tbuckley/cabot-search huggingface dataset:
Risk of left ventricular systolic dysfunction with sunitinib therapy in patients with metastatic renal cell carcinoma: A prospective cohort study.
Authors: Vivek Narayan, Le Wang, Mary Putt, Stephen Michael Keefe, Naomi B. Haas, Daniel John Lenihan, Igor Puzanov, Anna Catino, James Fang, Steven M. Ewer, Karen Moncher, Chantal ElAmm, Guilherme Oliveira, Hari Narayan, Bonnie Ky
Journal: Journal of Clinical Oncology (2016)

e16104 Background: Sunitinib is used widely as initial therapy for metastatic renal cell carcinoma (mRCC). However, sunitinib is associated with a risk of cardiovascular (CV) toxicities, including hypertension and left ventricular systolic dysfunction (LVSD). Our understanding of these cardiotoxicities, specifically LVSD, remains limited, and is largely defined by retrospective analyses in clinical trial populations without standardized CV assessment. The objective of our study was to prospectively define the incidence and clinical predictors of LVSD with sunitinib in the mRCC, non-clinical trial setting. Methods: In 92 mRCC patients newly initiating sunitinib, echocardiograms and CV clinical assessments were performed at baseline and at 3.5 weeks, 15 weeks, and 33 weeks following sunitinib therapy. These study visits typically coincided with cycles 1, 3, and 6 of therapy and occurred while patients were on drug. Kaplan-Meier conditional survival analysis was used to estimate risk of LVSD, defined as a decline in the LV ejection fraction (LVEF) by ≥ 10% to < 50%. Linear mixed effects models were used to define the univariable associations between clinical characteristics and LVEF decline. Results: The mean age was 61 years, and 66% of patients were male, 56% had baseline hypertension, and 59% had a sunitinib starting dose of 50 mg daily. At baseline, the overall risk of LVSD was 14% (95% CI 4 – 24%). The majority of these events occurred by 3.5 weeks of the first treatment cycle, with a substantial decrease in risk over time. At 33 weeks, the estimated risk of LVSD diminished to 3% and 0% in patients who had not experienced LVSD by the end of cycles 1 and 3, respectively. Age, sex, sunitinib dose, hypertension, and early increases in blood pressure were not associated with LVEF decline over time. Conclusions: In this prospective, non-clinical trial mRCC population, the risk of LVSD is modest, with the majority of events occurring early, often within the first treatment cycle. Our findings suggest that while CV testing early after the initiation of sunitinib therapy is likely prudent, routine monitoring in asymptomatic individuals is less likely to be of clinical benefit beyond cycle 3.
Phase 1 multicenter trial to assess the maximum tolerated dose, safety, pharmacokinetics, and pharmacodynamics of pazopanib in combination with irinotecan and temozolomide (PAZIT) for children and young adults with advanced sarcoma.
Authors: Kieuhoa Tran Vo, Jennifer Gibney Michlitsch, Avanthi T Shah, Janel Long-Boyle, Mi-Ok Kim, Clay Gustafson, Alejandro Sweet-Cordero, Katherine K. Matthay, Steven G. DuBois
Journal: Journal of Clinical Oncology (2018)

