R. Sadek

A Phase I study of NLG919 for adult patients with recurrent advanced solid tumors

Meeting abstracts Clinical Trial Registration Number: [NCT02048709][1] The enzyme Indoleamine 2,3-dioxygenase (IDO1) catalyzes the cleavage of L-tryptophan, resulting in the production of kynurenine. Tryptophan depletion and kynurenine metabolites enhance the number and function of Tregs (

Use a survival model to correlate single-nucleotide polymorphisms of DNA repair genes with radiation dose-response in patients with non-small cell lung cancer.

PURPOSE This study utilizes a survival model and clinical data with various radiation doses from prospective trials to determine radiation dose-response parameters, such as radiosensitivity, and identify single-nucleotide-polymorphism (SNP) biomarkers that can potentially predict the dose response and guide personalized radiotherapy. METHODS The study included 92 consecutive stage-III NSCLC patients with doses varying from 60 to 91Gy. Logistic regression analysis of survival varying with SNP genotype and radiation dose was used to screen candidates for dose-response analysis. The dose-response parameter, represented by D50, was derived by fitting survival data into a model that takes into account both tumor control and treatment mortality. A candidate would be considered as a predictor if the 90% confident intervals (90% CIs) of D50 for the 2 groups stratified by the SNP genotype were separated. RESULTS One SNP-signature (combining ERCC2:rs238406 and ERCC1:rs11615) was found to predict dose-response. D50 values are 63.7 (90% CI: 53.5-66.3) Gy and 76.1 (90% CI: 71.3, 84.6) Gy for the 2 groups stratified by the genotypes. Using this biomarker-based model, a personalized dose prescription may be generated to improve 2-year survival from ∼50% to 85% and ∼3% to 73% for hypothetical sensitive and resistant patients, respectively. CONCLUSIONS We have developed a survival model that may be used to identify genomic markers, such as ERCC1/2 SNPs, to predict radiation dose-response and potentially guide personalized radiotherapy.

Free Lung Cancer Screening Trends Toward a Twofold Increase in Lung Cancer Prevalence in the Underserved Southeastern United States

Objectives The National Lung Screening Trial (NLST) reported that the prevalence of lung cancer in individuals at high risk for the disease is 1%, and that screening these individuals using low-dose helical computed tomography of the chest saves lives. To increase screening accessibility in the underserved southeastern United States, we developed a free lung screening program, modeled after the Lahey Hospital & Medical Center Free Lung Screening Program, for individuals meeting National Comprehensive Cancer Network high-risk criteria. Methods This was a chart review of 264 participants screened in the first year of our program. Participants were divided into categories based on the Lung Imaging Reporting and Diagnostic System. Categories three and four were considered positive findings, with demographic and disease criteria collected on these patients. Results Of 264 participants screened, 28 (10.6%) were Lung Imaging Reporting and Diagnostic System category four, 23 (8.7%) were category three, 78 (29.5%) were category two, and 135 (51.1%) were category one. Eight of the 264 participants (3.0%) had lung cancer, with 75% detected in early stages. Conclusions We found a lung cancer prevalence in our high-risk screened population of 3.0% (8 of 264). After adjusting for patients who were symptomatic on clinical evaluation, we report a prevalence of cancer at 2.2% compared with 1.1% in the first year of the National Lung Screening Trial and a prevalence of 1.9% versus 0.6% compared with the National Comprehensive Cancer Network criteria in the first 10 months at Lahey Hospital & Medical Center. This study justifies low-dose helical computed tomography screening in high-risk regions because lung cancer treatment before symptoms appear is more effective, and the prevalence of disease in the detectable preclinical phase is high.

Treatment-related death during concurrent chemoradiotherapy for locally advanced non-small cell lung cancer: A meta-analysis of randomized studies

Treatment related death (TRD) is the worst adverse event in chemotherapy and radiotherapy for patients with cancer, the reports for TRDs were sporadically. We aimed to study TRDs in non-small cell lung cancer (NSCLC) patients treated with concurrent chemoradiotherapy (CCRT), and determine whether high radiation dose and newer chemotherapy regimens were associated with the risk of TRD. Data from randomized clinical trials for locally advanced/unresectable NSCLC patients were analyzed. Eligible studies had to have at least one arm with CCRT. The primary endpoint was TRD. Pooled odds ratios (ORs) for TRDs were calculated. In this study, a total of fifty-three trials (8940 patients) were eligible. The pooled TRD rate (accounting for heterogeneity) was 1.44% for all patients. In 20 trials in which comparison of TRDs between CCRT and non-CCRT was possible, the OR (95% CI) of TRDs was 1.08 (0.70–1.66) (P = 0.71). Patients treated with third-generation chemotherapy and concurrent radiotherapy had an increase of TRDs compared to those with other regimens in CCRT (2.70% vs. 1.37%, OR = 1.50, 95% CI: 1.09–2.07, P = 0.008). No significant difference was found in TRDs between high (≥ 66 Gy) and low (< 66 Gy) radiation dose during CCRT (P = 0.605). Neither consolidation (P = 0.476) nor induction chemotherapy (P = 0.175) had significant effects with increased TRDs in this study. We concluded that CCRT is not significantly associated with the risk of TRD compared to non-CCRT. The third-generation chemotherapy regimens may be a risk factor with higher TRDs in CCRT, while high dose radiation is not significantly associated with more TRDs. This observation deserves further study.

