tbuckley/cabot-search huggingface dataset:
Total neoadjuvant therapy with mFOLFIRINOX versus preoperative chemoradiation in patients with locally advanced rectal cancer: Final results of PRODIGE 23 phase III trial, a UNICANCER GI trial.
Authors: Thierry Conroy, Najib Lamfichekh, Pierre-Luc Etienne, Emmanuel Rio, Eric FRANCOIS, Nathalie Mesgouez-Nebout, Veronique Vendrely, Xavier Artignan, Olivier Bouché, Dany Gargot, Valerie Boige, Nathalie Bonichon-Lamichhane, Christophe Louvet, Clotilde Morand, Christelle De La Fouchardiere, Beata Juzyna, Eric Rullier, Frédéric Marchal, Florence Castan, Christophe Borg
Journal: Journal of Clinical Oncology (2020)

4007 Background: PRODIGE 23 investigated the role of neoadjuvant mFOLFIRINOX before preoperative (preop) chemoradiation (CRT), with TME-surgery and adjuvant chemotherapy (CT) in resectable locally advanced rectal cancer. Methods: PRODIGE 23 is a phase III multicenter randomized clinical trial. Eligible pts had cT3 or cT4, M0 rectal adenocarcinomas &lt;15 cm from the anal verge, age 18-75 years, and WHO PS ≤1. Randomization was stratified by center, T stage, N status, tumor location, and perirectal fat extramural extension. Primary endpoint was 3-yr disease-free survival (DFS). Main secondary endpoints were ypT0N0 rate, overall survival (OS) and metastasis-free survival (MFS). 460 pts were required to observe 136 events to show a gain in 3-year DFS from 75% to 85% (HR=0.56) with a 2-sided α=0.05 and 90% power. HR and 95% CI were estimated by a stratified Cox proportional hazard model. Arm A pts received preop CRT (50 Gy, 2 Gy/fraction [fr]; 25 fr + capecitabine), surgery, then adjuvant CT for 6 months (mos). Arm B pts received 6 cycles of mFOLFIRINOX (oxaliplatin 85 mg/m², leucovorin 400 mg/m², irinotecan 180 mg/m² D1, and 5-FU 2.4 g/m² over 46 h) every 14 days, followed by the same preop CRT, surgery and 3 mos of adjuvant CT. Adjuvant CT consisted of mFOLFOX6 or capecitabine, depending on the centre’s choice for all pts. Imaging work-up, operative and pathology reports were centrally reviewed. Results: (ITT) Between 6/2012 and 6/2017, 230 and 231 pts were randomly assigned in Arm A/B, respectively by 35 participating centers. Pts characteristics were well balanced. Neoadjuvant mFOLFIRINOX and CRT in both arms were well tolerated. Compliance to CRT and to adjuvant CT was not hampered by neoadjuvant CT. Surgical morbidity did not differ between the 2 arms. The ypT0N0 rate was 11.7 vs 27.5% in Arm A/B (p&lt;0.001). Median follow-up was 46.5 mos. 136 DFS events was reported. 3-yr DFS was significantly increased in arm B (HR 0.69, 95% CI 0.49-0.97, p=0.034): 68.5% (CI: 61.9-74.2) vs 75.7% (CI: 69.4-80.8) in arm A/B. The subgroup analysis showed no evidence of heterogeneity of the effect size of treatment on DFS. 3-yr MFS was also significantly higher in arm B: 71.7 in arm A vs 78.8% (HR 0.64, CI 0.44-0.93, p&lt;0.02) in arm B. 3-yr OS was 87.7 vs 90.8% (HR 0.65, CI 0.40-1.05, p=0.077) in arm A/B, with 54.2% of the pts with recurrence being alive. Conclusions: Neoadjuvant mFOLFIRINOX plus CRT is safe, and significantly increased ypCR rate, DFS and MFS. OS data are not mature. Clinical trial information: NCT01804790 .
