tbuckley/cabot-search huggingface dataset:
Efficacy of dendritic cell infusion in advanced hepatocellular carcinoma
Authors: L. Di, J. Ren, G. Song, J. Yu
Journal: Journal of Clinical Oncology (2005)

4168 Background: Some studies demonstrated that dentritic cell immunotherapy is positive effective therapy in melanoma and prostate cancer. We conducted a pilot study to evaluate the effect of dendritic cell infusion applying in advanced hepatocellular carcinoma. Methods: The 21 patients with hepatocellular carcinoma received chemotherapy and G-CSF used to mobilize peripheral blood hematopoietic stem cell. CD34+ stem cell were induced to differentiate into dendritic cell by cytokines IL-4, GM-CSF, and TNF-a. After cultured for 7 days, dendritic cell were infused into patient’s vein or directly injected into tumors tissue once a week over a 3 week. The response rate, Karnofsky score, AFP and HBV virus copy were checked before and after infusion or injection. Results: The response rate including SD rate is 76%, the tumor shrink demonstrate in 2 patients. Karnofsky score increases in 15 patients. Both the AFP and HBV virus copies decreased, a significant reduction (t=0.014) in AFP serum lever was found. No severe side-effects were found except for diarrhea in 1 patient, fever in 3 patients and liver pain in 2 patients after directly injection into tumor. Conclusions: Dendritc cell immunotherapy is of promising to treat advanced hepatocellular carcinoma without severe side effect. In order to get stronger immune response, loading tumor specialized antigen is crucial. No significant financial relationships to disclose.
Managing chemotherapy drug shortages in Ontario.
Authors: Leonard Kaizer, Sherrie Hertz, Lyndee Yeung, Lisa Milgram, Scott Gavura, Ram Iyer, Monika K. Krzyzanowska
Journal: Journal of Clinical Oncology (2013)

192 Background: Chemotherapy drug shortages are common and unpredictable. The causes are multifactorial and the negative effects on patients and practitioners have been well described. In an effort to mitigate the impact of this problem, Cancer Care Ontario (CCO) has developed a coordinated approach to the management of chemotherapy drug shortages. Tactics have included a system level strategy to promote communication through a virtual collaborative workspace for providers to network and share management strategies and inventory, where feasible. Disease site experts have also developed clinical guidance for the management of specific drug shortages which have then supported public funding decisions that enabled the use of substitute chemotherapy agents in a number of instances. Methods: The impact and management of a recent shortage of liposomal doxorubicin (LD), a publically funded drug for patients with platinum refractory ovarian cancer is described for both new chemotherapy starts and for prevalent LD treated cases. Expert clinical guidance supported a funding policy amendment so patients already on treatment could switch to a recognized substitute drug, topotecan (TT). This also became the preferred funded option for new platinum refractory patients. Results: LD was in short supply between August 2011 and December 2012. In the quarter prior to shortage, 83 new platinum refractory patients started on LD and 1 on TT. During that time, the average number of monthly prevalent LD and TT treated cases was 80 and 4 respectively. For the first quarter post shortage, 20 new patients started on LD and 34 patients started on TT. The average monthly prevalent treated cases were 49 and 21 respectively. Funding for the switch from LD to TT was requested in only 7 cases. Therefore, the total number of new and prevalent treated cases on either preferred therapy dropped post LD shortage. This decline worsened with each subsequent quarter and immediately returned to baseline when the shortage resolved. Drug procurement costs were lower during the period of shortage. Conclusions: Drug shortages have a significant impact on patients and providers. Even when appropriate substitutes are available, quality of care may be affected.
Phase II cancer vaccination trial with multiple peptides derived from novel oncoantigens against advanced esophageal cancer.
Authors: K. Kono, H. Iinuma, Y. Akutsu, H. Tanaka, N. Hayashi, Y. Uchikado, T. Noguchi, H. Fujii, R. Fukushima, H. Matsubara, K. Hirakawa, H. Baba, S. Natsugoe, S. Kitano, K. Yoshida, T. Tsunoda, Y. Nakamura
Journal: Journal of Clinical Oncology (2011)

