tbuckley/cabot-search huggingface dataset:
Preferences (PREFs) over time of chemo-experienced versus chemo-naïve patients (pts) for treatment-related side effects (SEs)
Authors: C. C. Sun, D. C. Bodurka, C. B. Weaver, D. L. Bethancourt, M. A. Fitzgerald, J. K. Wolf, D. M. Gershenson, J. J. Kavanagh, M. F. Munsell, M. L. Donato
Journal: Journal of Clinical Oncology (2005)

8222 Background: We previously reported PREFs of chemo-experienced pts with ovarian cancer (ovca) enrolled on phase II trials of high-dose chemo/stem cell support (HDCT). To determine whether PREFs of previously treated pts differ from chemo-naïve pts, we assessed longitudinal PREFs of newly diagnosed ovca pts scheduled to begin conventional-dose chemo (CDCT). Methods: Ovca pts receiving CDCT or HDCT were enrolled in this study. CDCT pts were newly diagnosed and dispositioned to receive 6 cycles of carboplatin/paclitaxel. HDCT pts received a mobilization regimen (MOB) of ifosfamide/etoposide and high-dose topotecan/melphalan/cyclophosphamide (TMC). Pts were interviewed at 2 points in time (T1, T2). For CDCT pts, T1 and T2 occurred at the 1st and 6th cycle of chemo. For HDCT pts, T1 occurred during MOB, T2 was after TMC. PREFs were assessed using a visual analog scale (VAS) and time trade-off (TTO) for the following SEs: alopecia, neuropathy, nausea/vomiting (NV), ototoxicity, fatigue, mucositis, dysuria, and hepatotoxicity (HEP) and pancytopenia (PAN). VAS asked pts to rate SEs from 0=least favorable to 1.0=most favorable. The TTO asked pts which they preferred: chemo resulting in 10 days with the SE in question, or number of days (X,where X<10) of chemo with multiple SEs. PREF scores were converted to 0=worst to 1=best. Data were analyzed using the Mann-Whitney U test. Results: 35 HDCT and 20 CDCT pts completed T1 and T2 interviews. CDCT pts gave more favorable scores for mucositis, NV and chemo involving multiple SEs. HDCT pts reported more favorable scores for PAN and HEP. CDCT PREFs for PAN, HEP and fatigue remained stable from T1 to T2. Conclusions: Our study suggests that compared to chemo-naive pts, chemo-experienced pts are more averse to NV and chemo involving multiple adverse SEs but less averse to PAN and HEP. For all pts, PREFs for NV worsened over time. Prior experience with chemo and duration of SEs appear to influence pt PREFs. No significant financial relationships to disclose.
Sarcomas as a subsequent malignancy in survivors of pediatric malignancy:The Childhood Cancer Survivor Study
Authors: T. Henderson, L. Robison, A. Mertens, J. Neglia, S. Hammond, A. Meadows, J. Whitton, E. F. Cook, M. Stovall, L. Diller
Journal: Journal of Clinical Oncology (2005)

8515 Background: Subsequent sarcomas (SS) in childhood cancer survivors have not been well-studied, with prior studies limited to smaller series of bone tumors. Methods: The Childhood Cancer Survivor Study (CCSS) is a multi-institutional cohort of 14,352 five-year survivors of childhood cancers, including leukemia, lymphoma, central nervous system tumors, neuroblastoma, kidney tumors, bone tumors and soft tissue sarcomas (STS), diagnosed between 1970 and 1986. SS were ascertained through self-administered questionnaires and confirmed with pathology reports. The risk factors for developing second sarcomas were assessed through univariate analysis as well as multivariate Cox regression analysis. Results: We describe a series of 91 SS [osteosarcoma (n=27), Ewing’s/PNET (n=5), rhabdomyosarcoma (n=3), other STS (n=36), malignant peripheral nerve sheath tumor (n=13), other (n=7)] The incidence rate of SS was 3.2 cases per 1,000 person-years (py) from 28,301 py of observation after primary cancer diagnosis. Risk of SS was associated with primary diagnosis (p<0.001), history of other subsequent malignant neoplasm (p=0.009), anthracycline exposure (p=0.009), alkylator exposure (p=0.002) and radiation therapy (RT; p<0.001) in univariate analysis. In a multivariate model, risk factors for the development of SS included anthracycline exposure and previous RT with respective rate ratios (RR) of 2.54 (p=0.008) and 2.58 (p=0.005), with these risks further influenced by primary diagnosis (p<0.001). Subgroup analysis of Hodgkin’s disease survivors revealed that alkylating agent exposure was associated with the development of SS with a RR of 4.26 (p=0.06). Subgroup analysis of STS survivors revealed that younger age at primary cancer diagnosis was associated with an increased risk of developing SS (p=0.01). Conclusions: Survivors of childhood malignancy are at increased risk of developing SS. Identified risk factors include exposure to anthracyclines, alkylators and RT, within diagnosis-specific subgroups. Analyses are underway to investigate standardized incidence ratios and absolute excess risk of SS in survivors, dose-response relationships as well as family history of cancer. No significant financial relationships to disclose.
Joint Effects of Systolic Blood Pressure and Serum Cholesterol on Cardiovascular Disease in the Asia Pacific Region
Journal: Circulation (2005)

Although interest in multifactorial interventions for cardiovascular disease is increasing, data on the strength and shape of the joint effects of blood pressure and cholesterol levels on the risk of cardiovascular disease are scarce, confined primarily to coronary heart disease (CHD) mortality in early middle-aged Western populations.This analysis included 29 cohorts from Asia (78% of the total 380,216 participants) and 7 from Australia and New Zealand, with a total of 2,547,447 person-years of observation. Stratified time-dependent Cox proportional-hazards analyses were used to regress time until first event against baseline systolic blood pressure (SBP) and total cholesterol levels. A total of 3079 CHD and 4247 stroke events occurred; stroke subtypes were confirmed by CT, MRI, or necropsy in 1471 (35%) stroke events. Usual values of SBP were strongly linearly associated with ischemic stroke, hemorrhagic stroke, and CHD. The slope of the association with SBP became steeper with decreasing levels of cholesterol for ischemic stroke (P=0.007) and CHD (P< or =0.0001). For example, for the cholesterol groups of <4.75, 4.75 to 5.49, 5.50 to 6.24, and > or =6.25 mmol/L, each 10-mm Hg-higher systolic pressure was associated with 34% (95% CI, 30% to 37%), 28% (95% CI, 21% to 35%), 25% (95% CI, 18% to 32%), and 21% (95% CI, 13% to 27%) higher CHD risk, respectively. Adjustments for other leading cardiovascular risk factors made no appreciable differences in these results.In Asia-Pacific populations, there are hazards of increasing SBP at all cholesterol levels and hazards of increasing cholesterol at all levels of SBP, but the associations of SBP with CHD risk and ischemic stroke risk are slightly steeper among those with low cholesterol levels. The joint effects of SBP and total cholesterol on cardiovascular disease seem consistent across various Western and Asian populations.
