Inverse-planned Intensity-modulated Radiotherapy Research Articles

Assessment of normal tissue objectives in RapidArc treatment for cervical cancer

Abstract Purpose: The normal tissue objective (NTO) is a tool used in inverse-planned intensity-modulated radiation therapy (IMRT) to minimize dose dispersion to surrounding tissues. The current study focuses on the NTO’s impact on RapidArc treatment plans for cervical cancer patients or its role in reducing doses to healthy surrounding tissues. Material and methods: This study included 11 cervical cancer patients who underwent RapidArc treatment. We assessed plans both with and without the NTO objective by evaluating parameters such as homogeneity, conformity, gradient index (GI), IMRT factor, integral dose and the volume of normal tissues receiving low doses of 40, 30, 20 and 10 Gy. Further, differences between automatic NTO and manual NTO were evaluated using Wilcoxon signed-rank test. Results: There were no significant differences in the conformity index, homogeneity index, IMRT factor and integral dose between plans with automatic NTO and those with manual NTO RapidArc plans. However, we did observe a clear advantage in using manual NTO for controlling low-dose exposure to normal tissues. The comparisons between automatic and manual NTO resulted in a GI of 3·1 ± 0·3 versus 2·7 ± 0·68 (p = 0·008). Furthermore, we noticed a significant reduction in the volumes receiving low doses (V10, V20, V30 and V40) with the manual NTO settings. Conclusion: The NTO plays a crucial role in optimizing RapidArc plans for treating cervical cancer. Based on the findings of this study, manual NTO settings of distance from PTV border xstart = 0·5 mm, start dose f0 = 105%, end dose f∞ = an average of 40%, dose fall-off 0·2 mm–1 were optimal. Further research involving a larger sample size and exploration of various NTO parameters is necessary to validate our results.

Different meaning of the mean heart dose between 3D-CRT and IMRT for breast cancer radiotherapy.

Previous studies in 2D and in 3D conformal radiotherapy concludes that the maximal heart distance and the mean heart dose (MHD) are considered predictive of late cardiac toxicities. As the use of inverse-planned intensity modulated radiation therapy (IMRT) is increasing worldwide, we hypothesized that this 3D MHD might not be representative of heart exposure after IMRT for breast cancer (BC). Patients with left-sided BC and unfavorable cardiac anatomy received IMRT. Their treatment plan was compared to a virtual treatment plan for 3D conformal radiotherapy with similar target volume coverage (study A). Then, a second 3D conformal treatment plan was generated to achieve equivalent individual MHD obtained by IMRT. Then the heart and left anterior descending (LAD) coronary artery exposures were analyzed (study B). Last, the relationship between MHD and the heart volume or LAD coronary artery volume receiving at least 30Gy, 40Gy and 45Gy in function of each additional 1Gy to the MHD was assessed (study C). A significant decrease of heart and LAD coronary artery exposure to high dose was observed with the IMRT compared with the 3D conformal radiotherapy plans that both ensured adequate target coverage (study A). The results of study B and C showed that 3D MHD was not representative of similar heart substructure exposure with IMRT, especially in the case of high dose exposure. The mean heart dose is not a representative dosimetric parameter to assess heart exposure following IMRT. Equivalent MHD values following IMRT and 3DRT BC treatment do not represent the same dose distribution leading to extreme caution when using this parameter for IMRT plan validation.

Preliminary Study on the Use of Fricke Gel Dosimeter for Verification of IMRT Beam Delivery

The goal of intensity-modulated radiation therapy (IMRT) is to deliver a uniform dose to the tumor with minimal margins around the target, in order to increase local control of the disease while reducing secondary effects. The research performed in this work has shown the potential usefulness of the Fricke-gel dosimeter as a quality assurance (QA) tool to verify IMRT treatments produced by inverse treatment planning. First, the 3D integrating Fricke-gel dosimeter was successfully compared to an accepted dosimetric tool. It was then used to measure relative 3D dose distributions of simple treatment plans with multiple square or rectangular fields and specific inverse-planned IMRT treatment plans. By combining the CT anatomical information and the plan contours with the gel-measured data, it was possible to display the contours on the measured dose and the measured isodose lines on the CT, in addition to measuring dose-volume histograms (DVH) for the plans. This demonstrated the usefulness of the gel dosimeter as a QA tool for IMRT and inverse planning.

