tbuckley/cabot-search huggingface dataset:
High-Throughput Genomics and Clinical Outcome in Hard-to-Treat Advanced Cancers: Results of the MOSCATO 01 Trial
Authors: Christophe Massard, Stefan Michiels, Charles Ferté, Marie-Cécile Le Deley, Ludovic Lacroix, Antoine Hollebecque, Loic Verlingue, Ecaterina Ileana, Silvia Rosellini, Samy Ammari, Maud Ngo-Camus, Rastislav Bahleda, Anas Gazzah, Andrea Varga, Sophie Postel-Vinay, Yohann Loriot, Caroline Even, Ingrid Breuskin, Nathalie Auger, Bastien Job, Thierry De Baere, Frederic Deschamps, Philippe Vielh, Jean-Yves Scoazec, Vladimir Lazar, Catherine Richon, Vincent Ribrag, Eric Deutsch, Eric Angevin, Gilles Vassal, Alexander Eggermont, Fabrice André, Jean-Charles Soria
Journal: Cancer Discovery (2017)

High-throughput genomic analyses may improve outcomes in patients with advanced cancers. MOSCATO 01 is a prospective clinical trial evaluating the clinical benefit of this approach. Nucleic acids were extracted from fresh-frozen tumor biopsies and analyzed by array comparative genomic hybridization, next-generation sequencing, and RNA sequencing. The primary objective was to evaluate clinical benefit as measured by the percentage of patients presenting progression-free survival (PFS) on matched therapy (PFS2) 1.3-fold longer than the PFS on prior therapy (PFS1). A total of 1,035 adult patients were included, and a biopsy was performed in 948. An actionable molecular alteration was identified in 411 of 843 patients with a molecular portrait. A total of 199 patients were treated with a targeted therapy matched to a genomic alteration. The PFS2/PFS1 ratio was >1.3 in 33% of the patients (63/193). Objective responses were observed in 22 of 194 patients (11%; 95% CI, 7%-17%), and median overall survival was 11.9 months (95% CI, 9.5-14.3 months).Significance: This study suggests that high-throughput genomics could improve outcomes in a subset of patients with hard-to-treat cancers. Although these results are encouraging, only 7% of the successfully screened patients benefited from this approach. Randomized trials are needed to validate this hypothesis and to quantify the magnitude of benefit. Expanding drug access could increase the percentage of patients who benefit. Cancer Discov; 7(6); 586-95. ©2017 AACR.See related commentary by Schram and Hyman, p. 552This article is highlighted in the In This Issue feature, p. 539.
Diabetes, metformin use, and colorectal cancer survival in women: A retrospective cohort study.
Authors: Furha Iram Cossor, Lucile L. Adams-Campbell, Rowan T. Chlebowski, Marc J Gunter, Karen Johnson, Robert E. Martell, Anne McTiernan, Michael S. Simon, Thomas Rohan, Robert B Wallace, Jessica Paulus
Journal: Journal of Clinical Oncology (2012)

e14005 Background: Observational studies have associated metformin use with lower colorectal cancer incidence but few studies have examined survival impact. We examined the relationship between metformin use, diabetes, and survival in postmenopausal women diagnosed with colorectal cancer while participating in the Women’s Health Initiative (WHI) Clinical Trial or Observational Study. Methods: 2,066 postmenopausal women with colorectal cancer diagnosed while enrolled in the WHI were followed for a median of 4.1 years, with 589 deaths overall and 414 colorectal cancer deaths. In this cohort, overall and colorectal cancer-specific survival were compared among women with diabetes who reported ever using metformin (n=84); those with no reported use of metformin (n=128); and women without diabetes (n=1854). Cox proportional hazard models were used to estimate the associations between metformin use, diabetes and survival outcomes from the time of colorectal cancer diagnosis. Two strategies were used to adjust for potential confounders: multivariate adjustment with known predictors of colorectal cancer survival and construction of a propensity score for the likelihood of receiving metformin, with model stratification by propensity score quintile. Results: After adjusting for age and stage at diagnosis, women with diabetes on metformin had no significant difference in colorectal-cancer specific survival compared to metformin non-users (HR 0.75; 95% CI 0.40 -1.38, p=0.67) or compared to women without diabetes (HR 1.00; 95% CI 0.61 - 1.66, p=0.99). With propensity score adjustment, the HR for colorectal cancer-specific survival in women with diabetes on metformin compared to non-users was 0.90 (95% CI 0.48 – 1.69, p=0.75). Women with diabetes reporting metformin use had no significant difference in overall survival compared to non-users (HR 0.84; 95% CI 0.51 – 1.37; p=0.48) or non-diabetics (HR 1.20; 95% CI 0.80 - 1.79; p=0.39). Conclusions: In postmenopausal women with colorectal cancer and diabetes, no statistically significant difference was seen in colon-cancer specific survival in those who used metformin. Analyses in larger populations of colorectal cancer patients are warranted.
