tbuckley/cabot-search huggingface dataset:
Grading system for costs and values of anti-cancer drugs in metastatic castrate-resistant prostate cancer.
Authors: Helmy M. Guirgis
Journal: Journal of Clinical Oncology (2016)

e16518 Background: Cancer patients desire to live longer with good quality of life (QoL). Cost-effectiveness of $100,000 quality adjusted life-year of anticancer drugs is considered acceptable. We postulated that the American society would be willing to pay up to $50,000 for overall survival (OS) and $50,000 for QoL. Objective: Grade drug costs and values in chemo-naïve (CNP) and chemo-treated (CTP) patients with metastatic castrate-resistant prostate cancer Methods: Published OS, hazard ratios (HR) and dosage were utilized.One-year drug costs were graded (gr) A up to $50,000, B > $50,000 - $75,000, C > $75,000 - $100,000, D > $100,000. Cost/life-year gain (C/LYG) were compared with C/(1.0 – HR) and graded A up to 100,000, B > 100,000 - 200,000, C > 200,000 - 300,000, D > 300,000. Relative values (RV) were sum of 50,000/C/LYG for OS and 50,000/C/LYG for QoL maintenance or improvement. Results: Docetaxel costs were $4,500/A, abiraterone $97,120/C, enzalutamide $108,348/D, radium-223 (Rad) $76,000/C and cabazitaxel $47,940/A. In CNP, abiraterone C/(1.0 - HR) was 489,600/D vs. C/LYG 267,055/C, compared with enzalutamide 361,160/D vs. 590,980/D respectively. Abiraterone RV in CNP was 0.37 vs. 0.39 CTP. Enzalutamide RV was 0.17 CNP vs. 0.37 CTP. Rad OS- and HR- values were similar at 253.333/C with RV 0.39. In refractory disease cabazitaxel C/(1.0-HR) was 159,800/B vs. C/LYG 239,700/C with RV 0.21. Conclusions: There was no correlation between costs and values. The wide differences between OS- and HR-linked values suggest parallel use during accounting. Enzalutamide value in CNP was questionable. Rad was noted by superimposed OS and HR-linked C values and high RV.
Primary outcomes analysis of a multicenter randomized controlled trial of an interactive decision tool for patients with breast cancer.
Authors: Sarah T. Hawley, Lawrence C. An, Yun Li, Ken Resnicow, Monica Morrow, Reshma Jagsi, Steven J. Katz
Journal: Journal of Clinical Oncology (2017)

6500 Background: High quality treatment decisions require that patients are well informed about treatment and that their values are considered. Yet studies show that patient knowledge about breast cancer treatment trade-offs is low and appraisal of decision-making is not optimal. Methods: We conducted a randomized controlled trial (RCT) of a tailored, comprehensive (locoregional and systemic treatment) and interactive decision tool (iCanDecide), compared with static online information. 537 newly diagnosed, early stage breast cancer patients were enrolled at the first visit in 22 surgical practices. Participants were surveyed 5 weeks (N = 496; RR 92%) post enrollment after locoregional treatment decision-making. The primary outcome was a high quality decision, including two components: high knowledge about treatment options and a values concordant treatment decision. The main secondary outcome was preparation for decision making. We evaluated the distribution of participants in each arm, and conducted logistic regression modeling to assess the association between the intervention and the outcomes controlling for patient characteristics and strength of treatment preference at enrollment. Results: Significantly more intervention than control patients had high knowledge (60% vs. 42%, p &lt; 0.001), although the majority of both groups reported values concordant treatment (~84%). Intervention patients also reported feeling prepared for decision making significantly more often than controls (45% vs. 32%, P &lt; 0.01). Patients randomized to the interactive intervention had higher knowledge (OR: 2.2; 95% CI 1.2-4.0) and preparation for decision making (OR: 1.5; 95% CI 1.1-1.4), even after adjusting for age, education, race, stage and clinical site. Conclusions: In this large RCT, a tailored, interactive treatment decision tool for breast cancer improved knowledge and prepared patients for complicated decision making, more than access to static online information. Future work to further integrate such tools into the clinical workflow is needed. Clinical trial information: NCT01840163.
