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Purpose: To use knowledge-based planning (KBP) as a method of producing high-quality, consistent, protocol-compliant treatment plans in a complex setting of spine stereotactic body radiation therapy on NRG Oncology Radiation Therapy Oncology Group (RTOG) 0631.Methods and Materials: An internally developed KBP model was applied to an external validation cohort of 22 anonymized cases submitted under NRG Oncology RTOG 0631. The original and KBP plans were compared via their protocol compliance, target conformity and gradient index, dose to critical structures, and dose to surrounding normal tissues.Results: The KBP model generated plans meeting all protocol objectives in a single optimization when tested on both internal and protocol-submitted NRG Oncology RTOG 0631 cases. Two submitted plans that were considered to have a protocol-unacceptable deviation were made protocol compliant through the use of the model. There were no statistically significant differences in protocol spinal cord metrics (D10% and D0.03cc) between the manually optimized plans and the KBP plans. The volume of planning target volume receiving prescription dose increased from 93.3% ± 3.2% to 98.3% ± 1.4% (P = .01) when using KBP. High-dose spillage to surrounding normal tissues (V105%) showed no significant differences (2.1 ± 7.3 cm3 for manual plans to 1.8 ± 0.6 cm3 with KBP), and dosimetric outliers with large amounts of spillage were eliminated through the use of KBP. Knowledge-based planning plans were also found to be significantly more consistent in several metrics, including target coverage and high dose outside of the target.Conclusion: Incorporation of KBP models into the clinical trial setting may have a profound impact on the quality of trial results, owing to the increase in consistency and standardization of planning, especially for treatment sites or techniques that are nonstandard. [ABSTRACT FROM AUTHOR]

Purpose: To quantify lung perfusion changes after breast/chest wall radiation therapy (RT) using pre- and post-RT single photon emission computed tomography/computed tomography (SPECT/CT) attenuation-corrected perfusion scans; and correlate decreased perfusion with adjuvant RT dose for breast cancer in a prospective clinical trial.Methods and Materials: As part of an institutional review board-approved trial studying the impact of RT technique on lung function in node-positive breast cancer, patients received breast/chest wall and regional nodal irradiation including superior internal mammary node RT to 50 to 52.2 Gy with a boost to the tumor bed/mastectomy scar. All patients underwent quantitative SPECT/CT lung perfusion scanning before RT and 1 year after RT. The SPECT/CT scans were co-registered, and the ratio of decreased perfusion after RT relative to the pre-RT perfusion scan was calculated to allow for direct comparison of SPECT/CT perfusion changes with delivered RT dose. The average ratio of decreased perfusion was calculated in 10-Gy dose increments from 0 to 60 Gy.Results: Fifty patients had complete lung SPECT/CT perfusion data available. No patient developed symptoms consistent with pulmonary toxicity. Nearly all patients demonstrated decreased perfusion in the left lung according to voxel-based analyses. The average ratio of lung perfusion deficits increased for each 10-Gy increment in radiation dose to the lung, with the largest changes in regions of lung that received 50 to 60 Gy (ratio 0.72 [95% confidence interval 0.64-0.79], P<.001) compared with the 0- to 10-Gy region. For each increase in 10 Gy to the left lung, the lung perfusion ratio decreased by 0.06 (P<.001).Conclusions: In the assessment of 50 patients with node-positive breast cancer treated with RT in a prospective clinical trial, decreased lung perfusion by SPECT/CT was demonstrated. Our study allowed for quantification of lung perfusion defects in a prospective cohort of breast cancer patients for whom attenuation-corrected SPECT/CT scans could be registered directly to RT treatment fields for precise dose estimates. [ABSTRACT FROM AUTHOR]

