tbuckley/cabot-search huggingface dataset:
<i>EGFR</i> mutations in NSCLC: Does ethnicity influence outcomes?
Authors: Pascale Tomasini, Mike Sung, Suzanne Kamel-Reid, Ming Sound Tsao, Geoffrey Liu, Penelope Ann Bradbury, Frances A. Shepherd, Ronald Feld, Natasha B. Leighl
Journal: Journal of Clinical Oncology (2015)

e17633 Background: EGFR mutations are more common in East Asians (EA) than in non-East Asians (non-EA) with non-small cell lung cancer (NSCLC), approximately 40% versus 10%. We explored whether there is a difference in outcomes by ethnicity in EGFR mutant NSCLC patients. Methods: We reviewed all cases of patients with EGFR mutation-positive NSCLC seen at a single cancer centre, treated in the Canadian public healthcare system. Differences in outcomes and EGFR TKI toxicities were explored by EA versus non-EA ethnicity. EA ethnicity was defined as ancestral origin from China, Taiwan, Hong Kong, Japan, Korea, Thailand or the Philippines. Outcome variables were explored using independent samples t-tests, Mann-Whitney, and log-rank tests as appropriate. Results: Of 148 cases reviewed, 68 patients were EA. The median age was 71, 50%/13%/35% had stage I-II/III/IV NSCLC, and 32% received EGFR TKI. Non-EA were more commonly female (71% vs 53%, p = 0.02). EA patients were more likely to be never smokers (81% vs 56%, p = 0.006). Other demographic characteristics were similar between groups. There was no difference in pathologic or EGFR mutation type. Median survival from diagnosis was similar in both groups (19.0 months in EA, 19.7 months in non-EA). EA patients with resected early stage NSCLC had longer 5-year disease free survival (DFS, 91% vs 75%, p = 0.04). Of note there were no differences between groups in rates of adjuvant chemotherapy, stage I vs II, nor EGFR mutation type. For stage IV patients, there were no significant differences by ethnicity in EGFR TKI response rate (74%), PFS (4.4 months in EA vs 10 months, p = 0.167) and OS from EGFR TKI start (9.6 months in EA vs 11 months). There were no differences in rates of EGFR TKI skin toxicity (75%) or diarrhea (43%). Conclusions: In this study of EGFR mutation positive NSCLC patients of EA and non-EA origin treated at the same cancer centre, we did not find any differences in EGFR TKI RR, PFS, OS or toxicity for stage IV patients. However in this small cohort, early stage EGFR mutant NSCLC EA patients had longer DFS than non-EA patients. This may be worth further exploration in larger trials, controlling for additional prognostic factors. It is likely that ethnicity does not influence outcome in this molecular subgroup of patients.
Capecitabine monotherapy for elderly patients with metastatic breast cancer
Authors: L. N. Minea, D. L. Stanculeanu, A. Cringeanu, R. M. Anghel
Journal: Journal of Clinical Oncology (2004)

797 Background: Single agent therapy with Capecitabine demonstrates a good activity, tolerability and efficacy in many solid tumors. Due to its particular mechanism of action and its oral administration, it is an attractive alternative for the palliative treatment on elderly breast cancer patients. Methods: To evaluate the toxicity and efficacy of capecitabine monotherapy in elderly patients with metastatic breast cancer. Secondary endpoint was time to progression. 63 patients were included between January 2001 -December 2002. The median age was 70 years, range 65–78. Patients could had prior chemotherapy and/or hormonotherapy, not for metastatic disease. All patients had measurable or evaluable disease. Performance status was ECOG 0–2. They had adequate bone marrow, renal, hepatic and cardiac functions. The metastatic sites were: liver -27, lung -19, bone -35, soft tissue -17, lymph nodes -11 and pleura -9 patients. There were no brain metastases in the study group. Treatment schedule: Capecitabine 1250 mg/m2 twice daily, days 1–14, repeated every 21 days, until the disease progression or experiencing unacceptable toxicities. Dose reduction was necessary in 26.98% (17 patients); the dose was reduced with 25%. A median number of 6 cycles per patients were administrated. Median follow-up time was 16.3 month. Results: All patients were evaluable for toxicity and 58 (92.06%) for response (5 did not received 2 cycles). Main toxicities according to WHO criteria was: grade 3–4 diarrhea 6 patients, grade 3 emesis 4 patients, grade 3 mucositis 2 patients, grade 3 asthenia 8 patients, grade 2–3 hand-foot syndrome 15 patients, grade 3 anemia 2 patients. Grade 1–2 gastrointestinal adverse events was commonly observed. No treatment related death were observed. Overall response rate was 26.98% (17 patients partial response); 27 patients had stable disease (42.86%) and 14 patients progressive disease (22.22%). The median time to progression was 3.5 month. Conclusion: our results suggest that single agent capecitabine has a good palliative activity in this subset of patients. All patients had a high compliance to this treatment. The regimen had an acceptable safety profile. No significant financial relationships to disclose.
Relationship of bone alkaline phosphatase and quality of life in men with hormone refractory prostate cancer
Authors: P. Mulani, D. J. Sleep, J. D. Isaacson, S. M. Hulting, T. Ashraf
Journal: Journal of Clinical Oncology (2004)

