tbuckley/cabot-search huggingface dataset:
Effectiveness and new safety profile of rasburicase (urate oxidase) in Japanese patients with malignant lymphoma and acute leukemia in phase II study (ARD5290)
Authors: M. Ogura, K. Ishizawa, M. Hamaguchi, T. Hotta, K. Ohnishi, T. Sasaki, H. Sakamaki, K. Tamura, N. Usui, Y. Morishima
Journal: Journal of Clinical Oncology (2006)

8566 Background: Rasburicase (RAS) for the prevention of tumor lysis syndrome (TLS) populations at high risk, and for the treatment of hyperuricemia (HU) has obtained approvals in most countries in the world except in Japan. Thus, we conducted licensing phase II study of RAS with primary endpoint of overall efficacy response (ER) rate. We report efficacy and the new safety profile of only RAS administration prior to chemotherapy. Methods: Fifty patients (pts) with ML and/or AL, were administered RAS for 5 days using two dose-levels (0.15 mg/kg/day or 0.20 mg/kg/day). Chemotherapies were started from 4 to 24 hours after RAS treatment. ER was defined as keeping plasma uric acid level 7.5mg/dL by 48 hr after the start of first RAS infusion and lasting until 24 hr after the start of final (Day5) RAS infusion. Results: The overall ER rate was 98%. 49 pts (98%) completed 5 days of treatment. Both doses provided equally effective reduction of uric acid under the study conditions. Seven drug-related adverse events of grade 1 or 2 by NCI-CTC occurred in 6 pts during using only RAS (before first chemotherapy). ‘Hypersensitivity’ occurred in 3 pts, and ‘rash’, ‘anorexia’, ‘application site pain’, and ‘pyrexia’ occurred in 1 patient each. No grade 3 or 4 adverse events were reported. Only five pts (10%) had anti-RAS antibodies by Day29. Conclusions: RAS has proved to be highly effective with a good safety profile including the new safety one as single agent without chemotherapy. Although both two levels were effective, level of 0.20 mg/kg seems to be an optimal dose because RAS was effective against serious cases of HU in this level. The presence of anti-RAS antibodies was very low suggesting that the possibility for retreatment maybe possible. No significant financial relationships to disclose.
Biopsychosocial distress assessment among testicular cancer survivors (TCS) using electronic patient reported outcomes (PROs).
Authors: Elizabeth A. Guancial, Jennifer Peckham, Judith Baumhauer, Supriya Gupta Mohile, Deepak M. Sahasrabudhe, Paul Duberstein, Chunkit Fung
Journal: Journal of Clinical Oncology (2017)

204 Background: Distressis a frequently endorsed experience by cancer patients.Many organizations advocate formal distress screening as part of clinical care in order to better meet the “psychological, social, and/or spiritual needs of patients that may interfere with the ability to cope effectively with cancer, its physical symptoms, and its treatments.” The primary objective of this study is to characterize distress levels among TCS using electronic PROs via a modified version of the National Comprehensive Cancer Network Distress Thermometer (DT) and Patient Reported Outcomes Measurement System (PROMIS). Methods: Eligible TCS ( &lt; 69 years at diagnosis, any treatments, not in active or maintenance stage of exercise behavior) enrolled onto a pilot study of an electronic, self-directed, individually tailored “EXercise for CAncer Patients” (EXCAP) program were offered iPad-based distress screening during routine medical oncology clinic visits. Screening consisted of a modified DT, where patients self-report distress on a scale of 1-10, wherein scores of greater than 4 refer to increased distress, as well as PROMIS domains for anxiety and depression, where scores range from 0-100, 50 is the average for the United States (US) general population, and higher values indicate more anxiety or depression. Results: A total of 18 TCS (median age 44) enrolled in the EXCAP study as of May 31, 2016. Among participants, 56%, 28% and 17% had stage I, II, and III testicular cancer, respectively. Treatment modality and median time from treatment to enrollment were: 78% orchiectomy, 23.5 months (range 1-204); 33% retroperitoneal lymph node dissection, 8 months (range 1-48); and 72% chemotherapy, 22 months (range 3-587). TCS completed a median of 2 distress screenings (range 1-8). The median DT score was 3 (range 1-8). Median PROMIS anxiety and depression scores were 52.88 (32.87-69.36) and 51.02 (34.17-6.65). Conclusions: TCS self-report low levels of distress on the DT and PROMIS scores for anxiety and depression that are comparable to the US general population. Future research will explore associations between patient- and disease-specific factors and distress in TCS.
Identification and validation of predictive biomarkers (BM) for everolimus (EVE) in metastatic renal cell carcinoma: Analysis of 442 patients on RECORD-3.
Authors: Martin Henner Voss, David Chen, Mahtab Marker, Mark Hamilton, Creton Kalfoglou, James Hsieh, Jennifer J. Knox, Oezlem Anak, Robert J. Motzer
Journal: Journal of Clinical Oncology (2014)

