tbuckley/cabot-search huggingface dataset:
A phase II study of oxaliplatin reintroduction in patients pretreated with oxaliplatin and irinotecan for advanced colorectal cancer (RE-OPEN study): Reports of interim analysis.
Authors: Mitsukuni Suenaga, Nobuyuki Mizunuma, Satoshi Matsusaka, Eiji Shinozaki, Masato Ozaka, Mariko Ogura, Keisho Chin, Toshiharu Yamaguchi
Journal: Journal of Clinical Oncology (2013)

580 Background: Re-introduction of oxaliplatin for patients with metastatic colorectal cancer refractory to standard chemotherapy regimens including oxaliplatin, irinotecan and fluorouracil (5-FU) was thought to be effective approach, but has not been prospectively explored. Thus, we performed a single arm, open-label phase II study (UMIN ID: 000004884). Methods: Patients with prior chemotherapy including oxaliplatin and irinotecan, achieved tumor response or stable disease during prior oxaliplatin-based therapy, and six months or over from confirmed progression disease during previous oxaliplatin-based therapy were eligible for this study. Patients received FOLFOX regimens every two weeks. Primary endpoint was disease control rate (DCR) after 12 weeks of treatment. Tumor response was evaluated by RECIST v1.1, and DCR was defined as complete response, partial response or stable disease. This trial followed a Simon’s two-stage minimax design. Interim analysis of efficacy was planned after 12 weeks of treatment in 18 patients (Step I). If disease control were confirmed in more than five patients, 15 patients would be newly enrolled in Step II. Results: Between 01-2011 and 07-2012, 18 patients were enrolled in Step I of this study. Characteristics of patients were as follows (N=18): median age, 61 yrs (range 35-75 yrs); male/female, 11/7; ECOG PS0, 94.4%; and colon/rectum, 8/10. All patients were assigned to receive mFOLFOX6 regimen. Disease control was observed in seven patients. There was no benefit in nine patients. Two patients refused to continue treatment and one patient gave up treatment due to oxaliplatin related allergic reaction. According to the interim analysis, DCR after 12 weeks of treatment was 38.9%. There were no severe adverse events and treatment related deaths. Conclusions: In interim analysis, initial efficacy of reintroduction of oxaliplatin after 12 weeks of FOLFOX regimen was confirmed. Step II part of this study is currently ongoing. Clinical trial information: UMIN000004884.
The effect of bridging locoregional therapies on survival in hepatocellular carcinoma patients undergoing orthotopic liver transplantation: UNOS population study.
Authors: Minzhi Xing, Hyun Sik Kim
Journal: Journal of Clinical Oncology (2015)

346 Background: The effect of bridging locoregional therapies (LRT) on overall survival (OS) in pts with hepatocellular carcinoma (HCC) undergoing orthotopic liver transplantation (OLT) has not been investigated in large-scale population studies. Methods: TheUnited Network for Organ Sharing (UNOS) database was used to identify pts with HCC who received OLT between 2002 and 2010. Pts within Milan Criteria for whom an HCC Model for End-Stage Liver Disease (MELD) exception was approved were included. OS was compared between pts who received bridging LRT (including transarterial chemoembolization (TACE)) and those who did not. Kaplan-Meier estimation and Cox proportional hazard models were used for OS analysis. Results: Of 11,287 pts with HCC who received OLT, 9,876 pts had LRT data, mean age 56.6 yrs, 77% male; 5,103 received bridging LRT, including 3,676 who received TACE. Comparison groups were similar for age at OLT, waitlist duration, sex, race, BMI and MELD score (p&gt;.05 for all). Significantly prolonged OS with bridging LRT vs. none was observed from both OLT (111.6 vs 106.4 mo, p&lt;.001) and from Listing (176.1 vs 169.4 mo, p=.001). Similarly, significantly prolonged OS with bridging TACE vs. none was observed from both OLT (112.0 vs 107.2 mo, p&lt;.001) and from Listing (177.7 vs 169.9 mo, p=.001). Conclusions: In HCC pts undergoing OLT, both bridging LRT and TACE correlated with prolonged survival from OLT and from Listing in a UNOS population-based study. [Table: see text]
Young adult female cancer survivors’ concerns about genetic cancer risk in offspring.
Authors: Nirupa Jaya Raghunathan, Bridgette Thom, Danielle Novetsky Friedman, Catherine Benedict, Joanne Frankel Kelvin
Journal: Journal of Clinical Oncology (2016)

