Second Malignancy Probabilities in Patients With Breast Cancer Treated With Conventional Versus Hypofractionated External Beam Radiation Therapy in the Adjuvant Setting.

AIMS: For women with breast cancer, seminal studies have shown that adjuvant hypofractionated external beam radiation therapy (hEBRT) maintains similar outcomes and may reduce overall costs compared with conventionally fractionated external beam radiation therapy (cEBRT). However, it is unclear whether hEBRT may be associated with differential risk of development of radiation-induced second malignancies compared with cEBRT. Because the occurrence of second malignancies is small, large databases may improve our understanding of the relative risk of second malignancies between hEBRT and cEBRT. MATERIALS AND METHODS: Using the National Cancer Database, we carried out a retrospective cohort analysis of women diagnosed with non-metastatic, stage 0-III breast cancer from 2004 to 2017. All patients had a lumpectomy or mastectomy and a follow-up time of at least 60 months after diagnosis. The probability of second malignancies in women receiving adjuvant cEBRT or hEBRT was compared using multivariable logistic regression adjusting for sociodemographic, geographical, clinical and treatment factors, allowing for relative (but not absolute) comparison of second malignancy risk. Temporal sensitivity analyses stratified by year of diagnosis and length of follow-up time were also conducted. RESULTS: Of the 125 228 women in our study, 115 576 (92.3%) received cEBRT and 9652 (7.71%) received hEBRT. The median age of the cohort was 60 (interquartile range 51-68) years at diagnosis and the median follow-up time was 99.61 (interquartile range 77.5-128.49) months. Upon adjusting for sociodemographic and clinical factors, patients who received hEBRT had no difference in relative risk than patients who received cEBRT (odds ratio 0.937, 95% confidence interval 0.869-1.010, P = 0.091). In analyses stratified by year of diagnosis, and stratified by length of follow-up, there was no difference in second malignancy probability between patients who completed hEBRT and patients who completed cEBRT. CONCLUSIONS: In this analysis of over 120 000 women with non-metastatic breast cancer, hEBRT was not associated with different odds of developing second malignancies compared with cEBRT. Our findings may inform patient counselling in the choice of radiation regimens for breast cancer and further support the safety of hypofractionated regimens for breast cancer.

Use of high and very high dose radiotherapy after radical prostatectomy for prostate cancer in the United States.

BACKGROUND: The cost-benefit tradeoff of radiation dose-intensification for prostate cancer in the post-prostatectomy setting is difficult to predict and is ideally studied in randomized trials. The purpose of this study was to assess the use of dose-escalated post-operative radiation (PORT) for prostate cancer in the United States, during a period in which there were no published level 1 studies on dose-escalation. METHODS: We performed analyses on pT2-3, N0, M0 prostate cancer patients who received PORT after an R0-1 resection within the National Cancer Data Base (NCDB), 2003-2012. We classified patients according to the use of high dose (>66.60 cGy) and very high dose (>70.20 cGy) radiation. We used regression analysis to assess the association of year of treatment with use of high and very high dose PORT. To demonstrate the potential of a registry-based network like the NCDB to prospectively monitor changes in radiation dosing patterns, we determined the year in which a significant change in dose could have been first detected had dose been actively monitored. RESULTS: Between 2003 and 2012, the use of high dose PORT increased from 29.9% CI (26.7-33.1) to 63.5% CI (60.6-66.5) and very high dose PORT from 4.5% CI (3.1-5.9) to 10.8% CI (8.9-12.6) (adjusted p < 0.01, for both trends). Patients diagnosed at community centers were less likely to be treated with high dose PORT compared to those at academic or comprehensive centers (p < 0.01 for both comparisons). Had the NCDB network been prospectively monitoring PORT dose, significant increases in dose would have been detected as early as 2004 and after every year of the study period. CONCLUSIONS: The use of both high dose and very high dose PORT increased two-fold from 2003 to 2012 in the absence of randomized studies. This change in practice may be exposing patients to excess toxicity without cancer control benefits. Monitoring dosing patterns using cancer registries is feasible.

SU-E-J-153: Volumetric and Dosimetric Variations of Post-Prostatectomy Patients Treated with Radiation Therapy and Endorectal Ballon.

PURPOSE: Post-prostatectomy patients may be treated with endorectal balloon (ERB) placed during the radiation therapy. The objectives of this tudy are to investigate geometrical variation of organs at risk (OAR) and CTVs (based on RTOG and EORTC guidelines) throughout the course of radiation therapy and their dosimetric impact. METHODS: Six consecutive post-prostatectomy patients enrolled on a prospective IRB approved institutional study were analyzed. Patients underwent CT/MRI simulation and treatment with daily endorectal balloon (ERB). Six T2-MRI scans were performed during the treatment course. Bladder, rectum and two sets of CTVs according to the RTOG and EORTC guidelines were contoured by physician on each of the weekly MRI scans. The MRI scans were subsequently rigidly fused to the CT simulation images to simulate daily kV-kV patient alignment. RESULTS: 1. A consistent trend of decreasing bladder volume was found after the first week of treatment and therefore the V65Gy was found to increase after the second week of the treatment.2. The rectal volume with ERB was found to be relatively consistent during the treatment course. Displacements of rectal contours were within 2mm in all directions. The V60Gy<20% (our institutional rectal constraint) varied on average less than 2%.3. We found that the CTV volumes contoured per EORTC guideline exhibits a larger variation than those drawn according to the RTOG guidelines most likely due to the bladder exclusion imposed by it. While the average variation of RTOG based CTV volume was found within 5%, the variation of CTV-EROTC volumes was more then 10%) (p = 0.06). CONCLUSIONS: In post-prostatectomy patients undergoing radiotherapy with daily ERB had a consistent decrease in the bladder volume during the treatment leading to increased bladder irradiation and changes in the CTV volumes predominantly when EORTC guideline were followed.

A phase I study of cranial radiation therapy with concomitant continuous infusion paclitaxel in children with brain tumors.

BACKGROUND: The prognosis of children with high-grade astrocytomas of the central nervous system is grim and has not been substantially improved by conventional chemoradiotherapy. We performed a multi-institutional phase I study to determine the toxicities and tolerance of concurrent external beam radiation of the brain and a unique dose-schedule of paclitaxel as a radiation sensitizer. PROCEDURE: Paclitaxel was delivered intravenously as a continuous 24 h/day, 7 days/week infusion during the entire 6-week course of fixed schedule standard radiation therapy. The dose of paclitaxel was escalated in patient cohorts in standard phase I design. RESULTS: Eleven patients (eight brain stem gliomas, one glioblastoma multiforme, and two gliomatosis cerebri) were treated. Dose-limiting toxicity was encountered in the two patients treated at 6 mg/(m(2)/24 h), both of whom developed severe obstipation requiring prolonged hospitalization. CONCLUSIONS: We have shown in this first study of its kind that paclitaxel can be administered safely to children as a 6-week continuous infusion concurrent with cranial irradiation. The maximally tolerated and recommended phase II dose is 4 mg/(m(2)/day). The benefits of taxanes as clinical radiation sensitizers for children with high-grade gliomas, if any, remain to be determined.