Faculty Bibliography

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.

BACKGROUND:To evaluate inter-fractional variations in bladder and rectum during prostate stereotactic body radiation therapy (SBRT) and determine dosimetric and clinical consequences. METHODS:Eighty-five patients with 510 computed tomography (CT) images were analyzed. Median prescription dose was 40 Gy in 5 fractions. Patients were instructed to maintain a full bladder and empty rectum prior to simulation and each treatment. A single reviewer delineated organs at risk (OARs) on the simulation (Sim-CT) and Cone Beam CTs (CBCT) for analyses. RESULTS:Bladder and rectum volume reductions were observed throughout the course of SBRT, with largest mean reductions of 86.9 mL (19.0%) for bladder and 6.4 mL (8.7%) for rectum noted at fraction #5 compared to Sim-CT (P < 0.01). Higher initial Sim-CT bladder volumes were predictive for greater reduction in absolute bladder volume during treatment (ρ = - 0.69; P < 0.01). Over the course of SBRT, there was a small but significant increase in bladder mean dose (+ 4.5 ± 12.8%; P < 0.01) but no significant change in the D2cc (+ 0.8 ± 4.0%; P = 0.28). The mean bladder trigone displacement was in the anterior direction (+ 4.02 ± 6.59 mm) with a corresponding decrease in mean trigone dose (- 3.6 ± 9.6%; P < 0.01) and D2cc (- 6.2 ± 15.6%; P < 0.01). There was a small but significant increase in mean rectal dose (+ 7.0 ± 12.9%, P < 0.01) but a decrease in rectal D2cc (- 2.2 ± 10.1%; P = 0.04). No significant correlations were found between relative bladder volume changes, bladder trigone displacements, or rectum volume changes with rates of genitourinary or rectal toxicities. CONCLUSIONS:Despite smaller than expected bladder and rectal volumes at the time of treatment compared to the planning scans, dosimetric impact was minimal and not predictive of detrimental clinical outcomes. These results cast doubt on the need for excessively strict bladder filling and rectal emptying protocols in the context of image guided prostate SBRT and prospective studies are needed to determine its necessity.