tbuckley/cabot-search huggingface dataset:
Analysis of post-study chemotherapy in patients (pts) enrolled in the X-ACT phase III trial of capecitabine (X) vs. bolus 5-FU/LV as adjuvant therapy for Dukes’ C colon cancer: No differences in treatment arms that could influence survival outcome
Authors: J. Cassidy, P. Koralewski, F. Husseini, C. Twelves
Journal: Journal of Clinical Oncology (2005)

3586 Background: The X-ACT trial evaluated adjuvant X vs. 5-FU/LV in colon cancer. Between Nov98 and Nov01, 1987 pts with resected Dukes’ C colon carcinoma were randomized to receive either oral X (1250mg/m2 bid d1–14, q3w) or i.v. 5-FU/LV (Mayo Clinic regimen: LV20 mg/m2 + 5-FU 425mg/m2 d1–5, q4w) for 24 weeks. X was at least equivalent to 5-FU/LV in terms of disease-free survival (DFS), with trends toward superior DFS and overall survival. Methods: We analyzed post-study chemotherapy in both treatment arms to determine whether there were any differences that could influence survival outcome. Results: At the time of this analysis, 629 events have occurred. 656 pts in the X and 603 in the 5-FU/LV arm are alive and disease-free, with 148 and 153, respectively, alive with relapse/new recurrence. 277 pts received post-study chemotherapy. Of these, 25 in the X and 10 in the 5-FU/LV arm received adjuvant chemotherapy following randomization into X-ACT either because they never received study treatment or at the investigator’s discretion (after early termination of study treatment for any reason). In addition, 13 pts in the X and 16 pts in the 5-FU/LV arm received post-study chemotherapy for new occurrences of cancer other than colon cancer (breast, prostate, lung) prior to relapse from the primary or a new occurrence of colon cancer. Pts meeting the entry criteria (free of disease at study entry and receiving ≥ 1 doses of study treatment) who were treated according to the protocol and experienced relapse or new occurrence of colon cancer formed the largest group receiving post-study chemotherapy (table). Conclusions: These data suggest that there are no differences in post-study chemotherapy that could influence survival outcome in pts who received either X or 5-FU/LV as adjuvant therapy in the X-ACT trial. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Roche Roche Roche
Chromosomal Deletions and Amplifications in Multiple Myeloma Detected by 500K Single Nucleotide Polymorphism Array Analysis.
Authors: Yu-Tzu Tai, Cheng Li, Rory Coffey, Iris Breitkreutz, Xian-Feng Li, Laurence Laurence Catley, Robert L. Schlossman, Paul G. Richardson, Kenneth C. Anderson, Nikhil C. Munshi
Journal: Blood (2005)
Use of radiation pathways to drive standardization of evidence-based care across a large network.
Authors: Kathleen Lokay
Journal: Journal of Clinical Oncology (2013)

27 Background: UPMC CancerCenter includes 37 academic and community based sites in western Pennsylvania. Consistency and quality of care are critical to such a diverse network. To meet these challenges, UPMC developed clinical pathways for medical and radiation oncology, now marketed as Via Pathways. The program has served UPMC well for over eight years and is now a key foundation for UPMC’s overall healthcare reform strategy for accountable care. Methods: Radiation treatment algorithms for 90% of cancers were developed by committees of academic and community radiation, surgical, and medical oncologists, with current representation from multiple cancer centers across the country. The committees meet semi-annually to interpret the literature and define the most efficacious and least toxic treatments for highly specific disease presentations (e.g., oropharynx, Stage III-IV, primary chemoradiation). Guidance for contouring, planning and delivery are provided along with applicable citations. Clinical trials open at UPMC sites are also imbedded into the algorithms. Converting these algorithms into measureable decision support is accomplished with a web portal that presents the individual pathways status through the physician’s daily schedule. Results: Thirty-one (31) radiation oncologists at UPMC use Via Pathways in their daily practice. For the 12 months ended May 31, 2013, UPMC physicians confirmed a pathways status for 98% of their patient visits (n=9,400) and achieved an On Pathway rate of 95% for their 5,575 treatment decisions. All off pathway treatment decisions were approved prior to treatment by a designated peer review radiation oncologist within UPMC. Reasons for going off pathway were recorded as well as what alternative approach to care was chosen. Conclusions: When appropriately developed and implemented, clinical pathways are a solution to standardizing care across multiple sites and physicians with the potential to improve the quality and cost effectiveness of cancer care. We continue to expand the scope of Via Pathways to include additional cancer types, surveillance protocols, and end of life prompts as well as surgical oncology pathways.
A review of the outcomes of patients with anal cancer enrolled in the Hurley Cancer Registry: 1987-2004
Authors: S. Subramonia Iyer, A. Akl
Journal: Journal of Clinical Oncology (2009)

