tbuckley/cabot-search huggingface dataset:
Response and tolerability of a 5-day azacytidine schedule in pateints with myelodysplastic syndromes
Authors: B. Haq, J. M. Rossetti, W. Kramer, J. M. Latsko, S. Jasthy, J. Lister, R. K. Shadduck
Journal: Journal of Clinical Oncology (2006)

16532 Background: Azacitidine (AZA) is a DNA methyltransferase inhibitor with activity in patients with myelodysplastic syndrome (MDS). The current approved schedule of AZA is 75 mg/m 2 /d for 7 days every 28 days. This schedule is inconvenient for patients and providers because of the need for weekend administration. Methods: The records of 9 patients who received AZA 100 mg/m 2 /d for 5 days with an anticipated 28 day cycle between 10/04 to 1/06 were reviewed to determine response, duration of response and tolerability. A minimum of two cycles were required for response evaluation (n = 8). All patients were assessed for tolerability. The International Working Group response criteria for MDS was utilized for evaluation. Results: Patients had secondary MDS (n = 4), chronic myelomonocytic leukemia (n = 2), refractory anemia (n = 2) and refractory anemia with ringed sideroblasts (n = 1). Of the 8 patients who received at least 2 cycles of therapy, 5 responded: 1 achieved partial response, 3 achieved hematologic improvement in at least one cell line and 1 remained in a stable disease state. The overall response rate was 63%. Average response duration was 6.2 months. The longest response duration was 10 months. Myelosuppression was seen in 2 of the 9 patients treated, one of whom continued treatment with growth factor support; therapy is currently on hold for the other patient. Injection site reaction was seen in 2 patients, resulting in discontinuation of treatment in one. One patient experienced severe malaise after 2 cycles and was given the standard dose for further therapy with a major hematologic improvement. Other isolated events included mouth ulcers, mild nausea and flare of erythema nodosum. Of the 5 responders, 1 later died of disease progression (after 7 cycles), 1 died of a complication of comorbidity (after 5 cycles), 1 is alive with disease progression (after 10 cycles) and 2 are continuing therapy with AZA (after 4 and 5 cycles, respectively). Conclusions: AZA 100 mg/m 2 /day for 5 days every 28 days seems to be tolerated as well as the 7-day treatment schedule. It also appears to have efficacy similar to the standard dose and schedule. If larger studies are confirmatory, this 5-day schedule may be more convenient for patients and providers. [Table: see text]
REGIONAL DIFFERENCES IN BICEPS FEMORIS FASCICLE LENGTH AND PENNATION ANGLE AFTER A SIMULATED SOCCER MATCH
Authors: Basílio Gonçalves, András Hegyi, Janne Avela, Neil Cronin
Journal: British Journal of Sports Medicine (2017)

Background Hamstring Strain Injuries (HSIs) represent 12% of all injuries in soccer players, and their incidence has increased in recent years. Between 53%-84% of HSIs involve the Biceps femoris muscle (BF). Recent studies have shown that soccer players with shorter BF fascicle length (FL) suffer more HSIs and exhibit regional differences in FL and pennation angle (PA) along BF. It is unclear whether there is any regional difference in the degree of change of these parameters after a soccer match. Objective Describe changes in BF muscle architecture after a simulated soccer match. Design Controlled laboratory study. Pre and Post single session. Setting Laboratory. Amateur Level. Participants Soccer players without acute injuries/illness and no previous lower limb injuries. Data collection is still ongoing. To date, 4 players have been measured and analysed. Assessment Randomized measurements of muscle architecture parameters at different submaximal contraction intensities, before and after a 45 min. soccer-specific fatigue protocol. Total time 3 hours. Main Outcome Measures Biceps femoris absolute and relative changes in PA and FL in 3 different regions of the muscle . Results from this ongoing study imply that relative changes in FL were region-dependent, whereby FL shortening after the protocol was greater in the proximal regions at higher contraction intensities (−2.0% vs 12.3% vs 19.5%), but greater in the distal regions at lower contraction intensities (−8.0% vs 6.7% vs 12.4%). Conclusions After a soccer-specific fatigue protocol, FL and PA of the BF muscle varied regionally and with contraction intensity. Greater FL shortening at proximal regions after a soccer match, especially at higher contraction levels, may be linked to the higher incidence of HSI in these areas, and might help to explain the injury mechanism.
Trial of exercise in ovarian cancer survivors.
Authors: Melinda Irwin, Linda Gottlieb, Brenda Cartmel, Elizabeth Ercolano, Marianna Rothbard, Yang Zhou, Peter E. Schwartz, Jennifer A. Ligibel, Vivian E. Von Gruenigen, Harvey Risch
Journal: Journal of Clinical Oncology (2012)

