tbuckley/cabot-search huggingface dataset:
Impact of adding nintedanib to neoadjuvant chemotherapy (NACT) for advanced epithelial ovarian cancer (EOC) patients: The CHIVA double-blind randomized phase II GINECO study.
Authors: Gwenael Ferron, Gaetan De Rauglaudre, Annick Chevalier, Pierre Combe, Florence Joly, Alain Lortholary, Nadia Raban, Salima Hamizi, Emmanuelle Malaurie, Marie-Christine Kaminsky, Patricia Pautier, Jérome Meunier, Jérôme Alexandre, Dominique Berton-Rigaud, Anne Floquet, Laurence Venat-Bouvet, Laure Favier, Nadine Dohollou, Coraline Dubot, Isabelle Laure Ray-Coquard
Journal: Journal of Clinical Oncology (2019)

5512 Background: Nintedanib, an oral inhibitor of VEGF-FGF-PDGF receptors, has been shown to prolong progression-free survival (PFS) when added to adjuvant chemotherapy after primary surgery (duBois A, Lancet Oncol 2015). CHIVA trial explored the role of nintedanib in combination with NACT. Methods: Patients (pts) with FIGO stage IIIC-IV chemotherapy-naive AEOC considered as unresectable after laparoscopic evaluation were randomized (2:1) to be treated with 3 to 4 cycles (cy) of carboplatin (AUC 5 mg/mL/min) and paclitaxel (175 mg/m²) (CP) before interval debulking surgery (IDS) followed by 2 to 3 cy of CP for a total of 6 cy, plus either 200 mg of Nin (armA) or placebo (armB) twice daily on days 2–21 q3week at cy 1&amp;2, 5&amp;6 and maintenance therapy for up to 2 years. The primary endpoint was PFS. Results: Between Jan. 2013 and May 2015, 188 pts were included (124 arm A, 64 arm B) with a median Peritoneal Cancer Index of 22 (range 19-27). Pts characteristics were well balanced between both arms. Median PFS was 14.4 mos (95%CI 12.2-15.4) and 16.8 (13.3-21.4) in arm A and B respectively (HR:1.50, p=0.02). Median OS was 37.7 mos (29.8-41.0) and 44.1 (32.7-not reached) in arm A and B respectively (HR:1.54, p=0.053). Arm A was associated with more toxicity compared to arm B respectively (Grade 3&amp;4 adverse events: 92 versus 71%), with increased early treatment discontinuation before the 3rd cy (14.5 vs 6.2%) &amp; CP dose reduction (12% vs 0%). Pts in Arm A reported inferior RECIST ORR to pre-IDS therapy compared to Arm B (35.1 vs 55.9%). IDS was performed significantly less frequently in arm A (58.1%) vs arm B (76.6%). However among pts who underwent IDS, complete surgical cytoreduction rate (76%) and peri/postoperative complication rate (11.2%) were similar in both arms. Conclusions: The addition of nintedanib to NACT increases toxicity and compromise chemotherapy efficacy leading to a reduced rate of IDS and worse PFS and OS for advanced EOC patient. Clinical trial information: 2011-006288-23.
Nomogram incorporated the number of adjuvant chemotherapy cycles for predicting the prognosis in stage II-III rectal cancer patients without neoadjuvant therapy.