Progression-free survival (PFS) and cardiac-toxicity-adjusted-PFS (CTA-PFS) as predictors of overall survival (OS) in locally advanced non-small cell lung cancers (LA-NSCLC) treated with concurrent chemoradiation (CCRT): A secondary analysis of NRG Oncology RTOG 0617.
Authors: Chen Hu, Mitchell Machtay, James J. Dignam, Rebecca Paulus, Jeffrey D Bradley
Journal: Journal of Clinical Oncology (2018)

8539 Background: OS is the gold standard for LA-NSCLC with CCRT, with complex relationships among RT dosimetry, systemic therapies, cardiopulmonary toxicity, progression (PD) and OS of growing scientific and clinical interest. Methods: RTOG 0617 (NCT00533949) randomized standard (SD, 60 Gy) versus high-dose (HD, 74 Gy) CCRT +/- cetuximab from 11/07-06/11. This analysis includes 469 patients (pts) given ≥50 Gy. A PFS event was defined as the first occurrence of local, regional, distant PD or death w/o documented PD. A CTA-PFS event was the first occurrence of grade 2+ treatment-related cardiac toxicity event or a PFS event. Landmark analyses at 6mo and 12mo were used to minimize the immortal time bias. Cox model with PD or CT/PD as a time-dependent covariate was used to evaluate their predictive roles. Median f/u time for surviving pts was 5.1 years. Results: As reported, pts treated with HD had significantly lower OS rates (HR = 1.28, 95%CI: 1.04-1.58, p = 0.018) and CTA-PFS rates (HR = 1.24, 95%CI: 1.02-1.51, p = 0.035), and marginally lower PFS rates (HR = 1.21, 95%CI: 0.99-1.47, p = 0.06) than pts treated with SD. Median survival time (MST) among pts having PD within 6mo versus not were 13.4mo (95%CI: 10.0-19.0) and 30.7mo (95%CI: 28.0-37.0) (p < 0.001). MST for pts having PD within 12mo versus not were 20.6mo (95%CI: 18.8-25.0) and 60mo (95%CI: 47.6-74.5)(p < 0.001). Results are similar when using CTA-PFS with 6mo or 12mo cutoff (p < 0.001). RT dose was no longer significantly associated with OS (p = 0.08 or p = 0.15) when PD or CT/PD was included in multivariable analysis (p < 0.001), suggesting OS differences in HD/SD may be partially captured by PFS or CTA-PFS. Conclusions: RTOG 0617 survival results suggest that PFS (or CTA-PFS) status at 6mo or 12mo predicts long-term OS, and may potentially be considered as a surrogate endpoint of OS in clinical trials. Pts who were progression-free at 12mo had a MST of 5 years. Further validation on external datasets and in the modern era of immunotherapy are needed.
