tbuckley/cabot-search huggingface dataset:
Lobectomy confers a survival benefit over gross-total resection without lobectomy in cases of primary glioblastoma in non-eloquent area: A retrospective study.
Authors: Euihyun Kim
Journal: Journal of Clinical Oncology (2019)

e13561 Background: Following resection, the microscopic remnants of glioblastomas in nearby tissue cause tumor recurrence more often than other tumors. Although surgical oncologists traditionally resect some of the surrounding normal tissue, whether further removal of nearby tissue may improve survival in cases of primary glioblastomas (pGBM) is unknown. In this single-center retrospective study, we assessed whether lobectomy confers a survival benefit over gross-total resection without lobectomy when treating pGBM in the non-eloquent area. Methods: We selected 28 patients who had complete resection of a histopathologically-diagnosed pGBM in the right frontal or temporal lobe, and divided them into two groups according to whether gross-total resection of the tumor involved lobectomy (SupTR group, n = 15) or did not (GTR group, n = 13). Progression-free survival (PFS), overall survival (OS), and Karnofsky Performance Status (KPS) scores were compared statistically between groups (p≤0.05 for significant differences). Results: Median post-operative PFS times (GTR, 9.7 months [95% CI 2.9-16.5]; SupTR, 35.0 months [95% CI 11.1–58.9]; p = 0.082) and mean KPS scores (GTR, 73.4; SupTR, 71.3; p = 0.586) were not significantly different; however, median post-operative OS times were (GTR, 14.4 months [95% CI 12.1–16.7]; SupTR, 35.0 months [95% CI 17.4–52.6]; p = 0.018). In multivariate analysis, the SupTR group was significantly better than the GTR group in terms of both OS (HR 0.249; 95% CI 0.085–0.730; p = 0.011) and PFS (HR 0.362; 95% CI 0.0134–0.982; p = 0.046). Conclusions: In cases of completely resectable, non-eloquent area pGBMs, including lobectomy improved overall survival without negatively impacting patient performance.
British Society of Gastroenterology and UK-PSC guidelines for the diagnosis and management of primary sclerosing cholangitis
Authors: Michael Huw Chapman, Douglas Thorburn, Gideon M Hirschfield, George G J Webster, Simon M Rushbrook, Graeme Alexander, Jane Collier, Jessica K Dyson, David EJ Jones, Imran Patanwala, Collette Thain, Martine Walmsley, Stephen P Pereira
Journal: Gut (2019)

These guidelines on the management of primary sclerosing cholangitis (PSC) were commissioned by the British Society of Gastroenterology liver section. The guideline writing committee included medical representatives from hepatology and gastroenterology groups as well as patient representatives from PSC Support. The guidelines aim to support general physicians, gastroenterologists and surgeons in managing adults with PSC or those presenting with similar cholangiopathies which may mimic PSC, such as IgG4 sclerosing cholangitis. It also acts as a reference for patients with PSC to help them understand their own management. Quality of evidence is presented using the AGREE II format. Guidance is meant to be used as a reference rather than for rigid protocol-based care as we understand that management of patients often requires individual patient-centred considerations.
Patient-reported outcomes (PROs) from KATHERINE: A phase III study of adjuvant trastuzumab emtansine (T-DM1) versus trastuzumab (H) in patients (pts) with residual invasive disease after neoadjuvant therapy for HER2-positive breast cancer.
