Schild, Steven E.

Background and purposeIntensity‐modulated proton therapy (IMPT) is highly sensitive to range uncertainties and uncertainties caused by setup variation. The conventional inverse treatment planning of IMPT based on the planning target volume (PTV) is not often sufficient to ensure robustness of treatment plans. We applied a probabilistic framework (chance‐constrained optimization) in IMPT planning to hedge against the influence of uncertainties.Material and methodsWe retrospectively selected one patient with lung cancer, one patient with head and neck (H&N) cancer, and one with prostate cancer for this analysis. Using their original images and prescriptions, we created new IMPT plans using two methods: (1) a robust chance‐constrained treatment planning method with the clinical target volume (CTV) as the target; (2) the margin‐based method with PTV as the target, which was solved by commercial software, CPLEX, using linear programming. For the first method, we reformulated the model into a tractable mixed‐integer programming problem and sped up the calculation using Benders decomposition. The dose‐volume histograms (DVHs) from the nominal and perturbed dose distributions were used to assess and compare plan quality. DVHs for all uncertain scenarios along with the nominal DVH were plotted. The width of the “bands” of DVHs was used to quantify the plan sensitivity to uncertainty. The newly developed Benders decomposition method was compared with a commercial solution to demonstrate its computational efficiency. The trade‐off between nominal plan quality and plan robustness was investigated.ResultsOur chance‐constrained model outperformed the PTV method in terms of tumor coverage, tumor dose homogeneity, and plan robustness. Our model was shown to produce IMPT plans to meet the dose‐volume constraints of organs at risk (OARs) and had better sparing of OARs than the PTV method in the three clinical cases included in this study. The chance‐constrained model provided a flexible tool for users to balance between plan robustness and plan quality. In addition, our in‐house developed method was found to be much faster than the commercial solution.ConclusionWith explicit control of plan robustness, the chance‐constrained robust optimization model generated superior IMPT plans compared to the PTV‐based method.

AbstractIntroductionRadiotherapy alone still is the most commonly delivered treatment modality for metastatic spinal cord compression (MSCC). MSCC is an emergency situation, which requires treatment as soon as possible. When radiotherapy is performed with the most commonly used approach 10 × 3 Gy (30 Gy in 10 fractions) over 2 weeks, the question has been asked whether an overall treatment time (OTT) of 14–15 days including two weekends without irradiation leads to worse outcomes than OTT of 12 days (beginning of radiotherapy on a Monday resulting in only one weekend break)?MethodsA total of 412 patients with MSCC were included in this retrospective study. Ninety‐two patients receiving 10 × 3 Gy over 12 days were compared to 320 patients with an OTT of 14–15 days. Ten additional factors were investigated.ResultsOn multivariate analysis, functional outcome was associated with tumour type (P < 0.001), time developing motor deficits (P < 0.001), ambulatory status (P = 0.018) and performance score (P < 0.001); OTT had no significant impact (P = 0.40). On univariate analysis of local control of MSCC (freedom from recurrence in irradiated spinal parts), no factor was significant including OTT (P = 0.66). On multivariate analysis, visceral metastases (P < 0.001), tumour type (P < 0.001), time developing motor deficits (P < 0.001), ambulatory status (P < 0.001) and performance score (P < 0.001) were associated with survival, OTT not even on univariate analysis (P = 0.55).ConclusionsSince an OTT of 14–15 days had no negative impact on outcomes compared to 12 days, compensation in form of an additional radiation fraction or continuation of radiotherapy during weekends is not required, if radiotherapy cannot be started on a Monday.