2504 Background: Since a phase I cancer vaccination trial using three novel HLA-A24-binding peptides derived from Oncoantigen, TTK protein kinase (TTK), lymphocyte antigen 6 complex locus K (LY6K), and IGF-II mRNA binding protein 3 (IMP-3), had revealed safety and immunogenicity in advanced esophageal squamous cell carcinoma (ESCC), we further performed a phase II trial to evaluate the survival benefit of the cancer vaccination. Methods: Sixty advanced ESCC patients who failed to standard therapy were enrolled to evaluate OS, PFS, immunological response employing ELISpot and pentamer assay, and adverse effect. Each of the three peptides (1 mg each) was subcutaneously administered with 1 ml of IFA weekly for five weeks. All enrolled patients had received the vaccination without knowing HLA-A status double-blindly, and the HLA genotype were key-opened at analysis point and then, the endpoints were evaluated between HLA-A*2402 positive (24(+), n=35) and HLA-A*2402 negative (24(-), n=25) group. Results: The treatment was well-tolerated without any treatment-associated adverse events of grade 3 or 4. The patient backgrounds did not differ between the 24(+) and 24(-) group. Although the difference in OS after the vaccination between the 24(+) and 24(-) group did not reach a significant level (4.6 vs. 2.6 month, respectively, p=0.136), the PFS in the 24(+) group was significantly better than that in the 24(-) group (p=0.032). The TTK-, LY6K-, and IMP-3-specific CTL responses were observed after the vaccination in 45%, 63%, and 57% of patients in the 24(+) group, respectively, and the peptide-specific responses were confirmed by the pentamer assay. In the 24 (-) group, the patients showing the peptide-specific CTL response analyzed by dump assay were observed in 12% of them, indicating the cross-reactivity against the vaccinated peptides with different HLA allele. The OS in patients having all of three peptide-specific CTL responses indicated much better prognosis (OS=7.5 month) compared to that in the other patients. Conclusions: The phase II cancer vaccine therapy demonstrated the promising survival benefit as well as good immunogenicity, and, therefore, warrants further clinical studies.
Examination of differences in quality of life and use of support services in urban versus rural breast cancer patients.
Authors: Sarah Roberts, Shahid Ahmed
Journal: Journal of Clinical Oncology (2013)

98 Background: Many patients travel great distances, both for testing and for medical care. Previous studies have indicated that there can be significantly poorer quality of life in urban cancer patients. The purpose of this study was to determine any differences in support service use and quality of life in rural versus urban patients in Saskatchewan. Methods: This study is a survey based qualitative and quantitative analysis of women with breast cancer receiving treatment at the Saskatoon Cancer Center (SCC) in Saskatchewan, Canada. Surveys included demographic information, support service utilization and suggestions, as well as the WHO-QOL-bref quality of life assessment. Surveys were collected from 51 women with an age range of 43 to 87 years with a median age of 63. Participants travelled a mean distance of 99.2km to treatment center (range 1.9 – 307.6 km, SD 101 km) with 49% women travelling greater than 100 km (rural group) and 51% travelling less than 100 km (urban group). Results: Only 50% of urban participants and 56% of rural participants reported using support services at the SCC though this was found to be statistically non-significant by Fisher Exact Testing (p= 0.781). The support services reported to be most useful were nursing phone assessments, medication information, pharmacist support and mailing of medications. Further support services that participants would like to have available include: online support groups and blogs, local support groups, physician visits to rural communities and patient liaisons to help navigate the system. Overall, urban participants rated their quality of life on average at 3.96 with rural participants reporting 3.84 on a five-point scale, though non-significant by t-test (p=0.617). The WHO-QOL-bref study examines quality of life in 4 domains: physical health, psychological wellbeing, social and environment. Urban participants scored 68%, 72%, 76% and 77% in the 4 domains respectively while rural participants scored 61%, 73%, 79% and 78% in the 4 domains respectively. Conclusions: Our study did not find any significant difference between urban and rural patients in reported quality of life or support service use.
Effects of realgar (tetra-arsenic tetra-sulfide) on malignant tumor cells.
Authors: S. Chen, L. Zheng, J. Liu, J. Li, L. Zhang, J. Gu, X. Li, W. Shen, F. Ma, Y. Yao, G. Wu, Q. Chen
Journal: Journal of Clinical Oncology (2011)

