OBJECTIVE: We present long-term outcomes from a phase 3 randomized controlled trial that compared helical tomotherapy with 3-dimensional conformal radiation therapy (3D-CRT) in the treatment of high-risk prostate cancer.
METHODS: Newly diagnosed patients with high-risk prostate cancer were randomly allocated to receive radical radiation therapy (RT) using 3D-CRT or helical tomotherapy. In both arms, patients received an initial dose of 46 Gy in 23 fractions to the prostate and pelvic lymph nodes, followed by an additional boost to the prostate of 32 Gy in 16 fractions. RT was combined with 3 years of adjuvant androgen deprivation. The primary endpoint was late (>90 days since RT initiation) rectal toxicity.
RESULTS: Overall,123 patients were randomly assigned to either the 3D-CRT (n = 60) or tomotherapy (n = 63) arms. The median follow-up was 161 months. Overall, the proportion of patients with grade ≥ 2 late rectal toxicity was 8.3% (95% CI, 3.1-19.1; n = 5) in the 3D-CRT arm and 11.1% (95% CI, 5.0-22.2; n = 7) in the tomotherapy arm with no significant between-arm difference (P = .83). There was no significant difference (P = .17) in the proportion of patients with late grade ≥ 2 genitourinary toxicity:10.0% (95% CI, 4.1-21.2) in the 3D-CRT arm and 20.6% (95% CI, 11.9-33.0) in the tomotherapy arm. There was no significant difference in the hazard of biochemical progression or death between the 2 groups (hazard ratio for the tomotherapy arm: 0.72; 95% CI, 0.46-1.15; P = .17).
CONCLUSIONS: In this phase 3 trial, the overall incidence of grade ≥ 2 rectal toxicity was low and was not significantly different between the 2 arms. There was no significant evidence of improved biochemical progression-free survival in patients treated with tomotherapy. These findings should be interpreted considering the possibility of type II errors due to limited sample size and low event rates.

A comparison of the radiation exposure to the left anterior descending artery (LAD) and left ventricle (LV) was performed for twenty-three left breast cancer patients. For each participant, two tangential fields 3D-CRT, two- and seven-field IMRT and two and four partial arcs VMAT plans were created. Dose constraints for CTV, ipsilateral lung and heart were followed. The V40Gy, V30Gy, Dav of LAD and V23Gy, V5Gy, Dav of LV were calculated and extracted from the plans. Parametric and non-parametric tests were applied to compare the parameters derived from the five treatment techniques. All generated plans fulfilled the dose constraints. The Dav ranges of the LAD and LV from all examined techniques were 11.77-14.73 Gy and 5.37-6.40 Gy, respectively. The V40Gy and V30Gy ranges of the LAD were 2.90-12.91% and 10.80-18.51%, respectively. The V23Gy and V5Gy of the LV were 4.29-7.43% and 18.24-30.05%, respectively. The VMAT plans and seven-field IMRT significantly reduced the V40Gy, V30Gy of LAD and V23Gy of LV compared with the two-field treatments (p < 0.05). However, 3D-CRT plans provided statistically lower values for V5Gy of LV over the other techniques (p < 0.05). The presented results provide a detailed dataset of the radiation burden of two critical cardiac structures from five radiotherapy techniques.

BACKGROUND: Ultra-hypofractionated radiotherapy (UHF-RT) mandates more accuracy in each part of the treatment cycle to maximize cure rates and minimize toxicities. In vivo dosimetry is a direct method for verifying overall treatment accuracy. This study evaluated uncertainties in the delivered dose of Hypofractionated (HF) and UHF Whole Breast Irradiation (WBI) and to analyze the accuracy of the workflow to pave the way for a wide-scale use of UHF-RT.
METHODS: Thirty-three breast cancer cases, including 16 HF-WBI and 17 UHF-WBI were treated with 3D conformal Radiotherapy (3D-CRT), where 79 fields were analyzed for dose verification. The measurement point was set at the beam entrance (1.5 cm depth). The expected dose at Dmax was calculated via TPS. Before in vivo measurements, diode detectors were tested and calibrated. We developed initial validation measurements for UHF-RT on an anthropomorphic breast phantom for the first time.
RESULTS: For RANDO phantom, the percentage difference between measured and calculated doses showed an average of -0.52 ± 5.4%, in addition to an excellent dose reproducibility within 0.6%. The overall in vivo measurements for studied cases showed that 83.5% of the measured doses were within ±5% and only 1.8% of the measured doses were greater than ±10% of the calculated doses. The percentage accuracy was slightly larger for UHF cohort (84.2%) compared to HF cohort (83.2%). The maximum percentage difference between them was less than 1%.
CONCLUSIONS: Breast in vivo dosimetry is an adequate tool for treatment verification that improves the accuracy of the treatment cycle. UHF-RT may contribute in reducing the long waiting lists, increasing patient convenience, and saving the available resources for breast cancer patients.

