Showing papers by "Mary J. Fidler published in 2019"

Results of a phase 2a, multicenter, open-label, study of RM-1929 photoimmunotherapy (PIT) in patients with locoregional, recurrent head and neck squamous cell carcinoma (rHNSCC).

Abstract: 6014Background: Patients with rHNSCC who have failed standard of care have poor prognoses and limited therapeutic options. In this study, final results are reported of a phase 2a trial of photoimmu...

Theoretical and Practical Implications of Treating Cachexia in Advanced Lung Cancer Patients.

Abstract: Lung cancer continues to be a major worldwide health issue, with more than 50% of patients having incurable metastatic disease at diagnosis. Fortunately, the advanced lung cancer treatment landscape is changing rapidly as a result of the positive impact of effective inhibitors of tumor driver mutations, and the more recent discovery that immune modulation with anti-PD-1/PD-L1 monoclonal antibodies results in tumor regression and prolonged survival. While a relatively small subset of lung cancer patients are candidates for inhibitors of driver mutations, the majority of advanced lung cancer patients are candidates for an immunotherapy regimen. Many of these patients have cachexia, which is associated with increased cancer therapy toxicity and possibly reduced responsiveness to immunotherapy. Two ongoing cachexia trials, one testing a ghrelin analogue and the other testing a multimodal strategy, have endpoints which assess clinical benefit-weight gain and relief of anorexia/cachexia symptoms. Provided that the trial objectives are achieved, these treatment strategies will provide a way to relieve suffering and distress for cachectic cancer patients. While awaiting the results of these trials, it would be reasonable to consider designing studies testing cachexia treatments combined with first-line immunotherapy and chemotherapy-immunotherapy in stage IV lung cancer patients, with enhanced overall survival being one of the endpoints.

Prognostic Significance of Skeletal Muscle Loss During Early Postoperative Period in Elderly Patients with Esophageal Cancer.

Abstract: In this issue of Annals of Surgical Oncology, Takahashi et al. report that skeletal muscle reduction in the highest tertile of their patient series was associated with worse cancer-free and overall survival after an oncologic esophagectomy. The patients were 65 years of age or older, had no cancer recurrence at 4 months, and had undergone R0 resections. The skeletal muscle index (SMI) analysis remained significant in the multivariate analysis for recurrence-free and overall survival. In fact, SMI loss in the highest tertile of patients had a hazard ratio (HR) of 5.405 for death (p\\ 0.001; 95% confidence interval [CI], 3.514–8.314) and showed similar findings for recurrence-free survival. The patients with the highest tertile of skeletal muscle loss had more node-positive pathology at the time of resection, suggesting that the presence of microscopic disease may have correlated with the loss of skeletal muscle. Pre-therapeutic sarcopenia in esophageal cancers is highly prevalent as well as significantly and independently associated with postoperative complications, chemotherapy-induced toxicity, and poor survival in cancer patients, as shown in a recent systematic review. Although we have no information on the use of postoperative enteral feeding and skeletal muscle index in this setting, enteral feeding has not demonstrated improvement in terms of postoperative weight loss. Nagata et al. also studied postoperative skeletal muscle mass after esophagectomy and found that reduced skeletal muscle in the psoas muscle 6 months after esophagectomy did not correlate with preoperative nutrition status or neoadjuvant therapy. Their series showed no association with cancer recurrence, although the patients with presarcopenia at the 6-month mark did have more pneumonia and a doubling of 12-month mortality (24.1% vs 11.7%; p = 0.11). The most accepted and current definition of sarcopenia as per the European Working Group on Sarcopenia in Older People (EWGSOP) is the accelerated loss of skeletal muscle mass and function. Sarcopenia is a hallmark of cancer cachexia, and its diagnosis is heavily reliant on measurement of the muscle mass. Among the objective noninvasive methods for evaluating sarcopenia, computed tomography (CT) and magnetic resonance imaging (MRI) are considered gold standards. Quantification and quality of muscle mass can easily be derived from CT and positron emission tomography (PET)CT studies routinely performed for staging and restaging in oncology patients without any extra cost. In particular, CTderived muscle mass at L3 has been shown to correlate well with whole-body muscle mass. Although semiautomatic muscle segmentation is the current trend for obtaining the CT-derived measures of muscle mass and myostatosis, the variations in the CT acquisition parameters and the image analysis techniques make it difficult to compare data across techniques. Although successful therapeutic targeting of cancer cachexia may not eliminate microscopic disease, it could alleviate some of the postoperative complications associated with cachexia. Findings have demonstrated that patients after esophagectomy have decreased ghrelin secretion, which can lead to early satiety, decreased Society of Surgical Oncology 2019

Decreasing BMI/weight immediately prior to starting anti-PD-1/PDL-1 monoclonal antibodies for treatment for stage IV non-small cell lung cancer is associated with shorter progression-free survival.

