tbuckley/cabot-search huggingface dataset:
A prospective study of capecitabine plus modified cisplatin (mXP) as first-line therapy in Japanese patients with metastatic gastric cancer (KSCC1104).
Authors: Ikuo Takahashi, Mototugu Shimokawa, Yasunori Emi, Hiroaki Tanioka, Takeshi Shiraishi, Eiji Oki, Hiroshi Saeki, Akihito Tsuji, Sumiya Ishigami, Yoshihiro Kakeji, Hideo Baba, Shoji Natsugoe, Yoshihiko Maehara
Journal: Journal of Clinical Oncology (2015)

129 Background: Capecitabine plus cisplatin (XP) is one of the standard therapies for metastatic gastric cancer (mGC). However there is no clinical practice date in Japan, and results from the ToGA and AVAGAST study suggested dose of cisplatin should be lower in Japanese. This study was designed to evaluate the efficacy and safety of mXP in the clinical practice in Japanese mGC patients (pts) including the elderly. Methods: The study design was multicenter, single-arm, open-label prospective study. The major inclusion criteria were previously untreated mGC; presence of measurable lesions; age 20 years; ECOG performance status (PS) 0–2; and adequate organ function. Pts received mXP (cisplatin 60 mg/m 2 d1 plus capecitabine 1,000 mg/m 2 bid d1-14) q3w. This schedule was repeated until unacceptable toxicity or disease progression occurred. The primary endpoint was RECIST-confirmed objective response rate (ORR). A sample size of 40 was planned for a threshold ORR of 30% and expected value of 50%, with one-sided alpha of 0.05 and beta of approximately 0.2. Results: Of the 42 pts (male/female, 34/8; median age, 63.5 years (range 50-81); PS 0/1/2, 34/8/0) enrolled from Nov 2011 to Oct 2013. One patient did not fulfill the eligibility criteria. Forty one pts were assessed for response; CR 2 pts, PR 16 pts, SD 14 pts, PD 8 pts, and NE 1 pts. The confirmed ORR was 43.9% (90% CI; 31.2-56.7%, 95% CI; 28.7-59.1%). Median PFS and mOS were 4.5 months (95% CI; 3.9 – 6.5M) and 11.4 months (95% CI; 7.7 – not reached). The most common grade 3/4 adverse events were anorexia 24.4%, neutropenia 36.6%, fatigue 9.8%, hand-foot syndrome 7.3%. Grade 3/4 peripheral neuropathy did not occur. Conclusions: First-line chemotherapy for HER2-negative patient of mXP showed a promising response rate and an acceptable tolerability profile in the clinical practice in Japanese mGC pts including the elderly. Clinical trial information: UMIN:000006668.
Supportive care organization in France: State of the art.
Authors: F. Scotte, C. Herve, R. Bugat, F. Farsi, B. Lucas, M. Namer, J. Tourani, C. Tournigand, G. Yazbek, S. Oudard, K. Tahiri, I. Krakowski
Journal: Journal of Clinical Oncology (2011)

e16575 Background: Second cancer plan was defined in France in December 2009 including enhancement of supportive care in cancer (SCC). Methods: We conducted this observational study to evaluate practices, organizations and information given to patients (pts) about SCC in 2010. Among 1621 french medical doctors (MD) caring cancer pts who were sent an adhoc questionnary, 20% (330 MD including 44% medical oncologists) answered. Results: Three different organizations were described: single MD, transversal team and specific structure specialized in global care (specifically developed in comprehensive cancer centers [CCC]). Psycho-oncology, palliative care, nutrition and pain care were the four top items considered as supportive care. During their disease, 68% of pts are receiving SCC, presented by their MD (88%) or nurse devoted to announcement of disease and SCC information (57%). Supportive care is more dispensed during palliative period (90%) than at diagnosis (44%). Patients information is rather supplied during palliative care (85%) than at diagnosis (52%) using a specific questionnary for outpatient (20%) or specific supportive care session (17%). 71% of cancer department have a cross team to provide supportive care, with specific SCC team particularly in CCC (67%). 37% have inpatient specific units (10 beds). Only 40% have a specific organization in home care connection. 73% use specific financial valorization of CSC activity. Adverse events information is dispensed to 54% of the pts for erythropoiesis stimulating agents (ASE), 74% for biphosphonates and 94% for opioids treatments. Conclusions: Specific organization developed especially in comprehensive cancer centers seems to facilitate SCC organization and information to pts. In the mean time, recommendations include this information, involvement in supportive care team and methods have to be enhanced. Further results compared with patient point of views are expected.
The Effects of Alemtuzumab (A) Dose-Sequence upon Rituximab (R)-Induced Reorganization of Lipid Raft Domains and In-Vitro/In Vivo Anti-Tumor Activity.
Authors: Francisco J. Hernandez-Ilizaliturri, Aruna C. Gowda, Dana Brombos, Dan Spear, Myron S. Czuczman
Journal: Blood (2004)
Phase I/II clinical trial of ALT-801, a T-cell receptor/IL-2 fusion protein, plus gemcitabine and cisplatin in urothelial cancer.
Authors: Mayer N. Fishman, Julio Hadjenberg, Timothy Kuzel, Amit Mahipal, Charles Joel Rosser, Danny Landau, Shilpa Gupta, Daniel A. Vaena, Sanjiv S Agarwala, John Francis Mahoney, Jean H. Hoffman-Censits, Wayne Harris, Mohammed M. Milhem, Jeffrey S. Weber, Peter Rhode, Tessa Schutt, Liza Hernandez, Bee-Yau Huang, Hing C. Wong
Journal: Journal of Clinical Oncology (2013)