Is Radiation-Induced Cardiac Toxicity Reversible? Prospective Evaluation of Patients With Breast Cancer Enrolled in a Phase 3 Randomized Controlled Trial

Myocardial perfusion defects after breast radiation therapy (RT) correlate with volume of irradiated left ventricle (LV). We aimed to determine the relationship between myocardial perfusion, LV dosimetry, and grade ≥2 late cardiac events in patients with breast cancer undergoing adjuvant RT. A randomized study evaluated the benefit of inverse-planned intensity modulated radiation therapy over forward-planned intensity modulated radiation therapy for radiation toxicity in breast cancer. A secondary endpoint was evaluating cardiac perfusion by single-photon emission computed tomography done at baseline, 6 months, 1 year, 2 years, and 5 years post-RT. We used receiver operating curve and regression analysis to identify association between perfusion, radiation dose-volumes, and the risk of late cardiac events. Of 181 patients who received adjuvant RT, 102 were patients with cancer in the left breast (called in this study the left-sided group) and 79 were patients with cancer in the right breast (called in this study the right-sided group). Median follow-up was 127 months (range, 19-160 months). A significant worsening of perfusion defects occurred after RT in the left-sided group, which improved by 1 year. Late cardiac events were found among 16 patients (17.2%) in the left-sided group and 4 patients (5.5%) in the right-sided group. Perfusion changes did not correlate with late cardiac events, but LV dose-volumes correlated with late cardiac events. Maintaining the LV volume receiving 5 Gy and 10 Gy to <42 cc and <38cc, respectively, can reduce the risk of radiation-related late cardiac events at 10 years to <5% over baseline. RT was associated with short-term perfusion defects that improved within 1 year and was not correlated with late cardiac events. The ventricular volumes receiving 5 Gy and 10 Gy were correlated with late cardiac events.

Comparative Effectiveness Analysis of 3D-Conformal Radiation Therapy Versus Intensity Modulated Radiation Therapy (IMRT) in a Prospective Multicenter Cohort of Patients With Breast Cancer

Simple intensity modulation of radiation therapy reduces acute toxicity compared with 2-dimensional techniques in adjuvant breast cancer treatment, but it remains unknown whether more complex or inverse-planned intensity modulated radiation therapy (IMRT) offers an advantage over forward-planned, 3-dimensional conformal radiation therapy (3DCRT). Using prospective data regarding patients receiving adjuvant whole breast radiation therapy without nodal irradiation at 23 institutions from 2011 to 2018, we compared the incidence of acute toxicity (moderate-severe pain or moist desquamation) in patients receiving 3DCRT versus IMRT (either inverse planned or, if forward-planned, using ≥5 segments per gantry angle). We evaluated associations between technique and toxicity using multivariable models with inverse-probability-of-treatment weighting, adjusting for treatment facility as a random effect. Of 1185 patients treated with 3DCRT and conventional fractionation, 650 (54.9%) experienced acute toxicity; of 774 treated with highly segmented forward-planned IMRT, 458 (59.2%) did; and of 580 treated with inverse-planned IMRT, 245 (42.2%) did. Of 1296 patients treated with hypofractionation and 3DCRT, 432 (33.3%) experienced acute toxicity; of 709 treated with highly segmented forward-planned IMRT, 227 (32.0%) did; and of 623 treated with inverse-planned IMRT, 164 (26.3%) did. On multivariable analysis with inverse-probability-of-treatment weighting, the odds ratio for acute toxicity after inverse-planned IMRT versus 3DCRT was 0.64 (95% confidence interval, 0.45-0.91) with conventional fractionation and 0.41 (95% confidence interval, 0.26-0.65) with hypofractionation. This large, prospective, multicenter comparative effectiveness study found a significant benefit from inverse-planned IMRT compared with 3DCRT in reducing acute toxicity of breast radiation therapy. Future research should identify the dosimetric differences that mediate this association and evaluate cost-effectiveness.

