tbuckley/cabot-search huggingface dataset:
Evaluating a high-dimensional machine-learning model to predict hospital mortality among elderly cancer patients.
Authors: Edmund Qiao, Alexander Qian, Vinit Nalawade, Terrence C. Lee, Nikhil V. Kotha, Rohith S. Voora, Christian Dameff, Christopher John Coyne, James Don Murphy
Journal: Journal of Clinical Oncology (2021)

1512 Background: Elderly hospitalized cancer patients face high risks of inpatient hospital mortality. Identifying patients at high risk of hospital mortality could help with risk stratification, and potentially help inform future interventions aimed at improving outcomes. We evaluated the predictive capacity of a high-dimensional machine-learning prediction tool to predict inpatient mortality, and compared the performance of this new tool to existing prediction indices. Methods: We identified cancer patients 75 and over who presented to an emergency department (ED) and were subsequently hospitalized from the National Emergency Department Sample (NEDS) between 2016 and 2018. We used an extreme gradient boosting approach to predict the risk of death during hospitalization. Model covariates included patient demographics, hospital characteristics, and International Classification of Diseases, version 10 (ICD-10) diagnosis codes recorded during the ED visit. The data were split 75%/25% into training/testing datasets. We constructed the model with training data and evaluated performance within the test data using area under the curve (AUC), with an AUC of 1.0 indicating perfect prediction. We compared the performance of this risk prediction model to standard prediction indices including the Hospital Frailty Risk Score, modified 5-item frailty index, and Charlson comorbidity index. Results: We identified 1,892,690 weighted-hospitalizations among elderly cancer patients, of which 133,379 (7.0%) who died in the inpatient setting. Our final predictive model included 238 features, which contained 5 demographic variables, 3 hospital characteristics, and 230 ICD-10 diagnosis codes. The predictive model achieved an AUC of 0.92. Our comparator models including the Hospital Frailty Risk Score, modified 5-item frailty index, and Charlson comorbidity index achieved AUCs of 0.67, 0.56, and 0.60, respectively. Conclusions: Using a high-dimensional machine-learning model enabled a high level of precision in predicting hospital mortality among elderly cancer patients, substantially out-performing existing prediction indices. High-dimensional prediction models show promise in helping to identify patients at risk of severe adverse outcomes, though additional validation is needed as well as research studying how to implement these tools into practice.
Symptom identification and management in epithelial ovarian cancer.
Authors: Ashley Hickman, Kathryn Jean Ruddy, Deirdre R. Pachman, Kristin Fischer, Parvez Rahman, Krista M. Goergen, Minji Lee, Andrea L. Cheville, Andrea Elisabeth Wahner Hendrickson
Journal: Journal of Clinical Oncology (2021)

5554 Background: A better understanding regarding the burden of treatment side effects in patients with gynecological malignancies could help guide symptom interventions and oncologic therapy decision-making. We aim to inform understanding of symptom burden in epithelial ovarian cancer (EOC) by analyzing patient-reported symptom data from patients treated for this condition over a 16-month period. Methods: Patients receiving medical oncology care at Mayo Clinic Rochester and at Midwest Mayo Clinic Health System community sites have received symptom-focused surveys prior to each medical oncology visit since March 28, 2019 through the Enhanced Electronic Health Record Facilitated Cancer Symptom Control Study (E2C2). These surveys, administered either through the electronic medical record portal or on a clinic tablet prior to each oncology office visit, no more frequently than every 2 weeks, include six linear analogue scales measuring sleep disturbance, pain, anxiety, emotional distress, and fatigue (SPADE), as well as physical dysfunction on a scale of 0 (none) to 10 (as bad as you can imagine). Scores of 0-3 were considered mild symptoms, 4-6 moderate symptoms, and 7-10 severe symptoms. We collected survey results from March 28, 2019 to July 20, 2020 for patients with EOC and reviewed the number of surveys per patient in addition to the average symptom scores. Results: From March 2019 to July 2020, for patients with EOC, there were 2974 encounter-based surveys from 762 patients. The number of surveys completed by each patient ranged from 1-20. The following number of patients returned the correlating number of surveys: 1 survey:240 patients; 2 surveys:145; 3 surveys:79; 4 surveys:56; 5 surveys:58; 6 surveys:45; 7 surveys:38; 8 surveys:27; 9 surveys:22; ≥10 surveys:52. The average score from all surveys for each symptom was: 2.41 for sleep disturbance, 2.03 for pain, 2.32 for anxiety, 1.97 for emotional distress, 3.26 for fatigue, and 2.50 for physical dysfunction. Please see the table for the proportion of surveys that reported symptoms as mild, moderate, or severe. Conclusions: Fatigue and physical dysfunction were reported most frequently in patients with EOC, while emotional distress and pain were reported least frequently. 20% of surveys reported moderate to severe emotional distress, while 40% reported moderate to severe fatigue. A targeted approach to symptom management is needed for patients undergoing EOC evaluation and treatment. Our next steps in this analysis include an assessment of potential predictors of greater symptom burden (e.g., specific treatments, age, and other clinical and sociodemographic characteristics). Clinical trial information: NCT03892967. [Table: see text]
Systemic Lupus Erythematosus
Authors: Sarah Ringold
Journal: JAMA (2005)