Purpose: The present treatment planning study compared whole breast radiotherapy (WBRT) to accelerated partial breast irradiation (APBI) for different external beam techniques and geometries (e.g., free breathing [FB] and deep inspiration breath hold [DIBH]). Methods and Materials: After approval by our institutional review board, a treatment planning study was performed of 10 patients with left-sided Stage 0-I breast cancer enrolled in a Phase I-II study of APBI using intensity-modulated radiotherapy (IMRT). After lumpectomy, patients underwent planning computed tomography scans during FB and using an active breathing control device at DIBH. For the FB geometry, standard WBRT and three-dimensional conformal radiotherapy (3D-CRT) APBI plans were created. For the DIBH geometry with active breathing control, WBRT, 3D-CRT, and IMRT APBI plans were created. Results: All APBI techniques had excellent planning target volume coverage. The maximal planning target volume dose was reduced from 116% of the prescription dose to 108% with the IMRT(DIBH) APBI plan. The maximal heart dose was >30 Gy for the WBRT techniques, 8.2 Gy for 3D-CRT(FB), and <5.0 Gy for 3D-CRT(DIBH) and IMRT(DIBH) techniques. The mean left anterior descending artery dose was significantly reduced from 11.4 Gy with WBRT(FB) to 4.2 with WBRT(DIBH) and <2.0 Gy with all APBI techniques. Conclusion: Although planning target volume coverage was acceptable with all techniques, the plans using the DIBH geometry resulted in a marked reduction in the normal tissue dose compared with WBRT planned in the absence of cardiac blocking. Additional study is needed to determine whether these techniques result in clinical benefits. [Copyright &y& Elsevier]

Purpose: Although previous work demonstrated superior dose distributions for left-sided breast cancer patients planned for intensity-modulated radiation therapy (IMRT) at deep inspiration breath hold compared with conventional techniques with free-breathing, such techniques are not always feasible to limit the impact of respiration on treatment delivery. This study assessed whether optimization based on multiple instance geometry approximation (MIGA) could derive an IMRT plan that is less sensitive to known respiratory motions. Methods and Materials: CT scans were acquired with an active breathing control device at multiple breath-hold states. Three inverse optimized plans were generated for eight left-sided breast cancer patients: one static IMRT plan optimized at end exhale, two (MIGA) plans based on a MIGA representation of normal breathing, and a MIGA representation of deep breathing, respectively. Breast and nodal targets were prescribed 52.2 Gy, and a simultaneous tumor bed boost was prescribed 60 Gy. Results: With normal breathing, doses to the targets, heart, and left anterior descending (LAD) artery were equivalent whether optimizing with MIGA or on a static data set. When simulating motion due to deep breathing, optimization with MIGA appears to yield superior tumor-bed coverage, decreased LAD mean dose, and maximum heart and LAD dose compared with optimization on a static representation. Conclusions: For left-sided breast-cancer patients, inverse-based optimization accounting for motion due to normal breathing may be similar to optimization on a static data set. However, some patients may benefit from accounting for deep breathing with MIGA with improvements in tumor-bed coverage and dose to critical structures. [Copyright &y& Elsevier]

Purpose: Regional nodal irradiation, including radiation therapy (RT) to the internal mammary node (IMN) region, improves oncologic outcomes in patients with node-positive breast cancer. Concern remains, however, given the proximity of the IMNs to the heart and the association between cardiac RT exposure and toxicity. The objective of the study was to evaluate rates of ischemic cardiac events (ICEs) and associated risk with treatment of the IMN region.Methods and Materials: The cardiac outcomes of 2126 patients treated with adjuvant breast RT or breast and nodal RT from 1984 to 2007 at a single institution were reviewed. The primary endpoint was an ICE following RT initiation. The association between IMN RT and ICEs was assessed using Cox proportional hazards models. Treatment with both IMN RT and 3-dimensional (3D) conformal radiation therapy (CRT) began in 1997; therefore, subset analyses of patients with only 3D CRT were performed to minimize bias associated with improved treatment technique.Results: The median follow-up period was 9.3 years. An ICE occurred in 87 patients (4.1%). No increased 10-year rate of ICEs was observed with IMN RT compared with no IMN RT in the total cohort (3.2% [95% confidence interval (CI), 2.4%-4.3%] vs 3.4% [95% CI, 1.5%-7.5%]; hazard ratio [HR], 0.88; P=.73). Similarly, no statistically significant difference was noted in the 3D CRT-planned, left-sided disease subset (5.1% [95% CI, 1.8%-14.1%] vs 4.0% [95% CI, 2.0%-8.0%]; HR, 1.18, P=.76). On multivariate analysis, adjusting for cardiac risk factor imbalances, no significantly increased hazard was noted with IMN RT (HR, 1.84; P=.28) in the 3D CRT-planned, left-sided disease subset.Conclusions: No statistically significant association between IMN RT and ICEs was demonstrated in a review of patients treated at a single institution from 1984 to 2007. Given the long natural history and low overall rate of ICEs, continued follow-up of this study, as well as additional studies in the 3D CRT era, is warranted to confirm these results. Minimizing cardiac exposure, when treating a limited IMN field, is critical to limit excess risk of ICEs. [ABSTRACT FROM AUTHOR]

