tbuckley/cabot-search huggingface dataset:
Aggressiveness of end-of-life care before and after the utilization of a palliative care service.
Authors: W. Gonsalves, T. Tashi, T. Davies, S. Ortman, R. Thota, J. Krishnamurthy, I. T. Aldoss, M. Kalaiah, A. Ganta, N. Didwaniya, C. Eberle, A. K. Ganti, S. Subbiah, P. T. Silberstein
Journal: Journal of Clinical Oncology (2011)

9135 Background: End of life (EOL) care in cancer pts is becoming more aggressive over the years. Utilization of palliative care services (PCS) may decrease aggressive care in terminally ill cancer pts. This study evaluates the effect of PCS on the aggressiveness of EOL care in cancer pts. Methods: This is a retrospective analysis performed at our Veteran’s Affairs hospital on the first 100 pts in each of the years, 2002 and 2008, who died with active cancer. Only pts in 2008 had access to a PCS team. Age, date of diagnosis, survival, date of PCS consult, hospice initiation, hospice duration, treatments received and location of pt in the last 30 days of life were recorded. Results: Median age of pts: 2002 was 74 years, 2008 was 72 years. In the last 30 days of life, cancer pts had more aggressive care in 2008 than 2002 in terms of: more incidences of chemo administered (18% vs. 5%, p = 0.004); more ICU admissions (33% vs. 6%, p < 0.001); >14 days of hospital stay (38% vs. 8%, p < 0.001); more hospital deaths (38% vs. 18%, p = 0.001) and more than one hospital admission (18% vs. 6%, p = 0.009). Pts with timely PCS consults (more than 2 wks before death) had a lower incidence of: chemo administration (12% vs. 20%), more than one ER visit (0% vs. 12%), more than one hospital admission (6% vs. 38%), >14 days of hospital stay (24% vs. 43%), ICU admissions (24% vs. 36%) and in-hospital deaths (18% vs. 43%), compared to pts without PCS consults or consults less than two wks before death. Conclusions: EOL cancer care has become more aggressive with time at one of the Veteran’s Affairs hospitals. Institution of a PCS service did not stop the increasing aggressiveness of EOL care. But, timely PCS consults may help attenuate the increase in aggressiveness of EOL care when compared to pts without PCS consults or late PCS consults. Last 30 days of life No of pts based on time from PCS consult to death 2002 2008 No PCS > 2 wks < 2 wks No PCS No of pts 100 25 33 42 Received chemo 5 (5%) 3 (12%) 8 (24%) 7 (17%) >1 ER visit 6 (6%) 0 (0%) 5 (15%) 4 (10%) Hospitalized >14d 8 (8%) 6 (24%) 16 (49%) 16 (33%) >1 hospital admit 6 (6%) 2 (8%) 10 (30%) 4 (10%) ICU admit 6 (6%) 6 (24%) 14 (42%) 13 (31%) < 3 days in hospice 25 (36%) 4 (16%) 13 (39%) 23 (55%) Hospice 69 (69%) 19 (76%) 25 (76%) 16 (38%) Hospital death 18 (18%) 6 (18%) 12 (36%) 20 (48%)
A randomized, phase III trial comparing BuCy and BuFlu as a myeloablative conditioning regimen.
