tbuckley/cabot-search huggingface dataset:
A randomized, placebo-controlled, double-blind phase II trial of peri-operative cimetidine in early colorectal cancer.
Authors: Michael B. Jameson, Michael P. N. Findlay, Ian Bissett, Ralph van Dalen, Simione Lolohea, Judith Warren, Claudia Romano
Journal: Journal of Clinical Oncology (2014)

509 Background: A Cochrane meta-analysis of randomised trials using histamine-type 2 receptor antagonists with surgery for colorectal cancer (CRC) demonstrated a hazard ratio of 0.53 for mortality if patients used cimetidine. The benefit is likely to be specific to patients whose tumours express the antigens that allow circulating cells to bind to endothelial selectin (E-selectin), the expression of which is induced by inflammatory cytokines perioperatively and inhibited by cimetidine. This trial sought to evaluate several key issues critical to informing the conduct of a phase 3 trial. Methods: Patients with non-metastatic CRC planned for curative-intent surgery were randomised to receive cimetidine 800mg BID or placebo orally for 5 weeks, starting 2-7 days preoperatively. A subset of patients had serial blood sampling for inflammatory cytokines. In addition to DFS and OS, endpoints assessed include treatment compliance and toxicity, recruitment issues, post-operative stay and complications, and tumour characteristics including expression of sialyl Lewis antigens and COX-2. Results: 123 patients (36% female) have been recruited in 4 centres over 3.5 years; another 4 are required to complete the planned 120 treated patients. The primary tumour was rectal in 45% and pathological postoperative tumour stage was 0-I, II, III, and IV in 29%, 33%, 35%, and 2% respectively. About 50% of CRC patients were eligible and fewer than half of those were recruited. Patient compliance was excellent with 89% of patients taking their medication orally in the first 2 days postoperatively. Inflammatory cytokines were commonly elevated postoperatively for up to 2 weeks but normalised by 4 weeks. Immunostaining for tumour antigens is in progress and will be presented. DFS and OS data are immature. Conclusions: Oral administration of cimetidine for 5 weeks is well-tolerated and feasible over the perioperative period, and covers the duration of elevated inflammatory cytokines. Correlative immunostaining studies will be presented. Clinical trial information: 12609000769280.
Economic impact associated with the management of dermatologic adverse drug reactions (dADRs) induced by EGFR inhibitors (EGFRIs) in lung cancer
Authors: T. Abraham, A. Rademaker, S. Ortiz, C. L. Bennett, E. Richey, N. J. Nonzee, D. P. West, J. D. Patel, M. E. Lacouture
Journal: Journal of Clinical Oncology (2008)

19094 Background: Dermatologic adverse drug reactions including rash, paronychia, xerosis, alopecia and pruritus occur in up to 75% of non-small cell lung cancer (NSCLC) patients treated with EGFRIs. In addition to the impact on psychosocial and physical health, there are also financial implications. This study seeks to evaluate the costs associated with the management of cutaneous side effects caused by EGFRIs in patients with NSCLC referred to a dermatology-based program for the management of dADRs in oncology, the SERIES (Skin and Eye Reactions to Inhibitors of EGFR and kinaseS) clinic. Methods: Medical records for a subset of 10 NSCLC patients treated with the EGFRI erlotinib was identified. Unit costs for each resource were obtained from the Red Book for pharmaceuticals and Medicare Physician Fee Schedule for outpatient services. Average total cost for treatment (including drug regimen and administration-related costs) were computed based on average wholesale drug price and procedure code, respectively. Costs were also evaluated separately for: drug treatment, clinic visits and other services such as laboratory tests and biopsies. Results: All patients (100%) developed rash in addition to paronychia (40%), xerosis (80%), pruritus (50%) and alopecia (10%). Average number of visits and treatment period was 5 and 38.7 weeks respectively. Mean total cost for treatment (including drugs, clinic visit and other services) was $2,715.56 per patient. A mean of 12.6 prescriptions (range 4–39) were filled per patient for drugs treating dADRs, imposing a mean cost of $1,347.06 per the average patient. A mean of 6.3 administration-related services (clinic visits, lab tests, biopsies) per patient (range 1–17) accounted for an average cost of $1,368.50 to the average patient. Conclusions: This study substantiates that there is a considerable financial impact in the management of EGFRI-induced dADRs in NSCLC patients. Interventions that prophylactically address such frequently occurring cutaneous toxicities are critical for the minimization of dADR treatment-related costs. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Amgen Inc, Bayer Pharmaceuticals, ImClone Systems
Possible predictive clinical factors for chemotherapy holiday in metastatic colorectal cancer: A single institution–based retrospective data analysis.
Authors: Praveen Kumar Tumula, Umit Tapan, Kevan L. Hartshorn
Journal: Journal of Clinical Oncology (2015)

