3-dimensional Conformal Radiotherapy Research Articles

Comparison Between Dose-Escalated Intensity Modulated Radiation Therapy and 3-Dimensional Conformal Radiation Therapy for Salvage Radiation Therapy After Prostatectomy

PurposeTo compare long-term outcomes and late toxicity between patients treated with 3-dimensional conformal radiation therapy (3D-CRT) and with dose-escalated intensity modulated radiation therapy (IMRT) as salvage radiation therapy (SRT) after prostatectomy. Methods and MaterialsA total of 110 patients who had been treated at our institution between 2010 and 2018 with SRT for biochemical recurrence after radical prostatectomy were included. The patients were treated either by 3D-CRT with 64 Gy (59 patients) or by IMRT with 70 Gy (51 patients). The irradiation target was the prostate bed only (106 patients) or the prostate bed and pelvic region (4 patients). Twelve patients (11%) received concurrent androgen deprivation therapy. The differences in clinical outcomes and late gastrointestinal (GI) and genitourinary (GU) toxicity between the 3D-CRT and IMRT groups were retrospectively assessed. Toxicities were recorded using the Common Terminology Criteria for Adverse Events, version 5.0. Prostate-specific antigen (PSA) progression after SRT was defined as an increase in the serum PSA level of 0.2 ng/mL from the PSA nadir after SRT and confirmed by a second PSA measurement that was higher than the first. ResultsThe median follow-up time was 7.8 years for 3D-CRT (range:,0.3-9.2 years) and 3.1 years for IMRT (range, 0.4-7.2 years). There was no significant difference in the 4-year biochemical no-evidence-of-disease (bNED) rate between the 3D-CRT and IMRT groups (43.5% vs 52.1%; P = .20). Toxicity analysis showed no significant difference in late GI or GU toxicities of grade 2 or greater between the 3D-CRT and IMRT groups. The respective 4-year cumulative rates of toxicity in the 3D-CRT and IMRT groups were as follows: grade ≥2 GI toxicity, 8.8% and 4.4% (P = .42); grade ≥2 GU toxicity, 19.1% and 20.3% (P = .93); and grade ≥2 hematuria, 5.3% and 8.0% (P = .67). In the 3D-CRT group, the 8-year cumulative rates of GI toxicity, GU toxicity, and hematuria of grade 2 or greater were 8.8%, 28.4%, and 12.6%, respectively. ConclusionsDose-escalated IMRT showed no improvements in bNED or late toxicity compared with 3D-CRT. In addition, the results suggest that GU toxicity can occur after a long period (even after 6 years), whereas GI toxicity is seldom newly observed after 4 years.

A Rare Case of Bilateral Carotid Glomus Jugulare with Partial Responses to Radiotherapy

Glomus jugulare is known as a benign tumor that could involve in different parts of the body. The most prevalent site of involvement is head and neck area. This disease is rare and few of the cases are bilateral. However, in familial cases bilateral or multicenter lesions are even rarer, in which there is an autosomal dominant pattern of inheritance. The most efficient treatment is believed to be surgery or radiotherapy depending on the location and certain other factors, such as age and performance status. Sporadic bilateral lesion is rarely seen and most bilateral cases are familial. Herein, we reported a case of bilateral glomus jugulare of carotid with no history of this tumor in family or any other familial diseases. Our subject was a 67-year-old man. The diagnosis was made via Tru-cut biopsy. He was treated successfully by 3- dimensional conformal radiotherapy up to a dose of 60 Gy. The follow-up computed tomography scan revealed partial tumor responses. He had no family history of any systemic disease related to functional glomus jugulare, such as uncontrolled hypertention or mass in the neck. He also had no history of catecholeamine exceretion-related symptoms.

Clinical outcome and toxicity of radiotherapy for inferior vena cava tumor thrombus in HCC patients: A retrospective study.

