tbuckley/cabot-search huggingface dataset:
Significance of thymidine phosphorylase, VEGF, and p53 in predicting response for metastatic colorectal cancer patients receiving 5-FU/LV + irinotecan or oxaliplatin
Authors: H.-S. Oh, M.-J. Ahn, J.-H. Choi, I.-S. Kim, Y.-Y. Lee, I.-Y. Choi, H.-W. Lee, C.-K. Park
Journal: Journal of Clinical Oncology (2004)

3733 Background: In the treatment of metastatic colorectal cancer, 5-fluorouracil (5-FU)/LV + irinotecan or oxaliplatin showed high response rate, progression free survival and overall survival compared to 5-FU/LV. However, the predictive marker for response rate was not fully determined. Expression level of thymidine phosphorylase (TP) is the crucial enzyme associated wtih clinical response to 5-FU based therapy and prognosis. VEGF expression has been known to be associated with poor survival in colorectal cancer. Methods: We evaluate the relationship between TP, VEGF, and p53 expression and response to 5-FU based chemotherapy in 34 metastatic colorectal cacner patients.Protein expression was analyzed by immunohistochemistry in paraffin embedded tissues with monoclonal antibody for TS, VEGF, and p53. Pearson's chi-square tests were used to assess the association between these markers and response to chemotherapy. Results: Nineteen patients were male and fifteen patients were female. The median age was 56 years old. Twenty-six patients were treated with 5-FU/LV/irinotecan and 8 treated with oxaliplatin/capecitabine. Overall response rate was 29.4% (10/34). Among 34 patients, 14.7% was positive for TP, 64.6% for VEGF, and 58.8% for p53, respectively. The response rate in TP positive group was 40% and 24.2% in TS negative group, but there was no significant difference. There was no correlation between VEGF or p53 expression and response to chemotherapy (31.8% vs 25% for VEGF; 35% vs 21.4% for p53). Conclusions: These results suggest that the TP expression might be associated with response to chemotherapy in colorectal cancer. Further investigation with large numbers of patients is required. No significant financial relationships to disclose.
The prognostic contribution of intrinsic breast cancer subtype, race, and age among patients with brain metastases.
Authors: C. K. Anders, A. M. Deal, C. Khorram, H. Meng, E. Burrows, C. Livasy, K. Fritchie, M. G. Ewend, C. M. Perou, L. A. Carey
Journal: Journal of Clinical Oncology (2010)

1027 Background: Brain metastases (BM) portend a poorer prognosis than other sites of breast cancer (BC) metastases. Triple-negative (TN) BCBM have worse survival than HER2+. TNBC is more common in premenopausal and African-American (AA) patients (pts); both are also poor prognostic factors. It is unclear if inferior outcome of TN BCBM reflects a higher-risk population versus subtype itself. In a single-institution cohort study, we examined characteristics and survival of pts with BCBM to identify dominant prognostic factors. Methods: The UNC Breast Cancer Database identified pts with BCBM diagnosed 1988–2008. BC subtype was assigned by IHC: Luminal A (ER+ and/or PR+/HER2-), Luminal B (ER+ and/or PR+/HER2+), HER2+ (ER-/PR-/HER2+) and TN (ER-/PR-/HER2-). Overall survival (OS) and survival after CNS recurrence (CNS survival) were evaluated by subtype, age (< vs ≥ 40 yrs) and race (AA vs non-AA) using the Kaplan-Meier method and Cox regression. Results: Of 98 pts with BCBM, 34 (35%) were AA; 30 (31%) were < 40 yrs at initial BC diagnosis. Race and age were associated with TNBC; 64% (9/14) of young, AA pts with BM had TNBC compared to 29% (14/48) of older, non-AA pts (p > 0.03). At median follow-up of 5.9 yrs, 77% of pts had died. Median OS did not differ by age or race, but was inferior for TNBC versus other subtypes (Table). CNS survival was shorter for TNBC, but no difference was seen by race or age. After stratifying by subtype, there was no difference in CNS survival by race or age. TNBC conferred higher risk of death and death after BM in uni- (p > 0.003, 0.0004) and multivariable analyses (adjusted for age, race, nodal status at primary BC diagnosis, > 3 CNS lesions; p > 0.04, 0.03). Conclusions: Among pts with BCBM, the TN subtype particularly affects young, AA pts and confers inferior OS and CNS survival. After adjustment for subtype, neither race nor age impact outcome after BM. The higher proportion of TNBC in younger, AA pts likely accounts for historically worse prognosis in this population. Luminal A Luminal B Triple-negative HER2+ p value All pts 29 (30%) 21 (21%) 30 (31%) 18 (18%) – OS, yrs 5.1 (3.2-7.2) 5.2 (2.1-10.1) 2.1 (1.1-3.5) 3.5 (1.6-7.5) 0.02 CNS survival, yrs 0.8 (0.35-1.5) 1.27 (0.65-3.4) 0.24 (0.17-0.48) 1.19 (0.3-3) 0.002 Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration University Genomics AstraZeneca, Banyu Pharmaceutical Co., Bristol-Myers Squibb, Genentech, GlaxoSmithKline, sanofi-aventis, Wyeth BioClassifier LLC
Panitumumab activity in metastatic colorectal cancer (mCRC) patients (pts) with low or negative tumor epidermal growth factor receptor (EGFr) levels: An updated analysis
Authors: E. P. Mitchell, J. R. Hecht, J. Baranda, I. Malik, D. Richards, M. Reiner, S. Stout, R. G. Amado
Journal: Journal of Clinical Oncology (2007)

