tbuckley/cabot-search huggingface dataset:
Tumor genetic urine test for hepatocellular carcinoma (HCC) screening.
Authors: Wei Song, Surbhi Jain, Ying-Hsiu Su
Journal: Journal of Clinical Oncology (2016)

e15640 Background: HCC is an aggressive cancer with a 5-year survival rate of 26% if detected early (stages 1 & 2), and a mere 2% in late stages, with an approximate 50% recurrence rate in 2 years after treatment. The most commonly used HCC screening biomarker is serum alpha-fetoprotein (AFP), which detects only 40-60% of cases highlights the urgent need for a more sensitive test for HCC screening. We have previously shown that urine contains circulation-derived, cell-free DNA that can be used for detection of cancer-related DNA markers, if a tumor is present. This study evaluated the potential for developing a urine DNA test for HCC screening. Methods: We developed a urine DNA test for HCC screening using short amplicon PCR-based assays for the most frequent occurred genetic hotspot mutations in TP53 (codon 249), TERT (-124, promoter), and CTNNB1 (hotspot in exon 3, codons 32-37), and for aberrant DNA methylation in GSTP1 (mGSTP1) and RASSF1A (mRASSF1A) in HCC. The performance of this five-marker panel in urine for HCC detection was evaluated by three statistical methods. Results: The five-marker urine test has AUROC of 0.914 (90.5% sensitivity at 80% specificity) in distinguishing primary HCC (n = 84) from non-HCC (n = 94, 50 cirrhosis and 44 hepatitis) by a logistic regression-based combination algorithm. Furthermore, these five urine DNA markers detected 93% (42/45) of AFP-negative ( < 20 ng/mL) HCC in this study cohort. In a small pilot longitudinal blinded study in which ten patients were monitored for HCC recurrence with serum AFP and urine DNA markers. Of the ten patients, four developed recurrence during the study. The urine DNA markers were detected in three of these four patients six months prior to MRI diagnosis, and detected concurrent with MRI diagnosis in the other patient. Conclusions: A urine DNA test outperformed not only the AFP serum test for HCC screening with a sensitivity of 90% at 80% specificity, but also enabling identification of recurrent HCC earlier or in concurrence with MRI. The potential of a urine HCC DNA test to replace AFP and ultrasound as the first line screening for HCC in high-risk surveillance populations is discussed.
Quality of life and cognitive functioning impairment associated with cisplatin-based chemotherapy in testicular cancer survivors.
Authors: Michal Chovanec, Lucia Vasilkova, Lucia Setteyova, Katarina Rejlekova, Jana Obertova, Zuzana Sycova-Mila, Patrik Palacka, Katarina Kalavska, Daniela Svetlovska, Beata Mladosievicova, Jozef Mardiak, Michal Mego
Journal: Journal of Clinical Oncology (2017)

e21607 Background: Testicular cancer (GCT) survivors are at risk for different types of late treatment sequelae. This study aimed to evaluate long-term quality of life (QOL), sexual (SexF) and cognitive functioning (CogF) issues resulting from cisplatin-based chemotherapy. Methods: QoL, SexF and CogF data were prospectively collected in 83 GCT survivors with median 9 year follow-up (range 5-32). The chemotherapy group (CTG) consisted of 53 and 18 patients receiving a cisplatin cumulative dose of ≤ 400mg/m 2 (LCD) and &gt; 400mg/m 2 (HCD), respectively. The control group (CG) included 12 patients treated with orchiectomy (6 pts) and adjuvant radiotherapy (6 pts). Data were collected using EORTC QLQ-C30, QLQ-TC26, FACT-Cog and sexual functioning questionnaires and analyzed according to the scoring guidelines. Results:The CTG survivors had significantly (all p &lt; 0.05) more limitations while working or doing daily activities (37% vs 8%), needed to rest more often (61% vs 33%) and feared the disease relapse more often (73% vs 50%) compared to the CG. A subscale for family problems within QLQ-TC26 have shown higher impairment in the CTG vs. CG (mean score ± SEM: 54.2 ± 26.7 vs. 38.8. ± 7.3, P &lt; 0.05). Cognitive abilities were perceived better in CG vs. CTG (mean score 24.5 ± 1.8 vs. 20.5 ± 0.7, P &lt; 0.05). The CG surivors had higher education level and fathered more children compared to the CTG. The CTG felt more unsettled than the CG (all P &lt; 0.05), however the impact of perceived cognitive impairment on their lives did not significantly differ ( P = 0.4). Patients who received HCD have suffered from dyspnea more often than patients treated with LCD (mean dyspnea subscale score ± SEM: 22.2 ± 4.4 vs 8.9 ± 2.6, P &lt; 0.05). The HCD group also reported more difficulties to concentrate while watching television/reading newspaper and struggled to name things during conversation compared with the LCD group ( P &lt; 0.05 for both). No impairment in sexual functioning was reported. Conclusions: Our study shows thatGCT survivors cured with cisplatin-based chemotherapy suffered from QoL issues and their perception of cognitive abilities was altered. The HCD of cisplatin further impaired several QoL and cognitive aspects.
Prevalence of germline genetic alterations in colorectal cancer patients.
Authors: Andrea Cercek, Yelena Kemel, Diana Mandelker, Carolyn Stewart, Angela G. Arnold, Margaret Sheehan, Rona Yaeger, Neil Howard Segal, Anna M. Varghese, Leonard B. Saltz, Luis A. Diaz, Jinru Shia, David Michael Hyman, Michael F. Berger, David B. Solit, Liying Zhang, Kenneth Offit, Mark E. Robson, Zsofia Kinga Stadler
Journal: Journal of Clinical Oncology (2018)