TPS1614 Background: Physical activity (PA) has been associated with improved QOL and survival in breast and colorectal cancer survivors, yet no study has examined the effect of exercise on ovarian cancer outcomes. The purpose of our NCI-funded trial is to examine, in 230 women diagnosed with Stage I-IV ovarian cancer, the impact of exercise vs. attention control on: QOL, body composition, and serum markers associated with ovarian cancer. This abstract presents preliminary recruitment and adherence results. Methods: Women are being recruited via Connecticut Tumor Registry and Yale Cancer Center into the Women’s Activity and Lifestyle Study in Connecticut (WALC). We are also recruiting patients nationally via self-referral and collaboration with medical oncologists at DFCI and Summa Akron City Hospital. Women are randomly assigned to exercise (n = 115) or attention control (n = 115). Both groups receive weekly telephone calls for six months from a certified health educator to discuss ovarian cancer health topics. In addition, the exercise group receives PA counseling to participate in 150 min/wk of aerobic exercise (primarily brisk walking) for six months. Results: Study recruitment began in March, 2010 and will be ongoing through December, 2013. As of December 31, 2011, we have identified 556 potentially eligible women. Of these, 145 are recently diagnosed and are awaiting screening, 115 were unable to be contacted, and 296 have completed the telephone screening. Of the 270, 46% were ineligible (e.g., already exercising, physical limitations); 30% were not interested, 24% (n = 66) have been randomized, and 9% (n = 24) are undergoing baseline visits. On average, women are 62 years old, diagnosed 1.8 years in the past, with primarily stage III disease. Thirty-three patients have completed the trial, with high adherence among women randomized to exercise (average 141 min/wk of exercise reported and 75% of exercisers participating in at least 150 min/wk of exercise). Conclusions: Women are interested in and able to participate in exercise after an ovarian cancer diagnosis. Our trial could suggest a unique and important role for exercise in ovarian cancer care given that physical and functional aspects of QOL are often the most compromised in ovarian cancer patients.
High activity rhenium-186 hydroxyethylidene diphosphonate (HEDP) with autologous peripheral blood stem cell (PBSC) transplant: A novel treatment strategy in hormone refractory prostate cancer metastatic to bone
Authors: J. M. O'Sullivan, A. R. Norman, V. R. McCready, G. Flux, G. Cook, B. Johnson, J. Treleaven, D. P. Dearnaley
Journal: Journal of Clinical Oncology (2004)

4562 Background: Bone marrow is the dose-limiting organ for bone seeking radionuclide therapy of bone metastases from prostate cancer. This prospective phase 2 trial investigated the potential for improvement in disease control by using autologous peripheral blood stem cell transplant to permit administration of high activities of a bone seeking radionuclide, Rhenium-186 HEDP in patients with progressive hormone refractory prostate cancer. Methods: Eligible patients had histologically confirmed prostate cancer metastatic to the skeleton, rising PSA despite castrate testosterone levels, WHO PS 0–1, and minimal soft-tissue disease. Patients received between 4500 and 5000MBq of Rhenium-186 HEDP i.v. (approximately 4 times the dose normally used for palliation), followed 14 days later by the return of pre-harvested PBSCs. Response was assessed using PSA, survival, pain scores, and quality of life measurement. Results: Thirty-eight patients with a median age of 67 years (range 50–77), and a median PSA of 57 ng/ml (range 4–3628) received a median activity of 4978 MBq Rhenium-186 HEDP (range 4400–5097). At a median follow up of 12 months (range 3–32), the most serious toxicity was short-lived (<7 days) grade 3 thrombocytopenia in 8 (21%) patients. The median survival of the group is 31 months with a Kaplan-Meier estimated 1 and 2-year survivals of 81% and 50% respectively. Twenty six patients (60%, 95% CI, 45–74%) had stable or reduced PSA levels 3 months post therapy, 10 of whom had PSA reductions of > 50% lasting > 4 weeks. Quality of life measures were stable or improved in 29 (76%) at 3 months. Conclusions: We believe the survival data and PSA response rates in this group of heavily pre-treated patients are encouraging and merit further investigation in a randomised trial. No significant financial relationships to disclose.
Aprepitant, granisetrone, and dexamethasone for prevention of CINV after high-dose melphalan in autologous transplantation: Results of a randomized, placebo-controlled phase III trial.
Authors: Thomas Schmitt, Hartmut Goldschmidt, Kai Neben, Anja Freiberger, Johannes Huesing, Martina Gronkowski, Markus Thalheimer, Le Hang Pelzl, Gerd Mikus, Juergen Burhenne, Anthony D. Ho, Gerlinde Egerer
Journal: Journal of Clinical Oncology (2013)

