Outcomes following proton therapy for pediatric esthesioneuroblastoma.

BACKGROUND: Pediatric esthesioneuroblastoma (EN) can infiltrate skull base anatomy, presenting challenges due to high radiation doses and pediatric tissue sensitivity. This study reports outcomes of pediatric EN treated with proton radiotherapy (PT). PROCEDURE: Using an IRB-approved prospective outcomes registry, we evaluated patient, tumor, and treatment-related variables impacting disease control and toxicity in pediatric nonmetastatic EN treated with modern multimodality therapy, including PT. RESULTS: Fifteen consecutive patients (median age 16) comprising Kadish stage B (n = 2), C (n = 9), and D (n = 4) tumors were assessed, including six with intracranial involvement, four with cranial nerve deficits, and four with cervical lymphadenopathy. Before radiation, two had subtotal and 13 had gross total resections (endoscopic or craniofacial). Two underwent neck dissection. Eleven received chemotherapy before radiation (n = 5), concurrent with radiation (n = 4), or both (n = 2). Median total radiation dose (primary site) was 66 Gy/CGE for gross disease and 54 Gy/CGE (cobalt Gray equivalent) for microscopic disease. Median follow-up was 4.8 years. No patients were lost to follow-up. Five-year disease-free and overall survival rates were 86% (no local or regional recurrences). Two patients developed vertebral metastases and died. Two required a temporary feeding tube for oral mucositis/dysphagia. Late toxicities included symptomatic retinopathy, major reconstructive surgery, cataracts, chronic otitis media, chronic keratoconjunctivitis, hypothyroidism, and in-field basal cell skin cancer. CONCLUSIONS: A multimodality approach for pediatric EN results in excellent local control. Despite the moderate-dose PT, serious radiation toxicity was observed; further dose and target volume reductions may benefit select patients. Longer follow-up and comparative data from modern photon series are necessary to fully characterize any relative PT advantage.

Long-term outcomes of fractionated proton beam therapy for benign or radiographic intracranial meningioma.

PURPOSE: Benign intracranial meningioma is one of the most common primary brain neoplasms. Proton therapy has been increasingly utilized for nonoperative management of this neoplasm, yet few long-term outcomes studies exist. METHODS: The medical records of a total of 59 patients with 64 lesions were reviewed under a prospective outcomes tracking protocol for histologically proven or radiographically benign meningioma. The patients were treated with proton therapy at the University of Florida Proton Therapy Institute between 2007 and 2019 and given a median dose of 50.4 GyRBE at 1.8 GyRBE (relative biological effectiveness) (range 48.6-61.2 GyRBE) in once-daily treatments. RESULTS: With a median clinical and imaging follow-up of 6.3 and 4.7 years, the rates of 5-year actuarial local progression and cumulative incidence of grade 3 or greater toxicity were 6% (95% confidence interval [CI] 1%-14%), and 2% (95% CI < 1%-15%), respectively. Two patients experienced local progression after 5 years. The 5-year actuarial overall survival rate was 87% (95% CI 74-94%). CONCLUSION: Fractionated PBT up to 50.4 GyRBE is a safe and highly effective therapy for treating benign intracranial meningioma.

Postoperative Radiotherapy for Cutaneous Melanoma in Patients at High Risk of Local-Regional Recurrence after Surgery Alone.

We evaluated outcomes in 131 patients with cutaneous melanoma (median follow-up, 3.6 years) considered at high risk of recurrence after surgery alone treated with surgery and postoperative radiotherapy. Eligible patients had one or more of the following: recurrence after surgery, positive lymph nodes, extracapsular extension, incomplete regional node dissection, microscopically positive margins, gross residual disease, or in-transit metastases. 102 patients received hypofractionated radiotherapy and 29 had conventional fractionation. 10-year outcomes were: in-field local-regional control, 87%; local regional control, 72%; distant metastasis-free survival, 48%; cause-specific survival, 44%; and overall survival, 31%. Three patients experienced acute toxicities while 6 experienced late toxicities.