4688 Background: Markers of osteoblastic activity, in particular bone alkaline phosphatase (BAP), increase in hormone refractory prostate cancer (HRPC) patients. BAP has been shown to be as valuable in predicting outcomes for men with HRPC as extent of bone disease, pain, or performance score. There are few data demonstrating prediction of quality of life (QOL) as a function of BAP. The relationship between BAP and QOL was explored in a study of atrasentan. Methods: Data from a randomized, double-blind, placebo-controlled phase 3 study of metastatic HRPC patients were analyzed (401 placebo, 408 atrasentan). Patients with a baseline BAP value and a baseline and final FACT-P score were analyzed and stratified according to baseline BAP value less than or equal to or greater than the median. Analysis of covariance (ANCOVA) was used to compare the mean change from baseline to final FACT-P assessment between baseline BAP stratified groups. In addition, ANCOVA was used to compare mean change from baseline to final BAP between treatment arms. Results: The median baseline BAP value was 25.2 ng/mL. Patients with baseline BAP level greater than the median experience a rapid clinically significant deterioration in disease-specific QOL compared to patients with baseline BAP level less than or equal to the median (table). The mean change from baseline to final is significantly smaller for atrasentan (13.19 ng/mL) versus placebo (33.86 ng/mL) (p=0.001). Conclusions: HRPC patients with high BAP levels experience significant rapid deterioration in disease-specific QOL. Therapies such as atrasentan, which have significant effect on lowering BAP levels, may reduce the rapid decline in the QOL of HRPC patients. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Abbott Laboratories Abbott Laboratories
The challenges of improving peripherally inserted central catheter (PICC) care instructions at hospital discharge.
Authors: Kerry L. Kilbridge, Brett Glotzbecker, Cecilia H. Rosenbaum, Erica Morelli, Candace Hsieh, Sherri Oliver Stuver, Eric Yenulevich, Joseph O. Jacobson
Journal: Journal of Clinical Oncology (2017)

175 Background: Teaching patients and caregivers to manage a Peripherally Inserted Central Catheter (PICC) line placed during hospitalization is essential to successful outpatient transitions. The aim was to improve written care instructions at hospital discharge (CIHD) given to solid tumor oncology patients with new PICC lines by creating an electronic template in the electronic health record. Methods: Inpatients with newly placed PICC lines discharged from the physician assistants' (PA) oncology teams at Brigham and Women's Hospital were identified through PICC team consult lists. We identified 9 elements of complete line care, modeled on National Quality Forum discharge metrics, to include in a template for PICC line care instructions at discharge. PAs received instruction on template use at their weekly meeting. A retrospective chart review of CIHD (February 19, 2016 and October 13, 2016) was performed. Results: A total of 47 cases were reviewed, 19 cases Pre-introduction and 28 cases Post. Before introduction of the template, 74% of cases lacked PICC care instructions (including 13 cases with no mention of the PICC line), 26% had incomplete care instructions, and none had full instructions. Following the intervention, 64% still lacked care instructions (16 cases with no mention of the PICC line), 21% had incomplete care instructions, and 4 patients (14%) had full instructions. Only those CIHD that used the template had complete care instructions. A c-chart demonstrated special cause variation following the intervention but the process was chaotic. Conclusions: The introduction of a template for PICC care instructions led to modest improvement in the number of patients discharged with full instructions. This project highlights the limitations of solutions that incorporate technical solutions but only weak adaptive ones. The next phase of our work will introduce human factors interventions (e.g. automation and forcing functions) to improve the success rate of this critically important function. [Table: see text]
Melanoma disparity in Hawaii: Germline alterations of MC1R in a non-Caucasian population.
Authors: Shane Young Morita, Christopher A. Lum
Journal: Journal of Clinical Oncology (2014)

