Photon Intensity-modulated Radiotherapy Research Articles

The impact of bolus on clinical outcomes for post-mastectomy breast cancer patients treated with IMRT: data from China

PurposeThis study aims to investigate the effects of chest wall bolus in intensity-modulated radiotherapy (IMRT) technology on clinical outcomes for post-mastectomy breast cancer patients.Materials and methodsThis retrospective study included patients with invasive carcinoma ((y)pT0-4, (y)pN0-3) who received photon IMRT after mastectomy at the Affiliated Hospital of Qingdao University from 2014 to 2019. The patients were divided into two groups based on whether they received daily bolus application or not, and the baseline characteristics were matched using propensity score matching (PSM). Cumulative incidence (CI) of local recurrence (LR), locoregional recurrence (LRR), overall survival (OS) and disease-free survival (DFS) were evaluated with a log-rank test. Acute skin toxicity and late radiation pneumonia was analyzed using chi-square test.ResultsA total of 529 patients were included in this study, among whom 254 (48%) patients received bolus application. The median follow-up time was 60 months. After matching, 175 well-paired patients were selected. The adjusted 5-year outcomes (95% confidence interval) in patients treated with and without bolus were, respectively: CI of LR 2.42% (0.04–4.74) versus 2.38% (0.05–4.65), CI of LRR 2.42% (0.04–4.74) versus 3.59% (0.73–6.37), DFS 88.12% (83.35–93.18) versus 84.69% (79.42–90.30), OS 94.21% (90.79–97.76) versus 95.86% (92.91–98.91). No correlation between bolus application and skin toxicity (P = 0.555) and late pneumonia (P = 0.333) was observed.ConclusionsThe study revealed a low recurrence rate using IMRT technology. The daily used 5 mm chest wall bolus was not associated with improved clinical outcomes.

Dose-Painting Proton Radiotherapy guided by Functional MRI in Non-Enhancing High-Grade Gliomas

PurposeThis study aimed to demonstrate the feasibility and to evaluate the dosimetric effect and clinical impact of dose-painting proton radiotherapy (PRT) guided by functional MRI in non-enhancing high-grade gliomas (NE-HGGs). Material and methodsThe 3D-ASL and T2 FLAIR MR images of ten patients with NE-HGGs before radiotherapy were studied retrospectively. The hyperintensity on T2 FLAIR was used to generate the planning target volume (PTV), and the high-perfusion volume on 3D-ASL (PTV-ASL) was used to generate the simultaneous integrated boost (SIB) volume. Each patient received pencil beam scanning PRT and photon intensity-modulated radiotherapy (IMRT). There were five plans in each modality: (1) Uniform plans (IMRT60 vs. PRT60): 60Gy in 30 fractions to the PTV. (2)-(5) SIB plans (IMRT72, 84, 96, 108 vs. PRT72, 84, 96, 108): Uniform plan plus additional dose boost to PTV-ASL in 30 fractions to 72, 84, 96, 108 Gy. The dosimetric differences between various plans were compared. The clinical effects of target volume and organs at risk (OARs) were assessed using biological models for both tumor control probability (TCP) and normal tissue complication probability (NTCP). ResultsCompared with the IMRT plan, the D2 and D50 of the PRT plan with the same prescription dose increased by 1.27–4.12% and 0.64–2.01%, respectively; the R30 decreased by > 32%; the dose of brainstem and chiasma decreased by > 27% and >32%; and the dose of normal brain tissue (Br-PTV), optic nerves, eyeballs, lens, cochlea, spinal cord, and hippocampus decreased by > 50% (P < 0.05). The maximum necessary dose was 96GyE to achieve > 98% TCP for PRT, and it was 84Gy to achieve > 91% TCP for IMRT. The average NTCP of Br-PTV was 1.30% and 1.90% for PRT and IMRT at the maximum dose escalation, respectively. The NTCP values of the remaining OARs approached zero in all PRT plans. ConclusionThe functional MRI-guided dose escalation using PRT is feasible while sparing the OARs constraints and demonstrates a potential clinical benefit by improving TCP with no or minimal increase in NCTP for tissues outside the PTV. This retrospective study suggested that the use of PRT-based SIB guided by functional MRI may represent a strategy to provide benefits for patients with NE-HGGs.

