Development and clinical implementation of a digital workflow utilizing 3D-printed oral stents for patients with head and neck cancer receiving radiotherapy.

OBJECTIVES: We describe the development of 3D-printed stents using our digital workflow and their effects on patients enrolled in the lead-in phase of a multi-center, randomized Phase-II trial. MATERIALS AND METHODS: Digital dental models were created for patients using intraoral scanning. Digital processes were implemented to develop the mouth-opening, tongue-depressing, and tongue-lateralizing stents using stereolithography. Time spent and material 3D-printing costs were measured. Physicians assessed mucositis using the Oral Mucositis Assessment Scale (OMAS) and collected MD Anderson Symptom Inventory (MDASI) reports and adverse events (AEs) from patients at various time points (TPs). OMAS and MDASI results were evaluated using paired t-test analysis. RESULTS: 18 patients enrolled into the lead-in phase across 6 independent clinical sites in the USA. 15 patients received stents (average design and fabrication time, 8 h; average material 3D-printing cost, 11 USD). 10 eligible patients with complete OMAS and MDASI reports across all TPs were assessed. OMAS increased significantly from baseline to week 3 of treatment (mean difference = 0.34; 95 % CI, 0.09-0.60; p = 0.01). MDASI increased significantly from baseline to week 3 of treatment (mean difference = 1.02; 95 % CI, 0.40-1.70; p = 0.005), and week 3 of treatment to end of treatment (mean difference = 1.90; 95 % CI, 0.90-2.92; p = 0.002). AEs (grades 1-3) were reported by patients across TPs. Mucositis and radiation dermatitis were primarily attributed to chemoradiation. CONCLUSIONS: 3D-printed stents were successfully fabricated and well tolerated by patients. As patients enroll in the randomized phase of this trial, data herein will establish a baseline for comparative analysis.

The State of Surgical Axillary Management and Adjuvant Radiotherapy for Early-stage Invasive Breast Cancer in the Modern Era.

BACKGROUND: For clinical T1-2N0 breast cancer, sentinel lymph node biopsy (SLNB) has been shown in American College of Surgeons Oncology Group (ACOSOG) Z0011 to be sufficient for women with 1 to 2 positive sentinel lymph nodes with no added benefit for completion axillary lymph node dissection (ALND). Z0011 specified whole breast radiotherapy (RT) using standard tangential fields; however, later analysis showed variation in field design. We assessed nationwide practice patterns and examined factors associated with patients undergoing completion ALND and subsequent radiation field design. PATIENTS AND METHODS: Women with clinical T1-2N0 breast cancer who underwent breast-conserving surgery, axillary staging, and whole breast RT in 2012 to 2013 were identified in the National Cancer Database. Multivariable logistic regression modeling was used to examine axillary management and RT, adjusting for demographic and clinicopathologic factors. RESULTS: Among 83,555 patients meeting criteria, 9.3% underwent upfront ALND, 75.8% underwent SLNB only, and 14.9% underwent SLNB with completion ALND. From 2012 to 2013, upfront SLNB increased from 90.1% to 91.4% (odds ratio, 1.14; P < .001). Among 9474 patients that underwent SLNB with 1 to 2 positive sentinel nodes, 31.2% received completion ALND. Among patients with 1 to 2 positive sentinel nodes, SLNB increased from 65.8% to 72.1% from 2012 to 2013 (P < .001). For patients with 1 to 2 positive lymph nodes that underwent SLNB only, 63.4% underwent breast RT, whereas 36.6% received breast and nodal RT. CONCLUSIONS: Nationwide practice patterns of axillary management vary. Despite an increasing rate of SLNB, many patients still receive upfront and completion ALND. Furthermore, there is significant variation in RT field design, and modern treatment guidelines are warranted for this patient population.

Excellent Long-term Breast Preservation Rate After Accelerated Partial Breast Irradiation Using a Balloon Device.