4082 Background: Panitumumab, a fully human monoclonal antibody against EGFr, is approved for EGFr-expressing mCRC pts with disease progression (PD) on or after fluoropyrimidine-, oxaliplatin-, and irinotecan-containing chemotherapy. However, the predictive value of EGFr tumor-membrane staining as measured by immunohistochemistry (IHC) is undetermined. Methods: This multicenter, single arm, phase 2 study enrolled pts with documented PD during or after fluoropyrimidine and adequate doses of irinotecan and oxaliplatin, and within 6 months after the most recent chemotherapy regimen (determined by an independent eligibility review committee [IERC]), 2–3 prior regimens, and low (1%-9%) or negative (&lt;1%) EGFr tumor membrane staining (by IHC). Pts received panitumumab 6mg/kg Q2W until PD or intolerability. Tumor assessments (modified WHO, blinded central review) were performed every 8 weeks until PD or discontinuation. Endpoints were objective response rate (ORR) through wk 16 (+ =4 wk confirmation; primary), overall ORR, response duration, progression-free survival (PFS), and safety (secondary). Results: In this interim analysis, 91 pts had =20 wks of potential follow-up and comprised the IERC efficacy set; 118 pts comprised the evaluable safety set (=20 wks potential follow-up). In the IERC efficacy set, 57% were male, 86% were white, and median age (range) was 61 (26–85) years. ORR through week 16 is shown; overall ORR was the same ( Table ). The most common adverse events (all, grade 3/4) were dermatitis acneiform (72%, 6%), erythema (69%, 6%), pruritus (65%, 4%), and hypomagnesaemia by lab values (53%, 10%). Four pts (3%) had an infusion reaction per investigator (1 was grade 3). Conclusions: This analysis confirms earlier findings that panitumumab has anti-tumor activity in pts with low or undetectable EGFr tumor membrane levels as measured by IHC. This study has completed enrollment, and updated data will be presented. [Table: see text] No significant financial relationships to disclose.
Adjuvant chemoradiotherapy with gemcitabine and cisplatin and postoperative radiotherapy (PORT) versus PORT alone in high risk bladder cancer patients. A phase III randomized controlled trial
Authors: M. S. Zaghloul, H. Khaled, M. Lotyef, H. William
Journal: Journal of Clinical Oncology (2004)