121 Background: More than 362,000 female cancer survivors under 40 years old live in the US. Research consistently shows no increased cancer risk among offspring of cancer survivors in the absence of a hereditary cancer. Still survivors voice concerns over the health of future children. This analysis explores young adult female cancer survivors’ (YAFCS) perceptions of genetic cancer risk and related reproductive concerns. Methods: Eligible females were aged 18-35, at least one year post-treatment. Participants were recruited using social media posts from 17 young adult cancer advocacy groups and directed to an anonymous web-based survey that included the Reproductive Concerns after Cancer Scale (RCACS), with a 3-item “Concerns about Future Child Health” subscale. Results: 346 YAFCS completed the full survey, and based on logic-based branching, 192 respondents could have completed the RCACS: 177 (92%) completed the entire scale and 187 (97%) completed the child’s health subscale. Mean RCACS score was 58.5 (sd = 11.6; range 22-86); mean child’s health score was 11.3 (sd = 3.3; range 3-15), with a negative skew. At the item-level, 65% of the sample worried about passing along cancer risk to offspring; 71% worried about family health history affecting future children; and 60% were afraid their children would have a high chance of getting cancer. RCACS and child’s health subscale scores did not vary by age, race, education, income, or diagnosis. Further, mean scores did not vary between survivors of family cancer syndromes (breast, ovarian, colorectal) and those with other diagnoses (RCACS: t = 1.4, df = 175, p = .14; child’s health: t = 0.02, df = 185, p = .99). Conclusions: Despite studies showing minimal genetic cancer risk in offspring of survivors, many YAFCS have concerns about the health of future children. This may be related to mistaken beliefs that genetic mutations within tumor cells are transmissible or unawareness of availability of pre-implantation genetic diagnosis for embryo selection in those with transmissible genetic mutations. There is a need to educate patients about these issues to enable them to make family building choices based on accurate information about genetic risk.
Characteristics and outcomes of pharmaceutical versus nonpharmaceutical affiliated phase III clinical trials on targeted agents for cancer therapy.
Authors: K. Fuh, T. Nguyen, S. M. Ueda, J. Shin, J. Tan, B. J. Monk, K. Osann, D. S. Kapp, J. K. Chan
Journal: Journal of Clinical Oncology (2010)

5073 Background: To compare the characteristics and outcomes of phase III clinical trials with or without pharmaceutical affiliation on targeted agent for cancer therapy. Methods: All phase III clinical trials using targeted agents in advanced cancers were identified in PubMed, Cochrane Central Register of Controlled Trials from 1986 to 2006. Chi-squared test and logistic regression analyses were employed for statistical analyses. Results: Of 159 phase III trials, 49 were affiliated with pharmaceutical institutions and 110 were from academic institutions, research institutes or cooperative groups. In the overall study, 82 trials were biologic vs. 77 trials were combination biologic and chemotherapy. 15 (9.4%) clinical trials were from single institutions vs. 143 (89.9%) from multiple institutions. 57 (35.8%) phase III trials were from the United States, 54 (34.0%) Europe, and 48 (30.2%) were from other countries including those from Asia and Australia. Pharmaceutical-affiliated trials enrolled a higher number of patients (p = 0.03), involved multiple institutions (p = 0.036), had shorter time to complete accrual (p = 0.011), were more likely to be performed outside the United States (p = 0.002), had a higher proportion of positive results (p = 0.02), had shorter follow-up (p = 0.001), and were published in journals with a higher impact factor (p = 0.043). Conclusions: Compared to nonpharmaceutical affiliated trials, pharmaceutical affiliated studies on anticancer targeted agents were more likely to involve multiple institutions, have shorter time to accrual, performed outside the United States, and result in a positive trial. However, the proportion of trials showing a survival benefit was not different between the two groups. No significant financial relationships to disclose.
Incidence, characteristics, and implications of thrombo-embolic events in patients with urothelial carcinoma of the bladder undergoing neoadjuvant chemotherapy.
Authors: Wilhelmina CM Duivenvoorden, Siamak Daneshmand, Daniel J. Canter, Yair Lotan, Peter C. Black, Hamidreza Abdi, Bas W.G. Van Rhijn, Elisabeth E. Fransen van de Putte, Peter J. Bostrom, Ilmari Koskinen, Piotr Zareba, Janet E. Baack Kukreja, Wassim Kassouf, Samer Traboulsi, Jehonathan H Pinthus
Journal: Journal of Clinical Oncology (2016)