Intensity-modulated proton and carbon-ion radiotherapy using a fixed-beam system for locally advanced lung cancer: dosimetric comparison with x-ray radiotherapy and normal tissue complication probability (NTCP) evaluation

Objective. To assess the dosimetric consequences and the normal tissue complication probability (NTCP) for the organs at risk (OARs) in intensity-modulated particle radiotherapy of proton (IMPT) and carbon-ion (IMCT) using a fixed-beam delivery system when compared with intensity-modulated photon radiotherapy (IMRT) for locally advanced small-cell lung cancer. Approach. The plans were all designed under the same total relative biological effectiveness (RBE)-weighted prescription dose, in which the planning target volume (PTV) of the internal gross target volume(IGTV) and the PTV of the clinical target volume was irradiated with 69.3 Gy (RBE) and 63 Gy (RBE), respectively, using a simultaneously integrated boosting (SIB) technique. NTCPs were estimated for heart, lung, esophagus and spinal cord by Lyman–Kutcher–Burman (LKB) and logistic models. Dose escalation was simulated under the desired NTCP values (0.05, 0.10 and 0.50) of the three radiation techniques. Main results. Under the similar target coverage, almost all OARs were significantly better spared (p < 0.05) when using the particle radiotherapy except for D1cc (the dose to 1 cm3 of the volume) of the proximal bronchial tree (p > 0.05). At least 57.6% of mean heart dose, 28.8% of mean lung dose and 19.1% of mean esophageal dose were reduced compared with IMRT. The mean NTCP of radiation-induced pneumonitis (RP) in the ipsilateral lung was 0.39 ± 0.33 (0.39 ± 0.31) in IMPT plans and 0.36 ± 0.32 (0.35 ± 0.30) in IMCT plans compared with 0.66 ± 0.30 (0.64 ± 0.28) in IMRT plans by LKB (logistic) models. The target dose could be escalated to 78.3/76.9 Gy (RBE) in IMPT/IMCT plans compared with 61.7 Gy (RBE) in IMRT plans when 0.50 of NTCP in terms of RP in the ipsilateral lung was applied. Significance. This study presents the potential of better control of the side effects and improvement of local control originating from the dosimetric advantage with the application of IMPT and IMCT with the SIB technique for locally advanced lung cancer, even with limited beam directions.

Dosimetric rationale and preliminary experience in proton plus carbon-ion radiotherapy for esophageal carcinoma: a retrospective analysis

BackgroundConcurrent chemoradiotherapy has been standard of care for unresectable esophageal carcinoma. There were no reports on proton radiotherapy (PRT) plus carbon-ion radiotherapy (CIRT) with pencil beam scanning (PBS) for esophageal carcinoma. This study evaluated the tolerability and efficiency of proton and sequential carbon-ion boost radiotherapy for esophageal carcinoma.MethodsFrom April 2017 to July 2020, 20 patients with primary esophageal carcinoma at stages II–IV were treated with PRT plus sequential CIRT with PBS. A median relative biological effectiveness-weighted PRT dose of 50 Gy in 25 fractions, and a sequential CIRT dose of 21 Gy in 7 fractions were delivered. Respiratory motion management was used if the tumor moved > 5 mm during the breathing cycle. A dosimetric comparison of photon intensity-modulated radiotherapy (IMRT), PRT, and CIRT was performed. The median times and rates of survivals were estimated using the Kaplan–Meier method. Comparison of the dose-volume parameters of the organs at risk employed the Wilcoxon matched-pairs test.ResultsTwenty patients (15 men and 5 women, median age 70 years) were included in the analysis. With a median follow-up period of 25.0 months, the 2-year overall survival and progression-free survival rates were 69.2% and 57.4%, respectively. The patients tolerated radiotherapy and chemotherapy well. Grades 1, 2, 3, and 4 acute hematological toxicities were detected in 25%, 30%, 10%, and 30% of patients, respectively. Grades 3–5 acute non-hematological toxicities were not observed. Late toxicity events included grades 1, 2, and 3 in 50%, 20%, and 10% (pulmonary and esophageal toxicity in each) of patients. Grades 4–5 late toxicities were not noted. PRT or CIRT produced lower doses to organs at risk than did photon IMRT, especially the maximum dose delivered to the spinal cord and the mean doses delivered to the lungs and heart.ConclusionsPRT plus CIRT with PBS appears to be a safe and effective treatment for esophageal carcinoma. PRT and CIRT delivered lower doses to organs at risk than did photon IMRT. Further investigation is warranted.

Modern Techniques in Re-Irradiation for Locally Recurrent Rectal Cancer: A Systematic Review.

Radiotherapy (RT) plays an important role in the treatment of patients with previously irradiated locally recurrent rectal cancer (LRRC). Over the years, numerous technologies and different types of RT have emerged. The aim of our systematic literature review was to determine whether the new techniques have led to improvements in both outcomes and toxicities. A computerized search was performed by MEDLINE and the Cochrane database. The studies reported data from patients treated with carbon ion radiotherapy (CIRT), intensity-modulated photon radiotherapy (IMRT), and stereotactic radiotherapy (SBRT). Seven publications of the 126 titles/abstracts that emerged from our search met the inclusion criteria and presented outcomes of 230 patients. OS was reported with rates of 90.0% and 73.0% at 1 and 2 years, respectively; LC was 89.0% and 71.6% at 1 and 2 years after re-RT, respectively. Toxicity data vary widely, with emphasis on acute and chronic gastrointestinal and urogenital toxicity, even with modern techniques. data on toxicity and outcomes of re-RT for LRRC with new technologies are promising compared with 3D techniques. Comparative studies are needed to define the best technique, also in relation to the site of recurrence.