4626 Background: Locally advanced bladder cancer patients have low survival rates after radical cystectomy. Postoperative radiotherapy though improved this survival, yet this improvement was not satisfactory. Methods: A prospective randomized trial started on August 2002 included 59 locally advanced bladder cancer patients so far. Patients who underwent radical cystectomy and had P3b, P4a, GIII and / or pelvic nodal involvement were randomized into 2 groups: Group I (27 patients) received post-operative radiotherapy (PORT) 45 Gy/30 fractions /3 weeks. Group II (32 patients) received adjuvant chemoradiotherapy in the form of 2 courses of Gemcitabine 1 g/m2 D1 and D8 and cisplatin 70 mg/m2 D2, same regimen of PORT as in group I followed by another 2 courses of Gemcitabine- cisplatin. The toxicities of both chemotherapy and radiotherapy were evaluated using WHO scoring system. The primary end point is disease-free survival (DFS). Results: Group II patients received 103 cycles of chemotherapy, only 3 patients (9%) could not complete their prescribed regimen. Chemotherapy was tolerated in most of the patients with grade 1/2 toxicities. Grade3/4 anemia were observed in 10% of the cycles. No grade 3/4 thrombocytopenia or neutropenia were observed in these patients. Grade 3 vomiting was observed in 38% of the cycles, while grade 3/4 renal complications were observed in one patient only. Early radiation reactions were also tolerable in both groups. Only 15% of the patients experienced grade 3 diarrhea with no differences between the 2 treatment groups. Severe abdominal colics (grade3) were experienced by 22% of patients, that was higher in group II(37.5%) than group I (4%) (p<0.001). Severe Tensmus (grade 3) were experienced by 2 patients (3%). Patients were followed up for 3–17 months. The one- year DFS rate for group I patients was 59±15% while that of group II patients was 64±11%, with no statistical difference of significancen (p=0.4). Conclusions: Adjuvant chemoradiotherapy using Gemcitabine- cisplatin and PORT were tolerable with minimal severe toxicities. The one year disease free survival was encouraging for such high risk patients. No significant financial relationships to disclose.
Breast cancer with HER2/neu over-expression and hormone receptor positive status: A distinct biology and natural history
Authors: S. Paluch-Shimon, N. Ben-Baruch, I. Wolf, L. Zach, A. Kruglikova, E. Landau, T. Modiano, R. Weitzen, R. Catane, B. Kaufman
Journal: Journal of Clinical Oncology (2005)

650 Background: HER2/neu over-expression (HER2+) occurs in approximately 25% of breast cancers and is often associated with a more aggressive disease. In this study we examined the effects of hormone receptor (HR) expression on clinical characteristics and natural history in HER2+ breast cancer. Methods: A retrospective review of 116 patients (pts) with HER2+, metastatic, breast cancer was performed. HER2+ was defined as positive if immunohistochemical staining was +3 or if FISH was positive. HR was defined as positive if either estrogen or progesterone receptors staining were positive, regardless of intensity. Results: Median age was 47 (range 26–69). The vast majority (90%) had invasive ductal carcinoma and 74% had grade III disease. Positive HR staining was found in 48 (41%) of the pts and negative HR staining in 68 (59%). No significant differences between the study groups were found in age, tumor histology, grade and number of involved metastatic sites at time of first recurrence. At first recurrence, HR positive (HR+) pts had significantly lower rates of liver or brain metastasis compared to HR negative (HR-) pts (27% vs. 50%, respectively, p=0.021) but significantly higher rates of soft tissue, bone or lung metastasis (94% vs. 69%, respectively, p=0.001). During follow-up, 94% of the HR+ pts developed soft tissue, bone or lung metastasis, compared with 85% in the HR- group (p=0.233), and 54% developed liver or brain metastasis compared with 77% in the HR- group (p=0.016).The mean disease free interval in the HR+ group was 27 months, compared to 16 months in the HR- group (p=0.0147 log-rank). The mean overall survival was 98.7 months in the HR+ group, compared to 68.7 months in the HR- group (p=0.064). Conclusions: Compared to HER2+ HR- breast cancer patients, patients with HER2+ HR+ disease had a lesser propensity for liver and CNS involvement, a markedly longer disease free interval, and a strong trend to increased overall survival. These results suggest that HER2+, HR positive tumors, have a distinct and favorable biological nature compared with HER2+, HR negative tumors. No significant financial relationships to disclose.
Laparoscopic renal cryoablation: Risk factor analysis to predict oncologic outcomes with minimum 5-year follow-up
Authors: K. Kamoi, A. Kawauchi, T. Miki, M. Aron, E. Remer, G. Haber, A. Berger, S. Crouzet, B. Ricardo, I. Gill
Journal: Journal of Clinical Oncology (2009)

