tbuckley/cabot-search huggingface dataset:
Cancer patients’ awareness about clinical research in the era of social media and “fake news”: Preliminary results from ELPIS Study.
Authors: Celeste Cagnazzo, Veronica Franchina, Giuseppe Toscano, Franca Fagioli, Tindara Franchina, Giuseppina Rosaria Rita Ricciardi, Lorenzo Antonuzzo, Alessandro Di Costanzo, Antonio Russo, Stefania Cusenza, Stefania Gori, Fabiana Marchetti, Margherita Tambaro, Patrizia Piccirillo, Oriana Nanni, Rosita Cenna, Sara Delfanti, Massimo Di Maio, Fabio Dascanio, Vincenzo Adamo
Journal: Journal of Clinical Oncology (2021)

e24121 Background: Barriers for low recruitment in clinical trials have been classified based on three main sources: physician, patient, system. A primary role is played by a low patient awareness, which often leads to a lack of confidence in science and a substantial inability to estimate the benefits deriving from trial participation, aggravated by the spread of fake news. A prospective observational study was conducted to investigate the views of cancer patients on aspects of clinical research, their expectations, the level of comprehensibility of informed consent and the impact of the fake news phenomenon. Methods: From January 2018, after Ethics Committees approval, the ELPIS study was initiated in 9 Italian Medical Oncology Units. After signing the informed consent, patients were asked to complete a questionnaire, consisting of a set of multiple choice and Likert-score questions. Results: As of January 2021, 115 patients were enrolled, with a balanced sex distribution and a prevalence of subjects older than 55-years (79.8%). Regarding the previous knowledge about clinical research, the average score was 3.9 (range 1-5). The vast majority of respondents (91.3%) had already started experimental therapy and many of them constantly used internet (65.2%) and social networks (34.8%). More than half (53.9%) stated the interview with the physician was sufficient for a full understanding of informed consent. In case of doubt, the majority seeked support in the clinician (39.1%) while very few (1.7%) relied on the web. The average score attributed to doctor-patient relationship was equal to 8.89 (range 1-10). Respondents were quite confident in their ability to independently search for information on their disease, discriminate fake news and identify reliable sites (average score 3.26, 3.27, 3.09 respectively, over a range of 1-5). The scores related to the presumed ability to understand the results of a clinical study and to actively collaborate to produce research were high (average score 4.72 and 4.39 over a range of 1-5). Conclusions: Preliminary data from our research show a good level of patient awareness and a fine ability to understand information, discerning real from fake news. Continuing and implementing the training initiatives of the population in the health sector will certainly contribute to further improvement, hopefully obtaining an even greater involvement of patients in the early phases of research.
Combination of pembrolizumab (PEMBRO) plus temozolomide (TMZ) therapy in Chinese patients (pts) with advanced acral and mucosal melanoma.
Authors: Tu Hu, Wei Sun, Yu Xu, Zhiguo Luo, Yong Chen
Journal: Journal of Clinical Oncology (2021)

e21505 Background: Acral and mucosal melanoma are rare in Caucasians but have higher incidence in Asians and have poor prognosis. However, it has been reported that monotherapy seems to have limited efficacy in these population. Therefore, new treatments especially novel combination therapy are needed to further improve the outcome for these two subtypes. Here, we present the efficacy and safety of PEMBRO combined with TMZ in previously untreated pts with advanced acral and mucosal melanoma in China. Methods: The records of pts in Fudan University Shanghai Cancer Center with metastatic and unresectable acral and mucosal melanoma firstly treated with PEMBRO plus TMZ, PEMBRO alone or TMZ/DTIC based chemotherapy (CHEMO) were reviewed. Data regarding to best objective response rate (ORR), progression free survival (PFS) and toxicities were estimated. Response to treatment was assessed based on direct review of scan images and radiology reports according to the RECIST 1.1 criteria. Safety and tolerability were assessed per NCI-CTCAE v 4.0. Results: From May 2018 to February 2020, 49 pts were identified, including 28 (57.1%) with acral melanoma, 21 (42.9%) with mucosal melanoma. 32 (65.3%) pts had prior received adjuvant treatment, of which most (15, 30.6%) were interferon-α (IFN-α) or interleukin-2 (IL-2). Among these pts, PEMBRO alone was received by 18 (36.7%) pts with standard dosing of 2 mg/kg every 3 weeks. 20 (40.8%) pts received CHEMO at standard recommended dosing schedule, of which TMZ was given at 200 mg/m 2 orally days 1–5, every 4 weeks. PEMBRO plus TMZ was given to 11 (22.4%) pts with the same dosing of each treatment alone. The ORR of PEMBRO plus TMZ (6/11, 54.5%) was significantly higher than PEMBRO alone (2/18, 11.1%; p = 0.011) or CHEMO(1/20, 5.0%; p = 0.002), however, the difference of ORR between PEMBRO alone and CHEMO was not statistically significant ( p = 0.485). The disease control rate of the three groups were 81.8%, 72.2% and 70.0% respectively (not significant). The median PFS of PEMBRO plus TMZ in the front-line therapy was 9.8 months (95% CI, 3.2 -16.4), as compared with 6.2 months (95% CI, 1.8 - 10.3) in PEMBRO alone and 4.2 months (95% CI, 2.8 - 5.6) in CHEMO ( p = 0.258). Grade 3 treatment-related adverse events (TRAEs) occurred in one acral melanoma patient (rash) in PEMBRO plus TMZ and two pts in CHEMO (one thrombocytopenia and one anemia, both were mucosal melanoma). No grade 3 TRAEs was reported in PEMBRO alone. There were no significant differences in grade 1/2 toxicity, with the common TRAEs including nausea, vomiting, fatigue, elevated transaminase and leukocytopenia. Conclusions: These results suggest that the combination of PEMBRO plus TMZ as first line therapy for advanced acral and mucosal melanoma could potentially be an effective strategy to enhance antitumor activity with a manageable toxicity profile. Need to be further evaluated in a large prospective study.
The importance of variants of unknown significance (VUS) in BRCA mutation.
Authors: N Mullai
Journal: Journal of Clinical Oncology (2021)

