tbuckley/cabot-search huggingface dataset:
Palliative care and health care utilization at the end of life.
Authors: Daniel P Triplett, Wendi G LeBrett, Rayna Matsuno, Lindsay Hwang, Isabel Boero, Eric Roeland, Heidi Yeung, James Don Murphy
Journal: Journal of Clinical Oncology (2016)

152 Background: Palliative care’s role in oncology has expanded, but its impact on aggressiveness of care at the end of life has not been characterized at the population level. Methods: This matched retrospective cohort study examined the effect of an encounter with palliative care on healthcare utilization at the end of life among 6,580 Medicare beneficiaries with advanced prostate, breast, lung, or colorectal cancer. We compared healthcare utilization before and after palliative care consultation to a matched non-palliative care cohort. Results: The palliative care cohort had higher rates of healthcare utilization in the 30 days prior to palliative care consult compared to the non-palliative cohort, with higher rates of hospitalization (risk ratio [RR] 3.33; 95% CI 2.87-3.85), invasive procedures (RR 1.75; 95% CI 1.62-1.88), and chemotherapy administration (RR 1.61; 95% CI 1.45-1.78). The opposite pattern emerged in the interval from palliative care consultation through death, where the palliative care cohort had lower rates of hospitalization (RR 0.53; 95% CI 0.44-0.65), invasive procedures (RR 0.52; 95% CI 0.45-0.59), and chemotherapy administration (RR 0.46; 95% CI 0.39-0.53). Patients with early palliative care consultation had larger absolute reductions in healthcare utilization compared to those with palliative care consultation closer to the end of life. Conclusions: This population-based study found that palliative care substantially decreased healthcare utilization among Medicare beneficiaries with advanced cancer. Given the increasing number of elderly patients with advanced cancer, this study emphasizes the importance of early integration of palliative care alongside standard oncologic care.
Analysis of overall survival and safety during the course of the phase III VELOUR trial comparing FOLFIRI and aflibercept or placebo in patients with mCRC that progressed on prior oxaliplatin treatment.
Authors: Paul Ruff, Radek Lakomy, Jana Prausová, Guy Van Hazel, Vladimir Mikhailovich Moiseyenko, Pankaj Bhargava, Josep Tabernero, Eric Van Cutsem
Journal: Journal of Clinical Oncology (2013)

451 Background: VELOUR is a large international, randomized placebo-controlled study that compared the efficacy and safety of FOLFIRI with aflibercept (ziv-aflibercept in the US) or with placebo in 1,226 mCRC patients who received prior oxaliplatin treatment. Aflibercept demonstrated statistically significant and clinically meaningful improvements in median OS (13.5 vs 12.06 months; HR=0.817, p=0.0032) as well as PFS and response rate. (Van Cutsem et al., J Clin Oncol. 2012). This analysis estimates the treatment effect and safety over the time course of the study. Methods: Hazard ratios (HR) by 6-month time periods were estimated using a piecewise Cox proportional hazard model. NCI-CTCAE version 3.0 was used to grade the severity of AEs. Results: There was improvement in the HR over time (Table) consistent with the survival curves that continue to separate past the median time point, indicating that the magnitude of the aflibercept treatment effect continues to increase over time. Incidence of grade 3 AEs (45.1% vs. 62.0%) was higher in the aflibercept + FOLFIRI arm; grade 4 AEs were placebo 17.4% vs. 21.4% aflibercept. More common AEs only occurred in a small proportion of aflibercept + FOLFIRI cycles (e.g., grade &gt;3 hypertension and diarrhea occurred in 3.6% and 2.8% of treatment cycles, respectively). The majority of grade 3-4 AEs occurred in early treatment cycles (first 3-4 cycles). Most patients experienced only a single episode of grade ≥3 AEs with aflibercept + FOLFIRI. Importantly, AEs in VELOUR did not impact patients’ ability to receive chemotherapy. Conclusions: Treatment with aflibercept plus FOLFIRI showed a continuous and consistent improvement in OS over time. Although combined grade 3-4 AEs were higher with aflibercept, AEs occurred early in treatment, in a small proportion of total cycles administered, and the majority were single episode in nature. Clinical trial information: NCT00561470. [Table: see text]
Modeling severe late rectal bleeding: Results on a large pooled population of prostate cancer patients.
Authors: Alessandro Cicchetti, Tiziana Rancati, Martin Ebert, Claudio Fiorino, Angel Kennedy, David John Joseph, James William Denham, Vittorio Vavassori, Giovanni Fellin, Riccardo Valdagni
Journal: Journal of Clinical Oncology (2016)

