Search

To assess the association between colorectal cancer (CRC) histology, dose, and local failure (LF) after stereotactic ablative radiation therapy (SABR) for pulmonary metastases, and to describe subsequent cancer progression, change of systemic therapy (CST), survival, and their association with treatment indications.From a prospective SABR cohort, 180 pulmonary metastases in 120 patients were identified. Treatment indications were single metastasis, oligometastases, oligoprogression, and dominant areas of progression. Doses of 48 to 52 Gy/4 to 5 fractions were delivered. Since 2010 the dose for peripheral CRC metastases was increased to 60 Gy/4 fractions. Cumulative incidence function (CIF) was used to report LF, progression probability, and CST. The Kaplan-Meier method estimated overall survival (OS). Univariate and multivariable analyses to assess variable associations were conducted.Median follow-up was 22 months (interquartile range, 14-33 months). At 24 months, the CIF of LF was 23.6% (95% confidence interval [CI] 15.1%-33.3%) and 8.3% (95% CI 2.6%-18.6%), respectively, for CRC and non-CRC metastases (P.001). This association remained significant after adjusting for confounders (subdistribution hazard ratio [SHR] 13.6, 95% CI 4.2-44.1, P.001). Among CRC metastases, 56 and 45 received60 Gy and 60 Gy, respectively. Delivering 60 Gy was independently associated with a lower hazard of LF (SHR 0.271, 95% CI 0.078-0.940, P=.040). At 12 months the CIF of progression was 41.67% (95% CI 21.69%-60.56%), 42.51% (95% CI 29.09%-55.29%), 62.96% (95% CI 41.25%-78.53%), and 78.57% (95% CI 42.20%-93.48%), respectively, for patients treated for single metastasis, oligometastases, oligoprogression, and dominant area of progression (P.001). A CST was observed, respectively, in 4 (17%), 17 (31%), 12 (44%), and 10 (71%) patients with a median time of 13.1, 11.1, 8.4, and 8.4 months.Colorectal cancer lung metastases are associated with a higher hazard of LF and require higher SABR doses. Outcomes for patients with oligometastases and oligoprogression treated with SABR seem favorable. Prospective clinical trials are needed to confirm these benefits.

Purpose This work presents the application of a machine learning (ML) algorithm to automatically generate high-quality, prostate low-dose-rate (LDR) brachytherapy treatment plans. The ML algorithm can mimic characteristics of preoperative treatment plans deemed clinically acceptable by brachytherapists. The planning efficiency, dosimetry, and quality (as assessed by experts) of preoperative plans generated with an ML planning approach was retrospectively evaluated in this study. Methods and Materials Preimplantation and postimplantation treatment plans were extracted from 100 high-quality LDR treatments and stored within a training database. The ML training algorithm matches similar features from a new LDR case to those within the training database to rapidly obtain an initial seed distribution; plans were then further fine-tuned using stochastic optimization. Preimplantation treatment plans generated by the ML algorithm were compared with brachytherapist (BT) treatment plans in terms of planning time (Wilcoxon rank sum, α = 0.05) and dosimetry (1-way analysis of variance, α = 0.05). Qualitative preimplantation plan quality was evaluated by expert LDR radiation oncologists using a Likert scale questionnaire. Results The average planning time for the ML approach was 0.84 ± 0.57 minutes, compared with 17.88 ± 8.76 minutes for the expert planner ( P =.020). Preimplantation plans were dosimetrically equivalent to the BT plans; the average prostate V150% was 4% lower for ML plans ( P =.002), although the difference was not clinically significant. Respondents ranked the ML-generated plans as equivalent to expert BT treatment plans in terms of target coverage, normal tissue avoidance, implant confidence, and the need for plan modifications. Respondents had difficulty differentiating between plans generated by a human or those generated by the ML algorithm. Conclusions Prostate LDR preimplantation treatment plans that have equivalent quality to plans created by brachytherapists can be rapidly generated using ML. The adoption of ML in the brachytherapy workflow is expected to improve LDR treatment plan uniformity while reducing planning time and resources.

