tbuckley/cabot-search huggingface dataset:
Effect of prior treatment status on the efficacy and safety of ipilimumab monotherapy in treatment-naive and previously treated patients with advanced melanoma
Authors: J. A. Thompson, D. Berman, J. Siegal, D. Minor, A. Amin, I. Ron, R. Ridolfi, H. Assi, O. Hamid, J. Weber
Journal: Journal of Clinical Oncology (2008)

9055 Background: Ipilimumab is a fully human, anti cytotoxic T-lymphocyte antigen-4 (CTLA-4) monoclonal antibody. Ipilimumab induced durable objective responses (OR) and stable disease in previously treated patients (pts) with advanced melanoma; its efficacy in treatment- naïve pts is being evaluated in an ongoing phase III study. Methods: In this randomized, double-blind, placebo- controlled, multicenter, phase II study, ipilimumab was administered ± prophylactic budesonide to treatment-naïve and previously treated pts with unresectable stage III/IV melanoma. Eligible pts received induction dosing with ipilimumab at 10 mg/kg every 3 weeks (Q3W) × 4 plus prophylactic budesonide or placebo, and received maintenance dosing Q12W starting at Week 24. In this analysis, the efficacy and safety of ipilimumab in treatment-naïve pts versus pts who had received prior systemic anticancer therapy was assessed. Response was defined using mWHO criteria. Follow-up tumor evaluation beyond PD by mWHO and before the administration of non-ipilimumab anticancer therapy was permitted as per protocol. Results: Of 115 treated pts, 53 received 1st-line ipilimumab, and 62 received it as > 2nd-line therapy. 21 1st-line (39.6%) and 37 > 2nd-line pts (59.7%) received assigned prophylactic budesonide. Per an Independent Review Committee (IRC), the observed best overall response rate (BORR [CR + PR]) and rate of Grade 2+ diarrhea prior to maintenance were similar between groups. Based on population pharmacokinetic analysis, the rate of clearance of the antibody did not appear different between the arms. Conclusions: Ipilimumab was associated with similar antitumor activity and toxicity when used as either 1st or > 2nd-line monotherapy in pts with advanced melanoma. 1st-line ipilimumab (n = 53) > 2nd-line ipilimumab (n = 62) Placebo (n = 25) Budesonide (n = 37) Placebo (n = 32) Budesonide (n = 21) BORR - %[95% CI] 15.6 [5.3 - 32.8] 9.5 [1.2 - 30.4] 16.0 [4.5 - 36.1] 13.5 [4.5 - 28.8] Inflammatory events - % [95% CI] Grade 2+ diarrhea beforeWeek 24 Bowel perforations - % 31.25 [16.12 - 50.01] 0 38.10 [18.11 - 61.56] 0 40.00 [21.13- 61.33] 0 29.73 [15.87- 46.98] 0 Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Bristol-Myers Squibb
Bezwoda: Evidence of Fabrication in Original Article
Authors: Andrew Vickers, Paul Christos
Journal: Journal of Clinical Oncology (2000)

Article Tools SPECIAL DEPARTMENTS Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.2000.18.15.2933 Journal of Clinical Oncology - published online before print September 21, 2016 PMID: 10920144 Bezwoda: Evidence of Fabrication in Original Article Andrew VickersxAndrew VickersSearch for articles by this author , Paul ChristosxPaul ChristosSearch for articles by this author Show More Memorial Sloan-Kettering Cancer Center New YorkNYMemorial Sloan-Kettering Cancer Center New YorkNY https://doi.org/10.1200/JCO.2000.18.15.2933 Full Text PDF Figures and Tables "Bezwoda: Evidence of Fabrication in Original Article ." Journal of Clinical Oncology, 18(15), p. 2933© 2000 by American Society of Clinical Oncology
Phase I/II dose-escalation trial of amonafide for treatment of advanced solid tumors: Genotyping to optimize dose based on polymorphic metabolism
Authors: J. G. Kuhn, H. A. Burris, S. F. Jones, D. W. Hein, N. T. Willcutt, F. A. Greco, D. S. Thompson, A. A. Meluch, R. S. Schwartz, D. M. Brown
Journal: Journal of Clinical Oncology (2007)