4531 Background: RECORD-3 is a phase 2 trial that compared 1st-line EVE then sunitinib (SUT) with first-line SUT then EVE at progression (1:1 randomization). The study did not meet its primary endpoint (median progression free survival (mPFS) non-inferiority) in unselected treatment-naïve mRCC pts. This work investigated BMs predictive of EVE efficacy (PFS in first-line). Methods: 121 cancer-related BMs were analyzed by multiplex ELISA on baseline plasma samples collected from 94% of the trial subjects. The subjects were divided into training (327) and validation (115) cohorts. Kaplan-Meier estimates of mPFS for individual BM (low vs high, relative to an optimal cut-point for each BM), hazard ratios (HR) from Cox proportional hazards model and log-rank test p-values for differences in PFS between treatments in BM subgroups were computed. Results: Three BM levels were predictive for mPFS with EVE in the training set (table). Similar mPFS between the treatments was seen in the low BM subgroups, while mPFS remained significantly shorter for EVE vs SUT in the high BM subgroups. mPFS for EVE was longer in low than in high BM patients, but independent of the BM levels in SUT treated patients. Some results were supported by the validation set. Conclusions: EVE and SUT efficacies were comparable for mRCC patients with low plasma levels of three novel BMs in the first-line setting. The correlation of these BMs with EVE efficacy may be due to their interactions with pathways associated with mTOR inhibitor resistance, such as activation of PI3K and MAPK pathways by RTK-AXL. Clinical trial information: NCT00903175. EVE SUT Cox PH Log-Rank BM level mPFS (m) 95% CI mPFS (m) 95% CI HR (EVE/SUT) 95% CI P-value Receptor tyrosine kinase AXL low 8.8 8.0 - 12.1 10.9 8.2 - 12.8 1.13 0.81 - 1.57 0.4355 high 5.1 2.9 - 5.8 10.6 7.2 - 15.6 3.09 2.00 - 4.76 <0.0001 Interferon-inducible T-cell α chemoattractant (ITAC) low 13.5 8.2 - 18.8 10.9 7.9 - 15.7 0.9 0.55 - 1.47 0.3783 high 5.8 5.3 - 8.1 10.7 8.2 - 12.1 2.03 1.49 - 2.77 0.0009 Kidney injury molecule-1 (KIM-1) low 15.5 10.5 - 24.0 13.4 10.7 - 30.8 1.05 0.62 - 1.77 0.3459 high 5.4 4.4 - 5.8 8.3 7.6 - 11.1 1.93 1.42 - 2.60 0.0001 Intent-to-treat population: mPFS for EVE and SUT: 7.9 m and 10.7 m; HR 1.43 (95% CI 1.15-1.77).
The unmet needs of cancer survivors and their preferences for discussing them with oncologists and general practitioners (GPs).
Authors: Kate Webber, Afaf Girgis, Barbara Kaye Bennett, Antonino Bonaventura, Frances M. Boyle, Eng-Siew Koh, Michael Friedlander, Eva Segelov, David Goldstein
Journal: Journal of Clinical Oncology (2013)

9602 Background: Cancer survivors experience a range of post-treatment issues which are not well met by current services. This study explores the unmet needs of adult cancer survivors and their levels of comfort in addressing issues with oncologists and GPs. Methods: A cross-sectional survey was mailed to adult cancer survivors 4 years from diagnosis from 6 oncology units. Self-report data were obtained ranking physical, psychological and practical areas of importance to survivors; unmet needs in these areas; and the providers with whom they were happy to discuss each issue. Descriptive statistics were obtained regarding needs and preferences. Univariate and multivariate logistic regression analyses assessed demographic and clinical variables associated with 4 or more unmet care needs. Results: 228 surveys were returned (response rate 50.5%). Respondents had a mean age of 59.3 years (range 32-87), 71.5% were female, with most common primary cancers being breast (71.5%), colorectal (13.9%), prostate (4.5%) and ovarian (2.2%). The most commonly reported unmet needs were information about late effects (50.3%), managing fatigue (41.7 %), genetic risk to family (34.7%), reassurance (32.0 %) and diet (31.4 %). The median number of unmet needs was 4 (range 0-23). On univariate analysis, female gender, younger age and tertiary education were associated with greater unmet needs (p&lt;0.001, p=0.01 and p=0.02). On multivariate analysis higher education (p=0.04) remained independently associated. Conclusions: Cancer survivors report significant unmet care needs, and their comfort levels for discussing them varies between providers. Some key issues are not entrusted to either oncologists or GPs. Models of care for survivors must address these potential deficits in care. [Table: see text]
Quality of life analysis of NCCTG N0877 (Alliance): Phase II trial of either dasatinib or placebo combined with standard chemoradiotherapy for newly diagnosed glioblastoma multiforme (GBM).
Authors: Rui Qin, Angelina D. Tan, Jeff A. Sloan, Derek Richard Johnson, Glenn Jay Lesser, S. Keith Anderson, Nadia N. Laack
Journal: Journal of Clinical Oncology (2015)

