Predictors of radiation-induced late rectal toxicity in prostate cancer treatment: a volumetric and dosimetric analysis.

Introduction: Prostate cancer (PCa) is a prevalent malignancy in European men, often treated with radiotherapy (RT) for localized disease. While modern RT achieves high success rates, concerns about late gastrointestinal (GI) toxicities persist. This retrospective study aims to identify predictors for late GI toxicities following definitive conventionally fractionated external beam RT (EBRT) for PCa, specifically exploring the dose to the rectal wall. Materials and methods: A cohort of 96 intermediate- to high-risk PCa patients underwent EBRT between 2008 and 2016. Rectum and rectum wall contours were delineated, and 3D dose matrices were extracted. Volumetric and dosimetric indices were computed, and statistical analyses were performed to identify predictors using the Mann-Whitney U-rank test, logistic regression, and recursive feature elimination. Results: In our cohort, 15 out of 96 patients experienced grade II late proctitis. Our analysis reveals distinct optimal predictors for rectum and rectum wall (RW) structures varying with α/ß values (3.0 and 2.3 Gy) across prescribed doses of 68 to 76 Gy. Despite variability, RW predictors demonstrate greater consistency, notably V68Gy[%] to V74Gy[%] for α/ß 3.0 Gy, and V68Gy[%] to V70Gy[%] for α/ß 2.3 Gy. The model with α/ß 2.3 Gy, featuring RW volume receiving 70 Gy (V70Gy[%]), stands out with a BIC value of 62.92, indicating its superior predictive effectiveness. Finally, focusing solely on the rectum structure, the V74Gy[%] emerges the best predictor for α/ß 3.0 Gy, with a BIC value of 66.73. Conclusion: This investigation highlights the critical role of V70Gy[%] in the rectum wall as a robust predictor for grade II late gastrointestinal (GI) toxicity following external beam radiation therapy (EBRT) for prostate cancer (PCa). Furthermore, our findings suggest that focusing on the rectum wall specifically, rather than the entire rectum, may offer improved accuracy in assessing proctitis development. A V70Gy (in EQD2 with α/ß 2.3 Gy) of ≤5% and if possible ≤1% for the rectal wall should be achieved to minimize the risk of late grade II proctitis.

Method to assess the need for re-planning HDR brachytherapy tandem and ring treatments.

High dose rate (HDR) brachytherapy procedures for cervical cancer require multiple applicator insertions for multiple (typically 5) fractions of a single plan, which carries a risk for variability in applicator position between fractions. Due to applicator displacement relative to patient anatomy, the dose to nearby organs-at-risk (OARs) may vary significantly from one fraction to the next. The purpose of this study was to evaluate the effect of changes in HDR tandem and ring (T&R) applicator position on doses to nearby OARs and to present a quick and simple method to estimate doses to OARs inter-fractionally without having to perform a re-plan. Ninety CT image sets for 20 patients, ages 44 to 86, undergoing T&R-based HDR for cervical cancer were used retrospectively for this study. Measures of applicator positional and angular changes relative to the bony anatomy were obtained using image fusion in MIM software, between the planning CT (plan CT) and the CT on the treatment day (CT-TX). Dosimetric data were determined, also using MIM software, using the original (first fraction) dose distribution applied to organs at risk (rectum and bladder), transferred via rigid registration from the plan CT to each CT-TX. Bladder and rectum contours were also transferred from each plan CT to each CT-TX and were tweaked manually to match anatomy on each CT-TX and examined visually for appropriateness. Differences in translation and rotation of the T&R applicator between the planning CT and subsequent individual fractions were recorded and plotted against dose differences between each fraction of treatment and the original (first) fraction. Absolute dose (D2cc) and volume (V50) differences vs positional shifts were calculated and plotted, and the Pearson Product-Moment correlation coefficient between dose parameters and measured positional shifts was determined. Average dosimetric differences between planned dose and subsequent fractional doses obtained through rigid registration were 1.48 ± 1.92 Gy, 14.91 ± 11.92 cm3, 0.56 ± 0.93 Gy, and 1.77 ± 2.18 cm3 for Bladder D2cc, Bladder V50, Rectum D2cc, and Rectum V50, respectively. Correlation between Bladder V50 and sagittal plane rotation gave an r2 of 0.4, showing the most correlation of all parameters studied. Bladder dose and volume increased by a maximum of about 2.7 Gy and 50 cm3 overall for Bladder D2cc and Bladder V50, respectively. Bladder V50 was most sensitive to T&R applicator displacements. We have quantified the effects of applicator positional changes on dose changes for the bladder and rectum. Even large changes in applicator position between fractions did not result in significant changes in dose to these normal tissues, indicating that adaptive re-planning is not necessary.

