Forward-planned Intensity-modulated Radiotherapy Research Articles

Study on Dosimetric Superiority of Forward Planned Intensity-Modulated Radiotherapy Treatment of Thoracic Esophageal Squamous Cell Carcinoma

Aim and Objectives: The study was conducted to to compare the dosimetric superiority between the Field in Field and Box techniques. Meterials and Methods: We have taken 22 Patients of Ca esophagus for our study from our Institute database. Patients were already treated Box (4 fields) plan. Retrospectively additional Field in Field (FIF) plan was created with Planning target volume (PTV) prescription dose of 59.4Gy in 33 fractions. Prescription dose of 95% of PTV was chosen for the comparison between two treatment planning strategies. The Dose volume histogram (DVH) was used to analyze and compare various plan quality index and doses to the organs at risk (OARs). For each patient, two treatment plans were created: Box 4FB and FIF. The parameters compared included the conformity index (CI), homogeneity index (HI), Conformation number (CN), DMean, DMax, V20Gy and V30Gy of the heart and lungs, and monitor units per fraction (MU/fr). Results: A paired t-test analysis significant differences (P < 0.05) between the two techniques in terms of the CI, HI, and CN when the FIF was applied. The Dmax of the PTV, lung, and spinal cord were also significantly better with the FIF. Moreover, the V20Gy of the significantly reduced when the FIF was used and the MU/fr was significantly decreased. The FIF technique enables better dose distribution in the PTV and reduces dose to OARs in esophageal radiotherapy. Conclusion: Although all plans were within acceptable limits, dosimetric comparison of different planning techniques revealed that FIF had statistically significant differences from Box planning technique in terms of planned target volume (PTV) coverage, OAR protection, HI, CI, CN, MU and treatment duration. From the aspect of treatment duration and MU parameters, FIF technique can be considered as an alternative planning option.

Comparison of Dosimetric Parameters and Clinical Outcomes in Inversely Planned Intensity-Modulated Radiotherapy (IMRT) and Field-in-Field Forward Planned IMRT for the Treatment of Breast Cancer.

IntroductionRadiotherapy has been an important component of the multimodality approach to breast cancer treatment. Newer techniques like three-dimensional radiotherapy had led to better dose distribution over the target volume, with tissue inhomogeneity corrections. To improve the uniformity in dose distribution, a newer technique of intensity modulation was developed, namely, intensity-modulated radiotherapy (IMRT). The present study was designed to compare inverse planned IMRT (IP IMRT) and field-in-field forward planned IMRT (FP IMRT) in patients with breast cancer receiving post-modified radical mastectomy (MRM) adjuvant radiotherapy in terms of dosimetric parameters and clinical outcomes.Materials and methodsFifty patients with breast cancer who have undergone MRM and need adjuvant radiotherapy were randomly assigned in a 1:1 ratio into two groups (25 each) of IP IMRT and FP IMRT techniques. The prescribed dose was 50 Gy in 25 fractions over five weeks. In IP IMRT, five to seven tangential beams were used for the chest wall, nodal volumes were placed at suitable angles with beam optimization, and calculation was carried out by the analytical anisotropic algorithm. For FP IMRT, two opposing tangential fields were created in such a way to achieve uniform dose distribution to the planning target volume (PTV), minimizing hot spot regions, and limiting dose to the ipsilateral lung and contralateral breast. Multiple subfields were manually designed to boost the area not included in the dose cloud. The dosimetric parameters were compared for PTV, lungs, heart, left anterior descending coronary artery (LAD), opposite breast, and esophagus.ResultsThe dosimetric parameters in terms of PTV are better for IP IMRT plans compared to FP IMRT plans (V95%: 92.3% vs 75.2%, p = 0.0001; D90%: 47.4 Gy vs 42.9 Gy, p = 0.0001; D95%: 44.9 Gy vs 37.1, p = 0.0004). The ipsilateral lung (V10Gy: 71.9% vs 41%, p = 0.00001; V20Gy: 42.14% vs 36.35%, p = 0.03; V40Gy: 17.31% vs 26.95%, p = 0.00004; Dmean: 20.91 Gy vs 17.88 Gy, p = 0.01) and contralateral lung (V5Gy: 31.8% vs 0.1%, p < 0.00001; V10Gy: 6.2% vs 0.08%, p = 0.0001) received statistically significant lesser doses in terms of low dose parameters in FP IMRT. In the heart, the dosimetric parameter V5 was significantly lower for FP IMRT (61.7% vs 9.7%, p = 0.00001) along with Dmean (10.92 Gy vs 4.01 Gy, p = 0.001). Similarly, LAD parameters showed comparable high dose volumes (V40Gy: 21.02% vs 16.26%; p = 0.29) in both groups and a trend toward reduction in mean dose (17.1% vs 9.2%; p = 0.05) in FP IMRT group, although low dose volumes were higher in IP IMRT group. In contralateral breast, doses in smaller volumes were better for FP IMRT plans (V0.5Gy: 59.7% vs 43.8%, p = 0.01; V0.6Gy: 54.07% vs 37.6%, p = 0.007; V1Gy: 40.9% vs 22.1%, p = 0.001; V2Gy: 28.7% vs 9.4%, p = 0.00003; V5Gy: 12.07% vs 4.2%, p = 0.0001). In esophagus, statistically significant lower doses were seen only in terms of Dmean (10.29 Gy vs 5.1 Gy; p = 0.03) with FP IMRT. No significant difference in terms of skin reactions and dysphagia was seen in both the groups.ConclusionBoth IP IMRT and FP IMRT techniques have advantages and disadvantages, and the superiority of one technique over another cannot be established in this study. The decision for choosing one technique over another can also be based on various patient-related factors weighing the risk of loco-regional recurrences to that of manifesting radiation-induced sequelae.