82 Background: To develop a model for grade 3 (G3) late rectal bleeding (LRB) after radical radiotherapy (RT) for prostate cancer, in a pooled population from 2 large prospective trials: Airopros0102 (Fellin RO2014) and TROG 03.04 RADAR (Ebert IJROBP2015). Methods: Both trials included patients (pts) treated with 3DCRT at 66-80Gy, conventional fractionation. Planning data were available for all pts, G3 LRB was prospectively scored using the SOMA/LENT, with a minimum follow-up of 3 years. Rectal dose-volume histograms were reduced to Equivalent Uniform Dose (EUD) calculated with volume parameter n derived by 3 studies: n=0.06 (Rancati RO2004), n=0.05 (Rancati RO2011) and n=0.018 (Defraene IJROBP2011). EUD was inserted into multivariable logistic regression (MVL) together with clinical and treatment features. Irradiation of seminal vesicles (SV), irradiation of pelvic nodes, hormonal therapy, hypertension, previous abdominal surgery (SURG), use of anticoagulants, diabetes, cardiovascular diseases and presence of acute toxicity were considered as potential dose-modifying factors. Goodness of fit was evaluated with Hosmer Lemeshow test (HL), calibration through calibration slope and AUC was used for discrimination power. Results: 1,337 pts were available: 708 RADAR and 669 Airopros. G3 LRB was scored in 95 pts (7.1%): 62 RADAR and 33 Airopros. EUD calculated with n=0.05 was the best dosimetric predictor for G3 LRB. A 4-variable MVL model was fitted including EUD (OR=1.07 p=0.16), SV (OR=4.75 p&lt;0.001), SURG (OR=2.30 p=0.02) and cardiovascular disease (OR=1.42 p=0.18). AUC=0.63, calibration slope=0.99 (R^2=0.89), p for HL=0.43. Inclusion of acute toxicity (OR=2.34 p&lt;0.001) slightly improved AUC (0.65), confirming a possible role of consequential injury. Conclusions: EUD with n=0.05 was predictive of G3 LRB in this pooled population, confirming the importance of sparing the rectum from high doses. Irradiation of seminal vesicles together with the presence of cardiovascular disease and previous abdominal surgery were relevant dose-modifying factors highly impacting the incidence of G3 LRB. The study was funded by: AIRC IG16087, Fondazione Monzino, NHMRC (300705, 455521, 1006447)
Ibrutinib (PCI 32765) Rapidly Improves Platelet Counts in Chronic Lymphocytic Leukemia / Small Lymphocytic Lymphoma (CLL/SLL) Patients and Has Minimal Effects On Platelet Aggregation
Authors: Mohammed Farooqui, Jay Nelson Lozier, Janet Valdez, Nakhle Saba, Ajunae Wells, Susan Soto, Delong Liu, Georg Aue, Adrian Wiestner
Journal: Blood (2012)
Bone mineral density and FRAX as predictors of fracture risk in women with breast cancer.
Authors: Beatrice J. Edwards, William John Gradishar, Maureen Smith, Jennifer A. Pacheco, Jaimee S Holbrook, June M Mckoy, Beatrice Nardone, Victoria Godinez-Puig, Andrew Bunta, Steven T. Rosen, Dennis P. West
Journal: Journal of Clinical Oncology (2013)

