tbuckley/cabot-search huggingface dataset:
Rolapitant for control of chemotherapy-induced nausea and vomiting (CINV) in patients with gynecologic cancer.
Authors: Bernardo Leon Rapoport, Lee Steven Schwartzberg, Sujata Arora, Daniel Powers, Karin Jordan, Rudolph M. Navari
Journal: Journal of Clinical Oncology (2016)

223 Background: Rolapitant, a long-acting neurokinin-1 receptor antagonist, protected against CINV in patients receiving highly or moderately emetogenic chemotherapy (HEC or MEC). Methods: In 3 double-blind phase 3 studies, patients were randomized to receive oral rolapitant 180 mg or placebo before administration of HEC or MEC. All patients received a 5-hydroxytryptamine type 3 receptor antagonist and dexamethasone. In a post hoc analysis of 3 pooled studies (2 HEC and 1 MEC), we assessed the efficacy and safety of rolapitant in patients with gynecologic (ovarian, uterine, or cervical) cancer. Endpoints included complete response (CR; no emesis and no use of rescue medication), no emesis, no nausea (maximum visual analogue scale [VAS] &lt; 5 mm), and complete protection (CP; no emesis, no use of rescue medication, and no significant nausea [maximum VAS &lt; 25 mm]) in the overall (0–120 h), acute (≤ 24 h), and delayed (&gt; 24–120 h) phases. Results: Of 201 patients with gynecologic cancer (60% ovarian, 28% uterine, and 12% cervical cancer), 55% received cisplatin-based HEC and 44% received MEC (99% of whom received carboplatin-based therapy). In the overall and delayed phases, improved rates of CR, no emesis, no nausea, and CP were observed with rolapitant compared with control (Table). The overall incidence of treatment-emergent adverse events was similar in the rolapitant and control groups (45% vs 54%). Conclusions: Rolapitant protected against overall and delayed CINV in patients with gynecologic cancer receiving HEC or MEC. Clinical trial information: NCT01500226, NCT01499849, NCT01500213. [Table: see text]
Mismatch of available cancer therapeutic trials to patient populations in community practices.
Authors: Lily L. Lai, Doni Woo, Yvonne Chapman, Nimit Sudan, Christina Haeyoung Yeon, Vijay Trisal, James Ross Waisman
Journal: Journal of Clinical Oncology (2014)

84 Background: Clinical cancer research has consistently been associated with improvements in the quality of cancer care in community practices. We initiated a project to better identify the barriers to enrollment into adult oncology therapeutic trials in a community setting. Methods: Over a 12-month period from June 2013 – May 2014, all consecutive new patients presenting to medical oncologists at two community practices (CP1 and CP2) affiliated with an NCI-designated Comprehensive Cancer Center (NCI CCC) were screened by trained clinical research nurses. Data captured included demographics, diagnoses, stage of disease, previous treatments. Therapeutic trials available through the NCI CCC were matched to the patients. Actual enrollments rates into the trials were calculated. Results: A total of 1,430 new patients was seen in the time period studied (CP1, n=1,088; CP2, n=342). Of these, 912 (CP1, n = 667; CP2, n = 245) patients had a cancer diagnosis. At CP1, 63 therapeutic trials were available through the NCI CCC. 64 (8.3%) patients matched the criteria for any of the available trials, 33 enrolled, 18 declined, 13 failed screening. The accrual rate was 51.5% (33/64) of the patients who matched available trials and 4.9% (33/667) of all new cancer patients. At CP2, 32 (13%) patients matched available trials. The factors associated with the inability to match therapeutic trials with the new patients included: adjuvant treatment status, disease sites, prior treatment requirements, protocol specific tests, protocol specific requirements for correlative studies. Conclusions: Of the 912 new cancer patients treated at 2 community sites affiliated with an NCI CCC, only 10.5% matched available therapeutic trials. Although the enrollment rate into therapeutic trials is high in patients who matched available trials (51.5%), the overall accrual rate of all new cancer patients is 4.9% and consistent with previous studies. Our study highlights the significant mismatch between available trials and clinical populations treated at community sites. We suggest that an improved process to better match patient populations and available trials will improve on clinical trial accruals and efficiencies.
History of The Joint Commission’s Pain Standards
Authors: David W. Baker
Journal: JAMA (2017)

