Faculty Bibliography

PURPOSE/OBJECTIVE:A 3D stereoscopic camera system developed by .decimal was commissioned and implemented into the clinic to improve the efficiency of clinical electron simulations. Capabilities of the camera allowed simulations to be moved from the treatment vault into any room with a flat surface that could accommodate patient positioning devices, eliminating the need for clinical patient setup timeslots on the treatment machine. This work describes the process used for these simulations and compares the treatment parameters determined by the system to those used in delivery. METHODS:The Decimal3D scanner workflow consisted of: scanning the patient surface; contouring the treatment area; determining gantry, couch, collimator, and source-to-surface distance (SSD) parameters for en face entry of the beam with sufficient clearance at the machine; and ordering custom electron cutouts when needed. Transparencies showing the projection of in-house library cutouts at various clinical SSDs were created to assist in choosing an appropriate library cutout. Data from 73 treatment sites were analyzed to evaluate the accuracy of the scanner-determined beam parameters for each treatment delivery. RESULTS:Clinical electron simulations for 73 treatment sites, predominately keloids, were transitioned out of the LINAC vault using the new workflow. For all patients, gantry, collimator, and couch parameters along with SSD and cone size were determined using the Decimal3D scanner with 57% of simulations using library cutouts. Tolerance tables for patient setup were updated to allow differences of 10, 20 and 5 degrees for gantry, collimator and couch, respectively. Approximately 7% of fractions (N=181 total fractions) were setup outside of the tolerance table based on physician-direction during treatment. This reflects physician preference to adjust the LINAC rather than patient position during treatment setup. No scanner-derived plan was untreatable due to cutout shape inaccuracy or clearance issues. CONCLUSION/CONCLUSIONS:Clinical electron simulations were successfully transitioned out of the LINAC vault using the Decimal3D scanner without loss of setup accuracy as measured through machine parameter determination and electron cutout shape.

INTRODUCTION:Radiation therapy is a promising modality for treating keloids after surgical excision. However, it is currently not standard practice among physicians because of concern surrounding the risk of radiation-induced secondary cancers, especially among pediatric patients. There is minimal research assessing the complications for radiation therapy in keloid management. AIM:The goal of this study was to determine radiation oncologists' perspectives about the utility and appropriateness of radiation therapy for keloid management in both adult and pediatric patients. This study also aimed to characterize radiation modality, dose, fractionation, and secondary complications observed by providers. METHODS:An electronic survey was delivered to 3102 members of the American Society for Radiation Oncology. The survey subjects were radiation oncologists who are currently practicing in the United States. Rates of responses were analyzed. RESULTS:A total of 114 responses from practicing radiation oncologists were received. Of these, 113 providers (99.1%) supported radiation therapy for keloid management in adults, whereas only 54.9% supported radiation therapy for pediatric patients. Of 101 providers that treated adults in the past year, the majority used external beam: electrons (84.2%), applied 3 fraction regimens (54.4%), and delivered radiation within 24 hours postexcision (45.5%). In pediatric patients, only 42 providers reported treating at least 1 patient. The majority used electron beam radiation (76.2%), applied 3 faction regimens (65%), and delivered radiation on the same day of keloid excision (50.0%) The main concern when treating pediatric patients were risk of secondary malignancy (92.1%). CONCLUSION:Although radiation therapy appears to be a widely accepted adjuvant treatment option for adults with keloids, the use of radiation therapy for pediatric patients is less widely accepted because of concerns regarding secondary malignancy. The findings suggest additional studies need to be carried out to assess the risk of those complications.

OBJECTIVE:To provide a critical overview of current radiation modalities for keloid management. BACKGROUND:Despite multimodal therapies, keloids that can develop following injury are poorly controlled. A number of studies have suggested that post-excisional radiation therapy can reduce rates of keloid recurrence. However, existing reports span multiple radiation modalities, including brachytherapy, electron beam radiation, and photon radiation. In this review, we describe the advantages and disadvantages of commonly used radiation techniques and highlight their efficacy in keloid management. RESULTS:Electron beam radiation and high-dose rate brachytherapy are the two most commonly used modalities for adjuvant radiotherapeutic management of keloids and can provide effective keloid control but may be suited for different kinds of keloid growth patterns. Increasing biologically equivalent dose (BED) likely improves rates of control, though the clinical significance of this finding remains to be elucidated. Though radiation treatments are associated with acute and chronic side effects, the risk of developing a secondary malignancy is minimal. CONCLUSIONS:While radiation therapy is a promising modality for treating keloids, more studies of a prospective, randomized nature are needed to standardize its utility.

