tbuckley/cabot-search huggingface dataset:
A model for delivering survivorship care: Integrating the oncology and the primary care setting: Follow-up of the first cohort of patients.
Authors: Elena Lorenzi, Lucia Morello, Rita Mazza, Isabella Maria Giovanna Garassino, Raffaele Cavina, Laura Giordano, Carmelo Carlo-Stella, Armando Santoro
Journal: Journal of Clinical Oncology (2017)

40 Background: In our Institution, we started a survivorship care program that integrates survivors’ health care provided by the oncologist and the primary care physician (PCP).We present the follow-up analysis of the first cohort of patients (pts) enrolled from April to July 2015. Methods: We included adult pts affected by hematologic or solid tumors without evidence of disease from at least 5 years (yrs). They are referred to the PCP with a survivorship care plan. An online platform for cancer survivors (CS) and their PCPs will be available. Progression free survival (PFS), overall survival (OS) and treatment related clinical events were calculated after 17 months from the start of the project. Results: We analyzed data from 269 CS. The median age was 67 yrs, they were mainly females (77%). The most frequent histological types were breast (157), colorectal (37), and hematologic (30) tumors. 189 pts had an early stage disease. 161 pts received chemotherapy with 95 pts receiving anthracycline-based-chemotherapy (ABC), 86% at a cumulative dose &gt; 240 mg/mq. 154 pts underwent radiation therapy (RT), 94% at a dose &gt; 30 Gy. 58 pts received both ABC and RT. The 10-yr cumulative risk of secondary cancer (SC) was 4% with a median latency period from the first cancer diagnosis of 11.3 yrs. 15-yr OS was 98% (one patient died of myocardial infarction), and 15-yr PFS was 96%. The 10-yr cumulative risk of late cardiologic toxicity (LCT) was 11% and 37 pts developed cardiologic complications with a median latency period from treatment of 10.5 yrs. The adhesion to the survivorship care plan was 84%. 13% of pts returned to our Center. The main non-clinical reason for returning was the lack of confidence in PCP. No association was observed between ABC and/or RT exposure and LCT or SC development. Conclusions: In this cohort of patients a high risk of LCT was observed. The risk and latency of SC was similar to the ones reported in literature. The number of cardiac events and SC is too low to give solid conclusions about the association with therapeutic exposure. So far, the compliance of patients and PCPs with the program was high. More data and longer follow-up period are necessary to confirm the accuracy of this model of care.
Activity of regorafenib (RE) in leiomyosarcomas (LMS) and other types of soft-tissue sarcomas (OTS): Results of a double-blind, randomized placebo (PL) controlled phase II trial.
Authors: Olivier Mir, Thomas Brodowicz, Jennifer Wallet, Antoine Italiano, Axel Le Cesne, Jean-Yves Blay, Thomas Ryckewaert, Francois Bertucci, Sophie Piperno-Neumann, Ferdinand Ploner, Maud Toulmonde, Julien Domont, Esma Saada, Corinne Delcambre, Nicolas Isambert, Stephanie CLISANT DELAINE, Sophie Taieb, Elisabeth Lindner, Bernadette Lieg-Atzwanger, Nicolas Penel
Journal: Journal of Clinical Oncology (2015)