Authors: Andreas Schneeweiss, Sibylle Loibl, Eleftherios P. Mamounas, Gunter von Minckwitz, Max S. Mano, Michael Untch, Chiun-Sheng Huang, Priya Rastogi, Pier Franco Conte, Veronique D'hondt, Andres Redondo, Ljiljana Stamatovic, Herve R. Bonnefoi, Hugo Raul Castro Salguero, Hans Holger Fischer, Tanya A. Wahl, Chunyan Song, Steven Blotner, Peter Trask, Charles E. Geyer
Journal: Journal of Clinical Oncology (2019)

513 Background: The phase 3 KATHERINE (NCT01772472) study, met its primary endpoint by demonstrating significantly improved invasive disease-free survival with adjuvant T-DM1 compared to H in pts with residual invasive disease after neoadjuvant chemotherapy plus HER2-targeted therapy. PROs are reported here. Methods: Eligible pts had HER2-positive early breast cancer, received taxane- and H-containing neoadjuvant therapy (with/without anthracyclines) followed by surgery, and had residual invasive disease in the breast and/or axillary nodes. Pts were randomized to 14 cycles of adjuvant T-DM1 (3.6 mg/kg IV q3w) or H (6 mg/kg IV q3w) and adjuvant endocrine and radiation therapy per standard of care. The EORTC Quality of Life Questionnaire–Core 30 (QLQ-C30) and QLQ–Breast Cancer (QLQ-BR23) were completed at screening, at day 1 of cycles 5 and 11, within 30 days after study drug completion, and at 6 and 12 months’ follow-up. Results: Of 1,486 pts randomized (T-DM1, n = 743; H, n = 743), 612 (82%) and 640 (86%), respectively, had valid baseline and ≥1 post-baseline PRO assessments. During the study, pts in both arms had similar mean scores on the QLQ-C30 and QLQ-BR23 function and symptom scales. There was no clinically meaningful change (≥10 points) from baseline in the mean scores in either arm, including on symptoms similar to AEs seen with T-DM1 (eg, fatigue). While more pts in the T-DM1 arm reported clinically meaningful deterioration in role functioning (49% vs 41%), appetite loss (38% vs 28%), constipation (47% vs 38%), fatigue (66% vs 61%), nausea/vomiting (39% vs. 30%), and systemic therapy side effects (49% vs 36%) at ≥1 assessment, the proportion reporting clinically meaningful change in functioning was similar between arms at any given assessment. Conclusions: Mean scores showed only small deterioration from baseline in patient-reported treatment-related symptoms in both study arms. While more pts in the T-DM1 arm reported deterioration at some point in several symptoms, baseline global health status and functioning were generally maintained in both arms over the treatment course. Clinical trial information: NCT01772472.
Role of the oral and gut microbiota as a biomarker in locoregionally advanced oropharyngeal squamous cell carcinoma (ROMA LA-OPSCC).
Authors: Marc Oliva Bernal, Pierre H.H. Schneeberger, Rachel Taylor, Victor Rey, Aaron Richard Hansen, Kirsty Taylor, Andrew Bayley, Andrew Hope, Ali Hosni, Scott Victor Bratman, Jolie Ringash, Ralph William Gilbert, Ilan Weinreb, Bayardo Perez-Ordonez, John Waldron, Wei Xu, David Guttman, Lillian L. Siu, Bryan Coburn, Anna Spreafico
Journal: Journal of Clinical Oncology (2019)

6045 Background: The ROMA LA-OPSCC ( NCT03759730) study prospectively evaluated the oral and gut microbiota in a single-centre cohort of LA-OPSCC patients (pts) receiving chemoradiotherapy (CRT). Methods: LA-OPSCC pts treated with definitive CRT (IMRT plus single-agent cisplatin) were eligible. Oral swabs over the tumor site and stool samples were collected at baseline and end of CRT (EOT). Taxonomic profiles were generated by 16S rRNA sequencing. ANOSIM/Kruskal-Wallis tests were used to identify differences between baseline and EOT samples. Results: A total of 96 samples were collected from 24 evaluable pts (100% compliance). Baseline characteristics: median age = 61 (range, 50-71); smoking status current/former/never = 5/11/8; HPV+/- = 23/1; stage I/II/III/IVA = 7/7/9/1; use of antibiotics = 12 pts. In oral swabs, decreased Shannon diversity ( p&lt; 0.01) and changes in abundance (adjusted p value: q&lt; 0.05) of multiple taxa including Prevotella, Veillonella, and