tbuckley/cabot-search huggingface dataset:
Gender and cause-specific survival in patients with stage III colon cancer: A SEER study.
Authors: D. Yang, L. Benhaim, W. Zhang, P. O. Bohanes, Y. Ning, A. Gerger, M. J. Labonte, S. G. Groshen, A. B. El-Khoueiry, S. Iqbal, H. Lenz
Journal: Journal of Clinical Oncology (2011)

e14006 Background: Our previous study based on the Surveillance, Epidemiology, and End Results (SEER) registry had shown that women survived longer than men after diagnosis with metastatic colorectal cancer (CRC). Estrogen has been shown to prevent colon polyps and colon cancer in women because it plays an important role in colon cancer carcinogenesis as well as tumor progression. We tested whether increased survival in women can be found in patients with stage III colon cancer. Methods: Patients with stage III colon cancer having colectomy were identified from the latest version of SEER registry (April 2010). Colon cancer cases registered prior to 1988 were excluded because of incomplete information on lymph nodes involvement. The role of gender on CRC specific survival, the primary endpoint, was investigated using a competing-risk model. Demographic and tumor characteristics, type of surgery, registry site and year of diagnosis were adjusted in the multivariable proportional hazards regression model for competing risks. The interactions between gender and age, race, N stage, grade and tumor site were examined by the likelihood ratio test. Results: 72,349 patients (34,229 men and 38,120 women) diagnosed from 1988 to 2007 were included in current analysis. Median follow-up was 76 months (range: 1-120 months). Women were older (median: 73 years old) at diagnosis, more likely to have proximal colon cancer (67%) and grade III/IV tumor (30%) than men (median 69 years old, 61% proximal colon, 26% grade III/VI). Women had longer CRC specific survival compared to men (HR=0.935, 95%CI: 0.909-0.961). The improved colon cancer specific survival among females was similar across race/ethnicity, age, and N stage (p for interaction > 0.10). The increased colon cancer specific survival among women was stronger in proximal colon and grade III/IV tumor than distal colon and grade I tumor (p for interaction = 0.0015 and 0.015 for tumor site and grade, respectively). Conclusions: Our analysis suggests that women with locally advanced colon cancer had longer CRC specific survival than men. These data warrant further studies to determine the role of estrogen as prognostic or predictive for the adjuvant therapy of colon cancer.
Uterine sarcoma - Accumulated 10 years experience
Authors: M. Steiner, O. Lavie, M. Leviov, S. Keren, R. Rubinov, Z. Shklar, A. Rabkin
Journal: Journal of Clinical Oncology (2005)

5175 Background: 40 patients with uterine sarcoma were treated at our service during the last 10 years. Their files were retrospectively reviewed and clinical data were collected and analyzed. Methods: The median age was 65 years (31–81). 39% had mixed mesodermal sarcoma, 29% had endometrial stromal sarcoma (16% high grade and 13% low grade), 27% had leyomiosacoma (17% high grade and 10% low grade) and 5% were classified as carcinosarcoma. 63% presented with stage I disease, 9% with stage II, 16% with stage III and 12% with metastatic disease. TAH+BSO was performed in 94% of patients. Adjuvant local radiotherapy was administered to 35% and adjuvant Adriamycin based chemotherapy to 12%. Results: Median follow up was 36 months. 11/28 (39%) of stage I-III patients radically operated recurred, 2 had local recurrence, 4 had local and distant failure and 5 had distant metastases only. The value of adjuvant post operative radiotherapy could not have been evaluated due to small number of patients in each subgroup. 5 year survival was 47% and it obviously correlated with disease stage (55% for stage I patients and 42% for stage II-IV) and histology and grade of the tumor (75% in low grade endometrial stromal and leyomiosarcoma, 60% in mixed mesodermal sarcoma, 50% in carcinosarcoma and 18% in high grade endometrial stromal and leyomiosarcoma). Conclusions: Our data are similar to other reported series as for prognostic factors and treatment results in this uncommon disease. No significant financial relationships to disclose.
Correlation of PDL1 tumor expression and outcomes in renal cell carcinoma (RCC) patients (pts) treated with pazopanib (paz).
Authors: David J Figueroa, Yuan Liu, Robert C. Gagnon, Christopher Carpenter, Mohammed Dar, Arundathy N. Bartlett-Pandite
Journal: Journal of Clinical Oncology (2013)