Prediction of response to chemotherapy using sequential F-18-fluorodeoxyglucose (FDG) positron emission tomography (PET) in patients with metastatic colorectal cancer
Authors: J. Kim, S. Choi, H. Yi, J. Lim, M. Lee, I. Hyun, C. Kim
Journal: Journal of Clinical Oncology (2007)

2536 Background: Clinical response is determined after 2 or 3 cycles of chemotherapy by changes in tumor size as assessed by conventional imaging procedures such as computed tomography (CT). The aim of this study was to evaluate the use of sequential F-18 FDG PET to predict response to standardized chemotherapy for metastatic colorectal cancer (mCRC). Methods: Clinical response, as assessed by RECIST criteria, served as the reference. Investigators were free to choose chemotherapy regimen. F-18 FDG PET images after every second cycles of chemotherapy were analyzed semiquantitatively for each metastatic lesion using standardized uptake values (SUVs) normalized to patients’ blood glucose levels. PET responses were prospectively assessed as either complete metabolic response (CMR), partial metabolic response (PMR), stable metabolic disease (SMD), or progressive metabolic disease (PMD). In addition, sum of SUV of all metastatic lesions (sSUV) and a maximal SUV (mSUV) were recorded each PET-CT scan. Results: Twenty-four patients underwent 73 PET-CT scans since March 2005. The response to chemotherapy included CR in 1 (4.2%), PR in 10 (42%) by RECIST criteria. Median duration of follow- up was 8.3 months (range, 1.7 - 16.2) and median progression free survival (PFS) time was 6.4 months. At the baseline evaluation, PET-CT was the more sensitive test to find metastatic lesion than conventional assessment in 12 (50.0%). Baseline sSUV and mSUV was not significantly different between clinical responders and non-responders. After 2 cycles of chemotherapy, sSUV and mSUV was more decreased in clinical responder with significance (P=.023 and .020, respectively). In the 22 evaluable patients, PET responses were as followed: CMR in 1 (4.5%), PMR in 11 (50.0%), SMD in 7 (31.8%) and PMD in 3 (12.0%). Estimated median PFS was significantly prolonged in metabolic responders: PMR 8.3 months, SMD 4.7 months and PMD 2.3 months (P=.040). Patient with CMR had no evidence of progression for 14.7 month follow-up. Conclusions: In patients with mCRC, sequential FDG-PET predicted PFS and was more accurate than clinical response criteria. FDG- PET appears to be a promising tool for early prediction of response to chemotherapy. No significant financial relationships to disclose.
Long-term rates of ipsilateral breast tumor recurrence (IBTR) for women with ductal carcinoma in situ (DCIS) meeting LORIS trial eligibility criteria undergoing standard therapy.
