tbuckley/cabot-search huggingface dataset:
Correlation of body mass index (BMI) with outcomes in endometrial cancer (EC) patients receiving adjuvant radiation (RT).
Authors: Yada Kanjanapan, Ming-Yin Lin, Kailash Narayan, Alan Herschtal, Linda R. Mileshkin
Journal: Journal of Clinical Oncology (2016)

e17115 Background: Obesity is a risk factor for developing EC, but its impact on treatment outcome is less clear. Previous studies, mostly of EC patients treated by surgery alone, found higher risk of death but not of disease recurrence in the obese. We specifically assessed women who additionally received adjuvant RT, for an association between BMI, recurrence pattern, survival and RT toxicity. Methods: A prospective unit database was retrospectively analysed for EC patients receiving adjuvant RT at an Australian comprehensive cancer centre between 1/2000-12/2013. Cox proportional hazards regression tested for a relationship between BMI and overall survival (OS), adjusting for potential confounders. Patients with BMI ≤ 30 and BMI > 30 were compared for relapse site (pelvic, paraaortic, distant) and RT toxicity using logistic regression. Results: 215 patients with 3.6 years median follow-up were identified. 105 (49%) had BMI > 30, with no significant differences in baseline characteristics to the BMI ≤ 30 group. 39 (35%) of BMI ≤ 30 and 43 (41%) of BMI > 30 patients had type 1 EC, p = 0.41. Lymphadenectomy was performed in 26/105 (25%) of BMI > 30 and 39/110 (35%) of BMI ≤ 30 patients, p = 0.09. Chemotherapy (adjuvant, concurrent with RT or both) was used for 23% of BMI ≤ 30 and 31% of BMI > 30 patients, p = 0.23. There was no association between BMI and OS (HR 0.97, 95% CI 0.93 – 1.01, p = 0.18); 5-year survival rate was 70% (BMI ≤ 30) and 78% (BMI > 30). On multivariate analysis, only stage (HR 1.49, 95% CI 1.07 – 2.08, p = 0.02) and tumour grade (HR 3.65, 95% CI 1.85 – 7.19, p < 0.001) were significantly associated with OS. 22/161 (13.7%) cases with a minimum of 2 years of follow-up relapsed; most commonly in the pelvis (n = 16) followed by paraaortic (n = 11) and distant sites (n = 8). Half of the patients who relapsed did so at multiple sites. No association was found between BMI and progression-free survival, site of relapse or toxicity rates. Conclusions: BMI did not affect outcome in this cohort of EC patients receiving adjuvant RT. Tumour stage and grade remained prognostic for survival. Obese patients did not have a propensity for increased pelvic relapse, supporting effective local therapy delivery without unacceptable toxicity.
Racial/ethnic differences in neurocognitive, emotional and quality of life outcomes in adult survivors of childhood cancer: A report from the Childhood Cancer Survivor Study (CCSS).
Authors: Stephanie Dixon, Nan Li, Yutaka Yasui, Smita Bhatia, Jacqueline N. Casillas, Todd M. Gibson, Wendy Leisenring, Kirsten K. Ness, Jerlym Porter, Leslie L. Robison, Melissa M. Hudson, Kevin R. Krull, Gregory T. Armstrong
Journal: Journal of Clinical Oncology (2018)

10567 Background: Survivors are at risk of impaired neurocognitive/emotional functioning and health related quality of life (HRQOL). The impact of CNS-directed therapy by race/ethnicity has not been reported. Methods: Analyses included 12,257 ≥5-yr survivors of childhood cancer: median age at follow-up 31.2 yrs (range 16.1-54.1), 490 non-Hispanic Black (NHB), 725 Hispanic (H) survivors and 2994 siblings. Self-reported neurocognitive (working memory, task efficiency, emotional regulation, organization), emotional (depression, anxiety, somatization) and HRQOL (components assess physical, emotional and mental health, social functioning, pain and vitality) outcomes were evaluated using the CCSS Neurocognitive Questionnaire, BSI-18 and SF-36. Impact of cranial radiotherapy (CRT) was investigated using general linear models adjusted for clinical/demographic factors to estimate differences in mean scores between survivors and siblings within racial/ethnic stratum. The magnitude of differences for NHBs and Hs were compared to those of non-Hispanic Whites (NHW). Results: Among non-CRT exposed survivors, no significant differences were observed between NHB, H and NHW for all neurocognitive, emotional, and HRQOL outcomes. Among CRT exposed survivors, while there were no significant differences for neurocognitive outcomes by race/ethnicity, mean scores for depression differed between H survivors vs siblings (49.9. vs 46.5, p < 0.001), which was greater than NHW survivors vs siblings (49.2 vs. 47.7, p < 0.001; p comparing differences in means between H and NHW = 0.047). Survivor-sibling differences in mean HRQOL scores for social functioning for NHB (-7.70, p = 0.02) and H (-6.27, p = 0.01) survivors exposed to CRT were greater than for NHW (-1.48). Conclusions: After CRT exposure, there were no differential effects on neurocognitive outcomes based on race/ethnicity. However, minority survivors who received CRT had increased risk for depression and reduced social function. The role of environmental and socio-economic factors in helping survivors recover from CRT exposure should now be investigated.