e13525 Background: Realgar, of which the main component is tetra-arsenic tetra-sulfide, has been widely used in Chinese traditional medicine. Its therapeutic effects in traditional remedies include anti-inflammation, antiulcer, anticonvulsion, and anti-schistosomiasis, etc. It can be taken orally and has much less toxicity than arsenic trioxide, another arsenic compound applied to treat malignant diseases. Recent studies indicated beneficial effects of Realgar in the treatment of hematological malignant diseases. However, its effect on solid malignant tumor was unclear. This study was aimed to investigate the effect of Realgar on some solid malignant tumor cells. Methods: Four human solid malignant tumor cell lines, MKN45 cells (gastric cancer), A375 cells (malignant melanoma), Patu8988 cells (pancreatic carcinoma) and HepG2 cells (hepatocellular carcinoma) were treated with Realgar in vitro. Cell morphology was observed under microscope. Cell proliferation and cell cycle distribution were determined using methyl thiazollyl tetrazolium assay and flow cytometry respectively. Caspases activity was measured by colorimetric assay. Nuclear translocation of NF-κB was examined by western blot. For in vivo study, tumor implanted mice were treated with Realgar. Upon sacrifice, tumor weight was recorded. IL-2, IFN-γ and TNFα in the circulation were measured by ELISA. Results: Realgar had a dose-dependent cytotoxic effect on those malignant cells. However, only a minor effect on normal human cells (L02 embryonic liver cell) was observed with a similar concentration of Realgar. Further, Realgar-treated MKN45 cells and A375 cells showed a hypodiploid peak by flow cytometry. This change was accompanied by aberrant-regulation of NF-κB nuclear translocation and up-regulation of caspase-3 and caspase-9 activities, indicating mitochondrial pathway mediated cell apoptosis. Moreover, in implanted mice the tumor weight decreased after Realgar administration. In additional, TNFα decreased while IL-2 increased. Conclusions: Realgar displayed a significant anticancer effect on malignant cells through induction of cell apoptosis. Our findings suggested a potential therapeutic effect of Realgar on some solid malignant tumors.
Analysis of response rate (RR), liver resection (LR), and toxicity (T) in 129 advanced colorectal cancer (CRC) patients (pts) treated with chronomodulated infusion of ironotecan (I), 5-fluorouracil/leucovorin (F/L), and oxaliplatin (O) (CHRONO-IFLO) with or without cetuximab (Cmab).
Authors: C. Garufi, A. Torsello, I. Sperduti, V. Ferraresi, M. Zeuli, A. Gelibter, C. Campanella, M. S. Pino, C. Nuzzo, S. Tumolo, F. Cognetti
Journal: Journal of Clinical Oncology (2011)

e14099 Background: Advanced CRC pts received chrono-IFLO in three sequential studies: (A) EORTC 05011: 54 pts (Garufi et ASCO 2007); (B) selected liver metastatic 43 pts (Garufi et al, POCHER study, BJC 2010) and (C) unselected CRC 32 pts (Garufi et al ASCO 2010). Cmab was added in groups B+C. Methods: Aim of the study was to retrospectively analyze activity, tolerability and outcomes. Results: Median (m) age 60 y (range 29-78), M/F:78/51 (60.5/39.5%), PS 0: 112 (87%) pts, 1: 16 pts, 2: 1 pt; synchro vs metachronous (s/m) metastases 105/24 (81/19%), 110 pts were treated as first with only 19 as second-line (15%). Groups A and B+C did not differ for m-age, sex, PS, s/m . RR was obtained in 71/129 pts (55%) while 21 pts progressed; LR was obtained in 52/129 pts (40.3%). G3-4 gastrointestinal T affected 67 pts (52%); dose-intensity (DI) >80% at c5: 63.4% of pts. m-Follow-up was 19.6 months (ms) (1-100), mPFS was 14 ms (CI95% 12-16), with 1-2-3 y PFS of 55%-23.8%-13.0, respectively; mOS was 31 ms (25-37 CI 95%), with 1-2-3 y OS of 84.1%-60.2%-36.8% respectively. PFS at 1-2 y was significantly longer in LR 77.5-37.9% vs non-LR pts 40.1-13.6% (p=0.0001). mPFS and mOS did not differ between pts treated ± Cmab, also for LR pts. There was neither difference in m-DI for I, F/L or O, nor 20%-dose-reduction due to T criteria in M/F in the entire population, in subgroups according to ± Cmab, or in group A alone but F-pts treated with Cmab experienced significant more T than M-pts in B+C, 32.3 vs 10.0% (p=0.002). In groups B+C vs A there was a RR of 64.0% vs 40.7% (p=0.009), LR 48.0% vs 29.6% (p=0.03), but Gr 3-4 GI-T was 57.3% vs 44.4.1% (p=0.15), There was no relationship between RR or LR with Gr 3-4 GI toxicity, m-DI, or 20% dose reduction in the entire population and in group A vs B+C. Predictive factors for response were PS 0 vs 1-2, first vs second line and Groups B+C vs A. RR was the only significant predictor factor for LR. At Cox multivariate analysis LR predicted PFS with HR 2.65 (1.68-4.19). Conclusions: LR is the most relevant prognostic factor for CRC pts treated with chrono-IFLO ± Cmab. LR were increased with Cmab.
Apixaban Versus Enoxaparin for Thromboprophylaxis After Joint Replacement Surgery: Pooled Analysis of Major Venous Thromboembolism and Bleeding In 8,464 Patients From the ADVANCE 2 and 3 Trials
Authors: Gary E. Raskob, Alexander S. Gallus, Graham F. Pineo, Dalei Chen, Luz Margarita Ramirez, Michael Rud Lassen
Journal: Blood (2010)
Hospitalizations and emergency department use in cancer clinical trial patients.
Authors: Ryan David Nipp, Elizabeth Powell, Beverly Moy
Journal: Journal of Clinical Oncology (2015)

