bluuebunny/crossref_metadata_2025_split huggingface dataset:
Patient, family member, and clinician perspectives on advance care planning (ACP) in hematology and hematopoietic stem cell transplantation (HSCT).
Authors: Booker Reanne , Simon Jessica , Raffin Bouchal Shelley ,   Advanced Care Planning CRIO Program
Published: February 2017

7 Background: Studies have found that ACP engagement remains low in patients undergoing HSCT in spite of the high risks of treatment-related morbidity and mortality. Methods: This qualitative study used Thorne’s Interpretive Description methodology. Participants were accrued from hematological malignancy outpatient clinics at a tertiary oncology center and underwent audio-recorded semi-structured interviews. Analysis involved meticulous review of interview transcripts. The constant comparative method was utilized; data collection occurred concurrently with analysis until saturation of themes was achieved. Results: The study involved 6 patients, 5 family members and 8 clinicians (physicians, nurses, social worker). Participants thought that ACP was both acceptable and important yet many had not engaged in ACP. Perceived barriers to ACP included: system-related barriers such as lack of process for ACP, lack of time and/or resources; patient-related factors such as lack of understanding of disease, prognosis and/or expectations of HSCT, lack of patient/family understanding of ACP, a desire to ‘focus on positives’; and disease/treatment-related factors such as unpredictability of the disease and treatment trajectories in hematology and HSCT. Potential facilitators identified by participants included: integrating ACP as part of routine HSCT care, involving the multidisciplinary team in ACP, and introducing ACP early and revisiting frequently. Conclusions: This study revealed various barriers and facilitators related to participation in ACP. We are using the results of this study to inform and tailor interventions on ACP at our center. Introducing ACP as part of standard care in HSCT and providing ongoing facilitation of ACP, including discussion of disease and treatment expectations at the outset, and when complications arise, may assist patients and families in recognizing how ACP fits into their care. Given the inherent unpredictability in this population, we suggest revisiting ACP frequently to optimize patient experience and ensure patients and family members are aware of other treatment options including supportive and palliative care.
Association between weight gain and sarcopenic obesity in patients treated with androgen deprivation therapy.
Authors: Mitsuzuka Koji , Kyan Atsushi , Sato Tomonori , Orikasa Kazuhiko , Namima Takashige , Aoki Hiroshi , Miyazato Minoru , Arai Yoichi ,   Tohoku Evidence-Based Medicine Study Group and Michinoku Urological Cancer Study Group
Published: February 2017

189 Background: Weight gain in response to androgen deprivation therapy (ADT) can be a marker for adverse effects of ADT. However, a concomitant decrease in lean mass in response to ADT may decrease the utility of weight gain in terms of sarcopenia. Therefore, the goal of the present study was to analyze the relationship among weight gain, obesity, and sarcopenia in patients undergoing ADT. Methods: Patients with prostate cancer who were hormone-naïve and scheduled to receive long-term ADT were recruited between 2011 and 2013. Body weight and results from blood tests of lipid and glucose metabolism were recorded every 3 months during 1 year of ADT. Computed tomography (CT) was performed to measure areas of subcutaneous and visceral fat and the psoas muscle before and after 1-year of ADT. ADT was limited to a luteinizing hormone-releasing hormone agonist with or without bicalutamide. Results: CT was performed in 72 patients before and after 1 year of ADT. Median age was 74 years (49-83). Median prostate-specific antigen before ADT was 21.9 ng/ml (0.3-3316). Clinical stage was B (43.1%), C (26.4%), and D (29.2%). Mean increase in weight was 2.7% after 1 year of ADT. Mean increase in the area of subcutaneous and visceral fat was 31.3% and 20.7%, respectively. Mean change in the area of the psoas muscle was -8.4%. When patients were divided into two groups according to weight change during 1 year of ADT (Group A (n = 34): weight gain < 3.0%, Group B (n = 38): weight gain ≥ 3.0%), an increase in subcutaneous and visceral fat was significantly more frequent in Group B, whereas the frequency of a decrease in psoas muscle area was not significantly different between the two groups (Group A: -9.5%, Group B: -7.5%, P = 0.11). Pearson correlation coefficients showed a moderate relationship between weight gain and fat accumulation (r = 0.44-0.52), but little relationship between weight gain and a decrease in psoas muscle area (r = 0.18). Conclusions: Fat accumulation tended to increase in patients who gained weight during ADT, whereas a decrease in psoas muscle area was not related to weight change. Sarcopenia could occur despite weight change during ADT. Clinical trial information: UMIN000018478.
Inducible MyD88/CD40 to allow rimiducid-dependent activation for control of proliferation and survival of chimeric antigen receptor (CAR) T cells targeting prostate stem cell antigen (PSCA).
Authors: Slawin Kevin Mark , Mahendravada Aruna , Shinners Nicholas , Chang Peter , Lu An , Crisostomo Jeannette , Morschl Eva , Shaw Joanne , Saha Sunandan , Spencer David M , Foster Aaron E 
Published: February 2017

