Small Cell Carcinoma of the Head and Neck: Update on the University of Florida Experience.

We updated the University of Florida experience treating head and neck small cell carcinoma. Eight patients received a median of 67.7 Gy between 1989 and 2017. The 2-year rates of local, regional, distant, and disease control were 73, 60, 33, and 13%, respectively. The 2-year overall survival rate was 38%; median survival was 1.4 years. The longest disease-free period was 9.5 years after treatment with no evidence of disease. Radiotherapy is an acceptable treatment for these patients, who tend to have poor outcomes and distant metastatic disease. Superior systemic chemotherapy may improve outcomes and decrease the likelihood of distant recurrence.

Outcomes following proton therapy for Ewing sarcoma of the cranium and skull base.

PURPOSE: Despite the dosimetric advantages of proton therapy, little data exist on patients who receive proton therapy for Ewing sarcoma of the cranium and skull base. This study reports local disease control and toxicity in such patients. MATERIALS/METHODS: We reviewed 25 patients (≤21 years old) with nonmetastatic Ewing sarcoma of the cranium and skull base treated between 2008 and 2018. Treatment toxicity was graded per the Common Terminology Criteria for Adverse Events v4.0. The Kaplan-Meier product limit method provided estimates of disease control and survival. RESULTS: Median patient age was 5.9 years (range, 1-21.7). Tumor subsites included the skull base (48%), non-skull-base calvarial bones (28%), paranasal sinuses (20%), and nasal cavity (4%). All patients underwent multiagent alkylator- and anthracycline-based chemotherapy; 16% underwent gross total resection (GTR) before radiation. Clinical target volume (CTV) 1 received 45 GyRBE and CTV2 received 50.4 GyRBE following GTR or 54-55.8 GyRBE following biopsy or subtotal resection. Median follow-up was 3.7 years (range, 0.26-8.3); no patients were lost. The 4-year local control, disease-free survival, and overall survival rates were 96%, 86%, and 92%, respectively. Two patients experienced in-field recurrences. One patient experienced bilateral conductive hearing loss requiring aids, two patients developed intracranial vasculopathy, and 6 patients required hormone replacement therapy for neuroendocrine deficits. None developed a secondary malignancy. CONCLUSION: Proton therapy is associated with a favorable therapeutic ratio in children with large Ewing tumors of the cranium and skull base. Despite its high conformality, we observed excellent local control and no marginal recurrences. Treatment dosimetry predicts limited long-term neurocognitive and neuroendocrine side effects.

Image-guided hypofractionated double-scattering proton therapy in the management of centrally-located early-stage non-small cell lung cancer.

BACKGROUND: The treatment of centrally-located early-stage non-small cell lung cancer (NSCLC) with image-guided stereotactic body radiotherapy (SBRT) is challenging due to the proximity of critical normal structures to the tumor target. The purpose of this study was to report the results of our experience in treating centrally-located early-stage NSCLC with hypofractionated proton therapy (PT). MATERIAL AND METHODS: Between 2009 and 2018, 23 patients with T1-T2N0M0 NSCLC (T1, 46%; T2, 54%) were treated with image-guided hypofractionated double-scattering PT. The median age at the time of treatment was 74 years (range, 58-88). Patients underwent 4-dimensional computed tomography (CT) simulation following fiducial marker placement, and daily image guidance was performed. All patients were treated with 60 GyRBE in 10 fractions. Patients were assessed for CTCAEv4 toxicities weekly during treatment, and at regular follow-up intervals with CT imaging for tumor assessment. Overall survival, cause-specific survival, local control, regional control, and metastases-free survival were evaluated using cumulative incidence with competing risks. RESULTS: Median follow-up for all patients was 3.2 years (range, 0.2-9.2 years). Overall survival rates at 3 and 5 years were 81% and 50% (95% CI, 27-79%), respectively. Cause-specific survival rates at 3 and 5 years were 81% and 71% (95% CI, 46-92%). The 3-year local, regional, and distant control rates were 90%, 81%, and 87%, respectively. Three patients (13%) experienced local recurrences as their first recurrence, at a median time of 28 months from completion of radiation (range, 18-61 months). Two patients (9%) experienced late grade 3 toxicities, including 1 patient who developed a bronchial stricture that required stent placement. CONCLUSION: Image-guided hypofractionated PT for centrally-located early-stage NSCLC provides excellent local control with low rates of grade ≥3 toxicities. For tumors in sensitive locations, PT may provide safer treatment than photon-based treatments due to its dosimetric advantages.

Patterns-of-care disparities among uninsured versus insured patients with anorectal carcinoma referred for radiotherapy at an Urban Safety-Net Hospital.

