Faculty Bibliography

PURPOSE/OBJECTIVE(S): Definitive radiation therapy (RT) is a curative treatment modality for gastric MALT. Reducing radiation dose to organs at risk (OAR) is imperative for patients with curative disease and excellent long-term prognosis. Advanced RT planning with DIBH and/or IMRT is available to improve the therapeutic ratio of RT by minimizing dose to normal tissues while maintaining adequate target coverage. We aimed to compare dosimetric parameters when using different radiation planning and delivery techniques in patients with gastric MALT. MATERIALS/METHODS: After institutional review board approval, we identified adult patients (age >= 18 years) with biopsy-proven gastric MALT who were treated at our institution from 2010 to 2020. Each patient underwent two simulation CT scans: free breathing (FB) and DIBH. Four plans were generated for each patient including DIBH-IMRT, DIBH-3DCRT, FB-IMRT, and FB-3DCRT with a prescribed dose of 30 Gy in 20 fractions. The CTV was defined as the entire stomach including the gastroesophageal junction to the pylorus. The PTV included a 1 to 1.5 cm expansion from the CTV. Paired t-tests were used to compare mean calculated dose values for each OAR based on treatment technique.
RESULT(S): Our cohort consisted of 8 patients (6 male, 2 female) with a median age 62.5 years (39 to 83 years). Compared to 3D-CRT, IMRT was associated with significantly decreased heart dose for both DIBH (Dmean 354.7 vs 440.5 cGY, P=0.029) and FB (Dmean 521.2 vs 699.6 cGY, P=0.006). IMRT was also associated with decreased dose to the left ventricle (LV), left anterior descending artery (LAD), liver, and lungs compared to 3D in both FB and DIBH. For IMRT plans, DIBH was associated with significantly lower heart V30 and V20 and a trend towards significance for lower heart Dmean (354.7 vs 521.2 cGY, P=0.059) in comparison to FB. For 3D plans, DIBH was associated with a lower heart V30 and V20, and a higher lung V20, V10, and V5 in comparison to FB.
CONCLUSION(S): Both IMRT and DIBH represent modalities for reducing heart dose in gastric MALT patients receiving definitive RT. IMRT also reduces LV, LAD, liver and lung dose regardless of technique used to account for respiratory motion whereas DIBH was not associated with reduced doses to the LAD, kidney, or liver.
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PURPOSE/OBJECTIVE(S): TBI is a backbone of many conditioning regimens for hematopoietic stem cell transplants but can lead to both acute and late toxicity including radiation-induced interstitial pneumonitis. The incidence of idiopathic pneumonia syndrome (IPS) after TBI-based myeloablative conditioning regimens ranges from 7% to 35%. The purpose of this study is to implement image guided volumetrically modulated technique (VMAT) for TBI with the goal of lung sparing and improved target coverage. MATERIALS/METHODS: Nine patients have been treated using image-guided VMAT based TBI at our institution as part of a single-arm phase 2 clinical trial for patients undergoing myeloablative conditioning regimens. The trial was approved by our internal review board (IRB) in September 2020 and aims to accrue 15 patients within one year. All patients enrolled in the trial have signed informed consent. The primary endpoints of the study are the following dosimetric constraints: V100% >= 90%, D98% >= 85% of Rx dose for the planning target volume (PTV), and a mean lung dose < 9 Gy. PTV is defined as the body contour cropped 5 mm from the surface and excluding lungs and kidneys but extended 3 mm into these organs. Additional secondary dosimetric endpoints include mean dose to each individual kidney < 11 Gy, and maximum dose to 2cc of the entire body < 130% of Rx dose. Clinical endpoints include the occurrence of IPS in the first 100 days after transplant, occurrence of acute graft versus host disease (GVHD), transplant related mortality or mortality in the first 100 days following transplant.