1577 Background: Although universal screening of all colorectal tumors for Lynch syndrome (LS) is recommended, the prevalence of other germline mutations, with potential clinical implications, in colorectal cancer (CRC) patients is less well-defined. We performed comprehensive germline testing (GT) in a prospective cohort of CRC patients in order to determine the proportion of clinically actionable germline mutations detected by universal tumor-normal sequencing. Methods: Between 11/2015 to 1/2018, 427 unselected CRC patients were prospectively consented to GT in 76-genes associated with cancer susceptibility using an IRB-approved protocol. Prevalence of likely pathogenic and pathogenic genetic alterations (PGAs) were reported and correlated with clinical and somatic findings. Results: Of 427 CRC patients, the median age was 52 years (range, 18-88 years), 54% were male. PGAs were present in 55 (13%) of CRC patients including 24 PGAs in high-penetrance (MLH1, MSH2, MSH6, EPCAM, PMS2) and 23 PGAs in moderate-low penetrance (CHEK2, mono-MUTYH, APC I1307K) CRC-associated risk genes. The prevalence of moderate/high PGAs was 12.5% (20/160) versus 6% (17/267) in patients with CRC age ≤50 versus age > 50, respectively (p-value = 0.045). LS accounted for 12 (60%) and 5 (30%) of high or moderate mutations in the age ≤50 versus age > 50 groups. All LS-associated tumors exhibited concordant tumor findings with high-frequency microsatellite instability, deficient mismatch repair protein expression, or high mutational load. Seventeen (31%) of patients with PGAs did not meet current guidelines for GT. PGAs not traditionally associated with CRC-risk were identified in 14 cases, including 7 high- (4 BRCA2, 1 FLCN, 1 NF1, 1SDHA) and 7 moderate-penetrance (3 BRIP1, 3 ATM, 1 HOXB13) genes. Correlative tumor data, including assessment of somatic mutations and loss of heterozygosity in the gene(s) corresponding to these germline mutations will be presented. Conclusions: Although the prevalence of PGAs is higher in patients with young-onset CRC(≤ 50), LS accounts for the vast majority of germline mutations in these patients. Analysis of PGAs not traditionally associated with CRC to evaluate for causality versus incidental findings will be performed.
Real-world evidence on treatment patterns and survival among ALK+ NSCLC patients in Canada who discontinue crizotinib treatment.
Authors: Sheena Kayaniyil, Manjusha Hurry, John Wilson, Paul Wheatley-Price, Barbara L. Melosky, Jeffrey Rothenstein, Victor Cohen, Caroline Koch, Jie Zhang, Katherine Osenenko, Geoffrey Liu
Journal: Journal of Clinical Oncology (2016)