Authors: Weiwei Chen, Wenling Wang
Journal: Journal of Clinical Oncology (2019)

e15163 Background: Current recommendations for adjuvant chemotherapy in rectal cancer are based on the studies in colon cancer. However, it is now known that rectal cancer differs from colon cancer significantly regarding clinical course and biology. No RCTs in the TME era have evaluated the value of postoperative chemotherapy and are unlikely to be performed as neoadjuvant treatment has become a “gold standard” approach. However, we found that not all patients with locally advanced rectal cancer underwent neoadjuvant chemoradiotherapy before TME in real-world clinical practice in China. Whether the number of adjuvant chemotherapy cycles is significantly related to the prognosis of these patients deserves further study. Methods: A total of 246 patients with stage II-III rectal cancer from January 2013 to April 2018 were enrolled. All patients underwent surgery and had not received neoadjuvant therapy. The survival curve was drawn by the Kaplan-Meier method, and the log-rank method was used for statistical analysis. The Cox proportional hazard model was used for multivariate analysis to determine the independent prognostic factors. Then, MFP(Multiple Fractional Polynominal) and stepwiseAIC were used for variable selection. The R software was used to establish the nomogram. The bootstrap method was employed to internal verification. Concordance index(C-index) was applied to evaluate the predictive power of nomogram. Calibration curves were drawn to compare the 3-year overall survival rate predicted by nomogram and that of actual observation. Results: 87.8% of patients received adjuvant chemotherapy including oxaliplatin combined with fluorouracil or capecitabine. Univariate and multivariate analysis showed that the number of adjuvant chemotherapy cycles was independent prognostic factors. Patients who received more than 5 cycles of chemotherapy (HR = 0.09, 95%CI(0.01,0.80)) had a significantly better overall survival than patients with less than 5 cycles (HR = 0.33,95%CI(0.12,0.89)) or no chemotherapy (p &lt; 0.05).Through MFP and the stepwiseAIC screening, a nomogram was established based on CEA, PLR, N, and the number of chemotherapy cycles, and the C-index of the model was 0.86. Conclusions: The number of adjuvant chemotherapy cycles is an independent prognostic factor in stage II-III rectal cancer patients without neoadjuvant therapy. Moreover, nomogram incorporated the number of chemotherapy cycles was accurate and visible.
Safety of denosumab in patients with refractory differentiated thyroid cancer and advanced medullary thyroid cancer.
Authors: Johanna Wassermann, Elise Mathy, Geraldine Lescaille, Marine Slim, Camille Buffet, Clotilde Saie, Yasmin Braik-Djellas, Jean-Marc Simon, Fabrice Ménégaux, Christophe Tresallet, Linda Chami, Charlotte Lussey-Lepoutre, Geneviève Hervé, Marie-Odile Bernier, Jean-Philippe Spano, Laurence Leenhardt
Journal: Journal of Clinical Oncology (2019)

e17578 Background: Few data exist regarding the use of denosumab in patients with bone metastases from radioactive iodine (RAI) refractory differentiated thyroid cancer (DTC) and advanced medullary thyroid cancer (MTC). We aimed to describe adverse events of specific interest - osteonecrosis of the jaw (ONJ) and severe hypocalcemia - in this rare setting. Methods: We retrospectively reviewed the charts of all the patients treated with denosumab for bone metastases from RAI-refractory DTC and advanced MTC in our institution. All patients had a calcium measurement and a clinical and radiological dental screening before denosumab initiation. All patients without hypercalcemia received a calcium supplementation. We assessed associations between ONJ or severe hypocalcemia ( &lt; 1.75mmol/L) and suspected risk factors by Fisher exact tests. Results: Between 2014 and 2018, 23 patients were treated with denosumab. Two-thirds of patients were male (n = 16), median age was 69 years (range 43-87). Histology was DTC and MTC in 19 (83%) and 4 (17%) patients, respectively. DTC patients had received a median cumulated dose (CD) of 300 mCi of RAI (range 100-700). Ten patients (43%) had at least one cervical surgery for recurrence or persistence, and 6 (26%) had cervical radiotherapy. Four patients had hypoparathyroidism before denosumab initiation. Two-thirds of patients ( n =15) received a tyrosine kinase inhibitor (TKI) in association with denosumab. The median duration of denosumab was 20 months (range 1-47). ONJ occurred in 6 patients (26%) and severe hypocalcemia in 3 patients (13%). Conclusions: Patients with RAI-refractory DTC and advanced MTC are at high risk of ONJ and severe hypocalcemia under denosumab treatment. Benefit/risk ratio should be highly weighted particularly when treatment is prolonged. Patients should be closely monitored for the risk of ONJ and hypocalcemia. [Table: see text]
Endogenous DNA damage levels in peripheral blood mononuclear cells in patients with muscle-infiltrating urothelial bladder carcinoma.
