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Purpose: Delayed charge is a small amount of charge that is delivered to the patient after the planned irradiation is halted, which may degrade the quality of the treatment by delivering unwarranted dose to the patient. This study compares two methods for minimizing the effect of delayed charge on the dose delivered with a synchrotron based discrete spot scanning proton beam. Methods: The delivery of several treatment plans was simulated by applying a normally distributed value of delayed charge, with a mean of 0.001(SD 0.00025) MU, to each spot. Two correction methods were used to account for the delayed charge. Method one (CM1), which is in active clinical use, accounts for the delayed charge by adjusting the MU of the current spot based on the cumulative MU. Method two (CM2) in addition reduces the planned MU by a predicted value. Every fraction of a treatment was simulated using each method and then recomputed in the treatment planning system. The dose difference between the original plan and the sum of the simulated fractions was evaluated. Both methods were tested in a water phantom with a single beam and simple target geometry. Two separate phantom tests were performed. In one test the dose per fraction was varied from 0.5 to 2 Gy using 25 fractions per plan. In the other test the number fractions were varied from 1 to 25, using 2 Gy per fraction. Three patient plans were used to determine the effect of delayed charge on the delivered dose under realistic clinical conditions. The order of spot delivery using CM1 was investigated by randomly selecting the starting spot for each layer, and by alternating per layer the starting spot from first to last. Only discrete spot scanning was considered in this study. Results: Using the phantom setup and varying the dose per fraction, the maximum dose difference for each plan of 25 fractions was 0.37-0.39 Gy and 0.03-0.05 Gy for CM1 and CM2, respectively. While varying the total number of fractions, the maximum dose difference increased at a rate of 0.015 Gy and 0.0018 Gy per fraction for CM1 and CM2, respectively. For CM1, the largest dose difference was found at the location of the first spot in each energy layer, whereas for CM2 the difference in dose was small and showed no dependence on location. For CM1, all of the fields in the patient plans had an area where their excess dose overlapped. No such correlation was found when using CM2. Randomly selecting the starting spot reduces the maximum dose difference from 0.708 to 0.15 Gy. Alternating between first and last spot reduces the maximum dose difference from 0.708 to 0.37 Gy. In the patient plans the excess dose scaled linearly at 0.014 Gy per field per fraction for CM1 and standard delivery order. Conclusions: The predictive model CM2 is superior to a cumulative irradiation model CM1 for minimizing the effects of delayed charge, particularly when considering maximal dose discrepancies and the potential for unplanned hot-spots. This study shows that the dose discrepancy potentially scales at 0.014 Gy per field per fraction for CM1. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented regarding treatment of choroidal melanoma with gamma knife radiosurgery (GKR) and carbon fiducials.

Background: In recent years, deep‐learning models have been used to predict entire three‐dimensional dose distributions. However, the usability of dose predictions to improve plan quality should be further investigated. Purpose: To develop a deep‐learning model to predict high‐quality dose distributions for volumetric modulated arc therapy (VMAT) plans for patients with gynecologic cancer and to evaluate their usability in driving plan quality improvements. Methods: A total of 79 VMAT plans for the female pelvis were used to train (47 plans), validate (16 plans), and test (16 plans) 3D dense dilated U‐Net models to predict 3D dose distributions. The models received the normalized CT scan, dose prescription, and target and normal tissue contours as inputs. Three models were used to predict the dose distributions for plans in the test set. A radiation oncologist specializing in the treatment of gynecologic cancers scored the test set predictions using a 5‐point scale (5, acceptable as‐is; 4, prefer minor edits; 3, minor edits needed; 2, major edits needed; and 1, unacceptable). The clinical plans for which the dose predictions indicated that improvements could be made were reoptimized with constraints extracted from the predictions. Results: The predicted dose distributions in the test set were of comparable quality to the clinical plans. The mean voxel‐wise dose difference was −0.14 ± 0.46 Gy. The percentage dose differences in the predicted target metrics of D1%${D}_{1{\mathrm{\% }}}$ and D98%${D}_{98{\mathrm{\% }}}$ were −1.05% ± 0.59% and 0.21% ± 0.28%, respectively. The dose differences in the predicted organ at risk mean and maximum doses were −0.30 ± 1.66 Gy and −0.42 ± 2.07 Gy, respectively. A radiation oncologist deemed all of the predicted dose distributions clinically acceptable; 12 received a score of 5, and four received a score of 4. Replanning of flagged plans (five plans) showed that the original plans could be further optimized to give dose distributions close to the predicted dose distributions. Conclusions: Deep‐learning dose prediction can be used to predict high‐quality and clinically acceptable dose distributions for VMAT female pelvis plans, which can then be used to identify plans that can be improved with additional optimization. [ABSTRACT FROM AUTHOR]