10504 Background: RE is a multikinase inhibitor that has demonstrated activity in gastrointestinal stromal tumors. We investigated its activity and safety in anthracycline pretreated metastatic soft tissue sarcomas (STS). Methods: REGOSARC (NCT01900743) consisted of four independent cohorts of patients (pts) with LMS, OTS, synovial, and adipocytic sarcomas who were randomized (1:1) to receive either RE (160 mg/d, 21/28 d) or PL, with optional cross-over. Key-eligibility criteria were age ≥ 18, measurable progressing STS not amenable to curative-intent surgery, ≤ 3 previous lines of treatment for metastatic STS. The primary endpoint was progression-free survival (PFS) with blinded central radiological review. Statistical assumptions for LMS and OTS cohorts were PFS = 1.6 months (mo) with PL, PFS = 4.6 mo with RE, 1-sided α = 0.1 and β = 0.05. Results: From July 2013 to July 2014, 57 LMS and 53 OTS pts were enrolled (55 with PL, 55 with RE). The two most common OTS types were Undifferentiated Pleomorphic Sarcomas (n = 21, 40%) and Solitary Fibrous Tumors (n = 7, 13%). Eighty-four (77%) tumors were grade 3. In both cohorts, the most common primary sites were retroperitoneum and uterus (n = 23, 21%, each). There were 48 men (44%). The median age was 60 (20-81) years. The median number of prior lines was 2 (1-3): 106 (97%), 59 (54%), 39 (35%) and 4 (4%) pts were previously treated with doxorubicin, ifosfamide, trabectedin and pazopanib, respectively. Both arms in each cohort were well balanced. The most common Gr 3 AEs were hypertension (10 vs 2 pts; RE vs PL), skin toxicity (9 vs 1), asthenia (9 vs 3) and diarrhea (6 vs 2). There was no Gr5 AE and 1 Gr4 AE (anemia in RE arm). The median PFS of LMS pts was 4.0 mo with RE versus 1.9 mo with PL (HR = 0.49; 95CI 0.27-0.89; p = 0.017). The median PFS of OTS pts were 4.6 and 1.0 mo, with RE and PL respectively (HR = 0.38, 95CI 0.20-0.74; p = 0.002). The 6-mo OS rate of LMS pts was higher in the RE arm (87.0% vs 75.9%; HR = 0.25; 95CI 0.08-0.81; p = 0.013), this difference was not significant in the OTS cohort (79.0 vs 62.0%; HR = 0.64, 95CI 0.23-1.74; p = 0.4). Conclusions: RE demonstrates promising activity and an acceptable toxicity profile that warrant further clinical evaluation in LMS and OTS pts. Clinical trial information: 2012-005743.
Comparison of adult oncology phase 1 trials to pediatric oncology phase 1 trials of targeted therapies.
Authors: Vivek Subbiah, Jitesh D Kawedia, Anthony Christensen, Kenneth R. Hess, Kayuri Patel, Elaine Wood, Ryan D Bitar, Najat C. Daw
Journal: Journal of Clinical Oncology (2015)

2581 Background: Intractable aggressive cancers continue to take the lives of children, adolescents and young adults at the prime of their lives. The prior era of drug development wherein pediatric cancer becomes the last cancer to be tested with novel agents, ‘if’ the agent seems promising in adult cancers may need to be re-visited. Phase 1 trials are the first critical step in drug development. Data based on cytotoxic chemotherapy phase 1 trials demonstrated a strong correlation between adult and pediatric maximum tolerated dose (MTD)s. We sought to compare pharmacokinetic (PK) parameters and dosing of small molecule inhibitors and monoclonal antibodies (MAbs) studied in adult vs. pediatric phase 1 trials. Methods: We conducted an extensive review of all published pediatric phase 1 trials of small molecule inhibitors and MAbs, and their corresponding adult phase 1 trials. Multiple data elements including MTD, recommended phase 2 dose (RP2D), and dose-limiting toxicity (DLT) were collected from pediatric and adult phase 1 trials. PK parameters for the small molecules including drug clearance (CL), area under the concentration curve (AUC), and half-life were analyzed. Results: We identified 25 targeted agents (21 small molecules, 4 MAbs) and compared data from the pediatric and adult trials. The MTD was not reached for 14 of the 25 (56%) agents in adults (3/25), pediatric patients (7/25), or both (4/25). Excluding the agents for which the MTD was not reached, the median ratio of pediatric to adult MTD was 1. PK data was available for 13 small molecules and 2 MAbs. The median ratio of pediatric to adult PK parameters for small molecules was: 0.9 for drug CL, 1 for AUC, and 0.8 for half-life. There was substantial heterogeneity in the PK parameters investigated across the studies. Conclusions: The PK and MTD of small molecule targeted agents in pediatric and adults patients are comparable. Initial pediatric dosing close to the adult MTD or RP2D and extrapolation of PK data from adults may help expedite drug development of these agents in children. Standardized strategies to study and report PKs are needed.
Change in patient weight during platinum/paclitaxel-based chemotherapy for ovarian cancer: A Gynecologic Oncology Group study
Authors: L. M. Hess, C. Tian, R. Barakat, R. Ozols, D. Alberts
Journal: Journal of Clinical Oncology (2006)

