Longitudinal Costs of Image-Guided Intensity-Modulated Radiation Therapy Versus Three-Dimensional Conformal Radiation: Lessons From Phase III PARCER Trial for Shaping Resource-Stratified Guidelines in Low- and Middle-Income Countries.

PURPOSE: The PARCER trial provided level I evidence for image-guided intensity-modulated radiation therapy (IG-IMRT) in patients with cervical cancer. Further information regarding long-term financial impact is imperative for adoption into the National Cancer Grid of India cervical cancer resource-stratified guidelines. METHODS: Patient data from the PARCER trial were analyzed to evaluate the cost implications of transitioning to IG-IMRT. Lacking differences in outcomes between the three-dimensional conformal radiation (3D-CRT) and IG-IMRT, differences in treatment costs, adverse event incidence, and toxicity management costs were examined. The overall financial impact was estimated by adding the treatment costs, toxicity management, and wage loss. This was extrapolated nationally to determine if a transition to IG-IMRT would be feasible for the Indian health care system. RESULTS: Of the 300 patients in the PARCER trial, 93 faced grades ≥2 adverse events (3D-CRT = 59, IG-IMRT = 34). Patients in the 3D-CRT and IG-IMRT arms spent an average of 2.39 years and 1.96 years in toxicity, respectively. The average toxicity management and the yearly financial impact per patient were, respectively, 1.50 and 1.44 times higher for 3D-CRT patients compared with IG-IMRT patients. Extrapolation to the national level showed that treatment with 3D-CRT led to a 2.88 times higher cost ratio when compared with treatment with IG-IMRT. CONCLUSION: Although the initial costs of IG-IMRT are high, on the basis of longitudinal data, it is financially inefficient to treat with 3D-CRT. Resource-stratified guidelines should include longitudinal health intervention costs rather than solely initial costs for policy decisions to implement advanced radiation technology.

Accelerated three-dimensional conformal radiotherapy for early-stage glottic cancer in reducing dose to the internal carotid artery and pharyngeal constrictor muscles.

BACKGROUND: 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. METHODS: We identified patients with ESGC who underwent definitive radiotherapy between June 2014 and May 2020. RESULTS: 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. CONCLUSION: Radiotherapy with AOP resulted in favorable clinical and dosimetric outcomes.

Radiation technique and outcomes following moderately hypofractionated treatment of low risk prostate cancer: a secondary analysis of RTOG 0415.

BACKGROUND: While moderately hypofractionated radiotherapy (MHRT) for prostate cancer (PC) is commonly delivered by intensity modulated radiation therapy, IMRT has not been prospectively compared to three-dimensional conformal radiotherapy (3D-CRT) in this context. We conducted a secondary analysis of the phase III RTOG 0415 trial comparing survival and toxicity outcomes for low-risk PC following MHRT with IMRT versus 3D-CRT. METHODS: RTOG 0415 was a phase III, non-inferiority trial randomizing low-risk PC patients to either MHRT or conventionally fractionated radiation with stratification by RT technique. A secondary analysis for differences in overall survival (OS), biochemical recurrence free survival (BRFS), or toxicity by EPIC scores and Common Terminology Criteria for Adverse Events (CTCAE) was performed. RESULTS: 1079 patients received the allocated intervention with a median follow up of 5.8 years. 79.1% of patients were treated with IMRT and radiation technique was balanced between arms. Across all patients, RT technique was not associated with significant differences in BRFS, OS, or rates of acute and late toxicities. For patients completing MHRT, there was a difference in the late GU toxicity distribution between 3D-CRT and IMRT but no difference in late grade 2 or greater GU or GI toxicity. Stratifying patients by RT technique and fractionation, no significant differences were observed in the minimal clinically important difference (MCID) in EPIC urinary and bowel scores following RT. CONCLUSIONS: RT technique did not impact clinical outcomes following MHRT for low-risk PC. Despite different late GU toxicity distributions in patients treated with MHRT by IMRT or 3D-CRT, there was no difference in late Grade 2 or greater GU or GI toxicity or patient reported toxicity. Increases in late GU and GI toxicity following MHRT compared to CFRT, as demonstrated in the initial publication of RTOG 0415, do not appear related to a 3D-CRT treatment technique.

Economical Evaluation of Prostate Cancer Treatment Using Intensity-Modulated Radiation Therapy, 3-Dimensional Conformal Radiation Therapy and Radical Prostatectomy: A Systematic Review.

