Faculty Bibliography

PURPOSE/OBJECTIVE:The omission of radiation therapy (RT) in elderly women with stage 1 estrogen-receptor positive (ER+) breast cancer receiving endocrine therapy (ET) is an acceptable strategy based on randomized trial data. Less is known about the omission of ET +/- RT. PATIENT AND METHODS/METHODS:We analyzed SEER-Medicare data for 13,321 women ≥ 66 years with stage I ER+ breast cancer from 2007-2012 who underwent breast conserving surgery. Patients were classified into 4 groups: 1) ET+RT (reference) 2) ET alone (ET), 3) RT alone (RT) and 4) neither RT nor ET (NT). Second breast cancer events (SBCE) were captured using Chubak's high-specificity algorithm. We used Chi-square tests for descriptive statistics, multivariable multinomial logistic regression to estimate relative risks (RR) of undergoing a treatment, and multivariable, propensity-weighted competing-risks survival regression to estimate standardized hazard ratio (SHR) of SBCE. We set significance at p≤0.01. RESULTS:Most women underwent both treatments, with 44% undergoing ET+RT, 41% RT, 6.6% ET, and 8.6% NT but practice patterns varied over time: from 2007-2012, RT decreased from 49% to 30%, whereas ET and ET+RT increased (ET: 5.4% to 9.6%; ET+RT: 38% to 51%). Compared to patients 66-69 years, patients 80-85 years were more likely to receive NT (OR=8.9), RT (OR=1.9), or ET (OR=8.8) vs. ET+RT (p<0.01).3% of subjects had an SBCE (2.2% ET+RT, 3.0% RT, 3.2% ET, 7.0% NT). Relative to ET+RT, NT and ET were associated with higher SBCE (NT: SHR 3.7, p<0.001; ET: SHR 2.2, p=0.008)), whereas RT was not associated with a higher SBCE (SHR 1.21, p=0.137). Clinical factors associated with higher SBCE were HER2 positivity and pT1c (SHR 1.7, p=0.006). CONCLUSIONS:Treatment with RT alone in older women with stage I ER+ disease is decreasing. RT alone is not associated with an increased risk for SBCE. By contrast, NT and ET are both associated with higher SBCE in multivariable analysis with propensity weighting. Further study of the omission of endocrine therapy in this patient population is warranted.

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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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): The supraclavicular (SCV), medial axillary and internal mammary nodes (IMNs) are not typically resected in breast cancer patients (pts). The optimal local therapy of pts with nodal disease in these regions is not well-studied. We aim to evaluate outcomes of breast cancer patients with unresected nodal disease. MATERIALS/METHODS: We identified 79 pts at our institution from 2016- 2021 with unresected nodal disease in the axilla, SCV and/or IMNs defined as grossly enlarged nodes on CT, MRI or PET scan +/- biopsy confirmation. Pts were treated with breast/chest wall and regional nodal irradiation with an additional boost to the unresected nodal region. Distant failure (DF) and local-regional failure (LRF) were assessed. Kaplan-Meier was used to calculate disease-free survival (DFS), overall survival (OS) and local recurrence-free survival (LRFS). Logistic regression was used to identify variables associated with worse DFS. Acute and late toxicity of RT were evaluated.
RESULT(S): 33% of pts were treated with breast-conserving surgery, 65% with mastectomy and all had axillary surgery (81% ALND, 19% SLNB). 47% of pts received IMN boost (IMN), 40% axillary/SCV boost (axSCV) and 15% both IMN and axSCV boost (IMN/axSCV). Most had cT2-3 (72%), hormone receptor positive (75%), and HER-2 negative disease (84%). 57% of axSCV had cN3A disease; 84% of IMN and 83% of IMN/axSCV had cN3b disease. 7% of axSCV and 17% of IMN/axSCV had cN3c disease. Most pts received chemotherapy (97%). Median nodal boost dose was 10 Gy (range 10-20 Gy), with 17% axSCV, 22% IMN, and 17% IMN/axSCV receiving 14-20 Gy. Rates of acute and late grade 3 toxicity did not differ by boost location (acute: IMN: 20%, axSCV: 11% and IMN/axSCV 20%, P=0.559; late: IMN: 40%, axSCV: 25%, IMN/axSCV: 40%, P=0.630) nor by boost dose (10 Gy vs 14-20 Gy). There were no grade 4+ toxicities. With a median follow up of 30 months, the 3-year LRR, DFS, and OS was 94.5%, 86.3% and 93.8% respectively. Crude rates of failure for the entire group were 13.9% (10.1% DF; 3.8% DF+LRF). Rates of failure by boost group were axSCV: 13.3% (10% DF; 3.3% DF+LRF), IMN: 5.4% (2.7% DF, 2.7% DF+LRF), IMN/axSCV 41.7% (33.3% DF, 8.3% DF+LRF). There were no LRFs without DFs. Median time to failure was 23 months (IQR 18-34). On univariate analysis clinical tumor size (cT) and IMN/axSCV vs. IMN or axSCV alone was associated with worse DFS (HR: 9.78 95% CI 2.07-46.2, P=0.004 and HR: 9.49 95% CI 2.67-33.7, P=0.001). On multivariate analysis, cT approached significance (HR 6.15; 95% CI 0.95-39.8, P=0.05). IMN/axSCV vs. IMN or axSCV alone retained significance (HR 4.80; 95% CI 1.27-18.13, P=0.02). The difference between the axSCV vs. IMN group was not significant.
CONCLUSION(S): In this population of pts with unresected nodal disease, boost RT to radiographically positive LN regions can be safely delivered with low rates of grade 3+ toxicity. The majority of failures were distant with no isolated LRFs. Failures were highest in the IMN/axSCV group (~40%). Further treatment escalation is necessary for these pts.
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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: 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: Multi-isocentric treatment delivery for CSI and TBI poses specific challenges for treatment delivery. We have developed a software tool to streamline all aspects of delivery for therapists and physicists at the machine, as well as to inform attending physicians of setup variability and image residuals at different locations.
Method(s): Our institution delivers VMAT-based CSI and TBI with up to 3 and 7 isocenters, respectively. A software tool was developed to assist with treatment delivery including initial patient setup, patient imaging, automatic calculation of the optimal global shift based on each isocenter's ideal shift, and automatic calculation of each isocenter's couch coordinates. Initial treatment couch coordinates are queried via the Eclipse scripting API. The global shift was calculated prioritizing the head isocenter for CSI treatments and the chest isocenter for TBI treatments by first maximizing residual tolerance at any other location prior to accepting any residual deviation at these locations. Maximum residuals tolerance was determined based on target margins, plan uncertainty and as per physician instructions. Delivery parameters are reported to a document uploaded to ARIA via API.
Result(s): The developed tool was employed for 11 cases. The software tool replaced the need for plan shift comments or instructions for therapists. In particular, its use eliminated the need to provide isocenter shifts to therapists by directly providing final couch parameters for treatment, greatly reducing the risk of delivery errors. The software effectively informed the therapists if any expected tolerance was surpassed, triggering a patient setup evaluation.
Conclusion(s): The described software tool is a core component to our multi-isocenter treatment programs and has streamlined delivery of these complex techniques that would otherwise require complicated instructions, including multiple shifts and on-the-fly calculations of optimal image alignment based on multiple imaging locations. This has substantially reduced the possibility of delivery errors

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