bluuebunny/crossref_metadata_2025_split huggingface dataset:
Implementing innovative, learner-centered methods to teach oncology fellows how to face difficult conversations.
Authors: Shaw Andrew , Reilley Matthew , McQuade Jennifer Leigh , Baile Walter F. , Epner Daniel E. 
Published: February 2017

27 Background: Oncologists engage in emotionally charged conversations with patients and families about prognosis, goals of care, and end of life transitions. Many oncologists lack key skills for guiding patients through such conversations. Key skills include posing open ended questions to elicit the patient’s perspective, using silence effectively, and responding to emotion with empathy. We previously described a communication skills curriculum for first year medical oncology fellows consisting of a series of one hour monthly seminars (Epner and Baile, Academic Medicine, 2014). We now describe improvements in the curriculum based on extensive feedback from learners and teaching assistants. Methods: Anonymous feedback from first year fellows indicated longer sessions would allow for sufficient warm up and more in depth reflection and opportunity to practice. We therefore consolidated the sessions into quarterly 4 hour workshops. Several fellows also expressed discomfort with participating in role play of clinical scenarios in front of colleagues, so we implemented small group learning in which 3-4 fellows practiced communication skills in facilitated role play scenarios. We also replaced large group role play with narrative medicine techniques, such as reading and discussing medically-themed short stories and reflective writing exercises to allow the greatest amount of participation among learners. Results: Fellows completed anonymous surveys on which they rated items on a 4 point scale, with 1 being best and 4 worst. The average score of the two survey items pertaining to large group role play was 2.6. After changes in the curriculum, items pertaining to narrative medicine averaged 1.3, which was very favorable. Items pertaining to relevance and value of the curriculum also averaged less than 1.5 for all years. Attendance was 100% with the exception of fellows who were on vacation. Conclusions: Learner-centered, interactive innovations to our previous communication skills curriculum were highly rated by fellows and addressed issues of enhanced participation in a learning environment in which fellows felt safe to actively participate, reflect, and interact extensively with their peers.
A novel scoring system to predict survival in patients with advanced pancreatic adenocarcinoma: The Memorial Prognostic Score (MPS).
Authors: Yang Andrew Chung , Wiesenthal Alison , Epstein Andrew S. , Zheng Junting , Goldberg Jessica , Meadows Jason , O'Reilly Eileen Mary , Glare Paul A. 
Published: February 2017

36 Background: A major limitation of prognostic tools such as the Eastern Cooperative Oncology Group (ECOG), Karnofsky, and Palliative Performance Scale is a reliance on subjective clinical assessment. An objective tool, the Glasgow Prognostic Score (GPS) is derived from C-reactive Protein (CRP) and albumin and has been validated in patients with operable and inoperable malignancies. One disadvantage of this tool is that CRP is not routinely measured in the United States. We examined if the Neutrophil-Lymphocyte Ratios (NLR) (Ahn, H.K., et al., Neutrophil-Lymphocyte Ratio Predicts Survival in Terminal Cancer Patients. J Palliat Med, 2016) could be substituted for CRP in the GPS to predict survival in patients with advanced pancreatic adenocarcinoma. Methods: A retrospective chart review identified patients at MSKCC with pathology-confirmed stage IV pancreatic adenocarcinoma diagnosed between 2011 to 2014. Pre-treatment absolute neutrophil count, absolute lymphocyte count, and albumin were extracted. The NLR for each patient was calculated and assigned: NLR ≤ 4 g/dl = 0, NLR > 4 g/dl = 1; serum albumin > 4 g/dl = 0, and serum albumin < 4 g/dl = 1. Combining NLR and albumin scores resulted in a composite MPS score of 0-2, similar to GPS. We evaluated the association of the MPS with overall survival. Results: N = 833 patients were identified with median survivals summarized in the table below. A log-rank test showed statistically significant differences in survival between MPS groups (p<0.00005). The MPS on univariate analysis had a HR of 1.36 (95% CI 1.23 – 1.50, p<0.0005) associated with overall survival. Conclusions: The MPS, a novel composite of NLR and albumin, is an objective prognostic tool that divided this sample of patients into three clinically distinct subgroups. Further interrogation will control for performance status, disease characteristics and anti-cancer therapy. [Table: see text]
Symptom burden to predict health care utilization in hospitalized patients with incurable cancer.
Authors: Nipp Ryan David , El-Jawahri Areej , Moran Samantha M.C. , D'Arpino Sara , Johnson Connor , Lage Daniel E. , Wong Risa , Xiao Yian , VanDusen Harry , Pirl William F. , Traeger Lara , Lennes Inga Tolin , Cashavelly Barbara J. , Martinson Holly S. , Jackson Vicki A. , Greer Joseph A. , Ryan David P. , Hochberg Ephraim P. , Temel Jennifer S. 
Published: February 2017

