Ipsilateral Lung V20 Research Articles

Abstract P4-12-20: Early toxicity and patient-reported cosmetic outcomes in patients treated with adjuvant proton-based radiotherapy after breast-conserving surgery

Abstract Background: As the number of proton centers continues to increase nationwide, the use of proton-based radiotherapy (RT) in the treatment of malignancies is expanding. Randomized trials to assess the efficacy and cardiovascular benefits of proton-based RT compared to photon-based RT in the treatment of breast cancer are underway. However, the data on early toxicity and cosmetic outcomes remains limited. In this study, we report dosimetric data, early toxicity, and patient-reported cosmetic outcomes in breast cancer patients treated with adjuvant proton-based RT after breast-conserving surgery. Methods: We performed a retrospective review of our institutional database to identify breast cancer patients treated with breast-conserving surgery followed by proton-based RT from 2015 to 2019. Patient-reported cosmetic outcomes were graded as excellent, good, fair, and poor. Early toxicity outcomes were graded by the treating physician during the treatment course using the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE), version 3.0. Dose-volume histograms (DVHs) were reviewed to obtain dosimetry data. Results: We identified 21 patients treated with adjuvant proton-based RT. Median age at diagnosis was 58 (range, 26-85). Median body mass index was 26.1 (range, 19.8-58.3). Three patients (14%) had a history of diabetes and three patients (14%) smoking. Three patients (14%) had a history of ipsilateral breast cancer treated with adjuvant RT, and one patient had a history of ipsilateral lung cancer treated with definitive RT. Eleven patients had T1 primary tumors (52%), fifteen (71%) were node-positive, and twelve (57%) had left-sided tumors. Twelve patients (57%) received neoadjuvant and five patients (24%) adjuvant chemotherapy. Median whole breast dose delivered was 46.8Gy (range, 40.0-50.4Gy). Target volumes included the regional lymph nodes in seventeen patients (81%). Seventeen patients (81%) received a lumpectomy boost with a median dose of 10Gy (range, 10-14Gy). The median planning target volume V95 was 94% (range, 77-100%), V100 71% (range, 60-97%), V110 2% (range 0-18%), and median max point dose was 115% (range, 105-120%). The median ipsilateral breast V105 was 367.3cc (range, 0-1172cc) and V110 was 24.1cc (range, 0-321.3cc). Median mean heart dose was 0.39Gy (range, 0-2.6Gy). Median ipsilateral lung V20 was 10% (range, 0-28%) and ipsilateral lung V5 was 28.5% (range, 0.8-55.7%). CTCAE grade 2 dermatitis occurred in 62% and grade 3 in 14% of patients. Grade 2 pain was reported by 33% and grade 3 by 10% of patients. Grade 2 fatigue was reported by 33% of patients. One patient developed acute esophagitis. Median follow-up at the time of cosmetic evaluation was 27 months (range, 5-42 months). Two patients died before cosmetic evaluation. Four patients (21%) reported fair cosmetic outcome and 15 patients (79%) reported good or excellent cosmetic outcome. No poor cosmesis was reported. Conclusions: Adjuvant proton-based radiotherapy after breast-conserving surgery results in low normal tissue exposure compared to typical photon-based plans, particularly when the regional lymphatics are targeted. Proton-based RT is well tolerated with acceptable rates of acute toxicities and a high rate of good-to-excellent patient-reported cosmetic outcomes. Citation Format: Mutlay Sayan, Yin Zhang, Bo Liu, Apar Gupta, Bruce Haffty, Nisha Ohri. Early toxicity and patient-reported cosmetic outcomes in patients treated with adjuvant proton-based radiotherapy after breast-conserving surgery [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P4-12-20.

Method to prevent the target volume from escaping out of the field in breast irradiation: Forming a "fall-off margin".

We aimed to obtain data that would enable the selection of the appropriate radiotherapy technique for whole breast irradiation (WBI) based on patients' physical characteristics and to evaluate the benefit of the new fall-off (FO) margin technique. Ten patients with left-sided breast-conserving surgery, treated for breast carcinoma between August 2016 and September 2017, were included. The FO margin was created in five different plans of which two were formed by expanding the target volume out of the skin. The dose evaluation planning was statistically compared by calculating the target volume dosimetric parameters and the doses received by the organs at risk (OARs) for each technique. The volumetric-modulated arc therapy (VMAT) and intensity-modulated radiation therapy plans were considered ideal for WBI homogeneity and conformity indices, while the three-dimensional conformal radiotherapy (3DCRT) plan was considered nonideal. The increase in the breast x-axis length values and equivalent spherical diameter (ESD) dimension decreased the ideal value, whereas the increase in y-axis length values and ESD dimension correlated significantly with the D98 increase. The techniques were significantly correlated with OARs, such as V5, heart max, left anterior descending artery maximum, ipsilateral lung V5 and V20, and contralateral breast V5. Monitor unit values were significantly low in the 3DCRT and VMAT plans. The new FO margin structure will have benefits for practical application because the head designs of linear accelerators and collimators and the target-Jaw/MLC distance are adjacent to the breast tissue, which moves during treatment.

The Physical Dose Difference of Three Types of Implantation on the CTV and Lungs in Interstitial Brachytherapy

Purpose: To study the difference of physical dose of target volume and lungs among actual irregular arrangement multi-needle interstitial brachytherapy plan (AIBP), virtual regular arrangement multi-needle interstitial brachytherapy plan (VRBP) and virtual single needle center point interstitial brachytherapy plan (VSBP). Methods: According to the inclusion criteria: the CTV shape was approximately spherical and multiply needles arrangement was irregular. Thirteen lung cancer patients underwent interstitial brachytherapy were collected. Based on the thirteen CT data sets, the AIBP, VRBP and VSBP were respectively designed, then we collected the dose metrics involving: the minimum dosage received by 95% of the CTV (D95), D90, D80, D50 and D30; the percentage of lung volume receiving a dose of ≥ 5 Gy (V5), V20, V30 and the mean lung dose (MLD); D50 of heart; the maximum dose (Dmax) of spinal cord and the Dmax of ribs. The differences were tested by the two-sample paired (Wilcoxon) signed rank test, a P value less than 0.05 was considered statistically significant. Result: The differences of D95, D90, D80, D50 and D30 of CTV, D50 of heart, Dmax of spinal and Dmax of ribs were not statistical significant (P>0.05) and the V5, V20, V30 and MLD of lungs and ipsilateral lung were statistical significant (P 0.05) except for D30 of CTV (P<0.05) between AIBP and VRBP. Conclusion: In interstitial brachytherapy for lung tumor, the arrangement of implantation needles could influenced the dose distribution in target and lungs. If the CTV shape could be approximately considered to be a spherical and a regular arrangement of multiply needles was difficult to achieve; the lung dose of the AIBP might have no obvious advantage over the VSBP and the VSBP should be worth a try.