Our randomized clinical study comparing stereotactic body radiotherapy (SBRT) and stereotactic body proton therapy (SBPT) for early stage non-small cell lung cancer (NSCLC) was closed prematurely owing to poor enrollment, largely because of lack of volumetric imaging and difficulty in obtaining insurance coverage for the SBPT group. In this article, we describe technology improvements in our new proton therapy center, particularly in image guidance with cone beam CT (CBCT) and CT on rail (CTOR), as well as motion management with real-time gated proton therapy (RGPT) and optical surface imaging. In addition, we have a treatment planning system that provides better treatment plan optimization and more accurate dose calculation. We expect to re-start the SBPT program, including for early stage NSCLC as well as for other disease sites soon after starting patient treatment at our new proton therapy center. [ABSTRACT FROM AUTHOR]

Purpose: To prospectively assess acute differences in patient‐reported outcomes in bowel and urinary domains between intensity‐modulated radiotherapy (IMRT) and proton beam therapy (PBT) for prostate cancer. Methods and Materials: Bowel function (BF), urinary irritative/obstructive symptoms (UO), and urinary incontinence (UI) domains of EPIC‐26 were collected in patients with T1‐T2 prostate cancer receiving IMRT or PBT at a tertiary cancer center (2015‐2018). Mean changes in domain scores were analyzed from pretreatment to the end of and 3 months post‐radiotherapy for each modality. A clinically meaningful change was defined as a score change >50% of the baseline standard deviation. Results: A total of 157 patients receiving IMRT and 105 receiving PBT were included. There were no baseline differences in domain scores between cohorts. At the end of radiotherapy, there was significant and clinically meaningful worsening of BF and UO scores for patients receiving either modality. In the BF domain, the IMRT cohort experienced greater decrement (−13.0 vs −6.7, P <.01), and had a higher proportion of patients with clinically meaningful reduction (58.4% vs 39.5%, P =.01), compared to PBT. At 3 months post‐radiotherapy, the IMRT group had significant and clinically meaningful worsening of BF (−9.3, P <.001), whereas the change in BF score of the PBT cohort was no longer significant or clinically meaningful (−1.2, P =.25). There were no significant or clinically meaningful changes in UO or UI 3 months post‐radiotherapy. Conclusions: PBT had less acute decrement in BF than IMRT following radiotherapy. There was no difference between the two modalities in UO and UI. [ABSTRACT FROM AUTHOR]