A Coordination Network Featuring Two Distinct Copper(II) Coordination Environments for Highly Selective Acetylene Adsorption.

Single crystals of 2D coordination network {Cu2 L2 ⋅ (DMF)3 (H2 O)3 }n (1-DMF) were prepared by reaction of commercial reagents 3-formyl-4-hydroxybenzoic acid (H2 L) and Cu(NO3 )2 in dimethylformamide (DMF). The single-crystal structure shows two distinct Cu(II) coordination environments arising from the separate coordination of Cu(II) cations to the carboxylate and salicylaldehydato moieties on the linker, with 1D channels running through the structure. Flexibility is exhibited on solvent exchange with ethanol and tetrahydrofuran, while porosity and the unique overall connectivity of the structure are retained. The activated material exhibits type I gas sorption behaviour and a BET surface area of 950 m2 g-1 (N2 , 77 K). Notably, the framework adsorbs negligible quantities of CH4 compared with CO2 and the C2 Hn hydrocarbons. It exhibits exceptional selectivity for C2 H2 /CH4 and C2 H2 /C2 Hn , which has applicability in separation technologies for the isolation of C2 H2 .

Disease Control after Radiotherapy for Adult Craniopharyngioma: Clinical Outcomes from a Large Single-Institution Series.

PURPOSE: To report disease control and treatment-related side effects among adult patients with craniopharyngioma treated with radiotherapy. METHODS: We performed a single-institution review of adult patients (> 21 years old) with craniopharyngioma treated with radiotherapy either definitively or postoperatively for gross residual disease. We report disease control, survival, and radiotherapy-related side effects. RESULTS: A total of 49 adult patients with craniopharyngioma were included, 27 of whom were treated at initial presentation and 22 for recurrent disease following initial surgery and observation. Overall, 77% received radiotherapy postoperatively (either after primary surgery or surgery for recurrence). With a median clinical and radiographic follow-up of 4.2 (range, 0.4-21.6) years and 3.0 (range, 0-21.5) years, the 5- and 10-year local control rates were 100 and 94%, respectively. The 5- and 10-year overall survival rates were 80 and 66%, respectively. Eleven percent of patients experienced grade 2 vision deterioration and 18% suffered grade 2 endocrinopathies following radiotherapy. CONCLUSIONS: Radiotherapy provides excellent disease control with acceptable toxicity among adult patients with craniopharyngioma. These data support the use of fractionated radiotherapy in adult patients with recurrent or gross residual disease after surgery. For inoperable patients or those with moderate or high surgical risk to neurologic and/or vascular structures, we advocate for limited surgical resection and postoperative radiotherapy to balance optimal tumor control with tumor- and treatment-related morbidity.

Five- and seven-year outcomes for image-guided moderately accelerated hypofractionated proton therapy for prostate cancer.