Background: To compare patterns-of-care and clinical outcomes among uninsured versus insured patients (IPs) with anorectal malignancies referred for radiotherapy at an urban safety-net hospital. This topic is important because uninsured patients (UPs) in the US often have limited access to health care, which can result in worse health outcomes. Methods: We reviewed the medical records of 59 patients with biopsy-proven, non-metastatic anal and rectal cancers who received curative-intent primary or neoadjuvant/adjuvant radiotherapy between May 2002 and August 2012. Data regarding patient and disease characteristics, weight loss, insurance status at symptom onset, date of first therapeutic intervention, and survival status at last follow-up, were collected and analyzed. Results: The percentage of IPs presenting with T4 tumors was 7% versus 40% among the uninsured (P=0.005). The median interval between first symptom onset and diagnosis date was 89 (range, 0-1,428) days for IPs and 221 (range, 0-1,576) days for UPs (P=0.01). The median interval between first symptom onset and treatment initiation was 172 (range, 9-1,498) days for IPs and 302 (range, 35-1,624 days) days for UPs (P=0.01). The 5-year overall survival rate was 59% for the entire cohort, 62% for the insured patients, and 55% for the uninsured patients (P=0.76). Conclusions: Differences in health insurance status demonstrated various disparities in patterns-of-care, including significant delay in diagnosis, more advanced-stage disease at presentation, and treatment initiation delays among UPs. Nevertheless, overall survival at 5 years was not statistically significant between the insured and the uninsured.

Reirradiation in Conservative Salvage of Recurrent Soft-tissue Sarcoma: An Analysis of Treatment Efficacy and Toxicities.

OBJECTIVE: Compared with radical resection alone, perioperative radiation therapy (RT) combined with neurovascular preserving surgery is the standard for the management of virgin soft-tissue sarcomas. Yet, the optimal management of a local recurrence remains unclear. We report outcomes of patients with locally recurrent soft-tissue sarcoma treated with resection and reirradiation at the University of Florida. MATERIALS AND METHODS: We reviewed the records of patients treated with primary conservative surgery and radiation for soft-tissue sarcoma followed by salvage resection and reirradiation for a local recurrence at our institution. RESULTS: We analyzed 23 patients treated between 1976 and 2014 (median follow-up, 46 mo). Tumor sites included: proximal extremity, 11 patients; trunk, 6; distal extremity, 5; and head and neck, 1. All patients had conservative gross total resection of their recurrent tumor, without amputation. For reirradiation, 16 patients received external-beam RT alone, 6 received external-beam RT and brachytherapy, and 1 received brachytherapy alone. Two patients received chemotherapy. After retreatment, the 5-year overall survival, cause-specific survival, local control, and distant control rates were 39%, 42%, 46%, and 60%, respectively. Ten patients experienced local recurrences, 1 experienced regional recurrence, and 9 developed distant metastases. Retreatment-related complications ranged from delayed wound healing to limb amputation; 8 patients required amputation. Only 3 patients remained disease-free at last follow-up. No statistically significant associations were found between treatment factors (eg, RT dose) and local control. CONCLUSIONS: Achieving local control of recurrent soft-tissue sarcoma is challenging. Treatment with reoperation and reirradiation can lead to debilitating complications affecting function and quality of life.

Postoperative or Salvage Proton Radiotherapy for Prostate Cancer After Radical Prostatectomy.

PURPOSE: Postprostatectomy radiation improves disease control, but limited data exist regarding outcomes, toxicities, and patient-reported quality of life with proton therapy. METHOD AND MATERIALS: The first 102 patients who were enrolled on an outcome tracking protocol between 2006 and 2017 and treated with double-scattered proton therapy after prostatectomy were retrospectively reviewed. Eleven (11%) received adjuvant radiation, while 91 (89%) received salvage radiation. Seventy-four received double-scattered proton therapy to the prostate bed only. Twenty-eight received a double-scattered proton therapy prostate-bed boost after prostate-bed and pelvic-node treatment. Eleven adjuvant patients received a median dose of 66.6 GyRBE (range, 66.0-70.2). Ninety-one salvage patients received a median dose of 70.2 GyRBE (range, 66.0-78.0). Forty-five patients received androgen deprivation therapy for a median 9 months (range, 1-30). Toxicities were scored using Common Terminology Criteria for Adverse Events v4.0 criteria, and patient-reported quality-of-life data were reviewed. RESULTS: The median follow-up was 5.5 years (range, 0.8-11.4 years). Five-year biochemical relapse-free and distant metastases-free survival rates were 72% and 91% for adjuvant patients, 57% and 97% for salvage patients, and 57% and 97% overall. Acute and late grade 3 or higher genitourinary toxicity rates were 1% and 7%. No patients had grade 3 or higher gastrointestinal toxicity. Acute and late grade 2 gastrointestinal toxicities were 5% and 2%. The mean values and SDs of the International Prostate Symptom Score, International Index of Erectile Function, and Expanded Prostate Cancer Index Composite bowel function and bother were 7.5 (SD = 5.9), 10.2 (SD = 8.3), 92.8 (SD = 11.1), and 91.2 (SD = 6.4), respectively, at baseline, and 12.1 (SD = 9.1), 10.1 (SD = 6.7), 87.3 (SD = 18), and 86.7 (SD = 13.8) at the 5-year follow-up. CONCLUSION: High-dose postprostatectomy proton therapy provides effective long-term biochemical control and freedom from metastasis, with low acute and long-term gastrointestinal and genitourinary toxicity.

