tbuckley/cabot-search huggingface dataset:
Final data of the multicenter phase II study of cisplatin (CDDP) and 5-fluorouracil (5-FU) in combination with G17DT Immunogen in chemonaive patients with locally recurrent or metastatic gastric and gastroesophageal cancer
Authors: D. Michaeli, J. R. Hecht, M. Oortgiesen, A. Eduljee, W. D. Perkins, J. A. Ajani
Journal: Journal of Clinical Oncology (2004)

4048 Background: G17DT is an immunogen designed to raise antibodies to the growth factor gastrin 17 (G17). The purpose of the study was to determine the safety and efficacy of G17DT in combination with CDDP and 5-FU. Interim data indicated a correlation between survival and anti-G17 immune response, which was further explored in analyses of the final data. Methods: Main eligibility criteria for the open label study were: metastatic or locally recurrent gastric/gastroesophageal cancer; measurable disease; chemotherapy naive; intact organ function; KPS≥70. Patients received G17DT (500 μg, im) treatments at wks 2, 6, 10 and 26; CDDP 100 mg/m2 d1; continuous infusion 5-FU 1000 mg/m2 /d d1–5 q28 days. Endpoints: tumor response (per RECIST), survival, immune response and safety. Results: A total of 102 patients were enrolled. The best overall tumor response was 1 CR (1%), 39 PR (49%), 25 SD (32%) and 14 PD (18%). One patient, with PR, converted to CR after additional G17DT treatment in an extension protocol. Overall median survival was 8.7 months. The immune response occurred in 63% patients with anti-G17 titer ≥ 1 ELISA unit for 2 consecutive wks; 75% with at least 1 titer ≥ 1. Toxicity was consistent with CDDP+5-FU except for 3 NCI-CTC Grade-3 injection site reactions attributed to G17DT. Multivariate analysis showed the immune response as a predictor of tumor response and survival (Log rank: p=0.032 and p<0.001, respectively). Median survival was 10 months for anti-G17 responders and 2.3 months for non-responders. With the exception of performance status, no baseline parameters such as sex, age, race, location of metastases or organ systems involved with metastasis(es) significantly correlated with the anti-G17 response. After adjustment for KPS, the correlation between the anti-G17 response and survival remained statistically significant (p<0.001). Conclusion: The G17DT immune response predicts response and survival in untreated, advanced gastric cancer patients, offering promising prospects for an improved anti-cancer treatment regimen. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Aphton Corp. Aphton Corporation
Predictors of microinvasion and its prognostic role in ductal carcinoma in situ.
Authors: Gloria Sue, Donald R. Lannin, Brigid K. Killelea, Nina Ruth Horowitz, Anees B. Chagpar
Journal: Journal of Clinical Oncology (2012)

188 Background: Predictors of microinvasion in ductal carcinoma in situ (DCIS) are not well understood. We sought to determine factors predicting microinvasion and the prognostic role this plays in patients with DCIS. Methods: A retrospective cohort study of 205 consecutive patients presenting to the Yale Breast Center with DCIS from 2000 through 2003 was performed. A chart review was conducted and bivariate and multivariate analyses comparing patients with and without possible microinvasion were performed. Statistical analyses were done using SPSS software version 19. Results: Of the 205 patients who presented with DCIS and were treated with surgical excision, 51 (24.9%) had evidence of possible microinvasion on final pathology. The median age of all patients was 53.0 years (range 35.8 to 88.9). On bivariate analysis, patients with microinvasion had larger areas of DCIS, and were more likely to have high grade DCIS, of solid type, associated with necrosis and microcalcifications (see table). There was a trend towards white women having a higher rate of microinvasion than black women (26.9% vs. 8.7%, p=0.061). On multivariate analysis, none of these factors were independent predictors of microinvasion. With a median follow-up of 8.5 years, there was no difference in the likelihood of recurrence in the microinvasion vs. no microinvasion groups (6.0% vs. 7.2%, p=1.000). 