BACKGROUND: To report 5- and 7-year outcomes after image-guided moderately accelerated hypofractionated proton therapy (AHPT) for prostate cancer. MATERIAL AND METHODS: We reviewed the first 582 prostate cancer patients enrolled on prospective outcomes tracking trial and treated with double-scattered moderately AHPT between 2008 and 2015. 269 patients had low-risk (LR) and 313 had intermediate-risk (IR) disease, including 149 with favorable intermediate-risk (FIR) and 164 with unfavorable intermediate-risk (UIR) disease. LR patients received a median 70.0GyRBE (2.5GyRBE/fraction) and IR patients received a median of 72.5 GyRBE. Seventeen patients (UIR, n = 12) received androgen deprivation therapy (ADT) for a median of 6 months. Toxicities were graded per the CTCAE, v4.0, and patient-reported quality-of-life data were reviewed. RESULTS: Median follow-up was 8.0 years (0.9-12.2). The 5- and 7-year rates of freedom from biochemical progression (FFBP) overall and in the LR and IR subsets, respectively, were 96.8/95.2%, 98.8/98.8%, and 95.0/91.9%. For the FIR and UIR subsets, they were 97.2/95.2% and 93.1/88.8%. Actuarial 5- and 7-year rates of late CTCAE, v4.0, grade 2 gastrointestinal (GI), grade 3 GI, and grade 3 genitourinary (GU) toxicities were 9.9%/11.2%, 1.4/1.4% and 1.3/2.1%, respectively. No grade ≥4 GI or GU toxicities occurred. The mean (standard deviation, SD) IPSS and EPIC Composite bowel function and bother scores were 7 (SD = 5), 97 (SD = 7), and 94 (SD = 6), respectively at baseline, 7 (SD = 5), 92 (SD = 13), and 92 (SD = 9) at the 5-year follow-up, and 7 (SD = 5), 93 (SD = 12), and 92 (SD = 10) at the 7-year follow-up. CONCLUSION: Image-guided AHPT 5- and 7-year outcomes show high efficacy, minimal physician-assessed toxicity, and excellent patient-reported outcomes in this cohort.

The incidence of brainstem toxicity following high-dose conformal proton therapy for adult skull-base malignancies.

BACKGROUND: Dose escalation for skull-based malignancies often presents risks to critical adjacent neural structures, including the brainstem. We report the incidence of brainstem toxicity following fractionated high-dose conformal proton therapy and associated dosimetric parameters. MATERIAL AND METHODS: We performed a single-institution review of patients with skull-base chordoma or chondrosarcoma who were treated with proton therapy between February 2007 and January 2020 on a prospective outcomes-tracking protocol. The primary endpoint was grade ≥2 brainstem toxicity. No patients received concurrent chemotherapy, and brainstem toxicity was censored for analysis if it coincided with local disease progression. RESULTS: We analyzed 163 patients who received a minimum of 45 GyRBE to 0.03 cm3 of the brainstem. Patients were treated to a median total dose of 73.8 (range 64.5-74.4) GyRBE at 1.8 GyRBE per fraction with 17 patients undergoing twice-daily treatment at 1.2 GyRBE per fraction. With a median follow-up of 4 years, the 5-year cumulative incidence of grade ≥2 brainstem injury was 1.3% (95% CI 0.25-4.3%). There was one grade 2, one grade 3, and no grade 4 or 5 events, with all patients recovering function with medical management. CONCLUSION: In delivering curative-intent radiotherapy for skull-base chordoma and chondrosarcoma in adults, small volumes of the brainstem can safely receive at least 64 GyRBE with minimal risk of serious brainstem injury.

Adjuvant I-131 therapy for T0-3 N1b M0 differentiated thyroid cancer with many (≥ 5) positive nodes.

Background: In patients with well-differentiated thyroid cancer, there is controversy about the prognostic importance of a large number of positive neck nodes and the potential value of radioiodine therapy. The purpose of this study was to evaluate this issue in the group of patients for whom it is most clinically important - those with classic histology and favorable T and M stage. Materials and methods: Twenty-five patients met the following inclusion criteria: classic histology of papillary or follicular thyroid carcinoma treated with total thyroidectomy and neck dissection followed by adjuvant I-131 treatment in our department between January 1, 2003, and December 31, 2013; adult age of > 21 years; and American Joint Committee on Cancer (AJCC ) stage (8th edition) of T0-3, N1b with ≥ 5 positive nodes, and M0. Results: The median positive node number was 10 (range, 5-31). The median adjuvant I-131 dose was 158 mCi (range, 150-219 mCi). The median follow-up in patients without recurrence after treatment was 7.3 years. The 10-year actuarial rates were favorable: overall survival, 100%; freedom from visible recurrence, 82%; and visible or biochemical recurrence, 72%. Conclusion: Recurrence was infrequent in our study population with ≥ 5 positive nodes following moderate-dose adjuvant I-131 treatment. These results are valuable in directing initial adjuvant therapy and follow-up intensity. Our results do not inform the question of the use of postoperative thyroglobulin (Tg) level to select N1b patients for low-dose I-131 treatment.