P04.52 Spontaneous intratumoral T cell responses against glioblastoma-associated antigens
Authors: K Lu, L Bunse, F Sahm, K Sanghvi, M Ratliff, D Hänggi, A von Deimling, U Sahin, W Wick, E Green, M Platten
Journal: Neuro-Oncology (2018)

Glioblastomas (GBMs) are so-called “cold tumors” with a low mutational load and low intratumoral T cell abundance. Hence, major histocompatibility class (MHC) I or II-restricted tumor-specific T cell responses are rare or not even identifiable. In our study, we aim at identifying spontaneous intratumoral tumor-associated antigen (TAA)-specific T cell responses. TAAs such as cancer/testis antigens (CTAs), are frequently overexpressed across multiple cancer entities. Previous studies have shown that certain TAAs show limited or no expression in normal brain tissue and can therefore be exploited as targets for glioblastoma immunotherapy. However, the presence and extent of spontaneous TAA-reactive T cells within the intratumoral T cell repertoire remains unclear. GBM tumor-infiltrating lymphocytes (TILs) from three patients were expanded in vitro with a combination of high dose interleukin (IL)-2 and anti-CD3 antibody. RNA-sequencing (RNA-seq) and quantitative PCR (qPCR) analyses from corresponding cryopreserved tissues were performed to evaluate individual TAA expression. Expression levels were compared to normal brain homogenates (n=50, cut-off: 1 rpkm). Patient-individual TAAs were ranked according to expression levels and in silico HLA-restricted binding predictions and compared to GBM-associated targets that were identified by RNA-seq of 144 archival GBM tissues. HLA-typing from PBMCs was performed by next generation sequencing. ELISpot peptide TIL-T cell co-culture assays were performed using expanded GBM-derived TILs and autologous dendritic cells. For HLA-A2-positive patients, K562 cells were transduced with HLA-A*02:01 and used as artificial antigen presenting cells. Four promising shared GBM-associated targets were identified by RNA-seq of 144 archival tissues and subsequently validated by Fluidigm analyses. Based on the applied selection criteria, there was no overlap between the top five ranked individual TAAs and the four identified shared GBM-associated antigens. Evaluation of intratumoral spontaneous T cell immune responses revealed reactivity in one of three evaluated patients against individual and shared overexpressed targets, respectively. For HLA-A2+ patients, artificial antigen presenting cells are reasonable off-the-shelf tools to evaluate intratumoral T cell responses. In contrast to spontaneous neoepitope-specific T cell responses, spontaneous intratumoral TAA-specific T cell responses can be identified. Thorough evaluation of expression levels, relative tumor-restriction and analyses of spontaneous intratumoral T cell responses may revive immunotherapeutic strategies targeting TAAs in the era of neo-epitopes.
Prevalence of HIV, hepatitis B virus (HBV), and hepatitis C virus (HCV) among newly diagnosed cancer patients treated in academic and community oncology practices: SWOG S1204.
Authors: Scott David Ramsey, Joseph M. Unger, Laurence H. Baker, Richard F. Little, Rohit Loomba, Jessica Hwang, Rashmi Chugh, Monica A Konerman, Kathryn B Arnold, Dawn L. Hershman
Journal: Journal of Clinical Oncology (2018)

6600 Background: Universal screening of newly diagnosed cancer patients for HIV, HBV and HCV viruses is not routine in oncology practice. Amid concerns about viral reactivation and adverse outcomes during antineoplastic therapy, experts disagree about whether testing should be routinely performed. In this study we estimated the prevalence of HIV, HBV, and HCV infection among persons with newly diagnosed cancer. Methods: This multicenter, prospective cohort study included 9 academic and 9 community SWOG oncology institutions. Eligible patients included those with any malignancy presenting to clinic within 120 days after cancer diagnosis. Patients either provided documentation of known viral status or were tested for HIV, HBV or HCV upon enrollment. Results: In total, 3,092 patients were registered. The median age of the cohort was 61 years old, most were female (60%), 18% were black, 18% were Hispanic and 3% were Asian. Screened patients had similar clinical and demographic characteristics to those registered. Infection rates adjusted for cancer type were 9.7% for HBV, 2.8% for HCV and 1.4% for HIV. At clinic presentation, observed viral status was previously diagnosed for 17% of HBV patients, 69% of HCV patients and 94% of HIV patients. Cancers that had the highest prevalence per infection (HBV, HCV) included liver (22%, 18%), lung cancer (13%, 5%), head and neck cancer (13%, 5%) and non-colorectal GI cancers (15%, 1%). HBV risk was highest in those who had sexual contact with HIV+ person(s) or were infected with HIV or HCV. HCV risk was highest in those who injected drugs or were tested because they had on-the-job blood exposure, injection drug use or transfusion before 1992. Conclusions: The overall prevalence of HBV and HCV in this population of cancer patients is substantially higher than the general population (3.9% and 1.3%, respectively). Much of the HBV and HCV infection detected in this study was previously undiagnosed, suggesting that screening may be desirable. The low rate of previously unknown HIV infection suggests routine testing is unnecessary except in cancers highly associated with HIV. Funding: NIH/NCI CA189974, CA180888, CA180819
Association of activating NOTCH1 mutations in adenoid cystic carcinoma with shorter progression-free survival to systemic therapy.