Community-based rehabilitation for patients with strake
Authors: 陈颖, 胡永善
Journal: BMJ (2011)

脑卒中是我国的常见病、多发病,并具有高死亡率、高复发率以及高致残率等特点[1],是严重影响人类生存质量和生命的疾病.虽然目前脑卒中的死亡率较前有减少,但是这些经过急诊科、神经内科、神经外科治疗的脑卒中患者,常遗留各种后遗症,不仅患者痛苦,也给家庭和社会造成沉重负担[2].国外研究表明,建立健全的社区康复治疗网络可有效提高患者的生存质量[3-5].近年来,我国社区康复服务开展迅速,其中以脑卒中后社区康复的相关研究最多.以下综述我国脑卒中社区康复治疗模式和问题。
Low-dose oral etoposide is an active option for patients with heavily pre-treated thymic epithelial tumors.
Authors: Margaret Ottaviano, Marianna Tortora, Mario Giuliano, Daniela Terracciano, Vincenzo Di Lauro, Fernanda Picozzi, Sara Parola, Vittorio Riccio, Pietro De Placido, Erica Pietroluongo, Antonietta Liotti, Evelina La Civita, Gianluca Guggino, Marcellino Cicalese, Carlo Curcio, Michele Longo, Gerardo Botti, Bruno Daniele, Sabino De Placido, Giovannella Palmieri
Journal: Journal of Clinical Oncology (2020)

9074 Background: Platinum based regimens are used in the first line setting for advanced Thymic Epithelial Tumors (TETs). Angiogenesis plays an important role in TETs: VEGF is overexpressed in TETs, and associated with aggressiveness and advanced stage. Etoposide inhibits angiogenesis in vitro and in vivo by decreasing VEGF production and microvessel density. The aim of this study is to assess the activity of metronomic oral etoposide, with identification of circulating predictive and pharmacodynamics biomarkers. Methods: Patients with advanced platinum pretreated TET referred from 2014 to 2019 at Rare Tumors Reference Center of Naples, were prospectively enrolled in this study. Oral etoposide 50 mg daily for 3 weeks on and 1 week off every 28 days, has been delivered until progression of disease, complete response or unacceptable toxicity. Response rate (RR), progression free survival (PFS), toxicity and ratio between time to etoposide progression (TTPe) and time to previous best treatment progression (TTPp) were evaluated. Serum samples were prospectively obtained from ten patients with simultaneously radiological assessment. cfDNA quantification was assessed using Qubit Fluorometric Quantitation. Results: 21 patients were enrolled: median age 59 years range (41 - 88); 70% male, 60% T (4 B1, 3 B2, 4 B3, 1 B1-B2); 40% had TC. A median of 5 (range 1-9) prior therapy regimens had been administered. Median follow-up since etoposide was 5 years (range 0.5-5). Obtaining an overall response rate of 85%, 3 patients achieved complete response and 15 partial response. Median PFS was 16 months [95%CI 3-60] with respectively a median PFS of 12 for T (95%CI 3-38) and 19 for TC (95%CI 6-60). No grade 3-4 related events occurred, G1-2 myelotoxicity has been registered in 20% of patients. Therapy is still ongoing for 15 patients and all are still alive. Median TTPe was 16 months, TTPp was 9 months and TTPe / TTPp ratio equal to 1.7. The median cfDNA of 8 responder patients, before starting therapy, was 2.2 ng/μl (0.178-5.24), dropping dramatically at radiological response to 0.5 ng/μl (0.323-2.56). 2 out of 3 non-responder patients had a median baseline value of 2.49 ng/μl, increasing to 4.6 ng/μl at progression. Variation of circulating VEGF correlates with radiological response. Conclusions: Taking into account that other antiangiogenic drugs, showing some activity in second and further lines treatment, are very expensive and associated with several side effects, we suggest that low dose oral etoposide might become the preferred treatment option in heavily pretreated TETs.
Machine learning analysis on American Gut Project microbiome data to identify subjects with cancer both with and without chemotherapy exposure.
