Machine learning models can predict benefit from CRT in margin/ECE negative pts, and outperform treatment according to EORTC or RTOG inclusion criteria in this cohort. External validation of these models is warranted. [Table: see text]
Prospective, longitudinal digital activity monitoring before and after treatment of low-risk oropharyngeal squamous cell carcinoma: A feasibility study.
Authors: Gunn Gary Brandon , Ferrarotto Renata , Johnson Faye M. , Bell Diana , Cardoso Richard , Johnson Jason Michael , Rubin M. Laura , Yuan Ying , Frank Steven J. , Fuller Clifton David , Rosenthal David Ira , Kupferman Michael Elliot , Goepfert Ryan , Hessel Amy Clark , Hutcheson Kate A. , Gross Neil D. 
Published: May 2020

6578 Background: Given the expected excellent prognosis of low-risk oropharyngeal squamous cell carcinoma (OPSCC), consideration of long-term toxicity and functional outcomes has become increasingly important. Activity monitors (e.g. FITBIT) are imperfect but have been shown to have reasonable validity in healthy adults. Here we aimed to test the feasibility of using medical grade longitudinal digital activity monitoring to better define objective functional outcomes after treatment of low-risk OPSCC. Methods: This prospective, observational parallel cohort study included patients with previously untreated stage I-III (AJCC 7) OPSCC eligible for standard of care single-modality treatment with either Intensity-Modulated Proton Therapy (IMPT) or TransOral Robotic Surgery (TORS). Objective Actigraph accelerometer data (Actigraph, Pensacola, FL) were collected continuously for 1 week at baseline, 3, 6 and 12 months after treatment along with subjective patient-reported outcome (PRO) measures. Results: Forty-four patients (34M, 10F) enrolled with median age 59 years (range: 42-78). Baseline, 3 and 6 month activity data were available for 40 patients (91%): 16 IMPT and 24 TORS. There was a significant decrease in mean percent of day performing moderate to vigorous physical activity (MVPA) (-0.78, 0.021) mean number of steps/minute (-1.1, p = 0.035), and mean kcals/day (-115.9, p < 0.001) from baseline to 3 months after treatment for the overall cohort. A significant decrease in mean kcals/day (-82.2, p = 0.004) persisted for the overall cohort at 6 months with no significant difference between groups. Conclusions: Longitudinal digital activity monitoring is feasible before and after treatment of low-risk OPSCC. This approach may offer objective functional endpoints for future de-escalation trials. Similar short-term decreases in objective activity measurements were observed after IMPT and TORS. Long-term (12 month) activity data and correlations to subjective PRO measures will be available at the time of presentation. Clinical trial information: 02663583 .
RAS-mutated sporadic medullary thyroid cancer: A single-center experience.
Authors: Brown Spandana , Gruschkus Stephen K. , Waguespack Steven G. , Dadu Ramona , Zafereo Mark , Cabanillas Maria E. , Grubbs Elizabeth Gardner , Sherman Steven I. , Hu Mimi I-Nan 
Published: May 2020

6584 Background: Activating RAS mutations are recognized as important drivers in sporadic medullary thyroid cancer (sMTC), with a reported prevalence between 0-43%. However, few studies have looked at correlations between RAS-mutated sMTC and clinicopathologic features. Methods: Patients with sMTC diagnosed between 1992 – 2019 with NGS testing for RET and RAS mutations seen at a tertiary cancer center were retrospectively evaluated. The objective was to analyze demographic and clinical features among patients with RAS-mutated sMTC and to evaluate associations between these features and overall survival (OS). Analyses were performed to correlate patient demographics and pathologic staging with treatment characteristics, disease course, and OS. Results: We identified 42 patients (50% female) with RAS-mutated sMTC out of 218 pts with sMTC. Median age at diagnosis was 50 years (range 24-78 years). 26 (62%) patients had stage IV disease at time of diagnosis. 28 (67%) of patients had HRAS mutations and 14 (33%) had KRAS mutations. HRAS Q61R was the most common HRAS mutation type (n = 19, 45%). Median follow-up time was 64 months (range 23-274 months) during which 11 (26%) patients died. The median OS was 16.2 years, with 5- and 10- year OS of 88% and 73% respectively. Of the 20 (48%) patients who received systemic therapy, 79% had stage IV disease and tended to be older (median age 54). Median time from diagnosis to initiation of systemic therapy was 33 months. Factors associated with worse OS included distant metastases at diagnosis, shorter time interval between diagnosis and treatment, and Ctn/CEA doubling times < 6 months. HRAS Q61R mutations were associated with a better prognosis, with 100% 10-year OS compared with 10-year OS of 39% and 51% (p = 0.02) for other HRAS and KRAS mutations respectively. Conclusions: At a tertiary cancer center, patients with RAS-mutated sMTC had a 10-year OS rate of 73%, with significantly worse OS in patients with HRAS/KRAS mutations other than HRAS Q61R. In comparison, prior studies have reported 10-year OS rates between ~71-90% in sMTC and 10-year OS rates as low as 56% for more aggressive RET M918T sMTC mutations. The findings here are consistent with other studies that have suggested patients with RAS-mutated sMTC are at intermediate risk for aggressive disease, though there are limited data on OS rates in RAS or RAS-/RET- sMTC. Future research comparing outcomes between various RAS mutations and in comparison to RET+ and RAS-/RET- patients is needed, especially as systemic therapy use in RAS-mutated sMTC evolves.
The oncology hospital at home: Health care utilization outcomes from the huntsman at home trial.
Authors: Mooney Kathi , Titchener Karen , Haaland Benjamin , Coombs Lorinda Adaire , O Neil Brock , Nelson Richard , McPherson Jordan P. , Kirchhoff Anne C. , Ameloot Karen , Beck Anna Catherine , Ward John Harris 
Published: May 2020

