tbuckley/cabot-search huggingface dataset:
Improving tolerability of pembrolizumab with weight based dosing: A meta-analysis.
Authors: Nabeela Khan Patail, Amna Falak Sher, Shenhong Wu
Journal: Journal of Clinical Oncology (2021)

2639 Background: Pembrolizumab, a PD-1 immune checkpoint inhibitor (ICI), has demonstrated significant clinical activity in various cancers. Despite a favorable toxicity profile, discontinuation due to adverse events including immune related adverse events (irAE) has been reported. We conducted a meta-analysis of published clinical trials to evaluate the tolerability of pembrolizumab in cancer patients. Methods: A systematic review was conducted of relevant studies from the databases of PubMed and abstracts presented at American Society of Clinical Oncology (ASCO) from June 2015 until September 2020. Eligible studies included prospective clinical trials that reported a discontinuation rate due to adverse effects. Incidence, relative risk and 95% confidence intervals (CI) were calculated by employing fixed or random effects models. Results: A total of 6,380 patients with a variety of hematologic and solid malignancies from 20 studies of pembrolizumab were included for analysis. The overall rate of pembrolizumab discontinuation due to adverse events was 8.2% (95% CI: 6.4-10.4%). The discontinuation rate of pembrolizumab was not significantly lower than the chemotherapy controls, with RR of 0.84 (95% CI: 0.58-1.12, p = 0.33). However, the discontinuation rate of pembrolizumab was significantly higher compared to placebo control with RR of 2.20 (95% CI: 1.36-3.54, p &lt; 0.001), and significantly lower compared to ipilimumab with RR of 0.58 (95% CI: 0.34-0.99, p = 0.04) respectively. The discontinuation rate varied widely among different tumor types with the lowest rate of 0.8% (95% CI: 0.2-3%) in gastric cancer, and the highest of 13.5% (95% CI: 10.8-16.8%) in head and neck squamous cell carcinoma. Interestingly, the discontinuation rate varied with pembrolizumab dosing, with the fixed dosing of 200mg being 9.2% (95% CI: 6.9-12%) and the weight-based dosing being 6.5% (95% CI: 4.8-8.8%). The weight-based dosing was associated with a significantly lower discontinuation rate compared to controls with RR of 0.62 (95% CI: 0.47-0.81, p &lt; 0.0001), while the fixed dosing had similar discontinuation rate with RR of 1.03 (95% CI: 0.89-1.20, p = 0.67). Conclusions: The tolerability of pembrolizumab may be comparable to chemotherapy in cancer patients and may vary with its dosing. Future studies are warranted to evaluate the impact of different dosing.
The impact of COVID-19 on breast cancer stage at diagnosis.
Authors: Maxwell Roger Lloyd, Sarah Jo Stephens, Julian C. Hong, Ted A. James, Tejas Mehta, Abram Recht, Daphna Spiegel
Journal: Journal of Clinical Oncology (2021)

528 Background: During the SARS-CoV-2 pandemic, routine screening mammography (SM) was stopped and diagnostic mammography (DM) was limited for several months across the United States in order to reduce patient exposure and redeploy medical personnel. We hypothesized that this delay would result in patients presenting with later-stage disease following the initial shutdown. Methods: Patients diagnosed with invasive breast cancers from 2016-2020 were identified using the Beth Israel Deaconess Medical Center Cancer Registry. Baseline patient characteristics, demographics, and clinical information were gathered and cross-referenced with our electronic medical record. Late-stage disease was defined as initial anatomic stage III-IV disease in the AJCC 8 th edition staging system. The control cohort consisted of patients diagnosed from 2016-2019; patients diagnosed in 2020 were the test cohort. Chi-squared analysis was used to compare monthly distributions in stage at diagnosis between the control and test cohorts. Multivariate analysis was performed using a logistic regression model. Results: There were 1597 patients diagnosed with invasive breast cancer between 2016-2019 and 333 in 