tbuckley/cabot-search huggingface dataset:
Association of diabetes mellitus with an increased risk of recurrence and disease progression in women with ovarian granulosa cell tumors.
Authors: Joan Tymon-Rosario, Eirwen Murray Miller, Gregory M. Gressel, Nicole Suzanne Nevadunsky
Journal: Journal of Clinical Oncology (2018)

e17521 Background: Granulosa cell tumors (GCTs) are a rare ovarian sex cord-stromal tumor. Diabetes is a predictor of GCT recurrence though data informing outcomes in racially diverse populations is limited. Our study aims to describe the clinicopathologic characteristics of racially diverse women with GCTs. Methods: Clinicopathologic and treatment data were abstracted from the medical records of all women diagnosed with GCTs who received treatment from 2005-2015. Two-sided analyses were performed using SAS 14.2. Results: Seventy-two cases were identified, of which histologically 96% and 4% were adult and juvenile subtype, respectively. Median age and BMI were 54.5 years and 31.2, respectively. 7% of patients were white. 93% percent of patients had stage I disease. Bilateral salpingo-oophorectomy, hysterectomy, and complete surgical staging were performed in 71%, 67%, and 32% of patients, respectively. Of 53 patients that underwent lymph node sampling, only one patient had nodal metastases. Seven and eight patients had concurrent endometrial cancer and hyperplasia, respectively. Fertility sparing surgery was performed in 24% of patients, of whom 35% subsequently had a live birth without assisted reproductive technology. 14% of patients received adjuvant chemotherapy; the most common regimen was bleomycin, etoposide and cisplatin. Eleven recurrences were diagnosed over a median follow up 58.5 months. There was only one recurrence among those that underwent fertility sparing surgery. Recurrent/progressive GCT was more common amongst women with diabetes (33.4%) when compared with women without diabetes (12.5%; OR 4.73, 95% CI 1.02- 21.85). No deaths were attributable to disease. One patient died of bleomycin induced pulmonary toxicity. Conclusions: In our racially diverse population, we observed no association between race and the clinicopathologic variables for women with GCTs. However, we did find a significant association between diabetes and an increased risk of GCT recurrence/progression. This finding is worthy of further investigation in multi-institutional studies and meta-analyses to achieve adequate power to control for confounding variables.
Circulating cell free tumor DNA detection as novel biomarkers to monitor desmoid tumors evolution.
Authors: S Bastien Salas, Nicolas Macagno, Nicolas Penel, Florence Duffaud, Isabelle Nanni, Corinne Bouvier, Raquel Rouah, L'houcine Ouafik, Toufik Bouhadiba, Sylvie Bonvalot, Frederic Fina
Journal: Journal of Clinical Oncology (2017)

11063 Background: Since desmoid tumors (DT) exhibit an unpredictable clinical course, with stabilization and/or spontaneous regression, an initial “wait-and-see” policy is the new standard of care to select best indications of active treatments in case of significant evolution. Therefore, translational research is crucial to identify predictive factors of progression. Most DT are characterized by CTNNB1 mutation (CM) in exon 3 (T41A, S45F, S45P). Circulating cell-free tumoral DNA (ctDNA), named "liquid biopsy", has emerged as a new promising non-invasive tool to detect biomarker in several cancers. Methods: We present a method of detection of DT-specific CM using a targeted strategy digital droplet PCR (ddPCR) on cell-free DNA (cfDNA) extracted from blood samples of 31 DT patients (pts). T41A, S45P, S45F and their respective CTNNB1 wild-type probe were designed for ddPCR. Furthermore, we analyzed the correlation of cfDNA levels (CTNNB1 wt/ml plasma) and evolution of the tumor. Results: Initial DT CM statuswas known for 28 pts and unknown for 3 pts. 24 pts presented a CM (17 pts T41A, 6 pts S45F and 1 pt S45P), 2 pts a mutation of APC, 2 pts were wild-type, and 3 pts were undetermined. Among pts with a CM, CTNNB1 mutants were detected in the cfDNA of 6 patients (19.4%). CM detection was not correlated with the quantity of cfDNA analyzed (p = 0,7263–Mann-Whitney (MW)). Absolute quantification of cfDNA (CTNNB1 wt) normalized by mL of plasma displayed higher levels for patients with progressive DT (p = 0,0009 - MW), this difference of cfDNA quantity was also present between progressive, stable and self-regressive DT (p = 0,0012 - MW). A threshold of 875 CTNNB1 copies/mL predicted DT progression with a sensibility of 100% (CI 95% : 59-100) and a specificity of 76.5% (CI 95% : 50.1-93.2). Absolute cfDNA quantity was also higher in patients harboring multiple desmoids (p = 0.0292 - MW). Conclusions: The absolute quantification of normalized cfDNA is correlated with evolution of the disease, independently of the initial tumor type of CM. This study opens the perspective of using cfDNA as a genomic biomarker to assess the tumor dynamics at initial diagnosis, and to monitor treatment strategy in case of tumor evolution.