2503 Background: Amonafide (AMF), a synthetic imide derivative of naphthalic acid, is a topoisomerase II inhibitor and is subject to polymorphic metabolism based on acetylation genotype. AMF is extensively metabolized by N-acetyltransferase 2 (NAT2) to N- acetylamonafide (AAMF) which has activity nearly equipotent to AMF. In our phase I evaluation, we observed a correlation between NAT2 genotype, AMF/AAMF pharmacokinetics and toxicity (J Clin Oncol 22 [14S]: 2023, 2004). Patients (pts) with slow (S) acetylator genotype tolerated higher doses than those with rapid/intermediate (R/I) acetylator genotype. The present Phase II portion was designed to prospectively determine the dose of AMF based on NAT2 genotype and focused on selected tumor types. Methods: NAT2 genotyping of genomic DNA from blood samples was done prospectively to determine acetylator status of each pt. AMF was administered IV weekly x 3 q4wk, escalation range 320 to 400 mg/m 2 for R/I and 400 to 500 mg/m 2 for S acetylators. Primary endpoints: safety, MTD, tumor measurements or sustained decreases in tumor markers. Results: Total 47 pts (21 M/26 F), median 66 yr, PS 0–2, acetylator status R/I (26), S (21) with ovarian (11) or prostate (9), breast (8), colon (4) cancers (CA) and other common tumors refractory to therapy were treated; 30 of 47 pts were dosed based on prospective genotyping. Of these 30 pts, 17 were R/I acetylators: no toxicity at 320 mg/m 2 AMF in 7/11 pts and manageable myelosuppresion in 4/11 pts observed days 15–21 of cycle but not dose-limiting (DLT); DLT in 3/6 pts at 400 mg/m 2 . In the 13 S acetylators: at 400 mg/m 2 no DLT in 8 pts; DLT in 2/5 pts treated at 500 mg/m 2 . Other side effects included nausea/vomiting, fatigue and anemia. Of all 47 pts, biologic activity was seen in 6 pts: 3/9 prostate CA (decreased PSA), 2/11 ovarian CA (decreased CA125) and 1/1 GIST (decreased lymph nodes). Conclusions: MTD determined to be 320 mg/m 2 in R/I and 400mg/m 2 weekly x 3q 4 weeks in S acetylators, respectively, supporting hypothesis that AMF dosing based on prospective NAT2 genotyping may allow for dose optimization based on drug metabolism and result in better tolerance. Phase II assessments at the MTD dose levels are currently ongoing for prostate cancer. No significant financial relationships to disclose.
Next-generation sequencing of genomic and cDNA to identify a high frequency of kinase fusions involving ROS1, ALK, RET, NTRK1, and BRAF in Spitz tumors.
Authors: Phil Stephens, Thomas Wiesner, Jie He, Roman Yelensky, Rosaura Esteve-Puig, Geoff Otto, Michael F. Berger, Doron Lipson, Kristina Brennan, Vincent A. Miller, Maureen T. Cronin, Boris C. Bastian
Journal: Journal of Clinical Oncology (2013)