Streptococcuswere observed at EOT vs baseline. Stool diversity did not differ between baseline and EOT ( p= 0.42), but abundance of Ruminoccocus and Roseburia decreased ( q&lt; 0.05). CRT-associated changes remained significant when controlled for stage, smoking, antibiotics, cisplatin dose and mucositis grade ( p&lt; 0.01). In HPV+ pts, stage I-II baseline oral swabs had higher relative abundance of Clostridium IV ( p= 0.02) and Escherichia ( p= 0.04) than stage III, which had higher Fusobacterium ( p =0.03) and Gemella ( p&lt; 0.01). Relative abundance of Actinobacteria (p &lt; 0.01), Proteobacteria (p &lt; 0.01) and Firmicutes (p = 0.03) was higher in stool from stage III pts . Akkermansia muciniphila was present in 57% of the stage I-II stool samples, and 11% in stage III ( p= 0.04). Conclusions: CRT in LA-OPSCC is associated with increases in potentially pathogenic genera in the oropharynx. HPV+ stage III disease was associated with higher Fusobacterium in the oropharynx, which has been implicated in tumor metastases, and with decreased prevalence of the immunotherapy-response-associated species Akkermansia in stool. These preliminary observations suggest an opportunity for the evaluation of IO based therapies or manipulation of the gut microbiota in this patient population. Clinical trial information: NCT03759730.
Depth of invasion in early oral cancers: Is it an independent prognostic factor?
Authors: Harsh Dhar, Anil D'Cruz, Richa Vaish, Rohini W Hawaldar, Sudeep Gupta, Gouri Pantvaidya, Devendra Chaukar, Pankaj Chaturvedi, P. S. Pai, Anuja Deshmukh, Shubhada Kane, Deepa Nair, Sudhir Vasudevan Nair, Sarbani Laskar, Jaiprakash Agarwal
Journal: Journal of Clinical Oncology (2019)

6058 Background: Depth of invasion (DOI) has been incorporated in the new AJCC TNM staging (8 th edition) for oral cancers. We hypothesized that the negative effect of increasing DOI on outcomes was a result of an increased propensity to node metastasis and appropriate neck treatment would negate its detrimental effect on outcomes. Methods: Patients with T1/ T2 oral squamous cell carcinoma, clinically node negative, from a previously reported Randomized Controlled Trial (NCT 00193765) formed the cohort for this study. Patients were restaged according to the new staging system . Overall survival(OS) was estimated by the revised T stage for the entire cohort and separately for those who underwent END and those who did not (TND arm) using Kaplan Meier and log rank test . Multivariate analysis was performed using Cox proportional hazard model making adjustment for neck treatment, T stage, site, prognostic factors and the interaction between revised T stage and neck treatment. Results: Of the 596 patients 577 were evaluable, with a median follow up of 77.57 months. Initial pT staging was pT1, 389(67.4%); pT2, 181(31.4%); pT3, 7(1.2%) and was modified to pT1, 195(33.8%); pT2, 280(48.5%); pT3, 102(17.7%) on restaging . 288 patients underwent END and 289 did not (TND arm). For the entire cohort 5-year OS rates were 79.0% [95 %CI, 73.12-84.88] for pT1, 69.4% [95% CI, 63.91-74.89] for pT2 and 53.0% [95% CI, 43.2 -62.8] for pT3 with significant difference between the 3 groups (p &lt; 0.001). In those without upfront neck treatment( TND ), OS difference was maintained between the pT1 and pT2 groups [81.1% (95%CI, 73.26-88.94) vs 65.0% (95%CI, 56.77-73.23)], p = 0.004. This difference was not apparent in the END arm ,pT1 -76.9% (95 %CI, 68.47-85.33) vs pT2 -73.7% (95%CI, 66.25-81.15), p = 0.73. T3 tumours had uniformly poor survival irrespective of neck treatment. On multivariate analysis of the revised pT1/T2 cohort (n = 475), pT stage, neck treatment and grade were independent prognostic factors impacting OS. There was a significant interaction between the T stage and neck treatment (p = 0.03). Conclusions: When DOI &lt; 10 mm, END supplants the prognostic implication of depth with similar outcomes for T1 and T2 tumours (new AJCC staging). The exact role of DOI on outcomes warrants further research. Clinical trial information: NCT00193765.
