Stereotactic radiosurgery with immunotherapy is associated with improved overall survival in patients with metastatic melanoma or non-small cell lung cancer: a National Cancer Database analysis

PurposeImmunotherapy is now a first-line treatment for metastatic non-small cell lung cancer (NSCLC) and melanomaQuery. It is important to understand the relationship between immunotherapy and radiation to the brain. The aim of this study was to assess the role of stereotactic radiosurgery (SRS) or WBRT in addition to immunotherapy in patients with melanoma or NSCLC metastatic to the brain.Methods/patientsUsing the National Cancer Database, 2951 patients with NSCLC and 936 patients with melanoma treated with immunotherapy were identified. Patients were classified as having received immunotherapy alone, immunotherapy with SRS, or immunotherapy with whole-brain radiation therapy (WBRT). Kaplan–Meier, multivariate Cox regression analyses, and propensity matching were performed to evaluate the impact of adding SRS to immunotherapy on overall survival (OS). Immortal survival bias was accounted for by only including patients who received radiation before immunotherapy and time zero was defined as the start of immunotherapy.Results205(6.9%) and 75(8.0%) patients received immunotherapy with no radiation, 822(27.9%) and 326(34.8%) received SRS and immunotherapy, and 1924(65.2%) and 535(57.2%) received WBRT and immunotherapy for NSCLC and melanoma, respectively. Adding SRS to immunotherapy was associated with improved OS in multivariate analyses (NSCLC HR = 0.81, 95% CI 0.66–0.99, p = 0.044; melanoma HR = 0.63, 95% CI 0.45–0.90, p = 0.011). The addition of WBRT to immunotherapy did not improve OS in patients with melanoma nor NSCLC.ConclusionsThis analysis suggests that treatment with SRS and immunotherapy is associated with improved OS compared to immunotherapy alone for patients with melanoma or NSCLC metastatic to the brain.

Stereotactic radiosurgery with immunotherapy is associated with improved overall survival in patients with metastatic melanoma or non-small cell lung cancer: a National Cancer Database analysis.

PURPOSE: Immunotherapy is now a first-line treatment for metastatic non-small cell lung cancer (NSCLC) and melanomaQuery. It is important to understand the relationship between immunotherapy and radiation to the brain. The aim of this study was to assess the role of stereotactic radiosurgery (SRS) or WBRT in addition to immunotherapy in patients with melanoma or NSCLC metastatic to the brain. METHODS/PATIENTS: Using the National Cancer Database, 2951 patients with NSCLC and 936 patients with melanoma treated with immunotherapy were identified. Patients were classified as having received immunotherapy alone, immunotherapy with SRS, or immunotherapy with whole-brain radiation therapy (WBRT). Kaplan-Meier, multivariate Cox regression analyses, and propensity matching were performed to evaluate the impact of adding SRS to immunotherapy on overall survival (OS). Immortal survival bias was accounted for by only including patients who received radiation before immunotherapy and time zero was defined as the start of immunotherapy. RESULTS: 205(6.9%) and 75(8.0%) patients received immunotherapy with no radiation, 822(27.9%) and 326(34.8%) received SRS and immunotherapy, and 1924(65.2%) and 535(57.2%) received WBRT and immunotherapy for NSCLC and melanoma, respectively. Adding SRS to immunotherapy was associated with improved OS in multivariate analyses (NSCLC HR = 0.81, 95% CI 0.66-0.99, p = 0.044; melanoma HR = 0.63, 95% CI 0.45-0.90, p = 0.011). The addition of WBRT to immunotherapy did not improve OS in patients with melanoma nor NSCLC. CONCLUSIONS: This analysis suggests that treatment with SRS and immunotherapy is associated with improved OS compared to immunotherapy alone for patients with melanoma or NSCLC metastatic to the brain.

Semi-automatic cone beam CT segmentation of in vivo pre-clinical subcutaneous tumours provides an efficient non-invasive alternative for tumour volume measurements.