2020. Median age at diagnosis was 60 years; 99% were female, and 69.1% were white. Mammography was limited from 3/16/20-6/8/20, with 90% reduction in volume during this time. The number of screening studies performed in March, April, May, and June of 2020 were 987, 1, 4, and 721 compared to 2042, 2141, 2241, and 2142 in 2019. The volume of new diagnoses per month decreased substantially during the shutdown (see table). The proportion of patients diagnosed with late-stage disease was 6.6% in the control cohort compared to 12.6% in the 2020 test cohort (p &lt; 0.001); 92.9% of late-stage diagnoses in 2020 occurred from June to December following the shutdown period. On multivariate analysis, year of diagnosis (2020 vs 2016-2019; OR = 4.25 95% CI 0.035-0.095, p &lt; 0.001), lower income (&lt;200% of the federal poverty level; OR = 2.73 95% CI 0.016-0.099, p = 0.006) and increased Charlson Comorbidity Index (OR = 12.01 95% CI 0.037-0.052, p &lt; 0.001) were associated with later stage at diagnosis. Conclusions: Patients were more likely to be diagnosed with late-stage breast cancer following the global shutdown due to the SARS-CoV-2 pandemic. Patients with lower income and medical comorbidities were disproportionately affected. These data raise significant concerns regarding the impact of SARS-CoV-2 on cancer diagnoses and long-term outcomes, especially in vulnerable patient populations.[Table: see text]
Monitoring of Circulating Tumor DNA Improves Early Relapse Detection After Axicabtagene Ciloleucel Infusion in Large B-Cell Lymphoma: Results of a Prospective Multi-Institutional Trial
Authors: Matthew J. Frank, Nasheed M. Hossain, Ali Bukhari, Erin Dean, Jay Y. Spiegel, Gursharan K. Claire, Ilan Kirsch, Allison P. Jacob, Chelsea D. Mullins, Lik Wee Lee, Katherine A. Kong, Juliana Craig, Crystal L. Mackall, Aaron P. Rapoport, Michael D. Jain, Saurabh Dahiya, Frederick L. Locke, David B. Miklos
Journal: Journal of Clinical Oncology (2021)

Although the majority of patients with relapsed or refractory large B-cell lymphoma respond to axicabtagene ciloleucel (axi-cel), only a minority of patients have durable remissions. This prospective multicenter study explored the prognostic value of circulating tumor DNA (ctDNA) before and after standard-of-care axi-cel for predicting patient outcomes.Lymphoma-specific variable, diversity, and joining gene segments (VDJ) clonotype ctDNA sequences were frequently monitored via next-generation sequencing from the time of starting lymphodepleting chemotherapy until progression or 1 year after axi-cel infusion. We assessed the prognostic value of ctDNA to predict outcomes and axi-cel-related toxicity.A tumor clonotype was successfully detected in 69 of 72 (96%) enrolled patients. Higher pretreatment ctDNA concentrations were associated with progression after axi-cel infusion and developing cytokine release syndrome and/or immune effector cell-associated neurotoxicity syndrome. Twenty-three of 33 (70%) durably responding patients versus 4 of 31 (13%) progressing patients demonstrated nondetectable ctDNA 1 week after axi-cel infusion (P < .0001). At day 28, patients with detectable ctDNA compared with those with undetectable ctDNA had a median progression-free survival and OS of 3 months versus not reached (P < .0001) and 19 months versus not reached (P = .0080), respectively. In patients with a radiographic partial response or stable disease on day 28, 1 of 10 patients with concurrently undetectable ctDNA relapsed; by contrast, 15 of 17 patients with concurrently detectable ctDNA relapsed (P = .0001). ctDNA was detected at or before radiographic relapse in 29 of 30 (94%) patients. All durably responding patients had undetectable ctDNA at or before 3 months after axi-cel infusion.Noninvasive ctDNA assessments can risk stratify and predict outcomes of patients undergoing axi-cel for the treatment of large B-cell lymphoma. These results provide a rationale for designing ctDNA-based risk-adaptive chimeric antigen receptor T-cell clinical trials.