OBJECTIVES: Prostate cancer is a common form of cancer among men worldwide. The objective of this study was to conduct a systematic review of the economic evaluations of prostate cancer treatment strategies. METHODS: This systematic review was conducted using multiple electronic databases up to May 2021. English-language economic evaluation studies that compared intensity-modulated radiation therapy (IMRT), 3-dimensional conformal radiation therapy (3DCRT), and radical prostatectomy (RP) were included. The studies were evaluated using the Consolidated Health Economic Evaluation Reporting Standards checklist. The search yielded 1151 potentially relevant publications, which were screened based on the title and abstract. After the removal of duplicates, 55 studies remained, and 9 studies were screened in full text. Finally, textual data were analyzed manually using by-content analysis method. RESULTS: All studies were cost-effective and evaluated quality-adjusted life year as the efficacy indicator. The studies were conducted from either payers' or health systems' perspectives, and the time horizon varied from 5 to 20 years. We included only full economic evaluation studies. The use of IMRT in comparison with 3DCRT was evaluated in 6 studies, based on which IMRT increased health and reduced side effects of treatment. According to incremental cost-effectiveness ratio (ICER) results, IMRT was more cost-effective than 3DCRT. Three studies evaluated the use of RP in comparison with radiotherapy. Based on these studies, radiotherapy was more effective than RP. CONCLUSION: IMRT was found to be more cost-effective than 3DCRT in all 6 studies compared with the threshold. Radiotherapy was found to be more effective than RP. However, long-term clinical trial studies are needed to confirm these findings and to provide more definitive conclusions.

Comprehensive geriatric assessment predicts radiation-induced acute toxicity in prostate cancer patients.

PURPOSE: The purpose of the present prospective study was to evaluate the significance of geriatric conditions measured by a comprehensive geriatric assessment (GA) for the prediction of the risk of high-grade acute radiation-induced toxicity. METHODS: A total of 314 prostate cancer patients (age ≥ 65 years) undergoing definitive radiotherapy at a tertiary academic center were included. Prior to treatment, patients underwent a GA. High-grade toxicity was defined as acute toxicity grade ≥ 2 according to standard RTOG/EORTC criteria. To analyze the predictive value of the GA, univariable and multivariable logistic regression models were applied. RESULTS: A total of 40 patients (12.7%) developed acute toxicity grade ≥ 2; high grade genitourinary was found in 37 patients (11.8%) and rectal toxicity in 8 patients (2.5%), respectively. Multivariable analysis revealed a significant association of comorbidities with overall toxicity grade ≥ 2 (odds ratio [OR] 2.633, 95% confidence interval [CI] 1.260-5.502; p = 0.010) as well as with high-grade genitourinary and rectal toxicity (OR 2.169, 95%CI1.017-4.625; p = 0.045 and OR 7.220, 95%CI 1.227-42.473; p = 0.029, respectively). Furthermore, the Activities of Daily Living score (OR 0.054, 95%CI 0.004-0.651; p = 0.022), social status (OR 0.159, 95%CI 0.028-0.891; p = 0.036), and polypharmacy (OR 4.618, 95%CI 1.045-20.405; p = 0.044) were identified as independent predictors of rectal toxicity grade ≥ 2. CONCLUSION: Geriatric conditions seem to be predictive of the development of high-grade radiation-induced toxicity in prostate cancer patients treated with definitive radiotherapy.

Clinical Implementation of "Plan of the Day" Strategy in Definitive Radiation Therapy of Cervical Cancer: Online Adaptation to Address the Challenge of Organ Filling Reproducibility.