Predictive clinical and dosimetric parameters for risk of relapse in early-stage non-small cell lung cancer treated by SBRT: A large single institution experience.

Purpose: To evaluate the impact of dosimetric parameters on efficacy of stereotactic body radiation therapy (SBRT) in early-stage non-small cell lung cancer (ES-NSCLC), using Hypofractionated Treatment Effects in the Clinic (HyTEC) reporting standards. Methods: From April 2010 to December 2020, 497 patients who received SBRT for ES-NSCLC at the University Hospital of Liège were retrospectively enrolled. A total dose of 40 to 60 Gy in 3-5 fractions (72-180 Gy biologically effective dose with an α/ß ratio of 10 (BED10)) was prescribed to the 80 % isodose line of the PTV. Potential clinical and dosimetric predictors of recurrence, overall survival (OS) and disease specific survival (DSS) were evaluated using univariate and multivariate analyses. Results: After a median follow-up of 32 months (range 3-143 months), the local control and disease-free survival (DFS) rates at 3 years were 91 % (95 % CI: 90 %-93 %) and 75 % (95 % CI: 73 %-77 %), respectively. The median OS was 41.6 months and the median DSS was not reached. On multivariate analysis, a higher gross tumor volume (GTV) Dmax (BED10) (cut-off 198 Gy) and a larger percent of the GTV receiving ≥110 % of the prescribed dose were predictive of a better local control, only GTV volume was correlated with DSS and no parameter was correlated with OS and regional or distant recurrences. Conclusion: Lung SBRT for ES-NSCLC in 3 to 5 fractions resulted in high local control rates. A higher percent of GTV receiving ≥110 % of the prescribed dose and a higher GTV Dmax (BED10) seem to allow a better local control.

Dosimetric analysis of brachial plexopathy after stereotactic body radiotherapy: Significance of organ delineation.

OBJECTIVES: Examine the significance of contouring the brachial plexus (BP) for toxicity estimation and select metrics for predicting radiation-induced brachial plexopathy (RIBP) after stereotactic body radiotherapy. MATERIALS AND METHODS: Patients with planning target volume (PTV) ≤ 2 cm from the BP were eligible. The BP was contoured primarily according to the RTOG 1106 atlas, while subclavian-axillary veins (SAV) were contoured according to RTOG 0236. Apical PTVs were classified as anterior (PTV-A) or posterior (PTV-B) PTVs. Variables predicting grade 2 or higher RIBP (RIBP2) were selected through least absolute shrinkage and selection operator regression and logistic regression. RESULTS: Among 137 patients with 140 BPs (median follow-up, 32.1 months), 11 experienced RIBP2. For patients with RIBP2, the maximum physical dose to the BP (BP-Dmax) was 46.5 Gy (median; range, 35.7 to 60.7 Gy). Of these patients, 54.5 % (6/11) satisfied the RTOG limits when using SAV delineation; among them, 83.3 % (5/6) had PTV-B. For patients with PTV-B, the maximum physical dose to SAV (SAV-Dmax) was 11.2 Gy (median) lower than BP-Dmax. Maximum and 0.3 cc biologically effective doses to the BP based on the linear-quadratic-linear model (BP-BEDmax LQL and BP-BED0.3cc LQL, α/ß = 3) were selected as predictive variables with thresholds of 118 and 73 Gy, respectively. CONCLUSION: Contouring SAV may significantly underestimate the RIBP2 risk in dosimetry, especially for patients with PTV-B. BP contouring indicated BP-BED0.3cc LQL and BP-BEDmax LQL as potential predictors of RIBP2.

Impact of planning organ at risk volume margins and matching method on late gastrointestinal toxicity in moderately hypofractionated IMRT for locally advanced pancreatic ductal adenocarcinoma.