7000 Background: Unplanned hospitalizations and emergency department (ED) visits are common during cancer care. Providing acute hospital level care at home may add value by decreasing hospital and ED use. We conducted the first evaluation of an oncology Hospital-at-Home program, Huntsman at Home (H@H). Methods: The Huntsman Cancer Institute began H@H services in 2018 and accepts referral of cancer patients for acute-medical or post-surgical care at home. Patients are admitted who require continued acute level medical care after hospitalization or have emergent unstable symptoms related to treatment or disease progression that would otherwise require ED evaluation or hospitalization. Prospectively, patients referred to H@H from 8/2018 through 10/2019 were compared to a usual care comparison group (UC) drawn concurrently from patients living within the Salt Lake City metropolitan area who qualified for admission to H@H, but lived outside the service zip codes. Probability of H@H enrollment propensity scores were constructed via random forest from patient descriptors and health care utilization at admission. We used an intent-to-treat approach for analysis. Primary outcomes were hospitalizations, length of stay (LOS), ED visits and cumulative charges over 30 and 90 days post admission to either group. Comparisons were made by generalized linear models, stratified by tertiles of H@H vs. UC propensity score. Results: 367 patients, 169 H@H and 198 UC, were evaluated. The average age was 62 yrs, 85% were Caucasian, and 77% had stage IV cancer. Propensity score distributions were overlapping, demonstrating group comparability. A variety of cancers were represented; the most common being colon, gynecologic, prostate and lung cancers. Compared to UC, H@H patients were more likely to be female (61% vs 43%) and during the month prior to admission, showed a trend towards longer LOS if hospitalized (6.7 vs 5.5 days). During the first 30 days after admission, propensity stratified comparisons showed H@H patients with lower hospital LOS (mean reduction 1.19 days, p=0.022), 56% lower odds of unplanned hospitalizations (OR 0.44, p=0.001), 45% lower odds of ED visits (OR 0.55, p=0.037) and 50% lower cumulative charges (mean ratio 0.50, p<0.001) compared to UC. Results over 90 days were similarly robust. Conclusions: In the first reported trial of an adult oncology Hospital at Home program, there was strong evidence for reduced hospitalizations, ED visits, and cost. Oncology Hospital at Home programs show promise for increased patient-centered care while simultaneously improving value.
Early discontinuation to adjuvant endocrine therapy in the ECOG-ACRIN TAILORx Trial.
Authors: Yanez Betina , Gray Robert James , Sparano Joseph A. , Carlos Ruth , Sadigh Gelareh , Garcia Sofia F. , Gareen Ilana F , Whelan Timothy Joseph , Sledge George W. , Cella David , Wagner Lynne I. 
Published: May 2020

7004 Background: The TAILORx study demonstrated women with an intermediate Oncotype DX score receive the same benefit with endocrine therapy (ET) compared to chemoendocrine therapy (CET). However, early discontinuation of adjuvant ET is problematic among breast cancer survivors, with previous studies suggesting that up to 50% of women do not adhere to the full 5 years of recommended ET treatment. The aim of this study was to identify patient-level risk factors associated with early discontinuation of ET in the TAILORx study. Methods: TAILORx was coordinated by the ECOG-ACRIN Cancer Research Group. Participants were a subgroup of 954 women who completed additional measures on health-related quality of life (HRQoL) including endocrine symptoms (ES) physical well-being (PWB) and social well-being (SWB) prior to initiating ET, which categorized into three groups by tertile for analysis. All participants were diagnosed with hormone-receptor–positive, human epidermal growth factor receptor 2–negative, axillary node–negative breast cancer who started ET within a year of study entry. Early discontinuation of ET, defined as discontinuation less than 4 years from initiation for reasons other than death or recurrence, was assessed by clinician report. Rate of discontinuation was calculated using Kaplan-Meier estimates, and Cox-proportional hazards joint models were used to analyze the association between rates of adherence to ET with patient-level factors. Results: In a joint model, receipt of CET therapy (vs receipt of ET only; HR = .59, 95% CI .38-.94, p = .02) and age above 40 (versus age < = 40; HR = .30, 95% CI .14-.66, p = .003) were associated with a lower probability of early discontinuation of ET. Adjusted for these factors, a history of depression compared to no history of depression (HR 1.82, 95% CI 1.19-2.77, p = 0.005), worse ES compared to better ES (HR 1.70, 95% CI 1.06-2.74, p = 0.03), worse PWB compared to better PWB (HR 2.12, 95% CI 1.30-3.45,p = 0.003), and worse SWB compared to better SWB (HR 1.94, 95% CI 1.20-3.13, p = 0.007) were individually and significantly associated with a higher probability of early discontinuation of ET, although none reached statistical significance when all were included in a joint model. Conclusions: Younger women are at risk for early discontinuation and modifiable characteristics such as HRQoL and history of depression are potential risk factors for early discontinuation of ET. These results support systematic screening for HRQoL and depressive symptoms to identify women at risk for discontinuation of ET. Clinical trial information: NCT00310180 .