tbuckley/cabot-search huggingface dataset:
Phase I study of ipilimumab (IPI) with biochemotherapy (BCT) for chemonaïve patients with metastatic melanoma (MM).
Authors: Rodabe Navroze Amaria, Roland L. Bassett, Lauren Simpson, Frances Delaney, Patrick Hwu, Kevin Kim, Wen-Jen Hwu, Sapna Pradyuman Patel, Isabella Claudia Glitza, Michael A. Davies, Scott Eric Woodman, Cassian Yee, Agop Y. Bedikian
Journal: Journal of Clinical Oncology (2015)

e20014 Background: Chemotherapy induced tumor cell death triggers immune response which can be potentiated by the use of immune stimulating checkpoint blockade. We have conducted a first in human, phase I, open-label, dose escalating clinical trial using BCT with IPI. Methods: Adult chemonaïve pts with MM with normal baseline organ function were eligible for this trial. The induction phase consisted of treatment with four courses of temozolomide 200mg/m2 orally days 2-5, cisplatin 25mg/m2 IV days 2-4, interferon alpha 2b 5 million u/m2 subcutaneous days 2-6 with interleukin-2 (IL2) (7 or 9 million IU/m2 as a 96 hour continuous infusion) and IPI (1mg/kg, 3mg/kg, 10mg/kg) d1 in a 3+3 dose escalation design. The consolidation phase consisted of 3 cycles of IPI with IL-2 and interferon and the maintenance phase consisted of IPI dosed every 3 months for a maximum of 6 cycles. Results: A total of 17 pts (14 men) have been treated to date and are evaluable for dose-limiting toxicity (DLT). The median age was 49 and all pts had ECOG PS of 0. The majority (12/17, 71%) were M1c. Dose finding is ongoing and the current cohort is being treated with IPI 10mg/kg and 7 million IU/m2 of IL2. There have been three dose limiting toxicities thus far including hypotension, vascular access complications and colitis. Grade 3-4 dermatitis was seen in 10 (59%) pts, in most cases starting after cycle 2 of induction therapy. Among pts evaluable for clinical response (n = 16) the overall response rate is 63% (1 CR, 9 PR), disease control rate is 94%, median progression-free survival is 6.7 months and the median overall survival is 16.2 months. One pt has completed the entire course of therapy, one is in the maintenance phase and the other 15 pts were removed from protocol early due to disease progression (6 pts), toxicity (6 pts) or the combination of both (3 pts). Conclusions: IPI with BCT is a highly efficacious regimen for patients with MM with promising clinical activity, response rates and disease control rates even in the phase I setting. Toxicities are cumulative with dermatitis in later courses primarily contributing to therapy discontinuation. Dose finding is ongoing and a dose expansion at the recommended phase II dose is planned. Clinical trial information: NCT01409174.
Variation in the use of granulocyte-colony stimulating factor (G-CSF) for dose dense paclitaxel: A single institution retrospective study.
Authors: Flavia Rocha Paes, Ines Maria Vaz Duarte Luis, Rafael Brant Costa, Otto Metzger Filho, Melissa E Hughes, Katya Losk, Kristen Camuso, Craig Alan Bunnell, Mehra Golshan, Eric P. Winer, Nancy U. Lin
Journal: Journal of Clinical Oncology (2015)