BACKGROUND: This study examined the differences in late gastrointestinal (GI) toxicities in moderately hypofractionated intensity-modulated radiation therapy (IMRT) for locally advanced pancreatic ductal adenocarcinoma (LA-PDAC) by changing the planning organs at risk volume (PRV) margin and the target matching method and assessed the causes of adverse events. METHODS: We examined 37 patients with LA-PDAC who underwent moderately hypofractionated IMRT between 2016 and 2020 at our institution; 23 patients were treated with wide PRV margins and soft tissue matching (Protocol A) and 14 with narrow PRV margins and fiducial marker matching (Protocol B). The GI toxicities, local control (LC) rate, and overall survival (OS) were assessed for each protocol. The initially planned and daily doses to the gross tumor volume (GTV), stomach, and duodenum, reproduced from cone-beam computed tomography, were evaluated. RESULTS: The late GI toxicity rate of grades 3-4 was higher in Protocol B (42.9%) than in Protocol A (4.3%). Although the 2-year LC rates were significantly higher in Protocol B (90.0%) than in Protocol A (33.3%), no significant difference was observed in OS rates. In the initial plan, no deviations were found for the stomach and duodenum from the dose constraints in either protocol. In contrast, daily dose evaluation for the stomach to duodenal bulb revealed that the frequency of deviation of V3 Gy per session was 44.8% in Protocol B, which was significantly higher than the 24.3% in Protocol A. CONCLUSIONS: Reducing PRV margins with fiducial marker matching increased GI toxicities in exchange for improved LC. Daily dose analysis indicated the trade-off between the GTV dose coverage and the irradiated doses to the GI. This study showed that even with strict matching methods, the PRV margin could not be reduced safely because of GI inter-fractional error, which is expected to be resolved with online adaptive radiotherapy.

Dosimetric Comparison of Hypofractionated Regimen in Breast Cancer Using Two Different Techniques: Intensity-Modulated Radiation Therapy (IMRT) and Volumetric-Modulated Arc Therapy (VMAT).

INTRODUCTION: Breast cancer treated with adjuvant hypofractionation radiotherapy with two different techniques, i.e., volumetric-modulated arc therapy (VMAT) and intensity-modulated radiation therapy (IMRT) and their effects in terms of loco-regional control and adverse effects in terms of cutaneous, pulmonary, and cardiac outcomes are compared. MATERIALS AND METHODS: This is a prospective non-randomized observational study. VMAT and IMRT plan for 30 breast cancer patients who were supposed to receive adjuvant radiotherapy were prepared using a hypofractionation schedule. The plans were dosimetrically evaluated. OBJECTIVE: Dosimetric comparative analysis of IMRT and VMAT in hypofractionated radiotherapy in breast cancer is done and tested whether VMAT has a dosimetric advantage over IMRT. These patients were recruited for a clinical assessment of toxicities. They were followed up for at least three months. RESULT: On dosimetric analysis, planning target volume (PTV) coverage (PTV_ V95) of both VMAT (96.41 ± 1.31) and IMRT (96.63 ± 1.56) were similar with significantly lower monitor units required with VMAT plans (1,084.36 ± 270.82 vs 1,181.55 ± 244.50, p = 0.043). Clinically, all patients tolerated hypofractionation through VMAT (n = 8) and IMRT (n = 8) satisfactorily in the short term. No cardiotoxicity or appreciable falls in pulmonary function test parameters were observed. Acute radiation dermatitis poses challenges similar to standard fractionation or any other delivery technique. CONCLUSION: PVT dose, homogeneity, and conformity indices were similar in both VMAT and IMRT groups. In VMAT, there was high-dose sparing of some critical organs like the heart and lungs at the cost of the low-dose baths to these organs. Increased risk of secondary cancer will require a decade-long follow-up study to indict the VMAT technique. As we move toward precision in oncology, "one-size-fits-all" can never be an acceptable dictum. Each patient is unique and therefore we must offer, and the patient must "choose wisely."

Dosimetric Comparison of Intensity-Modulated Radiation Therapy (IMRT) and Intensity-Modulated Proton Therapy (IMPT) for a Novel Oral Tongue Avoidance Concept in Low-Risk Squamous Cell Carcinoma of the Oral Tongue.

Purpose: After adequate surgical resection, early-stage oral tongue cancer patients can harbor a low risk of local recurrence but remain at risk of regional recurrence. Oral tongue avoidance during adjuvant radiation therapy is an attractive potential treatment strategy to mitigate treatment toxicity. We sought to quantify the dosimetric advantages of this approach and hypothesized that intensity-modulated proton therapy (IMPT) may further reduce organs at risk doses compared with intensity-modulated radiation therapy (IMRT). Materials and Methods: Five patients with oral tongue cancer treated with postoperative radiation therapy from August 2020 to September 2021 were retrospectively reviewed. Novel clinical target volume contours, excluding the oral tongue, were generated while maintaining coverage of bilateral at-risk lymph nodes. Comparison IMRT (X) and IMPT (PBT) plans were generated using standard treatment volumes (control) and avoidance volumes (study) (n = 4 plans/patient). Dosimetric variables for organs at risk were compared using the paired t test. Results: The prescribed dose was 60 Gy in 30 fractions. D95% clinical target volume coverage was similar between X and PBT plans for both control and study clinical target volumes. Comparing control with study plans, both X (58.9 Gy vs 38.3 Gy, P = .007) and PBT (60.2 Gy vs 26.1 Gy, P < .001) decreased the oral cavity dosemean. The pharyngeal constrictor dosemean was also reduced (P < .003). There was no difference between control and study plans for larynx (P = .19), parotid (P = .11), or mandible dose (P = .59). For study plans, PBT significantly reduced oral cavity dosemean (38.3 Gy vs 26.1 Gy, P = .007) and parotid dosemean (23.3 Gy vs 19.3 Gy, P = .03) compared with X. For control plans, there was no difference in oral cavity dosemean using PBT compared with X, but PBT did improve the parotid dosemean (26.6 Gy vs 19.7 Gy, P = .02). Conclusion: This study quantifies the feasibility and dosimetric advantages of oral tongue avoidance while still treating the at-risk lymph nodes for oral tongue cancer. The dosimetric difference between PBT and X was most prominent with an oral tongue-avoidance strategy.