e20610 Background: Crizotinib is indicated for treatment of patients with ALK-positive (ALK+) advanced or metastatic non-small cell lung cancer (NSCLC), yet patients eventually progress or develop drug resistance. Limited knowledge exists on crizotinib-resistant Canadian ALK+ NSCLC patients. The objective of this study was to provide real world evidence on treatment patterns and survival among ALK+ NSCLC patients in Canada who fail crizotinib treatment. Methods: A chart review study was conducted among patients with ALK+ locally advanced or metastatic NSCLC, diagnosed between 2010 and 2015, identified from six Canadian oncology centres. Data on treatment patterns and outcomes were collected from patient medical charts. Analyses focused on those who were intolerant to or progressed on crizotinib treatment. An exploratory analysis was conducted to determine factors associated with overall survival (OS) after crizotinib failure using a Cox proportional hazards model. Results: In total 97 patients were included, of whom 9 were crizotinib-naïve and 39 were currently receiving crizotinib; 49 patients who had failed crizotinib treatment were included in this analysis. Mean age at diagnosis was 53 years, with 53% female, 53% Caucasian, and 67% non-smokers. Post crizotinib treatment (median duration 7.8 months), 43% received ceritinib (at any time), 20% received systemic chemotherapy (but never ceritinib), and 37% received no additional treatment. Median OS was shorter in patients who did not receive any post-crizotinib treatment compared to those who received non-ceritinib systemic therapy or ceritinib (0.9 vs. 7.6 and 20.4 months, p < 0.001). In multivariable analysis, factors associated with poorer OS included lack of use of additional therapies (particularly ceritinib), male gender, and older age, but not smoking status; Asians had a non-significant trend for improved OS. Conclusions: After discontinuation of crizotinib, a substantial portion of patients received no further treatment, highlighting a significant unmet need in these patients. Treatment with systemic agents was associated with improved OS, with use of ceritinib associated with the longest survival.
Second primary thyroid cancer following index head and neck cancer.
Authors: Katherine M. Polednik, Matthew C Simpson, Eric Adjei Boakye, Kahee A. Mohammed, Nosayaba Osazuwa-Peters
Journal: Journal of Clinical Oncology (2018)

6060 Background: Thyroid cancer incidence has increased in the last three decades, and studies have shown that radiation treatment for index cancers may play a role in its development. We examined the rate of second primary thyroid cancer (SPTC) following index head and neck cancer (HNC) and determined whether radiation treatment among HNC survivors increased risk of developing SPTC. Methods: Patients with index HNC diagnosed from 1975-2014 in the Surveillance, Epidemiology, and End Results 9 database were included. We calculated incidence rate for SPTC per 100,000 person-years. A multivariable competing risk proportional hazards model tested risk of developing a SPTC following an index HNC. Covariates included age, county-level poverty percentage, year of diagnosis, anatomic site, stage, grade, surgery, radiation, chemotherapy, race, marital status, and sex. Two sensitivity analyses using proportional hazards models were also performed: (1) comparing patients who received both radiation and chemotherapy to those who did not receive both; and (2) restricting the main model to patients who received radiation. Results: There were 229 SPTC cases out of 127,563 HNC patients (0.2% SPTC). The rate of SPTCs was 26.1 per 100,000 person-years. In the main model, for every increasing year of age at diagnosis, patients were 3% less likely to develop an SPTC (adjusted hazard ratio [aHR] = 0.97, 95% confidence interval [CI]: 0.96, 0.98. Compared with non-Hispanic white patients, non-Hispanic Asian/Pacific Islander/Native American/Alaskan Native patients were 66% more likely to develop an SPTC (aHR = 1.66, 95% CI: 1.10, 2.50). Males were 27% less likely to develop an SPTC than females (aHR = 0.73, 95% CI: 0.55, 0.96). Radiation (aHR = 0.92, 95% CI: 0.68, 1.25), surgery (aHR = 0.79, 95% CI: 0.56, 1.11), and chemotherapy (aHR = 1.13, 95% CI: 0.76, 1.69) were not significantly associated with developing SPTC. The sensitivity models also did not find an association between treatment and risk of SPTC. Conclusions: Rate of developing SPTC following index HNC was very low, and previous exposure to radiation did not significantly increase risk in our study population. More studies are needed to understand the increasing incidence of thyroid cancer across the United States.
The effect of treatment delay on survival in patients with hepatocellular cancer.
Authors: Mehmet Akce, Shubhada Sansgiry, Sarah Louise Temple, Jessica Davila, Yvonne Sada
Journal: Journal of Clinical Oncology (2017)