Prospective study to evaluate impact of support group participation in women with gynecological cancer.

243 Background: Unlike breast cancer support group literature, there is no data in women with gynecologic cancers who have different perspective about their disease and therapy. We have a well-established (10 years old) active grass root level support group unique to women with gynecologic cancers that meets monthly. Our goal was to investigate perceived benefits of support group participation. METHODS We developed a prospective questionnaire to evaluate the CSRA Gynecologic Oncology Support Group (CGOSG) participants perceived effects of attending the group on their side effects and disease status. The questionnaire was distributed to patients attending CGOSG meetings over a 4 month period. 47 surveys were collected for analysis; Wilcox rank sum test was used as appropriate. RESULTS The common cancers were 52% ovarian, 26% endometrial and 62% were currently on therapy. The 3 top reasons that patients attended CGOSG were physician driven (28%), to meet other women with the same diagnosis (26%) and to learn more about their cancer (22%). The top 3 expectations of patients were emotional support (28%), bonding/companionship (21%), and cancer education (14%). The top 3 concerning physical side effects from their cancer or therapy were fatigue (21%), memory loss (14%), and peripheral neuropathy (14%). Patients with more than 5 visits reported that CGOSG participation improved their most concerning physical side effect (fatigue) with a median score of 7.5 ± 4 out of 10. The top 3 concerning emotional side effects identified were fear of recurrence (26%), living with uncertainty (20%) and defining a new sense of normal (15%). Patients reported the CGOSG improved their most concerning emotional side effect (fear of recurrence) with a median score of 9 ± 2 out of 10. Patients with more than one visit, not on treatment reported a higher quality of life score (p = 0.001) and perceived a positive impact on cancer therapy (p = 0.02) compared to patients on treatment. CONCLUSIONS This is a first of a kind attempt to understand the impact of a well-organized support group on women with gynecological cancers which indicates that these women struggle with fear of recurrence and uncertainty, but are able to find some solace.

Impact of support group participation in women with gynecologic cancer.

252 Background: Unlike breast cancer support group literature, there is no data in women with gynecologic cancer who have different perspectives about their disease and therapy. We have a well-established, grass root level support group unique to women with gynecologic cancers that meets monthly. Our goal was to investigate perceived benefits of support group participation. METHODS We developed an original questionnaire to evaluate the CSRA Gynecologic Oncology Support Group (CGOSG) participants perceived effects of attending the group on their side effects and disease status which was distributed to patients attending CGOSG meetings. 47 surveys were collected for analysis; Wilcox rank sum test was used as appropriate. Patients were also administered the validated FACT-G questionnaire addressing physical well-being (PWB), emotional well-being (EWB), social well-being (SWB), and functional well-being (FWB). 33 surveys were collected, and t-tests were conducted using FACIT SAS scoring program. RESULTS In the original questionnaire, the 2 top reasons that patients attended CGOSG were physician driven (28%) and to meet other women with the same diagnosis (26%). The most concerning physical side effect from their cancer or therapy was fatigue (21%), and patients with more than 5 visits reported that CGOSG participation improved their fatigue with a median score of 7.5 ± 4 out of 10. The most concerning emotional side effect was fear of recurrence (26%), and patients reported the CGOSG improved their fear of recurrence with a median score of 9 ± 2 out of 10. Patients with more than one visit, not on treatment reported a higher quality of life score (p = 0.001) and perceived a positive impact on cancer therapy (p = 0.02) compared to patients on treatment. Among patients who took the validated FACT-G questionnaire, those on active treatment had a lower PWB than patients not on therapy (p = 0.01). The mean subscale scores were PWB 21.99, SWB 24.26, EWB 20.08, FWB 20.92 with patients faring best in social well-being. CONCLUSIONS This is a first of a kind attempt to understand the impact of a well-organized support group on women with gynecological cancers which indicates that these women struggle with fear of recurrence but are able to find some solace.