tbuckley/cabot-search huggingface dataset:
Use of pre-trial EBV titres as a measure of immune status: Further support for independence from health status of immunological response to G17DT in gemcitabine—G17DT combination pancreatic cancer trial patients
Authors: P. Broome, G. Mudde, R. Kircheis, A. Takhar, S. A. Watson
Journal: Journal of Clinical Oncology (2006)

4108 Background: In a Phase III pancreatic cancer trial combining G17DT with gemcitabine (Gem) vs Gem alone [ASCO 2005, Abstract 4012], a significant survival effect, independent of baseline KPS, was seen in patients with gastrin antibody response (Placebo + Gem 178 days vs 264 for antibody responders &gt; 16U, p = 0.03). A consistent criticism of such analyses of vaccine trials in cancer patients is that the immuno-responders reflect a fitter sub-population. To show that response to G17DT was at least partially independent of health status, pre-trial EBV titres, which can be considered as a marker of immunological status, were shown to be predictive of survival in the placebo group. However, in the G17DT treated group, antibody responders and non-responders had similar distributions of anti EBV titres. Methods: Baseline PC4 patient sera from both Gem alone (placebo) and Gem + G17DT groups were examined for antibodies against EBV by ELISA. The placebo patients were assigned high or low EBV status if they were respectively above or below the mean titre. Kaplan-Meier curves for these sub-populations were compared using the log rank statistic. G17DT-treated patients were grouped into high, low and non-responders. Mean EBV titres of the G17DT subgroups were compared with each other and with the placebo group using the t-test. Results: HighEBV titre was shown to predict improved survival in the placebo arm of the Phase III trial (Gem treatment only, p = 0.049). However, mean EBV titres were similar in high G17DT antibody responders cf non-responders (EBV titre 125 vs 159, p = 0.13) and in placebo patients cf non-responders (160 vs 159, p = 0.98). Conclusions: Pre-trial EBV titre, found to be predictive of survival in pancreatic cancer patients treated with gemcitabine, was similar between G17DT responders and non-responders, adding further weight to the hypothesis that G17DT response is substantially independent of health status. [Table: see text]
Bortezomib/dexamethasone versus VAD as induction prior to autologous stem cell transplantion (ASCT) in previously untreated multiple myeloma (MM): Updated data from IFM 2005/01 trial
Authors: J. L. Harousseau, C. Mathiot, M. Attal, G. Marit, D. Caillot, C. Hullin, T. Facon, I. Webb, H. Avet-Loiseau, P. Moreau
Journal: Journal of Clinical Oncology (2008)

8505 Background: ASCT is the standard of care for MM patients (pts) aged ≤65 yrs with high complete plus very good partial remission (CR+VGPR) rate. Improving CR rate has been associated with prolonged PFS and OS. Phase 2 studies have shown bortezomib (VELCADE)/dexamethasone (Vel/Dex) as an effective induction therapy. Methods: In this phase 3 study, Vel/Dex (4 cycles) was compared with vincristine/doxorubicin/dexamethasone (VAD; 4 cycles) as induction prior to ASCT in 482 MM pts aged ≤65 years. Primary objective was CR+near-CR (nCR) rate. Planned enrolment (480 pts) provided 80% power to detect a 10% difference in CR+nCR rate (10% vs 20%). Consolidation with 2 cycles of Dex, cyclophosphamide, etoposide, platinum (DCEP) was also evaluated. Pts were randomized to 4 arms: A1: VAD (N=121), A2: VAD+DCEP (N=121), B1: Vel/Dex (N=121), and B2: Vel/Dex+DCEP (N=119). Results: In the intent-to-treat analysis (ITT) Vel/Dex had significantly higher CR+nCR/≥VGPR vs VAD post-induction (21.3%/46.7% vs 8.3%/18.6%, P=0.0023/<0.0001); Vel/Dex was also superior in pts with >3mg/L or ≤3mg/L β2M and in pts with or without del(13). The significant CR+nCR/≥VGPR Vel/Dex advantage was maintained post-ASCT, both in pts who received ASCT (40.8%/71.8% vs 28.8%/51%, P=0.0089/<0.0001) and in the ITT population (35%/61.7% vs 23.6%/41.7%, P=0.0056/<0.0001); DCEP did not increase response rates. During induction, grade ≥3 adverse events (AEs) rates were similar with Vel/Dex and VAD (38.2% vs 40.6%); serious AE rates (25.2% vs 31.0%) and AEs leading to death (0.8% vs 2.9%) were lower with Vel/Dex, while neuropathic symptoms (all grades) were higher with Vel/Dex (35.3% vs 22.6%). Stem cell collection was adequate (>2×106 CD34+/kg) in 97% and 99% of Vel/Dex and VAD pts, respectively. First analyses of the survival data will be presented at the meeting. Conclusion: Vel/Dex significantly improved post-induction response rates vs VAD, which translated into significantly better ≥VGPR rates post-ASCT. Vel/Dex should now be considered the standard induction treatment prior to ASCT. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Millennium Celgene, Jansen Cilag, Pharmion Millennium Celgene, Jansen Cilag, Ortho Biotech, Pharmion
The in vivo targeting of tumor antigens to DCs by administration of transduced autologous lymphocytes results in robust and prolonged immunization: Pre-clinical validation and results of a pilot clinical studies of vaccination for metastatic melanoma
Authors: V. Russo, A. Cipponi, R. Fontana, D. Maggioni, F. Ciceri, F. Lunghi, M. Bregni, C. Bordignon, C. Traversari
Journal: Journal of Clinical Oncology (2006)