TPS10576 Background: Sarcomas express pro-angiogenic factors that may represent therapeutic targets. Pazopanib, an oral multi-kinase inhibitor of VEGFR-(1-3), c-kit, and PDGFR, is FDA-approved for the treatment of advanced soft tissue sarcomas. In a phase 1 study of single-agent pazopanib in children with recurrent or refractory solid tumors, this agent was well tolerated and the clinical activity was encouraging in this heavily pre-treated population. Preclinical studies have demonstrated a potential additive or synergistic interaction between anti-angiogenic agents and cytotoxic chemotherapy. The combination of irinotecan and temozolomide is well tolerated and provides a modest degree of antitumor activity in heavily pre-treated sarcoma patients, thus making it a useful platform onto which new compounds may be tested. Methods: This is a phase 1, open-label, multicenter trial of pazopanib in combination with irinotecan and temozolomide (PAZIT) in children and young adults ages 6-30 years with relapsed or refractory sarcomas (NCT03139331). The primary objectives are to determine the recommended phase 2 dose, describe toxicities, and describe pharmacokinetic parameters in this population. Secondary and exploratory objectives include evaluation of disease response and exploration of pharmacodynamic effects of PAZIT. Pazopanib is administered orally on days 1-21 of 21-day cycles according to assigned dose level. All patients receive fixed doses of irinotecan IV (50 mg/m2/day) or PO (90 mg/m2/day) and temozolomide 100 mg/m2/day PO on days 1-5. Oral cephalosporin diarrhea prophylaxis is required. Dose escalation follows a standard 3+3 design evaluating up to three pazopanib dose levels. Following dose escalation, up to 10 additional patients will be enrolled to the dose expansion cohort to obtain additional toxicity and efficacy data. Correlative studies include changes in plasma angiogenic factors and circulating tumor DNA. Enrollment began in May 2017 and is ongoing. Clinical trial information: NCT03139331.
TCT-201 Discharge Antithrombotic Medication and Clinical Events Through 1 Year in the Global Amulet Observational Study
Authors: David Hildick-Smith, Boris Schmidt, Patrizio Mazzone, Sergio Berti, Sven Fischer, Matteo Montorfano, Simon Lam, Juha Lund, Ignacio Cruz-Gonzalez, Heyder Omran, Giuseppe Tarantini, Jens Erik Nielsen-Kudsk
Journal: Journal of the American College of Cardiology (2018)
PD.1.05 Molecular Characterization of EGFR Somatic Mutations in Lung Adenocarcinoma Tumors from Chilean Patients
Authors: G. Sepúlveda-Hermosilla, A. Blanco, R. Lizana, L. Ramos, M. Freire, M. Spencer, S. Chernilo, O. Aren, P. Perez, R. Armisen
Journal: Journal of Thoracic Oncology (2018)
Fatty-acid-binding proteins as a novel target for the treatment of anti-PD-1-resistant tumors.
Authors: James William Welsh, Sharareh Niknam, Jonathan E. Schoenhals, Hampartsoum B. Barsoumian, Ahmed I. A. Younes, Ailin Li, Maria Angelica Cortez
Journal: Journal of Clinical Oncology (2017)

11562 Background: The mechanisms underlying immunosuppression and resistance to PD1 inhibitors in cancer are not well understood. We attempted to fill this gap with an integrated transcriptome analysis in an anti-PD1-resistant lung adenocarcinoma mouse model. The model was created by in vivo passage of 344SQ murine lung cancer cells (p53 R172HΔg /+K-ras LA1/+) in a syngeneic host repeatedly dosed with anti-mouse PD1 antibodies. Anti-PD1-resistant 344SQ (344SQ_R) and 344SQ parental (344SQ_P) cells were then inoculated into syngeneic 129Sv/ev mice, which were then dosed twice with anti-PD1 or control IgG antibodies. Methods: Tumor tissues were collected and analyzed as follows: transcriptome with Affymetrix; protein levels by reverse phase protein array analysis; signature enrichment by gene set enrichment analysis; metabolome by mass spectrometry; and lipid content with fluorescent probes Oil O and BODIPY. We also isolated tumor-infiltrating immune cells for flow cytometry and gene expression analyses. Results: We identified lipid-related metabolic pathways as being the most highly enriched in anti-PD1-resistant tumors (344SQ_R) vs. their 344SQ_P counterparts; the resistant cells also had more lipid droplets than the 344SQ_P cells. The anti-PD1-resistant tumors overexpressed several genes involved in lipogenesis and fatty acid pathways, including fatty acid binding proteins (FABPs). Specifically, FABP overexpression promoted fatty acid uptake and lipid-droplet accumulation in resistant tumors. 344SQ_R tumors promoted immune suppressive cells by upregulating FABPs expression in M2-like macrophages, marked by increased fatty acid intake and fatty acid oxidation. Conversely, percentages of CD4+ and CD8+ tumor-infiltrating lymphocytes were reduced in the resistant tumors. Conclusions: These results suggest that lipid metabolic rewiring drives resistance PD1 inhibitors supporting the accumulation of immunosuppressive cells, including M2-like macrophages, preventing type I immune responses elicited by T cells. Collectively, these findings reveal new potential lipid-related targets for drug development or new treatments combining inhibitors of these targets with anti-PD1 therapy.
Differences in survival between symptomatic versus asymptomatic recurrence following cystectomy for bladder cancer.
Authors: Chelsea K Osterman, Jaber Alanzi, Elizabeth L Kaufman, Vivek Narayan, Ben Boursi, Christine Cambareri, S. Bruce Malkowicz, Ronac Mamtani
Journal: Journal of Clinical Oncology (2017)