Small Animal IMRT Using 3D-Printed Compensators

Preclinical radiation replicating clinical intensity modulated radiation therapy (IMRT) techniques can provide data translatable to clinical practice. For this work, treatment plans were created for oxygen-guided dose-painting in small animals using inverse-planned IMRT. Spatially varying beam intensities were achieved using 3-dimensional (3D)-printed compensators. Optimized beam fluence from arbitrary gantry angles was determined using a verified model of the XRAD225Cx treatment beam. Compensators were 3D-printed with varied thickness to provide desired attenuation using copper/polylactic-acid. Spatial resolution capabilities were investigated using printed test-patterns. Following American Association of Physicists in Medicine TG119, a 5-beam IMRT plan was created for a miniaturized (∼1/8th scale) C-shape target. Electron paramagnetic resonance imaging of murine tumor oxygenation guided simultaneous integrated boost (SIB) plans conformally treating tumor to a base dose (Rx1) with boost (Rx2) based on tumor oxygenation. The 3D-printed compensator intensity modulation accuracy and precision was evaluated by individually delivering each field to a phantom containing radiochromic film and subsequent per-field gamma analysis. The methodology was validated end-to-end with composite delivery (incorporating 3D-printed tungsten/polylactic-acid beam trimmers to reduce out-of-field leakage) of the oxygen-guided SIB plan to a phantom containing film and subsequent gamma analysis. Resolution test-patterns demonstrate practical printer resolution of ∼0.7 mm, corresponding to 1.0 mm bixels at the isocenter. The miniaturized C-shape plan provides planning target volume coverage (V95% = 95%) with organ sparing (organs at risk Dmax < 50%). The SIB plan to hypoxic tumor demonstrates the utility of this approach (hypoxic tumor V95%,Rx2 = 91.6%, normoxic tumor V95%,Rx1 = 95.7%, normal tissue V100%,Rx1 = 7.1%). The more challenging SIB plan to boost the normoxic tumor rim achieved normoxic tumor V95%,Rx2 = 90.9%, hypoxic tumor V95%,Rx1 = 62.7%, and normal tissue V100%,Rx2 = 5.3%. Average per-field gamma passing rates using 3%/1.0 mm, 3%/0.7 mm, and 3%/0.5 mm criteria were 98.8% ± 2.8%, 96.6% ± 4.1%, and 90.6% ± 5.9%, respectively. Composite delivery of the hypoxia boost plan and gamma analysis (3%/1 mm) gave passing results of 95.3% and 98.1% for the 2 measured orthogonal dose planes. This simple and cost-effective approach using 3D-printed compensators for small-animal IMRT provides a methodology enabling preclinical studies that can be readily translated into the clinic. The presented oxygen-guided dose-painting demonstrates that this methodology will facilitate studies driving much needed biologic personalization of radiation therapy for improvements in patient outcomes.

Skin Toxicity in Early Breast Cancer Patients Treated with Field-In-Field Breast Intensity-Modulated Radiotherapy versus Helical Inverse Breast Intensity-Modulated Radiotherapy: Results of a Phase III Randomised Controlled Trial

AimsSkin toxicity is a common adverse effect of breast radiotherapy. We investigated whether inverse-planned intensity-modulated radiotherapy (IMRT) would reduce the incidence of skin toxicity compared with forward field-in-field breast IMRT (FiF-IMRT) in early stage breast cancer. Materials and methodsThis phase III randomised controlled trial compared whole-breast irradiation with either FiF-IMRT or helical tomotherapy IMRT (HT-IMRT), with skin toxicity as the primary end point. Patients received 50 Gy in 25 fractions and were assessed to compare skin toxicity between treatment arms. ResultsIn total, 177 patients were available for assessment and the median follow-up was 73.1 months. Inverse IMRT achieved more homogeneous coverage than FiF-IMRT; erythema and moist desquamation were higher with FiF-IMRT compared with HT-IMRT (61% versus 34%; P < 0.001; 33% versus 11%; P < 0.001, respectively). Multivariate analysis showed large breast volume, FiF-IMRT and chemotherapy were independent factors associated with worse acute toxicity. There was no difference between treatment arms in the incidence of late toxicities. The 5-year recurrence-free survival was 96.3% for both FiF-IMRT and HT-IMRT and the 5-year overall survival was 96.3% for FiF-IMRT and 97.4% for HT-IMRT. ConclusionsOur study showed significant reduction in acute skin toxicity using HT-IMRT compared with FiF-IMRT, without significant reduction in late skin toxicities. On the basis of these findings, inverse-planned IMRT could be used in routine practice for whole-breast irradiation with careful plan optimisation to achieve the required dose constraints for organs at risk.

The Influence of Normal Tissue Objective in the Treatment of Prostate Cancer

PurposeThe normal tissue objective (NTO) is a tool used in inverse-planned intensity-modulated radiation therapy to reduce dose spreading to the surrounding tissues. Only a few studies in the present literature are dedicated to understanding the influence of the NTO in radiation therapy planning in patients with prostate cancer or its consequences in the reduction of the dose in the surrounding healthy tissues. Material and methodsOur sample consists of 25 patients submitted to different treatment doses. Averages of plans with and without the NTO were obtained from the dose-volume histogram, and behaviours, comparisons, and quality were assessed considering homogeneity, conformity, and radiation plan indexes. ResultsWe were not able to find significant differences in the conformity index, homogeneity index, and radiation planning index between groups with and without the NTO or between treatment times. We observed a small advantage in NTO plans regarding hot spots in the central region of the planning target volume. ConclusionThe NTO is an important tool used in the optimization of plans; however, possibly due to the anatomical location of the prostate, we failed to find a significant contribution of its use in the treatment of prostate cancer. Further studies, using a larger sample and different NTO parameters, are needed to confirm our results.