Cancer risk management decisions of women with BRCA variants of uncertain significance
Authors: K. J. Ready, A. M. Gutierrez-Barrera, D. Atchley, K. K. Solomon, C. Amos, F. Meric-Bernstam, K. H. Lu, G. N. Hortobagyi, B. Arun
Journal: Journal of Clinical Oncology (2008)

22021 Background: One result of BRCA genetic testing is a variant of uncertain significance (VUS). VUS are changes in the BRCA genes that may or may not be associated with an increased risk of cancer. Women found to have a VUS are a growing population, making up to 21% of patients who undergo genetic testing. Since the cancer risks associated with VUS are unknown, cancer risk managment recommendations are difficult and patients must make decisions regarding risk management for cancers that they may or may not be at risk for. The objective of this study was to describe the risk management decisions (RMD) undertaken by women who have a BRCA VUS. Methods: A retrospective chart review was performed. Women who underwent genetic testing for the BRCA genes at M.D. Anderson Cancer Center between 1997 and 2007 and had a VUS were included in the study. The RMD undertaken by these women were evaluated. Results: 83 women with BRCA VUS were identified. 24 were excluded from the study due to concomitant presence of a known deleterious mutation. Of the remaining 59 women, 45 had a personal history of breast cancer (PHBC), 7 had no personal history of cancer (NPHC), and 8 had a personal history of ovarian cancer (PHOC). The breast cancer RMD of the 45 women with PHBC included: 3 (7%) had bilateral mastectomies as treatment for bilateral cancer, and 18 (40%) had contralateral prophylactic mastectomy. The remaining women all have yearly mammograms. The ovarian cancer RMD of the 45 women with PHBC included: 4 (9%) had TAH/BSO prior to genetic testing; 4 (9%) had prophylactic TAH/BSO, and 16 (36%) undergo ovarian cancer screening. The breast cancer RMD of the 7 women with NPHC included: none had prophylactic mastectomy; 1 (14%) takes tamoxifen; and 5 (71%) have yearly mammograms. The ovarian cancer RMD of the 7 women with NPHC included: 2 (29%) had prophylactic TAH/BSO; and 2 (29%) undergo ovarian cancer screening. The breast cancer RMD of the 8 women with PHOC included: 1 had bilateral mastectomies as treatment for bilateral cancer; none had prophylactic mastectomy; 1 (13%) takes tamoxifen; and 6 (86%) undergo yearly mammograms. Conclusions: Women who have a BRCA VUS and a PHBC appear to be more aggressive in their RMD than women who have a VUS and have NPHC or PHOC. To our knowledge, this is the first study to describe the RMD of the BRCA VUS population. No significant financial relationships to disclose.
An <b><i>ex vivo</i></b> chemoresponse assay predicts carboplatin-induced progression-free interval in ovarian cancer
Authors: R. Coleman, T. Herzog, S. Hosford, B.-U. Sevin, A. Wells, L. Fiori, H. Gallion
Journal: Journal of Clinical Oncology (2004)

5134 Background: Carboplatin is the mainstay of primary ovarian cancer and is often used in recurrent ovarian cancer. The ability to identify tumors that will respond to this drug prior to selection of therapy would allow patients to avoid ineffective treatments and should lead to an improvement in outcome. Methods: We evaluated an ex vivo chemoresponse assay in predicting progression-free interval (PFI) in patients with ovarian cancer in response to Carboplatin-containing regimens. 128 women with primary or recurrent ovarian carcinoma, who were subsequently treated with a Carboplatin-containing regimen, had tumors tested with an ex vivo chemoresponse assay between 4/30/1997 and 4/30/2002. The assay results were scored for sensitivity or resistance based on live cell number after exposure to varied concentrations of Carboplatin. PFI and assay results were linked by an independent contract research organization. Cox Proportional Hazard Model analysis was used to identify independent prognostic factors. Results: Results of the Carboplatin assays for these patients were a significant independent predictor of PFI (p=0.049, Hazard Ratio (HR) of cases with a Resistant assay result vs. a Sensitive assay result (HRR-S)=2.52 [95% CI: 1.01 to 6.30], HR of patients with a Resistant assay result vs. an Intermediate assay result (HRR-I)=1.59 [95% CI: 1.00 to 2.51]). Further, the predictive accuracy of the assay improved as process improvements were implemented: 70 primary assays before 1/1/2001 were suggestive (p=0.16, HRR-S=2.60 [95% CI: 0.69 to 9.86]); whereas 43 primary assays since 1/1/2001 were significant (p=0.048, HRR-S =4.58 [95% CI: 1.01 to 20.80]). Conclusion: These data demonstrate the utility of an ex vivo chemoresponse assay in predicting the clinical outcome of ovarian cancer patients treated with Carboplatin-containing regimens. Moreover, continuous quality improvements enhanced the efficacy of the ex vivo chemoresponse assay. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Precision Therapeutics, Inc. Precision Therapeutics, Inc. Precision Therapeutics, Inc.
