Defining Optimal Comorbidity Measures for Patients With Early-Stage Non-small cell lung cancer Treated With Stereotactic Body Radiation Therapy

Purpose

Comparison of overall survival (OS) between stereotactic body radiation therapy (SBRT) and other treatments for early-stage non-small cell lung cancer is confounded by differences in age, performance status, and medical comorbidity. We sought to define the most robust measurement for this population among 5 indices: age, Eastern Cooperative Oncology Group performance status, Adult Comorbidity Evaluation 27, Charlson Comorbidity Index (CCI), and age-adjusted CCI (CCIa).

Geriatric Assessment and Frailty Scores Predict Mortality in Myeloma: Systematic Review and Meta-analysis

The incidence of multiple myeloma is increasing as the proportion of older adults is growing rapidly. A critical evaluation of the evidence available is needed to guide the management of older patients with myeloma. A systematic review was conducted to report the prognostic value of geriatric assessment and frailty scores in older patients with multiple myeloma. We conducted a literature search in February and August 2018. Two researchers extracted the data and assessed the quality of the studies. Geriatric assessment and frailty scores were defined as those evaluating at least 2 geriatric domains. Main outcomes were mortality or toxicity. We estimated the pooled hazard ratios (HR) with 95% confidence intervals (CIs) using a random-effects model. We screened titles and abstracts of 1672 citations for eligibility. Seven studies were included in the qualitative analysis, of which 3 were included in the meta-analysis. Two studies reported similar risks of hematologic adverse events in intermediate-fit and in frail patients compared to frail, but a significantly increased risk of nonhematologic adverse events in frail patients compared to fit patients. In meta-analysis, a significantly increased HR for death was observed in patients with activity of daily living score ≤ 4 (pooled HR = 1.576; 95% CI, 1.051-2.102; χ² = 0.87; P = .647; I² = 0). Patients classified as frail showed higher risk of death than fit patients (pooled HR = 2.169; 95% CI, 1.002-2.336; χ² = 3.02; P = .221; I² = 33.7%). GA and frailty score are effective in predicting mortality in older adults with myeloma.     

Delineation of a Cardiac Planning Organ-At-Risk Volume Using Real-Time Magnetic Resonance Imaging for Cardiac Protection in Thoracic and Breast Radiation Therapy

PurposeCardiac radiation is associated with cardiotoxicity in patients with thoracic and breast malignancies. We conducted a prospective study using cine magnetic resonance imaging (MRI) scans to evaluate heart motion. We hypothesized that cine MRI could be used to define population-based cardiac planning organ-at-risk volumes (PRV).Methods and MaterialsA total of 16 real-time acquisitions were obtained per subject on a 1.5 Tesla MRI (Philips Ingenia). Planar cine MRI was performed in 4 sequential sagittal and coronal planes at free-breathing (FB) and deep-inspiratory breath hold (DIBH). In-plane cardiac motion was assessed using a scale-invariant feature transformation–based algorithm. Subject-specific pixel motion ranges were defined in anteroposterior (AP), left-right (LR), and superoinferior (SI) planes. Averages of the 98% and 67% of the maximum ranges of pixel displacement were defined by subject, then averaged across the cohort to calculate PRV expansions at FB and DIBH.ResultsData from 20 subjects with a total of 3120 image frames collected per subject in coronal and sagittal planes at DIBH and FB, and 62,400 total frames were analyzed. Cohort averages of 98% of the maximum cardiac motion ranges comprised margin expansions of 12.5 ± 1.1 mm SI, 5.8 ± 1.2 mm AP, and 6.6 ± 1.0 mm LR at FB and 6.7 ± 1.5 mm SI, 4.7 ± 1.3 mm AP, and 5.3 ± 1.3 mm LR at DIBH. Margins for 67% of the maximum range comprised 7.7 ± 0.7 mm SI, 3.2 ± 0.6 mm AP, and 3.7 ± 0.6 mm LR at FB and 4.1 ± 0.9 mm SI, 2.7 ± 0.8 mm AP, and 3.2 ± 0.8 mm LR at DIBH. Subsequently, these margins were simplified to form PRVs for treatment planning.ConclusionsWe implemented scale-invariant feature transformation-based motion tracking for analysis of the cardiac cine MRI scans to quantify motion and create cohort-based cardiac PRVs to improve cardioprotection in breast and thoracic radiation.     