Systemic Lupus ErythematosusS ystemic lupus erythematosus (SLE), also called lupus, is an autoimmune disorder in which the body' s immune system (the cells in the body that fight infection) incorrectly attack the body' s own tissues and organs, leading to inflammation and damage.Lupus most commonly affects women of childbearing age but also occurs in children, adolescents, and men.The cause of lupus is unknown, but it has been associated with genetic, environmental, and infectious causes.The disorder may affect almost all organs in the body, with the kidney being most commonly involved.The disorder may be mild in some cases (for example, only involving the skin) and very severe in other cases (affecting multiple organs, including the brain).The disease course is characterized by flares (intervals of active disease) and remissions (intervals of inactive disease).The June 22/29, 2005, issue of JAMA includes an article that describes the available treatments for the kidney disease associated with lupus.
Trends in breast cancer survival by race-ethnicity in Florida.
Authors: Robert Brooks Hines, Asal Johnson, Eunkyung Lee, Stephanie Erickson, Saleh M.M. Rahman
Journal: Journal of Clinical Oncology (2021)

e18556 Background: Considerable efforts to improve disparities in breast cancer outcomes for underserved women have occurred over the past 3 decades. This study was conducted to evaluate trends in survival, by race-ethnicity, for women diagnosed with breast cancer in Florida over a 26-year period to assess potential improvement in racial-ethnic disparities. Methods: This was a retrospective cohort study of women diagnosed with invasive breast cancer in Florida between 1990-2015. Data were obtained from the Florida Cancer Data System. Women in the study were categorized according to race (white/black) and Hispanic ethnicity (yes/no) as non-Hispanic white (NHW), non-Hispanic black (NHB), Hispanic white (HW), and Hispanic black (HB). Cumulative incidence estimates of 5- and 10-year breast cancer death with 95% confidence intervals (CI) were obtained by race-ethnicity, according to diagnosis year. Subdistribution hazard models were used to obtain subdistribution hazard ratios (sHR) for the relative rate of breast cancer death accounting for competing causes. Results: Compared to NHW women, minority women were more likely to be younger, be uninsured or have Medicaid as health insurance, live in high poverty neighborhoods, have more advanced disease at diagnosis, have high grade tumors, have hormone receptor negative tumors, and receive chemotherapy as treatment. Minority women were less likely to receive surgery. Over the course of the study, breast cancer mortality decreased for all racial-ethnic groups, and racial-ethnic minorities had greater absolute and relative improvement in breast cancer survival for nearly all metrics compared to non-Hispanic white (NHW) women. However, for the most recent time period (2010-2015), black women still experienced significant survival disparities with non-Hispanic black (NHB) women having twice the rate of 5-year (sHR = 2.04: 95% CI; 1.91-2.19) and 10-year (sHR = 2.02: 95% CI; 1.89-2.16) breast cancer death. Conclusions: Despite efforts to improve disparities in breast cancer outcomes for underserved women in Florida, additional targeted approaches are needed to reduce the poorer survival in black (especially NHB) women. Our next step is to conduct a mediation analysis of the most important factors driving racial/ethnic disparities in breast cancer outcomes for women in Florida.
REPLY:
Authors: Jasmohan S. Bajaj, Guadalupe Garcia‐Tsao, Patrick S. Kamath, Jacqueline G. O’Leary, K. Rajender Reddy, Florence Wong
Journal: Hepatology (2021)