A dosimetric study to improve the quality of nodal radiotherapy in breast cancer.

Objectives:Field-based planning for regional nodal breast radiotherapy (RT) used to be standard practice. This study evaluated a field-based posterior axillary boost (PAB) and two forward-planned intensity-modulated RT (IMRT) techniques, aiming to replace the first.Methods:Supraclavicular and axillary nodes, humeral head, brachial plexus, thyroid, and oesophagus were retrospectively delineated on 12 CT scans. Three plans, prescribed to 40.05 Gy, were produced for each patient. Breast plans consisted of field-in-field IMRT tangential fields in all three techniques. Nodal plans consisted of a field-based PAB (anterior and posterior boost beam), and 2 forward-planned techniques: simple IMRT 1 (anterior and posterior beam with limited segments), and a more advanced IMRT 2 technique (anterior and fully modulated posterior beam).Results:The nodal V90% was similar between IMRT 1: mean 99.5% (SD 1.0) and IMRT 2: 99.4% (SD 0.5). Both demonstrated significantly improved results (p = 0.0001 and 0.005, respectively) compared to the field-based PAB technique. IMRT 2 lung V12Gy and humeral head V10Gy were significantly lower (p = 0.002, 0.0001, respectively) than the field-based PAB technique. IMRT 1 exhibited significantly lower brachial plexus Dmax and humeral head V5, 10, and 15Gy doses (p = 0.007, 0.013, 0.007 and 0.007, respectively) compared to the field-based PAB technique. The oesophagus and thyroid dose difference between methods was insignificant.Conclusions:Both IMRT techniques achieved the dose coverage requirements and reduced normal tissue exposure, decreasing the risk of radiation side effects. Despite the increased cost of IMRT, compared to non-IMRT techniques 1, both IMRT techniques are suitable for supraclavicular and axillary nodal RT.Advances in knowledge:Forward-planned IMRT already resulted in significant dose reduction to organs at risk and improved planning target volume coverage.1 This new, simplified forward-planned IMRT one technique has not been published in this context and is easy to implement in routine clinical practice.

Impact of molecular subtype on 1325 early-stage breast cancer patients homogeneously treated with hypofractionated radiotherapy without boost: Should the indications for radiotherapy be more personalized?

AimWe report molecular subtype impact on 1325 early breast cancer (BCa) patients treated with whole breast hypofractionated (WBH) adjuvant forward-planned intensity modulated radiotherapy (F-IMRT) without boost. Methods and materialsFrom 02/2009-05/2017 1325 patients with pTis-pT3, pNx-N1aM0 BCa who underwent breast conservation surgery were treated with WBHF-IMRT in our institute, to a total dose of 40 Gy/15 fractions, without boost. Median age: 62 (interquartile range-IQR-:51.14–70.53) years. Histology: 8% in situ carcinoma (ISC), 92% invasive tumors. Molecular subtypes (invasive tumors): 49.9% Luminal A, 33.1% Luminal B Her2 negative (−), 6.2% Luminal B Her2 positive (+), 3.6% Hormone Receptor (HR)- Her2+, 7.1% Triple negative (TNBC), and 0.2% HR+. Chemotherapy (CT) was prescribed in 28% of patients, hormonal therapy in 80.3%, monoclonal antibodies (MAb) in 86.8% of Luminal B Her2+ and 97.7% of HR- Her2+ patients. ResultsMedian follow up was 72.43 (IQR: 44.63–104.13) months. The 5-year Kaplan-Meier estimates of local relapse-free survival (LRFS) was 97.8%, regional-(RRFS) 98.6%, loco-regional- (LRRFS) 96.9%, distant- (DRFS) 96.6%, disease-free survival (DFS) 94.8% and overall survival (OS) 95.5%. Considering molecular subtypes, 5-year LRFS was: 99.8% for Luminal A, 96.7% for Luminal B Her2-, 94.1% for Luminal B Her2+, 87.9% for HR- Her2+, 95.1% for TNBC and 99.1% for in situ carcinoma. ConclusionWhile the overall estimated probability of LR within 5 years after WBHF-IMRT without boost is good (2.2%), molecular subtypes have a strong impact, despite MAb therapy in Her2+ patients, and CT for TNBC patients, and could be used as a parameter in deciding the boost prescription.