Paclitaxel in doxorubicin-refractory or mitoxantrone-refractory breast cancer: a phase I/II trial of 96-hour infusion.
Authors: W H Wilson, S L Berg, G Bryant, R E Wittes, S Bates, A Fojo, S M Steinberg, B R Goldspiel, J Herdt, J O'Shaughnessy
Journal: Journal of Clinical Oncology (1994)

PURPOSE A phase I study of paclitaxel infused over 96-hours was performed to determine toxicity, maximum-tolerated dose (MTD), and pharmacokinetics in patients with incurable lymphomas and solid tumors. A phase II study was performed at the MTD of paclitaxel in patients with doxorubicin/mitoxantrone-refractory metastatic breast cancer. PATIENTS AND METHODS In the phase I study, paclitaxel dose levels ranged from 120 to 160 mg/m2, administered on a 21-day cycle. Patients with metastatic breast cancer who had either no response or a partial response (PR) to doxorubicin or mitoxantrone and had measurable disease were eligible for the phase I and II studies. Expression of the multidrug resistance (mdr-1) gene was determined in tumor biopsies by mRNA quantitative polymerase chain reaction. RESULTS Twelve patients received a total of 73 cycles of paclitaxel on the phase I study. Dose-limiting mucositis and/or grade IV granulocytopenia was reached at 160 mg/m2, and 140 mg/m2 was selected as the phase II dose. Thirty-six consecutive patients with metastatic breast cancer were treated, of whom three were not assessable. The median age was 49 years, with disease in the liver and/or lung in 76%. Patients received a median of two prior regimens for metastatic disease, and 73% had no response to prior doxorubicin or mitoxantrone. Of 33 patients treated with paclitaxel, 16 patients (48%) achieved a PR and five (15%) achieved a minor response (MR). With a median potential follow-up duration of 60 weeks, the median progression-free and overall survival durations were 27 and 43 weeks, respectively. No correlation was found between extent of prior treatment or prior response to doxorubicin/mitoxantrone, and response to paclitaxel. Paclitaxel pharmacokinetics showed a correlation between both granulocyte and mucosal toxicity, and serum steady-state concentrations (Css) more than 0.07 mumol/L. Patients with liver metastases had significantly decreased paclitaxel clearance and higher paclitaxel Css. Levels of mdr-1 were uniformly low in all tumor biopsies studied. CONCLUSION The recommended phase II dose of paclitaxel is 140 mg/m2 in patients without liver metastases and 105 mg/m2 in patients with liver metastases. Ninety-six-hour infusions of paclitaxel were effective and well tolerated in patients with doxorubicin/mitoxantrone-refractory breast cancer. Prolonged infusion schedules may be more effective than shorter schedules and deserve further study.
In Vitro Hematopoietic and Endothelial Cell Development From Cells Expressing TEK Receptor in Murine Aorta-Gonad-Mesonephros Region
Authors: Isao Hamaguchi, Xu-Ling Huang, Nobuyuki Takakura, Jun-ichi Tada, Yuji Yamaguchi, Hiroaki Kodama, Toshio Suda
Journal: Blood (1999)
The value of transurethral resection of bladder tumor in one piece (TURBO).