9002 Background: Spitz tumors are melanocytic neoplasms with characteristic morphologic features that can overlap with melanoma. Predicting biologic behavior, which can range from an indolent disease to metastasis confined to regional lymph nodes and infrequent incidences of widespread metastatic disease with lethal outcome, is unreliable based on histopathological criteria and the genetic underpinnings of the disease as a whole are poorly understood. Methods: Genomic DNA and total RNA was isolated from 40 microns of FFPE sections from 20 benign Spitz nevi and 8 atypical Spitz tumors (with morphological features inconsistent with HRAS or BRAF/BAP1 mutations) in a CLIA-certified lab (Foundation Medicine). DNA sequencing was performed for 3230 exons of 182 cancer-related genes plus 37 introns of 14 genes commonly fused on indexed hybridization-captured libraries to an average unique coverage of 997x, with 99.96% of exons being sequenced at ≥100x coverage. RNA sequencing was performed on indexed libraries captured using the cDNA Kinome hybridization kit (Agilent) generating &gt;50,000,000 unique pairs per specimen. Results: Only a single case harbored a point mutation in a gene known to be recurrently mutated in melanocytic neoplasms, HRAS Q61L and no known alterations were found in BRAF, NRAS, KIT, GNAQ or GNA11. Remarkably, genomic rearrangements were observed in 19/28 (68%) of cases. The rearrangements fused the intact kinase domains of ROS1 (36%), ALK (14%), RET (7%), NTRK1 (7%) and BRAF (4%) to a wide range of predominantly novel 5’ partners including PWWP2A, PPFIBP1, ERC1, MYO5A, CLIP1, HLA-A, ZCCHC8, DCNT1, LMNA and CEP89. These gene rearrangements, which were all expressed, formed constitutively activated chimeric oncogenes. All fusions occurred in a mutually exclusive pattern and were more common in younger patients compared to patients whose tumors did not harbor fusions (median age 14 versus 24 years, p=0.02). Conclusions: Next generation sequencing identified gene fusions in two thirds of Spitz tumors which are likely to be useful as diagnostic markers that may also serve as therapeutic targets for the rare subset of these tumors that metastasize.
Salvage surgery for local recurrence after breast conservation therapy—Is re-lumpectomy an appropriate treatment?
Authors: T. Ofuchi, A. Amemiya, M. Ono, J. Hatayama, A. Takeda
Journal: Journal of Clinical Oncology (2006)

608 Background: Since 1983 through 2005, 2439 clinical stage I or II patients (pts) were treated with lumpectomy and postoperative irradiation. During median follow-up of 75 months, 142 patients experienced local recurrence as first and sole event were judged as candidate for further local therapy. The purpose of this study is to evaluate the outcome of salvage treatment, with specific reference to feasibility of second breast conservation surgery. Methods: Among those with operable local recurrences, 73 pts who requested conservation of their breasts and whose recurrences were judged to be small enough to be locally re-excised with adequate margins underwent second lumpectomy (Re-LMP). 51 pts were treated by mastectomy with or without immediate reconstruction (MAS). Adjuvant systemic therapy of limited duration was given at the discretion of patients and therapists. Survival and local re-recurrence after salvage surgery were estimated by Kaplan-Meier method. Results: Age of patients ranged from 28–69 (mean: 41). Median follow-up length after salvage surgery was 53 months (6–194 months). Patient/Tumor characteristics were similar in Re-LMP and MAS groups. Local re-recurrence: Re-LMP: 31 pts developed in-breast re-recurrence (34% at 3yrs, 49% at 5yrs). MAS: 6 pts experienced chest wall recurrence (11% at 3yrs, 11% at 5yrs, p=0.0005). Independent risk factor for re-recurrence was not identified. Survival: In initial clinical stage I patients, 3 pts treated with Re-LMP died after salvage surgery and all treated with MAS survived (94% and 100% at 5yrs, p=0.2). In clinical stage II patients, 6 in Re-LMP and 8 patients in MAS died (89%, 57% at 5yrs after salvage surgery, p=0.02). Poor prognostic factors for both groups were initial stage and stage at the time of local failure. Conclusions: For an isolated in-breast recurrence, salvage mastectomy with or without immediate reconstruction provides excellent local control. At the present time, mastectomy should be offered as 1 st treatment option. Although survival is not jeopardized, Re-LMP alone does not offer adequate local control. Additional local therapy i.e. re-radiotherapy or aggressive systemic therapy may improve this poor result. Prospective studies should be initiated. No significant financial relationships to disclose.
Low molecular weight heparin (LMWH) increases the efficacy of immunotherapy in metastatic renal cell carcinoma patients with abnormal coagulation
Authors: I. Tsimafeyeu, A. Madzhuga, L. Demidov, O. Somonova, G. Kharkevich, A. Yelizarova, N. Petenko
Journal: Journal of Clinical Oncology (2007)