Hepatocellular carcinoma (HCC) involving the inferior vena cava rarely occurs, but its prognosis is extremely poor, with no established treatment to date. This study aimed to analyze the clinical outcome and toxicity of radiotherapy (RT) targeting inferior vena cava tumor thrombus (IVCTT) in HCC patients.From November 2011 to July 2020, medical record of 19 HCC patients who were treated with RT for IVCTT was retrospectively reviewed. RT was delivered using 3-dimensional conformal radiation therapy, intensity-modulated radiation therapy, and stereotactic body radiation therapy. The median radiation dose was 50 Gy (range, 45–55.8 Gy) for intensity-modulated radiation therapy and three-dimensional conformal radiotherapy. Stereotactic body radiation therapy was performed in 5 patients, for a total of 32 Gy in 4 fractions.The median follow-up duration was 8.1 months (range, 3.3–26.5 months). The median overall survival was 9.4 months (range, 3.7–26.5 months), and the 1-year overall survival rate was 37.1%. Eight of 19 patients (42.1%) had extrahepatic metastasis at the start of RT. Six of 11 patients (54.5%) who did not have extrahepatic metastasis at the start of RT showed extrahepatic metastasis after RT. The major cause of death was progression of extrahepatic metastasis (11 patients, 57.9%). The overall response rate of IVCTT for RT was 84.2%, and the local control rate at the time of the last follow-up was 89.4%. After RT, the most common first progression site was the lungs (9 patients, 47.4%). Most toxicities were grade 1 to 2 gastrointestinal (26.3%) and liver enzyme elevation (68.4%). Three patients occurred pulmonary embolism after RT later than 5 months after.RT is a feasible and safe local therapy for IVCTT, with favorable tumor control and acceptable toxicity. Extrahepatic metastasis is the major progression pattern and a leading cause of death in patients treated with RT. The combination of effective systemic therapy with RT may have to be considered.

Assessment of Variations in Serum Testosterone, Follicle Stimulating Hormone, and Luteinizing Hormone Levels in Patients Receiving Radiotherapy for Rectal Cancer

Background: Testes being in close proximity to radiation fields in patients of rectal cancer treated with radiotherapy, inadvertently receive a part of the radiation dose. This study was conducted to evaluate the variation of male sex hormones during the course of radiotherapy in patients with rectal cancer. Method: In this single-institution prospective study, 20 patients with carcinoma rectum were included. The patients were treated with 3-dimensional conformal radiation therapy or intensity modulated radiation therapy technique to a dose of 50.4 Gy for five weeks. Serum testosterone, follicle stimulating hormone (FSH), and luteinizing hormone (LH) levels were obtained prior to and in the meantime of radiotherapy. The post treatment hormone levels were compared to the baseline values. The mean, percentage, standard deviation, and Paired t-test were used for statistical analysis. Results: The mean dose received by the testes was 2.65 Gy (1.96 Gy to 4.96 Gy), which accounted for 5.25% of the total dose. The baseline values of serum testosterone, FSH, and LH were 4.65±0.7 ng/ml, 7.57±1.2 mIU/ml, and 7.93±1.1 mIU/ml, respectively. There was a 32.1% drop in the post treatment testosterone levels compared to the baseline. There was a 77% rise in the post treatment FSH and 40.2% rise in the post treatment LH levels compared to the baseline. There was a significant difference in the rise of LH levels in the patients who received a testicular dose more than 2Gy compared to those who received a dose less than 2 Gy. Conclusion: Radiation therapy was found to have a significant acute impact on male sex hormones in patients receiving radiotherapy for rectal cancer.

NTCP Modeling of Late Effects for Head and Neck Cancer: A Systematic Review.

NTCP Modeling of Late Effects for Head and Neck Cancer: A Systematic Review.

Secondary cancer risk from modern external-beam radiotherapy of prostate cancer patients: Impact of fractionation and dose distribution.