Comparison of Estimated Late Toxicities between IMRT and IMPT when Treating Retroperitoneal Sarcoma Preoperatively with Ultra-Hypofractionation

While preoperative radiation did not improve abdominal recurrence-free survival for retroperitoneal sarcoma (RPS) in the randomized STRASS trial, it did reduce rates of local recurrence. The risk of radiation-associated toxicity is substantial, with 77% of irradiated patients experiencing grade ≥3 lymphopenia in STRASS. Thus, finding methods to mitigate the issues of delaying surgery and irradiating normal tissue may provide a path towards affording the benefits of radiation while limiting its downside. One potential solution involves the use of hypofractionation to limit delay from radiation initiation to surgery, and proton therapy to limit dose to surrounding organs at risk (OARs). We conducted a dosimetric comparison of preoperative ultra-hypofractionated intensity-modulated photon radiotherapy (IMRT) and proton therapy (IMPT) for RPS, comparing estimated rates of late toxicity using published normal tissue complication probability (NTCP) models. Volumetric modulated arc therapy IMRT and IMPT plans were generated on 10 RPS patients previously treated with preoperative radiation. The prescription was 25 Gy radiobiological equivalent (GyE) to the clinical target volume (CTV) and 30 GyE to the margin-at-risk, all in five fractions. Proton doses were calculated using a radiobiological effective dose of 1.1. NTCPs were calculated for each OAR as a function of equivalent uniform dose. The ΔNTCP (difference in absolute NTCP between IMRT and IMPT plans) for each of the toxicity domains was calculated. Student T-tests were used to compare differences in dosimetric and NTCP outcomes. CTV coverage was met for all IMRT and IMPT plans with >99% of CTVs receiving ≥100% of prescription doses. The following endpoints were significantly lower with IMPT than IMRT: mean doses to liver, bone, and all analyzed genitourinary and gastrointestinal OARs; bowel, kidney, and bone V5-V20; stomach V15; liver V5; maximum doses to stomach, spinal canal, and body; and whole-body integral dose. No OAR endpoint was significantly higher with IMPT. The average ΔNTCP for grade 3 bowel ulceration/perforation and renal toxicity was 1.9% (p = .037) and 43.0% (p = .023), respectively, favoring IMPT. Using a model-based selection threshold of any ΔNTCP >10%, 50% (n = 5) of patients would be eligible for IMPT. IMPT maintained target coverage while significantly reducing dose to adjacent OARs and integral dose compared to IMRT. This translated to significantly lower risks of estimated late gastrointestinal and renal toxicities with IMPT. Further investigation is warranted to validate these findings and potential clinical benefit in the management of RPS. A prospective trial treating RPS with preoperative ultra-hypofractionated IMPT at our institution is currently being pursued (NCT05302570).

Characterization of Photon Intensity Modulated Radiation Therapy Robustness in Patients With Prostate Cancer as a Proposed Benchmark for Proton Therapy Robustness Evaluation

Robustness evaluation is increasingly used in particle therapy planning to assess clinical target volume (CTV) coverage in the setting of setup and range uncertainty. However, no clear standard exists as to an acceptable degree of plan robustness. The aim of this study is to quantify x-ray robustness parameters, as this could inform proton planning when held to a similar standard. Consecutive patients with prostate adenocarcinoma treated with definitive x-irradiation to the prostate alone at a single institution in 2019 were retrospectively reviewed. CTV to planned target volume (PTV) margins of 7 mm in all directions, except 4 mm posteriorly, were used in the main cohort. Plans were normalized to PTV V100% ≥ 95%. Patient setup errors were simulated by shifting the isocenter relative to the patient in each of the cardinal directions. The magnitude of each shift equaled the magnitude of the CTV to PTV expansion in that direction. Range uncertainty was set to 0%. A total of 27 patients were evaluated. The mean (SD) nominal plan CTV V100% was 99.6% (1.1%). The mean (SD) worst-case shift CTV V100% was 97.2% (2.8%). The mean (SD) nominal and worst-case CTV V95% were 100% (0%) and 99.7% (0.5%), respectively. A worst-case CTV V100% > 90% and a worst-case CTV V95% > 99% were achieved in over 95% of plans. The mean (SD) nominal and worst-case rectal V70 Gy were 2.37 cc (1.00 cc) and 11.60 cc (3.16 cc), respectively. The mean (SD) nominal and worst-case bladder V60 Gy were 7.8% (4.8%) and 14.5% (9.3%), respectively. Paired 2-tailed t tests comparing the nominal to worst-case dose-volume histograms were significant for each dosimetric parameter (P < .01). X-ray planning uses PTV margins to inherently provide robustness to patient setup errors. Although the prostate remains well covered in various setup uncertainty scenarios, organs at risk routinely exceeded nominal treatment plan institutional constraints in the worst-case scenarios. Robustness metrics obtained from x-ray plans could serve as a benchmark for proton therapy robust optimization and evaluation.