• Compared to VMAT, IMPT is associated with less PEG placement for the treatment of OPC. • IMPT is associated with decreased acute hospitalizations compared to VMAT. • Provider-reported acute toxicities show less mucositis, dysphagia, and pain with IMPT. • Patient-reported outcomes improved with IMPT included cough and dysgeusia. • Benefits were predominantly seen in those treated definitively or with adjuvant CRT. IMPT improves normal tissue sparing compared to VMAT in treating oropharyngeal cancer (OPC). Our aim was to assess if this translates into clinical benefits. OPC patients treated with definitive or adjuvant IMPT or VMAT from 2013 to 2018 were included. All underwent prospective assessment using patient-reported-outcomes (PROs) (EORTC-QLQ-H&N35) and provider-assessed toxicities (CTCAEv4.03). End-of-treatment and pretreatment scores were compared. PEG-tube use, hospitalization, and narcotic use were retrospectively collected. Statistical analysis used the Wilcoxon Rank-Sum Test with propensity matching for PROs/provider-assessed toxicities, and t -tests for other clinical outcomes. 46 IMPT and 259 VMAT patients were included; median follow-up was 12 months (IMPT) and 30 months (VMAT). Baseline characteristics were balanced except for age (p = 0.04, IMPT were older) and smoking (p < 0.01, 10.9% IMPT >20PYs, 29.3% VMAT). IMPT was associated with lower PEG placement (OR = 0.27; 95% CI: 0.12–0.59; p = 0.001) and less hospitalization ≤60 days post-RT (OR = 0.21; 95% CI:0.07–0.6, p < 0.001), with subgroup analysis revealing strongest benefits in patients treated definitively or with concomitant chemoradiotherapy (CRT). IMPT was associated with a relative risk reduction of 22.3% for end-of-treatment narcotic use. Patients reported reduced cough and dysgeusia with IMPT (p < 0.05); patients treated definitively or with CRT also reported feeling less ill, reduced feeding tube use, and better swallow. Provider-assessed toxicities demonstrated less pain and mucositis with IMPT, but more mucosal infection. IMPT is associated with improved PROs, reduced PEG-tube placement, hospitalization, and narcotic requirements. Mucositis, dysphagia, and pain were decreased with IMPT. Benefits were predominantly seen in patients treated definitively or with CRT. [ABSTRACT FROM AUTHOR]

• Radiotherapy is an effective local therapy option for metastatic colorectal cancer. • KRAS or combined KRAS and TP53 mutation are associated with worsened survival. • Combined KRAS and TP53 mutation are associated with increased local failure. To report tumor genomic factors associated with overall survival (OS) and local failure (LF) for patients with colorectal cancer (CRC) who received metastasis-directed stereotactic body radiation therapy (SBRT). This was a retrospective review of patients with CRC who received metastasis-directed SBRT. Tumor genomic alterations were identified through KRAS , BRAF, or a 50-gene next generation sequencing panel. OS and LF were estimated using Kaplan-Meier and competing-risk methods. Eighty-five patients and 109 lesions were treated between 2008 and 2018. The median patient follow-up was 50 months (IQR: 28–107). The median and 5-year OS was 34 months and 26% (95% CI: 16–41%), respectively. The 2-year cumulative incidence of LF was 30% (95% CI: 23–41%). Univariate associates with OS included patient age ≥60 years, bone metastasis, increasing tumor size, KRAS mutation, and combined KRAS and TP53 mutation, while increasing tumor size, bone metastasis, biologically effective dose <100 Gy, and combined KRAS and TP53 mutation were associated with LF. Multivariate associates with OS included patient age ≥60 years (HR: 2.4, 95% CI: 1.2–4.8, p = 0.01), lesion size per 1 cm (HR: 1.3, 95% CI: 1.1–1.5, p < 0.01), and KRAS mutation (HR: 2.2, 95% CI: 1.2–4.3, p < 0.01), while no multivariable model for LF retained more than a single variable. Genomic factors, in particular KRAS and TP53 mutation , may assist in patient selection and radiotherapeutic decision-making for patients with oligometastatic CRC. Prospective validation, ideally with genomic correlation of all irradiated metastases, is warranted. [ABSTRACT FROM AUTHOR]