Intraoperative radiation therapy for early-stage breast cancer: a single-institution experience.

Background: To assess outcomes and toxicity after low-energy intraoperative radiotherapy (IORT) for early-stage breast cancer (ESBC). Materials and methods: We reviewed patients with unilateral ESBC treated with breast-conserving surgery and 50-kV IORT at our institution. Patients were prescribed 20 Gy to the surface of the spherical applicator, fitted to the surgical cavity during surgery. Patients who did not meet institutional guidelines for IORT alone on final pathology were recommended adjuvant treatment, including additional surgery and/or external-beam radiation therapy (EBRT). We analyzed ipsilateral breast tumor recurrence, overall survival, recurrence-free survival and toxicity. Results: Among 201 patients (median follow-up, 5.1 years; median age, 67 years), 88% were Her2 negative and ER positive and/or PR positive, 98% had invasive ductal carcinoma, 87% had grade 1 or 2, and 95% had clinical T1 disease. Most had pathological stage T1 (93%) N0 (95%) disease. Mean IORT applicator dose at 1-cm depth was 6.3 Gy. Post-IORT treatment included additional surgery, 10%; EBRT, 11%; adjuvant chemotherapy, 9%; and adjuvant hormonal therapy, 74%. Median total EBRT dose was 42.4 (range, 40.05-63) Gy and median dose per fraction was 2.65 Gy. At 5 years, the cumulative incidence of ipsilateral breast tumor recurrence was 2.7%, the overall survival rate was 95% with no breast cancer-related deaths, and the recurrence-free survival rate was 96%. For patients who were deemed unsuitable for postoperative IORT alone and did not receive recommended risk-adapted EBRT, the IBTR rate was 4.7% versus 1.7% (p = 0.23) for patients who were either suitable for IORT alone or unsuitable and received adjuvant EBRT. Cosmetic toxicity data was available for 83%, with 7% experiencing grade 3 breast toxicity and no grade 4-5 toxicity. Conclusions: IORT for select patients with ESBC results in acceptable outcomes in regard to ipsilateral breast tumor recurrence and toxicity.

Proton therapy for adult medulloblastoma: Acute toxicity and disease control outcomes.

PURPOSE: We report disease control, survival outcomes, and treatment-related toxicity among adult medulloblastoma patients who received proton craniospinal irradiation (CSI) as part of multimodality therapy. METHODS: We reviewed 20 adults with medulloblastoma (≥ 22 years old) who received postoperative proton CSI ± chemotherapy between 2008 and 2020. Patient, disease, and treatment details and prospectively obtained patient-reported acute CSI toxicities were collected. Acute hematologic data were analyzed. RESULTS: Median age at diagnosis was 27 years; 45% of patients had high-risk disease; 75% received chemotherapy, most (65%) after CSI. Eight (40%) patients received concurrent vincristine with radiotherapy. Median CSI dose was 36GyE with a median tumor bed boost of 54GyE. Median duration of radiotherapy was 44 days. No acute ≥ grade 3 gastrointestinal or hematologic toxicities attributable to CSI occurred. Grade 2 nausea and vomiting affected 25% and 5% of patients, respectively, while 36% developed acute grade 2 hematologic toxicity (36% grade 2 leukopenia and 7% grade 2 neutropenia). Those receiving concurrent chemotherapy with CSI had a 38% rate of grade 2 hematologic toxicity compared to 33% among those not receiving concurrent chemotherapy. Among patients receiving adjuvant chemotherapy (n = 13), 100% completed ≥ 4 cycles and 85% completed all planned cycles. With a median follow-up of 3.1 years, 4-year actuarial local control, disease-free survival, and overall survival rates were 90%, 90%, and 95%, respectively. CONCLUSIONS: Proton CSI in adult medulloblastoma patients is very well tolerated and shows promising disease control and survival outcomes. These data support the standard use of proton CSI for adult medulloblastoma.