Severe Lymphopenia During Chemoradiation Therapy for Esophageal Cancer: Comprehensive Analysis of Randomized Phase 2B Trial of Proton Beam Therapy Versus Intensity Modulated Radiation Therapy

Lymphocytes play an important role in antitumor immunity; however, they are also especially vulnerable to depletion during chemoradiation therapy (CRT). The purpose of this study was to compare the incidence of grade 4 lymphopenia (G4L) between proton beam therapy (PBT) and intensity modulated photon radiation therapy (IMRT) in patients with esophageal cancer treated with CRT in a completed randomized trial and to ascertain patient heterogeneity to G4L risk based on treatment and established prognostic factors. Between April 2012 and March 2019, a single-institution, open-label, nonblinded, phase 2 randomized trial (NCT01512589) was conducted at the University of Texas MD Anderson Cancer Center. Patients were randomly assigned to IMRT or PBT, either definitively or preoperatively. This secondary analysis of the randomized trial was G4L during concurrent CRT according to Common Terminology Criteria for Adverse Events version 5.0. Among 105 patients evaluable for analysis, 44 patients (42%) experienced G4L at a median of 28 days after the start date of concurrent CRT. Induction chemotherapy (P=.003), baseline absolute lymphocyte count (P < .001), radiation therapy modality (P=.002), and planning treatment volume (P=.033) were found to be significantly associated with G4L. Multivariate classification analysis partitioned patients into 5 subgroups for whom the incidence of G4L was observed in 0%, 14%, 35%, 70%, and 100% of patients. The benefit of PBT over IMRT was most pronounced in patients with an intermediate baseline absolute lymphocyte count and large planning treatment volume (P=.011). This is the first prospective evidence that limiting dose scatter by PBT significantly reduced the incidence of G4L, especially in the intermediate-risk patients. The implication of this immune-sparing effect of PBT, especially in the context of standard adjuvant immunotherapy, needs further examination in the current phase 3 randomized trials.

3D-conformal very-high energy electron therapy as candidate modality for FLASH-RT: A treatment planning study for glioblastoma and lung cancer.

Pre-clinical ultra-high dose rate (UHDR) electron irradiations on time scales of 100ms have demonstrated a remarkable sparing of brain and lung tissues while retaining tumor efficacy when compared to conventional dose rate irradiations. While clinically-used gantries and intensity modulation techniques are too slow to match such time scales, novel very-high energy electron (VHEE, 50-250MeV) radiotherapy (RT) devices using 3D-conformed broad VHEE beams are designed to deliver UHDR treatments that fulfill these timing requirements. To assess the dosimetric plan quality obtained using VHEE-based 3D-conformal RT (3D-CRT) for treatments of glioblastoma and lung cancer patients and compare the resulting treatment plans to those delivered by standard-of-care intensity modulated photon RT (IMRT) techniques. Seven glioblastoma patients and seven lung cancer patients were planned with VHEE-based 3D-CRT using 3 to 16 coplanar beams with equidistant angular spacing and energies of 100 and 200MeV using a forward planning approach. Dose distributions, dose-volume histograms, coverage (V95% ) and homogeneity (HI98% ) for the planning target volume (PTV), as well as near-maximum doses (D2% ) and mean doses (Dmean ) for organs-at-risk (OAR) were evaluated and compared to clinical IMRT plans. Mean differences of V95% and HI98% of all VHEE plans were within 2% or better of the IMRT reference plans. Glioblastoma plan dose metrics obtained with VHEE configurations of 200MeV and 3-16 beams were either not significantly different or were significantly improved compared to the clinical IMRT reference plans. All OAR plan dose metrics evaluated for VHEE plans created using 5 beams of 100MeV were either not significantly different or within 3% on average, except for Dmean for the body, Dmean for the brain, D2% for the brain stem, and D2% for the chiasm, which were significantly increased by 1, 2, 6, and 8Gy, respectively (however below clinical constraints). Similarly, the dose metrics for lung cancer patients were also either not significantly different or were significantly improved compared to the reference plans for VHEE configurations with 200MeV and 5 to 16 beams with the exception of D2% and Dmean to the spinal canal (however below clinical constraints). For the lung cancer cases, the VHEE configurations using 100MeV or only 3 beams resulted in significantly worse dose metrics for some OAR. Differences in dose metrics were, however, strongly patient-specific and similar for some patient cases. VHEE-based 3D-CRT may deliver conformal treatments to simple, mostly convex target shapes in the brain and the thorax with a limited number of critical adjacent OAR using a limited number of beams (as low as 3 to 7). Using such treatment techniques, a dosimetric plan quality comparable to that of standard-of-care IMRT can be achieved. Hence, from a treatment planning perspective, 3D-conformal UHDR VHEE treatments delivered on time scales of 100ms represent a promising candidate technique for the clinical transfer of the FLASH effect.