393 Background: Neoadjuvant chemotherapy (NAC), in combination with radical cystectomy (RC), is associated with a significant survival advantage for patients with muscle-invasive bladder cancer. Chemotherapy as well as pelvic surgery are significant risk factors for thrombo-embolic events (TEE). The objectives of this study were to investigate the incidence and characteristics of TEE during and after NAC and subsequent RC for urothelial bladder cancer patients. Methods: A retrospective study was carried out on 827 consecutive patients who underwent NAC and cystectomy for urothelial bladder carcinoma from 2002 to 2014 at ten different tertiary centers across North America and Europe. The median time of follow-up from bladder cancer diagnosis was 13 months (range 1-119 months). The incidence (venous, arterial, port-site or deep vein thrombosis, thrombosis, clinical or incidentally detected pulmonary embolism) and timing of TEE (before or after ( &lt; or &gt; 30 days) RC) and Khorana score (based on baseline hemoglobin, platelet and leukocyte counts, BMI and tumor site, which was established for cancer patients treated with chemotherapy) was determined for all patients. Multivariate analysis was performed on 827 patients. Kaplan Meier survival curves and log rank test were used to compare survival between patients who developed TEE and those who did not. Results: The Khorana criteria indicated intermediate TEE risk in most patients. Khorana risk score was 1 or 2 in 88% of patients. Nevertheless, the incidence of TEE in patients undergoing NAC was 15%. 59 TEE were detected pre-operatively (7.1%), 21 early within 30 days of RC (2.5%) and 36 late post-operatively (4.3%). 32% of the TEE events were detected incidentally by imaging, 68% were detected clinically. Median overall survival of patients who developed TEE was 28 months compared to 71 months for those who did not develop TEE (p = 0.012). Conclusions: This multi-centre retrospective study suggests that TEE are very common in bladder cancer patients undergoing NAC followed by RC and is associated with poorer survival. Further investigation with a prospective prevention trial is warranted.
Modified Kegel exercise regimen following definitive and adjuvant prostate cancer radiotherapy.
Authors: Libni Eapen, John Ionescu, Amira Eapen
Journal: Journal of Clinical Oncology (2016)

e629 Background: 5-15% of patients treated with curative radiotherapy for prostate cancer experience some degree of urinary or fecal leakage. We hypothesized that a regimen of postradiotherapy perineal exercises would reduce this problem of sphincter dysfunction Methods: Upon completion of either conformal- or intensity-modulated radiotherapy to 76 Gy in 38 fractions (definitive) or 66 Gy in 33 fractions (postprostatectomy) patients were advised to commence a life-long program of daily perineal strengthening exercises. This consisted of a modified Kegel regimen for 5 minutes at a time, four times daily, and continued indefinitely. Patients have been monitored in regard to compliance and sphincter dysfunction at scheduled cancer clinic followup visits as well as by telephone survey. Results: 530 patients have been engaged in this postradiotherapy sphincter conditioning program. Parameters being analyzed are compliance with the regimen, frequency of exercise performance, urinary and fecal incontinence rates Conclusions: Pending the final tabulation of results the practical feasibility of such a prophylactic perineal exercise regimen as well as its impact on post radiotherapy sphincter integrity will be ascertained.
Prognostic impact of phosphorylated HER2 in HER2-positive primary breast cancer using reverse-phase protein array.
Authors: N. Hayashi, T. Iwamoto, A. M. Gonzalez-Angulo, J. Ferrer-Lozano, A. Lluch, N. Niikura, C. Bartholomeusz, S. Nakamura, G. N. Hortobagyi, N. T. Ueno
Journal: Journal of Clinical Oncology (2011)