Authors: Patrik Palacka, Zuzana Sestakova, Andrea Holickova, Katarina Kalavska, Katarina Rejlekova, Boris Kollárik, Michal Chovanec, Jana Obertova, Zuzana Sycova-Mila, Valentina De Angelis, Jan Slopovsky, Daniela Svetlovska, Michal Mego, Miroslav Chovanec
Journal: Journal of Clinical Oncology (2019)

e16020 Background: Cisplatin-based combination chemotherapy is used as a standard neoadjuvant treatment of patients with muscle-infiltrating urothelial bladder carcinoma (MIUBC). DNA damage represents one of the most important factors contributing to its toxicity. The objective of this prospective study is to evaluate the prognostic value of the endogenous DNA damage level in peripheral blood mononuclear cells (PBMCs) from MIUBC patients before treatment with neoadjuvant chemotherapy. Methods: PBMCs isolated from 25 consecutive MIUBC patients (16 men, 64%) were included into this study. Karnofsky index &lt; 80% was present in 1 patient (4%). DNA damage levels in PBMCs were evaluated by the Comet assay and scored as percentage of DNA in tail by the Metafer-MetaCyte analyzing software. Cut-off of 5.25 was used to dichotomize DNA damage level as “high” or “low” based on the previous study. Results: At the median follow-up 12.1 months, 13 patients progressed (52%) and 8 patients (32%) died. The median and IQR (interquartile range) of endogenous DNA damage level was 7.52 (4.07-27.9). Patients with low DNA damage levels had non-significantly better progression free survival (HR = 0.33, 95% CI: 0.09-1.29) and overall survival (HR = 0.64, 95% CI: 0.11-3.87) compared to patients with high DNA damage levels. Conclusions: These data suggest that endogenous DNA damage levels in PBMCs from MIUBC patients may serve as a prognostic marker early identifying patients with poor outcome. This study is supported by VEGA 2/0053/19 and APVV-17-0384.
Common cold in Team Finland during 2018 Winter Olympic Games (PyeongChang): epidemiology, diagnosis including molecular point-of-care testing (POCT) and treatment
Authors: Maarit Valtonen, Matti Waris, Tytti Vuorinen, Erkki Eerola, Antti J Hakanen, Katja Mjosund, Wilma Grönroos, Olli J Heinonen, Olli Ruuskanen
Journal: British Journal of Sports Medicine (2019)

Objectives The common cold is the main cause of medical time loss in elite sport. Rapid diagnosis has been a challenge that may be amenable to molecular point-of-care testing (POCT). Methods We performed a prospective observational study of the common cold in Team Finland during the 2018 Winter Olympic Games. There were 44 elite athletes and 68 staff members. The chief physician recorded the symptoms of the common cold daily on a standardised form. Two nasal swabs were taken at the onset of symptoms. One swab was analysed within 45 min using a molecular POCT for respiratory syncytial virus and influenza A and B viruses. After the Games, the other swab was tested for 16 possible causative respiratory viruses using PCR in laboratory-based testing. Results 20 out of 44 (45%) athletes and 22 out of 68 (32%) staff members experienced symptoms of the common cold during a median stay of 21 days. Eleven (26%) samples tested virus-positive using POCT. All subjects with influenza (n=6) and 32 close contacts were treated with oseltamivir. The aetiology of the common cold was finally detected in 75% of the athletes and 68 % of the staff members. Seven virus clusters were identified. They were caused by coronaviruses 229E, NL63 and OC43, influenza B virus, respiratory syncytial virus A, rhinovirus and human metapneumovirus. The virus infections spread readily within the team, most commonly within the same sport discipline. Conclusions The cold was indeed a common illness in Team Finland during the Winter Olympic Games. POCT proved to be clinically valuable, especially for influenza. The aetiology of the common cold was identified in most cases.
