tbuckley/cabot-search huggingface dataset:
Risk of missing advanced stage or high grade tumors during active surveillance (AS) even in favorable-risk prostate cancer (PC).
Authors: Jeri Kim, John Francis Ward, Curtis A. Pettaway, Xuemei Wang, Deborah A. Kuban, Steven J. Frank, Andrew Lee, Louis L. Pisters, Surena F. Matin, Jay Bakul Shah, Jose A. Karam, Brian Francis Chapin, John N. Papadopoulos, Mary F. Achim, Karen Elizabeth Hoffman, Thomas J. Pugh, Seungtaek Choi, Christopher Logothetis, Patricia Troncoso, John W. Davis
Journal: Journal of Clinical Oncology (2013)

5069 Background: Owing to tumor heterogeneity, no standard selection criteria exist among prospective AS cohorts. Generally, men with low-stage, -volume, and -grade PC and low prostate-specific antigen (PSA) are eligible. In our prospective single-institution AS trial, men with early-stage PC were stratified: Gr I (favorable risk), II (pt’s choice), or III [competing comorbidities prevent local therapy (Tx)]. We report our experience with Gr I. Methods: Eligibility for Gr I: Gleason score (GS) ≤6, 1 positive (pos) core (&lt;3 mm), and PSA &lt;4 ng/mL or GS 7 (3+4), 1 pos core (&lt;2 mm), and PSA &lt;4 ng/mL. Monitoring q6mo included PSA, testosterone, and digital rectal exam. All pts had repeat biopsy (re-BX) at 1 y and then on predetermined BX scheme. Later, re-BX was required within 6 mo of study entry per an 11-core BX scheme (also used during AS). Definitive Tx was offered to pts who met reclassification based on clinical, BX (upgrading, ↑ in pos core BX, and/or ↑ tumor length), and/or radiographic progression. Imaging studies [bone/CT scans, endorectal MRI (eMRI)] were at physician’s discretion. Results: From 2/2006 to 2/2012, 585 pts enrolled; 191 met Gr I criteria (41 before, 150 after re-BX requirement). Median age was 64 y (range, 36–83); 82% were white, 8% African-American, 8% Hispanic, 2% Asian; 4% had cT1a/cT1b, 84% cT1c, and 12% cT2 disease. Most (189/191) had GS 6 [1 had GS 5, and 1, GS 7 (3+4)]. Median PSA was 3.3 (range, 0.2–10). With median follow-up of 36.2 mo (95% CI: 30.6–41.7), 32/191 (17%) were reclassified [20/41 (49%) before and 12/150 (8%) after re-BX requirement]. Of 32 reclassified, 17 were due to GS: 11 to GS 7 (3+4), 4 to GS 7 (4+3), and 2 to GS 8 (4+4). Ten of the 32 reclassified chose Tx [4 radical prostatectomy (RP); 4 radiation; 2 cryotherapy]. RP showed a pT2N0 GS9 (4+5) apical tumor in 1 at 5 y, a pT3aN0 GS7 (4+3) tumor in 1 at 3 y, a pT2N0 GS7 (4+3) tumor in 1 at 1 y, and a T2N0 GS 7 (3+4) tumor in 1 at 2 y. Conclusions: Restrictive selection criteria and re-BX at study entry improve clinical risk classification; however, other improvements, including imaging and markers of disease progression could enhance pt selection for AS.