5-year actuarial overall survival was also not different between the two groups (96% vs. 94%, p=0.202, respectively). Conclusions: Patients with larger DCIS size, higher grade, solid histology, necrosis, and microcalcifications have a higher likelihood of microinvasion. However, the presence of possible microinvasion does not significantly increase risk of recurrence or decrease survival. [Table: see text]
Fixed dose-rate gemcitabine (GEM) infusion in advanced pancreatic (PDAC) and biliary tree (BTC) carcinoma: A phase II study
Authors: A. Gelibter, S. Di Cosimo, E. M. Ruggeri, P. Carlini, E. Bria, P. Malaguti, M. Pellicciotta, E. Terzoli, F. Cognetti, M. Milella
Journal: Journal of Clinical Oncology (2004)

4182 Background: Weekly GEM infused over 30 min is considered the standard of care for advanced PDAC and has activity in advanced BTC. However, a fixed dose-rate infusion at the rate of 10 mg/m2/min has theoretical pharmacokinetic advantages and may result in improved therapeutic efficacy. Methods: From April 2002 to September 2003, 40 advanced PDAC (n = 27) or BTC (n = 13) pts (median age: 63 yrs, range 45–77; M/F: 21/19; PDAC/BTC: 27/13; LA/Met: 9/31; PS 0/1/2: 18/15/7) were treated with GEM 1000 mg/m2 at the fixed dose-rate of 10 mg/m2/min for 7 consecutive wks and weekly x 3 q4 wks thereafter (FDR-GEM). All 40 patients and 427 treatment weeks were evaluable for toxicity, 38 patients had measurable/evaluable disease according to WHO criteria and were evaluable for response, 32 patients were evaluable for clinical benefit response (CBR) according to Burris criteria, and 25 patients had elevated CA19.9 serum levels at entry. Results: Median number of treatment wks delivered was 6 (range 2–22); toxicity was mild with G3–4 neutropenia in 18/427 (4,2%) wks, G3 anemia and thrombocytopenia in 9/427 (2,1%) and 6/427 (1,4%) wks, respectively, G3 ASAT elevation in 5/427 (1,1%) wks, and G3–4 ALAT elevation in 16/427 (3,7%) wks. Six out of 38 evaluable pts had a PR, 7 had a MR, 13 had SD, and 12 had PD. ORR according to the intent-to-treat was 15% (95% CI 4–26%). A positive CBR was obtained in 14/32 (44%) pts. Seventeen out of 25 (68%) pts had a reduction in CA19.9 >25%. Median TTF and median TTP were 17 (95% C.I.: 13–22) and 19 (95% C.I.: 15–23) weeks, respectively. Median OS was 40 weeks (95% C.I.: 36–45) and 1-year actuarial survival rate was 25.8%. At multivariate analysis, PS 0–1 at entry and locally advanced disease were the only independent predictors of longer TTP and OS, while a reduction in circulating CA19.9 serum levels >75% was an independent predictor of longer TTP, but had no impact on OS. Conclusions: In terms of cost/benefit ratio, the results obtained with FDR-GEM compare favorably with those reported in the literature for GEM-based combinations and indicate that pharmacokinetically rationale GEM scheduling may improve its therapeutic index. No significant financial relationships to disclose.
Abstract 12107: Increased Expression and Plasma Levels of Neopterin are Associated with Left Ventricular Remodeling after Reperfusion in Patients with Acute Myocardial Infarction
Authors: Kei Yunoki, Takahiko Naruko, Kazuki Mizutani, Ryushi Komatsu, Kazuo Haze, Akira Itoh, Kenichi Sugioka, Mayumi Inaba, Makiko Ueda
Journal: Circulation (2012)

Background: Neopterin is produced by activated monocytes/macrophages after stimulation by interferon-γ. In this study, we investigated whether plasma neopterin levels are associated with LV remodel...
