tbuckley/cabot-search huggingface dataset:
Inferring the effects of concurrent chemotherapy with or without adjuvant chemotherapy versus radiotherapy alone in stage II-IVB nasopharyngeal carcinoma: Comparison of results from meta-analysis of observational studies and randomized trials.
Authors: Teng Hwee Tan, Yu Yang Soon, Timothy Cheo, Jeremy Chee Seong Tey, Ivan Weng Keong Tham
Journal: Journal of Clinical Oncology (2017)

e17573 Background: Multiple randomized trials (RCTs) reported that concurrent chemotherapy (CCT) with or without adjuvant chemotherapy (AC) improves survival in stage II-IVB nasopharyngeal carcinoma (NPC) compared to radiation therapy alone. However, it is unclear if similar benefits can be observed in routine practice as patients included in RCTs could be very different from patients in routine practice. The aim of this study is to compare the effects of CCT with or without AC as estimated from observational studies (OBS) with findings from RCTs. Methods: We searched MEDLINE for eligible studies determining the effect of addition of CCT with or without AC in stage II-IVB NPC. Outcome of interest was overall survival (OS). We performed the meta-analysis with random effects model to estimate the pooled hazard ratios (HR), confidence intervals (CI), and I squared statistic (I 2 ) for both RCTs and OBS and compared them using Altman interaction test. Results: We found nine RCTs and 19 OBS including 6523 patients. Eight RCTs and 14 OBS had at least 75% of its patients with stage III-IVB NPC while only one RCT and five OBS had at least 75% of its patients with stage II NPC. The survival benefit associated with chemotherapy was similar in both RCTs and OBS focusing on stage III-IVB NPC (RCTs HR 0.67, 95% CI 0.56 – 0.81, I 2 = 48% vs OBS HR 0.71 95% CI 0.62 – 0.82, I 2 = 4%, interaction P (IP) = 0.67). Similarly, there was no significant difference in OS for RCT and OBS focusing on stage II NPC (RCTs HR 0.34, 95% CI 0.17 to 0.66, I 2 = non-applicable due to single study vs OBS HR 0.61, 95% CI 0.37 to 1.02, I 2 = 0%, IP = 0.17). Conclusions: Patients with stage II and stage III-IVB nasopharyngeal carcinoma treated in routine practice received similar survival benefits associated with concurrent chemotherapy with or without adjuvant chemotherapy as patients treated in randomized trials.
Total number of circulating tumor DNA (ctDNA) genomic alterations and outcome after checkpoint inhibitor-based immunotherapy.
Authors: Yulian Khagi, Aaron Goodman, Gregory A. Daniels, Sandip Pravin Patel, Lyudmila Bazhenova, Razelle Kurzrock
Journal: Journal of Clinical Oncology (2017)

e14504 Background: High tumor mutational burden on tissue biopsy correlates with efficacy of checkpoint immunotherapy in cancers, such as non-small cell lung cancer and melanoma. However, the relationship between mutational burden detected in non-invasive surrogates, such as blood-derived ctDNA genomic alterations, and outcome after immunotherapy, has not been evaluated. Methods: We analyzed 69 patients with diverse malignancies whose plasma-derived ctDNA had undergone next generation sequencing (NGS) (54 to 70 genes: Guardant Health) and who had received checkpoint inhibitor-based immunotherapy. Data was assessed to correlate total number of alterations (characterized alterations and variants of unknown significance, VUS) in ctDNA and outcome: stable disease (SD) &gt;6 months, complete or partial remission (CR or PR), progression-free and overall survival (PFS and OS), from date of immunotherapy initiation. Results: The69 patients had 23 different diagnoses. All individuals received checkpoint inhibitor-based immunotherapy, with the majority receiving anti-PD1/PD-L1 monotherapy. Evaluable patients with ≥6 vs. &lt;6 total ctDNA alterations had significantly higher rates of SD≥6 months/CR/PR: 40.9% (9/22) vs. 15.9% (7/44) (p=0.035) (Table). Median PFS was 2.85 months vs. 2.1 months (p=0.046). OS was not statistically different. A landmark analysis at 2 months showed that median PFS in the ≥6 alterations group was 23.2 months for responders (CR/PR) vs. 2.3 months for non-responders (p=0.0006); for the group with &lt;6 alterations, the median PFS was 12.6 vs. 3.3 months (p = 0.0006). Conclusions: Total number of ctDNA genomic alterations merits further exploration as a potential predictive biomarker for outcome with checkpoint inhibitor-based immunotherapy. Achieving response to checkpoint-based immunotherapy strongly predicts PFS from the 2-month mark. [Table: see text]
Predicting factors of cognitive function, depression and anxiety in hispanic patients with breast cancer.