Objective: To determine radiation dose volume threshold in predicting the development of hypothyroidism in cancer patients following neck irradiation. Methods: This is a cross sectional follow up study for patients who had been previously irradiated, prior to enrolment in the study. We have done thyroid dose-volumetric analysis on 120 histologically proven cancer patients in the age group of 18-75 years who received neck irradiation as a part of their definitive or adjuvant radiotherapy with three-dimensional conformal or intensity-modulated radiotherapy technique (3D -CRT or IMRT) and completed at least six months post-radiotherapy. Primary tumor sites included carcinoma or lymphoma of the head and neck, breast, cervical, and upper thoracic esophagus, requiring neck irradiation. Results: The proportion of patients who tested positive for Radiation induced hypothyroidism (RIHT) was found to be 40%, with clinical hypothyroidism and subclinical hypothyroidism being 25.8% and 14.2%, respectively. Time to develop hypothyroidism peaks around two years. Mean thyroid gland dose (Dmean) >28 Gy, thyroid gland volume receiving 40 Gy dose (i.e. V40) >49% and age <50 years were found to be significant risk factors for the development of RIHT on binary logistic regression. RT dose >50 Gy and thyroid gland volume spared from 40 Gy (i.e. VS40) < 2.12cm3 were statistically significant predictors for RIHT on chi-square and (Receiver operating characteristic) ROC curve analysis respectively but not on regression analysis. Conclusion: Dose-volume threshold for the thyroid gland as Dmean <28 Gy and V40 <49% may prevent the development of RIHT.

We evaluated clinical and dosimetric outcomes of radiotherapy using two anterior oblique portals (AOP), to reduce the dose to the bilateral internal carotid arteries (CAs) and pharyngeal constrictor muscle (PCM) during early-stage glottic cancer (ESGC) treatment.
We identified patients with ESGC who underwent definitive radiotherapy between June 2014 and May 2020.
Among the 66 patients, 32 (48%) underwent radiotherapy using AOP, and the remaining underwent typical radiotherapy using parallel opposed lateral portals (POLP). The median follow-up duration was 53 months. No significant differences were observed in the 5-year local failure (0%/9.4%), progression-free survival (90.6%/90.8%), and overall survival (90.6%/91.0%) rates between the two groups. The grade ≥2 acute mucositis incidence rate was significantly lower in the AOP group (44%/85%). Radiotherapy using AOP maintained an adequate dose coverage to the target while markedly reducing the CAs and PCM doses.
Radiotherapy with AOP resulted in favorable clinical and dosimetric outcomes.

UNASSIGNED: The study was to evaluate the effectiveness of dose distribution of four-dimensional computed tomography (4DCT) simulation.
UNASSIGNED: The gross tumor volume (GTV) and clinical target volume (CTV) were contoured in all 10 respiratory phases of 4DCT in 30 patients with non-small cell lung cancer (NSCLC). Both 3D and 4D treatment plans were made individually for each patient using the planning volume (PTV). The PTV3D was taken from a single CTV plus the recommended margin, and the PTV4D was taken from the 4D internal target volume, including all 10 CTVs plus the setup margins.
UNASSIGNED: The mean PTV was 460 ± 179 (69-820) cm3 for 3DCT and 401 ± 167 (127-854) cm3 for 4DCT (p = 0.0018). The dose distribution (DD) of organs at risk, especially the lungs, was lower for the 4DCT simulation. The V5%, V10%, and V20% of the total lung dose for 4DCT were significantly lower for the 3DCT. However, lung V30% the heart, esophagus, and spinal cord were not significantly different. In addition, the conformity index and the dose heterogeneity index of the PTV were not significantly different. The normal tissue complication probability (NTCP) of the lung and heart was significantly lower for 4DCT than for 3DCT.
UNASSIGNED: The 4DCT simulation gives better results on the NTCP. The organs at risk, especially the lungs, receive a significantly lower DD compared with the 3DCT. The conformity index (CI), heterogeneity index (HI) and the DD to the heart, spinal cord, and esophagus were not significantly different between the two techniques.