Imatinib for the treatment of aggressive fibromatosis/desmoid tumors (AF/DT) failing local treatment: updated outcome and predictive factors for progression free survival. A FNCLCC French Sarcoma Group-GETO study
Authors: J. Fayette, A. Dufresne, N. Penel, A. Le Cesne, B. Bui Nguyen, M. Tubiana-Hulin, C. Guillemet, S. Chabaud, M. Jimenez, J. Y. Blay
Journal: Journal of Clinical Oncology (2007)

10062 Background: The optimal treatment of AF/DT failing local treatments is not defined. We report long term results and predictive factors for response to imatinib in AF/DT. Methods: Pts =18 years with advanced AF/DT from all sites in whom neither curative surgery nor radiotherapy (RT) was possible were eligible. Imatinib was given at the dose of 400mg/d (and increased to 800 mg/d if progression) during 1 year then stopped. Primary endpoint was the progression free at 3 months. A two stages Simon‘s optimal design was used with p 0 =10%, p 1 =30%, a=0.05 and 90% power (18 pts first stage, total of 35 evaluable pts). Predictive factors were investigated using tissue-microarrays (TMA) and KIT mutation analysis. Results: Between 09/2004 and 10/2005, 40 pts were included in 15 centers. Median age was 40 (range 20–72) with 30% males. Primary sites were extra abdominal, mesenteric, and abdominal wall in 69, 18, and 13% of pts respectively. 23% had received RT. Prior systemic treatments were: NSAID, hormonotherapy or chemotherapy (CT) in 33%, 45% and 20% of pts respectively. Median treatment duration of imatinib is 9 months (range 0.8–13.8). G4 and G3 toxicities were notified in 0 and 17 patients (42.5%) respectively: rash (4 pts), abdominal pain (3 pts), and vomiting (3 pts). 38 pts (95%) are evaluable at 3 months, with 1 (3%) CR, 3 (8%) RP, 31 (82%) SD and 3 (8%) PD. With a median follow-up of 13.8 months, 13 of the 40 pts had progressed. PFS at one year is 71% and 1 patient died (PD). 8 patients received an increased dose of imatinib upon progression under a 400mg/d dose: 3 reprogressed and 5 achieved tumor stabilization during 5+, 6+, 8+ months. PFS was correlated to weight or to previous CT, but not to gender, Gardner, age, PS, size, site. Using TMA, the expression of PDGFR β and a β catenin, E-cadherine, cyclinD1, M-CSFR, estrogen receptor β, ERK, phospho-Akt-Ser473, phospho-MEK1–2 were investigated. None of the CycD1+ tumors have progressed so far. 3 mutations of KIT exon 10 were detected in 10 patients tested. All achieved tumor control. Conclusions: Imatinib induces prolonged disease stabilization in the majority of evaluable patients with AF/DT. Prognostic factors were identified. [Table: see text]
A phase I trial of bexarotene, a retinoid X receptor agonist, in relapsed or refractory non-M3 acute myeloid leukemia (AML)
Authors: D. E. Tsai, S. M. Luger, A. W. Loren, A. Kemner, J. Thompson, S. J. Schuster, A. Perl, D. L. Porter, A. Bagg, M. Carroll
Journal: Journal of Clinical Oncology (2006)

6567 Background: In vitro, bexarotene inhibits the proliferation of non-M3 AML cell lines and induces differentiation of leukemic blasts. This phase I study was designed to evaluate the safety of escalating doses of bexarotene in patients with relapsed or refractory non-M3 AML. Methods: Bexarotene was administered orally daily until disease progression occurred. Five dose levels ranging from 100 to 300 mg/m 2 were planned. Dose escalation occurred in cohorts of 3–6 patients based on dose-limiting toxicity. Results: Fourteen patients have been enrolled in 4 dose cohorts (100–250 mg/m 2 ) with enrollment demographics: 8M/6F, median age 63 (range 51–76), 6 prior MDS, 6 primary refractory, median number of induction attempts 2, prior autologous stem cell transplant 4, 14 blood transfusion dependent, 12 platelet transfusion dependent, and 12 neutropenic. Two patients developed hypothyroidism. Despite