Potential conflict of interest: Nothing to report. We thank Drs. Jindal and Sharma for their letter, which raised several points that we will clarify in this response.(1) We studied biofluids in nonconsecutive patients because of several stringent criteria needed for inclusion into the study, one of these being sample collection as close to admission as possible to reduce the impact of in‐hospital treatments on metabolomics. In any multicenter cohort, outside of a strict prospective clinical trial of a narrow, highly selected patient population, it is not possible to expect all centers to follow the same diagnostic/treatment algorithm as suggested. Serum and urine were collected within the first day of admission and analyzed separately. Because serum was more informative than urine in predicting outcomes, our data do not support the need to collect both. The quest for new biomarkers was necessitated because previously studied ones, including neutrophil gelatinase–associated lipocalin that is not commercially available, have value in determining the type of acute liver injury (AKI) rather than predicting its development. We set out to discover new biomarkers for the prediction of prognosis, and not to identify AKI phenotypes or response to treatment, given that these often involve more than one metabolic system.(2,3) Therefore, no comparison was indicated. Understanding the results also requires familiarity with random forest analyses. The mean decrease accuracy analysis refers to the ranking, but not cut‐off values (we showed the top 30 metabolites), relative to all others, based on their predictive importance. Jindal and Sharma propose that we only study patients requiring dialysis or patients with a high likelihood of developing irreversible renal damage. This is not intuitive given that these subgroups are already known to have a poor prognosis. Instead, we evaluated patients with AKI who later required dialysis. The diagnosis of chronic kidney disease in cirrhosis is challenging in the best of cases, but in the inpatient setting, where there may or may not be access to outpatient renal function labs, it is even more challenging.(4) Therefore, we refrained from making claims regarding acute‐on‐chronic kidney disease, which we recognize needs to be studied further. Our conclusions remain that a specific group of metabolites collected at admission in patients with cirrhosis add significant value to clinical parameters in predicting the development of AKI. The data from our study warrant external validation to enable the development of laboratory‐based panels capable of predicting AKI in clinical practice. Author Contributions All authors contributed substantially to drafting of the article and its final approval.
A pilot study of the combination of checkpoint inhibition with ablation in subjects with biliary tract cancer.
Authors: Rebecca Wetzel, M. Cecilia Monge B., Changqing Xie, Donna Mabry-Hrones, Santhana Webb, Elizabeth Akoth, Bernadette Redd, Elliot B Levy, Bradford Wood, Tim F. Greten
Journal: Journal of Clinical Oncology (2021)

e16150 Background: Immune checkpoint inhibition has demonstrated modest activity in biliary tract carcinoma (BTC). Augmentation of the immune response by ablative procedures to improve efficacy of immune checkpoint inhibition has been previously demonstrated in hepatocellular carcinoma, however the outcome of the combination of immune checkpoint inhibition with tremelimumab (anti-CTLA4) and durvalumab (anti-PD1) with ablation in advanced biliary tract carcinoma is unclear. The primary objective of this study was to establish the efficacy via 6-month progression-free survival (PFS) of combining tremelimumab and durvalumab in patients with advanced BTC either alone or with tumor ablation. Secondary objectives were safety and feasibility of combination treatment. An exploratory objective was overall survival (OS). Methods: Eligible patients had histologically confirmed advanced or unresectable BTC (intra- or extrahepatic cholangiocarcinoma, gallbladder cancer, or ampullary cancer) who had progressed on, been intolerant to, or refused prior chemotherapy. Disease had to be technically amenable to cryoablation with at least two measurable lesions. Adequate organ function and an ECOG of 0 or 1 were required. Patients were treated with tremelimumab and durvalumab with or without tumor ablation. Tremelimumab and durvalumab were administered intravenously every 28 days for four cycles followed by durvalumab every 28 days until disease progression. Cryoablation was performed on day 36. Patients were imaged every 8 weeks and response was defined per RECIST v 1.1 criteria. Results: In total, 22 patients have been enrolled into the BTC cohort. Half underwent ablation and half received immunotherapy alone. The median age was 59 years (range 21-80). All patients had received prior systemic chemotherapy, locally advanced disease was present in 68% of patients. Median PFS was 2.1m and median OS was 5.6 m. DCR was 45% (SD). Median OS and PFS was similar in the group that received ablation vs immunotherapy alone with a median OS of 6.8 m vs 6.7 m and 2.0 m vs 2.7 m respectively. The most common grade 3- 4 adverse events were lymphopenia (27%), increased AST (41%), increased alkaline phosphatase (32%) and elevated bilirubin (27%). Conclusions: Combination checkpoint inhibition combined with tumor ablative procedures is a safe and effective treatment strategy for patients with advanced BTC, however the addition of ablative therapy may not enhance efficacy in this small cohort of patients. Results illustrate the poor prognosis of advanced BTC and may represent a non-chemotherapeutic approach to treatment in this patient population. Further studies are warranted to identify patient populations most likely to respond to these interventions. Clinical trial information: NCT02821754.
RARE-10. PRIMARY INTRACRANIAL EWING SARCOMA IN A 12 MONTH OLD MALE
Authors: Clay Hoerig, Aaron Goldberg, Jody Pathare, Tuan Dao, Ali Nael Amzajerdi, William Loudon, Ashley Plant-Fox, Joffre Olaya, Chenue Abongwa
Journal: Neuro-Oncology (2021)

