tbuckley/cabot-search huggingface dataset:
Influence of hypothyroidism post chemo radiation on outcomes in head and neck cancer.
Authors: Tanmoy Kumar Mandal, Vijay Maruti Patil, Amit Joshi, Atanu Bhattacharjee, Alok Goel, Vikas Talreja, Arun Chandrasekharan, Nikhil Pande, Anant Ramaswamy, Kumar Prabhash, Vanita Noronha
Journal: Journal of Clinical Oncology (2018)

e18066 Background: The development of treatment induced hypothyroidism and its correlation with improvement in outcomes has been noted in certain cancers. It is unknown, whether such a phenomenon exists in head and neck cancer. Methods: In this study, locally advanced head and neck cancer patients were treated either with weekly or 3 weekly cisplatin concurrent with radiation. Patients post treatment completion underwent thyroid function test at 3 monthly intervals for first 2 years and then at 6 monthly intervals. Impact of development of hypothyroidism on loco-regional failure rate (LRFR), PFS (progression free survival) and overall survival (OS) was studied using Cox proportional hazard regression with time varying covariate function. The impact of duration of hypothyroidism and the level of thyroid stimulating hormone (TSH) on the above mentioned outcomes were also studied. Results: The cumulative incidence of hypothyroidism at 2 years was 38.73% (33.11-44.35%). Development of hypothyroidism had a favourable impact on the 2 year LRFR (HR-0.342, 95%CI 0.121-0.968, p-0.043), PFS (HR 0.579,95%CI 0.329-1.022, p-0.059) and OS (HR 0.336, 95%CI 0.175-0.643, p-0.001). A longer duration of hypothyroidism and hypothyroidism with TSH levels up to 40 (versus values above 40) were associated with favourable impact on LRFR, PFS and OS among the hypothyroid cohort. Conclusions: The development of hypothyroidism is associated with an improvement in LRFR and overall survival in head and neck cancer treated with concurrent chemoradiation.
The FUNNEL: A molecular multiplex triage for precision medicine in metastatic colorectal cancer.
Authors: Francesco Leone, Andrea Bertotti, Cosimo Martino, Paola Cassoni, Francesca Maletta, Giuseppe Tonini, Salvatore Siena, Patrizia Racca, Vittorina Zagonel, Andrea Ardizzoni, Fortunato Ciardiello, Ilaria Depetris, Andrea Sartore-Bianchi, Daniele Regge, Angelo Vanzulli, Massimo Aglietta, Giulia Siravegna, Alberto Bardelli, Livio Trusolino, Silvia Marsoni
Journal: Journal of Clinical Oncology (2016)

TPS3636 Background: The goal of precision medicine is to match a selective drug with a genetic lesion that predicts for drug sensitivity. Over 50% of metastatic colorectal cancer (mCRC) patients (PTS) harbor KRAS, NRAS and BRAF mutations not responsive to anti-EGFR therapies. Recent data from our patient-derived mCRC xenografts platform support the presence of further negative predictors of response to anti-EGFRs in a further 10-15% of cases (Bertotti A. et al, Nature 2015). Therapeutic resistance to EGFR blockade was overcome in tumour graft models through therapies targeting actionable genes, suggesting the need for an expanded molecular classification of mCRC requiring clinical validation. Methods: We translated this list of potential mCRC drivers in the customized molecular diagnostic panel FUNNEL. FUNNEL primary goal is to identify PTS harboring low prevalence (~3%) markers potentially predictive for response to available targeted therapies other than anti-EGFR. To this end, the paraffin sample of 1000 newly diagnosed mCRC PTS from 8 Italian cancer centers are centrally genotyped with Sequenom and NanoString technologies. Centralized DNA extraction and analysis is performed after histology revision in the FUNNEL pathology hub. Whenever possible, patients with ensuing specific molecular features will be recruited, after standard primary treatment, in proof-of-concept trials with a targeted therapy already proven positive in the matching preclinical model. Beyond ‘molecular triage’ purposes, FUNNEL will build an integrated repository of life-time clinical and molecular information, including proteomics from initial tissue micro arrays and dynamic data of centralized disease assessments imaging coupled with longitudinal liquid biopsies collected, until death, whenever a significant clinical event occurs (baseline, response to therapy and progression of sequential treatment’s lines). Altogether these data will give a comprehensive insight of mCRC clonal evolution laying the groundwork to design further innovative trials, and, eventually, inform patient care. EudraCT 2016-000448-33, Funded by AIRC Grant 9970; Italian Ministry of Health grant NET-2011-02352137. Clinical trial information: 2016-000448-33.
Percutaneous electrochemotherapy of malignant main portal veins thrombosis: a prospective case series.
Authors: Luciano Tarantino, Giuseppina Busto, Aurelio Nasto, Raffaele Fristachi, Luigi Cacace, Maria Talamo, Pasquale Ambrosino, Paolo Gallo, Paolo Tarantino, Catello Accardo
Journal: Journal of Clinical Oncology (2016)