271 Background: ALT-801, a T-cell receptor/IL-2 fusion protein, activates NK and CD4 + lymphocytes to secrete IFN-gamma which re-polarizes tumor associated macrophages from M1 to M2 in various murine tumor models. CD8 + memory cells also acquire an innate immune phenotype and become expanded upon ALT-801 activation. Via this novel mechanism, ALT-801 mounted effective immune responses and maintained immunological memory against urothelial cancer in these models. Pretreatment chemotherapy eliminated myeloid-derived suppressive cells, potentiating the anti-tumor effects of ALT-801 (Wong, unpublished data). Previous clinical studies with ALT-801 (advanced malignancy; Fishman 2011 CCR 17:7765) and ALT-801 + cisplatin (melanoma; NCT01029873) showed anti-tumor activity in these settings. Methods: We evaluated co-administration of gemcitabine [G] (1000 mg/m 2 /dose, day 1 and 8) and cisplatin [C] (70 mg/m 2 /dose, day 1) with ALT-801 (escalating doses; days 3, 5, 8, 10) for three 21-day cycles, in patients with metastatic urothelial cancer. Those with at least stable disease after 3 courses could receive 4 additional weekly doses of ALT-801 alone. ALT-801 doses were planned at 0.04 to 0.12 mg/kg/dose in 5 cohorts with a 3+3 escalation design. Results: The dose-escalation is completed, with a recommended dose of ALT-801 of 0.06 mg/kg/dose. The best objective response rate (ORR, RECIST v1.1) among 5 chemo-naïve subjects was 100% (2 CR, 3 PR) and among 5 previously treated patients 60% (1 CR, 2 PR), for an overall total of 80% (3 CR, 5 PR, 1 SD, 1 PD). One of 2 patients who underwent radical cystectomy was confirmed pathologically free of tumor. Responding lesions included bulky and extensive liver and pulmonary metastases, and adenopathy. ALT-801 at the 0.06 mg/kg/dose level in this combination was adequately-tolerated. Grade 3/4 toxicities including neutropenia, thrombocytopenia and lymphopenia, appear consistent with known G, C, and ALT-801 effects. Conclusions: ALT-801 is a novel and potentially active immunotherapy for urothelial cancer. More patients are in treatment on the open phase 2 expansion portion of the study (NCT01326871), and updated interim results are anticipated (CA097550). Clinical trial information: NCT01326871.
Symptoms associated with circadian rest-activity rhythm disruption in 237 patients with metastatic colorectal cancer.
Authors: Pasquale F. Innominato, Oxana Palesh, Georg A. Bjarnason, Ayhan Ulusakarya, David Spiegel, Francis Levi
Journal: Journal of Clinical Oncology (2015)