Abstract: e20710Background: Currently, prognostic markers associated with immunotherapy treatment outcomes in patients with metastatic NSCLC include PDL-1 expression, tumor mutational burden (TBM), and neutr...

Abstract 426: Autoantibodies: A promising prognostic tool for immunotherapy response in advanced non-small cell lung cancer

Abstract: Background: Immune-checkpoint blockade has revolutionized cancer therapy in advanced non-small cell lung cancer (NSCLC). Tissue expression of programmed death protein ligand (PD-L1) remains the gold standard for patient stratification, however, the limited performance of this marker encourages investigations for improved molecular diagnostics. The objective of this study is to identify and evaluate the role of neoantigen-associated autoantibodies to predict the clinical response to anti-PD-1/-L1 in advanced stage NSCLC. Method: Lung adenocarcinoma A549 and H358 cell lysate proteins were resolved via 2-dimensional electrophoresis, electroblotted onto nitrocellulose, and immunoprobed with pooled, pretreatment sera (n= 4/ group) derived from patients with advanced NSCLC who received PD-1/-L1 directed immunotherapy. These patients have documented disease progression within 12 weeks (“rapid progression”) or demonstrated radiographical stable disease/progression after the first 180 days of therapy (“late progression”). Immunoreactive spots were detected with an HRP-conjugated, anti-human IgG secondary antibody with digital densitometry. A 4-fold cutoff threshold in expression was used to prioritize spots for identification via tandem mass spectrometry. From A549 cells, recombinant proteins were selected for STIP-1, annexin A2, HSPA8, and GAPDH. These proteins were then analyzed via immunoblotting methods using sera from each indicated group (n=4 per group). In addition, identified proteins from H358 cells include FH, HSP70B, IMPDH2, NY ESO-1, PGAM-1, and vimentin. Recombinant versions of a selection of autoantigens identified in this manner were commercially acquired and used to develop custom Luminex immunobead assays to quantitatively assess autoantibody production in individual patient sera (rapid progressors, n=14; late progressors, n=18). Values were statistically compared via Mann-Whitney test. Results: Series of differentially expressed autoantigens predictive of clinical response to PD-1/-L1 directed immunotherapy were identified. Western blots of neoantigens identified from A549 cells; STIP-1, annexin A2, HSPA8, and GAPDH were significantly able to distinguish between response groups (p-value Conclusion: Our study demonstrates that serum autoantibodies have great promise to serve as a robust tool to prognosticate response for patients receiving PD-1/-L1 directed immunotherapy and potentially aid current treatment selection methods. Additional targets are currently being developed into multiplexed immunobead assays for evaluation across larger cohorts of patients. Citation Format: Imad Tarhoni, Cristina Fhied, Melissa Pergande, Revathi Kollipara, Connor J. Wakefield, Katherine Gallo, Apoorva Tangri, Marta Batus, Mary Jo Fidler, Philip Bonomi, Jeffrey A. Borgia. Autoantibodies: A promising prognostic tool for immunotherapy response in advanced non-small cell lung cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 426.

Changes in skeletal muscle mass during PD-1 and PD-L1 checkpoint inhibitor therapy in advanced-stage non-small cell lung cancer patients.

Abstract: e14061Background: Severe skeletal muscle loss (sarcopenia) is a principle property of cancer cachexia and is found to be a hallmark of poor prognosis in patients with advanced non-small cell lung c...

Clinical benefit of next generation sequencing in soft tissue and bone sarcoma: Rush University Medical Center’s experience.

Abstract: e22552Background: The overall survival for metastatic sarcoma has remained at only 18-20%. In the era of next generation sequencing (NGS), much research is ongoing on identifying optimal treatments...

Associations between baseline serum biomarker levels and cachexia/precachexia in pretreated non-small cell lung cancer (NSCLC) patients.

Abstract: 3054Background: We previously reported associations of pretreatment serum biomarkers with clinical outcomes in a cohort of advanced NSCLC patients that progressed on front-line therapy. This study ...