Dosimetric Comparison of HDR Brachytherapy and VMAT for Accelerated Partial Breast Irradiation (APBI)

Accelerated partial breast irradiation is an option for some early stage breast cancer patients. The rationale of APBI consists of irradiating only the lumpectomy cavity and a margin that defines a volume where about 95% of the recurrence occurs after surgery. A smaller treated volume means a higher achievable dose per fraction and fewer fractions for a treatment with similar tumor control and toxicity rates. Its utilisation is increasing and a variety of technics can be used. The objective of this study is to compare the dosimetry of APBI plans delivered by high dose rate (HDR) brachytherapy and volumetric modulated arc therapy (VMAT). Twelve patients treated with brachytherapy were retrieved from our database. Eight patients were treated by APBI and received 33 Gy in 9 fractions BID (prescribed at V95≥5 %). Four patients received a boost as part of their treatment and their plans were adjusted to match the APBI prescription. All patients had a pre-implantation CT scan which was used to create VMAT plans following the OPAR protocol. The 30 Gy in 5 fractions prescription dose (prescribed at D100≥95%) was used to yield a biological equivalent dose similar to the HDR prescription. The t-test was used to compare HDR and VMAT dose distributions in terms of Dmax, Dmin, Dmean, and Vdose to targets and organs at risk. Firstly, the cavity’s volumes were similar (VmeanVMAT=17.38±23.95 cc; VmeanHDR=18.40±20.13 cc) but not the CTV (VmeanVMAT=74.45±71.04 cc; VmeanHDR=18.40±20.13 cc). The HDR offers a higher cavity Dmean (DmeanVMAT=30.2±0.4 Gy; DmeanHDR=44.6±3.5 Gy). Small differences (p<0.001) were observed to the conformity index (CIVMAT=1.19±0.07 ; CIHDR=1.12±0.12), the ipsilateral lung V30 (V30VMAT=5.3±3.5 %; V30HDR=1.2±1.5 %) the contralateral breast Dmax (DmaxVMAT=0.622±0.236 Gy; DmaxHDR=0.246±0.163 Gy), and the heart Dmean (DmeanVMAT=0.433±0.193 Gy; DmeanHDR=0.624±0.355 Gy). No statistical difference were found in the dose to the contralateral lung, the contralateral breast Dmean (DmeanVMAT=0.141±0.063 Gy; DmeanHDR=0.047±0.029 Gy), the ipsilateral lung V10 (V10VMAT=12.8±5.6 %; V10HDR=12.7±9.3 %) and the heart Dmax (DmaxVMAT=0.472±0.633 Gy; DmaxHDR=0.324±0.280 Gy). Comparing VMAT and HDR APBI plans is complex due to their intrinsic differences, such as the prescription of the dose. That and the small number of patients included limit the conclusions that can be draw from our data. With that in mind, in this study, HDR brachytherapy allowed a higher dose at the cavity while effectively sparing OAR. Tough, both techniques offer a safe treatment, an adequate dose to the cavity and doses to the OAR well below the constraints, with minor dosimetric differences. Those nuances can guide the choice of a method to use for a specific patient considering some particularities such as the tumor location, the patient’s comorbidities, previous irradiation and the preference of the patient.

Deep Inspiration Breath Hold Technique for Right Breast Irradiation with Supraclavicular and Internal Mammary Lymph Nodes

To reduce the volume of the ipsilateral lung included in the radiation fields for right breast cancer patients receiving radiation to the breast/chest wall and to the supraclavicular and internal mammary lymph nodes (LN). Based on available literature, it is accepted practice to keep the ipsilateral mean lung dose (MLD) below 15 Gy and the V20 to 20% and when internal mammary LN are included to 30% in order to minimize the risk of radiation pneumonitis. Deep inspiration breath hold (DIBH) increases the lung volume and might help in reducing the ipsilateral lung doses when irradiating the nodes. Nine right breast cancer patients were CT simulated twice, first while free breathing (FB) and then simulated using DIBH technique. All nine patients were contoured on both CT scans for the right and left lungs, heart, breast PTV, tumor bed and tumor bed PTV (for patients suitable to receive simultaneous integrated boost), supraclavicular and internal mammary lymph nodes, according to the ESTRO contouring atlas. 3D plans were created for both FB and DIBH scans. We attempted to keep the ipsilateral lung V20 and the MLD as low as possible without compromising breast and node coverage. For all patients the coverage of the breast PTV was kept identical. The MLD was 15.4±3.2 Gy and 11.3±2.8 Gy for the FB and the DIBH plans, respectively. The V20 for the ipsilateral lung was 30%±7 for the FB plans and 20.9%±6.7 for the DIBH plans. For five patients the ipsilateral lung V20 values for the FB plans were above 30% of the ipsilateral lung volume, which is higher than we accept clinically. With DIBH technique we were able to keep the values below 30%. For those patients who had a V20 value of less than 30%, DIBH still reduced this value from an average of 23.9%±2.6 to 15.8%±3.4 of the ipsilateral lung volume. For patients receiving radiotherapy to the right breast with supraclavicular and internal mammary lymph nodes an additional simulation using the DIBH technique should be considered, so as to spare as much dose as possible to the ipsilateral lung.

