Analysis of Radiation Dose to the Shoulder by Treatment Technique and Correlation With Patient Reported Outcomes in Patients Receiving Regional Nodal Irradiation.

BACKGROUND/PURPOSE: Shoulder/arm morbidity is a late complication of breast cancer treatment with surgery and regional nodal irradiation (RNI). We set to analyze the impact of radiation technique [intensity modulated radiation therapy (IMRT) or 3D conformal radiation therapy (3DCRT)] on radiation dose to the shoulder with a hypothesis that IMRT use results in smaller volume of shoulder receiving radiation. We explored the relationship of treatment technique on long-term patient-reported outcomes using the quick disabilities of the arm, shoulder, and hand (q-DASH) questionnaire. MATERIALS/METHODS: We identified patients treated with adjuvant RNI (50 Gy/25 fractions) from 2013 to 2018. We retrospectively contoured the shoulder organ-at-risk (OAR) from 2 cm above the ipsilateral supraclavicular (SCL) planning target volume (PTV) to the inferior SCL PTV slice and calculated the absolute volume of shoulder OAR receiving 5-50 Gy (V5-V50). We identified patients that completed a q-DASH questionnaire ≥6 months from the end of RNI. RESULTS: We included 410 RNI patients: 54% stage III, 72% mastectomy, 35% treated with IMRT. IMRT resulted in significant reductions in the shoulder OAR volume receiving 20-50 Gy vs. 3DCRT. In total, 82 patients completed the q-DASH. The mean (SD) q-DASH=25.4 (19.1) and tended to be lower with IMRT vs. 3DCRT: 19.6 (16.4) vs. 27.8 (19.8), p=0.078. CONCLUSION: We found that IMRT reduces radiation dose to the shoulder and is associated with a trend toward reduced q-DASH scores ≥6 months post-RNI in a subset of our cohort. These results support prospective evaluation of IMRT as a technique to reduce shoulder morbidity in breast cancer patients receiving RNI.

Dosimetric parameters associated with radiation-induced esophagitis in breast cancer patients undergoing regional nodal irradiation.

BACKGROUND/PURPOSE: Rates of acute esophagitis in breast cancer patients undergoing regional nodal irradiation (RNI) are under-reported. We set to identify esophageal dose-volume constraints associated with grade 2 esophagitis (G2E). We hypothesized that the G2E rate was higher with intensity modulated radiation therapy (IMRT) vs. 3D conformal radiation therapy (3DCRT). MATERIALS/METHODS: We identified patients that received RNI (50 Gy/25 fractions) from 1/2013 to 6/2019. We retrospectively contoured the esophagus in a consistent manner and recorded esophageal mean dose, max dose, and V10-V50. Our primary endpoint was the G2E rate. Receiver operating characteristics curves analysis (e.g., Youden's J statistic) were used to determine the cutpoints for the dosimetric parameters which were then tested in logistic regression models. RESULTS: We identified 531 patients (50% left-sided; 41% IMRT; 16.2% G2E). G2E was significantly higher in IMRT vs. 3DCRT patients (23.6% vs. 10.9%, p < 0.0001). All esophageal dosimetric parameters were significantly associated with G2E after adjusting for age and laterality. The cutpoints for esophageal mean dose, V10 and V20 were 11 Gy, 30%, and 15%, respectively. The associations between the dichotomized dose-volume parameters and G2E were OR = 3.82 (95% CI 2.28-6.40, p < 0.0001) for esophageal mean dose, OR = 5.37 (95% CI 3.01-9.58, p < 0.0001) for esophageal V10, and OR = 3.23 (95% CI 1.93-5.41, p < 0.0001) for esophageal V20. CONCLUSION: In patients receiving RNI with modern techniques, we found that G2E occurs in >15%, and more frequently with IMRT. These data strongly support the routine contouring of the esophagus in RNI planning, and our constraints should be incorporated in future prospective protocols of RNI.

Clinical Effectiveness of an Adaptive Treatment Planning Algorithm for Intensity Modulated Radiation Therapy Versus 3D Conformal Radiation Therapy for Node-Positive Breast Cancer Patients Undergoing Regional Nodal Irradiation/Postmastectomy Radiation Therapy.