Modern radiotherapy (RT) uses altered fractionation, long beam-on time and image-guided procedure. This study aimed to compare secondary cancer risk (SCR) associated with primary field, scatter/leakage radiations and image-guided procedure in prostate treatment using intensity-modulated RT (IMRT), CyberKnife stereotactic body RT (CK-SBRT) in relative to 3-dimensional conformal RT (3D-CRT). Prostate plans were generated for 3D-CRT, IMRT (39 fractions of 2 Gy), and CK-SBRT (five fractions of 7.25 Gy). Excess absolute risk (EAR) was calculated for organs in the primary field using Schneider’s mechanistic model and concept of organ equivalent dose (OED) to account for dose inhomogeneity. Doses from image-guided procedure and scatter/leakage radiations were determined by phantom measurements. The results showed that hypofractionation relative to conventional fractionation yielded lower SCR for organs in primary field (p ≤ 0.0001). SCR was further modulated by dose-volume distribution. For organs near the field edge, like the rectum and pelvic bone, CK-SBRT plan rendered better risk profiles than IMRT and 3D-CRT because of the absence of volume peak in high dose region (relative risk [RR]: 0.65, 0.22, respectively, p ≤ 0.0004). CK-SBRT and IMRT generated more scatter/leakage and imaging doses than 3D-CRT (p ≤ 0.0002). But primary field was the major contributor to SCR. EAR estimates (risk contributions, primary field: scatter/leakage radiations: imaging procedure) were 7.1 excess cases per 104 person–year (PY; 3.64:2.25:1) for CK-SBRT, 9.93 (7.32:2.33:1) for IMRT and 8.24 (15.99:2.35:1) for 3D-CRT (p ≤ 0.0002). We conclude that modern RT added more but small SCR from scatter/leakage and imaging doses. The primary field is a major contributor of risk which can be mitigated by the use of hypofractionation.

Deep-inspirational breath-hold (DIBH) technique in left-sided breast cancer: various aspects of clinical utility

BackgroundStudying the clinical utility of deep-inspirational breath-hold (DIBH) in left breast cancer radiotherapy (RT) was aimed at focusing on dosimetry and feasibility aspects.MethodsIn this prospective trial all enrolled patients went through planning CT in supine position under both DIBH and free breathing (FB); in whole breast irradiation (WBI) cases prone CT was also taken. In 3-dimensional conformal radiotherapy (3DCRT) plans heart, left anterior descending coronary artery (LAD), ipsilateral lung and contralateral breast doses were analyzed. The acceptance of DIBH technique as reported by the patients and the staff was analyzed; post-RT side-effects including radiation lung changes (visual scores and lung density measurements) were collected.ResultsAmong 130 enrolled patients 26 were not suitable for the technique while in 16, heart or LAD dose constraints were not met in the DIBH plans. Among 54 and 34 patients receiving WBI and postmastectomy/nodal RT, respectively with DIBH, mean heart dose (MHD) was reduced to < 50%, the heart V25 Gy to < 20%, the LAD mean dose to < 40% and the LAD maximum dose to about 50% as compared to that under FB; the magnitude of benefit was related to the relative increase of the ipsilateral lung volume at DIBH. Nevertheless, heart and LAD dose differences (DIBH vs. FB) individually varied. Among the WBI cases at least one heart/LAD dose parameter was more favorable in the prone or in the supine FB plan in 15 and 4 cases, respectively; differences were numerically small. All DIBH patients completed the RT, inter-fraction repositioning accuracy and radiation side-effects were similar to that of other breast RT techniques. Both the patients and radiographers were satisfied with the technique.ConclusionsDIBH is an excellent heart sparing technique in breast RT, but about one-third of the patients do not benefit from that otherwise laborious procedure or benefit less than from an alternative method.Trial registration: retrospectively registered under ISRCTN14360721 (February 12, 2021)

Brainstem Infiltration Predicts Survival in Patients With High-grade Gliomas Treated With Chemoradiotherapy.