Background XmAb20717 is a humanized bispecific monoclonal antibody that simultaneously targets PD-1 and CTLA-4. We report preliminary data from an ongoing, multicenter, Phase 1 study investigating the safety/tolerability, pharmacokinetics/ pharmacodynamics, and clinical activity (RECIST 1.1) of XmAb20717 in patients with selected advanced solid tumors. Methods A 3+3 dose-escalation design was used to establish a maximum tolerated (MTD)/recommended dose for evaluation in parallel expansion cohorts, including melanoma, renal cell carcinoma, non-small cell lung cancer (NSCLC), prostate cancer, and a basket of tumor types without an FDA-approved checkpoint inhibitor (CI; n20 each). XmAb20717 was administered as an infusion on Days 1 and 15 of each 28-day cycle. Results As of 08Jul2020, 109 patients had been treated (table 1), and 30 were continuing treatment. In escalation, 6 dose levels (0.15-10.0 mg/kg) were evaluated (n=34); an MTD was not established. Expansion cohorts were initiated at 10 mg/kg (n=72), and a 15 mg/kg escalation cohort was added (n=3). T-cell proliferation was noted in peripheral blood at doses as low as 3 mg/kg and was highest at 10 mg/kg. At this dose, consistent proliferation of CD8+ and CD4+ T cells was observed, indicative of dual PD-1 and CTLA-4 checkpoint blockade (figure 1). Paired pre- and post-dosing biopsies showed increased intratumoral T-cell infiltration and IFNresponse signatures following treatment. Grade 3/4 treatmentrelated adverse events (TRAEs) reported for >=3 patients included rash (13%), transaminase elevations (7%), lipase increased (4% [2% with amylase increased]), and acute kidney injury (3%), all considered immune-related. There were 2 Grade 5 TRAEs: immune-mediated pancreatitis (in the pres- ence of pancreatic metastases) and immune-mediated myocarditis (Grade 4) that contributed to respiratory failure. A complete response was reported as the best overall response for 1 patient (melanoma); partial responses were reported for 5 patients (2 melanoma, 2 NSCLC, 1 ovarian). The objective response rate was 13% overall and 21% at 10 mg/kg (6/46 and 6/29 evaluable patients, respectively). All responders had prior CI exposure. Responses were observed only at 10 mg/kg and, within the 10 mg/kg group, appeared to correlate with higher peak serum concentration and area under the curve. Conclusions XmAb20717 induced T-cell proliferation in peripheral blood consistent with dual-checkpoint blockade. Preliminary data indicate XmAb20717 was generally well-tolerated and associated with evidence of antitumor activity in CIpretreated patients with various types of advanced solid tumors

OBJECTIVE: To compare clinical and treatment characteristics and outcomes in locally advanced anal cancer, a potentially curable disease, in patients referred from a public or private hospital. METHODS: We retrospectively reviewed 112 anal cancer patients from a public and a private hospital who received definitive chemoradiotherapy at the same cancer center between 2004 and 2013. Tumor stage, radiotherapy delay, radiotherapy duration, and unplanned treatment breaks >/=10 days were compared using t-test and chi(2) test. Overall survival (OS), disease free survival (DFS), and colostomy free survival (CFS) were examined using the Kaplan-Meier method and compared with the log-rank test. Cox proportional hazard models for OS and DFS were developed. RESULTS: The follow-up was 14.9 months (range, 0.7-94.8 months). Public hospital patients presented with significantly higher clinical T stage (P<0.05) and clinical stage group (P<0.05), had significantly longer radiotherapy delays (P<0.05) and radiotherapy duration (P<0.05), and had more frequent radiation therapy (RT) breaks >/=10 days (P<0.05). Three-year OS showed a marked trend in favor of private hospital patients for 3-year OS (72.8% vs. 48.9%; P=0.171), 3-year DFS (66.3% vs. 42.7%, P=0.352), and 3-year CFS (86.4% vs. 68.9%, P=0.299). Referral hospital was not predictive of OS or DFS on multivariate analysis. CONCLUSIONS: Public hospital patients presented at later stage and experienced more delays in initiating and completing radiotherapy, which may contribute to the trend in poorer DFS and OS. These findings emphasize the need for identifying clinical and treatment factors that contribute to decreased survival in low socioeconomic status (SES) populations.

