tbuckley/cabot-search huggingface dataset:
Predictors of clinical outcomes in patients undergoing curative treatment for esophageal or gastroesophageal junction adenocarcinoma.
Authors: Tara Magge, Robert Van Haren, Sandra Lynne Starnes, Gregory Wilson, Sameer H. Patel, Jordan Kharofa, Davendra Sohal
Journal: Journal of Clinical Oncology (2021)

e16067 Background: Management of locally advanced esophageal and gastroesophageal junction (E/GEJ) adenocarcinoma is typically managed with neoadjuvant treatment followed by surgery. Clinical outcomes remain suboptimal and a considerable proportion of patients develop recurrence. However, prognostic and predictive factors are not well-defined. We thus aimed to identify any factors that were associated with disease recurrence and decreased overall survival (OS) among patients with E/GEJ adenocarcinoma treated with curative intent. Methods: A retrospective study spanning 2011-2020 was performed, which identified 56 patients who underwent esophagectomy for E/GEJ adenocarcinoma at the University of Cincinnati. Data on baseline demographic and clinical characteristics, treatment details, pathologic outcomes, recurrence patterns, and survival were extracted from the electronic medical record. Predictors of recurrence and OS, using multivariable logistic regression and Cox proportional hazards analyses, respectively, were identified using all potential predictors and parsimonious modeling. The study was approved by the UC IRB; statistical analyses were performed using SAS 9.2; 95% confidence intervals and two-sided p-values were calculated. Results: Of the 56 patients included, 50 (89%) were White and 6 (11%) were Black; 46 (82%) were male and 48 (85%) were current or former smokers. Tumor location was E in 37 (66%) and GEJ in 19 (34%) patients; 30 (64%) had cT3 or cT4 tumors and 27 (55%) had node-positive disease. Neoadjuvant treatment included platinum-based chemotherapy for 43 (77%) and radiation for 40 (71%) patients; all patients underwent esophagectomy. Median OS for the entire cohort was 4.2 (95% CI 1.8-NR) years and 23(41%) had recurrence after resection. Multivariable modeling showed body mass index (BMI) &lt; 25 (OR vs. BMI ≥ 25: 5.41, 95% CI 1.4-20.4, p = 0.01) to be associated with recurrence; a higher pathologic T stage showed a trend toward increased risk (pT stages 1, 2, and 3 patients (vs. pT 0) were 0.2, 1.1, and 2.5 times more likely to have recurrent disease, respectively. OS was inferior for patients with recurrence (HR for death, vs. no recurrence: 5.42, 95% CI 2.1-13.8, p &lt; 0.001) and a baseline ECOG PS ≥2 (HR vs. ECOG PS &lt; 2: 2.36, 95% CI 0.87-6.4, p = 0.09). Conclusions: In this dataset of patients with E/GEJ adenocarcinoma treated with curative-intent resection, baseline clinical parameters of lower BMI and worse ECOG PS (rather than disease characteristics such as T and N stage) were the main predictors of recurrence and decreased OS. These findings suggest that improving clinical outcomes may at least partly depend on prehabilitation targeting nutrition and physical therapy for patients undergoing curative treatment for E/GEJ adenocarcinoma.
Anlotinib plus sintilimab in patients with recurrent advanced endometrial cancer: A prospective open-label, single-arm, phase II clinical trial.