3021 Background: The interaction between PDL1 (B7H1) and its receptor PD-1 on activated T cells plays an important role in the inhibition of T-cell responses and contributes to suppression of antitumor immune responses. Tumor PDL1 expression has been associated with poor outcomes in RCC. This study investigates the correlation between PDL1 tumor expression and outcomes in RCC pts treated with paz. Methods: Using IHC, we retrospectively analyzed baseline FFPE tumor samples for PDL1 from 2 paz RCC studies: a single arm phase II trial and randomized placebo (pbo)-controlled phase III study. PDL1 expression was analyzed by MedTox Laboratories using the anti-PDL1 MouseIgG1 clone 5H1 (Thompson) on the Leica automated IHC platform. Additional dual PDL1/CD68 staining was carried out to delineate tumor and macrophage PDL1 expression. Tumor PDL1 expression was quantified by H-Score (HS) and PDL1+ macrophages were assessed semi-quantitatively. Association between PDL1H scores and PFS was investigated by Kaplan-Meier analysis using optimal cutoff of PDL1tumor HS (minimum p value, log rank test). Results: The optimal cut-point of PD-L1 tumor HS, relative to PFS, was identified as HS &gt; 3. In the phase II study (46 available samples out of 225), HS range was 0-150 and most samples had negative (HS = 0, n = 34, 74%) or low (HS 1-3, n=4, 9%) PDL1 expression. Pts with HS &gt; 3 (n = 8, 17%) had significantly shorter PFS (2.6 mo) than those with HS ≤ 3 (12 mo; p = .0005). In the phase III study (N = 160 available samples: paz, 113 of 290; pbo, 47 of 145), HS range was 0-280. Most patients had negative (n = 122/160, 76%) or low (n = 9/160, 6%) PD-L1 expression, with 18% (29/160) having HS &gt; 3. Pbo-arm pts with HS &gt; 3 (n = 6/47, 13%) had shorter PFS (2.3 vs 5.5 mo p = .0207). Paz-arm pts with HS &gt; 3 (n = 23/113, 20%) trended toward shorter PFS (7.3 vs 11 mo, p = .1405). Conclusions: PDL1 appears to be a prognostic marker with PDL1 HS &gt; 3 associated with shorter PFS. Limitations of the study include the retrospective nature of the analysis with limited pt samples available, low or negative PDL1 expression in the vast majority of pts, and use of archival samples that may not accurately reflect PDL1 status at study entry. Additional results (tumor volume, OS) will be presented.
A phase II study of FolateImmune (EC90 with GP1–0100 adjuvant followed by EC17) with low dose cytokines interleukin-2 (IL-2) and interferon-α (IFN-α) in patients with refractory or metastatic cancer
Authors: R. Messmann, R. Amato, J. Hernandez-McClain, B. Conley, H. Rogers, J. Lu, P. Low, S. Bever, D. Morgenstern
Journal: Journal of Clinical Oncology (2007)

13516 Background: FolateImmune is a folate-receptor (FR)-targeted immunotherapy that induces an immune response against tumor cells by marking them with a folate-hapten conjugate. The conjugate is specifically designed to target FR, which is over-expressed in a variety of cancers. FolateImmune therapy is comprised of a vaccine fluorescein conjugate (EC90), an adjuvant (GP-0100), and a folate-hapten conjugate (EC17). Patients (pts) receive a series of subcutaneous (SQ) injections of EC90 vaccine to stimulate the production of antibodies to the fluorescein-hapten, followed by SQ injections of EC17, which forms a molecular bridge between the tumor cell and the endogenous circulating anti-fluorescein IgG antibody. This is thought to initiate an Fc-mediated immune response leading to antibody-dependent cellular cytotoxicity and/or phagocytosis. IL-2 and IFN are utilized at low doses (7 MIU and 3 MIU, respectively) to further promote an immune response. The Phase Ib objective is to determine the safety of EC90 vaccine/EC17 folate-targeted therapy in combination with IL-2 and IFN. The previous phase I trial explored the safety of FolateImmune without cytokines. Methods: This phase 1b safety study treated eligible patients with FolateImmune therapy at dose levels of 1.2 mg EC90 and EC17 of 0.3 mg/kg. Results: As of Jan 2, 2007, all patients have tolerated therapy without significant toxicity. Grade 1–2 toxicity included: chills, fever, and nausea. One patient has had a minor response and continues on study. Laboratory studies revealed decline in circulating FR+ cells. Of 6 pts enrolled, 5 had a pathologic classification of renal cell cancer (RCC). Conclusion: Preliminary data suggest that FolateImmune therapy, with the addition of low dose cytokines, may be administered in a safe and well-tolerated manner. Phase II trials are planned for RCC. No significant financial relationships to disclose.
Tle3 is a Useful Marker for Predicting the Therapeutic Effect of Eribulin Chemotherapy for Triple-Negative Breast Cancer
Authors: S. Kashiwagi, Y. Asano, K. Kurata, T. Morisaki, S. Noda, H. Kawajiri, T. Takashima, N. Onoda, K. Maeda, K. Hirakawa
Journal: Annals of Oncology (2014)
A randomized trial comparing local recurrence (LR) rates between short-course (SC) and long-course (LC) preoperative radiotherapy (RT) for clinical T3 rectal cancer: An intergroup trial (TROG, AGITG, CSSANZ, RACS).
Authors: S. Ngan, R. Fisher, D. Goldstein, M. Solomon, B. Burmeister, S. P. Ackland, D. J. Joseph, B. McClure, S. McLachlan, J. Mackay
Journal: Journal of Clinical Oncology (2010)