2525 Background: Genetically-modified-lymphocytes (GML) can induce a specific immune response against the transgene product (HSV-TK), when injected into immunocompetent patients (Science 276:1719, 1997). In tumor-bearing mice the infusion of tumor-associated-antigen (TAA)-transduced lymphocytes induced protective immunity and long-term memory. In this experimental setting, the T-cell effectors were generated by a cross-presentation pathway, mediated by host dendritic cells (DCs). Indeed, DCs isolated from lymph nodes of treated mice contained fragments of labeled GML and were able to elicit antigen-specific responses ex vivo. Methods: To validate this novel vaccination strategy in humans, we treated 10 patients affected by stage IIIc/IV MAGE-A3+ melanomas with escalating doses of autologous GML expressing MAGE-A3 and the tracer antigen HSV-TK. HSV-TK allows to monitor the immune status of the patients. Immune responses were monitored by DTH and in vitro T cell assays (semi-quantitative recall assays and ELISPOT). Tumor status was monitored by conventional imaging analyses. Results: No toxicity was reported. From the 10 patients, 9 were clinically evaluable because responding to the tracer antigen HSV-TK. We observed one complete response with vitiligo surrounding the lesions and one long lasting stable disease (50 mo). Moreover, one patient with no evidence of disease remained free of disease at &gt;48 mo. The 3 responding patients experienced both DTH reactivity to MAGE-A3 and sustained increase of circulating CD8+ and CD4+ MAGE-A3-specific effectors. The immune response was long lasting since MAGE-A3-specific effectors were still detectable both in vivo and in vitro 1 year after the last vaccination. Conclusions: We describe a new method for in vivo loading of TAA on DCs that may circumvent the limitations of ex vivo manipulation of DCs. Genetically modified lymphocytes, acting as antigen carriers, efficiently target DCs in vivo in tumor-bearing mice and in melanoma patients, resulting in the generation of TAA-specific effectors that correlate with clinical benefit. [Table: see text]
Use of the internet for self-education by adults with cancer
Authors: K. Castleton, M. A. Waqar, T. H. Fong, D. B. Jeffe, L. Kehlenbrink, F. Gao, R. Govindan
Journal: Journal of Clinical Oncology (2008)

6606 Background: Recently published articles have established that a substantial number of cancer patients are utilizing the internet to gather information about their respective diagnoses. The challenges for medical providers include understanding the prevalence of self-help internet usage, the time-point of access during care, and the use of specific online resources. Methods: Adults with cancer were asked to complete a self-administered, anonymous, 21-item questionnaire upon registration at Siteman Cancer Center at Washington University School of Medicine. Results: The characteristics of 500 participants who responded to the questionnaire: mean age 58 years (range 18- 90), 83% Caucasian and 15% African American. The most common diagnoses included breast (25%), blood/bone marrow (25%), gastro-intestinal (16%), lung/esophageal (15%), and head/neck (7%) cancers. Three hundred ninety eight reported access to the internet and of those, 315 participants reported searching for information about cancer on the internet. Patients accessing the internet for cancer information tended to be younger on average than those who did not (56 vs. 63 years; p< 0.001). Internet usage for cancer information differed by race (p<0.0001) and education (p<0.0001). Those with education beyond the twelfth grade were more likely to search the internet for cancer information. Fifty-four percent searched the internet for cancer information prior to their first oncologist visit and 71% used search engines to produce websites. Among patients who searched the internet for cancer information, 78% were familiar with the American Cancer Society website, 43% WebMD, 37% National Cancer Institute, 10% People Living With Cancer, and 10% American Society of Clinical Oncology. Conclusions: Approximately two-thirds of patients with cancer use the internet to obtain information about their disease. Factors affecting internet use for cancer information include age, race and level of education. A number of highly reputable cancer-organization websites are under-utilized by patients. No significant financial relationships to disclose.
Safety and efficacy of third-line bosutinib in imatinib (IM) and dasatinib (DAS) resistant or intolerant chronic phase (CP) chronic myeloid leukemia (CML).
Authors: H. J. Khoury, D. Kim, A. Zaritskey, J. Apperley, N. Besson, A. Volkert, J. Wang, S. Arkin, J. E. Cortes
Journal: Journal of Clinical Oncology (2010)