e15586 Background: We report our experience in thrombosis of portal vein and/or 1st order branches (Vp3-4PVTT) from Hepatocellular carcinoma (HCC) treated with Percutaneous Electrochemotherapy (ECT) . Methods: Six cirrhotics (5 males; 61 – 85 years, 4 in Child-Pugh A, 2 in Child-Pugh B class) prevously studied with three-phase CT, contrast enhanced Ultrasound (CEUS) and US guided percutaneous biopsy of the thrombus , underwent ECT (Cliniporator Vitae - IGEA, Carpi, Italy) of Vp3-4PVTT and the associated HCC nodule in the same session, in general anesthesia. Results: 24 hours posttreatment CEUS showed complete absence of enhancement of the treated trhombus in all cases. Post-treatment biopsy showed apoptosis and necrosis of tumor cells in all cases. The follow-up ranges from 3 to 12 months (mediane: 8 months). In 1 patient, the 3-6-9-12 months CEUS and CT demonstrate complete recanalization of the treated PVTT; in another patient, 3-6-9 months CEUS and CT show a partially patent portal vein; other 3 patients (8, 4 and 3 month follow-up, respectively) show avascular complete thrombosis at CEUS and CT . In all 5 patients, CEUS and CT show absence of abnormal intravascular or perivascular enhancement consistent with residual tumor or local recurrence. One patient, was lost to follow-up because of death from gastrointestinal hemorrage 5 weeks after ECT. Conclusions: ECT seems effective and safe for curative treatment of Vp3-Vp4 PVTT from HCC.
Epidemiological study of unknown primary melanoma patients from the French national melanoma database RIC-Mel.
Authors: Emilie Varey, Stéphane Dalle, Jean-Michel NGuyen, Alain Dupuy, Jean-Philippe Lacour, Bernard Guillot, Laurent Mortier, François Skowron, Philippe Celerier, Nicolas Meyer, Patrick Combemale, Caroline Dutriaux, Beatrice Crickx, Eve Maubec, Sophie Dalac-Rat, Marie Thérèse Leccia, Amir Khammari, Celeste Lebbe, Brigitte Dreno
Journal: Journal of Clinical Oncology (2018)

e21571 Background: Melanomas of unknown primary (MUP) are considered as metastatic disease. Epidemiologic features of MUP patients have been described in several studies, but never yet from the French national melanoma active file. Methods: Data collected between March 2012 and April 2017 were retrieved from the database of the RIC-Mel (Research and Clinical Investigation on Melanoma) network and have been analyzed. Skin, mucous membranes and eyes of all MUP patients were examined in search of a primitive lesion by a dermatologist. Results: Among the 18,379 patients included, 2.6% (n = 480) were MUP and 24.3% (n = 4,348) were in metastatic diseases (AJCC stage III/IV) with a known primary melanoma (MKP). Epidemiologic analysis showed that MUP and metastatic MKP patients were comparable regarding sex distribution and age at metastatic diagnosis. Regarding mutational statues, BRAF alterations were more often reported in MUP than metastatic MKP patients (47% vs 39%, p = 0.01). Death rate analysis indicates that MUP patients had a most pejorative prognosis as compared to metastatic MKP patients (18% vs 16%, p < 0.001). The MUP patients had also a greater tumor load supported by a more frequent visceral dissemination (41% vs 24% for metastatic MKP patients) (p < 0.001). Conclusions: This first analyze of MUP in the French melanoma active file showed that this subpopulation had a poorer prognosis than metastatic MKP patients. This could be supported by many hypotheses such as the lack of specific cytotoxic T cells development due to a shorter time to develop a melanoma-specific immunity, more BRAF mutations correlated with a most aggressive profile and more visceral metastasis. Furthermore, no statistical difference was founded regarding the age at metastatic diagnosis. Our results supported the need to set up a close monitoring for MUP patients.
Impact of corticosteroid administration on outcomes following stereotactic ablative radiotherapy for non-small cell lung cancer.
Authors: Hongqi LI, Vivek Verma, Eric Brooks, Lei Feng, James William Welsh, Steven H. Lin, Daniel Richard Gomez, Saumil Gandhi, John Heymach, Joe Y. Chang
Journal: Journal of Clinical Oncology (2018)