e22507 Background: Genetic testing of patients for BRCA mutation may report variants of unknown significance (VUS). The use of multi-gene panels in clinical care has been increasing. Consequently, the reporting of variants of unknown significance has also increased. More than two decades of research and testing have elevated the status of BRCA1 and BRCA2 genes as the most well characterized genes. However, VUS are found even in BRCA1/2 testing. This raises many ethical and policy issues including communicating the significance of the results and possible clinical management options to patients. The practicing physicians would face the ethical and potential legal burden of contacting and explaining to patients, when any role of VUS changes and gets reclassified as potentially harmful. Methods: Data were collected retrospectively from medical records of patients tested for BRCA mutations. The results of fifty-two patients were analyzed. Eight patients had BRCA1 and BRCA2 mutations and twelve patients had variants of unknown significance. Results: When the results of thirteen patients with BRCA mutations with VUS were analyzed further, the variants included POLE, CHEK2, PALB2, MUTHYH, BR1P1, MSH3, ATM, RAD51C, GALNT12, etc. The age of these patients ranged from 39 years to 69 years. Four patients had ovarian cancer and eight patients had breast cancer, and one patient had both breast and ovarian cancers. The number of patients with stage IV, III, II, and I diseases were six, one, two, and two respectively. One patient had bilateral breast cancer and one patient had carcinoma in-situ. Eight patients had family histories of various cancers, including cancers of the breast, uterine, and prostate cancer. All patients were treated appropriately and three patients died due to their disease. Conclusions: Based on patients’ age, family histories, and disease characteristics BRCA mutation analyses were done. All patients tested positive for BRCA mutations and VUS were informed about their results. Variants of BRCA1 and BRCA2 occur in 2%-4% of tests depending on the laboratories, where the tests were performed. There is no concordance as to how VUS results were reported. There is conflicting evidence regarding the pathogenicity of VUS. These make clinical recommendations very complex. Based on existing guidelines, physicians can explain the details of the significance of BRCA! And BRCA2 mutations to patients with clarity. However, it is difficult and unclear to give recommendations regarding prophylactic measures, specific treatment options for BRCA mutation positive breast and ovarian cancer, follow-ups, and family testing in patients with VUS. Therefore, during BRCA testing, when VUS are reported routinely along with mutations of known significance, the treating physicians would need a better guidance to advise their patients without unduly increasing their anxiety, fear, and potential for misunderstanding.
Definitive chemoradiotherapy for squamous cell carcinoma of the anal canal (SCCAC) with cisplatin and capecitabine: A prospective cohort—preliminary results.
Authors: Abraão Dornellas, Priscila Muniz Moraes, Carolina Ribeiro Victor, Renata Colombo Bonadio, Maria Ignez Braghiroli, Andre Tsin Chih Chen, Cinthia Ortega, Caio Nahas, Paulo Marcelo Hoff, Camila Motta Venchiarutti Moniz
Journal: Journal of Clinical Oncology (2021)