Outcomes following limited-volume proton therapy for multifocal spinal myxopapillary ependymoma.

PURPOSE: Spinal myxopapillary ependymoma (MPE) often presents with a multifocal distribution, complicating attempts at resection. There remains no standard approach to irradiating these patients. We report disease control and toxicity in pediatric patients with multifocal spinal MPE treated with limited-volume proton therapy. MATERIALS/METHODS: Twelve patients (≤21 years old) with multifocal spinal MPE were treated between 2009 and 2018 with limited-volume brain-sparing proton therapy. Median age was 13.5 years (range, 7-21). Radiotherapy was given as adjuvant therapy after primary surgery in five patients (42%) and for recurrence in seven (58%). No patient received prior radiation. Eleven patients (92%) had evidence of gross disease at radiotherapy. Eleven patients received 54 GyRBE; one received 50.4 GyRBE. Treatment toxicity was graded per the CTCAEv4.0. We estimated disease control and survival using the Kaplan-Meier product-limit method. RESULTS: The median follow-up was 3.6 years (range, 1.8-10.6). The five-year actuarial rates of local control, progression-free survival, and overall survival were 100%, 92%, and 100%, respectively. One patient experienced an out-of-field recurrence in the spine superior to the irradiated region. No patients developed in-field recurrences. Following surgery and irradiation, one patient developed grade three spinal kyphosis and one patient developed grade 2 unilateral L5 neuropathy. CONCLUSION: 54 GyRBE to a limited volume appears effective for disseminated spinal MPE in both the primary and salvage settings, sparing children the toxicity of full craniospinal irradiation. Compared with historical reports, this approach using proton therapy improves the therapeutic ratio, resulting in minimal side effects and high rates of disease control.

Second tumor risk in children treated with proton therapy.

BACKGROUND: Out-of-field neutron dissemination during double-scattered proton therapy has raised concerns of increased second malignancies, disproportionally affecting pediatric patients due to the proportion of body exposed to scatter dose and inherent radiosensitivity of developing tissue. We sought to provide empiric data on the incidence of early second tumors. METHODS: Between 2006 and 2019, 1713 consecutive children underwent double-scattered proton therapy. Median age at treatment was 9.1 years; 371 were ≤3 years old. Thirty-seven patients (2.2%) had tumor predisposition syndromes. Median prescription dose was 54 Gy (range 15-75.6). Median follow-up was 3.3 years (range 0.1-12.8), including 6587 total person-years. Five hundred forty-nine patients had ≥5 years of follow-up. A second tumor was defined as any solid neoplasm throughout the body. RESULTS: Eleven patients developed second tumors; the 5- and 10-year cumulative incidences were 0.8% (95% CI, 0.4-1.9%) and 3.1% (95% CI, 1.5-6.2%), respectively. Using age- and gender-specific data from the Surveillance, Epidemiology, and End Results (SEER) program, the standardized incidence ratio was 13.5; the absolute excess risk was 1.5/1000 person-years. All but one patient who developed second tumors were irradiated at ≤5 years old (p < .0005). There was also a statistically significant correlation between patients with tumor predisposition syndromes and second tumors (p < .0001). Excluding patients with tumor predisposition syndromes, 5- and 10-year rates were 0.6% (95% CI, 0.2-1.7%) and 1.7% (95% CI, 0.7-4.0%), respectively, with all five malignant second tumors occurring in the high-dose region. CONCLUSION: Second tumors are rare within the decade following double-scattered proton therapy, particularly among children irradiated at >5 years old and those without tumor predisposition syndrome.

Clinical outcomes following proton therapy for adult craniopharyngioma: a single-institution cohort study.

