Intercenter validation of a knowledge based model for automated planning of volumetric modulated arc therapy for prostate cancer. The experience of the German RapidPlan Consortium.

PURPOSE: To evaluate the performance of a model-based optimisation process for volumetric modulated arc therapy applied to prostate cancer in a multicentric cooperative group. The RapidPlan (RP) knowledge-based engine was tested for the planning of Volumetric modulated arc therapy with RapidArc on prostate cancer patients. The study was conducted in the frame of the German RapidPlan Consortium (GRC). METHODS AND MATERIALS: 43 patients from one institute of the GRC were used to build and train a RP model. This was further shared with all members of the GRC plus an external site from a different country to increase the heterogeneity of the patient's sampling. An in silico multicentric validation of the model was performed at planning level by comparing RP against reference plans optimized according to institutional procedures. A total of 60 patients from 7 institutes were used. RESULTS: On average, the automated RP based plans resulted fully consistent with the manually optimised set with a modest tendency to improvement in the medium-to-high dose region. A per-site stratification allowed to identify different patterns of performance of the model with some organs at risk resulting better spared with the manual or with the automated approach but in all cases the RP data fulfilled the clinical acceptability requirements. Discrepancies in the performance were due to different contouring protocols or to different emphasis put in the optimization of the manual cases. CONCLUSIONS: The multicentric validation demonstrated that it was possible to satisfactorily optimize with the knowledge based model patients from all participating centres. In the presence of possibly significant differences in the contouring protocols, the automated plans, though acceptable and fulfilling the benchmark goals, might benefit from further fine tuning of the constraints. The study demonstrates that, at least for the case of prostate cancer patients, it is possibile to share models among different clinical institutes in a cooperative framework.

Single brain metastasis: resection followed by whole-brain irradiation and a boost to the metastatic site compared to whole-brain irradiation plus radiosurgery.

OBJECTIVE: The most appropriate treatment for a single brain metastasis is still controversial. This matched-pair analysis compared whole-brain irradiation plus radiosurgery (WBI+RS) to neurosurgical resection followed by whole-brain irradiation and a boost to the metastatic site (NR+WBI+B). METHODS: The data of 46 patients treated with WBI+RS were matched 1:1 to 46 patients treated with NR+WBI+B with respect to age, gender, Karnofsky performance score (KPS), tumor type, extracerebral metastases, and interval from first diagnosis of cancer to treatment of the metastasis, RPA class, and GPA score. Both groups were compared for local control of the treated metastasis, intracerebral control, and survival. RESULTS: The 1-year local control rates were 85% after WBI+RS and 78% after NR+WBI+B (p=0.35). The 1-year intracerebral control rates were 74% and 68% (p=0.33), respectively. The 1-year survival rates were 64% and 58% (p=0.70), respectively. A multivariate analysis was not performed for local and intracerebral control, because no factor achieved significance on univariate analyses for these endpoints. Improved survival was associated with KPS>70 (p=0.032), absence of extracerebral metastases (p=0.003), RPA-class 1 (p=0.014), and GPA score of 3.0-4.0 (p=0.010). CONCLUSION: Treatment outcomes were not significantly different after WBI+RS or NR+WBI+B. Because WBI+RS is less invasive, it may be preferable for many patients with a single brain metastasis.

Prognostic factors for outcomes after whole-brain irradiation of brain metastases from relatively radioresistant tumors: a retrospective analysis.

BACKGROUND: This study investigated potential prognostic factors in patients treated with whole-brain irradiation (WBI) alone for brain metastases from relatively radioresistant tumors such as malignant melanoma, renal cell carcinoma, and colorectal cancer. Additionally, a potential benefit from escalating the radiation dose was investigated. METHODS: Data from 220 patients were retrospectively analyzed for overall survival and local control. Nine potential prognostic factors were evaluated: tumor type, WBI schedule, age, gender, Karnofsky performance score, number of brain metastases, extracerebral metastases, interval from diagnosis of cancer to WBI, and recursive partitioning analysis (RPA) class. RESULTS: Survival rates at 6 and 12 months were 32% and 19%, respectively. In the multivariate analysis, WBI doses >30 Gy (p = 0.038), KPS ≥70 (p < 0.001), only 1-3 brain metastases (p = 0.007), no extracerebral metastases (p < 0.001), and RPA class 1 (p < 0.001) were associated with improved survival. Local control rates at 6 and 12 months were 37% and 15%, respectively. In the multivariate analyses, KPS ≥70 (p < 0.001), only 1-3 brain metastases (p < 0.001), and RPA class 1 (p < 0.001) were associated with improved local control. In RPA class 3 patients, survival rates at 6 months were 10% (35 of 39 patients) after 10 × 3 Gy and 9% (2 of 23 patients) after greater doses, respectively (p = 0.98). CONCLUSIONS: Improved outcomes were associated with WBI doses >30 Gy, better performance status, fewer brain metastases, lack of extracerebral metastases, and lower RPA class. Patients receiving WBI alone appear to benefit from WBI doses >30 Gy. However, such a benefit is limited to RPA class 1 or 2 patients.