Use of Moderate Deep Inspiration Breath Hold for Loco-Regional Radiotherapy of Right Breast Cancer including Internal Mammary Lymph Nodes

Loco-regional radiotherapy (RT) of the breast or chestwall may include the internal mammary lymph nodes (IMN). Inclusion of these lymph nodes with a conventional four field technique may give rise to an increased volume of lung in the treated volume. At our centre patients receiving RT to the left breast are usually simulated and treated using a moderate Deep Inspiration Breath Hold (mDIBH) technique in an attempt to reduce dose to the heart. Patients receiving RT to the right breast or chestwall including the IMN may benefit from treatment with the mDIBH technique by reducing doses to organs at risk (OAR). The aim of this work is to compare the dose to OARs for patients receiving loco-regional radiotherapy treatment of the right breast/chestwall including IMN using free breathing and mDIBH CT simulation datasets. Patients who are to receive loco-regional RT to the right breast or chestwall by default are CT simulated while free breathing. The IMN target is contoured by the radiation oncologist. A treatment plan is generated using the free breathing dataset. Review of this treatment plan specifically the volume of right lung receiving 20 Gy (V20) is undertaken. Right lung V20 greater than 35% triggers re-simulation with mDIBH in an attempt to reduce the V20. If a patient is unable to tolerate the mDIBH apparatus, the clinical management may be changed such that IMN may be excluded in the tangent fields thereby ensuring an acceptable dose to the right lung. Simulation and delivery of RT to patients in mDIBH can reduce the ipsilateral lung V20. Resources are impacted by utilizing this treatment technique to the right breast/chestwall loco-regional patient population. Additional resources include the following: additional CT simulation, additional contouring time and treatment plan generation, additional time on the treatment unit to treat in mDIBH, additional cost per fraction for mDIBH consumables. Right breast/chestwall loco-regional RT treatment using a mDIBH technique allows inclusion of the IMN where indicated whilst maintaining acceptable ipsilateral lung doses. In our experience the right lung V20 is reduced by 8% on average for mDIBH technique as compared with the free breathing technique with the reduction in right lung V20 ranging from 3% to 22%. A reduction of 5% in the V20 of both lungs is observed for the mDIBH technique as compared with the free breathing technique. Slight reductions in the mean heart dose are observed for mDIBH as compared with free breathing. When tolerated by patients, the mDIBH treatment enables inclusion of the IMN in the tangential beams where previously the IMN may have been omitted due to ipsilateral lung dose metrics being exceeded. Future direction includes investigating the role of mDIBH for this population as a standard of care considering resources and implementation of a voluntary breath hold delivery technique.

Dosimetric Evaluation of TF-3DCRT, FIF-Forward IMRT and FF Inversely Optimized IMRT for Breast Conserving Treatment

Objective: To compare the dosimetric characteristic of tangential field 3D conformal (TF-3DCRT, TF), field-in-field intensity-modulated (FIF-IMRT, FIF) and fixed-field inversely optimized intensity-modulated Radiotherapy (FFIO-IMRT, FFIO) for breast conserving treatment, and explore the benefit and efficiency for the three techniques. Materials and Methods: TF-3DCRT, FIF-IMRT and FFIO-IMRT treatment plans were analyzed for 16 breast patients (8 right-sided and 8 left-sided) after breast-conserving surgery. The target and organs at risk (OARs) were contoured by the same physician in the CT images. The prescription dose was 50Gy/25f. TF-3DCRT and FIF-IMRT were designed using Varian Eclipse Ver10.0 planning system, and FFIO-IMRT in the planning system of Pinnacle Ver9.6. Treatment plans were compared according to dose volume histogram (DVH) analysis in terms of PTV homogeneity and conformity indices (HI and CI) as well as OARs dose and volume parameters, and the efficiency was also evaluated. Results: In all cases, the treatment plans showed statistically significant difference between TF-3DCRT, FIF and FFIO-IMRT. The MUs were 244.9±8.3MU vs 285.9±20.3MU vs 534.0±56.2MU (p<0.001), the CIs of dose distribution and the target were 0.40±0.12 vs 0.48±0.12 vs 0.57±0.12 (p<0.01), and the HIs were 0.20±0.02 vs 0.13±0.02 vs 0.17±0.02 (p<0.01). Compared with TF and FFIO, FIF-IMRT showed smaller in the dose of D2 and volume of V107 and V110 in the target. FFIO-IMRT generally increased the D mean, V10 and V20 of ipsilateral lung, the D1 of contralateral breast and the mean dose of contralateral lung, heart, esophagus, and spinal cord relative to TF and FIF techniques. Conclusion: In breast-conserving RT, FIF-IMRT improved the overall quality of dose distribution and delivery efficiency, and the patients are most likely to benefit from FIF-IMRT.

Evaluating risk factors of radiation pneumonitis after stereotactic body radiation therapy in lung tumor: Meta-analysis of 9 observational studies.

BackgroundIn this study, we assessed the association of SBRT (stereotactic body radiotherapy) dose and volume with radiation pneumonitis (RP) risk in lung tumor.MethodsRelevant articles were identified up to April 2018, using following databases; Medline, EMBASE, Cochrane Library, and China National Knowledge Infrastructure (CNKI). The pooled OR (odds ratio) with 95% CI (confidence interval) data [mean ± SD (standard deviation)] obtained from different studies was analyzed by statistical analysis using a fixed-effects model or a random-effects model when appropriate.ResultsThe analysis was based on nine observational studies, which were identified based on the study selection criteria. Between RP and non-RP patients, no difference was observed based on age, but significant differences were observed based on planning target volume (PTV), mean ipsilateral lung dose (MLD), total MLD, and V5, V10, V20 and V40 (the percentage of lung volume exceeding 5, 10, 20 and 40 Gy). In addition, PTV >145 cm3, total MLD ≥4.7 Gy, V5 ≥26.8%, V10 >12% and V20 ≥5.8 were associated with RP risk. Overall, the grade assessments of V5 and V20 revealed moderate quality evidence.ConclusionThe present study indicated V5 and V20 as major risk factors for RP after SBRT treatment in lung tumor. In addition, it was observed that lung DVH (Dose Volume Histogram) patterns should be assessed more carefully, while predicting RP incidence after SBRT.