206 Background: PSCA is a cell surface antigen that is overexpressed in a majority of metastatic prostate, transitional cell and pancreatic carcinomas. We describe a novel T cell costimulation switch, inducible MyD88/CD40 (iMC), activated by a small molecule, rimiducid, to enhance survival, proliferation and anti-tumor activity of CAR-T cells targeting PSCA. Methods: T cells were transduced with a retrovirus encoding tandem rimiducid-binding domains,cloned in-frame with MyD88 and CD40 signaling elements and first generation CARs (CAR.ζ) targeting PSCA (SFG-iMC-2A-PSCA.ζ). iMC activation was assessed with and without rimiducid treatment of T cells. Coactivation via iMC and CAR was tested in coculture assays with or without rimiducid using various PSCA+tumor cells, e.g. Capan-1 and HPAC pancreatic adenocarcinoma. Efficacy of iMC-modified CAR-T cells in vivo was assessed using an NSG mouse tumor model. Results: T cells transduced with iMC-PSCA.ζ produced cytokines (e.g., IFN-γ and IL-6) in response to rimiducid; however, IL-2 was only produced when both iMC and CAR were activated simultaneously by rimiducid and tumor antigen. Treatment of NSG mice bearing large (> 200 mm3) HPAC tumors with a single i.v. dose of 1x107 iMC-PSCA.ζ cells resulted in complete tumor elimination in 10/10 mice including both rimiducid-treated and untreated animals, compared to mice receiving non-transduced T cells (p = 0.0003). Weekly rimiducid administration dramatically increased CAR-T cell numbers, resulting in a 23-fold expansion of iMC-PSCA.ζ-modified T cells in the spleen compared to mice not receiving rimiducid four weeks after infusion (p = 0.02). In a dose-titration study, rimiducid administration was required for tumor control, and led to 565- and 948-fold T cell expansion at the tumor site, respectively, when lower numbers (1.25x106 or 6.25x105, respectively) of iMC-PSCA.ζ-modified T cells were given. Conclusions: GoCAR-T cells targeting PSCA, which contain an inducible MyD88/CD40 activation switch, may be an effective adoptive cell therapy for patients with pancreatic, prostate, bladder, and other cancers that overexpress PSCA.
Imaging response during therapy (tx) with radium-223 (Ra-223) for castrate resistant prostate cancer (CRPC) with bone metastases (BM).
Authors: Keizman Daniel , Peer Avivit , Neumann Avivit , Rosenbaum Eli , Neiman Victoria , Gottfried Maya , Kuchuk Iryna , Sarid David , Gez Eliahu , Mermershtain Wilmosh , Rouvinov Keren 
Published: February 2017

282 Background: Ra-223 is an alpha emitter that selectively targets BM. It was shown to improve the survival of patients (pts) with CRPC and BM, and thus is approved as a standard tx for these pts. However, the imaging response during Ra-223 tx is poorly defined. We aimed to describe the imaging response in pts with CRPC and BM treated with Ra-223. Methods: We evaluated the CT and bone scans response among pts with CRPC and BM, who were treated with Ra-223. Tx consisted of an injection administered q 4 weeks up to 6 injections. Scans were done at baseline, after 3 injections, and upon completion of 6 injections. Logistic regression model was used to analyze clinicopathologic factors associated with scans response. Results: 51 pts were included (median age 72). 59% (n = 30) were treated post docetaxel chemotherapy. 47% (n = 24) were treated concomitantly with a systemic standard therapy (e.g enzalutamide or abiraterone). 76% (n = 39) completed the planned 6 injections. A clinical benefit (improvement of skeletal pain and performace status) was noted in 67% (n = 34). 53% (n = 27) had a decrease of alkaline phosphatase. The response of bone metastatic disease (number of lesions) at 3 months was improvement in 22% (n = 11), stable in 53% (n = 27), and progression in 25% (n = 13). 1/13 (8%) pts evaluated at 6 months, had a progression of BM versus the 3 months status. Progression (RECIST ) of extraskeletal sites (lymph nodes, lungs, liver, adrenal) at 3 months was noted in 35% (n = 18). Concurrent systemic standard therapy (e.g enzalutamide or abiraterone) (OR 3.3, p = 0.04), Pre-tx PSADT ≥ 3 months (OR 2.62, p = 0.02) and on treatment stable/decreasing LDH (OR 2.9, p = 0.05) were associated with on treatment stable extraskeletal metastatic disease. Conclusions: Progression of BM during Ra-223 was uncommon. A bone flare may be noted during the first 3 months, and should not be confused with BM progression. Clinician should consider repeating a CT scan at 3 months in pts with short pre-tx PSADT, and LDH increase during tx, to exclude extraskeletal metastatic disease progression.
Genomic alterations in upper tract urothelial carcinoma (UTUC) versus urothelial carcinoma of the bladder (UBC).
Authors: Mullane Stephanie A. , de Velasco Guillermo , Choueiri Toni K. , Kantoff Philip W. , Bellmunt Joaquim 
Published: February 2017