• Proton therapy provides exceptional normal tissue sparing in women with reconstruction. • Like photons, proton therapy increases reconstruction complications. • Unexpectedly, hypofractionation was associated with reconstruction failure. • Further investigation of optimal dose-fractionation for reconstructed breasts is needed. To report reconstructive outcomes of patients treated with post-mastectomy intensity modulated proton therapy (IMPT) following immediate breast reconstruction (IBR). Consecutive women with breast cancer who underwent implant-based IBR and post-mastectomy IMPT were included. Clinical characteristics, dosimetry, and acute toxicity were collected prospectively and reconstruction complications retrospectively. Fifty-one women were treated between 2015 and 2017. Forty-two had bilateral reconstruction with unilateral IMPT. The non-irradiated contralateral breasts served as controls. Conventional fractionation (median 50 Gy/25 fractions) was administered in 37 (73%) and hypofractionation (median 40.5 Gy/15 fractions) in 14 (27%) patients. Median mean heart, ipsilateral lung V20Gy, and CTV-IMN V95% were 0.6 Gy, 13.9%, and 97.4%. Maximal acute dermatitis grade was 1 in 32 (63%), 2 in 17 (33%), and 3 in 2 (4%) patients. Surgical site infection (hazard ratio [HR] 13.19, 95% confidence interval [CI] 1.67–104.03, p = 0.0012), and unplanned surgical intervention (HR 9.86, 95% CI 1.24–78.67, p = 0.0068) were more common in irradiated breasts. Eight of 51 irradiated breasts and 2 of 42 non-irradiated breasts had reconstruction failure (HR 3.59, 95% CI 0.78–16.41, p = 0.084). Among irradiated breasts, hypofractionation was significantly associated with reconstruction failure (HR 4.99, 95% CI 1.24–20.05, p = 0.024), as was older patient age (HR 1.14, 95% CI 1.05–1.24, p = 0.002). IMPT following IBR spared underlying organs and had low rates of acute toxicity. Reconstruction complications are more common in irradiated breasts, and reconstructive outcomes appear comparable with photon literature. Hypofractionation was associated with higher reconstruction failure rates. Further investigation of optimal dose-fractionation after IBR is needed. [ABSTRACT FROM AUTHOR]

Purpose: To report early adverse events and patient-reported outcomes (PROs) of 3-fraction intracavitary catheter-based partial breast brachytherapy (ICBB).Materials and Methods: Eligible women ≥50 years of age with ≤2.5-cm, lymph node-negative invasive or in situ breast cancer underwent breast-conserving surgery and placement of a brachytherapy applicator. ICBB was initiated on the second weekday after surgery and prescribed to 21 Gy in 3 once-daily fractions. Common Terminology Criteria for Adverse Events, version 4.0; 10-point linear analog scale assessment; the PRO version of the Common Terminology Criteria for Adverse Events; and the Harvard Breast Cosmesis Scale were used for provider and patient-reported assessments.Results: Seventy-three women were treated for invasive (79%) or in situ (21%) breast cancer. The median time to completion of surgery and radiation therapy was 6 days. After 14-months median follow-up, 2 patients (3%) had developed breast infections that resolved with oral antibiotics. There was no other treatment-associated adverse event grade ≥2. The grade 1 seroma rate at 3 months was 20%, which dropped to 8% at 12 months; no events required intervention. At 12 months, 91% of patients reported an overall quality of life score as ≥8 of 10, and patient-reported cosmesis was good or excellent in 95%. All patients are alive without relapse at the last follow-up.Conclusions: Three-fraction ICBB is associated with low rates of early provider and patient- reported adverse events and compares favorably with early outcomes of more protracted ICBB regimens, including twice-daily (3.4 Gy × 10) fractionation studied in the National Surgical Adjuvant Breast and Bowel Project (NSABP) B-39. Further investigation is warranted. [ABSTRACT FROM AUTHOR]