Authors: S. Kim, J. Lee, Y. Joo, H. Kim, H. Ryoo, M. K. Kim, G. Lee, J. Lee, W. Lee, J. H. Park, S. H. Bae, M. S. Hyun, D. Kim, Y. J. Min
Journal: Journal of Clinical Oncology (2011)

6524 Background: Although busulfan-cyclophosphamide (BuCy) has been commonly used as a myeloablative conditioning (MC) regimen for allogeneic hematopoietic cell transplantation (HCT), a new MC regimen using busulfan-fludarabine (BuFlu) showed less regimen-related toxicities and lower non-relapse mortality (NRM) compared to BuCy in several non-randomized studies. Thus, we performed a prospective, multicenter, open-label, phase III trial to compare BuCy and BuFlu as a MC regimen for allogeneic HCT in leukemia and myelodysplastic syndrome. Methods: A total of 130 were enrolled between Nov 2005 and Sep 2009, but 4 patients were removed from the study and the remaining 126 patients were analyzed. Median age was 41 years (range, 17 to 59). Underlying disease was as followings: AML 70, ALL 47, CML 2, MDS 6, MDS/MPN 1. After random assignments, 64 patients received busulfan (3.2mg/kg/d x 4d) plus cyclophosphamide (60mg/kg/d x 2d) [BuCy arm] and 62 received busulfan plus fludarabine (30mg/m2/d x 5d) [BuFlu arm]. Results: Baseline patient and donor characteristics were well balanced between two arms. Five patients experienced engraftment failure (primary 1, secondary 4), which occurred only in BuFlu. Incidence and severity of acute GVHD, chronic GVHD, hepatic SOS, CMV disease, interstitial pneumonitis, and hemorrhagic cystitis were not significantly different between two arms. Adverse events (AE) within 100 days after HCT were graded using NCI CTCAE v3.0. Both upper and lower gastrointestinal (GI) AEs were more frequent in BuCy compared to BuFlu (P=0.018 for upper GI, P=0.050 for lower GI). NRM was similar between BuCy and BuFlu (13.4% vs. 22.3% at 1 year, P=0.291), whereas relapse-free survival in BuCy was higher than that in BuFlu (67.7% vs. 50.7% at 4 year, P=0.039). Thus, overall and event-free survivals in BuCy were significantly higher than those in BuFlu (overall, 51.1% vs. 36.1%, P=0.008; event-free, 46.2% vs. 33.3%, P=0.023). Conclusions: BuFlu caused less GI toxicities than BuCy, but NRM was similar. BuFlu showed lower survivals than BuCy mainly due to higher incidence of relapse. BuFlu cannot replace BuCy in patients who are eligible to myeloablative conditioning therapy before allogeneic HCT.
The influence of seminal events on the transition from adjuvant to neoadjuvant chemoradiation in the treatment of locally advanced rectal adenocarcinoma (LARC).
Authors: Jeremy Warner, Rebecca A. Miksad, Deborah Nagle, Robert Najarian, Michael Goldstein
Journal: Journal of Clinical Oncology (2012)

631 Background: Factors leading to uptake of new oncology treatment innovations are poorly understood. In particular, the degree to which seminal events, such as report of pivotal phase III trials, influence practice is unclear. For example, preoperative (pre-op) 5-fluorouracil + radiation (5-FU + RT) is the current standard of care for definitive treatment of LARC. However, postoperative (post-op) 5-FU + RT was standard before the seminal German Rectal Cancer Study Group (GRCSG) results were published. We investigated the impact of seminal events on the change in practice pattern from pre- to post-op 5-FU + RT at our institution. Methods: Patients with LARC (T2N+; any T3; any T4) treated at our institution between 1994-2010 were identified from the cancer registry. The date of diagnosis was compared to the dates of three seminal events: A) JAMA meta-analysis publication; B) publication of GRCSG results; C) founding of a multidisciplinary clinic at our institution. Pearson Chi square was used for univariate analysis. Results: 334 patients were evaluable. RT +/- 5-FU was delivered pre-op for 207 patients, post-op for 127 patients. The unadjusted odds ratio (OR) for receiving pre-op treatment after vs. before each seminal event was similar: (A) 4.16; (B) 4.08; (C) 3.91. When patients diagnosed prior to (A) or after (C) were excluded, (B) appeared to have a smaller effect, OR 2.07 (p = .053) (Table). Conclusions: All seminal events had similar associated OR, indicating that the process of uptake of the innovation of pre-op 5-FU + RT was gradual. The seminal GRCSG publication, when temporally isolated, had only modest effect. This suggests that report of seminal results is necessary but not sufficient for uptake of a new therapy innovation in LARC at our institution. Whether this pattern of uptake is generalizable is worthy of further investigation. [Table: see text]
Analysis of CTLA-4 gene polymorphisms in patients with advanced melanoma treated with anti-CTLA-4 therapy.