e15131 Background: This paper describes the outcomes of patients with anal cancer enrolled in the Hurley Cancer Registry. Methods: Retrospective registry and chart review study. The Hurley cancer registry was searched using diagnosis codes for anal cancer. The records retrieved, were reviewed for demographic and pathologic details,cancer recurrence, and vital status at last follow up. Relative survival was calculated for the patient cohort. Results: Over a period of 18 years (1987 - 2004), there were 36 patients enrolled in the registry, with a diagnosis of anal cancer. There were 18 males and 18 females. Mean age at diagnosis was 59.3 (SD 17.6) years for males, and 64.6 (SD 13.8) years for females. Squamous cell cancers were the most common: 27 / 36 (75%). The median survival of these 36 patients was 6 years. The median disease free survival was 5.3 years. Five patients (14%) developed recurrent disease during follow up, after a median of 1.8 years (range: 0.67- 4.2 years). Four of these patients had local recurrence only. One patient had local, regional recurrence with distant metastases. Three of the five (60%) recurrent cancers were associated with HIV infection. For all patients without recurrence, the median survival is 7.1 years. Relative survival is the observed survival adjusted for expected mortality. The expected survival probabilities for 3-yr and 5-yr intervals were calculated using the age, sex and race- matched survivorship information U.S. population life tables for 1989–91 and 1999–2001. Cumulative survival functions for the cohort were derived for the time points of 3-yrs and 5-yrs after diagnosis. The relative survival for the cohort was 84.6% at 3 years and 79.8% at the end of five years of follow up. These results appear superior when compared to the overall 5-year relative survival rate for 1996–2004 from 17 SEER geographic areas, which was 66.5%. Conclusions: Among patients in the Hurley Cancer Registry, 1. Squamous cell carcinoma is the commonest (75%) anal cancer. 2. The risk of recurrence of anal cancer was 14% over 6-years, and 80% of recurrence was localised to the anal canal. 3. The relative survival for the cohort was 79.8% at the end of five years of follow up. This was 78.9% for the subgroup of patients without recurrence, and 86.1% for the subgroup with recurrent disease. No significant financial relationships to disclose.
Phase II trial of bevacizumab and high-dose interferon alpha-2b in metastatic melanoma.
Authors: V. P. Grignol, T. Olencki, C. Taylor, A. Kibler, C. Kefauver, L. Wei, M. J. Walker, H. X. Chen, K. L. Kendra, W. E. Carson
Journal: Journal of Clinical Oncology (2010)