Authors: Wei Wei, Xiaohua Ban, Fan Yang, Yongwen Huang, Jibin Li, Ya Qiu, Xiaqin Cheng, Jundong Li, Min Zheng
Journal: Journal of Clinical Oncology (2021)

5583 Background: Endometrial cancer is one of the most common gynecologic malignancies in the world. however, the effects of systemic chemotherapy are limited. The combination of targeted therapy with immunotherapy is a new research field in the treatment of malignant tumors. Anlotinib is a novel tyrosine kinase inhibitor with highly selective inhibition effects on multi-targets, especially on vascular endothelial growth factor receptor, Platelet-derived growth factor receptor and Fibroblast growth factor receptor. Sintilimab is a highly selective, fully humanized, monoclonal antibody, which blocks the interaction between Programmed death 1 and its ligands. This research aimed to evaluate the efficacy and safety of the combination of anotinib and sintilimab in patients with recurrent advanced endometrial cancer. Methods: Patients who received at least one platinum-based systemic chemotherapy, had an Eastern Cooperative Oncology Group performance status of 0 or 1 were considered eligible for enrollment. Sintilimab was administered intravenously (200mg，q3w); anlotinib was taken orally (12mg qd, d1-14, 21 days per cycle). The treatment was continued until disease progression, death or intolerant toxicity. The primary endpoint was objective response rate (ORR) and the secondary endpoints included duration of response, disease control rate (DCR), progression-free survival (PFS), overall survival and safety. Results: From November 2019 to to September 2020, 23 patients with a median age of 56 years (range: 37-70), FIGO stage IA (21.7%), IB (8.7%), II (4.4%), IIIA (13.1%)，IIIC (30.4%), IVB (21.7%) were enrolled. Among these participants, 22 patients were evaluable. The therapeutic evaluation showed the incidence of complete response, partial response, stable disease and progression disease was 13.6%, 63.7%, 13.6% and 9.1% respectively, yielding the ORR of 77.3% (95%CI: 58.3%-96.3%) and the DCR of 91.7% (95%CI: 79.8%-100%). ≥1 and ＜1 Combined Positive Score of PD-L1 expression were observed in 66.7% (14/21) and 33.3% (7/21) patients respectively, and the ORR was 92.9% (95%CI: 77.4%-100%) and 57.1% (95%CI: 18.4%-90.1%) in the two groups. The median time of the first response was 1.5 months (range, 0.7-12.8). The median PFS was not reached. Most of the occurring adverse events (AEs) were grade 1 or 2. Grade 3 AEs included ileus (4.3%), immune myocarditis (4.3%) immune peritonitis (4.3%), hand-foot syndrome (8.7%), neutropenia (4.3%), neutrophils decrease (4.3%), and hypertension (4.3%); Grade 4 AE was lymphocytosis (4.3%). Neither unexpected safety signals nor treatment-related death occurred. Conclusions: Anlotinib plus sintilimab showed a promising antitumor activity with a favorable toxicity profile for patients with recurrent advanced endometrial cancer. We will report more data in the future. Clinical trial information: NCT04157491.
Effect of time to surgical intervention in stage 3 cutaneous melanoma.
Authors: Seyed Saeed Pairawan, Matthew J. Selleck, David Caba Molina, Naveenraj Livingstone Solomon, Mark Evan Reeves, Carlos A. Garberoglio, Jukes P. Namm
Journal: Journal of Clinical Oncology (2021)

e21571 Background: Delay in surgical resection has been found to be associated with poorer overall survival (OS) in patients with stage 1 cutaneous melanoma. However, the impact of surgical timing on survival in stage 3 cutaneous melanoma remains unknown, especially in the era of immunotherapy. We sought to evaluate to the effect of time to definitive surgical intervention on OS in stage 3 cutaneous melanoma at Commission on Cancer accredited institutions. Methods: The National Cancer Database (2012-2016) was used to identify patients who underwent biopsy and definitive surgical intervention of cutaneous melanoma. Time to intervention (TTI) was analyzed from the time of initial biopsy to definitive surgical resection and classified into quartiles, (Q1≤22 days; Q2 = 23-33 days; Q3 = 34-49 days; Q4≥50 days) using χ2 and multivariable logistic regression. Survival was analyzed using Kaplan-Meier and Cox proportional hazard models. Results: We analyzed 4560 patients with a median age of 61 years (18-90) and most patients being non-Hispanic white and male (91.6% and 63%, respectively). Median Breslow thickness was 2.8 mm (0-9.8 mm). Median TTI was 33 days (0-352 days) with a mean OS of 52, 49.8, 48.4, 48.3 months for Q1 to Q4 respectively (p = 0.008). Age ≤50 years, treatment at a comprehensive community cancer center and only 1 positive lymph node (LN) were all associated with Q1 TTI (p = 0.002, p &lt; 0.001 and p &lt; 0.001, respectively). Black race, treatment at an academic facility, &gt; 4 LN positive, &gt; 4 mm thickness, and no administration of immunotherapy were all associated with Q4 TTI (p = 0.002, p &lt; 0.0001, p &lt; 0.0001, p &lt; 0.0001 and p &lt; 0.0001 respectively) on univariate analysis. Patients in Q4 TTI were more likely to be older (OR 1.01, 95% CI 1.00-1.02, p = 0.01), have T2-T4 tumors (OR 1.6, 95% CI 1.2-2.2, p &lt; 0.001), and be treated at an academic facility (OR 2.4, 95% CI 1.8-3.5, p &lt; 0.001) on multivariable analysis. In the survival analysis, multiple positive LNs (2, 3-4, &gt; 4 LNs; HR 1.4, 1.6 and 2.9, p &lt; 0.001), lymphovascular invasion (HR 1.4, p &lt; 0.001), Breslow thickness &gt; 4 mm (HR 1.7, p &lt; 0.001), Charlson-Deyo score ≥2 (HR 1.5, p &lt; 0.001), increasing age (HR 1.03, p &lt; 0.001), and longer TTI (Q3-Q4) (HR 1.2, p = 0.001) were all associated with worse OS. There was no difference in survival based on TTI in patients who had received adjuvant immunotherapy in Q1-Q2 vs Q3-Q4 (p = 0.3). Conclusions: In stage 3 cutaneous melanoma, longer TTI ( &gt; 33 days) was associated with worse OS but may be due to older age, higher T stage, and barriers to access. However, adjuvant immunotherapy may offer protection from delays in definitive surgery.