Authors: Oscar Galindo-Vazquez, Luis Vazquez-Rodriguez, Enrique Bargallo-Rocha, Paula Cabrera-Galeana, Abelardo Meneses-Garcia, Abel Lerma-Talamantes, Angel Herrera, Jose Luis Aguilar, Jaime G. De La Garza
Journal: Journal of Clinical Oncology (2018)

e22162 Background: Depressive and anxious symptoms combined with cognitive function impairments represents mental health problems in patients with breast cancer that affect their functionality and quality of life. Objective: Identify the predictors factors for cognitive impairment, anxiety and depression symptoms in breast cancer patients. Methods: We analyzed 174 patients diagnosed with breast cancer under oncological treatment, they were evaluated with the Mini Mental State Examination (MMSE) and the Hospital Anxiety and Depression Scale (HADS). We look for association with psychosocial, clinical and sociodemographic variables. Results: Median age was 45 years (38 - 51). Clinical stage IV was found in 36%, III 33.1%. Depression levels of 40%, anxiety 45%, and cognitive impairments of 58% were identified. The presence of depression and anxiety were factors associated with cognitive impairment (p < 0.001). The partner absence, advanced disease and anxiety were associated with depression (p < 0.001). Anxiety was also related with poor cognitive function and depression (p < 0.001). Conclusions: Anxiety, depression and cognitive impairment are clinically significant problems in patients with breast cancer. Psychosocial care programs must be developed in a timely manner for the group of patients with these affectations.
Lung endothelial cell-targeted peptide-guided bFGF promotes the regeneration after radiation induced lung injury
Authors: Dongwei Guan, Junwei Mi, Xi Chen, Yonghui Wu, Yuanjiang Yao, Linjie Wang, Zhifeng Xiao, Yannan Zhao, Bing Chen, Jianwu Dai
Journal: Biomaterials (2018)
Cultural pressures, confidence, and quality of life in women with suspected gynecologic cancer.
Authors: Mackenzi Pergolotti, Kemi Morenikeji Doll
Journal: Journal of Clinical Oncology (2016)

e17104 Background: Women internalize cultural pressures to participate in activities, particularly in sexual activities and care-taking, which can be measured by the Possibilities for Activity Scale- Gynecologic Oncology (PAcTS- GO). For women with gynecologic cancers, it is unknown how these internalized pressures correlate to health-related quality of life (HRQOL). Methods: This was a cross-sectional study of women with suspected gynecologic cancer, enrolled in an institutional health registry 1- month after their primary surgery. Comprehensive HRQOL assessments, the Functional Assessment of Cancer Therapy- General Population (FACT) and Patient Reported Outcomes Measurement Informational System (PROMIS) global health, and the PActS-GO were administered. PActS-GO is a 12-item scale measuring the internalized cultural pressures (expectations and self-efficacy) of 6 activities: sex, driving, exercise, care-taking, service and working. Higher scores indicate greater expectations and confidence in those activities. Multivariate regression was used to determine correlates of HRQOL. Results: Of 231 women enrolled, 208 completed 1-month post-surgical follow-up. Mean age was 57 years (range 22-93), 78% were White, and 58% were married. Nearly half (96, 46%) of women had stage I disease. For the HRQOL instruments, mean scores (range) were: FACT 83 (9-108), PROMIS mental 51 (25-68), and physical health 45 (23-68). The PActS-GO mean score was 39 (range: 12-60). In the multivariable model, adjusted for demographics, cancer type and stage, higher PActS-GO scores were significantly associated with all three measures of HRQOL (p < .001). Overall, a 7-point change in the PActS-GO, was associated with at least a 5- point change in FACT-GP scores. Conclusions: In women with gynecologic cancers, HRQOL was shaped and influenced by activity expectations and confidence. Women with gynecologic cancers may be uniquely affected by pressures to maintain certain activities, including sex and taking care of others. When confidence is low for participating in those activities, their HRQOL suffers. Interventions targeting self-efficacy of activity may improve HRQOL in this population.
