MATERIALS/METHODS: Multivariable models developed to predict atomised and generalised urinary symptoms, both acute and late, were considered for validation using a dataset representing 754 participants from the TROG 03.04-RADAR trial. Endpoints and features were harmonised to match the predictive models. The overall performance, calibration and discrimination were assessed.
RESULTS: 14 models from four publications were validated. The discrimination of the predictive models in an independent external validation cohort, measured using the area under the receiver operating characteristic (ROC) curve, ranged from 0.473 to 0.695, generally lower than in internal validation. 4 models had ROC >0.6. Shrinkage was required for all predictive models' coefficients ranging from -0.309 (prediction probability was inverse to observed proportion) to 0.823. Predictive models which include baseline symptoms as a feature produced the highest discrimination. Two models produced a predicted probability of 0 and 1 for all patients.
CONCLUSIONS: Predictive models vary in performance and transferability illustrating the need for improvements in model development and reporting. Several models showed reasonable potential but efforts should be increased to improve performance. Baseline symptoms should always be considered as potential features for predictive models.
METHODS: Optimal RTU (oRTU) rates were determined for nine middle-income countries, following the epidemiological evidence-based method. The actual RTU (aRTU) rates were calculated dividing the total number of new notifiable cancer patients treated with radiotherapy in 2012 by the total number of cancer patients diagnosed in the same year in each country. An analysis of the characteristics of patients and treatments in a series of 300 consecutive radiotherapy patients shed light on the particular patient and treatments profile in the participating countries.
RESULTS: The median oRTU rate for the group of nine countries was 52% (47-56%). The median aRTU rate for the nine countries was 28% (9-46%). These results show that the real proportion of cancer patients receiving RT is lower than the optimal RTU with a rate difference between 10-42.7%. The median percent-unmet need was 47% (18-82.3%).
CONCLUSIONS: The optimal RTU rate in middle-income countries did not differ significantly from that previously found in high-income countries. The actual RTU rates were consistently lower than the optimal, in particular in countries with limited resources and a large population.
METHODS: To explore differences between these two modalities, we assessed the immune cell infiltrate into EMT6.5 mammary tumors after CRT and MRT.
RESULTS: CRT induced marked increases in tumor-associated macrophages and neutrophils while there were no increases in these populations following MRT. In contrast, there were higher numbers of T cells in the MRT treated tumors. There were also increased levels of CCL2 by immunohistochemistry in tumors subjected to CRT, but not to MRT. Conversely, we found that MRT induced higher levels of pro-inflammatory genes in tumors than CRT.
CONCLUSION: Our data are the first to demonstrate substantial differences in macrophage, neutrophil and T cell numbers in tumors following MRT versus CRT, providing support for the concept that MRT evokes a different immunomodulatory response in tumors compared to CRT.
METHOD: We conducted an international survey among experts from medical oncology (MO), clinical oncology (CO), radiation oncology (RO), and neurosurgery (NS) about treatment recommendations for patients with asymptomatic BRAF+ or BRAF mutation negative (BRAF-) MBM. Eighteen specific clinical scenarios were presented and a total of 267 responses were collected. Answers were grouped and compared using Fisher's exact test.
RESULTS: In most MBM scenarios, survey respondents, regardless of specialty, favored RT in addition to systemic therapy. However, for patients with BRAF+ MBM, MO and CO were significantly more likely than RO and NS to recommend BRAF/MEK inhibitors alone, without the addition of RT, including the majority of MO (51%) for patients with 1-3 MBM, all <2 cm. Likewise, for BRAF- MBM, MO and CO more commonly recommended single or dual agent ICI only and dual agent ICI therapy alone was the most common recommendation from MO or CO for MBM <2 cm. When at least 1 of 3 MBM (BRAF+ or BRAF-) was >2 cm, upfront Sx was recommended by all groups with the exception that MO and RO recommended RT for BRAF- MBM.
CONCLUSIONS: In most clinical settings involving asymptomatic MBM, experts recommended RT in addition to systemic therapy. However, recommendations varied significantly according to specialty, with MO and CO more commonly recommending dual systemic therapy alone for up to 9 BRAF- MBM <2 cm.