Authors: Renata Ferrarotto, Alper H Duran, Wei Wei, Brett W. Carter, Adel K. El-Naggar, Shirley Y Su, Diana Bell, Merrill S. Kies, William N. William, Bonnie S. Glisson, Myrna Godoy, John Heymach
Journal: Journal of Clinical Oncology (2017)

6089 Background: We previously reported that activating NOTCH1 mutations occurs in approximately 20% of ACCs and drive a phenotype with solid histology, liver and bone metastases, poor prognosis, and potential responsiveness to Notch1 inhibitors; however the impact of NOTCH1mutations on responsiveness to systemic therapy in ACC is unknown. The aim of this study was to evaluate the ORR and median PFS (mPFS) to systemic therapy in patients with metastatic ACC according to their Notch1 status. Methods: We identified 20 ACC patients with measurable disease that underwent treatment at MDACC and had tumor molecular profile. A radiologist blinded to the patient’s NOTCH1status performed review of all images. Measurement of target lesions was captured by a quantitative imaging analysis tool for ORR assessment by RECIST 1.1. PFS was estimated by Kaplan-Meier method. Comparisons of PFS between groups were performed using log-rank test. P≤0.05 was considered statistically significant. Results: Out of 20 patients, 4 (20%) were NOTCH1 mutant. Notch1 pathway activation status by immunohistochemistry (NICD) was available for 15 patients, 10 were positive. The median number of therapy lines was 2 (range 1-6). Best ORR among 49 treatment plans across all lines of systemic therapy including chemotherapy (15), anti-EGFR (10), anti-VEGFR (11), and others (13) was PR in 2 (4%), SD in 29 (59%), and PD in 18 (37%). During first line treatment, patients with NOTCH1 mutations had significantly shorter mPFS compared to NOTCH1 wild-type (2.97 vs. 6.92 months, P = 0.02). The PFS rate at 3 months was 25% for NOTCH1mutants vs. 81% for wild-type. A trend towards shorter PFS was seen in NICD positive vs. negative (3.58 vs. 6.74 months, P = 0.2). Conclusions: NOTCH1 mutations in ACC are associated with shorter PFS during first-line treatment. Validation of these findings is warranted in larger patient cohorts.
Comparative analysis of target gene exon sequencing by cognitive technology using next generation sequencing platform in Chinese patients with lung cancer.