1 Background: The circadian timing system exerts temporal control over physiology, generating rhythms of about 24 hours. Its alteration in benign conditions has been associated with several systemic symptoms, including fatigue, appetite loss and poor sleep. However, the clinical impact of circadian disruption in cancer patients remains overlooked. We hypothesized that patients with circadian disruption would report more severe symptoms than those with robust circadian function. Methods: Data were available for 237 patients with metastatic colorectal cancer: M/F ratio: 1.66; median age: 60.4 years; range: 20.7-77.6; WHO Performance Status (PS) = 0/1: 59.7%/33.5%. We estimated the occurrence of circadian disruption using a validated parameter (the dichotomy index I &lt; O), derived from wrist-actigraphy for at least 72 consecutive hours. Symptoms were self-reported by the patients using the EORTC QLQ-C30 questionnaire. Mann-Whitney U test was used to compare symptom severity according to the presence or absence of circadian disruption. Cohen’s d effect sizes were computed to evaluate the clinical meaningfulness of the observed differences. Subgroup analyses were performed according to gender, age, and WHO Performance Status (PS). Results: Circadian disruption (I &lt; O lower than or equal to 97.5%) occurred in 130 (54.9%) patients. Fatigue (p &lt; 0.0001), appetite loss (p &lt; 0.0001), difficulty sleeping (p = 0.009), pain (p &lt; 0.0001) and dyspnea (p = 0.001) were significantly more severe in patients with circadian disruption than in those with robust circadian function. Largest effect sizes were observed for fatigue (0.64), appetite loss (0.59) and pain (0.57). Subgroup analyses showed similar results, regardless of gender, age or PS. Conclusions: In this large international study, the presence of circadian disruption was associated with a clinically meaningfully higher severity of fatigue, appetite loss, pain, dyspnea and sleep problems. Correcting circadian dysfunction with the use of pharmacological and/or behavioural interventions could improve these often difficult-to-manage systemic symptoms.
The effectiveness of behavioural and psychosocial HIV/STI prevention interventions for MSM in Europe: A systematic review
Authors: R Berg
Journal: Eurosurveillance (2009)

Given the need of programme planners and policy makers for descriptions of specific interventions and quantitative estimates of intervention effects to make informed decisions concerning prevention funding and research, there is a need for a systematic review that updates the current knowledge base about HIV/STI preventive interventions targeted at men who have sex with men (MSM) in Europe. The aim was to summarise and assess the effectiveness of HIV/STI prevention interventions for MSM living in Europe, and to identify intervention characteristics associated with effectiveness as well as potential gaps in the evidence base. A systematic search for relevant literature in eight international databases and in reference lists of relevant reviews and included studies was performed. Studies were selected according to pre-specified criteria and appraised for risk of bias. We summarised results using tables and calculated effect estimates for sexual behaviour outcomes. Results from six controlled studies, involving a total of 4,111 participants at entry from four different European countries were summarised. The results showed that there was 'high' or 'unclear' risk of bias in one or more of the assessed domains in all studies. The pooled effect estimate of the four interventions for which data were available suggested that MSM who participate in HIV/STI prevention initiatives may be somewhat less likely to report unprotected anal intercourse (UAI). The evidence base was insufficient to examine characteristics of interventions most closely associated with magnitude of effect and to draw solid conclusions about unique gaps in the evaluation literature. Despite the maturity of the HIV epidemic, rigorous outcome evaluations of any form of behavioural HIV/STI intervention for MSM in Europe are scarce. The results point to possible short term effects of interventions in terms of reductions in the proportion of MSM who engage in UAI, but the paucity of controlled studies demonstrates the need for research in this area. There is an overall deficit in outcome evaluations of interventions aimed at reducing HIV/STI risk behaviour among MSM in Europe. Designing behavioural HIV/STI preventive strategies to avert new infections, and the evaluation of such prevention programmes for MSM is an important component of a comprehensive HIV/STI containment strategy across the continuum of prevention and care.
Novel agents’ sequencing following first-line docetaxel in mCRPC patients: CAPRO study.
Authors: Javier Puente, Aranzazu Gonzalez del Alba, Nuria Sala, María José Méndez-Vidal, Alvaro Pinto, Angel Rodriguez Sanchez, Jose Miguel Cuevas Sanz, Josep Guma, Pablo Borrega, Carmen Molins, Rocío García Domínguez, Laura Basterrechea, Antonio López Jiménez, Enrique Gonzalez-Billalabeitia, Guillermo Crespo, Montserrat Domenech, Miguel Ángel Cabrera Suárez, Raquel Luque, Pedro Ruiz, Sergio Vazquez-Estevez
Journal: Journal of Clinical Oncology (2016)