e17715 Background: Patients newly diagnosed with glioblastoma multiforme (GBM) must undergo extensive chemo-radiation therapy, but quality of life during treatment has not been fully evaluated. Functional Assessment of Cancer Therapy-Brain (FACT-Br) is a commonly used instrument measuring general quality of life (QoL) that reflects symptoms or problems associated with brain malignancies. EORTC QLQ-C15-PAL and QLQ-BN20 are shortened questionnaires for cancer patients in palliative care and brain module, respectively. Neither has been fully validated in this patient population. Methods: Patients enrolled in a randomized phase II clinical trial of dasatinib in combination with standard chemo-radiotherapy (ClinicalTrials.gov identifier: NCT00869401) were asked to complete FACT-Br and both EORTC QLQ questionnaires at baseline and at each MRI evaluation (cycles 4, 6, 8, 10, 12) for a maximum of six assessments. Standard scoring algorithms were used to compute overall, domain or symptom scores which were converted to a 0—100 scale. Two-sample t-test and Wilcoxon rank-sum test were used for exploratory analysis without an adjustment for multiplicity. Results: After nearly full-compliance at baseline, follow-up QoL compliance rates fell significantly to 56.6%, 29.1% and 14.8% prior to cycles 4, 8, and 12, respectively. Major reasons for not completing QoL assessments were disease progression (45.4%), adverse event (13.8%) and refusal of further treatment (12.2%). Patients responded with slight preference of FACT-Br over EORTC questionnaire (13.3% vs 6.7%). The addition of dasatinib to standard chemo-radiotherapy did not impact patient overall QoL. The overall and functional domains of QoL by either questionnaire were comparable and showed similar time trends. Conclusions: The use of EORTC QLQ C15-PAL plus BN20 was feasible and produced consistent QoL information with the FACT-Br. Both QoL questionnaires adequately captured QoL of GBM patients during treatment; however, significant decline in compliance with these instruments was observed secondary to disease progression and health deterioration. Clinical trial information: NCT00869401.
Implementing mental health screening, assessment, and navigation program in a community-based survivorship program.
Authors: Laura Howe-Martin, Stephanie L. Lawrence, Bryan Jester, Nancy de la Garza, Natalie Benedetto, Tracy Mazour, Robrina Walker, Manish Jha, Keith Edward Argenbright, Madhukar H Trivedi
Journal: Journal of Clinical Oncology (2017)

36 Background: ASCO guidelines recommend cancer survivors be evaluated, treated, &amp; reassessed for depression &amp; anxiety along the trajectory of care. To meet these guidelines, UT Southwestern Moncrief Cancer Institute instituted an integrated approach to mental health screening, assessment, &amp; navigation called MH-SCAN. (Andersen, BL, Rowland, JH, Somerfield, MR. Screening, assessment, and care of anxiety and depressive symptoms in adults with cancer: an American Society of Clinical Oncology guideline adaptation.J Onc Prac, 2015. 11(2): p. 133-134.) Methods: MH-SCAN uses the Vital Sign 6 (VS 6 ) program, a web-based application to screen &amp; monitor psychiatric symptoms, and to give feedback regarding measurement-based care (MBC). Measures are repeated at 2-week intervals when possible for those who need treatment. Our implementation process, including training &amp; workflows, will be reviewed. Results: Patients (N = 415) enrolled from 9/1/15 to 8/1/16 in our community-based Survivorship Program (see table) were screened using VS 6 , of which 119 reported symptoms indicating potential depression. Over 90% of that subset reported moderately severe symptoms and 87% endorsing comorbid symptoms of anxiety. Approximately 60% of the original sample completed reassessment within 4 weeks. Over half continued to endorse significant depressive symptoms, as well as suicidal ideation and comorbid anxiety. Conclusions: Implementing ASCO recommendations for mental health screening, assessment, and treatment adherence, while challenging, is feasible. Our preliminary data underscores its importance among survivors. The MH-SCAN protocol provides a useful approach to implementing screening guidelines efficiently and effectively, thus addressing mental health comorbidities within oncology and primary care.[Table: see text]
Serum procarboxypeptidase combined with CA19-9 and accuracy of detection of pancreatic cancer.
Authors: Michelle A. Orlowski, William R Bamlet, Ann L. Oberg, Gloria M. Petersen, Suresh T. Chari, Arthur Topilow, John Davis, Charles Gilvarg
Journal: Journal of Clinical Oncology (2014)