Purpose: To report the final cosmetic results from a single-arm prospective clinical trial evaluating accelerated partial breast irradiation (APBI) using intensity modulated radiation therapy (IMRT) with active-breathing control (ABC). Methods and Materials: Women older than 40 with breast cancer stages 0-I who received breast-conserving surgery were enrolled in an institutional review board-approved prospective study evaluating APBI using IMRT administered with deep inspiration breath-hold. Patients received 38.5 Gy in 3.85-Gy fractions given twice daily over 5 consecutive days. The planning target volume was defined as the lumpectomy cavity with a 1.5-cm margin. Cosmesis was scored on a 4-category scale by the treating physician. Toxicity was scored according to National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE version 3.0). We report the cosmetic and toxicity results at a median follow-up of 5 years. Results: A total of 34 patients were enrolled. Two patients were excluded because of fair baseline cosmesis. The trial was terminated early because fair/poor cosmesis developed in 7 of 32 women at a median follow-up of 2.5 years. At a median follow-up of 5 years, further decline in the cosmetic outcome was observed in 5 women. Cosmesis at the time of last assessment was 43.3% excellent, 30% good, 20% fair, and 6.7% poor. Fibrosis according to CTCAE at last assessment was 3.3% grade 2 toxicity and 0% grade 3 toxicity. There was no correlation of CTCAE grade 2 or greater fibrosis with cosmesis. The 5-year rate of local control was 97% for all 34 patients initially enrolled. Conclusions: In this prospective trial with 5-year median follow-up, we observed an excellent rate of tumor control using IMRT-planned APBI. Cosmetic outcomes, however, continued to decline, with 26.7% of women having a fair to poor cosmetic result. These results underscore the need for continued cosmetic assessment for patients treated with APBI by technique. [ABSTRACT FROM AUTHOR]

Purpose: To quantify cardiac radiation therapy (RT) exposure using sensitive measures of cardiac dysfunction; and to correlate dysfunction with heart doses, in the setting of adjuvant RT for left-sided breast cancer. Methods and Materials: On a randomized trial, 32 women with node-positive left-sided breast cancer underwent pre-RT stress single photon emission computed tomography (SPECT-CT) myocardial perfusion scans. Patients received RT to the breast/chest wall and regional lymph nodes to doses of 50 to 52.2 Gy. Repeat SPECT-CT scans were performed 1 year after RT. Perfusion defects (PD), summed stress defects scores (SSS), and ejection fractions (EF) were evaluated. Doses to the heart and coronary arteries were quantified. Results: The mean difference in pre- and post-RT PD was −0.38% ± 3.20% (P=.68), with no clinically significant defects. To assess for subclinical effects, PD were also examined using a 1.5-SD below the normal mean threshold, with a mean difference of 2.53% ± 12.57% (P=.38). The mean differences in SSS and EF before and after RT were 0.78% ± 2.50% (P=.08) and 1.75% ± 7.29% (P=.39), respectively. The average heart Dmean and D95 were 2.82 Gy (range, 1.11-6.06 Gy) and 0.90 Gy (range, 0.13-2.17 Gy), respectively. The average Dmean and D95 to the left anterior descending artery were 7.22 Gy (range, 2.58-18.05 Gy) and 3.22 Gy (range, 1.23-6.86 Gy), respectively. No correlations were found between cardiac doses and changes in PD, SSS, and EF. Conclusions: Using sensitive measures of cardiac function, no clinically significant defects were found after RT, with the average heart Dmean <5 Gy. Although a dose response may exist for measures of cardiac dysfunction at higher doses, no correlation was found in the present study for low doses delivered to cardiac structures and perfusion, SSS, or EF. [Copyright &y& Elsevier]

