tbuckley/cabot-search huggingface dataset:
Physical function and quality of life in frail and/or elderly metastatic colorectal cancer patients treated with bevacizumab and capecitabine: An exploratory analysis.
Authors: Peter Richard Ward, Andre K. D. Liem, He-jing Wang, Ravi Patel, Eddie Hong-Lung Hu, Nerses Simon Tchekmedyian, Zev A. Wainberg, J. Randolph Hecht, Arash Naeim
Journal: Journal of Clinical Oncology (2012)

627 Background: Optimal treatment strategies in frail and/or elderly patients with metastatic colorectal cancer have not been well defined. Although the safety and efficacy of bevacizumab and capecitabine in this population has been reported, the impact on functional measures and quality of life has not been well described. In a prospective, phase II study of elderly metastatic colorectal patients with ECOG performance status (PS) 1 or 2 treated with first-line bevacizumab and capecitabine, we collected data on geriatric functional status and quality of life. The primary aim of this analysis was to explore the differences in geriatric health measures between patients with ECOG status 1 and 2. Methods: Functional status was measured by patient-reported limitations in ADLs and IADLs and ECOG PS was assessed. A “Get up and Go” test, hearing test, and 3-item recall exam was also performed. Quality of life (QoL) was assessed by means of the FACT-C questionnaire and patient-rated health status was measured by the EQ-5D questionnaire. The prognostic impact of baseline characteristics on survival was studied using univariate Cox-regression analysis. Results: The majority (62%) of the 45 participants treated were ECOG 2. This group had more limitations in IADLs, lower baseline QoL, and a lower patient-rated health score. For all participants, QoL significantly improved from baseline to the start of cycle 2 (FACT-C: 99.9 vs. 105.4, p=0.01) and did not deteriorate when baseline scores were compared to when participants went off study. (FACT-C: 99.9 vs. 98.6, p=0.59). In the Cox-regression analysis, the participant’s ability to perform the “Get up and Go” test was the only baseline characteristic that was prognostic for improved survival (HR = 0.31, p = 0.01). Conclusions: Our analysis shows that in this study of frail and/or elderly patients with metastatic colorectal cancer treated with bevacizumab and capecitabine, there is a significant amount of heterogeneity between the ECOG 1 and 2 groups in both functional measures and quality of life. We also showed that the “Get up and Go” test may be a useful prognostic indicator for survival in this population.
Evidence for scaling up HIV treatment in sub-Saharan Africa: A call for incorporating health system constraints
Authors: Evelinn Mikkelsen, Jan A. C. Hontelez, Maarten P. M. Jansen, Till Bärnighausen, Katharina Hauck, Kjell A. Johansson, Gesine Meyer-Rath, Mead Over, Sake J. de Vlas, Gert J. van der Wilt, Noor Tromp, Leon Bijlmakers, Rob M. P. M. Baltussen
Journal: PLoS Medicine (2017)

The ever-growing HIV treatment programs in sub-Saharan Africa (SSA) present local policy makers with complex decision dilemmas, as international guidelines emphasize the need for expanded access to antiretroviral therapy (ART), yet funding has flatlined.• We argue that the current evidence base for prioritizing ART scale-up strategies results in recommendations that are theoretically optimal but practically infeasible to implement.• Cost-effectiveness analyses (CEAs) of scaling up ART in SSA should be made more responsive to the needs of policy makers by taking into account the local health system.• We provide suggestions for a better integration of health system constraints into CEA by integrating supply-and demand-side constraints in mathematical models and improving the dialogue between researchers and policy makers.
Prevalence of vitamin D deficiency among palliative care cancer outpatients: Prospective analysis of 347 cases of single individual medical practice.
Authors: Janusz Wojtacki, Agnieszka Labuc, Piotr Banach
Journal: Journal of Clinical Oncology (2015)