Socioeconomic disparities among uninsured cancer patients: A free clinic study.
Authors: Madeline MacDonald, Yuanyuan Lu, Ethan Song, Noura Ayoubi, Katherine Robinson, Amber Todd, Abu-Sayeef Mirza
Journal: Journal of Clinical Oncology (2019)

e18110 Background: Cancer is the second leading cause of death in the United States and approximately 38.4% of Americans will be diagnosed with cancer during their lifetime. Cancer treatment and follow-up care is expensive and uninsured individuals may face barriers to receiving necessary treatments. Minorities may encounter additional barriers to accessing healthcare. There is limited research about socioeconomic disparities in uninsured cancer patients seen at free clinics in the United States. Methods: A retrospective chart review was conducted to collect chronic disease parameters from electronic medical records and paper charts at nine free clinics in the Tampa Bay area in Florida. Demographics were compared between cancer patients and the non-cancer population via chi-square test or independent samples t-test. Results: Between January 2016 and December 2017, 9127 uninsured patients were seen at nine free clinics. 2137 patients were excluded from the study because there was no cancer data in their charts. Of the patients included in the study, 221 (3.2%) had a current or past diagnoses of cancer. Cancer patients were more likely to be female (n = 145, 65.9), p = 0.048, compared to non-cancer patients. Cancer patients were more likely to be Caucasian (n = 106, 89.1%), p &lt; 0.001 compared to non-cancer patients (n = 2489, 69.3%). Cancer patients were less likely to be African American compared to non-cancer patients (n = 6, 5.0% vs. n = 754, 21%), p &lt; 0.001. Cancer patients were significantly older than non-cancer patients (M = 54.1, SD = 12.0) vs. (M = 41.0, SD = 16.7), p &lt; 0.001. Patients who had cancer were more likely to be unemployed compared to non-cancer patients (n = 78, 54.9% vs. n = 1685, 46.6%), p = 0.050. Conclusions: The study revealed that uninsured cancer patients are more likely to be unemployed, female, of older age, and Caucasian compared to non-cancer patients. It appears that uninsured African Americans are not utilizing free clinics for their healthcare and may be lost to follow-up. A variety of factors may have contributed to these disparities in this vulnerable population including lack of transportation, lack of awareness of free resources in the area, and more. This study increases awareness of disparities in uninsured, cancer patients.
Safety and interim results from a phase II, single-arm study of atezolizumab and bevacizumab in Merkel cell carcinoma (MCC).
Authors: Renata Ferrarotto, Javier Mata, Frank Mott, Priya Bhosale, M. Laura Rubin, Mehmet Altan, Shannon Dervin, Cindy Yun, James C. Yao, Daniel M. Halperin
Journal: Journal of Clinical Oncology (2019)

e21006 Background: MCC is an aggressive neuroendocrine carcinoma of the skin. Avelumab (anti-PD-L1) was FDA approved for the treatment of metastatic MCC based on an overall response rate (ORR) of 32% in chemotherapy-refractory pts. In first line, responses to PD1/PD-L1 have been reported in 56-62% of pts. Atezolizumab (Atezo) targets PD-L1 and bevacizumab (bev) inhibits VEGF. Pre-clinical data suggests atezo + bev improves antigen-specific T-cell migration, and encouraging clinical activity of this regimen has been reported in renal cell and hepatocellular carcinoma. Here we report safety and interim results of atezo + bev in MCC. Methods: In this phase II single-arm study the efficacy and safety of atezo + bev was evaluated