121 Background: The number of cancer survivors is rising in the USA, the 2007 CDC analysis of the SEER database estimated 11 million cancer survivors, with 90% being over the age of 65 years. Of these, 70% are women, and the most common cancer in survivors is breast cancer. Cancer therapy induced bone loss (CTIBL) contributes to an increase in fracture risk in women with breast cancer. Fractures are responsible for considerable morbidity, disability, hopitalizations and mortality in older adults. Fractures are often the cause for nursing home placement in seniors. Our objective was to analyze the prevalence of fractures after breast cancer therapy and to assess the effect of cancer therapy, clinical risk factors, bone density and the World Health Oragnization (WHO) fracture risk assessment [FRAX] as predictors of fracture occurrence. Methods: The study population consisted of breast cancer patients with invasive breast cancer who participated in a genetic databank within a NCI-Comprehensive Cancer Center. Demographic and clinical characteristics were abstracted from the EMR. Participants were followed for 6-12 years. Results: A total of 439 women with breast cancer were assessed; 79 had sustained fractures during the observation period (116 fractures), fractures occurred at multiple skeletal sites in 27 cases. The prevalence of fractures was 18%. Baseline characteristics revealed that women who sustained fractures were mostly Caucasian (91%, p=0.08), and had a family history of osteoporosis (36.9%, p=0.03). The time to fracture was 4.0 years (range 0-12 years) from diagnosis. Fracture cases had lower BMD at the femoral neck 0.86 ± 0.13 gm/cm2 (T-score= -1.0, p=0.04) than non- fracture cases, although BMD was in the low normal range. Eight cases of hip fractures were identified with a median age of 55 years (32-67 years) Median T-score -0.75. Cox proportional hazard analysis failed to identify any specific risk factors for fractures. Conclusions: Fractures occur shortly after commencing cancer therapy. BMD and FRAX risk calculation were not able to identify women who fractured. Occurrence of fractures in breast cancer raises the possibility of cancer-induced impairment in bone quality.
Maintenance bevacizumab after first-line treatment in HER2-negative metastatic breast cancer patients.
Authors: A. Fabi, M. Russillo, G. Metro, P. Papaldo, C. Nisticò, G. Ferretti, F. Cuppone, G. D'Auria, D. Giannarelli, F. Cognetti
Journal: Journal of Clinical Oncology (2011)

e11027 Background: Bevacizumab plus chemotherapy (BCt) is an effective combination for HER2 negative metastatic breast cancer (MBC). However, at the present time efficacy data on maintenance B after best response to BCt are lacking. Methods: An analysis of MBC patients (pts) treated with BCt followed by B maintenance therapy (BMT) was conducted, aiming at evaluating the outcome of B-maintenance therapy (BMT). Tumor assessment was conducted every three cycles and safety was evaluated every cycle. Maintenance-PFS was calculated from the start of BMT to the evidence of disease progression. Results: Out of 37 pts treated with BCt (B 10 mg/kg every 2 weeks + docetaxel 100 mg/m2 every 21 days or paclitaxel 80-90 mg/m2 on day 1,8,15 every 28 days for a total of 6-8 cycles), 29 pts (19 pts on B+docetaxel and 10 pts on B + paclitaxel) were not progressing and continued BMT at 15mg/kg every 3 weeks. Patients characteristics were as follows: median age 51 years (35-72), performance status 0 and 1 in 22 (76%) and 7 (24%) pts respectively, hormonal receptor positive (HR+) in 25 (86%), median disease free survival was 39 months (range: 0-362), untreated-CT pts for MBC 12 pts (41%), visceral metastatic sites in 19 (64%). Nineteen HR+ pts (65%) received BMT combined with hormonal agents (tamoxifen 1, AI 18). Median number of BMT administrations was 9 (1-28). Twenty-eigth patients were evaluable for response and safety: complete and partial responses from previous BCt were maintained in 3 (10%) and 11 (38%) pts, respectively (response maintenance: 48%). Ten pts (34%) maintained stability and 4 pts (14%) experienced progression. Median maintenance-PFS was 6.8 months (95% c.i.: 0.5-16.7). B+hormonal agents significantly increased PFS as compared with B monotherapy (p=0.03). No grade ≥3 B-related adverse events (GI perforation, wound-healing complications, arterial/venous thromboembolism or proteinuria) were reported during BMT. Five pts discontinued BMT for G3 proteinuria in 3 pts, G2 bleeding in 1 pt, G2 hypertension in 1 pt. Conclusions: BMT could be a feasible strategy in MBC. The efficacy in HR positive patients warrants further investigations.
Contemporary treatment patterns and short-term outcomes in men with very high-risk prostate cancer.
Authors: Jeffrey J. Tosoian, Debasish Sundi, Brian Francis Chapin, Emmanuel S. Antonarakis, Meera Chappidi, Ridwan Alam, Stephanie Glavaris, R. Jeffrey Karnes, Kenneth J. Pienta, Phuoc T. Tran, Edward M. Schaeffer, Ashley Ross
Journal: Journal of Clinical Oncology (2016)

