tbuckley/cabot-search huggingface dataset:
Stereotactic radiosurgery (SRS) for brain metastasis (BM) in hormone receptor positive (HR+) HER2 negative breast cancer (BC).
Authors: Akshara Singareeka Raghavendra, Chao Gao, Fuchenchu Wang, Ran An, Yan Wang, Dima Suki, Amy B. Heimberger, Debu Tripathy, Jing Li, Nuhad K. Ibrahim
Journal: Journal of Clinical Oncology (2021)

1069 Background: With the increase of the utilization of SRS for the treatment of oligometastatic BM over surgical reaction or whole brain radiation therapy (WBRT), we sought to evaluate the impact of SRS on overall survival in HR+Her2- BC and prognostic factors associated with SRS. Methods: We reviewed prospectively collected data in the electronic data bases of the breast medical, surgical and radiation oncology departments at MD Anderson cancer center. We aimed at identifying HR+HER2- BC patients who received upfront SRS for BM’s between 08/10/2009 and 02/27/2018.Overall survival was defined as the time from the first SRS to last follow-up/death. Multivariate analysis by the Cox proportional hazards regression analysis was performed to evaluate the prognostic factors (age at BM, stage, Karnofsky performance score (KPS), symptomatic BM, BM at 1stdistant metastatic presentation, extracranial Disease, treatment history, salvage therapy, number of brain lesion treated) of SRS that influenced survival. Results: A total of 125 patients were identified, and we are reporting on 68 with completed analysis. Median age at time of first SRS was 53.86 years. 51 patients of the 68 were deceased at the time of this analysis and 17 patients were alive at the time of last follow-up. 49 patients (72.06 %) presented with radiation necrosis after SRS; 36 patients (52.94 %) presented with BM as 1st distant metastasis including metastasis to other sites. Number of BM’s lesions &lt;4 was 60 (88.2%) and &gt;=4 was 7 (10.3%). The median follow-up from time of first SRS for survivors was 10.84 months. 24 (35.29%) received two or more sessions of SRS and the mean time between first and second SRS sessions for these patients was 14.24 months. Median time from first SRS to second SRS for ER+HER2− patients was 10.84 months (n = 24); on multivariable analysis, higher Karnofsky performance score (KPS) was associated with better survival compared to no salvage therapy. Patients with KPS&gt;90 (p=0.005) had better survival and reduced the hazard by a factor of 0.33 (or 67%). Receiving SRS (p=0.0003) or SRS+WBRT (0.0001) as salvage therapy reduced the hazard (risk of death) by 86% and 85%, respectively. Conclusions: SRS is an effective treatment modality for HR+HER2- BM from BC. Patients who received SRS or SRS and WBRT, KPS &gt;90 had better survival than patients who didn’t receive any salvage therapy. Updated data will be available at the time of the presentation.[Table: see text]
A novel outpatient regimen in management of fluoropyrimidine-induced cardiotoxicity.