PURPOSE: Definitive pelvic intensity modulated radiation therapy (IMRT) in cervical cancer is susceptible to geographic miss due to daily positional and volumetric variations in target and organs at risk. Hence, despite evidence of reduced acute and late treatment-related toxicities, implementation of image-guided IMRT (IG-IMRT) with a reasonable safety margin to encompass organ motion is challenging. METHODS AND MATERIALS: In this prospective, nonrandomized phase 2 study, patients with cervical cancer International Federation of Gynecology and Obstetrics (2009) stage IB2-IIIB between the ages of 18 and 65 years were treated with definitive pelvic chemoradiotherapy with a prespecified organ (bladder and rectum) filling protocol. Reproducibility of organ filling was assessed along with the implementation of daily comprehensive adaptive image-guided radiotherapy (IGRT), with a library of 3 IMRT (volumetric modulated arc therapy) plans with incremental expansions of clinical target volume (CTV) to planning target volume (PTV) (primary) margins (small, 0.7 cm; adequate, 1 cm; and large, 1.5 cm) and a backup motion robust 3-dimensional conformal radiotherapy plan; the appropriate plan is chosen based on pretreatment cone beam computed tomography (CBCT) ("plan of the day" approach). RESULTS: Fifty patients with a median age of 49 years (IQR, 45-56 years) received definitive radiation therapy (45-46 Gy in 23-25 fractions to pelvis, with simultaneous integrated boost to gross nodes in 15 patients) with the aforementioned IGRT protocol. In the analysis of 1171 CBCT images (in 1184 treatment sessions), the mean planning computed tomography (CT) and CBCT bladder volumes were 417 and 373 cc, respectively. Significant interfractional variation in bladder volume was noted with a mean absolute dispersion of 29.5% with respect to planning CT; significant influential random factors were postchemotherapy sessions (P ≤ .001), pre-CBCT protocol duration (P = .001), and grades of chemotherapy induced nausea vomiting (P = .001). Significantly higher variation in bladder filling was noted in patients with older age (P = .014) and larger planning CT bladder volume (P ≤ .001). Time trend analysis of fraction-wise bladder volume revealed an absolute systemic reduction of 16.3% in bladder volume means from the first to the fifth week. Variation in rectal diameter was much less pronounced, with 19.2% mean dispersion and without any significant factors affecting it. Although in 19% and 2% of sessions large IMRT PTV and 3-dimensional conformal radiotherapy were necessary to cover the primary target, respectively, reduction in treated volume was possible in 43% of sessions with small PTV selection instead of standard adequate PTV (36% sessions). Plan of the day selection had a moderate to strong correlation with nonabsolute dispersion of bladder filling (Spearman ρ =0.4; P = .001) and a weak (but significant) correlation with grades of acute toxicities. The planned protocol was well tolerated with no radiation-induced local grade 3 toxicity. CONCLUSIONS: Interfractional variation in organ filling (especially bladder) is inevitable despite fixed pretreatment protocol in definitive settings (intact cervix). Despite the logistical challenges, adaptive IGRT in the form of plan of the day based on incremental CTV-to-PTV margins is a relatively simple and feasible strategy to minimize geometric uncertainties in radical IG-IMRT of cervical cancer.

Long-Term Outcomes After Abdominal Radiation for Wilms Tumor: A 20-Year Experience.

BACKGROUND: As radiation therapy (RT) for Wilms tumor (WT) evolves with more conformal techniques, it is necessary to evaluate patterns of failure and toxicity. We sought to determine the rate of local failure (LF) after abdominal RT in WT, specifically focusing on those with contained rupture treated with whole abdominal and pelvic RT (WAPRT) vs flank RT. Secondary objectives were to determine overall survival (OS), distant failure (DF), and late toxicities. METHODS: A single institution retrospective study of 54 pediatric patients with WT treated with abdominal RT between May 2000 and October 2022. LF and DF were calculated through cumulative incidence function and OS by Kaplan-Meier method. RESULTS: The median age was 4.5 years and the median follow-up was 6 years. Most patients (91%) had favorable histology. Only 1 patient experienced LF, 15 months from completion of RT (cumulative incidence 2% at 5 y). All patients who received unilateral flank radiation for contained rupture/spillage (n=13) experienced long-lasting intra-abdominal tumor control. A total of 5 patients experienced a DF at a median of 7 months, all in the lung. No patient relapsed in the lungs after upfront whole lung irradiation (n=16). OS was 96% at 5 years. Among 28 patients who followed through puberty, 4 female patients with prior WAPRT experienced hormonal irregularities/infertility. CONCLUSIONS: Unilateral flank radiation may be a viable alternative to WAPRT for contained rupture/spillage and should be further explored prospectively. Our results may also be utilized in the future for outcome and toxicity comparison as conformal radiation techniques evolve.

Risk evaluation of secondary malignancies after radiotherapy of breast cancer in light of the continuous development of planning techniques.

Secondary cancer risk is a significant concern for women treated with breast radiation therapy due to improved long-term survival rates. We evaluated the potential of new advanced automated planning algorithms together with hybrid techniques to minimize the excess absolute risk (EAR) for secondary cancer in various organs after radiation treatment for early staged breast cancer. Using CT data set of 25 patients, we generated 4 different radiation treatment plans of different complexity, including 3-dimensional conformal radiotherapy (3D-CRT), field-in-field (FinF), hybrid-IMRT (HMRT) and automated hybrid-VMAT (HVMAT) techniques. The organ-equivalent dose (OED) was calculated from differential dose-volume histograms on the basis of the "linear-exponential," "plateau," and "full mechanistic" dose-response models and was used to evaluate the EAR for secondary cancer in the contralateral breast (CB), contralateral lung (CL), and ipsilateral lung (IL). Statistical comparisons of data were performed by a Kruskal-Wallis analysis of variance. The planning objectives were fulfilled with all the planning techniques for both target coverage and organs-at-risk sparing. The differences in EAR for CB, CL and IL secondary tumor induction were not significant among the 4 techniques. For the CB and CL, the mean absolute difference did not reach 1 case of 10000 patient-years. For the IL, the mean absolute difference was up to 5 cases of 10,000 patient-years. In conclusion, the automated HVMAT technique allows an EAR reduction at the level of well-consolidated tangential 3D-CRT or FinF techniques, keeping all the HVMAT dosimetric improvements unchanged. On the basis of this analysis, the adoption of the HVMAT technique poses no increase in EAR and could be considered safe also for younger patients.