Optimization of tangential fields arrangement in the breast cancer 3D conformal radiation therapy

Introduction: The incidence of breast cancer increases with the rate of 1-2% at the world. Radiation therapy is one of the available choices for breast cancer treatment. The single isocentre half-beam block technique is considered as a standard technique to avoid hot and cold spots within the PTV. The major advantage of half beam technique is that the both contralateral breast and lung are completely spared. Also, using this technique, we don’t have any field matching problem. But, Lateral and medial movement of isocenter in conjunction of supraclavicular and tangential beams affect the divergence of tangential fields. Therefore, opposite tangential field can be parallel either in posterior border or beam central axis. The aim of this study is to compare the dosimetric parameters of three plans for tangential beams arrangement and select the optimal one. Materials and Methods: In this study, we selected 6 patients with breast cancer that underwent breast conserving surgery and considered for radiotherapy. CT simulation of patients were done based on standard protocols and imported to Isogray treatment planning system. Contouring of target volume and organs at risk (OARs) was done by radiotherapist. The tangential fields were considered in three different geometries of parallel in the posterior border with divergence in back jaws, parallel in central axis with divergence in back jaws and Parallel in posterior border without divergence of back jaws (half beam). Dosimetric parameters of each plan for OARs and target volumes extracted from DVHs data and compared statistically using ANOVA one-way repeated measurement test. Results: There was no statistical difference between dosimetric parameters (D95, V95, Dmax, and Dmean) of the target volume in three mentioned plans (P-value = 0.93). Although, there was no statistical difference between mean dose of the ipsilateral lung, the difference of V10 and V20 parameters for this organ is significant (P=0.01). Furthermore, there was no statistical difference in dosimetric parameters of OARs such as contralateral breast, lung, heart, and spinal cord. Conclusion: This study showed that back jaw divergence and arrangement of parallel opposite field can affect the ipsilateral lung dose. The V20 and V10 of ipsilateral lung are two dose constraints parameters in quantitative treatment planning evaluation of breast treatment. Quantitative variations of these parameters with changing the tangential field’s arrangement was significant which depends on the isocenter position and back jaw divergence. The values of these parameters were the highest when tangential fields were arranged as parallel in posterior border with divergence in the back jaw.

Different optimizing strategies based on spot scanning carbon ion therapy for non-small cell lung cancer

Objective To evaluate the dose variation of target coverage and organs at risk (OARs) among four planning strategies using spot-scanning carbon-ion radiotherapy for non-small cell lung cancer (NSCLC). Methods Ten NSCLC patients utilizing gating motion control were selected to receive dose calculation over multiple acquired 4DCT images. Four optimizing strategies consisted of intensity-modulated carbon-ion therapy (IMCT-NoAS), IMCT combined with internal gross tumor volume (IGTV) assigned muscle (IMCT-ASM), single beam optimization (SBO)(SBO-NoAS) and SBO combined with IGTV assigned muscle (SBO-ASM). The initial plan was re-calculated after the 4DCT data were reviewed and then compared with the initial plan in the dosimetry. Results For re-calculation plans with two reviewing CTs, all four strategies yielded similar planning target volume (PTV) coverage. Merely IMCT-NoAS strategy presented with relatively significant variations in dose distribution. Dose variation for OARs between initial and re-calculated plans: for all four strategies, V20 of ipsilateral lung was increased by approximately 2.0 Gy (relative biological effective dose, RBE), V30 of heart was increased by approximately 1.0 Gy (RBE) for both IGTV assigned muscle strategies, whereas decreased by approximately 0.2 Gy (RBE) for both IGTV non-assigned muscle strategies. The maximum dose of spinal cord was changed by 2.5 Gy (RBE). Conclusions Carbon-ion radiotherapy is sensitive to the anatomic motion within the tumors along the beam path. When the tumor motion along the head-foot (H-F) direction exceeds 8 mm, SBO-ASM strategy provides better dose coverage of target. Strategies with IGTV assignment may result in dose overshoot to a position deeper than the initial planning dose distribution. Key words: Lung neoplasms/intensity-modulated carbon-ion therapy; Single beam optimization; Spot scanning carbon-ion; Plan evaluation

Predictors of Local Control and Symptomatic Pneumonitis after Lung SBRT

Stereotactic body radiation therapy (SBRT) is commonly used to treat primary or oligometastatic malignancies in the lung, though most of the available data describing the safety and efficacy of SBRT is for smaller tumors. The purpose of this study was to evaluate the impact of tumor size, among other factors, on local control (LC) and radiation pneumonitis (RP) in patients who received lung SBRT. This retrospective study included patients with primary and metastatic lung tumors treated with SBRT at a single institution from 2012 - 2017. Patients were excluded for prior radiation to the targeted site. All patients underwent 4D-CT simulation with respiratory motion management as needed, and received 3-5 fractions of varying doses prescribed to the PTV on a linear accelerator using a highly conformal IMRT or VMAT technique. Factors evaluated for association with LC included GTV diameter and volume, PTV diameter and volume, volumetric ratio of PTV:GTV, histology, prescription biologically effective dose (BED10), and PTV maximum dose (Dmax). Additional factors evaluated for association with grade 2 or higher (symptomatic) RP included BED3, conformity index (CI), max and mean dose to the heart and central airway, mean lung dose (MLD), and the volume of lung that received at least 2.5 Gy (V2.5), 5 Gy (V5), 13 Gy (V13), 20 Gy (V20), 30 Gy (V30), 40 Gy (V40), and 50 Gy (V50). Analysis included the Mann-Whitney U-test and binary logistic regression. Recursive partitioning analysis was used to determine the optimal dose constraint (OC) predictive of RP. A total of 125 patients with 150 irradiated sites, consisting of 104 (69.3%) primary lung tumors and 46 (30.7%) metastatic lung tumors were included in the study. The median follow-up for survival/toxicity analysis and LC analysis were 13.0 months (IQR 7.0 - 26.0) and 11.5 months (IQR 6.0 – 20.0), respectively. A large range of tumor sizes were represented with a median GTV volume of 6.02 cm3 (IQR 2.19 – 13.79). LC rates at 12 and 24 months post-treatment were 92.6% and 85.9%, respectively. LC was associated with higher BED10 (median 112.5 Gy vs. 92.8 Gy, p=0.02), PTV Dmax (62.5 Gy vs. 53.1 Gy, p<0.01), and PTV:GTV (5.8 vs. 3.5, p=0.01), and there was a trend towards improved LC with smaller tumor diameter (2.8 cm vs. 4.0 cm, p=0.08). RP was associated with higher ipsilateral lung MLD (7.3 Gy vs. 5.3 Gy, p=0.02, OC=8.6 Gy), V2.5 (38.8% vs. 32.0%, p=0.03, OC=30.8%), V5 (32.9% vs. 24.9%, p=0.02, OC=26.8%), V13 (18.8% vs. 13.4%, p=0.03, OC=21.8%), V20 (11.7% vs. 8.0%, p=0.05, OC=14.9%), and heart Dmax (14.4 Gy vs. 6.1 Gy, p=0.02, OC=31.7 Gy). A higher PTV prescription dose, greater dose heterogeneity within the target, and larger PTV margins were significantly associated with improved LC, whereas a weaker association was observed between tumor size and LC. Ipsilateral lung doses were most correlated with RP.