Concordance of blood- and tumor-based detection of RAS mutations to guide anti-EGFR therapy in metastatic colorectal cancer
Authors: J. Grasselli, E. Elez, G. Caratù, J. Matito, C. Santos, T. Macarulla, J. Vidal, M. Garcia, J.M. Viéitez, D. Paéz, E. Falcó, C. Lopez Lopez, E. Aranda, F. Jones, V. Sikri, P. Nuciforo, R. Fasani, J. Tabernero, C. Montagut, D. Azuara, R. Dienstmann, R. Salazar, A. Vivancos
Journal: Annals of Oncology (2017)

Circulating tumor DNA (ctDNA) is a potential source for tumor genome analysis. We explored the concordance between the mutational status of RAS in tumor tissue and ctDNA in metastatic colorectal cancer (mCRC) patients to establish eligibility for anti-epidermal growth factor receptor (EGFR) therapy.A prospective-retrospective cohort study was carried out. Tumor tissue from 146 mCRC patients was tested for RAS status with standard of care (SoC) PCR techniques, and Digital PCR (BEAMing) was used both in plasma and tumor tissue.ctDNA BEAMing RAS testing showed 89.7% agreement with SoC (Kappa index 0.80; 95% CI 0.71 - 0.90) and BEAMing in tissue showed 90.9% agreement with SoC (Kappa index 0.83; 95% CI 0.74 - 0.92). Fifteen cases (10.3%) showed discordant tissue-plasma results. ctDNA analysis identified nine cases of low frequency RAS mutations that were not detected in tissue, possibly due to technical sensitivity or heterogeneity. In six cases, RAS mutations were not detected in plasma, potentially explained by low tumor burden or ctDNA shedding. Prediction of treatment benefit in patients receiving anti-EGFR plus irinotecan in second- or third-line was equivalent if tested with SoC PCR and ctDNA. Forty-eight percent of the patients showed mutant allele fractions in plasma below 1%.Plasma RAS determination showed high overall agreement and captured a mCRC population responsive to anti-EGFR therapy with the same predictive level as SoC tissue testing. The feasibility and practicality of ctDNA analysis may translate into an alternative tool for anti-EGFR treatment selection.
A revised RTOG recursive partitioning analysis (RPA) model for glioblastoma based upon multiplatform biomarker profiles.
Authors: Arnab Chakravarti, Meihua Wang, Kenneth D. Aldape, Erik P. Sulman, Markus Bredel, Anthony M. Magliocco, Alexander C. Klimowicz, Monika Hegi, Roger Stupp, Mark R. Gilbert, Walter J. Curran, Maria Werner-Wasik, Anita Mahajan, Christopher J. Schultz, Minesh P. Mehta
Journal: Journal of Clinical Oncology (2012)

2001 Background: The Radiation Therapy Oncology Group (RTOG) recursive partitioning analysis (RPA) model, which relies on clinical variables, has been used worldwide to establish distinct prognostic classes of patients (pts) with malignant glioma as well as eligibility criteria for clinical trials. In the present study, we have updated the RPA to include additional molecular variables, specifically for glioblastoma (GBM) patients treated in the temozolomide (TMZ)-era, to make the model more relevant, contemporary, and discriminatory. Methods: The dataset utilized was from RTOG 0525, a phase III study examining radiation (RT) with concurrent TMZ, followed by adjuvant standard dose vs. dose-dense TMZ in pts with newly-diagnosed GBM. 162 pts from RTOG 0525 had available tissues for profiling of key signaling molecules using the AQUA platform. Results: pAKT, c-met, and MGMT protein were each found to be significantly associated with adverse outcome on multivariate analysis. These variables were combined with clinical and genetic biomarkers (e.g., MGMT promoter methylation, IDH1 mutation, mRNA profiling) previously found to be of significance (MCP model, ASCO, 2011) to generate an even more robust, discriminatory RTOG RPA model. The explained variation for these three classification models was found to be 41.7 (Current RPA), 19 (MCP), and 14.9% (Clinical RPA), respectively, with higher values indicating better separation of prognostic groups (see table). Conclusions: The current RTOG RPA classification model, based upon incorporation of multi-platform biomarker analysis, holds promise for RT+TMZ-treated GBM patients; further validation of this model is planned. Financial Support: NCI grants U10 CA21661, U10 CA37422, U24 CA114734, 1RC2CA148190, 1RC2CA148190, RO1CA108633, and BTFC grant. [Table: see text]
A phase III randomized trial of cisplatin and paclitaxel administered by either 24 hour or 96 hour infusion in patients with selected stage III or stage IV epithelial ovarian cancer (GOG162)