15591 Background: Antitumor effects of LMWH are unclear. Heparin can bind with fibroblast-growth factor, other heparine-binding angiogenic factors, their receptors, and/or impact on coagulation system which induces angiogenesis. We previously revealed hypercoagulation is a frequent symptom in metastatic renal cell carcinoma (MRCC) patients (pts) and clinically correlates with progression of the disease. Methods: Pts with MRCC and high level of fibrinogen, D-dimer or fibrin, antithrombin III and prothrombin were stratified by MSKCC prognostic criteria and included to receive immunotherapy plus LMWH (IL-2, 1 MIU, i.v, 3 tiw + IFN alpha, 5 MU, s.c, 3 tiw ± 5-FU 500 mg/m 2 , i.v. once a week, and Dalteparin, LMWH, 5000 IU, s.c, every day, for 3 weeks) or immunotherapy alone. Demographic and treatment characteristics were similar between both arms. The primary endpoint was cancer-related overall survival (OS). Results: Flu-like syndrome, hypotension, anorexia were most common side effects (CTC grade 1). There were no bleedings in LMWH group. Conclusions: These results demonstrate that Dalteparin significantly improves cancer specific overall survival and decreases disease progression rate in combination with immunotherapy in MRCC pts with abnormal coagulation. Phase II randomized multicenter open-label discontinuation trial will be conducted. [Table: see text] No significant financial relationships to disclose.
Translumbar inferior vena cava catheter for long-term hemodialysis.
Authors: A Gupta, P K Karak, S Saddekni
Journal: Journal of the American Society of Nephrology (1995)

Vascular access failure is a major cause of morbidity and even mortality in patients on chronic hemodialysis. The failure of conventional vascular access and thrombosis of the superior vena cava in a patient with ESRD was successfully treated by the percutaneous insertion of a hemodialysis catheter directly into the inferior vena cava. The translumbar access to the inferior vena cava has been used successfully in bone marrow transplant recipients and may also be used as a last choice for long-term hemodialysis when conventional access is difficult.
Granulocyte-macrophage colony stimulating factor (GM-CSF) &amp; Interleukin-2 (IL-2) combination as adjuvant therapy in cutaneous melanoma. Early results of a phase II clinical trial
Authors: E. G. Elias, J. L. Zapas, S. L. Beam, S. D. Brown
Journal: Journal of Clinical Oncology (2004)