RESULT(S): Patients were treated to 12 Gy in 8 BID fractions (n=6) or 13.2 Gy in 8 BID fractions (n=3) over four consecutive days. All patients were able to complete treatment to the prescribed dose as planned. All patient plans met dosimetric constraints of the study. The median PTV V100% was 93.2% of Rx dose (Max: 95.6%, Min: 92.1%), the median PTV D98% was 90.2% of Rx dose (Max: 94.3%, Min: 88.3%), and the median lung dose mean was 7.63 Gy (Max: 7.94 Gy, Min: 7.29 Gy). In addition, individual kidney mean doses were < 11 Gy, and body maximum dose (D2cc) was < 130% of Rx dose for all patients. At this time, only one patient (12 Gy treatment) has reached the 100 day post-transplant follow-up with the following findings: no relapse on bone marrow biopsy, no pneumonitis, resolved acute GVHD overall grade 1 (skin: 1, GI: 0, Liver: 0), resolved dermatitis (grade 1), resolved vomiting (grade 2), ongoing diarrhea and nausea (grade 1, previously grade 2).
CONCLUSION(S): Our initial results indicate that primary and secondary dosimetric endpoints were achievable for all protocol patients treated thus far. As the trial progresses, secondary clinical endpoints at 100 day follow-up will be analyzed to evaluate occurrence of IPS, survival, and treatment related toxicities.
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BACKGROUND:Young women with ductal carcinoma in situ (DCIS) represent a unique cohort given considerations for future risk reduction and treatment effects on fertility and quality of life. We evaluated national patterns of care in the treatment of young women and the impact of those treatments on overall survival (OS). METHODS:Women younger than 50 years of age diagnosed with pure DCIS from 2004 to 2016 in the National Cancer Database (NCDB) were identified. Clinical, demographic, and choice of local therapy are summarized and trended over time. OS was analyzed using Cox proportional hazard models. RESULTS:A total of 52,150 women were identified, and the most common surgical treatment was breast-conservation surgery (BCS; 59%). Bilateral mastectomy (BM) increased in frequency from 2004 to 2016 (11-27%; p < 0.001). In women < 40 years of age, BM (39%) surpassed BCS (35%) in 2010 with a continued upward trend. On multivariable analysis, no OS benefit of BM (hazard ratio [HR] 0.99, p = 0.90) or unilateral mastectomy (UM; HR 0.98, p = 0.80) was observed when compared with BCS + radiation therapy (RT). Inferior OS was seen with BCS, Black race, estrogen receptor (ER)-negative, and tumor ≥ 2.5 cm (p ≤ 0.006). In ER+ patients, there was a significant difference in endocrine therapy (ET) use between BM (11%), UM (33%), and BCS (28%) compared with BCS + RT (64%, p < 0.001). CONCLUSION/CONCLUSIONS:The use of BM for DCIS is increasing in younger patients and now exceeds breast-conservation approaches in women < 40 years of age with no evidence of improved OS. Among ER+ patients, the rates of ET are lower in the BM, UM, and BCS-alone groups compared with BCS + RT.

BACKGROUND:) that evaluates recurrence risk has been developed and validated. We evaluated the impact of DCISionRT on clinicians' recommendations for adjuvant RT. METHODS:The PREDICT study is a prospective, multi-institutional, observational registry in which patients underwent DCISionRT testing. The primary endpoint was to identify the percentage of patients where testing led to a change in RT recommendations. RESULTS:Overall, 539 women were included in this study. Pre DCISionRT testing, RT was recommended to 69% of patients; however, post-testing, a change in the RT recommendation was made for 42% of patients compared with the pre-testing recommendation; the percentage of women who were recommended RT decreased by 20%. For women initially recommended not to receive an RT pre-test, 35% had their recommendation changed to add RT following testing, while post-test, 46% of patients had their recommendation changed to omit RT after an initial recommendation for RT. When considered in conjunction with other clinicopathologic factors, the elevated DCISionRT score risk group (DS > 3) had the strongest association with an RT recommendation (odds ratio 43.4) compared with age, grade, size, margin status, and other factors. CONCLUSIONS:DCISionRT provided information that significantly changed the recommendations to add or omit RT. Compared with traditional clinicopathologic features used to determine recommendations for or against RT, the factor most strongly associated with RT recommendations was the DCISionRT result, with other factors of importance being patient preference, tumor size, and grade.