720 Background: During the last decade, numerous new agents were introduced into the therapy of metastatic colorectal cancer. For those patients who are not curable by resection, life can be extended with chemotherapy. However, it is not possible to predict who can safely take breaks without compromising survival. We sought to evaluate the relationship between various possible predictive factors and the duration of break from chemotherapy in patients with metastatic colorectal cancer. Methods: The hospital’s cancer registry was used to identify metastatic colon cancer cases diagnosed from January 2008 to December 2012. To be included in the study, the patient must have been diagnosed with colorectal adenocarcinoma, treated with a fluoropyrimidine based chemotherapy regimen and had planned treatment breaks. Retrospective chart review of electronic medical records was used to collect patient characteristics, including age, performance status (ECOG), comorbidities, disease burden (number of metastasis), and response to the initial treatment. Multivariate regression analysis was performed to observe impact of various variables on the duration of break from chemotherapy. Results: A total of 110 patients were diagnosed with metastatic colorectal cancer between 2008 to 2012 and 27 (24.5%) subjects in the initial analysis met the inclusion criteria, with a mean age of 56 years. The percentage of male and female patients was 37% and 63%, respectively. Patients who had a complete response to the initial chemotherapy (n=6) had 69±23 week breaks which was significantly longer (p&lt;0.01) than the 17±2 and 13±5 week breaks of those with partial response or stable disease. In multivariate regression analysis, degree of response was a significant predictor for chemotherapy breaks (CI 0.36 – 1.77, p=0.005). No statistical difference was noted in other variables. Conclusions: These preliminary findings suggest that complete response to initial chemotherapy may be a strong predictor of patients who can safely undergo chemotherapy breaks. This study also raises the possibility that various factors could influence break from chemotherapy.
A germ line polymorphism in the RET proto-oncogene predicts risk and recurrence in desmoplastic melanoma.
Authors: N. Kounalakis, C. M. Amato, J. Barr, W. Robinson
Journal: Journal of Clinical Oncology (2011)

8558 Background: Desmoplastic malignant melanoma (DMM) has a unique pathological and clinical behavior which distinguishes it from other melanomas. DMM has a low incidence of nodal involvement, a significantly higher local recurrence rate and a predilection for perineural invasion. GDNF, glial cell line-derived neurotrophic factor, is a major ligand for the RET proto-oncogene and acts as a neural growth factor. GDNF has a germline polymorphism at G691S juxtamembrane region (RETp) which is frequently found in cutaneous melanoma. We propose that the presence of RETp in peripheral blood is associated with an increased risk for the development of desmoplastic melanoma and also predicts a greater risk for locoregional recurrence. Methods: Clinical and pathological data were extracted from a retrospective data base of patients with DMM treated from 2005-present. Blood samples were available from 60 patients and were analyzed for RETp using polymerase chain reaction. Results:RETp was detected in the peripheral blood samples of 32% of patients with DMM and 23% of patients without DMM. In those patients with DMM and RETp, 43% experienced either a systemic or local recurrence. When DMM occurred without the presence of RETp, the rate of local or distant recurrence was zero. Median follow up was 3.8 years for all 60 patients. Conclusions: These studies suggest that the germline polymorphism RETp may be a predisposing factor to development of DMM and predicts a greater risk for both local and distant recurrence after surgical resection. Future studies are warranted to further understand the role of RETp in DMM.
Single-fraction radiosurgery for treatment of spinal and cerebral metastases from renal cell carcinoma under systemic tyrosine kinase inhibition.
Authors: M. D. Staehler, N. Haseke, P. Nuhn, C. Nordhaus, C. G. Stief, B. Wowra, A. Muacevic
Journal: Journal of Clinical Oncology (2010)