6514 Background: Bosutinib (SKI-606) is an oral Src/Abl kinase inhibitor, evaluated in an ongoing phase I/II study in CML patients (pts) with resistance/intolerance to IM ± other tyrosine kinase inhibitors. Methods: 88 CP pts previously exposed to IM and DAS received bosutinib 500 mg daily. Results: Data are reported for 36 DAS-resistant pts and 52 DAS-intolerant pts, of which 32/36 and 29/52 respectively, were IM-resistant. Median age was 57 (21-79) years; time from diagnosis to start of bosutinib was 6 (0.6-18.3) years. Self-limited (median duration 27.5 days), early onset (median onset 1 day) gastrointestinal adverse events (AEs) were the most common treatment-emergent side effects, and included diarrhea (81%), nausea (45%), and vomiting (38%). Grade 3-4 nonhematologic AEs (≥5% of pts) were diarrhea (7%), rash (7%), and increased ALT (5%). A single pt experienced grade 3 pleural effusion in the setting of concomitant pneumonia and a history of recurrent pleural effusions on DAS. Grade 3-4 hematologic abnormalities included thrombocytopenia (21%), neutropenia (10%), and anemia (9%). 32 pts (36%) required dose reductions, and median daily dose was 454 mg for DAS-resistant, 393 mg for DAS-intolerant pts; 19 pts (22%) discontinued bosutinib for toxicity. The efficacy is summarized in the Table according to the response at time of study entry. 55 pts had BCR-ABL mutations analyses and 13 different mutations were found in 17 pts (31%). Responses in evaluable pts with and without mutations were as follows: 86% and 95% CHR, 42% and 44% MCyR, respectively. Conclusions: Bosutinib is an effective and well tolerated third-line agent in CP CML after IM/DAS failure. Transient and manageable gastrointestinal AEs are the most common side effects. Third-line pts DAS-resistant n (%) DAS-intolerant n (%) Hematologic response Evaluable* 23 24 Complete 16 (70) 19 (79) Cytogenetic response Evaluable* 20 26 Major 5 (25) 10 (38) Complete 3 (15) 9 (35) Molecular response Evaluable* 20 35 Major 2 (10) 13 (37) Complete 1 (5) 9 (26) Median follow-up duration (months) 13.1 (0.2-35.1) 16.5 (0.3-33.9) * Pts without CHR, CCyR, or CMR at baseline, and with ≥ 1 post-baseline assessment for respective response. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Pfizer, Wyeth Bristol-Myers Squibb, Novartis, Pfizer, Wyeth Bristol-Myers Squibb, Novartis Bristol-Myers Squibb, Novartis, Pfizer, Wyeth
The clinical impact of proliferative high-risk lesions presenting concurrently with ductal carcinoma in situ (DCIS) in patients (pts) treated with breast conserving therapy (BCT)
Authors: L. J. Adepoju, W. F. Symmans, G. V. Babiera, S. E. Singletary, N. Sneige, T. A. Buchholz, K. K. Hunt, F. Meric-Bernstam, B. Arun, H. M. Kuerer
Journal: Journal of Clinical Oncology (2005)