Authors: Xuchao Zhang, Yu Chen, Yi-xuan Yang, Wei-bang Guo, Zhi Xie, Wen-qing Yan, Kai Yin, Qi Zhang, Yi-Long Wu
Journal: Journal of Clinical Oncology (2018)

e24254 Background: Next generation sequencing (NGS) technology is becoming increasingly important as a clinical application for therapeutic decision. However, interpretation of NGS data is a further challenges. This study aimed to compare annotation and reporting differences between a curated actionable gene list generated by a cognitive technology and that of a bioinformatics molecular tumor team at Guangdong Lung Cancer Institute (GLCI) by manual curation with the goal to detect gene mutations of potential significance in Chinese patients with lung cancer. Methods: Data from exon sequencing of a total of 285 genes previously conducted on 115 patients’ tissue samples between (January, 2014 and December, 2016), and subsequently manually annotated and evaluated by GLCI bioinformatics team. The same batch of data was also analyzed by the Watson for Genomics (WFG) cognitive genomics technology. A comparative analysis of the annotation results of the two methods was conducted to identify differences in mutations generated. Results: The complete congruence rate of annotation results between WFG analysis and GLCI bioinformaticians was 43.48%. Mainly including actionable mutations in common genes like EGFR, KRAS, ERBB2 and TP53. Of the 65 (56.52%) samples, WFG analysis could interpret more mutation sites, with 1.54 more mutation sites in each sample averagely. These mutation sites were located on 27 genes like EP300, ARID1A, STK11 and DNMT3A, among which EP300 gene had mutations in up to 30.77% samples. EP300 gene mutations were associated with the histology of lymph-epithelial-like cancers. TMB (1.82) interpreted by WFG analysis was significantly higher than the TMB (0.73) interpreted by GLCI experts. Conclusions: Compared with manual curation by a lung cancer expert, except for those common actionable genes, WFG analysis provided valuable insights and additional genetic alterations in additional genes to inform clinical therapeutic strategies for patients with lung cancer. These findings suggest cognitive computing could increase efficiency in the annotation of genetic alterations which may inform opportunities for investigational targeted therapies.
Survival disparities among African American (AA) patients (pts) with <i>EGFR</i>-mutated non-small cell lung cancer (NSCLC).
Authors: Haiying Cheng, H. Dean Hosgood, Qian Ye, Janaki Neela Sharma, Christopher Su, Balazs Halmos, Roman Perez-Soler
Journal: Journal of Clinical Oncology (2018)

9054 Background: Little is known about whether AA pts with EGFR-mutated NSCLC exhibit similar clinical characteristics and outcomes compared to non-AA pts. Methods: We retrospectively reviewed the cancer registry at Montefiore Medical Center, a community-based academic center, for lung cancers diagnosed between 01/2009 and 12/2015 (n = 2773). We restricted our analyses to nonsquamous NSCLC pts with available pathology (n = 1350). EGFR testing was performed via PCR-based technology spanning exons 18-21 (n = 672) during that period. Results: Our patient population was 38% AA, 45% White, and 17% other. The EGFR mutation rate was 15% (98/672) in all pts, compared to 13% (35/266) in AA and 16% (63/406) in non-AA. The mutational spectrum varied by race with Del 19, L858R and uncommon mutations being 46%, 23% and 31% in AA, compared to 43%, 35% and 22% in non-AA. Among pts with EGFR-mutated NSCLC, AA pts had shorter survival in comparison to non-AA pts (p = 0.015, using cox proportional hazard model after adjusting for smoking, gender and age) (2-yr survival rates: 33% vs. 61%), which was evident for earlier stages (I-III) (p = 0.0078) (2-yr survival rates: 50% vs. 87%) and suggested for metastatic disease (p = 0.10). However, there was no evidence for racial disparity in survival among patients with EGFR wild type (wt) (p = 0.80) (2-yr survival rates: 38% vs. 39%). Further, AA pts were heavier than non-AA pts with EGFR mutations (75.1 kg vs. 65.6 kg, p = 0.012). No significant differences were identified for age at diagnosis, gender, presenting stages, smoking history, socioeconomic status, and the standard uses of EGFR TKIs between AA and Non-AA. The similar survival among EGFR wt pts argues further against the treatment disparity between AA and non-AA pts. Conclusions: This is the first report of inferior survival among AA NSCLC pts with EGFR mutations, relative to non-AA pts. These results may be related to higher frequency of uncommon mutations or possibly PK differences secondary to higher average weight. Confirmation studies in larger pt cohorts and further investigation on how weight difference and tumor biology may contribute to the racial disparity in survival are warranted.
KEYNOTE-667: Phase 2, open-label study of pembrolizumab in children and young adults with newly diagnosed classical Hodgkin lymphoma (cHL) with slow early response (SER) to frontline chemotherapy.
