tbuckley/cabot-search huggingface dataset:
Pharmacokinetics (pk) and tolerance of infusional vincristine (vcr) for aggressive lymphomas indicate dose reductions for excretory organ dysfunction are not necessary
Authors: D. E. Cole, F. M. Balis, N. Grant, T. White, K. Dunleavy, J. E. Janik, L. Whalen, W. Goodspeed, W. H. Wilson
Journal: Journal of Clinical Oncology (2008)

2550 Background: Hepatic and renal dysfunction routinely results in empirical chemotherapy dose reductions that may compromise efficacy. We compared vcr pk during Dose-Adjusted-EPOCH (96 h infusion of doxorubicin, etoposide, vcr [0.4 mg/m2/d], bolus cytoxan and oral prednisone) for lymphoma in patients (pts) with normal (nl) and abnormal (abn) excretory organ function. Methods: Plasma vcr concentration (conc) was quantified by LC-MS/MS in 25 pts with nl organ function, 10 pts with a median bilirubin (bili) of 2.0 mg/dL (range, 1.2–12), and 5 pts with a median serum creatinine (cr) of 2.5 mg/dL (range, 2.1–19). Vcr dose was empirically reduced to 0.2 or 0.3 mg/m2/d based on severity of organ dysfunction. Vcr clearance (Cl) = infusion rate/94 hr steady-state conc (Css). Results: Median vcr Cl with nl organ function was 252 mL/min/m2 (range, 146–390) and median Css was 1.2 nM (range, 0.77–2.1). With abn bili, median (range) vcr Cl was 206 (171–243, p=0.03, Mann-Whitney U) and Css with a reduced dose in 5/10 pts was 0.86 nM (0.62–1.8, p=0.1). There was no correlation between vcr Cl and bili level in the pts with abn bili. With abn cr, median (range) vcr Cl was 256 (170–325) and Css was 1.2 nM (0.8–1.7). Four of 5 pts with abn bili and 1/2 pts with abn cr who received a reduced dose on cycle 1, were escalated to full dose vcr by cycle 3. A pt with history of renal transplant and cr 19 mg/dL (vcr Cl 309 mL/min/m2) started at full dose, but had vcr dose reductions on cycle 2 (25%) and 3 (50%) and vcr was discontinued at cycle 4 due to neuropathy. Five of 25 pts with nl organ function had dose reductions for neurotoxicity. Conclusions: Although vcr Cl was 18% lower in pts with abn bili (p=0.03), it fell within the range of Cl values for pts with nl organ function, and the severity of vcr toxicity was similar in the nl and abn organ function groups. Vcr Cl was unaffected by renal dysfunction. Vcr dose need not be routinely reduced for elevated bili or cr with CHOP-based regimens. No significant financial relationships to disclose.
Outcomes of patients (pts) with metastatic non-clear-cell renal cell carcinoma (nccRCC) treated with pazopanib.
Authors: Marc Ryan Matrana, Ali Baiomy, Khaled M. Elsayes, Aditya Shetty, Purnima Sravanti Teegavarapu, Lianchun Xiao, Eric Jonasch, Nizar M. Tannir
Journal: Journal of Clinical Oncology (2014)

