Abstract
PurposeFor patients with high-risk bladder cancer (pT3+ or N+), local regional failure remains a challenge after chemotherapy and cystectomy. An ongoing prospective phase 2 trial (NCT01954173) is examining the role of postoperative photon radiation therapy for high-risk patients using volumetric modulated arc therapy. Proton beam therapy (PBT) may be beneficial in this setting to reduce hematologic toxicity. We evaluated for dosimetric relationships with pelvic bone marrow (PBM) and changes in hematologic counts before and after pelvic radiation therapy and explored the potential of PBT treatment plans to achieve reductions in PBM dose.Materials and MethodsAll enrolled patients were retrospectively analyzed after pelvic radiation per protocol with 50.4 to 55.8 Gy in 28 to 31 fractions. Comparative PBT plans were generated using pencil-beam scanning and a 3-beam multifield optimization technique. Changes in hematologic nadirs were assessed using paired t test. Correlation of mean nadirs and relative PBM dose levels were assessed using the Pearson correlation coefficient (CC).ResultsEighteen patients with a median age of 70 were analyzed. Mean cell count values after radiation therapy decreased compared with preradiation therapy values for white blood cells (WBCs), absolute neutrophil count (ANC), absolute lymphocyte count (all P < .001), and platelets (P = .03). Increased mean PBM dose was associated with lower nadirs in WBC (Pearson CC −0.593, P = .02), ANC (Pearson CC −0.597, P = .02), and hemoglobin (Pearson CC −0.506, P = .046), whereas the PBM V30 to V40 correlated with lower WBC (Pearson CC −0.512 to −0.618, P < .05), and V20 to V30 correlated with lower ANC (Pearson CC −0.569 to −0.598, P < .04). Comparative proton therapy plans decreased the mean PBM dose from 26.5 Gy to 16.1 Gy (P < .001) and had significant reductions in the volume of PBM receiving doses from 5 to 40 Gy (P < .001).ConclusionIncreased PBM mean dose and V20 to V40 were associated with lower hematologic nadirs. PBT plans reduced PBM dose and may be a valuable strategy to reduce the risk of hematologic toxicity in these patients.
Highlights
The current standard of care for locally advanced urothelial bladder carcinoma is neoadjuvant chemotherapy, followed by radical cystectomy
Proton beam therapy (PBT) plans reduced pelvic bone marrow (PBM) dose and may be a valuable strategy to reduce the risk of hematologic toxicity in these patients
Results from a recent Egyptian National Cancer Institute (NCI) trial [7] randomizing the use of 3-dimensional-conformal radiation therapy (RT) after radical cystectomy and chemotherapy showed promising 2-year results, including clear improvement in locoregional recurrence–free survival compared with adjuvant chemotherapy alone (96% versus 69%, P, .01) and trends towards improved disease-free survival (68% versus 56%, P 1⁄4 .07) and overall survival (71% versus 60%, P 1⁄4 .11)
Summary
The current standard of care for locally advanced urothelial bladder carcinoma is neoadjuvant chemotherapy, followed by radical cystectomy. Patients with high-risk disease, defined as stages pT3 and T4 or positive pelvic lymph nodes, continue to have a substantial risk of local regional failure (LRF), despite that treatment paradigm. In SWOG (formerly the Southwest Oncology Group, Portland, Oregon) 8710, a randomized trial of radical cystectomy with or without neoadjuvant MVAC (methotrexate, vinblastine sulfate, doxorubicin hydrochloride [adriamycin], and cisplatin) chemotherapy, the 5-year cumulative incidence of LRF for patients with ! The use of adjuvant radiation therapy has, been studied to address this pattern of failure [5,6,7]. Despite historical randomized data supporting improvements in local regional control with the use of adjuvant radiation therapy (RT), this treatment paradigm has not been widely adopted because of concerns of excessive toxicity in an often-frail patient population
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