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.

Hypofractionated radiotherapy after conservative surgery may increase low-intermediate grade late fibrosis in breast cancer patients.

AimTo compare late toxicity after postoperative hypofractionated radiotherapy (RT) and standard fractionated RT in patients with early-stage breast carcinoma.MethodsThis retrospective study included 447 patients (Modulated Accelerated Radiotherapy [MARA-1]: 317 patients, and control group [CG]: 130 patients). In the CG, the whole breast received 50.4 Gy in 28 fractions (fx) using 3D-radiotherapy, plus a sequential electron boost (10 Gy in 4 fx) to tumor bed. In MARA-1 group, a forward-planned intensity-modulated radiotherapy technique with 40 Gy in 16 fx with a concomitant boost of 4 Gy to breast was used. The primary endpoint was to evaluate late toxicity, and secondary endpoints were acute toxicity, local control, and survival. ClinicalTrials.gov: NCT03461224.ResultsMedian follow-up was 52 months (range: 3–115 months). Late skin and subcutaneous toxicity were acceptable: 5-year actuarial cumulative incidence of Grade (G) 3 late skin toxicity was 1.5% in CG and 0.0% in MARA-1. Five-year actuarial cumulative incidence of G3 late subcutaneous toxicity was 0.8% in CG and 0.3% in MARA-1. On multivariate analysis, tobacco smoking and planning target volume were associated with an increased risk of late G1 skin toxicity (HR: 2.15, 95% CI: 1.38–3.34 and HR: 1.12, 95% CI: 1.07–1.18, respectively), whereas patients with a larger planning target volume also showed an increased risk of G1 and G2 late subcutaneous toxicity (HR: 1.14, CI 95%: 1.08–1.20 and HR: 1.14, 95% CI: 1.01–1.28, respectively). MARA-1 patients also showed an increased risk of late G1 and G2 subcutaneous toxicity (HR: 2.35, 95% CI: 1.61–3.41 and HR: 3.07, 95% CI: 1.11–8.53, respectively) compared to CG.ConclusionIn this retrospective analysis, postoperative accelerated-hypofractionated RT for early-stage-breast carcinoma was associated with higher incidence of subcutaneous side effects. However, this increase was limited to G1–G2 toxicity. In the future, development of predictive models could help in tailoring dose and fractionation based on the risk of toxicity.

Modifiable risk factors for acute skin toxicity in adjuvant breast radiotherapy: Dosimetric analysis and review of the literature

Acute skin toxicity in adjuvant breast radiation can be reduced with modern radiotherapy (RT) techniques. However, having reviewed the literature, we found no dosimetric constraint for acute skin toxicity that would be applicable to modern RT planning. This study aimed to identify dosimetric factors that are associated with higher rates of acute skin toxicity. A retrospective review was carried out including women who received adjuvant forward-planned intensity-modulated radiotherapy (IMRT) after breast-conserving surgery. Acute skin toxicity grade was prospectively recorded. A total of 131 patients were analyzed. On multivariate analysis, the V105% > 30 cc (p = 0.013) and the use of conventional fractionation (CF) (p = 0.001) were statistically significant for acute skin toxicity. On literature review, current quantitative dosimetric parameters that have shown statistical significance include a V107% > 3 cc in hypofractionation (HF), V107% > 9 cc in CF, treated volume 110% > 5.13%, and V107% > 28.6%. There is little evidence on the predictive value of clinically applicable dosimetric factors in acute skin toxicity. Given the recent improvements in RT planning, we would consider a V107% or a V110% too high a dosimetric value to be useful for the majority of patients. We have shown that a V105% of greater than 30 cc is significantly associated with acute skin toxicity, controlling for other variables. We suggest that this is currently the most useful modifiable parameter available to reduce skin toxicity and is applicable to modern RT planning. We also suggest that consideration be given to hypofractionated schedules to further reduce acute skin toxicity.