4118 Background: Pancreatic cancer continues to have a dismal prognosis when diagnosed at an advanced stage. Thus, there is need for an early detection test. CA19-9 is the “gold standard”, but fails as a means for detecting early stage disease. Previous studies have shown that pancreatic cancer, particularly in its early stages, is characterized by elevation in serum procarboxypeptidase A (PCPA) and high ratios of PCPA to free carboxypeptidase A (FCPA). The ratio can also enhance the diagnostic efficacy for some late stage tumors when the PCPA is within the normal range. The purpose of this study was to evaluate the performance of the assay alone and with CA19-9 in an independent cohort. Methods: Pre-treatment serum from 224 subjects recruited at Mayo Clinic were used (74 early and 75 late stage clinically and/or histologically proven pancreatic adenocarcinoma patients, and 75 healthy primary care controls). 111 cases had a head lesion and 38 had a body/tail lesion. All had CA19-9 measured. Blinded to clinical status, PCPA and FCPA were measured using a newly-automated method on the Beckman Coulter UniCel DxC 800 Synchron Clinical System. Patients were classified as having cancer if they had CA19-9 >55 and/or PCPA/FCPA ratio either <1 or >33, based on previous studies. Results: As single biomarkers, CA19-9 and PCPA/FCPA ratio have similar sensitivity (73.2 vs. 72.5, respectively), but specificity was higher for CA19-9 (98.7 vs. 78.7, respectively). A biomarker panel containing both the PCPA/FCPA ratio and CA19-9 improves sensitivity (73.2% to 87.2%, McNemar’s test p-value < 0.0001) when compared to CA19-9 alone; specificity is decreased (98.7% to 82.7%, McNemar’s test p-value = 0.0005). However, overall accuracy is increased relative to CA19-9 alone (81.7% to 85.7%). Conclusions: In a blinded, single draw independent sample, the combination of the PCPA/FCPA ratio and CA19-9 has demonstrated 87.2% sensitivity and 82.7% specificity for pancreatic cancer in a heterogeneous patient population. The addition of the PCPA assay may provide some promise for the development of a screening tool for the early detection of pancreatic cancer in high risk patients and studies are needed to further validate the utility of the assay.
A phase I/II study with a CNS-penetrant, selective ALK inhibitor alectinib in <i>ALK</i>-rearranged non-small cell lung cancer (<i>ALK</i>+ NSCLC) patients (pts): Updates on progression free survival (PFS) and safety results from AF-001JP.
Authors: Yuichiro Ohe, Makoto Nishio, Katsuyuki Kiura, Takashi Seto, Kazuhiko Nakagawa, Makoto Maemondo, Akira Inoue, Toyoaki Hida, Hiroshige Yoshioka, Masao Harada, Naoyuki Nogami, Haruyasu Murakami, Kengo Takeuchi, Tadashi Shimada, Hiroshi Kuriki, Tomohiro Tanaka, Tomohide Tamura
Journal: Journal of Clinical Oncology (2015)

8061 Background: Alectinib, a CNS-penetrant, selective ALK inhibitor with a novel scaffold, was granted approval in Japan 2014, since it showed good efficacy and tolerability in ALK+ NSCLC pts without previous ALK inhibitor treatment (CMSTO2014). This report describes the updated data of the 46 pts enrolled in phase II part of AF-001JP. Methods: ALK+ NSCLC pts without previous ALK inhibitor treatment were given alectinib at 300 mg b.i.d to investigate the efficacy and safety until no further clinical benefits as assessed by investigator. Results: Alectinib showed good tumor response to ALK+ NSCLC in AF-001JP study and has been already approved in Japan. Further evaluation is ongoing for PFS and OS. 28 of 46 pts were on treatment with alectinib as of October 31, 2014. In spite of the fact that median follow-up duration had passed 30 months (range: 1-36) as of then, progressive disease (PD) was confirmed in only 12 pts (26.1%) (CNS progression: 4 pts, Non-CNS progression: 8 pts).Of them, 3 pts received alectinib later than PD. Though median PFS had not been reached then, it is expected to be at least longer than 29 months. 7 of 14 pts with baseline brain metastasis still remained in the study without CNS or systemic progression at that time. PFS with brain metastasis was similar to the one without brain metastasis. There were no treatment-related Grade 4 or 5 AEs. Since safety profile was consistent with the one in the previous reports, high tolerability of long term administration of alectinib was observed. The results suggested that alectinib showed high efficacy and safety for longer period. Conclusions: Alectinib is a novel therapeutic option for the treatment of ALK+ NSCLC, since in ALK+ NSCLC pts without previous ALK inhibitor treatment, alectinib demonstrated excellent efficacy and tolerability for longer administration. Clinical trial information: JapicCTI-101264.
Human cost of delivering healthcare in unhealthy prisons
Authors: Alison Frater, Annie Bartlett
Journal: BMJ (2017)