Outcome of EGFR mutant patirnts included in a clinical trial after progression on EGFR TKI.
Authors: Nuria Pardo Aranda, Jordi Remon, Alex Martinez Marti, Ana Maria Martinez de Castro, Susana Cedres Perez, Alejandro Navarro, Eulalia Scheenaard, Adelaida Piera, LLuisa Carbonell, Ana Vivancos, Enriqueta Felip, Esther Gámez Córdoba
Journal: Journal of Clinical Oncology (2017)

e20555 Background: EGFR mutant(EGFRm) NSCLC patients develop adquired resistance after 12 months on EGFR TKI. Acquired T790mutation(T790M) is the most common mechanism of resistance in around 60% of patients, followed by MET amplification in 20% of cases. Inclusion in a clinical trials at progression may have an impact in patients’ outcome. Methods: We retrospectively assessed the overall survival in EGFRm patients according to post-progression treatment on 1 st /2 nd generation EGFR TKI: standard vs. experimental (clinical trial). Also, we assessed the survival in the cohort of acquired T790M NSCLC patients(p). X 2 test and long rank test P values are described. OS was defined since progression 1 st /2 nd generation EGFR TKI to death or last follow up Results: 42p EGFRm were enrolled. According to EGFRm subtype (24 p EGFR del19, 14p EGFR L858R, 1p EGFR exon18, 1 EGFR exon20 ,2p unknown). Median age was 58 (33-83) and 27 (64%) females. First-line EGFR TKI was 30% gefitinib / 58 % erlotinib /10 % afatinib/2% dacotinib At PD, in 51 biopsies (b) were performed,11p were biopsy twice.Tumor tissue for molecular determinations was available in in 86% of cases. Druggable molecular alterations were detected in 57% of cases: 20 acquired T790M and 4 MET amplification. According to these results all 24 p were enrolled in a clinical trial (NCT02108964,NCT01802632,NCT02147990,NCT02335944, NCT02151981), and 18p were screening failure; 8p (45%) of them due to abscense of adquired resistance mechanisms. 10 received platinum-based chemotherapy and 6 only received best supportive care. OS metastatic disease was 51 months for patients included in a clinical trial vs 22 months for those on standard treatment (p &lt; 0.001; 95%CI: 14.4-47). OS was: 34 months vs 10 months for those included in a clinical trial vs standard, respectively (p &lt; 0.001; 95%CI: 8.88-25). For T790M tumours, OS post-progression was 25 months Conclusions: Enrolling patients in clinical trials may allow personalised treatment according to mechanisms of resistance improving survival after 1st/2nd generation EGFR TK progression disease.
Malignant pleural effusions: Do race, obesity and comorbidities play a role?