Natural History and Outcomes of Asymptomatic IgM Monoclonal Gammopathy
Authors: Efstathios Kastritis, Nikolaos Kanellias, Maria Gavriatopoulou, Evangelos Eleutherakis-Papaiakovou, Maria Roussou, Alexandra Papathoma, Ioannis Panagiotidis, Magdalini Migkou, Despina Fotiou, Dimitrios C. Ziogas, Ioannis Ntanasis-Stathopoulos, Marilyn Spyropoulou-Vlachou, Anna Tasidou, Evangelos Terpos, Meletios A. Dimopoulos
Journal: Blood (2017)
Outcomes of non-treatment naive melanoma patients with central nervous system relapse.
Authors: Thiago Pimentel Muniz, Hadee Lone, Diana Paola Arteaga, Diana Gray, Maysa Tamara Silveira Vilbert Pereira, Luke Mantle, Raviya Singh, Sofia Genta, Samuel Saibil, David Hogg, Anna Spreafico, Marcus O. Butler
Journal: Journal of Clinical Oncology (2021)

9557 Background: Melanoma has a high probability of central nervous system (CNS) spread. Although first line nivolumab and ipilimumab resulted in 56% response rate and 29.2 months median overall survival (OS) in patients with melanoma brain metastases (MBM), there is paucity of data for patients who develop MBM after prior systemic therapy. As this subgroup is often underrepresented in clinical trials, we aimed to evaluate the OS of non-treatment naïve patients who develop MBM and identify factors related to survival. Methods: In this single-center, retrospective study, consecutive melanoma patients with &gt; 90 days from exposure to either immune checkpoint inhibitor (ICI), targeted therapy (TT), or chemotherapy, to CNS relapse were included. OS was defined as the time between CNS relapse and death by any cause. The Log-Rank method was used to calculate OS. Cox regression analysis was used to identify differences between subgroups. Variables with a p value &lt; 0.1 were included in a multivariate model. A p value &lt; 0.05 was considered statistically significant. Results: Between 2012 and 2018, 135 patients were identified. Median age was 57 (29-92) years, 92 (68%) were male, and median number of prior systemic therapies was 2 (1-6). One-hundred and nine (81%) patients had cutaneous melanoma; acral lentiginous melanoma (ALM) comprised 11 (8%) patients. Molecular studies were available for 123 patients, of whom 61 (50%) were BRAF V600 mutant. Eighty-nine (66%) patients had prior ICI, of whom 33 (37%) had prior exposure to both anti-PD1 and anti-CTLA-4, either as monotherapy or combination. Amongst the BRAF V600 mutant population, 48 (79%) had prior TT. Radiotherapy was given to 112 patients, of whom 55 (49%) had SRS. Median follow-up was 41 (95% CI 30-51) months. Median OS was 6.4 (95% CI 5.3-7.5) months. Patients with ALM, &gt; 3 MBM, ECOG 2-4 and active treatment at CNS relapse (&lt; 30 days from last dose of treatment to MBM diagnosis) were at increased risk of death, whilst subsequent treatment with ICI was related to better survival (Table). On multivariate analyses, age ( p = 0.007), subtype ( p = 0.04), number of MBM ( p = 0.01), active treatment at CNS relapse ( p &lt; 0.001) and subsequent ICI ( p = 0.002) remained statistically significant. Exploratory analyses suggested subsequent treatment with anti-PD1 + anti-CTLA-4 (n = 42) compared favourably to subsequent anti-CTLA-4 only (n = 21) (13 x 7 months, p = 0.004), and was independent of prior ICI. Conclusions: Previously treated melanoma patients who develop MBM have a poor prognosis, but subsequent ICI therapy seems to be associated with better OS. Further clinical investigation to identify optimal anti-PD1-based therapies is warranted for non-treatment naïve patients who develop MBM.[Table: see text]
Clinical predictive markers of response to immune checkpoint inhibitor therapy in advanced non-small cell lung cancer.