456 Background: Pazopanib prolongs progression-free survival (PFS) in treatment-naive and cytokine-refractory metastatic clear-cell RCC. Outcomes and safety data with pazopanib in metastatic nccRCC are limited. Methods: We retrospectively reviewed records of metastatic nccRCC pts who received pazopanib in the frontline and salvage settings (11/2009-11/2011). Response was assessed by a blinded radiologist (RECIST v1.1). PFS and overall survival (OS) were estimated by Kaplan-Meier methods. Log rank tests and univariate Cox models were used to evaluate the associations of OS and PFS with pt characteristics. Results: 29 pts were identified (frontline, 9; salvage after PD with other targeted therapies, 20). Seven (24%) had papillary, 4 (14%) chromophobe, 5 (17%) unclassified, and 13 (45%) other subtypes. PFS, OS, and objective response rates (ORR) are shown in the table. Improved OS was associated with prior nephrectomy in frontline pts, and in salvage pts with younger age, non-white race, absence of bone metastases, normal platelet count, higher albumin level, KPS&gt;80, and MSKCC good-risk disease. There were no significant associations between frontline pt characteristics and PFS, but improved PFS was associated with normal platelet count, KPS&gt;80, lower LDH, and higher albumin level in the salvage setting. Common adverse events (AEs): fatigue (31%), elevated transaminases (24%), diarrhea (21%), nausea/vomiting (17%), anorexia (17%), hypothyroidism (7%), and hypertension exacerbation (7%); 83% of AEs were grade 1/2. Six (21%) discontinued therapy due to AEs. There were no treatment-related deaths. Conclusions: Pazopanib demonstrated efficacy in pts with metastatic nccRCC. Toxicity was mild/moderate and manageable. [Table: see text]
Are patients with cancer concerned about burdening their families?
Authors: Sukhi Kaur, Kelly Choi, Ruth Pe Benito, Victoria DeVincenzo, Emily Sassano, Brooke Gruman, Katherine DeMarco, Jose Contreras, Kathryn Tanenbaum, Jennifer Covington, Dhakshila Paramanathan, Stuart L. Goldberg
Journal: Journal of Clinical Oncology (2016)

86 Background: A diagnosis of advanced cancer frequently thrusts family members into the role of caregiver. Although caregiver burdens have been well documented, less is known about the level of concern borne by the patient (pt) with cancer in placing a family member in this role, known as self-perceived burden (SPB). Methods: As part of the larger “Living with Cancer” project we prospectively surveyed 1307 pts with advanced malignancies receiving treatment with non-curative intent at 17 New Jersey cancer programs within the Regional Cancer Care Associates network between Sept 2015 and Apr 2016. Pts were asked one question about SPB on family members (5-level Likert scale). Results: Pts felt that “Living with Cancer burdens my family” all day every day 68 pts (5%), part of each day 109 pts (8%), most days 136 pts (10%), occasionally 571 pts (44%) or not at all 423 pts (32%). Twenty-four percent of responses were flagged as concerned (rated most days or greater by 313 pts). In a logistic regression model, SPB was correlated with marital status (married and divorced more concerned than single) and younger age (both p &lt; 0.05). Patients living in lower median income neighborhoods also appeared to have a higher frequency of concern (p &lt; 0.1) Factors not correlating with the level of SPB included gender, race, solid vs liquid tumor type, and length of cancer diagnosis. SPB was also not influenced by DNR status, having developed a Living Will, or documentation of power of attorney. Distance from the pt’s home to the cancer center was not associated with SPB on the caregiver. For comparison, on the same LWC project 38% of pts with advanced cancer were concerned about the financial toxicity of their care and 33% were concerned about pain (both p &lt; 0.01 compared to SPB). Conclusions: Self-perceived burden on a caregiver was identified in 24% of pts with advanced cancer, less than those concerned about financial toxicity or pain, in this NJ series. Divorced/married pts and younger pts with cancer are more likely to express concern. Developing an EOLC plan (DNR/Living will/POA) does not appear to influence SPB concerns.
Involving clinic patients in systematic symptom reporting to improve cancer care: Exploring prevalence of sleep disturbances (SD) and fatigue (FAT).
Authors: Margaret Irwin, Catherine Brown, Ashlee Vennettilli, Lawson Eng, Aein Zarrin, Aditi Dobriyal, Linda Chen, Maryam Mirshams, Deval Patel, Henrique Hon, Vivien Pat, Anthea Ho, Hannah Solomon, Kyoko Tiessen, Henry Thai, Valerie Ho, Mary Mahler, Wei Xu, Geoffrey Liu, Doris Howell
Journal: Journal of Clinical Oncology (2014)