EDMONd: A feasibility study of elemental diet as an alternative to parenteral nutrition for ovarian cancer patients with inoperable malignant bowel obstruction.
Authors: Agnieszka Michael, Eleanor Smith, Adele Hugg, Thomas Kilpatrick
Journal: Journal of Clinical Oncology (2018)

TPS5605 Background: Inoperable bowel obstruction (IBO) occurs in up to 50% of patients diagnosed with ovarian cancer. Nutrition support for patients with IBO is challenging. Parenteral feeding (PN) is the recommended route for patients with a prognosis of > 2 months, however there is little evidence that it improves quality of life and the cost of it is very high . If PN is not available patients are frequently discharged home from hospital with sips of clear fluids only. Management of inoperable bowel obstruction remains a major challenge and clear guidelines are needed. Elemental diet (ED) is a liquid diet that contains proteins in the form of amino acids, fats in the form of medium chain triglycerides, vitamins and trace minerals. EDs are almost completely absorbed in the upper small intestine Methods: The primary objective of the study is to establish if ED can be used as an alternative to home PN in patients with IBO by providing a ‘proof of concept’ of ED as an acceptable and useful feeding option. The secondary aim is to examine the impact of ED on quality of life. The primary endpoints of the study are taste acceptability (graded 1-5 on a purposely designed Elemental Diet data collection chart), incidence of vomiting and incidence of pain. The secondary endpoints include the number of women who can tolerate ED and can subsequently be treated with palliative chemotherapy (as per standard of care), the number of patients alive at the end of the study, quality of life and nutritional intake. This is a mixed-method single arm feasibility study of 34 patients diagnosed with IBO and who can tolerate 500ml of liquid. Patients are provided with ED and followed-up for 2 weeks. Patients’ symptoms and quality of life are assessed using the Memorial Symptoms Assessment Scale (MSAS) and EORTC Quality of Life QLQ-C30 questionnaire. As this is a feasibility study to evaluate whether ED is an acceptable intervention for patients with IBO, recruiting 25 patients into the study will provide an answer to the question. As the prognosis is poor in this cohort we assumed 25% attrition rate 8 out of 34 patients have been recruited and the recruitment continues. Clinical trial information: ISRCTN16862540.
Olaparib combined with abiraterone in patients (pts) with metastatic castration-resistant prostate cancer (mCRPC): A randomized phase II trial.