e17567 Background: Melanoma is a global problem. Since Caucasians are primarily affected by melanoma, most of the focus is on this cohort. In minorities, melanoma is usually associated with a worse survival. Hawaii provides a rare opportunity to study different aspects of the disease in unique ethnicities. Our objective was to explore early detection of melanoma in minority groups by performing germline genotyping for high-risk variants of the MC1R (melanocortin-1 receptor) gene. Recent studies have chronicled the relevance that individuals with specific MC1R variants had an increased risk of melanoma despite possessing traditional low-risk phenotypic features such as dark complexion. There have been no studies of genotyping for high-risk variants of the MC1R gene in a multi-ethnic population that is comprised of Native Hawaiians, Filipinos, and Pacific Islanders. Methods: From 2003-2012, ten non-Caucasian patients were histologically confirmed to have cutaneous non-acral melanoma were analyzed at a tertiary academic center in Hawaii. Data including age, gender Breslow thickness, ulceration and mitosis per mm2 were compiled. Targeted exome sequencing was performed on melanoma tissue from formalin fixed paraffin embedded archived biospecimens. Formalin-fixed-paraffin-embedded tissue was utilized to perform targeted exome sequencing. Next generation sequencing was performed. Variants were annotated and sequences confirmed. Results: The demographics of our population included a mean age of 55.5 years with 60% females. Pathologic variables included a median Breslow thickness of 1.96 mm and mean mitoses per mm squared of 5.2. Our findings included identification of the high risk variant R160W of the MC1R gene (recall that D84E, D29H, R160W, or R151C were found to associated with a 2 X increased risk of melanoma). Additionally, 5/10 (50%) of our cohort had the R163Q variant which is typically not associated with the development of melanoma (in Caucasians). Conclusions: A known high-risk variant of the MC1R gene was identified. Additionally, novel alterations were discovered. This is compelling data that may be applied to screening and prevention efforts for minority populations that traditionally overlooked.
Understanding the financial impact of beyond use date in a publicly funded cancer system.
Authors: Erin Redwood, Kathy Vu, Ron Fung, Heekyung Han, Megan Teimoortagh, Elaine Meertens, Leta Forbes, Vishal Kukreti, Daniella Santaera
Journal: Journal of Clinical Oncology (2017)

13 Background: According to USP 797 and the National Association of Pharmacy Regulatory Authorities standards, the Beyond Use Date (BUD) based on sterility for single-dose vials is 6 hours, after which the contents must be discarded. In Ontario, centres have traditionally based BUD on stability data, not sterility data. This change presents concern about potential drug waste so an analysis was done to estimate the financial impact to the 76 systemic treatment facilities in Ontario. Methods: Using an administrative database that records the daily total dose of drugs administered by facility, annual drug waste cost was calculated using daily dose administered, cost per milligram, and available vial size(s) for 26 publicly funded drugs. Two different methods were used to determine the amount of drug waste. Method 1 used the largest vial size matched to the closest amount of drug required. Method 2 used the optimal vial size mix, when there are multiple vial sizes, to minimize wastage across all configurations of vial size. Some assumptions made include: 1) each facility had access to all available vial sizes, and 2) single-dose vial contents were true to the stated quantity as per the manufacturer. Results: The 10 facilities with the highest waste estimates are summarized in the table. The total waste estimates for all facilities are $25,927,861 (method 1) and $12,945,353 (method 2). Waste estimates were also calculated by drug, with rituximab, bevacizumab and pemetrexed having the highest waste costs. These drugs are only available in vials with a large range in size (100 and 500 mg), but could waste more than drugs with more size options or less variance between sizes. Conclusions: Assigning a BUD based on 6 hour sterility standards will have significant financial implications to facilities in Ontario. Development of mitigation strategies should be explored to provide guidance to Ontario and other jurisdictions on how to curtail the budget impact.[Table: see text]
Androgen receptor modulation optimized for response: Splice variant (ARMOR3-SV)–Randomized, open-label, multicenter, controlled study of galeterone vs enzalutamide in men with metastatic castration-resistant prostate cancer (mCRPC) expressing AR-V7 splice variant.
Authors: Mary-Ellen Taplin, Emmanuel S. Antonarakis, Daniel T. Dransfield, Karen J. Ferrante, Johann Sebastian De Bono
Journal: Journal of Clinical Oncology (2015)