Location of Recurrence in Women Treated with Conventionally Planned Whole Breast Radiotherapy

Whole breast radiotherapy (RT) following breast-conserving therapy is known to reduce local recurrence in early-stage breast cancer. Conventionally, the external palpable breast has been used as the clinical target volume (CTV). In the era of CT simulation/planning, post-operative tumour bed (cavity) localization is also important as it is a high risk area of local recurrence. This study evaluates the location of the tumour bed cavity and its relationship to the area of recurrence in women previously treated with whole breast RT without explicit delineation of the cavity. A consecutive sample of 50 women with breast tumours (Tis-T3,Nx-1) previously treated with whole breast RT+/-boost was identified. The planning CTV was based on patient's palpable breast wired with radio-opaque markers during CT simulation and treated to a minimum of 92% prescription dose (50Gy-25fx or 40/42.4Gy-16fx) using forward planned intensity modulated RT (IMRT). The tumour bed was retrospectively contoured and expanded by 10mm (excluding skin and lung) for the planning target volume (cPTV). Geographic miss was defined as any part of the target volume receiving <50% of the prescription dose (D50). Five-year follow-up and the location for local and/or distant recurrence were collected. Descriptive statistics and unpaired Student's t-tests were performed, p-values <0.05 were considered as statistically significant. Five (10%) women had geographic miss to the cavity contours (CAVmiss). Women with CAVmiss had cavities located in extreme aspects of the breast: lateral (3); medial (1); or superior (1). The median follow-up was 4.5years and time to failure was 3.5years (1 to 5 years). Within the CAVin cohort (45), 2 (6%) patients recurred locally within the ipsilateral breast (1-year and 3-year follow-up, respectively); 1 (3%) patient developed regional disease to the infraclavicular lymph nodes at 4-year follow-up, and 1 (3%) developed contralateral inflammatory breast disease at 4-year follow-up; 11 patients were lost to follow-up. Of the 5 women with CAVmiss: 1 developed local recurrence at the edge of the original fields near the tumour bed and regional disease to the axilla and supraclavicular nodal basins (4yr follow-up); 1 developed distance disease (3yr follow-up). Local recurrence can occur near the tumour bed following whole breast RT. Without delineation of the post-operative cavity, 10% of women had inadequate coverage to their tumor bed despite the use of standard tangential RT fields. The adoption of cavity delineation would reduce the risk of geographic miss and ensure the accuracy of radiotherapy.

Actual gains in dosimetry and treatment delivery efficiency from volumetric modulated arc radiotherapy for inoperable, locally advanced lung cancer over five-field forward-planned intensity-modulated radiotherapy

Volumetric modulated arc radiotherapy (VMAT) is used for inoperable, locally advanced nonsmall cell lung cancer, where three-dimensional conformal radiotherapy (3D-CRT) cannot yield an acceptable plan. The planning and treatment data were prospectively collected on the first 18 patients treated using VMAT plans. We analyzed the actual dosimetric gain and impact on treatment, compared with complex multisegment 3D-CRT (five-field forward-planned intensity-modulated radiotherapy [IMRT]) that were generated for treatment. Proportion of planning target volume (PTV) receiving 95% dose (PTV-V95%) conformity index (CI), conformity number (CN), dose homogeneity index (DHI), monitor units (MUs), and treatment time were also analyzed. The PTV coverage (PTV-V95%) was improved from a median of 91.41% for 5-F forward-IMRT to 98.25% for VMAT (P < 0.001). The CI improved with a mean of 1.12 for VMAT and 1.31 for 5-F forward-IMRT (P < 0.001). The mean DHI improved from 1.15 for forward-IMRT to 1.08 for VMAT (P < 0.001). The mean CN improved from 0.62 for forward-IMRT to 0.87 for VMAT (P < 0.001). No significant increase in the low-dose bath (V5, V10 and mean lung dose) to the lung was seen. Significantly higher number of MUs (P < 0.001) and shorter treatment delivery times (P = 0.03) were seen with VMAT. VMAT resulted in improvement in target volume coverage, demonstrated by PTV-V95%, CI, CN, and DHI, without any increase in the low-dose bath to the lung. For conventional fractionation, VMAT requires more MUs (P < 0.001) but has a shorter treatment delivery time (P = 0.03) per fraction.

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.