Intensity-Modulated Radiation Therapy versus 3D Conformal Radiation Therapy in Patients Undergoing Regional Nodal Irradiation/Postmastectomy Radiation Therapy for Breast Cancer: Looking Beyond Dosimetric Outcomes

Prospective data and meta-analyses support the use of adjuvant regional nodal irradiation (RNI)/postmastectomy radiation therapy (PMRT) for the majority of women with axillary lymph node positive breast cancer. However, RNI increases dose to the heart and lung compared resulting in increased toxicity. Inverse-planned intensity modulated radiation therapy (IMRT) has the ability to reduce high dose to the heart/lung compared to traditional 3D conformal radiation therapy (3DCRT). Early concerns with IMRT were that it may be too conformal resulting in increased risk of local-regional failures (LRF). To date, clinical outcomes with IMRT have not been well studied in patients receiving RNI/PMRT. We have used planning target volume (PTV)-based, dose-volume analysis driven RNI/PMRT planning since 2013 using primarily 3DCRT but IMRT as needed to meet heart/lung planning objectives. We hypothesize that toxicity and LRF rates are similar between patients treated with IMRT and 3DCRT. We identified patients that received RNI/PMRT from 2013-2016. Patients received conventional fractionation (200 cGy/day) to the breast/chestwall, axillary, supraclavicular (SCV), and internal mammary chain (IMC) PTVs. We divided the cohort into 2 groups (IMRT vs. 3DCRT). We collected patient and disease characteristics, acute toxicity, LRF, and distant metastases (DM) events. Differences in characteristics were evaluated with the t-test or Chi-square test. The primary endpoint was the cumulative incidence of LRF as a first failure. We also evaluated the cumulative incidence of DM. We included 241 patients (69 IMRT, 172 3DCRT): 60% had stage III disease; 60% (ER+ or PR+)/HER2-; 20% triple-negative; 20% HER2+. IMRT group had higher rates of left-sided (65% vs. 47%, p=0.009) and grade 3 (58% vs. 43%, p=0.04) disease. The IMCs were irradiated in 97%. Treatment was well tolerated: grade 3 dermatitis 6% in each group with no other grade 3 toxicities. Grade 2 pneumonitis occurred in 2 (0.83%), both 3DCRT. Median follow-up is 3.5 years. There were 5 LRF events (2 IMRT, 3 3DCRT): 2 patients with isolated LRF (iLRF) and 3 patients with simultaneous LRF+DM resulting in 4-year LRF=2.1% (4.1% IMRT vs. 1.4% 3DCRT, p=0.55) and 4-yr iLRF=1.1% (1.5% vs. 0.8%, p=0.43). The iLRF (1 IMRT, 1 3DCRT) both occurred in the SCV region. The other LRF+DM event in the IMRT group was a chestwall/axillary/IMC recurrence post-mastectomy. The additional 2 LRF+DM events in the 3DCRT group included: ipsilateral SCV and level V nodes post-lumpectomy; and a lumpectomy bed recurrence. Most failures were DM: 4-year rate=15% (21.0% IMRT vs. 13.2% 3DCRT, p=0.58). In this modern cohort of patients receiving RNI/PMRT with a PTV-based approach, we saw rare high-grade toxicity, and we found no difference in LRF and DM rates between IMRT and 3DCRT patients. These data should provide reassurance that IMRT does not compromise disease outcomes and that IMRT can safely be used when needed to meet normal tissue constraints.

Radiotherapy Quality Assurance for the CHHiP Trial: Conventional Versus Hypofractionated High-Dose Intensity-Modulated Radiotherapy in Prostate Cancer

AimsThe CHHiP trial investigated the use of moderate hypofractionation for the treatment of localised prostate cancer using intensity-modulated radiotherapy (IMRT). A radiotherapy quality assurance programme was developed to assess compliance with treatment protocol and to audit treatment planning and dosimetry of IMRT. This paper considers the outcome and effectiveness of the programme. Materials and methodsQuality assurance exercises included a pre-trial process document and planning benchmark cases, prospective case reviews and a dosimetry site visit on-trial and a post-trial feedback questionnaire. ResultsIn total, 41 centres completed the quality assurance programme (37 UK, four international) between 2005 and 2010. Centres used either forward-planned (field-in-field single phase) or inverse-planned IMRT (25 versus 17). For pre-trial quality assurance exercises, 7/41 (17%) centres had minor deviations in their radiotherapy processes; 45/82 (55%) benchmark plans had minor variations and 17/82 (21%) had major variations. One hundred prospective case reviews were completed for 38 centres. Seventy-one per cent required changes to clinical outlining pre-treatment (primarily prostate apex and base, seminal vesicles and penile bulb). Errors in treatment planning were reduced relative to pre-trial quality assurance results (49% minor and 6% major variations). Dosimetry audits were conducted for 32 centres. Ion chamber dose point measurements were within ±2.5% in the planning target volume and ±8% in the rectum. 28/36 films for combined fields passed gamma criterion 3%/3 mm and 11/15 of IMRT fluence film sets passed gamma criterion 4%/4 mm using a 98% tolerance. Post-trial feedback showed that trial participation was beneficial in evolving clinical practice and that the quality assurance programme helped some centres to implement and audit prostate IMRT. ConclusionOverall, quality assurance results were satisfactory and the CHHiP quality assurance programme contributed to the success of the trial by auditing radiotherapy treatment planning and protocol compliance. Quality assurance supported the introduction of IMRT in UK centres, giving additional confidence and external review of IMRT where it was a newly adopted technique.