High-grade gliomas have a poor prognosis despite standard treatment. The aim of the study was to identify new prognostic factors to select patients who need more intense treatment. Forty-three consecutive patients underwent surgery plus chemoradiotherapy for pathologically diagnosed high-grade gliomas (grade III, IV). The median survival time was 989 days, and the 1-year survival rate was 87.6%. Among patients with grade IV disease, the median survival time, 1-year, and 2-year survival rate were 814 days, 82.6%, and 58.7%, respectively. In the univariate analysis, unmethylated MGMT promoter (p=0.0495), brainstem infiltration (p=0.0004), basal ganglia as the primary lesion site (p=0.0056), 3-dimensional conformal radiotherapy (p=0.0286), and <50 Gy (p=0.0049) were associated with a poor prognosis. In the multivariate analysis, only brainstem infiltration retained significance (HR for death, 0.21; 95% CI=0.06-0.70; p=0.011). Brainstem infiltration is a novel prognostic factor for poor prognosis in patients with high-grade gliomas.

84P Prospective comparative study of dosimetric parameters and acute radiation toxicity of 3-dimensional conformal radiotherapy (3DCRT) and volumetric modulated arc therapy (VMAT) in post mastectomy carcinoma breast patients

Radiation therapy (RT) is an integral component of breast cancer management. For mitigating the normal tissue toxicity, many radiotherapy techniques have been explored and utilized. In the present study, we compare post modified radical mastectomy (PMRM) radiotherapy plans utilizing 3DCRT and VMAT techniques.

Clinical effects of rectal retractor application in prostate cancer radiotherapy.

Background: Radiation-induced rectal toxicities remain as a major risk during prostate radiotherapy. One approach to the reduction of rectal radiation dose is to physically increase the distance between the rectal wall and prostate. Therefore, the aim of this study was to evaluate whether the application of the rectal retractor (RR) can reduce rectal dose and toxicity in prostate cancer 3-dimensional conformal radiotherapy (3D-CRT). Methods: Overall, 36 patients with localized prostate cancer were randomized into the 2 groups, 18 patients with RR in-place and 18 without RR. All patients underwent planning computed tomography (CT). Patients were treated with 70 Gy in 35 fractions of 3D-CRT. In the RR group, RR was used during cone-down 20 treatment fractions. Acute and late gastrointestinal (GI) toxicities were assessed using EORTC/RTOG scoring system weekly during radiotherapy, 3, and 12 months after treatment. Device-related events were recorded according to CTCAE version 4.0. Patient characteristics, cancer differences, and dosimetric data for the RR and non-RR groups were compared using a Man-Whitney U test for continuous variables, and Fisher exact test for categorical data. The EORTC/RTOG scores for the 2 groups were compared using Fisher exact test. A P value <0.05 was considered statistically significant. Results: A RR significantly reduced mean dose (Dmean) to the rectum as well as rectal volume receiving 50% to 95% (V50-95%) of prescribed dose. The absolute reduction of rectal Dmean was 10.3 Gy. There was no statistically significant difference in acute GI toxicity between groups during treatment or at 3 months. At 12 months, 2 patients in the RR group and 9 in the control group experienced late grade ≥ 1 GI toxicity (p=0.027). No patients in the RR group reported late grade ≥ 2 GI toxicity, whereas 3 patients in the control group experienced late grade 2 GI toxicity. In the RR group, 6 patients reported grade 1 rectal discomfort and pain according to CTCAE version 4.0. Conclusion: The application of the RR showed a significant rectum sparing effect, resulting in substantially reducing late GI toxicity.

