Craniospinal irradiation prior to stem cell transplant for hematologic malignancies with CNS involvement: Effectiveness and toxicity after photon or proton treatment.

PURPOSE/OBJECTIVE(S): Craniospinal irradiation (CSI) improves local control of leukemia/lymphoma with central nervous system (CNS) involvement; however, for adult patients anticipating stem cell transplant (SCT), cumulative treatment toxicity is a major concern. We evaluated toxicities and outcomes for patients receiving proton or photon CSI before SCT. METHODS AND MATERIALS: We identified 37 consecutive leukemia/lymphoma patients with CNS involvement who received CSI before SCT at our institution. Photon versus proton toxicities during CSI, transplant, and through 100 days posttransplant were compared using Fisher exact and Wilcoxon rank sum tests. Long-term neurotoxicity, disease response, and overall survival were analyzed. RESULTS: Thirty-seven patients (23 photon, 14 proton) underwent CSI for CNS involvement of acute lymphoblastic leukemia (49%), acute myeloblastic leukemia (22%), chronic lymphocytic leukemia (3%), chronic myelocytic leukemia (14%), lymphoma (11%), and myeloma (3%). CSI was used for consolidation (30 patients, 81%) and gross disease treatment (7 patients, 19%). Median radiation dose (interquartile range) was 24 Gy (23.4-24) for photons and 21.8 Gy (21.3-23.6) for protons (P = .03). Proton CSI was associated with lower rates of Radiation Therapy Oncology Group grade 1-3 mucositis during CSI (7% vs 44%, P = .03): 1 grade 3 with protons versus 5 grade 1, 3 grade 2, and 2 grade 3 with photons. During CSI, other toxicities (infection, gastrointestinal symptoms) did not differ. Allogeneic stem cell transplant (SCT) was used in 95% of patients, with 53% of patients in remission before SCT. Myeloablative conditioning was used for 76%. During SCT admission and 100 days post-SCT, toxicities did not differ by CSI technique. Successful engraftment occurred in 95% of patients (P = .67). Progression or death occurred for 47% of patients, with only 1 CNS relapse. CONCLUSION: In our cohort, CSI offered excellent local control for CNS-involved hematologic malignancies in the pre-SCT setting. Acute mucositis occurred less frequently with proton CSI with comparable peritransplant/long-term toxicity profile, suggesting the need to further explore the benefit/toxicity profile of this technique.

Reproducibility of Volumetric Computed Tomography of Stable Small Pulmonary Nodules with Implications on Estimated Growth Rate and Optimal Scan Interval.

PURPOSE: To use clinically measured reproducibility of volumetric CT (vCT) of lung nodules to estimate error in nodule growth rate in order to determine optimal scan interval for patient follow-up. METHODS: We performed quantitative vCT on 89 stable non-calcified nodules and 49 calcified nodules measuring 3-13 mm diameter in 71 patients who underwent 3-9 repeat vCT studies for clinical evaluation of pulmonary nodules. Calculated volume standard deviation as a function of mean nodule volume was used to compute error in estimated growth rate. This error was then used to determine the optimal patient follow-up scan interval while fixing the false positive rate at 5%. RESULTS: Linear regression of nodule volume standard deviation versus the mean nodule volume for stable non-calcified nodules yielded a slope of 0.057 ± 0.002 (r2 = 0.79, p<0.001). For calcified stable nodules, the regression slope was 0.052 ± 0.005 (r2 = 0.65, p = 0.03). Using this with the error propagation formula, the optimal patient follow-up scan interval was calculated to be 81 days, independent of initial nodule volume. CONCLUSIONS: Reproducibility of vCT is excellent, and the standard error is proportional to the mean calculated nodule volume for the range of nodules examined. This relationship constrains statistical certainty of vCT calculated doubling times and results in an optimal scan interval that is independent of the initial nodule volume.