Forward- and Inverse-Planned Intensity-Modulated Radiotherapy in the CHHiP Trial: A Comparison of Dosimetry and Normal Tissue Toxicity

AimsThe CHHiP (Conventional or Hypofractionated High-dose Intensity Modulated Radiotherapy In Prostate Cancer; CRUK/06/016) trial investigated hypofractionated radiotherapy for localised prostate cancer. Forward- (FP) or inverse-planned (IP) intensity-modulated techniques were permitted. Dose–volume histogram and toxicity data were compared to explore the effects of planning method. Materials and methodsIn total, 337 participants with intermediate-risk disease and prospectively collected toxicity data were included. Patients were matched on prostate and rectum/bladder volumes and on radiotherapy dose for toxicity comparisons. The primary outcome was grade 2 or higher Radiation Therapy Oncology Group (RTOG) bowel or bladder toxicity at 2 years. ResultsIP patients had smaller volumes of rectum irradiated to 50–70 Gy (P < 0.001); FP patients had smaller volumes of bladder irradiated to 74 Gy (P = 0.001). Acute grade 2 + bowel toxicity was worse with FP (27/53 [52%]; 11/53 [21%] IP; P = 0.0002); with no significant differences in acute urinary toxicity. At 2 years, RTOG grade 2 + bowel toxicity rates were FP 0/53 and IP 2/53 and RTOG grade 2 + bladder rates were FP 0/54 and IP 1/57. ConclusionsSignificant differences were found between dose–volume histograms from FP and IP methods. IP may result in small reductions in acute bowel toxicity but both techniques were associated with low rates of late radiotherapy side-effects.

Long-Term Pulmonary Outcomes of a Feasibility Study of Inverse-Planned, Multibeam Intensity Modulated Radiation Therapy in Node-Positive Breast Cancer Patients Receiving Regional Nodal Irradiation

Multibeam intensity modulated radiation therapy (IMRT) enhances the therapeutic index by increasing the dosimetric coverage of the targeted tumor tissues while minimizing volumes of adjacent organs receiving high doses of RT. The tradeoff is that a greater volume of lung is exposed to low doses of RT, raising concern about the risk of radiation pneumonitis (RP). Between July 2010 and January 2013, patients with node-positive breast cancer received inverse-planned, multibeam IMRT to the breast or chest wall and regional nodes, including the internal mammary nodes (IMNs). The primary endpoint was feasibility, predefined by dosimetric treatment planning criteria. Secondary endpoints included the incidence of RP grade 3 or greater and changes in pulmonary function measured with the Common Terminology Criteria for Adverse Events version 3.0 scales, pulmonary function tests and community-acquired pneumonia questionnaires, obtained at baseline and 6months after IMRT. Clinical follow-up was every 6months for up to 5years. Median follow-up was 53.4months (range, 0-82months). Of 113 patients enrolled, 104 completed follow-up procedures. Coverage of the breast or chest wall and IMN was comprehensive (median 48.1Gy and 48.9Gy, respectively). The median volume of lung receiving a high dose (V20Gy) and a low dose (V5) was 29% and 100%, respectively. The overall rate of respiratory toxicities was 10.6% (11/104), including 1 grade 3 RP event (0.96%). No differences were found in pulmonary function test or community-acquired pneumonia scores after IMRT. The 5-year rates of locoregional recurrence-free, disease-free, and overall survival were 93.2%, 63.6%, and 80.3%, respectively. Multibeam IMRT in patients with breast cancer receiving regional nodal irradiation was dosimetrically feasible, based on early treatment planning criteria. Despite the large volume of lung receiving low-dose RT, the incidence of grade 3 RP was remarkably low, justifying inverse-planned IMRT as a treatment modality for patients with high-risk breast cancer in whom conventional RT techniques prove inadequate.

Impact of modern radiotherapy techniques on survival outcomes for unselected patients with large volume non-small cell lung cancer.