204 Background: In spite of the fact that cancer patients under palliative care represent the group of high risk for vitamin D deficiency (e.g. changed nutritional patterns and UV exposure), data reporting vitamin D levels in palliative care setting are rather scarce. Methods: Between Jan-02/2014 and June-20/2015 circulating 25-hydroxyvitamin-D (25-OH-D) levels were analyzed in 76% consecutive patients’ samples of a single individual cancer practice located in Gdansk, Poland. Three hundred forty seven patients (female: 72.5%, median age 64, range: 23-89 years; breast cancer: 57.8%, colon cancer 27.7%) were admitted for palliative care due to: disseminated cancer (18%), side effects of anticancer therapy (56.6%) or symptom control in non-cancer diseases (24.5%). Results of fast 25-OH-D blood tests were correlated with selected clinical factors. Results: The median 25-OH-D level of all our cohort patients was 15.85 ng/mL (range: 0.40 – 62.00 ng/mL); 65.0% of subjects were vitamin D deficient (25-OH-D &lt; 20 ng/mL) and 23.5% insufficient (20-30 ng/mL); only 3.30% patients were taking vitamin D supplements before they entered the study. The univariate analysis identified the following risk factors for inadequate 25-OH-D levels: active cancer disease (median 25-OH-D: 12.50 ng/mL versus 17.86 ng/mL in patients without evidence of disease, p &lt; 0.001) and current glucocorticoids use (at least 14 days within the last month: 11.58 ng/mL versus 17.12 ng/mL in glucocorticoids nonusers; p &lt; 0.01). Age, gender, body mass index values, primary cancer location, dominant metastatic site and higher antibiotics use did not influence 25-OH-D levels. Conclusions: 1) Low (deficient or insufficient) 25-OH-D serum levels were highly prevalent in palliative cancer care outpatients, mostly in those with clinically active disease and using glucocorticoids; 2) the study will continue to address the correlation between 25-OH-D concentrations and symptom burden as well as the potential feasibility of vitamin D supplementation to improve symptoms management of patients in palliative care setting.
Phase I study of weekly docetaxel (T), cisplatin (P) with daily celecoxib (C) and concurrent radiotherapy (RT) for patients with locally advanced head and neck cancer (HNC)
Authors: R. S. Axelrod, M. Machtay, P. R. Anne, A. Dicker, K. Sidhu, M. Jacobs, M. Rosen, W. Keane
Journal: Journal of Clinical Oncology (2005)

5598 Background: Substantial locoregional recurrence rates and metastatic disease shorten survival for patients (pts) with locally advanced HNC despite advances in concomitant chemotherapy and RT. Cox 2 inhibitors are over-expressed in HNC and show preclinical benefit when combined with RT. We explored the use of a cox 2 inhibitor, celecoxib, in combination with weekly chemotherapy and RT in a phase I study. Methods: Eligibility: Stage III, IV squamous cell cancer of oral cavity, oropharynx, hypopharynx, larynx; PS 0,1,2; adequate hepatic, hematologic and renal function; no prior radiotherapy/chemotherapy for this site. Pts received: weekly T 12.5/C20, iv per M2 day 1 x 6, RT single fraction d 1–5 x 7 wks or to total standard dose (70Gy) and celecoxib 400 mg BID po or per feeding tube for duration of RT. Feeding tubes were placed prophylactically. Pts: Age: 36–69, median 52; 3 females, 4 males. Sites: tonsil 4, base of tongue 2, supraglottic larynx 1. Results: The first cohort was expanded to 7 since one pt did not complete P/C past week 2 and was inevaluable for toxicity. Five pts received 6 cycles of T, P; one received 5. Four patients completed celecoxib without interruption, one received 21 d, one 36 days (of 49+). Pts completed RT in median 52 d (49–67). Toxicity during treatment (at time of analysis): Grade (gr) 4: 0/7; Gr3: mucositis 6/7; ANC, 1/7; nausea, vomiting 1/7; dehydration 6/7; skin 4/7; diarrhea 1/7. There was one thrombotic event related to indwelling venous catheter. One pt had 2 wk delay in therapy for comorbid infectious colitis. Complete response was achieved in 5/5; 2 were too early to evaluate. Conclusions: Combination of cox 2 inhibitor C with concurrent RT and weekly T, P was feasible and did not appear to influence expected toxicity in this early phase I study. Supported by Aventis. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Aventis
Symptom burden and distress in patients with cancer in Africa.
Authors: John K. Weru
Journal: Journal of Clinical Oncology (2016)