prophylactic use of antihyperlipidemic agents, 4 patients developed grade 2 or 3 hypertriglyceridemia. Two patients developed a syndrome reminiscent of retinoic acid syndrome, consisting of dyspnea/hypoxia, pleural/pericardial effusions, weight gain/edema and dry cough in the setting of a rapidly rising neutrophil count. This syndrome resolved within 48 hours of stopping bexarotene and initiating steroids. One patient had a WBC rise from 1.7×10 3 /μL (ANC 1,037/μL, 18% blasts) pre-bexarotene to 23.9×10 3 /μL (ANC 19,368/μL, 3% blasts) during this syndrome. Flow cell sorted peripheral blood neutrophils all contained this patient’s original t(8;21) by FISH, suggesting differentiation of the leukemic blasts. Bone marrow blasts decreased to ≤5% in two patients. Three platelet transfusion dependent patients had increases in their platelet counts to a peak count of 40–292×10 3 /μL on bexarotene. Conclusion: Daily oral bexarotene is well tolerated at the dose levels studied to date. Early evidence for activity has been seen as exemplified by improvement in platelet counts, decreased bone marrow blast counts, blast differentiation and possible retinoic acid syndrome. Patient enrollment is ongoing. [Table: see text]
Updated results, multivariate and subgroups analysis confirm improved activity and efficacy for FOLFOXIRI versus FOLFIRI in the G.O.N.O. randomized phase III study in metastatic colorectal cancer (MCRC)
Authors: A. Falcone, M. Andreuccetti, I. Brunetti, S. Ricci, C. Barbara, W. Evangelista, V. Passeri, S. Chiara, G. Allegrini, G. Masi
Journal: Journal of Clinical Oncology (2007)

4026 Background: As previously reported (ASCO 2006) the G.O.N.O. conduced a phase III study comparing FOLFIRI to FOLFOXIRI in 244 patients (pts) with not resectable MCRC. At a median follow-up of 18.4 months (mos) we reported significant improvements in response-rate (RR), R0 resection of metastases (mts), PFS and OS for FOLFOXIRI. Methods: Results have been updated (median follow-up of 36.2 mos) and 14 variables were tested as possible prognostic factors for response, R0 resection, PFS and OS. Results: At this updated analysis 225 (111 vs 114) pts have progressed and 180 (84 vs 96) have died. Results confirm the significant improvements for FOLFOXIRI in terms of confirmed RR (60% vs 34% p&lt;0.001), R0 resection of residual mts (15% vs 6% p=0.033 and 36% vs 12% p=0.017 for pts with liver only mts), PFS (median 9.8 vs 6.9 mos p&lt;0.001) and OS (median 23.6 vs 16.7 mos p=0.042) at the cost of a modest and acceptable increase in toxicity. In the logistic regression multivariate analysis treatment with FOLFOXIRI was the only independent predictive factor for response (HR:2.9, p&lt;0.001) and for achieving an R0 surgical resection of mts (HR:3.1, p=0.018). The Cox’s multivariate analysis demonstrates that independent prognostic factors for improved time to progression were treatment with FOLFOXIRI (HR:0.64, p&lt;0.001), and ECOG PS = 0 (HR:0.73, p=0.02) and for time to death were treatment with FOLFOXIRI (HR:0.74, p=0.04) and liver involvement &lt;25% (HR:0.57, p=0.006). The benefits of FOLFOXIRI was consistent across all subgroups, including those with unfavorable prognosis such as pts with time from diagnosis to randomization &lt;3 mos, multiple site of disease or liver involvement ≥ 25%. Conclusions: FOLFOXIRI confirms to be the first combination demonstrated to be superior to an infusional 5FU containing doublet as FOLFIRI in terms of RR, R0 resections, PFS and OS. FOLFOXIRI represents a new treatment option in MCRC and its use and study is of particular interest in a neoadjuvant strategy, in pts with few chances to achieve a three-drug exposure in a sequential strategy and in combination with targeted agents. Partially supported by Fondazione ARCO. No significant financial relationships to disclose.
