tbuckley/cabot-search huggingface dataset:
Prospective study of health-related quality of life in men with high- and intermediate-risk prostate cancer who received secondary therapy.
Authors: Mazen Alsinnawi, Jennifer Cullen, Lauren Hurwitz, John Samuel Banerji, Katherine Levie, Erika Wolff, Inger L. Rosner, Joseph Sterbis, Timothy Brand, John Massman, April Slee, Christopher R. Porter
Journal: Journal of Clinical Oncology (2016)

5054 Background: Men with high risk (HR) and intermediate risk (IR) prostate cancer (CaP) require definitive therapy and may require secondary therapy (2*T) after primary treatment (1*T). Study aims were to assess the impact of receiving 1*T and/or 2*T on Health Related Quality of Life (HRQoL) in HR and IR CaP patients. Methods: A prospective cohort study was initiated in 2007 at Center for Prostate Disease Research Multicenter National Database sites. Longitudinal patterns in HRQoL were examined for patients with HR & IR CaP, treated by: RP only, EBRT only, EBRT + ADT, or RP with 2*T within 12 months of CaP diagnosis. HRQoL trends were examined as annual change from pre-treatment baseline to 5 yrs post baseline using the Expanded Prostate Cancer Index Composite (EPIC) & Medical Outcomes Study Short Form (SF36). HRQoL change over time was modeled using generalized estimating equations for repeated measures outcomes, adjusting for baseline HRQoL & clinical characteristics. Results: Of 445 men with IR and HR CaP: 228 underwent RP, 79 EBRT only, 64 EBRT + ADT. Thirty five men post RP received 2*T and were considered for this analysis. All treatment groups showed 5-year declines in HRQoL. Sexual function (SF) analysis: 2*T in the RP group showed the most significant drop in SF and sexual bother (SB) (36 pt. drop vs 23 in RP only group at 48 mos). The EBRT & ADT group showed evidence of SF recovery starting at 24 mos and achieved scores close to EBRT only group at 60 mos (21 pt. decline vs 18 for EBRT only group). Urinary Function (UF) analysis: 2*T group (post RP) was the only group to show significant drop in urinary bother (UB) from 36 mos onwards. Changes in bowel function were minor amongst all groups exposed to EBRT including men post RP receiving 2*T. Conclusions: CaP patients suffer significant declines in HRQOL after 1*T. The impact of 2*T in RP group on HRQoL was significant and greater than other treatment modalities. These results have implications for treatment decision making for patients with HR and IR CaP.
Neoadjuvant chemotherapy followed by concomitant chemoradiation with gemcitabine in muscle invasive bladder cancer.
Authors: Abdul Mateen, Allah Rakha Adil, Quratul Ain Hashmi, Arif Moin Duraishi, Famya Abdullah
Journal: Journal of Clinical Oncology (2017)

4541 Background: Urinary bladder cancer is one of the most prevelent genitourinay cancer in Pakistan. It is especially common in population that consumes smokeless tobacco. Advanced stage at diagnosis is usual presentaion due to illiteracy, poverty and lack of primary health facilities. The study was aimed to optimize treatment of muscle invasive bladder cancer in poor resource country. Methods: A total of 65 patients were enrolled for the study. All patients had muscle invasive disease on transurethral resection. Patients were to in stage range from T2-3, N0 and M0 to be selected. The patients were planned for gemcitabine and cisplatinum (GC) every three weeks in a dose of 1000 mg/m² and 40 mg/m² on D1 and D8 of each cycle respectively. Ultrasonography was performed to assess for any bladder mass at this point. The patients with no visible tumor were planned for whole bladder external radiotherapy (ERT) along with weekly gemcitabine 100 mg/m². A total of 63 Gray (Gy) was planned with 1.8 Gy per fraction and five fractions a week. Gemcitabine was given on 1st day of every week during whole course of ERT.Treatment interruptions were allowed depending upon chemotherapy and ERT related toxicity. Primary end point was to assess disease free survival (DFS) while overall survival was also assessed as a secondary end point. Results: 54 patients (83%) were available for assessment to treatment and to assess DFS and OS. Rest of the patients 11/65 (17%) were excluded from the analysis due to inability to complete the treatment. Five patients (8%) showed disease recurrence during treatment and were switched to other treatment. 11 patients (20%) showed bowel, 15 patients (28%) showed bladder and 8 patients (15%) showed hematological related grade 1-2 toxicity. Four year DFS and OS were 43% and 52% respectively. Mean and median DFS (year) were 3.16±0.36 (95% confidence interval [CI] 2.91 to 3.42) and 2.68±0.54 (95% CI 2.41 to 2.93) respectively. Mean and median OS (year) were 3.95±0.43 (95% CI 3.67 to 4.21) and 3.55±0.31 (95% CI 3.37 to 3.76) respectively. Conclusions: Neoadjuvant chemotherapy with GC followed by concomitant CRT using gemcitabine is an excellent choice for bladder preservation in poor resource countries.
ReTHINK: A randomized, double-blind, placebo-controlled, multicenter, phase 3 study of ruxolitinib in early myelofibrosis patients.
Authors: Francesco Passamonti, Jean-Jacques Kiladjian, Alessandro M. Vannucchi, Andreas Reiter, Savita Bharathy, Dana Iommazzo, Viktoriya Stalbovskaya, Prashanth Gopalakrishna, Ruben A. Mesa
Journal: Journal of Clinical Oncology (2016)