Proton Therapy for Bilateral Breast Cancer Maximizes Normal-Tissue Sparing.

Purpose: Treatment for bilateral breast cancer with radiation therapy is technically challenging. We evaluated the clinical and dosimetric outcomes of a small series of patients with synchronous bilateral breast cancer, including a photon dosimetric comparison, to identify optimal treatment planning approaches. Materials and Methods: We reviewed a registry of patients (simultaneously) diagnosed with synchronous bilateral breast cancers who underwent postoperative definitive adjuvant proton therapy at our institution between 2012 and 2021. All patients were treated with double-scattered proton or pencil-beam scanning therapies. For comparison, intensity-modulated radiation therapy photon plans optimized for organ sparing and coverage were generated after treatment. Results: Six patients were included. The median patient age was 66 years; all were female with no history of breast cancer or radiation therapy. Two (33%) patients received breast/chest wall-only treatments, 1 (17%) required breast plus level I axillary treatment to one side and breast plus regional nodal irradiation (RNI) to the other, and 3 (50%) received bilateral breast/chest plus RNI; dosimetric results are reported for each group's median. Analysis showed clinical target coverage was comparable between proton and photon techniques (V95% of 96.4% with proton, 97.8% with photon). However, protons could deliver superior organ sparing at clinically relevant dose metrics for virtually all structures: a 6.7 Gy absolute reduction in the mean heart dose (7.5 Gy with photons to 0.7 Gy with protons), a 47% to 57% relative reduction in D0.1cm3 to coronary arteries, a 54% relative reduction in lung V20 Gy, and an absolute 7.6 Gy reduction to the brachial plexus. There was also greater esophagus and spinal cord sparing. The overall survival rate was 100% at 1.5 years of median follow-up (0.5-4.9), and all patients were free of disease. For toxicity, all patients had some form of acute side effects: 66% experienced grade 2 breast/chest pain or soreness; 100% had grade 2 radiation dermatitis or skin induration; 33% had grade 2 fatigue; and 17% had grade 2 esophagitis (per the Common Terminology Criteria for Adverse Events [CTCAE] version 5.0; US National Cancer Institute, Bethesda, Maryland). Subacute toxicity (within 6 months) was observed for 17% of patients with delayed onset of grade 3 dermatitis in the setting of preexisting lupus, 17% with a delayed surgical wound complication, and 17% with grade 2 soft tissue fibrosis. No grade 4 or 5 events were observed. Conclusions: Substantial dose reductions to multiple organs at risk while maintaining target coverage make proton the preferred modality for bilateral breast cancer treatment when available.

Interobserver Variations in Target Delineation in Intensity-Modulated Radiation Therapy for Nasopharyngeal Carcinoma and its Impact on Target Dose Coverage.

BACKGROUND: To investigate the differences between physicians in target delineation in intensity-modulated radiation therapy for nasopharyngeal carcinoma as well as their impact on target dose coverage. METHODS: Ninety-nine in-hospital patients were randomly selected for retrospective analysis, and the target volumes were delineated by 2 physicians. The target volumes were integrated with the original plans, and the differential parameters, including the Dice similarity coefficient (DSC), Hausdorff distance (HD), and Jaccard similarity coefficient (JSC) were recorded. The dose-volume parameters to evaluate target dose coverage were analyzed by superimposing the same original plan to the 2 sets of images on which the target volumes were contoured by the 2 physicians. The significance of differences in target volumes and dose coverage were evaluated using statistical analysis. RESULTS: The target dose coverage for different sets of target volumes showed statistically significant differences, while the similarity metrics to evaluate geometric target volume differences did not. More specifically, for PGTVnx, the median DSC, JSC, and HD were 0.85, 0.74, and 11.73, respectively; for PCTV1, the median values were 0.87, 0.77, and 11.78, respectively; for PCTV2, the median values were 0.90, 0.82, and 16.12, respectively. For patients in stages T3-4, DSC, and JSC were reduced but HD was increased compared to those in stages T1-2. Dosimetric analysis indicated that, for the target volumes, significant differences between the 2 physicians were found in D95, D99, and V100 for all the target volumes (ie, PGTVnx, PCTV1, and PCTV2) across the whole group of patients, as well as in patients with disease stages T3-4 and T1-2. CONCLUSIONS: The target volumes delineated by the 2 physicians had a high similarity, but the maximal distances between the outer contours of the 2 sets were significantly different. In patients with advanced T stages, significant differences in dose distributions were found, stemming from the deviations of target delineation.