255 Background: Cancer has become a significant public health problem in Africa but still most diagnoses are made late, Sitas et al (2006). The need for palliative care is significant due to the late contact with health care providers and the many symptoms they present with. No study has been undertaken to assess symptomatology for these patients in Africa. Objective: To study the prevalence of symptoms in patients with cancer in an African setting. Methods: Symptom studies from records of patients with cancer referred to the Palliative Care Services at the Aga Khan University Hospital, Nairobi in 6 months. Symptoms charted on Edmonton Symptom Assessment Scale. Results: 42 patients were referred to the service in this period. All the patients reported &gt; 3 symptoms which cut across the physical, social, psychological and spiritual concerns. The most common symptoms were pain in the physical dimension (90%) as reported by the patient. Fatigue was reported by (93%).Family wellbeing was the main worry in psychological dimension (95%). 94 % reported social disconnect due to the diagnosis, job losses and huge cost of health care. 96% suffered from the existential question of why me and worry about the future. Conclusions: Cancer has become a major burden to patients, families, societies and nations in Africa. Patients suffering from this illness experience a myriad of symptoms which require holistic approach to care. Social wellbeing remains a major concern for patients with cancer in Africa.
Randomized comparison of ibrutinib versus ofatumumab in relapsed or refractory (R/R) chronic lymphocytic leukemia/small lymphocytic lymphoma: Results from the phase III RESONATE trial.
Authors: John C. Byrd, Jennifer R. Brown, Susan Mary O'Brien, Jacqueline Claudia Barrientos, Neil E. Kay, Nishitha M. Reddy, Steven E. Coutre, Constantine Tam, Stephen P. Mulligan, Ulrich Jäger, Steve Devereux, Paul M. Barr, Richard R. Furman, Thomas J. Kipps, Florence Cymbalista, Maria Fardis, Jesse S. McGreivy, Fong Clow, Danelle Frances James, Peter Hillmen
Journal: Journal of Clinical Oncology (2014)

LBA7008 Background: Treatment options for CLL/ SLL patients (pts) who fail chemoimmunotherapy are limited. We report interim results from a phase III randomized study of ibrutinib (ibr), a first in class covalent BTK inhibitor, vs ofatumumab (ofa) in R/R CLL/SLL. The Data Monitoring Committee recommended this analysis be considered final, based on meeting the primary and a key secondary endpoint. Methods: R/R CLL/SLL pts who failed ≥1 therapy received 420 mg oral ibr daily until progression or IV ofa 300/2000mg for 12 doses. Primary endpoint was progression-free survival (PFS) assessed by an independent review committee (IRC). Secondary endpoints included overall survival (OS), IRC assessed overall response rate (ORR) and safety. Results: Of 391 pts enrolled (median age 67 years; 40% ≥70 years; 57% Rai stage III/IV disease; 30% del 17p), 195 were randomized to ibr and 196 to ofa. Ibr pts had median 3 prior therapies vs 2 for ofa. Median follow-up was 9.4 months (m). Ibr significantly lengthened PFS (median not reached vs 8.1 m; HR 0.215, CI 0.146–0.317, p&lt;0.0001; 78.5% risk reduction), and significantly improved OS (median not reached; HR 0.434, CI 0.238–0.789, p=0.0049) compared with ofa. ORR was 42.6 vs 4.1% (p&lt;0.0001) and ORR+PR with lymphocytosis was 62.6 vs 4.1% for ibr vs ofa. Similar effects were seen in del17p and purine analog refractory subsets. In each arm 2 pts had confirmed Richter’s transformation. Most frequent adverse events (AE) for ibr vs ofa were diarrhea (47.7 vs 17.8%) fatigue (27.7 vs 29.8%), and nausea (26.2 vs 18.3%). Atrial fibrillation was more frequent with ibr (5.1 vs 0.5%). Major hemorrhages were reported in 1.0 vs 1.6% for ibr vs ofa. Drug discontinuation due to AE was 4.1 vs 3.6% for ibr vs ofa. 86% of ibr pts were continuing treatment. 57 pts randomized to ofa with confirmed PD had initiated ibr at cross-over. Conclusions: Compared with ofa, ibr significantly improved PFS, OS and ORR in pts with R/R CLL/SLL. The safety profile was comparable with that previously reported (Byrd NEJM 2013). These results support ibr as a beneficial therapy for R/R CLL patients irrespective of del 17p or purine analog refractory disease. Clinical trial information: NCT01578707.
Tools to accurately identify veterans who undergo molecular diagnostic testing.
Authors: Michael J. Kelley, Julie Ann Lynch
Journal: Journal of Clinical Oncology (2013)