Authors: Lauren Schmalz, Zachary Michael Trisel, Stuthi Perimbeti, William May Lee, David Lane Topolsky, Pamela A. Crilley, Kristine Marie Ward, Michael Styler
Journal: Journal of Clinical Oncology (2018)

e18679 Background: Malignant pleural effusions (MPE) are a common complication of many neoplasms. No research to date has identified the impact of demographics, comorbidities, and lifestyle choices associated with MPE. Thus, we sought to identify predicting factors associated with the development of MPE in patients with breast (BC), lung (LC), ovarian cancer (OC), and lymphoma (L). By helping identify patients at risk for developing MPE, would heighten vigilance in screening for this complication. Methods: We analyzed data from the Healthcare Cost and Utilization Project’s National Inpatient Sample between 1999-2014 using ICD 9 codes to identify a primary diagnosis of BC, LC, L, OC with MPE. Statistical significance was determined using chi-square testing for bivariate analysis for frequency distribution and multivariate analysis to determine the hazard ratios. Multivariate analysis was performed using Cox Proportional hazard assumption and Charlson comorbidity index to identify risk factors for MPE. Results: Conclusions: Understanding risk factors involved in the development of malignant pleural effusions can help guide prudence in obtaining a diagnosis as well as anticipation of treatment strategies. Further research is needed to explain why there is a higher incidence of MPE in African Americans, obesity, and ESRD, in contrast to LC which had a lower incidence of MPE in ESLD. MPE in Obese (O) vs Non-Obese (NO) Pts P-Value BC NO 2.3678 0.0016 O 3.0905 LC NO 9.2024 < .0001 O 15.7651 L NO 1.4048 < .0001 O 2.1203 OC NO 2.3833 0.0016 O 3.668 Risk for mortality for MPE relative to Caucasians BC LC L OC P-Value Hazard Ratio P-Value Hazard Ratio P-Value Hazard Ratio P-Value Hazard Ratio AA 0.3525 0.954 < .0001 0.83 0.5302 1.03 < .0001 1.328 Hispanic 0.2453 0.917 < .0001 0.802 0.0177 0.898 0.7638 0.979 Other 0.0437 0.842 0.0018 0.908 0.1068 0.917 0.1277 0.881 MPE in Pts with/without ESRD* and ESLD# BC P-value LC P-value L P-value OC P-value No ESRD 2.3954 < .0001 9.3425 < .0001 2.4513 < 0001 1.4154 < .0001 ESRD 8.5061 18.9315 8.6655 5.064 No ESLD 2.4055 0.0032 9.4084 0.0002 2.4656 0.757 1.4343 0.9763 ESLD 5.658 3.0665 3.0623 1.459 *ESRD - end stage renal disease #ESLD - end stage liver disease
TCT-456 Association of Immediate Improvement in Renal function after Transcatheter Aortic Valve Replacement and Post-operative Outcomes in Patients with Renal Dysfunction
Authors: Alexis Okoh, Kamrani Kambiz, Setri Fugar, Dileep Unnikrishnan, Mohammad Thawabi, Amer Hawatmeh, Bruce Haik, Chunguang Chen, Marc Cohen, Mark Russo
Journal: Journal of the American College of Cardiology (2018)
Patterns of care and outcome of patients (pts) with metastatic soft-tissue sarcoma (STS) according to histological subtype and treatment setting: The METASTAR study.