A systematic review of the normal tissue complication probability models and parameters: Head and neck cancers treated with conformal radiotherapy.

This systematic review study aims to provide comprehensive data on different radiobiological models, parameters, and endpoints used for calculating the normal tissue complication probability (NTCP) based on clinical data from head and neck cancer patients treated with conformal radiotherapy. A systematic literature search was carried out according to the PRISMA guideline for the identification of relevant publications in six electronic databases of Embase, PubMed, Scopus, and Google Scholar to July 2022 using specific keywords in the paper's title and abstract. The initial search resulted in 1368 articles for all organs for the review article about the NTCP parameters. One hundred and seventy-eight articles were accepted for all organs with complete parameters for the mentioned models and finally, 20 head and neck cancer articles were accepted for review. Analysis of the studies shows that the Lyman-Kutcher-Burman (LKB) model properly links the NTCP curve parameters to the postradiotherapy endpoints. In the LKB model for esophagus, the minimum, and maximum corresponding parameters were reported as TD50 = 2.61 Gy with grade ≥3 radiation-induced esophagitis endpoints as the minimum TD50 and TD50 = 68 Gy as the maximum ones. nmin = 0.06, nmax = 1.04, mmin = 0.1, and mmax = 0.65, respectively. Unfortunately, there was not a wide range of published articles on other organs at risk like ear or cauda equina except Burman et al. (Fitting of normal tissue tolerance data to an analytic function. Int J Radiat Oncol Biol Phys Ther. 1991;21:123-135). Findings suggest that the validation of different radiobiological models and their corresponding parameters need to be investigated in vivo and in vitro for developing a more accurate NTCP model to be used for radiotherapy treatment planning optimization.

Recent trends in radiotherapy use for major cancers in Korea.

BACKGROUND: Although the trend in radiotherapy in all cancer patients has been studied, changes in radiotherapy modalities for specific cancer types have not been reported. This study aimed to analyze radiotherapy patterns for major cancers in Korea in recent years. MATERIALS AND METHODS: We collected data from claims and reimbursement records of the Health and Insurance Review and Assessment Service from 2017 to 2020, according to initial diagnostic codes. The radiotherapy modalities for major cancers, such as lung, stomach, colorectal, breast and liver cancer, were analyzed. The radiotherapy modalities consisted of two-dimensional radiotherapy, three-dimensional conformal radiotherapy, intensity-modulated radiotherapy, proton radiotherapy and stereotactic body radiotherapy. RESULTS: Overall, from 2017 to 2020, the use of two-dimensional radiotherapy and three-dimensional conformal radiotherapy decreased, and intensity-modulated radiotherapy increased. In 2017, three-dimensional conformal radiotherapy accounted for approximately half of the radiotherapy in patients for lung and colorectal cancer, which was replaced by intensity-modulated radiotherapy in 2020. In 2020, stereotactic body radiotherapy also accounted for a large proportion of radiotherapy used in liver cancer cases. Intensity-modulated radiotherapy was most used, followed by three-dimensional conformal radiotherapy and two-dimensional radiotherapy for breast cancer in 2020. Among major cancers, radiotherapy utilization for breast cancer is the highest. Compared with other cancers, the number of patients receiving radiotherapy for stomach cancer was low. CONCLUSION: The number of patients receiving radiotherapy for major cancers has increased. The use of advanced forms of radiotherapy, such as intensity-modulated radiotherapy, is rapidly increasing for major cancers. The rate of radiotherapy utilization was higher in major cancer patients than in all cancer patients.

Post-operative flank irradiation using conformal versus highly conformal radiotherapy techniques for paediatric renal tumours: Results from the French registry PediaRT.