Authors: Oguz Akbilgic, Ibrahim Karabayir, Hakan Gunturkun, Joseph F Pierre, Ashley C Rashe, Alexandra Thomas
Journal: Journal of Clinical Oncology (2020)

e14069 Background: There is growing interest in the links between cancer and the gut microbiome. However, the effect of chemotherapy upon the gut microbiome remains unknown. We studied whether machine learning can: 1) accurately classify subjects with cancer vs healthy controls and 2) whether this classification model is affected by chemotherapy exposure status. Methods: We used the American Gut Project data to build a extreme gradient boosting (XGBoost) model to distinguish between subjects with cancer vs healthy controls using data on simple demographics and published microbiome. We then further explore the selected features for cancer subjects based on chemotherapy exposure. Results: The cohort included 7,685 subjects consisting of 561 subjects with cancer, 52.5% female, 87.3% White, and average age of 44.7 (SD 17.7). The binary outcome variable represents cancer status. Among 561 subjects with cancer, 94 of them were treated with chemotherapy agents before sampling of microbiomes. As predictors, there were four demographic variables (sex, race, age, BMI) and 1,812 operational taxonomic units (OTUs) each found in at least 2 subjects via RNA sequencing. We randomly split data into 80% training and 20% hidden test. We then built an XGBoost model with 5-fold cross-validation using only training data yielding an AUC (with 95% CI) of 0.79 (0.77, 0.80) and obtained the almost the same AUC on the hidden test data. Based on feature importance analysis, we identified 12 most important features (Age, BMI and 12 OTUs; 4C0d-2, Brachyspirae, Methanosphaera, Geodermatophilaceae, Bifidobacteriaceae, Slackia, Staphylococcus, Acidaminoccus, Devosia, Proteus) and rebuilt a model using only these features and obtained AUC of 0.80 (0.77, 0.83) on the hidden test data. The average predicted probabilities for controls, cancer patients who were exposed to chemotherapy, and cancer patients who were not were 0.071 (0.070,0.073), 0.125 (0.110, 0.140), 0.156 (0.148, 0.164), respectively. There was no statistically significant difference on levels of these 12 OTUs between cancer subjects treated with and without chemotherapy. Conclusions: Machine learning achieved a moderately high accuracy identifying patients’ cancer status based on microbiome. Despite the literature on microbiome and chemotherapy interaction, the levels of 12 OTUs used in our model were not significantly different for cancer patients with or without chemotherapy exposure. Testing this model on other large population databases is needed for broader validation.
Pathological complete response rates in HER2 amplified breast cancers based on levels of HER2 amplification.
Authors: Ina Patel, Yasmeen Hashimie, James Hall, Ashwini Bhat
Journal: Journal of Clinical Oncology (2020)

e12632 Background: Untreated HER2 (Human Epidermal Growth Factor) amplified breast cancer has poorer prognosis, compared to those with HER2 negative status with shorter time to relapse and increased incidence of metastases and higher mortality. Both Trastuzumab and Pertuzumab (humanized monoclonal antibodies against HER2) have shown to improve PCR (Pathological Complete Response) rates when used in the neoadjuvant setting. However, whether the quantitative level of HER2 amplification affects PCR rates or disease-free survival/overall survival has not been well studied. If the level of HER2 amplification correlates with PCR rates, this could be a tool for clinicians to use as a predictive marker for response to therapy. Methods: This is a retrospective chart review of community oncology clinic patients with HER2 amplified breast cancer Stage I-III to evaluate the rates of PCR after HER2 targeted neo-adjuvant therapy categorized by HER2 CISH (Chromogenic in situ hybridization) amplification and stratified based on levels of amplification of &lt; 3, 3 to 5, or &gt; 5. Pathology reports were reviewed for report of PCR. Inclusion criteria was women age 19 to 90, HER2 positive biopsy proven breast cancer, Stage I-III, patients treated with neoadjuvant chemotherapy, adequate renal function, and left ventricular ejection fraction within normal range. Exclusion criteria was pregnancy, metastatic disease, history of other malignancies, and impaired renal or cardiac function. Results: The data consisted of 36 unique patients, 25% of whom had a HER2 below 3, 22.2% had a HER2 between 3 and 5, and 52.8% had a HER2 value &gt; 5. There was found to be a statistically significant association between the level of HER2 amplification and PCR rates with increased amplification of HER2 relates with increased PCR rates (p value &lt; 0.0176). Both three-year disease-free survival and three-year overall response rates were not statistically significantly associated with HER2 category (p value -0.2691 and 0.4692 respectively). Conclusions: The information from this study may introduce a future systematic approach to further risk stratify patients based upon their quantitative HER2 amplification level to help predict response to therapy. We have noted that a level of HER2 amplification &gt; 5 led to significant association with PCR compared to &lt; 3 and 3-5 values.