PURPOSE/OBJECTIVE:Autoimmune connective tissue disease (CTD) has historically represented a relative contraindication to breast conservation (BC) among patients with early stage breast cancer. Controversy exists regarding hypofractionated radiotherapy (RT) among patients with CTDs. We evaluated acute and late toxicity in patients with breast cancer and CTD treated with BC. METHODS AND MATERIALS/METHODS:Of 1983 patients treated with BC from 2012 to 2016, we identified 91 patients with autoimmune disease (AD). Each patient was matched to a control without AD based on age, RT field and fractionation. RT toxicity and clinician-rated cosmesis were compared between cases and controls. Overall survival, disease-free survival, and local recurrence free survival were estimated using the Kaplan-Meier method. RESULTS:Median follow-up was 49.9 months for cases and 53.0 months for controls. 67% of cases and controls were treated with hypofractionated RT. There was no difference in grade 2/3 acute toxicity between cases and controls (26.4% vs. 16.5%, p=0.148, respectively). There was a significantly higher rate of grade 2/3 late toxicity among cases (25.8% vs 12.1%, p=0.049). Active AD at the time of RT increased the rate of grade 2/3 late toxicity compared to controls (41.7% vs. 11.4%, p=0.018). Among patients treated with hypofractionated RT, there was no difference in acute or late grade 2/3 toxicity between cases and controls (acute: 13.1% cases vs. 11.5% controls, p=1; late: 11.9% in cases vs 13.1% in controls, p=1). Rate of good/excellent clinician- rated cosmesis was similar between groups (92.9% vs 98.9%, p=0.142). CONCLUSIONS:In the largest matched case control study of patients with CTD treated with conventional and hypofractionated RT, we demonstrate low rates of radiation toxicity, with good to excellent clinician-rated cosmesis. There was increased late toxicity in cases, especially in patients with active AD at time of RT. There was no increase in acute or late toxicity in the patients treated with hypofractionation.

Purpose: To investigate the effect of patient positioning in Volumetric Modulated Arc Therapy (VMAT) for Total Body Irradiation (TBI) given the use of multiple isocenters, by simulating offsets in patient positioning and evaluating changes to planned dose distributions.
Method(s): VMAT treatment plans for seven TBI patients treated as part of a prospective stage II clinical trial were evaluated. Plan uncertainties were calculated by introducing 5mm and 10mm translational shifts to the plans' isocenters in the lateral (x), vertical (y), and longitudinal (z) directions. Dose distributions were then re-calculated in the treatment planning system (Eclipse), in order to evaluate dosimetric robustness to one global imaging shift at treatment. Differences in target volume (PTV) coverage and doses to organs at risk were evaluated based on four parameters: lung mean dose, PTV-V100%, PTV-D98%, and kidney mean doses.
Result(s): Lung mean dose increased an average of 8.2cGy, 4.4cGy, and 3.3cGy when shifted 5mm in the x, y, z directions (respectively) across seven patients; 33.2CGy, 18.5cGy, 18.3cGy for 10mm shifts in x, y, z. Target coverage V100% decreased an average of 0.3%, 0.03%, 0.1% for 5mm shifts, and 1.1%, 0.8%, 0.4% for 10mm shifts in x, y, z. D98% decreased 0.9%, 0.3%, 0.3% when shifted 5mm; 3.5%, 2.1%, 1.0% when shifted 10mm in x, y, z. Mean dose to the left kidney increased 6.6cGy, 9.7cGy, 2.8cGy for 5mm, and 28.1cGy, 32.7cGy, 18.0cGy for 10mm shifts in x, y, z. Right kidney mean dose increased 11.9cGy, 8.9cGy, 3.1cGy for 5mm, and 36.5, 30.5, 19.8cGy for 10mm.