Background: Diagnosis and management of squamous cell carcinoma of head and neck (SCCHN) involves a multidisciplinary approach. Navigation at a public hospital can be difficult and lead to delays. In a previous study, we reported English-speaking and employed patients having longer provider delays (Lai 2011). In July 2010, we instituted the use of patient navigators, bimonthly management conferences, and improved inter-disciplinary communication in order to improve the patient experience. Aims: 1. Study differences in "provider delay" (time between first contact with health care provider and positive biopsy) between patients in cohort A (diagnosed between 1/2007 and 6/2010) and cohort "B" (diagnosed between 7/2010 and 6/ 2011). 2. Study differences in "treatment delay" (time between biopsy and initiation of treatment) between the two cohorts. 3. Determine what factors influence delays in both cohorts. Methods: The delays of the two cohorts were compared using the student t-test. Independent t-test and chi-square tests were used to examine associations between delays and the following characteristics: language, employment, presence of partner, gender, ethnicity, age, cancer sub-site, staging, number of co-morbidities, tobacco use, and alcohol use. The likelihood ratio test was used for multivariate analysis. Results: 133 patients in cohort A and 20 patients in cohort B were evaluable. Both provider and treatment delays in cohort B (50.5 and 39.3 days, respectively) were shorter than cohort A (60.2 and 41.6 days), but this was not statistically significant. The standard deviations of both delays were lower in cohort B, pointing towards a greater consistency in this group. In cohort A, provider delay was significantly shorter (p-value=0.003) for non-English speakers than English speakers on univariate and multivariate analysis. Other trends were not observed. Conclusions: Simple interventions can reduce provider and treatment delays. Our observations suggest that these interventions can mitigate t!

BACKGROUND: Plate osteosynthesis is a widely used technique in head and neck reconstructive surgery. The objective of this study was to determine whether postoperative chemoradiotherapy, which was recently introduced for high-risk head and neck cancer, affects plate and osteosynthesis related complications. METHODS: Fifty-two consecutive patients, who had undergone plate osteosynthesis for mandibular reconstruction between October 2003 and September 2006, were included in the study. The patients were divided into 3 groups: (1) surgery alone (n = 19), (2) surgery with postoperative radiotherapy (n = 14), and (3) surgery with concurrent chemoradiotherapy (n = 19). Outcome measures included any bone or plate related complications. RESULTS: The plate and osteosynthesis related complications occurred in 10.5% of patients in surgery-alone group, 28.6% in surgery with postoperative radiation group, and 63.2% in surgery with postoperative concurrent chemoradiotherapy group. The differences in the complication rates among these 3 groups were statistically significant (p = .003). In univariate analysis, postoperative radiation (p = .007) and concurrent chemotherapy (p = .003) were found to be significantly associated with complications. In multivariate analysis, only concurrent chemotherapy was found to be statistically significant (p = .002) with odds ratio of 7.72. CONCLUSION: Postoperative concurrent chemoradiotherapy significantly increases plate and osteosynthesis related complications in oral cancer.

PURPOSE/OBJECTIVE:The epidermal growth factor (EGF) receptor is frequently overexpressed in epithelial tumors. C225 is a human-to-murine chimeric monoclonal antibody that binds to the receptor and inhibits growth of cancer cells expressing the receptor. We evaluated the pharmacokinetics and toxicity of C225 in patients with advanced tumors overexpressing EGF receptors. PATIENTS AND METHODS/METHODS:We treated 52 patients in three successive phase I clinical trials of C225 as a single dose (n = 13), weekly multiple dose (n = 17), and weekly multiple dose with cisplatin (n = 22). C225 dose levels were 5, 20, 50, and 100 mg/m(2). In the study combining C225 with cisplatin, limited to patients with either head and neck or non-small-cell lung cancer, C225 was further escalated to 200 and 400 mg/m(2). Cisplatin was given at a dose of 60 mg/m(2) once every 4 weeks, and treatment was continued for up to 12 weeks if no disease progression occurred. RESULTS:C225 displayed nonlinear pharmacokinetics, with antibody doses in the range of 200 to 400 mg/m(2) being associated with complete saturation of systemic clearance. C225 clearance did not change with repeated administration or with coadministration of cisplatin. Antibodies against C225 were detected in only one patient, and C225-associated toxicity was minimal. Patients experiencing disease stabilization were seen in all studies. In the study combining C225 and cisplatin, nine (69%) of 13 patients treated with antibody doses >/= 50 mg/m(2) completed 12 weeks of therapy, and two partial responses were observed. CONCLUSION/CONCLUSIONS:C225 has dose-dependent pharmacokinetics, and doses that achieve saturation of systemic clearance are well tolerated. C225 given in combination with cisplatin has biologic activity at pharmacologically relevant doses.