431 Background: Defining the landscape of genomic alterations in UTUC as well as identifying the genomic differences from UBC, may provide insights into the treatment of UTUC. Methods: We interrogated our enterprise-wide institutional targeted next generation tumor sequencing data to compare genomic alterations in patients with UTUC (n = 25) with UBC (n = 72), irrespective of tumor stage. We described differences in frequencies of somatic mutations and copy number alterations in 300 relevant cancer-associated genes. Results: UTUC and UBC demonstrated differences in somatic alterations. Genes more commonly found in UTUC included FGFR3 (20% v. 7.5%), STAG2 (16% v. 7.5%), RB1 (24% v. 16%), TSC1 (16% v. 5.4%), EP300 (12% v. 5.4%), IGFIR (20% v. 0%), and Notch1 (24% v. 0%) (see table). Alterations in FGFR3 and TP53 co-existed in only on patient. We did identify two UTUC patients with MSH2 alterations, both of whom had previously been diagnosed with Lynch Syndrome. Conclusions: Biologically relevant differences exist between UTUC and UBC. We observed an enrichment of potentially targetable mutations including TSC1 and FGFR3. Findings in the genomic profile underline the need to consider these two locations as unique entities for future biologically driven trials. [Table: see text]
Actionable targets in patients with cisplatin-resistant advanced germ cell tumors.
Authors: Bagrodia Aditya , Kaffenberger Samuel D. , Lee Byron , Lee William , Cha Eugene K. , Sfakianos John , Gao Sizhi Paul , Zabor Emily Craig , Ostrovnaya Irina , Eng Jana , Berger Michael F. , Bajorin Dean F. , Schultz Nikolaus , Sheinfeld Joel , Bosl George J. , Al-Ahmadie Hikmat , Solit David B. , Feldman Darren R. 
Published: February 2017

473 Background: Approximately 30% of patients with advanced germ cell tumor (aGCT) will progress after first-line chemotherapy. Nearly half of these patients will die of progressive GCT. We describe potentially actionable mutations in a cohort of patients with platinum-resistant aGCT through targeted sequencing. Methods: 76 patients with cisplatin-resistant (CR) disease were sequenced using the Memorial Sloan Kettering Integrated Mutation Profiling of Actionable Cancer Targets (MSK-IMPACT) assay that examines 341 cancer-related genes. Patients were categorized as CR if they met any of the following criteria: 1) incomplete response to first-line cisplatin-based chemotherapy; 2) nonteratomatous tumor progression after standard chemotherapy; 3) nonteratomatous GCT identified at postchemo surgery. We grouped all somatic mutations into core signal transduction pathways or canonical cell functions to identify potential precise targets for therapy. Results: The majority of patients had nonseminoma histology (n = 64, 84%). International Germ Cell Cancer Collaborative Group risk was good, intermediate, and poor in 34%, 13%, and 53% of patients. 17 patients died of disease. In total, 51 potentially actionable alterations were identified in 36/76 (47%) patients. In the TP53 pathway, 7 MDM2 amplifications and 4 MYCN amplifications that may sensitize to nutlin-3 inhibitors were identified. Within the receptor tyrosine kinase pathway, 3 KIT mutations, 1 KDR amplification, and 1 MET amplification were seen that may sensitize to tyrosine kinase inhibitors. Eleven KRAS mutations, 3 NRAS mutations, 3 BRAF mutations, and 2 RAC1 mutations were see among the RAS pathway with preclinical data suggesting efficacy towards respective inhibitors. Actionable targets were also among the PI3-K, WNT, and cell cycle pathways. Potential targets with chromatin modifying or tumor suppressor functions were also seen. Conclusions: We describe actionable alterations that may guide treatment selection in a significant proportion of patients with CR aGCT. Targeted sequencing of these patients may allow us to enrich future clinical trials with patients whose tumors harbor alterations in the drug target of interest.
Prognostic value of hemoglobin level increase during axitinib treatment for metastatic renal cell carcinoma.
Authors: Johnson Alison Claire , Matias Margarida , Coquan Elodie , Brachet Pierre-Emmanuel , Dugue Audrey Emmanuelle , Molinier Alicia , Mourey Loic , Boyle Helen Jane , Laguerre Brigitte , Helissey Carole , Escudier Bernard J. , Joly Florence 
Published: February 2017