4625 Background: Angiogenic therapy shows promising treatment effects in patients with metastatic renal cell carcinoma (RCC). Limited response has been documented for metastatic lesions in the brain and spine. High-dose local radiation treatment (stereotactic radiosurgery, or SRS) was added for selected patients to improve local control and overall survival. We report on toxicity and local tumor control in patients with metastatic renal cell carcinoma who were simultaneously treated with angiogenic therapy and aggressive local irradiation. Methods: 88 patients with spinal (n=47) or cerebral (n=41) metastatic lesions from RCC and an eastern cooperative oncology group (ECOG) status of 0 or 1 were treated systemically with sorafenib or sunitinib and additional SRS. Patients with surgically removable cerebral lesions were not included. Dose was not withheld or delayed while patients were simultaneously treated with SRS. Results: Median time from initial diagnosis to metastatic spread was 0.6 years (range 0 - 3.5 years). Median follow-up was 14.7 months (range 1-42 months). Twenty-seven patients were treated with sunitinb (50 mg pod, 4 weeks on 2 weeks off) and 61 patients were treated with sorafenib (400 mg bid). One patient suffered a tumor hemorrhage after SRS that did not require treatment. No skin toxicity occurred after SRS, and SRS did not alter the side effect profile of systemic angiogenic therapy. Neither neurotoxicity nor myelopathy was observed. Local tumor control 15 months after SRS was 98% (95% CI: 89-99%). The median pain score on the visual analogue scale before spinal treatment was 5 (range 1-8). After SRS the median pain score was significantly lowered to 0 (range 0-2, p<0.001). There were no treatment related deaths, and late complications after SRS were not noted so far. Conclusions: Systemic angiogenic therapy and SRS for selected RCC patients with cerebral and spinal metastases is safe and effective. Single-fraction delivery as an outpatient procedure allows for convenient integration of SRS into various oncological treatment concepts. Further studies are needed to determine the limits of SRS for RCC metastases outside the brain and spine. No significant financial relationships to disclose.
Cigarette smoking, fitness, and alcohol use as predictors of cancer outcomes among women in the National Surgical Adjuvant Breast and Bowel Project (NSABP) Breast Cancer Prevention Trial (BCPT).
Authors: S. R. Land, N. Christian, D. L. Wickerham, J. P. Costantino, P. A. Ganz
Journal: Journal of Clinical Oncology (2011)

1505 Background: The double-blind, prospective, BCPT demonstrated a 50% reduction in the risk of breast cancer for tamoxifen (T) v placebo (P). We present the risk of cancer at the most common sites, based on the participants’ baseline self-reported cigarette smoking, alcohol use, and leisure-time physical activity. Methods: 13,338 women at high risk of bc. Were randomly assigned 6/92-9/97 to 20 mg/day T v P; we analyzed the 11,064 enrolled more than 3 years (yrs) before the trial unblinding 3/98. Endpoints invasive cancer of the breast (ibc), endometrium (ec), lung (lc), and colon (cc) were analyzed with Cox proportional hazards regression. Covariates were baseline estimated breast cancer risk, treatment assignment, race, age, and co-morbidities. Hazards ratios (HR) are given with 95% bracketed confidence intervals. Results: At baseline, 45.7% had moderate/heavy physical activity. 20.5%, 65.8%, 13.3% drank 0, 0-1, 1+ alcoholic drinks/day. 12.8% were current smokers. At median 8.7 years potential follow-up, baseline smoking predicted ibc (p=.021; HR=1.40 [1.05-1.86]; n=360 events) and lc (p<.001; HR=7.66 [4.62-12.70], n=64). Low physical activity predicted ec (p=.030, HR=1.8 [1.1-3.0], n=68). Moderate alcohol use (0-1 drink/day) was associated with decreased risk of cc (p=.017; HR=.38 [.18-.81] versus no alcohol, n=36). 1+ drinks/day was not associated with increased cancer risk. Conclusions: This prospective study in women at high risk of breast cancer confirms previously reported cancer risk associated with smoking and fitness, but did not confirm previously reported associations with excessive alcohol use.
Comparison of physical function and falls among women with persistent symptoms of chemotherapy-induced peripheral neuropathy.
Authors: Kerri M Winters-Stone, Coleman Hilton, Shiuh-Wen Luoh, Peter Jacobs, Sarah Faithfull, Fay B Horak
Journal: Journal of Clinical Oncology (2016)

