Cost-effectiveness of prophylactic cranial irradiation with hippocampal avoidance in limited stage small cell lung cancer.

BACKGROUND AND PURPOSE: Prophylactic cranial irradiation (PCI) in limited stage small cell lung cancer (LS-SCLC) prevents brain metastases and improves survival, with the potential for neurocognitive toxicity. RTOG0933 demonstrated that hippocampal avoidance (HA) during whole brain radiotherapy preserves neurocognition. This study's objective was to evaluate the cost-effectiveness of HA-PCI in LS-SCLC through decision analysis. MATERIALS AND METHODS: A Markov model was developed to simulate the clinical course of LS-SCLC who received HA-PCI or conventional PCI (C-PCI). A willingness-to-pay threshold of $100,000/QALY was used. Incremental cost effectiveness ratio was calculated (ICER). Sensitivity analyses were performed to determine the parameter thresholds and to assess the robustness of the model. RESULTS: In the base case scenario, HA-PCI is more cost-effective than C-PCI, with an ICER of $47,107/QALY. HA-PCI was preferred over C-PCI provided that the risk of developing brain metastases was not increased by at least 14%, or if neurocognitive dysfunction rates were reduced by at least 40%. HA-PCI was the cost-effective strategy in 68% of tested iterations in probabilistic sensitivity analysis. CONCLUSION: This study demonstrates that HA-PCI is more cost-effective than C-PCI in LS-SCLC. Our results support the use of HA-PCI in this patient population, should results from RTOG0933 be confirmed by the ongoing NRGCC003 trial.

Assessment of function and quality of life in a phase II multi-institutional clinical trial of fractionated simultaneous in-field boost radiotherapy for patients with 1-3 metastases.

We examined functional outcomes and quality of life of whole brain radiotherapy (WBRT) with integrated fractionated stereotactic radiotherapy boost (FSRT) for brain metastases treatment. Eighty seven people with 1-3 brain metastases (54/87 lung primary, 42/87 single brain metastases) were enrolled on this Phase II trial of WBRT (30 Gy/10) + simultaneous FSRT, (60 Gy/10). Median overall follow-up and survival was 5.4 months, 6 month actuarial intra-lesional control was 78 %; only 1 patient exhibited grade 4 toxicity (worsened seizures); most treatment related toxicity was grade 1 or 2; 2/87 patients demonstrated asymptomatic radiation necrosis on follow-up imaging. Mean (Min-Max) baseline KPS, Mini Mental Status Exam (MMSE) and FACT-BR quality of life were 83 (70-100), 28 (21-30) and 143 (98-153). Lower baseline MMSE (but not KPS or FACT-Br) was associated with worse survival after adjusting for age, number of metastases, primary and extra-cranial disease status. Crude rates of deterioration (>10 points decrease from baseline for KPS and FACT-Br, MMSE fall to <27) ranged from 26 to 38 % for KPS, 32-59 % for FACT-Br and 0-16 % for MMSE depending on the time-point assessed with higher rates generally noted at earlier time points (≤6 months post-treatment). Using a linear mixed models analysis, significant declines from baseline were noted for KPS and FACT-Br (largest effects at 6 weeks to 3 months) with no significant change in MMSE. The effects on function and quality of life of this integrated treatment of WBRT + simultaneous FSRT were similar to other published series combining WBRT + radiosurgery.

Assessment and improvement of radiation oncology trainee contouring ability utilizing consensus-based penalty metrics.

INTRODUCTION: The objective of this study was to develop and assess the feasibility of utilizing consensus-based penalty metrics for the purpose of critical structure and organ at risk (OAR) contouring quality assurance and improvement. METHODS: A Delphi study was conducted to obtain consensus on contouring penalty metrics to assess trainee-generated OAR contours. Voxel-based penalty metric equations were used to score regions of discordance between trainee and expert contour sets. The utility of these penalty metric scores for objective feedback on contouring quality was assessed by using cases prepared for weekly radiation oncology radiation oncology trainee treatment planning rounds. RESULTS: In two Delphi rounds, six radiation oncology specialists reached agreement on clinical importance/impact and organ radiosensitivity as the two primary criteria for the creation of the Critical Structure Inter-comparison of Segmentation (CriSIS) penalty functions. Linear/quadratic penalty scoring functions (for over- and under-contouring) with one of four levels of severity (none, low, moderate and high) were assigned for each of 20 OARs in order to generate a CriSIS score when new OAR contours are compared with reference/expert standards. Six cases (central nervous system, head and neck, gastrointestinal, genitourinary, gynaecological and thoracic) then were used to validate 18 OAR metrics through comparison of trainee and expert contour sets using the consensus derived CriSIS functions. For 14 OARs, there was an improvement in CriSIS score post-educational intervention. CONCLUSIONS: The use of consensus-based contouring penalty metrics to provide quantitative information for contouring improvement is feasible.

Technology assessment of automated atlas based segmentation in prostate bed contouring.

BACKGROUND: Prostate bed (PB) contouring is time consuming and associated with inter-observer variability. We evaluated an automated atlas-based segmentation (AABS) engine in its potential to reduce contouring time and inter-observer variability. METHODS: An atlas builder (AB) manually contoured the prostate bed, rectum, left femoral head (LFH), right femoral head (RFH), bladder, and penile bulb of 75 post-prostatectomy cases to create an atlas according to the recent RTOG guidelines. 5 other Radiation Oncologists (RO) and the AABS contoured 5 new cases. A STAPLE contour for each of the 5 patients was generated. All contours were anonymized and sent back to the 5 RO to be edited as clinically necessary. All contouring times were recorded. The dice similarity coefficient (DSC) was used to evaluate the unedited- and edited- AABS and inter-observer variability among the RO. Descriptive statistics, paired t-tests and a Pearson correlation were performed. ANOVA analysis using logit transformations of DSC values was calculated to assess inter-observer variability. RESULTS: The mean time for manual contours and AABS was 17.5- and 14.1 minutes respectively (p = 0.003). The DSC results (mean, SD) for the comparison of the unedited-AABS versus STAPLE contours for the PB (0.48, 0.17), bladder (0.67, 0.19), LFH (0.92, 0.01), RFH (0.92, 0.01), penile bulb (0.33, 0.25) and rectum (0.59, 0.11). The DSC results (mean, SD) for the comparison of the edited-AABS versus STAPLE contours for the PB (0.67, 0.19), bladder (0.88, 0.13), LFH (0.93, 0.01), RFH (0.92, 0.01), penile bulb (0.54, 0.21) and rectum (0.78, 0.12). The DSC results (mean, SD) for the comparison of the edited-AABS versus the expert panel for the PB (0.47, 0.16), bladder (0.67, 0.18), LFH (0.83, 0.18), RFH (0.83, 0.17), penile bulb (0.31, 0.23) and rectum (0.58, 0.09). The DSC results (mean, SD) for the comparison of the STAPLE contours and the 5 RO are PB (0.78, 0.15), bladder (0.96, 0.02), left femoral head (0.87, 0.19), right femoral head (0.87, 0.19), penile bulb (0.70, 0.17) and the rectum (0.89, 0.06). The ANOVA analysis suggests inter-observer variability among at least one of the 5 RO (p value = 0.002). CONCLUSION: The AABS tool results in a time savings, and when used to generate auto-contours for the femoral heads, bladder and rectum had superior to good spatial overlap. However, the generated auto-contours for the prostate bed and penile bulb need improvement.