In 2000, as part of a national effort to address the widespread problem of underassessment and undertreatment of pain, The Joint Commission (formerly the Joint Commission on Accreditation of Healthcare Organizations [JCAHO]) introduced standards for organizations to improve care for patients with pain (eAppendix in the Supplement). After initial positive responses and small studies showing the benefits of following the standards, reports emerged about adverse events from overly aggressive treatment of pain. A 2002 report from the Institute for Safe Medication Practices (ISMP) asked, “[I]n our noble efforts to alleviate pain, has safety been compromised?”1 In response, the standards and related materials were changed to address the problems.
Candidate gene analysis of gastrointestinal stromal tumors and paragangliomas in patients with carneys triad.
Authors: E. R. Ball, E. S. Saloustros, P. Xekouki, A. Horvath, G. Assie, S. Yehuda, C. A. Stratakis
Journal: Journal of Clinical Oncology (2011)

e12018 Background: Carneys triad (CT) describes the association of paragangliomas (PGLs) with gastrointestinal stromal tumors (GISTs) and pulmonary chondromas (PCH). CT is unique compared to other multiple neoplasia syndromes in that it is an apparently sporadic condition affecting mainly young females. CT is not always complete, with approximately ¼ of patients having all three components, and ½ having only 2 of the three (PCH and GIST). A similar syndrome (the Carney-Stratakis syndrome) is characterized by the familial association of GIST and PGL and can be inherited as an autosomal-dominant disorder due to mutations in SDHB,-C, and –D. The association of three rare tumors is strongly suggestive of a genetic disorder, yet no gene has been linked to CT. Using a novel CGH method, SOMATICS, chromosome 1p losses were determined to be frequent in both PGLs and GISTs from CT patients. Recent data implicate ARID1A as a tumor-suppressor gene frequently disrupted in ovarian clear-cell and endometrioid carcinomas. Using a candidate gene-based approach, we sequenced tumor suppressor genes in GISTs and PGLs from patients with CT. Methods: Gene candidacy was determined either by genome location (ARID1A 1p35.3), or potentially oncogenic pathway-defects in mitochondrial complex II activity (SDHAF1). Coding regions and exon-intron boundaries for ARID1A and SDHAF1 were PCR-amplified and sequenced using the Sanger method on tumor DNA from 13 patients with CT (7 paragangliomas and 11 GISTs). Results: All DNA specimens were confirmed to be negative for mutations in SDHA, SDHB, SDHC, SDHD, KIT and PDGFRA. Sequencing analysis revealed only polymorphisms, but no somatic mutations in both ARID1A and SDHAF1. Conclusions: Although the loss of chromosome 1p is a frequent feature, the ARID1A tumor suppressor gene that is located in this region, does not seem to harbor sequence alterations. These data indicate that another gene (or genes) is probably responsible for the tumor genesis in patients with CT. Further research using next generation sequencing is ongoing in our institution.
Rate of immunological recovery in children with ALL at the end of intensive therapy, at the completion of therapy and 6 months thereafter
Authors: S. P. Kosmidis, M. Baka, C. Kallergi, D. Doganis, N. Douladiris, D. Bouhoutsou, M. Varvoutsi, A. Pourtsidis, P. S. Papageorgiou, H. V. Kosmidis
Journal: Journal of Clinical Oncology (2005)

8541 Background: Children undergoing therapy for ALL are known to have impaired immune function. Methods: We prospectively evaluated the humoral and cellular immunity in children with ALL at the end of intensive therapy (Evaluation 1 -E1) and values were compared to those at the completion of therapy (E2) and 6 months thereafter (E3). Investigations among others included CBC, lymphocyte subpopulation by flow cytometry (CD3, CD4, CD8, CD16, CD19, CD3 DR), immunoglobulin levels by nephelometry and antibody titers to MMR immunization. Fifty three children with ALL, 35 boys, 18 girls with median age 4 years(1.5–14) treated according to BFM 95 protocol were evaluated. Of the 74 evaluations, 25 were E1, 29 E2 and 20 E3 and data were analyzed with a non parametric Mann Whitney test. Results: Increasing values statistically significant were seen at E1, E2 and E3 for WBC (p=0.000 and p=0.000), absolute neutrophil count (p=0.003 and p=0.039) and absolute lymphocyte count (p=0.016 and p=0.001).Immunoglobulin levels at E1 were low in the majority of children (68% had low IgG and 80% had low IgM) and were increasing at E2 and E3 (median values of parameters studied are shown in the table in mg/dl for immunoglobulins and % for CD’s). Values remained abnormal 6 months after the completion of therapy in 85% for CD4, 45% for CD8,40% for CD19, 30% for CD3, 25% for CD16, 20% for IgG, 15% for CD3DR and 10% for IgA and IgM. Of the 51 children immunized with MMR only 7 had absent IgG antibodies of whom 4 had low IgG levels. Conclusions: Children with leukemia experience severe immunological damage after intensive therapy which is gradually improving overtime although some values remain abnormal 6 months after the completion of therapy. It is worth mentioning that despite impaired immune function serious infections were not documeneted after the first six months of intensive therapy in this on going study. No significant financial relationships to disclose.
Concomitant treatment of patients with relapsed/refractory CLL using a combination of fludarabine and alemtuzumab is highly effective: Final results of a phase-II study
Authors: A. Engert, T. Elter, P. Borchmann, H. Schulz, M. Reiser, S. Trelle, P. Staib, T. Schinkoethe, M. Hallek
Journal: Journal of Clinical Oncology (2005)