98 Background: Patients with incurable cancer are often hospitalized and have frequent readmissions after discharge. Considering the high physical and psychological symptom burden in this population, we sought to investigate symptoms as predictors of hospital length of stay (LOS) and time to first unplanned readmission. Methods: We consecutively enrolled incurable cancer patients with unplanned hospital admissions from 9/2014-4/2016. Within the first 5 days of admission, we assessed physical (Edmonton Symptom Assessment System [ESAS]; scored 0-10) and mood symptoms (Patient Health Questionnaire 4 [PHQ-4]; scored categorically). We created summated ESAS total and physical symptom variables. To identify predictors of LOS we used linear regression and for time to readmission we used Cox regression, with all models adjusted for age, sex, marital status, comorbidity, education, cancer type and time since incurable diagnosis. Results: We enrolled 1,000 of 1,227 (81%) eligible patients (mean age = 63.4; 50% female; 66% married). Gastrointestinal (33%) and lung (18%) cancers were the most common. Mean hospital LOS was 6.2 days and 30-day readmission rate was 25%. Over half of patients reported moderate/severe fatigue, drowsiness, lack of appetite, pain and poor well-being. Over one-fourth screened positive for PHQ depression and anxiety. All physical and mood symptoms individually predicted for longer LOS. Pain, nausea, poor well-being, ESAS total, ESAS physical and PHQ anxiety predicted for shorter time to readmission. Conclusions: Hospitalized patients with incurable cancer experience a high symptom burden, which correlates with their health care utilization. Both physical and psychological symptoms predict for longer hospital LOS and shorter time to readmission. These findings can inform interventions targeting patients’ symptoms during hospital admissions in an effort to improve health care delivery and utilization. [Table: see text]
ProCAID: A phase I clinical trial to combine the AKT inhibitor AZD5363 with docetaxel and prednisolone (DP) chemotherapy for metastatic castration resistant prostate cancer (mCRPC).
Authors: Crabb Simon J. , Birtle Alison J. , Martin Karen , Downs Nichola , Bowers Megan , Ratcliffe Ian , Ellis Mary , Griffiths Gareth , Thompson Stuart , Khoo Vincent , Jones Robert J. 
Published: February 2017

228 Background: DP extends survival in mCRPC. However emergent clinical resistance is effectively inevitable. Serine/threonine protein kinase AKT (protein kinase B) pathway activation is highly prevalent in mCRPC contributing to disease progression and DP therapeutic resistance. AZD5363 is a potent oral pan-AKT inhibitor. Pre-clinical data suggest activity in mCRPC and synergy with docetaxel. This phase I trial was to develop a DP/AZD5363 combination in mCRPC. Methods: Eligibility included chemotherapy naive histologically/cytologically proven measurable/evaluable mCRPC, PSA or radiographic disease progression, ECOG performance status 0 or 1, serum testosterone <1.7 nmol/L. Treatment comprised DP up to 10 cycles (75 mg/m2, IV, day 1; prednisolone 5 mg BID, PO, day 1–21) and AZD5363 to disease progression. Planned AZD5363 dose levels were 320 mg (DL1), 400 mg (DL2) and 480 mg (DL3), BID, PO, 4 days on/3 days off, from cycle 1, day 2. We utilised a conventional 3+3 dose escalation to determine a recommended phase II dose (RP2D) for AZD5363 combined with DP according to defined dose limiting toxicity (DLT) using CTCAEv4. Results: 10 patients were recruited (4 DL1, 6 DL2), median age 67.5 (Range: 56-72). A median of 6.5 cycles (Range: 3-10) of DP and 4 cycles (Range: 1-13) of AZD5363 were administered. No DLTs were seen in DL1. 2 patients in DL2 experienced DLTs (G3 rash, G3 diarrhoea). 7 pts (70%) had at least one G3/4 IMP-related AE with neutropenia (n=3) and maculo-papular rash (n=3) the most common. G3/4 AEs considered related to AZD5363 occurred in 3 patients (0 DL1, 3 DL2) including maculo-papular rash, diarrhoea and neutropenia. Transient hyperglycaemia occurred in all patients (Random glucose C1D2 pre dose mean 6.0 mmol/L, 2 hour mean 8.7 mmol/L, 4 hour mean 9.5 mmol/L, 8 hour mean 6.5 mmol/L). Conclusions:The RP2D for AZD5363 is 320 mg bd 4 days on/3 days off in combination with full dose DP for mCRPC. A placebo controlled randomised phase II trial for this approach has commenced recruitment. This work was supported by CRUK [C9317/A16029]. CRUK Reference: CRUK/12/042. This research was conducted with support from the Investigator-Sponsored Study Collaboration between AstraZeneca and the National Cancer Research Network. Clinical trial information: NCT02121639.
A phase 2 study of BIND-014 (PSMA-targeted docetaxel nanoparticle) administered to patients with chemotherapy-naïve metastatic castration-resistant prostate cancer (mCRPC).
Authors: Autio Karen A. , Garcia Jorge A. , Alva Ajjai Shivaram , Hart Lowell L. , Milowsky Matthew I. , Posadas Edwin M. , Ryan Charles J. , Summa Jason Mark , Youssoufian Hagop , Scher Howard I. , Dreicer Robert 
Published: February 2017