Comparative In Silico Analysis of Ultra-Hypofractionated Intensity-Modulated Photon Radiotherapy (IMRT) Versus Intensity-Modulated Proton Therapy (IMPT) in the Pre-Operative Treatment of Retroperitoneal Sarcoma

Background: While pre-operative radiation did not improve abdominal recurrence-free survival for retroperitoneal sarcoma (RPS) in the randomized STRASS trial, it did reduce rates of local recurrence. However, the risk of toxicity was substantial and the time to surgery was prolonged. A combination of hypofractionation and proton therapy may reduce delays from the initiation of radiation to surgery and limit the dose to surrounding organs at risk (OARs). We conducted a dosimetric comparison of the pre-operative ultra-hypofractionated intensity-modulated photon (IMRT) and proton radiotherapy (IMPT). Methods: Pre-operative IMRT and IMPT plans were generated on 10 RPS patients. The prescription was 25 Gy radiobiological equivalents (GyEs) (radiobiological effective dose of 1.1) to the clinical target volume and 30 GyEs to the margin at risk, all in five fractions. Comparisons were made using student T-tests. Results: The following endpoints were significantly lower with IMPT than with IMRT: mean doses to liver, bone, and all genitourinary and gastrointestinal OARs; bowel, kidney, and bone V5–V20; stomach V15; liver V5; maximum doses to stomach, spinal canal, and body; and whole-body integral dose. Conclusions: IMPT maintained target coverage while significantly reducing the dose to adjacent OARs and integral dose compared to IMRT. A prospective trial treating RPS with pre-operative ultra-hypofractionated IMPT at our institution is currently being pursued.

Reduced radiation exposure to circulating blood cells in proton therapy compared with X-ray therapy in locally advanced lung cancer: Computational simulation based on circulating blood cells.

We estimated the dose of circulating blood cells (CBCs) in patients with locally advanced non-small cell lung cancer for predicting severe radiation-induced lymphopenia (SRIL) and compared pencil-beam scanning proton therapy (PBSPT) and intensity-modulated (photon) radiotherapy (IMRT). After reviewing 325 patients who received definitive chemoradiotherapy with PBSPT (n = 37) or IMRT (n = 164). SRIL was diagnosed when two or more events of an absolute lymphocyte count < 200 µL occurred during the treatment course. Dose information for the heart and lungs was utilized for the time-dependent computational dose calculation of CBCs. The dose distribution of CBCs was significantly lesser in the PBSPT group than that in the IMRT group. Overall, 75 (37.3%) patients experienced SRIL during the treatment course; 72 and 3 patients were treated with IMRT and PBSPT, respectively. SRIL was associated with poor progression-free and overall survival outcomes. Upon incorporating the dose information of CBCs for predicting SRIL, CBC D90% > 2.6 GyE was associated with the development of SRIL with the baseline lymphocyte count and target volume. Furthermore, PBSPT significantly reduced the dose of CBC D90% (odds ratio = 0.11; p = 0.004) compared with IMRT. The results of this study demonstrate the significance of the dose distribution of CBCs in predicting SRIL. Furthermore, reducing the dose of CBCs after PBSPT minimized the risk of SRIL. Lymphocyte-sparing radiotherapy in PBSPT could improve outcomes, particularly in the setting of maintenance immunotherapy.

Comparison of intensity-modulated radiation therapy (IMRT), 3D conformal proton therapy and intensity-modulated proton therapy (IMPT) for the treatment of metastatic brain cancer.

