Faculty Bibliography

Purpose/Objective(s): Stereotactic body radiotherapy (SBRT) is increasingly utilized in the treatment of spine metastasis. Preliminary data suggest that higher doses may improve local control, but may also increase risk of toxicity including vertebral compression fracture (VCF). Our single institution study recently found that a minimum dose of at least 21 Gy to 80% of planning target volume (PTV D80%) in 2 fractions was associated with higher risk of VCF. The purpose of this study is to assess this variable's relationship with local failure (LF) and VCF in an international, multi-institutional cohort. Materials/Methods: Patients with radiation naive solid tumor spine metastases treated with SBRT at 5 international institutions from 2010 - 2020 were included. Patients with surgical stabilization were excluded. LF was defined per spine response assessment in neuro-oncology criteria. Variables examined included spinal instability neoplastic score (SINS) factors and dosimetric/volumetric characteristics of radiation planning. All fractionation scheme doses were converted to 2-fraction equivalent doses (2fxED) using the linear quadratic model with an alpha/beta of 3 and used in analyses of PTV D80%. Univariate and multivariate Cox proportional hazard models for LF and VCF were constructed using the Fine and Gray competing risk method.
Result(s): 357 vertebral segments from 234 patients were treated with SBRT. Common primary tumor types were prostate (n = 50, 22%), non-small cell lung cancer (n = 42, 18%), breast (n = 35, 15%), and kidney (n = 25, 11%). Most (n = 199 pts, 242 segments) were treated with 2 or 3 fractions with a median prescription dose of 24 Gy or 27 Gy, respectively (range: 14-45 Gy in 1-5 fractions). Median follow was 21.1 months (0.6-88.4 mo). LF was 12.6% and 18.1% at 1- and 2-years, respectively. Variables associated with increased LF on univariate analysis were lower PTV D80% at 2fxED <=21 Gy (HR 0.36, 95% CI 0.20-0.65, p = 0.001) and lower prescription dose BED3 (HR 0.98 as continuous variable, CI 0.97-0.99, p = 0.03). On multivariate analysis, only PTV D80% at 2fxED <=21 Gy remained associated with increased risk of LF (HR 0.46, CI 0.24-0.85, p = 0.01). VCF incidence was low, at 4.2% and 6.7% at 1- and 2-years, respectively. Higher SINS was predictive of VCF (HR 1.22, CI 1.1-1.36, p <0.001). Patients with higher PTVD80% at 2fxED>21 Gy had a higher, albeit non-significant, risk of VCF (HR 3.30, CI 0.80-13.6, p = 0.10), consistent with our previous single institution study.
Conclusion(s): This multi-institutional, international study suggests that a PTV D80% at 2fxED <=21 Gy may increase the risk of LF, while >21 Gy may increase the likelihood of VCF. Prospective studies are needed to further explore this complex relationship and identify the dose/fractionation schedule that best balances local control with normal tissue toxicity including VCF.
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We present the case of a 56-year-old female with a diagnosis of acute T-cell lymphoblastic leukemia who received myeloablative conditioning for bone marrow transplant with total body irradiation (TBI) using volumetric modulated arc therapy (VMAT) to the upper body and anterior-posterior/posterior-anterior (AP/PA) open fields to the lower body followed by hematopoietic stem cell transplant. Her clinical course was complicated by high-grade pulmonary toxic effects 55 days after treatment that resulted in death. We discuss the case, planning considerations by radiation oncologists and radiation physicists, and the multidisciplinary medical management of this patient.

BACKGROUND:Computerized surgical planning (CSP) in osseous reconstruction of head and neck cancer defects has become a mainstay of treatment. However, the consequences of CSP-designed titanium plating systems on planning adjuvant radiation remains unclear. METHODS:Two patients underwent head and neck cancer resection and maxillomandibular free fibula flap reconstruction with CSP-designed plates and immediate placement of osseointegrated dental implants. Surgical treatment was followed by adjuvant intensity modulated radiation therapy (IMRT). RESULTS:Both patients developed osteoradionecrosis (ORN), and one patient had local recurrence. The locations of disease occurred at the areas of highest titanium plate burden, possibly attributed to IMRT dosing inaccuracy caused by the CSP-designed plating system. CONCLUSION/CONCLUSIONS:Despite proven benefits of CSP-designed plates in osseous free flap reconstruction, there may be an underreported risk to adjuvant IMRT treatment planning leading to ORN and/or local recurrence. Future study should investigate alternative plating methods and materials to mitigate this debilitating outcome.

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.

OBJECTIVE:Neoadjuvant chemoradiation (NA-CRT), followed by resection of high-risk soft tissue sarcoma (STS), may offer good disease control and toxicity outcomes. We report on a single institution's modern NA-CRT experience. MATERIALS AND METHODS/METHODS:Delay to surgical resection, resection margin status, extent of necrosis, tumor cell viability, presence of hyalinization, positron emission tomography (PET)/computed tomography data, and treatment toxicities were collected. Using the Kaplan-Meier survival analysis, 5-year overall survival, disease-free survival, distant metastasis-free survival, and local control (LC) were estimated. Clinicopathologic features and PET/computed tomography avidity changes were assessed for their potential predictive impact using the log-rank test. RESULTS:From 2011 to 2018, 37 consecutive cases of localized high-risk STS were identified. Twenty-nine patients underwent ifosfamide-based NA-CRT to a median dose of 50 Gy before en bloc resection. At a median follow-up of 40.3 months, estimated 5-year overall survival was 86.1%, disease-free survival 70.2%, distant metastasis-free survival 75.2%, and LC 86.7%. Following NA-CRT, a median reduction of 54.7% was observed in tumor PET avidity; once resected, median tumor necrosis of 60.0% with no viable tumor cells was detected in 13.8% of the cases. Posttreatment resection margins were negative in all patients, with 27.6% having a margin of ≤1 mm. Delays of over 6 weeks following the end of radiation treatment to surgical resection occurred in 20.7% cases and was suggestive of inferior LC (92.8% vs. 68.6%, P=0.025). CONCLUSIONS:This single-institution series of NA-CRT demonstrates favorable disease control. Delay in surgical resection was associated with inferior LC, a finding that deserves further evaluation in a larger cohort. LEVEL OF EVIDENCE/METHODS:Level III-retrospective cohort study.

OBJECTIVE:To characterize immune checkpoint inhibitor-associated diabetes mellitus (ICI-DM) in a single-institution case series. RESEARCH DESIGN AND METHODS:Retrospective chart review of 18 patients with new-onset ICI-DM following anti-programmed cell death protein 1 (PD-1)/anti-programmed cell death protein ligand 1 (PD-L1) therapy for advanced carcinomas. RESULTS:Of 18 patients, 9 had diabetic ketoacidosis (median glucose 27.92 mmol/L; median glucose before presentation 6.35 mmol/L). Median C-peptide at ICI-DM diagnosis was low, and it declined during follow-up. Median anti-PD-1/anti-PD-L1 duration before ICI-DM was 3.65 months (range 0.56-12.23 months). Time to ICI-DM onset was a median 1.4 months/3 ICI cycles and 6 months/10 cycles in those patients who were positive and negative for GAD65 autoantibodies, respectively. Time to ICI-DM onset was a median 2.5 months/3 ICI cycles and 4.8 months/8 cycles after anti-PD-L1 or anti-PD-1 therapy, respectively. Significant pancreatic atrophy was seen radiographically. CONCLUSIONS:ICI-DM presents abruptly, appears irreversible, is characterized by pancreatic atrophy, and may occur both earlier following PD-L1 blockade compared with PD-1 inhibition and in those who have positive GAD65 autoantibodies.