5073 Background: Platinum/paclitaxel (P)-based chemotherapy is current treatment (tx) for advanced epithelial ovarian cancer (EOC). Previous studies suggest this regimen may induce weight change, which is a surrogate for body reaction to tx and may predict quality of life and clinical outcomes. We sought to explore the association between weight change during treatment and survival. Methods: A retrospective data review was conducted of 792 patients who participated in a Gynecologic Oncology Group (GOG) phase III randomized treatment trial (GOG 158) using cisplatin (Cis)/P vs carboplatin (Carbo)/P in optimal stage III EOC. Pretreatment body mass index (BMI) was calculated based on patient height and weight following surgery. Weight change during tx was defined as the ratio of body weight at completion of protocol therapy to pretreatment body weight. Progression-free survival (PFS) and overall survival (OS), classified by BMI or relative weight change, were estimated by Kaplan-Meier, and the associations between BMI, relative weight change and PFS and OS were assessed using Cox model controlled for known prognostic variables. Results: The median BMI was 24.9. There was no significant difference in PFS or OS related to BMI; however, there was a significant relationship between median OS and weight change as follows: &gt;5% decrease = 48.0 months; 0–5% decrease = 49.3 months; 0–5% increase = 61.1 months; and &gt;5% increase = 68.2 months (p = 0.006). The relative risk of death increased by 7% for each 5% decrease in body weight (HR = 0.93, 95% CI = 0.88–0.99; p = 0.013) adjusted for covariates. Results suggest more evident weight loss in the Cis/P arm than the Carbo/P arm during the first cycle of tx (−2.2 kg vs. −1.2 kg), and decreased weight was more likely to return to pretreatment level in the Carbo/P arm. Conclusions: Loss of body weight, but not BMI, during platinum/P-based chemotherapy is an indicator for poor OS in EOC patients. Cis/P may be associated with more weight loss compared to Carbo/P. This exploratory study supports the development of treatment strategies that minimize weight loss-producing toxicities to improve outcomes in this patient population. No significant financial relationships to disclose.
Molecular abnormalities of 17 types of gastrointestinal cancer in an international cohort of 11,324 patients.
Authors: Gargi Dan Basu, Zoran Gatalica, Sherri Z. Millis, Fadi S. Braiteh
Journal: Journal of Clinical Oncology (2014)

11053 Background: Gastrointestinal cancers (GICs) are classified based on both organ and tissue of origin, but might be better classified based on their molecular profile. We performed a multiplatform biomarker analysis of the main 17 types of GICs to identify molecular abnormalities and their associations. Methods: We analyzed 11,324 cases of GIC (96% from USA) using gene sequencing (up to 44 different genes, Sanger, NGS), protein expression by immunohistochemistry (up to 28 gene products) and gene amplification by CISH or FISH (up to 8 genes). Further, we performed heat map analysis of the 70 molecular anomalies in 17 GIC sites. Results: Steroid receptor (ER, PR) expression was distinctively high in neuroendocrine cancers (CA) (10-40%) while AR expression was elevated in hepatocellular carcinoma (HCC) (20%). HER2 overexpression and amplification was distinctively elevated in gastric, GEJ, esophageal and gall bladder CA (up to 20%). Overexpression of TOP2a was noted in most of the GICs, reflecting their highly proliferative and aggressive nature. Overexpression of cMET (up to 82%) and EGFR amplification (up to 32%) was noted in a majority of GICs suggesting benefit from cMET and EGFR targeted therapies. HCC had a high frequency of CTNNB1 (19%, 11/58) and low frequency of ABL1 mutation (3%, 2/59). Distribution of APC mutations in GIC ranged from 10-73%. PIK3CA mutation and PTEN loss were frequent events (up to 15% and 89% respectively) in a majority of GIC, suggesting potential benefit of targeting the PI3K pathway. Based on the RAS/RAF and PI3K/PTEN/Akt/mTOR pathway alterations, colon and rectal CA share similar molecular signatures but gall bladder and biliary tract CA, as well as colon and appendix CA, are molecularly distinct. Small bowel and duodenal CA exhibited different molecular signatures based on APC, ATM, SMAD4 and p53 mutations. Conclusions: Molecular profiling of GICs might allow us to reconsider clinical trial design and disease management based on individual cancer molecular abnormalities. Protein expression and copy number alterations should be considered together with mutational analysis to refine cancer treatment in GI tract malignancies.
A phase II study of docetaxel (D) plus imatinib (I) in patients with previously treated non-small cell lung cancer
Authors: L. A. White, A. M. Schmidt, N. N. Sjak-Shie, A. O. Greco, B. Cronin, K. L. Fisher, J. R. Eckardt
Journal: Journal of Clinical Oncology (2007)