Lorlatinib for advanced ALK and ROS1+ non-small cell lung cancer (NSCLC): Efficacy and treatment sequences in the IFCT-1803 LORLATU expanded access program (EAP) cohort.
Authors: Simon Baldacci, Virginie Avrillon, Benjamin Besse, Bertrand Mennecier, Michael Duruisseaux, Julien Mazieres, Renaud Descourt, Helene Doubre, Pascale Dubray-Longeras, Jacques Cadranel, Denis Moro-Sibilot, Charles Ricordel, Sigolène Galland-Girodet, Isabelle Monnet, Josiane Otto, Sophie Schneider, Pascale Missy, Franck Morin, Virginie Westeel, Nicolas Girard
Journal: Journal of Clinical Oncology (2020)

9615 Background: Lorlatinib, a third-generation tyrosine kinase inhibitor targeting ALK and ROS1, has been made available in France starting October 2015 through an EAP for advanced, refractory, ALK+ NSCLC after the failure of chemotherapy and TKIs. Besides the landmark, multi-cohort phase II trial that assessed lorlatinib in ALK+ NSCLC, real-life evidence regarding the efficacy and safety, as well as treatment sequences including lorlatinib, is lacking. Methods: We report the cohort of consecutive patients with advanced, refractory, ALK or ROS1+ NSCLC enrolled in the French EAP of lorlatinib from October 2015 to October 2019. Data were collected from medical records by French Cooperative Thoracic Intergroup (IFCT) research study assistants on site. Primary endpoint was progression-free survival. Results: 200 patients were included: 143 (71.5%) ALK+, 57 (28.5%) ROS1+, 87 (44%) men, 127 (66%) never-smokers, and 167 (85%) stage IV disease. Mean age was 59 years. At the time of initiation of lorlatinib, 146 (74%) patients had Central Nervous System (CNS) disease (78 % for ALK+, 63% for ROS1+), 131 (76%) were PS 0/1. Lorlatinib was delivered as 2nd/3rd/4th/5th+ line in 3%/17%/27%/53%of ALK+ patients and in 30%/30%/16%/24%of ROS1+ patients, respectively. 150 (75%), 185 (93%), 138 (69%), and 80 (40%) patients had received prior chemotherapy, crizotinib, 2nd generation TKIs, and brain radiotherapy, respectively. Median PFS and OS from the initiation of lorlatinib were 11.8 (95% CI 7.3-14.6) months and NR (95% CI 18.6-NR) months, respectively for ALK+ patients and 7.6 (95% CI 6.2-10.2) months and 20.9 (95% CI 10.0-NR) months, respectively for ROS1+ patients. ORR and DCR were 46.2% (95% CI 37.6-54.7) and 86.2% (95% CI 80.2-92.1), respectively for ALK+ patients and 47.1% (95% CI 33.4-60.8) and 88.2% (95% CI 79.4-97.1), respectively for ROS1+ patients. CNS ORR was 41.7% (95% CI 33.3-50.1) and 37.7% (95% CI 24.7-50.8), respectively. With a median follow-up of 15.6 (95% CI 14.0-17.6) months, progression under lorlatinib treatment was observed in 71 (50%) ALK+ patients and 35 (61%) ROS1+ patients, and CNS progression in 24 (34%) and 8 (23%) patients, respectively. The safety profile of lorlatinib was consistent with published data. Conclusions: These real-life results confirmed lorlatinib as a major treatment option for patients with advanced refractory ALK or ROS1+ NSCLC.