OBJECTIVE: To evaluate the feasibility and accuracy of using cone beam CT (CBCT) scans obtained in radiation studies using the small-animal radiation research platform to perform semi-automatic tumour segmentation of pre-clinical tumour volumes. METHODS: Volume measurements were evaluated for different anatomical tumour sites, the flank, thigh and dorsum of the hind foot, for a variety of tumour cell lines. The estimated tumour volumes from CBCT and manual calliper measurements using different volume equations were compared with the "gold standard", measured by weighing the tumours following euthanasia and tumour resection. The correlation between tumour volumes estimated with the different methods, compared with the gold standard, was estimated by the Spearman's rank correlation coefficient, root-mean-square deviation and the coefficient of determination. RESULTS: The semi-automatic CBCT volume segmentation performed favourably compared with manual calliper measures for flank tumours ≤2 cm(3) and thigh tumours ≤1 cm(3). For tumours >2 cm(3) or foot tumours, the CBCT method was not able to accurately segment the tumour volumes and manual calliper measures were superior. CONCLUSION: We demonstrated that tumour volumes of flank and thigh tumours, obtained as a part of radiation studies using image-guided small-animal irradiators, can be estimated more efficiently and accurately using semi-automatic segmentation from CBCT scans. ADVANCES IN KNOWLEDGE: This is the first study evaluating tumour volume assessment of pre-clinical subcutaneous tumours in different anatomical sites using on-board CBCT imaging. We also compared the accuracy of the CBCT method to manual calliper measures, using various volume calculation equations.

PET/CT-guided treatment planning for paediatric cancer patients: a simulation study of proton and conventional photon therapy.

OBJECTIVE: To investigate the impact of including fluorine-18 fludeoxyglucose ((18)F-FDG) positron emission tomography (PET) scanning in the planning of paediatric radiotherapy (RT). METHODS: Target volumes were first delineated without and subsequently re-delineated with access to (18)F-FDG PET scan information, on duplicate CT sets. RT plans were generated for three-dimensional conformal photon RT (3DCRT) and intensity-modulated proton therapy (IMPT). The results were evaluated by comparison of target volumes, target dose coverage parameters, normal tissue complication probability (NTCP) and estimated risk of secondary cancer (SC). RESULTS: Considerable deviations between CT- and PET/CT-guided target volumes were seen in 3 out of the 11 patients studied. However, averaging over the whole cohort, CT or PET/CT guidance introduced no significant difference in the shape or size of the target volumes, target dose coverage, irradiated volumes, estimated NTCP or SC risk, neither for IMPT nor 3DCRT. CONCLUSION: Our results imply that the inclusion of PET/CT scans in the RT planning process could have considerable impact for individual patients. There were no general trends of increasing or decreasing irradiated volumes, suggesting that the long-term morbidity of RT in childhood would on average remain largely unaffected. ADVANCES IN KNOWLEDGE: (18)F-FDG PET-based RT planning does not systematically change NTCP or SC risk for paediatric cancer patients compared with CT only. 3 out of 11 patients had a distinct change of target volumes when PET-guided planning was introduced. Dice and mismatch metrics are not sufficient to assess the consequences of target volume differences in the context of RT.

The impact of involved node, involved field and mantle field radiotherapy on estimated radiation doses and risk of late effects for pediatric patients with Hodgkin lymphoma.