Intensity modulated radiotherapy (IMRT) is used, where necessary, for bulky or complex-shaped, locally advanced, non-small cell lung cancer (NSCLC). We evaluate our real-world experience with radical radiotherapy including concurrent chemoradiation (CCRT), and analyse the impact of IMRT on survival outcomes in patients with larger volume disease. All patients treated between May 2011 and December 2017 were included. Analyses were conducted for factors affecting survival, including large volume disease that was defined as planning target volume (PTV) > 500 cc. In 184 patients with large volume disease, the median overall survival was 19.2 months, compared to 22 months seen with the overall cohort of 251 patients who received radical radiotherapy. PTV and using CCRT were significant predictors for survival. IMRT was used in 93 (50.5%) of 184 patients with large PTV. The patients treated using IMRT had significantly larger disease volume (median PTV = 859 vs 716 cc; p-value = 0.009) and more advanced stage (proportion of Stage IIIB: 56 vs 29%; p-value = 0.003) compared to patients treated with three-dimensional conformal radiotherapy. Yet, the outcomes with IMRT were non-inferior to those treated with 3DCRT. CCRT was used in 103 (56%) patients with large volume disease and resulted in a significantly better median survival of 24.9 months. The proportional benefit from CCRT was also greater than in the overall cohort. Despite being used for larger volume and more advanced NSCLC, inverse-planned IMRT resulted in non-inferior survival. IMRT enables the safe use of curative CCRT for large-volume, locally-advanced NSCLC.

Hypofractionated Whole-Breast Irradiation in Large-Breasted Women—Is There a Dosimetric Predictor for Acute Skin Toxicities?

Underutilization of hypofractionated whole-breast irradiation (HF-WBI) in large-breasted women may be partially explained by concerns about dose heterogeneity. Although modern planning may mitigate this issue, validated dosimetric guidelines are lacking. Our clinical pathway mandates hypofractionation, guided by institutional dosimetric criteria for plan evaluation. We examined acute radiation dermatitis rates with HF-WBI in large-breasted patients when our guidelines are followed and evaluated factors predictive for dermatitis. Patients with whole-breast clinical target volumes (WB-CTV) of ≥1000cm3 treated with HF-WBI were reviewed. WB-CTV V105, V107, and V110 were assessed. Our guidelines recommend limiting V105 to <10% to 15% and V110 to 0%. The highest grade of acute dermatitis was recorded. Potential clinical and dosimetric predictors of dermatitis were analyzed using logistic regression. From 2012 to 2017, 505 breasts in 502 patients were treated with HF-WBI. The median WB-CTV was 1261.3cm3 (interquartile range [IQR], 1115.3-1510.0). Most plans (99%) delivered 42.56Gy in 16 fractions. A cavity boost of 10Gy in 4 fractions was delivered in 99% of plans. Electrons were used in 69% of boost plans. Three-dimensional field-in-field technique was used in 68% of plans and inverse-planned intensity modulated radiation therapy in 32%. The median WB-CTV V105 was 9.7% (IQR, 5.6%-13.3%); the median WB-CTV V107 was 0.8% (IQR, 0.0%-2.5%). The WB-CTV V110 was 0% in 97.4% of plans (median, 0.0%; IQR, 0.0%-0.0%). Grade 1, 2, and 3 dermatitis rates were 55.0%, 40.8%, and 3.4%, respectively. On multivariate analysis, age >64years (P=.016; odds ratio [OR] 4.0; 95% confidence interval [CI], 1.3-12.3), WB-CTV >1500cm3(P=.006; OR, 4.3; 95% CI, 1.5-12.3), body mass index ≥34 (P=.044; OR, 3.9; 95% CI, 1.0-14.5), and WB-CTV V105>10% (P=.011; OR, 5.3; 95% CI, 1.5-19.3) predicted for grade 3 dermatitis. With our institutional dosimetric guidelines, grade 3 dermatitis rates with HF-WBI in large-breasted women was <5%. WB-CTV V105 should be optimized to <10% to keep grade 3 dermatitis rates <2%.

A Randomized Comparison of Radiation Therapy Techniques in the Management of Node-Positive Breast Cancer: Primary Outcomes Analysis

Although inverse-planned intensity modulated radiotherapy (IMRT) and deep inspiration breath hold (DIBH) may allow for more conformal dose distributions, it is unknown whether using these technologies reduces cardiac or pulmonary toxicity of breast radiotherapy. A randomized controlled trial compared IMRT-DIBH versus standard, free-breathing, forward-planned, three-dimensional conformal radiotherapy in patients with left-sided, node-positive breast cancer in whom the internal mammary nodal region was targeted. Endpoints included dosimetric parameters and changes in pulmonary and cardiac perfusion and function, measured by single photon emission computed tomography (SPECT) scans and pulmonary function testing performed at baseline and 1year post treatment. Of 62 patients randomized, 54 who completed all follow-up procedures were analyzed. Mean doses to the ipsilateral lung, left ventricle, whole heart, and left anterior descending coronary artery were lower with IMRT-DIBH; the percent of left ventricle receiving ≥5Gy averaged 15.8% with standard radiotherapy and 5.6% with IMRT-DIBH (P<.001). SPECT revealed no differences in perfusion defects in the left anterior descending coronary artery territory, the study's primary endpoint, but did reveal statistically significant differences (P=.02) in left ventricular ejection fraction (LVEF), a secondary endpoint. No differences were found for lung perfusion or function. The small but statistically significant benefit in preservation of cardiac LVEF observed here should motivate future studies that include LVEF as a potentially meaningful endpoint. Future studies should disaggregate the impact of IMRT from that of DIBH. Clinical practice should recognize the importance of minimizing cardiac dose, even when already low in comparison to historical levels.