PURPOSE: Three-dimensional conformal RT (3D-RT) techniques are gold standard for post-operative flank radiotherapy (RT) in paediatric renal tumours. Recently, highly conformal RT (HC-RT) techniques have been implemented without comparative clinical data. The main objective of this multicentre study was to compare locoregional control (LRC) in children treated either with HC-RT or 3D-RT techniques. METHODS: Patients treated with post-operative flank RT for renal tumour registered in the national cohort PediaRT between March 2013 and September 2019 were included. Treatment and follow-up data, including toxicities and outcomes, were retrieved from the database. LRC was calculated, and dose reconstruction was performed in case of an event. RESULTS: Seventy-nine patients were included. Forty patients were treated with HC-RT and 39 with 3D-RT. Median follow-up was 4.5 years. Three patients had locoregional failure (LRF; 4%). HC-RT was not associated with a higher risk of LRF. Three-year LRC were 97.4% and 94.7% in the HC-RT and 3D-RT groups, respectively. The proportion of planning target volumes receiving 95% or more of the prescribed dose did not significantly differ between both groups (HC-RT 88%; 3D-RT 69%; p = .05). HC-RT was better achieving dose constraints, and a significant mean dose reduction was observed in the peritoneal cavity and pancreas associated with lower incidence of acute gastrointestinal toxicity. CONCLUSION: LRF after post-operative flank RT for renal tumours was rare and did not increase using HC-RT versus 3D-RT techniques. Dose to the pancreas and the peritoneal cavity, as well as acute toxicity, were reduced with HC-RT compared to 3D-RT.

Locally advanced cervical cancer: how the improvement in techniques in external beam radiotherapy and brachytherapy impacts on survival outcomes and long-term toxicities.

BACKGROUND: Platinum-based chemoradiotherapy and brachytherapy are the standard treatment for locally advanced cervical cancer. Reported long-term outcomes for treated with both IMRT and 3D-Image-guided-adaptive brachytherapy are lacking. METHODS: This retrospective study included 165 patients with FIGO Stage IB-IVB cervical cancer, treated with chemoradiotherapy in combination with brachytherapy. External beam radiotherapy was delivered as IMRT/VMAT/TOMO helical or 3DCRT. The intracavitary brachytherapy treatment (ICBT) was performed using two different planning system (with or without optimization). RESULTS: Among the patient subgroups, comprising those who received IMRT/VMAT/Tomo helical and 3DCRT, as well as those who underwent ICBT planning optimization and those who did not, homogeneity was observed in terms of age, performance status, T stage, N status, TNM stage, and histology. With a median follow-up time of 60.5 months, the 5-year overall survival (OS) in the 3DCRT and IMRT groups was 74.9% and 92.8%, respectively (p = 0.033). The 5-year OS in the ICBT planning optimization group was 93.7%, compared to 75% in the non-optimization group (p = 0.014). Regarding late radiation toxicities, patients in the IMRT group had a lower incidence of chronic rectal toxicity compared to those in the 3DCRT group (6.5% vs. 34.1%, p = 0.001). The group with ICBT planning optimization had a lower incidence of late urinary toxicities (10.4%) compared to the non-optimized ICBT planning group (18.2%, p = 0.012). Similarly, the ICBT planning optimization group had a lower incidence of late rectal toxicity (6.5% with 80% grade 1 and 20% grade 2) compared to the non-optimized ICBT planning group (34.1%, p = 0.001). CONCLUSION: In this series, the group of patients receiving optimized ICBT had an advantage in terms of OS and CSS suggesting that the use of new Treatment Planning Systems associated with 3D imaging, improves the long-term survival. Additionally, a significant reduction in late rectal and urinary toxicity has been observed.

Quality-adjusted survival in women with gynecologic malignancies receiving IMRT after surgery: A Ppatient Rreported Ooutcome study of NRG oncology's RTOG 1203.

INTRODUCTION: NRG/RTOG 1203 compared 3-D conformal radiotherapy (3D CRT) to intensity-modulated radiotherapy (IMRT) in patients with endometrial or cervical cancer requiring post-operative radiotherapy after hysterectomy. The purpose of this study was to report the first quality-adjusted survival analysis comparing the two treatments. METHODS: NRG/RTOG 1203 randomized patients having undergone hysterectomy to either 3DCRT or IMRT. Stratification factors included RT dose, chemotherapy, and disease site. The EQ-5D, both index and visual analog scale (VAS), were obtained at baseline, 5 weeks after the start of RT, 4-6 weeks post RT and 1 and 3-years post RT. EQ-5D index and VAS scores along with quality-adjusted survival (QAS) were compared between treatment arms using the t-test at a two-sided significance level of 0.05. RESULTS: NRG/RTOG 1203 enrolled 289 patients of which 236 consented to participate in the patient reported outcome (PRO) assessments. QAS was higher in women treated with IMRT, 1374 vs 1333 days (p = 0.5) compared to patients treated with 3DCRT, but this difference was not statistically different. Patients treated with IMRT had less of a decline in VAS score 5 weeks post RT, -5.04, compared to patients treated with 3DCRT, -7.48, although not statistically significant (p = 0.38). CONCLUSION: This is the first report of the use of the EQ-5D comparing two radiotherapy techniques in the treatment of gynecologic malignancies after surgery. While there were no significant differences in QAS and VAS scores between patients who received IMRT vs. 3DCRT, RTOG 1203 was not powered to show statistical differences in these secondary endpoints.