High-dose-rate brachytherapy boost plus external beam radiation therapy is an established option for intermediate-risk prostate cancer (PCa). Stereotactic body radiation therapy (SBRT) boost can potentially mimic high-dose-rate boost and could be a viable alternative. Here we report the long-term outcomes of a phase 1 dose-escalation trial of single-fraction SBRT boost.Patients had intermediate-risk PCa and were accrued to 3 different SBRT single-fraction dose-level cohorts (10 Gy, 12.5 Gy, and 15 Gy). All received supplemental radiation therapy afterwards (37.5 Gy in 15 fractions). Three gold fiducials were implanted for image guidance. Patients were simulated and treated with a foley catheter and intrarectal balloon. A T2 magnetic resonance imaging scan was used for contouring, and a cine magnetic resonance imaging scan was used to calculate patient-specific internal target volume margins. Toxicity and quality-of-life data were collected using Common Terminology Criteria for Adverse Events v3.0 and the Expanded Prostate Cancer Index Composite.30 patients were accrued, 10 in each cohort. Median follow-up was 72 months. 60% had unfavorable intermediate-risk PCa. Two patients in the 15 Gy cohort developed late grade ≥3 gastrointestinal and genitourinary toxicity, with 1 patient suffering from a grade-4 rectal fistula after a rectal ulcer was biopsied repeatedly. Two patients had biochemical failure. Median PSA nadir was 0.4 ng/mL with 10 Gy, 0.09 ng/mL with 12.5 Gy and 0.07 ng/mL with 15 Gy. Median PSA at 4 years as well as proportion achieving a nadir0.2 ng/mL improved significantly with higher doses. There was no significant change in quality of life from baseline in any of the domains, and the minimal clinically important change was not statistically different between the 3 cohorts.Other than a grade 4 toxicity, which may in part be due to repeated biopsies of a rectal ulcer, single-fraction SBRT boost was feasible and well tolerated. Larger studies are warranted to better document the outcomes of such an approach.

Purpose Gold nanoparticles (GNPs) have been shown to cause sensitization with kilovoltage (kV) radiation. Differences in the absorption coefficient between gold and soft tissue, as a function of photon energy, predict that maximum enhancement should occur in the kilovoltage (kV) range, with almost no enhancement at megavoltage (MV) energies. Recent studies have shown that GNPs are not biologically inert, causing oxidative stress and even cell death, suggesting a possible biological mechanism for sensitization. The purpose of this study was to assess GNP radiosensitization at clinically relevant MV X-ray energies. Methods and Materials Cellular uptake, intracellular localization, and cytotoxicity of GNPs were assessed in normal L132, prostate cancer DU145, and breast cancer MDA-MB-231 cells. Radiosensitization was measured by clonogenic survival at kV and MV photon energies and MV electron energies. Intracellular DNA double-strand break (DSB) induction and DNA repair were determined and GNP chemosensitization was assessed using the radiomimetic agent bleomycin. Results GNP uptake occurred in all cell lines and was greatest in MDA-MB-231 cells with nanoparticles accumulating in cytoplasmic lysosomes. In MDA-MB-231 cells, radiation sensitizer enhancement ratios (SERs) of 1.41, 1.29, and 1.16 were achieved using 160 kVp, 6 MV, and 15 MV X-ray energies, respectively. No significant effect was observed in L132 or DU145 cells at kV or MV energies (SER 0.97–1.08). GNP exposure did not increase radiation-induced DSB formation or inhibit DNA repair; however, GNP chemosensitization was observed in MDA-MB-231 cells treated with bleomycin (SER 1.38). Conclusions We have demonstrated radiosensitization in MDA-MB-231 cells at MV X-ray energies. The sensitization was cell-specific with comparable effects at kV and MV energies, no increase in DSB formation, and GNP chemopotentiation with bleomycin, suggesting a possible biological mechanism of radiosensitization.