Authors: Melissa Louise Pilewskie, Cristina Olcese, Sujata Patil, Kimberly J. Van Zee
Journal: Journal of Clinical Oncology (2015)

560 Background: Identification of DCIS patients at low risk for progression to invasive carcinoma could obviate the need for standard surgery and radiation therapy (RT). The “Surgery versus Active Monitoring for LOw RISk DCIS [LORIS]” trial is studying the safety of monitoring low-risk DCIS without excision, although IBTR rates in this population undergoing standard therapy are unknown. Methods: Women with DCIS treated with breast-conserving surgery (BCS) with or without RT from 1996-2010 were included from a prospectively maintained database. IBTR rates were compared between those who did and did not meet LORIS eligibility criteria (age ≥46yrs, screen-detected calcifications, non-high grade DCIS diagnosed on needle biopsy, absence of nipple discharge, minimal family history). Results: 2,537 women were identified; 405 met LORIS criteria. LORIS cohort median age was 60yrs (range 46-86yrs); 210 (52%) underwent RT, 81 (20%) received endocrine therapy. Median follow-up was 5.8yrs (range 0-18yrs). 24 experienced an IBTR (14 DCIS, 10 invasive) (see table for overall IBTR rates). 5 and 10yr invasive-IBTR rates for women meeting LORIS criteria by treatment group were: 1.7% and 5.3% BCS with or without RT; 3.0% and 6.0% no RT; 0.55% and 4.6% with RT, respectively. Conclusions: LORIS eligibility criteria identify women with DCIS at somewhat lower risk for IBTR, yet among such women treated with BCS alone, the 10yr overall IBTR rate was 12% and invasive-IBTR rate was 6%. Given that approximately 20% of women with core biopsy proven non-high grade DCIS have invasive cancer at excision, women managed with observation alone would be expected to incur significantly higher rates of invasive cancer development. Additional risk predictors are needed to identify women who do not require intervention for DCIS. 5 yr IBTR (%) 95% CI 10 yr IBTR 95% CI P value Entire cohort 0.083 LORIS (n=405) Non-LORIS (n=2132) 4.5 7.7 2.7-5.4 6.5-9 10.2 15.3 6.4-16.3 13.2-17.6 No RT 0.099 LORIS (n=194) Non-LORIS (n=900) 6.9 11.2 3.8-12.2 9.1-13.7 12.0 20.5 7-20.3 17.1-24.4 RT 0.28 LORIS (n=210) Non-LORIS (n=1212) 2.3 5.2 0.9-6 3.9-6.7 8.7 11.3 3.7-19.9 9-14.2
Cardiac safety in a phase II study of trastuzumab emtansine (T-DM1) following anthracycline-based chemotherapy as adjuvant or neoadjuvant therapy for early-stage HER2-positive breast cancer.
Authors: Chau T. Dang, Luca Gianni, Gilles Romieu, Luc Dirix, Mario Campone, Marc L. Citron, Claudio Zamagni, Ian E. Krop, Na Xu, Melanie Smitt, Thomas Suter
Journal: Journal of Clinical Oncology (2012)

532 Background: T-DM1 has demonstrated clinical activity as a single agent in patients (pts) with previously untreated MBC. In a previous phase II randomized trial of T-DM1 vs trastuzumab + docetaxel, T-DM1 had no clinically significant cardiac events, no cases of post-baseline left ventricular ejection fraction (LVEF) ≤40%, and fewer grade ≥3 adverse events (AEs; Hurvitz, ESMO 2011). This phase II study assessed the clinical safety and feasibility of T-DM1 following anthracycline-based chemotherapy in the adjuvant or neoadjuvant setting for early-stage HER2-positive breast cancer. Methods: TDM4874g (NCT01196052) is a phase II single-arm, open-label study of T-DM1 (3.6 mg/kg q3w IV; up to 17 cycles) following completion of doxorubicin/cyclophosphamide (AC; q2w or q3w for 4 cycles), or 5-fluorouracil/epirubicin (100 mg/m 2 )/cyclophosphamide (FEC; q3w for 3-4 cycles) chemotherapy in pts with early-stage HER2-positive breast cancer. Pre-chemotherapy LVEF by MUGA/ECHO ≥55% was required for enrollment. Co-primary endpoints are safety and rate of pre-specified cardiac events following initiation of T-DM1 treatment. An interim analysis was planned for the first 60 pts evaluable for cardiac safety (received ≥1 T-DM1 dose). Results: For pts in the interim analysis (20 received AC, 40 FEC), the most common all-grade T-DM1-related AEs were nausea (n=20), asthenia (n=17), and headache (n=17); 8 pts had grade 3/4 T-DM1-related AEs (including 3 with grade 3 increased aspartate aminotransferase [AST] and/or alanine aminotransferase [ALT]). No deaths occurred. Two pts had AEs leading to T-DM1 discontinuation (grade 3 AST and grade 2 ALT increase; grade 3 thrombocytopenia). No pre-specified cardiac events occurred; no pts delayed or discontinued T-DM1 due to cardiac AEs; there were no reports of grade ≥2 left ventricular systolic dysfunction, heart failure, or LVEF &lt;50%. Results will be updated with data from all 153 enrolled pts. Conclusions: T-DM1 following anthracycline-based chemotherapy was not associated with cardiac toxicity in pts with early-stage HER2-positive breast cancer; this study continues without modification.
Loss in working years after a breast cancer diagnosis: A population-based study (Sweden).
Authors: Mats Lambe, Paul Lambert, Irma Fredriksson, Anna Plym
Journal: Journal of Clinical Oncology (2017)

209 Background: More than half of all women with breast cancer are diagnosed during working age. We present a new measure of clinical and public health relevance to estimate the loss in working years after a breast cancer diagnosis. Methods: Women of working age diagnosed with breast cancer between 1997 and 2012 were identified in the Breast Cancer Data Base Sweden (N = 19,661), together with a breast cancer-free comparison cohort (N = 81,303). Women were followed until permanent exit from the labour market (defined as receipt of disability pension, old-age retirement or death) or censoring. Using flexible parametric survival modelling, the loss in working years was calculated as the difference in the remaining years in the work force between women with and women without breast cancer. Results: The loss in working years was most pronounced in women of younger ages and in women with advanced stage disease. Women aged 50 years at diagnosis with stage I disease lost on average 0.6 years (95% CI, 0.4-0.8) of their remaining working time; the corresponding estimates were 1.2 years (1.0-1.5) in stage II, 3.2 years (2.7-3.7) in stage III, and 8.8 years (7.9-9.8) in stage IV disease. Type of treatment was a clear determinant in women with early stage disease, with a higher loss in working years among women treated with axillary surgery, mastectomy and chemotherapy. Conclusions: Our measure provides a new perspective of the burden of breast cancer in women of working age. The modest loss in working years in women with early stage disease is reassuring, although the economic consequences on a population-level are likely to be high given the large number of women diagnosed with breast cancer every year.
Neoadjuvant versus adjuvant treatment: Which one is better for resectable locally advanced esophageal squamous cell carcinoma?