5094 Background: We analysed risk factors to predict oncologic outcomes at 5–11 year after laparoscopic renal cryoablation (LRC). Methods: Between 09/1997 and 010/2008, we performed renal cryoablation in 340 patients. Of these, 102 patients treated before 10/2003 (all laparoscopic) have minimum 5-year follow-up. Follow-up involved MRI imaging on postoperative day 1, 3 months, 6 months, 12 months, and then annually. Cryolesion biopsy was performed at 6-months. All data were prospectively accrued. Results: In the 102 patients with minimum 5-year follow-up, mean age was 66 years. Mean tumor size was 2.3 cm (0.9–5.0 cm). Median ASA score was 3 and mean BMI was 28. Six patients developed locoregional recurrence, 2 had locoregional recurrence with metastases, and 5 had distant metastases without locoregional recurrence. Overall, there were 7 cancer deaths. In the 69 patients with biopsy-proven renal cell cancer (median follow-up 81 mos; range 60–132 mos), 5-year overall, disease-specific, and disease- free survival was 75%, 92%, and 82%, respectively, while 10-year overall, disease-specific, and disease-free survival was 46%, 83%, and 79%, respectively. On multivariate analysis, previous radical nephrectomy for RCC was the only significant predictor for both recurrence- free survival and cancer-specific survival (p = 0.023 and 0.030, respectively). Relative risk of patients who has a history of radical nephrectomy for RCC treatment was 4.1 (95% CIs, 1.2 to 13.4), and 5.4 (95% CIs, 1.2 to 27.7) for disease-free survival and disease-specific survival, respectively. Conclusions: Laparoscopic renal cryoablation is effective oncologic treatment for renal mass in select patients. Disease-specific survival of 92% at 5-years and 83% at 10-years is possible. Preceding radical nephrectomy for RCC treatment was the only independent predicting factor for both disease-free and disease-specific survival. [Table: see text] No significant financial relationships to disclose.
PAX5 Mutations Occur Frequently in Adult B-Cell Acute Lymphoblastic Leukemia (B-ALL) and Is Significantly Associated with BCR-ABL1 Fusion Gene.
Authors: Julien Familiades, Marina Bousquet, Nicole Dastugue, Marina Lafage-Pochitaloff, Béné Marie-Christine, Kheira Beldjord, Jean-Michel Cayuela, Nathalie Grardel, Claude Preudhomme, Hélène Cavé, Véronique Lhéritier, André Delannoy, Yves Chalandon, Norbert Ifrah, Arnaud Pigneux, Hervé Dombret, Elizabeth A. Macintyre, Françoise Huguet, Pierre Brousset, Cyril Broccardo, Eric Delabesse
Journal: Blood (2007)
Second-line therapy with paclitaxel and carboplatin for recurrent disease following first-line therapy with paclitaxel and platinum in ovarian or peritoneal carcinoma.
Authors: P G Rose, N Fusco, L Fluellen, M Rodriguez
Journal: Journal of Clinical Oncology (1998)

PURPOSE The combination of paclitaxel and a platinum compound is the most active first-line regimen for advanced ovarian carcinoma. The current study was undertaken to evaluate this combination in the re-treatment of patients with ovarian or peritoneal carcinoma who had disease recurrence &gt; or = 6 months following this combination. METHODS Twenty-five patients with recurrent ovarian or peritoneal carcinoma &gt; or = 6 months after a complete clinical response with first-line paclitaxel and platinum chemotherapy were studied. Recurrent disease was documented by computed tomography (CT), elevated CA 125 level, or surgical findings. Second-line chemotherapy consisted of paclitaxel 135 mg/m2 as a 24 hour infusion and carboplatin at an area under the concentration-time curve (AUC) of 5 to 6 every 21 days. Response to therapy was classified as measurable or assessable. RESULTS The median time to recurrence after first-line therapy was 10 months (range, 6 to 30). Among 20 measurable and assessable patients, 14 (70%) demonstrated a complete clinical response and four (20%) a partial clinical response. The response rate with measurable disease was 91% and with assessable disease was 89%. The median progression-free interval for all patients was 9.0+ months (range, 2 to 15). The median progression-free interval for patients with measurable or assessable disease was 9.0+ months and for nonassessable disease was 7.0+ months. Fifteen patients (60%) have developed recurrence after secondary therapy at a median interval of 9.0 months (range, 2 to 15). Only two patients have died with a median survival after secondary therapy of 10.0+ months (range, 2.0 to 21.0+). CONCLUSION The use of this combination, in this sensitive population, has a high response rate and long progression-free interval. In a chemotherapy-sensitive population, the activity of alternative second-line agents must be interpreted with this perspective.
Cytoprotection of amifostine (A) in ovarian cancer patients receiving paclitaxel/carboplatin (PC) first line chemotherapy in a multicenter phase III trial
Authors: P. Sevelda, U. Sevelda, U. Denison, A. Kaider
Journal: Journal of Clinical Oncology (2004)