Hybrid planning techniques for early-stage left-sided breast cancer: dose distribution analysis and estimation of projected secondary cancer-relative risk.

PURPOSE: 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. MATERIALS AND METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Comparing Risk for Second Primary Cancers After Intensity-Modulated vs 3-Dimensional Conformal Radiation Therapy for Prostate Cancer, 2002-2015.

Importance: Compared with 3-dimensional conformal radiotherapy (3DCRT), intensity-modulated radiotherapy (IMRT) can spare nearby tissue but may result in increased scatter radiation to distant normal tissue, including red bone marrow. It is unclear whether second primary cancer risk varies by radiotherapy type. Objective: To evaluate whether radiotherapy type (IMRT vs 3DCRT) is associated with second primary cancer risk among older men treated for prostate cancer. Design, Setting, and Participants: In this retrospective cohort study of a linked database of Medicare claims and Surveillance, Epidemiology, and End Results (SEER) Program population-based cancer registries (2002-2015), male patients aged 66 to 84 diagnosed with a first primary nonmetastatic prostate cancer from 2002 to 2013, as reported to SEER, and who received radiotherapy (IMRT and/or 3DCRT without proton therapy) within the first year following prostate cancer were identified. The data were analyzed from January 2022 through June 2022. Exposure: Receipt of IMRT and 3DCRT, based on Medicare claims. Main Outcomes and Measures: The association between radiotherapy type and development of a subsequent hematologic cancer at least 2 years after prostate cancer diagnosis or a subsequent solid cancer at least 5 years after prostate cancer diagnosis. Hazard ratios (HRs) and 95% CIs were estimated using multivariable Cox proportional regression. Results: The study included 65 235 2-year first primary prostate cancer survivors (median [range] age, 72 [66-82] years; 82.2% White patients) and 45 811 5-year survivors with similar demographic characteristics (median [range] age, 72 [66-79] years; 82.4% White patients). Among 2-year prostate cancer survivors (median [range] follow-up, 4.6 [0.003-12.0] years), 1107 second hematologic cancers were diagnosed (IMRT, 603; 3DCRT, 504). Radiotherapy type was not associated with second hematologic cancers overall or any specific types evaluated. Among 5-year survivors (median [range] follow-up, 3.1 [0.003-9.0] years), 2688 men were diagnosed with a second primary solid cancer (IMRT, 1306; 3DCRT, 1382). The overall HR for IMRT vs 3DCRT was 0.91 (95% CI, 0.83-0.99). This inverse association was restricted to the earlier calendar year period of prostate cancer diagnosis (HR2002-2005 = 0.85; 95% CI, 0.76-0.94; HR2006-2010 = 1.14; 95% CI, 0.96-1.36), with a similar pattern observed for colon cancer (HR2002-2005 = 0.66; 95% CI, 0.46-0.94; HR2006-2010 = 1.06; 95% CI, 0.59-1.88). Conclusions and Relevance: The results of this large, population-based cohort study suggest that IMRT for prostate cancer is not associated with an increased risk of second primary cancers, either solid or hematologic, and any inverse associations may be associated with calendar year of treatment.

Impact of Radiation Dose on Treatment of Maxillary Cancer With Superselective Intra-arterial Cisplatin With Radiotherapy.

BACKGROUND/AIM: Maxillary sinus cancer is a relatively rare disease, and treatment is still evolving. We compared the efficacy of superselective intra-arterial infusion of high-dose cisplatin (CDDP) with concomitant radiotherapy (RADPLAT) using three-dimensional conformal radiotherapy (3DCRT) or intensity-modulated radiotherapy (IMRT) and analyzed the relationship between the total radiation dose and the treatment outcome in localized maxillary sinus cancer. PATIENTS AND METHODS: We reviewed the cases of 58 patients with localized maxillary sinus cancer treated with RADPLAT at our institution from March 2004 to November 2020. These 58 patients included 34 who received 3DCRT and 24 who received IMRT. RESULTS: The median follow-up period was 38.4 months. The median prescribed dose to the local lesion was 66 Gy in the 3DCRT group and 70 Gy in the IMRT group. CDDP (100-120 mg/m2) was administered once a week for a median of 6 cycles. The 5-year local control rate and overall survival rate were 69.9% and 72.2%, respectively. The patients treated with 70 Gy had a significantly higher local control rate (87.7%) than those treated with 60 Gy or less (41.0%) (p=0.011). No late grade 3 or higher eye disorders except for cataracts developed in the IMRT group, while grade 4 eye disorders occurred in four patients receiving 3DCRT. CONCLUSION: IMRT can escalate radiation dose safely with acceptable toxicities. The total dose may have an impact on the local control rate in RADPLAT.