A matched-pair analysis comparing whole-brain radiotherapy plus stereotactic radiosurgery versus surgery plus whole-brain radiotherapy and a boost to the metastatic site for one or two brain metastases.

PURPOSE: To compare the results of whole-brain radiotherapy plus stereotactic radiosurgery (WBRT+SRS) with those of surgery plus whole-brain radiotherapy and a boost to the metastatic site (OP+WBRT+boost) for patients with one or two brain metastases. METHODS AND MATERIALS: Survival, intracerebral control, and local control of the treated metastases were retrospectively evaluated. To reduce the risk of selection bias, a matched-pair analysis was performed. The outcomes of 47 patients who received WBRT+SRS were compared with those of a second cohort of 47 patients who recieved OP+WBRT+boost. The two treatment groups were matched for the following potential prognostic factors: WBRT schedule, age, gender, performance status, tumor type, number of brain metastases, extracerebral metastases, recursive partitioning analysis class, and interval from tumor diagnosis to WBRT. RESULTS: The 1-year survival rates were 65% after WBRT+SRS and 63% after OP+WBRT+boost (p = 0.19). The 1-year intracerebral control rates were 70% and 78% (p = 0.39), respectively. The 1-year local control rates were 84% and 83% (p = 0.87), respectively. On multivariate analyses, improved survival was significantly associated with better performance status (p = 0.009), no extracerebral metastases (p = 0.004), recursive partitioning analysis Class 1 (p = 0.004), and interval from tumor diagnosis to WBRT (p = 0.001). Intracerebral control was not significantly associated with any of the potential prognostic factors. Improved local control was significantly associated with no extracerebral metastases (p = 0.037). CONCLUSIONS: Treatment outcomes were not significantly different after WBRT+SRS compared with OP+WBRT+boost. However, WBRT+SRS is less invasive than OP+WBRT+boost and may be preferable for patients with one or two brain metastases. The results should be confirmed by randomized trials.

Whole brain radiotherapy plus stereotactic radiosurgery (WBRT+SRS) versus surgery plus whole brain radiotherapy (OP+WBRT) for 1-3 brain metastases: results of a matched pair analysis.

This study is the first one to compare WBRT+SRS to OP+WBRT for 1-3 brain metastases. Survival (OS), intracerebral control (IC) and local control (LC) of the treated metastases were retrospectively evaluated in 52 patients undergoing WBRT+SRS and in 52 patients undergoing OP+WBRT. Both groups were matched for WBRT schedule, age, gender, performance status, tumour, number of brain metastases, extracerebral metastases, RPA class and interval from tumour diagnosis to WBRT. One-year OS was 56% after WBRT+SRS and 47% after OP+WBRT (p=0.034). One-year IC was 66% and 50% (p=0.003). One-year LC was 82% and 66% (p=0.006). On multivariate analyses, it was found that improved OS was associated with younger age (p=0.044), no extracerebral metastases (p<0.001), RPA class 1 (p<0.001) and longer interval from tumour diagnosis to WBRT (p=0.001). IC was associated with younger age (p=0.002) and longer interval (p=0.004); WBRT+SRS achieved borderline significance (p=0.052). Improved LC was associated with longer interval (p=0.017); WBRT+SRS showed a trend (p=0.09). WBRT+SRS appears at least as effective as OP+WBRT.

Comparison of stereotactic radiosurgery (SRS) alone and whole brain radiotherapy (WBRT) plus a stereotactic boost (WBRT+SRS) for one to three brain metastases.

BACKGROUND: The best available treatment of patients with one to three brain metastases is still unclear. This study compared the results of stereotactic radiosurgery (SRS) alone and whole brain radiotherapy (WBRT) plus SRS (WBRT+SRS). PATIENTS AND METHODS: Survival (OS), intracerebral control (IC), and local control of treated metastases (LC) were retrospectively analyzed in 144 patients receiving SRS alone (n=93) or WBRT+SRS (n=51). Eight additional potential prognostic factors were evaluated: age, gender, Eastern Cooperative Oncology Group performance score (ECOG-PS), tumor type, number of brain metastases, extracerebral metastases, recursive partitioning analysis (RPA) class, and interval from tumor diagnosis to irradiation. Subgroup analyses were performed for RPA class I and II patients. RESULTS: 1-year-OS was 53% after SRS and 56% after WBRT+SRS (p=0.24). 1-year-IC rates were 51% and 66% (p=0.015), respectively. 1-year-LC rates were 66% and 87% (p=0.003), respectively. On multivariate analyses, OS was associated with age (p=0.004), ECOG-PS (p=0.005), extracerebral metastases (p<0.001), RPA class (p<0.001), and interval from tumor diagnosis to irradiation (p<0.001). IC was associated with interval from tumor diagnosis to irradiation (p=0.004) and almost with treatment (p=0.09), and LC with treatment (p=0.026) and almost with interval (p=0.08). The results of the subgroup analyses were similar to those of the entire cohort. The increase in IC was stronger in RPA class I patients. CONCLUSION: WBRT+SRS resulted in better IC and LC but not better OS than SRS alone. Because also IC and LC are important end-points, additional WBRT appears justified in patients with one to three brain metastases, in particular in RPA class I patients.