BACKGROUND: Craniopharyngioma is a benign tumor that commonly develops within the suprasellar region. The tumor and treatment can have debilitating consequences for pediatric and adult patients, including vision loss and pituitary/hypothalamic dysfunction. Most craniopharyngioma series focus on treatment of the pediatric population. We evaluated the outcomes of all adult craniopharyngioma patients treated at our institution using proton therapy to report outcomes for disease control, treatment-related toxicity, and tumor response. METHODS: We analyzed 14 adult patients (≥ 22 years old). All patients had gross disease at the time of radiotherapy. Five were treated for de novo disease and 9 for recurrent disease. Patients received double-scattered conformal proton therapy to a mean dose of 54 GyRBE in 1.8 GyRBE/fraction (range 52.2-54 GyRBE). Weekly magnetic resonance imaging (MRI) helped to evaluate tumor changes during radiotherapy. RESULTS: With median clinical and radiographic follow-up of 29 and 26 months, respectively, the 3-year local control and overall survival rates were both 100%. There were no grade 3 or greater acute or late radiotherapy-related side effects. There was no radiotherapy-related vision loss or optic neuropathy. No patients required intervention or treatment replanning due to tumor changes during radiotherapy. Two patients experienced transient cyst expansion at their first post-radiotherapy MRI. Both patients were followed closely clinically and radiographically and had subsequent dramatic tumor/cyst regression, requiring no interventions. CONCLUSIONS: Our data support the safety and efficacy of proton therapy in the treatment of adult craniopharyngioma as part of primary or salvage treatment. We recommend early consideration of radiotherapy. This trial was registered at www.clinicaltrials.gov as #NCT03224767.

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.

Visual decline in pediatric survivors of brain tumors following radiotherapy.

PURPOSE: Radiotherapy-related visual decline is a significant concern in survivors of childhood cancer; however, data establishing the dose-response relationship between dose to the optic apparatus and visual acuity decline in children are sparse. We aimed to determine this relationship in a cohort of children treated with proton therapy. MATERIAL AND METHODS: We identified 458 children with 875 eyes at risk treated with proton therapy for intracranial malignancy between December 2006 and September 2018. Eyes were considered at risk if either the ipsilateral optic nerve or optic chiasm received ≥30 GyRBE to 0.1 cm3. Kaplan-Meier and Normal Tissue Complication Probability modeling was used to establish the relationship between radiotherapy dose and risk of visual decline. RESULTS: Excluding children with tumor progression, no patient experienced complete vision loss. The actuarial 5-year rate of any visual acuity decline was 2.6% (95% confidence interval [CI]: 1.5%-4.6%). The dose to 0.1 cm3 of the ipsilateral optic nerve or optic chiasm resulting in a 1%, 5%, and 10% risk of acuity decline were 52.7 GyRBE, 56.6 GyRBE, and 58.3 GyRBE. Visual decline was only seen in children with primary tumors of the optic pathway or suprasellar region. CONCLUSIONS: Visual acuity decline following radiotherapy for intracranial malignancies in children is rare. A dose of approximately 56 GyRBE to 0.1 cm3 results in an approximately 5% risk of visual acuity decline for children with suprasellar or optic pathway tumors. A dose to 0.1 cm3 of 56 GyRBE appears to be safe for children with tumors elsewhere in the brain.

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.

Serum Testosterone 60 Months after Passive-Scatter Proton Therapy for Localized Prostate Cancer.

Studies demonstrate a decline of ∼10% in serum testosterone (ST) level after X-ray radiotherapy for prostate cancer. We evaluated changes in ST for patients with low- and intermediate-risk prostate cancer receiving 70-82Gy(RBE) using passive-scatter proton therapy (PT). ST was checked at baseline (n = 358) and at 60+ months after PT (n = 166). The median baseline ST was 363.3 ng/dl (range, 82.0-974.0). The median ST 5 years after PT was 391.5 ng/dl (range, 108.0-1061.0). The difference was not statistically significant (p = 0.9341). Passive-scatter PT was not associated with testosterone suppression at 5 years, suggesting that protons may cause less out-of-field scatter radiation than X-rays.