Authors: Noel Clarke, Pawel J. Wiechno, Boris Alekseev, Nuria Sala, Robert Jones, Ivo Kocak, Vincenzo Emanuele Chiuri, Jacek Jassem, Aude Flechon, Charles Redfern, Carsten Dietrich Goessl, Joseph Burgents, Robert Kozarski, Darren R. Hodgson, Fred Saad
Journal: Journal of Clinical Oncology (2018)

5003 Background: mCRPC pts with a homologous recombination repair mutation (HRRm) previously showed improved response to the PARP inhibitor olaparib (Lynparza) as monotherapy vs pts without a HRRm (Mateo J et al, NEJM 2015). We report data from a Phase II, placebo-controlled trial of olaparib combined with the anti-hormonal therapy abiraterone in post-chemotherapy mCRPC pts whose tumors did not need to have a HRRm (NCT01972217). Methods: mCRPC pts were randomized (1:1) post-docetaxel to olaparib 300 mg bid (tablets; combination) or placebo (comparator) plus abiraterone (1000 mg od) and treated until disease progression. Primary endpoint was investigator-assessed radiologic progression-free survival (rPFS; RECIST 1.1, PCWG-2). HRRm status was assessed using optional tumor (n = 68), whole-blood and plasma samples. Results: 142 pts (median age: 69 yrs) were randomized and treated (both arms, n = 71). Overall, a statistically significant increase in rPFS was seen with the combination vs comparator (Table; P= 0.03). A rPFS benefit in the combination arm was suggested irrespective of HRRm status. Median overall survival was 23.3 vs 20.9 mths in the combination vs comparator arms, respectively (HR 0.89, 95% CI 0.58–1.35). 54% vs 28% of pts, respectively, had grade ≥3 AEs; 34% vs 18% reported serious AEs, including more cardiovascular AEs with the combination. 30% vs 10% of pts, respectively, discontinued treatment due to an AE. Median time to deterioration in quality of life (QoL; FACT-P) was 5.7 vs 6.0 mths, respectively (HR 0.97, 95% CI 0.68–1.40). Conclusions: This is the first trial to show clinical benefit for mCRPC pts treated with a PARP inhibitor combined with abiraterone, regardless of HRRm status. Safety data were less favorable for the combination, but no detriment to QoL was seen. Our study indicates synergy between olaparib and abiraterone. Clinical trial information: NCT01972217.rPFS by HRRm status. Pt group Median rPFS,* mths (combination vs comparator) HR (95% CI) Overall, n = 142 13.8 vs 8.2 0.65 (0.44–0.97) HRRm, n = 21 17.8 vs 6.5 0.74 (0.26–2.12) HRRwt,† n = 35 15.0 vs 9.7 0.52 (0.24–1.15) HRRm unknown, n = 86 13.1 vs 6.4 0.67 (0.40–1.13) *Kaplan-Meier method; †tumor test result required. wt, wild-type.
Factors and conditions affecting the antitumor effect of magnetite nanoparticles in the experiments in vivo.
Authors: Galina Vitalyevna Zhukova, Alla Ivanovna Shikhlyarova, Tatiana Albertovna Barteneva, Marina Igorevna Bragina, Elena Alekseevna Shirnina, Oleg Evgenevich Polozhentsev, Tatiana Anatolevna Kurkina
Journal: Journal of Clinical Oncology (2017)

e14051 Background: Independent antitumor effects of magnetite nanoparticles (NPs) in animals, up to complete regression of large tumors, have been demonstrated. Factors and conditions that contribute to the appearance and enhancement of such effects are an important issue. Our purpose was to study the dependence of antitumor effects of magnetite NPs on characteristics of animals, ways of preparation and injection of NPs and weak magnetic fields (WMF). Methods: The experiment included 380 white outbred rats with transplantable sarcoma 45 (S45), Pliss lymphosarcoma (PL) and Heren carcinoma (HC) and 230 С57Black/6 mice with B16 melanoma. The animals received 6-8 1.25-35.4 mg/kg peritumoral or intraperitoneal injections of a water-based magnetite NP ferrofluid (FF) diluted with saline solution. WMF parameters were: 0.03-9 Hz frequency, 0.7-3.2 mT induction, exposure on the head. Dynamics of tumor sizes, histological changes and FF characteristics after the dilution with saline (X-ray absorption spectroscopy analysis) were evaluated. Results: An effective single dose in S45 female rats with peritumoral injections was higher than in males (35.4 and 17.7 mg/kg, respectively). Female rats with HC were sensitive to small NP doses (1.25 mg/kg) in intraperitoneal (but not peritumoral) injections (regression in &gt; 30%). Peritumoral injections of small NP doses were most effective in PL males, while a number of experiments did not show benefits of small NP doses for mice. NP solution storage led to its lower effect due to the oxidation of Fe +2 to Fe +3 , and even FF dilution ex tempora decreased the effect as SS pH changed to 7.4. WMF was able to enhance the effect of NPs by up to 1.5 times but not in intraperitoneal injections. Conclusions: Antitumoral effects of NPs depended on species of animals and their gender, tumor types, doses and methods of NP injections, storage time of diluted FF prior to its injection, saline pH, and WMF. WMF effects were different depending on NP injection methods.