BACKGROUND: The use of radiotherapy (RT) is debated for pediatric patients with Hodgkin lymphoma (HL) due to the late effects of treatment. Radiation doses to the thyroid, heart, lungs, and breasts are compared with the extensive mantle field (MF), Involved Field RT(IFRT), Modified IFRT (mIFRT), and Involved Node RT (INRT) and the risk of radiation-induced cardiovascular disease, secondary cancers, and the corresponding Life Years Lost (LYL) is estimated with each technique. PROCEDURE: INRT, mIFRT, IFRT, and MF plans (20 and 30 Gy) were simulated for 10 supradiaphragmatic, clinical stage I­II classical HL patients <18 years old, total of 4 x 2 plans for each patient. The lifetime excess risks of cardiac morbidity, cardiac mortality, lung, breast, and thyroid cancer with each technique were estimated. The estimated excess risks attributable to RT were based on HL series with long-term follow-up, treating death from other causes as competing risks. The corresponding LYL were derived from the estimated excess risks. Statistical analyses were performed with repeated measures ANOVA. RESULTS: Both a reduction in field size and in prescribed radiation dose significantly lowered the estimated dose to the heart, lungs, breasts, and thyroid compared to past,extended fields, even for patients with mediastinal disease. This translated into a significantly reduced estimated risk of cardiovascular disease, secondary cancers, and LYL. CONCLUSIONS: Involved Node Radiotherapy should be considered for pediatric patients with Hodgkin lymphoma since it is estimated to substantially lower the risk of severe long-term complications.

Doses to head and neck normal tissues for early stage Hodgkin lymphoma after involved node radiotherapy.

PURPOSE: To evaluate dose plans for head and neck organs at risk (OARs) for classical Hodgkin lymphoma (HL) patients using involved node radiotherapy (INRT) delivered as 3D conformal radiotherapy (3DCRT), volumetric modulated arc therapy (VMAT), and intensity modulated proton therapy (PT), in comparison to the past mantle field (MF). MATERIALS AND METHODS: Data from 37 patients with cervical lymph node involvement were used. All patients originally received chemotherapy followed by 3DCRT-INRT (30.6 Gy). A VMAT-INRT, PT-INRT (both 30.6 Gy), and a MF plan (36 Gy) were simulated. Doses to head and neck OARs were compared with cumulative DVHs and repeated measures ANOVA. RESULTS: The estimated median mean doses were 15.3, 19.3, 15.4, and 37.3 Gy (thyroid), 10.9, 12.0, 7.9, and 34.5 Gy (neck muscles), 2.3, 11.1, 1.8, and 37.1 Gy (larynx), 1.7, 5.1, 1.3, and 23.8 Gy (pharynx), 0.5, 0.8, 0.01, and 32.3 Gy (ipsilateral parotid), and 2.4, 3.8, 0.7, and 34.7 Gy (ipsilateral submandibular) with 3DCRT, VMAT, PT, and MF (all p<0.0001), respectively. CONCLUSION: The use of INRT significantly lowered the estimated radiation dose to the head and neck OARs. VMAT appeared suboptimal compared to 3DCRT and PT, and for some patients, PT offered an additional gain.

Estimated risk of cardiovascular disease and secondary cancers with modern highly conformal radiotherapy for early-stage mediastinal Hodgkin lymphoma.

BACKGROUND: Hodgkin lymphoma (HL) survivors have an increased morbidity and mortality from secondary cancers and cardiovascular disease (CD). We evaluate doses with involved node radiotherapy (INRT) delivered as 3D conformal radiotherapy (3D CRT), volumetric modulated arc therapy (VMAT), or proton therapy (PT), compared with the extensive Mantle Field (MF). PATIENTS AND METHODS: For 27 patients with early-stage, mediastinal HL, treated with chemotherapy and INRT delivered as 3D CRT (30 Gy), we simulated an MF (36 Gy), INRT-VMAT and INRT-PT (30 Gy). Dose to the heart, lungs, and breasts, estimated risks of CD, lung (LC) and breast cancer (BC), and corresponding life years lost (LYL) were compared. RESULTS: 3D CRT, VMAT or PT significantly lower the dose to the heart, lungs and breasts and provide lower risk estimates compared with MF, but with substantial patient variability. The risk of CD is not significantly different for 3D CRT versus VMAT. The risk of LC and BC is highest with VMAT. For LYL, PT is the superior modern technique. CONCLUSIONS: In early-stage, mediastinal HL modern radiotherapy provides superior results compared with MF. However, there is no single best radiotherapy technique for HL-the decision should be made at the individual patient level.