8520 Background: Bevacizumab (Bev) is a recombinant monoclonal antibody that neutralizes vascular endothelial growth factor, a potent factor for the induction of tumor angiogenesis in melanoma. Interferon-alpha (IFN) has antiangiogenic properties via downregulation of basic-fibroblast growth factor. We hypothesized that the coadministration of these two agents would lead to tumor regression. Methods: Patients with metastatic melanoma who had not received prior antiangiogenic therapy were enrolled. Patients received Bev at 15 mg/kg iv on day 1 of the 2 week cycle. IFN was administered thrice weekly at 5 MU/m2 scduring cycle 1, then increased to 10 MU/m2 during cycle 2. Patients with intracranial metastases or an abnormal Factor V Leiden, protein C/S, or antithrombin III were excluded. D-dimer, fibrinogen, INR, PT/PTT were obtained at the beginning of each cycle. Patients were restaged every 6 cycles. Patients with stable disease or a response (per RECIST) continued on therapy. Results: 25 patients were accrued (16 male, 9 female). Mean age was 58.4 years. 64% of patients had visceral metastases and 32% had prior therapy. Overall, the regimen was well-tolerated. Common grade 3 toxicities associated with IFN included fatigue and muscle weakness. 11 patients required IFN dose reductions due to toxicity. Bev was associated with grade 3 proteinuria in 3 patients. There were three grade 4 adverse events; pulmonary embolus (1), MI (1), and stroke (1) which occurred at 4, 14, and 51 weeks of therapy respectively. Screening for coagulation abnormalities did not prevent or predict thromboembolic events. Six patients had a partial response to therapy, including one patient who remains on therapy at 212 weeks. Five patients exhibited stable disease for < 24 weeks (30, 38+, 36, 50, 122 weeks). 14 patients had progressive disease at 12-20 weeks. Median PFS and OS were 4.9 months and 18.4 months respectively. Conclusions: Administration of Bev plus IFN led to a clinical response in 24% of patients with stage 4 melanoma and prolonged stabilization of disease in another 20%. In a previous trial of Bev alone at this facility median PFS and OS were 3 and 8.5 months and no responses were observed. This drug combination has activity in advanced melanoma. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Genentech
Application Of BOS 0-Potential Criteria As a Predictor For Bronchiolitis Obliterans Syndrome In Allogeneic Stem Cell Transplant Patients
Authors: Sameem Abedin, Gregory A. Yanik, John M. Magenau, Steven C. Goldstein, Attaphol Pawarode, John E. Levine, Carrie L. Kitko, Daniel R. Couriel
Journal: Blood (2013)
Quantitative imaging by automated bone scan index (BSI) as a response biomarker in standard clinical care of patients with metastatic castration-resistant prostate cancer (mCRPC) treated with enzalutamide.
Authors: Aseem Anand, Sarah Lindgren Belal, Mariana Reza, Lars Edenbrandt, Anders Bjartell
Journal: Journal of Clinical Oncology (2015)

288 Background: Enzalutamide (ENZ), an androgen receptor antagonist therapy, was approved for patients (pts) with mCRPC. However, in standard of care for mCRPC pts, change in prostate specific antigen (PSA) is not accepted as an efficacy response measurement and the radiological change is inadequately measured in an interpreter-dependent subjective analysis of bone scan. Therefore, an objective efficacy response biomarker is warranted. In this registry study, we evaluated BSI as a quantitative analysis of bone scintigraphy, to access response in mCRPC pts being treated with ENZ. Methods: Pts with mCRPC, at Skåne University Hospital (SUH), Sweden, who initiated treatment with ENZ after failing chemotherapy were eligible for the study. Primary objective was to associate the change in BSI and PSA, after 12 weeks (wks) of treatment with EZN, with overall survival (OS). Automated BSI generated by EXINI bone BSI platform is quantitative representation of tumor burden as a percent of total skeletal mass. Bivariate cox regression analysis was used to evaluate the association of BSI and PSA with OS. Results: Thirty-five pts, who initiated ENZ treatment at (SUH), were eligible for the BSI analysis. Follow-up scans for the BSI analysis were available from 24 pts. Median baseline BSI value was 2.92 (range: 0.0 - 11.72) and at follow-up the median BSI value was 2.83 (range: 0.0 - 12.65). OS was associated with BSI at both baseline and at follow-up as opposed to that of PSA (table 1). The change in BSI between baseline and follow-up was also significantly associated with OS, whereas the change in PSA was not. Conclusions: Automated BSI and its relative change were observed to be associated with OS in mCRPC pts receiving ENZ as standard of care treatment. The result deserves further validation, in controlled investigational studies, of BSI as a quantitative imaging biomarker indicative of efficacy response to second-line treatment in mCRPC pts. [Table: see text]
Population pharmacokinetic of total cisplatinum: Application to adaptative dosing with feed back in testicular cancer patient
Authors: S. Salas, C. Mercier, J. Ciccolini, B. Pourroy, C. Dupuis, J. Deville, M. Baciuchka-Palmaro, A. Durand, F. Duffaud, B. Tranchand, R. Favre
Journal: Journal of Clinical Oncology (2006)