Living with the Elekta Compact: Limitations and ways around them.

Elekta AB, Sweden has recently propagated the Elekta Compact--a low-cost, small-footprint, single energy (6MV), linear accelerator, in India. The absence of electron beams and the inability to seamlessly deliver inverse planned intensity modulated radiotherapy (IMRT) segments, mean that some out-of-the-box thinking is mandatory for the full range of required treatments in different clinical settings, but is ultimately very rewarding. Our department started off in July 2011, with the Elekta Compact, equipped with MLCi2 and a camera-based electron portal imaging device. For head-neck cancers, we have successfully utilized a 3D conformal class-solution of eight-to-nine oblique beams, with multiple segments, to deliver an adequate dose to the posterior neck, respecting spinal cord tolerance. Parotid gland sparing is possible in selected node-negative hypopharyngeal/laryngeal cancers. For prostate cancers, we have developed a forward-planned IMRT protocol to routinely deliver 76-80 Gy to the prostate, with margins, while conforming to the same rectal dose-volume constraints as in inverse IMRT. Response and tolerance have been excellent so far. In head-neck cancers, the majority (71%) of patients was locally advanced; however, complete response was achieved in 75% of the cases. Grade 3 acute toxicities were seen in only 7% of the cases and compliance overall was excellent, with no patients requiring a gap in treatment. We achieved biochemical control in 100% of the prostate cancer patients; no patients had grade 3 acute toxicities, and with a median follow-up of 12 months, have yet to see any late rectal bleeding. Although engineered for simplicity and versatility, the Compact requires some innovative thinking by clinicians/physicists to optimize the full range of its possibilities. However, upgrades like inverse IMRT delivery, which are in the pipeline, are urgently needed for it to be viable, especially in a single-accelerator department.

Radiation doses to axillary lymph nodes in patients with early breast cancer receiving field-in-field forward-planned intensity-modulated radiotherapy for whole breast irradiation after breast-conserving surgery

Objective To evaluate the radiation doses to the axillary lymph nodes in patients with early breast cancer receiving field-in-field forward-planned intensity-modulated radiotherapy (FIF-FP-IMRT) for whole breast irradiation after breast-conserving surgery,and to analyze the factors influencing the doses to the axillary lymph nodes.Methods Thirty-seven patients with breast cancer treated by breast-conserving surgery were evaluated.All patients received FIF-FP-IMRT for whole breast irradiation (not involving regional lymph nodes).Delineation of axillary levels Ⅰ-Ⅲ,interpectoral lymph nodes,and axillary vein was made on CT images,and a dosimetric analysis was made using 3D treatment planning software.The influential factors for the dose distribution in axillary lymph nodes were analyzed by paired t-test.Results The mean percent volumes receiving at least 95％ of the prescribed dose (50 Gy/25 fractions for whole breast PTV)(V95) for axillary levels Ⅰ,Ⅱ,and Ⅲ and interpectoral lymph nodes were 34.7％,6.1％,0.4％,and 39.6％,respectively,and the mean doses to axillary levels Ⅰ,Ⅱ,Ⅲ and interpectoral lymph nodes were 30.8 Gy,15.7 Gy,5.0 Gy,and 28.8 Gy,respectively.The mean V95 values for the lymph node areas below and above the axillary vein were 45.6％ and 0.7％,respectively,and the mean doses were 38.2 Gy and 6.7 Gy,respectively.The distance between the upper border of the radiation field and the humeral head was the only significant factor influencing the mean dose to the lymph node area below the axillary vein (P =0.037).Conclusions In FIF-FP-IMRT for whole breast irradiation,the actual dose delivered to the axillary lymph nodes below the axillary vein cannot be neglected and should be taken into consideration when analyzing the local control of the axillary lymph nodes after breast-conserving surgery. Key words: Breast neoplasms/three-dimensional conformal radiotherapy; Axillary lymph nodes; Dosimetry

Analysis of predictive factors for lung injury after forward-planned intensity-modulated radiotherapy in whole breast irradiation.