The purpose of this study has been to compare photon intensity modulated radiation therapy (IMRT) against both conformal and intensity modulated proton therapy (IMPT) plans for metastatic brain cancer. Ten IMRT patients with brain cancer were chosen retrospectively, with prescription doses in the range of 20 to 40 Gy, delivered in 3 to 5 fractions using Varian TrueBeam STx machine. Three proton plans with proton double scattering, single collimation static-IMPT, and energy layer by layer collimation dynamic-IMPT were then generated for the same patients using the Mevion S250 system for conformal plans and the S250i system for IMPT plans. Each plan had respective treatment planning systems that include Brainlab iPlan for IMRT, Varian Eclipse for proton double scattering, and RaySearch Raystation for IMPT. Dosimetric and radiobiologic comparisons were made through dose-volume histogram (DVH) analysis of the target and the organs at risk (OAR); and with parameters of equivalent uniform dose (EUD), tumor control probability (TCP), and normal tissue complication probability (NTCP), respectively. A set of variables α/β ratio, survival fraction, and clonogenic cell density were selected and varied to observe their effect on the abovementioned parameters. Doses were observed to be more homogeneous for patients with brain malignancies with photon IMRT treatments, while dose conformity is improved with proton PBS treatments. Normal tissue is, on average, spared more through both proton treatment options. The minimum doses, closely approximated by dose to 98% of the target volume, are similar across treatment modalities with slight variations.

Proton and Carbon Ion Radiation Therapy Decreased Severe Lymphopenia by Reducing Thoracic Vertebra and Aortic Doses in Non-Small Cell Lung Cancer Versus Intensity Modulated Radiation Therapy

Lymphopenia is a common adverse effect of radiotherapy (RT). Little is known about the difference in lymphopenia between intensity-modulated (photon) radiation therapy (IMRT) and proton and carbon ion radiotherapy (PCIRT). This study aimed to investigate lymphopenia differences between IMRT and PCIRT in non-small cell lung cancer (NSCLC). Clinical and dosimetric parameters were collected from 343 patients who received definitive IMRT or PCIRT for NSCLC. Severe lymphopenia (SRL) was defined as an absolute lymphocyte count (ALC) ≤0.5*103 cells/μL. Overall survival (OS) was analyzed using the Kaplan-Meier method. Propensity score matching was performed between the IMRT and PCIRT groups. LASSO analysis was used to select appropriate dosimetric parameters. Univariate and multivariate logistic regression analyses were conducted to identify the predictors of SRL. Compared to the IMRT group, the PCIRT group was less likely to develop SRL (p <0.001). Compared with non-SRL group, SRL group showed significant association with poorer OS, with median survival time of 29.2 vs. 15.0 months (p = 0.046). IMRT was an independent risk factor of SRL (p = 0.004). A lower ALC before RT (p = 0.030) and larger planning target volume (PTV) (p = 0.002) were also significant independent risk factors for SRL. Moreover, the majority of dosimetric parameters of organ at risks in PCIRT were lower than those in IMRT (p <0.001). Thoracic vertebra V5 (p =0.002) and aorta V5 (p =0.026) were identified as independent risk predictors of SRL after adding dosimetric parameters to the regression model. Compared with IMRT, PCIRT could reduce the SRL incidence, possibly by limiting thoracic vertebra and aortic doses, and SRL was associated with poor outcomes in NSCLC patients.

In Silico Dosimetric Comparison of Intensity-Modulated Proton Radiotherapy (IMPT) vs. Intensity-Modulated Photon Radiotherapy (IMRT) in the Preoperative Treatment of Retroperitoneal Sarcoma

<h3>Purpose/Objective(s)</h3> With the results of the randomized STRASS trial, the benefit of preoperative radiation has been called into question in the treatment of retroperitoneal sarcoma. Given the large amount of normal tissue which often resides in close proximity to retroperitoneal sarcomas, the risk of radiation-associated toxicity is substantial, with 77% of irradiated patients experiencing grade ≥3 lymphopenia in STRASS. The exit dose and integral exposure associated with photon irradiation limits its therapeutic ratio. Our purpose was to evaluate a dosimetric comparison between ultra-hypofractionated modern scanning beam intensity-modulated proton therapy (IMPT) and intensity-modulated photon radiotherapy (IMRT) for the preoperative treatment of retroperitoneal sarcoma. We hypothesized that IMPT would significantly reduce dose to the to the liver, bowel and kidneys without sacrificing clinical target volume (CTV) coverage. <h3>Materials/Methods</h3> Ultra-hypofractionated IMRT and IMPT plans were generated using TPS on 10 patients previously treated with conventionally fractionated preoperative photon irradiation for retroperitoneal sarcoma. The prescription was 25 Gy radiobiological equivalent (GyE) to the entire CTV and 30 GyE to the margin-at-risk (CTV_Boost), all in five fractions. IMPT doses are reported in GyE = 1.1 Gy. Target coverage goals, OAR constraints, and integral dose were compared by student T-test with <i>p</i> < .050 considered significant. <h3>Results</h3> Target coverage goals, OAR constraints, and integral dose are reported in Table 1. Mean dose to liver, bowel, and ipsilateral and contralateral kidneys were all significantly lower with IMPT than IMRT, as was integral dose. <h3>Conclusion</h3> IMPT maintained target coverage while significantly reducing integral dose and mean dose to nearby OARs compared to IMRT. Further investigation is warranted to validate these dosimetric findings and potential clinical benefit in the management of retroperitoneal sarcoma.