Image-Guided Hypofractionated Proton Therapy in Early-Stage Non-Small Cell Lung Cancer: A Phase 2 Study.

PURPOSE: Due to the excellent outcomes with image-guided stereotactic body radiotherapy for patients with early-stage non-small cell lung cancer (NSCLC) and the low treatment-related toxicities using proton therapy (PT), we investigated treatment outcomes and toxicities when delivering hypofractionated PT. MATERIALS AND METHODS: Between 2009 and 2018, 22 patients with T1 to T2 N0M0 NSCLC (45% T1, 55% T2) received image-guided hypofractionated PT. The median age at diagnosis was 72 years (range, 58-90). Patients underwent 4-dimensional computed tomography simulation following fiducial marker placement, and daily image guidance was performed. Nine patients (41%) were treated with 48 GyRBE in 4 fractions for peripheral lesions, and 13 patients (59%) were treated with 60 GyRBE in 10 fractions for central lesions. Patients were assessed for CTCAEv4 toxicities with computed tomography imaging for tumor assessment. The primary endpoint was grade 3 to 5 toxicity at 1 year. RESULTS: The median follow-up for all patients was 3.5 years (range, 0.2-8.8 years). The overall survival rates at 3 and 5 years were 81% and 49%, respectively. Cause-specific survival rates at 3 and 5 years were 100% and 75%, respectively. The 3-year local, regional, and distant control rates were 86%, 85%, and 95%, respectively. Four patients experienced in-field recurrences between 18 and 45 months after treatment. One patient (5%) developed a late grade 3 bronchial stricture requiring hospitalization and stent. CONCLUSION: Image-guided hypofractionated PT for early-stage NSCLC provides promising local control and long-term survival with a low likelihood of toxicity. Regional nodal and distant relapses remain a problem.

Radiation Treatment for Ewing Sarcoma Family of Tumors in Adult Patients: A Single Institution's Experience Over 40 Years.

PURPOSE/OBJECTIVES: To report prognostic factors and long-term outcomes in adults with Ewing sarcoma treated with definitive radiotherapy. MATERIALS AND METHODS: We reviewed patients 18 years old and above with nonmetastatic Ewing sarcoma treated with radiotherapy +/- chemotherapy or surgery. Outcomes were stratified by age (30 and above vs. younger than 30 y), soft tissue extension, tumor size (≥8.5 vs. <8.5 cm), tumor location, resection (yes vs. no), and treatment era (1970-1992 vs. 1993-2012). Toxicities were scored using the RTOG criteria. RESULTS: Fifty-five patients (21 women) were treated with radiotherapy. Average age at diagnosis: 26.7 years (38 patients below 30 vs. 17 patients 30 y and above). A total of 43 had soft tissue extension (78%). Median tumor size: 8.5 cm. Most tumors were in the pelvis (40%), followed by the lower (27%) and upper (24%) extremities. All but 1 patient received chemotherapy; 13 underwent resection. Median dose: 55 Gy. Median follow-up: 3.6 years; 17.5 years for living patients. The 5-year overall (OS) and cause-specific survival (CSS) rates were both 46%. OS and CSS rates were unaffected by age (P=0.97), tumor size (P=0.12), or tumor location (P=0.99). Soft tissue extension portended a significantly poorer prognosis for 5-year OS and CSS: 37% vs. 82% (with and without, respectively; P=0.04). Patients who underwent resection had improved 5-year OS and CSS: 77% vs. 37%, respectively (P=0.01). Patients treated after 1993 had improved 5-year OS: 58% vs. 37% (P=0.0264). CONCLUSIONS: Adult patients with Ewing sarcoma experience similar treatment outcomes regardless of age at diagnosis. Soft tissue extension represents a poor prognostic factor. Aggressive trimodality therapy achieved the highest OS and CSS.

Fractionated Radiation Therapy for Benign Nonacoustic Schwannomas.