Authors: D. R. Spriggs, M. Brady, S. Rubin, M. Hanley, L. J. Copeland, D. Clarke-Pearson, R. Burger
Journal: Journal of Clinical Oncology (2004)

5004 Background: Although taxane / platinum combinations have become the standard of care for advanced epithelial ovarian cancer (EOC), the impact of prolonged paclitaxel (pctl) in the treatment of ovarian cancer is unknown. Methods: Patients (pts) with suboptimal Stage III and Stage IV EOC and Primary peritoneal cancer were eligible for this randomized trial. Stage III suboptimal pts were only eligible if organ involvement precluded their participation in GOG 152, an interval debulking study. Normal organ function and a PFS ≤2 were required. The pts were randomized to 6 cycles of cisplatin (CDDP) 75 mg/m and either pclt135 mg/m2 over 24h (arm A) or pclt 120 mg/m2 over 96h (arm B). The primary endpoint was overall survival. Results: 293 pts of a planned 324 pts were enrolled before the study was closed. 140 pts were evaluated in each arm (13 ineligible). In arm A, 80% of pts completed all 6 cycles while in arm B, 82% completed their treatment. Granulocytopenia was more severe for arm A (p<0.001) while anemia was more severe in arm B (p<0.003). The accrual into this study was terminated 8/00 due to a scheduled interim futility analysis. As of 12/03, the median duration of follow-up is 4.5 years with 213 deaths reported. The median PFS was 12.4 vs 12.6 mo for arm A and B, respectively. The median survival for arms A and B was 29.9 mo and 30.5 mo, respectively. The relative death rate was approximately 5% greater among those randomized to prolonged infusion regimen (hazard ratio: 1.047; 95% CI: 0.798 – 1.372). Conclusions: The median survival duration for these patients, who have a relatively poor prognosis, is 2.5 years. Prolonged pclt infusions do not significantly increase duration of survival over a 24 h infusion. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Bristol-Myers Squibb Bristol-Myers Squibb
Prognostic value of various summary measures of prostate-specific antigen (PSA) kinetics for overall survival (OS) in patients (pts) with metastatic castrate-resistant prostate cancer (mCRPC) who failed first-line chemotherapy (TROPIC trial).
Authors: Catherine Legrand, Stephane Oudard, A. Oliver Sartor, Johann Sebastian De Bono, Liji Shen, Jean-Pascal H. Machiels
Journal: Journal of Clinical Oncology (2013)

e16010 Background: PSA kinetic measures are often reported as prognostic factors for overall survival (OS) in mCRPC pts. The objective of this study is to investigate the prognostic value of various summary measures of pre- and post-treatment PSA kinetics on OS in patients treated with cabazitaxel or mitoxantrone following progression during or after docetaxel in the TROPIC trial. Methods: PSA data from the phase III TROPIC trial that randomized 755 docetaxel pre-treated mCRPC pts between cabazitaxel and mitoxantrone were used. Baseline was defined as the time of randomization. The prognostic value of pre- and post-baseline PSA kinetic measures (percentage decline (PSA-D) / increase (PSA-I) and PSA velocity (PSA-V) within 2 months (m) before and post-baseline (B)) was systematically assessed for OS according to several cut-offs. PSA-V was computed as the slope of individual regression line over at least 3 measurements. The Kaplan-Meier estimator was used to compute median OS [95% CI]. Uni- and multivariate analyses were based on the Cox model. Results: Pre-B PSA-I, and Post-B PSA-D/I were found to be significant prognostic factor for various cut-off, e.g. pts with a PSA-I above 25% within 2 months after randomization were significantly more at risk [median OS: 11.4m[10.0-12.7] vs. 14.6m [13.0-17.9], p=0.0005]. For Post-B PSA-D, all cut-offs between 20 and 70% were significant, but the 30% one led to the more significant p-value. OS for the 224 pts with a Pre-B PSA-V below the median (1.07) was significantly better than for the 228 pts with a value above (median OS: 16.3m[14.3-18.8] vs. 12.9m [11.4-14.1], p&lt;0.0001). Post-B PSA-V below (n=325) or above (n=312) the median (-0.012) also led to a significantly different OS (median OS: 16.3m [15.2-18.8] vs. 12.3m [11.3-13.4], p&lt;0.0001). All results remain significant while adjusting for ECOG-PS, measurable disease, baseline pain, time of last docetaxel infusion and treatment. Conclusions: Our data suggests that pre and post-treatment PSA velocity is an independent prognosis factor for OS in mCRPC pts treated with chemotherapy.