18200 Background: Docetaxel(D) has been shown to improve overall survival in pts with previously treated NSCLC. Pre-clinical data suggest synergistic activity with the combination of D and I. Paul Matthew; et al demonstrated the safety of this combination in pts with prostate cancer. Methods: This is a Phase II study of the combination of D and I in prev tx NSCLC to determine response rate, toxicity and assess overall survival. Pts must have received at least 1 prior regimen and have an ECOG PS of 2 or less. Prior tx with D was allowed. D was admin at 30 mg/m 2 on a weekly schedule for 3 weeks followed by 1 week rest. I was admin at a starting dose of 600 mg/day throughout the study. Results: A total of 10 pts were enrolled. Seven male and 3 female with a median age of 66 years (range 58 - 74). A total of 26 cycles were delivered to 10 pts (mean = 3). Responses included 1 PR/3SD/2PD/4NE. One pt with a PR responded after cycle 4 but progressed after cycle 6. One pt maintained SD for 21 wks then expired due to an unrelated PE (h/o peripheral vascular disease). Grade 4 toxicity included periorbital edema (1 pt), pneumonia (2 pts), diarrhea (1 pt), dehydration (1 pt), dyspnea (1pt), anorexia (1 pt), pleural effusion (1 pt), and neutropenia (2 pts). Grade 3 toxicity included hyponatremia (1 pt), renal failure (1 pt), hypotension (2 pts), mental status changes (1 pt), anorexia (1 pt), azotemia (1 pt), dyspnea (1 pt), herpetic esophageal ulcer (1 pt), pneumonia (1 pt), neutropenia (2 pts), weakness &amp; fatigue (1 pt), and anemia (1 pt). Four of 10 pts received only 1 cycle. (Three of those 4 suffered a fatal adverse event during cycle 1, not felt to be treatment related. The fourth developed herpetic esophageal lesions and was taken off study prior to tumor assessment.) Conclusions: The study was closed before the initial planned pts were enrolled due to low activity and unexpected high tox. Only 1 of 10 pts achieved a PR. Stable disease was observed in 3 pts but was of short duration in 2 of the 3. Despite supportive treatment, nausea, vomiting, diarrhea, and anorexia were difficult to control. Hematologic toxicity was encouragingly infrequent with only 2 pts experiencing Grade 4 neutropenia. Alternative dosing schedules would be recommended before pursuing this combination in NSCLC pts. Study supported by a grant from Novartis. No significant financial relationships to disclose.
Conditional Greenlight for Future Trials of Heritable Genome Editing
Authors: Jennifer Abbasi
Journal: JAMA (2017)

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Trastuzumab treatment in patients with advanced breast cancer (ABC) confined to locoregional and skeletal sites: Results from a large noninterventional study.
Authors: Christian Jackisch, Winfried Schoenegg, Johannes Selbach, Manfred Welslau, Hanns-Detlev Harich, Jan Schroeder, Marcus Schmidt, Thomas Goehler, Axel Hinke, Heidi Eustermann, Ralf Ringel
Journal: Journal of Clinical Oncology (2012)

640 Background: In a prospective observation study routine trastuzumab (T) treatment in HER2+ ABC was evaluated in a total of 1,687 patients (pts) since 2001. This large number allows the subgroup analysis of patients with the involvement of specific sites. Methods: Information on extent of advanced disease was available in 1,674 pts (99%) with HER2 overexpressing ABC. Pts were either pre-treated (39%) or naïve to palliative chemotherapy (CT). The following subgroups and their characteristics were analysed: I: locally ABC only; II: bone metastases allowing for concomitant local tumour; III: other. Results: Locally advanced lesions were found to be the sole BC manifestation in 145 pts (8.7%), while bone metastases ± locally ABC were found in 209 pts (12.5%). This leaves a comparative population of 1320 pts with metastases to other sites, predominantly visceral metastases. The table shows the baseline and treatment characteristics, as well as the long term outcome based on progression/death observed in 79%/56% of pts. Concurrent CT (74% of total group) predominantly consisted of a taxane (46%) or vinorelbin (24%), with no major differences between the groups. Conclusions: In this HER2+ cohort, palliative pts with local lesions only show a comparatively high-risk profile with respect to grading, hormone receptor status and adjuvant CT. Nevertheless, locally ABC only is a significant favourable prognostic factor in HER2+ BC treated with T combinations, with a median survival of 4 to 5 years. [Table: see text]
Risk assessment for lymphedema in breast cancer survivors.
Authors: Martha Bonney Lyman, Marita Ferro Truax
Journal: Journal of Clinical Oncology (2017)