OBJECTIVES: We analyzed the outcomes of patients with benign nonacoustic schwannomas treated with fractionated radiation therapy (RT). METHODS: Between October 1987 and March 2013, 11 patients with benign nonacoustic schwannomas diagnosed radiographically (n=3) or pathologically (n=8) were treated with fractionated RT with curative intent at the University of Florida. We reviewed patients' medical records to assess outcomes and toxicities from treatment. RESULTS: The median follow-up for all patients was 8.2 years (range, 2.2 to 22.7 y) and 8 years for all living patients (range, 2.2 to 22.7 y). Of the 11 patients included in the analysis, 8 (73%) were treated solely with RT, 1 (9%) was treated with postoperative RT after subtotal resection, and 2 (18%) were treated with postoperative RT after recurrence following initial surgical resection. The 5-year overall survival, disease-free survival, and local control rates were 100%. There were no grade 2 to 5 treatment toxicities. CONCLUSIONS: RT for benign nonacoustic schwannoma may be effective when used alone or in addition to surgery. Irradiation should be considered in patients for whom resection is likely to result in one or more neurological deficits. Fractionated RT to a total dose of 50 Gy provides excellent local control and minimal morbidity.

Radiotherapy in the Management of Orbital Lymphoma: A Single Institution's Experience Over 4 Decades.

PURPOSE: To report our institution's treatment techniques, disease outcomes, and complication rates after radiotherapy for the management of lymphoma involving the orbits. PATIENTS AND METHODS: We retrospectively reviewed the medical records of 44 patients curatively treated with radiotherapy for stage IAE (75%) or stage IIAE (25%) orbital lymphoma between 1969 and 2013. Median follow-up was 4.9 years. Thirty-eight patients (86%) had low-grade lymphoma and 6 (14%) had high-grade lymphoma. Radiation was delivered with either a wedge-pair (61%), single-anterior (34%), or anterior with bilateral wedges (5%) technique. The median radiation dose was 25.5 Gy (range, 15 to 47.5 Gy). Lens shielding was performed when possible. Cause-specific survival and freedom from distant relapse were calculated using the Kaplan-Meier method. RESULTS: The 5-year local control rate was 98%. Control of disease in the orbit was achieved in all but 1 patient who developed an out-of-field recurrence after irradiation of a lacrimal tumor. The 5-year regional control rate was 91% (3 patients failed in the contralateral orbit and 1 patient failed in the ipsilateral parotid). Freedom from disease, cause-specific survival, and overall survival rates at 5 and 10 years were 70% and 55%, 89% and 89%, and 76% and 61%, respectively. Acute toxicity was minimal. Ten patients (23%) reported worsened vision following radiotherapy, and cataracts developed in 17 patients. Cataracts developed in 13 of 28 patients treated without lens shielding (46%) and 4 of 16 patients (25%) treated with lens shielding. CONCLUSION: Radiotherapy is a safe and effective local treatment in the management of orbital lymphoma.

Pregnancy testing in patients undergoing radiation therapy.

Radiation therapy (RT) can be lethal to a developing fetus; therefore, determining pregnancy status before RT is essential. We here sought to determine how many women treated with RT at our institution for over one year were at risk for pregnancy when starting RT. We retrospectively reviewed the medical records of all female patients 12-55 years old treated with radiation, i.e. 1 October 2012 to 31 September 2013. Patients were categorised as 'at risk' if they had a uterus and 'no risk' if they had a hysterectomy. Documented birth control, pregnancy test status, and timing of the pregnancy test in relation to the radiation start date were recorded. We included 131 female patients with a median age of 48 years (range 14-55 years). Breast cancer was the most prevalent disease site (18%) followed by head/neck and central nervous system (both 11%). Of the 131 patients, 35 were deemed 'no risk' and 95 (72%) were 'at risk'. Pregnancy testing of the 'at risk' population was done in 47%, but only 17% of the pregnancy testing was performed accurately, which we defined as a test performed within 14 days before starting RT. Over one year, 66% (63/95) of 'at risk' women were not tested appropriately before starting RT. Most (66%) women of child-bearing age with an intact uterus receiving RT at our institution were not appropriately tested for pregnancy before the initiation of RT. These data laid the foundation for our formal pregnancy testing policies for women undergoing RT.

Impact of helmet use in traumatic brain injuries associated with recreational vehicles.

Objective. To study the impact of helmet use on outcomes after recreational vehicle accidents. Methods. This is an observational cohort of adult and pediatric patients who sustained a TBI while riding a recreational vehicle. Recreational vehicles included bicycles, motorcycles, and all-terrain vehicles (ATVs), as well as a category for other vehicles such as skateboards and scooters. Results. Lack of helmet use was significantly associated with having a more severe traumatic brain injury and being admitted to the hospital. Similarly, 25% of those who did wearing a helmet were admitted to the ICU versus 36% of those who did not (P = 0.0489). The hospital length of stay was significantly greater for patients who did not use helmets. Conclusion. Lack of helmet use is significantly correlated with abnormal neuroimaging and admission to the hospital and ICU; these data support a call for action to implement more widespread injury prevention and helmet safety education and advocacy.