Potential utility of cone-beam CT-guided adaptive radiotherapy under end-exhalation breath-hold conditions for pancreatic cancer.

PURPOSE: The purpose of this study was to demonstrate the potential utility of cone-beam computed tomography (CBCT)-guided online adaptive radiotherapy (ART) under end-exhalation breath-hold (EE-BH) conditions for pancreatic cancer (PC). METHODS: Eleven PC patients who underwent 15-fraction volumetric-modulated arc therapy under EE-BH conditions were included. Planning CT images and daily 165 CBCT images were imported into a dedicated treatment planning system. The prescription dose was set to 48 Gy in 15 fractions. The reference plan was automatically generated along with predefined clinical goals. After segmentation was completed on CBCT images, two different plans were generated: One was an adapted (ADP) plan in which re-optimization was performed on the anatomy of the day, and the other was a scheduled (SCH) plan, which was the same as the reference plan. The dose distributions calculated using the synthetic CT created from both planning CT and CBCT were compared between the two plans. Independent calculation-based quality assurance was also performed for the ADP plans, with a gamma passing rate of 3%/3 mm. RESULTS: All clinical goals were successfully achieved during the reference plan generation. Of the 165 sessions, gross tumor volume D98% and clinical target volume D98% were higher in 100 (60.1%) and 122 (74.0%) ADP fractions. In each fraction, the V3 Gy  < 1 cm3 of the stomach and duodenum was violated in 47 (28.5%) and 48 (29.1%), respectively, of the SCH fractions, whereas no violations were observed in the ADP fractions. There were statistically significant differences in the dose-volume indices between the SCH and ADP fractions (p < 0.05). The gamma passing rates were above 95% in all ADP fractions. CONCLUSIONS: The CBCT-guided online ART under EE-BH conditions successfully reduced the dose to the stomach and duodenum while maintaining target coverage.

Dosimetric analysis and biological evaluation between proton radiotherapy and photon radiotherapy for the long target of total esophageal squamous cell carcinoma.

Objective: The purpose of this study is to compare the dosimetric and biological evaluation differences between photon and proton radiation therapy. Methods: Thirty esophageal squamous cell carcinoma (ESCC) patients were generated for volumetric modulated arc therapy (VMAT) planning and intensity-modulated proton therapy (IMPT) planning to compare with intensity-modulated radiation therapy (IMRT) planning. According to dose-volume histogram (DVH), dose-volume parameters of the plan target volume (PTV) and homogeneity index (HI), conformity index (CI), and gradient index (GI) were used to analyze the differences between the various plans. For the organs at risk (OARS), dosimetric parameters were compared. Tumor control probability (TCP) and normal tissue complication probability (NTCP) was also used to evaluate the biological effectiveness of different plannings. Results: CI, HI, and GI of IMPT planning were significantly superior in the three types of planning (p < 0.001, p < 0.001, and p < 0.001, respectively). Compared to IMRT and VMAT planning, IMPT planning improved the TCP (p<0.001, p<0.001, respectively). As for OARs, IMPT reduced the bilateral lung and heart accepted irradiation dose and volume. The dosimetric parameters, such as mean lung dose (MLD), mean heart dose (MHD), V 5, V 10, and V 20, were significantly lower than IMRT or VMAT. IMPT afforded a lower maximum dose (D max) of the spinal cord than the other two-photon plans. What's more, the radiation pneumonia of the left lung, which was caused by IMPT, was lower than IMRT and VMAT. IMPT achieved the pericarditis probability of heart is only 1.73% ± 0.24%. For spinal cord myelitis necrosis, there was no significant difference between the three different technologies. Conclusion: Proton radiotherapy is an effective technology to relieve esophageal cancer, which could improve the TCP and spare the heart, lungs, and spinal cord. Our study provides a prediction of radiotherapy outcomes and further guides the individual treatment.