7559 Background: GM-CSF leads to dendritic cell priming and activation, and also increases IL-2 receptor expression on T-lymphocytes. IL-2 creates LAK cells and TIL cells. Therefore, it was compelling to combine these 2 agents, each with a different function but a complimentary action. Methods: This is an open label, single arm study. 16 patients participated and underwent potentially curative surgery. Post-operatively, each patient received GM-CSF: 125μgm/m2/day, sc ×14 days; followed by IL-2: 9 million IU/m2/day, sc ×4 days, then 10 –12 days of no treatment. This cycle was repeated once/month for 6 months, i.e., 6 cycles. In addition, patients with large tumors received autologous melanoma vaccine. All the patients were observed, and in the event of recurrence or metastases, the patient was evaluated for resection and was re-treated on the same program. Results: The patient population consisted of: 8 patients with T3b-T4b primary melanoma. The remaining 8 patients had metastases to regional lymph nodes (LN), iliac LN ± intransit metastases, and resected distant metastases. 6 patients had large enough tumors that yielded sufficient tumor cells and received autologous tumor vaccine with the biotherapy. This program was well tolerated with minimal complaints, and good patient compliance. 9 patients developed WBC >20,000/cmm with a high eosinophil count. 2 patients developed subcutaneous nodules away from any site of GM-CSF or IL-2 injections. Pathology proved these to be LN packed with T lymphocytes and a few foci of β cells. Fifteen patients are alive free of disease (including 2 who were re-treated) after 6–26 months of follow-up (median 14). Conclusions: 1. In an attempt to intensify this therapy without increasing the dosage (because of the leucocytosis) we plan to extend this treatment to one year. 2. It seems that surgical resection of recurrences and metastases followed by Biotherapy or Bio-Immunotherapy can be an effective approach in the management of this disease. No significant financial relationships to disclose.
CADET II: A prospective trial of computer-aided detection (CAD) in the UK Breast Screening Programme
Authors: F. J. Gilbert, S. M. Astley, M. G. Gillan, O. F. Agbaje, M. G. Wallis, J. James, C. R. Boggis, S. W. Duffy
Journal: Journal of Clinical Oncology (2008)

508 Background: Computer-aided detection (CAD) systems that attract the reader's attention to potentially suspicious features on a mammogram are now in clinical use in screening mammography in the USA. Double reading increases small cancer detection by up to 10%, and the aim of this trial was to evaluate whether the performance of a single reader using CAD can match that of standard double reading in the UK Breast Screening Programme. Methods: Information about the study was posted to women invited for routine screening mammography at three UK screening centers. Informed consent was obtained at the time of the mammography appointment. Film batches were randomly assigned in a ratio of 28:1:1 to one of three film reading regimes: mammograms double read and single read with CAD, mammograms double read only, mammograms single read with CAD only. Double reading was conducted according to standard protocol. For single reading with CAD, mammograms were digitized and analyzed by an ImageChecker CAD system V8.1 and readers viewed the CAD prompted images on a low resolution computer display screen or hard copy printouts. The study was designed as a prospective multicenter randomized trial with matched comparison of single reading with CAD and double reading in terms of the number of women recalled for assessment, cancer detection rate and staging of the two reading regimes. Equivalence was defined as a 95% confidence interval on the difference between cancer detection rates of no more than 10% in either direction and the estimated sample size was 30,000 women. Results: 31,293 women were recruited into the trial between September 2006 and August 2007. The cancer detection rates of the two reading regimes were comparable (86.5% for single reading with CAD and 87.8% for double reading). This equates to a difference of −1.3% (95%CI −8.4%, +5.7%; p=0.7). Recall rates were 3.9% for single reading with CAD and 3.3% for double reading, a small but significant, absolute difference of 0.6% (95%CI 0.3%, 0.8%; p<0.007), a relative difference of 18%. Conclusions: The cancer detection rate of single reading with CAD was comparable to that achieved by double reading with only a small increase in recall rate. The results of this study should inform policy on the potential of CAD to improve efficiency in the UK Breast Screening Programme. No significant financial relationships to disclose.
An exploratory study of the biologic effects of nivolumab (Anti-PD-1; BMS-936558; ONO-4538) treatment in patients (pts) with advanced (unresectable or metastatic) melanoma (MEL).
Authors: Jeffrey Alan Sosman, Salvador Martin-Algarra, Jedd D. Wolchok, William Howard Sharfman, Shailender Bhatia, F. Stephen Hodi, Wen-Jen Hwu, Thomas Gajewski, Craig L. Slingluff, Howard Kaufman, Manish Gupta, Analia McGirr, Christine E. Horak, Christoph Matthias Ahlers, Jon M. Wigginton, Walter John Urba
Journal: Journal of Clinical Oncology (2013)