Authors: Christine Mauz-Korholz, Kara M. Kelly, Frank G. Keller, Lisa Giulino-Roth, Akash Nahar, Arun Balakumaran
Journal: Journal of Clinical Oncology (2018)

TPS7583 Background: High risk for relapse is observed in cHL patients (pts) with SER to initial chemotherapy and the burden of late organ toxicities may be higher following dose intensification. Methods: The phase 2, open-label KEYNOTE-667 (NCT03407144) study will enroll 400 pts aged 3 to 17 (children) or 18 to 25 years (young adults) with newly diagnosed, confirmed stage IA, IB, or IIA cHL without bulky disease (Group 1 [low-risk]) or stage IIEB, IIIEA, IIIEB, IIIB, IVA, or IVB cHL (Group 2 [high-risk]); measurable disease; and performance status per Lansky Play-Performance Scale ≥50 (age ≤16 years) or Karnofsky score ≥50 (age > 16 years). Pts will receive induction with doxorubicin, bleomycin, vinblastine, dacarbazine (ABVD; Group 1) or vincristine, etoposide/etoposide phosphate, prednisone/prednisolone, doxorubicin (OEPA; Group 2) for 2 cycles, followed by early response assessment by PET/CT/MRI. Pts with rapid early response (Deauville score 1-3) will receive standard therapy. Pts with SER (Deauville score 4-5) will receive consolidation with pembrolizumab 2 mg/kg Q3W up to 200 mg (children) or 200 mg Q3W (young adults) plus 2 cycles AVD (Group 1) or 4 cycles cyclophosphamide, vincristine, prednisone/prednisolone, dacarbazine (COPDAC-28; Group 2). PET/CT for late response assessment (LRA) will be performed after consolidation. After LRA, Group 1 pts with SER will receive radiotherapy (RT); in Group 2, pts with Deauville score 4-5 will receive RT. All pts will receive maintenance with pembro Q3W concomitantly with RT. Pembro dosing will continue up to 17 administrations, with an option to stop after 24 weeks due to CR, or until progression, unacceptable toxicity, or withdrawal. The primary endpoint is objective response rate (ORR) per Cheson 2007 IWG criteria by group in SER pts. Secondary endpoints include SERs with PET negativity after consolidation, event-free survival (EFS), overall survival (OS), and radiotherapy frequency and details by group. ORR with 95% CI will be estimated using the Clopper-Pearson method. EFS and OS will be estimated by Kaplan-Meier methods. Safety will be assessed in all treated pts. Clinical trial information: NCT03407144.
Comparison of effectiveness between complex decongestive therapy and stellate ganglion block in breast cancer related lymphedema patients: A prospective randomized study.
Authors: Myungwoo Park, Kwan Sik Seo
Journal: Journal of Clinical Oncology (2016)

e21619 Background: The aim of this study was to compare the effectiveness between the stellate ganglion block (SGB) and complex decongestive therapy (CDT) in patients with breast cancer related lymphedema (BCRL). Methods: In total, 18 patients with BCRL were recruited. Patients were divided randomly into 2 groups. Patients CDT was tried for 2 weeks in group CDT, and patients in group SGB received 3 consecutive SGBs in every 2 weeks. Changes of circumference, volume, and bioimpedance in upper extremity were measured at baseline and 2 weeks after treatment, and compared between two groups. EQ-5D score for quality of life and subjective improvement were monitored. Results: In both groups, changes of circumference, volume, and bioimpedance showed the tendency of improvement. Comparing with both groups, more improvement of circumference in forearm was observed in CDT patients. SGB patients showed more changes in volume reduction and bioimpedance in whole arm. There were no significant statistical differences in EQ-5D score and subjective symptoms between the two groups. Conclusions: In the patients with breast cancer related lymphedema, stellate ganglion block can be alternative tools to reduce swelling after breast cancer treatment. Clinical trial information: 0420150420.