561 Background: In randomized trials, administration of dose dense (dd) doxorubicin and cyclophosphamide (AC) followed by paclitaxel (T) with G-CSF support improved outcomes compared with every 3 week dosing in the adjuvant treatment of early breast cancer. However, the use of G-CSF in dd regimens is associated with increased cost and its utility for the T portion of this regimen is unclear. We studied patients (pts) treated with ddACT to investigate variation in the use of G-CSF among the medical oncologists at our NCI designated cancer center. Methods: Among 523 pts treated with adjuvant chemotherapy from 01/2011 to 12/2013, we identified pts who received ddACT. Descriptive analyses were used to analyze patterns of G-CSF use in the T portion of this regimen, and the impact of G-CSF use on delays, toxicity and treatment completion. Results: Overall, 155 pts (29.6%) were treated with ddACT by 26 providers during the study period. Variation in the use of G-CSF by provider and by patient was found. 21 (13.6%) pts did not receive any G-CSF support during the T portion of ddACT, with 11 providers choosing this approach in at least one pt. The majority of pts (134, 86%) received G-CSF support in at least one of the cycles, ranging from 17% of pts receiving G-CSF in one cycle to 48% of pts receiving G-CSF in all 4 cycles. Reasons for omitting of G-CSF included high baseline absolute neutrophil count and pain. Among the 21 pts who did not receive G-CSF with any cycle there were no treatment delays and no reports of febrile neutropenia; 90.4% (n = 19) completed treatment. Among the 134 pts treated with G-CSF during at least 1 cycle, 6 % had a treatment delay and 94.7% (n = 127) completed treatment. Conclusions: We identified variation in the use of G-CSF among medical oncologists in the administration of ddACT at our comprehensive cancer center. In addition, many physicians did not utilize G-CSF in a consistent fashion. Omitting of G-CSF was not associated with treatment delays or adverse events, though our sample size was small. To provide data to support uniform institutional practice, a prospective study formally evaluating the feasibility of delivering dd paclitaxel without routine G-CSF support is planned.
Permanent seed brachytherapy for low risk prostate cancer, long term outcome, and urinary toxicity.
Authors: Hamid Raziee, Alejandro Berlin, Peter W. M. Chung, Joelle Antoine Helou, Haiyan Jiang, Juanita M. Crook, Charles N Catton
Journal: Journal of Clinical Oncology (2017)

66 Background: Low dose rate seed brachytherapy is an established treatment modality for low risk prostate cancer (CaP). Herein, we report long term biochemical control and urinary toxicity from a single institution. Methods: Data from a prospectively-collected institutional database was used, completed with retrospective chart reviews. All patients with low-risk CaP (NCCN criteria) who underwent ultrasound-guided permanent iodine-125 brachytherapy from March 1999 to December 2005 were included. Urinary function was evaluated by the International Prostate Symptom Score (IPSS). PSA relapse was defined by Phoenix Criteria (nadir + 2 ng/ml). Time to IPSS return-to-baseline score ±3 was recorded. Results: 582 patients with a median age of 64 years were included. Median initial PSA was 5.5 ng/ml (0.3-10). 66% and 34% were T1 and T2a, respectively. Gleason score was 6 (96%) and &lt; 6 (4%). Prescription dose was 145Gy, with a median V100 coverage of 94% (IQR [interquartile range] 89-97%) and median D90 of 157Gy (IQR 144-171 Gy). With a median follow up of 131 months (IQR 94-149 months), 27 patients showed biochemical failure (4.6%), and PSA bounce was detected in 38 cases (7%). Biochemical progression-free rates were 97% (96-98%), 96% (94-97%), and 94% (91-96%) at 5, 10, and 15 years, respectively. Median PSA level at 5, 10 and 15 years was 0.06, 0.05 and 0.018 ng/ml, respectively. PSA relapses were observed out to 148 months. At 1, 5, 10 and 15 years, 5.5%, 16.5%, 39.5% and 89.2% of patients were lost to PSA follow up. Median baseline IPSS score was 5. In 515 (88.5%) patients IPSS returned to baseline, with a median time to return-to-baseline of 9 months. The proportion of return-to-baseline at 1, 2, 5, and 10 years was 62%, 75%, 88%, and 90%, respectively. 22 (4%) patients required post-implant urinary catheter. After 3, 6 and 12 months, 9 (1.5%), 6 (1%) and 4 (0.7%) patients continued to be catheterized. Conclusions: Within the limits of retrospective analysis, permanent seed brachytherapy for low risk prostate cancer is an effective treatment modality with low urinary toxicity. Treatment resulted in excellent long-term biochemical control although late relapses were observed.
Vaccine nanocarriers: Coupling intracellular pathways and cellular biodistribution to control CD4 vs CD8 T cell responses
Authors: Marcela Rincon-Restrepo, Aaron Mayer, Sylvie Hauert, Daniel K. Bonner, Edward A. Phelps, Jeffrey A. Hubbell, Melody A. Swartz, Sachiko Hirosue
Journal: Biomaterials (2017)
Brain metastases (BM) from renal cell carcinoma treated with nivolumab: Evidence of early brain flare?
Authors: Laurence Albiges, Ronan Flippot, Julia Arfi-Rouche, Caroline Caramella, Fiorella Ruatta, Lisa Derosa, Guillaume Louvel, Pierre Maroun, Alberto Bossi, Bernard J. Escudier
Journal: Journal of Clinical Oncology (2017)