Proton therapy for skull-base chondrosarcoma, a single-institution outcomes study.

BACKGROUND: We sought to evaluate the effectiveness of definitive or adjuvant external-beam proton therapy on local control and survival in patients with skull-base chondrosarcoma. METHODS: We reviewed the medical records of 43 patients with a median age of 49 years (range, 23-80 years) treated with double-scattered 3D conformal proton therapy for skull-base chondrosarcomas between January 2007 and February 2016. Proton therapy-related toxicities were scored using CTCAE v4.0. RESULTS: The median radiotherapy dose was 73.8 Gy(RBE) (range, 64.5-74.4 Gy[RBE]). Thirty-six (84%) and 7 (16%) patients underwent surgical resection or biopsy alone. Tumor grade distribution included: grade 1, 19 (44%) patients; grade 2, 22 (51%); and grade 3, 2 (5%). Forty patients had gross disease at the time of radiotherapy and 7 patients were treated for locally recurrent disease following surgery. The median follow-up was 3.7 years (range, 0.7-10.1 years). There were no acute grade 3 toxicities related to RT. At 4 years following RT, actuarial rates of overall survival, cause-specific survival, local control, and RT-related grade 3 toxicity-free survival were 95%, 100%, 89%, and 95%. CONCLUSION: High-dose, double-scattered 3D conformal proton therapy alone or following surgical resection for skull-base chondrosarcoma is an effective treatment with a high rate of local control with no acute grade 3 radiation-related toxicity. Further follow-up of this cohort is necessary to better characterize long-term disease control and late toxicities.

Impact of unfavorable factors on outcomes among inoperable stage II-IV Nonsmall cell lung cancer patients treated with proton therapy.

PURPOSE: To investigate the impact of unfavorable risk factors among patients with locally advanced nonsmall cell lung cancer (LA-NSCLC) treated with proton therapy (PT). MATERIAL AND METHODS: From May 2008 through July 2015, 90 consecutive patients with unresectable stage II-IV (oligometastatic) NSCLC were treated with PT. Unfavorable factors including age ≥80 years, stage IV, weight loss >10% in 3 months, performance status (PS) ≥2, FEV1 < 1.0 or O2 dependency, prior lung cancer, prior lung surgery, prior 2nd cancer in the past 3 years, and prior chest irradiation were evaluated. All patients received standard fractionation of 1.8-2 Gy(RBE) (median dose, 70 Gy[RBE]). Overall survival (OS) and progression-free survival (PFS) were calculated with the Kaplan-Meier method. The impact of unfavorable factors was analyzed in Cox regression models. RESULTS: Twenty-six percent were favorable-risk, while 42%, 22%, and 10% had 1-, 2-, or ≥3 unfavorable factors. The 2-year OS was 52% and 45% (p = .8522), and 2-year PFS was 21% and 44% (p = .0207), for favorable and unfavorable risk patients, respectively. Among patients with stage III-IV, only PS ≥2 adversely impacted OS (p = .0015). CONCLUSION: Most patients treated with PT for LA-NSCLC have unfavorable risk factors. These patients had similar outcomes to favorable-risk patients. Enrollment in future clinical trials may improve if eligibility is less restrictive.

Radiotherapy for Orbital Pseudotumor: The University of Florida Experience.

BACKGROUND: To evaluate outcomes after definitive radiotherapy for orbital pseudotumor. METHODS: We reviewed adult patients treated between 1971 and 2012. RESULTS: 20 patients with 8.0-year median follow-up were analyzed. Symptoms improved in 75% of patients: 40% showed a complete response, 35% partial response, and 20% had stable disease. The disease progressed in 1 and recurred in 8 patients. Local control rates were 63% and 53% at 5 and 10 years, respectively. The most common toxicities were cataracts (10%) and dry eye (10%). CONCLUSIONS: Radiotherapy for orbital pseudotumor is well-tolerated and results in long-term control in most patients, with local control in over half.