RESUMO
PURPOSE: Standardized reporting of treatment response in oncology patients has traditionally relied on methods like RECIST, PERCIST and Deauville score. These endpoints assess only a few lesions, potentially overlooking the response heterogeneity of all disease. This study hypothesizes that comprehensive spatial-temporal evaluation of all individual lesions is necessary for superior prognostication of clinical outcome. METHODS: [18F]FDG PET/CT scans from 241 patients (127 diffuse large B-cell lymphoma (DLBCL) and 114 non-small cell lung cancer (NSCLC)) were retrospectively obtained at baseline and either during chemotherapy or post-chemoradiotherapy. An automated TRAQinform IQ software (AIQ Solutions) analyzed the images, performing quantification of change in regions of interest suspicious of cancer (lesion-ROI). Multivariable Cox proportional hazards (CoxPH) models were trained to predict overall survival (OS) with varied sets of quantitative features and lesion-ROI, compared by bootstrapping with C-index and t-tests. The best-fit model was compared to automated versions of previously established methods like RECIST, PERCIST and Deauville score. RESULTS: Multivariable CoxPH models demonstrated superior prognostic power when trained with features quantifying response heterogeneity in all individual lesion-ROI in DLBCL (C-index = 0.84, p < 0.001) and NSCLC (C-index = 0.71, p < 0.001). Prognostic power significantly deteriorated (p < 0.001) when using subsets of lesion-ROI (C-index = 0.78 and 0.67 for DLBCL and NSCLC, respectively) or excluding response heterogeneity (C-index = 0.67 and 0.70). RECIST, PERCIST, and Deauville score could not significantly associate with OS (C-index < 0.65 and p > 0.1), performing significantly worse than the multivariable models (p < 0.001). CONCLUSIONS: Quantitative evaluation of response heterogeneity of all individual lesions is necessary for the superior prognostication of clinical outcome.
RESUMO
PURPOSE: We have previously reported that a plasmid DNA vaccine encoding prostatic acid phosphatase (pTVG-HP) had greater clinical activity when given in combination with pembrolizumab to patients with metastatic, castration-resistant prostate cancer. The current trial was conducted to evaluate vaccination with PD-1 blockade, using nivolumab, in patients with early, recurrent (M0) prostate cancer. METHODS: Patients with M0 prostate cancer were treated with pTVG-HP (100 µg administered intradermally) and nivolumab (240 mg intravenous infusion) every 2 weeks for 3 months, and then every 4 weeks for 1 year of total treatment. Patients were then followed for an additional year off treatment. The primary objectives were safety and complete prostate-specific antigen (PSA) response (PSA<0.2 ng/mL). RESULTS: 19 patients were enrolled. No patients met the primary endpoint of complete PSA response; however, 4/19 (21%) patients had a PSA decline >50%. Median PSA doubling times were 5.9 months pretreatment, 25.6 months on-treatment (p=0.001), and 9.0 months in the subsequent year off-treatment. The overall median radiographic progression-free survival was not reached. Grade 3 or 4 events included adrenal insufficiency, fatigue, lymphopenia, and increased amylase/lipase. 9/19 (47%) patients developed immune-related adverse effects (irAE). The development of irAE and increased CXCL9 were associated with increased PSA doubling time. Quantitative NaF PET/CT imaging showed the resolution of subclinical lesions along with the development of new lesions at each time point. CONCLUSIONS: In this population, combining nivolumab with pTVG-HP vaccination was safe, and immunologically active, prolonged the time to disease progression, but did not eradicate disease. Quantitative imaging suggested that additional treatments targeting mechanisms of resistance may be required to eliminate tumors. TRIAL REGISTRATION NUMBER: NCT03600350.