3509 Background: Both SC and LC preoperative radiotherapy have been accepted as standard of care for locally advanced rectal cancer. The primary aim of the trial was to compare LR rates (cumulative incidences) at 3 years between SC and LC. Methods: Main eligibility criteria were clinical T3NxM0 rectal adenocarcinoma, with the lower border within 12 cm of the anal verge, and ECOG performance status 0-2. SC consisted of pelvic RT 25 Gy in 5 fractions in 1 week, followed by surgery the following week, and 6 (monthly) courses of postoperative chemotherapy. LC consisted of pelvic RT 50.4 Gy, 1.8 Gy/fraction, in 5.5 weeks, continuous infusion 5-FU 225 mg/m2/day during RT, followed by surgery in 4 to 6 weeks, and 4 (monthly) courses of postoperative chemotherapy. Each course of postoperative chemotherapy was to be 5-FU 425 mg/m2 and folinic acid 20 mg/m2 for 5 days. The trial was powered (80%; 310 patients) to detect a difference of 15% versus 5% in LR rates at 3 years. Results: 326 patients, accrued from 2001-06 from 27 Australian and New Zealand centres, were randomly assigned to SC (163) and LC (163). 92.5% were staged by MRI or endorectal ultrasound. The median potential follow-up time was 5.9 years and ranged from 3.0 to 7.8 years. The 3-year LR rates were 7.5% (SC) and 4.4% (LC); difference = 3.1%, 95% CI -2.0 to 8.3 (p = 0.24). There were no apparent differences in rates of distant recurrence (5-year distant recurrence-free rates were 72% SC, 69% LC; logrank p = 0.85; HR (SC:LC) = 0.96, 95% CI 0.64 to 1.45). The overall survival rates at 5 years were 74% SC and 70% LC (logrank p = 0.56; HR (SC:LC) = 0.89, 95% CI 0.60 to 1.32). Late treatment-related toxicity rates were not substantially different between arms (RTOG grade 3-4: SC 7.6%, LC 8.8%; p = 0.84). Conclusions: There was no clear evidence for a difference between SC and LC in terms of LR at 3 years. Distant recurrence and overall survival rates were similar. Both SC and LC provided good local control. Late toxicity rates were not substantially different. Longer term follow-up of outcomes, including quality of life, is planned. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration GlaxoSmithKline, Merck AG, Novartis, Pfizer, Roche Novartis Novartis, Roche
Preoperative treatment of potentially-resectable pancreatic adenocarcinoma with fixed-dose rate gemcitabine (GEM), bevacizumab (BEV), and 30 Gy radiotherapy (RT)
Authors: A. J. Moser, H. J. Zeh, R. K. Ramanathan, A. M. Krasinksas, M. E. Tublin, R. P. Smith, F. S. Stover, K. K. Lee, S. J. Hughes, D. L. Bartlett
Journal: Journal of Clinical Oncology (2008)