632 Background: Atypical ductal hyperplasia (ADH), atypical lobular hyperplasia, and lobular carcinoma in situ (ALH/LCIS) are associated with an increased risk of development of breast cancer. The clinical significance of a concurrent diagnosis of ADH and or ALH/LCIS with DCIS in pts treated with BCT is unknown with respect to risk of local recurrence and subsequent risk of contralateral breast cancer (CBC). Methods: Following IRB approval, 313 pts were identified from our prospective institutional database. Pts were treated with BCT from 1968 to 1999 for a diagnosis of DCIS and their complete medical records were analyzed with particular attention to pathology reports noting the presence of ADH or ALH/LCIS within the tumor or within normal adjacent tissue. Actuarial local recurrence rates were calculated by the Kaplan-Meier method and differences between groups were tested using the log-rank test. Results: Median follow-up time was 94 months. Of the 313 pts with DCIS, 73 also had ADH, 27 also had ALH/LCIS and 12 also had both ADH and ALH/LCIS. Ten-year ipsilateral local recurrence was 7.93% for pts with ADH, ALH/LCIS, or both compared with 13.8% for pts without these lesions (P=0.39). The rate of CBC development in pts with a diagnosis of DCIS with concurrent ADH was 3 times greater than pts with a current diagnosis of DCIS alone (P<0.01). The cumulative risk of CBC development was 10.7% in pts with a diagnosis of DCIS and ADH compared with 3.52% in pts with DCIS alone (P<0.01). Pts with a diagnosis of DCIS and ADH or ALH/LCIS also had a statistically higher rate of contralateral breast cancer prior to their diagnosis of DCIS compared to pts without these proliferative lesions (11.76% vs. 5.26%, P=0.04). Conclusions: The additional risk of development of CBC associated with a diagnosis of DCIS alone compared with a concurrent diagnosis of DCIS and proliferative breast lesions has not been previously reported. Pts with this clinical entity may be appropriate candidates for additional chemoprevention strategies. The presence of ADH and ALH/LCIS in pts with DCIS does not preclude BCT. No significant financial relationships to disclose.
Evaluation of local control in patients with non-metastatic Ewing sarcoma of the bone: A report from the Children's Oncology Group
Authors: S. G. DuBois, M. D. Krailo, E. F. Cook, N. J. Tarbell, C. J. Fryer, M. C. Gebhardt, K. Brown, J. S. Miser, N. M. Marina, H. E. Grier
Journal: Journal of Clinical Oncology (2007)

10013 Background: Options for local control in patients (pts) with Ewing sarcoma (EWS) include surgery (S), radiation (R), or surgery plus radiation (S+R). The choice of local control depends on factors that also impact outcome in EWS, including tumor site, tumor size, and age. Our objective was to determine if risk of disease progression differs between local control methods, after controlling for potential confounders. Methods: We analyzed the cohort of pts with non-metastatic EWS of the bone treated on Intergroup Study-0091 (Grier et al, NEJM, 2003). Local control decisions were made on an individual basis. We excluded pts with tumors of the skull/face, progression prior to end of local control, or incomplete local control data. Disease progression was recorded from end of local control. Cumulative incidence of disease progression was determined using a competing risks approach. We constructed a Cox proportional hazards model of progression free survival incorporating local control mode and potential confounders into the model. Secondary analyses evaluated overall survival, local failure, and distant failure. Results: 329 pts met eligibility criteria for analysis. 122 pts received S, 142 received R, and 65 received S+R. The cumulative incidence of disease progression at 5 years was 22.1% (95% CI 15.1–29.9%) for S, 36.9% (29.0–44.9%) for R, and 48.1% (35.5- 59.7%) for S+R. Using R as the reference group and controlling for age, tumor size, tumor location, and chemotherapy regimen, the hazard ratio for progression was 0.66 (95% CI 0.38–1.13) for S and 1.55 (0.96–2.49) for S+R. The hazard ratio for death was 0.77 (95% CI 0.44–1.34) for S and 1.46 (0.88–2.42) for S+R. The hazard ratio for local failure was 0.38 (95% CI 0.15–0.98; p=0.04) for S and 0.77 (0.34–1.75) for S+R. The hazard ratio for distant failure was 0.78 (0.42–1.46) for S and 1.60 (0.91–2.82) for S+R. Conclusions: Observed differences in outcome between local control groups are largely due to confounding factors that affect outcome and local control choice. Risk of disease progression, distant failure, or death does not differ between pts who receive S or R. Pts who receive S have a decreased risk of local failure compared to pts who receive R. No significant financial relationships to disclose.
Feasibility study of TS-1 additional therapy for the triple-negative breast cancer received neoadjuvant or adjuvant chemotherapy (SBCCSG14).
Authors: Kazushige Futsuhara, Kenichi Inoue, Shigenori E. Nagai, Tsuyoshi Saito, Takashi Sakurai, Kei Kimizuka, Masafumi Kurozumi, Toshio Tabei, Hirofumi Yamada, Masato Kojima, Satoshi Hata, Yasuo Yamazaki
Journal: Journal of Clinical Oncology (2014)