PD-1 or PD-L1 co-localizes with immune cells for prediction of prognosis in non-small cell lung cancer.
Authors: Chengzhi Zhou, Jinhuo Lai, Yanhui Chen, Yating Wang, Henghui Zhang
Journal: Journal of Clinical Oncology (2020)

e21029 Background: A number of studies have shown that tumor cells expressing PD-L1 correlate with a better prognosis of immunotherapy in patients with non-small cell lung cancer(NSCLC). However, there were few studies on the immune cells that expressing PD-1 or PD-L1 affect the clinical outcome of patients with NSCLC. Therefore, further research is needed Methods: A total of 336 tumor tissues from patient with non-small cell lung cancer were collected and divided into two cohorts, discovery cohort (174 patients) and validation cohort (162 patients). We used multiplex IHC to identify and quantify CD8, CD57, CD68, CD163, PD-1 and PD-L1 positive rate in tumor tissues, and analyzed its relationship with clinical prognosis. Results: Both PD-1 and PD-L1 were detected on CD8+, CD57+, CD68+, and CD163+ immune cells, but the positive rate were different. PD-1 was higher on cytotoxic T cells (CD8+PD-1+) and PD-L1 was higher on macrophages and cytotoxic T cells (CD68+PD-L1+ and CD8+PD-L1+). By undifferentiated clustering analysis in discovery cohort, the survival rate of tumors with more immune cells expressing PD-1 or PD-L1 was worse. Univariate analysis using X-tile plots to generate the optimum cut off score for all features revealed that immune cells expressing PD-1 or PD-L1 were adverse factors of clinical prognosis of patients with NSCLC, and this result was also confirmed in the validation cohort. Conclusions: In 336 non-small cell lung cancer cases, the expression characteristics of PD-1 and PD-L1 on tumor-infiltrating immune cells were related to survival of patient. In this study, high level of PD-1 and PD-L1 expression on immune cells were associated with lower survival rate, and biomarker characteristics based on this analysis probably enables us to better guide clinical treatment
Incidence and prognosis of patients with pulmonary metastases at diagnosis of primary extrapulmonary malignancy: A population-based study.
Authors: Hao Li, Xiaoyi Zhao, Zuli Zhou, Shaonan Ning
Journal: Journal of Clinical Oncology (2020)

e19353 Background: As a sign of advanced malignancy, pulmonary metastases often predict poor prognosis and are notoriously difficult to treat, requiring an interdisciplinary combination of chemotherapy, surgery and radiotherapy. Large-scale and generalizable studies examining the incidence and prognosis of patients with pulmonary metastases are still lacking. Methods: We identified 2,649,261 patients with diagnoses of nonhematologic malignancies originating outside of the pulmonary between 2010 and 2016 from the Surveillance, Epidemiology, and End Results (SEER) program. We described the incidence proportion and survival of patients with pulmonary metastases, and determined risk factors and prognostic factors of for pulmonary metastasis. Results: We identified 68,474 patients with pulmonary metastases at diagnosis, accounting for 3.19% of all patients with cancer and 35.94% of those patients with metastatic disease. Tumors with higher lung metastasis rates were pancreas cancer, esophageal cancer, sarcoma, renal cancer, hepatobiliary cancer, all other type of cancer, ovarian cancer and gastric cancer (10.54%, 9.32%, 8.75%, 7.48%, 6.43%, 5.96%, 5.79% and 5.26%, respectively). When considering only patients with distant metastases at diagnosis, The top five types of cancer with pulmonary metastasis were testicular cancer (82.82%), thyroid cancer (72.80%), endometrial cancer (66.87%), renal cancer (66.59%) and cervical cancer (64.89%). Multivariable logistic regression identified several oncology characteristics, such as synchronal bone, brain or liver metastasis (vs without), higher N-stage, and tumor poor pathological differentiation were associated with higher risk of pulmonary metastases. Similar to the risk factors for incidence, more distant metastasis, poor differentiation, higher staging, positive lymph node might also associate with shorter overall survival and cancer-specific survival. Surgery of primary site was a protect factor for survival. Conclusions: For the first time, we provided current generalizable estimates of the incidence and prognosis of patients with pulmonary metastases at diagnosis of an extrapulmonary malignancy. This data may lead to evaluation of early screening of the pulmonary using chest CT scan among patients with newly diagnosed primary extrapulmonary malignancies, and further shape the development of screening and treatment guidelines about pulmonary metastases.