Therapy selection and monitoring of early and late stage non small cell lung cancer (NSCLC) using a novel circulating tumor cells (CTCs) PD-L1 blood test.
Authors: Yen-Lin Chen, Wen-Jie Huang, Bruce Kendrick Patterson, Amanda Chargin, Chia-Hsin Hsieh, Ruey Kuen Hsieh, Mahul Amin, Oscar Segurado, Hung-Jen Shao, Feng-Ming Lin, Shih-En Chang, Jen-chia Wu, Jr-Ming Lai, Ben Hsieh, Mana Javey, Rui Mei
Journal: Journal of Clinical Oncology (2018)

e15107 Background: PD-L1 expression on circulating tumor cells (CTCs) is an alternative to checkpoint inhibitor selection by IHC and it offers possibility for serial monitoring following chemotherapy, immunotherapy or radiation therapy. Here we report a sensitive technique to assess PD-L1 expression by CTCs for early and late stage lung cancer. Methods: Two mL blood from 40 patients diagnosed with NSCLC, as well as PD-L1 positive cell lines from lung and breast cancer were processed with the proprietary CMx microfluidic platform. This test captures EpCAM+ cells, which are subsequently confirmed as CTCs based on size, morphology and CK18+/CD45- staining. Expression of PD-L1 is assessed by staining intensity using PD-L1 monoclonal antibody BioINK with cutoffs established by negative control cells. Results: Cell lines showing heterogeneous expression levels for EpCAM, CK18 and PD-L1 reminiscent of CTCs were spiked into healthy donor bloods at various concentrations (10/30/90 per 2mL blood) and assessed for PD-L1 expression. Capture efficiency correlated with EpCAM expression levels and PD-L1 staining intensity levels were concordant with those reported in the literature. Circulating tumor cells were detected in 35/40 (88%) of NSCLC patients across Stages I-IV (range 1-32 CTCs; median 4 CTCs). CTCs were detected in 91% (21/23) of early, and 11/13 (85%) of late stage patients with known staging. 55% (22/40) patients were found to have at least one PD-L1 expressing CTC. IHC PD-L1 results were available in 28 NSCLC patients with detectable CTCs. The PD-L1 CTC assay was positive in 6/8 (75%) patients expressing high levels of PD-L1 by IHC, using the > = 50% cutoff for 1st line immunotherapy selection, including two early stage patients. Importantly, 8 patients who were IHC negative were PD-L1 positive by the CTC test, including 5 early and 3 late stage patients. Conclusions: To the best of our knowledge this is the first study showing high sensitivity of CTCs in detecting PD-L1 in early stage NSCLC. This CellMax CTC blood test can be used for immunotherapy selection and treatment monitoring of NSCLC patients regardless of treatment modality or stage of cancer.
Follow-up of patients with complete remission of locally advanced basal cell carcinoma treated with vismodegib after treatment discontinuation: A retrospective multicentric French study.