in pts with recurrent/metastatic PD-1/PD-L1-inhibitor naive MCC. Patients were treated with atezo 1200 mg + bev 15 mg/kg IV Q3W. Primary endpoint was ORR (RECIST 1.1) by blinded independent radiologist. Secondary endpoints included ORR by iRECIST, PFS, DOR, DCR, OS, and safety. Results: 11 pts enrolled. Median age was 70 (range:57-84), (7) 63% were male, and 7 (63%) had been treated with curative intent. Five (45%) pts had received platinum/etoposide (2 in the neo-adjuvant setting and 3 in first-line). Median follow-up is 9.7 months (range:2.8-15.9). Adverse events (AEs) that occurred in &gt; 1 pt: hypertension (7), proteinuria (3), fatigue (2), peripheral edema (2), epistaxis (2), and transaminitis (2). Grade 3 AEs: hypertension (2), proteinuria (1), and auto-immune hepatitis (1); all manageable. Only 1 subject discontinued treatment due to toxicity (auto-immune hepatitis). There were no grade &gt; 3 AEs. Objective response occurred in 7 (64%) pts, including 3 (27%) complete responses (CR). One partial response was unconfirmed (patient discontinued treatment after 1 dose of atezo/bev due to grade 3 hepatitis). 4 pts remain on treatment (1 pt with CR withdrew consent for further therapy and has not recurred). Median PFS is 6.3 months (95% CI:4.5-NA). Conclusions: Atezo + bev was well tolerated in MCC pts. Safety was consistent with that of the individual agents. Activity is encouraging with 64% ORR (27% CR rate) and mPFS of 6.3 months. Clinical trial information: NCT03074513.
Multiplatform molecular profiling: Observational study to determine the effect of treatment selection in advanced or refractory metastatic solid tumors.
Authors: Faraz A. Khan, Maroun EL Khoury, Thalia Safar, Mona Tareen, Kadriya Sayed
Journal: Journal of Clinical Oncology (2019)

e14730 Background: To assess the clinical benefit of treatment in advanced and refractory solid tumors utilizing evidence-guided molecular profiling (MP) of tumors in routine clinical practice. Methods: This retrospective observational study was conducted on patients with advanced or refractory metastatic solid tumors, whose tumor biopsy samples were referred for profiling using a multi-platform tumor profiling service (Caris Molecular Intelligence) between January 2014 and April 2017. Specific testing was performed per physician’s request and included a combination of next-generation sequencing (NGS), protein expression (IHC), gene amplification (CISH or FISH), and/or RNA fusion analysis. Results: Data of twenty five patients with solid tumors was analyzed (median age of 58 years, range 25-82 years). Patients had received a median of 2 prior lines of therapy (range 0-6). In evaluable patients, 1 (4%) patient had a complete response, 10 (46%) patients had a partial response, 5 (23%) had stable disease and 6 (27%) had progressive disease, giving a disease control rate of 73%. The majority of patients received chemotherapy (CT) alone (13; 56%). Five patients received CT combined with targeted therapy (TT), 2 received TT alone, 2 received TT combined with hormone therapy (HT), 2 have received immunotherapy and 1 received HT alone. Two patients were not evaluable for response. In responding patients, median duration of response was 7 months (3-18 months). Conclusions: The result of this study show that treatment based on Broad tumor profiling in a select group of advanced and refractory solid tumors was associated with a high disease control rate.
Polygenic risk of subsequent thyroid cancer after childhood cancer: A report from St. Jude lifetime cohort (SJLIFE) and Childhood Cancer Survivor Study (CCSS).