68 Background: SD and FAT occur in 30-50% of cancer patients. Patient-reported outcome measure surveys are avenues through which healthcare providers (HCP) can receive symptom-related clinically relevant information directly from patients, and engage them in their own care plan. By asking patients to report symptoms rapidly through tablet/computer-based technology, HCPs can involve patients in the delivery of care. Methods: In a pilot study evaluating utility of systematic symptom reporting, 336 adult cancer patients across all stages and disease sites who were attending outpatient cancer clinics at Princess Margaret Cancer Centre (PMCC) (Toronto, Canada) completed electronic tablet-administered secure surveys on SD (Insomnia Severity Index) and FAT patterns (FACT-fatigue). These tools measured both symptom severity and interference with function. Results: With a median age of 59 (19-91) years, 55% female, across a broad distribution of cancer sites, 56% of our sample reported moderate to very severe (MTVS) SD over the last 7 days: 31% had MTVS difficulty falling asleep; 43% had MTVS difficulties staying asleep; 36% had MTVS problems waking up too early. While 62% who had MTVS SD were not distressed by their SD, 95% who were distressed by their SD met the criteria of MTVS SD. 78% of patients had any level of FAT over the last 7 days, with 40% reporting MTVS FAT. While 40% who had MTVS FAT were still able to perform their usual activities, 67% of patients who were not able to do their usual activities had MTVS FAT. Conclusions: Across all stages and disease sites of cancer patients at PMCC, the prevalence of SD and FAT was both high. Severity and interference with function by FAT and SD were often distinct and non-overlapping. Involving patients in the systematic evaluation of symptoms, particularly using newer tablet-based technology within the clinic, was feasible. Through the use of patient reported electronic applications, patients could easily and systemically report their symptoms in real-time. FAT management has always been a high priority at our institution. However, based on our results, a cancer center-wide self-management plan is being considered for SD.
Pathoepidemiological patterns of contralateral breast cancers in Black and White women.
Authors: H. Nsouli-Maktabi, A. M. Schwartz, S. D. Cleary, N. Younes, H. A. Young, D. E. Henson
Journal: Journal of Clinical Oncology (2011)

10628 Background: Women with one primary breast cancer are at greater risk for developing a second cancer in the contralateral breast, despite the protective effect of Tamoxifen treatment. Breast cancer incidence exhibits a Black-to-White incidence crossover at age 40. The purpose of this study was to investigate whether the patho-epidemiological patterns of second primary contralateral breast cancers in Black and White women are similar to those of the first primary tumors according to age at diagnosis of the first primary breast cancer. Methods: The Surveillance, Epidemiology, and End Results’ (SEER) Registry 9 database was used to follow a total of 455,551 women, 415,664 White (91.24%) and 39,887 Black (8.76%) female breast cancer survivors, diagnosed at age 19 or older, for the occurrence of a second primary contralateral breast cancer between 1973 and 2007. Black and White women with a first primary in-situ or invasive breast cancer and a second primary contralateral breast cancer were analyzed by age at diagnosis, histologic tumor type, histological grade, tumor size, tumor markers, and number of positive lymph nodes. The cumulative incidence of a second contralateral breast cancer, which accounts for the competing risks of death and second non-breast cancers, was also explored among Black and White breast cancer survivors. Results: Second contralateral breast cancers in Black women were characterized by an earlier onset (Blacks= 59 yrs; Whites=67 yrs), higher incidence (Blacks= 8. 7%, 95% CI = 8.3– 9.1; Whites= 7.7%, 95% CI=7.6 - 7.8) and more aggressive clinical presentation than in Whites. In contrast to first primary breast cancers, second primary breast cancers are more common in Black than in White women of all ages. Conclusions: Our results point to the possible bilaterality of many cases of breast cancer, and to a possible shared etiology between cancers in the two contralateral breasts.
Treatment outcomes and patterns of failure following autologous stem cell transplant for relapsed/refractory Hodgkin’s disease
Authors: N. Mohideen, U. Khan, M. Parthasarathy, A. Toor, T. Rodriguez, J. Klein, P. Stiff
Journal: Journal of Clinical Oncology (2005)