Authors: Qixun Chen, Yaping Xu, Yuanda Zheng, Xinmin Yu, Qingren Lin, Youhua Jiang, Xinming Zhou, Weimin Mao
Journal: Journal of Clinical Oncology (2014)

4060 Background: In China, the main treatment of esophageal squamous cell carcinoma (ESCC) is surgery combined with postoperative adjuvant chemoradiotherapy.The role of preoperative neoadjuvant chemoradiotherapy is not well established. We compared neoadjuvant chemoradiotherapy followed by surgery with surgery followed by adjuvant chemoradiotherapy in a Chinese ESCC population. Methods: We randomly assigned patients with resectable locally advanced tumors (T3-4N0-1M0, T1-2N1M0) to receive surgery and weekly administration of carboplatin (AUC=2) and paclitaxel (50 mg/m2) for 6 weeks and concurrent radiotherapy (50.4 Gy/28f, 5 days per week) at preoperative (the neoadjuvant group) or postoperative (the adjuvant group). Results: From April 2011 through December 2013, we enrolled 42 patients: 23 were randomly assigned to chemoradiotherapy followed by surgery, and 19 to surgery followed by adjuvant chemoradiotherapy. Among these 42 patients, the most common major hematologic toxic effects were leukopenia (9.5%), neutropenia (11.9%), thrombocytopenia (14.3%), and anaemia (16.6%); the most common major nonhematologic toxic effects were anorexia (14.3%), fatigue (11.9%), and cervical anastomotic fistula (19.1%). Complete resection with no tumor of the resection margins (R0) was achieved in 100% of patients in the neoadjuvant group versus 90.4% in the adjuvant group. A pathological complete response was achieved in 8 of 23 patients (34.8%) who underwent resection after chemoradiotherapy. Postoperative complications and treatment-related mortality were similar in the two groups. The disease free survival rate at 18 months was 78.7% in the neoadjuvant group as compared with 63.6% in the adjuvant group, which exceeded the goal of this study design. Conclusions: Our preliminary result suggests that, in patients with resectable locally advanced ESCC, there is a benefit tendency for the preoperative neoadjuvant chemoradiotherapy compared with postoperative adjuvant chemoradiotherapy. The regimen was associated with acceptable adverse-event rates. These trends warrant further study. Clinical trial information: ChiCTR-TRC-12002665.
A multisite cancer survivorship clinical placement program for primary care practitioners (PCPs).
Authors: Michael Jefford, Georgina Wiley, Amanda Piper, Judy Evans, Linda Nolte, Allison Drosdowsky, Liz Simkiss, Kathryn Whitfield, Julie Cairns, Giovanna Raco, Bruce Mann, Kerry Shanahan, Meron Pitcher, Bianca Bell
Journal: Journal of Clinical Oncology (2017)

95 Background: Following a successful pilot, a survivorship placement program for PCPs (general practitioners (GPs) and general practice nurses (GPN)) was refined and extended to additional sites. The program aimed to facilitate collaborative learning, with an emphasis on the post treatment phase. Objectives were to improve clinical knowledge of the health needs of survivors and enhance confidence with shared care (ShC). Methods: Four cancer centres participated. Each received an implementation toolkit and videos, developed to promote the role of PCPs in survivorship care. PCPs received pre-placement materials and attended multidisciplinary meetings and specialist clinics for 10 hours. PCPs and hospital-based specialists completed pre and post-placement surveys, assessing perceptions of the program, perceived barriers to ShC, perceived knowledge regarding survivorship issues (9 items), confidence managing survivorship issues (8 items) and with ShC (1). Results: Forty-seven PCPs (32 GPs, 15 GPN) completed placements and pre and post-placement surveys. Median scores for all confidence items and 8 of 9 knowledge items increased; 1 remained the same. Matching of pre and post responses assessed individual changes. Across the 9 knowledge items, 57-86% of PCPs reported an increase; for the 9 confidence items, 68-89% reported improvement (no decreases). Data from specialists is currently available from 1 site; 16 specialists completed the pre- and 14 (88%) the post-survey. The majority of median knowledge and confidence scores were high and remained unchanged. Specialists (n=14, 88%) and PCPs (n=37, 76%) identified the biggest barrier to ShC as ‘lack of systems to support transition of care.’ All PCPs and specialists agreed/strongly agreed the ‘program was relevant to my clinical practice.’ Conclusions: The program enhanced PCP’s knowledge and confidence regarding survivorship care, was highly regarded and identified perceived barriers to ShC.