162 Background: Prospective randomized clinical trials have demonstrated a significant advantage from postoperative adjuvant chemotherapy for patients with breast cancer. However, triple-negative breast cancer is high rate of early recurrence. Therefore, patients who do not achieve pathological complete response (pCR) for neoadjuvant chemotherapy have worse long-term survival than patients who achieve pCR. Treatment after adjuvant chemotherapy and neoadjuvant chemotherapy is not established yet. We notice that TS-1 improve early recurrent rate of breast cancer. TS-1 proved good response for advanced breast cancer and long-term therapy is possible. We planned the study for the purpose of inspecting it about the safety, completion and efficacy of giving TS-1 after standard therapy of triple negative breast cancer for one year. Methods: The patients with stage ±/II/ III triple negative breast cancer received neoadjuvant or adjuvant chemotherapy and surgery and/or radiotherapy. Furthermore, the cases of neoadjuvant chemotherapy did not achieved pCR. After that, dose of TS-1 is 80mg/m² administered orally daily for 2 weeks followed by a 1-week rest period given as 3-week cycles. Results: 63 patients were enrolled, including 44 patients received neoadjuvant chemotherapy and 19 patients received adjuvant chemotherapy. The average age is 50 years (28-68 years). 38 cases (60.3%) brought oral administration for one year to completion. The reasons of discontinuance were 15 cases of toxicity and 10 cases of recurrence. Average relative dose intensity was 80%. The compliance of TS-1 was 70.1% (222.4 days). Overall survival of 3 years was 86.47%, progression-free survival 50.8%. The overall incidence of toxicity was 54 cases (85.7%), and grade 3 toxicity occurred in 21 cases (33.3%). Conclusions: The compliance of TS-1 was approximately equal to the compliance for gastric cancer in spite of receiving treatments of anthracycline and/or taxane. The toxicity was approximately equal to the results for metastatic breast cancer. TS-1 administered orally for one year was feasible for triple negative breast cancer received standard therapy. Clinical trial information: UMIN000001414.
Urine di-acetyl sperimine (DiAcSpm) as a new cancer screening marker for colorectal cancer
Authors: K. Takahashi, K. Hiramatsu, T. Yamaguchi, H. Matsumoto, H. Miyamoto, S. Saji, T. Mori, M. Kawakita
Journal: Journal of Clinical Oncology (2005)

3731 Backgrounds: For colorectal cancer screening fecal-occult blood test (FOBT) is the standard screening test all over the world. But the positive predict value (PPV) in colorectal cancer is about 60%. Fecal DNA analysis is too expensive and is difficult to use colorectal cancer screening in clinical practice. It is necessary to combine another non-invasive new test with FOBT to improve the PPV. In this paper we clarified the possibility to use urine 1N12N-di-acetyl spermine (DiAcSpm) for colorectal cancer screening. DiAcSpm increases for several kinds of cancer. We succeeded the quantity of DiAcSpm by ELIZA. Method: In this paper we examined urine DiAcSpm(normal range: 0∼0.25μmol/g · creatinine) and serum CEA(normal range: 0∼5.0ng/ml) for 185 colorectal cancer patients and 9 hemorrhoid patients preoperatively. The study endpoint was the definition of pathological diagnosis. Results: Positive rate of each stage in 185 cases was as follows;stage 0 (N=21): 62% for urine DiAcSpm and 9.5% for serum CEA respectively, stageI (N=40):60% and 10%, stageII(N=60):70% and 42%, stageIII(N=113):82% and 47%, and stageIV(N=16):88% and 63%. In proportion to staging, the positive rates for both markers became high. Especially urine DiAcSpm level for stage 0 and stage 1 colorectal cancer showed statistically significant higher than serum CEA(p<0.0001). Both of urine DiAcSpm level and serum CEA level for all of hemorrhoid patients were within normal range. Conclusions: The positive rate of urine DiAcSpm showed more than 60% even for early colorectal cancer. It suggested that the combination of FOBT and urine DiAcSpm realized the improvement of colorectal cancer screening. No significant financial relationships to disclose.