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18F-FDG PET response and clinical outcomes after stereotactic body radiation therapy for metastatic melanoma.

ABSTRACT: Clinical data that support stereotactic body radiation therapy (SBRT) metastatic malignant melanoma (MM) are limited. Furthermore, functional imaging with 18F-fludeoxyglucose positron emission tomography (PET) may offer a more accurate post-SBRT assessment. Therefore, we assessed the clinical outcomes and metabolic response of metastatic MM after SBRT.Patients with MM who were treated with SBRT and had pre- and post-PET scans (>1) were included in this study. A total of 390 pre- and post-SBRT PET/computed tomography (CT) scans for 80 metastases were analyzed. The PET metabolic response was evaluated per the PET Response Criteria in Solid Tumors (PERCIST), version 1.0, criteria. Single-fraction equivalent dose (SFED) was calculated as per the standard. The Kaplan-Meier method was used for estimates of overall survival (OS) and progression-free survival. The cumulative incidence method was used to estimate metastasis control (MC). A Wilcoxon test was used to compare survival estimates. The prognostic factors for MC and OS were assessed using the Cox proportional hazards model, and the Likelihood Ratio was also used for comparisons between groups.A median of 6 PET scans (range, 2-6 scans) was evaluated for each metastasis. The median SFED was 42.8 Gy (range, 18-56.4 Gy) and the median biologically effective dose was 254.4 Gy2.5 (range, 100.8-540 Gy2.5). Twenty percent of patients received chemotherapy and 59% received immunotherapy: granulocyte-macrophage colony-stimulating factor (64%) and ipilimumab (34%). MC was 94% and 90% at 1 year and 3 years, respectively. The OS was 74% and 27% and 1 year and 3 years, respectively. Complete response was achieved in 90% at a median of 2.8 months (range, 0.4-25.2 months). SFED >24 Gy correlated with improved MC (93% vs 75%, P = .01). Acute and late grade 3+ toxicities were 4% and 11%, respectively, with no grade 5 toxicity.Post-SBRT PET/CT for extracranial metastatic MM resulted in high rates of complete response at a median of 2.8 months, and durable MC was achieved with SFED >24 Gy. SBRT, in addition to surgery and ablation, should be discussed with patients with MM, especially those with oligometastases.

SUBMITTER: Youland RS

PROVIDER: S-EPMC5514257 | biostudies-other | 2017 Apr-Jun

REPOSITORIES: biostudies-other

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Project description:Combined whole-body dual-tracer ((18)F-FDG and (11)C-acetate) PET/CT is increasingly used for staging hepatocellular carcinoma, with only limited studies investigating the radiation dosimetry data of these scans. The aim of the study was to characterize the radiation dosimetry of combined whole-body dual-tracer PET/CT protocols.Consecutive adult patients with hepatocellular carcinoma who underwent whole-body dual-tracer PET/CT scans were retrospectively reviewed with institutional review board approval. OLINDA/EXM 1.1 was used to estimate patient-specific internal dose exposure in each organ. Biokinetic models for (18)F-FDG and (11)C-acetate as provided by ICRP (International Commission on Radiological Protection) publication 106 were used. Standard reference phantoms were modified to more closely represent patient-specific organ mass. With patient-specific parameters, organ equivalent doses from each CT series were estimated using VirtualDose. Dosimetry capabilities for tube current modulation protocols were applied by integrating with the latest anatomic realistic models. Effective dose was calculated using ICRP publication 103 tissue-weighting coefficients for adult male and female, respectively.Fourteen scans were evaluated (12 men, 2 women; mean age ± SD, 60 ± 19.48 y). The patient-specific effective dose from (18)F-FDG and (11)C-acetate was 6.08 ± 1.49 and 1.56 ± 0.47 mSv, respectively, for male patients and 6.62 ± 1.38 and 1.79 ± 0.12 mSV, respectively, for female patients. The patient-specific effective dose of the CT component, which comprised 2 noncontrast whole-body scans, to male and female patients was 21.20 ± 8.94 and 14.79 ± 3.35 mSv, respectively. Thus, the total effective doses of the combined whole-body dual-tracer PET/CT studies for male and female patients were 28.84 ± 10.18 and 23.19 ± 4.61 mSv, respectively.Patient-specific parameters allow for more accurate estimation of organ equivalent doses. Considering the substantial radiation dose incurred, judicious medical justification is required with every whole-body dual-tracer PET/CT referral. Although radiation risks may have less impact for the population with cancer because of their reduced life expectancy, the information is of interest and relevant for both justification, to evaluate risk/benefit, and protocol optimization.