Authors: Florian Herms, Luc Haudebourg, Martine Bagot, Caroline Dutriaux, Jean Jacques Grob, Bernard Guillot, Geraldine Jeudy, Jérôme Lambert, Celeste Lebbe, Christine Mateus, Nicolas Meyer, Sandrine Monestier, Laurent Mortier, Nicolas Poulalhon, Sorilla Prey, Caroline Robert, Pierre Vabres, Mehdi Mouri, Nicole Basset-Seguin
Journal: Journal of Clinical Oncology (2017)

9535 Background: Vismodegib is a Hedgehog Pathway inhibitor (HPI) indicated for treatment of inoperable locally advanced basal-cell carcinoma (laBCC). Previous studies showed an objective response (OR) rate of 67%, including 34% of complete response (CR). Discontinuation of vismodegib is very frequent, mostly due to intolerable side-effects. Long-term response and predictive factors of relapse after suspension of vismodegib have not yet been evaluated, but should play a crucial role in the management of laBCC patients. Methods: We conducted an observational retrospective study in 9 onco-dermatological French units. Medical charts of laBCC patients treated with vismodegib from March 2012 until June 2016 were reviewed and patients with CR who stopped treatment were selected. Relapse was diagnosed clinically and/or histologically. A survival analysis was conducted, and predictive factors, characterization and management of relapse were studied. Results: 119 laBCC patients achieved CR and stopped treatment. 21 were lost to follow-up and 6 died before relapse. Event-free survival median was 18.4 months (12.1 – 24.1) and cumulative incidence of relapse at 36 months was 59.04% (48.05 - 70.04), implying that more than 40% of patients do not relapse. Multiple BCC and BCC not localized on the head and neck were associated with a higher risk of relapse, independently of the existence of Gorlin syndrome (HR = 3.3 (IC95 = 1.6 - 6.7) and 2.01 (IC95 = 1.05 - 3.87) respectively). Total duration of treatment was not associated with relapse. 50% (n = 27) of patients who relapsed during follow-up were retreated with vismodegib, with an OR of 85.2% (n = 23). 42% (n = 24) were eligible to surgery only and other patients received local treatments. Conclusions: Long term responders after vismodegib treatment discontinuation are frequent independently of the time exposure to the drug before and after CR. Most patients who relapse are still responder to vismodegib rechallenge. Patients with multiple or laBCC not localized on the head and neck are more at risk of relapse after discontinuation. This study emphasizes the interest of treatment of laBCC with HPI.
Guideline: USPSTF recommends against PSA screening except in men 55 to 69 years who express a preference for it
Authors: James A. Dickinson
Journal: Annals of Internal Medicine (2018)

Source Citation US Preventive Services Task Force, Grossman DC, Curry SJ, et al. Screening for prostate cancer: US Preventive Services Task Force recommendation statement. JAMA. 2018;319:1901-13. 29801017
Frailty score: Prediction of postoperative morbidity and mortality in surgical oncology?
Authors: Guelhan Inci, Louise Anders, Hannah Woopen, Jacek Grabowski, Radoslav Chekerov, Jalid Sehouli
Journal: Journal of Clinical Oncology (2016)

e21526 Background: Frailty Scores have developed as important prognostic tools to risk stratify especially for older adults and have recently been applied to the surgical field. In this systematic review, we examined the utility of Frailty Scores as predictors of adverse outcomes among patients undergoing major oncologic surgery. Methods: The electronic database MEDLINE was searched between November 25 and December 10, 2015 for association of „frailty“ or „fragility“, and „surgery“ and „oncology“ published in the last 10 years. Outcome parameters included 30-d postoperative complications and mortality. Results: The initial search identified 58 potentially relevant articles, with eight (6 prospective/ 2 retrospective) studies meeting inclusion criteria. Two models based on the conceptual framework of frailty were associated with increased postoperative complications. The most used Fried Frailty score, a phenotype model as a biologic syndrome is associated with decreased physiological reserve (strength/power, walking speed, activity, nutritional status). In Contrast, frailty index a geriatric assessment based on accumulation deficit model is assessed with comorbidities, social well-being, the ability to manage activities of daily living, functional and cognitive deficits, as well as laboratory abnormalities. Both models in individual correlation with ASA, age, albumin, sarcopenia, hemoglobin, BMI and severity of surgery are robust predictors of adverse outcomes. Conclusions: In general, frailty scores emerge as a good predictor of postoperative complications and mortality in patients undergoing oncological surgery. However, identifying the best tool to assess a patients’ fitness for surgery is challenging. This is due to the many heterogeneous definitions of frailty, as well as the lack of consensus in the existing literature regarding the most appropriate and feasible measurement. Frailty Scores are currently in focused in geriatric and surgical oncology and need further research. An evidence-based frailty score might also be an advantage if it provides the option for interventions that reduce the amount of vulnerability, and therefore improve the outcomes of pre-identified frail patients.