5021 Background: The primary objectives of the study were to evaluate, if A can prevent or reduce the WHO grade of haematological and non haematological toxicities induced by PC and to determine if A enables to adhere to the planned chemotherapy regimen (interval and dosage). Methods: 89 patients with primary epithelial ovarian cancer FIGO Stage IC – IV were entered into this prospective randomised phase III trial between 1998 and 2/2002. In all patients first line chemotherapy of P 175 mg/m2 i.v. within 3 hours day 1 and C AUC 5 on day 2 was planned for 6 cycles. 44 patients were randomised to the A arm and received 740 mg/m2 A before P on day 1 and 740 mg/m2 before and 2 hours after C on day 2. 41 patients received chemotherapy only. Results: The planned number of 40 patients in each treatment arm was achieved with 85 eligible patients. This number was calculated to confirm a reduction of granulocytopenia by 50% and prevention of neurotoxicity difference in score increase by 2 units) in the A therapy arm. Grad 3 and 4 granulocytopenia developed in 52,3 % of the patients in the A arm and 71,8 % in the control group (one-sided chi-square test X2= 3,32; p=0,034). Neurotoxicity and all other toxicities were identical in both treatment arms. Only nausea and vomiting was significantly increased in the A therapy arm with 20,5% grade 3 and 4 versus 5,1% in the control arm (chi-square test X2=4,22; p= 0,04). Quality of life analysis showed a significant lower deterioration of the global health score in the A group (Wilcoxon test p=0,035). Treatment delay was not significantly different in both groups. Conclusions: A was able to reduce granulocytopenia and had a positive influence on global health score. According to neurotoxicity and other toxicities A did not prove efficacy. At present we cannot recommend A as standard cytoprotective agent in ovarian cancer patients treated with this PC chemotherapy. This study was supported by AESCA Austria and Bristol Myers Squibb Austria Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration AESCA Bristol-Myers Squibb AESCA Austria; Bristol-Myers Squibb
Cancer patients’ attitudes toward future research uses of their donated tissue: Preliminary results of a mail survey study
Authors: P. R. Helft, R. E. Eckles, J. Kempf, C. S. Johnson-Calley, J. Brooks, E. M. Meslin
Journal: Journal of Clinical Oncology (2006)

6009 Background: Millions of tissue samples are stored in the United States, but little is known about the attitudes of tissue donors. Understanding the attitudes of those who donate tissue for use in future research would inform the design of studies using stored tissues (ST). Methods: Eligible subjects included cancer patients who donated remaining tissue after biopsy or surgery to the Indiana University Cancer Center Tissue Bank. All subjects signed informed consent to donate tissue. A convenience sample were approached for participation. A survey instrument was developed from literature review and expert input, and refined by focus groups. Results: 243 surveys were mailed, and 196 completed surveys were returned (response rate 80.7%). Respondents were 70% married, 93% white, 54% female. 57% had completed at least some college. Average age was 60. Average time since diagnosis was 13.8 months. 81% of respondents remembered donating tissue. 61% were not at all or a little concerned about the privacy of their ST. &gt;80% of subjects agreed that their ST could be used in future research on their type of cancer, other cancers, and other diseases,. Non-whites were less likely than whites to allow tissue to be used in research (p = 0.0128). Around 40% of respondents agreed that researchers should have to recontact them before using their ST. Non-whites and less educated subjects were more likely to want to be recontacted for each research use of their ST. 90% of subjects would allow their ST to be used by university researchers, but only 60% agreed that ST could be used by pharmaceutical companies. 39% objected to the use of STs to develop a treatment for profit. No differences were found in willingness of ST to be used in future research whether samples were identified, de-identified, or linked. 60% of respondents wanted to be notified of research results that would impact their, or their children’s, health whether treatments were available or not, and whether results had been validated or not. Conclusions: This cohort of cancer patients was very willing to allow their ST to be used in future research on all conditions, but a significant minority desired to be recontacted each time ST were used. These findings do not support policies based on a simple presumed consent model. No significant financial relationships to disclose.