Carbon ion radiotherapy for bone and soft tissue sarcomas
Authors: T. Kamada, R. Imai, H. Tsujii, H. Tsuji, I. Serizawa
Journal: Journal of Clinical Oncology (2008)

10538 Background: Carbon ion radiotherapy showed promising clinical outcomes in 57 patients with bone and STS during the phase I study (Kamada, JCO 22 4466–4471, 2002). This phase II study was planned thereafter. Methods: From April 2000 to February 2007, 301 lesions of 282 patients with bone and STS not suited for surgical resection were enrolled in this phase II study. A total dose of 64.0 GyE in 16 fractions over 4 weeks was indicated for 15 lesions, that of 70.4 GyE for 276 and remaining 10 receiving 73.6 GyE. Mean age was 52 yrs, (range 12–85); site of origin was the pelvis in 74%, spine or para-spinous soft tissue in 20%, extremities in 5%; bone primary was in 78% and soft tissue in 22%; pathologic subtype in bone sarcoma was chordoma in 42%, chondrosarcoma in 21%, osteosarcoma in 21%; pathologic subtype in STS was MFH in 23%, MPNST in 21%, synovial sarcoma in 13%. Results: The 3- and 5-year overall actuarial survival rates were 68% (95% CI, 61%-75%) and 52% (95% CI, 43%-61%), respectively, and the actuarial overall local control rates were 85% (95% CI, 80%- 90%), and 81% (95% CI, 74%-88%) at 3 years and 5 years of follow-up, respectively. Overall toxicity was acceptable, with 2% skin/soft tissue late G3/4 toxicity. Conclusions: Carbon ion radiotherapy shows a substantial local control in the patients with bone and soft tissue sarcomas not suited for surgical resection with acceptable morbidity. No significant financial relationships to disclose.
Impact of cetuximab-irinotecan salvage combination on overall survival (OS) in refractory metastatic colorectal cancer (mCRC)
Authors: J. F. Seitz, L. Dahan, K. Richard
Journal: Journal of Clinical Oncology (2005)

3737 Background: Cetuximab (CTX) is an IgG1 monoclonal antibody targeting the EGFR, shown to be effective in patients with EGFR+, irinotecan (IRI)refractory mCRC: in heavily pretreated patients with progressive disease under IRI, CTX combined with IRI gave an additional TTP of 4.1 months (vs 1.5 mo with CTX alone), and a median survival of 8.6 mo (vs 6.9 mo with CTX alone) from the beginning of salvage CTX treatment (Cunningham NEJM 2004). However we don’t know the OS of these pts, calculated from the beginning of the first line chemotherapy. The purpose of our study was to evaluate this OS. Methods: this retrospective monocentric study involved 24 patients with IRI-refractory mCRC, included in two open multicenter phase II trials, in which pts were treated with CTX-IRI combination or CTX alone (and then the combination in case of progression). The treatment associated CTX (400 mg/m2 week 1 and 250 mg/m2 weekly thereafter) and IRI according to the regimen before inclusion. Results: median age of these 24 patients was 53 yrs [31–78], median PS 1 [0–2], median number of previous chemotherapies was 3 [1–4], 22/24 received prior oxaliplatin tratment. 21/24 were EGFR+ (87,5%). Among them, only 18 patients initiated treatment. The 18 patients received CTX-IRI combination, either first (15 patients), or after progression under CTX alone (3 patients). Among 14 evaluable pts, 3 had partial response (21.4%), 6 a stabilization (42.9%): disease control was 64.3%. The OS of these 24 pts was 31.8 mo [24.2–39.4]; it was 23.1 months [11,4 - 34,7] for the 6 patients not treated by CTX, and 34,6 months [25.2 - 44.1] for the 18 patients treated (p=0.58). Overall survival at 2 years was 68.5% (83.3% for the 18 treated patients and 44.4% for the 6 untreated). The median PFS of the treated pts is 3.87 mo [2.95–9.34]. The median number of weekly cycles of CTX was 12 [1–42]. Conclusions: These results (median OS: 31.8 mo from the beginning of 1st line chemotherapy in mCRC pts receiving CTX-IRI salvage combination) compare favourably with the recent trials (OS 20–21 mo: Tournigand JCO 2004, Hurwitz NEJM 2004) or subset analysis (OS 25 mo: Hedrick ASCO 2004) in which pts received all 3 active agents (5FU/LV, OXA, IRI). Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Merck
Distinct Profiles of in Vivo Class Switch Recombination in Chronic Lymphocytic Leukemia Subsets with Stereotyped B Cell Receptors, Suggestive of Distinct Modes of Activation by Antigen
Authors: Aliki Xochelli, Evangelia Stalika, Lesley-Ann Sutton, Vassiliki Douka, Maria Karypidou, Michalis Iskas, Maria Chatzouli, Antonis Dagklis, Achilles Anagnostopoulos, Paolo Ghia, Richard Rosenquist, Nikos Darzentas, Chrysoula Belessi, Kostas Stamatopoulos
Journal: Blood (2012)
Effects of ethnicity on genotype-phenotype correlations in individuals with a <i>BRCA1</i> or <i>BRCA2</i> mutation.