Authors: Antoine Italiano, Axel Le Cesne, Jean-Yves Blay, Isabelle Laure Ray-Coquard, Olivier Mir, Maud Toulmonde, Philippe Terrier, Dominique Ranchère-Vince, Pierre Meeus, Eberhard Stoeckle, Charles Honoré, Paul Sargos, Marie-Pierre Sunyach, Cecile Le Pechoux, Antoine Giraud, Carine A. Bellera, Marion Savina, Jean-Michel Coindre
Journal: Journal of Clinical Oncology (2016)

11014 Background: There are only limited data on the outcome of pts with metastatic STS according to the histological subtype and the treatment setting. Methods: Data from 2225 pts with metastatic STS and included in the CONTICANET database were analyzed. Histological diagnosis was centrally reviewed in all the cases. Time to next treatment (TNT) was defined time from systemic treatment onset to next treatment or death of any cause, whichever comes first. Overall survival (OS) was defined time from systemic treatment onset to last patient contact or death of any cause. Results: Median follow-up was 58 months. Median age was 56 yrs (range 18-93). The five most frequent histological subtypes were: leiomyosarcoma/LMS (22.4%), undifferentiated pleomorphic sarcoma/UPS (19.4%), dedifferentiated liposarcoma/DDLPS (9.3%), synovial sarcoma/SS (8.7%), and MPNST (3.7%). 1600 (72%), 950, 650, 496, 232, 134 received 1, 2, 3, 4, 5 or ≥ 6 lines of treatment respectively. Age > 75 yrs (11.5% of all pts) was significantly associated with a lower probability to receive a treatment. The 1st line regimen contained anthracycline and more than one drug in 56% and 46% of cases respectively. 175 pts (8%) received an investigational agent during the course of their disease. The objective response rates in the 1st, 2nd, 3rd, and 4rd line setting was 32%, 19.5%, 12%, and 10.5% respectively. TTNT and OS according to the treatment line setting for the 5 five most frequent histological subtypes are described in the table. 222 pts were alive at 5 years (10%). Conclusions: Patients with metastatic LMS have the best outcome and those with UPS the worst. The benefit of systemic therapy beyond the 2nd line setting is limited except for LMS. Prognostic analyses, correlation between tumor response, TTNT and OS, and impact of local therapy, off-label and investigational agents will be presented at the meeting. TTNT/OS (months) TTNT1/OS1 TTNT2/OS2 TTNT3/OS3 TTNT4/OS4 LMS 7.6/24.4 5.7/17 4.6/12 4.3/9 UPS 4.2/9.3 3.5/6.2 2.5/5.2 2.5/5.2 DDLPS 4.3/11.7 5.6/9.5 2.4/6.5 3.2/3.9 SS 8.3/18.6 5.7/11.7 3.4/7.7 2.3/5.9 MPNST 3.9/12.2 2.8/6.8 3.3/7.9 2.7/5.4
Successes and challenges faced by tissue collection during trials by oncology translational sciences.
Authors: Martine P Roudier, Vidalba Rocher Ros, Caroline Hirst, Myria Nikolaou, Gemma N Jones, Sophie E Willis, William J Howat, J Carl Barrett, Elizabeth Harrington
Journal: Journal of Clinical Oncology (2018)

2538 Background: Knowledge of the success rates in obtaining baseline and on treatment tumour biopsies with sufficient evaluable tumour tissue is valuable in guiding strategies for evaluation of PD biomarker analysis in future clinical trials. Methods: We present a 12 month translational experience collecting patient paired-biopsies for pharmacodynamic (PD) biomarker evaluation in a multi-centre, multi-trial context. We analysed - 152 specimens, 72 pairs, for tumour content success rate and pair biopsy success rate in 8 investigational clinical trials. The tumour content was defined as successful when the biopsy contained greater than 100 tumour cells. All biopsies were formalin fixed paraffin embedded at the clinical sites and blocks or unstained slides were sent to a central pathologist for evaluation of tumour content and relevant PD biomarkers. Results: Tumour organ sites were per pair: bone (n = 14), lung (n = 16), prostate (n = 11), liver (n = 11), and no organ site (n = 20). Tissue size was an average of 17.25 mm2 (range: 2-88 mm2). Tumour content in skin biopsies was 42.7% (range 0-80%) and yielded the best tumour content sampling as compared to deep organ biopsies: bone:2.2% (range 0-20%); prostate: 20.3% (range 0-80%), liver: 27% (0.1-60%; lung: 28.1 % (0-60), no indication of organ site: 42.6% (range 1-90%). There was no correlation between tissue size and tumour content (r = - 0.083). Tumour content success rate was globally 40%. Conclusions: In summary, paired biopsies were 40% successful in sampling patient tumour. However 30% of them were evaluated without indication of primary or metastatic tumour status or initial tumour histopathology diagnosis. Processes to link meta-data collection (organ site or pathology report) with biopsies are in progress as well as encouragement to bone scan guiding when bone metastasis biopsies are necessary.