Intensity-modulated proton radiation therapy as a radical treatment modality for nasopharyngeal carcinoma in China: Cost-effectiveness analysis.

Compared to conventional intensity-modulated photon radiation therapy (IMRT), intensity-modulated proton radiation therapy (IMPT) has potential to reduce irradiation-induced late toxicities while maintaining excellent tumor control in patients with nasopharyngeal carcinoma (NPC). However, the relevant cost-effectiveness remains controversial. A Markov decision tree analysis was performed under the assumption that IMPT offered normal tissue complication probability reduction (NTCP reduction) in long-term dysphagia, xerostomia, and hearing loss, compared to IMRT. Base-case evaluation was performed on T2N2M0 NPC of median age (43 years old). A Chinese societal willingness-to-pay threshold (33558 US dollars [$])/quality-adjusted life-year [QALY]) was adopted. For patients at median age and having NTCP reduction of 10%, 20%, 30%, 40%, 50%, and 60%, their incremental cost-effectiveness ratios were $102684.0/QALY, $43161.2/QALY, $24134.7/QALY, $13991.6/QALY, $8259.8/QALY, and $4436.1/QALY, respectively; IMPT should provide an NTCP reduction of ≥24% to be considered cost-effective. IMPT has potential to be cost-effective for average Chinese NPC patients and should be validated clinically.

Mixed-Beam Approach for High-Risk Prostate Cancer Carbon-Ion Boost Followed by Photon Intensity-Modulated Radiotherapy: Preliminary Results of Phase II Trial AIRC-IG-14300.

PurposeThis study represents a descriptive analysis of preliminary results of a Phase II trial on a novel mixed beam radiotherapy (RT) approach, consisting of carbon ions RT (CIRT) followed by intensity-modulated photon RT, in combination with hormonal therapy, for high-risk prostate cancer (HR PCa) with a special focus on acute toxicity.MethodsPrimary endpoint was the evaluation of safety in terms of acute toxicity. Secondary endpoints were early and long-term tolerability of treatment, quality of life (QoL), and efficacy. Data on acute and late toxicities were collected according to RTOG/EORTC. QoL of enrolled patients was assessed by IPSS, EORTC QLQ-C30, EORTC QLQ-PR25, and sexual activity by IIEF-5.ResultsTwenty-six patients were enrolled in the study, but only 15 completed so far the RT course and were included. Immediately after CIRT, no patients experienced GI/GU toxicity. At 1 and 3 months from the whole course RT completion, no GI/GU toxicities greater than grade 2 were observed. QoL scores were overall satisfactory.ConclusionsThe feasibility of the proposed mixed treatment schedule was assessed, and an excellent acute toxicity profile was recorded. Such findings instil confidence in the continuation of this mixed approach, with evaluation of long-term tolerability and efficacy.

A Systematic Review on Intensity Modulated Radiation Therapy for Mediastinal Hodgkin's Lymphoma.

Secondary malignant neoplasms (SMNs) and cardiovascular diseases induced by chemotherapy and radiotherapy represent the main cause of excess mortality for early-stage Hodgkin lymphoma patients, especially when the mediastinum is involved. Conformal radiotherapy techniques such as Intensity-Modulated Radiation Therapy (IMRT) could allow a reduction of the dose to the organs-at-risk (OARs) and therefore limit long-term toxicity. We performed a systematic review of the current literature regarding comparisons between IMRT and conventional photon beam radiotherapy, or between different IMRT techniques, for the treatment of mediastinal lymphoma. IMRT allows a substantial reduction of the volumes of OARs exposed to high doses, reducing the risk of long-term toxicity. This benefit is conterbalanced by the increase of volumes receiving low doses, that could potentially increase the risk of SMNs. Treatment planning should be personalized on patient and disease characteristics. Dedicated techniques such as "butterfly" VMAT often provide the best trade-off.

Acute Toxicity Following Ipsilateral Head and Neck Radiation Therapy: Proton vs. Intensity-Modulated Photon Radiotherapy

