tbuckley/cabot-search huggingface dataset:
Juul: less than half of e-cigarette trial outcomes were properly reported or declared, study finds
Authors: Elisabeth Mahase
Journal: BMJ (2021)

Researchers have called for clearer reporting requirements and better enforcement of reporting laws to ensure that tobacco companies are being transparent with data, after a review of clinical trials sponsored by US electronic cigarette company Juul found results were not being published correctly.1

The researchers compared the reporting of clinical trials against the accepted standards and found that just 28 of 61 (46%) prespecified outcomes across five trials identified were reported or properly declared.

“Our findings raise substantial concerns regarding these trials,” the paper, published in Tobacco Control , said. “Clinicians, public health professionals, and the public cannot make informed choices about the benefits or hazards of e-cigarettes if the results of clinical trials are not completely and transparently reported. Clarification and potential enforcement of reporting laws may be required.”

The Food …
Evaluating real-world overall survival (rwOS) across oncology data sources: Friends of Cancer Research non-small cell lung cancer pilot study.
Authors: Laura Lasiter, Shrujal Baxi, Andrew J. Belli, Marley Boyd, Jennifer Christian, Aaron B. Cohen, Janet L Espirito, Liz Garrett-Mayer, Eric Hansen, Monika A. Izano, Yanina Natanzon, Donna Rivera, Nicholas J. Robert, Mackenzie Small, Connor Sweetnam, Olga Tymejczyk, Joseph Wagner, Jeff Allen
Journal: Journal of Clinical Oncology (2021)

e18749 Background: Friends of Cancer Research and five data partners used electronic health record-sourced datasets to conduct parallel analyses in real-world data (RWD). The study assessed estimates of rwOS among patients taking platinum doublet chemotherapy (chemo) or pembrolizumab in combination with chemo (IO+chemo) in first-line treatment for metastatic non-small cell lung cancer (mNSCLC). Methods: The KEYNOTE-189 clinical trial was selected as a reference for cohort selection in the RWD. We applied select available KEYNOTE-189 eligibility criteria to compare rwOS in a homogenous real-world population. Analyses were conducted following a mutually developed statistical analysis plan that was harmonized across data partners. Twelve-month rwOS, and unadjusted and adjusted hazard ratios (HR) for death were calculated using time-to-event methods with patients censored at last structured activity prior to the data cutoff. Results: The five datasets included patients treated with chemo (range of n=155 to 1501) and IO+chemo patients (n=36 to 405, Table). Twelve-month rwOS estimates ranged from 45% to 58% in the chemo arm and 44% to 68% in the IO +chemo arm. The HR for death comparing IO+chemo to chemo varied across groups, ranging from 0.79 (95% CI: 0.68, 0.92) to 1.10 (95% CI: 0.70, 1.72). The HR for death adjusted for age, gender, performance status, and smoking status did not significantly alter results, ranging from 0.80 (95% CI: 0.69, 0.93) to 1.15 (96% CI: 0.71, 1.85). Conclusions: The systematic evaluation of reproducibility and performance of rwOS across five real-world cohorts and the impact of implementing consistent eligibility criteria and methods was useful to understand the consistency of results in real-world populations and relationship between treatments and outcomes in the absence of randomization. A well-articulated research question and a pre-specified analytic plan that includes covariate definitions are necessary preliminary steps to guide data harmonization, standardization, and analysis. A range of observed results highlights the complexity of real-world data, including differences in sample size, underlying patient variability across datasets, and missing covariate data. The harmonization process and observed results underscore the importance of a well-articulated research question and a pre-specified analytic plan to guide data harmonization, standardization, and analysis. [Table: see text]
Anlotinib plus chemotherapy as neoadjuvant treatment of high-risk, early-stage triple-negative breast cancer: A prospective, single-arm, single-center, phase II clinical study.
Authors: Xi Chen, Shuqun Zhang, Xuexin Li, Yinbin Zhang, Youhuai Li, Huafeng Kang, Guan Haitao, Qing She, Xiaobin Ma, Yan Diao, Di Liu, Weili Min, Mengjie Liu, Fei Wu, Cong Feng
Journal: Journal of Clinical Oncology (2021)