TPS7080 Background: Myelofibrosis (MF) is a clonal hematologic neoplasm characterized by bone marrow fibrosis, splenomegaly, anemia, and debilitating constitutional symptoms. Currently, most patients (pts) without overt splenomegaly or disease-related symptoms or cytosis are managed through a “watch and wait” strategy treating only when signs of the disease are present. However, recent evidence has suggested that pts with high molecular risk (HMR) mutations (ASXL1, EZH2, SRSF2, and IDH1/2) experience a more aggressive form of disease (Guglielmelli, et al. Leukemia 2014). This subset of pts might be candidates for earlier intervention. Ruxolitinib (Rux), a JAK1/2 inhibitor approved in advanced MF, has been shown to improve symptoms and splenomegaly, and prolong survival in 2 phase 3 COMFORT studies. The ReTHINK study investigates the potential benefits of Rux in pts with early nonsymptomatic MF who harbor at least 1 HMR mutation and for whom Rux is currently not used. Methods: The ReTHINK study is a multicenter, randomized (1:1), double-blind, placebo-controlled, phase 3 study investigating the efficacy and safety of Rux (10 mg twice daily) in early MF pts with HMR mutations. The planned enrollment is 320 pts. Key inclusion criteria, in addition to a mutation in at least 1 of 5 HMR genes, include criteria for early MF with nonpalpable spleen or palpable spleen ≤ 5 cm and MF 7-item symptom scale (MF-7) score of ≤ 15 (with each individual symptom score of ≤ 3). Prior treatment with Rux or other JAK inhibitors, eligibility for allogeneic stem cell transplantation, inadequate liver function, and severely impaired renal function are key exclusion criteria. Primary objective is to evaluate clinical benefit of Rux in delaying progression of MF from early disease to more advanced disease stages. Primary analysis will be performed at 90 progression-free survival (PFS-1) events as assessed via the protocol-defined criteria for disease progression. Other objectives include evaluation of PFS beyond the first occurrence of disease progression (PFS-2), time to progression, change in spleen length and volume from baseline, change in symptoms using MF-7, EQ-5D, and PGIC, safety, and overall survival. Clinical trial information: NCT02598297.
Persistence of AR signaling in small cell neuroendocrine prostate cancer (SCNC) and intermediate atypical carcinoma (IAC): Results from the SU2C/PCF/AACR West Coast Prostate Cancer Dream Team (WCDT).
Authors: Rahul Raj Aggarwal, Jack Youngren, Artem Sokolov, Jiaoti Huang, George V. Thomas, Lawrence D. True, Adam Foye, Joshi J. Alumkal, Charles J. Ryan, Tomasz M. Beer, Christopher P. Evans, Martin Gleave, Matthew Rettig, Joshua M. Stuart, Primo Lara, Theodore C. Goldstein, Li Zhang, Robert Evan Reiter, Kim N. Chi, Eric Jay Small
Journal: Journal of Clinical Oncology (2016)