Active and passive smoking in relation to lung cancer incidence in the Women's Health Initiative prospective cohort study.
Authors: Ange Wang, Jessica Kubo, Juhua Luo, Manisha Desai, Michael T Henderson, Rowan T. Chlebowski, Hilary Tindle, Chu Chen, JoAnn E Manson, Ann G. Schwartz, Michele L Cote, Jean Wactawski-Wende, Scarlett Lin Gomez, Manali I. Patel, Marcia L Stefanick, Heather A. Wakelee
Journal: Journal of Clinical Oncology (2013)

1504 Background: The relationship between both active and passive smoking and lung cancer incidence in post-menopausal women was examined in theWomen’s Health Initiative Observational Study (WHI-OS). Methods: The WHI-OS, a prospective cohort study conducted at 40 U.S. centers, enrolled women ages 50-79 from 1993-1998.Among 93,676 participants, 76,304 women with complete smoking and covariate data comprised the analytic cohort, in which the association of lung cancer incidence with active and passive (childhood, adult home, and work) smoking exposure was studied. Results: Over 10.5 meanyears of follow-up with 901 lung cancer cases, lung cancer incidence was higher in current smokers (HR 13.44, 95% CI 10.80-16.75) and former smokers (HR 4.20, 95% CI 3.48-5.08), compared to never smokers. This relationship was dose-dependent for both current and former smokers. Risk of all lung cancer subtypes, particularly small cell lung cancer (SCLC) and squamous cell carcinoma (SqCC), was higher in smokers. Among never smokers, any passive smoking exposure (HR 0.88, 95% CI 0.52-1.49) and most passive smoking categories did not significantly increase lung cancer risk, compared to no passive exposure; however, passive exposure as an adult at home for &gt;=30 years was associated with increased risk, of borderline significance (HR 1.61, 95% CI 1.00-2.58). Current smokers had an annualized lung cancer incidence rate of 472.9 cases/100,000 person-years, compared to 158.1 for former smokers and 36.2 for never smokers (112.3 overall). Conclusions: To our knowledge, this is the first study to examine both active and passive smoking in relation to lung cancer incidence in a complete prospective cohort of U.S. women. Active smoking is associated with significant increases in incidence of all lung cancer subtypes in post-menopausal women, particularly SCLC and SqCC. Smoking cessation decreases lung cancer risk. Prolonged exposure as an adult at home may be the strongest passive smoking contributor to lung cancer risk in this cohort. The findings support continued need for investment in smoking prevention and cessation, research on passive smoking, and understanding of lung cancer risk factors other than smoking.
MAGE-A3 expression in patients screened for the DERMA trial: A phase III trial testing MAGE-A3 immunotherapeutic in the adjuvant setting for stage IIIB-C-Tx melanoma.