Abstract Background Uncertainty exists whether patients with spinal cord compression (SCC) from a highly radiosensitive tumor require decompressive spinal surgery in addition to radiotherapy (RT). This study addressed the question by evaluating patients receiving RT alone for SCC from myeloma. Patients and methods Data of 238 patients were retrospectively analyzed for response to RT and local control of SCC. In addition, the effect of RT on motor function (improvement, no further progression, deterioration) was evaluated. Overall response was defined as improvement or no further progression of motor dysfunction. Prior to RT, patients were presented to a neurosurgeon for evaluation whether upfront decompressive surgery was indicated (e.g. vertebral fracture or unstable spine). Results In the entire cohort, the overall response rate was 97% (53% improvement plus 44% no further progression). Following RT, 88% of the patients were able to walk. Of the 69 non-ambulatory patients 44 patients (64%) regained the ability to walk. Local control rates at 1, 2 and 3 years were 93%, 82% and 82%, respectively. A trend towards better local control was observed for patients who were ambulatory before starting RT (p = 0.08) and those with a more favorable performance status (p = 0.07). Conclusions RT alone provided excellent response rates, functional outcomes and local control in patients with SCC from myeloma. These results should be confirmed in a prospective randomized trial.

AbstractTo examine, in a prospective fashion, the utilization and efficacy of adjuvant radiation therapy (RT) in patients with resected desmoplastic melanoma (DM). Adult patients with resected, margin‐negative, and nonmetastatic DM were eligible for this single‐arm prospective phase II study. Patients were to receive postoperative RT, 30 Gy in five fractions, to the operative bed with 2‐ to 3‐cm margins (depending on the tumor location). Nodal basin RT was not allowed. The primary study endpoint was the 2‐year local recurrence rate (LRR). Secondary endpoints included the incidence of regional and distant metastatic disease, progression‐free survival, overall survival (OS), and treatment‐related toxicity. Twenty patients with a single de novo DM lesion meeting trial eligibility criteria were enrolled and treated. The 2‐year LRR was 10%, with two patients demonstrating a LR within 2 years of completion of protocol therapy. No regional or distant failures occurred. OS at 2 and 5 years was 95 and 77%, respectively. There were no grade 3 or higher acute or late adverse events that were related to the protocol therapy. Adjuvant RT after wide local excision (WLE) for DM is efficacious and well tolerated. It should be considered for DM patients after margin‐negative WLE. Additional study is needed to further refine low‐risk patient populations that can potentially have adjuvant RT omitted as part of the treatment plan.

Objective To update a previously proposed prognostic scoring system that predicts risk of biochemical recurrence ( BCR ) after salvage radiation therapy ( SRT ) for recurrent prostate cancer when using additional patients and a PSA value of 0.2 ng/ mL and rising as the definition of BCR . Patients and Methods We included 577 patients who received SRT for a rising PSA after radical prostatectomy in this retrospective cohort study. Clinical, pathological, and SRT characteristics were evaluated for association with BCR using relative risks ( RR s) from multivariable Cox regression models. Results With a median follow‐up of 5.5 years after SRT , 354 patients (61%) experienced BCR . At 5 years after SRT , 40% of patients were free of BCR . Independent associations with BCR were identified for the PSA level before SRT ( RR [doubling]: 1.25, P < 0.001), pathological tumour stage ( RR [T3a vs T2] 1.21, P = 0.19; RR [T3b/T4 vs T2] 2.09, P < 0.001; overall P < 0.001), Gleason score ( RR [7 vs <7] 1.63, P < 0.001; RR [8–10 vs <7] 2.28, P < 0.001; overall P < 0.001), and surgical margin status ( RR [positive vs negative] 0.71, P = 0.003). We combined these four variables to create a prognostic scoring system that predicted BCR risk with a c ‐index of 0.66. Scores ranged from 0 to 7, and 5‐year freedom from BCR for different levels of the score was as follows: Score = 0–1: 66%, Score = 2: 46%, Score = 3: 28%, Score = 4: 19%, and Score = 5–7: 15%. Conclusion We developed a scoring system that provides an estimation of the risk of BCR after SRT . These findings will be useful for patients and physicians in decision making for radiation therapy in the salvage setting.