Investigation of HBOC germline mutations in women diagnosed with breast cancer in Trinidad and Tobago.
Authors: Gerneiva Parkinson, Anees B. Chagpar, Kellie Alleyne-Mike, Marcella Nunez-Smith, Alicia Zhou, Lily Servais, Erin Wysong Hofstatter
Journal: Journal of Clinical Oncology (2019)

6574 Background: Trinidad and Tobago (T&amp;T) is the southern-most Caribbean island, and according to the WHO/PAHO, it has the 2nd highest breast cancer mortality rate in the region. Notably, a large proportion of breast cancer cases in T&amp;T occur at a young age; with nearly 36% of them being diagnosed under the age of 50. There is a known association between a younger age at diagnosis and Hereditary Breast and Ovarian Cancer syndrome (HBOC). Yet, the prevalence of HBOC mutations remains unknown in T&amp;T, as genetic counseling and testing services are extremely limited in the region. Therefore, we sought to determine the prevalence and spectrum of HBOC mutations in T&amp;T. Methods: At the National Radiotherapy Center, T&amp;T’s main oncology unit, female breast cancer patients, who met NCCN criteria for further genetic counseling and testing were recruited through chart reviews. After pre-test counseling, enrolled subjects had a detailed interview about their personal breast cancer diagnosis and family history. A saliva sample was collected using an Oragene kit, and analyzed by Color Genomics Inc. for 30 genes associated with hereditary cancers. Finalized results were returned to patients by genetic counselors from Color Genomics. Results: A total of 118 female patients who met NCCN guidelines for HBOC testing received genetic testing. A majority were 50 years of age or younger (69/118, 59%). The cohort was ethnically diverse: 34% African, 15% Asian, 48% multiple ethnicity, and 3% other/unknown. A pathogenic or likely pathogenic variant (positive result) was identified in 21.2% of the cohort (25/118) - most commonly identified in the BRCA1 gene (13/25, 52%), followed by BRCA2 (5/25, 20%), PTEN (2/25, 8%), BRIP1 (1/25, 4%), CHEK2 (1/25, 4%), MSH6 (1/25, 4%), PALB2 (1/25, 4%), and RAD51C (1/25, 4%). Conclusions: We found a strikingly high HBOC germline mutation prevalence rate of 21.2% among a cohort of female breast cancer patients meeting NCCN criteria for HBOC testing in T&amp;T. Given the growing implications of germline HBOC mutations for breast cancer treatment and prevention, our results demonstrate an urgent need for funding, as well as the development of robust genetic counseling and testing services in T&amp;T.
KEYNOTE-689: Phase 3 study of adjuvant and neoadjuvant pembrolizumab combined with standard of care (SOC) in patients with resectable, locally advanced head and neck squamous cell carcinoma.