Authors: John F Thompson, Mario Santinami, Thomas Jouary, Eugeny Levchenko, Bernard Mark Smithers, Laurent Mortier, Jean Jacques Grob, Uwe Trefzer, Ralf Gutzmer, Corinne Jamoul, Olivier Peeters, Brigitte Dreno, John M. Kirkwood
Journal: Journal of Clinical Oncology (2012)

8559 Background: Administration of MAGE-A3 immunotherapeutic involves the active immunization of patients (pts) with tumors expressing the MAGE-A3 protein. This new investigational approach has been previously assessed in two phase II trials, one in pts with metastatic melanoma (NCT00086866) and another in pts with completely resected non-small cell lung cancer (NCT00290355). Based on the positive responses observed in both studies, a randomized phase III placebo controlled trial assessing MAGE-A3 immunotherapeutic as adjuvant treatment in pts with resected, regionally advanced melanoma (stage IIIB-C-Tx AJCC/UICC 2010) is currently ongoing (DERMA Phase III trial, NCT00796445). Methods: Formalin-fixed, paraffin-embedded tumor tissues were prepared from surgically removed metastatic lymph nodes and tested for MAGE-A3 expression by qRT-PCR. Other baseline patient and tumor characteristics were collected during screening to further investigate factors that could potentially influence MAGE-A3 expression. Results: Between Dec 1, 2008 and Oct 25, 2011, 3917 pts were screened. Of the 3,183 valid samples (excluding the 513 inconclusive tests [66% for poor quality, 27% out-of range, 7% miscellaneous]) and the 221 missing samples, 2,092 (65.7%) were positive for MAGE-A3 expression. In these stage III melanoma pts, no difference in MAGE-A3 expression levels were identified with regard to (1) disease stage - IIIB (62.6%), IIIC (66.5%) and IIITx (66.2%); (2) gender - male (64.2%), female (68.1%); (3) age group - 18 to 39 years (63.2%), 40 to 49 years (65.3%), 50 to 59 years (66.8%), 60 to 69 years (68.1%) and 70 years and over (63.4%) and (4) region: Europe (66.1%), North America (63.0%) and rest of the world including Argentina, Brazil, Australia, Mexico, Taiwan, Japan, Korea (67.9%). Conclusions: Expression of the MAGE-A3 gene in the DERMA trial population (stage IIIB-IIIC-IIITx) was 66%. It was not correlated with age, gender, disease stage or geographic region. This expression frequency is consistent with published data in metastatic melanoma (Van den Eynde, 1997; Vourc’h-Jourdain et al, 2009) and has potentially important clinical implications.
分岐部冠状動脈損傷部の治療における,Rota‐Cypherの効果と安全性
Authors: Ohta Hiroshi, Kurata Takeshi, Okazaki Shinya, Yokoyama Ken, Nishino Akihisa, Yaginuma Kennji, Tamura Hiroshi, Kojima Takahiko, Akimoto Yoshinori, Miyauchi Katsumi, Daida Hiroyuki
Journal: Circulation (2006)
Evaluation of Quality-of-life (QoL) in patients(pts) with advanced solid tumors as screening tool during phase 1 clinical trial recruitment- risk assessment for adverse events and subject replacement.