Authors: Zhaoming Wang, Qi Liu, Carmen Louise Wilson, Yadav Sapkota, Todd M. Gibson, Lindsay M. Morton, Joshua N Sampson, Joseph Philip Neglia, Michael A. Arnold, Michael C Rusch, Heather Mulder, John Easton, Jinghui Zhang, James Downing, Smita Bhatia, Gregory T. Armstrong, Wassim Chemaitilly, Melissa M. Hudson, Leslie L. Robison, Yutaka Yasui
Journal: Journal of Clinical Oncology (2019)

10060 Background: Subsequent thyroid cancer (STC) is among the most common malignancies in childhood cancer survivors, especially those with thyroid exposure to radiotherapy (RT). Identification of genetic risk factors may inform screening practices. Methods: Twelve SNPs were previously identified as thyroid cancer risk loci in the general population of European ancestry. A polygenic risk score (PRS) was calculated as a sum of risk alleles carried by a survivor, weighted by the natural logarithm of the published per-allele odds ratios (range: 1.2-1.8). With piecewise exponential models, associations of STC rates with PRS were assessed, both overall and stratified by neck RT exposure. Models were adjusted for sex, age at primary diagnosis, attained age, neck RT dose, epipodophyllotoxin therapy, and eigenvectors within survivors of European ancestry from SJLIFE with whole-genome sequencing data and CCSS with SNP data imputed to Haplotype Reference Consortium. Results: Among 2,324 SJLIFE survivors, 61 (43 with, 18 without neck RT) developed STC. The rate of STC was increased by 5.3-fold (95% confidence interval (CI), 2.2-12.6) and 3.1-fold (CI, 1.3-7.7) for survivors in the third and second PRS tertiles, respectively, compared to those in the first tertile, with corresponding cumulative incidence at age of 40 years of 5.3% (CI, 3.3-7.3%), 2.5% (CI, 1.1-3.9%), and 1.0% (CI, 0.005-2.0%), respectively. Stratified by neck RT, the corresponding rate increases were 7.6 (CI, 2.3-25.3) and 3.8 (CI, 1.1-13.4), respectively, among survivors exposed to neck RT; however, no association was observed among survivors without neck RT (only 18 STC cases). Replication was performed among 4,302 CCSS survivors, 100 (61 with, 39 without neck RT) developed STC. The rates of STC were increased by 2.3-fold (CI, 1.4-3.9) and 1.7-fold (CI, 1.0-2.9) for survivors in the third and the second PRS tertiles, compared to those in the first tertile. The similar significant associations were observed in survivors with and without neck RT ( P trend = 0.04 and 0.02, respectively). Conclusions: High PRS conferring STC risk can inform screening practices and help personalize and improve survivorship care.
The relationship of lncRNA NR2F1 and breast cancer angiogenesis via IL-8/lncRNA NR2F1/miR-200s/IL-8 loop.
Authors: Qi Zhang, Jin Zhang, Sihong Lu, Nan Shao, Ying Lin
Journal: Journal of Clinical Oncology (2019)

e12573 Background: Angiogenesis is key for metastasis and predicts a poor prognosis in breast cancer. Among the pro-angiogenic factors, interleukin-8 (IL-8) could be secreted by tumor cells mediated by microRNA-200 family (miR-200s). Long non-coding RNA (LncRNA), was reported to absorb microRNA to play multiple roles in various diseases including breast cancer. Our preliminary results recognized lncRNA NR2F1 through Agilent Human LncRNA array from breast cancer cells overexpressing IL-8. However, the relationship between LncRNA NR2F1 and breast cancer angiogenesis remains unknown. Methods: Breast cancer cell migration, invasion, proliferation and angiogenesis were assessed by Transwell, CCK8, tube formation, and wound healing assays. The expression of LncRNA NR2F1, miR-200s and IL-8 were detected by qPCR, Western blotting and ELISA. Breast cancer metastasis and angiogenesis in vivo were measured in a zebrafish model. Results: We found that the basal expression of lncRNA NR2F1 is higher in breast cancer cell lines than it in normal cells. In vitro, lncRNA NR2F1 induced breast cancer migration, invasion, and proliferation. Meanwhile, lncRNA NR2F1 promoted human umbilical vascular endothelial cell (HUVEC) proliferation, tube formation, and migration both via breast cancer conditioned medium and via direct HUVEC transfection. In the zebrafish model, lncRNA NR2F1 promoted breast cancer cell metastasis and neo-angiogenesis. Further study disclosed that lncRNA NR2F1 downregulated the expression of miR-200s, which in turn upregulated the expression of IL-8 in breast cancer cells. Conclusions: Our findings suggest that LncRNA NR2F1, as a potential promoter of breast cancer, may induce breast cancer angiogenesis through IL-8/lncRNA NR2F1/miR-200s/IL-8 loop.