e15506 Background: SCCAC is a rare disease. The standard care treatment with curative intent is chemoradiation with mitomycin (MMC) or cisplatin (CDDP) plus infusional 5-FU. Capecitabine may replace 5-FU in MMC doublet. However, MMC and infusional pumps are unavailable in many underdeveloped countries, and there is a lack of prospective data regarding the feasibility and safety of capecitabine combined with CDDP in definitive chemoradiotherapy. Methods: A Prospective cohort study aimed to evaluate the safety and efficacy of treatment with chemoradiation with CDDP60mg/m2 D1 and D29 plus capecitabine 825mg/m2/day BID in a population without MMC and infusional pump access. Eligible pts had T2-4/N0-3/M0 disease and were candidates to full curative CRT. Toxicity evaluation was the primary endpoint, secondary endpoint was response by RECIST v.1.1 at 8 weeks(w) and 6 months(m). The study data were prospectively collected using REDCap. Results: 23 pts were enrolled from Aug/2019 to Oct/2020 with a median follow-up of 7m. Median age 59 years; 76% (n=16) were stage III, 48% (n=11) were ECOG1, and 15% (n=3) were HIV+. All pts received concomitant radiotherapy, MVAT, with a median dose 54Gy in the primary tumor and 45Gy in elective nodes. At 8w, 18 patients were evaluable for response, 56% (n=10) had complete response (CR),39% (n=7) had partial response (PR) and 5% (n=1) progressive disease (PD). At 6 months 11 patients were evaluable for response, 64%(n=7) had CR, 18% (n=2) PR and 18% (n=2) PD. Any grade 3/4 toxicity was present in six pts, four of them radiodermatitis. The most frequent grade toxicities were nausea and radiodermatitis in all pts, anemia 81% (n=17), diarrhea 62% (n=13). Two older pts had definitive suspension of treatment due to toxicity. Three pts had hospitalization because of a skin infection. Six pts had disease recurrence, and two died by the cutoff date. One death related to diarrhea and vomiting toxicity in an older 84-year pt. OS and PFS are not reached. Conclusions: Definitive chemoradiotherapy with cisplatin and capecitabine is feasible; however, the older population is more vulnerable to treatment complications. Further prospective studies with a higher number of patients and longer follow up are required to evaluate SLP and OS.
Novel Conjugates of Butyrate and δ-Aminolevulinate Increase γ-Globin Gene Expression and Fetal Hemoglobin Synthesis in Erythroid Progenitors
Authors: Aluya R. Oseghale, Marjorie M. Johnson, Xingguo Zhu, Abraham Nudelman, Ada Rephaeli, Betty S. Pace
Journal: Blood (2017)
Inductive camrelizumab and apatinib for patients with locally advanced and resectable oral squamous cell carcinoma: A single-arm trial (Icemelting trial).
Authors: Lai-Ping Zhong, Wu-tong Ju, Rong-hui Xia, Qi Zhu, Guopei Zhu, Shengjin Dou, Jiang Li, Min-jun Dong
Journal: Journal of Clinical Oncology (2021)

6052 Background: In patients with locally advanced oral squamous cell carcinoma (LAOSCC), major pathologic response (MPR) to induction therapy may translate into improved survival. The induction therapy using chemo-free drugs, such as the combination of anti-PD1 and anti-VEGFR drugs, has not been well issued in LAOSCC. Methods: A prospective single arm trial (NCT04393506) has been performed to evaluate the induction therapy of anti-PD1 and anti-VEGFR protocol in LAOSCC patients at clinical stage III and IVA. The patients received three cycles of intravenous Camrelizumab (PD-1 antibody, 200mg) on d1, d15, d29; and oral Apatinib (anti-VEGFR inhibitor, 250mg) daily, initiating on d1, ending on the 5th day before surgery. Radical surgery was planned on d42-d45. Post-operative radiotherapy was planned within 1.5 months after surgery, based on clinical and pathological stage. The primary endpoints were MPR and safety; primary tumors were assessed for the percentage of residual viable tumor that was identified on HE staining, and tumors with no more than 10% viable tumor cells were considered as MPR. This study has been approved by institutional ethics committee at Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine. Results: From April to December 2020, 21 patients were enrolled in this trial, and one patient withdraw from the trial at the beginning of treatment. The induction therapy was well-tolerated with no grade 3-4 toxicity or serve induction therapy-related AEs. One patient required surgery delay for 7 days due to unexplainable cTnI elevation. One patient put off Camrelizumab for 14 days due to grade 2 thrombocytopenia. One patient suspended Apatinib for 21 days due to grade 2 Hyperbilirubinemia. The induction therapy did not effect on the subsequent standard treatment. MPR rate was 40% (8/20), including 5% (1/20) pCR. Radiological evaluation of response to induction therapy showed 3 PR, 10 SD, 5 PD and 2 NA. Weak correlation was found between pathologic and radiological evaluation on induction therapy. Combined positive score (CPS) of PD-L1 expression in biopsy was evaluated in 19 patients; all 4 patients with CPS≥ 20 had MPR, 3 out of 11 patients with 1≤CPS &lt; 20 had MPR, and 1 out of 4 patients with CPS &lt; 1 had MPR. Conclusions: The chemo-free protocol of induction therapy using Camrelizumab and Apatinib is safe and well-tolerated for the patients with LAOSCC. The MPR rate is much higher using the anti-PD1 and anti-VEGFR protocol than the traditional induction chemotherapy protocol in LAOSCC. Clinical trial information: NCT04393506.
Associations of Vaccination and of Prior Infection With Positive PCR Test Results for SARS-CoV-2 in Airline Passengers Arriving in Qatar
Authors: Roberto Bertollini, Hiam Chemaitelly, Hadi M. Yassine, Mohamed H. Al-Thani, Abdullatif Al-Khal, Laith J. Abu-Raddad
Journal: JAMA (2021)