Understanding the molecular and genomic differences between primary germ cell tumors and late relapse.
Authors: Aabha Oza, Bradley Allen Hancock, Milan Radovich, Nasser H. Hanna
Journal: Journal of Clinical Oncology (2018)

e16542 Background: Germ cell tumor (GCT) is the most common cancer effecting males aged 15 to 35. With the implementation of cisplatin-based chemotherapy and/or surgery, the cure rate in early-stage disease is 95-100%. Even in advanced stages, cure rates exceed 70%. Up to 10% of patients who achieve an initial CR will relapse. Most relapses occur within 2 years of initial treatment. These early relapses remain potentially curable with chemotherapy and sometimes stem cell transplant. However, 2-3% of patients relapse more than 2 years later (LR). These tumors are clinically distinct from the primary disease. While LR GCT remains sensitive to chemotherapy, it is rarely curative. In two large series of LR GCT from Indiana University, a small minority of patients remained NED at follow-up after chemotherapy. In these series, 69% and 88% of patients treated with surgery at the time of LR had NED at follow-up. The molecular and genomic changes underlying these differences have yet to be determined. Methods: We generated whole-exome somatic mutation and copy number variation (CNV) from 3 matched primary-LR GCT pairs as well as 3 primary tumors from patients who did not develop LR during the study timeframe. Sequencing data was generated using a 51 megabase (Mb) targeted capture panel and Illumina HiSeq 2500. Somatic mutations were called using matched germline DNA and 3 separate mutation calling algorithms. CNV was determined using FACETs and Titan algorithms. Results: Primary tumors resembled the TCGA repository with low total mutation burdens (TMB; 0.16-0.43 mutations/Mb) and recurrent CNVs such as well known gains in chromsome 12p. LR tumors were associated with higher TMBs (1.80-3.61; p = 0.0002), and CNVs of LR tumors were more numerous and fragmented. Copy number gains of 20q including the gene locus of the oncogenic transcription factor E2F1 were present in all 3 LR tumors and not present in matched or unmatched primary tumors. Conclusions: GCT LR tumors are more highly mutated than primary tumors, which may potentially explain their clinically distinctive behavior between initial presentation and LR. Our study also warrants further interrogation into the oncogenic and therapeutic capacity of genes on 20q including E2F1.
A real-world multicenter analysis of first (1L) and second line (2L) treatment of advanced pancreatic adenocarcinoma (APC).