201 Background: Yearly, 52,000 veterans are diagnosed with cancer. Minorities represent 18.5% (9,651) of these patients. The rapid and explosive growth of molecular diagnostics (MDx) has created challenges for large healthcare systems such as the Veterans Health Administration (VA) to integrate genomic data into the EMR. Yet, this is an important component of high quality cancer care. In 2011, the VA cancer registry (VACCR) began reporting molecular data. This presentation will describe one project to improve integration of genomics into the EMR and the VACCR. Methods: Using ICD diagnosis codes, we identified veterans diagnosed in 2011 with brain, breast, colon, gastrointestinal stromal, lung, and melanoma cancers. Administrative data was obtained to identify MDx testing. These data were then compared to random chart audits. Significant discrepancies between these sources of data prompted collaboration with national and proprietary reference labs (ARUP, LabCorp, Quest, Genomic Health) to obtain the volume of testing by each VAMC. These data were used to conduct targeted chart reviews to identify the location, processes of care, free and structured text information. These data informed the development of natural language processing (NLP) tools to automatically identify patients that underwent testing. Results: Laboratories had the most accurate source of data. Data from ARUP, Quest, and LabCorp identified a significantly higher volume of testing than reported by administrative data. Applying NLP tools to patients diagnosed with breast cancer identified 44 of the 116 tests ordered for the 21-gene risk score tests. Conclusions: Decision support systems are needed to link tumor SNOMED code to diagnostic testing. Until systems are developed, collaborations with reference labs may be an effective method for identifying molecular data. NLP tools may also serve as an adjunct method for capturing MDx tests ordered from smaller labs.
Lymphopenia and breast cancer subtypes as prognostic factors in patients with locally advanced breast cancer.
Authors: A. R. Capellino, C. R. Desposorio, F. Hurtado de Mendoza, S. G. Falcon, B. E. Beltran, R. Lujan, D. Morales, J. J. Castillo
Journal: Journal of Clinical Oncology (2011)