6671 Background: To evaluate all patients with relapsed or refractory HD who underwent autologous transplants with either chemotherapy or total body irradiation (TBI) based preparative regimens to determine their outcomes and analyze their pattern of failure. Methods: Retrospective chart review of 63 patients with relapsed/refractory HD who were treated with high dose therapy at Loyola University Medical Center over the past 7 years. Overall Survival (OS) and Progression-Free Survival (PFS) were analyzed with the Kaplan Meier method and the log rank test was used to test for differences. Patient, disease, and treatment factors were analyzed for their influence on relapse and survival. Results: 63 patients underwent transplant from February 1997 to February 2004. median age was 35 years, median follow-up was 27 months. The preparative regimens were TBI-based in 36 (57%) patients and chemotherapy-based in 27 (43%). Of the patients with chemo sensitive disease, only 3 of 27 (11%) who achieved complete remission (CR) prior to transplant failed compared to 4/12 (33%) who achieved a PR and 7 of 16 who had a minor response and 6/8 who had progressive disease (p <0.05). Of the 20 who relapsed after their transplant, 13 (65%) relapsed in the same site as their disease at relapse, 4 relapsed in the same and new sites of disease and 2 relapsed in new sites. The 5-year OS and PFS for the whole group of patients are 60% and 65%. The 5-year PFS for the TBI group is 69% vs. 57% for the non-TBI group (p=0.23). The 5-year OS for the patients who relapsed after autologous transplant was 25%, 5 of those who relapsed were salvaged with either an allogeneic transplant (4 patients) or radiotherapy (1 patient). 3 additional patients had therapy-related myelodysplastic syndrome or leukemia and two of them were salvaged with an allograft. Conclusions: The PFS at 5-years for TBI-based transplants appears to be better than non TBI regimens (69 vs 57%) although not statistically significant. Those transplanted in CR have the best outcome, thus attention to optimizing tumor cytoreduction prior to transplant should be a priority. A significant minority of patients who relapse after an autograft can be long-term survivors after an allograft. No significant financial relationships to disclose.
Retrospective review of colorectal cancer specimens in individuals younger than age 50 for microsatellite instability testing and DNA mismatch repair enzyme expression.
Authors: N. Durie, H. Staszewski, T. Palaia, L. Ragolia, W. Nugent
Journal: Journal of Clinical Oncology (2011)

392 Background: Data from studies performed at tertiary referral centers suggest that the yield of patients with the underlying defect in hereditary non-polyposis colon cancer (HNPCC) could be improved by screening every colon cancer for the phenotypic expression of the MMR defect by immunohistochemistry (IHC) and/or an assay for microsatellite instability (MSI). We propose to determine the incidence of microsatellite unstable colon cancers and the incidence of absence of expression of DNA MMR enzymes in de-identified colorectal cancer specimens from patients under the age of 50 who have presented to Winthrop University Hospital over the past ten years. This incidence will be compared with those suggested by recent large retrospective studies in tertiary care centers. Methods: Immunoperoxidase staining for MLH1, MSH2, MSH6 and PMS2 were performed on formalin-fixed tissue. MSI assays were performed on microdissected DNA from paraffin-embedded tissue blocks. All cases were tested with five mononucleotide repeat markers (BAT-25, BAT-26, NR-21, NR-24 and MONO-27) and two pentanucleotide repeat markers (Penta C and Penta D). Tumor samples in which two or more altered monoclonal repeat markers were found out of five were classified as MSI-H. Results: Screening for expression of DNA mismatch repair enzymes and MSI in an enriched selected (by age &lt;50) population of colorectal cancer patients resulted in detection of 7/51 (14%) specimens that were MSI-H and 7/61 (12%) that were “positive” for lack of expression of at least one DNA mismatch repair enzyme. Conclusions: Our results are similar to those reported in the literature in unselected series of patients with colorectal cancer. IHC staining or MSI analysis alone may be insufficient in selecting those colorectal cancer patients that should be referred for genetic testing for HNPCC. However, screening of an unselected population with both these modalities should have a low but clinically significant yield. Since other research have shown that traditional criteria such as the Bethesda guidelines are inadequate, we support the use of both measures prospectively in all colorectal cancer patients. No significant financial relationships to disclose.
Matching physician resources with demand in a cancer hospital emergency center.
Authors: John Allen Terrell, Knox H. Todd, Laura Burke
Journal: Journal of Clinical Oncology (2012)