Reduced Risk of Lymphedema With Intensity-modulated Radiation Therapy Compared With 3-dimensional Conformal Radiation Therapy in Patients With Cervical Cancer Who Received Postoperative Pelvic Radiation Therapy.

OBJECTIVES: To compare the long-term adverse events of intensity-modulated radiation therapy (IMRT) with those of 3-dimensional conformal radiation therapy (3D-CRT) in patients with intermediate-risk and high-risk uterine cervical cancer who underwent postoperative pelvic radiation therapy (PORT). METHODS: We reviewed the medical records of 177 patients with cervical cancer who underwent radical surgery and PORT. IMRT and 3D-CRT were administered to 93 and 84 patients, respectively. Follow-up and toxicity assessments were then carried out. RESULTS: The median follow-up period was 63 months (range: 3 to 177). There was a significant difference in the follow-up period between the IMRT and 3D-CRT cohorts (median: 59 vs. 112 mo, P <0.0001). The crude incidences of acute grade 2+ and grade 3+ gastrointestinal toxicities were significantly lower with IMRT than with 3D-CRT (22.6% vs. 48.1%, P =0.002, and 3.2% vs. 11.1%, P =0.04, respectively). The Kaplan-Meier estimates of late toxicities revealed that IMRT significantly reduced grade 2+ genitourinary (GU) toxicity and lower-extremity lymphedema ([LEL] requiring intervention) compared with 3D-CRT ([6.8% vs. 15.2% at 5-year, P =0.048] and [3.1% vs. 14.6% at 5-year, P =0.0029], respectively). IMRT was the only significant predictor of reducing LEL risk. CONCLUSIONS: The risks of acute gastrointestinal toxicity, late GU toxicity, and LEL from PORT for cervical cancer were reduced by IMRT. Lower inguinal doses may have contributed to a lower risk of developing LEL, which should be validated in future studies.

Does shortening the duration of radiotherapy treatment in breast cancer increase the risk of radiation pneumonia: A retrospective study.

Randomized studies evaluating hypofractionation and conventional fractionation radiotherapy treatments (RT) in patients with breast cancer have shown that hypofractionation achieves similar results to conventional fractionation in terms of survival and local control rates. It has also been shown that their long-term toxicities are similar. This study aimed to evaluate the effects of hypofractionated radiotherapy (H-RT) and conventional radiotherapy (C-RT) on lung toxicity and identify factors affecting this toxicity in patients with breast cancer. The study included 118 patients who underwent adjuvant RT following breast-conserving surgery (BCS). Out of these, 63 patients were assigned to receive C-RT, while the remaining 55 were assigned to receive H-RT. To clarify, we treated 63 patients with C-RT and 55 patients with H-RT. 60 patients were treated using 3-dimensional conformal radiotherapy (3DCRT) and 58 patients were treated using intensity modulated radiotherapy (IMRT). The patients were evaluated weekly for toxicity during radiotherapy (RT) treatment and were called every 3 months for routine controls after the treatment. The first control was performed 1 month after the treatment. Statistical analysis was performed using the SPSS20 program, and a P value of <.005 was considered statistically significant. The study found that the median age of the participants was 54.9 years and tomographic findings were observed in 70 patients. Radiological findings were detected at a median of 5 months after RT. The mean lung dose (MLD) on the treated breast side (referred to as ipsilateral lung or OAR) was 10.4 Gy for the entire group. Among patients who received 18 MV energy in RT, those with an area volume (V20) of the lung on the treated breast side >18.5%, those with a mean dose of the treated breast side lung (ipsilateral lung) >10.5 Gy, and those who received concurrent hormone therapy had significantly more tomographic findings. However, patients treated with YART had fewer tomographic findings. No symptomatic patients were observed during the follow-up period. Our findings show that the risk of lung toxicity is similar with H-RT and C-RT, and H-RT can be considered an effective and safe treatment option for breast cancer. The key factors affecting the development of lung toxicity were found to be the type of RT energy used, RT to the side breast, volume receiving 20 Gy in the side lung, side lung mean dose, and simultaneous hormonal therapy.