9612 Background: Aprepitant (A) is a NK1-antagonist approved for prevention of chemotherapy-induced nausea and vomiting (CINV). Though melphalan (M) is regarded only moderately emetogenic, CINV after high-dose M conditioning in autologous TPX can severely interfere with patients’ (pts) quality of life. Here we present the results of our monocentric, randomized (1:1), placebo-controlled, double-blind phase IIIb trial of A, granisetrone (G) and dexamethasone (D) in this setting. Methods: Pts were treated with A 125 mg po day 1, A 80 mg po days 2-4, G 2 mg po days 1-4 and D 4 mg po day 1, D 2 mg po days 2-3 (arm A) or placebo (P) days 1-4, G 2 mg po days 1-4 and D 8 mg day 1, D 4 mg days 2-3 (arm B). Melphalan 100 mg/m² iv was administered days 1-2. Episodes of emesis, modified functional living index – emesis questionnaire (FLIE) and intensity of nausea by visual analogue scale (VAS) were recorded between days 1-6. Primary endpoint was defined as no episode of vomiting and no additional antiemetic therapy within 120h of M administration. Results: Between 07/05 and 01/12 a total of 362 pts were randomized. 361 subjects (arm A=180; arm B=181; male n=229; female n=132; median age arm A=59.5 years; median age arm B=58 years) were available for the efficacy analysis. There were no significant differences in gender distribution and previous experience of CINV. Significantly less pts receiving A failed the primary endpoint (42% vs. 59%, OR=0.53 [0.34; 0.82], p=.0046). This effect was stressed in women (57% vs. 82%, OR=0.30) and patients with previous CINV (48% vs. 71%, OR=0.38). Emesis within 120h occurred in 22% of pts receiving A and 35% receiving P (OR=0.5 [0.31; 0.80], p=.0036). Though differences in overall nausea (16% vs. 22%, OR=0.65 [0.83; 1.10], p=.11) did not reach statistical significance, major nausea (VAS &gt;25mm) was reduced (6% vs. 12%, OR=0.42 [0.19; 0.92], p=.026). Difference in FLIE score was -8.2 (p=.0007). Study medication was well tolerated. PK analyses showed no interaction between M and A. Conclusions: The combination therapy with A resulted in significantly less CINV compared to placebo. This effect was pronounced in women and pts with previous CINV. Clinical trial information: NCT00571168.
Target wise and pound foolish: A simple technique to evaluate the trade-off between economic burden and clinical benefit of monoclonal antibodies.
Authors: Matt Christopher Brennan, Timothy J Brown, Kristian Michael Koller, Monali K. Vasekar, Peter Hubert Cygan, Jeffrey Michael Sivik, Michael J. Glantz
Journal: Journal of Clinical Oncology (2015)