Authors: Ravindra Uppaluri, Nancy Y. Lee, William Westra, Ezra E.W. Cohen, Robert I. Haddad, Stephane Temam, Christophe Le Tourneau, Rebecca Chernock, Sufia Safina, Arkadiy Klochikhin, Amichay Meirovitz, Irene Braña, Joy Yang Ge, Ramona F. Swaby, Behzad Bidadi, Douglas Adkins
Journal: Journal of Clinical Oncology (2019)

TPS6090 Background: Evidence of efficacy and pathological response at the time of surgery was reported in two phase 2 studies (NCT02296684 and NCT02641093) of preoperative pembrolizumab in patients with high-risk, resectable, locally advanced (LA) head and neck squamous cell carcinoma (HNSCC). The randomized, open-label, phase 3 KEYNOTE-689 trial ( NCT03765918) will evaluate efficacy and safety of pembrolizumab as neoadjuvant and adjuvant therapy in combination with SOC (radiotherapy ± cisplatin) in patients with previously untreated, resectable LA HNSCC. Methods: Patients with newly diagnosed LA HNSCC will be randomly assigned 1:1 to two treatment arms. Patients in arm A will receive neoadjuvant pembrolizumab (200 mg Q3W for two cycles) followed by surgical resection then SOC plus adjuvant pembrolizumab (15 cycles). Patients in arm B will undergo only surgical resection followed by adjuvant SOC. Eligibility criteria will include age ≥18 years; newly diagnosed, resectable, stage III/IVA HNSCC (AJCC Cancer Staging Manual, 8th edition); and ECOG performance status 0-1. Randomization will be stratified by primary tumor site (oropharynx/oral cavity vs larynx vs hypopharynx), tumor stage (III vs IVA), and HPV p16 status (oropharynx p16 positive vs oropharynx p16 negative or larynx/hypopharynx/oral cavity). Treatment will continue until disease progression, unacceptable toxicity, or decision to withdraw. Patients in arm A will undergo the first radiologic imaging assessment after two cycles of neoadjuvant pembrolizumab and before surgery. In both arms, postoperative imaging will be performed 12 weeks after SOC, then every 3 months until the end of year 3, and then every 6 months until the end of year 5. Dual primary end points are major pathological response, defined as ≤10% invasive squamous cell carcinoma within resected primary tumor and sampled regional lymph nodes per blinded central pathology, and event-free survival. Secondary end points include overall survival, pathological complete response, and safety and tolerability. Recruitment is ongoing and will continue until ~600 patients are enrolled. Clinical trial information: NCT03765918.
Qualifying sites for oncology clinical trials.
Authors: Dax Kurbegov, Edward S. Kim, Patricia A. Hurley, David Michael Waterhouse
Journal: Journal of Clinical Oncology (2019)

6619 Background: Current methods to assess trial sites for clinical trial participation are onerous, with unnecessary redundancies and “no-value” steps that impact clinical trial participation. This project assessed the impact of current sponsor and contract research organizations (CRO) methods to evaluate sites for trials. Methods: A survey was conducted with community- and academic-based trial sites. Samples of feasibility questionnaires (FQs) used by sponsors and CROs were also compiled. An ASCO sponsored multi-stakeholder meeting was held to identify strategies to more effectively assess trial sites. Results: 113 oncology practices (63 community, 50 academic) reported completing 11 FQs and 4 pre-study site visits (PSV) on average per month. On average, each FQ took 4 hours (528 hours/site and 59,664 hours for all respondents, annually) and each PSV took 10 hours (480 hours/site and 54,240 hours for all respondents, annually) to complete. Thus, the total staff hours required to complete site feasibility assessments was 113,904 annually. Respondents reported that content in both FQs (82%) and PSVs (91%) was redundant to information previously provided and FQs were redundant between different sponsors (86%). The 42 sample FQs had a median 45 questions (range 13 to 96). Respondents noted that sponsors/CROs provided insufficient study documentation to accurately complete FQs. It took 7 months on average from first contact to first patient enrolled. Respondents also provided feedback about standardizing and streamlining site qualification processes. Conclusions: The current methods of assessing site feasibility for clinical trials poses tremendous burden on site resources and is not sustainable. New methods are needed that standardize, harmonize, and streamline criteria and site assessments. Such changes will reduce burden and costs for all stakeholders, and will expedite and increase patient enrollment onto clinical trials.
Enhanced family history screening is crucial to individualized cancer surveillance.