2043 Background: Cisplatinum (CDDP) is major drug used in germ cell testicular cancer. Pharmacokinetics (PK)/pharmacodynamics relationships have been described after measurement of free CDDP in plasma, and subsequently, CDDP administration is standardized using body surface area (BSA) for only dose tailoring. Methods: Based on a rapid assay of total CDDP in plasma we have developed an alternative 120-hours continuous infusion schedule, coupled to a Bayesian adaptive dosing strategy. We present a retrospective evaluation of this schedule in 19 patients (66 courses) treated for testicular germ cell tumors. A NONMEM analysis was then performed to identify the covariates associated with total CDDP clearance. We compared doses effectively given to our patients with the ones calculated with BSA. Results: Plasma samples were analyzed to allow real-time Bayesian estimation of individual PK parameters with subsequent daily dose adjustment in order to reach a target Cend of 1.95 mg/l of total platinum. No statistical difference was observed between experimental and target values, and Cend adjustment was achieved with an overall 6.6% precision, a performance to be compared with the 54% inter-patient variability observed in drug clearance. Course number (CNB) was the only covariate to be correlated with total CDDP clearance. A weaker correlation was found with BSA, and only when considering first courses. Moreover, doses of CDDP administered were significantly higher than the ones classically normalized with BSA, thus leading to an overall greater exposure in our patients. Only few severe toxicities were reported, and all of the patients presented in this study were still alive and disease-free after a follow up of up to 15 years. Conclusions: Our alternative schedule is a convenient and safe strategy to ensure administration of optimal dose-intensity of CDDP, with limited side-effects in patients with testicular cancer. We demonstrate a linear correlation between course number and decrease of CDDP clearance (25%). This, highlights the critical importance of total drug accumulation on CDDP PK when several infusions are to be administered in a row, and therefore the need for developing dynamic dose individualization strategies that includes CNB. No significant financial relationships to disclose.
Vemurafenib-associated bullous DRESS syndrome: A very severe cutaneous reaction.
Authors: Aurelia Gey, Thomas Jouary, Christine Mateus, Caroline Robert, Gerard Perro, Brigitte Milpied
Journal: Journal of Clinical Oncology (2013)

e20041 Background: Vemurafenib, a selective BRAF inhibitor, has recently demonstrated improved overall survival in metastatic melanoma. Frequent cutaneous side effects have been reported with vemurafenib, mostly non severe. We report the first case of bullous DRESS syndrome (Drug Reaction with Eosinophilia and Systemic Symptoms) related to vemurafenib. Methods: Case report: A 69 year old man presented with a BRAF mutated multimetasatic melanoma. Vemurafenib, 960 mg orally twice daily, was started in August 2012. Treatment was discontinued 1 month later because of a grade 2 rash and nausea. Treatment was re-introduced 10 days later with reduction of the dose, 480 mg twice daily. Four days later, the patient had fever, diffuse rash with pustular blistering and eosinophilia up to 1000/mm3. Despite withdrawal of vemurafenib, skin detachment appeared with extension on more than 90% of the body surface and erosions involving oral and genital mucosa requiring admission in intensive care burn unit. A skin biopsy revealed infiltration of the epidermis and the upper dermis with lymphocytic lichenoid vasculitis and focal necrolytic keratinocytes. Intravenous steroids were provided and lesions rapidly resolved with total epithelisation within 15 days. To date, the patient is still alive and undergoes active palliative care. Results: Discussion: DRESS syndrome is a severe drug reaction defined as an acute and severe heterogeneous rash with general symptoms, biological abnormalities, and visceral damages. It occurs from 3 to 6 weeks after drug administration. With a Kardaun score of 4, there were several arguments for a DRESS syndrome to vemurafenib: diffuse and acute rash occurring after 5 weeks of treatment, initial eosinophilia, aggravation of skin lesions despite withdrawal of the culprit drug, histological features and rapid improvement after steroid treatment. With more than 90% of body surface skin detachment, requiring treatment in burn center, the diagnosis was a very severe bullous DRESS syndrome. Vemurafenib was the only culprit drug in our case, as the patient did not received any other drug. Conclusions: Though toxic epidermal necrolysis has been reported yet with vemurafenib, no case of DRESS syndrome has been described to date.
Leisure-time Physical Inactivity and Risk of Myocardial Infarction and All-cause Mortality : a Case-control Study
Authors: Fredrik Calais, Ole Frobert, Andreas Rosenblad, Pär O. Hedberg, Kristian Wachtell, Jerzy Leppert
Journal: Circulation (2013)

Leisure-time Physical Inactivity and Risk of Myocardial Infarction and All-cause Mortality : a Case-control Study
Elevated GM-CSF in COPD may drive defective macrophage phenotype
Authors: Amy Day, Peter Barnes, Louise Donnelly
Journal: European Respiratory Journal (2014)

Healthy pulmonary macrophages (mΦ) respond to environmental change by altering their phenotype. In COPD, mΦ are phenotypically distinct with increased pro-inflammatory mediator release and defective phagocytosis. The reasons for this are unclear, but the growth factors GM-CSF and M-CSF can determine mΦ differentiation.