Zion Congrave-Wilson, MS; Yesun Lee, PhD; Jaycee Jumarang, MD; Stephanie Perez, BS; Jeffrey M. Bender, MD; Jennifer Dien Bard, PhD; Pia S. Pannaraj, MD, MPH
Bone safety profile of steroidal aromatase inhibitor in comparison to non-steroidal aromatase inhibitors in postmenopausal women with breast cancer: A network meta-analysis.
Authors: Shanshan Chen, Bo Lan, Dan Lv, Fei Ma
Journal: Journal of Clinical Oncology (2021)

527 Background: Steroidal and non-steroidal aromatase inhibitors (AIs) provide better therapeutic response in comparison to other endocrine therapies in the adjuvant treatment of breast cancer (BC). They interfere with bone turnover which may lead to increased incidence of bone related safety events. There are no head-on studies comparing the incidence of bone safety events and hence we performed this network meta-analysis (NMA) to compare the incidence of bone safety events among patients treated with steroidal and non-steroidal AIs. Methods: Literature searches were performed in PubMed and Embase with key words to identify randomized controlled trials in BC patients treated with AIs in adjuvant settings compared against tamoxifen or other AIs, reporting any bone-related safety events. The study was designed as per PRISMA guidelines; publication bias was evaluated by comparison-adjusted funnel plots. Bayesian NMA was done by R software (ver 3.2), GemtC package. Odds ratio (OR) and the surface under the cumulative ranking curve (SUCRA) values were used to interpret the results. Results: 15 studies reporting 6 different bone-related endpoints were included. Treatment with steroidal AI, exemestane led to lower incidence of bone pain (OR Vs anastrozole and letrozole: 0.59, p=0.63; 0.54, p=0.75), fracture episodes (OR Vs anastrozole and letrozole: 0.84, p=0.41; 0.85, p=0.73), joint stiffness (OR Vs anastrozole: 0.55, p=0.73) and osteoporosis (OR Vs anastrozole and letrozole: 0.86, p=0.41; 0.74, p=0.29) (Table) in comparison to letrozole and anastrozole. Reduction in bone mineral density was also lesser in exemestane than anastrozole (mean reduction in hip: 1.08; lumbar spine: 1.34). SUCRA values suggested exemestane to be the drug with maximum likelihood for reducing the incidence of bone-related adverse events. Conclusions: This NMA suggested that bone-related safety events might be lower in early BC patients treated with exemestane in comparison to non-steroidal AIs, anastrozole and letrozole. Although there was no statistical significance, further head-on studies are required to substantiate our results.[Table: see text]
Imaging-based patient inclusion model for clinical trial performance optimization.
Authors: Michal R Tomaszewski, Shuxuan Fan, Jin Qi, Alberto Garcia, Youngchul Kim, Matthew B. Schabath, Robert A Gatenby, William D. Tap, Denise K. Reinke, Rikesh J Makanji, Damon R. Reed, Robert J Gillies
Journal: Journal of Clinical Oncology (2021)