Authors: Irene S. Yu, Jennifer L. Spratlin, Patricia A. Tang, Richard M. Lee-Ying, Rachel Anne Goodwin, Brandon Matthew Meyers, Ravi Ramjeesingh, Dawn Elizabeth Armstrong, Michael M. Vickers, Hanbo Zhang, Christina Kim, Winson Y. Cheung
Journal: Journal of Clinical Oncology (2018)

e16210 Background: FOLFIRINOX (FFX), gemcitabine/nab-paclitaxel (GN) and gemcitabine (GEM) are 3 available treatments for locally advanced (LAPC) and metastatic (MPC) pancreatic cancer. Without a head-to-head trial, optimal 1L and 2L treatments and their impact on outcomes in the real world remain unclear. Methods: Pooled data from multiple cancer centers across provinces in Canada were analyzed. LAPC and MPC patients (pts) diagnosed from 2014 to 2016 who received at least 1 cycle of systemic therapy were included. Analyses were conducted to characterize 1L and 2L treatment sequences and predictive factors. We also assessed the relationship with overall survival (OS). Results: We identified 302 pts: median age 63 (IQR 56-69), 163 (54%) men, 127 (42%) ECOG ≥ 2, and 221 (73%) MPC. In the 1L setting, 48%, 38% and 14% of pts received FFX, GN and GEM, respectively. FFX was more likely used in younger pts (54% in age < 65 vs. 41% in age ≥ 65, p = 0.04) and those with favorable ECOG (63% in ECOG 0 vs. 13% in ECOG ≥ 2, p < 0.01). Over time, there was increased preference for GN (21% in 2014 vs. 63% in 2016, p < 0.01) and decreased FFX use (66% in 2014 vs. 27% in 2016, p < 0.01). Gender, tumor location and LAPC vs. MPC status did not influence 1L selection (all p > 0.05). Among the 107 (35%) pts who proceeded to 2L, 66%, 25% and 8% received 1L FFX, GN and GEM, respectively. The preferred treatment sequences were FFX to GN (51/107; 48%), FFX to GEM (16/107; 15%), GN to fluoropyrimidine (9/107; 8%) and GN to oxaliplatin-based therapy (7/107; 7%). The receipt of any 2L therapy was associated with higher mOS (14 vs. 7 months, p < 0.01). Similar OS was observed between those who received 2L therapy after 1L FFX vs. after 1L GN (15 vs. 11 months, p = 0.43), and both conferred a survival advantage over 2L therapy after 1L GEM (15 vs. 7 months, p < 0.01 and 11 vs. 7 months, p = 0.02). Adjusting for confounders, 1L FFX and 1L GN followed by 2L therapy were associated with improved OS (HR 0.42, 95% CI 0.24-0.74, p < 0.01 and HR 0.49, 95% CI 0.36-0.68, p < 0.01). Conclusions: In this multicenter study, more than one-third of pts received 2L treatment for APC. Both 1L FFX and 1L GN treatment followed by 2L non-cross-resistant combinations can be considered as they showed similar survival.
Phase Ib trial of tepotinib in Asian patients with advanced hepatocellular carcinoma (HCC): Final data including long-term outcomes.
Authors: Shukui Qin, Tae-You Kim, Ho Yeong Lim, Baek-Yeol Ryoo, Jürgen Scheele, Dongli Zhou, Andreas Becker, Ann-Lii Cheng
Journal: Journal of Clinical Oncology (2017)

4087 Background: The incidence of hepatocellular carcinoma (HCC), a leading cause of cancer death, is increasing with the increasing incidence of chronic liver disease. Sorafenib, the only approved systemic therapy for advanced HCC, provides modest improvement in overall survival. Preclinical studies suggest c-Met is a valid target in HCC, but non-selective TKIs with c-Met inhibitory activity have not shown efficacy in trials, possibly due to lack of c-Met inhibition. Tepotinib (MSC2156119J) is a highly selective c-Met inhibitor that has favorable safety and promising activity, particularly against c-Met+ solid tumors. We report the final results of a phase Ib trial of tepotinib in patients (pts) with advanced HCC. Methods: Pts were Asian adults with confirmed HCC of BCLC Stage C, Child-Pugh Class A liver function without encephalopathy, and ECOG PS 0–2. Pts received tepotinib 300, 500 (the RP2D) or 1,000 mg/day on a 21-day cycle. c-Met expression status was retrospectively determined by IHC. Results: 27 pts were enrolled (median age 57 [38-69]; male 23; ECOG PS 0/1 11/16); 7 received tepotinib 300 mg/day, 14 500 mg/day, and 6 1,000 mg/day (3 with dose reduction). No DLTs were observed. 22 pts experienced treatment-related treatment-emergent adverse events (TRTEAEs), most commonly diarrhea (n = 10), nausea (8), elevated AST (7), and elevated ALT (6). 9 pts had grade ≥3 TRTEAEs, including elevated AST (3) and elevated ALT (3). Best overall response (BOR) was partial response (PR) in 2 pts, one of whom received tepotinib 500 mg (response duration 16.1 months) and one 1,000 mg (4.4 months); both had c-Met+ tumors. A further 8 pts had a BOR of stable disease (SD), 1 pt non-complete response (CR)/non-progressive disease (PD), and 14 pts had PD (2 pts not evaluable). Five pts had progression free survival &gt; 8 months. PK were as expected from previous studies. Conclusions: Tepotinib at doses of up to 1,000 mg/day was well tolerated by Asian pts with advanced HCC and a maximum tolerated dose was not reached. Antitumor activity was observed, particularly in pts with c-Met+ tumors. The ongoing phase II part of this study is comparing the efficacy and safety of first-line tepotinib and sorafenib in pts with c-Met+ HCC. Clinical trial information: NCT01988493.