229 Background: Novel agents, such as abiraterone (A), cabazitaxel (CZ), and enzalutamide are currently available for the treatment of docetaxel (D)-treated metastatic castration resistant prostate cancer (mCRPC). The sequencing approach following D progression is still unknown. We now explore which factors are driving sequencing decisions in routine clinical practice in Spain. Methods: A prospective multicenter national observational descriptive study collecting data of 2 nd line (L) treatments in mCRPC patients to analyze responses and progression to 1 st L D. Results: 149 patients have been recruited from July 2013 to January 2015. Median age was 72 (48-89). Median D cycles was 6 (1-24), and median dose: 75 mg/m 2 (30-75). 24 patients (16%) required dose reduction. The reasons for D ending were treatment completion (40%, n = 60), toxicity (15.3%, n = 23), progression (radiological, biochemical, clinical; 42%, n = 63), or others (2.7%, n = 4). 67% (n = 100) of the patients received A, 25% (n = 44) CZ, and 8% (n = 5) other treatments as 2 nd L. From those who completed or progressed to D (n = 123), 2 nd L initiation was mainly determined by two progression criteria (2C; biological and radiological), followed by one progression criteria (1C). This was independent of the 2 nd L treatment chosen, and it was observed in similar ratios in both A (2C: 50%, n = 39; 1C: 37.2%, n = 29) and CZ (2C: 62.5%, n = 25; 1C: 27.5%, n = 11). Nevertheless, A was predominantly given when patients progressed after D ending, whereas CZ was mostly given when progressing during D (Table 1). Conclusions: A is the 2 nd L treatment of choice in routine clinical practice in Spain, independent of the type and time of progression. CZ is preferentially used in patients progressing during D treatment. [Table: see text]
Phase II study to evaluate the efficacy and safety of bortezomib (PS-341) in chemotherapy-naïve patients with advanced stage non-small cell lung cancer (NSCLC)
Authors: L. Ho, T. Li, B. Piperdi, M. Macapinlac, J. R. Rigas, F. Camacho, R. Perez-Soler, R. Gucalp
Journal: Journal of Clinical Oncology (2008)

19096 Background: The primary objective of this study was to determine the complete, partial response rate and stable disease rate of bortezomib as a first line therapy in advanced NSCLC. Methods: Advanced NSCLC patients with measurable disease, adequate organ function, ECOG performance status of 0–1, and no prior chemotherapy for metastatic disease were eligible. Bortezomib was administrated at 1.3 mg/m2/day intravenously on days 1, 4, 9 and 11 every 21 days (defined as one cycle). Response was evaluated by RECIST every 2 cycles. Patients were to continue treatment for a maximum of 8 cycles, or until disease progression, or unacceptable toxicity. Results: The study was terminated in the first stage (Simon’s Minimax Two-Stage design) after 14 patients enrolled at 4 institutions between September 2004 and February 2007. Twelve patients (median age 70 years, range 50–84; female/male 6/6; median ECOG performance status 1) received at least one dose and a median of 2 cycles of bortezomib. There was no objective response observed. Three patients (25%) had stable disease and received 8, 6 and 4 cycles of treatment; the duration of response was 11.0, 2.8 and 2.0 months, respectively. Median time to progression was 1.4 months (range, 0.6 to11.5 months). Median overall survival was 10.2 months (range, 1.9 to 29.0 months). One-year and two-year survival rates were 41.7% and 25%, respectively. There were no treatment related deaths or grade 4 toxicities. Grade 3 toxicities included fatigue (8%), deep vein thrombosis (8%) and thrombocytopenia (8%). Conclusions: Bortezomib monotherapy is not active in chemotherapy-naïve, advanced NSCLC patients. Further study in combination therapy may be warranted. No significant financial relationships to disclose.
Deep brain stimulation of the subcallosal cingulate for treatment-refractory anorexia nervosa: 1 year follow-up of an open-label trial
Authors: Nir Lipsman, Eileen Lam, Matthew Volpini, Kalam Sutandar, Richelle Twose, Peter Giacobbe, Devin J Sodums, Gwenn S Smith, D Blake Woodside, Andres M Lozano
Journal: The Lancet Psychiatry (2017)
Hypofractionated radiotherapy (66Gy at 3Gy per fraction) for favorable-risk prostate cancer: Long-term outcomes.
Authors: Nita Patel, Sergio Faria, Fabio L. Cury, Marc David, Marie Duclos, George Shenouda, Luis Souhami
Journal: Journal of Clinical Oncology (2013)