TPS5069 Background: mCRPC patients with tumors expressing the androgen receptor (AR) splice variant-7 (AR-V7), a constitutively-active truncated form of the AR lacking the ligand-binding domain, have been shown to have worse clinical outcomes after AR-targeting drugs than those without detectable AR-V7. Galeterone, a small molecule drug, disrupts AR signaling via selective inhibition of CYP17 lyase, AR blockade, and enhanced degradation of the AR protein. In preclinical models, galeterone showed activity against the full-length AR and AR alterations including AR-V7 and ARv567es splice variants, and against activating AR mutations (eg, AR-T878A, AR-F876L). Given the encouraging results in patients with AR C-terminal loss in the galeterone Phase 2 ARMOR2 trial, further research is warranted in this patient subset. Methods: ARMOR3-SV is a Phase 3, randomized, open-label, multicenter study of galeterone vs enzalutamide in men with mCRPC expressing AR-V7 mRNA in circulating tumor cells (CTCs). Among other inclusion criteria, eligible patients must continue medical castration or have had surgical castration, and must not have received prior chemotherapy, abiraterone, or enzalutamide. Eligible patients will be prescreened and subsequently enrolled only if AR-V7 is detected in CTCs using a CLIA-certified, analytically-validated assay. A total of 148 patients will be randomized (1:1) to receive once-daily oral galeterone 2550 mg or enzalutamide 160 mg. The primary endpoint is radiographic progression-free survival determined by independent blinded, central radiologic review. Secondary endpoints include time to cytotoxic therapy or next anticancer intervention and overall survival. Other endpoints include time to first skeletal related event, decline in PSA, time to PSA progression, and best objective response rate (in men with measureable soft tissue disease [RECIST1.1]). Safety and pharmacokinetics of galeterone will also be assessed. CTCs will be enumerated and characterized molecularly in an exploratory fashion.
Blood Donor Characteristics On Transfusion Outcomes—Should Obesity Be Assessed in Future Clinical Trials?—Reply
Authors: Michaël Chassé, Dean A. Fergusson
Journal: JAMA Internal Medicine (2017)

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Phase 1 Study of Carfilzomib for the Prevention of Relapse and Graft-Versus-Host Disease in Allogeneic Hematopoietic Cell Transplantation for High-Risk Hematologic Malignancies
Authors: Attaphol Pawarode, Steven Goldstein, Daniel R. Couriel, Thomas Braun, John M. Magenau, Mary Mansour Riwes, Brian Parkin, Vedran Radojcic, David Frame, Sung Choi, James Connelly, John E. Levine, Gregory A. Yanik, Pavan Reddy
Journal: Blood (2015)
A multicenter study of 66 patients with spinal cord compression at diagnosis of B-cell non-Hodgkin lymphoma.
Authors: Isabelle Fleury, Sandy Amorim, Nicolas Mounier, Bertrand Coiffier, Jehan Dupuis, Herve Tilly, Mohamed Amine Mazari, Lauriane Filliatre, Josette Briere, Pauline Brice, Eric de Kerviler, Catherine Thieblemont
Journal: Journal of Clinical Oncology (2014)