616 Background: Tyrosine 1248 is one of the autophosphorylation sites of HER2. Our goal was to determine the prognostic value of expression level of tyrosine 1248-phosphorylated HER2 (pHER2) in patients with HER2-positive primary breast cancer. Methods: pHER2 expression level was measured using a reverse-phase protein array (RPPA), which can quantify the expression level of proteins as a continuous value, and compared with 5-year disease-free survival (DFS) using both derivation (n = 162) and validation (n = 227) in log-rank analysis. DFS was estimated with the Kaplan-Meiermethod. The Cox proportional hazards model was used in multivariate analysis. Results: Concordance of HER2 expression levels by RPPA and standard HER2 status by immunohistochemistry or FISH was confirmed in the derivation cohort (area under the curve [AUC] = 0.873, kappa’s coefficient: 0.679, Fisher’s exact test: p= 0.000, sensitivity = 73.8%, specificity = 94.9%). The optimal cutoff value of pHER2 levels (high vs. low) associated with DFS was developed using a receiver operating characteristic curve (AUC =0.662). Having a tumor with high expression of pHER2 levels (HR, 5.7; 95% CI, 1.25 to 25.7; p = 0.024) was independent predictors of DFS in the multivariate analysis. In the validation cohort, the difference between high and low expression of pHER2 tumor status was marginal when estimating DFS (57.1% vs. 84.5%, p = 0.077). Conclusions: In HER2-positive breast cancer patients, high expression of pHER2 was associated with lower DFS rates than low expression of pHER2. Quantification of pHER2 expression level may provide further prognostic information in HER2-positive breast cancer patients in addition to the current pathologic findings. Definitive prospective studies are warranted to further elucidate this relationship. Derivation Validation All patients (n = 162) HER2+ by RPPA (n = 26) All patients (n = 227) HER2+ by RPPA (n = 61) pHER2 status by RPPA n 5-y DFS (%) P n 5-y DFS (%) P n 5-y DFS (%) P n 5-y DFS (%) P High expression 19 11.7 0.000 17 65.4 0.020 7 57.1 0.001 7 57.1 0.077 Low expression 143 88.3 9 34.6 220 84.1 54 84.5
Influence of social demographics and African-American race on outcomes in testicular cancer: Analysis of 75,902 patients in the National Cancer database.
Authors: Craig R. Nichols, Claudio Jeldres, Khanh Pham, Siamak Daneshmand, Christian K. Kollmannsberger, Brandon M. Hayes-Lattin, Katherine Odem-Davis, Erika Wolff, Christopher R. Porter
Journal: Journal of Clinical Oncology (2014)

391 Background: While there have been substantial advances in treatment and outcomes in testicular cancer, most of the data are derived from large institutionals or clinical trials. Testicular germ cell tumors are uncommon (8,000 new patients annually in US). The incidence among patients (pts) of African origins is extremely low. Most of the conclusions regarding outcomes are based on Caucasian pts from research institutions. Information about modern outcomes in non-Caucasian races is scant and little is known about the influence of various social demographic parameters on presentation patterns and survival. Using this population-based database available through the NCDB, we sought to better understand social and racial variations in outcomes. Methods: Within the NCDB, 75,902 testicular cancer pts were available for review. Tools available through the NCDB were utilized for analysis. Herein, we evaluated social demographics (insurance type, educational achievement, annual income, type of treating institution) and racial/ethnic characteristics as they pertained to stage at presentation and survival. Results: 75,902 pts were available from the timeframe of 1998 through 2011 for aggregation of social demographic features as well as racial/ethnic characteristics. Overall survival was available on 48573 pts through 2006. Racial-ethnic breakdown at presentation was 84.1% (n=63,867) Caucasian and African-American 2.7% (n=2,083). Overall, insurance type, education (% without high school degree), income (&lt; $ 30000 to &gt;$46,000) and type of treating hospital were analyzed using univariate and multivariate models. Full details will be presented. Conclusions: Unfavorable presentations and outcomes in testicular cancer are seen by race and social demographics. In depth analytics are being performed to characterize the variations as related to biological/genetic differences and/or differences in social demographics. In this very large cohort, the National Cancer database demonstrates a 2-fold risk increase in death in African American pts relative to Caucasian pts with similar stage at presentation.
The implementation of Lean Six Sigma methodology in a multidisciplinary outpatient clinic for gastrointestinal cancer.
Authors: Yara Basta, Matthijs Monster, Thomas Rohof, Kristien M. A. J. Tytgat, Jean H. G. Klinkenbijl
Journal: Journal of Clinical Oncology (2014)