Purpose Determine feasibility and resultant dosimetry of an intraoperatively placed multichannel intracavitary brachytherapy catheter for accelerated partial breast irradiation (APBI). Methods Patients with breast cancer underwent intraoperative brachytherapy catheter placement based on frozen section analysis with immediate postoperative APBI. The planning target volume evaluation (PTVEval) and organs at risk were contoured on daily pretreatment CT scans for each patient, and the original treatment plan was applied to assess full-course dosimetry. Results Of the first 21 patients consented for intraoperative catheter placement, 20 (95%) were able to proceed with treatment as planned. The mean volume of PTVEval receiving 90% of prescription dose ( V 90% ) and mean percentage of prescription dose to 90% of the PTVEval ( D 90% ) on initial planning were 96.7 (±1.1%) and 100.2 (±2.1%), respectively. Full-course dose coverage remained excellent with a mean PTVEval V 90% and D 90% of 95.0 (±4.4%) and 100.2 (±9.6%), respectively. Mean full-course maximum dose constraints for chest wall and skin were met by 70% and 95% of patients, respectively. Air accumulation >1 cc during treatment increased the risk of a daily fraction with PTVEval coverage below goal (odds ratio, 9.8; p = 0.05), whereas those with applicators <0.5 cm from the chest wall at planning were at risk of exceeding that organ's maximum dose constraint on a daily fraction (odds ratio, 45; p = 0.02). Conclusions Intraoperative catheter placement and early initiation of APBI based on frozen section pathology is feasible, yields acceptable dosimetry, and is an option for completing breast conserving therapy in less than 10 days. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this analysis was to evaluate dose-volume relationships associated with a higher probability for developing chest wall toxicity (pain) after accelerated partial breast irradiation (APBI) by using both single-lumen and multilumen brachytherapy. Methods and Materials: Rib dose data were available for 89 patients treated with APBI and were correlated with the development of chest wall/rib pain at any point after treatment. Ribs were contoured on computed tomography planning scans, and rib dose-volume histograms (DVH) along with histograms for other structures were constructed. Rib DVH data for all patients were sampled at all volumes ≥0.008 cubic centimeter (cc) (for maximum dose related to pain) and at volumes of 0.5, 1, 2, and 3 cc for analysis. Rib pain was evaluated at each follow-up visit. Patient responses were marked as yes or no. No attempt was made to grade responses. Eighty-nine responses were available for this analysis. Results: Nineteen patients (21.3%) complained of transient chest wall/rib pain at any point in follow-up. Analysis showed a direct correlation between total dose received and volume of rib irradiated with the probability of developing rib/chest wall pain at any point after follow-up. The median maximum dose at volumes ≥0.008 cc of rib in patients who experienced chest wall pain was 132% of the prescribed dose versus 95% of the prescribed dose in those patients who did not experience pain (p = 0.0035). Conclusions: Although the incidence of chest wall/rib pain is quite low with APBI brachytherapy, attempts should be made to keep the volume of rib irradiated at a minimum and the maximum dose received by the chest wall as low as reasonably achievable. [ABSTRACT FROM AUTHOR]

Background and Purpose: To report dosimetry and early adverse effects, aesthetic, and patient-reported outcomes of a prospective study of 3-fraction pencil-beam scanning (PBS) proton accelerated partial irradiation (APBI).Materials and Methods: Eligibility included women age ≥ 50 years with estrogen receptor positive (ER+), sentinel lymph node negative invasive or in-situ breast cancer measuring ≤2.5 cm. The prescription was 21.9 Gy (RBE 1.1) in 3 daily fractions to the post-operative tumor bed with a 1 cm expansion. Toxicities were collected using Common Terminology Criteria for Adverse Events (CTCAE) version 4.0, 10-point Linear Analog Scale Assessment, Patient-Reported Outcomes Version of the CTCAE, and the Harvard Breast Cosmesis Scale.Results: Seventy-six women were treated between 2015 and 2017. The median breast volume receiving 50% of prescription or more was 28%. Median mean heart, mean ipsilateral lung, and maximum skin dose were 0 Gy, 0.1 Gy, and 20.6 Gy, respectively. With a median follow-up of 12 months, no treatment-related toxicity grade ≥ 2 has been observed. Most common grade 1 adverse events were dermatitis (68%) and skin hyperpigmentation (18%). At 12 months, the only persistent toxicities were one patient with grade 1 breast edema and one patient with a grade 1 seroma. 90% of patients reported quality of life as ≥7 out of 10 (0 indicating "as bad as it can be" and 10 indicating "as good as it can be") and 98% of patients reported excellent or good cosmesis.Conclusion: 3-fraction PBS proton APBI is well tolerated with low rates of physician and patient reported early adverse effects. Follow-up is ongoing to assess late toxicities and disease control outcomes. Further investigation of this novel adjuvant treatment strategy is warranted. [ABSTRACT FROM AUTHOR]