Authors: P. Queirolo, A. Morabito, P. Piccioli, S. Lastraioli, S. Callegari, M. Camoriano, P. A. Ascierto, S. Laurent, B. Dozin, M. P. Pistillo
Journal: Journal of Clinical Oncology (2011)

8588 Background: It has been suggested that specific CTLA-4 gene polymorphisms may have an important role in advanced melanoma patients (pts) receiving CTLA-4 blockade therapy (Breunis W. et al. J Immunother 31:586,2008). We therefore evaluated five CTLA-4 single nucleotide polymorphisms (SNPs) in metastatic melanoma (MM) pts treated with anti-CTLA-4 blocking antibodies Ipilimumab or Ticilimumab. Methods: The analysis was performed in 14 pts with unresectable MM enrolled in multi-center, single arm, phase II studies of Ipilimumab (CA184008) or Ticilimumab (A3671009) monotherapy, with a median follow up of 8.4 months (range 0.8-50.9 months). Clinical response was evaluated according to modified WHO (mWHO) criteria and scored as complete response (CR), partial response (PR), stable disease (SD), or progressive disease (PD). The primary end point was overall survival (OS) defined as the time from the 1st anti-CTLA-4 treatment to the last contact or death. Genotyping of the CTLA-4 SNPs, -1660A>G, -657C>T, -318C>T (promoter), +49A>G (exon 1) and CT60A>G (3’UTR), was performed by tetra-primer amplification refractory mutation system (T-ARMS-PCR), RFLP analysis and confirmed by direct sequencing on genomic DNA extracted from pts peripheral blood. Correlation between each CTLA-4 genotype/haplotype distribution and OS was performed by Kaplan Meier method whereas correlation with response to therapy was analysed by the Pearson chi-square test. Results: No deviation from the Hardy-Weinberg equilibrium was observed for all polymorphisms analyzed. Five patients were alive and 9 were dead at the end of the observation period. All 5 alive pts carried the CT60 G/A genotype, which, at variance with CT60 A/A or G/G genotypes, strongly correlated with better response (CR, PR or SD) (chi-square P=0.054) and significantly with OS (4-years cumulative OS, 53.3% CI 95% 50.2-56.4, log rank P=0.001). No significant association was observed with the other CTLA-4 SNPs or haplotypes analysed. Conclusions: Our data suggest the possible impact of CTLA-4 polymorphisms on the clinical outcome of metastatic melanoma patients receiving antibody-mediated CTLA-4 blockade.
Phase II trial of aprepitant on days 1 to 7 for patients with germ cell tumors having cisplatin on days 1 to 5.