Abstract Background Ewing sarcoma (EWS) is a rare type of pediatric bone and soft tissue tumor that accounts for approximately 1% of all pediatric malignancies. It most commonly occurs in the long bones or axial skeleton, and rarely includes extraosseous sites or intracranial involvement. Reports of primary intracranial EWS are minimal. Pediatric intracranial EWS is even more rare with less than 15 cases reported. Case Description We describe the case of primary intracranial EWS in a 12 month old male. The patient’s initial MRI showed a large heterogeneous supratentorial cystic and solid mass centered in the right parietal region measuring 9.1cm x10.3cm x 7.6cm. No distant metastases were detected. The patient underwent surgical resection and pathology was consistent with a small round blue cell tumor. Further pathological evaluation revealed presence of EWSR1-FLI1 fusion and was negative for CD99, GFAP, synaptophysin, Olig2, desmin, and CAM5.2. Stains for INI1 and BRG1 were retained. The patient was treated with adjuvant chemotherapy and focal proton beam radiation (as per AEWS0031). Conclusion Primary intracranial Ewing Sarcoma is a rare pediatric brain tumor and, to our knowledge, this would be the youngest reported case to date. This case demonstrates the successful application of a sarcoma-based regimen to a primary intracranial EWS tumor with no evidence of residual tumor on MRI at 8 months into treatment. Future studies should be directed at understanding the biology of these rare tumors and optimizing treatment approaches.
A multicenter, randomized, phase II trial of anlotinib plus docetaxel versus docetaxel in EGFR-negative NSCLC patients after progression on first-line platinum-base chemotherapy: ALTER-L018.
Authors: Lin Wu, Zhijun Wu, Zemin Xiao, Zhongsha Ma, Jie Weng, Yanhua Chen, Yongqing Cao, Peiguo Cao, Maoliang Xiao, Hui Zhang, Huaxin Duan, Qianzhi Wang, Jia Li, Yan Xu, Xingxiang Pu, Kang Li
Journal: Journal of Clinical Oncology (2021)