BACKGROUND: Accelerated partial breast irradiation (APBI) using a balloon device has been well tolerated. A recent retrospective population-based study showed an increase in the rate of subsequent mastectomy for patients who undergo APBI compared with whole breast radiation therapy. Our aim was to analyze the long-term results of patients treated with APBI at our institution to determine the salvage mastectomy and locoregional recurrence rates and cosmesis outcomes. MATERIALS AND METHODS: After institutional review board approval, we conducted a retrospective review of 111 patients treated from June 2003 to October 2014 at our institution for early-stage breast cancer using a balloon device. After lumpectomy and nodal staging, the patients underwent APBI with high-dose rate iridium-192 brachytherapy. A computed tomography-based 3-dimensional plan was created, and a dose of 34 Gy in 10 fractions was given twice daily, 6 hours apart, over 5 days. Follow-up examinations were performed 2 to 3 times annually by either a surgeon and/or a radiation oncologist. Annual mammograms were obtained. The patients included postmenopausal women with node-negative early-stage invasive ductal carcinoma with a tumor size < 3 cm (n = 93) or ductal carcinoma in situ (n = 18). Cosmesis was evaluated using the Harvard criteria, as excellent, good, fair, or poor. RESULTS: At a median follow-up period of 66 months (range, 1-139 months) after completing treatment, with a minimum of 5 years of follow-up data for 62 patients (55.9%), the incidence of ipsilateral breast tumor recurrence (IBTR) was 2.7% (n = 3) and the incidence of ipsilateral axilla nodal recurrence was 1.8% (n = 2). The ipsilateral breast preservation rate was 97.3%. The salvage mastectomy rate was 2.7% (n = 3), and the 5-year salvage mastectomy-free rate was 98.7% (95% confidence interval, 91.0%-99.8%). No distant failure developed, and no breast cancer-related deaths occurred. The 5-year overall survival rate was 91.7% (95% confidence interval, 83.2%-96.0%), and the 10-year breast cancer-specific survival rate was 100%. Of the 3 cases of IBTR, 2 were estrogen receptor negative (P = .076). The mean interval to IBTR was 78.7 ± 27.5 months from treatment completion. A significant association was noted between African-American ethnicity and IBTR (P = .0398). Excellent to good cosmesis was observed in 98.1% of the patients. The maximum skin dose (mean value) for patients with excellent, good, and fair cosmesis was 302.2 Gy, 315.4 Gy, and 372.5 Gy (88.9%, 92.7%, and 109.5% of the prescription dose), respectively. The maximum skin dose was < 340 Gy (100% of the prescribed dose) in 69.9% of patients with excellent to good cosmesis. CONCLUSION: The long-term follow-up data of patients receiving APBI with a balloon device showed a low salvage mastectomy rate with durable long-term breast preservation. Excellent local control with good cosmesis was noted in these postmenopausal patients treated with APBI.

FDA Adverse Event Reporting System: Recruiting Doctors to Make Surveillance a Little Less Passive.

Within the last few decades, a shift has taken place in FDA's approach to drug development, with greater emphasis put on postmarketing data collection and less on the traditional premarketing scheme. The FDA Adverse Event Reporting System (FAERS) is the primary system for collecting Adverse Events, but has been criticized for years for the low reporting rate into the system and the poor quality of the information submitted. This paper argues that physicians need to be required to submit adverse event reports to FAERS, because such a requirement (1) would produce a greater number of the high quality reports necessary to better determine causality; (2) is merely an extension of physicians' ethical obligations; and (3) aligns with the approach in the Vaccine Adverse Event Reporting System (VAERS). Furthermore, advances in electronic health records can aid in reporting efficiency.

Radiation-induced epithelial-myoepithelial carcinoma in a patient previously treated with mantle-field radiation therapy for Hodgkin lymphoma.

BACKGROUND: Radiation-induced salivary gland tumors are well described in the literature, with mucoepidermoid cancer being the most common histologic entity. Epithelial-myoepithelial carcinoma is a rare tumor accounting for <1% of all tumors in the salivary glands. METHODS AND RESULTS: We describe the first case of radiation-induced epithelial-myoepithelial carcinoma in the English-language medical literature. A 48-year-old man presented with right-sided mandibular pain and trismus, 25 years after mantle-field radiation therapy (RT) for Hodgkin lymphoma. He underwent excision of a right submandibular mass, which revealed a diagnosis of epithelial-myoepithelial carcinoma. Although typically a low-grade tumor, the histology revealed extensive necrosis and high mitotic activity. The patient required multiple resections and adjuvant therapy after multiple recurrences over a 4-year period. CONCLUSION: Reports of epithelial-myoepithelial carcinoma are relatively rare and this case highlights the importance of long-term follow-up and increased awareness of the risks of salivary gland tumors in this population.

Routine histopathologic characteristics can predict oncotype DX(TM) recurrence score in subsets of breast cancer patients.

This study assessed whether routine pathologic parameters could predict Oncotype DX(TM) recurrence score (RS) in 72 breast cancers diagnosed from 2008-2012. Comparing patients with low RS (0-17) vs. intermediate RS (18-30) vs. high RS (>30), the mean Nottingham score increased (5.5 vs. 6.3 vs. 7.2, respectively, p = .001) and the mean PR Allred score decreased (6.7 vs. 4.9 vs. 3.3, respectively, p = .001). A high RS was least likely for low-grade tumors (0% had high RS, p = .005), and strong PR positivity (9% had high RS, p = .017). A low RS was least likely for cancers that were both high grade and PR weak/negative.