e12585 Background: Anlotinib is an oral multi-targeted tyrosine kinase inhibitor (TKI) that strongly inhibits VEGFR, PDGFR, FGFR, and c-kit. Combining anti-angiogenesis with chemotherapy yielded increased response rates in patients with early-stage triple-negative breast cancer (TNBC). This phase II study aims to evaluate the efficacy and safety of adding anlotinib to standard neoadjuvant chemotherapy in primary TNBC. Methods: Patients aged 18 years or older with previously untreated stage ⅡB-IIIA histologically documented TNBC were assigned to receive chemotherapy plus oral Anlotinib (12 mg qd, d1-14; 21 days per cycle; total 8 cycles). Chemotherapy comprised of epirubicin at 90 mg/m 2 and cyclophosphamide at 600 mg/m2 followed by docetaxel at 100 mg/m 2 , (21 days per cycle; both total 4 cycles), which was then followed by surgery. The primary endpoint was pathologic complete response (pCR) (no invasive carcinoma in breast or axilla). Stratification was based on the clinical breast cancer stage. This study is registered on Chinese Clinical Trials.gov (ChiCTR2000038174), and still ongoing. Results: Between July 2019 to June 2020, 18 patients (female) with pathological stage ⅡB (83.3%), and IIIA (16.7%) were enrolled with a median age of 46 years (range: 32-72). Overall pCR rate was 44.4% (8/18, CI 95%: 24.6%-66.3%). The pCR rate of pathological stage IIB patients was 46.7%(CI 95%: 26.7%-69.9%), which is tend to be better than the pCR rate of 33.3%(CI 95%: 6.2%-79.2%) for patients with pathological stage IIIA. There are 21 kind of AEs were observed, all including 56 times grade 1 AEs and 34 times grade 2 AEs, no grade 3 or higher AE was observed. The most common AEs included hand-foot syndrome(55.6% in total with 33.3% grade 2 and 22.2% grade 1), oral mucositis(50.00% in total with 33.3% grade 2 and 16.67% grade 1), fatigue(61.1%, all grade 1), hoarse voice(33.3%, all grade 1), nasal bleeding(27.8%, all grade 1), hypertension(22.2% with 5.6% grade 2) and diarrhea(22.2% with 5.6% grade 2). Neither unexpected safety signals nor treatment-related death occurred. Conclusions: The addition of anlotinib to neoadjuvant chemotherapy showed manageable toxicity and promising antitumor activity for patients with high-risk, early-stage TNBC. Clinical trial information: ChiCTR2000038174.
Methodological needs in the quality and safety characterisation of nanotechnology-based health products: Priorities for method development and standardisation
Authors: B. Halamoda-Kenzaoui, R.J. Vandebriel, A. Howarth, M. Siccardi, C.A.W. David, N.J. Liptrott, M. Santin, S.E. Borgos, S. Bremer-Hoffmann, F. Caputo
Journal: Journal of Controlled Release (2021)

Nanotechnology-based health products are providing innovative solutions in health technologies and the pharmaceutical field, responding to unmet clinical needs. However, suitable standardised methods need to be available for quality and safety assessments of these innovative products prior to their translation into the clinic and for monitoring their performance when manufacturing processes are changed. The question arises which technological solutions are currently available within the scientific community to support the requested characterisation of nanotechnology-based products, and which methodological developments should be prioritized to support product developers in their regulatory assessment. To this end, the work presented here explored the state-of-the-art methods to identify methodological gaps associated with the preclinical characterisation of nanotechnology-based medicinal products and medical devices. The regulatory information needs, as expressed by regulatory authorities, were extracted from the guidance documents released so far for nanotechnology-based health products and mapped against available methods, thus allowing an analysis of methodological gaps and needs. In the first step, only standardised methods were considered, leading to the identification of methodological needs in five areas of characterisation, including: (i) surface properties, (ii) drug loading and release, (iii) kinetic properties in complex biological media, (iv) ADME (absorption, distribution, metabolism and excretion) parameters and (v) interaction with blood and the immune system. In the second step, a detailed gap analysis included analytical approaches in earlier stages of development, and standardised test methods from outside of the nanotechnology field that could address the identified areas of gaps. Based on this analysis, three categories of methodological needs were identified, including (i) method optimisation/adaptation to nanotechnological platforms, (ii) method validation/standardisation and (iii) method development for those areas where no technological solutions currently exist. The results of the analysis presented in this work should raise awareness within the scientific community on existing and emerging methodological needs, setting priorities for the development and standardisation of relevant analytical and toxicological methods allowing the development of a robust testing strategy for nanotechnology-based health products.
Investigating tumor molecular profiling as a possible contributor to racial/ethnic disparities in pancreatic cancer.
Authors: Evan Justin Walker, Sorbarikor Piawah, Ann Griffin, Julia C. Carnevale, Pelin Cinar, Eric Andrew Collisson, Margaret A. Tempero, Andrew H. Ko
Journal: Journal of Clinical Oncology (2021)