Given its unique properties, proton beam radiation therapy has the ability to reduce dose to at-risk organs. Proton's Bragg peak gives sharp distal dose fall off, which results in little or no dose beyond this region. As such, ipsilateral head and neck radiation with protons can spare the contralateral side to a greater extent than photon-based radiation, potentially causing reduced acute toxicity.Eighty-six patients (59 protons and 27 intensity modulated radiation therapy [IMRT]) who received primary or adjuvant ipsilateral head and neck radiation were retrospectively reviewed. Patients received radiation to one side and this must have included at least the parotid region in the treatment field. Primary disease site was major salivary gland in 40, cutaneous in 23, tonsil in 19 and other in 4 patients. Passive scatter proton therapy was delivered with 1-3 fields daily. Median dose delivered was 66 cobalt gray equivalent with protons and 60 gray with IMRT.No grade 4 or greater acute mucositis was present in either group. Median acute mucositis was grade 1 for protons and 2 for IMRT. Grade 0, 1, 2 or 3 acute mucositis toxicity was present in 28 (47%), 11 (19%), 17 (29%) and 3 patients (5%) respectively with proton treatment and present in 7 (26%), 3 (11%), 12 (44%) and 5 patients (19%) respectively with IMRT (P = 0.053). Percutaneous endoscopic gastrostomy (PEG) tube was placed during radiation treatment for 1 patient (2%) with protons and 4 patients (15%) for IMRT (P = 0.032). Two patients in the proton group had a PEG tube placed prior to starting radiation and one patient in the IMRT group refused PEG tube placement despite treating physician recommendation. No grade 4 or greater acute radiation dermatitis was experienced by patients in either group. Median acute radiation dermatitis was grade 2 for protons and 2 for IMRT. Grade 0, 1, 2 or 3 toxicity was present in 0 (0%), 7 (12%), 47 (80%) and 4 patients (7%) respectively with proton treatment and present in 0 (0%), 5 (19%), 20 (74%) and 2 patients (7%) respectively with IMRT (P = 0.718). The majority of patients in both treatment groups completed treatment with ≤ 5 days of missed fractions (86.4% with protons, 85.1% with IMRT). Median number of missed treatment days was 2 in both groups.Ipsilateral radiation therapy is well tolerated with IMRT and proton based radiation therapy. Fewer patients underwent PEG tube placement in the proton cohort, however these results should be further validated with prospective patient-toxicity centered studies.

Indications of IMRT, PRT and CIRT for HCC from comparisons of dosimetry and normal tissue complication possibility.

To identify the indications for hepatocellular carcinoma (HCC) irradiated by intensity-modulated photon radiotherapy (IMRT), proton radiotherapy (PRT) or carbon-ion radiotherapy (CIRT) by comparing of dosimetric parameters and incidences of classic radiation-induced liver disease (RILD). In all, 40HCCs were divided into groupA (tumors located > 1 cm away from gastrointestinal [GI] tract), and groupB (tumors located < 1 cm away from GI tract). The prescribed curative doses were 60 Gy (relative biological effectiveness [RBE]) in 10fractions for groupA, and 67.5 Gy (RBE) in 15fractions for groupB. IMRT, PRT and CIRT plans were separately generated to reach the curative doses and coverage. Dosimetric parameters evaluated were mean dose to normal liver (MDTNL) and the volume of normal liver receiving more than 1 Gy (RBE) (V1). Lyman-Kutcher-Burman model was used to determine the incidences of classic RILD, and Power model of non-linear regression, to estimate the tumor volume that could be irradiated with the curative doses within dose constraint of MDTNL. With comparable target doses, the MDTNL (Gy [RBE]) were 18.8 ± 3.7, 13.5 ± 3.1 and 12.8 ± 2.7 in groupA and 24.9 ± 7.1, 18.2 ± 3.7 and 17.5 ± 3.7 in groupB, respectively, for IMRT, PRT and CIRT. The classic RILD incidences (%) were 22.3 ± 30.0 in IMRT, 2.3 ± 4.9 in PRT and 1.2 ± 2.4 in CIRT. V1 (%) were 89.9 ± 8.8, 43.0 ± 10.2 and 45.9 ± 8.8, respectively, for IMRT, PRT and CIRT. PRT and CIRT could spare the liver more than IMRT. IMRT could deliver the curative doses to HCC up to adiameter of 7.9 cm; PRT, up to 13.2 cm; and CIRT, up to 14.8 cm.

Retrospective comparison of rectal toxicity between carbon-ion radiotherapy and intensity-modulated radiation therapy based on treatment plan, normal tissue complication probability model, and clinical outcomes in prostate cancer.

This retrospective study assessed the treatment planning data and clinical outcomes for 152 prostate cancer patients: 76 consecutive patients treated by carbon-ion radiation therapy and 76 consequtive patients treated by moderate hypo-fractionated intensity-modulated photon radiation therapy. These two modalities were compared using linear quadratic model equivalent doses in 2Gy per fraction for rectal or rectal wall dose-volume histogram, 3.6Gy per fraction-converted rectal dose-volume histogram, normal tissue complication probability model, and actual clinical outcomes. Carbon-ion radiation therapy was predicted to have a lower probability of rectal adverse events than intensity-modulated photon radiation therapy based on dose-volume histograms and normal tissue complication probability model. There was no difference in the clinical outcome of rectal adverse events between the two modalities compared in this study.