Successive domain rearrangements underlie the evolution of a regulatory module controlled by a small interfering peptide
Authors: João Raimundo, Rómulo Sobral, Sara Laranjeira, M Manuela R Costa
Journal: Molecular Biology and Evolution (2018)

The establishment of new interactions between transcriptional regulators increases the regulatory diversity that drives phenotypic novelty. To understand how such interactions evolve, we have studied a regulatory module (DDR) composed by three MYB-like proteins: DIVARICATA (DIV), RADIALIS (RAD), and DIV-and-RAD-Interacting Factor (DRIF). The DIV and DRIF proteins form a transcriptional complex that is disrupted in the presence of RAD, a small interfering peptide, due to the formation of RAD-DRIF dimers. This dynamic interaction result in a molecular switch mechanism responsible for the control of distinct developmental processes in plants. Here, we have determined how the DDR regulatory module was established by analyzing the origin and evolution of the DIV, DRIF, and RAD protein families and the evolutionary history of their interactions. We show that duplications of a pre-existing MYB domain originated the DIV and DRIF protein families in the ancestral lineage of green algae, and, later, the RAD family in seed plants. Intraspecies interactions between the MYB domains of DIV and DRIF proteins are detected in green algae, whereas the earliest evidence of an interaction between DRIF and RAD proteins occurs in the gymnosperms, coincident with the establishment of the RAD family. Therefore, the DDR module evolved in a stepwise progression with the DIV-DRIF transcription complex evolving prior to the antagonistic RAD-DRIF interaction that established the molecular switch mechanism. Our results suggest that the successive rearrangement and divergence of a single protein domain can be an effective evolutionary mechanism driving new protein interactions and the establishment of novel regulatory modules.
Indication specific pricing for targeted therapies: Using bevacizumab as an example.
Authors: John P. Geisler, Kelly J Manahan
Journal: Journal of Clinical Oncology (2018)

e18939 Background: Medications in the U.S. are approved by the FDA based upon safety and efficacy data, not price. The object of this study was to model (or forecast) potential prices for bevacizumab in cervical and colon cancer using indication specific prices using various willingness-to-pay (WTP) thresholds ($50,000 – 150,000 per QALY), a cost-utility economic methodology. Methods: Information from phase III studies was examined with pharmacoeconomic techniques, specifically Markov analysis and deterministic sensitivity analysis. Results: The per cycle cost of bevacizumab for both indications is currently $11,481 for a 100 kg patient ($76.54/10mg, Medicare Average Sales Price (ASP)+6%). If a WTP of $50,000/QALY was used, the cost of bevacizumab should be lowered to $29.15/10mg for cervical cancer and $11.80/10mg for colon cancer. If instead a WTP of $100,000/QALY was the target, the cost should be decreased to $63.38/10mg for cervical cancer and $30.22/10mg for colon cancer. Alternatively, if a WTP $150,000/QALY was chosen, the price would be increased to $97.63/10mg for cervical cancer and still decreased to $48.78/10mg for colon cancer. This would be a 36% increase in cost per dose for a cervical cancer indication and a 32% decrease in cost per dose for an indication of colon cancer. Conclusions: Indication specific pricing would change prices for bevacizumab when used for cervical cancer and colon cancer depending on the WTP target.
Nanoparticle micellar formulation of paclitaxel in combination with carboplatin for women with recurrent platinum sensitive ovarian cancer (OAS07-OVA): Overall survival results of a phase 3 randomized trial.