Authors: Raena Rhone, Katerine Dumais, Herman W. Powery, Frank Gentile, Luis E. Raez
Journal: Journal of Clinical Oncology (2021)

e21044 Background: Overweight and obesity have been associated with improved overall survival (OS) and progression-free survival (PFS) in patients treated with immune checkpoint inhibitors (ICI). EPSILoN score (EPSILoN), comprised of five clinical variables (smoking, Eastern Cooperative Oncology Group performance status, liver metastases, lactate dehydrogenase (LDH), and neutrophil-lymphocyte ratio), is a known predictive marker of response to ICI. This study aims to validate body mass index (BMI) and EPSILoN as predictive markers of response in frontline treatment of advanced non-small cell lung cancer (NSCLC) with ICI with or without concomitant chemotherapy. Methods: Patients with advanced NSCLC who received frontline ICI were identified using the electronic medical record. PFS and OS were retrospectively evaluated and stratified based on baseline BMI and EPSILoN. Due to lack of routine LDH testing, a modified EPSILoN (mEPSILoN) was used. For statistical analysis, log-rank tests were used to compare PFS and OS between groups, and Kaplan-Meier survival curves were used to report PFS and OS. Results: Thirty-six normal weight (NW) and 25 overweight and obese (OWO) patients were studied. Median PFS (mPFS) for OWO vs NW patients was 8.90 months vs 5.53 months (HR 0.54; 95% CI, 0.30-0.96; p = 0.04). mPFS at 12 months was 45% for OWO patients vs 23% for NW patients. Of the patients with PD-L1 ≥ 50%, 14 patients were NW and 11 patients were OWO. Among patients with PD-L1 ≥ 50%, mPFS for OWO was not reached (NR) vs 6.73 months in NW patients (HR 0.23; 95% CI, 0.09-0.60; p = 0.003), and the percent of patients that were PF at 12 months was 71% vs 15%. Of 56 patients with a calculable mEPSILoN, 29 patients had baseline mEPSILoN 1 and 27 patients had mEPSILoN 2-3. Median OS for patients with mEPSILoN 1 vs 2-3 was NR vs 11.13 months (HR 0.32; 95% CI, 0.14-0.76; p = 0.01) and 78% vs 49% survived at 12 months. Conclusions: OWO and lower mEPSILoN were associated with longer PFS and OS, respectively, in patients with advanced NSCLC who were treated with frontline ICI with or without concomitant chemotherapy, regardless of PD-L1 expression. These findings are consistent with recent studies that have reported these parameters as predictive markers of response in patients with NSCLC. However, this is the first study to our knowledge to evaluate these markers in frontline ICI treatment with or without chemotherapy.[Table: see text]
Patients’ perceptions of care coordination among NCORP therapeutic clinical trial participants: A matched case-control study.
Authors: Izumi Okado, Ian Pagano, Jessica Rhee, Jeffrey L. Berenberg, Randall F. Holcombe
Journal: Journal of Clinical Oncology (2021)

e13504 Background: Effective coordination of care (CC) is a critical component of high-quality cancer care; however, many patients with cancer continue to receive poorly coordinated care. CC experiences among therapeutic clinical trial (CT) participants are relatively unknown. We examined cancer patients’ perceptions of CC among CT participants using a validated Care Coordination Instrument (CCI). Methods: The study sample (N = 90) consisted of 45 CT participants and 45 matched non-participants from archival data from our prior CC studies. 171 patients who participated in therapeutic cancer clinical trials through the Hawaii Minority/Underserved NCI Community Oncology Research Program (NCORP) between 2015 and 2020 were contacted for study participation, and 26% completed the CCI. The CCI measures overall perceptions of CC and across 3 domains (Communication, Navigation, Operational). Paired t-tests were used to compare overall and domain scores between CT participants and non-participants. The two groups were matched by age, gender, cancer type (breast, GI, other), and clinical stage. Results: Among CT participants, the mean age was 61.7 ( SD = 9.4), and the majority were female (67%) and Asian (56%). The most common cancer types were breast (27%) and GI (16%), with 24% with stage III disease. CT participants reported significantly higher total CC scores than non-participants (62.5 vs. 55.8; p = .0008). Similar trends were found for Navigation ( p = .007) and Operational ( p = .001) domain scores. 29% of CT participants reported receiving high-intensity CC assistance from their clinical research associates (CRAs), and 27% indicated receiving moderate-level CC assistance. Responses to open-ended questions regarding CC revealed that CT participants received assistance with a variety of CC activities from their CRAs, including scheduling appointments and explaining test results and procedures. Conclusions: Patients who participate in therapeutic cancer clinical trials report more positive perceptions of CC compared to non-participants. Qualitative data suggest that significant care coordination support is provided by the clinical research associate. The results underscore the importance of CC support provided by CRAs who may be an unrecognized component of the healthcare delivery team. CC provided by CRAs may contribute to improved quality and value of cancer care for patients enrolled on therapeutic clinical trials.