e21100 Background: Lymphopenia has been shown to be an important prognostic factor for survival in patients with lymphomas and solid tumors. The aim of this study was to evaluate if lymphopenia is a prognostic factor for survival in patients with locally advanced breast cancer after relapse or progression of disease. Methods: We retrospectively evaluated 163 consecutive locally advanced breast cancers patients who received preoperative treatment from January 2003 to December 2005 in the pre trastuzumab era. We classified them according to subtypes: Luminal A, Luminal B, HER2 and Triple Negative (TN). Lymphopenia at the time of relapse/progression was defined as an absolute lymphocyte count (ALC) < 1000/mm3. Kaplan-Meier, log-rank and Cox regression analysis were used to look for prognostic factors. Results: 101 (62%) patients were Luminal A, 35 (21%) were TN, 18 (11%) were Luminal B and 9 (6%) were HER-2. With a mean follow-up of 77.8 months, 83 patients (50.9%) relapsed or progressed during treatment with a median survival after relapse/progression of 22.6 months. 29 (34.9%) patients had lymphopenia with a median survival of 7.3 months, significantly lower than for those without lymphopenia (Not reached; p<0.0001). Median survival after relapse/progression was also different between subtypes, being significantly lower for TN patients with 10.6 months, compared to Luminal A with 44.7 months (p=0.025). Other variables such as age, histological grade, HER-2 status, ER status and visceral metastasis at the time of the occurrence of relapse/progression, did not influence survival. In the multivariate Cox regression analysis, lymphopenia (RR=3.6; 95% CI, 1.80-7.02; p<0.0001) and being a subtype other than Luminal A (RR=2.5; 95% CI, 1.28-5.07; p=0.008) were independent prognostic factors of survival. Conclusions: Lymphopenia is a prognostic factor of survival in patients with locally advanced breast cancer at the time of relapse or progression. Lymphopenia was a stronger prognostic factor than the different breast cancer subtypes, which could mean that the host immune response play an important role regardless of tumor biology. Studies with larger numbers of patients are needed to validate these results.
Clinical activity and safety of antiprogrammed death-1 (PD-1) (BMS-936558/MDX-1106/ONO-4538) in patients (pts) with previously treated, metastatic renal cell carcinoma (mRCC): An updated analysis.
Authors: David F. McDermott, Charles G. Drake, Mario Sznol, Toni K. Choueiri, John D. Powderly, David C. Smith, Jon M. Wigginton, Georgia Kollia, Ashok Kumar Gupta, Michael B. Atkins
Journal: Journal of Clinical Oncology (2013)

351 Background: BMS-936558 is a fully human monoclonal antibody that blocks the PD-1 coinhibitory receptor expressed by activated T cells. In the initial portion of a phase I study (CA209-003), BMS-936558 showed promising activity in pts with various solid tumors, including mRCC. Accrual was expanded to better characterize antitumor, safety, and dose effects. Methods: Pts with RCC were treated with BMS-936558 IV q2wk at 10 mg/kg initially, followed by additional pts at 1 mg/kg. Pts received up to 12 cycles (4 doses/cycle) of treatment or until unacceptable toxicity, confirmed progressive disease, or complete response (CR). Clinical activity was assessed by RECIST v1.0. Results: As of July 3, 2012, 34 mRCC pts had been treated at 1 mg/kg (n=18) or 10 mg/kg (n=16). ECOG performance status was 0 in 13 pts and 1 in 21 pts. More than 40% of study patients received ≥3 prior therapies, &gt;70% received prior antiangiogenic therapy, and &gt;50% received prior immunotherapy. Sites of metastatic disease included lung (n=30), lymph node (n=28), bone (n=10), and liver (n=9). The incidence of grade 3-4 related adverse events was 21% and included hypophosphatemia (6%) and respiratory disorders (6%); there were no drug-related deaths among mRCC pts. Ongoing durable clinical responses were observed at both 1 and 10 mg/kg doses (Table) with some continuing off treatment. Three pts demonstrated nonconventional response patterns and were not categorized as responders by conventional RECIST. Current median duration of response was 12.9 months for both 1 and 10 mg/kg doses. Conclusions: BMS-936558 is tolerable and exhibits ongoing durable clinical activity in pts with previously treated mRCC. Clinical trial information: NCT00730639. [Table: see text]
Risk group stratification in patients with micropapillary bladder cancer treated with radical cystectomy and/or neoadjuvant chemotherapy.
Authors: Stephen Bentley Williams, Mario Fernandez, Daniel Levi Willis, Rebecca Slack, Arlene O. Siefker-Radtke, Neema Navai, Rian J. Dickstein, Charles Guo, Bogdan Czerniak, David James McConkey, Sahil Parikh, Louis L. Pisters, Jay Bakul Shah, H. Barton Grossman, Colin P. N. Dinney, Ashish M. Kamat
Journal: Journal of Clinical Oncology (2015)