580 Background: Axitinib is used after failure of first line treatment for metastatic renal cell carcinoma (mRCC). A common side effect of axitinib is the increase of hemoglobin level (HbL) during treatment with a suspected correlation with better outcome. We examined whether HbL increase during the first 3 months of axitinib treatment is associated with better prognosis. Methods: Retrospective multicenter analysis including patients with mRCC treated with axitinib for at least 3 months from 2012 to 2014 as part of the French temporary use authorization cohort. Progression-free survival (PFS) was analyzed according to the following factors: gender, International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) prognostic score at axitinib initiation, polycythemia (HbL above 16.5/18.5 g/dL or hematocrit above 56/60% for women/men), and maximum increase in HbL within the first 3 months of treatment. Results: 97 patients were analyzed (71% men; median age at diagnosis: 54.7 years [22; 80]; IMDC: 23%, 49%, and 27% in the favorable, intermediate, and poor-risk group, respectively). Patients received axitinib for a median of 8 months [3; 30]. Grade 2-3 toxicities were observed in 81% of patients. Objective response rate was 32%. The median PFS and OS were 8.9 [7.4; 9.3] and 22 [19.4; not reached] months, respectively. During the first 3 months, 81 patients (84%) experienced HbL increase with a median increase of +2.3g/dL [-1.1; 7.2] and 40 of them (51%) had an increase above this median. Eight patients (8%) presented polycythemia. In univariate analysis, significantly longer PFS was observed for men (p = 0.02), for patients who had a better IMDC prognostic score (p = 0.004), and for patients who experienced an increase of HbL ≥ 2.3 g/dL (with a median PFS of 11.7 vs. 7.4 months; p = 0.025), but not for patients with polycythemia. In a multivariate analysis, after adjustment for IMDC score (p < 0.0001) and gender (p = 0.029), an increase in HbL ≥ 2.3 g/dL was significantly associated with a longer PFS (HR = 0.57, 95%CI [0.34; 0.95]). Conclusions: HbL increase ≥ 2.3g/dL in the first 3 months of axitinib treatment was associated with longer PFS. These results require validation in a prospective trial setting.
Clinical, pathologic, and genomic profiles of exceptional responders to anti−PD1 therapy in renal cell carcinoma.
Authors: Ball Mark Wayne , Johnson Michael Hiroshi , Gorin Michael A. , Rodriguez Maria , Diaz Luis A. , Haffner Michael , Netto George J. , Drake Charles G. , Allaf Mohamad E. 
Published: February 2017

625 Background: Previous studies have correlated response to PD−1 blockade with PD−L1 over−expression, as well as cell−mediated immune transcripts). However, factors associated with long−term, durable response to nivolumab in patients with RCC have not yet been elucidated. To better understand these factors, we conducted a study to characterize the two extremes of response to therapy – exceptional responders who had durable, complete response and patients who had primary refractory disease. Methods: Patients with durable, complete response (“exceptional responders”) (n=4) and primary refractory disease (n=3) were analyzed. Immunohistochemical staining for PD−L1, CD8 and FOXP3, whole−exome sequencing and quantitative RNA expression profiling was performed and correlated with clinical outcomes. Results: Exceptional responders had trends toward greater CD8+ lymphocyte infiltrate (126.7 vs 28.8 lymphocytes/hpf), higher number of somatic mutations (67 vs 35 somatic mutations/genome), and higher number of predicted mutation associated neoantigens than primary refractory patients (44 vs 8). Expression analysis demonstrated acute phase and immune tolerance signatures in primary refractory patients, while exceptional responders had higher expression of T cell and innate immune signatures. Conclusions: Exceptional responders and primary refectory patients have distinct pathologic, genomic and RNA expression profiles. Larger studies are needed to fully elucidate the basis of response to PD−1 blockade in patients with renal cell carcinoma.
The Commission on Cancer Psychosocial Distress Screening Standard: The first year in review.
Authors: Miller Nina S. , McCabe Ryan M. , Knutson Allison 
Published: February 2017