4631 Background: Nearly 80% of patients with resected pancreatic cancer develop local or distant failure within two years. We hypothesized that short-course neoadjuvant treatment with systemically-active doses of combination chemotherapy and RT to the surgical margin may improve outcomes. Methods: This is a single center, two stage phase II trial of induction fixed-dose rate (FDR) GEM (1,500 mg/m2) plus BEV (10 mg/kg) q 2 weeks for three cycles, followed by BEV (10 mg/kg) with accelerated RT (30 Gy in 10 fractions) directed at the gross tumor volume and a 1–2 cm vascular margin. Eligible pts had FNA-proven pancreatic adenocarcinoma and were potentially-resectable on screening pancreas protocol CT scan. Stage I required six pts; 48 resected pts are required to evaluate dual primary endpoints: a 25% improvement in the margin-negative resection rate (65% to 80%) and a 10% pathological response rate (≥80% power; combined type I error 0.14). Results: This is an exploratory analysis of stage I data. Fourteen pts completed treatment: 10 males; median Karnofsky score 90; and median age 57 (37–75). Lesions measured 1.6–4.5 cm with CT criteria for portal venous invasion (n=5) and malignant adenopathy (nodes ≥ 1 cm; n=6). Median treatment duration was 56 days (55–71 days) with three delays. Only one of six pts experienced treatment-related grade 3 toxicity, while two pts required dose reduction due to grade 2 events. Median Ca 19–9 decreased from 128 to 32 U/ml. Radiographic responses included 1 CR, 2 PR, and 10 SD upon completion. Ten pts underwent pancreatoduodenectomy with two portal vein resections. Eight of ten pts had negative surgical margins (80%) with three (30%) near-complete pathological responses (microscopic foci of residual tumor only). Four pts (4/14) had metastatic disease; all had nodes ≥ 1 cm on pretreatment CT (p<0.02). Median length of stay was 10 days (2–17). Four pts had grade 3 wound complications (29%) with one grade 2 pancreatic leak (10%). Conclusions: Induction therapy with FDR GEM and BEV, followed by concurrent BEV/RT to 30 Gy, is safe neoadjuvant treatment for patients with resectable pancreatic cancer. The resectability rate and evidence for pathologic downstaging meet criteria for accrual to stage II. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Genentech Genentech
Trends in the application of dynamic allocation methods in multiarm cancer clinical trials
Authors: G. R. Pond, P. A. Tang, S. A. Welch, E. X. Chen
Journal: Journal of Clinical Oncology (2009)

6550 Background: In multiarm oncology clinical trials there is always a risk that the treatment groups could be imbalanced for a prognostic factor, potentially biasing treatment comparisons and compromising the validity of the results. Stratified randomization (SR) is frequently used to reduce imbalances. Dynamic allocation (DA), also known as minimization, is a controversial and largely nonrandom method of treatment allocation that can incorporate more prognostic factors than traditional SR methods. Proponents argue that results from clinical trials implementing DA are potentially more credible, while opponents claim there is little added benefit, increased complexity, and the statistical properties are not fully understood. We reviewed multi-arm cancer trials published between 1995–2005 to describe trends in the application of DA methods. Methods: 476 clinical trials with at least 100 patients in each arm, published in 13 major journals were reviewed. Manuscripts were grouped by impact factor (IF) of the publishing journal into low (&lt;10), medium (10–20) and high (20+) categories. Trial-specific factors associated with publication were collected along with details of allocation method. Results: 112 (24%) trials described using DA for assigning patients to treatment. 79% of trials employing DA methods included 3 or more stratification factors, compared with only 36% of other trials (p &lt; 0.001). Reported use of DA was similar between industry and non-industry sponsored studies (p = 0.85) and by geographical region (p = 0.73). Of 364 trials which did not describe using DA, 103 (28%) reported using SR, but a statement describing stratification on at least one factor was included in 291 (80%) trials. A trend was observed that reported use of both DA (p = 0.072) and SR (p = 0.067) methods increased over time. DA was associated with publication in higher IF journals univariately (OR = 1.67, 95% CI 1.11–2.52, p=0.014) and after adjusting for identified prognostic factors (OR = 1.70, 95% CI 1.06–2.73, p = 0.028). No association between SR and higher IF journal publication was observed (p = 0.52 univariately and p = 0.44 adjusting for other factors). Conclusions: DA is frequently used in cancer clinical trials. Reported use of DA, but not SR, is associated with publication in high IF journals. No significant financial relationships to disclose.
Phase I study of CT-2106 (polyglutamate camptothecin) in patients with advanced malignancies
Authors: G. M. Springett, C. Takimoto, M. McNamara, J. H. Doroshow, S. Syed, E. Eastham, D. Spriggs, S. Pezzulli, G. Michelson, J. Dupont
Journal: Journal of Clinical Oncology (2004)