Conclusion(s): Though small in relation to total dose, the largest increase in mean lung dose and decrease in coverage was seen with lateral shifts as compared to vertical or longitudinal shifts. These results support the use of an approach with preferential alignment to the chest region (lung-sparing), as long as residual imaging alignment outside the chest is kept below 10mm. Jose Teruel has received honorarium from Varian Medical Systems

Purpose: In-vivo dosimetry for conventional total body irradiation (TBI) utilize point detectors placed along the patient surface to confirm the delivered dose matches prescription dose. However, in the volumetrically modulated arc therapy (VMAT) approach to TBI, the electronic portal imager device (EPID) can be utilized to acquire a 2-dimensional transmission fluence plane. This work explores the relationship between patient setup accuracy with transit in-vivo dosimetry.
Method(s): A total of 192 fields were investigated. Each VMAT plan consisted of four isocenters: head, chest, abdomen, and pelvis. Prior to treatment, the patient was imaged at the head, pelvis, and chest. Optimal couch shifts were determined for each isocenter under image guidance. The optimal IGRT shifts were determined using an inhouse application that minimized dose deviation using criteria established through plan uncertainty analysis performed in Eclipse. Translational couch residuals were recorded and defined as the difference in the global shift calculated and the optimal couch position with shifts. Transit dosimetry was measured per arc, and analyzed using SNC PerFRACTION with a gamma criteria of 10%/5mm, 5%/5mm, and 5%/7mm.
Result(s): Based on plan uncertainty analysis, clinical threshold for couch residuals were set to 7 mm (5 mm for chest isocenter) as there would be minimal impact on target coverage and organ sparing at those levels. Transit dosimetry showed that the average pass rate across all fields was 99.6%, 97.0%, and 99.2% for 10%/5mm, 5%/5mm, and 5%/7mm gamma criteria, respectively. Pearson correlation tests showed that there was weak correlation between gamma criteria and couch residuals. At stringent 3%/5mm gamma criteria, moderate correlation was found between lateral couch residuals for the head and chest and the head and chest arc analysis.
Conclusion(s): Transit dosimetry showed high pass rates using our couch residual tolerances, which confirmed the plan uncertainty analysis performed during treatment planning

Purpose: Patients receiving myeloablative total body irradiation (TBI) doses >= 12Gy are at risk of developing interstitial pneumonitis. At our institution, TBI transitioned from extended distance opposed Laterals to image-guided VMAT, in an effort to improve coverage while sparing lungs and kidneys. This work presents a dosimetric comparison between 3D Laterals and VMAT.
Method(s): Nine patients were treated with VMAT as part of an ongoing phase II single-arm clinical trial. VMAT patients were CT-simulated supine, with thermoplastic masks for head/neck, chest/abdomen/pelvis and feet. VMAT planning (12Gy (n=6) or 13.2Gy (n=3) in 8-BID fractions) utilizes 6MV multi-isocentric arcs and AP/PA beams to treat the upper and lower body, respectively. Ten 3D Lateral patients were CT-simulated supine with arms positioned/immobilized for lung shielding, with rice compensation between legs/feet. Laterals plan (12Gy in 8-BID fractions) uses 15MV, beam spoiler, head compensation, and subfields to maintain coverage and mean-lungs dose <10.5Gy. Target (Body-5mm, extending 3mm into lungs and kidneys for VMAT; Body-2cm for Laterals) coverage was evaluated at V100%, and D98% (percentage of Rx). Absolute dose to lungs and kidneys were reportedResults: Median Target V100% and D98% for VMAT was 93.2% (Range: 95.6% to 92.1%) and 90.2% (94.3% to 88.3%), whereas for Laterals V100% and D98% was 57.3% (66.5% to 46.3%) and 80.6% (75.5% to 84%). The median Lung mean dose was 7.6Gy (7.3Gy to 7.9Gy) for VMAT. The median mean dose to kidney was 10.4Gy (10.1Gy to 10.7Gy) for VMAT, and 12.5Gy (11.9Gy to 13.5Gy) for Laterals.
Conclusion(s): We have established a VMAT-TBI program for patients requiring myeloablative irradiation. Improvement in target coverage is demonstrated by V100% and D98%, while reducing the mean dose to the lungs significantly from 10.5Gy to 8Gy