Role of adjuvant chemotherapy in the treatment of patients with node-positive bladder adenocarcinoma: An analysis of the National Cancer Database.
Authors: Akshay G Reddy, Andrew D Sparks, Michael Joseph Whalen
Journal: Journal of Clinical Oncology (2021)

e16504 Background: Given the rarity of bladder adenocarcinoma, there is a paucity of data examining the role of adjuvant chemotherapy (AC) in patients with regional lymph node positivity. This study aims to elucidate the oncologic and survival outcomes of patients with node-positive disease treated with or without AC. Methods: A retrospective cohort analysis of patients with node-positive primary bladder adenocarcinoma who had either received AC or did not receive AC after either radical (RC) or partial cystectomy (PC) was performed using the National Cancer Database from 2006 to 2016. Non-metastatic node-positive was defined as pT(any)N1-3 (pN+) disease. Demographic and clinicopathological variables were compared to adjust for confounding covariates in multivariable analysis to determine appropriate oncologic and surgical outcomes. Results: A total of 106 patients met inclusion criteria, of whom 38 received AC and 68 did not. Receipt of AC was significantly associated with improved survival relative to those who did not receive AC (overall survival: 29% vs 2.7%; adjusted hazards ratio = 0.43; p = 0.003) independent of extent of surgery. There was a trend toward higher receipt of adjuvant radiation along with AC, independent of surgical margin status. Receipt of AC additionally trended towards a significant association with decreased odds of 90-day mortality and 30-day unplanned readmission (Table). Conclusions: Based on the improved survival outcomes, positive nodal status may be a useful indicator of those who may benefit from AC, and potentially adjuvant radiation therapy, in bladder adenocarcinoma. Though compelling, larger studies will be required to make more conclusive statements regarding the most appropriate treatment course in these patients.[Table: see text]
A real-world study of camrelizumab in the treatment of advanced lung cancer patients.
Authors: Kangsheng Gu, Minghong Bi, Dong Zhao, Huaidong Cheng, Genhe Wang, Hong Qian, Xuhong Min, Xiaoyang Xia, Fan Wang, Zhiqiang Hu
Journal: Journal of Clinical Oncology (2021)

e21056 Background: Camrelizumab, as a humanized antibody against PD-1, has shown high efficiency and survival benefits in clinical studies on lung cancer treatment. This study aims to observe the efficacy and safety of Camrelizumab in the treatment of advanced lung cancer in the real world. Methods: This is a prospective, open, multi-center observational study that includes patients with advanced lung cancer who are older than 18 years of age, regardless of gender, with an ECOG score of 0-2. Results: As of November 18, 2020, a total of 253 patients have been enrolled. Males accounted for 187 cases (74.2%). The ECOG PS score was 0 in 44 cases (17.3%), 1 in 162 cases (64.0%), and 2 in 47 cases (18.6%). There were 181 patients (71.5%) of stage IV, 96 patients (37.9%) of adenocarcinoma, and 98% of patients did not undergo PD-L1 testing. A history of radiotherapy accounted for 31.2%, and a history of surgery on the primary lesion accounted for 20.2%. Camrelizumab accounted for 29.6% of the first-line treatment, 27.2% of the second-line treatment, and 43.1% of the third-line and above. Camrelizumab monotherapy accounted for 20.1%, camrelizumab combined with chemotherapy accounted for 56.3%, combined anti-angiogenesis therapy accounted for 22.1%, and combined anti-angiogenesis + chemotherapy accounted for 1.5%. Among the 199 patients with evaluable efficacy, 4 were CR, 46 were PR, 116 were SD, and 33 were PD. The ORR reached 25.1% and the DCR reached 83.4%. The overall adverse event rate was 33.7%, the major adverse event RCCEP rate was 22.6%, appetite loss was 5%, and fatigue was 3.5%. There were 4 cases (2%) of RCCEP with adverse events greater than or equal to grade 3. Conclusions: In this real-world study of lung cancer, most of the patients enrolled were patients with poor PS score and late stage, but the efficacy and safety of camrelizumab in patients with advanced lung cancer were still confirmed. The dominant population and combination therapy are still under study. Clinical trial information: ChiCTR2000034595.