3127 Background: CT-2106, a camptothecin (CPT) conjugate, is a new generation of topoisomerase I inhibitors designed to deliver higher, more effective chemotherapy to tumor tissue with less toxicity to normal tissues. Covalent binding through the hydroxyl group of CPT to poly-glutamate, a biodegradable polymer of glutamic acid, enhances CPT aqueous solubility and prevents opening of the lactone ring and subsequent CPT binding to albumin. This allows enhanced distribution to tumor tissues. Covalent binding of CPT through the lactone ring hydroxyl to PG is expected to decrease renal clearance of free CPT and reduce the likelihood of hemorrhagic cystitis. CT-2106 has significant anti-tumor activity in multiple human tumor cell lines in vivo. This study is designed to determine the maximum tolerated dose (MTD) of CT-2106. Methods: A dose escalation study with patients (pts) treated with CT-2106 as a 10 min IV infusion every 21 days. Toxicity and tumor response were assessed using NCI CTC v2 and RECIST, respectively. Results: Twenty-four pts have been treated at doses of 12 mg/m2 (3 pts), 25 mg/m2 (7), 50 mg/m2 (3), 75 mg/m2 (8), and 105 mg/m2 (3). Data is available for 19 pts (median age 63, range 46–77). Dose limiting toxicities include grade 3/4 neutropenia with concomitant grade 3 thrombocytopenia in 3 pts (105 mg/m2) and grade 2 hematuria in 1 pt (25 mg/m2). The only serious related toxicity was grade 4 hypersensitivity in a pt with a history of hypersensitivity to irinotecan. Other related adverse events were grade 3 anemia in 1 pt and grade 1/2 anemia (14), fatigue (10), nausea (8), diarrhea (7), vomiting (5), and alopecia (5). Four pts had stable disease (SD) for >9 weeks; 2 lung cancer pts (25 mg/m2) had SD for >27 weeks. Plasma Cmax and AUC for conjugated and unconjugated CPT indicate pharmacokinetic linearity from 12–75 mg/m2. The apparent termination t1/2 of unconjugated CPT is approximately 40 hours. Conclusions: CT-2106 is easily administered by 10 min IV infusion every 3 weeks and has been well tolerated to date. This study is ongoing to determine the MTD. The results demonstrated thus far warrant further clinical development. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Cell Therapeutics, Inc. Cell Therapeutics, Inc.
Adjuvant chemotherapy use in a diverse population-based sample of women with breast cancer
Authors: J. J. Griggs, P. H. Abrahamse, A. S. Hamilton, J. J. Graff, M. S. Mujahid, C. H. Jagielski, S. J. Katz
Journal: Journal of Clinical Oncology (2008)

6539 Background: Racial, ethnic, and social disparities in the use of chemotherapy have been demonstrated in women with breast cancer in numerous clinical settings. The purpose of this study was to investigate patterns and correlates of chemotherapy use in a recently- treated population-based sample of black, Latina, and non-Hispanic white women with invasive breast cancer. Methods: Women diagnosed with breast cancer between August 2005 and May 2006 (n = 2,030) and reported to the Los Angeles County Surveillance Epidemiology and End Results (SEER) Registry was identified and invited to complete a survey about their treatment experiences. Patient responses were linked to SEER data. Black women and Latinas were oversampled. Chemotherapy was considered indicated for Stage I - III estrogen receptor (ER)-negative breast cancer and Stage II - III ER-positive disease. Multivariate analyses examined the relationships between race/ethnicity, education, income, age, comorbidity, marital status, employment characteristics, and disease characteristics. Results: The survey response rate was 71.2% (n=1338). Of the 1,338 respondents, 917 (68.5%) met the clinical criteria for consideration of chemotherapy. Black women (68.5%) and Latinas (77.0%) were more likely than non-Hispanic white women (58.2%) to receive adjuvant chemotherapy (p <.001). Women with less than a high school education (73.4%) were more likely than college graduates (64.4%) to receive chemotherapy (p =.045). Latinas were more likely to receive chemotherapy than whites in adjusted models (OR 2.94, 95% C.I. 1.04 - 8.28). There was no difference in receipt of chemotherapy between blacks and non-Hispanic whites. Education and income were also not associated with chemotherapy receipt in multivariate analysis. Age and tumor characteristics were also significantly associated with receipt of chemotherapy in adjusted models. Conclusions: In contrast to practice-based studies of chemotherapy use in cohorts treated in older time periods, we have identified no evidence of racial/ethnic or social disparities in the use of chemotherapy in this diverse population-based sample of recently-treated women. Unmeasured clinical factors may account for the higher use of chemotherapy among Latinas. No significant financial relationships to disclose.