6558 Background: Combined immuno-chemotherapy has given superadditive effects in different lymphoma entities, both in preclinical models and in clinical studies. In order to develop a more convenient active regimen for patients with relapsed CLL, we evaluated the combined application of fludarabine and alemtuzumab in a phase-II study. Methods: Fludarabine 30mg/m2 per day iv immediately followed by alemtuzumab 30 mg absolute dose iv was given on days 1 - 3 and repeated on day 29 for up to six cycles. Minimal residual disease (MRD) was measured by 4-color flow cytometry. Results: A total of 37 patients were included in this phase-II study at a median age of 61 years. Pretreatment consisted of fludarabine (23/36), fludarabine + rituximab (10/36), and monoclonal antibodies in 20/36. Thrombocytopenia and neutropenia were the most serious side effects detected in 30% and 26% of all cycles given (WHO III/IV). There were 5 grade III/IV infections, one of which was fatal due to e.coli sepsis in a patient with refractory disease. The overall response rate was 83% with 11 CR and 19 PR. 47% of the patients became MRD negative in peripheral blood or bone marrow. The freedom from treatment failure for responding patients is 12.8 months with the median overall survival for responding patients not reached. Based on these promising results, an ongoing phase-II study evaluates the effectivity of fludarabine, cyclophosphomide and alemtuzumab. In addition, a prospectively randomised phase-III trial has been initiated to confirm the impact of this new combination (FluCam) in CLL patients with first relapse. Conclusions: The concomitant application of fludarabine and alemtuzumab appears as a new promising approach for patients with relapsed CLL. No significant financial relationships to disclose.
The status of oncofertility resources at NCI-designated comprehensive cancer centers.
Authors: M. L. Clayman, M. Harper, G. P. Quinn, S. Shah, J. Reinecke
Journal: Journal of Clinical Oncology (2011)

9123 Background: NCI-designated Comprehensive Cancer Centers (CCCs) have a reputation for providing exemplary patient care. ASCO guidelines suggest quality care includes discussions of and provision of referrals to fertility specialists for patients who may be at risk for sterility. Yet there is evidence that fertility preservation (FP), also known as oncofertility, is not universally offered at CCCs. The goal of this study was to determine what FP resources are available and how well those are integrated into patient care at NCI-designated CCCs. Methods: The director of the Lurie CCC sent a letter by e-mail attachment to leaders at each CCC, including center directors and program leaders in areas such Survivorship. The letter requested a 30 minute telephone interview with a person (or persons) at the CCC who could provide information about the institution’s FP resources. Interviews were conducted using a semi-structured interview guide and responses audio-recorded. Content analysis was used to identify key themes across the centers. Results: Interviews were conducted with leaders at 30 of the 39 CCCs that see adult patients. Of the other sites, 4 did not respond to repeated requests, 3 referred us to clinics for childhood cancer survivors, 1 refused, and 1 could not identify any FP resources. Participants were based primarily in reproductive endocrinology (n=15) and hematology/oncology (n=10). Only 4 sites reported having any institutional guidelines regarding FP, while 20 have some form of educational material for patients. Models of practice varied widely: few sites had formal FP programs, with directors affiliated in reproductive endocrinology, survivorship clinics, and hematology/oncology. Those that reported good coordination among subspecialties used means such as patient navigators or fertility hotlines to ensure timely access to referral. Conclusions: CCCs have variable policies and procedures for providing information about and access to FP resources. CCCs are in a position to set the standard for providing exemplary oncofertility care, but most need to better integrate FP information and referral into their cancer treatment and survivorship models. Currently, few CCCs seem to be following ASCO guidelines.
Cancer of the uterine cervix at the University of Calabar Teaching Hospital, Calabar, Nigeria.
Authors: B. U. Ago, T. U. Agan, E. I. Ekanem
Journal: Journal of Clinical Oncology (2011)