141 Background: Breast cancer patients are receiving survivorship care plans that describe potential late effects of treatment. The potential for lymphedema ranges from 5% to 53% and is a serious long term problem. In the past, water displacement was the “gold standard” for measuring lymphedema; this involves placing the arm into a large graduated cylinder filled with water to measure displacement compared with the opposite arm. This method is inconvenient for both patient and practitioner and can cause significant anxiety. Methods: In 2010 we began assessing women undergoing unilateral axillary surgery for preclinical and clinical lymphedema using a method that measures bioimpedance, using the L-Dex U400 analyzer. L-Dex uses a mild electrical current to assess fluid levels in the extracellular compartment, earlier than a patient might feel a change in size or weight. One hundred thirty -seven patients were assessed using both volume displacement and L-Dex preoperatively, as a baseline and repeating at 3 to 6 month intervals for three years. Results: Of the patients followed, 83% had sentinel node excision only and 17% had completion axillary dissection. Our study identified an overall lymphedema rate of 7%. Of the patients with full axillary dissection the lymphedema rate was 9% and those with sentinel node excision were found to have no clinical lymphedema (0%). In every case where the patients developed lymphedema the L-Dex bioimpedance measurement identified a change 100% of the time before fluid volume displacement became out of range. Conclusions: Based on our results and the ease of use of the bioimpedance analysis, we have added lymphedema assessment using the L-Dex analyzer to our survivorship process. Patients with invasive cancer undergoing unilateral axillary node surgery are assessed at the same time they receive their sentinel node tracer injection. If there is a sentinel node excision only they are checked once or with any symptom. Patients who have a complete axillary dissection are to be followed for three years. This modest intervention should reduce anxiety surrounding one of the most serious late effects of breast cancer.
VALORACIÓN DE LA CICATRIZ TRAS RESECCIÓN ENDOSCÓPICA DE LESIONES COLORRECTALES GRANDES CON ENDOSCOPIA DE ALTA DEFINICIÓN Y NBI: ¿ES NECESARIO BIOPSIAR?
Authors: D Martinez Ares, B Romero Mosquera, N Quintáns Pinazas, L Cid Gómez, A Martínez Turnes, S Vázquez Rodríguez, JA Hermo Brión, A Alonso Rodríguez, C Núñez Amigo, JI Rodríguez Prada
Journal: Endoscopy (2015)

La resección endoscópica de las lesiones colorrectales grandes mediante técnica de resección fragmentada presenta un cierto número de recidivas, lo que exige una control posterior de la escara, acompañado de biopsias de la misma. Ello supone un consumo de recursos, tanto endoscópicos como del servicio de anatomía patológica.
Clinical evaluation of neoadjuvant chemotherapy for locally advanced cervical cancer and analysis of survival rate.
Authors: Lin Gong, Jia-Wen Zhang, Ru-tie Yin, Ping Wang, Hui Liu, Ying Zheng, Jiang-Yan Lou, Zhi-Lan Peng
Journal: Journal of Clinical Oncology (2015)

e16508 Background: Cervical cancer is the most common malignant tumor of the female reproductive system. Globally, there are an estimated 530,000 new cases of cervical cancer each year. One third of these cases occur in China, where the average age of cervical cancer patients is decreasing. To evaluate the efficacy of neoadjuvant chemotherapy (NACT) followed by radical surgery (RS) among patients with locally advanced cervical cancer (LACC) and survival outcomes. Methods: From January 2008 to December 2012, 800 previously untreated patients with LACC (stage IB2、IIA2 and part IIB, tumor diameter > 4 cm) from West China Second Hospital were assigned to receive either NACT followed by radical surgery (NACT- RS) or RS directly for clinical evaluation. Results: 36.63% of cervical cancer patients were under 40 years. The clinical response for NACT was 89.54%.Catheter removal time was shorter (29.84 days vs. 32.14 days, P < 0.05), percentage of operative complications (7.30% vs. 13.62%, P < 0.05) and radiochemotherapy side effect (3.16% vs. 4.63%, P < 0.05) was less in NACT-RS than in RS. The 5-year progression-free survival and 5-year overall survival were 80.30% and 81.10% in the NACT-RS group, and 81.00% and 78.50% in the RS group (P > 0.05). Poor pathological differentiation, non-squamous cell carcinoma, parametrial invasion, positive pelvic lymph node and lymphovascular invasion (LVSI) (P < 0.05) were independent risk factors for recurrence. Conclusions: Compared with RS, NACT-RS did not prolong the survival rate for patients with locally advanced cervical cancer. However, NACT could reduce the operation complications and radiochemotherapy side effect. NACT may be an alternative treatment for young patients.