Authors: Anup Kasi, Pramod Gaudel, Joseph Bennett, Raed Moh'd Taiseer Al-Rajabi, Anwaar Saeed, Joaquina Celebre Baranda, Weijing Sun, Charles B. Porter
Journal: Journal of Clinical Oncology (2021)

e15613 Background: Fluoropyrimidines, such as 5-fluorouracil (5-FU) and capecitabine, are commonly used chemotherapies for solid tumors, and essential for curative intent treatment of colorectal cancer. But sometimes, their use may be limited by cardiac toxicity limiting the possibility of cure in some patients. Cardiotoxicity could be asymptomatic (EKG changes) or manifested as chest pain, arrhythmias, acute coronary syndrome or death. Rechallenging may be daunting and it may result in interruption or even discontinuation of planned chemo. Traditionally, nitrates and/or IV/oral calcium channel blockers (CCB) have been used for management of fluoropyrimidine-induced cardiotoxicity but without much benefit. Ranolazine, an oral antianginal drug approved for chronic angina, diminishes myocardial ischemia by reducing calcium overload caused by inhibition of late sodium current and it does not affect heart rate or blood pressure. Our objective was to evaluate the efficacy of our novel approach using ranolazine with other traditional drugs. Methods: 8 patients (median age 49.5 yrs) with fluoropyrimidine induced cardiotoxicity were retrospectively analyzed. They were rechallenged with the planned fluoropyrimidine regimen with our 3 drug cardioprotective regimen (KU protocol). This included oral Ranolazine 1000mg BID and Amlodipine 2.5 mg daily to start the day before starting 5FU infusion/oral capecitabine and to continue it until the day after completion of infusion/treatment, and Nitroglycerin paste 1 inch every 6 hours starting before infusion and continue until it was completed. These meds were discontinued upon completion of chemo. Results: 8 patients were rechallenged with fluoropyrimidine utilizing KU protocol, 6 patients (75%) were able to complete previously planned fluoropyrimidine regimen. One pt (*) discontinued capecitabine due to recurrent chest pain and treatment was switched to 5FU based regimen with KU protocol, which pt was able to complete without chest pain. Another pt (**), 5FU was stopped due to severe diarrhea, not due to cardiotoxicity. All pts tolerated KU protocol well. Conclusions: In our small, single center experience, we were able to safely and effectively rechallenge pts with fluoropyrimidines and complete curative intent treatment with our KU protocol. This protocol uses FDA approved oral and transcutaneous drugs without requiring a healthcare personnel to administer an IV CCB that can cause precipitous bradycardia and/or hypotension. Our results need validation in a larger cohort. [Table: see text]
Effective oral delivery of Exenatide-Zn2+ complex through distal ileum-targeted double layers nanocarriers modified with deoxycholic acid and glycocholic acid in diabetes therapy
Authors: Ying Han, Wei Liu, Liqing Chen, Xin Xin, Qiming Wang, Xintong Zhang, Mingji Jin, Zhonggao Gao, Wei Huang
Journal: Biomaterials (2021)
Management of light chain deposition disease: A systematic review.
Authors: Adeel Masood, Moazzam Shahzad, Ahsan Wahab, Pranali Santhoshini Pachika, Tehniat Faraz Ahmed, Razwana Khanam, Hamid Ehsan, Karun Neupane, Saher Nasir Amin, Muhammad Umair Mushtaq, Faiz Anwer
Journal: Journal of Clinical Oncology (2021)

e20042 Background: Light-chain deposition disease (LCDD) is part of a wide spectrum of plasma cell proliferation disorders. LCDD predominantly affects kidneys by systemic deposition of congo red negative non-fibrillar light chains. Due to the rarity of disease, no prospective data is available, and clear guidelines don’t exist for the treatment. We reviewed data to summarize effective treatment strategies. Methods: A literature search was conducted on PubMed, Cochrane, and ClinicalTrials.gov with final update in November 2020 using terms ‘light chain deposition disease’, ‘therapy,’ and ‘disease management’. Library was manually screened to remove articles on LCDD in transplant kidneys. We identified 63 case reports/series and 11 retrospective studies n=365. Results: Retrospective Studies: 9 studies (n=283) identified various combinations of LCDD and plasma cell dyscrasias given the rarity of idiopathic LCDD. Lorenz et al. reported 6 patients (pts) that received ASCT with MEL preconditioning with 92% improved proteinuria and 95% improved eGFR. Pozzi et al. reported 63 pts (32% idiopathic LCDD, 65% concurrent MM and 3% concurrent CLL) where all pts received a combination of vincristine, doxorubicin, dexamethasone/methylprednisolone. 5/63 patients received ASCT. The median survival was 4.1 years. Bortezomib (V) based regimens: Most experts favor V based regimens to treat LCDD, but no dedicated trials exist. 26 case reports/case series (37 pts) included; 23 pts with idiopathic LCDD and rest with a concurrent disorder. Daratumumab: Milani et al. treated 8 pts with LCDD and concurrent MM with single agent daratumumab who failed at least one regimen. Autologous stem cell transplant (ASCT): 13 case reports/case series (20 pts) identified who received ASCT with melphalan (MEL) conditioning with/without various combinations of chemotherapies before and after ASCT. 14 pts had LCDD, and 6 pts had concurrent clonal cell dyscrasia. Miscellaneous regimens: Various other regimens showed promising results with improved renal functions but not well studied e.g., thalidomide and dexamethasone (Haruyuki et al.). Conclusions: Dedicated clinical trials are difficult given rarity of LCDD but needed. Bortezomib based regimens seem to be good options, ASCT with MEL conditioning is a suitable choice for younger and fit pts.[Table: see text]
Mental health care utilization among veterans with castration-resistant prostate cancer receiving abiraterone or enzalutamide.