160 Background: Cancer clinical trials (CTs) often represent the best available treatment for many patients, but little is known about the health care utilization of these patients. We examined correlates of hospitalizations and emergency department (ED) use in cancer CT patients to determine those at greatest risk for these outcomes. Methods: We prospectively collected data on patient characteristics, hospitalizations and ED use among all patients enrolled in cancer CTs at Massachusetts General Hospital in 2014. We calculated the number of hospitalizations and ED visits in the 6-month interval following patients’ CT enrollment. We used linear regression with purposeful selection of covariates to identify factors associated with hospitalizations and ED use. Results: Of 1,218 CT patients (mean age = 58 years; 575 (47%) male), 781 (64%) were married and 851 (70%) had metastatic disease. All cancer types were represented, but hematologic cancers (21%) were most common. Within 6 months following CT enrollment, 519 (43%) and 327 (27%) had at least one hospitalization and ED visit, respectively. At any time during their cancer course, 177 (15%) received a palliative care (PC) consult. Controlling for presence of metastatic disease, PC consults correlated with both hospitalizations and ED visits. Having a hematologic cancer and being unmarried correlated with more hospitalizations and ED visits, respectively. Conclusions: Hospitalizations and ED visits occur in a substantial proportion of cancer CT patients. We need to better understand reasons for these high rates of health care utilization, but the correlations with PC consults suggest that CT patients have unique supportive care needs and that PC services are being targeted to a population particularly in need. [Table: see text]
Benchmarking of oncology clinical trial metrics across AACI member centers.
Authors: D. C. Stahl, S. K. Cheng, E. Lee, D. M. Dilts
Journal: Journal of Clinical Oncology (2011)

e16613 Background: Benchmarking through the utilization of standardized metrics is critical to understanding baseline performance, capturing best practices, and identifying systemic barriers across institutions. We apply this principle to analyze the approval times of oncology clinical trials (CT) in cancer centers within the Association of American Cancer Institutes (AACI). Methods: A 36-item survey was developed based upon study demographic and timing data for specific CT development milestones. 40 AACI member centers were invited to share data on all oncology therapeutic trials submitted for development between 1/2008 and 1/2009. Results were analyzed for data integrity, variation across institutions, and overall portfolio composition. Results: 35% centers participated in submitting a total of 1,161 studies. No study had complete timing data in the survey. Missing data for various data elements ranged from 20% for first receipt date to over 75% for elements involved with contract negotiations. The predominate type of trials were Industry (44%), Cooperative Group (36%), and Investigator initiated (13%). Development time from first submission to CT activation was 185 days; time to first patient enrollment was 66 days. Contract negotiation required the greatest amount of time compared to the other categories (Mann-Whitney: p<0.001). Conclusions: This study highlights the findings that opening of an oncology CT is a long process, highly variable, and inconsistently captured. Additionally this research identifies the need for a standardized methodology to capture metrics across groups of cancer centers. Industry Cooperative group Investigator initiated Consortium Other Total n mdn (IQR) n mdn (IQR) n mdn (IQR) n mdn (IQR) n mdn (IQR) n mdn (IQR) Scientific review 321 25 (12-50) 182 7 (1-15) 96 52 (16-80) 8 33 (27-56) 39 27 (9-79) 646 19 (7-44) Institutional Review Board 350 35 (21-59) 231 36 (18-57) 112 42 (27-73) 9 15 (8-46) 37 48 (40-61) 739 37 (21-59) Contracts 195 75 (39- 151) 3 61 (1-210) 23 84 (42-131) – – 19 181 (131-207) 240 76 (35-152) Total development time 283 214 (153-304) 210 120 (64-198) 76 239 (153-343) 8 112 (82-184) 31 287 (107-313) 608 185 (109-300) Time to 1st patient 97 57 (22 - 117) 68 78 (23-213) 32 65 (43-139) – – 2 183 199 66 (24-146)
Final report of post-marketing survey of panitumumab in Japanese patients with unresectable advanced or recurrent colorectal cancer.
Authors: Tetsuya Hamaguchi, Narikazu Boku, Kenichi Sugihara, Yuko Kitagawa, Hiroya Takiuchi, Kiyohiko Hatake, Kei Muro, Takayuki Yoshino, Naoya Yamazaki, Akihiko Gemma, Ikuo Yana, Hiroshi Ueno, Atsushi Ohtsu
Journal: Journal of Clinical Oncology (2013)