Randomized phase II study on gemcitabine with or without ramucirumab as second-line treatment for advanced malignant pleural mesothelioma (MPM): Results of Italian Rames Study.
Authors: Maria Pagano, Giovanni Luca Ceresoli, Paolo Andrea Zucali, Giulia Pasello, Marina Chiara Garassino, Federica Grosso, Marcello Tiseo, Hector J. Soto Parra, Francesca Zanelli, Federico Cappuzzo, Francesco Grossi, Filippo de Marinis, Paolo Pedrazzoli, Roberta Gnoni, Candida Bonelli, Annalisa Berselli, Luca Boni, Nicola Normanno, Carmine Pinto
Journal: Journal of Clinical Oncology (2020)

9004 Background. The RAMES Study (EudraCT Number 2016-001132-36) is a multicenter, double-blind, randomized phase II trial exploring the efficacy and the safety of the addition of ramucirumab to gemcitabine as the second-line treatment in MPM patients (pts) after platinum/pemetrexed regimens. Methods. The pts were assigned (1:1) to receive Gemcitabine 1000 mg/m 2 i v on days 1 and 8 every 21 days with Placebo (Arm A) or Ramucirumab 10 mg/kg i v on day 1, of a 21-day cycle (Arm B), until tolerability or progressive disease. Pts was stratified by ECOG/PS (0-1 vs 2), age (≤ 70 vs &gt; 70 yrs), histology (epithelioid vs non-epithelioid) and time to progression (TTP) after first-line therapy. The primary endpoint was overall survival (OS). Assuming a proportion of OS equal to 40% at 1 year in arm A, a 12% absolute improvement in OS at 1 yrs was expected in Arm B (hazard ratio = 0.70).114 events (156 subjects) are required for a one-sided log-rank test with α = 0.15 to have 80% power. Results. From December 2016 to July 2018, 164 pts were randomized, 81 pts in Arm A and 80 Arm B; 3 pts were randomized but not treated. Characteristics of pts were: median age 69 yrs (44-81), males 119 (73.9%), females 42 (26.1%); ECOG/PS0 96 (59.6%) ECOG/PS1-2 65 (40.4%); histotype epithelioid 132 (81.9%), non-epithelioid 29 (18.1%); stage III 98 (60.7%), stage IV 60 (37.3%), 3 (2.0%) missing; asbestos exposure assessed 80 (49.7%). Median of courses was 3.50 in Arm A and 7.50 in Arm B. OS was significantly longer in Arm B with median 13.8 mths (70% CI 12.7-14.4) vs Arm A with 7.5 mths (70% CI 6.9-8.9), HR 0.71 (70% CI 0.59-0.85, p = 0.057). OS at 6 and 12 mths was in Arm A 63.9% and 33.9%, and in Arm B 74.7% and 56.5%, respectively. In Arm B OS was not correlated to TTP at first-line therapy (13.6 mths in TTP ≤6 mths and 13.9 mths in TTP &gt; 6 mths) and histotypes (13.8 months in the epithelioid and 13.0 months in non-epithelioid). No significant differences in thromboembolism G3-4 events were observed in Arm A vs Arm B (p= 0.64). None hypertension G3-4 was reported in Arm A vs 5 pts (6.3%) in Arm B (p= 0.022). No significant differences in G3-4 haematological toxicities between the two arms were reported. Conclusion: In the RAMES Study the addition of Ramucirumab to Gemcitabine significantly improved OS regardless of age of pts, tumor histotype and TTP at the first-line treatment. Gemcitabine plus Ramucirumab can be considered a manageable regimen in second-line treatment of advanced MPM pts. Clinical trial information: NTC03560973.