6598 Background: Monoclonal antibodies (mabs) have great clinical potential for individual patients, but also substantial cost to society. We propose a very simple, transparent calculation to frame this debate in objective terms for practicing oncologists and policy makers. We then apply this strategy to all mabs currently approved for hematology/oncology indications. Methods: Mabs were identified from the FDA’s approved drug products list. Approved indications for each mab in the clinical practice of hematology/oncology were extracted from section 14 of the approved prescribing information. All comparative studies used to support each drug’s approval for each indication were analyzed. Cost data was obtained from publically available sources. Using this data, we calculated the cost to achieve one additional good outcome as defined by each study. Overall survival was our preferred outcome measure. If not explicitly stated, OS was calculated from the Kaplan-Meier curves using pixel coordinates. If OS data was not collected, the primary endpoint used in the trial was substituted. Total cost to achieve one additional good outcome was calculated as: cost = (cost per dose)*(median number of doses)*NNT. Results: Forty-four mabs were identified; 19 have hematology-oncology-relevant indications. Of 66 studies listed in the prescribing information leading to FDA approval, 47 were comparative and were included. The costs for each mab to achieve one improved outcome at the study-specified time were calculated. An abbreviated table is shown in the table below. Conclusions: NNT provides a simple, clinically relevant, robust way of framing the critical debate between individual benefit and public health priorities. Some monoclonal antibodies for some hematology/oncology indications may not meet reasonable thresholds for widespread use. Drug Indication Trial mOS (exp/control) in months Endpoint NNT Cost ($) Ramucirumab Gastric Cancer RAINBOW 9.6/7.4 6 mo OS 7 1,079,568 12 mo OS 10 1,542,240 Bevacizumab mCRC ECOG E3200 12.9/10.8 12mo OS 8 254,880 24mo OS 16 509,760 Rituximab DLBCL GELA Not reached 24 mo OS 8 433,126 60 mo OS 9 487,267 Trastuzumab Adj HER2 + breast HERA Not reached 24 mo OS 12 1,785,028
Clofarabine therapy for the treatment of relapsed or refractory pediatric acute leukemias
Authors: S. Jeha, B. Razzouk, P. Gaynon, R. Kadota, S. Rheingold, L. Luchtman-Jones, R. Arceci, M. Fernandez, S. Weitman, P. Steinherz
Journal: Journal of Clinical Oncology (2004)

8504 Background: Despite marked improvement in pediatric leukemia outcome, children with refractory disease or early relapse have a dismal prognosis with the current salvage regimens. Leukemia remains the leading cause of disease-related death in children. New therapeutic options are needed. Clofarabine, a next-generation nucleoside analogue, has shown clinical activity when used as a single agent in heavily pretreated children with relapsed or refractory acute leukemias. Methods: Two Phase 2 multicenter, open-label studies are being conducted with clofarabine in children with refractory or relapsed ALL or AML. Clofarabine is administered at 52 mg/m2/day over 5 consecutive days. Cycles are repeated every 2 to 6 weeks based on response and toxicity. Results: To date 69 patients (40 ALL, 29 AML) have been treated. Median age is 12 years (range 1 to 22 years) and median prior regimens is 3 (range 1 to 6). Forty-one percent had received prior transplant. As determined by independent review, preliminary data indicate overall response rates of 28% in ALL (4 CR, 3 CRp, and 4 PR) and 24% in AML (1 CRp and 6 PR). Median duration of remission is 12 weeks and 6 patients remain in remission with a range of 1 to 65+ weeks. Eight of 18 responding patients (44%) proceeded to bone marrow transplant (BMT). One responding AML patient had previously failed an induction therapy regimen that included cladribine, and 5 other responding patients (2 ALL, 3 AML) had received prior fludarabine as part of a conditioning regimen for BMT. Most drug-related adverse events were transient including fever, nausea/vomiting, headache, skin rash, hand-foot syndrome, elevation in liver enzymes and bilirubin, and infusion-related flushing and anxiety. Pharmacokinetic studies have been performed on the first 28 patients. Conclusions: Clofarabine, a next-generation nucleoside analogue, is active in multiply relapsed or refractory pediatric leukemia patients, including those who have failed prior nucleoside therapies such as cladribine or fludarabine. The toxicity profile is expected and acceptable for this patient population. Remissions are relatively durable, allowing responders to proceed to transplant. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration ILEX Products, Inc., an affiliate of ILEX Oncology ILEX Oncology, Inc.; ILEX Products, Inc., an affiliate of ILEX Oncology ILEX Oncology, Inc. ILEX Oncology, Inc.; ILEX Products, Inc., an affiliate of ILEX Oncology ILEX Oncology, Inc.
DNA repair gene expression profile and risk of locoregional relapse in locally advanced breast cancer patients
Authors: R. Le Scodan, G. Cizeron-Clairac, E. Fourme, D. Meseure, S. Vacher, F. Spyratos, F. Cvitkovic, B. de la Lande, R. Lidereau, I. Bieche
Journal: Journal of Clinical Oncology (2009)