233 Background: BIND-014 is a novel PSMA-targeted Accurin (polymeric nanoparticle) that contains docetaxel (D). BIND-014 is anticipated to improve the therapeutic index of D by increasing its intratumoral concentration and duration of exposure. In a phase 1 study, BIND-014 was generally well-tolerated and displayed anti-tumor effects, including in two patients with chemotherapy-naïve mCRPC. Methods: A phase 2 study was conducted of BIND-014 administered by a 60-min IV infusion at 60 mg/m² on day 1 of a 21-day cycle in combination with 5 mg of prednisone twice per day to patients with chemotherapy-naïve mCRPC. Prior treatment included abiraterone acetate (AA, 48%), enzalutamide (E, 12%) or both (14%). Of these 31 patients 19% progressed within ≤ 6 months on prior AA and/or E. The primary endpoint was radiographic progression-free survival (rPFS) using PCWG2 for bone and RECIST v1.1. Other endpoints included prostate specific antigen (PSA) and circulating tumor cell count (CTC) conversions, objective response rate (ORR), and overall survival (OS). Results: Forty-two patients were enrolled and received a median of 6 doses (range 1 – 21). Median rPFS was 7.1 months (95% CI: 2.6 – 9.9) with 4 patients (10%) censored. PSA response ( ≥ 50% reduction from baseline) was observed in 12 of 40 patients (30%). CTC conversions (from ≥ 5 CTCs/7.5 mL of blood at baseline to < 5 CTCs) occurred in 13 of 26 patients (50%). ORR was 32% with 3 confirmed responses (1 complete response and 2 partial responses) and 3 unconfirmed responses out of 19 patients with measurable disease. Estimated median OS was 13.4 months (95% CI: 9.9 – 18.6) with 14 patients (33%) censored. The most common hematological treatment-related adverse events (TRAEs) observed were lymphopenia (26%), and anemia (19%).Fatigue (69%), nausea (55%), diarrhea (45%), dyspnea (36%), and neuropathy (33%) were the most common non-hematological TRAEs. The most common TRAEs were generally grade 1 and 2. Conclusions: BIND-014 administered at 60 mg/m² on day 1 of a 21-day cycle is clinically active and well-tolerated when administered to patients with chemotherapy-naïve mCRPC including those with prior AA and/or E. Clinical trial information: NCT01812746.
Elevated HOXC6/DLX1 mRNA biomarker levels in urine to help select patients at increased risk for high-grade prostate cancer detection upon prostate biopsy.
Authors: Hendriks Rianne , Dijkstra Siebren , Cornel Erik Bastiaan , Jannink Sander , de Jong Hans , Hessels Daphne , Melchers Willem , Smit Frank , Leyten Gisele , De Reijke Theo , Vergunst Henk , Kil Paul , Knipscheer Ben , Hulsbergen-van de Kaa Christina , Mulders Peter , Van Oort Inge , Schalken Jack 
Published: February 2017