Authors: Phoebe A. Tsao, Jennifer A. Burns, Shami Entenman, Kyle Kumbier, Jordan Sparks, Amy S. B. Bohnert, Ted A. Skolarus, Megan Veresh Caram
Journal: Journal of Clinical Oncology (2021)

e18680 Background: Abiraterone and enzalutamide are oral therapies widely used to treat men with castration-resistant prostate cancer (CRPC). Recent data have suggested potentially worsened quality of life and depression with use of enzalutamide compared to abiraterone. Because Veterans are at a higher risk for mental health conditions, we sought to compare mental health service utilization in Veterans with CRPC receiving enzalutamide to those receiving abiraterone. Methods: The Veterans Health Administration Corporate Data Warehouse was used to identify men with CRPC who received abiraterone or enzalutamide for ≥ 30 days as first-line treatment between 2010-2017. We compared the rate of mental health visits per 100 patient-months for men on abiraterone versus enzalutamide using an exact rate ratio test, assuming Poisson counts. Results: Among 2902 male Veterans, 68.6% (n=1992) received abiraterone and 31.4% (n=910) enzalutamide as first-line therapy. Men who received enzalutamide were older (76 vs 74, p&lt;0.01) and had a higher comorbidity burden (Charlson Comorbidity Index [CCI] ≥ 2 in 28.7% vs 21.6%, p&lt;0.01); no differences were noted in race or prevalence of preexisting documented mental health diagnoses. Median time on drug was 8 months for both medications. There was no difference in the rate of mental health visits per 100 patients-months on enzalutamide versus abiraterone (6.6 v. 6.7, p=0.66). However, within patient sub-groups, men who were age 75 or older, not married, or without notable comorbidities had lower rates of mental health visits with enzalutamide compared to abiraterone; whereas those who were younger than 75, married, had higher comorbidities, or a preexisting mental health diagnosis had higher rates of mental health visits with enzalutamide (Table). Conclusions: Among Veterans with CRPC who received a novel antiandrogen therapy first-line, there was no difference in engagement in mental health care between those who received abiraterone versus enzalutamide. Sub-group analysis revealed significant differences between patients on the two medications in demographic and diagnostic characteristics associated with number of visits, suggesting that vulnerability for mental health symptoms may vary by medication type. Further work in understanding the long-term impact of novel antiandrogens on mental health is needed.[Table: see text]
Measurement tools for gender identity, gender expression, and gender dysphoria in transgender and gender-diverse children and adolescents: a systematic review
Authors: Thea M Bloom, Thomas P Nguyen, Francesca Lami, Carmen C Pace, Zeffie Poulakis, Michelle Telfer, Amelia Taylor, Kenneth C Pang, Michelle A Tollit
Journal: The Lancet Child & Adolescent Health (2021)
Outcomes and prediction of lethal recurrence after transoral robotic surgery for HPV+ head and neck cancer.