198 Background: In response to recommendations from the 2007 Institute of Medicine report, Cancer Care for the Whole Patient, the American College of Surgeons’ Commission on Cancer developed a set of Continuum of Care standards, including a patient-centered standard regarding the delivery of psychosocial distress screening to all cancer patients. According to Cancer Program Standards 2012: Ensuring Patient-Centered Care, the accredited cancer program must implement a process to integrate and monitor on-site psychosocial distress screening and referral for the provision of psychosocial care. Patients experience psychological, social, financial, and behavioral issues that can interfere with their treatment plan and adversely affect outcomes. Screening processes result in the identification of distressed cancer patients and assessment and referral pathways to ensure appropriate psychosocial care provision can be obtained. The standard was established in 2012 with a 2015 implementation period allowing programs time to develop a screening, assessment, and referral process tailored to their patient population. Methods: Programs submit documentation to describe their process for delivery of care through an electronic activity report. Documentation of this standard includes the timing for delivery of the psychosocial distress screening tool; methodology; the specific tools selected with preference to validated and reliable screening tools; and a process for assessment, referral and documentation. This presentation will summarize the program submissions for 2015 and include an analysis of the details of the standard compliance as reported by accredited programs. Results: This analysis will include responses from all Commission on Cancer accredited programs reporting on this standard. The analysis will provide information about the trends in the timing, methods, and tools used by programs implementing a psychosocial distress screening process. Conclusions: This analysis will inform future decisions about standardization of a screening process and the feasibility of pooling data across centers.
Impact of preoperative sarcopenia on recurrecnce in gastric cancer surgery.
Authors: Sato Tsutomu , Aoyama Toru , Maezawa Yukio , Kano Kazuki , Segami Kenki , Nakajima Tetsushi , Ikeda Kosuke , Hayashi Tsutomu , Yamada Takanobu , Oshima Takashi , Rino Yasushi , Masuda Munetaka , Cho Haruhiko , Ogata Takashi , Yoshikawa Takaki 
Published: February 2017

120 Background: Our previous study clarified that morbidity was a negative prognostic factor and sarcopenia defined by of the handgrip strength was a risk factor for the morbidity in gastric cancer surgery. Sarcopenia was reportedly a negative prognostic factor in colorectal cancer, hepatocellular carcinoma and malignant melanoma. This study aimed to evaluate impact of preoperative sarcopenia on recurrence-free survival (RFS) in gastric cancer surgery. Methods: Between May 2011 and June 2013, 256 consecutive primary gastric cancer patients who underwent curative surgery were retrospectively examined. Patients who received neoadjuvant chemotherapy or were diagnosed with pathological stage IV were excluded. Preoperative skeletal muscle mass was evaluated by bioelectrical impedance analysis and was expressed as skeletal muscle index or SMI (muscle mass/height2) by adjusting absolute muscle mass with height. Preoperative muscle function was measured by hand grip strength (HGS). Each cutoff value was determined as the gender-specific lowest 20% of the distribution of each measurement. Univariate and multivariate analyses were preformed to identify risk factors for RFS using a Cox proportional hazards model. Results: Median age (range) was 66 years (37-85 years). Male to female ratio was 168:88. Median follow-up period was 33.4 months. Pathological stage was I in 160, II in 48 and III in 48 patients. Univariate analysis showed that age, adjuvant chemotherapy, pT, pN, histological type, tumor size, total gastrectomy, low SMI and low HGS were significant risk factors for RFS. Multi-variate Cox’s proportional hazard analyses demonstrated that pT (HR 2.76, p = 0.0001), pN (HR 1.375, p = 0.037), histological type (HR 3.46, p = 0.014), low SMI (HR2.17, p = 0.036) were the significant risk factors for RFS. The three-year RFS was 89.1% in the patients with high SMI and 73.2% in those with low SMI (p = 0.007). Conclusions: Low SMI was an independent risk factor for RFS in Stage I-III gastric cancer. Low HGS, a risk factor for morbidity shown in our previous study, was not a risk independent factor for RFS. Preoperative sarcopenia as the short- and long-term outcomes has a value to be tested in the future prospective studies in gastric cancer surgery.