103 Background: Beginning in 2014, the National Comprehensive Cancer Network (NCCN) recognized very high-risk (VHR) prostate cancer (cT3b-T4, or primary Gleason pattern 5, or more than 4 biopsy cores with Gleason score 8-10, or multiple HR features) as a classification distinct from high-risk (HR) disease. Using prospectively collected institutional data, we describe contemporary treatment patterns and short-term outcomes in the VHR population. Methods: Men who underwent radical prostatectomy (RP) between January 2010 and June 2015 were identified using the Johns Hopkins RP database, and trends in management were compared across the study period. Pathological and short-term clinical outcomes were assessed in men with VHR cancer. Non organ-confined disease (NOCD) was defined as ≥ pT3 disease or lymph node positivity, persistent postoperative PSA as ≥ 0.2 ng/mL, and biochemical recurrence (BCR) as a PSA ≥ 0.2 ng/mL following an initial undetectable postoperative PSA. Results: During the study period, 4,954 men underwent RP, of which 161 (3.2%) men had VHR cancer at diagnosis. The annual proportion of men who underwent RP with VHR cancer increased over the study period (chronologically 1.8%, 1.0%, 3.3%, 4.1%, 5.6%, and 5.2%; p&lt;0.001). Sixteen percent of men with VHR disease were enrolled in pre-surgical clinical trials, with an increase from 0% of men in 2010 to 19.1% in 2015 (p=0.11). At RP, 39% of the VHR cohort had seminal vesicle invasion, 26% had lymph node involvement, and a total of 74% had NOCD. Following surgery, 33% of men had PSA persistence, and 40% experienced either PSA persistence or BCR during follow-up (median 13.4 months). Of 136 men with at least one follow-up assessment, 15 (11.0%) developed metastasis; 33% of the cohort was treated with radiation therapy, 42% with androgen deprivation, and 15% with docetaxel. Conclusions: The VHR population carries the greatest risk of clinical progression following local treatment. Over the past five years, we have observed increasing surgical treatment and clinical trial enrollment at our institution. Continued assessment of post-operative interventions and outcomes will help to facilitate counseling and establish point estimates from which to power clinical trials.
Sex and funding trends in phase 3 oncology trials registered with clinicaltrials.gov.
Authors: Nicholas M. Moloci, Sarah Yee, David Tomczyk, Gordon Sun
Journal: Journal of Clinical Oncology (2014)

295 Background: Women have been historically underrepresented as authors of clinical research, which may obscure important scientific interpretations and perspectives. We examined whether primary investigator sex was associated with funding sources of registered phase 3 oncology trials. Methods: We searched ClinicalTrials.gov, identifying completed phase 3 oncology trials registered from 1/1/2005 to 12/31/2010. The first investigator sex and nationality, funding source, and cancer type were collected. Bivariate associations between first investigator and funding source were analyzed with chi-square tests. Temporal trends were analyzed using the Cochran Armitage test. Results: Of 1,365 trials, 882 listed an individual as first investigator and were eligible for analysis; 195 (22.1%) listed a woman as first investigator. From 2005 to 2010 the proportion of women as first investigator across all funding sources did not change significantly (p for trend &gt;.05). The proportion of breast and gynecological cancer trials led by women was significantly higher than the proportion led by men (29.3% of all trials led by women vs. 17.8% of all trials led by men, p&lt;.001). In contrast, the proportions of prostate cancer trials led by women and men were similar (7.7% vs. 6.8%, p&gt;.05). The National Institutes of Health (NIH) funded 95 trials with 32.6% led by women. Private industry funded 305 trials with 19.3% led by women. Of 659 trials funded by other sources such as universities and community-based organizations, 22.6% were led by women. The proportion of women leading industry trials increased from 11.3% to 27.3% (p for trend=.02), while the proportion of women leading trials by the NIH or other sources remained stagnant (p for trend&gt;.05). However, the odds of a woman leading a trial funded by the NIH were 1.84 (95% confidence interval: 1.16-2.92) times greater than the odds for a man (15.9% vs. 9.3%). Conclusions: Women may be underrepresented as lead investigators of oncologic clinical trials, though they do appear to lead a substantial number of breast and gynecologic cancer trials. Primary investigator sex was associated with both funding source and cancer type.
Phase l study of sorafenib in combination with radiation therapy and temozolomide for the first-line treatment of patients with high grade glioma.
Authors: A. F. Hottinger, A. Ben Aissa, A. Bodmer, D. Squiban, N. Dunkel, N. Maradan, M. I. Vargas, D. C. Weber, E. Brendel, P. Dietrich
Journal: Journal of Clinical Oncology (2011)