Authors: Sidra Anwar, Wei Tan, Chi-Chen Hong, Sonal Admane, Askia Dozier, Francine Siedlecki, Amy Whitworth, Ann Marie DiRaddo, Dawn DePaolo, Sandra M Jacob, Wen Wee Ma, Austin Miller, Alex A. Adjei, Grace K. Dy
Journal: Journal of Clinical Oncology (2015)

e17755 Background: Serious adverse events (SAEs) and subject replacements occur frequently in phase I studies. Whether QoL or other clinical features can predict SAEs or subject replacement among pts participating in phase I clinical trials is not known. Methods: 92 eligible pts with solid tumors were included into this analysis after enrolling into one of 23 phase 1 solid tumor clinical trials at Roswell Park Cancer Institute. QoL questionnaires (FACT-G, EORTC QLQ-C30 and Medical Outcomes Study Social Support Survey) were administered at baseline at the time of screening. Baseline Charlson comorbidity scores (CCS), Royal Marsden scores (RMS) and Neutrophil to Lymphocyte ratios (NLR) were obtained. Frequency of dose limiting toxicities (DLTs), subject replacement and all SAEs that occurred within the first 4 cycles of treatment were recorded. Fisher’s exact test was used to study the association between categorical variables. Mann-Whitney-Wilcoxon test was used to compare different groups in regards to continuous variables. A linear transformation was used to standardize QoL scores. A p-value ≤ 0.05 was considered statistically significant. Results: Mean age of the pts was 61 years, and 41% were male. Majority of malignancies were of gastrointestinal origin (42%) followed by the respiratory system (24%). Baseline QOL, CCS, and RMS were not associated with DLTs nor subject replacement. Baseline EORTC QLQ-C30 scores and NLR were significantly different among pts who encountered SAEs (p = 0.01 and 0.04, respectively). When EORTC QLQ-C30 scores were further analyzed according to specific domains, worse global health status, functional and symptom scores were each associated with occurrence of SAEs (p = 0.05, 0.03 and 0.02, respectively). Conclusions: Baseline EORTC QLQ-C30 score and NLR are associated with risk of SAEs during phase 1 trial therapy in pts with advanced solid malignancies. Additional studies are needed to validate this observation and assess efficacy of interventions, such as early palliative care, that might mitigate the risk for SAE in this population.
Long term results of a prospective study of internal mammary chain (IMC) brachytherapy.
Authors: Rima Sanjay Pathak, Umesh Mahantshetty, Rajesh Kinhikar, Rakesh Jalali, Vani Parmar, Ashwini Budrukkar, Anil Tibdewal, Rajendra A. Badwe, Rajiv Sarin
Journal: Journal of Clinical Oncology (2015)

e12061 Background: Recent evidence suggest improved Disease Free Survival (DFS) and Overall Survival (OS) with IMC radiotherapy (RT) for inner / central quadrant breast cancers. Long term results of a prospective study using a novel method of IMC RT with HDR catheter placed in the Internal Mammary Vessel are presented. Methods: In women with inner or central quadrant T3/4 or axillary node +ve breast cancer, IMC HDR brachytherapy was given along with standard surgery, external RT and systemic therapy as appropriate for the stage. Clinical outcomes in terms of DFS and OS (Kaplan Meier method), factors affecting DFS and OS (Cox proportional hazard model) and toxicity were assessed. Results: From 2001 to 2008, 506 breast cancer patients received IMC brachytherapy with single intraluminal flexible catheter to a dose of 34Gy/10#, treating an average length of 7.5 cm (range 4 – 12cm).This was followed by standard external RT to breast or chest wall and SCF to a dose of 45 – 50Gy/ 25# over 5 weeks. The median T size was 4.5 cm and 50% cases were Locally Advance Breast Cancer (LABC). Majority (83%) of the tumors were high grade and node positive (86%) on pathology. Neoadjuvant and adjuvant chemotherapy was given to 282 (55%) and 173 (34%) patients respectively. IMC nodes were sampled in 112 (22.1%) cases of which IMC node were identified in 73/112 (65%) cases. In 14/73 (19%),the sampled IMC nodes were metastatic. The median follow up was 70 months (range 0 – 160 months). Locoregional and distant failure was seen in 103 (20.3%) and 140 (27.6%) respectively. Isolated regional relapse was seen in only 8 (1.5%) patients. The DFS and OS at 5 years was 67.8% and 90.1% and at 8 years was 60% and 84.5% respectively. Locally advanced disease, node positivity, estrogen and progesterone receptor negativity and inner quadrant tumors predicted significantly poor DFS, whereas Inner quadrant tumor and node positivity were the only factors that significantly predicted poor OS. Conclusions: IMC brachytherapy is a safe and simpler technique with equivalent outcomes as compared to external beam technique and should be encouraged in developing countries with resource constraints.