31 Background: The major challenge in prostate cancer (PCa) diagnostics is to improve the early detection of clinically significant or high-grade PCa, especially in the sPSA "grey-zone" (4-10 ng/ml). Ideally, PCa-specific biomarkers would be obtained non-invasively, for example derived from urine. The aim of this study was to evaluate the expression levels and clinical utility of the recently identified urinary HOXC6-DLX1 mRNA biomarker combination in men at risk of having high-grade PCa. Methods: From two prospective, multicenter studies, a total of 863 post-DRE urine samples were collected from men with elevated sPSA levels before undergoing a prostate biopsy procedure. The HOXC6-DLX1 mRNA biomarkers were measured in urine using RT-qPCR and results were quantified using the Delta DeltaCt method (ΔΔCT), normalized and expressed in a score from 1 to 1421. Results: The HOXC6-DLX1 risk score was significantly higher in urine from patients with high-grade PCa upon prostate biopsy compared to no PCa and PCa Gleason score ≤6. In the sPSA "grey-zone", the HOXC6-DLX1 combination had the highest area-under-the-curve (AUC) of 0.67 (95% confidence interval (CI): 0.58-0.75) for prediction of high-grade PCa upon prostate biopsy in cohort A and 0.68 (95% CI: 0.59-0.76) in cohort B; as compared to sPSA with an AUC of 0.60 (95% CI: 0.51-0.70) and 0.62 (95% CI: 0.52-0.73) respectively. Overall, elevated HOXC6-DLX1 risk scores correlated with an increased risk of high-grade PCa detected on biopsy; 47% of men with a score >108 had significant cancer as compared to 6% with a risk score <17. Using a HOXC6-DLX1 risk score cut-off of 27.5 in the sPSA "grey-zone", 165 biopsies (31%) could have been avoided, and only 4% of patients with high-grade PCa would have been missed. Conclusions: The urine-based HOXC6-DLX1 assay provides a non-invasive solution to improve the selection of patients at increased risk for high-grade PCa who would benefit most from a prostate biopsy procedure, while reducing the number of unnecessary biopsies, particularly in the sPSA "grey-zone".
A randomized clinical trial comparing adjuvant radiation versus chemo-RT versus chemotherapy alone after radical cystectomy for locally advanced bladder cancer.
Authors: Zaghloul Mohamed S. , Christodouleas John Paul , Smith Andrew , Abdalla Ahmed , William Hany , Khaled Hussein Mustafa , Hwang Wei-Ting , Baumann Brian Christopher 
Published: February 2017

356 Background: There is growing interest in using adjuvant radiation therapy (RT) to reduce local failures (LF) after radical cystectomy (RC) for locally advanced bladder cancer. A previous RCT demonstrated significantly improved LF & OS with adjuvant RT vs. RC alone. An RCT was performed to compare the efficacy of adjuvant RT vs chemo-RT vs chemo alone after RC. The primary endpoint was disease-free survival (DFS). Secondary endpoints were OS, LRFS, DMFS and toxicity. Methods: Patients ≤ 70 yrs with ECOG PS ≤ 2 with locally advanced bladder cancer and ≥ 1 high-risk feature who underwent RC with negative margins at the Egyptian National Cancer Institute from 2002 – 2008 were enrolled. High risk features included stage ≥ pT3b, grade 3, or positive nodes. Patients were randomized following RC to RT (45 Gy in 1.5 Gy/fx given BID with 3D-conformal RT), chemo-RT with 2 cycles of gemcitabine/cisplatin before and after RT, or 4 cycles of chemo alone. The chemo alone arm was added as a 2nd randomization in 2007. Patients were followed regularly with CT scans q 6 months in the first 2 years & then yearly. Results: 198 patients were enrolled. 78 received RT, 75 chemo-RT and 45 received chemo alone. Median age was 54 (range 27 – 70) and the M:F ratio was 4:1. 53% had urothelial carcinoma, 41% had SCC and 6% other. Median follow-up was 19 mo (range 1 – 127 mo). The RT, chemo-RT and chemo alone arms had similar characteristics except for age (median 55, 52 and 55, respectively, p = 0.03) and tumor size (p = 0.02). There was no significant difference in DFS, DMFS or OS, although there was a trend toward improved DFS favoring the RT-containing arms with 3 yr rates of 63%, 68% and 56% in the RT, chemo-RT and chemo arms (p = 0.25). LRFS was significantly improved for the RT arms vs. chemo alone, with 3 yr rates of 87%, 96% and 69% (p < 0.01), regardless of histology. Treatment was reasonably well-tolerated with late grade ≥ 3 GI toxicity of 8%, 7% & 2%, respectively. Conclusions: This is the first RCT comparing adjuvant RT (+/- chemo) vs. adjuvant chemo following cystectomy for bladder cancer. RT was associated with significantly improved local control compared to chemo alone. There was no significant difference in DFS, DMFS, or OS. Clinical trial information: NCT01734798.
Phase II trial of gemcitabine + cisplatin + ipilimumab in patients with metastatic urothelial cancer.
Authors: Galsky Matt D. , Hahn Noah M. , Albany Costantine , Fleming Mark T. , Starodub Alexander , Twardowski Przemyslaw , Pal Sumanta K. , Hauke Ralph J. , Sonpavde Guru , Oh William K. , Bhardwaj Nina , Gnjatic Sacha , Kim-Schulze Seunghee , Liu Ziyue 
Published: February 2017