e21186 Background: Docetaxel is one of the standard second-line treatments for advanced non-small cell lung cancer (NSCLC), but the effect is limited. The combination of docetaxel and antiangiogenic drug (ramucirumab/nintedanib) has demonstrated antitumor activity as second-line therapy in advanced NSCLC. Anlotinib, an oral multi-target angiogenesis TKI targeting the VEGFR, FGFR, PDGFR and c-Kit, can prolong both PFS and OS of refractory advanced NSCLC patients in phase III trial (ALTER0303). We conducted ALTER-L018 to evaluate improvement of the efficacy and safety of anlotinib plus docetaxel in EGFR-negative refractory advanced NSCLC. Methods: ALTER-L018 (NCT03624309) is an ongoing, open-label, multicenter, randomized, controlled comparative, phase II trial, which was performed at 10 sites in China. Eligible EGFR-negative NSCLC patients (pts), who has been assessed progression after first-line platinum-based chemotherapy (combined with or without Immune checkpoint inhibitors), were randomly assigned (in a 1:1 ratio) to group A (anlotinib: 12mg QD from day 1 to 14 of a 21-day cycle +docetaxel: 75mg/m 2 Q3W) and group B (docetaxel: 75mg/m 2 Q3W). The primary end point was PFS, and secondary end points included OS, ORR, DCR and safety. Results: Between Jan 14, 2019, and Feb 7, 2021, 73 patients (pts.) were enrolled and 8 pts. were excluded from the safety and efficacy analysis set (n = 65) due to inclusion violations. 65 pts characteristics (28 pts in group A / 37 pts in group B): median age: 55(40-71)/57(39-74); male: 82% / 78%; non-squamous NSCLC: 75% / 65%; Immunotherapy in the front line: 18% / 22%. Median PFS were 4.03 months (95%CI: 2.98-5.08) in group A and 1.7 months (95%CI: 0.45-2.95) in group B (HR 0.40; 95% CI :0.21-0.77; p = 0.004); In group A and B, ORR and DCR were 32.14% versus 8.11%(p = 0.042), 82.12% versus 54.05%(p = 0.29), respectively. The adverse events that possibly or definitely related to therapy occurred in 26 (93%) of pts. experienced total of 52 grade 1-2 adverse events in group A, and in 25 (68%) of pts. experienced total of 25 grade 1-2 adverse events in group B. The most common grade ≥3 TRAE were leukopenia (5, 18%), neutropenia (5, 18%) and thrombocytopenia (3, 11%) in group A, and leukopenia (3, 8%), neutropenia (2, 5%) and thrombocytopenia (1, 3%) in group B. Conclusions: This combination of anlotinib and docetaxel showed clinical benefit in EGFR-negative NSCLC patients in terms of PFS, ORR, and with manageable safety profile. It is a viable option for relapsed NSCLC, who has been assessed progression on first-line platinum-base chemotherapy combined with/without Immune checkpoint inhibitors, or who can’t tolerate Immunotherapy. Clinical trial information: NCT03624309.
Combination of atezolizumab and pirfenidone in second-line and beyond NSCLC: A phase I/II study.
Authors: Takefumi Komiya, Jun Zhang, Prakash C. Neupane, Kathan Mehta, Chao Hui Huang
Journal: Journal of Clinical Oncology (2021)

TPS2678 Background: Checkpoint inhibitors (CPI) targeting the PD1/PD-L1 axis significantly improved patient outcomes in stage IV non-small cell lung cancer (NSCLC). However, these patients will eventually develop resistance and progression. There is a need to identify novel treatment options. Poor response to PD-L1 antibody was correlated with increase in cancer-associated fibroblasts (CAF), which is known to interact with cytotoxic T cells (CTLs) by suppressing their function in a manner similar to regulatory T cells (Tregs). Production of cytokines by CAFs leads to impaired antitumor immunity by impairing CTL function (TGF beta) and prevent recruitment/mobilization of CTLs into tumors. These effects suggesting that CAF can be a therapeutic target in lung cancer resistant to checkpoint inhibitors. Pirfenidone (P) is approved to treat pulmonary fibrosis with anti-fibrotic effect by blocking the differentiation of fibroblasts into CAFs and suppress the production of TGF beta and TGF beta-induced signaling pathways/collagens. Atezolizumab is a humanized immunoglobulin (Ig) G1 monoclonal antibody that targets PD-L1 and inhibits the interaction between PD-L1 and its receptors, PD-1 and B7-1 (CD80), both of which function as inhibitory receptors expressed on T cells. We proposed a phase I/II trial to test the combination of atezolizumab (A) with P in patients with recurrent non-small cell lung cancer (NSCLC) after progression with CPI. The primary objective of phase I is to determine the maximum tolerated (MTD) dose of P in combination with A and assess the safety and tolerability of this combination. The secondary objective is to determine the efficacy of AP in all NSCLC participants treated in this study. Exploratory objectives include the measurement of circulating levels of TGF beta and research in expression of CAF related proteins. Methods: The initial phase I will enroll 3 patients using P at 801 mg po TID. A will be at 1200mg iv every 3 weeks. If there is ≤ 1 DLT, the study will proceed to phase II If there are 2- 3 DLT, P will be reduced to 534 mg TID. If there is ≤ 1 DLT, then this dose will proceed to phase II. If there is 2-3 DLT, then the study will be terminated. The phase II will enroll 16 patients to assess efficacy. Main inclusion criteria are patients with recurrent NSCLC after progression with first-line therapy CPI with or without chemotherapy, measurable disease, ECOG 0-2, and adequate organ function. Clinical trial information: NCT04467723.