Purpose: To report interim cosmetic results and toxicity from a prospective study evaluating accelerated partial-breast irradiation (APBI) administered using a highly conformal external beam approach. Methods and Materials: We enrolled breast cancer patients in an institutional review board–approved prospective study of APBI using beamlet intensity-modulated radiotherapy (IMRT) at deep-inspiration breath-hold. Patients received 38.5 Gy in 3.85 Gy fractions twice daily. Dosimetric parameters in patients who maintained acceptable cosmesis were compared with those in patients developing unacceptable cosmesis in follow-up, using t-tests. Results: Thirty-four patients were enrolled; 2 were excluded from analysis because of fair baseline cosmesis. With a median follow-up of 2.5 years, new unacceptable cosmesis developed in 7 patients, leading to early study closure. We compared patients with new unacceptable cosmesis with those with consistently acceptable cosmesis. Retrospective analysis demonstrated that all but one plan adhered to the dosimetric requirements of the national APBI trial. The mean proportion of a whole-breast reference volume receiving 19.25 Gy (V50) was lower in patients with acceptable cosmesis than in those with unacceptable cosmesis (34.6% vs. 46.1%; p = 0.02). The mean percentage of this reference volume receiving 38.5 Gy (V100) was also lower in patients with acceptable cosmesis (15.5% vs. 23.0%; p = 0.02). Conclusions: The hypofractionated schedule and parameters commonly used for external beam APBI and prescribed by the ongoing national trial may be suboptimal, at least when highly conformal techniques such as IMRT with management of breathing motion are used. The V50 and V100 of the breast reference volume seem correlated with cosmetic outcome, and stricter limits may be appropriate in this setting. [Copyright &y& Elsevier]

Purpose: The short-term displacement and reproducibility of the breast or chest wall, and the internal mammary (IM), infraclavicular (ICV), and supraclavicular (SCV) nodal regions have been assessed as a function of breath-hold state using an active breathing control (ABC) device for patients receiving loco-regional breast radiation therapy.Methods and Materials: Ten patients underwent computed tomographic scanning using an ABC device at breath-hold states of end-exhale and 20%, 40%, 60%, and 80% of vital capacity (VC). Patients underwent scanning before treatment and at one third and two thirds of the way through treatment. A regional registration was performed for each target using a rigid-body transformation with mutual information as a metric.Results: Between exhale and 40% of VC, the mean displacement was 0.27/0.34, 0.24/0.31, 0.22/0.19, and 0.13/0.19 cm anterior/superior for the breast or chest wall, and IM, ICV, and SCV nodes, respectively. At 80% of VC, the mean displacement from exhale was 0.84/.88, 0.76/.79, 0.70/0.79, and 0.54/0.56 cm anterior/superior for the breast or chest wall, and IM, ICV, and SCV nodes, respectively. The short-term reproducibility (standard deviation) was <0.3 and Conclusions: The short-term reproducibility of target position is

Purpose: To reduce cardiotoxicity from breast radiotherapy (RT), innovative techniques are under investigation. Information about cardiac motion with respiration and positional reproducibility under active breathing control (ABC) is necessary to evaluate these techniques.Methods and Materials: Patients requiring loco-regional RT for breast cancer were scanned by computed tomography using an ABC device at various breath-hold states, before and during treatment. Ten patients were studied. For each patient, 12 datasets were analyzed. Mutual information-based regional rigid alignment was used to determine the magnitude and reproducibility of cardiac motion as a function of breathing state. For each scan session, motion was quantified by evaluating the displacement of a point along the left anterior descending artery (LAD) with respect to its position at end expiration. Long-term positional reproducibility was also assessed.Results: Displacement of the LAD was greatest in the inferior direction, moderate in the anterior direction, and lowest in the left-right direction. At shallow breathing states, the average displacement of LAD position was up to 6 mm in the inferior direction. The maximum displacement in any patient was 2.8 cm in the inferior direction, between expiration and deep-inspiration breath hold. At end expiration, the long-term reproducibility (SD) of the LAD position was 3 mm in the A-P, 6 mm in the S-I, and 4 mm in the L-R directions. At deep-inspiration breath hold, long-term reproducibility was 3 mm in the A-P, 7 mm in the S-I, and 3 mm in the L-R directions.Conclusions: These data demonstrate the extent of LAD displacement that occurs with shallow breathing and with deep-inspiration breath hold. This information may guide optimization studies considering the effects of respiratory motion and reproducibility of cardiac position on cardiac dose, both with and without ABC. [ABSTRACT FROM AUTHOR]