e20518 Background: Because radiotherapy(RT) induces antitumoral immune responses, administering corticosteroids (CS) for other medical issues is a major oncologic concern. This is the only study evaluating the impact of CS on outcomes of early-stage non-small cell lung cancer (NSCLC) following stereotactic ablative RT (SABR). Methods: A prospectively-registered institutional database of SABR for early-stage non-metastatic NSCLC was queried (2005-2015). CS administration was dichotomized based on two definitions: 1) CS receipt within two days of the SABR course, and 2) CS delivery between up to 6 months before SABR and the date of last follow-up or any progressive disease (LFU/PD). Statistics included Kaplan-Meier survival analysis, Cox proportional hazards modeling, and cumulative incidence analysis utilizing death as a competing risk model evaluated with Gray’s test. Results: Of 912 patients, 87 (10%) received CS based on the ± 2-day definition, and 211 (23%) based on the LFU/PD definition. The most common CS agents were prednisone (62%) and dexamethasone (19%); most common CS indications were COPD (34%) and pneumonitis caused by SABR or other previous treatments (24%). Median follow-up was 45 months. Patients receiving CS appears to have a significant change in blood white cell parameters. Although CS administration associated with worse isolated locoregional recurrence-free survival, distant metastasis-free survival, recurrence-free survival, and overall survival on Kaplan-Meier and Cox multivariate analysis, there were no differences in cumulative incidences of recurrence (local, regional, isolated locoregional, distant, any) when using death as a competing risk model, in both definitions (p > 0.05 for all). Conclusions: Although further corroboration is required and causation is not implied, these data do not suggest a detriment in outcomes if corticosteroids are administered in proximity with SABR. Individualized judgment in administering CS for these settings is still recommended. These data have implications not only for ongoing cooperative group trials, but also the construction and implementation of immunotherapy-SABR trials.
TCT-77 Procedural success and outcomes with increasing use of enabling strategies for chronic total occlusion intervention: an analysis of 28,050 cases from the British Cardiovascular Intervention Society database
Authors: Tim Kinnaird, James Cockburn, Alexander Sirker, Peter Ludman, Mark de Belder, Elliot Smith, Richard Anderson, Julian Strange, Mamas Mamas, David Hildick-Smith
Journal: Journal of the American College of Cardiology (2018)
A claims data analysis of single institution for comorbidity among various types of cancer.
Authors: Kazuhiro Araki, Hideto Nakagawa, Yasuo Miyoshi
Journal: Journal of Clinical Oncology (2018)

e18843 Background: Improvements of treatment have reduced cancer-related mortality. However, managements of complications are important. Morbidities are key factors to manage treatments. This study is to evaluate both frequency, and types of morbidity among various types of cancer. Methods: A retrospective cohort of a various type of cancer was identified from the claims data using the Japanese national health insurance systems in our hospital during August 2017. Results: We identified 1179 various types of cancer, including 702 males and 477 females. Five percent were less than 41 years old (yo) (adolescent young adult generation), while 74% were more than 60 yo (geriatric generation). Remaining were active workers generation (21%). More than 15 types of cancer were included in this cohort including followings; thoracic cavity (22%), upper gastrointestinal (GI) (21%), lower GI (13%), hematologic malignancy (Hem) (10%), hepatobiliary and pancreatic (HepP) (9%), breast (8%), and genitourinary (GU) (6%). In terms of comorbidities, 68% of those were complicated with gastroenteritis (GEs). Additionally, more than one thirds of patients (pts) had following comorbidities: hypertension (HTN) (37%), diabetes mellitus (DM) (35%), liver disease (LivDs) (34%), ischemic heart disease (IHD) (30%). In a Hem, HTN (54%), IHD (42%), LivDs (56%) and GEs (87%) were more frequent than average. In GU cancer including prostate cancer, IHD (41%) were more frequent than average. In HepP cancer, both DM (46%) and LivDs (53%) were more frequent than average. In geriatric generation, HTN (42%), IHD (35%), and DM (38%) were more frequent than other generations (24%, 17%, and 25%, respectively). Next, we evaluated the frequency of prescription for each comorbidity. More than 80% of both LivDs and GEs were prescribed the approval medication, while less than half of pts who had comorbidities with HTN, IHD, and DM, were treated with the appropriate prescriptions. Conclusions: More than three quarter of pts were geriatric generation. Of those, more than one thirds of pts have life-style related disease. However, frequency of prescription was less than half without clear reasons. Therefore, we are launching comprehensive multimodality team for geriatric pts.
A gene expression signature of <i>FOXM1-AURKB-CDKN1A</i> to recapitulate molecular characteristics of standardized uptake value of <sup>18</sup>F-FDG-PET in breast cancer.
Authors: Sung Gwe Ahn, Seon-Kyu Kim, Soong June Bae, Chang-Ik Yoon, Joon Jeong, In-Sun Chu
Journal: Journal of Clinical Oncology (2018)