e16021 Background: The benefit of surveillance after curative treatment in bladder cancer is controversial, but might be justified if early detection of asymptomatic recurrence improves survival. Prior studies demonstrating a benefit of surveillance may have been impacted by lead-time bias, which is the overestimation of survival duration due to earlier detection of disease. To avoid this bias, we examined time-dependent differences in survival with symptomatic vs. asymptomatic diagnosis of recurrence after cystectomy. Methods: We conducted a retrospective cohort study among 463 cystectomy patients between 1987 and 2011 at the University of Pennsylvania. Patients were followed by standardized protocol and classified by mode of recurrence detection (asymptomatic or symptomatic). Primary outcome was all-cause mortality. To reduce lead-time bias, we used cox regression models with varying cohort-entry times to assess the impact of mode of recurrence on survival from both time of cystectomy (Model 1) and time of recurrence (Model 2), adjusted for time to recurrence. Results: 197 patients (42.5%) recurred; 71 were asymptomatic (36.0%), 107 were symptomatic (54.3%), and 19 (9.6%) were unknown. In all models, relative to asymptomatic patients, patients with symptomatic recurrence had significantly increased risk of death (Model 1 HR 1.74, 95% CI 1.13-2.68, Model 2 HR 1.98, 95% CI 1.27-3.10) and had lower 1 year overall survival (30.43% vs. 55.66%). Group differences in median survival (246 days) were greater than the estimated lead-time (10 days). Conclusions: Symptomatic recurrence is associated with worse outcomes than asymptomatic recurrence, even after lead-time bias adjustment. These data support consensus guidelines for intensive surveillance post-cystectomy. Similar methods to account for lead-time bias should be considered in future studies evaluating the benefit of surveillance following curative cancer resection.
Patient and physician satisfaction with analgesic treatment in Southeast Asia (SEA): Findings from the analgesic treatment for cancer pain in Southeast Asia (ACE) study.
Authors: Hanlim Moon, Dang Huy Quoc Thinh, Wimonrat Sriraj, Marzida Binti Mansor, Kian Hian Tan, Suhana Yusak, Johan Kurnianda, Yen Phi Nguyen, Annielyn Beryl Ong-Cornel, Yacine Hadjiat, Francis Javier
Journal: Journal of Clinical Oncology (2017)

e21698 Background: Adequate dosing of analgesics is important for optimum cancer pain control &amp; quality of life (QoL). To understand current attitudes toward analgesic treatment for cancer pain in SEA, the ACE study explored patient &amp; physician satisfaction with pain control in 6 SEA countries. Methods: This cross-sectional observational study included 465 adult outpatients prescribed analgesics for cancer pain for ≥1 month in Indonesia, Malaysia, Philippines, Singapore, Thailand, &amp; Vietnam. Pain intensity, sleep disturbance, QoL, satisfaction with pain control, &amp; physicians’ assessment of adequacy of analgesics were recorded via questionnaires. Current analgesic doses prescribed were extracted from medical records. Results: Most patients (84%) had stage 3 or 4 cancer. While 91% were prescribed opioids, mean reported pain intensity was 4.1 (0/no pain, 10/worst possible pain) &amp; most had problems with sleep (55%) &amp; QoL (problems with pain/discomfort [82%], usual activities [66%] &amp; anxiety/depression [56%]). 60% of patients were satisfied with their pain control status &amp; 30% found it acceptable. Physicians more often reported dissatisfaction with patients’ pain control status compared with patients (21% vs 10%). Patient-physician concordance in satisfaction with pain control was low (weighted Kappa 0.36; 95% CI 0.30-0.43). More than 1 in 4 physicians (29%) assessed prescribed analgesics to be “inadequate” for pain control. Median daily dose prescribed in oral morphine equivalents was 30 mg for both morphine &amp; tramadol. Of the SEA countries included, prescribed doses of opioids were generally lower in Indonesia &amp; higher in Vietnam. Conclusions: The results highlight the complexity of managing cancer pain in SEA. Despite unrelieved pain, sleep disturbance &amp; QoL issues, many patients still reported satisfaction with pain control. Notably, physicians expressed dissatisfaction more frequently than patients. These findings suggest a need for all-round pain status assessment (including pain intensity, sleep disturbance, QoL) &amp; improved patient-physician communication about analgesic treatment expectations, pain control &amp; adverse effects.
Vaginal laser to improve symptomatic vulvovaginal atrophy and sexual function in breast cancer patients: Report from LAAVA pilot study.
Authors: Antonia Pearson, Andrew Booker, Martin Tio, Gavin M. Marx
Journal: Journal of Clinical Oncology (2018)