528 Background: The cytotoxicity of radiation therapy appears mainly mediated through the induction of DNA-double strand breaks. We explore whether DNA repair gene expression could be associated with the risk of locoregional recurrence (LRR) in locally advanced breast cancer patients. Methods: mRNA levels of 21 selected DNA repair genes were measured in tumors samples of 97 locally advanced breast cancer patients included in a phase III trial (CRH cohort), using quantitative reverse-transcriptase polymerase chain reaction. Normalized mRNA levels were evaluated for association with LRR-free survival (LRR-FS) and overall survival (OS). Results were validated in an independant cohort (Netherlands Cancer Institute: NKI cohort). Multivariate analysis, including known prognostic factors, was done to assess the association between gene expression profile of DNA repair genes and outcomes. Results: Overexpression of RAD51, PRKDC, and XRCC6 were associated with a higher risk of LRR in the CRH cohort. RAD51 was the only gene associated with LRR in the NKI cohort. With a median follow-up of 126 months (CRH cohort), the 5-year LRR-FS rates were 100% in patients (n = 61) with low RAD51, compared with 70% in patients (n = 36) with high RAD51 (p &lt; 0.0001). The 5-year OS rates were 95% in patients with low RAD51, compared with 69% in patients with high RAD51 (p = 0.00026). RAD51 overexpression was associated with a higher risk of LRR (multiadjusted hazards ratio [HR], 12.83, 95% CI: 3.6 - 45.6) and a higher risk of death (multiadjusted hazards ratio [HR], 4.10, 95% CI: 1.7 - 9.7). RAD51 was also significantly associated with shorter LRR-FS and OS in the NKI cohort. Conclusions: Our results suggest that overexpression of RAD51, a key component of the homologous recombination and the DNA DSBs repair, is associated with a higher risk of LRR and death, and may be a prognostic marker of LRR in locally advanced breast cancer patients. No significant financial relationships to disclose.
Patient-related predictors of poor-quality pain care in advanced lung cancer patients.
Authors: Inga Tolin Lennes, Jennifer S. Temel, Emily R. Gallagher, Joseph A. Greer, William F. Pirl
Journal: Journal of Clinical Oncology (2012)

6062 Background: Unrelieved pain remains a major problem for all patients, including those with cancer, despite national standards for pain management. Screening and addressing pain is an integral part of oncology visits and an ASCO QOPI indicator of quality oncology care. The goal of this study was to assess associations between patient-related factors, particularly patient distress, and meeting ASCO quality metrics for appropriate management of pain in patients with advanced lung cancers. Identification of patient related factors could lead to targeted quality improvement efforts. Methods: From 8/07 to 9/10, we recruited consecutive new patients in a multidisciplinary thoracic oncology clinic to participate in a research database for which patients completed self-report instruments for distress, depression (PHQ-9) and anxiety (GAD-7), at their first oncology visit. We then performed a QOPI chart audit for patients with advanced lung cancer who received care at our institution. A composite measure of appropriate pain management was calculated. Components of the composite measure included 1) documentation of pain assessment, and 2) for patients with moderate-severe pain (≥4 on 10 point scale) plan of care documentation. Results: 253 patients completed baseline assessments and had follow up. Pain was assessed in 252 (99%) patients. Over a third (88/253) of newly diagnosed advanced lung cancer patients had at least moderate pain on their first visit to the medical oncologist. Almost half of patients with moderate-severe pain were depressed (40/88). Of the patients with moderate-severe pain, 54/88 (63%) had a plan of care related to pain documented in the oncologist’s note. In total, 219 (87%) patients received appropriate pain assessment and care. In a multivariate model including age, sex, histology, ECOG PS, provider, depression, and anxiety, only depression independently predicted inadequate pain care. Depressed patients were 3 times more likely to receive poor quality pain care (OR 2.75, 95% CI 1.04-7.25, p=0.04). Conclusions: At initial oncology visit, pain is present in over a third of patients with advanced lung cancer. Depression is highly co-morbid with pain and appears to be a risk factor for inadequate pain care.