357 Background: Immune checkpoint blockade, with anti-PD-1/PD-L1 antibodies, has shown striking results in patients (pts) with mUC. While CTLA4 blockade has demonstrated pharmacodynamic effects in localized bladder cancer (Carthon, Clin Can Res, 2010), the role of CTLA4 blockade in mUC remains undefined. We hypothesized that chemotherapy may lead to immunogenic cell death, and other immunomodulatory effects, which could subsequently be exploited with the addition of ipilimumab. Methods: Pts with mUC received 2 cycles of gemcitabine + cisplatin (GC) alone followed by 4 cycles of GC + ipilimumab (GCIpi). The primary endpoint was % of patients alive at 1 year. Secondary endpoints included safety, objective response rate, and progression-free survival. Immune monitoring was performed at baseline, after GC alone, and after GCIpi. Results: 36 pts with mUC (median age 60; range: 33-80) were enrolled; KPS was 80%, 90% and 100% in 30%, 45%, and 25%; 58% had visceral metastases and 20% had liver metastases. Pts received a median of 5 cycles of GC (range: 1-6) and 3 doses of Ipi (range: 1-8). The most common grade 3-4 adverse events were neutropenia (36%), thrombocytopenia (19%), anemia (25%), hyponatremia (31%), thromboembolism (11%), and renal insufficiency (19%). The most common grade 3-4 immune-related adverse events were colitis (6%), hypophysitis (3%), hyperthyroidism (1%), and rash (1%). The objective response rate is shown in the Table. Median progression-free survival is 8 months (95% CI 6.2-9.8 months). Median follow-up is 10.4 months (range: 2.8-35.3 months). The primary endpoint analysis will be mature for the meeting. GC alone had no significant impact on circulating immune cell subsets; Ipi significantly expanded circulating CD4 and CD8 T cells. Conclusions: A phased schedule of GC plus immune checkpoint blockade was feasible in pts with mUC. Ipi induced immunomodulatory effects despite concurrent chemotherapy. Survival data are not yet mature. Ongoing analyses are exploring the impact of GC alone, and GCIpi, on antigen-specific T cell immunity and correlating such findings with “outlier” survival times. Clinical trial information: NCT01524991. [Table: see text]
The hotspot mutational landscape of upper tract and bladder urothelial cancers and correlation to survival.
Authors: Campbell Matthew T. , McConkey David James , Matin Surena F. , Kamat Ashish M. , Dinney Colin P. N. , Wang Jennifer , Gao Jianjun , Siefker-Radtke Arlene O. 
Published: February 2017

466 Background: The prevalence of potentially targetable molecular mutations in urothelial carcinoma of the upper tract and bladder carcinoma are beginning to emerge. Important differences of molecular alterations may exist between upper tract and bladder primary tumors necessitating different treatment approaches and drug development strategies for these patients. Methods: All patients with urothelial carcinoma at UT MD Anderson who had undergone the CLIA-certified 50 gene panel utilizing next generation sequencing for detection of hotspot mutations were retrospectively reviewed. The prevalence of mutations was tabulated and compared between upper tract and bladder primary tumor locations using the Fisher’s exact test. Survival comparisons were calculated using the Kaplan-Meier technique and the Log Rank Test. Results: 136 patients with urothelial carcinoma were included in the analysis of which 41 were upper tract and 95 had bladder primary tumors. Of the 136 patients, 132 had de novo or developed metastatic/recurrent disease. The most prevalent mutations in the upper tract primary cohort included FGFR3, TP53, EGFR, FBXW7, PIK3CA, and KRAS. The most prevalent mutations in the bladder primary tumors were TP53, PIK3CA, RB1, FGFR3, HRAS, KRAS, BRAF, and FBXW7. In both upper tract and bladder tumors, a mutation in FGFR3 was nearly mutually exclusive for having a TP53 mutation. Compared to bladder primary tumors, upper tract tumors were more likely to have an FGFR3 mutation (36.5% vs. 7.4%, p < 0.0001), while the prevalence of TP53 (34% vs. 49%) and or a mutation in PIK3CA, HRAS, or KRAS (12.2% vs. 20.8%) was not significantly different. In the 132 patients with metastatic disease, the presence of a mutation in PIK3CA, HRAS, or KRAS was associated with inferior survival (HR 2.342, 95% CI: 1.32-8.67, p = 0.012), while the presence of an FGFR3 or TP53 mutation was not associated with a statistically different survival when compared to patients with wild type mutational status. Conclusions: Patients with upper tract and bladder primary sites have different molecular mutation rates. Understanding how these mutations in differing sites affect tumor biology may have important clinical implications.