Authors: D. B. Thomson, P. S. Grimison, M. D. Chatfield, M. R. Stockler, G. C. Toner, V. Gebski, R. A. Harrup, C. Underhill, G. Kichenadasse, N. Singhal, A. L. Boland, A. McDonald, I. N. Olver
Journal: Journal of Clinical Oncology (2011)

e19577 Background: There is no established aprepitant-containing anti-emetic regimen for multi-day, cisplatin-based chemotherapy. The aim of this single-arm, multi-centre, phase II trial was to determine the efficacy of giving aprepitant for 7 days to patients having 5 days of cisplatin and etoposide as first line chemotherapy for germ cell tumors (BEP, accelerated BEP, or EP). Methods: Patients received oral aprepitant 125 mg day 1 and 80 mg days 2 to 7, a 5HT3 antagonist days 1 to 5, and dexamethasone 8 mg days 1 to 8. The primary endpoint was “nil emesis” during days 1 to 7 of cycle 1 assessed by patients with a self-completed diary. Key secondary endpoints are listed in the table. Results: 50 patients recruited from May 2009 to December 2010 had a median age of 30 years and ECOG performance status 0 or 1. Compliance rates for anti-emetics during cycle 1 were 92% for aprepitant, 86% for dexamethasone, and 96% for 5HT3 antagonist. There were no serious unexpected adverse events attributed to aprepitant. Efficacy results are tabulated. Conclusions: The nil emesis rate during days 1 to 7 of 84% (95% CI 70%, 93%) was substantially better than the historical control rate of 50%. These results support the safety, efficacy and further consideration of using aprepitant on days 1 to 7 for patients with germ cell tumours having cisplatin on days 1 to 5. Supported in part by supply of drug from Investigator-Initiated Studies Program of Merck and Co. and research grant from Merck Sharp & Dohme (Australia) Pty Limited. Cycle 1 Historical control of 5HT3 antagonist and dexamethasone (Einhorn, Supp Care Cancer 2007; 15: 1293) Day 1 Days 1 to 5 Days 1 to 7 Day 1 Days 1 to 5 Nil emesis 98% 88% 84% 88% 51% Nil emesis and nil rescue therapy 84% 47% 43% 83% 34% No significant nausea (< 2/10 on VAS) 84% 45% 41% *Currently awaiting diary for one patient.
Application of a novel method weighing drug costs against survival in castrate-resistant prostate cancer cancer.
Authors: Helmy M. Guirgis
Journal: Journal of Clinical Oncology (2013)

271 Background: In the last few years, 5 new anticancer drugs have been introduced for the treatment of castration-resistant prostate cancer (CRPC). The objective was to apply a simplified methodology of weighing drug costs against overall survival (OS) in CRPC. Methods: Estimated cost in United Sates (US) dollars of an entire treatment course of an evaluated drug was divided by previously reported median OS gain over control. An initial survey of 45 drugs demonstrated that the maximal cost/OS/day gain was $757. Accordingly, a scale of crude scores was constructed with a 0% assigned to a cost/OS gain greater than $1,000 and 100% to a cost/OS gain of $1. Value scores were calculated after adjusting for quality of life (QoL), adverse events (AEs), and specialized administration and preparation (AP). Results: The lowest cost/OS gain and highest value score were demonstrated by generic docetaxel. Enzalutamide in previously-treated and abiraterone in chemo-naïve and treated patients x 6 months showed cost/OS gain lower than that of docetaxel but significantly higher than cabazitaxel. Pricing of sipuleucel-T based on cost of the entire course partly accounted for its highest cost/OS and lowest scores. Extending abiraterone and enzalutamide treatment to 12 months increased cost/OS gain and decreased scores. Conclusions: Methodology was proposed to weigh drug cost against OS/day gain with and without adjustment for QoL, AEs, and AP. Results in CRPC tend to support use of docetaxel, abiraterone, and enzalutamide rather than cabazitaxel and sipuleucel-T. Varying drug indications and different populations within the CRPC spectrum preclude direct drug comparison.
Early ultrasound criteria drive sensitivity for detection of sentinel node metastases in melanoma patients: A prospective study in 800 patients.