Efficacy, safety, and feasibility of volumetric modulated arc therapy for synchronous bilateral breast cancer management.

Purpose: Volumetric Modulated Arc Therapy (VMAT) exhibits potent advantages regarding target volume coverage and protection of organs at risk, notably in the context of anatomical constraints. Nevertheless, reports concerning VMAT for the treatment of synchronous bilateral breast cancers (SBBC) have been scarce to date. As such, we conducted this observational study to assess efficacy, safety and feasibility of VMAT in SBBC. Materials and Methods: From August 2011 to December 2017, 54 consecutive patients with SBBC with or without axillary nodes involvement underwent a treatment protocol containing radiotherapy using VMAT. A total dose (TD) of 52.2Gy in 29 fractions was delivered to breast and internal mammary chain (IMC) nodes Planning Target Volume (PTV) plus, if applicable, a TD of 49.3Gy in 29 fractions to the supra- and infra-clavicular nodes PTV and a TD of 63.22Gy in 29 fractions to tumor boost PTV. Lungs, heart, esophagus, trachea, liver, thyroid and spinal cord were considered as organs at risk. VMAT feasibility and organ at risk sparing were evaluated by treatments planning of the 20 first enrolled patients. Tolerance and patients' outcome were prospectively monitored by acute/late toxicities records and by the analysis of overall survival (OS), locoregional recurrence-free survival (LRFS) and recurrence-free survival (RFS). Results: Breast, supraclavicular nodes and boost PTV coverage was adequate with at least 98% of PTV encompassed by more than 95% of the prescribed dose. Less than 90% of IMC PTV was encompassed by 95% of the prescribed dose. Mean lung dose was 12.3Gy (range: 7.7 - 18.7); mean heart dose was 10.7Gy (range: 6.2 - 22.3). Concerning acute toxicities, only 2 patients experienced grade 3 skin toxicity (3.7%) and only 1 patient developed grade 1 pneumonitis. After a median follow-up of 5.3 years, grade 2 fibrosis and/or shrinking was observed in 5 patients (10%), and grade 3 fibrosis in 1 patients (2%). The 5-year LRFS-rate, RFS-rate and OS were 98% [95% CI= 86.12-99.70%], 96% [95% CI= 84.63-98.96%] and 100%, respectively.

Risk of Diabetes Mellitus after Radiotherapy for Gastric Mucosa-Associated Lymphoid Tissue Lymphoma.

The long-term effect of radiation on the pancreas in pediatric patients has been studied without individual radiation dosimetric data. This study investigated the effect of radiotherapy on the risk of developing diabetes mellitus (DM) in patients with gastric mucosa-associated lymphoid tissue lymphoma (GML), using individual radiation dosimetric analysis. Retrospective analysis reviewed the data of 225 patients without a history of DM receiving curative treatment for stage IE GML. Involved-site radiotherapy was delivered to the whole stomach in 83 patients. The pancreas was delineated in each patient's computed tomography scan for dosimetric analysis. At a median follow-up of 49.0 months, the 5-year cumulative incidence of DM was 4.5%, 9.6%, and 1.6% in all patients, patients who received radiotherapy, and patients who did not receive radiotherapy, respectively (p = 0.009). Mean pancreatic dose (Dmean; p = 0.009), sex (p = 0.043), and body mass index (BMI; p = 0.008) were independently associated with DM. Using recursive partitioning analysis, patients were classified into low, intermediate, and high-risk groups, with 5-year DM incidence rates of 0.0%, 3.1%, and 15.6%, respectively (p < 0.001). Incidental irradiation of the pancreas can increase the risk of DM, which may be stratified according to patient sex and BMI.

Ways to unravel the clinical potential of carbon ions for head and neck cancer reirradiation: dosimetric comparison and local failure pattern analysis as part of the prospective randomized CARE trial.

BACKGROUND: Carbon ion radiotherapy (CIRT) yields biophysical advantages compared to photons but randomized studies for the reirradiation setting are pending. The aim of the current project was to evaluate potential clinical benefits and drawbacks of CIRT compared to volumetric modulated arc therapy (VMAT) in recurrent head and neck cancer. METHODS: Dose-volume parameters and local failure patterns of CIRT compared to VMAT were evaluate in 16 patients from the randomized CARE trial on head and neck cancer reirradiation. RESULTS: Despite an increased target dose, CIRT resulted in significantly reduced organ at risk (OAR) dose across all patients (- 8.7% Dmean). The dose-volume benefits were most pronounced in the brainstem (- 20.7% Dmax) and the optic chiasma (- 13.0% Dmax). The most frequent local failure was type E (extraneous; 50%), followed type B (peripheral; 33%) and type A (central; 17%). In one patient with type A biological and/or dosimetric failure after CIRT, mMKM dose recalculation revealed reduced target coverage. CONCLUSIONS: CIRT resulted in highly improved critical OAR sparing compared to VMAT across all head and neck cancer reirradiation scenarios despite an increased prescription dose. Local failure pattern analysis revealed further potential CIRT specific clinical benefits and potential pitfalls with regard to image-guidance and biological dose-optimization.