PurposeThis study was performed to assess frequency, timings of occurrence, and predictors of radiologic lung damage (RLD) after forward-planned intensity-modulated radiotherapy (FIMRT) for whole breast irradiation.MethodsWe retrospectively reviewed medical records of 157 breast cancer patients and each of their serial chest computed tomography (CT) taken 4, 10, 16, and 22 months after completion of breast radiotherapy (RT). FIMRT was administered to whole breast only (n=152), or whole breast and supraclavicular regions (n=5). Dosimetric parameters, such as mean lung dose and lung volume receiving more than 10 to 50 Gy (V10-V50), and clinical parameters were analyzed in relation to radiologic lung damage.ResultsIn total, 104 patients (66.2%) developed RLD after whole breast FIMRT. Among the cases of RLD, 84.7% were detected at 4 months, and 15.3% at 10 months after completion of RT. More patients of 47 or younger were found to have RLD at 10 months after RT than patients older than the age (11.7% vs. 2.9%, p=0.01). In univariate and multivariate analyses, age >47 and V40 >7.2% were significant predictors for higher risk of RLD.ConclusionRLD were not infrequently detected in follow-up CT after whole breast FIMRT. More detected cases of RLD among younger patients are believed to have developed at later points after RT than those of older patients. Age and V40 were significant predictors for RLD after whole breast intensity-modulated radiotherapy.

Evaluation of dosimetric variance in whole breast forward-planned intensity-modulated radiotherapy based on 4DCT and 3DCT

This study was performed to explore and compare the dosimetric variance caused by respiratory movement in the breast during forward-planned IMRT after breast-conserving surgery. A total of 17 enrolled patients underwent the 3DCT simulation scans followed by 4DCT simulation scans during free breathing. The treatment planning constructed using the 3DCT images was copied and applied to the end expiration (EE) and end inspiration (EI) scans and the dose distributions were calculated separately. CTV volume variance amplitude was very small (11.93 ± 28.64 cm3), and the percentage change of CTV volumes receiving 50 Gy and 55 Gy between different scans were all less than 0.8%. There was no statistically significant difference between EI and EE scans (Z =–0.26, P = 0.795). However, significant differences were found when comparing the Dmean at 3DCT planning with the EI and EE planning (P = 0.010 and 0.019, respectively). The homogeneity index at EI, EE and 3D plannings were 0.139, 0.141 and 0.127, respectively, and significant differences existed between 3D and EI, and between 3D and EE (P = 0.001 and 0.006, respectively). The conformal index (CI) increased significantly in 3D treatment planning (0.74 ± 0.07) compared with the EI and EE phase plannings (P = 0.005 and 0.005, respectively). The V30, V40, V50 and Dmean of the ipsilateral lung for EE phase planning were significantly lower than for EI (P = 0.001–0.042). There were no significant differences in all the DVH parameters for the heart among these plannings (P = 0.128–0.866). The breast deformation during respiration can be disregarded in whole breast IMRT. 3D treatment planning is sufficient for whole breast forward-planned IMRT on the basis of our DVH analysis, but 4D treatment planning, breath-hold, or respiratory gate may ensure precise delivery of radiation dose.

Organ-sparing Intensity-modulated Radiotherapy for Anal Cancer using the ACTII Schedule: A Comparison of Conventional and Intensity-modulated Radiotherapy Plans

AimsConventional external beam radiotherapy for anal cancer is associated with a high rate of treatment-related morbidity. The purpose of this retrospective study was to compare the dosimetric advantages of three intensity-modulated radiotherapy (IMRT) plans with the conventional plan with regards to organs at risk avoidance delivering the ACTII schedule of 50.4 Gy in 1.8 Gy/fraction: 17 fractions for phase 1 and 11 fractions for phase 2. Materials and methodsTen anal cancer patients (T1-3 N0-3) treated with the conventional plan using four fields and conformal boost were identified. The phase 1 planning target volume (PTV) included tumour, anal canal and inguinal, peri-rectal and internal/external iliac nodes. Phase 2 included identifiable disease only. Three step-and-shoot IMRT plans were generated: IMRT1: phase 1 inverse-planned IMRT with two- to four-field conformal phase 2; IMRT2: both phase 1 and phase 2 inverse-planned IMRT; IMRT3: phase 1 IMRT and phase 2 forward-planned IMRT. All IMRT plans were then compared against the conventional plan on PTV coverage, small bowel, genitalia, femoral heads, bladder and healthy tissue dose volume information. ResultsWhile achieving similar PTV coverage compared with the conventional plan, significant dose reductions were observed for IMRT plans in external genitalia, small bowel and healthy tissue. Reductions were also observed in the femoral heads and bladder. ConclusionsIMRT significantly reduces the dose to organs at risk while maintaining excellent PTV coverage in anal cancer radiotherapy.