6522 Background: A variety of biologic, socioeconomic, and treatment-related factors may contribute to the racial/ethnic disparities observed in pancreatic ductal adenocarcinoma (PDAC) outcomes. As tumor molecular profiling (TMP) is now recommended for patients (pts) with advanced PDAC to inform treatment selection, we hypothesized that rates of TMP, detection of actionable alterations (AA), and use of molecularly-targeted treatments differ across different racial/ethnic groups and may contribute to disparate outcomes. Methods: This retrospective analysis included all Non-Hispanic White (NWH), Asian, Hispanic/Latinx (H/L), and Black/African American (B/AfrAm) pts with PDAC who underwent TMP at UCSF over a 4-yr period. Medical records were reviewed for demographic and disease-specific data. Alterations classified as ‘pathogenic’ or ‘likely pathogenic’ in TMP clinical reports were included, and were categorized as ‘actionable’ if there was clinical or preclinical evidence of benefit from targeted therapy in any cancer. Associations between NHW and other groups were tested with Fishers exact test. Results: Between 1/2016-1/2020, 159/727 (22%) pts underwent PDAC TMP. 60 AA were detected in 54 pts. Rates of TMP or AA detection were not associated with racial/ethnic group (Table). Most AA (33/60, 55%) were associated with the Homologous Recombination DNA Damage Repair (HR-DDR) pathway ( ARID1A n = 15 , ATM n = 7 , and BRCA1 n = 5). Other common AA included PIK3CA alterations (n = 6), CDK4/6 amplifications (n = 5), AKT2 amplifications (n = 4) and KRAS G12C mutation (n = 4). Molecular targets differed between groups (HR-DDR genes comprised 55% AA in NHW vs 100% in H/L, p = 0.03). Regarding treatment, rates of platinum chemotherapy for HR-DDR gene-altered PDAC differed significantly between groups. Three NHW pts with HR-DDR alterations received a PARP-inhibitor +/- ATR inhibitor. Conclusions: To our knowledge, this is the first study to report PDAC TMP rates and therapeutic implications across racial/ethnic groups. Acknowledging the limitations of sample size and what defines AA, we observed no significant differences in rates of testing nor AA detection. Further study is needed to evaluate whether rates of molecularly-informed treatment selection contribute to racial/ethnic disparities in clinical outcomes. As therapeutic advances increase the likelihood of identifying AA, equitable access to both TMP and targeted treatments must be ensured for all pts with PDAC.[Table: see text]
Antibody and T Cell Response to SARS-CoV-2 Messenger RNA BNT162b2 Vaccine in Kidney Transplant Recipients and Hemodialysis Patients
Authors: Dominique Bertrand, Mouad Hamzaoui, Veronique Lemée, Julie Lamulle, Mélanie Hanoy, Charlotte Laurent, Ludivine Lebourg, Isabelle Etienne, Mathilde Lemoine, Frank Le Roy, Dorian Nezam, Jean-Christophe Plantier, Olivier Boyer, Dominique Guerrot, Sophie Candon
Journal: Journal of the American Society of Nephrology (2021)

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is associated with a high rate of mortality in patients with ESKD, and vaccination is hoped to prevent infection.
Neoadjuvant transarterial infusion chemotherapy with FOLFOX could improve outcomes of resectable BCLC stage A/B hepatocellular carcinoma patients beyond Milan criteria: An interim analysis of a multi-center, phase 3, randomized, controlled clinical trial.
Authors: Shaohua Li, Chong Zhong, Qiang Li, Jingwen Zou, Qiaoxuan Wang, Changzhen Shang, Yuan Cheng, Mingrong Cao, Huakun Huang, Jie Mei, Lianghe Lu, Rongce Zhao, Wenping Lin, Yuhua Wen, Zhixing Guo, Yihong Ling, Lie Zheng, Wei Wei, Rongping Guo
Journal: Journal of Clinical Oncology (2021)