130 Background: Chemotherapy-induced peripheral neuropathy (CIPN) is a side effect of cancer treatment that may persist and impact physical function. Studies that quantify functional consequences associated with CIPN in post-treatment cancer survivors are rare, based on self-report, or use small samples. The purpose of this study was to compare objective and self-report measures of physical function, gait patterns, and falls between women cancer survivors with or without symptoms of CIPN. Methods: Baseline assessments from 678 women cancer survivors enrolled in exercise trials were available for analysis. Women who self-reported symptoms of CIPN (CIPN + ) were compared to asymptomatic women (CIPN - ) on the following: maximal leg press strength (LPmax); timed chair stand (CS), physical performance battery (PPB), gait patterns (speed (SP), step number (SN), stride length (SL), base of support (BOS), % time in double support (%DS)), self-report physical function (PF) and disability (DIS), and falls in the past year (% fallers). Group comparisons were made using analysis of covariance, adjusting for time since diagnosis and cancer site (breast or other). Results: After excluding women who had diabetes, were premenopausal at cancer diagnosis or had not received chemotherapy, 462 cases were analyzed (age: 62±6yrs; time since diagnosis: 5.8±4.1yrs). CIPN + (N = 210) and CIPN - (N = 252) groups significantly differed on all measures (*p &lt; 0.05; **p &lt; 0.01), except maximal leg strength and base of support during a usual walk, with worse performance for CIPN + . Conclusions: In our sample of women cancer survivors, 45% had symptoms of CIPN an average of 6 years post treatment and significantly worse physical function, altered gait patterns and more falls than asymptomatic women. CIPN should be addressed early in treatment and strategies to improve function and mobility and prevent falls need to be tested. [Table: see text]
A pilot study of endogenous heat shock protein vaccines for metastatic melanoma.
Authors: J. M. Heun, W. K. Nevala, J. B. Allred, V. Suman, M. R. Callstrom, T. D. Atwell, M. A. Farrell, E. Galanis, L. A. Erickson, W. J. Charboneau, S. Markovic
Journal: Journal of Clinical Oncology (2011)

8593 Background: Heat shock proteins (HSP) can be heat induced and when released into the extracellular environment, act as immunomodulatory molecules attracting antigen-presenting cells to the sites of immunogenetic peptides. Previous studies have isolated HSP from autologous melanoma tumors in vitro and then re-inoculated into patients as exogenous therapeutic vaccines. In this feasibility study, we attempt to create an endogenous HSP vaccine in patients with metastatic melanoma through the use of sublethal radiofrequency treatment (RFT, see below) and intra-lesional GM-CSF plus or minus subsequent ablation with radiofrequency ablation (RFA) or cryoablation. Methods: With IRB approval, consenting HLA-A2 positive patients with metastatic melanoma were placed into 1 of 3 cohorts. Cohort 1 received RFT (50°C for 30 minutes) to the target lesion followed by intra-lesional injection of 500 mcg of GM-CSF. Cohorts 2 and 3 received the same with the addition of tumor ablation (RFA in cohort 2 and cryoablation in cohort 3). Serum HSP70 was measured at baseline and every 3 hours for the first 24 hours. Melanoma specific tetramer analysis was performed on blood at baseline, 3 and 6 weeks postprocedure to evaluate for the primary endpoint of melanoma specific cytotoxic T lymphocyte (CTL) production. Positive tetramer results were identified by detection of a previously negative, or a doubling in value of a previously detected, melanoma specific CTL. Results: Nine patients (3 per cohort) completed the treatment. HSP70 levels doubled from baseline in 5 of 9 patients. Positive tetramer results were identified in 7 of 8 patients (1 patient in cohort 2 developed brain metastasis and had no tetramer testing). No patient received significant clinical benefit with median progression free survival and overall survival of 1.6 and 7.6 months respectively. No grade 3/4 adverse events attributable to the treatment were reported. Conclusions: Melanoma specific CTLs can be induced endogenously, but alone, this approach is not sufficient to affect clinical outcomes. However, this approach does appear effective in “priming” the immune system and may be complementary with other efforts aimed at non-specific activation of systemic T cells (e.g. ipilimumab).
Performance of the Gail model in individual women with benign breast disease.
Authors: Y. Tarabishy, L. C. Hartmann, M. H. Frost, S. D. Maloney, R. A. Vierkant, V. S. Pankratz
Journal: Journal of Clinical Oncology (2011)