Radical external beam reirradiation of recurrent head and neck cancer

BACKGROUND Recurrent head and neck carcinomas represent a therapeutic challenge for the surgeons as well as for the treating radiation oncologists. Despite advances in the treatment of newly dia-gnosed head and neck carcinomas, relapses occur very frequently and contribute significantly to patient mortality. External beam reirradiation is still considered to be a controversial therapeutic intervention. Historically, in the era of 2- and 3-dimensional conformal radiotherapy, its narrow therapeutic ratio has long led to a general concern that the potential benefit could not sufficiently outweigh the high risk associated with the treatment. The unfavorable therapeutic ratio, however, could be positively influenced by the use of modern techniques of intensity-modulated radiation therapy (IMRT), volumetric-modulated arc therapy (VMAT), stereotactic body radiation therapy (SBRT) and heavy-ion radiotherapy (protons, carbon ions). PURPOSE The purpose of this review is to create a practical tool for clinical decision-making on the type of patient suitable for reirradiation and the exact type of radiotherapy technique with respect to its expected therapeutic effect, toxicity profile and availability throughout the institutions. In the introductory section, selection of patients is defined with an emphasis on factors that significantly affect overall survival and may be particularly useful in shared decision-making approach within multidisciplinary teams. Furthermore, the text deals with the individual types of external beam radiotherapy techniques (IMRT, SBRT, heavy-ion radiotherapy) with a clear summary of therapeutic outcomes and toxicity from published scientific evidence that had a significant impact on clinical practice.

Clinical Observation of Three Dimensional Conformal Intensity-modulated Radiotherapy Combined with Cisplatin Chemotherapy and Nituzumab in the Treatment of Locally Advanced Nasopharyngeal Carcinoma

Objective . To observe the clinical effect of three-dimensional conformal intensity-modulated radiotherapy combined with cisplatin chemotherapy and nituzumab in the treatment of locally advanced nasopharyngeal carcinoma. Selection method. From January 2016 - January 2019 in fujian province third hospital treated 62 cases of patients with locally advanced nasopharyngeal carcinoma were selected as the research objects, which randomly divided into observation group (31 cases) and control group (31 cases). Control group were treated by three-dimensional conformal intensity modulated radiation therapy synchronous paclitaxel and cisplatin chemotherapy, observers group on the basis of control group, this bead sheet were given, and the treatment. Clinical efficacy and adverse reactions of 2 groups were compared. Results . The CR rate of nasopharyngeal primary foci 2 months after radiotherapy, the CR rate of cervical lymph node, the control rate of primary foci 1 year after radiotherapy . The rate of no distant metastasis in observation group were all higher than those in control group (P 0.05). Conclusion. Three-dimensional conformal intensity-modulated radiotherapy combined with cisplatin chemotherapy and nituzumab in the treatment of advanced nasopharyngeal carcinoma can improve the short-term efficacy, but in terms of improving the long-term efficacy and survival rate of patients, further follow-up investigation is needed.

Investigation of The Compliance of Planned Dose Distribution on The Treatment Planning System with Measured Dose Distribution in Rando Phantom For IMRT and Conformal Radiotherapy Applications

Purpose This study investigates planned and measured dose differences for 3 dimensional conformal radiotherapy (3DCRT), Field in Field (FinF) and Intensity-Modulated Radiation Therapy (IMRT) techniques for breast cancer radiotherapy. Material and Method Breast shaped phantom (BSP) was fabricated with water equevelent bolus material and BSP was placed on Alderson rando phantom, then planning computerized tomography (CT) images were obtained. Target volume andnormal tissues were delineated on these images. Treatment planning was performed for 3DCRT, FinF and IMRT techniques (Varian, Eclipse 8,6, PencilBeam). EBT2 films were placed into sagittal and transverse planes of BSP which intersect with the isocenter. After thatfilms were irradiated for each calculated plans in two times. The measured doses with film from the isocenter and from the axes passing 1 cm anterior-posterior, superior – inferior and right-left of the isocenter were compared with the doses read from the treatment planning system (TPS) on the same axes. Results Among applied techniques, the maximum and minimum dose differences for measured and calculated doses were 4.5 % and 0.05 % for FinF and IMRT techniques, respectively. Measured doses were higher than calculated doses for 66.6% of all points; however 93% of total points had a difference less than 3 %. Dose differences were minimum on axes that intersect with the isocenter and were directly correlated with the distance from the isocenter. There was no relation between dose differences and directions on axes. Conclusion Dose distributions calculated in TPS were found to be compatible for all three techniques when compared to dose distributions measured by film on rando Phantom. The best compliance was found for IMRT technique.