141 Background: Hypofractionated radiotherapy (HypoRT) is increasingly being used to treat prostate cancer to take advantage of its likely low α/β ratio. There is limited experience in delivering a high biologically equivalent dose with HypoRT. We report long-term outcomes from patients treated with high-dose HypoRT. Methods: Patients with low and intermediate risk prostate cancer were treated using 3-dimensional conformal radiotherapy at a dose of 66Gy in 22 daily fractions of 3Gy without hormonal therapy. A uniform 7mm margin was created around the prostate for the planning target volume (PTV) and treatment was prescribed to the isocentre. Treatment was delivered using daily ultrasound image guided radiotherapy (IGRT). The CTCv3.0 was used to prospectively score toxicity. Biochemical failure was defined using the Phoenix criteria of nadir+2ng/ml. Results: A total of 129 patients were treated between November 2002 and December 2005. With a median follow-up of 90 months, the 5- and 8-year actuarial biochemical control rate was 97% and 92% respectively. The 5- and 8-year actuarial overall survival was 92% and 88% respectively. Only one patient died from prostate cancer at 92 months after treatment resulting in an 8-year actuarial cancer specific survival of 98%. Radiotherapy was well tolerated with 57% of patients experiencing no acute gastrointestinal (GI) or genitourinary (GU) toxicity. For late toxicity, the worst grade ≥2 rate for GI and GU toxicity was 27% and 33% respectively, but at the last follow-up the rate of grade ≥2 was only 1.5% for both GI and GU toxicity (Table). Conclusions: High dose HypoRT delivering 66 Gy in 22 fractions at 3Gy per fraction is a safe, effective and convenient modality of delivering radiotherapy to patients with favorable risk prostate cancer with excellent biochemical control rates and acceptable rates of acute and late GI and GU toxicity. [Table: see text]
Where you stand depends on where you sit: Alignment of quality measures to strategic intentions.
Authors: David M. Dilts, Christopher Peters, Steven Kunyuan Cheng, Steven Stadum
Journal: Journal of Clinical Oncology (2012)

265 Background: Identifying quality measurements for discovering and delivering effective cancer care are dependent on the strategic vision of the cancer center and its respective units yet, each unit encompasses a distinctive set of competencies. We propose a framework for evaluating and structuring the alignment of quality and unit strategy measures within the overall vision of a cancer center. Methods: Prospective analysis was conducted with structured interviews across leadership and key opinion leaders (1) at the executive level, (2) within cancer center units (including basic science, cores, clinical research, and oncology service lines) and (3) across key hospital and research integration points. Quality and strategic areas reviewed were success measures, strategic focus, competitive dimensions, key strategies, and significant barriers. Risk of bias was accounted for through interrater reliability across the consensus of three independent reviewers. Measures of consistency were quantitatively assessed through triangulation of multiple perspectives based on roles and responsibilities. Results: 61 individuals were interviewed, generating 875 responses across the five areas. Responses were grouped into 303 categories, and then into 32 specific perspectives. These perspectives were linked with each of the five quality and strategic categories. Assessment and prioritization of quality and strategic measures were calculated based on tabulation of responses. Conclusions: While overarching strategy is well understood throughout the cancer center, quality, and strategic measures must be developed to integrate activities of each functional units across the cancer center to support overall goals. The framework for aligning quality measures to strategy facilitates the ability for centers to develop, align, and prioritize quality measures across the institution. [Table: see text]
Cancer-related fatigue and sexual functioning in women with early breast cancer: Is there a link?
Authors: K. Webber, K. Mok, B. K. Bennett, I. Juraskova, D. Goldstein, M. Friedlander, A. R. Lloyd
Journal: Journal of Clinical Oncology (2011)

9072 Background: We have previously reported on the natural history of cancer related fatigue (CRF) after adjuvant breast cancer therapy in a prospective cohort study (FOLCAN). The aim of this paper is to report on sexual functioning (SF), and its relationship to CRF, mood disorder and quality of life (QOL). Methods: Women were recruited after surgery but prior to commencing adjuvant treatment. Self-report standardised questionnaires assessed SF, CRF, mood, menopausal symptoms, disability and QOL at baseline, completion of therapy, and at 6 and 12 months post-therapy. SF was assessed using the Cancer Rehabilitation Evaluation System (CARES) sexual subscale which includes sexual interest, physical sexual function and overall satisfaction items. One way repeated measures ANOVA was used to assess temporal changes in CARES scores, whilst Spearman’s correlations and multivariate regression models were employed to assess potential and actual predictors of SF. Results: 92 of the 218 participants completed the SF measure (mean age 49.8 years). They were significantly younger, more likely to be married or in a de facto relationship and less likely to be post-menopausal at baseline than non-reporters. At baseline, 40% reported problems with sexual interest and 60% with physical sexual function. SF scores declined across all domains at end-treatment, then improved but remained below baseline at 12 months; with a significant temporal effect in the physical SF subscale (Wilks’ λ 0.827, p=0.034) and a trend for overall satisfaction (λ 0.869, p=0.094). There were significant correlations between sexual dysfunction and QOL domains (physical and emotional health, social functioning and general health). None of fatigue, demographic or treatment variables were significant predictors of sexual dysfunction. The presence of mood disorder was the only significant independent predictor of poorer overall sexual satisfaction (p=0.005 at baseline, p<0.001 at 6 months, p=0.036 at 12 months). Conclusions: Sexual dysfunction over the first 12 months after breast cancer therapy is a common problem and impacts significantly on QOL. Interventions designed to address this must include identification and treatment of concomitant mood disorder.