12105 Background: We previously showed that standardized uptake value (SUV), an indicator of the degree of glucose uptake in 18F-FDG-PET, could be used as a prognostic marker in breast cancer and has a correlation with 21-gene recurrence score. We explored genomic features associated with SUV and identified a molecular signature reflecting SUV in breast cancer. Methods: Transcriptomic profiling was carried out using gene expression data from 60 breast cancer patients who underwent preoperative FDG-PET to identify a molecular signature associated with SUV. The prognostic value of the signature was verified in other three cohorts (namely YSU, UNC, and TCGA cohorts, n = 301, 500, and 815, respectively). The association between the SUV signature and prognosis of breast cancer patients was assessed. To compare mutation profiles between two patient subgroups divided by SUV signature in the TCGA cohort, we obtained two predefined gene sets involved in oncogenic or metabolic pathways and estimated a difference of their mutation frequencies. Results: The determination of gene expression patterns by transcriptome data analysis identified 1,528 genes associated with SUV (|r| > 0.35, p < 0.01 by Pearson correlation test). The patient subgroups classified by those genes (i.e., SUV-high-cluster and SUV-low-cluster) were significantly similar with patient classification by SUV (p < 0.001). When estimating prognostic value of the molecular signature associated with SUV in three cohorts, the signature showed a strong prediction ability in breast cancer prognosis (each p < 0.05 by log-rank test). Gene network analyses revealed that a signaling defined by FOXM1-AURKB-CDKN1A could be an important pathway reflecting SUV characteristics. Lastly, a mutation profiling in the TCGA cohort showed that POLD1, UGT2A1, and UGT1A3 involved in tumor metabolism would be important mediators. Conclusions: Our results unveil genomic characteristics of increasing glucose uptake of breast cancer captured by FDG-PET, supporting a poor prognosis in patients with high SUV. Our works shed light on understanding a molecular basis of glucose metabolism in patients with breast cancer.
Multicenter feasibility study of chemoradiation, trastuzumab and pertuzumab in resectable HER2+ esophageal carcinoma: The TRAP study.
Authors: Stephanie van der Woude, Sybren L. Meijer, Maarten Hulshof, Suzanne S Gisbertz, Sheila Krishnadath, Cornelis J. A. Punt, Marc J. van de Vijver, Fabienne Warmerdam, Geert-Yan Creemers, Marije Slingerland, Maartje Los, Geke Hospers, Laurens Victor Beerepoot, Nadia Haj Mohammad, Jolanda van Dieren, Mark I. van Berge Henegouwen, Hanneke W.M. Van Laarhoven
Journal: Journal of Clinical Oncology (2016)