Authors: Devraj Basu, David Shimunov, Roger B. Cohen, Alexander Lin, Samuel Swisher-McClure, John Nicholas Lukens, Joshua Bauml, Lee P. Hartner, Charu Aggarwal, Umamaheswar Duvvuri, Karthik Rajasekaran, Ara Chalian, Christopher Rassekh, Steven Cannady, Jason Newman, Bert W. O'Malley, Gregory S. Weinstein, Phyllis A. Gimotty, Robert Brody
Journal: Journal of Clinical Oncology (2021)

6047 Background: Increasing use of transoral robotic surgery (TORS) for human papilloma virus-related (HPV+) head and neck squamous cell carcinomas (HNSCCs) is likely to impact recurrence patterns and outcomes. Profiling HPV+ HNSCC recurrences after TORS and identifying features predictive of lethal outcome would facilitate tailoring adjuvant therapy and guide surveillance post-therapy. This study uses long term follow-up of patients at the first institution to bring TORS into clinical use to describe the recurrence patterns, distinguish outcomes associated with distinct patterns, and create a risk model for lethal recurrence. Methods: This retrospective cohort study at a single academic tertiary center analyzed 634 consecutive, treatment-naïve HPV+ HNSCC patients receiving TORS and neck dissection for clinical features at presentation and pathologic traits identified by surgical resection. The main outcomes were distant metastatic recurrence (DMR) and locoregional recurrence (LRR). Multivariate logistic regression with backward stepwise elimination was used to identify features associated with recurrence. Results: 6.5% of patients developed DMR at a median of 12.4 months after surgery and had a 5-year overall survival (OS) of 52.5% (95% CI, 33.9%-68.2%), whereas the 6.2% patients developing LRR alone had 5-year OS of 83.3% (95% CI, 66.2%-92.2%; P =.01). After recurrence, 5-year progression-free survival was 24.7% (95% CI, 11.4%-40.7%) for DMR cases and 85.7% (95% CI, 65.1-94.6%) for cases with LRR alone (P &lt;.001). Comparing recurrent cases to recurrence-free controls showed DMR to be independently associated with positive surgical margins (AOR 5.7; 95% CI, 2.1-15.7) and advanced clinical stage at presentation (AOR 6.5; 95% CI, 1.9-23.0). Positive margins increased DMR risk by 4.2-fold and reduced 5-year disease-free survival (P &lt;.001) in early-stage cases (Table), which comprised 95% of the cohort. By contrast, isolated LRR was associated with failure to receive indicated adjuvant therapy and was usually controllable by salvage therapy. Conclusions: Based on the largest single institution cohort reported to date, long term oncologic outcomes for HPV+ HNSCCs after TORS are excellent overall. While DMR is often fatal, LRR is salvageable with durable disease control. In addition to standard staging criteria, positive margins indicate substantially higher risk of DMR but not LRR. A risk model for DMR that incorporates margin status after TORS is relevant for guiding clinical trial design and whole-body surveillance.[Table: see text]
The epidemiology of psychiatric disorders in Africa: a scoping review
Authors: M Claire Greene, Tenzin Yangchen, Thomas Lehner, Patrick F Sullivan, Carlos N Pato, Andrew McIntosh, James Walters, Lidia C Gouveia, Chisomo L Msefula, Wilza Fumo, Taiwo L Sheikh, Melissa A Stockton, Milton L Wainberg, Myrna M Weissman
Journal: The Lancet Psychiatry (2021)
Clinical and genetic characteristics of EGFR-mutant lung adenocarcinoma transformed SCLC.