Comparison of acute toxicities between contemporary forward-planned 3D conformal radiotherapy and inverse-planned intensity-modulated radiotherapy for whole breast radiation

The use of inverse-planned intensity-modulated radiation therapy for whole breast radiation treatment has become more prevalent, but this may impose an increased cost on the health system. We hypothesized that when applied with the same treatment planning goals, tangential forward-planned field-in-field 3D conformal radiotherapy and tangential inverse-planned intensity-modulated radiotherapy would be associated with comparable toxicities. Women who underwent tangential whole breast irradiation at our institution from 2011 to 2015 planned using either forward-planned field-in-field 3D conformal radiotherapy or intensity-modulated radiotherapy were retrospectively analyzed. Grade 2+ Radiation dermatitis was the primary endpoint. A total of 201 and 212 women had undergone field-in-field 3D conformal radiotherapy and intensity-modulated radiotherapy, respectively. No differences were observed between the two modalities regarding acute radiation dermatitis, breast pain, or fatigue. In a multivariable logistic regression that incorporated the use of boost, hypofractionation, use of chemotherapy, patient positioning, use of a supraclavicular field, and breast planning target volume, intensity-modulated radiotherapy was not correlated with different rates of Grade 2+ radiation dermatitis. This study supports the routine first-line use of field-in-field 3D conformal radiotherapy for whole breast radiation instead of tangential intensity-modulated radiotherapy from the standpoint of equivalence in acute toxicity. Further investigation is needed to assess whether there are subgroups of women who may still benefit from intensity-modulated radiotherapy.

In vivo dosimetry with optically stimulated luminescent dosimeters for conformal and intensity-modulated radiation therapy: A 2-year multicenter cohort study

PurposeOptically stimulated luminescent dosimeters (OSLDs) are utilized for in vivo dosimetry (IVD) of modern radiation therapy techniques such as intensity modulated radiation therapy (IMRT) and volumetric modulated arc therapy (VMAT). Dosimetric precision achieved with conventional techniques may not be attainable. In this work, we measured accuracy and precision for a large sample of clinical OSLD-based IVD measurements. Methods and materialsWeekly IVD measurements were collected from 4 linear accelerators for 2 years and were expressed as percent differences from planned doses. After outlier analysis, 10,224 measurements were grouped in the following way: overall, modality (photons, electrons), treatment technique (3-dimensional [3D] conformal, field-in-field intensity modulation, inverse-planned IMRT, and VMAT), placement location (gantry angle, cardinality, and central axis positioning), and anatomical site (prostate, breast, head and neck, pelvis, lung, rectum and anus, brain, abdomen, esophagus, and bladder). Distributions were modeled via a Gaussian function. Fitting was performed with least squares, and goodness-of-fit was assessed with the coefficient of determination. Model means (μ) and standard deviations (σ) were calculated. Sample means and variances were compared for statistical significance by analysis of variance and the Levene tests (α = 0.05). ResultsOverall, μ ± σ was 0.3 ± 10.3%. Precision for electron measurements (6.9%) was significantly better than for photons (10.5%). Precision varied significantly among treatment techniques (P < .0001) with field-in-field lowest (σ = 7.2%) and IMRT and VMAT highest (σ = 11.9% and 13.4%, respectively). Treatment site models with goodness-of-fit greater than 0.90 (6 of 10) yielded accuracy within ±3%, except for head and neck (μ = –3.7%). Precision varied with treatment site (range, 7.3%-13.0%), with breast and head and neck yielding the best and worst precision, respectively. Placement on the central axis of cardinal gantry angles yielded more precise results (σ = 8.5%) compared with other locations (range, 10.5%-11.4%). ConclusionsAccuracy of ±3% was achievable. Precision ranged from 6.9% to 13.4% depending on modality, technique, and treatment site. Simple, standardized locations may improve IVD precision. These findings may aid development of patient-specific tolerances for OSLD-based IVD.

Clinical impact of IMPORT HIGH trial (CRUK/06/003) on breast radiotherapy practices in the United Kingdom.