Authors: H. Ikeda, Y. Ishida, S. Seko, T. Dejima, T. Shou, K. Ishikawa, M. Nomura, H. Sanefuji
Journal: Journal of Clinical Oncology (2010)

e15143 Background: Since transurethral resection of bladder tumor in one piece (TURBO) was reported in the Journal of Urology in 2000 by Ukai, some urologists carried out TURBO. We analyzed treatment results of TURBO in our hospital and examined the value of this procedure. Methods: A total of 14 patients with bladder tumors carried out TURBO under spinal anesthesia, in some cases blocking the obtulater nerve, from April 2006 to June 2009 in our hospital. The procedure is 1. point marking, 2. circular incision, 3. level incision and 4. specimen retrieval using a needle electrode in accordance with the Ukai's method. We investigated pathological findings, operation time and complications. Results: It is possible to diagnose the precise pathlogical findings by TURBO. All resected edge had no cancer. There were no recurrence on the same location. There were no complications during and after the operation. Operation time of TURBO (35-223 min) was longer than TUR-BT. Urethral catheter holding period and hospitalization period after TURBO was the same as TUR-BT. TURBO is a relatively safe procedure even for beginners. Conclusions: TURBO is a safe and useful procedure that provides precise pathological findings with minimal complications. Second TUR is not necessary for TURBO. TURBO has a possibility to be gold standard of the treatment for non muscle invasive bladder cancer. No significant financial relationships to disclose.
Prognostic significance of c-Fos expression in epithelial ovarian carcinoma
Authors: S. Mahner, C. Baasch, L. Woelber, K. Beck, J. Schwarz, F. Jaenicke, K. Milde-Langosch
Journal: Journal of Clinical Oncology (2008)

16540 Background: Members of the Fos protein-family dimerize with Jun proteins to form the AP-1 transcription factor complex. They play a central role in proliferation and differentiation of normal tissue as well as in oncogenic transformation and tumor progression. To elucidate the role of Fos transcription factors in ovarian cancer, we analyzed the expression of c-Fos, FosB, FosB2, Fra-1 and Fra-2 in patients with invasive epithelial ovarian carcinoma. Methods: In 101 consecutive ovarian cancer patients who presented for initial surgery, tumor tissue was intraoperatively snap-frozen for later examination by Western Blot Analysis. Expression of c-Fos, FosB, FosB2, Fra-1 and Fra-2 was evaluated with commercially available antibodies and quantified by densitometry. Patients were divided into three equal groups representing low, moderate and high protein expression, and correlation with clinicopathologic factors (age, FIGO-stage, histology, grade, nodal involvement, CA-125) as well as progression-free survival and overall survival was performed. Results: Reduced c-Fos expression was associated with significantly shorter overall survival (23.8, 46.0 and 55.5 months for patients with low, moderate and high c-Fos expression; p= 0.003) as well as progression-free survival (20.6, 31.6 and 51.2 months for low, moderate and high c- Fos levels; p=0.003). In addition, an inverse correlation with tumor grade (p=0.038) was noticed. No correlations were observed for FosB, FosB2, Fra-1, Fra-2 and the other clinicopathologic factors evaluated. Conclusions: Our study demonstrates for the first time, that loss of c-Fos expression correlates with tumor progression and suggests that c-Fos may be an independent prognostic factor in ovarian carcinoma. These results are in contrast to the classic concept of c-Fos as an oncogene, but are well supported by the recently discovered tumor-suppressing and pro-apoptotic function of c-Fos in colorectal, gastric and hepatic carcinoma. No significant financial relationships to disclose.