Competing risk events determining probability of cause-specific failure in nasopharyngeal carcinoma
Authors: Y. Huang, B. Zee, M. Lam, P. Teo
Journal: Journal of Clinical Oncology (2006)

10082 Background: The commonly employed Kaplan-Meier (KM) method is based on the assumption that different failure types (local-regional, distant, etc.) are independent. In reality, these failures occur at different stages in disease progression and are strongly correlated with each other. The assumption of independence of different failure types may violate certain assumptions in the modeling, and hence may affect the clinical interpretation and treatment selection. A better approach to estimate cause-specific failure probability is to calculate cumulative incidence rates by taking into account other events within a competing risk framework, in which the dependency of different failures are considered. Methods: The data was based on a large retrospective cohort study conducted at the Prince of Wales Hospital in Hong Kong, China, in 1996–97. 945 patients with nasopharyngeal carcinoma (NPC) had been treated with a standard protocol and been followed up regularly with a median follow-up period of 69 months (1–122 months). We calculated the cumulative incidence rates of local-regional failure and distant metastasis, and compared the result against KM method. In competing risk analysis, local regional failure, distant metastases and death were considered as competing events during the remaining lifetime of NPC patients from first presentation. Results: The probability of local-regional failure and distant metastasis was higher by KM method than by competing risk method. The result indicated that KM analysis overestimated event rate and the difference became larger in a longer follow-up period, when more competing events occurred. Conclusion: Kaplan-Meier analysis overestimates the probability of cause-specific failure. Competing risk analysis provides us a more accurate method in the determination of the pattern of failure. It provides better evidence to clinicians to enable them to predict the prognosis and select proper therapy. [Table: see text] No significant financial relationships to disclose.
Venous thromboembolism (VTE) and glioblastoma.
Authors: Jacob Joseph Mandel, Shlomit Yust-Katz, Jimin Wu, Ying Yuan, Courtney C. Webre, Harshad Ladha, Tushar Pawar, Mark R. Gilbert, Terri S. Armstrong
Journal: Journal of Clinical Oncology (2014)

2033 Background: The risk of VTE is very high for patients with brain tumors, with Glioblastoma (GB) considered one of the most at risk cancers. The aim of this study is to describe the occurrence and associated risk factors for the development of VTE among GB (patients) pts. Methods: In this IRB approved retrospective study, our neuro-oncology longitudinal database was screened for pts with GB, who were treated with concurrent radiation and Temozolomide (TMZ) followed by adjuvant TMZ from 2005-2011. 543 pts were identified. Results: 134 (24.6%) pts developed VTE, with 139 documented events. 56 pts (42%) were diagnosed with deep vein thrombosis (DVT) , 27 pts (20%) with pulmonary emboli (PE) with no evidence of DVT, and 51 pts (38%) had both DVT and PE. The majority were diagnosed after starting adjuvant TMZ (61%) with a median time of 6.5 months from starting adjuvant TMZ (range 0.03-120) with only 22 (16%) pts developing VTE before starting post surgery treatment and 32(23%) during chemoradiation. At time of VTE diagnosis, 44 (32%) patients had stable disease, 61 (43%) were clinically or radiographically progressing and the rest were newly diagnosed or during concurrent treatment. 56 (40%) patients were admitted secondary to their VTE. Treatment with anticoagulation alone was given to 68 (52%) pts, IVC filter only was inserted to 6 (5%) pts and 56 (43%)pts were treated with both modalities). 15 pts developed complications secondary to anticoagulation(5 brain haemorrhage , 6 bleeding in other locations and 4 thrombocytopenia). On univariate analysis risk factor associated with development of VTE after starting adjuvant TMZ treatment were: sex, prior history of venous thrombosis, poor KPS, requiring assistive device for ambulation, paresis, high BMI, pre chemotherapy WBC counts, and various medications (including anticoagulation, blood pressure drugs, anti-acid drugs and corticosteroids) (p<0.05). On multivariate analysis sex, poor KPS, high BMI, history of VTE and use of corticosteroids were significant risk factors for the development of VTE (P<0.05). Conclusions: VTE is a common complication of GB and can occur during the course of the disease. Factors associated with increased risk have been identified and will be useful in developing risk models in this patient population.