Early Toxicity and Patient Reported Outcomes of Post-Mastectomy Pencil-Beam Scanning Proton Therapy in Women with Immediate Tissue Expander Breast Reconstruction

We previously reported the feasibility of intensity modulated proton postmastectomy radiotherapy (P-PMRT) in women with immediate tissue expander (TE) reconstruction with metallic ports. Our purpose is to analyze early complication rates and patient reported outcomes of this novel treatment approach. All patients underwent mastectomy, axillary staging, and immediate TE placement. P-PMRT was delivered to the chest wall and regional lymphatics, including the internal mammary nodes, to a median dose of 50 Gy (RBE1.1) in 25 fractions with a median of two multifield optimized beams. Second-stage implant or autologous reconstruction took place a minimum of 6 months after the completion of P-PMRT. Adverse effects, patient-reported quality of life (QOL), and breast cosmesis were prospectively-assessed with the CTCAEv4.0, linear analog 10-point scales, and the Harvard Breast Cosmesis Scale, respectively. Between 2015 and 2017, 53 patients underwent mastectomy with immediate TE reconstruction followed by P-PMRT. TE placement was prepectoral in 40 (75%) and subpectoral in 13 (25%). Forty patients (75%) underwent contralateral prophylactic mastectomy with TE reconstruction. Median age was 49 (interquartile range [IQR] 43-57). The tumor was left-sided in 36 (68%), right-sided in 14 (26%), and bilateral in 3 (6%). Chemotherapy [neoadjuvantly (68%) or adjuvantly (15%)] was delivered in 44 (83%) patients, prior to P-PMRT. Median time from surgery to initiation of P-PMRT in the 45 patients who did not receive adjuvant chemotherapy was 59 days (IQR 53 - 71). The median mean heart dose and ipsilateral lung V20 Gy was 0.65 Gy (IQR 0.44 - 0.92) and 13.9 % (IQR 10.3% - 15.3%), respectively. Maximal acute dermatitis grade was 1 in 60%, 2 in 26%, and 3 in 8%. Median follow-up after P-PMRT was 8 months. Six of 56 (11%) irradiated and 1 (3%) non-irradiated implants had been removed due to complications. Other reconstruction complications are shown in the table. QOL was reported as ≥7 in 75% at baseline prior to P-PMRT initiation, with improvement to 83% at 6-months post-treatment. Eighty-six percent of responding patients reported good or excellent cosmesis at 6-month follow-up. Early toxicity and patient reported outcomes of P-PMRT appear favorable in patients with immediate TE reconstruction, although complications remain higher on irradiated vs non-irradiated sides. Intensity modulated P-PMRT is a promising cardiopulmonary sparing modality for women with immediate reconstruction.Abstract TU_2_3341; Table 1ComplicationsIrradiated, n = 53Non-irradiated, n= 43Total19 (36%)2 (5%) Prior to P-PMPT2 (4%)2 (5%) <30 days after completion of P-PMPT2 (4%)0Infection >30 days of P-PMPT to second stage procedure7 (13%)0 After second stage procedure4 (8%)0Implant removal6 (11%)1 (2%)Seroma4 (8%)0Mastectomy skin flap necrosis2 (4%)0Capsular contracture1 (2%)0 Open table in a new tab

Advantages of Continuous Positive Airway Pressure (CPAP) in Left-Sided Breast Radiation Therapy

To assess the utility of continuous positive airway pressure (CPAP) as an adjunct and an alternative to deep inspiration breath hold (DIBH) in the treatment of left-sided breast cancers. Ten patients with left-sided breast cancer whose heart or lung dose constraints were not met during free breathing (FB) or DIBH simulations were included in this study. All patients were simulated using FB, DIBH, CPAP with FB, and CPAP with DIBH. Treatment plans were calculated to cover the breast/chest wall and regional nodes including the supraclavicular fossa, the axilla, and the internal mammary chain. Dose-volume histograms were calculated for heart, ipsilateral lung, and contralateral breast for each simulation. Dosimetric parameters of organs at risk were compared using the Wilcoxon signed-rank test. All simulations met current RTOG acceptable criteria for coverage of chest wall/whole breast and all regional lymph node fields. For all patients, mean heart dose was lower for simulations with CPAP, both with FB (mean 3.4 vs. 7.4, p=0.001) and with DIBH (mean 2.5 vs. 7.4, p=0.006), as compared to FB alone. For 7 out of 8 patients who had unacceptable mean heart doses in the FB and DIBH simulations, CPAP reduced mean heart dose to meet acceptable constraints (≤5Gy). CPAP significantly increased ipsilateral lung volume as compared to FB (mean 1616.8 vs. 1028.7, p=0.005). CPAP with DIBH significantly reduced mean lung dose as compared to both FB (mean 14.4 vs. 20.1, p=0.005) and DIBH alone (mean 14.4 vs. 17.4, p=0.007). Eight out of 10 patients did not meet ipsilateral lung V20 dose constraints (≥35% of lung receiving 20Gy) in either the free breathing or DIBH simulations, but all patients met acceptable criteria using at least one of the CPAP simulations, and 8 out of 10 met lung V20 goal constraints (≤30% of lung receiving 20Gy) in the CPAP with DIBH simulation. Contralateral breast dose was acceptable (<5% of breast receiving 4.1Gy) for all simulations, and CPAP provided no significant dose reductions. Among women with left-sided breast cancer, irradiation of the heart and lung is a major concern due to anatomical proximity of these structures to the target area. Evidence and clinical practice suggest that DIBH may reduce exposure to these non-target tissues, but may be difficult to execute in some patients and may not show acceptable benefits in others. Our results suggest that CPAP may be a viable alternative to DIBH for these patients, and that it may further reduce non-target radiation exposure when used in conjunction with DIBH.