Authors: C. A. Voit, A. C. Van Akkooi, G. Schaefer-Hesterberg, A. Schoengen, W. Sterry, A. M. Eggermont
Journal: Journal of Clinical Oncology (2010)

8514 Background: Ultrasound (US) guided FNAC (fine needle aspiration cytology) prior to surgical sentinel node (SN) staging is an emerging new cost-effective approach to melanoma lymph node metastases. Previously, we have shown in 400 patients (pts) that the introduction of new morphology criteria, combined with more frequently performed FNAC and overnight cytology reports can accurately identify up to 65% of lymph node metastases. The current study aim was to increase statistical power with twice as many patients and prolonged follow-up. Methods: Currently, 800 stage I/II melanoma pts have been analyzed of the 880 pts in the database. All pts underwent lymphoscintigraphy followed by an US-exam. US images were scored for our morphology criteria, FNAC was performed in all suspicious US results. All pts underwent a SN. Sensitivity (sens), specificity (spec) and negative/positive predictive value (NPV and PPV) were calculated. SN tumor burden and survival analyses were performed. Results: Since 2001, 800 consecutive pts with a mean follow-up of 37 months (1-104) with a median/mean Breslow of 1.6/2.68 mm were analyzed. 56% were male, ulceration was present in 27%. SN positivity rate was 21% (n = 167). Sens and spec of US-guided FNAC (overall) was 93/167 (56%) and 625/633 (99%). PPV and NPV of the overall technique were 92% and 89%. 5-ys OS was 50% for US-guided FNAC pos vs 92% for neg. Sens, spec, PPV and NPV of balloon shaped (BS) were 29%, 99%, 94%, 83% respectively, whereas, sens, spec, PPV and NPV of peripheral perfusion (PP) were 72%, 82%, 53%, 91% respectively. The limit for a positive FNAC was metastases of 0.4 mm in maximum diameter. Sensitivity of US-guided FNAC increases with increasing T stage and increasing SN tumor burden. Conclusions: This largest prospective study worldwide on the subject of pre-SN ultrasound-guided FNAC confirms our previous results that US-guided FNAC can be a cost-effective alternative to the SN. Tumor stage and SN tumor burden drive the yield of US-guided FNAC. Peripheral perfusion is an early sign of metastases and has significantly increased the sensitivity of US-guided FNAC. No significant financial relationships to disclose.
Clinical characteristics and outcomes for gastric cancer patients over age 80: A retrospective case-control study.
Authors: Hee-Jung Park, Ji Yong Ahn, Hwoon-Yong JUNG, Jeong Hoon Lee, Kwi-Sook Choi, Kee Wook Jung, Do Hoon Kim, Kee Don Choi, Ho June Song, Gin Hyug Lee, Jin-Ho Kim, Seungbong Han
Journal: Journal of Clinical Oncology (2015)

30 Background: The average human life expectancy is increasing worldwide, thus proportion of elderly gastric cancer patients are also increasing. In this study, we investigated the clinical and oncologic outcomes of gastric cancer in patients over 80 years old through a case-control study. Methods: From January 2004 to December 2010, 291 patients aged over 81 years old (case group) were diagnosed and treated with gastric cancer at the Asan Medical Center. During the same period, 291 patients aged 18 to 80 years old were selected as control group. The clinical findings, histopathological parameters, and clinical outcomes of gastric cancer were reviewed retrospectively and compared between the two groups. Results: There were significant differences in overall 5-year survival rate between the two groups (30.9% vs 73.8%, P&lt; 0.001). When analysis was confined to resectable elderly patients with favorable performance of American Society of Anesthesiologists (ASA) score 1 or 2, curative resection group showed significantly better overall 3- and 5-year survival rate than the conservative treatment group (73.7% and 58.8% vs 29.8% and 0%, respectively). In multivariate analysis, lower BMI and advanced TNM stage were found to be independent prognostic predictors for poorer survival. ASA score showed borderline significance for predictors for poorer survival (P=0.087). Conclusions: Although elderly patients showed advanced stage at diagnosis and poor prognosis compared to non-elderly patients, elderly patients with good performance could benefit from curative resection of gastric cancer, thus the clinical decision whether to undergo curative resection or conservative management should be made on individualized approach.
Barriers to patient accrual in Ontario oncology clinical trials: Attitudes of oncologists and clinical research personnel.