e15645 Background: Hepatocellular cancer (HCC) is the fastest increasing cause of cancer related death in the U.S. Only one-third of patients are candidates for curative treatment, and treatment delays occur in 30% of patients. Data on the effect of treatment delays on HCC survival outcomes are limited to small single center studies. The aim of this study was to identify predictors of treatment delays and the impact of treatment delay on survival. Methods: We conducted a retrospective study using a national cohort of patients from the Department of Veterans Affairs who were diagnosed with HCC from October 1, 2004 to September 30, 2011. Demographics, clinical factors, treatment and death were ascertained from the medical records. Treatment delay was defined as greater than 60 days between HCC diagnosis and first treatment. Treatment was categorized as curative (surgery or ablation), liver-directed therapy, or chemotherapy. Cox Proportional Hazard models were used to examine the effect of treatment delay on survival stratified by stage (BCLC 0 and A, B, or C). Results: Among 742 patients with HCC, 223 (30%) had a treatment delay. The majority of patients were Barcelona Stage C (43%), and 131 patients (17.7%) had metastatic disease. On univariate analysis, patients with treatment delay were more likely to have tumor board discussion, single tumors, and PTSD (p &lt; 0.05). Treatment delay was not associated with increased risk of death for patients with BCLC stage 0 and A (HR 0.74 [0.48-1.14]) or BCLC stage B (HR 0.83 [0.61-1.14]). For BCLC stage C, treatment delay was associated with a 50% decrease in risk of death (HR 0.50 [0.37-0.67]), adjusting for demographics, clinical factors, stage, and treatment. Patients with BCLC stage C HCC and treatment delay were more likely to have curative intent therapy (32.9% vs 16.3%) or liver directed therapy (43.4% vs 36.3%, p = 0.0006) than those with no delay. Conclusions: Treatment delays occurred in 30% of patients. Treatment delay was not associated with increased risk of death for earlier stage HCC, but treatment delay was associated with decreased risk of death for patients with BCLC stage C. This finding may be due to delays from coordination of curative and liver directed therapy that may result in improved survival.
P01.113 Increasing TTFields dose to the tumor bed improves overall survival in newly diagnosed glioblastoma patients
Authors: M Ballo, Z Bomzon, N Urman, G Lavy-Shahaf, S A Toms
Journal: Neuro-Oncology (2018)

It has been hypothesized that increasing Tumor Treating Fields (TTFields) dose to the tumor leads to better patient outcome. However, to date, this hypothesis has not been demonstrated using clinical data. Here we present a simulation based study testing this hypothesis. The study was performed utilizing data collected during the pivotal EF-14 trial that demonstrated the clinical benefit of combining TTFields with chemoradiation in newly diagnosed Glioblastoma patients. Patient treated with TTFields for at least 2 months as part of the EF-14 trial ere included in the study. In addition, patients for whom the quality of the MRIs at baseline was insufficient for creation of computational models excluded, leaving n=317 cases. Realistic computational models of these patients were created. The transducer array layouts assigned to the patients, their average monthly compliance (fraction of time patient was on active treatment), and the average electrical current delivered to each patient (calculated from log files of the TTFields generators) were derived. These data were combined into numerical simulations, which yielded an estimate of the TTFields distribution within all patients. During treatment TTFields are delivered in two roughly orthogonal directions by two pairs of transducer arrays. To combine the two roughly orthogonal fields into a single measure of dose, we defined the Local Minimum Dose Density (LMiDD) as the lower of the power densities delivered by the two fields to each point in the model, multiplied by the average compliance of the patient. For each patient, average LMiDD within a tumor bed combining the Gross Tumor Volume and a Peritumoral Boundary Zone 3 mm wide was calculated. To test the hypothesis that maximizing TTFields dose at the tumor beds improves patients’ outcome, they were divided into two groups based on a threshold value of average LMiDD within the tumor bed that yielded the most statistically significant difference in median OS between the groups. The optimal threshold of average LMiDD within the tumor bed was found to equal 1.6 MmW/cm3. Splitting the population using this threshold resulted in two groups with similar demographics. OS and PFS were significantly higher in the group that received higher doses of TTFields (OS: 25.1 months vs. 20.9 months, p=0.002, HR=0.69; PFS: 8.8 months vs. 6.5 months, p=0.006 HR=0.66). In addition the median OS and PFS were longer with TTFields when average electric field in the tumor bed was >1.05 V/cm OS (25.0 months vs. 21.6 months, p=0.043, HR=0.76) and PFS (8.1 months vs. 7.9 months, p=0.006 HR=0.74). This study is the first to demonstrate a connection between TTFields dose and efficacy in a clinical setting. This study emphasizes the importance of TTFields treatment planning for improving patients’ outcome.
Defining adverse events of anti-programmed-death-1 (Anti-PD1) agents using FDA adverse event reporting system (FAERS).
Authors: Kun Xiao, Zhesi Lian, Robert Collins, Anastasios Dimou, Elizabeth Garrett-Mayer, Harry A. Drabkin
Journal: Journal of Clinical Oncology (2017)