REACH-2: A randomized, double-blind, placebo-controlled phase 3 study of ramucirumab versus placebo as second-line treatment in patients with advanced hepatocellular carcinoma (HCC) and elevated baseline alpha-fetoprotein (AFP) following first-line sorafenib.
Authors: Andrew X. Zhu, Yoon-Koo Kang, Chia-Jui Yen, Richard S. Finn, Peter R. Galle, Josep M. Llovet, Eric Assenat, Giovanni Brandi, Ho Yeong Lim, Marc Pracht, Kun-Ming Rau, Philippe Merle, Kenta Motomura, Izumi Ohno, Bruno Daniele, Dongbok Shin, Guido Gerken, Paolo Abada, Yanzhi Hsu, Masatoshi Kudo
Journal: Journal of Clinical Oncology (2018)

4003 Background: Patients (pts) with advanced HCC and elevated AFP have a poorer prognosis compared to the general HCC population, and need effective, well tolerated treatment options. Increased VEGF and VEGFR2 expression is associated with high AFP expression in HCC tumors. Ramucirumab (RAM), a human IgG1 mAb, inhibits activation of VEGFR2. REACH-2 was designed to confirm the benefit of RAM treatment observed in the REACH study in pts with baseline AFP ≥400 ng/mL. Methods: Eligible pts were ≥18 yrs, had HCC with BCLC stage C or B disease refractory or not amenable to locoregional therapy, baseline AFP ≥400 ng/mL, Child-Pugh A, ECOG PS 0 or 1, adequate hematologic and biochemical parameters, had progressed on or following, or were intolerant to sorafenib. Pts were randomized (2:1) to receive RAM 8 mg/kg iv or placebo (PL) Q2W plus best supportive care, until disease progression or unacceptable toxicity. Primary endpoint was overall survival (OS). Secondary objectives included progression-free survival (PFS), objective response rate (ORR) per RECIST v1.1 and safety. Results: 292 pts were randomized to RAM (197) or PL (95). Baseline characteristics were generally balanced between arms. RAM treatment significantly improved OS (median OS 8.5 mo vs 7.3 mo PL; HR 0.710; 95% CI 0.531, 0.949; p=.0199). RAM significantly improved PFS (median PFS 2.8 mo vs 1.6 mo PL; HR 0.452; 95% CI 0.339, 0.603; p<.0001). ORR was 4.6% RAM vs 1.1% PL (p=.1156) and disease control rate (ORR + stable disease) was 59.9% RAM vs 38.9% PL (p=.0006). Grade ≥ 3 adverse events occurring in ≥ 5% pts in the RAM arm were hypertension (12.2% RAM, 5.3% PL) and hyponatremia (5.6%, 0%). Conclusions: REACH-2 met its primary endpoint showing a significant survival benefit, with RAM treatment reducing the risk of death (29%) in pts with HCC and AFP ≥ 400 ng/mL who progressed on or were intolerant to sorafenib. Treatment was well tolerated, with a safety profile consistent with the established profile for single agent RAM. REACH-2 is the first positive phase 3 study conducted in a biomarker-selected pt population with HCC. Clinical trial information: NCT02435433.
TCT-124 Impact of level of anaesthesia using the Vancouver Clinical Pathway for transcatheter aortic valve replacement: Insights from the 3M TAVR Study
Authors: Janarthanan Sathananthan, John Webb, Sandra Lauck, John Cairns, Dale Murdoch, Richard Cook, Karin Humphries, Julie Park, Yinshan Zhao, Robert Welsh, Jonathon Leipsic, Danny Dvir, Benjamin Tyrrell, Faisal Alqoofi, James Velianou, Madhu Natarajan, Harindra Wijeysundera, Sam Radhakrishnan, Eric Horlick, None mark osten, Anita Asgar, Jean-Bernard Masson, Susheel Kodali, Tamim Nazif, Vinod Thourani, Vasilis Babaliaros, David Cohen, Rael Klein, Kevin Rondi, Martin Leon, David Wood
Journal: Journal of the American College of Cardiology (2018)