4008 Background: The efficacy of operation, as the only radical option for resectable BCLC stage A/B hepatocellular carcinoma (HCC) patients beyond Milan criteria, is still unsatisfactory. This study aimed to investigate to efficacy and safety of preoperative neoadjuvant transarterial infusion chemotherapy (TAI) with FOLFOX regimen for these patients. Methods: In this multi-center, prospective, phase 3, randomized, open-labeled, controlled clinical trial, resectable BCLC stage A/B HCC patients beyond Milan criteria were randomly assigned (1:1) before hepatectomy to receive either neoadjuvant TAI (NT group) or operation directly without any neoadjuvant treatment (OP group). The primary endpoint was overall survival (OS), the secondary endpoints are progression-free survival (PFS), recurrence free survival (RFS), and safety. Results: Between March, 2016 and July, 2020, 208 patients enrolled from five Chinese hospitals were randomly assigned to NT group (n=104) or OP group (n=104)， with 99 patients in NT group and 100 patients in OP group included in the efficacy and safety analysis. Clinicopathological characteristics were balanced between the two groups. The 1-, 2-, and 3-year OS rates for NT group were 92.9%, 78.6%, and 63.5%, and were 79.5%, 62.0%, and 46.3% for OP group, respectively. The 6-, 12-, and 18-month PFS rates for NT group were 77.6%, 50.4%, and 47.4%, and were 52.7%, 42.8%, and 34.8% for OP group, respectively. The OS and PFS were significantly better in NT group than in OP group (p=0.016 and 0.017, respectively). The 6-, 12-, and 18-month RFS rates for NT group were 63.8%, 47.3%, and 47.3%, and were 52.7%, 42.8%, and 34.8% for OP group, respectively. The RFS between the two group had no difference (p=0.385). No patients in NT group experienced grade 3 or more severe TAI related adverse events. The operation related adverse events were similar between two groups (p=0.300). Conclusions: Neoadjuvant TAI before hepatectomy may bring survival benefits for resectable BCLC stage A/B HCC patients beyond Milan criteria. Trial number: NCT03851913. Clinical trial information: NCT03851913.
Anthracycline exposure and breast cancer risk in female Hodgkin lymphoma survivors.
Authors: Suzanne I.M. Neppelenbroek, Yvonne M. Geurts, Berthe M.P. Aleman, Cecile P.M. Janus, Saskia E Rademakers, Roel J. de Weijer, Richard W.M. Van Der Maazen, Josée M. Zijlstra, Max Beijert, Karijn M.S. Verschueren, Bastiaan Ta, Marten R. Nijziel, Eduardus F.M. Posthuma, Marie José Kersten, Karin Muller, Liane te Boome, Yavuz Bilgin, Eva de Jongh, Michael Schaapveld, Flora Van Leeuwen
Journal: Journal of Clinical Oncology (2021)

12074 Background: Female Hodgkin lymphoma (HL) survivors treated with chest radiotherapy (RT) at a young age have a strongly increased risk of breast cancer (BC). Recently concern has been raised that anthracyclines may also increase BC risk, based on studies in childhood cancer survivors with/without a history of chest RT. So far, the association between anthracyclines and BC risk has not been examined in cancer survivors treated at adolescent/adult ages. Now that RT dose and volumes are decreasing, the potential contribution of anthracyclines to BC risk is an important issue. Methods: We assessed BC risk in a cohort of 2314 female 5-year HL survivors, treated at ages 15-50 years and diagnosed between 1965 and 2008 in 20 Dutch hospitals. Treatment factors were time-dependently included in the analysis, focusing on the effect of anthracycline exposure on BC risk. Results: After a median follow-up of 18.8 years, 258 women developed invasive BC or ductal carcinoma in situ as a subsequent malignancy. The 30-year cumulative incidence was 15.0% (95% Confidence Interval (CI) 12.8-17.4%). Mantle field RT (or other RT involving both axillae) was associated with increased risk of BC (Hazard ratio (HR) 1.9; 95% CI 1.2-2.8) compared to no supradiaphragmatic RT or RT to the neck only (Table 1). Gonadotoxic treatment (&gt;4.2 g/m 2 procarbazine or pelvic RT) significantly decreased this risk. In a multivariable analysis, anthracycline exposure was associated with increased BC risk (HR 1.8; 95% CI 1.3-2.5) in patients who received a cumulative dose of &gt;200 mg/m 2 . Among patients exposed to gonadotoxic treatment, the HR of BC associated with &gt;200mg/m 2 anthracyclines was 3.8 (95% CI 2.0-7.2), with a trend for higher risk with higher anthracycline dose (HR 1.58 per 100mg/m 2 anthracycline, p&lt;0.001). Conclusions: Our results suggest an association of anthracyclines with BC risk in HL survivors. Also when accounting for the protective effect of gonadotoxic treatment on RT-associated BC risk, anthracyclines significantly contributed to a higher BC risk.[Table: see text]
A retrospective analysis of real-world time on treatment and overall survival in patients with metastatic colorectal cancer receiving cetuximab in third line.
Authors: Wambui Gathirua-Mwangi, Tony Yang, Taha Khan, Yixun Wu, Manuel Afable
Journal: Journal of Clinical Oncology (2021)