Objective: Prostate cancer (PCa) is one of the most common cancers in the world. The potential benefits of intensity modulated radiation therapy (IMRT) over three-dimensional conformal radiation therapy (3D-CRT) for PCa primary radiation therapy treatment have not yet been clarified. Therefore, this meta-analysis was conducted to assess whether IMRT could improve clinical outcomes in comparison with 3D-CRT in patients diagnosed with PCa. Materials and methods: Relevant studies were identified through searching related databases till December, 2022. Hazard ratio (HR) or risk ratio (RR) with its corresponding 95% confidence interval (CI) was used as pooled statistics for all analyses. Results: The incidence of grade 2 or worse acute adverse gastrointestinal (GI) event was analyzed and the pooled data revealed a clear decreasing trend in the IMRT compared with 3D-CRT (RR=0.62, 95% CI: 0.45-0.84, p=0.002). IMRT slightly increased the grade ≥ 2 acute genitourinary (GU) adverse event in comparison with the 3D-CRT (RR=1.10, 95% CI: 1.02-1.19, p=0.015). The IMRT and the 3D-CRT of patients showed no substantial differences in grade ≥ 2 late GI adverse event (RR =0.62, 95% CI: 0.36-1.09, p=0.1). In those included studies, there was no significant difference between IMRT and 3D-CRT in grade 2-4 late GU adverse event (RR =1.08, 95% CI: 0.77-1.51, p=0.65). There was a significant difference in biochemical control favoring IMRT (RR =1.13, 95% CI: 1.05-1.22, p=0.002). IMRT showed modest increase in biochemical control in comparison with 3D-CRT. Conclusion: In general, based on the above results, IMRT should be considered as a better choice for the treatment of PCa. More randomized controlled trials are needed to determine the subset of patients diagnosed with PCa.

BACKGROUND: To evaluate the possible advantages of a simple spinal cord (SC) dose-limiting three-dimensional conformal radiotherapy (3D-CRT) technique in comparison to conventional two-dimensional (2D) techniques and other 3D-CRT techniques for spinal bone irradiation.
METHODS: For 41 spinal target volumes, seven different techniques were evaluated, using a standard schedule of 30 Gy in 10 fractions. The SC dose-limiting 3D-CRT technique 1F2S-18MV using a single posterior field (F) supplemented by two anterior segment fields (S) and 18-MV photon beams was compared to two conventional 2D techniques (a single posterior field, PA, and two opposed anterior-posterior fields, APPA), three other 3D-CRT techniques (a single posterior field supplemented by four segment fields, 1F4S; two wedged fields, WD, and the SC dose-limiting variant using 6 MV, 1F2S-6MV) along with the original clinically applied plans.
RESULTS: 1F2S-18MV demonstrated notably better results for all target volume parameters compared to the conventional 2D techniques (p < 0.001). Limitation of the SC dose was significantly superior with 1F2S-18MV in comparison to PA and APPA (SC Dmean: 28.9 ± 0.4  vs. 30.1 ± 0.6 Gy and 30.1 ± 0.4 Gy; SC Dmax: 30.9 ± 0.7  vs. 32.5 ± 1.0 Gy and 31.8 ± 0.7 Gy; SC D1cm3 : 30.1 ± 0.6  vs. 31.7 ± 0.9 Gy and 31.1 ± 0.6 Gy; p < 0.001). Likewise, lower mean SC doses with 1F2S-18MV were observed in comparison to the more treatment time-consuming 3D-CRT techniques (1F4S, WD) and the original plans without relevant compromises on the dose homogeneity in the target volume and the dose exposure to the other OARs.
CONCLUSIONS: In treatment planning of spinal metastases, simple variants of 3D-CRT-techniques like 1F2S-18MV can offer a significant dose limitation to the SC while providing a sufficient dose coverage of the target volume. Especially in patients with favorable life expectancy and potential need for re-irradiation, such SC dose-limiting 3D-CRT techniques may be a reasonable approach.