Creation and validation of the “myMPN” prospective patient registry of myeloproliferative neoplasm patients.
Authors: Robyn Marie Scherber, Lindsey J Whyte, Michelle Woehrle, Amylou C. Dueck, Srdan Verstovsek, Claire Harrison, Ruben A. Mesa
Journal: Journal of Clinical Oncology (2018)

e19031 Background: The myeloproliferative neoplasms (MPNs) are a rare hematologic malignancy with significant symptom burden. Disease-related registries can be a useful and important tool for rare disease research and surveillance. Aims: The MPN research foundation steering committee aimed to create a prospective patient-reported MPN registry to capture demographics, disease related events, and symptom burden. Methods: Using the Genetic Alliance platform, an online registry was created which assessed MPN patients’ baseline demographics and disease history with prospective patient-reported disease events and symptom burden. 50 MPN patients assisted with registry beta testing. Survey registration information was disseminated among multiple MPN-related websites. Results: Accrual: A total of 454 MPN patients initiated the online registry process. Of these, 355 individuals completed introductory demographic and disease information. Respondents were predominantly female (63.7%). Disease-related information: The disease distribution of participants included 45% with essential thrombocythemia, 39% with polycythemia vera, and 12% with myelofibrosis. Most frequent therapies included aspirin (75.5%), hydroxyurea (42.1%), JAK inhibitor (17.6%), or no therapies (9.9%). To date, 436 surveys were logged reporting 902 disease events by 303 users (Table 1). Disease Symptom Burden: At the time of data analysis, 250 participants completed a 418 MPN10 symptom surveys. Mean MPN10 score was 1.9 for ET, 2.3 for PV, and 1.9 for MF. Conclusions: An MPN patient registry has the capabilities of addressing key critical questions regarding MPN patient symptom and treatment needs. Its dynamic nature allows researchers and patient advocates to prospectively connect with individual patients regarding additional information and unmet needs in this rare population. Table 1. MyMPN Registry distribution of disease events. Blood Draw 37.3% Phlebotomy 14.2% Change to MPN Medicine 9.6% Bone Marrow Biopsy 6.9% Transfusion 4.8% Unplanned Hospital Stay 4.5% Outpatient Procedure 3.8% Change in MPN Diagnosis 3.3% Thrombotic or Bleeding Events 2.4% Planned Hospital Stay 1.1% Pregnancy 0.2% Splenectomy 0.1%
Defining survivorship and surveillance with evidence.