Proton Beam Therapy in the Treatment of Periorbital Malignancies.

PurposePeriorbital tumor location presents a significant challenge with 3-dimensional conformal radiation therapy or intensity modulated radiation therapy due to high tumor dose needed in the setting of close proximity to orbital structures with lower tolerance. Proton beam therapy (PBT) is felt to be an effective modality in such cases due to its sharp dose gradient.Materials and MethodsWe reviewed our institutional PBT registry and identified 17 patients with tumor epicenters within 2 cm of the eye and optic apparatus treated with passive scatter PBT with comparison volumetric arc therapy plans available. Maximum and mean doses to organs at risk of interest, including optic nerves, optic chiasm, lens, eye ball, pituitary, cochlea, lacrimal gland, and surrounding brain, were compared using the paired Wilcoxon signed rank test. Overall survival was determined using the Kaplan-Meier method.ResultsMedian age was 67. Median follow-up was 19.7 months. Fourteen patients underwent upfront resection and received postoperative radiation and 3 received definitive radiation. One patient received elective neck radiation, 2 underwent reirradiation, and 3 had concurrent chemotherapy. There was a statistically significant reduction in mean dose to the optic nerves and chiasm, brain, pituitary gland, lacrimal glands, and cochlea as well as in the maximum dose to the optic nerves and chiasm, pituitary gland, lacrimal glands, and cochlea with PBT. The 18-month cumulative incidence of local failure was 19.1% and 1-year overall survival was 80.9%.ConclusionProton beam therapy resulted in significant dose reductions to several periorbital and optic structures compared with volumetric arc therapy. Proton beam therapy appears to be the optimal radiation modality in such cases to minimize risk of toxicity to periorbital organs at risk.

Normal Tissue Injury Induced by Photon and Proton Therapies: Gaps and Opportunities.

Despite technological advances in radiation therapy (RT) and cancer treatment, patients still experience adverse effects. Proton therapy (PT) has emerged as a valuable RT modality that can improve treatment outcomes. Normal tissue injury is an important determinant of the outcome; therefore, for this review, we analyzed 2 databases: (1) clinical trials registered with ClinicalTrials.gov and (2) the literature on PT in PubMed, which shows a steady increase in the number of publications. Most studies in PT registered with ClinicalTrials.gov with results available are nonrandomized early phase studies with a relatively small number of patients enrolled. From the larger database of nonrandomized trials, we listed adverse events in specific organs/sites among patients with cancer who are treated with photons and protons to identify critical issues. The present data demonstrate dosimetric advantages of PT with favorable toxicity profiles and form the basis for comparative randomized prospective trials. A comparative analysis of 3 recently completed randomized trials for normal tissue toxicities suggests that for early stage non-small cell lung cancer, no meaningful comparison could be made between stereotactic body RT and stereotactic body PT due to low accrual (NCT01511081). In addition, for locally advanced non-small cell lung cancer, a comparison of intensity modulated RTwith passive scattering PT (now largely replaced by spot-scanned intensity modulated PT), PT did not provide any benefit in normal tissue toxicity or locoregional failure over photon therapy. Finally, for locally advanced esophageal cancer, proton beam therapy provided a lower total toxicity burden but did not improve progression-free survival and quality of life (NCT01512589). The purpose of this review is to inform the limitations of current trials looking at protons and photons, considering that advances in technology, physics, and biology are a continuum, and to advocate for future trials geared toward accurate precision RT that need to be viewed as an iterative process in a defined path toward delivering optimal radiation treatment. A foundational understanding of the radiobiologic differences between protons and photons in tumor and normal tissue responses is fundamental to, and necessary for, determining the suitability of a given type of biologically optimized RT to a patient or cohort.