5045 Background: De novo small cell neuroendocrine prostate carcinoma (SCNC) is an AR-null subtype observed in ~ 1% of patients (pts). We have observed a higher frequency of SCNC in castration-resistant metastatic biopsies (12%) as well as a morphologically distinct entity termed intermediate atypical carcinoma (IAC) (29%), both associated with shortened survival. We sought to determine whether treatment-emergent IAC and SCNC biopsies retained AR expression and signaling as compared with adenocarcinoma (adeno). Methods: Pts underwent a metastatic tumor biopsy of bone or soft tissue at one of 5 participating centers. Formalin fixed, paraffin-embedded tissue underwent pathologic review, fluorescence in situ hybridization (FISH) for assessment of AR amplification, and assessment of AR expression by immunohistochemistry (IHC). An AR transcriptional signature was applied to RNA sequencing (seq) data from frozen tissue. Results: Median serum PSA at the time of biopsy was 29 ng/mL (range 4-2250) for adeno, 123 (0.4-1600) for IAC, and 51 (0.6-930) for SCNC. AR amplification was seen in similar proportions of adeno (53%), IAC (58%), and SCNC tumors (53%) (p = ns). 2+/3+ nuclear AR expression by IHC was observed in 27/31 (87%), 21/24 (87%), and 7/9 (78%) of evaluable adenocarcinoma, IAC, and SCNC biopsies, respectively (p = ns). AR expression level by RNA-seq was likewise similar across histologies. AR transcriptional signature scores were similar between adeno and IAC histologies and lower in SCNC (p = 0.006), with considerable inter-patient variability noted in IAC. Conclusions: Contrary to the classical description of SCNC as an AR-null phenotype, the majority of metastatic SCNC and IAC biopsies were positive for AR amplification and expression. AR transcriptional activity was lower in SCNC, whereas IAC AR activity was comparable to adeno, potentially supporting IAC as a transitional state in which progressive loss of AR activity occurs. Longitudinal studies are ongoing to test this hypothesis. As novel therapeutic targets are identified in IAC and/or SCNC, continued co-targeting of the AR may be warranted. Clinical trial information: NCT02432001.
P05.77 Echoes from the past- an historical cohort study of low dose radiation for tinea capitis and brain tumor incidence in Israel
Authors: S Yust-Katz, T Siegal, A Amiel, E Derazne, J Kark
Journal: Neuro-Oncology (2018)

Ionizing radiation is the only established environmental risk factor for brain tumors. Treatment with low dose radiation was the standard of care for treatment of tinea capitis till 1960 and was given in Israel mainly to children immigrating to Israel from North Africa and the Middle East between 1948–1960. The aim of this study was to evaluate the influence of sequelae of treatment with low dose radiation on the epidemiology of brain tumors in Israel. This study analyzed two cohorts of Jewish men and women who underwent health examinations at the age of 17 years between 1967 and 1991 and were followed by linkage to the national cancer registry up to 2012. The first cohort included 376,336 participants born in 1948–1959 and the second cohort included 474923 participants born in 1960–1971. The incidence of all brain tumors was 541 in the first cohort (crude rate 5.14) and 629 in the second cohort (crude rate 4.72). There was a significant decrease in the rate of meningioma in the second cohort [crude rate in the second cohort 1.36 expected crude rate 1.67 (p=0.041)]. In the first cohort there was important impact to origin- with higher incidence among those from north Africa and Middle East. This effect was ablated in the second cohort that included participants who had not been exposed to radiation treatment. The effect of origin was mainly evident in the incidence of all brain tumors grouped together (p=0.0003), meningiomas (p=0.00015) and cranial nerve tumors (p=0.006) and was strongest among those originating from North Africa. Our study reveals that treatment with low dose radiation for tinea capitis- appears to have affected the incidence of meningiomas in the cohort exposed to irradiation and dramatically changed the association of ethnicity with brain tumors in Israel, an effect that disappeared once treatment with low dose radiation was halted.
Abstract 12261: Improving Discharge Timeliness on a Pediatric Inpatient Cardiology Unit Through the Implementation of Medical Discharge Criteria Decreases Length of Stay and Reduces Hospital Charges
Authors: Andrew Porter, Rhonda Cable, Amanda Kolb, Angela Statile, Christine White, Angela Lorts, Samuel Hanke, Nicolas L Madsen
Journal: Circulation (2015)