276 Background: In early 2010 the Emergency Center (EC) at MD Anderson Cancer Center identified a need to adjust the physician staffing to better meet the demand of increasing patient work-load and improve physician satisfaction. There was also a strong interest in learning more about variations in work methods and how physician time was spent in the EC. Methods: The EC partnered with the Office of Performance Improvement (OPI) to perform a work sampling study and analyze how physicians’ time is spent by physician, time of day, and day of week. Also needed to properly match resources to demand was how the patient demand varied with time of day and day of week. Before the study was performed the tasks and categories of interest were established and training as well as a measurement study to ensure consistency from one data collector to another. A sampling plan and method were then developed to identify and record the frequency of tasks performed to be studied by shift, day, and physician. Patient data was collected through the internal computerized whiteboard to identify patient arrivals and occupancy. Results: The results showed the variation in tasks performed was most highly attributable to the individual physician rather than time of day and day of week. Percentages of the shifts were calculated, summarized, and presented to the EC leadership. This data was then combined with the patient volumes data in an interactive spreadsheet to simulate different scheduling patterns and provide recommendations to best match resources with workload. Conclusions: The project provided a valuable resource to contribute to identifying the best scheduling pattern for the EC including start times and shift length. The results have been further used to strive towards inter-physician consistency over the past two years and have led to additional studies and opportunities for improvement. By using a data based methods, even for qualitative studies, important process understanding and opportunities are available which can help break through barriers and improve data based decision making in health care.
Stereotactic volumetric resection, intracavitary carmustine wafers, and radiation therapy for brain metastases: The Moffitt Cancer Center experience.
Authors: S. Brem, R. Sampath, D. Yu, A. Staller, M. Obadia, M. G. Ewend
Journal: Journal of Clinical Oncology (2011)

2077 Background: NCCN guidelines for brain metastases (BM) endorse surgery and whole brain radiation therapy (WBRT). Early clinical data suggest that addition of intracavitary carmustine wafers yields superior local control. Methods: A retrospective analysis of 49 consecutive BM patients undergoing MR-guided, gross total resection with chemowafers was compared to a similar cohort of 174 BM patients treated without wafers during a 6-year period at Moffitt Cancer Center. Results: Of the 49 patients, 4 had two sites of resection/wafer placement; 45 had a single surgical bed. The median age was 59 years; 49% had lung cancer, 24% melanoma, 26% were other histologies. Thirty-five patients had newly diagnosed BM; 14 were recurrent tumors. Fifteen patients were RPA class I, 27 class II, and 7 class III. The maximal resection bed diameter ranged from 1.0 to 7.2 cm (mean, 3.1). The median post-operative stay was one day. There were no infections. The KPS was stable or improved in 90% of the patients at 3 months, and 73% at 6 months (Table). The median survival for newly diagnosed patients was 9 months, and for those with recurrences, 6 months. For newly diagnosed metastases, treated with surgery + wafers + WBRT, only 1/35 (3%) patients had local recurrence. In 14 patients with recurrent metastases, there were no recurrences in those treated using surgery + wafer. By contrast, in tumor resected without wafers, local recurrence was 13% (17/130) and in those resected at recurrence, further recurrence occurred in 40% (6/15). The wafers were well-tolerated in tumors located within or near the primary motor cortex. Conclusions: Intracavitary carmustine wafers can be used in the treatment of upfront and recurrent brain metastases with excellent local control, minimal morbidity, and good neurological outcomes. Chemowafers can be useful near eloquent brain where the tumor-brain interface limits the surgical resection. KPS change from day of surgery Stable Improved (neurological) Declined (systemic) 3 months 59% 31% 10% 6 months 46% 27% 27%
Refining the paediatric Ebola case definition: a study of children in Sierra Leone with suspected Ebola virus disease
Authors: Felicity Fitzgerald, Kevin Wing, Asad Naveed, Musa Gbessay, J C G Ross, Francesco Checchi, Daniel Youkee, Mohammed Boie Jalloh, David Baion, Ayeshatu Mustapha, Hawanatu Jah, Sandra Lako, Shefali Oza, Sabah Boufkhed, Reynold Feury, Julia Bielicki, Elizabeth Williamson, Diana M Gibb, Nigel Klein, Foday Sahr, Shunmay Yeung
Journal: The Lancet (2017)