Feasibility of a virtual hybrid resistance and balance training program for older patients with cancer and its preliminary effects on lower body strength and balance.
Authors: Schroder Sattar, Corrie Effa, Joni Nedeljak, Kristen R Haase, Shabbir M.H. Alibhai, Shawn Kuster, Eitan Amir, Diane Campbell, Margaret McNeely
Journal: Journal of Clinical Oncology (2021)

12002 Background: Falls are a major issue among older patients with cancer and can lead to interruption in cancer treatment. Ample evidence shows resistance and balance training can prevent falls in older adults; however, there is a paucity of evidence regarding exercise on fall prevention in the older cancer population, who often have unique risk factors for falls. Given the new reality of the COVID-19 pandemic, minimizing group gatherings and its associated risks is imperative for older patients, who are a vulnerable population. This study sought to investigate the feasibility of an 8-week, virtual exercise program and its preliminary effects on lower body strength and balance in community-dwelling cancer patients. Methods: Study participants were recruited for this pretest-posttest intervention study using consecutive sampling over a one-year period from the Cross Cancer Institute in Edmonton, Alberta. The intervention entailed leg muscle strengthening and balance training exercises that progressed in difficulty as outlined by the Otago program, and involved a virtual component (facilitated live by a certified exercise physiologist via Zoom meeting platform once a week) and independent at-home training component (twice a week). Lower body strength and balance were assessed using the 5-times chair-stand and the 4-stage balance test, respectively, and were analyzed using the Wilcoxon Signed Rank test. Results: Twenty-seven older patients (mean age 70.1, range 65-76) participated. The most common cancer sites were breast (48%) and prostate (41%). One participant withdrew due to personal reasons unrelated to the program. The remaining 26 participants completed the intervention. Attendance rate for the virtual component was 97.6% and independent component 84.7%. Participants perceived the program as rewarding and enjoyable (100%), felt this program prepared them to exercise on their own (92%), were confident to continue exercising on their own (81%), and would recommend the program to other patients (100%). At baseline, 33% (n = 9) ≥1 fall over the past 6 months. A statistically significant improvement in lower body strength was detected post-intervention ( p =.001), whereas no difference was detected in balance ( p =.059). Conclusions: This virtual, hybrid resistance and balance training program was feasible, overwhelmingly accepted by our older participants, and appeared effective in improving lower body strength. Findings from this study may have potential to inform design of a larger, randomized multi-site study.
Dynamic Changes in Ultrasound Quality for Hepatocellular Carcinoma Screening in Patients With Cirrhosis
Authors: Haley Schoenberger, Nicolas Chong, David T. Fetzer, Nicole E. Rich, Takeshi Yokoo, Gaurav Khatri, Jocelyn Olivares, Neehar D. Parikh, Adam C. Yopp, Jorge A. Marrero, Amit G. Singal
Journal: Clinical Gastroenterology and Hepatology (2021)
Racial differences in incidence, outcomes, and genomic alterations in small cell lung cancer.