e14568 Background: Anti-PD1 inhibitors are a promising therapeutic option in oncology. They have received FDA-approval in treating metastatic and relapsed non-small cell lung cancer, kidney cancer, head-and-neck cancer, and melanoma. Yet its adverse event profile is still being defined. The FAERS database contains information on adverse events and medication error reports submitted to the FDA and serves to support the post-marketing safety surveillance program for drug and therapeutic biologic products. Methods: We searched the FAERS database from January 1, 2015 to June 30, 2016. Only initial cases reported by an MD or pharmacist for treatment of cancers of the lung, kidney, head and neck, or melanoma were included. Cases with incomplete starting, ending or event dates were excluded. The primary outcome was time from drug initiation to onset of the event. Cox proportional hazard model was used to evaluate the association between time to AE and age, gender, disease, and time of report. Results: A total of 105 adverse events (AEs) were identified. Of those AEs, 68 were related to nivolumab, 35 to pembrolizumab, and 2 to atezolizumab. Fifty-six AEs were seen in lung cancer patients, whereas 46 were in melanoma, 2 in kidney cancer and 1 in a head and neck cancer patient. Thirty-three AEs involved pulmonary complications, 30 gastrointestinal systems, 17 endocrine, and 9 were constitutional in nature. The median onset of AEs from the start of therapy was 31 days (range: 2 - 459 days). Using a Cox regression analysis, pembrolizumab was associated with a longer time to AEs compared to nivolumab (HR 0.48, 95%CI: 0.26 - 0.89). Also age between 60 and 70 was associated with a longer time to the onset of AEs compared to age &lt; 60 (HR 0.61, 95%CI: 0.37-0.99). Conclusions: FAERS is a vigilance system to monitor AEs from anti-PD1 inhibitors. Pembrolizumab and age between 60 and 70 were associated with less AEs. Ongoing data accrual will increase the statistical power and analysis of AEs from anti-PD1 inhibitors in greater detail.
The stability of treatment preferences of advanced cancer patients over time.
Authors: Lea Jasmina Jabbarian, Renee Maciejewski, Paul K Maciejewski, Holly Gwen Prigerson
Journal: Journal of Clinical Oncology (2017)

e21501 Background: The stability of patient treatment preferences has important implications for the optimal timing of advance care planning. Nevertheless, longitudinal data on cancer patients in real-life settings have not examined stability of treatment preferences over time. This study examines the stability of treatment preferences of advanced cancer patients over time and the potential influence of changes in physical functioning. Methods: The patient sample (N = 104) was drawn from a multi-institutional, longitudinal cohort study of patients recruited between 2010 and 2015. Patients with metastatic solid tumor cancer that had progressed on prior chemotherapy regimens were interviewed after an initial clinic meeting in which their most recent scan results were discussed (baseline) and, subsequently, completed monthly follow-ups. Patients reported their treatment preferences (i.e., comfort versus life-extending care) and physical functioning at each assessment. Results: The treatment preferences of the majority of patients (80.8%) remained stable within the first month of follow-up. Patient characteristics, such as age or type of cancer, were not significantly associated with treatment preference stability. The proportion of patients whose preferences changed in favor of comfort care (10.6%) was only slightly higher than the proportion of patients whose preferences changed in favor of life-extending care (8.7%). The same pattern held for the two- and three-month follow-up assessments. Improvement in physical functioning was significantly associated with change in treatment preferences. However, the vast majority of patients (72.2%) had stable or declining physical functioning. Conclusions: Most advanced cancer patients have stable treatment preferences regarding comfort versus life-extending care in the months leading up to their death. Thus, advance care planning earlier in the course of illness may not be premature for the vast majority of patients. As physical functioning changes, treatment preferences should be re-evaluated.