Prognostic Impact of 18F-FDG PET/CT in Patients With Aggressive B-Cell Lymphoma Treated With Anti-CD19 Chimeric Antigen Receptor T Cells
Authors: Pierre Sesques, Jérémie Tordo, Emmanuelle Ferrant, Violaine Safar, Florent Wallet, Anthony Dhomps, Gabriel Brisou, Fadhela Bouafia, Lionel Karlin, Dana Ghergus, Camille Golfier, Helène Lequeu, Anne Lazareth, Marlène Vercasson, Carole Hospital-Gustem, Vérane Schwiertz, Marion Choquet, Pierre Sujobert, Silvana Novelli, Valérie Mialou, Olivier Hequet, Sylvain Carras, Ludovic Fouillet, Laure Lebras, Yann Guillermin, Cécile Leyronnas, Doriane Cavalieri, Marc Janier, Hervé Ghesquières, Gilles Salles, Emmanuel Bachy
Journal: Clinical Nuclear Medicine (2021)

Purpose of the Report We aimed to evaluate the role of 18 F-FDG PET/CT in predicting patient outcome following chimeric antigen receptor T (CAR T) cells infusion in aggressive B-cell lymphoma. Methods 18 F-FDG PET/CT data before leukapheresis, before CAR T-cell infusion and 1 month (M1) after CAR T-cell infusion, from 72 patients were retrospectively analyzed. SUVmax, total lesion glycolysis (TLG), metabolic tumor volume (MTV), and parameters describing tumor kinetics were calculated for each 18 F-FDG PET/CT performed. The aim was to evaluate the prognostic value of 18 F-FDG PET/CT metabolic parameters for predicting progression-free survival (PFS) and overall survival (OS) following CAR T-cell therapy. Results Regarding PFS, ∆MTV pre-CAR and ∆TLG pre-CAR were found to be more discriminating compared with metabolic parameters at preinfusion. Median PFS in patients with a ∆MTV pre-CAR of less than 300% was 6.8 months (95% confidence interval [CI], 2.8 months to not reached) compared with 2.8 months (95% CI, 0.9–3.0 months) for those with a value of 300% or greater ( P = 0.004). Likewise, median PFS in patients with ∆TLG pre-CAR of less than 420% was 6.8 months (95% CI, 2.8 months to not reached) compared with 2.7 months (95% CI, 1.3–3.0 months) for those with a value of 420% or greater ( P = 0.0148). Regarding OS, metabolic parameters at M1 were strongly associated with subsequent outcome. SUVmax at M1 with a cutoff value of 14 was the most predictive parameter in multivariate analysis, outweighing other clinicobiological variables ( P &lt; 0.0001). Conclusions Disease metabolic volume kinetics before infusion of CAR T cells seems to be superior to initial tumor bulk itself for predicting PFS. For OS, SUVmax at M1 might adequately segregate patients with different prognosis.
Challenges in lung cancer multidisciplinary collaboration experienced by specialists in four countries.