Project description:Purpose:This study aimed to report on our institutional experience in the use of stereotactic body radiation therapy (SBRT) for the treatment of adrenal gland metastases. Specifically, we examined the outcomes and toxicity from this treatment modality on adjacent organs at risk. Methods and Materials:Data were retrieved from patients with adrenal metastases who were treated with SBRT between 2008 and 2017. Patients with primary adrenal malignancies were excluded. Toxicities were graded in accordance with the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.03. Time-to-event rates were calculated from the date of SBRT delivery. Results:In total, 35 patients with adrenal metastases were identified. Four patients were treated for bilateral disease. The median dose was 40?Gy (range, 20-54?Gy) in 5 fractions (range, 1-6 fractions). The median follow-up time was 37 months (range, 14-451 months) from disease diagnosis and 7 months (range, 1-54 months) from the SBRT start date. With death treated as a competing risk event, the cumulative incidence of local failure was 7.6% at 1 year after SBRT and 19.2% at 3 years. The median overall survival (OS) time was 19 months (95% confidence interval, 8-54 months) and tumor size correlated with survival (P?=?.0006). Patients with metastases <2.9?cm had a median OS of 54 months compared with 11 months for those with adrenal metastases ?2.9?cm (P?=?.01). Incidence of grade 2 toxicity was 17% with no case of grade ?3 toxicity. SBRT did not impact renal function with a mean estimated decline in glomerular filtration rate of only 2.6?±?8?mL/min/1.73?m2 compared with baseline. Combined kidneys V5 and combined renal cortex V17.5 did not correlate with a change in estimated glomerular filtration rate (P?=?.7 and P?=?.9, respectively). Conclusions:SBRT offers excellent local control for the treatment of adrenal gland metastases with very low toxicity rates and no significant short-term impact on renal function.

Project description:PurposeTo investigate the possibility of reducing the injected activity for whole-body [18F]FDG-PET/CT studies of paediatric oncology patients and to assess the usefulness of time-of-flight (TOF) acquisition on PET image quality at reduced count levels.ProceduresTwenty-nine paediatric oncology patients (12F/17M, 3-18 years old (median age 13y), weight 45±20 kg, BMI 19±4 kg/m2), who underwent routine whole-body PET/CT examinations on a Siemens Biograph mCT TrueV system with TOF capability (555ps) were included in this study. The mean injected activity was 156 ± 45 MBq (3.8 ± 0.8 kg/MBq) and scaled to patient weight. The raw data was collected in listmode (LM) format and pre-processed to simulate reduced levels of [18F]FDG activity (75, 50, 35, 20 and 10% of the original counts) by randomly removing events from the original LM data. All data were reconstructed using the vendor-specific e7-tools with standard OSEM only, with OSEM plus resolution recovery (PSF). The reconstructions were repeated with added TOF (TOF) and PSF+TOF. The benefit of TOF together with the reduced count levels was evaluated by calculating the gains in signal-to-noise ratio (SNR) in the liver and contrast-to-noise ratio (CNR) in all PET-positive lesions before and after TOF employed at every simulated reduced count level. Finally, the PSF+TOF images at 50, 75 and 100% of counts were evaluated clinically on a 5-point scale by three nuclear medicine physicians.ResultsThe visual inspection of the reconstructed images did not reveal significant differences in image quality between 75 and 100% count levels for PSF+TOF. The improvements in SNR and CNR were the greatest for TOF reconstruction and PSF combined. Both SNR and CNR gains did increase linearly with the patients BMI for both OSEM only and PSF reconstruction. These benefits were observed until reducing the counts to 50 and 35% for SNR and CNR, respectively.ConclusionsThe benefit of using TOF was noticeable when using 50% or greater of the counts when evaluating the CNR and SNR. For [18F]FDG-PET/CT, whole-body paediatric imaging the injected activity can be reduced to 75% of the original dose without compromising PET image quality.

Project description:BACKGROUND:Immune checkpoint blockade such as ipilimumab and anti-PD1 monoclonal antibodies have significantly improved survival in advanced melanoma. Biomarkers are urgently needed as a majority of patients do not respond, despite treatment-related toxicities. We analysed pre-treatment 18F-fluorodeoxyglucose positron emission tomography/computerised tomography (FDG PET/CT) parameters to assess its correlation with patient outcome. METHODS:This retrospective study evaluated pre-treatment FDG PET/CT scans in a discovery cohort of patients with advanced melanoma treated with ipilimumab or anti-PD1. Pre-treatment scans were assessed for maximum tumoral standardised uptake value (SUVmax), metabolic tumour volume (MTV) and spleen to liver ratio (SLR). Progression-free survival (PFS) and overall survival (OS) were characterised and modelled using univariable and multivariable analyses. Correlation of SLR and OS was validated in an independent cohort. Blood parameters and stored sera of patients from the discovery cohort was analysed to investigate biological correlates with SLR. RESULTS:Of the 90 evaluable patients in the discovery cohort: 50 received ipilimumab monotherapy, 20 received anti-PD1 monotherapy, and 20 patients received ipilimumab followed by anti-PD1 upon disease progression. High SLR?>?1.1 was associated with poor PFS (median 1 vs 3?months; HR 3.14, p?=?0.008) for patients treated with ipilimumab. High SLR was associated with poor OS after ipilimumab (median 1 vs 21?months; HR 5.83, p?=?0.0001); as well as poor OS after first line immunotherapy of either ipilimumab or anti-PD1 (median 1 vs 14?months; HR 3.92, p?=?0.003). The association of high SLR and poor OS after ipilimumab was validated in an independent cohort of 110 patients (median 2.3?months versus 11.9?months, HR 3.74). SLR was associated with poor OS in a multi-variable model independent of stage, LDH, absolute lymphocyte count and MTV. CONCLUSIONS:Pre-treatment Spleen to liver ratio (SLR)?>?1.1 was associated with poor outcome after ipilimumab in advanced melanoma. This parameter warrants prospective evaluation.

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18F-FDG PET response and clinical outcomes after stereotactic body radiation therapy for metastatic melanoma.

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