520 Background: Brain metastases (BMs) are associated with poor prognosis in metastatic renal cell carcinoma (mRCC). Patients with BM were excluded from pivotal studies of nivolumab in mRCC. Therefore, activity of nivolumab in BM is currently unknown. Methods: Data from mRCC patients with BMs, treated at Gustave Roussy with nivolumab, were collected. RECIST 1.1 assessments of both BM and metastatic sites outside the brain have been prospectively centrally reviewed. Treatment for BM: surgery, stereotactic radiation therapy (SBRT), whole brain radiotherapy (WBRT), and systemic treatment were collected. Results: Between February 2016 and September 2016, 62 consecutive patients have been treated with nivolumab in 2 nd /3 rd line at Gustave Roussy as part of the GETUG-AFU-26 NIVOREN trial (EudraCT 2015-004117). Among those, 8 patients (13%) had baseline non symptomatic BM, either untreated (n=6), or after SBRT (n=2). Among the 8 patients, median follow up from study enrollment is 8.1 months (range: 3.7-8.5). All 8 patients are alive at the time of analysis, only one still receiving nivolumab. 6/6 patients previously untreated required focal therapy to the brain due to early symptomatic disease progression to the brain: SBRT=5; surgery=1; WBRT=1 (one patient had SBRT +WBRT). Disease progression of BM was symptomatic in 8/8 patients and required steroid use as well as nivolumab discontinuation in 7/8 patients due to either brain and/or systemic disease progression. Conclusions: To our knowledge,this is the first experience evaluating BMs from mRCC treated with nivolumab. Our report suggests that BM from mRCC may not derive benefit from nivolumab and that prior focal therapy to the brain may be discussed in patients before nivolumab start. This finding is currently being investigated in the entire GETUG-AFU-26 NIVOREN trial population (n=499 patients, from 27 centers), which included 54 patients (11%) with BM at treatment start, to be presented at ASCO GU.[Table: see text]
Carboplatin (CBP) versus cisplatin (CP) within prognostic groups in pediatric extracranial malignant germ cell tumors (MGCTs).
Authors: Juliet Hale, Thomas Arthur Olson, James Nicholson, Ha Dang, Mark D. Krailo, Deborah Billmire, Paul Donachie, Claire Thornton, Carlos Rodriguez-Galindo, A. Lindsay Frazier
Journal: Journal of Clinical Oncology (2012)

9539 Background: It is established that CBP is inferior to CP in adult MGCTs when used at AUC 5 or 400mg/m 2 . There are no randomised data for paediatric MGCTs, so conclusions from adult MGCTs have been generalised despite differences in site, histology and biology. A database, pooling patients from US and UK paediatric MGCT studies, was established to determine prognostic factors in paediatric MGCTs. We examined the effect of CBP and CP in identified prognostic groups. Methods: A dataset of 1110 paediatric MGCTs was created, treated 1983 to 2009. Treatment was CBP (JEB, AUC 7.9) in the UK and CP (PEB) in the US. After excluding patients with surgery only, pure germinoma or immature teratoma , 697 patients remained. The cure model was used to assess the prognostic significance of chemotherapy regimen after adjustment for patient characteristics. Results: Analysis stratified prognosis according to age (0-10 v 11+yrs) and stage (1-3 v 4) at diagnosis by site (testis: ovary: extragonadal). Outcome for CBP and CP in these prognostic groups is shown in the table. Conclusions: Interpretation of the results of this nonrandomised comparison requires caution. However, after adjustment for other prognostic factors, the risks of failure for JEB and PEB were not statistically different . This is particularly true for 0-10yrs. At AUC7.9 CBP is tolerable in paediatric patients, with potentially fewer late toxicities than CP. [Table: see text]
Contribution of cancer care to total spending among high-cost Medicare beneficiaries.
Authors: Miranda Kim, Brian Michael Alexander, Laura Burke, Ashish Jha
Journal: Journal of Clinical Oncology (2015)