Phase I,Open-Label,Dose-Escalation Study of the Safety,Pharmacokinetics, Pharmacodynamics,and Efficacy of GSK2879552 in Relapsed/Refractory SCLC

IntroductionThis first-time-in-humans study assessed the safety, pharmacokinetics (PK), pharmacodynamics (PD), and clinical activity of GSK2879552 in patients with relapsed or refractory SCLC.MethodsThis phase I, multicenter, open-label study (NCT02034123) enrolled patients (≥18 years old) with relapsed or refractory SCLC (after ≥1 platinum-containing chemotherapy or refusal of standard therapy). Part 1 was a dose-escalation study; Part 2 was a dose-expansion study. Dose escalations were based on safety, PK, and PD. The primary end point (Part 1) was to determine the safety, tolerability, and recommended dose and regimen of GSK2879552. Secondary end points were to characterize PK and PD parameters and measure disease control rate at week 16. Part 2 was not conducted.ResultsBetween February 4, 2014, and April 18, 2017, a total of 29 patients were allocated to one of nine dose cohorts (0.25 mg–3 mg once daily and 3-mg or 4-mg intermittent dosing). In all, 22 patients completed the study; 7 withdrew, primarily owing to adverse events (AEs). Most patients (24 of 29 [83%]) had at least one treatment-related AE, most commonly thrombocytopenia (12 of 29 [41%]). Twelve serious AEs (SAEs) were reported by nine patients; six were considered treatment related, the most common of which was encephalopathy (four SAEs). Three patients died; one death was related to SAEs. PK was characterized by rapid absorption, slow elimination, and a dose-proportional increase in exposure.ConclusionsGSK2879552 is a potent, selective inhibitor of lysine demethylase 1A and has demonstrated favorable PK properties but provided poor disease control and a high AE rate in patients with SCLC. The study was terminated, as the risk-benefit profile did not favor continuation.     

Impact on Health-Related Quality of Life of Induction Chemotherapy Compared With Concurrent Cisplatin and Radiation Therapy in Patients With Head and Neck Cancer

AimsOrgan preservation, an important goal in the treatment of head and neck squamous cell carcinoma (HNSCC), may include induction chemotherapy and cisplatin with radiation therapy (CRT). To our knowledge, no reports have directly compared the impact of induction chemotherapy with that of CRT on health-related quality of life (HRQOL).Materials and methodsIn a phase II trial, we assessed the HRQOL of patients treated with induction chemotherapy followed by CRT. Eligible patients had stage III–IV HNSCC. HRQOL questionnaires were administered at baseline, the end of induction (EOI), the end of CRT (EOCRT) and after CRT. Functional Assessment of Cancer Therapy (FACT version 4) assessed HRQOL. We carried out a comparison of changes in HRQOL from baseline to EOI and from EOI to EOCRT. This trial is registered with ClinicalTrials.gov (NCT01566435).ResultsThirty patients were enrolled in the study. Most HRQOL questionnaires were completed (88%). The mean total FACT scores did not differ from baseline to EOI (general: 83.8 versus 79.1, P = 0.08; head and neck: 109.7 versus 105.8, P = 0.33; Total Outcome Index: 69.7 versus 62.3, P = 0.03; respectively, using P ≤ 0.01 to adjust for multiple simultaneous tests of differences). However, total FACT scores significantly worsened from EOI to EOCRT (79.1 versus 62.3, P = 0.01; 105.8 versus 74.2, P < 0.01; 62.3 versus 34.2, P = 0.01; respectively). Within domains, the head and neck cancer subscale score did not differ from baseline to EOI (median 28.5 versus 27.0, P = 0.69), but significantly worsened from EOI to EOCRT (27.0 versus 9.5, P < 0.01). Swallowing, oral pain and voice quality improved from baseline to EOI, but worsened from EOI to EOCRT. Physical and functional scores worsened from baseline to EOI and from EOI to EOCRT. The emotional well-being score improved from baseline to EOI but worsened from EOI to EOCRT.ConclusionsOverall, HRQOL did not significantly change from baseline to EOI but dramatically worsened from EOI to EOCRT.