NABTT 2105: A phase I dose-escalation trial of GliaSite brachytherapy with conventional radiation therapy for newly diagnosed glioblastoma multiforme
Authors: V. W. Stieber, S. Tatter, T. Mikkelsen, G. Barnett, K. Judy, X. Ye, S. Desideri
Journal: Journal of Clinical Oncology (2005)

1570 Background: NABTT opened trial 2105 to determine the maximum tolerated dose (MTD) of GliaSite Brachytherapy (GSBT) with external beam radiation therapy (EBRT) in the treatment of newly-diagnosed GBM (NDGBM). Methods: Patients were enrolled in cohorts of 5 and received postoperative GSBT followed by conventional EBRT to 46 Gy +14 Gy boost. EBRT began within 30 days after GSBT, but not more than 60 days post surgery. A DLT was defined as CTC 2.0 grade 3/4 toxicity not resolved within 1 month of onset or 3 months from end of GSBT (whichever was longer), any Grade 5 toxicity, or radiation necrosis requiring craniotomy within 3 months from completion of brachytherapy. Progressive disease (PD) was defined as progressive neurologic abnormalities not explained by causes unrelated to tumor progression; > 25% increase in the volume of enhancing tumor; or new enhancement on MRI. Results: 13 patients were screened. 10 were treated with GSBT of which 8 were replaced: 5 had imaging progression before the evaluation endpoint was reached; 1 died of PE; 1 was taken off study to start new therapy; and 1 received incorrect dose of GSBT. The median patient age was 57 years (27–68); median KPS was 90 (60–100); median balloon size was 3 cm (2–4); median GSBT dose was 70 Gy at 1 cm depth (53–70); median dwell time was 95 hrs (92–165); and median delivered radioactivity was 365 mCi (195–419). No DLT was encountered. 6 patients were alive at last follow up. The median time of survival will be presented as data mature. Conclusions: As a significant number of patients did not reach the evaluation endpoint, it was determined that this trial could not be completed. Analysis of the MRIs suggested that radiographic changes may have represented treatment response and not PD. Phase III EORTC trial data showed that patients with NDGBM should be treated with concomitant temozolomide. It was therefore decided to close the trial and replace it with a Phase II trial using fixed-dose GSBT with temozolomide, the goal being to characterize the associated imaging changes and correlate these with pathologic findings at the time of imaging progression. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Proxima Therapeutics Proxima Therapeutics
Use of an in vitro chemoresponse assay to define a subset of colorectal carcinomas responsive to cetuximab
Authors: S. D. Rice, P. R. Ervin, S. L. Brower
Journal: Journal of Clinical Oncology (2009)

e15127 Background: Cetuximab (Erbitux) is a chimeric monoclonal antibody that binds to the extracellular domain of the epidermal growth factor receptor. This interaction interferes with ligand binding and activation of the receptor blocking the downstream signaling of EGFR and impairing cell growth and proliferation. Cetuximab also has been shown to mediate antibody dependent cellular cytotoxicity. Thus, a singular approach to drug mechanism likely would not capture the true effects of cetuximab. Cetuximab is FDA-approved to treat head and neck cancer and colorectal carcinomas and is being evaluated for use in non-small cell lung and endometrial cancer. Due to the low population response rate of cetuximab, an integrated biomarker that can identify patients with an increased likelihood for response would be of great clinical utility. The current study describes an in vitro chemoresponse assay to predict response of primary cultures of human colorectal tumor specimens to cetuximab. Methods: The chemoresponse assay (ChemoFx) was developed using four different immortalized carcinoma cell lines (NCI-H292, NCI-H522, NCI-H1666, Calu3). The chemoresponse assay was also performed on 54 first passage primary cultures of human colorectal tumor specimens. Cell lines and specimens were treated with a 10 dose concentration range of cetuximab for 72 hours, stained with a nuclear dye, and remaining post-treatment live cells were counted. Resulting dose-response curves were analyzed. Results: Two of the examined cell lines showed response to cetuximab treatment; EC50 values for NCI-H292 and NCI-H1666 were 825nM and 13nM, respectively. NCI-H522 and Calu3 were deemed non-responsive to cetuximab. Dose-response curves of the 54 primary colorectal cultures revealed that 8% of the cultures tested were responsive to cetuximab, 22% had an intermediate response, and 70% were deemed non-responsive. These results are consistent with a reported clinical response rate of 11% for cetuximab in colorectal carcinoma patients. Conclusions: Initial results demonstrate that in vitro chemoresponse testing may be useful in predicting patient response to cetuximab. This could increase the efficacy of the current chemotherapy decision-making process for oncologists and their patients. No significant financial relationships to disclose.