Authors: Suzanne Murray, Vivek Subbiah, Christian Grohé, Kazuhiko Nakagawa, Sacha Zahabi, Anthony Sireci, Steven I. Sherman, Elizabeth Kelly, Patrice Lazure
Journal: Journal of Clinical Oncology (2021)

e23002 Background: The importance and challenges of Multidisciplinary Team (MDT) collaboration in managing lung cancer have been increasingly recognized in an ever more complex therapeutic environment. Data on physicians’ viewpoints regarding MDT collaboration in lung cancer care, collected in a broader study assessing challenges related to lung/thyroid cancer patient management, are presented. Methods: A mixed-methods approach was used to analyze this data, combining qualitative interviews and a quantitative survey. Pulmonologists (PLM), oncologists (ONC) and pathologists (PTH) from Germany (GE), Japan (JP), the United Kingdom (UK) and the United States (US) were recruited. Results: A total of 44 specialists participated in interviews and 377 in a survey. Quantitative data reveal that 53% of pulmonologists in JP and 39% in GE have suboptimal knowledge of the timing of patient referral to an oncologist. Fewer PLM/PTH from JP (43%/47%) report a fully integrated MDT team approach in their clinical setting, compared to those from GE (80%/95%), the UK (96%/82%) and the US (82%/97%). Qualitative data indicate that current MDT team practices are perceived as delaying patient care due to significant inefficiencies (sometimes due to lack of knowledge/skills) and unclear responsibilities within the team. Around half of ONC in each country and 78% of PLM from the UK report a gap in knowledge and relevance of each genetic biomarker test according to clinical presentation. PTH in the UK (70%), the US (50%), and JP (72%) report sub-optimal skills identifying biomarker tests to inform the progression of lung cancer (also a challenge for PLM/ONC). Conclusions: This study indicates a need for multi-level interventions addressing systemic and attitudinal barriers as well as knowledge gaps which affect physicians’ ability to collaborate in lung cancer care.
Impact of machine learning-directed on-treatment evaluations on cost of acute care visits: Economic analysis of SHIELD-RT.
Authors: Divya Natesan, Samantha M. Thomas, Eric Eisenstein, Neville Eclov, Nicole Dalal, Sarah J. Stephens, Mary Malicki, Stacey Shields, Alyssa Cobb, Yvonne Marie Mowery, Donna Niedzwiecki, Jessica Tenenbaum, Manisha Palta, Julian C. Hong
Journal: Journal of Clinical Oncology (2021)

1509 Background: SHIELD-RT was a randomized controlled quality improvement study (NCT03775265) that implemented electronic health record-based machine learning (ML) to direct supplemental visits for high risk (HR) patients undergoing radiotherapy (RT). Acute care visits (ER visits or hospitalizations) were reduced from 22% to 12%. We evaluated the costs associated with acute visits in this study. Methods: Patients who initiated RT between 1/7/19 and 6/30/19 at a single institution were evaluated by a ML algorithm to identify HR courses (&gt;10% risk of acute visit during RT). HR patients were randomized to standard weekly (S) or intervention of twice weekly (TW) evaluation during RT. Cost data associated with acute visits were obtained and compared between patients who underwent S or TW evaluations. Missing cost data were imputed using disease related groups (DRGs). Mean costs (standard deviation) were compared between arms with non-parametric Wilcoxon Rank Sum tests. Results: 311 HR courses were identified and randomized to either S (n=157) or TW (n=154) evaluations during RT. 85 patients (S: 51; TW: 34) had 121 distinct acute care visits (S: 74; TW: 47). Patients in the TW evaluation arm had fewer hospitalizations (29 vs 41) and ER visits (18 vs 33) than those in the S arm. There were fewer acute visits per patient in the TW arm (0.34) compared to S arm (0.49). Actual cost data was available for 102 visits at our institution, and imputed for 19 outside hospital visits. Mean cost associated with acute visits was lower in the TW arm ($1939, SD $5912) compared with the S arm ($4002, SD $11568; p=0.03). Differences in mean cost between arms are presented in the table. Conclusions: ML-directed evaluations for HR patients undergoing RT resulted in decreased costs of ER visits and hospitalizations. Costs were decreased across revenue centers, with the largest difference related to inpatient room costs. Future analyses will incorporate intervention costs, which are currently bundled with RT reimbursement.[Table: see text]