3D Printing of Abdominal Immobilization Masks for Therapeutics: Dosimetric, Mechanical and Financial Analysis.

Molding immobilization masks is a time-consuming process, strongly dependent on the healthcare professional, and potentially uncomfortable for the patient. Thus, an alternative sustainable automated production process is proposed for abdominal masks, using fused deposition modelling (FDM) 3D printing with polylactic acid (PLA). Radiological properties of PLA were evaluated by submitting a set of PLA plates to photon beam radiation, while estimations of their mechanical characteristics were assessed through numerical simulation. Based on the obtained results, the abdominal mask was 3D printed and process costs and times were analyzed. The plates revealed dose transmissions similar to the conventional mask at all energies, and mechanical deformation guarantees the required immobilization, with a 66% final cost reduction. PLA proved to be an excellent material for this purpose. Despite the increase in labour costs, a significant reduction in material costs is observed with the proposed process. However, the time results are not favorable, mainly due to the printing technique used in this study.

The Impact of an Incidental Dose on Axillary Tumor Control and Toxicity in Localized Breast Cancer: A Retrospective Analysis.

PURPOSE: The dosimetric analysis of the incidental axillary dose delivered to axillary lymph node levels I-III by different techniques of whole breast irradiation and the analysis of prognostic factors of axillary recurrence of breast cancer. METHODS: We perform a retrospective analysis that includes 171 patients with localized breast carcinoma irradiated at Centre Paul Strauss. To be included in the study, patients had to have a histological confirmation of breast cancer diagnosis, surgical treatment without axillary lymph node dissection (ALND), whole breast irradiation without axillary irradiation by a specific field, and a treatment plan available. RESULTS: Three patients had lymph node recurrence. There was no significant correlation between the maximal or mean dose delivered at the three axillary levels and the risk of axillary lymph node recurrence. There was no significant correlation between the irradiation technique and the risk of axillary lymph node recurrence. Two patients, both in the HT group, had lymphoedema. There was significantly more lymphoedema in the HT group than in the ST and IMRT groups (p < 0.048). The mean dose in level II was significantly higher in the group of patients with lymphoedema (3.45 Gy (1.08; 9.62) vs. 23.4 Gy (23.1; 23.6)) (p < 0.02). CONCLUSION: The irradiation technique has an influence on the incidental dose delivered to the axillary area, but has no influence on the risk of axillary recurrence. The risk of lymphoedema could be related to the use of HT and the mean dose delivered at level II.

Evaluating the efficacy of anti-fungal blue light therapies via analyzing tissue section images.

Anti-fungal blue light (ABL) therapies have been studied and applied in treating various diseases caused by fungal infection. The existing work has been mainly devoted to study the effect of various light dosages on the fungal viability and on the induced cytotoxic reactive oxygen species (ROS) in the pathogens. While in vivo experimental studies have also been reported, there is still no work targeted on quantifying the effect of light on prohibiting the pathogens from invading into the deeper sites in the skin of their host. This can be attributed to the lack of methods to analyze the tissue section images, which are the main means of examining infected tissues. This work has been devoted to solve such problems, so as to improve dosimetric analyses of ABL therapies on treating fungal infections. Specifically, the invasion depth of the fungi and their ratios to the tissue in four bins at different depths inside the skin were extracted from the tissue section images. The significance of the treatment with different dosages on inhibiting the fungi was also tested by each of these depth-related metrics. The ABL experiments using 415-nm-wavelength LED light were performed on BALB/c mice, whose skin was infected by Candida albicans (C. albicans). The proposed methods were applied to the tissue sections of the experimental animals. The results clearly verified that the fluence up to 180J/cm2 can significantly prohibit the fungal infection into the skin in terms of almost all the newly proposed metrics.

Customization of a Model For Knowledge-Based Planning to Achieve Ideal Dose Distributions in Volume Modulated arc Therapy for Pancreatic Cancers.