8560 Background: Spinal cord compression (SCC) in non-Hodgkin lymphoma (NHL) is rare but associated with an increased risk of central nervous system (CNS) relapse. Our objective was to retrospectively analyze the outcome of patients with SCC caused by B-cell NHL and their CNS relapse risk. Methods: Patients with SCC at diagnosis of B-cell NHL from six centers in France were eligible. Burkitt and HIV-related lymphoma were excluded. Intradural extension on spine imaging was centrally reviewed. The primary endpoints were progression-free survival (PFS) and relapse site. Survival functions were estimated by the Kaplan-Meier method and compared by the log-rank tests. Results: We identified sixty-six patients treated between 1987 and 2012. Median age was 61,5 years. Histology was: diffuse large B cell (DLBCL) (71%), follicular (19%), small lymphocytic (6%), marginal zone (3%) and B-cell unclassified (3%) lymphomas. An intradural extension of lymphoma was detected in 29% (10/35) of the patients and cytological analysis of cerebrospinal fluid (CSF) revealed an infiltration in 9% (5/58) of the patients. Twenty-eight (42%) patients were managed by a surgical decompressive procedure before chemotherapy. All but two patients received CHOP or CHOP-like regimen and 61% received rituximab. Forty-six patients received CNS prophylaxis based on intravenous methotrexate and/or intrathecal therapy. At a median follow-up of 53 months, 5-year OS was 64% and 5-year PFS was 53%. CNS relapses occurred in 4 (6%) patients with DLBCL, all involving the cerebellum. Non-CNS relapse occurred in twenty (30%) patients. Neither CSF involvement nor intradural extension influenced PFS (p = 0.5544 and p = 0.3399 respectively). Initial decompressive surgery did not influence PFS or OS (p = 0.4231, and p = 0.1823 respectively). The use of at least 3 g/m2 of MTX or the lack of any CNS prophylaxis modality did not influence PFS (p = 0.1414 and p = 0.8221 respectively). Conclusions: SCC at diagnosis of B-cell NHL carries a low risk of CNS relapse. Outcomes were not improved by CNS prophylaxis. Benefit from CNS prophylaxis according to intradural extension needs prospective evaluation.
Randomized phase 2 trial comparing amrubicin (A) with re-challenge of platinum doublet (P) in patients (pts) with sensitive-relapsed small-cell lung cancer (SCLC).
Authors: Atsushi Nakamura, Akira Inoue, Makoto Maemondo, Yoshiaki Mori, Satoshi Oizumi, Masao Harada, Shingo Takanashi, Naoto Morikawa, Takashi Ishida, Ichiro Kinoshita, Hiroshi Watanabe, Toshiro Suzuki, Taku Nakagawa, Ryota Saito, Toshihiro Nukiwa
Journal: Journal of Clinical Oncology (2014)

7520 Background: When this trial was planned, A was believed to be a promising new anthracycline agent for sensitive-relapsed SCLC. While re-challenge of P that had been used for the first-line treatment was also believed to be effective for sensitive-relapsed SCLC, although prospective evaluation of it had not been reported. Thus this randomized phase 2 study was conducted to select A or P for future phase 3 trial. Methods: Sensitive-relapsed SCLC pts were randomized to receive A (40 mg/m2, day1-3, every 3 weeks) or P (every 3-4 weeks). The modification of P such as the 20%-dose reduction of combined third-generation or change of platinum agent from cisplatin to carboplatin according to patients’ condition was permitted. The primary endpoint was overall response rate (ORR), and secondary endpoints were progression-free survival (PFS) and toxicity profile. According to the Simon’s Two-Stage phase 2 design, 28 pts were required in each arm (p0=0.3, p1=0.5, alpha=0.10, beta=0.20), and the treatment that achieved > 12 out of 28 pts with partial response would be judged as effective. Results: From February 2008 to June 2013, 60 pts were enrolled from 14 institutions. Two patients in A arm and one patient in P arm did not receive any protocol treatment due to rapid disease progression. Evaluated patients’ characteristics were as follows: Male/Female, 53/4; median age, 66 (range 44-80); Performance status 0/1/2, 32/21/4. The median numbers of treatment cycles were 4 (range 2-8) in A arm and 3 (range 1-7) in P arm. ORRs and disease control rates were 67% (90%CI, 52-82) and 86% for A, and 43% (90%CI, 28-58) and 80% for P, respectively. Median PFS was 5.4 months in A arm and 5.0 months in P arm. Grade 3 toxicity was observed in 33% of patients in A arm including 19% of febrile neutropenia, while 17% in P arm without any febrile neutropenia. There was no grade 4 toxicity or treatment-related death in this trial. Conclusions: Both treatments met the primary endpoint. Since A produced higher ORR and median PFS than P with acceptable toxicity, we select A for subsequent phase 3 trial. Clinical trial information: UMIN000002617.