TPS4142 Background: Despite multimodality treatment the outcome of esophageal adenocarcinoma (EAC) is poor. In EAC, human epidermal growth factor receptor 2 (HER2) is overexpressed in 19% to 43% of cases. Based on the positive results of the ToGA trial in metastatic esophagogastric cancer, HER2 targeting is currently investigated in patients treated with curative intent. Most patients, however, develop resistance to trastuzumab. Recent studies in breast cancer evaluating the effect of combined HER2/HER3 targeting with trastuzumab and pertuzumab showed improved efficacy. To explore if combined HER2 targeting added to multimodality treatment is feasible and has potential benefit in HER2 overexpressing resectable EAC, we are currently conducting the TRAP study. The primary objective is the feasibility of preoperative treatment with chemoradiation combined with pertuzumab and trastuzumab. Secondary objectives include: toxicity, surgery withdrawal rate, R0 resection rate, pathological reponse and pharmacokinetics. Methods: Patients with resectable EAC who are in a good clinical condition and considered operable are treated in one of the 9 participating centers with paclitaxel 50 mg/m2 and carboplatin AUC = 2 on days 1, 8, 15, 22 and 29. Trastuzumab is administered at a dose of 4 mg/kg on day 1, followed by 2 mg/kg at week 2-6. From week 7 onwards trastuzumab is dosed at 6 mg/kg every 3 weeks. Pertuzumab is administered on day 1, 22, 43, 64, and 85 using a fixed dose of 840 mg. Radiotherapy is delivered to a total dose of 41.4 Gy, starting the first day of chemotherapy. Surgical resection follows in week 14. Treatment with trastuzumab and pertuzumab during chemoradiation is regarded feasible if ≥ 80% of patients complete treatment. Primary analysis will be performed in all patients who received at least one dose of pertuzumab and/or trastuzumab. Currently, 21 of planned 40 patients have been enrolled. The data safety monitoring board did not find any safety concerns after the first 10 operated patients. Clinical trial information: NCT02120911.
Tissue signals imprint ILC2 identity with anticipatory function
Authors: Roberto R. Ricardo-Gonzalez, Steven J. Van Dyken, Christoph Schneider, Jinwoo Lee, Jesse C. Nussbaum, Hong-Erh Liang, Dedeepya Vaka, Walter L. Eckalbar, Ari B. Molofsky, David J. Erle, Richard M. Locksley
Journal: Nature Immunology (2018)
Impact of chemoradiotherapy on PD1/PDL1 expression and clinical outcomes in gastroesophageal cancers.
Authors: Arsen Osipov, Quanlin Li, Shant Thomassian, Lakshmanan Annamalai, Jennifer Holmes Yearley, Joanne K Rutgers, Andrew Eugene Hendifar, Richard Tuli
Journal: Journal of Clinical Oncology (2017)

4031 Background: Expression of the immune modulating proteins, programmed death receptor-1 (PD1) and its ligand (PDL1), in gastrointestinal malignancies is associated with poor prognosis. PD1/PDL1 expression levels have also been identified as predictors of response to checkpoint inhibition. Minimal data is available on how expression of PD1 and PDL1 is influenced by chemoradiotherapy (CRT). In this study, we investigated the relationship between PDL1/PD1 expression, CRT, and clinical outcomes in gastroesophageal (GE) cancer. Methods: With IRB approval, we identified 28 patients with gastric cardia or GE junction tumors who underwent neoadjuvant standard CRT followed by surgical resection. Pre-CRT biopsies and post-CRT surgical specimens were analyzed using quantitative immunohistochemistry for the expression of PDL1 and PD1. Samples were categorized as trace-low (TL) or moderate-high (MH) expressors of PDL1 and PD1. The impact of these and other clinical and pathologic variables on overall survival (OS) was assessed using multivariate cox proportional hazards modeling. Co-expression of PDL1 and PD1 in matched samples was determined by regression analysis. Results: Following CRT, PDL1 and PD1 expression increased in 54% and 32% of patients, respectively. On multivariate analysis, patients with MH expression of PD1 after CRT irrespective of pre-CRT expression levels had a significant decrease in OS compared to those with TL expression (median survival 23.1 vs 74.1 months; HR,3.31; CI,1.05-10.35; p = 0.039). In patients with gastric confined tumors, an increase in PD1 expression from TL to MH after CRT was associated with significantly lower OS rates (p = 0.003). Regression analysis of PD1 to PDL1 was significant (p &lt; 0.01) both before and after CRT, with a correlation coefficient of 0.34 in pre-CRT and 0.49 in post-CRT specimens. Conclusions: Elevated expression of PD1 is associated with poor OS in patients with GE cancer. Neoadjuvant CRT upregulates both PDL1 and PD1. In gastric cancer patients, this led to significantly worse survival. These data identify potential mechanisms of resistance and suggest a role for checkpoint inhibitors in combination with CRT.