PURPOSE: Clinical trials support adjuvant regional nodal irradiation (RNI) after breast-conserving surgery or mastectomy for patients with lymph node-positive breast cancer. Advanced treatment planning techniques (eg, intensity modulated radiation therapy [IMRT]) can reduce dose to organs at risk (OARs) in this situation. However, uncertainty persists about when IMRT is clinically indicated (vs 3-dimensional conformal radiation therapy [3DCRT]) for RNI. We hypothesized that an adaptive treatment planning algorithm (TPA) for IMRT adoption would allow OAR constraints for RNI to be met when 3DCRT could not without significantly changing toxicity and locoregional recurrence (LRR) patterns. METHODS AND MATERIALS: Since 2013, all RNI patients also underwent an adaptive TPA that began with 3DCRT and then changed to IMRT when OAR constraints (mean heart dose ≤500 cGy; ipsilateral lung V20 ≤35%) could not be met. Patients received 2 Gy/d to the prospectively contoured target volumes (including internal mammary nodes). We retrospectively evaluated the dosimetry and clinical outcomes of the treatment groups (IMRT vs 3DCRT). The primary endpoint was the cumulative incidence of LRR as the site of first recurrence, and we specifically address patterns of failure based on dose to the posterior supraclavicular nodal region (SCL-post). RESULTS: Two hundred forty patients (60% stage III; mean 4.0 + nodes) underwent an adaptive-TPA for RNI after mastectomy (74%) or breast-conserving surgery (26%), resulting in 168 patients treated with 3DCRT and 72 patients treated with IMRT. There were 7 LRRs (2 IMRT, 5 3DCRT) resulting in 4-year LRR of 2.8% for IMRT versus 1.8% for 3DCRT (P = .99). Three patients (2 IMRT, 1 3DCRT) had SCL nodal failures (1 in the SCL-post). CONCLUSIONS: An adaptive TPA for use of IMRT when 3DCRT does not meet critical OAR constraints resulted in rare high-grade toxicity and no difference in failure patterns between patients treated with IMRT and 3DCRT. These data should provide reassurance that IMRT maintains the therapeutic ratio by preserving cancer control outcomes without excess toxicity when 3DCRT fails to meet OAR constraints.

Likelihood of unacceptable normal tissue doses in breast cancer patients undergoing regional nodal irradiation in routine clinical practice.

PURPOSE: As indications for regional nodal irradiation (RNI) for breast cancer have expanded, so too has scrutiny over potential late toxicity from radiotherapy. This emphasizes the need for careful radiation treatment planning to maximize the therapeutic ratio. We sought to evaluate how often unacceptable doses (UDs) to organs at risk (OARs) occur and the associated factors for patients receiving RNI in daily practice. METHODS AND MATERIALS: Treatment records of patients who received RNI from February 2012 to May 2015 were studied. The NSABP B51/RTOG 1304 clinical dose-volume constraints for targets/OARs receiving RNI were used as the benchmark. Dose-volume histograms were analyzed for the rate of ≥1 UD delivered to the following organs: heart, mean >5 Gy; ipsilateral lung, V20 >35%, V10 >60%, V5 >70%; contralateral lung (CL), V5 >15%; and contralateral breast, V4.1 >5%. Logistic regression was used to test the association between UDs to OAR and key variables. RESULTS: Two hundred three consecutive cases received RNI (105 left, 98 right), to the chest wall in 171 (84%) and to the internal mammary nodes in 170 (84%); 77.4% of cases met all OAR constraints. The most common OAR UDs were delivered to the contralateral breast (n = 32, 15.7%) and ipsilateral lung V5 (n = 22, 10.8%). On multivariate analysis, use of intensity modulated radiation therapy (odds ratio [OR], 64.7; 95% confidence interval, 20.8-201.5; P < .001) and use of nodal boost (OR, 5.5; 95% confidence interval, 1.1-27.1; P = .04), but not internal mammary node irradiation (OR, 2.7; P = .35) or reconstruction (OR, 0.62; P = .33), were independently associated with higher OAR UD rate. For 3-dimensional conformal radiation therapy plans, 7.9% had OAR UDs. CONCLUSION: The OAR UD rate with 3-dimensional conformal radiation therapy ± deep inspiration breath-hold in routine clinical practice is low and not independently associated with internal mammary node irradiation or reconstruction presence. Women treated with intensity modulated radiation therapy had a significantly higher overall OAR UD rate, and clinicians should be aware of this as they initiate RNI treatment planning.

Dosimetric Considerations in Respiratory-Gated Deep Inspiration Breath-Hold for Left Breast Irradiation.

PURPOSE: To present our clinical workflow of incorporating AlignRT for left breast deep inspiration breath-hold treatments and the dosimetric considerations with the deep inspiration breath-hold protocol. MATERIAL AND METHODS: Patients with stage I to III left-sided breast cancer who underwent lumpectomy or mastectomy were considered candidates for deep inspiration breath-hold technique for their external beam radiation therapy. Treatment plans were created on both free-breathing and deep inspiration breath-hold computed tomography for each patient to determine whether deep inspiration breath-hold was beneficial based on dosimetric comparison. The AlignRT system was used for patient setup and monitoring. Dosimetric measurements and their correlation with chest wall excursion and increase in left lung volume were studied for free-breathing and deep inspiration breath-hold plans. RESULTS: Deep inspiration breath-hold plans had significantly increased chest wall excursion when compared with free breathing. This change in geometry resulted in reduced mean and maximum heart dose but did not impact lung V20 or mean dose. The correlation between chest wall excursion and absolute reduction in heart or lung dose was found to be nonsignificant, but correlation between left lung volume and heart dose showed a linear association. It was also identified that higher levels of chest wall excursion may paradoxically increase heart or lung dose. CONCLUSION: Reduction in heart dose can be achieved for many left-sided breast and chest wall patients using deep inspiration breath-hold. Chest wall excursion as well as left lung volume did not correlate with reduction in heart dose, and it remains to be determined what metric will provide the most optimal and reliable dosimetric advantage.