IMPORT HIGH is a multicentre randomized UK trial testing dose-escalated intensity-modulated radiotherapy (IMRT) after tumour excision in females with early breast cancer and higher than average local recurrence risk. A survey was carried out to investigate the impact of this trial on the adoption of advanced breast radiotherapy (RT) techniques in the UK. A questionnaire was sent to all 26 IMPORT HIGH recruiting RT centres to determine whether the trial has influenced non-trial breast RT techniques in terms of volume delineation, dosimetry, treatment delivery and verification. In order to compare the clinical practice of breast RT between IMPORT HIGH and non-IMPORT HIGH centres, parts of the Royal College of Radiologists (RCR) breast RT audit result were used in this study. 26/26 participating centres completed the questionnaire. After joining the trial, the number of centres routinely using tumour bed clips to guide whole-breast RT rose from 5 (19%) to 21 (81%). 20/26 (77%) centres now contour target volumes and organs at risk (OARs) in some or all patients compared with 14 (54%) before the trial. 14/26 (54%) centres offer inverse-planned IMRT for selected non-trial patients with breast cancer, and 10/14 (71%) have adopted the IMPORT HIGH trial protocol for target volume and OARs dose constraints. Only 2/26 (8%) centres used clip information routinely for breast treatment verification prior to IMPORT HIGH, a minority that has since risen to 7/26 (27%). Data on 1386 patients was included from the RCR audit. This suggested that more cases from IMPORT HIGH centres had surgical clips implanted (83 vs 67%), were treated using CT guided planning with full three-dimensional dose compensation (100 vs 75%), and were treated with photon boost RT (30 vs 8%). The study suggests that participation in the IMPORT HIGH trial has played an important part in providing the guidance and support networks needed for the safe integration of advanced RT techniques, where appropriate, as a standard of care for breast cancer patients treated at participating cancer centres. We investigated the impact of the IMPORT HIGH trial on the adoption of advanced breast RT techniques in the UK and the trial has influenced non-trial breast RT techniques in terms of volume delineation, dosimetry, treatment delivery and verification.

Dosimetric comparison of left-sided whole-breast irradiation with 3DCRT, forward-planned IMRT, inverse-planned IMRT, helical tomotherapy, and volumetric arc therapy

PurposeThis study evaluated the dose distribution and homogeneity of four different types of intensity-modulated radiotherapy (IMRT) in comparison with standard wedged tangential-beam three-dimensional conformal radiotherapy (3DCRT) of the left breast in patients who had undergone lumpectomy. Materials and methodsFive radiotherapy treatment plans, including 3DCRT, forward-planned IMRT (for-IMRT), inverse IMRT (inv-IMRT), helical tomotherapy (HT) and volumetric-modulated arc therapy (VMAT), were created for 15 consecutive patients. ResultsAll modalities presented similar target coverage. Target max doses were reduced with for-IMRT compared to 3DCRT, and these doses were further reduced with inv-IMRT and HT. HT resulted in the lowest max doses delivered to the heart, left anterior descending artery (LAD), and ipsilateral lung, but had higher mean, max, and low doses delivered to contralateral breast. HT resulted in increased low doses to a large volume of healthy tissue. Compared to other techniques, all inverse-planned modalities significantly improved conformity number; however, VMAT had worse homogeneity. The for-IMRT plan significantly lowered monitor unit (MU) compared to the inverse-planned techniques. ConclusionAll modalities evaluated provide adequate coverage of the whole breast. For-IMRT improves target homogeneity compared with 3DCRT, but to a lesser degree than the inverse-planned inv-IMRT and HT. HT decreases the ipsilateral OAR volumes receiving higher and mean doses with an increase in the volumes receiving low doses, which is known to lead to an increased rate of radiation-induced secondary malignancies.

Effect of Non-Delineated Normal Volumes in IMRT Treatment for Left Breast Cancer: A Treatment Planning Study

Introduction: Intensity Modulated Radiation Therapy (IMRT) planning dose calculation process depends on IMRT dose constraints. So, if there was any structure along the treatment beam path not delineated, it would not be taken into account during that calculation process. During IMRT routine practical work, it is noticed that there are some non-delineated normal tissue volumes that received un-aimed dose. Aim: The purpose of this study was to study the effect of unusually delineated normal volumes in IMRT treatment for left sided breast cancer. Method: Ten left sided breast cancer patients were planned with IMRT inverse planning system. The unusually delineated normal volumes were delineated and taken into account in IMRT dose constraints as an Organ at Risk. Doses received by that volume were compared in the two methods quantitatively from Dose Volume Histograms (DVHs) and qualitatively from (axial cuts). Results: The results showed that doses received by the unusually delineated volume when they were delineated and taken into account in IMRT dose constraints were significantly higher than when they were not. Conclusions: The results showed that for IMRT planning technique used for treating left-sided breast cancer, all of the normal tissues/structures that are closed to the treatment targets must be delineated and taken into account in the IMRT planning dose constraints.