10064 Background: Vulvovaginal atrophy (VVA) is a commonly reported issue among breast cancer patients (pts), and its etiology is multifactorial. The use of systemic and topical estrogens to treat VVA has traditionally been discouraged in hormone positive breast cancer. Laser therapy has been reported to improve symptoms from VVA in women with menopause. We aimed to assess the symptomatic benefit and the impact on sexual function of this treatment in women with early breast cancer (EBC). Methods: We performed a single arm investigator initiated pilot study of female EBC pts with symptomatic VVA. 29 pts were recruited between February 2016 and August 2017. 3 pts were not enrolled; 2 had medical conditions that excluded them from treatment, 1 withdrew consent prior to commencing. Baseline demographic data was collected on all pts. A total of 3 vaginal fractional CO2 laser treatments were administered approximately 4 weeks apart for each pt. Questionnaires were completed at baseline, prior to each subsequent treatment and 4 weeks after completion of treatment. Our primary endpoint was symptomatic improvement of VVA (dryness, itch, burning, dysuria and dyspareunia) at 12 weeks on a 10cm visual analog scale (VAS). Our secondary endpoint was improvement in sexual function using the Female Sexual Function Index (FSFI) at 12 weeks. Statistical analysis was performed with a Wilcoxon Signed Rank test. Results: 26 pts were enrolled in our study with a median age of 55. All pts were post-menopausal. 25 pts had received anti-estrogen therapy as a part of their breast cancer treatment. All pts received the 3 pre-planned laser treatments, and questionnaire compliance was high (98%). There was significant improvement in VVA symptoms after treatment on a 10cm VAS (table 1) and in sexual function demonstrated on the FSFI (p = < 0.001). Conclusions: EBC pts had improvement in all 5 domains of VVA symptoms, as well as improvement in sexual function. Further randomized sham-controlled trials are needed to further assess this treatment. Change in VVA symptoms on 10cm VAS score. Variable Mean absolute change P value Dryness 4.33 < 0.001 Itch 3.67 < 0.001 Burning 2.93 0.003 Dysuria 3.53 < 0.001 Dyspareunia 3.84 < 0.001
Efficacy of abemaciclib, palbociclib and ribociclib among the older compared with younger women in HR-positive/HER2-negative, advanced breast cancer.
Authors: Thierry Landre, Anna Fain, Emmanuelle Langeron, Lakhdar Mokrane, Cherifa Taleb
Journal: Journal of Clinical Oncology (2018)

e13043 Background: The inhibition of cyclin-dependent kinases 4 and 6 (CDK4/6) could potentially overcome or delay resistance to endocrine therapy in advanced breast cancer that is positive for hormone receptor and negative for human epidermal growth factor receptor 2 (HER2). To our knowledge, there are few studies comparing the benefit of CDK4/6 inhibitors in advanced breast cancer among elderly or younger patients. Methods: The search was conducted in PubMed, ASCO, ESMO and SABCS meeting abstract databases. We identified phase 2 or 3 trials recruiting patients with breast cancer, randomized to receive hormonal treatment (HT) plus either CDK4/6 inhibitors or placebo. The primary end point was PFS. We performed two distinct Meta-Analyses (MAs); one among the older and the other among the younger patients. Hazard Ratios (HRs) with their 95% confidence intervals (CIs) were collected from the studies and pooled to compare the CDK4/6 effect among elderly and younger patients. Results: This MA included 7 studies, five in first line setting (MONALEESA-2 and 7 for abemaciclib, MONARCH-3 for ribociclib and PALOMA-1 and 2 for palbociclib) and two in second line setting (MONARCH-2 and PALOMA-3). This MA included 2664 patients in first line and 1190 patients in second line: 2625 patients were younger than 65 years old and 1229 were older. More than 95% of patients had a Performance Status 0 or 1. The addition of CDK4/6 inhibitors to HT significantly improved PFS among elderly patients in first line (HR = 0.57, 95 % CI 0.45-0.72) and in second line (HR = 0.55, 95 % CI 0.41-0.73). Among younger patients, there was also a statistically difference in PFS in first line (HR = 0.51, 95 % CI 0.43-0.61) as well as in second line (HR = 0.49, 95 % CI 0.40-0.60) in favour of CDK4/6 inhibitors. There were no significantly differences between the 2 age groups (P = 0.75). Conclusions: This analysis suggests the use of a CDK4/6 inhibitor in combination with HT for the first or second line treatment of hormone receptor-positive / HER2-negative, advanced breast cancer in older women results in similar efficacy benefit as seen in younger women. Overall survival results are expected to confirm this benefit.
A description of a small cohort of Argentinian women presenting with cervical cancer (CC) highlighting the need for CC control in Latin America (LA).
Authors: Brittany L. Bychkovsky, Mayra Ferreyra, Kathrin Strasser-Weippl, Cristina Herold, Cristina Eliz Rosales, Guillermo Luis Lerzo, Patricia Bogado Pino, Gilberto Lopes, Don S. Dizon, Kathleen M. Schmeler, Marcela G. del Carmen, Thomas Christopher Randall, Angelica Noguelra Rodrigues, Aknar Calabrich, Jessica St. Louis, Caroline Vail, Paul E. Goss
Journal: Journal of Clinical Oncology (2016)