e15518 Background: This study was carried out to highlight the prevalence of cancer of the uterine cervix and shortcoming in the management of cervical cancer in our hospital. There is the need to improve on our personnel training and equipment acquisition. Methods: This was a retrospective study. Case folders of forty-seven patients who were diagnosed with cancer of the cervix were retrieved and reviewed. Information on age, parity, clinical presentation, stages of the disease and management as well as management problems were analyzed. Data were analyzed using tables showing figures and simple percentages and arithmetic mean was used to depict the mean age that patients present with the disease. Results: There were 1,450 gynaecological admissions during the study. Forty patients had histologically confirmed cancer of the cervix. This gave a prevalence of 2.76% of gynaecological admissions in this center. Majority of the women (52.5%) were aged 40-59 years. The youngest patient in the study was aged 30 years. The mean age at diagnosis was 51.5 years. Vaginal bleeding and offensive vaginal discharge was present in 85.5% and 80.0% of patents respectively. The lesions were commonly exophytic/hard, or fungating and friable in 77.5% of cases. 82.5% presented with late stage disease where little or nothing could be done for them. Twelve patients (30.0%) had total abdominal hysterectomy. This was done for stages 1 and II diseases. Two (16.7%) had vault recurrence. Fifty-five percent of the patients had referrals for radiotherapy. Three patients (13.6%) died in the ward after discharge. Conclusions: Cancer of the uterine cervix is still a problem in our setting where uptake of screening methods and the availability of cytopathologists are still dismally low. There is the clear need for training in gynecologic oncology especially in the area of radical surgeries and use of current therapeutic options in the care of these patients.
ERCC1 as a prognostic factor for survival in patients with advanced urothelial cancer treated with platinium-based chemotherapy: A systematic review and meta-analysis.
Authors: Yuksel Urun, Jeffrey J. Leow, Andre Poisl Fay, Laurence Albiges, Toni K. Choueiri, Joaquim Bellmunt
Journal: Journal of Clinical Oncology (2015)

351 Background: Platinium based chemotherapy (CT) is an essential part in the treatment of advanced urothelial cancer (AUC). However, not all patients derive benefit. A body of evidence suggests that excision repair cross-complementation group 1 (ERCC1) expression level may correlate with outcome in platinum treated patients. We thought to perform a systematic review and meta-analysis to better elucidate its role in AUC. Methods: A comprehensive literature review was performed to identify all studies comparing platinum-based regimens according to expression levels of ERCC1 for patients with AUC. The search included the PubMed, Embase, Cochrane Central Register of Controlled Trials databases, and abstracts from the American Society of Clinical Oncology meetings up to June 2014. Pooled analyses were conducted using fixed and random effects models. Results: A total of 554 patients included in eight studies were evaluated. ERCC1 expression was positive in 270 (49%) patients and negative in 284 (51%) patients. The median age of patients was 63 years. The overall survival (OS) was significantly better in patients with negative ERCC1 expression (pooled hazard ratio (HR) 1.90 (95% confidence interval [CI], 0.98–3.67; p=0.006). There was moderate amount of between-study heterogeneity present (I-square 70%). Conclusions: This study's findings support the hypothesis that low ERCC1 expression is associated with benefit from cisplatin-based treatment. The substantial amount of between-study heterogeneity may indicate the need for standardized methods to classify ERCC1 expression level. Prospective studies are necessary to determine the role of ERCC1 levels for treatment selection in patients with AUC.
Renal Function Measures Improve on Lenalidomide and Dexamethasone and Compete with Patient Characteristics to Predict Lenalidomide Dose Density and Hematologic Toxicity: An E4A03 Analysis
Authors: R. Donald Harvey, Susanna Joan Jacobus, S. Vincent Rajkumar, Philip R. Greipp, Sagar Lonial
Journal: Blood (2011)
Effect of genetic counseling on detection of Lynch syndrome (LS) in colorectal cancer (CRC) patients (pts).
Authors: Sigurdis Haraldsdottir, Heather Hampel, Wendy Frankel, Christina Sing-Ying Wu, Xueliang Jeff Pan, Tanios S. Bekaii-Saab, Richard M. Goldberg
Journal: Journal of Clinical Oncology (2014)