Authors: Kristin Clift, Sarah K Macklin, Michael B Wallace, R. John Presutti
Journal: Journal of Clinical Oncology (2019)

e13161 Background: Capturing family health history is a simple and cost-effective way to identify individuals at increased risk for hereditary cancers. Several barriers exist to family history collection in the clinical setting. Self-reported histories can be limited, inaccurate or static. Physicians are often overwhelmed with data and “alert fatigue.” These complex factors make it difficult to quantify hereditary risks. Patients with increased genetic predisposition may be missed and may not receive individualized cancer surveillance measures. Methods: A practice improvement project was implemented at Mayo Clinic Florida to enhance family history screening. A questionnaire and simple scoring algorithm were developed to prompt referral for genetic counseling. This tool was pilot tested in a multi-specialty gastroenterology clinic. The questionnaire was administered in the waiting room (tablet interface). Patients with significant risk factors identified were contacted and offered genetic counseling. Results: Currently, 291 patients have completed the questionnaire. Thirty of the 60 patients identified to have significant familial risk factors met with a genetic counselor. Of the twenty who completed genetic testing, 9 patients received one or more variants of unknown significance. Two pathogenic variants were identified. One patient was molecularly confirmed to have multiple endocrine neoplasia type 2, which can allow for cascade screening in her unaffected sibling. A pathogenic ATM variant was found in a patient with a recent personal history of pancreatic cancer. The result prompted consideration of platinum based chemotherapy and/or PARP inhibitors in her cancer management. She has had a visible response thus far with the treatment. Her sister implemented a new surveillance regimen after testing positive for the familial variant. Conclusions: Enhanced family history screening is a low cost, effective method for the identification of patients who may benefit from hereditary cancer screening and genetic testing. Increased attention to family history is a vital component of precision medicine in any care setting.
Strategy for hypertrophic scar therapy: Improved delivery of triamcinolone acetonide using mechanically robust tip-concentrated dissolving microneedle array
Authors: Shiqi Lin, Guilan Quan, Ailin Hou, Peipei Yang, Tingting Peng, Yukun Gu, Wanbing Qin, Rongben Liu, Xiangyu Ma, Xin Pan, Hu Liu, Lili Wang, Chuanbin Wu
Journal: Journal of Controlled Release (2019)
Prospective cardiac function monitoring in immunotherapy-treated patients.
Authors: Mandar A Aras, Lauren Cuevas, Dwight Bibby, Qizhi Fang, Adil Daud, Nelson B Schiller, Katy K. Tsai
Journal: Journal of Clinical Oncology (2019)

e14157 Background: Immune checkpoint inhibitors (ICI) demonstrate activity and long-term benefit in melanoma and other cancers. While certain immune-related toxicities have been well described, cardiac toxicities remain poorly characterized. We sought to characterize changes in cardiac function in advanced melanoma patients (pts) starting ICI treatment. Methods: A prospective, observational, single institution trial was performed to monitor cardiac function in pts receiving ICI. Eligible pts were adults with stage III/IV melanoma and ECOG 0-1, determined safe to exercise and without unstable cardiac symptoms. Pts received PD-1 monotherapy or combination ipilimumab/pembrolizumab. Rest and exercise stress cardiac testing (EKG, echocardiography) was conducted at baseline, at 3 months (mo), and at 6 mo. Patient-reported surveys were administered at baseline and at 6 mo. Results: Between Feb 2018 to Jan 2019, we prospectively identified 8 pts who completed baseline cardiac testing. As of Feb 2019, 6 pts completed 3-mo testing, and 4 completed 6-mo testing. Mean age was 57 years (range 34-68). 5 pts received pembrolizumab or nivolumab monotherapy, and 3 received ipilimumab/pembrolizumab. Resting LVOT-VTI decreased from 23.1±2.8 cm at baseline to 20.7±2.8cm at 6 mo (p = 0.047). Maximum HR at peak exercise decreased over time from 149.7±13 bpm at baseline to 114±20.5 bpm at 6 mo (p = 0.085) with concurrent decrease in maximum BP. Enrollment is ongoing. Conclusions: These data suggest measurable changes in left ventricular cardiac function at rest over time, in a prospective cohort of ICI-treated advanced melanoma pts. Further, we observe progressive loss of chronotropic and blood pressure response to exercise. These data have important implications for cancer survivorship in the era of immunotherapy. Updated data to be presented at the meeting include correlation with patient-reported symptoms. [Table: see text]