Feasibility Study for 3-Dimensional Treatment Planning with Flattening Filter Free (FFF) Beam and Jawless Dual-Level MLC Collimation for Breast Irradiation

Varian Halcyon system with 6MV flattening filter free (FFF) beam and jawless dual-level MLC collimation is mainly intended for faster IMRT/VMAT delivery. We examined if three- dimensional (3D) treatment planning is feasible for breast irradiation with Varian Halcyon system. Ten left sided breast cancer patients treated with conventional 6MV and 3D field in field (FIF) technique (group1; breast volume < 1000 cc) and 5 patients treated with mixed energy of 6/18 MV and 3D FIF technique (group2; breast volume ≥ 1000 cc) were selected to re-plan with Varian Halcyon system using 3D FIF technique. Treatment plans for both groups with Varian Halcyon system using 3D FIF were generated using a treatment planning system based on reference plan parameters previously used for the treatment. FIF planning process with Halcyon system for each case was similar to conventional 3D FIF technique, and the plan criteria was to achieve the same (or similar) D95% for breast planning target volume (PTV) as the reference plan. Plan quality was assessed using 1) V105% (PTV covered by 105% of prescription dose; dose homogeneity), 2) mean heart dose, 3) maximum heart dose, 4) V20Gy (ipsilateral lung volume covered by 20Gy) and compared to the reference plan for each case. In addition, three tangential beam IMRT breast plans treated with 6/18 MV mixed energies (group3) were re-planned with Halcyon system using IMRT technique. The mean breast volume for group 1 and group 2 were 548 cc (ranges 312-912 cc) and 1172 cc (ranges 1000- 1360 cc), respectively. D95% for PTV was almost identical between reference plan and Halcyon plan for both groups. Other mean dosimetric values with group1 were as following; 1) V105: 5.8 % vs. 8.3 % (p = 0.006), 2) Mean heart dose: 0.88 Gy vs. 1.13 Gy (p = 0.01), 3) Max heart dose: 13.1 Gy vs. 13.5 Gy (p = 0.8), 4) Ipsilateral lung V20 Gy: 8.7 % vs. 10.4 % (p = 0.26) for reference plan and Halcyon plan, respectively. Similarly for group 2; 1) V105: 5.9 % vs.22.2 % (p = 0.03), 2) Mean heart dose: 0.73 Gy vs. 1.18 Gy (p < 0.001), 3) Max heart dose: 7.7 Gy vs. 11.6 Gy (p = 0.2), 4) Ipsilateral lung V20 Gy: 7.0 % vs. 7.4 % (p = 0.85) for reference plan and Halcyon plan, respectively. For the IMRT plan comparison (group 3; breast volume ranges 1255-1687 cc), all 3 reference plans showed better dosimetric results compared to Halcyon plans; 1) V105: 5.2 % vs.18.1 %, 2) Mean heart dose: 0.85 Gy vs. 3.0 Gy, 3) Max heart dose: 10.6 Gy vs. 40.3 Gy, 4) Ipsilateral lung V20 Gy: 5.3 % vs. 14.9 % for reference plan and Halcyon plan, respectively. The 3D treatment planning with Varian Halcyon system is feasible for breast irradiation with comparable dose homogeneity and critical organs dosimetry for breast volume < 1000 cc. However, for large breast volumes the dose homogeneity is significantly worse with both 3D plan and IMRT probably because of having only low energy with non-flattened beam.

Impact of Tumor Size on Local Control and Pneumonitis After Stereotactic Body Radiation Therapy for Lung Tumors

PurposeStereotactic body radiation therapy (SBRT) is commonly used to treat primary or oligometastatic malignancies in the lung, but most of the available data that describe the safety and efficacy of SBRT are for smaller tumors. The purpose of this study was to evaluate the impact of tumor size, among other factors, on local control (LC) and radiation pneumonitis (RP) in patients who received lung SBRT. Methods and materialsThis retrospective study included 144 patients with 100 primary (57.1%) and 75 metastatic (42.9%) lung tumors treated with SBRT between 2012 and 2018. Measurements of tumor size, treatment volume, histology, and radiation dose were evaluated for association with LC. Additional factors evaluated for association with the development of symptomatic RP included volume of the lung, heart, and central airway exposed to relevant doses of radiation. ResultsThe median follow-up time was 15.0 months (interquartile range, 8.0-26.0 months). LC rates at 12 and 24 months posttreatment were 95.1% and 92.7%, respectively. LC at 1 year was higher for tumors <5 cm in diameter than for tumors >5 cm in diameter (98.2% vs 79.8%, respectively; P < .01). On univariate analysis, LC was associated with a smaller gross tumor volume (GTV) diameter (P < .01), GTV volume (P < .01), planning target volume (PTV) diameter (P < .01), PTV volume (P < .01), and larger PTV-to-GTV ratio (P = .04). Tumor histology and treatment intent were not correlated with LC. RP was associated with a higher ipsilateral lung mean lung dose (P = .02), V2.5 (P = .03), V5 (P = .02), V13 (P = .03), V20 (P = .05), V30 (P = .02), V40 (P = .02), and V50 (P = .03), and several similar total lung dose parameters and heart maximum point dose (P = .02). The optimal mean ipsilateral lung dose cutoff predictive of RP was 8.6 Gy. ConclusionsA larger tumor size and smaller PTV-to-GTV ratio was associated with local recurrence of lung tumors treated with SBRT, but ipsilateral lung doses were most associated with symptomatic RP.