419 Background: LS, characterized by germline mutations in MLH1, MSH2, MSH6, or PMS2, leads to defective DNA mismatch repair (dMMR) and causes 2%-3% of CRC cases. Ohio State University (OSU) began immunohistochemistry (IHC) screening on all CRC cases in 2006. In 2006 results were reported in pathology reports without further follow-up. From 2007 to 2010 genetic clinic (GC) counselors contacted pts and recommended further testing. Since 2011, GC counselors met pts at a follow-up appointment. This retrospective study aims to assess if type of follow-up after abnormal IHC, affects rate of conclusive testing. Methods: All CRC pts diagnosed at OSU from 03/06-06/12 had MMR testing per IHC. All pts’ charts were reviewed. Conclusive testing, following the initial MMR IHC, includes either MLH1-hypermethylation testing and/or gene sequencing to identify LS from non-LS pts. Chi-square test was used for categorical parameters and t-test for continuous variables to compare differences between pts with conclusive test vs those without. Results: One-hundred and twenty two tumors of 777 (15.7%) tested had dMMR by IHC. The GC follow-up of abnormal results significantly affected the rate of conclusive testing. The rate of conclusive testing went from 14.3% in 2006 to 38.4% in 2007-2010 and after 2011, 90.5% of the pts had conclusive testing done. Among 51 pts undergoing full testing, 13 pts were diagnosed with LS, 29 pts had MLH1-hypermethylated tumors, and 9 pts were not found to have any mutations on gene sequencing. Conclusions: Conclusive testing rates after abnormal universal screening with IHC improved significantly with GC involvement and was most effective when GC counselors met with the pts during their appointment. [Table: see text]
Pharmacodynamics and pharmacokinetics study of pegylated liposomal doxorubicin combined with cyclophosphamide, vincristine, and prednisolone in patients with peripheral T-cell lymphomas.
Authors: F. Yun
Journal: Journal of Clinical Oncology (2010)

e18548 Background: Peripheral T-cell lymphoma (PTCL) has poor prognosis and there is no standard treatment regimen. Pegylated liposomal doxorubicin (PLD) are capable of improving safety and efficacy compared with conventional chemotherapy. To investigate the pharmacodynamic and pharmacokinetic parameters of PLD combined with cyclophosphamide, vincristine and prednisolone in Chinese patients with PTCL. Methods: Eleven cases with chemonaïve (7 cases) or relapsed(4 cases) patients of PTCL were treated with CCOP regimen(cyclophosphamide 750 mg·m-2 iv d1, vincristine 1.4mg·m-2 iv d1, pegylated liposomal doxorubicin 30mg·m-2 iv d1, prednisolone 60mg·m-2 po d1-5) and repeated every 21 days. Clinical response and toxicity of the regimen were monitored. In addition, the plasma concentration of PLD in different time points were detected before and after treatment, further, the PKS software was used to estimate the pharmacokinetic parameters of PLD. Results: The 11 PTCL patients received 35 cycles treatment. 3 CR, 2 PR, 4 SD, 2 PD, and ORR 45.5%, CR 27.3%. For the 7 chemonaive patients, ORR 71.4% (5/7), CR 42.9% (3/7). The median follow-up time was 10 months (from 2 to 36 months) in the 11 patients, The mPFS and mOS were 8.2 and 13 months, respectively. the main toxicity was myelosuppression, the oral mucositis and hand-foot syndrome seldomly occurred. 9 patients finished plasma sample collection and concentration determination, the PLD plasma concentration was 1.7036-9.2207μ g·mL-1 after administration 0-168h, the pharmacokinetic parameters such as AUC0-∞, CL, t1/2, Vd were 902.015(L·h) - 1, 0.063L·h-1, 68.295h,5.161L, respectively. Conclusions: The CCOP regimen was effective and well tolerated in patients with peripheral T-cell lymphomas. From the result of pharmacokinetic parameters, it suggested that PLD persists in the blood circulation significantly longer. No significant financial relationships to disclose.