6620 Background: Medicare spending is highly concentrated, with the top decile of Medicare patients accounting for more than half of total Medicare expenditures. Understanding the patterns of spending that contribute to these high costs may lead to important policy changes and innovative programs aimed at successfully reducing spending and potentially improving outcomes. We know little about the contribution of cancer as a diagnosis and types of cancers present among high cost Medicare beneficiaries. Methods: We used 20% of the 2012 Medicare data to identify fee-for-service (FFS) beneficiaries who were continuously enrolled for the year and were age 65 or older. High cost patients were defined as those in the top decile of spending in 2012 and non-high cost patients were the remaining patients. To identify patients with a cancer diagnosis, we used ICD-9 codes for the top 10 cancer killers. Results: Among all Medicare fee-for-service beneficiaries, 18% carried a cancer diagnosis. A cancer diagnosis was far more likely to be present among high-cost patients compared to non-high-costs patients: 26.2% versus 17.1% (p < .001). Cancer diagnoses found more frequently in the high-cost group as compared to the rest of Medicare beneficiaries included colorectal (32.7% vs. 24.8%, p < .001), head and neck (3.2% vs. 0%, p < .001), lymphoma (1.0 vs. 0%, p < .001), pancreatic (9.9 vs. 6.8%, p < .001) and esophageal cancer (2.7% vs. 0.8%, p < .001). There were significantly fewer breast (3.6% vs. 9.2%, p = < .001) and prostate (2.4% vs. 12.3%, p < .001) patients in the high-cost group. Conclusions: Among elderly Medicare recipients, high-cost patients are significantly more likely to carry a cancer diagnosis, suggesting that interventions aimed reducing cancer costs may be highly effective in reducing overall healthcare spending. Certain cancer diagnoses are particularly overrepresented in this cohort, pointing to a need for further studies aimed at understanding specific components driving cancer costs in this population.
Prognostic relevance of genetic variations of tuberous sclerosis complex gene in advanced non-small cell lung cancer patients treated with platinum doublets.
Authors: Jeong Seon Ryu, Seul-Ki Lee, Azra Memon, Hyun-Jung Kim, Hae-Seong Nam, Jae-Hwa Cho, In-Jae Oh, Sei-Hoon Yang, Joo Han Lim
Journal: Journal of Clinical Oncology (2014)

e22074 Background: Tuberous sclerosis complex (TSC) 1 or 2 gene is known to have a role as tumor suppressor through inactivation of mammalian target of rapamycin (mTOR) which increase cell proliferation and growth. Association of genetic variations of TSC 1 or 2 genes with survival of cancer patients or effect of chemotherapeutic agent such as platinum was not evaluated. Methods: A total of 309 NSCLC patients who were treated with platinum doublets as front line treatment were retrospectively enrolled in this study: stages IIIA (10%), IIIB (26%), and IV (64%). Direct sequencing for TSC1 and 2 was performed. Associations of genetic variations of TSC1 and 2 with treatment outcome (progression free survival, PFS) were evaluated. Results: The median age was 64 years (range, 32 to 86 years). Histologically, 171 (55.3%) of the patients had adenocarcinoma; 138 (44.7%) had non-adenocarcinomas (109 squamous cell, 24 others, 5 large cell). Median PFS of the patients was 4.93 months. Patients with variant genotype of TSC1 (rs1073123, Met322Thr) showed better PFS compared to those with variant genotype (PFS = 5.93 vs 4.83 months, log-rank P < 0.0001), even after adjustment for age, gender, ECOG performance status, smoking habit, histology, stage, and second line treatment (adjusted HR = 0.071, 95% confidence interval = 0.017 to 0.306, P < 0.001). Conclusions: These findings suggest that the genetic variation of TSC1 gene is an important prognostic marker in NSCLC patients treated with platinum combination chemotherapy.
Acute effects of bronchial thermoplasty: a matter of concern or an indicator of possible benefit to small airways?
Authors: Louis-Philippe Boulet, Michel Laviolette
Journal: European Respiratory Journal (2017)

Bronchial thermoplasty (BT) is a non-pharmacological treatment developed in the last two decades that has been proposed for the treatment of difficult-to-control asthma despite current standard asthma treatment [1–3]. This technique consists of delivering temperature-controlled radio-frequency energy to bronchi from about 3 to 10 mm in diameter through an endoscope. The initial concept underlying this technique was to improve airway function in decreasing airway smooth mass in the treated area, as shown in animal models and in a study of subjects undergoing lung surgery for cancer [4, 5]. Acute effects of bronchial thermoplasty on small airways and lung parenchyma: good or bad? <http://ow.ly/T6Uu309keuf>
The long-term benefits of the LIVESTRONG at the YMCA program.
Authors: Erin L Ratterman, Kelly Standage, Lynda M. Beaupin
Journal: Journal of Clinical Oncology (2017)