Authors: Ammar Bookwala, Daisy Dastur, Audrey Wong, Christina Marchand, Jalal Ebrahim, Sophie Hogeveen, Ata Ansari, Laura Sevick, Christine B. Brezden
Journal: Journal of Clinical Oncology (2012)

36 Background: The medical specialty of oncology relies heavily on clinical trials to advance policies and practices related to cancer care. However, oncology clinical trial accrual in Ontario has dropped from 12.4% in 2007, to 8.5% in 2009. The objective of this study was to determine barriers experienced by Oncologists and Clinical Research Personnel (CRP) in recruiting patients to oncology trials in Ontario. Methods: In June 2012, an electronic survey was emailed to about 400 oncologists and CRP across Ontario. Variables of interest included demographic data, clinical trial involvement, and perceived barriers to participation in clinical trials amongst three previously identified barrier domains. Barriers were ranked, from 1 (least significant) to 5 (most significant). Statistics were compiled using Graphpad Prism software. Differences in responses were analyzed using the Kruskal – Wallis test and Dunn’s Multiple Comparison Test. Results: Of the 400 emails sent, there were 126 respondents (32%). Of the 126 respondents, 82 fully completed the survey (64.6% useable response rate). Amongst system related barriers, “time related” (Median Agreement (M): 4, Inter Quartile Range (IQR): 3-5), and “resource related” barriers (M: 4, IQR: 3-5) had the most negative effect on accrual (p&lt;0.05). Amongst trial design barriers, “Relevance to patient population” (M: 3, IQR: 3-5), “Deviation from Standard of Care” (M: 3, IQR: 3-5) and “Complexity of Trial Protocol” (M: 4, IQR: 3-5) were the most significant barriers (p&lt;0.05). Lastly, amongst personal barriers, “Commitment of the Principal Investigator/Research Staff” (M: 4, IQR: 3-5) and Drug Safety (M: 4, IQR: 2-4) were the most significant barriers to recruitment (p&lt;0.05). Conclusions: Multiple barriers were identified as having a significant impact on patient accrual in clinical trials. Addressing these barriers prospectively in clinical trial design may benefit future studies to successfully accrue cancer patients. Also, creating clinical trial collaboration vehicles amongst sites in similar geographical areas may contribute to improving patient accrual to clinical trials.
Capecitabine in combination with interferon-alpha in interleukin-2-refractory metastatic renal cell carcinoma (MRCC)
Authors: L. V. Demidov, I. V. Tsimafeyeu, U. A. Naidzionak
Journal: Journal of Clinical Oncology (2008)

16088 Background: Capecitabine (CAP) and Interferon alpha-2b (IFN) are two well-known substances with anti-tumor activity in MRCC. This open label, non-randomized, phase II study evaluated the safety and efficacy of CAP+IFN combination in MRCC patients (pts) previously progressed on IL-2-based regimens. Methods: Pts had progressive, any histology advanced RCC, measurable disease, and prior IL-2 based therapy. Eligible pts received CAP 1,250 mg/m2 orally twice a day, days 1–14 and IFN 5 MIU s.c. t.i.w., days 1–21 in repeated cycles followed by a 2 week break. Re-evaluation was assessed every 2 cycles using RECIST criteria. Results: 49 pts (median age, 61 (43–74), male/female, 67.3/32.7%) were entered on study during 19-month period. Baseline demographics included 11 pts (22.5%) with non-clear cell histology; 4 pts (8.2%) with primary tumor; 12 (24.5%) and 12 (24.5%) pts with ECOG PS 2 and 3, respectively. Treatment related adverse events (grade 1/2) were fatigue, weakness, flu-like syndrome, nausea and vomiting, hand-foot skin reaction, alopecia, neutropenia, elevated alkaline phosphatase. 1 pt (2%) was excluded due to grade 4 thrombocytopenia. Efficacy data for 48 evaluable pts showed an objective response of 18.8% (2 CR, 7 PR), stable disease of 50%, median progression-free survival (PFS) of 8.0 months (95% CI: 4.7, 11.4). 10 pts remain on treatment. Longest response is 20.1 months (till present date) in patient with good prognosis, lung mts and clear type of RCC. 16 (57.1%) pts are alive. Conclusions: Combination of CAP and INF has promising anti-tumor activity in second-line in MRCC pts as demonstrated by a 68.8% disease control rate (CR/PR/SD). Regimen is well tolerated. No significant financial relationships to disclose.