Dosimetric impact of volumetric modulated arc therapy for nasopharyngeal cancer treatment

The purpose of the study was to evaluate the toxicity and outcome of nasopharyngeal carcinoma patients treated using 3-dimensional conformal radiotherapy (3DCRT) or volumetric modulated arc therapy (VMAT) technique. 68 patients treated between 2006 and 2018 were retrospectively analysed. Since 2009 patients received 3DCRT with 50/70 Gy to the elective/boost volumes in 35 fractions; from then, VMAT with simultaneous integrated boost (SIB) with 54.45/69.96 Gy in 33, or 54/66 Gy in 30 fractions. Induction chemotherapy was administered in 74% of the patients, concomitant cisplatinum in 87%. Acute and late toxicity data, progression-free survival PSF and overall survival OS, and toxicity correlations with dose metrics were reported. With a median follow-up of 64 months, complete remission at the last evaluation was in 68% of the patients, while 28% and 9% had locoregional relapse and distant disease, respectively. The 5- and 10-year progression free survival (PFS) rates were 62.7 ± 6.5% and 53.2 ± 8.7%, respectively. The 5- and 10-year OS rates were 78.9 ± 5.5% and 61.4 ± 9.2%, respectively. At the multivariate Cox analysis TNM stage (p = 0.02) and concomitant chemotherapy (p = 0.01) resulted significant for PFS, concomitant chemotherapy (p = 0.04) for OS.Improvements in acute toxicity were presented for VMAT patients due to its ability to spare OARs. Odds ratio (OR) for acute salivary toxicity, between VMAT and 3DCRT, was 4.67 (p = 0.02). Dosimetrically, salivary toxicity correlated with mean parotid dose (p = 0.05), dysphagia with laryngeal (p = 0.04) and mean oral cavity (p = 0.06) doses, when dose-volume histograms (DVHs) are corrected for fractionation. This study is a proof of a significant benefit of the VMAT technique compared with 3DCRT in terms of side effects in nasopharynx patients, and adds dosimetric correlations.

Proton Radiotherapy Could Reduce the Risk of Fatal Second Cancers for Children with Intracranial Tumors in Low- and Middle-Income Countries.

PurposeTo test our hypothesis that, for young children with intracranial tumors, proton radiotherapy in a high-income country does not reduce the risk of a fatal subsequent malignant neoplasm (SMN) compared with photon radiotherapy in low- and middle-income countries.Materials and MethodsWe retrospectively selected 9 pediatric patients with low-grade brain tumors who were treated with 3-dimensional conformal radiation therapy in low- and middle-income countries. Images and contours were deidentified and transferred to a high-income country proton therapy center. Clinically commissioned treatment planning systems of each academic hospital were used to calculate absorbed dose from the therapeutic fields. After fusing supplemental computational phantoms to the patients' anatomies, models from the literature were applied to calculate stray radiation doses. Equivalent doses were determined in organs and tissues at risk of SMNs, and the lifetime attributable risk of SMN mortality (LAR) was predicted using a dose-effect model. Our hypothesis test was based on the average of the ratios of LARs from proton therapy to that of photon therapy ResultsProton therapy reduced the equivalent dose in organs at risk for SMNs and LARs compared with photon therapy for which the for the cohort was 0.69 ± 0.10, resulting in the rejection of H0 (P < .001, α = 0.05). We observed that the younger children in the cohort (2-4 years old) were at a factor of approximately 2.5 higher LAR compared with the older children (8-12 years old). ConclusionOur findings suggest that proton radiotherapy has the strong potential of reducing the risk of fatal SMNs in pediatric patients with intracranial tumors if it were made available globally.