Background: Prior improvement work integrating standardized medical discharge criteria in general pediatric inpatients led to improved discharge timeliness and reduced length of stay (LOS). Our aim was to develop standardized medical discharge criteria on a quaternary pediatric cardiology unit in an effort to improve the timeliness of discharge. We hypothesized that timely discharge would lead to cost savings and a reduced LOS. Methods and Results: Over 18 months (Jan. 2014 - June 2015), a multi-disciplinary team worked toward the quality improvement aim of increasing the percentage of pediatric cardiology inpatients discharged within 2 hours of achieving medical discharge criteria. We established preset ‘medically ready’ discharge criteria in our hospital EMR, initiated upon admission for all inpatients and modified daily as needed. We organized criteria into 7 categories (congenital heart disease (CHD) medical, CHD post-operative, heart failure/transplant medical, transplant post-operative, electrophysiology (EP) medical, EP post-procedure, and catheterization post-procedure). The median percentage of patients discharged within 2 hours of meeting criteria increased steadily from 35% to 78% over the project period. Concurrently, the median number of patients discharged before noon increased from 18% to 31%. Physician and nursing compliance with necessary process measures was 87% and 89%, respectively. LOS decreased by 8% (3.6 to 3.3 days) from the first 6 months of work to the last 6 months. All-cause readmission remained stable at 15% over the improvement time frame. Review of inpatient charges between Oct. 2014 and June 2015 demonstrated 169 patients (190 discharges) who experienced a delayed discharge based on the set criteria. The sum of charges from care provided after meeting criteria was $231,201 (average of $1,217 per delayed discharge). Conclusions: Discharge timeliness in pediatric cardiology patients can be improved by standardizing medical discharge criteria. We demonstrate that this can be achieved across all subcategories of pediatric cardiology without increasing the rate of readmission. Improved discharge timeliness not only reduces LOS; it provides an opportunity to substantially decrease medical charges.
Discrepancy between physician-assessed and patient-reported oxaliplatin-induced peripheral neuropathy in patients with metastatic colorectal cancer who received mFOLFOX6 plus bevacizumab: A post-hoc analysis (WJOG4407GSS2).
Authors: Yuji Miura, Masahiko Ando, Kentaro Yamazaki, Shuichi Hironaka, Kei Muro, Narikazu Boku, Ichinosuke Hyodo
Journal: Journal of Clinical Oncology (2018)

e22165 Background: Cumulative neurotoxicity of oxaliplatin (Ox), a key drug for metastatic colorectal cancer (mCRC), impairs patients’ quality of life. The purpose of this study is to evaluate the discrepancy between physician (Phy)-assessed and patient (Pt)- reported Ox-induced peripheral neuropathy (OIPN) in mCRC. Methods: This study is a post-hoc analysis using the data from WJOG4407G trial, an open-label randomized phase III trial in previously untreated mCRC Pts. Among 198 Pts randomized to mFOLFOX6 plus bevacizumab arm, 191 Pts were analyzed, excluding 7 Pts with intermittent Ox administration. Phy-assessed OIPN was graded by CTCAE version 3.0 every two weeks. Pt-reported OIPN was assessed with FACT/GOG-Ntx (Ntx) (11 items, best score 44) at baseline, 3, 6, 9, 12 and 18 months. Results: Pt characteristics were male 117 (61%), median age 62 years, PS 0/1 148/43 (78/23%). Median number of courses and total dose of Ox was 10 (range 1-70) and 762 (range 85-5950) mg/m2, respectively. Ox dose was reduced in 91 Pts (48%). Ox was discontinued in 78 Pts (41%), and 58 Pts out of them (74%) were due to OIPN. The mean Ntx scores (± standard error) estimated by linear mixed model were 36.1(±0.8), 33.8 (±0.9), 29.4 (±1.0) and 26.6 (±1.1) in CTCAE grade 0, 1, 2 and 3, respectively. Ntx scores were weakly-moderately correlated with CTCAE grades (Spearman r= -0.34 [p < 0.0001], -0.47 [p < 0.0001] and -0.51 [p < 0.0001] at 3, 6 and 9 months). Among Pts assessed as CTCAE grade 0 (98, 36 and 11 Pts at 3, 6 and 9 months, respectively), the numbers of Pts whose Ntx score decreased by ≥4/≥8/≥12 points from baseline were 48 (49%)/21 (21%)/13 (13%), 20 (56%)/8 (22%)/5 (14%) and 6 (55%)/4 (36%)/2 (18%) at 3, 6 and 9 months, respectively. On the other hand, Pts with CTCAE grade 2-3 who showed less than 4 points decrease of Ntx scores were 30% (3/10 Pts), 10% (4/39 Pts) and 9% (3/32 Pts) at 3, 6 and 9 months, respectively. Conclusions: Approximately half of Pts with CTCAE grade 0 reported some sort of decrease in Ntx scores. Phy-assessed CTCAE might underestimate the symptom of OIPN in mCRC Pts who received Ox-based chemotherapy. Clinical trial information: UMIN000001356.
Active surveillance and watchful waiting for localized prostate cancer in elderly patients &gt;70 years in a community-based setting: Results from the HAROW study.
Authors: Jan Herden, Dietrich Schnell, Axel Heidenreich, Lothar Weissbach
Journal: Journal of Clinical Oncology (2017)