167 Background: Up to 35% of cancer survivors report physical dysfunction. Exercise programs are beneficial for cancer survivors, yet adherence to exercise long-term remains a challenge. This study examines the efficacy of the Livestrong at the YMCA Program on the physical function of cancer survivors and its influence on habitual exercise. Methods: This retrospective study analyzed data from 158 participants between 2013-16. Each 12-week program consisted of two 1.5 hour sessions per week led by YMCA trainers with LIVESTRONG certification. Sessions included group exercises and education on nutrition and healthy eating, yoga and meditation. Demographic forms completed upon enrollment and Functional Assessments performed at the beginning and close of each 12-week program were analyzed. The demographic data was compiled to produce aggregate characteristics and matched Functional Assessments scores were used to determine changes in each measure over the course of the program. Data analysis included who obtained YMCA membership and continued to have active membership. Results: Matched pre- and post-program Functional Assessments and demographic data were available for 112 participants (71%). Thirty-four percent were over 65 years of age, 94% Caucasian, 52% had breast cancer, and 55% completed treatment within the past two years. We observed improvements in all measures within the Functional Assessment, including upper and lower body strength, flexibility, balance, and 6-minute walk test. Thirty-nine percent are currently YMCA members, and 78% of those have checked into the YMCA within the last 3 months. A post-program potluck dinner is hosted and attendance from prior participants is over 50%. Participant feedback indicates that the program promotes socialization and peer support among cancer survivors. Conclusions: Similar to other exercise programs, the Livestrong at the YMCA program improves physical function scores. Nearly 40% of participants maintain a YMCA membership and over 75% of these members continue to exercise at the YMCA. Promotion of peer support and education on healthy lifestyle behaviors by the Livestrong at the YMCA program may have an impact on the long-term adherence to exercise among cancer survivors.
Association of prior rituximab exposure among patients undergoing autologous stem cell transplantation for relapsed/refractory diffuse large B-cell lymphoma with inferior outcomes in males compared with females.
Authors: Aleksandr Lazaryan, Edward Alan Copelan, Nelli Bejanyan, Robert M. Dean, Ronald M. Sobecks, Brian Thomas Hill, Brad L. Pohlman, Matt E. Kalaycio, Brian James Bolwell, John W. Sweetenham
Journal: Journal of Clinical Oncology (2012)

8055 Background: The combination of rituximab with CHOP remains the standard upfront therapy of patients (pts) with advanced diffuse large B-cell lymphoma (DLBCL). Gender disparity in survival of pts with DLBCL appears to be significantly modified by the use of rituximab in both upfront (Ngo, 2008; Pfreundschuh, 2009; Riihijarvi, 2010) and post-transplant maintenance (CORAL trial) settings. The presence of interaction between gender and prior rituximab exposure remains unknown in pts with relapsed/refractory DLBCL undergoing autologous stem cell transplantation (ASCT). Methods: We conducted a retrospective cohort study of 320 consecutive pts who underwent ASCT for relapsed/refractory DLBCL at our center from 01/1998 to 12/2010. Relapse-free survival (RFS) and overall survival (OS) were estimated by Kaplan-Meier method and by Cox proportional hazards regression analysis in SAS 9.1 (Cary, NC). Results: Among all pts (median age=54 yrs (IQR, 45-61); 92% Caucasians) 210 (66%) were males and 110 (34%) were females. 85 pts (27%) received more than two prior chemotherapy regimens. 174 pts (55%) had pre-ASCT exposure to rituximab as a part of induction or salvage regimens. Preparative regimen for ASCT uniformly consisted of Bu/Cy/VP-16. In the stratified univariate analysis of pts treated with rituximab prior to the ASCT, male pts had inferior RFS (p=0.02; hazard ratio [HR]=1.86, 95% CI, 1.09-3.18) and OS (p=0.03; HR=1.94, 95% CI, 1.05-3.58). In pts who did not receive rituximab prior to the ASCT, no difference in RFS or OS according to gender was observed (all p&gt;0.4). Gender disparity among rituximab recipients was even more evident for both RFS (p=0.004; HR=2.22, 95% CI, 1.28-3.83) and OS (p=0.005; HR=2.42, 95% CI, 1.3-4.5) in the multivariable analyses controlling for age at transplant, number of prior chemotherapies, and pre-ASCT disease response. Conclusions: Our data support an emerging concern that male patients with DLBCL have inferior outcomes when treated with rituximab. The present study has extended this observation to pts with relapsed/refractory DLBCL treated with ASCT.