Reduction in low-dose to normal tissue with the addition of deep inspiration breath hold (DIBH) to volumetric modulated arc therapy (VMAT) in breast cancer patients with implant reconstruction receiving regional nodal irradiation

BackgroundDespite dosimetric benefits of volumetric modulated arc therapy (VMAT) in breast cancer patients with implant reconstruction receiving regional nodal irradiation (RNI), low dose to the thoracic structures remains a concern. Our goal was to report dosimetric effects of adding deep inspiration breath hold (DIBH) to VMAT in left-sided breast cancer patients with tissue expander (TE)/permanent implant (PI) reconstruction receiving RNI.MethodsTen consecutive breast cancer patients with unilateral or bilateral TE/PI reconstruction who were treated with a combination of VMAT and DIBH to the left reconstructed chest wall and regional nodes were prospectively identified. Free breathing (FB) and DIBH CT scans were acquired for each patient. VMAT plans for the same arc geometry were compared for FB versus DIBH. Prescription dose was 50 Gy in 25 fractions. Dosimetric differences were tested for statistical significance.ResultsFor comparable coverage and target dose homogeneity, the mean dose to the heart reduced on average by 2.9 Gy (8.2 to 5.3 Gy), with the addition of DIBH (p < 0.05). The maximum dose to the left anterior descending (LAD) artery was reduced by 9.9 Gy (p < 0.05), which related closely to the reduction in the maximum heart dose (9.4 Gy). V05 Gy to the heart, ipsilateral lung, contralateral lung and total lung (p < 0.05) decreased on average by 29.6%, 5.8%, 15.4% and 10.8% respectively. No significant differences were seen in the ipsilateral lung V20 Gy or mean dose as well as in the mean contralateral breast/implant dose. However, V04 Gy and V03 Gy of the contralateral breast/implant were respectively reduced by 13.2% and 18.3% using DIBH (p < 0.05).ConclusionCombination of VMAT and DIBH showed significant dosimetric gains for low dose to the heart, lungs and contralateral breast/implant. Not surprisingly, the mean and maximum dose to the heart and to the LAD were also reduced. DIBH should be considered with the use of VMAT in breast cancer patients with implant reconstructions receiving RNI.

P136] The correlation of infrared reflecting marker movement and lung expansion with deep inspiration breath-hold technique for left-sided breast cancer radiotherapy

Purpose This study was to quantify the correlation of the infrared reflecting marker movement and deep inspiration breath-hold (DIBH) lung expansions by setting the infrared reflecting marker below the xiphoid process on the abdominal wall. Methods Ten patients with left breast cancer post operation underwent free-breathing (FB) and DIBH computed tomography (CT) using infrared reflecting marker on the abdominal wall. Therapists coached patient breathing maneuvers before CT scans. The breath-hold level (BHL) was recorded by infrared reflecting marker in the anteroposterior (AP) direction by Real-time Position Management system (RPM) system during CT procedure. Lung diameter in AP direction on both free-breathing (FB) and DIBH images were measured at 4 levels: half upper, upper border of heart, half lower and diaphragm levels of lung. The first CT slice with visible lung tissue and diaphragm level were identified for lung diameter in superioinferior (SI) direction corresponding Z values (slice position). Pearson correlation test was used to examine the correlation significance among BHL, lung AP diameter, lung SI diameter, heart dose, and left lung dose. Results The BHL had strongly positive correlation with lung expansion in SI direction (Pearson correlation r = 0.770). When BHL increased 1.0 cm, the lung expansion in SI direction increased 2.6 cm. Also, moderately positive correlation was revealed between BHL and total lung volume (Pearson correlation r = 0.596). When BHL increased 1.0 cm, the total lung volume increased 414.1c.c. Heart mean dose and maximum dose were strongly negative correlated to BHL according to inverse square law. Weak or no correlation was noted between BHL and lung expansion in AP direction at 4 levels (Pearson correlation r = 0.318, 0.009, −0.105 and −0.238). DIBH plans had lower heart dose (2.64 vs. 1.32 Gy; P = 0.005) and ipsilateral lung V20 (%) relative volume (13.6 vs. 10.9 %; P = 0.007) than FB plans as previous studies. Conclusions Setting infrared reflecting marker below the xiphoid process on the abdominal wall is sufficient for DIBH technique to detect lung expansion in SI direction and decrease the heart dose significantly. Patient couching before CT scans is recommended.

Preliminary toxicity results using partial breast 3D-CRT with once daily hypo-fractionation and deep inspiratory breath hold

BackgroundTo evaluate the clinical outcomes of patients treated with 3D conformal Hypo-fractionated, deep Inspiratory breath-hold (DIBH), Partial breast radiotherapy, termed “HIP.” HIP was implemented to merge the schedule of once-daily breast hypofractionation with partial breast treatment.MethodsWe identified 38 breast cancers in 37 patients from 2013 to 2014 treated at our institution with HIP following lumpectomy for early stage breast cancer. Patients received a hypo-fractionated course (≤ 20 fractions) of once daily radiation to the partial breast (lumpectomy cavity + margin) utilizing DIBH regardless of laterality. Clinical and treatment-related characteristics were obtained, including target volume and organ at risk (OAR) dosimetric characteristics. Patients were followed clinically and with at least yearly mammograms for up to 36 months (range 5–36 months). Acute and late toxicity was scored using the Common Terminology Criteria for Adverse Events (CTCAE) v4.03.ResultsPatients received a median dose of 42.56 Gy in 16 Fractions (Fx) (range 40.05–53.2 Gy; and 15–20 Fx). OAR doses were low, with a mean heart dose of 0.37 Gy, an ipsilateral lung V20 mean of 4%, and a contralateral lung V5 of 1%. Acute toxicity (≤ grade 2) was present in 79% (n = 30) of the cases, with dermatitis being the most common finding (63%). Late grade 1–2 toxicity was present in 42% (n = 16) of the cases, with hyperpigmentation being the most common finding (n = 9). There were no severe acute or late toxicities (≥ grade 3). At a median follow up of 21 months, there were no local, regional, or distant failures.ConclusionsWe report limited toxicity in this low risk cohort of patients with early stage breast cancer treated with HIP, a unique and logical combination of 3-D conformal external beam radiotherapy, moderate hypo-fractionation, and DIBH.