TPS3114 Background: Programmed death-1 (PD-1) is an immune checkpoint receptor expressed by T cells that negatively regulates T-cell activity and may promote tumor immune evasion by binding to its ligands (PD-L1/L2) on tumor cells and/or antigen-presenting cells. Nivolumab is a fully human IgG4 PD-1 receptor blocking monoclonal antibody that has shown antitumor activity in phase I trials in pts with solid tumors, including advanced MEL. Objective responses were observed in pts whose diseases were refractory to multiple prior therapies. We describe an ongoing exploratory, open-label, multicenter translational study designed to further investigate the immunoregulatory activity and mechanisms of action of nivolumab in advanced MEL, including ipilimumab (anti-CTLA-4) naïve and refractory pts. Methods: This study is enrolling advanced MEL pts who are either ipilimumab naive (n=40) or refractory (n=40). Eligible pts must not have received &gt;3 prior therapies for metastatic disease and must consent to pre-and on-treatment biopsy (after 2 doses of nivolumab [Day 28]) of an accessible tumor. Nivolumab will be administered IV every 2 weeks (wks) at a dose of 3mg/kg and may continue for up to 13 cycles (104 wks) until clinically significant progression or treatment discontinuation criteria are met. Tumor responses will be assessed every 8 wks using RECIST 1.1 criteria. The primary objective is to investigate the pharmacodynamic (immunoregulatory) activity of nivolumab in the peripheral blood (PB), tumor, and tumor microenvironment. Secondary objectives include evaluation of safety and tolerability, preliminary antitumor activity, and immunogenicity of nivolumab, as well as the association between tumor PD-L1 expression and clinical efficacy. Exploratory objectives include characterization of pharmacokinetics (PK) and evaluation of the potential association between selected PB and/or tumor biomarkers and PK, clinical safety, and efficacy (eg, progression-free and overall survival). Clinical trial information: NCT01621490.
Truth telling to cancer patients: Views of Myanmar primary care physicians
Authors: S. Mon, A. Pe
Journal: Journal of Clinical Oncology (2007)

17030 Background: Due to cultural and social concern, non oncology physicians are still practicing nondisclosure in Myanmar. The views of Myanmar primary care physicians about truth telling to cancer patients were studied. Methods: A Questionnaire about revealing diagnosis and prognosis to cancer patients was prepared and given to 150 qualified Primary care physicians attending the oncology related lecture in CME course for General Practitioners in 2006, Yangon, Myanmar. Results: A total of 145 completed forms (96.66%) were returned. Age of primary care physicians range from 23 yrs to 52 yrs. 90 doctors (62.06%) were under age of 35 yrs (mean 29.94 yrs) and practicing experience ranged from 1 to 10 yrs. The remaining 55 (37.93%) were over 35 yrs of age (mean 44.52 yrs) with practicing duration of 10 to 28 yrs. The common cancer patients they have seen in daily practice were breast cancer (40%), lung cancer (28.96%), GI cancer (15.17%), cervical cancer (8.96%), ovarian cancer (3.4%), head and neck cancer ( 2.06%) and hematological malignancies (1.37%).A total of 73 doctors (50.34%) answered that they let the patient know they were suffering from a serious disease (not mentioning the word cancer) that needs further specialized treatment. Interestingly, 69.09% of physicians over 35 yrs of age agree with this approach, whereas only 38.88% of young physicians prefer it. Besides, 56.6% of senior primary care physicians prefer to reveal the diagnosis and prognosis to one or more family members first. Although all doctors are aware of the psychological distress on patients by painful truth telling, 58.8% of younger generation prefer to practice full disclosure to patients. Altogether, 105 physicians (72.41%) agree that disclosure of diagnosis and prognosis depends on education status of the individual patient. Conclusions: In this study, there were variations in physicians’ attitude and practice of truth telling. Full disclosure was preferred more by young physicians in Myanmar. Further studies on patients’ preference of telling the truth will help to better understand doctor-patient communication in Myanmar. No significant financial relationships to disclose.