We generated monocyte-derived macrophages (MDM) from non-smokers (NS=5), smokers (S=4) and COPD patients (COPD=5) using GM-CSF (GmΦ) or M-CSF (MmΦ) and then examined plasticity by switching culture conditions. Phagocytosis of Streptococcus pneumoniae (SP) and Haemophilus influenzae (HI) was measured fluorometrically at baseline, 2, 4 and 6 days post-switching.

Baseline MmΦ phagocytosed more SP and HI than GmΦ in all subject groups (NS 170±40%, S 180±60%, COPD 110±20%). Switching to M-CSF significantly increased phagocytosis in non-smokers (SP:280±25% HI:200±40%) (p<0.05) but to a far lesser extent in smokers (SP:170±30% HI:70±50%) and COPD mΦ (SP:2%±1% HI:50±20%) by day 6. Switching to GM-CSF for decreased phagocytosis by half in all subject groups.

As GM-CSF suppressed phagocytosis, GM-CSF and M-CSF sputum levels were analysed using ELISA. GM-CSF was significantly higher in COPD sputum (183±32pg/ml, n=9) compared to sputum from non-smokers (47±3pg/ml, n=5) and smokers (36±4pg/ml, n=8) (p<0.05). M-CSF was lower in sputum from COPD patients (14±7pg/ml, n=9) and smokers (9±4pg/ml, n=8) compared to sputum from non-smokers (22±12pg/ml, n=5).

Regardless of culture changes, COPD macrophages retain phagocytic defects indicating lack in plasticity. This may be further exacerbated by a pro-inflammatory, GM-CSF-rich lung environment.
Cytotoxic T lymphocyte-associated antigen 4 blockade with ipilimumab: Long-term follow-up of 179 patients with metastatic melanoma.
Authors: P. A. Prieto, J. C. Yang, R. M. Sherry, M. S. Hughes, U. S. Kammula, D. E. White, C. L. Levy, S. A. Rosenberg, G. Q. Phan
Journal: Journal of Clinical Oncology (2010)

8544 Background: We have previously shown objective clinical responses in patients with metastatic melanoma treated with CTLA-4 blockade using ipilimumab. We have treated 179 patients in 3 separate clinical trials and now have long-term follow-up to evaluate the durability and unique features of this immunotherapy. Methods: A total of 179 patients with metastatic melanoma were treated in 3 trials: In Protocol 1, 56 patients received ipilimumab with gp100 peptide vaccines. In Protocol 2, 36 patients received ipilimumab with high-dose interleukin-2 (IL-2). In Protocol 3, 87 patients received intra-patient dose escalation of ipilimumab and were randomized to receive gp100 peptides. We have updated and analyzed the follow-up and survival data for these trials. Results: With median follow-up for Protocol 1, 2, and 3 being 80, 71, and 60 months, median survival was 15, 16, and 13 months, respectively. Objective tumor regression was 12% for Protocol 1, 25% for Protocol 2, and 21% for Protocol 3. Patients in Protocol 2 had a 17% complete response rate (6 patients: 77+, 74+, 72+, 71+, 71+, and 69+ months), as compared to 7% in Protocol 1 (4 patients: 82+, 81+, 79+, and 66+ months) and 8% in Protocol 3 (5 patients: 64+, 63+, 62+, 60+, and 55+ months); all complete responses are ongoing. Many patients who eventually became complete responders had continual tumor shrinkage after stopping therapy. Conclusions: CTLA-4 blockade with ipilimumab can achieve durable objective tumor regression in patients with metastatic melanoma. The combination of ipilimumab and IL-2 appears to have an increased complete response rate, although this needs to be tested in a prospective randomized trial. This report represents the largest single-institution experience with the longest follow-up for this agent; our results support its role as a viable treatment option for patients with metastatic melanoma. No significant financial relationships to disclose.