e16577 Background: Since more than half of patients with prostate cancer (PCa) are older than 70 years, this age group remains underrepresented in clinical trials. Possible non-invasive treatment options for these patients include Active Surveillance (AS) and Watchful Waiting (WW). In this prospective, non-interventional, health services research study, the use of different treatment options for localized PCa are observed under everyday conditions. The subgroups of patients ≥ 70 years, receiving AS- or WW are presented in terms of inclusion criteria, follow-up examinations and changes in treatment strategy. Methods: The study was conducted from July 2008 to July 2013 at 259 study centers in Germany, mainly office based urologists. The mean follow-up was 27.6 months. Clinical data (tumor category, digital rectal examination, PSA level, Gleason score, Charlson Comorbidity Index = CCI) and information about therapy and disease progression were collected at the time of study inclusion and subsequently at six-month intervals. According to the non-interventional study design, only recommendations were made for enrollment, course and discontinuation of AS and WW. The final therapeutic decision rested with treating physicians. Results: Overall, 2957 patients were enrolled, of whom 1165 were ≥ 70 years. 210 patients received AS and 87 patients received WW. AS patients were younger (73.9 vs. 76.8 years, p ≤ 0.001). The rate of low, intermediate and high risk tumors was 81.6%, 14.6% and 3.9% in the AS- and 39.1%, 43.5% and 17.4% in the WW-group (p ≤ 0.001). No differences were seen in the average number of PSA testing during the course of follow-up (AS = 3.97 vs WW = 3.79, p = 0.95). 37.6% of the AS patients and 12.4% of the WW patients received at least one follow-up biopsy. Conclusions: The results of HAROW indicate a clear distinction between AS and WW in terms of inclusion criteria. Interestingly, no clear distinction was seen in terms of follow-up examinations, since both groups were monitored frequently with PSA tests and even re-biopsies were performed in WW patients, neither of which is usually provided in WW programs.
Final results of a phase I prospective trial evaluating the combination of stereotactic body radiotherapy (SBRT) with concurrent pembrolizumab in patients with metastatic non-small cell lung cancer (NSCLC) or melanoma.
Authors: Allison M. Campbell, Roy S. Herbst, Scott N. Gettinger, Sarah B. Goldberg, Harriet M. Kluger, Anne C. Chiang, Rogerio Lilenbaum, Kurt A. Schalper, Ryan T. Sowell, Susan M. Kaech, Roy H. Decker
Journal: Journal of Clinical Oncology (2018)

9099 Background: We report final Phase I results of a Phase I/II prospective trial assessing safety and tolerability of SBRT and concurrent pembrolizumab. Methods: Eligible patients had metastatic NSCLC or melanoma and ≥ 2 sites of disease. Patients who had received prior anti-PD1 therapy were eligible if their disease had progressed by RECIST criteria; these patients received SBRT at enrollment. Immunotherapy naïve patients were treated with 200 mg of pembrolizumab q3 weeks until disease progression, then received SBRT. After SBRT, patients received pembrolizumab q3 weeks until disease progression. Patients were assigned to an SBRT dose escalation arm based on target location: either in the lung (arm A) or elsewhere (arm B). Results: 24 patients were enrolled (melanoma n=5; NSCLC n=19). 9 patients had received prior anti-PD-1 therapy and therefore got SBRT at enrollment. 15 patients were immunotherapy naïve and received a mean of 8.3 cycles of pembrolizumab before disease progression and SBRT. The target SBRT dose of 30 Gy in 3 fractions was reached for each arm. No dose limiting toxicities (DLTs) were observed within 60 days of SBRT. Non-hematologic toxicities of > grade 2 occurring during the 60 day DLT window or during subsequent pembrolizumab treatment are presented in the table below, with immune-related adverse events noted. 5 of 24 patients (21%) had an immune mediated grade 2 or 3 adverse event during post SBRT immunotherapy. Patients received pembrolizumab for a mean of 19.8 weeks post-SBRT (range 0-52 weeks) before disease progression. Conclusions: Dose escalation to 30 Gy in 3 fractions was completed for both arms without dose limiting toxicity. Combination therapy was well tolerated. Preliminary efficacy data indicates that addition of SBRT to a single site resulted in a mean of 19.8 weeks of continued response. Clinical trial information: NCT02407171. Pre SBRT Arm A (Lung Target) Arm B (Non Lung Target) 30 Gy in 5 fx 30 Gy in 3 fx 30 Gy in 5 fx 30 Gy in 3 fx n 15 7 6 4 7 Gr 2 4 hypothyroid; n=1pneumonitis; n=1 2 2 colitis; n=1 0 3 pneumonitis; n=1 Gr 3 1 hypothyroid; n=1 1 pneumonitis; n=1 2 enterocolitis; n=1pneumonitis; n=1 0 1 colitis; n=1 Gr 4 0 0 0 0 0 Gr 5 0 0 0 0 0