e17026 Background: Cervical cancer (CC) is the second most common cause of cancer in Latin America (LA) and a leading cause of cancer mortality among women. Each year 27% of newly diagnosed CCs in LA occur in women who are < 40 years of age compared to only 23% in developed countries. There is little epidemiologic data available on these young women in LA with CC. Methods: To better understand current trends in CC among young women in LA, we conducted a retrospective cohort study at a single institution in Argentina (Maria Curie Hospital). Data collected included social/demographic information, clinical characteristics, pathologic findings, treatment information and current disease status. We reviewed this case series considering the current control efforts in the region (Bychkovsky et al. Cancer. 2015 Dec 15). Results: Between 6/2015 and 1/2016, we identified 20 women who were < 35 years of age and were diagnosed with CC. All 20 women had not received the HPV vaccine or undergone recent CC screening. All women presented with symptoms of advanced disease including abnormal vaginal bleeding, abdominal pain and/or renal failure. 13/20 arrived un-referred either from Bolivia or Paraguay, the median age was 28.5 (range 21-35), and 16/20 had young children. On reviewing CC control in LA, we found most countries offer HPV vaccination, but not all programs are comprehensive and reach vulnerable populations (the poor, rural or underinsured) as exemplified by our small cohort and < 55% of women in LA eligible for CC screening receive it. Conclusions: In a six-month period at a single institution in Argentina, we identified 20 patients who were < 35 years of age, newly diagnosed with CC and presented with symptoms of advanced disease. These findings highlight the need for better CC prevention and screening programs in Argentina, Bolivia and Paraguay. In our previous review, we found that overall in LA, there is a need to build capacity for CC control and that the best strategy (HPV vaccination plus screening) will depend on each country/region. Importantly, CC programs must be tailored considering the needs of each population and available resources.
Patient-level predictors of lack of healthcare provider recommendation for human papillomavirus (HPV) vaccination as reported by childhood cancer survivors and their families.
Authors: Jocelyn M York, James L. Klosky, Yanjun Chen, James A. Connelly, Karen Wasilewski-Masker, Anna Giuliano, Leslie L. Robison, F. Lennie Wong, Melissa M. Hudson, Smita Bhatia, Wendy Landier
Journal: Journal of Clinical Oncology (2018)

10514 Background: Childhood cancer survivors are at increased risk for HPV-related morbidities, yet HPV vaccine initiation rates in survivors are low. Lack of healthcare provider recommendation for HPV vaccination is strongly associated with vaccine non-initiation (OR = 10.8, 95%CI, 6.5-18.0; J Clin Oncol, 2017; 35:3582-90). We aimed to examine patient-level predictors of lack of provider recommendation for HPV vaccination as reported by childhood cancer survivors and their families (hereafter referred to as NO RECOMMENDATION). Methods: Cancer survivors age 9-26y and 1-5y post-treatment completed a cross-sectional survey (parent-completed for survivors age 9-17y). NO RECOMMENDATION was evaluated as the outcome of interest in a multivariate logistic regression model that included relevant patient-level sociodemographic, clinical, and vaccine-related variables. Results: Participants included 955 survivors; 54% were male, 66% were non-Hispanic white, 59% had leukemia/lymphoma. Survivor age at survey (Mean±SD) was 16.3±4.7y; time off therapy was 32.8±14.7 months; 72% of participants reported NO RECOMMENDATION. Patient-level predictors associated with increased odds of NO RECOMMENDATION included perceived lack of insurance coverage for vaccine (OR = 3.7, p < .0001), male sex (OR = 3.2, p < .0001), black race (OR = 2.4, p = .003), and endorsement of barriers to vaccination (e.g., time, cost; OR = 1.8, p = .003). Predictors associated with decreased odds of NO RECOMMENDATION included older age (13-17y: OR = 0.3, p < .0001; 18-26y: OR = 0.3, p < .0001; referent group: 9-12y), non-Christian religion (OR = 0.4, p = .02), parent-child communication regarding HPV vaccine (OR = 0.6, p = .0001), and endorsement of social influences (e.g., opinions of friends/family) as important in HPV vaccine decision-making (OR = 0.8, p = .03). Conclusions: Nearly 3 in 4 childhood cancer survivors reported not receiving a healthcare provider recommendation for HPV vaccination. Interventions targeted to increase vaccine uptake should focus on factors influencing the provision of provider recommendation for HPV vaccination to all young cancer survivors.