PURPOSE: To evaluate customizing a knowledge-based planning (KBP) model using dosimetric analysis for volumetric modulated arc therapy for pancreatic cancer. MATERIALS AND METHODS: The first model (M1) using 56 plans and the second model (M2) using 31 plans were created in the first 7 months of the study. The ratios of volume of both kidneys overlapping the expanded planning target volume to the total volume of both kidneys (Voverlap/Vwhole) were calculated in all cases to customize M1. Regression lines were derived from Voverlap/Vwhole and mean dose to both kidneys. The third model (M3) was created using 30 plans which data put them below the regression line. For validation, KBP was performed with the three models on 21 patients. RESULTS: V18 of the left kidney for M1 plans was 7.3% greater than for clinical plans. Dmean of the left kidney for M2 plans was 2.2% greater than for clinical plans. There was no significant difference between all kidney doses in M3 and clinical plans. Dmean of the left kidney for M2 plans was 2.2% greater than for clinical plans. Dmean to both kidneys did not differ significantly between the three models in validation plans with Voverlap/Vwhole lower than average. In plans with larger than average volumes, the Dmean of validation plans created by M3 was significantly lower for both kidneys by 1.7 and 0.9 Gy than with M1 and M2, respectively. CONCLUSIONS: Selecting plans to register in a model by analyzing dosimetry and geometry is an effective means of improving the KBP model.

Personalized Radiation Attenuating Materials for Gastrointestinal Mucosal Protection.

Cancer patients undergoing therapeutic radiation routinely develop injury of the adjacent gastrointestinal (GI) tract mucosa due to treatment. To reduce radiation dose to critical GI structures including the rectum and oral mucosa, 3D-printed GI radioprotective devices composed of high-Z materials are generated from patient CT scans. In a radiation proctitis rat model, a significant reduction in crypt injury is demonstrated with the device compared to without (p < 0.0087). Optimal device placement for radiation attenuation is further confirmed in a swine model. Dosimetric modeling in oral cavity cancer patients demonstrates a 30% radiation dose reduction to the normal buccal mucosa and a 15.2% dose reduction in the rectum for prostate cancer patients with the radioprotectant material in place compared to without. Finally, it is found that the rectal radioprotectant device is more cost-effective compared to a hydrogel rectal spacer. Taken together, these data suggest that personalized radioprotectant devices may be used to reduce GI tissue injury in cancer patients undergoing therapeutic radiation.

Personalized Treatment Planning Automation in Prostate Cancer Radiation Oncology: A Comprehensive Dosimetric Study.

BACKGROUND: In radiation oncology, automation of treatment planning has reported the potential to improve plan quality and increase planning efficiency. We performed a comprehensive dosimetric evaluation of the new Personalized algorithm implemented in Pinnacle3 for full planning automation of VMAT prostate cancer treatments. MATERIAL AND METHODS: Thirteen low-risk prostate (without lymph-nodes irradiation) and 13 high-risk prostate (with lymph-nodes irradiation) treatments were retrospectively taken from our clinical database and re-optimized using two different automated engines implemented in the Pinnacle treatment system. These two automated engines, the currently used Autoplanning and the new Personalized are both template-based algorithms that use a wish-list to formulate the planning goals and an iterative approach able to mimic the planning procedure usually adopted by experienced planners. In addition, the new Personalized module integrates a new engine, the Feasibility module, able to generate an "a priori" DVH prediction of the achievability of planning goals. Comparison between clinically accepted manually generated (MP) and automated plans generated with both Autoplanning (AP) and Personalized engines (Pers) were performed using dose-volume histogram metrics and conformity indexes. Three different normal tissue complication probabilities (NTCPs) models were used for rectal toxicity evaluation. The planning efficiency and the accuracy of dose delivery were assessed for all plans. RESULTS: For similar targets coverage, Pers plans reported a significant increase of dose conformity and less irradiation of healthy tissue, with significant dose reduction for rectum, bladder, and femurs. On average, Pers plans decreased rectal mean dose by 11.3 and 8.3 Gy for low-risk and high-risk cohorts, respectively. Similarly, the Pers plans decreased the bladder mean doses by 7.3 and 7.6 Gy for low-risk and high-risk cohorts, respectively. The integral dose was reduced by 11-16% with respect to MP plans. Overall planning times were dramatically reduced to about 7 and 15 min for Pers plans. Despite the increased complexity, all plans passed the 3%/2 mm γ-analysis for dose verification. CONCLUSIONS: The Personalized engine provided an overall increase of plan quality, in terms of dose conformity and sparing of normal tissues for prostate cancer patients. The Feasibility "a priori" DVH prediction module provided OARs dose sparing well beyond the clinical objectives. The new Pinnacle Personalized algorithms outperformed the currently used Autoplanning ones as solution for treatment planning automation.