659 Background: In order to reduce long waiting times, a one-stop fast-track multidisciplinary outpatient clinic for gastrointestinal malignancies was initiated. Lean Six Sigma (LSS) is a combination of Lean-management and the Six Sigma methodology. LSS incorporates means to systematically identify and address suboptimal performance of a process. Lean and Six Sigma have their origin in the manufacturing industry, like the Toyota car factory, with largely homogenous products. In contrast, a complex high care oncology facility deals with heterogeneous patients. Our aim is to use the tools and strategies of LSS to increase the number of patients with an admission time (AT) of five days or less to ≥ 85% and to ensure that ≥ 90% of referring physicians receive the decisions formulated at the Multidisciplinary Team Meeting (MDTM) within one day. Methods: We have applied the DMAIC-cycle (Define, Measure, Analyse, Improve and Control) to our processes. The DMAIC-cycle is the management cycle of Lean Six Sigma. Results were measured before implementation of LSS and after for at least one month. Results: After implementing LSS causes for lags in AT, as well as for sending the documented decisions were identified. The lags in AT included patient delay, incomplete referral, official holidays and absences due to medical conferences. After the obstacles were successfully addressed we increased the percentage of patients with an AT ≤ 5 days from 48% to 70%, a 45% improvement. Causes for lags in sending the decisions, included verifying and signing the missive. Currently 99% of referring physicians receive the decision formulated by the MDT in ≤ 1 day. This is a substantial improvement from 2% to 99%. Conclusions: Lean Six Sigma is applicable in a multidisciplinary high care medical facility. Obstacles in the logistics of a complex medical facility can be identified and greatly improved.
Clinical and technical validation of a genomic classifier (ColoPrint) for predicting outcome of patients with stage II colon cancer.
Authors: Josep Tabernero, Victor Moreno, Robert Rosenberg, Ulrich Nitsche, Thomas Bachleitner-Hofmann, Giovanni Lanza, Jeroen van den Akker, Paul Roepman, Iris Simon, Ramon Salazar
Journal: Journal of Clinical Oncology (2012)

384 Background: Between 25 and 35% of stage II colon cancer patients will experience a relapse of their disease and may benefit from adjuvant chemotherapy. ColoPrint is a gene expression classifier that can predict disease relapse in patients with early-stage colorectal cancer (Salazar et al. JCO 2011). Methods: ColoPrint was developed using gene expression data from whole genome microarrays and was validated in in-silico datasets and independent patient cohorts from 5 European hospitals. Fresh frozen tissues, clinical parameters, MSI-status and follow-up data for patients were available. Samples were hybridized to Agilent microarrays and the ColoPrint index was determined. Uni-and multivariate analysis was performed on the pooled stage II patient set (n=320) who had a median follow-up of 70 months. Reproducibility and precision studies were performed using clinical and control samples specific for each outcome level (high risk, low risk). Experiments were performed on 20 days with 2 runs per day by multiple technicians reflecting daily diagnostic conditions. Results: Performance of the prognostic classifier was confirmed in reproducibility and stability assays and stringent quality controls were established. In the clinical validation, ColoPrint classified two-third of patients (209/320) as low risk. The 3-year relapse-free survival was 94% for low risk patients and 79% for high risk patients with a HR of 2.74 (95% CI 1.54-4.88; p=0.006). MSI-status and the number of assessed lymph nodes were the only significant clinical parameters in the univariate analysis. Using parameters from the ASCO recommendation (T4, perforation, less than 12 LN assessed and/ or high grade) for the identification of high risk patients was not significant (HR 1.43, 95% CI 0.81-2.55; p= 0.22) and no clinical parameter added power to the ColoPrint classification in multivariate analysis. Conclusions: ColoPrint is available as a routine diagnostic test with a high precision and reproducibility. ColoPrint significantly improves the prognostic accuracy of pathologic factors and MSI and facilitates the identification of low risk patients with stage II disease who may be safely managed without chemotherapy.