Conformal Radiation Therapy for Ependymoma at Age ≤3 Years: A 25-Year Experience.

PURPOSE: Adjuvant radiation therapy (RT) affects survival after surgery for young children (age <3 years) diagnosed with intracranial ependymoma. Conformal photon RT promised to spare normal tissue and was introduced more than 25 years ago to improve outcomes for these vulnerable patients. Long-term results for those first treated with conformal methods provide valuable information and serve as a comparison against newer methods. METHODS AND MATERIALS: Between 1997 and 2018, 101 patients <3.1-years-old were treated with conformal and intensity modulated photon therapy after definitive surgery for intracranial ependymoma. The median age at RT was 2.1 years and the time from diagnosis to the start of RT was 10 weeks. The extent of resection was gross-total in 82%, and 38% underwent more than 1 attempt at resection. The total prescribed dose was 54 to 59.4 Gy at 1.8 Gy per fraction. RESULTS: The 10-year event-free and overall survivals were 58.5% ± 5.0% and 72.6% ± 4.5%, respectively, with a median follow-up of 18.4 years (range, 4.2-23.3 years). Tumor progression occurred in 34 patients with a median time of 1.6 years. Death occurred in 34 patients from ependymoma (n = 24), secondary malignancy (n = 6), necrosis (n = 2), shunt failure (n = 1), and anaphylactic reaction (n = 1). Twenty-three patients developed a secondary tumor including 6 cases of fatal high-grade glioma. Of the surviving cohort and those ≥18 years old, 98% obtained a high school diploma, 64% had a current driver's license, 89% were students or employed full or part time, 32% were living independently, and 70% received higher education or training. CONCLUSIONS: Long-term results of children treated using photon conformal RT after surgery demonstrate that adjuvant RT resulted in long-term disease control and functional independence. These results point to the need for new treatment strategies to improve tumor control and provide investigators hope that newer RT methods will further reduce complications.

Three-dimensional conformal radiotherapy (3D-CRT) vs. volumetric modulated arc therapy (VMAT) in deep inspiration breath-hold (DIBH) technique in left-sided breast cancer patients-comparative analysis of dose distribution and estimation of projected secondary cancer risk.

PURPOSE: The purpose of this study was to compare two techniques of irradiation of left-sided breast cancer patients who underwent breast-conserving surgery, three-dimensional conformal radiotherapy technique (3D-CRT) and volumetric modulated arc therapy (VMAT), in terms of dose distribution in the planning target volume (PTV) and organs at risk (OARs). The second aim of the study was estimation of the projected risk of radiation-induced secondary cancer for both radiotherapy techniques. MATERIALS AND METHODS: For 25 patients who underwent CT simulation in deep inspiration breath-hold (DIBH), three treatment plans were generated: one using a three-dimensional conformal radiotherapy technique and two using volumetric modulated arc therapy. First VMAT-DIBH geometry consisted of three partial arcs (ARC-DIBH 3A) and second consisted of four partial arcs (ARC-DIBH 4A). Cumulative dose-volume histograms (DVHs) were used to compare dose distributions within the PTV and OARs (heart, left anterior descending coronary artery [LAD], ipsilateral and contralateral lung [IL, CL], and contralateral breast [CB]). Normal tissue complication probabilities (NTCPs) and organ equivalent doses (OEDs) were calculated using the differential DVHs. Excess absolute risks (EARs) for second cancers were estimated using Schneider's full mechanistic dose-response model. RESULTS: All plans fulfilled the criterium for PTV V95% ≥ 95%. The PTV coverage, homogeneity, and conformity indices were significantly better for VMAT-DIBH. VMAT showed a significantly increased mean dose and V5Gy for all OARs, but reduced LAD Dmax by 15 Gy. For IL, CL, and CB, the 3D-CRT DIBH method achieved the lowest values of EAR: 28.38 per 10,000 PYs, 2.55 per 10,000 PYs, and 4.48 per 10,000 PYs (p < 0.001), compared to 40.29 per 10,000 PYs, 15.62 per 10,000 PYs, and 23.44 per 10,000 PYs for ARC-DIBH 3A plans and 41.12 per 10,000 PYs, 15.59 per 10,000 PYs, and 22.73 per 10,000 PYs for ARC-DIBH 4A plans. Both techniques provided negligibly low NTCPs for all OARs. CONCLUSION: The study shows that VMAT-DIBH provides better OAR sparing against high doses. However, the large low-dose-bath (≤ 5 Gy) is still a concern due to the fact that a larger volume of normal tissues exposed to lower doses may increase a radiation-induced risk of secondary cancer.