Incidence and Risk Factors of Symptomatic Radiation Pneumonitis in Non–Small-Cell Lung Cancer Patients Treated with Concurrent Chemoradiotherapy and Consolidation Durvalumab

IntroductionData on the risk factors for symptomatic radiation pneumonitis (RP) in non–small-cell lung cancer (NSCLC) patients treated with concurrent chemoradiotherapy (CCRT) and consolidation durvalumab are limited; we aimed to investigate these risk factors. Materials and MethodsThis multicenter retrospective study, conducted at 15 institutions in Japan, included patients who were ≥20 years of age; who started definitive CCRT for NSCLC between July 1, 2018, and July 31, 2019; and who then received durvalumab. The primary endpoint was grade 2 or worse (grade 2+) RP. ResultsIn the 146 patients analyzed, the median follow-up period was 16 months. A majority of the patients had stage III disease (86%), received radiation doses of 60 to 66 Gy equivalent in 2-Gy fractions (93%) and carboplatin and paclitaxel/nab-paclitaxel (77%), and underwent elective nodal irradiation (71%) and 3-dimensional conformal radiotherapy (75%). RP grade 2 was observed in 44 patients (30%); grade 3, in four patients (3%); grade 4, in one patient (1%); and grade 5, in one patient (1%). In the multivariable analysis, lung V20 was a significant risk factor, whereas age, sex, smoking history, irradiation technique, and chemotherapy regimen were not. The 12-month grade 2+ RP incidence was 34.4% (95% confidence interval [CI], 26.7%-42.1%); the values were 50.0% (95% CI, 34.7%-63.5%) and 27.1% (95% CI, 18.8%-36.2%) in those with lung V20 ≥ 26% and < 26%, respectively (P = .007). ConclusionThe incidence of grade 2+ RP was relatively high in this multicenter real-world study, and its risk increased remarkably at elevated lung V20. Our findings can aid in RP risk prediction and the safe radiotherapy treatment planning.

A Multi-Institutional Analysis of Radiation Dosimetric Predictors of Toxicity After Trimodality Therapy for Esophageal Cancer

PurposeThis multi-institutional review explored associations between radiation dose-volume histogram (DVH) parameters and cardiopulmonary toxicities with trimodality therapy for esophageal cancer. Methods and MaterialsWe reviewed 465 consecutive patients with esophageal cancer treated with chemoradiation therapy followed by surgery at 2 tertiary-care institutions between 2007 and 2013. Using logistic regression, we assessed associations between lung and heart DVH parameters and cardiopulmonary toxicities and survival. Statistically significant variables were subsequently included in multivariable models, which incorporated age, smoking history, previous history of heart disease, and type of chemotherapy. ResultsThe median age of the patients was 61 years (interquartile range, 54-68 years), and 86% were men. At baseline, 60% of the patients had known cardiac risk factors, 64% were current or former smokers, and 10% had other pulmonary comorbidities. Most patients had stage II to III (96%) adenocarcinoma (94%) of the distal esophagus. The radiation therapy (RT) modalities used were 3-dimensional conformal RT (38%), intensity modulated RT (41%), and proton therapy (20%). An increased heart dose was associated with increased risk of cardiac toxicity on univariable analysis (V20 Gy: odds ratio [OR], 1.20; 95% CI, 1.08-1.33; P = .001) (V30 Gy: OR, 1.24; 95% CI, 1.11-1.38; P < .0001) (V40 Gy: OR, 1.18; 95% CI, 1.03-1.35; P = .018). No lung DVH metrics were associated with lung toxicity. Heart V30 Gy was associated with adverse events on multivariable analysis (OR, 1.15; 95% CI, 1.04-1.26; P = .0047). ConclusionsWe observed an association between heart dose and cardiac toxicity for esophageal cancer. The risk of cardiac toxicity was 5%, 10%, and 15% when the heart V30 Gy dose was 14%, 20%, and 30%, respectively. For every 10% increase in V30 Gy, there was a corresponding 24% increase in the relative risk of cardiac toxicity.

A Prospective Cohort Study Analysing 3-Dimensional Conformal Radiotherapy and Salivary Glands Preserving Intensity Modulated Radiotherapy with/without Concomitant Cisplatin Chemotherapy in Head and Neck Malignancies

A Prospective Cohort Study Analysing 3-Dimensional Conformal Radiotherapy and Salivary Glands Preserving Intensity Modulated Radiotherapy with/without Concomitant Cisplatin Chemotherapy in Head and Neck Malignancies