Authors: M. Jackson, A. Brandt, A. Gutierrez-Barrera, F. Meric-Bernstam, J. K. Litton, K. H. Lu, G. N. Hortobagyi, B. Arun
Journal: Journal of Clinical Oncology (2010)

6060 Background: Genotype-phenotype correlations have yet to be established of know BRCA1/2 mutations. A recent study found that mutations in BRCA1 were most frequently located in exons 2, 11, 13, 20, and mutations in exon 2 had lower penetrance comparatively. However, no study has examined the influence of ethnicity. The study aim was to evaluate the influences of ethnicity on mutation location. Methods: Women who were evaluated in the Clinical Cancer Genetics Program and were found to have a deleterious BRCA1 or BRCA2 mutation were included in the study. BRCA1 and BRCA2 mutation location and self-reported ethnicity were obtained through a retrospective review of a prospectively maintained research database. Results: Of 443 women identified, 250 (56.4%) had a BRCA1 mutation and 193 (43.6%) had a BRCA2 mutation. The most common ethnicities identified in this population were as follows: 297 (67%) were non-Ashkenazi Jewish European including women of Caucasian ancestry, 58 (13.1%) were Ashkenazi Jewish, 32 (7.2%) were Hispanic, 23 (5.2%) were African American, and 33 (7.4%) were of “other” ancestry. Exon 2 (16.5%), exon 11 (42.6%), and exon 20 (10.4%) were the most common locations for BRCA1 mutations and the remaining were located elsewhere (30.5%). For BRCA2, exon 10 (14%), exon 11 (48.2%), and exon 25 (6.2%) were the most common locations and the rest were in the other exons (31.6%). Conclusions: Women with a BRCA mutation were mostly non- Ashkenazi Jewish Europeans. Ashkenazi Jewish women had mutations most often in exons 2 and 20 in BRCA1 and exon 17 in BRCA2, since those are the locations of the three founder mutations. For Hispanics and African Americans, mutations were frequently in exon 11 of BRCA1. The implications of exon 11 in BRCA1/2 on breast cancer risk in certain ethnic populations need to be further evaluated. BRCA1 (exon location) BRCA2 (exon location) 2 n = 41 (%) 11 n = 107 (%) 20 n = 26 (%) 10 n = 27 (%) 11 n = 93 (%) 25 n = 12 (%) Non-Ashkenazi Jewish European 11 (26.8) 82 (76.6) 15 (57.7) 20 (74.1) 65 (70) 6 (50) Ashkenazi Jewish 25 (61) 0 (0) 11 (42.3) 2 (7.4) 17 (18.3) 0 (0) Hispanic 2 (4.9) 13 (12.1) 0 (0) 1 (4.2) 4 (4.3) 2 (16.7) African American 0 (0) 5 (4.7) 0 (0) 4 (14.8) 3 (3.2) 1 (8.3) Other 3 (7.3) 7 (6.5) 0 (0) 0 (0) 4 (4.3) 5 (41.6) No significant financial relationships to disclose.