Authors: Robert Dood, Yang Zhou, Shannon Dawn Armbruster, Shelley Tworoger, Robert L. Coleman, Anil Sood, Keith A. Baggerly
Journal: Journal of Clinical Oncology (2018)

6528 Background: Survivorship involves a multidisciplinary approach to surveillance and management of comorbidities and secondary cancers, however timing is based on arbitrary 5 year cutoffs. Here, we used a novel method analyzing annualized mortality rates to systematically define these cut-offs for transitions of care. Methods: The SEER database was queried for survival data on patients aged 18-100 years with any incident diagnosis of any cancer, grouped by ICD-O-3 tumor type. Excess mortality hazard, calculated as an annualized mortality risk above the baseline population was plotted over time. The time this hazard took to stabilize defined a high-risk period. The % morality elevation above age/sex-matched controls in the latter low-risk stable period was reported as the mortality gap. Results: Over 2.3 million patients with 68 different primary tumor types were evaluated. High risk surveillance periods ranged from 1 month to 21 years. High risk period durations ranged from under 1 year (breast, prostate, lip, ocular, and parathyroid cancers) up to 19 years (unspecified gastrointestinal cancers). Cluster analysis produced 6 groups. Subanalyses of selected tumor types revealed that stratifying on stage and histologic type can change the risk cluster and guidance for care. Conclusions: These findings indicate that a standardized 5 year surveillance period is both inadequate for some cancers while excessive for others. High risk cancers require the most resources with the longest high-risk period, highest persistent baseline mortality risk, and longest period of primary cancer mortality, all arguing for longer follow-up with an oncologist. Medians by cluster (5-95 %ile). Cluster High-risk period, yrs Mortality gap, % Cancer types 1 2.5 (0.0-5.0) 1.4% (0.3-2.4) Prostate, Breast, Cervix, Skin, Uterine corpus, Thyroid 2 7.5 (5.0-12.6) 2.9% (1.4-4.8) Hematologic, Ovary, Gum/mouth, Tongue, Oropharynx 3 5.0 (4.0-8.0) 2.4% (0.9-4.5) Colon, Bladder, Lymph node, Kidney, Rectum, Larynx 4 6.5 (5.3-10.8) 3.4% (2.0-8.5) Hypopharynx, Pharynx, Ill-defined, Uterine NOS 5 9.0 (6.4-16.9) 2.4% (1.1-6.0) Lung/bronchus, stomach, Brain/CNS, Esophagus 6 12.0 (9.3-12.9) 3.0% (1.1-4.2) Intrahepatic bile ducts, Pleura, Pancreas
c-Cbl expression as a novel predictive marker of survival in patients with metastatic colorectal cancer.
Authors: Shin Yin Lee, Vijaya B. Kolachalama, Umit Tapan, Janice Weinberg, Jean M. Francis, Qing Zhao, Kevan L. Hartshorn, Nader Rahimi, Vipul Chitalia
Journal: Journal of Clinical Oncology (2017)

e15090 Background: Aberrant hyperactive Wnt/ß-catenin signaling is critical in colorectal cancer (CRC) tumorigenesis. Casitas B-lineage Lymphoma (c-Cbl) is a negative regulator of Wnt signaling, and functions as a tumor suppressor. The objective of this study was to evaluate c-Cbl expression as a predictive marker of survival in patients with metastatic CRC (mCRC). Methods: Patients with mCRC treated at Boston University Medical Center between 2004 and 2014 were analyzed. c-Cbl and nuclear ß-catenin expression was quantified in explanted biopsies using a customized color-based image segmentation pipeline. Quantification was normalized to the total tumor area in an image, and deemed ‘low’ or ‘high’ according to the mean normalized values of the cohort. A supervised machine-learning model based on bootstrap aggregating was constructed with c-Cbl expression as the input feature and 3-year survival as output. Results: Of the 72 subjects with mCRC, 52.78% had high and 47.22% had low c-Cbl expression. Patients with high c-Cbl had significantly better median overall survival than those with low c-Cbl expression (3.7 years vs. 1.8 years; p = 0.0026), and experienced superior 3-year survival (47.37% vs 20.59%; p = 0.017). Intriguingly, nuclear ß-catenin expression did not correlate with survival. No significant differences were detected between high and low c-Cbl groups in baseline characteristics (demographics, comorbidities), tumor-related parameters (primary tumor location, number of metastasis, molecular features) or therapy received (surgery, chemotherapy regimen). A 5-fold cross-validated machine-learning model associated with 3-year survival demonstrated an area under the curve of 0.729, supporting c-Cbl expression as a predictor of mCRC survival. Conclusions: Our results show that c-Cbl expression is associated with and predicts mCRC survival. Demonstration of these findings despite the small cohort size underscores the power of quantitative histology and machine-learning application. While further work is needed to validate c-Cbl as a novel biomarker of mCRC survival, this study supports c-Cbl as a regulator of Wnt/ß-catenin signaling and a suppressor of other oncogenes in CRC tumorigenesis.