2054 Background: Sorafenib (Sb), an oral dual-action Raf kinase and VEGFR inhibitor, inhibits tumor cell proliferation and angiogenesis. Sb may further act as a potent radiosensitizer as it causes a time- and concentration-dependent arrest in G1, the most radiosensitive cell cycle phase. We conducted a phase I study to determine the safety and MTD of Sb in combination with radiation therapy and temozolomide (TMZ) as first line treatment of patients with high-grade gliomas. Methods: A traditional 3+3 dose escalation schema was employed. Patients were treated with radiation therapy (RT) to 60 Gy in 2 Gy fractions with TMZ 75 mg/m2 daily and Sb administered at 3 dose levels (DL1: 200 mg Sb daily, DL2: 200 mg Sb BID, DL3: 400 mg Sb BID) starting on day 8 of RT. Thirty days after the end of RT, patients were treated with monthly maintenance TMZ (150-200 mg/m2 D1-5/28) and Sb (400 mg BID). PK analyses were performed on day 8 for TMZ and day 21 for TMZ and Sb. Results: To date 14/15 planned patients with GBM have completed treatment. M/F: 5/9, median age: 52 years (range: 38-70). 6 patients have been treated at DL1 with 1 dose limiting toxicity (DLT) consisting of grade 4 pulmonary embolism, 5 at DL2 without DLT and 3 at DL3 with 2 DLTs (grade 4 dyslipidemia and grade 4 thrombocytopenia). The most common drug-related toxicities were thrombocytopenia (4 patients), fatigue (4), hypertension (4), hand-foot skin syndrome (3), skin reactions (3), leucopenia (1), constipation (1) and diarrhea (1). Geometric mean (GM) of Cmax of T were 6.18 (SD: 1.40) mg/L on day 8 (T alone) and 6.22 (1.79) mg/L on day 21 (T+S). GM of AUC(0-24) of T were 11.9 (1.18) mg*h/L and 13.6 (1.19) mg*h/L on day 8 and 21 respectively. GM of Cmax and AUC(0-12) for S on day 21 were 2.54 (1.95) mg/L and 19.8 (1.69) mg*h/L respectively. Studies for the other DLs are ongoing. Conclusions: The combination of Sb with RT and TMZ is safe and well tolerated at a dose of 200 mg Sb BID + 75 mg TMZ daily. PK parameters indicated that Sb had no effect on the bioavailability of TMZ. Outcome results will be available at the meeting.
Randomized, multicenter phase II study of erlotinib (E) or E plus fulvestrant (F) in previously treated advanced non-small cell lung cancer (NSCLC).
Authors: E. B. Garon, S. M. Dubinett, F. F. Kabbinavar, K. L. Reckamp, D. C. Marquez-Garban, L. Goodglick, S. Sharma, L. P. Stabile, J. Siegfried, R. J. Pietras
Journal: Journal of Clinical Oncology (2011)

TPS216 Background: Inhibition of the EGFR pathway with E is an established therapy for second- and third-line NSCLC. Estrogen receptors (ERs) and aromatase are expressed in most NSCLC specimens. NSCLC growth is stimulated by estrogens, and this effect is blocked by antiestrogens (including F) in preclinical models (Weinberg et al. Cancer Res, 2005; Siegfried et al. Semin Oncol, 2009). An increased incidence (Slatore et al. J Clin Oncol, 2010) and risk of death (Chlebowski et al. Lancet, 2009) from NSCLC is reported in patients randomized to receive hormone replacement therapy. A reduced risk of death from lung cancer is found in breast cancer patients treated with antiestrogens (Bouchardy et al. Cancer, 2011). Extensive cross-talk occurs between ER and EGFR pathways in lung cancer (Stabile et al. Cancer Res, 2005; Marquez et al. Steroids, 2007). Methods: This Phase II clinical study evaluates whether F adds to antitumor efficacy of E. Patients are randomized in a 2:1 ratio to receive E (150 mg PO qd) + F (500 mg IM q2wk x 3, then q4wk) or E alone. Response rate is the primary endpoint, and secondary endpoints include correlation between clinical response and expression of ERα, ERβ, EGF/HER-1 receptor and HER-2/neu biomarkers. Targeted enrollment is 102 patients. Eligibility: Men and women (pre- and post-menopausal) with advanced NSCLC and at least one prior chemotherapy regimen (unless patient refuses) are eligible. Patients must have sufficient available tissue for study of biologic correlates, including EGFR mutation analysis and gene copy number and studies evaluating ERα, ERβ and aromatase. Current Enrollment: More than half of the study has been enrolled to date, with recruitment ongoing in the TORI network at sites located in Southern California, Nevada, Colorado and Indiana. Supported by NIH Lung Cancer SPORE P50-CA90388 and P50-CA090440, AstraZeneca, Genentech, Stiles Program.