Randomized Controlled Trial of Forward-Planned Intensity Modulated Radiotherapy for Early Breast Cancer: Interim Results at 2 Years

This single-center randomized trial was designed to investigate whether intensity-modulated radiotherapy (IMRT) reduces late toxicity in patients with early-stage breast cancer. The standard tangential plans of 1,145 nonselected patients were analyzed. The patients with inhomogeneous plans were randomized to a simple method of forward-planned IMRT or standard radiotherapy (RT). The primary endpoint was serial photographic assessment of breast shrinkage. At 2 years, no significant difference was found in the development of any photographically assessed breast shrinkage between the patients randomized to the interventional or control group (odds ratio, 1.51; 95% confidence interval, 0.83-1.58; p = .41). The patients in the control group were more likely to develop telangiectasia than those in the IMRT group (odds ratio, 1.68; 95% confidence interval 1.13-2.40; p = .009). Poor baseline surgical cosmesis resulted in poor overall cosmesis at 2 years after RT. In patients who had good surgical cosmesis, those randomized to IMRT were less likely to deteriorate to a moderate or poor overall cosmesis than those in the control group (odds ratio, 0.63; 95% confidence interval, 0.39-1.03, p = .061). IMRT can lead to a significant reduction in telangiectasia at comparatively early follow-up of only 2 years after RT completion. An important component of breast induration and shrinkage will actually result from the surgery and not from the RT. Surgical cosmesis is an important determinant of overall cosmesis and could partially mask the longer term benefits of IMRT at this early stage.

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

Background and purposeTo compare left-sided whole breast conventional and intensity-modulated radiotherapy (IMRT) treatment planning techniques. Materials and methodsTreatment plans were created for 10 consecutive patients. Three-dimensional conformal radiotherapy (3DCRT), forward-planned IMRT (for-IMRT), and inverse-planned IMRT (inv-IMRT) used two tangent beams. For-IMRT utilized up to four segments per beam. For helical tomotherapy (HT) plans, beamlet entrance and/or exit to critical structures was blocked. Topotherapy plans, which used static gantry angles with simultaneous couch translation and inverse-planned intensity modulation, used two tangent beams. Plans were normalized to 50Gy to 95% of the retracted PTV. ResultsTarget max doses were reduced with for-IMRT compared to 3DCRT, which were further reduced with HT, topotherapy, and inv-IMRT. HT resulted in lowest heart and ipsilateral lung max doses, but had higher mean doses. Inv-IMRT and topotherapy reduced ipsilateral lung mean and max doses compared to 3DCRT and for-IMRT. ConclusionsAll modalities evaluated provide adequate coverage of the intact breast. HT, topotherapy, and inv-IMRT can reduce high doses to the target and normal tissues, although HT results in increased low doses to large volume of normal tissue. For-IMRT improves target homogeneity compared with 3DCRT, but to a lesser degree than the inverse-planned modalities.

A Review of the Clinical Evidence for Intensity-modulated Radiotherapy

Aims Intensity-modulated radiotherapy (IMRT) is a development of three-dimensional conformal radiotherapy that offers improvements in dosimetry in many clinical scenarios. Here we review the clinical evidence for IMRT and present ongoing or unpublished randomised controlled trials (RCTs). Methods We identified randomised and non-randomised comparative studies of IMRT and conventional radiotherapy using MEDLINE, hand-searching Radiotherapy and Oncology and the International Journal of Radiation Oncology, Biology and Physics and the proceedings of the American Society for Therapeutic Radiology and Oncology and the European Society for Therapeutic Radiology and Oncology annual meetings. The metaRegister of Controlled Trials was searched to identify completed-unpublished, ongoing and planned RCTs. Results Sixty-one studies comparing IMRT and conventional radiotherapy were identified. These included three RCTs in head and neck cancer (205 patients) and three in breast cancer (664 patients) that had reported clinical outcomes; these were all powered for toxicity-related end points, which were significantly better with IMRT in each trial. There were 27 additional non-randomised studies in head and neck (1119 patients), 26 in prostate cancer (>5000 patients), four in breast cancer (875 patients) and nine in other tumour sites. The results of these studies supported those of the RCTs with benefits reported in acute and late toxicity, health-related quality of life and tumour control end points. Twenty-eight completed-unpublished, ongoing or planned RCTs incorporating IMRT were identified, including at least 12,310 patients, of which 15 compared conventional radiotherapy within IMRT as a randomisation or pre-planned stratification. Discussion Inverse-planned IMRT maintains parotid saliva production and reduces acute and late xerostomia during radiotherapy for locally advanced head and neck cancer, reduces late rectal toxicity in prostate cancer patients allowing safe dose escalation and seems to reduce toxicity in several other tumour sites. Forward-planned IMRT reduces acute toxicity and improves late clinician-assessed cosmesis compared with conventional tangential breast radiotherapy.