105 Background: In the era of precision medicine, development of new cancer therapies relies strongly on effective selection of target patient population. We hypothesize that computational analysis of imaging data can be used for development of a quantitative population enrichment strategy in clinical trials and thus we aim to establish an appropriate framework for this analysis. Methods: This hypothesis was tested among soft-tissue sarcoma (STS) patients accrued into a randomized Phase III clinical trial (SARC021) that evaluated the efficacy of evofosfamide (Evo), a hypoxia activated prodrug, in combination with doxorubicin (Dox). Notably, SARC021 failed to meet its survival objective (PMC7771354). We tested whether an inclusion/exclusion model based on radiomic analysis and relevant clinical covariates could have been employed to result in a significant treatment benefit of the Evo+Dox combination compared to the standard Dox monotherapy. A total of 163 radiomics features were extracted from lung metastases of 303 patients from the SARC021 trial, divided into demographically matched training and test sets. Stability analysis identified the most reproducible features. Univariable and multivariable models were utilized to discriminate OS in the two treatment groups. Results: A bespoke enrichment framework was established for individualized patient selection, based on model-derived risk score threshold. A radiomic feature, Short Run Emphasis, was identified as the most informative. When combined with tumor histology and smoking history information, an enriched subset (42%) of patients had longer OS in Evo+Dox vs. Dox groups [p = 0.01, Hazard Ratio (HR) = 0.57 (0.36-0.90)], overperforming a clinical-only approach. Application of the same model and threshold value in an independent test set confirmed the significant survival difference (p = 0.002, HR = 0.29 (0.13-0.63), 38% patients included). The breakdown of Dox+Evo treatment benefit depending on proportion of patients included based on the model is shown in the Table. Notably, this process also identified patients most likely to benefit from doxorubicin alone. Conclusions: The study presents a first of its kind radiomic approach for patient enrichment in clinical trials based on a quantitative score. In particular, we have shown that had the novel model been used for selective patient inclusion into the SARC021 trial, it would have met its primary survival objective for patients with metastatic STS.[Table: see text]
Analyzing inmuno-related adverse event: A real-world DATA study.
Authors: Blanca Cantos, Juan Cristobal Sanchez, Beatriz Nuñez García, Miriam Mendez, Aranzazu Gonzalez del Alba, Antonio Sanchez, Ricardo Cubedo, Roberto Hernandez Lopez, Virginia Calvo, Mariano Provencio
Journal: Journal of Clinical Oncology (2021)

e18751 Background: In the last years, Immunotherapy (IT) has emerged as a standard treatment in an increasing number of tumors. This type of treatment has a specific toxicity profile which is clearly different from chemotherapy, known as an Immuno-related Adverse Event (AEir). We know the data from clinical trials, but little about the incidence and impact of this EAir in our clinical practice. Methods: A retrospective observational study was carried out including all patients from our institution (HUPHM in Madrid) who had received IT, either in monotherapy or in combination between January 2014 and December 2019. A total of 279 patients were included and data were collected between January and July 2020, guaranteeing a minimum 6-month follow-up after receiving the first dose of immunotherapy. The toxicities found were classified into four categories: pulmonary, digestive, endocrine and others, and have been graded according to CTCEA v.5 (Common Terminology Criteria for Adverse Event) published in November 2017 and analyzed according to drug and tumor. Results: The most frequent diagnoses in our patients were: 60% lung carcinoma, 15% melanoma, 8% kidney carcinoma, and 6% bladder carcinoma. 76% of the patients received IT as first or second line in a metastatic context, 6% in the initial stage (clinical trials) and the rest in more advanced lines of treatment (3 or more). 67% received anti-PD1 drug, 6% anti-PDL1, 4% anti-CTL4 monotherapy, 10% a combination of several IT drugs, and 14% an IT combination and chemotherapy. 45% of the total presented EAir (16% grade I, 14% grade II, 11% grade III and 4% grade IV). 1/5 of the patients had manifestations in more than one organ. The incidence of the different toxicities in our population was listed in the table below. These patients reported 8% dermatological toxicities, 6% had renal toxicity (most of them grade III or IV), only 2% had arthralgia or myalgia, and 3% asthenia. Combined IT treatment had significantly higher rates of pneumonitis, colitis, and endocrine toxicities. These differences were not observed between the monotherapy treatment and the combination of immunotherapy plus chemotherapy. Conclusions: Immunotherapy has represented an important advance in oncology, achieving long survivals in a growing group of tumors. Immunotherapy has a unique toxicity profile that is very different from chemotherapy and with which we must become familiar. Most of the adverse events are mild and if they are diagnosed early and with the appropriate treatment, maintenance of IT is possible. Severe toxicity (III-IV) means in most cases the suspension of treatment, compromising its efficacy. Therefore, we must learn to recognize these toxicities early and apply the recommended treatments as soon as possible.[Table: see text]