Deep Inspiration Breath Hold Techniques in the Radiotherapeutic Management of Left-Sided Breast Cancer-Active Breathing Coordinator vs. Voluntary Breath Hold

Purpose: Deep Inspiration Breath Hold (DIBH) is a well-established method in reducing their radiation of the heart and lung when treating Left sided Breast cancer with EBRT. There is, however, limited literature comparing different methods of DIBH. The purpose of our study is to compare the efficacy of Active Breathing Co-ordinator (ABC) against Voluntary Breath Hold (VBH). Methods and Materials: 20 patients were selected whom had left sided Breast cancer and underwent EBRT. 10 patients underwent Active Breathing Coordinator (ABC) using specialized Elekta equipment and 10 performed Voluntary Breath Hold (VBH) following the JOVE protocol. All 20 patients had two CT simulation scans: one in FB and the other in DIBH. Treatment plans were generated using a tangential radiation therapy technique. A dosimetric comparison was made between the two plans as per EviQ guidelines. Measurements were collected for Lung V20 (%), Ipsilateral Lung Maximum Depth (cm), Heart V25 (%), Heart (Gy), and Contralateral Breast V3 (%). 9 patients had LAD mean values measured. Results: When using the Mann-Whitney U test to compare ABC to VBH: the VBH technique yielded a median Heart (Gy) of 1.75 (IQR=1.15) and median Contralateral Breast V3 of 0.31% (IQR=0.89%). The ABC technique yielded a median Heart (Gy) of 1.44 (IQR=.60) and for the Contralateral Breast V3 a median of 0.00% (IQR=0.00%). The ABC technique was statistically superior with U=15.000 p =.008 (Heart (Gy)) and U=24.500 p=.035 (Contralateral Breast V3) respectively. None of the other parameters had statistically significant median differences. When using the Wilcoxon signed-rank test to compare DIBH to FB: The VBH technique yielded a median Ipsilateral Lung max (cm) of 2.3, Ipsilateral Lung V20 of 13.92%, Lung V20 of 6.45%, Heart V25 of 2.41%, Heart (Gy) of 2.7, and LAD mean (Gy) of 23.4. The DIBH technique was statistically superior in these parameters and yielded a median Ipsilateral Lung max (cm) of 2.6 (Z=-3.072 p=.002), Ipsilateral Lung V20 of 12.33% (Z=-2.576 p=.01), Lung V20 of 5.84% (Z=-2.296 p=.01), Heart V25 of 0.26% (Z=- 3.921 p<.001), Heart (Gy) of 1.43 (Z=-3.921 p<.001), and LAD mean (Gy) of 7.7 (Z=-2.201 p=.028). Conclusion: ABC is a superior breath hold technique when compared to VBH and will yield lesser long-term cardiac complications. However, it is a more expensive modality and can be poorly tolerated by patients. Surrounding structures incur significantly less radiation when using DIBH than FB which is consistent with previous studies in the literature. Further studies are required to confirm this data.

A Six-year Experience of Using Moderate Deep Inspiration Breath-Hold for Patients With Early-Stage Breast Cancer and Dosimetric Comparison

We present our six-year experience of using moderate deep inspiration breath-hold (mDIBH) with an active breathing control (ABC) device for patients with early-stage breast cancer and dosimetric comparison to evaluate the benefit of mDIBH on the heart, lung, and liver. We retrospectively reviewed all patients with newly diagnosed early, node-negative breast cancer treated between November 2010 and October 2016. Among the 312 patients included in this study, 94 patients were treated with mDIBH and 218 patients were treated with free breathing. Dosimetric analysis was performed to compare dose distribution in the heart, lung, and liver between the two treatment groups. All planning and dosimetric evaluations were performed on the treatment planning system. The calculated DVH was compared between the non-ABC and ABC groups. The chi-square test was used to compare the distribution of stage and tumor site between the two groups. The independent samples t-test was used to compare the remaining parameters between the two groups. Analysis was performed using SPSS v.19. There was no significant difference in the distribution of stage (p=0.130), tumor site (p=0.068), age (p=0.065), volume of CTV (p=0.119), and volume of heart (p=0.851) between the non-ABC and ABC groups. For all 312 patients, there was a significantly lower ipsilateral lung V5 (p<0.001), ipsilateral lung V10 (p<0.001), ipsilateral lung V20 (p<0.001), mean ipsilateral lung dose (p<0.001), whole lung V5 (p<0.001), whole lung V10 (p<0.001), whole lung V20 (p<0.001), mean whole lung dose (p<0.001), heart V10 (p<0.001), heart V30 (<0.001), heart V40 (<0.001), and mean heart dose (<0.001) in the ABC group. For 158 patients with a left-sided breast tumor, significantly lower ipsilateral lung V5 (p=0.004), ipsilateral lung V10 (p<0.001), ipsilateral lung V20 (p<0.001), mean ipsilateral lung dose (p<0.001), heart V10 (p<0.001), heart V30 (p<0.001), heart V40 (p<0.001), and mean heart dose (p<0.001) were observed in the ABC group. For 154 patients with a right-sided breast tumor, significantly lower ipsilateral lung V5 (p=0.006), ipsilateral lung V10 (p<0.001), ipsilateral lung V20 (p<0.001), mean ipsilateral lung dose (p<0.001), heart V10 (p<0.001), heart V30 (p=0.012), heart V40 (p=0.046), mean heart dose (p<0.001), liver V30(p<0.001), and mean liver dose (p<0.001) were observed in the ABC group. For early-stage breast cancer patients, mDIBH reduces not only the heart dose but also the lung and liver doses. Our study showed that mDIBH can significantly reduce the heart and lung dose for left-sided breast cancer patients and also reduce the liver, lung, and heart dose for right-sided breast cancer patients. The routine integration of mDIBH using an ABC device may decrease radiation-induced toxicity in the heart, lung, and liver.