Survey of the Availability and Use of Advanced Radiotherapy Technology in the UK

Aims To determine the availability of intensity-modulated radiotherapy (IMRT) treatment in the UK and to assess the magnitude of the shortfall in terms of patient treatments. In addition, the availability of image-guided radiotherapy (IGRT) was also reviewed. Materials and methods A survey was carried out between July and September 2008 of the use of advanced technology in radiotherapy. Results In total, 50 centres responded out of the 58 National Health Service centres canvassed, representing about 89% of patients treated in the UK. Forty-six centres had at least two machines capable of IMRT and 26 centres had at least one machine capable of IGRT. Thirty-two centres were carrying out forward-planned IMRT and 18 centres were carrying out the more complex inverse-planned IMRT. In all, 38 centres (76% of respondents) were offering either forward- or inverse-planned IMRT to some of their patients. All the centres with IGRT capability were using IGRT for at least some of their patients. Respondents were asked to list the total number of radical and palliative patients being treated according to the treatment site. Forty-two per cent of respondents took the option to list the total number of radical and palliative patients only. Based on these data, 10.7% of radical patients are currently being given forward-planned IMRT, mainly for breast cancer (18.6% of such patients) and 2.2% of radical patients are being given inverse-planned IMRT, mainly for prostate (7.5% of such patients) and head and neck cancer (6.7% of such patients). Whereas at present only 18 centres are able to treat with inverse-planned IMRT, 45 centres expected to be able to do so by 2010. Respondents were asked to estimate the percentage of patients who should be given IMRT for each site and this was used to estimate the shortfall in IMRT provision. Conclusions Based on the consensus of opinion, 32% of radically treated patients should receive inverse-planned IMRT and 22% forward-planned IMRT, making a total of 55%. In fact, 2% receive inverse-planned IMRT and 11% the less complex forward-planned IMRT. Thus, with an estimated 75 948 radical treatments being carried out with megavoltage radiotherapy, the professional opinion is that 41 421 of patients would benefit from treatment with IMRT. In fact, only 9775 were so treated in 2008; a shortfall of 32 497 patients treated instead with conventional radiotherapy.

A Randomised Controlled Trial of Forward-Planned Intensity Modulated Radiotherapy (IMRT) for Early Breast Cancer: Interim Results at 2 Years Follow-Up.

Abstract Background: This large single centre trial was designed to investigate whether correction of dose inhomogeneities using IMRT reduces late toxicity and improves quality of life in patients with early breast cancer. We report interim results at 2 years follow-up.Materials and Methods: Standard tangential breast radiotherapy plans of 1145 trial patients were assessed for dose inhomogeneity as defined by ICRU recommendations. Patients with inhomogeneous plans were randomised to either IMRT or standard radiotherapy. Patients with homogenous plans were treated with standard radiotherapy, but were followed up within the trial as per randomised patients. The primary endpoint of the trial was photographic assessment of breast shrinkage. Secondary endpoints included photographic assessment of final cosmesis, clinical assessment of toxicity, and patient-reported symptoms and quality of life. All endpoints were scored using validated assessment methods. Data were collected on potential confounding factors which included: age at randomisation, smoking history, body mass index, co-morbidity such as diabetes mellitus, cardiovascular and peripheral vascular disease, use of hormones and/or chemotherapy, treated breast volume, and presence or absence of breast boost.Results: 330/1145 (29%) of patients had adequate dosimetry with standard 2D radiotherapy and were not randomised. In the 815 randomised patients, dosimetry was significantly improved in the interventional (IMRT) arm compared to the control. Currently, data from 632 randoimsed patients who have reached 2 years of follow up have been analysed. This interim analysis demonstrates that the incidence of telangiectasia in the control arm was significantly greater than in the interventional group (P = 0.024). Pre-radiotherapy surgical cosmesis significantly affected photographic assessment of final cosmesis, and clinical assessment of breast shrinkage and induration (P &amp;lt; 0.0001). In randomised patients who had good surgical cosmesis, there was a significant difference improvement in final cosmesis with the use of IMRT (P = 0.038). The quality of life data has not been analysed at this stage.Discussion: This trial shows that the use of forward-planned IMRT can significantly improve dose homogeneity, and suggests that this translates into improvements in late toxicity at only 2 years from completion of radiotherapy. Surgical cosmesis appears to be a very important determinant of overall final cosmesis after 2 years of follow-up, and may mask any beneficial effects of IMRT at this early stage. It is highly likely that these trial patients will have not expressed their final level of toxicity at 2 years post-radiotherapy, and re-analysis is planned at 5 years from completion of radiotherapy. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 71.