Purpose: To compare the estimated radiation doses delivered to the cardiac chambers (CC) and coronary arteries (CA) for 5 postmastectomy radiotherapy (PMRT) techniques.Methods and materials: A dosimetry study of 20 left-sided PMRT cases was conducted. Cardiac chambers (left and right atria [LA/RA] and left and right ventricles [LV/RV]) and coronary vessels (left main [LM], left anterior descending [LAD], left circumflex [LCX], right coronary [RCA] and posterior descending [PDA] arteries) were contoured on contrast-enhanced CT scans and verified by a cardiologist (T.K.). Five PMRT techniques were applied to each case; 50 Gy in 2 Gy fractions was delivered to the chest wall ± internal mammary node targets. The techniques were: (1) standard tangents (TAN); (2) cobalt (Co); (3) reverse hockey stick (RHS); (4) mixed photon/electron beam (20/80); and (5) partially wide tangent fields (PWTF). Three-dimensional dose calculations for 100 plans were performed for all structures. Plans were compared by using the mean dose (Dmean) and the volume that received more than 30 Gy (V30) and 45 Gy (V45) for each structure.Results: Cobalt and 20/80 techniques delivered higher Dmeans to the whole heart and individual cardiac chambers (RA, RV, LA, and LV) as compared with the other three techniques. The heart received a Dmean of 21.03 ± 3.5 Gy from Co and 11.87 ± 5.22 Gy from 20/80. The remaining techniques delivered heart Dmeans of 2.90–4.94 Gy. When V30 was used as a metric, all techniques had comparably low V30 to the heart, except for Co, which resulted in a significantly higher irradiated volume of right-sided cardiac chambers (59.06% ± 30.7 for RA F-test < 0.0001; and 61.46% ± 22.13 for RV, F-test < 0.0001). Dmean to the proximal LAD (LAD_p) was significantly higher for RHS (17.64 ± 7.43 Gy) and 20/80 (20.52 ± 8.36 Gy) and lowest for PWTF (9.5 ± 4.16 Gy). The Dmean for the distal LAD (LAD_d) was significantly lower with PWTF (11.02 ± 7.34 Gy) than with all other techniques, including TAN (p < 0.0001). Similar results for PWTF and TAN were observed when V30 and V45 were used.Conclusions: Cardiac substructures receive the most radiation exposure after PMRT with CO, 20/80 or both and least exposure with PWTF. Although TAN resulted in significant sparing of the majority of the cardiac structures, a significantly higher dose and volume of LAD was exposed when compared with PWTF. Although the clinical relevance of these dose differences is not clearly understood, these dosimetric estimates can serve as a baseline in the development of new techniques for locoregional treatment that will further reduce cardiac exposure. [Copyright &y& Elsevier]

Purpose: To compare seven techniques for irradiation of the postmastectomy chest wall (CW) using normal tissue complication probability (NTCP) predictions for pneumonitis and ischemic heart disease and dose-volume histogram analyses for normal and target tissues.Methods and Materials: Plan comparisons were performed for 20 left-sided postmastectomy CW RT cases using target volumes based on clinical delineation of standard field borders. Seven common treatment techniques were planned for each case, using a prescription of 50 Gy in 25 fractions to the CW and internal mammary node (IMN) targets. NTCP model metrics were used to quantify the risks of pneumonitis and ischemic heart disease, supplemented by dose-volume metrics to assess the target coverage to the CW and IMNs, as well as normal tissue dose (lung and heart).Results: Overlap in the distributions of the CW mean dose for all plans was found, except cobalt, which was significantly less than the remaining techniques (global F test, F = 21.90, p <0.0001). Standard tangents produced a significantly lower IMN mean dose than all other methods, as expected (F = 59.55, p < 0.0001); the reverse hockey stick and cobalt techniques were lower than the other methods, which were statistically similar. Cobalt produced a significantly higher percentage of the heart that received >30 Gy (V30) than the other methods (F = 49.76, p <0.0001). Use of partially wide tangent fields (PWTFs) resulted in the smallest heart V30. Use of cobalt fields resulted in a significantly greater NTCP estimate for ischemic heart disease than all the remaining techniques (F = 70.39, p <0.0001). Standard tangents resulted in a percentage of the lung receiving >20 Gy (V20) significantly less than with PWTFs, 30/70 and 20/80 photon/electron mix, and reverse hockey stick techniques. NTCP estimates for pneumonitis revealed significantly better results with standard tangents (F = 6.57, p <0.0001).Conclusion: No one technique studied combines the best CW and IMN coverage with minimal lung and heart complication probabilities. The choice of technique should be based on clinical discretion and the technical expertise available to implement these complex plans. Of the seven techniques studied, this analysis supports PWTFs as the most appropriate balance of target coverage and normal tissue sparing when irradiating the CW and IMN. [Copyright &y& Elsevier]