Authors: Linping Gu, Bei Zhang, Ding Zhang, Hong Jian
Journal: Journal of Clinical Oncology (2021)

e20588 Background: Transformation from non-small cell lung cancer (NSCLC) to small cell lung cancer (SCLC) is one of the resistance mechanism of EGFR tyrosine kinase inhibitors. However, the clinical course of transformed SCLC and the difference of genomic profiling between de novo SCLC patients and transformed SCLC patients are still poorly characterized. Methods: Patients from our hospital diagnosed with SCLC were enrolled retrospectively in this study, including de novo SCLC patients and SCLC patients transformed from EGFR-mutant lung adenocarcinomas. Genomic profiling was performed on formalin-fixed paraffin-embedded tumor samples by next generation sequencing (NGS). In statistical analysis, fisher ‘exact test was used. All tests were bilateral, with P&lt;0.05 indicating significant statistical difference. Results: In total, 16 patients with SCLC transformed from EGFR-mutant lung adenocarcinomas and 230 de novo SCLC patients were included in our study. Transformed SCLC patients were more in younger (p=0.007), female (p&lt;0.001) and non-smokers (p&lt;0.001) than de novo SCLC patients. In transformed SCLC patients, 12 patients (75%) occurred SCLC transformation within 2 years after the lung adenocarcinomas diagnosis. Median transformation time was 20 months. During the treatment of adenocarcinomas, the overall response rate (ORR) was 75% and the median progression-free survival was 12 months. After the initiation of SCLC therapy, the ORR of 1st line chemotherapy was 40%. For the genomic profiling, EGFR mutations, including exon 19 deletion (56%), L858R (38%), and others (6%), were detected. 11 patients with acquired resistance were received EGFR T790M test, 82% of patients had acquired EGFR T790M mutation. 11 patients after transformation to SCLC had NGS test, 100% maintained their founder EGFR mutation, and other recurrent mutations included TP53, RB1 and EGFR amplification. Compared with the genetic alterations in de novo SCLC patients, TP53 mutations were significantly decreased (p=0.006) while EGFR mutations were significantly elevated (p&lt;0.001) in transformed SCLC patients. However, no significant difference on RB1, ALK and ROS1 mutations were observed. Interestingly, a 60-year-old woman in our transformed SCLC cohort harbored EGFR 19 del mutant at allele frequency of 50.39%，she received osimertinib plus epirubicin/cyclophosphamide as 1st line treatment and reached partial response, with survival of 4 years to date. Conclusions: We demonstrated the clinical and genetic characteristics of EGFR-mutant lung adenocarcinoma transformed SCLC and found one patient still benefited from EGFR-TKI. Our study suggested that SCLC patients with EGFR mutation who transformed from lung adenocarcinoma may be potential benefit population using EGFR inhibitors.
Chronic immune checkpoint inhibitor (ICI) pneumonitis in patients (pts) with non-small cell lung cancer (NSCLC).
Authors: Jessica Stuart, Biagio Ricciuti, Joao Victor Machado Alessi, Mizuki Nishino, Mark M. Awad
Journal: Journal of Clinical Oncology (2021)

9103 Background: ICI pneumonitis is an immune-related adverse event (irAE) of the lung and often requires discontinuation of ICI. While some pneumonitis cases resolve within the recommended 4-6-week period of corticosteroid therapy, others either fail to improve or have multiple flares necessitating longer or repeated courses of steroids. We investigated the clinical features and courses of pts with chronic pneumonitis. Methods: We analyzed 869 pts with NSCLC initiated on ICIs at our institution between 2011 and 2019 for development of ICI pneumonitis. Chronic pneumonitis was defined as any pneumonitis requiring a total of ≥12 weeks of steroids, given either continuously or over multiple courses of treatment. Cases of chronic pneumonitis in which the initial course of steroids lasted ≥12 weeks without interruption were termed “primary refractory pneumonitis”. Subsequent episodes of pneumonitis were categorized as either “recurrent pneumonitis” from ICI rechallenge or “pneumonitis flare” after steroid taper without ICI rechallenge. Chest