Authors: Nina Heldring, Helena Bjermo, Arija Brize, Alla Sergeevua Lisyanskaya, Ignace Vergote
Journal: Journal of Clinical Oncology (2018)

5560 Background: The primary objective in the pivotal trial OAS-07OVA was reached and it was demonstrated that Paclical, a nanoparticle micellar formulation of paclitaxel (Oasmia Pharmaceutical AB) is non-inferior to Cremophor-EL Paclitaxel in terms of progression free survival (PFS) in the treatment of recurrent platinum-sensitive ovarian, fallopian tube or peritoneal carcinoma. Paclical is given as 1-h infusion without standard use of premedication. The follow-up analyses presented here includes overall survival (OS) and subgroups of PFS and OS. Methods: In this open 1:1 randomized 2-armed phase 3 study, 789 patients were included 2009 - 2012 in 81 centers. Non-inferiority in terms of OS was included as a secondary objective, anddefined as the time between date of randomization and death. Following the end of study, information of the death of participating patients was collected on a special form until August 2016. The upper non-inferiority limit of the one-sided confidence interval of the hazard ratio of the two treatment arms was set to 1.185. Results: Non-inferiority of OS was showed as the hazard ratio estimated based on a Cox proportional hazards model stratified by CA125 and relapse was 0.95 (95% CI: 0.78; 1.16) in the PP population. The median overall survival time was 25.7 months in the Paclical arm and 24.8 months in the Taxol arm. Non-inferiority of OS was also seen in patients experiencing their first relapse, and patients with serous adenocarcinoma at diagnosis. In addition, sensitivity analyses as well as subgroup analyses showed a consistent tendency of favor for Paclical in terms of PFS. Conclusions: Paclical is non-inferior to Taxol with respect to OS and PFS for patients with recurrent platinum-sensitive ovarian cancer. Even though the pivotal study was not designed to show superiority, subgroup analyses show a consistent tendency of favor for Paclical in terms of OS and PFS indicating a benefit for the Paclical group. Clinical trial information: NCT00989131, Eudra CT: 2008-002668-32 Clinical trial information: 2008-002668-32.
A randomized phase II study evaluating efficacy and safety of SOX versus mFOLFOX6 as neoadjuvant chemotherapy for patients with resectable rectal cancer (KSCC1301).
Authors: Kenji Katsumata, Eiji Oki, Hiroyuki Kato, Keisuke Miwa, Masahiko Sugiyama, Hidetsugu Murakami, Hiroshi Hasegawa, Shinichiro Mori, Goro Nakayama, Hiroshi Saeki, Mototsugu Shimokawa, Yoshihiro Kakeji, Hideo Baba, Yoshito Akagi, Yoshihiko Maehara
Journal: Journal of Clinical Oncology (2017)

3549 Background: Neoadjuvant radiotherapy is the current standard of care for rectal cancer. However, radiation therapy is sometimes associated with short-term severe toxicity and long-term morbidity. Perioperative introduction of new chemotherapy agents without radiotherapy for locally advanced rectal cancer (LARC) may be a promising option. Several studies of combination chemotherapy with oxaliplatin plus S-1 (SOX) have reported promising efficacy and safety in patients with metastatic colorectal cancer, suggesting a potential replacement for mFOLFOX6. Methods: A randomized phase II trial was undertaken to compare the efficacy and safety of SOX and mFOLFOX6 as neoadjuvant chemotherapy for patients with LARC. Patients were randomly assigned to receive mFOLFOX6 (every 2 weeks; day 1: 400 mg/m 2 bolus 5-fluorouracil [5-FU]; days 1 and 2: 2,400 mg/m 2 continuous 5-FU; day1: 200mg/m 2 l-LV; and day 1: 85 mg/m 2 oxaliplatin) or SOX (every 3 weeks; days 1–14: 80 mg/m 2 oral S-1; and day 1: 130 mg/m 2 oxaliplatin). The protocol period for neoadjuvant chemotherapy was 3 months. The primary endpoint was the 3-year disease-free survival rate (3y DFS), and the secondary endpoints included pathological effect, R0 resection rate, survival and safety. Results: Between September 2013 and October 2015, 110 patients were enrolled and randomized (56 received SOX and 54 received mFOLFOX6). Baseline characteristics were balanced between the two arms. The major adverse events were neutropenia, peripheral neuropathy, loss of appetite, and fatigue. The incidence of grade 3 or higher neutropenia based on the CTCAE Vers.4.0was 13.2% in the SOX group and 32.0% in the mFOLFOX6 group. The surgical completion rate was 100% for the SOX group and 96% for the mFOLFOX6 group. The incidence of grade II or more surgical site infection based on Clavien-Dindo classification (CD) was 11.3% and 4.2% for the SOX and mFOLFOX6 groups, respectively. The CD grade III anastomosis-related complications developed in 7 cases in total. Conclusions: The KSCC1301 study suggests that neoadjuvant chemotherapy without radiation is active and safe. The results of pathological response will be provided. Clinical trial information: UMIN000011486.