Government must commit to urgent reform or risk more avoidable deaths in custody

Successive UK governments have received strikingly similar recommendations on prison reform from chief inspectors,1 Justice Select Committees,2 and independent parliamentary inquiries,3 yet largely ignored them. Now, an unprecedented increase in rates of deaths in custody4 suggests that deteriorating conditions are compromising the delivery of adequate physical and mental health services. It remains to be seen whether the government’s new Prison and Courts Bill5 will go beyond rhetoric about improving safety and security and tackle current realities.

The public has been briefed about high levels of violence, bullying and intimidation, self inflicted death, self harm, and murder in prisons. Health professionals must now be heard—speaking up for evidence based recommendations at a time when prisoners’ health and humanity are at risk.

Concerns expressed by the House of Commons Justice Select Committee in its 2015 report foreshadowed the current crisis: a 28% reduction in prison staff between 2010 and 2014, poor …
Recurrence score and quantitative ER expression to predict in late distant recurrence risk in ER+ BC after 5 years of tamoxifen.
Authors: Norman Wolmark, Eleftherios P Mamounas, Frederick L. Baehner, Steven M. Butler, Gong Tang, Farid Jamshidian, Amy P. Sing, Steven Shak, Soonmyung Paik
Journal: Journal of Clinical Oncology (2014)

11024 Background: Identification of molecular determinants predicting late recurrence (>5 yrs) in stage I and II breast cancer has become clinically important in light of data demonstrating a benefit for ten yrs of tamoxifen administration. Since the 21-gene Recurrence Score (RS) is commonly utilized in early stage BC, we wished to determine its utility in predicting distant recurrences beyond five yrs as a function of quantitative ER expression. Methods: The 21-gene RS was assessed in 1,065 chemo and tam-treated, ER+, node-positive pts from NSABP B-28 and 668 tam-treated, ER+, node-negative pts from NSABP B-14. Cox PH models, KM estimates and log rank statistics were used to assess the association of the RS with risk of DR by quantitative ER expression, using the 21-gene assay, in pts event-free after 5 yrs. We established an ER cut-point (high vs low) in B-28, and tested the cut-point in B-14, formally evaluating the interaction of RS and ER. Results: Median follow-up was 11.2 yrs (B-28) and 14.5 yrs (B-14). 832 B-28 pts and 564 B-14 pts were DR-free after 5 yrs. A reference normalized ER cut-point of 9.1 CTwas established in B-28 based on the association of the RS with DR after 5 yrs. Of the event-free pts at 5 yrs, 68% in B-28 and 88% in B-14 had ER>9.1. In B-28 the RS result was strongly associated with DR after 5 yrs in the higher ER expressing pts (log rank P=0.001), but not in the lower ER expressing pts (log rank P=0.87). It was confirmed in the B-14 data that RS was associated with DR after 5 yrs in higher ER pts (Table) but not in the lower ER pts (interaction P=0.03). Conclusions: For late recurrences (beyond 5 yrs), the RS is strongly prognostic in pts with higher quantitative ER expression (>9.1). The findings suggest that extending tamoxifen beyond 5 yrs may be most beneficial in pts with high (and intermediate) RS with higher quantitative ER expression and of limited benefit in pts with a low RS (>50% of population under study). DR Risk after 5 yrs in B-14 by RS risk group for pts with ER>9.1 CT. RS risk group N (%) pts %DR KM estimate (95% CI) 5 to 10 yrs % 5 to 15 yrs % Low 289 (58%) 4.7 (2.8 - 8.0) 6.8 (4.4 - 10.6) Intermediate 111 (22%) 4.1 (1.6 - 10.6) 11.2 (6.2 - 19.9) High 97 (20%) 12.6 (7.4 - 21.2) 16.4 (10.2 - 25.7) Log rank P=0.01