e15575 Background: Colorectal cancer (CRC) is the 3 rd leading cause of cancer-related deaths in the US. Anti-epidermal growth factor receptor agents improve outcomes of patients with metastatic CRC (mCRC) and are used in multiple lines of therapy. However, real-world time on treatment (TOT) and overall survival (OS) of cetuximab in third-line (3L) have not been described. Therefore, we sought to evaluate TOT, OS, and associated factors in a retrospective study. Methods: A total of 617 patients diagnosed with mCRC and received 3L treatment with cetuximab containing regimens regardless of prior therapies were selected from the nationwide Flatiron electronic health record database (January 2013 - August 2020). TOT was defined as the time from initiation of cetuximab in 3L (index date), to the last recorded date of cetuximab administration. End of therapy was defined if the patients progressed to subsequent line of therapy, or had a record of death. OS was calculated from the index date to date of death or censored to last visit date available. The Kaplan-Meier estimates, and stepwise Cox models were adapted to identify and calculate hazard ratios (HR), and 95% confidence intervals (CI) for factors associated with TOT and OS. Results: Majority of patients receiving 3L treatment with cetuximab containing regimens were: treated in the community setting (96%), less than 65 years old (58%), overweight with a median body mass index (BMI) of 26.2 kg/m² and, received FOLFOX regimens in 1L (46%) and FOLFIRI in 2L (47%). The most common cetuximab containing regimens were cetuximab+irinotecan (36%) and cetuximab+FOLFIRI (34%) and cetuximab monotherapy. The median TOT (mTOT) for patients receiving 3L cetuximab containing regimens was 3.48 months (median interquartile range (mIQR) 3.02-4.17). Higher BMI (obese vs. underweight HR = 0.44, 95% CI 0.28-0.68) was associated with a longer mTOT, while having an ECOG score ≥1 was associated with a shorter mTOT (vs. ECOG = 0, HR = 1.37, 95% CI 1.10-1.72). Also, of all cetuximab containing regimens in 3L cetuximab + FOLFIRI (vs. cetuximab monotherapy) was associated with a longer mTOT (4.63 months, mIQR 3.45-5.55). The median OS (mOS) for patients receiving 3L cetuximab containing regimens was 11.99 months (mIQR 10.87-12.94). Similarly, higher BMI (obese vs. underweight HR = 0.25, 95% CI 0.16-0.40) and 3L cetuximab + FOLFIRI (mOS= 14.3 months, mIQR 11.66-16.85) vs. cetuximab monotherapy were associated with a longer mOS. OS did not differ by patients geographic region (South vs Midwest, p-value 0.35). Conclusions: In this real-world retrospective analysis cetuximab + irinotecan and cetuximab + FOLFIRI were the most common 3L cetuximab regimens. The most common treatment regimens in 1L and 2L were FOLFOX and FOLFIRI respectively. Overall, BMI and treatment regimens received in 3L were associated with mTOT and mOS.
Too Little or Too Much? Extracellular Matrix Remodeling in Kidney Health and Disease
Authors: Sergi Clotet-Freixas, Ana Konvalinka
Journal: Journal of the American Society of Nephrology (2021)

The extracellular matrix (ECM) is a network of collagen fibers and interconnecting proteins that surrounds the cells, providing structural support and the capacity to adhere to and communicate with neighboring cells.[1][1] The ECM is a dynamic structure undergoing balanced remodeling. In aging and