525 Background: Panitumumab (P-mab) was approved in Japan in Apr. 2010 for the treatment of unresectable, advanced or recurrent colorectal cancer with wild-type KRAS, both in monotherapy and in combination with chemotherapy for all lines of treatment. All-case surveillance of P-mab was conducted to assess safety and efficacy in practical use since clinical data on Japanese patients were limited. Methods: All patients were registered before starting P-mab containing therapy by central registration method since the launch of P-mab in Japan. Patients were examined for eligibility requirements such as KRAS genotype (wild), ECOG PS (0-2) and interstitial pneumonitis (-). Skin disorder, infusion reaction(IR), electrolyte abnormality, cardiac disorder, interstitial lung disease (ILD) were surveyed with special interest. Results: 3,091 patients were registered from Jun. 2010 to Nov. 2010 and interim analysis were made with 3,005 patients at the point of Oct. 2011. The interim analysis; male: 63.6%, mean age: 65 y.o., KRAS wild/ mutant/ not determinable: 97.3%/0.1%/2.6%. Proportion of first line/second line/third line or later treatment: 10.4%/18.0%/71.6%, PS 0-1/2/3/4: 91.3%/7.9%/0.7%/0.1%. P-mab monotherapy/combination: 41.0%/58.8%. Combination regimens: FOLFOX/FOLFIRI/other regimens: 18.7%/33.4%/15.2%. Overall incidence of ADRs:83.7 %, and that of Grade 3 or higher ADRs:24.7 %. Incidence of ADRs of special interest: skin disorder 77.8%, IR 1.5%, electrolyte abnormality18.3%, cardiac disorder 0.2%, ILD 1.3% (0.6% fatal). Incidences of ILD were similar in monotherapy and in combination. The median survival time of patients with P-mab monotherapy as third line or later treatment was 10.3 months, 95%CI (9.0-11.3). Result of final analysis with 3086 patients(99.8% of registerd patients) at the point of Jun. 2012 is to be presented in this meeting. Conclusions: The safety profile of P-mab in the post-marketing use was similar to that previously reported in the clinical trials. The risk/benefit balance for use of P-mab in patients with unresectable colorectal cancer remains favorable.
Impact of early palliative care consultation on inpatient length of stay and discharge disposition among oncology patients.
Authors: Ajay Dhakal, Suvash Shrestha, Peter Homel, Beth Popp
Journal: Journal of Clinical Oncology (2014)

53 Background: As palliative care develops as a medical subspecialty, studies are needed to assess its impact on patient care. Studies examining the effect of inpatient palliative care consult (PCC) on the admission length of stay (LOS) for non-ICU patients have failed to demonstrate consistent results. Also, there is a paucity of data on the effect of PCC on discharge disposition. The objective of this study is to examine the effect of early PCC on the length of stay and discharge disposition among cancer patients discharged alive. Methods: A retrospective review of oncology inpatients (pts) from January 2011 to Jan 2014 of whom 307 had PCC (PC group) and 305 pts did not have PCC (NC group). Visits less than 4 days, those ending with in-hospital deaths and those with PCC called more than 3 days into the admission were excluded. Groups were randomly matched based on All Patient Refined Diagnosis Related Group (APR DRG) Severity of Illness scores. Median LOS was compared with the Mann Whitney test. Pts coming from home without services (certified home health agency, advanced illness management, hospice, skilled nursing facility, or rehabilitation center) and discharged with services were considered favorable dispositions; any discharge without services was considered unfavorable disposition; all other dispositions considered neutral. Chi Square test was used to analyze discharge disposition. Results: The demographic profiles of 2 groups were similar in age, race, religion, marital status, insurance and living condition; females were more likely to get PCC (60 % vs 44 %, p&lt;0.001). Median (minimum, maximum) LOS for PC group was longer by 1 day: 8 (4, 76) days vs 7 (4, 251) days for NC group (p=0.003). PC group was more likely to receive a favorable discharge disposition (45 % vs 36 %); less likely to receive unfavorable discharge (13 % vs 28 %, overall p &lt; 0.001). Neutral dispositions were similar (41% vs 35 %). Conclusions: Oncology pts with PCC have 1 day longer LOS compared to those without it but are more likely to get a favorable discharge disposition. This may favorably impact readmission rates, which we hope to study in the future.