1525 Background: More than 1 million women undergo breast biopsy with benign findings in the USA annually. One feature in the Gail model is the number of prior breast biopsies, and the Gail model is commonly used to counsel these women regarding their risk of breast cancer. However, to our knowledge, the model has not been validated in this population. Using the Mayo Benign Breast Disease (BBD) cohort, we analyzed the performance of the Gail model in predicting breast cancer risk for women with benign breast disease. Methods: Between 1982 and 1991, 4,726 women had a benign breast biopsy at Mayo Clinic. We collected Gail model risk factors for these women, and used the Gail model to predict 5-year and follow-up-specific risks for each woman, using the Gail model’s rules to account for missing data. We assessed the calibration of the model by comparing the observed and predicted numbers of breast cancers. We assessed the accuracy of the model by computing the c-statistic, which measures the concordance between individual-specific predicted risk and breast cancer outcomes. Results: Over a median follow-up of 16.3 years, 356 women developed breast cancer, while the Gail model predicted 269, for an observed to predicted ratio of 1.32 (95% CI, 1.19-1.47; P<0.001). The concordance between predicted and observed outcomes identified for individual women, as measured by the c-statistic, was 0.635 (95% CI, 0.615-0.656). When examining 5-year risk, the Gail model performed better, with an observed to predicted ratio of 1.08 (95% CI, 0.88-1.33; P < 0.470), and a concordance statistic for individual women of 0.669. Conclusions: When used for women with benign breast disease, the Gail model performed modestly. It under predicted risk over long-term follow-up and its discriminatory accuracy, while not high, was comparable to what has been reported in other assessments of the Gail model. Clinicians need to be aware of the limitations of using the Gail model in this population.
Automated extraction of Quality Oncology Practice Initiative (QOPI) quality measures from the Veterans Health Administration (VHA) electronic health record system.
Authors: C. D. Williams, M. J. Kelley
Journal: Journal of Clinical Oncology (2011)

e16560 Background: ASCO’s QOPI is a program that requires manual data abstraction of medical record data to measure quality of cancer care, a necessary component of quality improvement programs. Improving quality of care for veterans is a long-standing goal of the VHA. The VHA’s electronic health record (EHR) is a fully integrated health information system used in all VA healthcare settings. It is unknown whether automated data extraction from the VHA EHR is feasible to assess quality of cancer care. Methods: Using non-small cell lung cancer (NSCLC) as an example, we examined the quality measure data elements needed to assess the fall 2010 QOPI measures. We then determined which data elements could be electronically collated from the VHA EHR. To complement and improve upon this method, we designed and implemented a note template in the VHA EHR at the Durham VA Medical Center. This template allows the oncologist to enter at the time of care delivery those required data elements not currently electronically retrievable from the EHR in a structured format suitable for automated retrieval. Results: Based on data currently in the EHR not including data in the note template, data elements for 7/25 (28%) core measures, 7/9 (78%) symptom/toxicity management measures, 9/16 (56%) end-of-life measures and 0/9 (0%) NSCLC QOPI measures can be obtained automatically. Combined with data from the note template, data elements for 16/25 (64%) Core measures, 9/9 (100%) symptom/toxicity management measures, 14/16 (88%) end-of-life measures and 100% (9/9) NSCLC QOPI measures are able to be obtained electronically. Conclusions: A majority of data required to assess adherence with QOPI measures are readily available in the VHA EHR, particularly for measures common for all cancers. A note template is useful for structuring and capturing electronic data for cancer-specific measures. A comparison of manually abstracted data from the Fall 2010 QOPI data collection to electronically captured data will be available by June 2011. Embedding quality measures into the VHA’s EHR system will allow real time quality assessment and improvement in cancer care.
Erratum
Authors: J Ring, C Akdis, H Behrendt, R.-P Lauener, G Scha¨ppi, M Akdis, W Ammann, O De Beaumont, T Bieber, J Bienenstock, K Blaser, B Bochner, J Bousquet, R Crameri, A Custovic, C Czerkinsky, U Darsow, J Den- Burg, J Drazen, E.-M De Villiers, A Fire, S Galli, T Haahtela, H Zur Hausen, S Hildemann, S Holgate, P Holt, T Jakob, A Jung, M Kemeny, H Koren, D Leung, R Lockey, G Marone, M Mempel, B Menne´3, G Menz, U Mueller, E Von Mutius, M Ollert, L O'mahony, R Pawankar, H Renz, T Platts-Mills, C Roduit, C Schmidt-Weber, C Traidl-Hoffmann, U Wahn, E Rietschel
Journal: Allergy (2012)