Authors: Leyla Bayat, Pingfu Fu, Shufen Cao, Afshin Dowlati
Journal: Journal of Clinical Oncology (2021)

8514 Background: While the incidence of small cell lung cancer (SCLC) has been decreasing in recent years, an increasing proportion of our patients are younger African American (AA) women. There have been no studies describing these changes as well its impact on outcome and potential genomic differences amongst white and AA populations. Methods: We maintain a clinical/genomic/pathological database of all patients with SCLC treated at our comprehensive cancer center starting from 1998. We compared the baseline characteristics and outcomes (Overall survival [OS] and progression-free survival [PFS]) between AA and white patients, and between females and males. In addition, we looked at genomic alterations in &gt;350 cancer-related genes and compared the frequency and types of mutations in our study population. Results: A total of 917 patients with SCLC were included (median age 66 years, 486 female, 179 African American). Amongst the African American patients, 67.6% were female, a striking difference compared to the white population, where only 49.1% were women (P&lt;0.001). In multivariable analysis, there was no association between gender or race with OS or PFS (P&gt; 0.05). There was an increase in mutational frequency in AA women compared to both AA men and white patients. PIK3CA and KIT mutations were more frequent in females while APC mutations were more frequent in males (P=0.041 for all comparisons). There was a trend toward increased mutational frequencies in TP53, PTEN, and NOTCH1 in AA patients. The relative frequency of gene alterations is shown in the table. In univariable analysis, NOTCH1 mutation was associated with improved OS (HR 0.24 [0.06-0.96], P=0.04). Conclusions: In this large cohort of patients with SCLC followed over 2 decades, there was a striking 2-fold higher incidence of SCLC in AA females than in AA males, although there were no differences in OS or PFS by sex or race. Several genomic alterations occur in higher frequencies in AA patients and AA women, in particular, have higher mutational frequencies.[Table: see text]
Predictive value of germline <i>ATM</i> mutations in the CCTG PA.7 trial: Gemcitabine (GEM) and nab-paclitaxel (Nab-P) versus GEM, nab-P, durvalumab (D) and tremelimumab (T) as first-line therapy in metastatic pancreatic ductal adenocarcinoma (mPDAC).
Authors: Daniel John Renouf, Jonathan M. Loree, Jennifer J. Knox, Petr Kavan, Derek J. Jonker, Stephen Welch, Felix Couture, Frederic Lemay, Mustapha Tehfe, Mohammed Harb, Nathalie Aucoin, Yoo-Joung Ko, Patricia A. Tang, James T. Topham, Shidong Jia, Pan Du, David F. Schaeffer, Sharlene Gill, Dongsheng Tu, Christopher J. O'Callaghan
Journal: Journal of Clinical Oncology (2021)

4135 Background: PA.7 evaluated whether combining PD-L1 and CTLA-4 inhibition with GEM and Nab-P increases efficacy. A previous analysis of the PA.7 data demonstrated high plasma based TMB (≥9 mut/Mb) was associated with improved OS in the Gem, Nab-P, D+T arm. DNA repair pathway aberrations beyond mismatch repair have been associated with potential immune sensitivity. We assessed the predictive value of germline ATM mutations in the PA.7 trial. Methods: This randomized phase II study (ClinicalTrials.gov NCT02879318) assessed the efficacy and safety of GEM, Nab-P, D, and T (arm A) vs. GEM and Nab-P (arm B) in patients (pts) with mPDAC (n = 180). The primary endpoint was overall survival (OS). Pre-treatment plasma was sequenced with the Predicine ATLAS next generation assay (600 gene, 2.4 Mb panel). 2-sided alpha set at 0.1. Results: 180 pts were randomized (119 to arm A and 61 to arm B) There was no significant difference in OS (9.8 months in arm A vs. 8.8 months in arm B, p-value 0.72) or PFS (5.5 months and 5.4 months respectively, HR 0.98, p-value 0.91). Plasma analysis was performed on 174/180 pts with available samples. 16/174 (9.2%) pts had germline ATM mutations, 12 in arm A and 4 in arm B. GEM, Nab-P, D+T was associated with improved OS in patients with ATM mutations (HR 0.10, 90% CI 0.03-0.37; median OS 13.9 months vs. 4.9 months) while no activity was seen in pts with ATM Wild Type (HR 0.99, 90% CI 0.73-1.33; median OS 9.79 months vs. 10.2 months); interaction p = 0.014. Germline ATM mutation status was independent of plasma TMB levels (Wilcoxon p = 0.76). Conclusions: Germline ATM mutation appeared predictive of benefit from the addition of dual immune checkpoint inhibitors (D and T) to Gem and Nab-P, with a significant interaction p-value. In addition to previous data from this trial regarding the predictive value of high plasma TMB (≥9 mut/Mb), this data further supports that there may be independent subgroups of PDAC, beyond MSI-H, that may benefit from immunotherapy, and trials evaluating immunotherapy in subgroups of PDAC with these profiles are warranted. Clinical trial information: NCT02879318.