This study provided normal tissue complication probability (NTCP) calculations from photon radiotherapy techniques in eleven patients with thymoma. Five plans were created for each participant using three-dimensional conformal radiotherapy (3D-CRT), five-field intensity modulated radiotherapy (5F-IMRT), seven-field IMRT (7F-IMRT), and volumetric modulated arc therapy with full arcs (FA-VMAT) and partial arcs (PA-VMAT). The target coverage, homogeneity index and conformation number for the planning target volume (PTV) and dosimetric parameters for the organs-at-risk (OARs) were taken from the fifty-five generated plans. The patient-specific NTCP of the lungs, heart and esophagus was calculated with an in-house software tool using differential dose-volume histograms and the equivalent uniform dose model. The PTV dose metrics from 3D-CRT were inferior to those from IMRT and VMAT plans. The dose constraints for the OARs were met in all treatment plans. The NTCP range of the lungs, heart and esophagus was 0.34-0.49%, 0.03-0.06% and 0.08-0.10%, respectively. The NTCPs of the heart for the incidence of peridarditis from IMRT and VMAT were significantly smaller than those from conformal treatment (p < 0.05). The 7F-IMRT was significantly superior to FA-VMAT in reducing the NTCP of the lungs and the risk of pneumonitis (p = 0.001). Similar superiority of 5F-IMRT over PA-VMAT for lung protection was found (p = 0.009). The presented results may be employed in the selection of the appropriate irradiation technique for restricting the complications in the adjacent OARs.

UNASSIGNED: The purpose of this study was to evaluate three techniques of irradiation of left-sided breast cancer patients, three-dimensional conformal radiotherapy (3D-CRT), hybrid Intensity-Modulated Radiotherapy (h-IMRT), and hybrid Volumetric-Modulated Arc Therapy (h-VMAT, h-ARC), in terms of dose distribution in the planning target volume (PTV) and organs at risk (OARs). The second aim was to estimate the projected relative risk of radiation-induced secondary cancers for hybrid techniques.
UNASSIGNED: Three treatment plans were prepared in 3D-CRT, h-IMRT, and h-VMAT techniques for each of the 40 patients, who underwent CT simulation in deep inspiration breath-hold (DIBH). For hybrid techniques, plans were created by combining 3D-CRT and dynamic fields with an 80%/20% dose ratio for 3D-CRT and IMRT or VMAT. Cumulative dose-volume histograms were used to compare dose distributions within the PTV and OARs (heart, left anterior descending coronary artery [LAD], left and right lung [LL, RL], right breast [RB]). Projected risk ratios for secondary cancers were estimated relative to 3D-CRT using the organ equivalent dose (OED) concept for the Schneider\'s linear exponential, plateau, and full mechanistic dose-response model.
UNASSIGNED: All plans fulfilled the PTV criterium: V95%≥95%. Compared to 3D-CRT, both hybrid techniques showed significantly better target coverage (PTV: V95%>98%, p < 0.001), and the best conformality was achieved by h-ARC plans (CI: 1.18 ± 0.09, p < 0.001). Compared to 3D-CRT and h-ARC, h-IMRT increased the average sum of monitor units (MU) over 129.9% (p < 0.001). H-ARC increased the mean dose of contralateral organs and the LL V5Gy parameter (p < 0.001). Both hybrid techniques significantly reduced the Dmax of the heart by 5 Gy. Compared to h-IMRT, h-ARC increased secondary cancer projected relative risk ratios for LL, RL, and RB by 18, 152, and 81%, respectively.
UNASSIGNED: The results confirmed that both hybrid techniques provide better target quality and OARs sparing than 3D-CRT. Hybrid VMAT delivers less MU compared to hybrid IMRT but may increase the risk of radiation-induced secondary malignancies.