CT scans were analyzed to classify the imaging patterns. Results: Of the 869 pts analyzed, 44 developed ICI pneumonitis (5.1%) and 22 of the 44 (50%) experienced chronic pneumonitis (Grade 2 in 11, Grade 3 in 9, and Grade 4 in 2). A cryptogenic organizing pneumonia (COP) pattern was the most common CT pattern among all pneumonitis cases (30/44) and in chronic pneumonitis cases (14/22). Among chronic pneumonitis cases, the median number of total weeks on corticosteroid therapy was 25.9 (range: 12.4 – 114.4 weeks). Four pts required additional immunosuppressive agents including mycophenolate or infliximab. Fourteen of 22 pts with chronic pneumonitis had primary refractory pneumonitis, while the remaining 8 pts were weaned off of steroids within 12 weeks but later developed additional episode(s) of pneumonitis, ultimately resulting in a total steroid duration of ≥12 weeks. The 14 pts with primary refractory pneumonitis had significantly shorter time to pneumonitis onset compared to the other 8 pts (median time to onset: 1.8 vs. 5.5 months, Wilcoxon ranksum p = 0.04). Seventeen of 22 patients had their ICI permanently discontinued; of these, 9 pts subsequently experienced pneumonitis flare after steroid taper, necessitating additional course(s) of steroid therapy. 5 of the 22 patients were rechallenged with ICI, and 4 of them had recurrent pneumonitis with ICI rechallenge. Conclusions: Half of the pts diagnosed with pneumonitis developed chronic pneumonitis requiring at least 12 weeks in aggregate of glucocorticoid therapy. Some patients had an initial prolonged steroid course while others initially improved and then flared, even after ICI discontinuation. Recognition of chronic pneumonitis as a distinct and common clinical entity is important in management of pts with ICI pneumonitis.
Evidence-based Definition for Extensively Drug-Resistant Tuberculosis
Authors: Maroussia Roelens, Giovanni Battista Migliori, Liudmila Rozanova, Janne Estill, Jonathon R. Campbell, J. Peter Cegielski, Simon Tiberi, Domingo Palmero, Greg J. Fox, Lorenzo Guglielmetti, Giovanni Sotgiu, James C. M. Brust, Didi Bang, Christian Lienhardt, Christoph Lange, Dick Menzies, Olivia Keiser, Mario Raviglione
Journal: American Journal of Respiratory and Critical Care Medicine (2021)

Rationale: Until 2020, extensively drug-resistant tuberculosis (XDR-TB) was defined as TB with resistance to rifampicin and isoniazid (multidrug-resistant TB [MDR-TB]), any fluoroquinolone (FQ), and any second-line injectable drug (SLID). In 2019, the World Health Organization issued new recommendations for treating patients with drug-resistant TB, substantially limiting the role of SLIDs in MDR-TB treatment and thus putting the definition of XDR-TB into question. Objectives: To propose an up-to-date definition for XDR-TB. Methods: We used a large data set to assess treatment outcomes for patients with MDR-TB exposed to any type of longer regimen. We included patients with bacteriologically confirmed MDR-TB and known FQ and SLID resistance results. We performed logistic regression to estimate the adjusted odds ratios (aORs) for an unfavorable treatment outcome (failure, relapse, death, loss to follow-up), and estimates were stratified by the resistance pattern (FQ and/or SLID) and group A drug use (moxifloxacin/levofloxacin, linezolid, and/or bedaquiline). Measurements and Main Results: We included 11,666 patients with MDR-TB; 4,653 (39.9%) had an unfavorable treatment outcome. Resistance to FQs increased the odds of an unfavorable treatment outcome (aOR, 1.91; 95% confidence interval [CI], 1.63-2.23). Administration of bedaquiline and/or linezolid improved treatment outcomes regardless of resistance to FQs and/or SLIDs. Among patients with XDR-TB, compared with persons receiving no group A drug, aORs for an unfavorable outcome were 0.37 (95% CI, 0.20-0.69) with linezolid only, 0.40 (95% CI, 0.21-0.77) with bedaquiline only, and 0.21 (95% CI, 0.12-0.38) with both. Conclusions: Our study supports a new definition of XDR-TB as MDR-TB and additional resistance to FQ plus bedaquiline and/or linezolid and helps assess the adequacy of this definition for surveillance and treatment choice.