302 Background: Micropapillary bladder cancer (MPBC) is an aggressive variant of urothelial carcinoma. We have previously published clinical risk stratification groups for patients with conventional urothelial carcinoma and sought to identify if these were valid in patients with this variant histology. Methods: An IRB approved review of 1910 patients in our radical cystectomy database revealed 106 patients with preoperative diagnosis of ≤cT4aN0M0 MPBC between December 1992 and January 2012 who underwent upfront radical cystectomy (RC, n = 74) or neoadjuvant chemotherapy (NAC) followed by RC (n = 32). To determine whether patients with MPBC can be risk stratified using traditional risk factors, a recursive partitioning analysis (RPA) was performed. Results: In multivariate analyses, hydronephrosis (HR=3.1; p=0.01), and extent of MPBC at transurethral resection (TUR) (HR=1.9; p=0.04) were associated with shortened OS. In the reduced model, clinical stage also achieved significance (HR=2.8; p=0.03). Results were similar for DSS: hydronephrosis (HR=2.4, p=0.03), extent of MPBC (HR=2.1, p=0.03) and clinical stage (HR=4.7, p=0.02). Using the RPA analysis, following risk groups were identified according to OS or DSS: 1) cT1 disease with no hydronephrosis; 2) cT2 or higher with no hydronephrosis; or 3) hydronephrosis (with any cT stage). These groups corresponded to a low, intermediate and high-risk groups with 5-year OS and DSS rates of 85% and 91%, 50% and 57% and 16% and 17%, (p&lt;0.001), respectively. We found these risk groups to hold true in those treated with NAC or upfront RC; those who received NAC trended towards better outcomes. Conclusions: In patients with MPBC, preoperative risk factors can help stratify patients into different risk groups similar to what is seen in patients with conventional UC. Presence of hydronephrosis is an especially ominous sign.
Does incidental FDG PET uptake in the prostate have significance?
Authors: Anna Mary Brown, Maria Liza Lindenberg, Sandeep Sankineni, Linda M Johnson, Suneha Pruthy, Maria J Merino, Bradford J. Wood, Peter A. Pinto, Peter L. Choyke, Baris Turkbey
Journal: Journal of Clinical Oncology (2015)

115 Background: 18 F-FDG PET/CT is widely used to diagnose malignancy, but is not recommended for localized prostate cancer. This study explores the value of multi-parametric MRI (mpMRI) in characterizing incidentally detected prostate FDG uptake. Methods: Thirty-one patients who underwent FDG PET/CT and prostate MRI were eligible for this study. 14 patients were excluded (n=8 insufficient histopathology, n=6 radical prostatectomy before PET), with final analysis of 17 patients. The mpMRI sequences included T2-weighted, dynamic contrast enhancement (DCE), apparent diffusion coefficient (ADC), and MR spectroscopy (MRS). Nuclear medicine physicians, blinded to clinicopathologic findings, identified suspicious areas and maximum standardized uptake values (SUVmax) on FDG PET/CT. The lesion and sector-based imaging findings were correlated with annotated histopathology from whole-mount or MRI/TRUS fusion biopsy samples. Positive predictive values (PPVs) were estimated using generalized estimating equations with logit link. Results were evaluated with Kruskal-Wallis and Dunn’s multiple comparisons tests. Results: The PPV of FDG PET alone in detecting prostate cancer was 0.56. Combining FDG (base parameter) with mpMRI modalities (T2, DCE, ADC, MRS) increased the sector-based PPV to 0.79, 0.82, 0.80, and 0.89, respectively. All benign lesions had SUVmax &lt; 5, and malignant lesions had higher mean SUVmax values that correlated with Gleason scores [Table]. This relationship between SUVmax and Gleason score was significant, with p=0.012 on the Kruskal-Wallis test and p=0.015 on the Dunn’s multiple comparisons test for Gleason 0 vs Gleason ≥ 4+5. Conclusions: Incidental prostate FDG uptake has low clinical utility alone, but these areas may harbor high-grade prostate cancer, especially if the SUVmax is greater than 5. [Table: see text]