Purpose: To perform a multi-institutional analysis following treatment of limited osseous and/or nodal metastases in patients using a novel hypofractionated image-guided radiotherapy with simultaneous-integrated boost (HIGRT-SIB) technique. Methods: Consecutive patients treated with HIGRT-SIB for ≤5 active metastases at Duke University Medical Center or Durham Veterans' Affairs Medical Center between 2013-2018 were analyzed to determine toxicities and recurrence patterns following treatment. Most patients received 50 Gy to the PTVboost and 30 Gy to the PTVelect simultaneously in 10 fractions. High-dose treatment volume recurrence (HDTVR) and low-dose treatment volume recurrence (LDTVR) were defined as recurrences within PTVboost and PTVelect, respectively. Marginal recurrence (MR) was defined as recurrence outside PTVelect, but within the adjacent bone or nodal chain. Distant recurrence (DR) was defined as recurrences not meeting HDTVR, LDTVR, or MR criteria. Freedom from pain recurrence (FFPR) was calculated in patients with painful osseous metastases prior to HIGRT-SIB. Outcome rates were estimated at 12 months using the Kaplan-Meier method. Results: 42 patients met inclusion criteria with 59 sites treated with HIGRT-SIB (53% nodal and 47% osseous). Median time from diagnosis to first metastasis was 31 months and the median age at HIGRT-SIB was 69 years. The most common primary tumors were prostate (36%), gastrointestinal (24%), and lung (24%). Median follow-up was 11 months. One acute grade ≥3 toxicity (febrile neutropenia) occurred after docetaxel administration immediately following HIGRT-SIB. Four patients developed late grade ≥3 toxicities: two ipsilateral vocal cord paralyses and two vertebral compression fractures. The overall pain response rate was 94% and the estimated FFPR at 12 months was 72%. The estimated 12-month rate of HDTVR, LDTVR, MR, and DR was 3.6%, 6.2%, 7.6%, and 55.8%, respectively. DR preceded MR, HDTVR, or LDTVR in each instance. Conclusion: Targeting areas at high-risk for occult disease with a lower radiation dose, while simultaneously boosting gross disease with HIGRT in patients with limited osseous and/or nodal metastases, has a high rate of treated metastasis control, a low rate of MR, acceptable toxicity, and high rate of pain palliation. Further investigation with prospective trials is warranted.
Primary meningeal rhabdomyosarcoma is a rare primary brain malignancy, with scant case reports. While most reports of primary intracranial rhabdomyosarcoma occur in pediatric patients, a handful of cases in adult patients have been reported in the medical literature. We report the case of a 44-year-old male who developed primary meningeal rhabdomyosarcoma. After developing episodes of right lower extremity weakness, word finding difficulty, and headaches, a brain magnetic resonance imaging (MRI) demonstrated a vertex lesion with radiographic appearance of a meningeal-derived tumor. Subtotal surgical resection was performed due to sagittal sinus invasion and initial pathology was interpreted as an anaplastic meningioma. Re-review of pathology demonstrated rhabdomyosarcoma negative for alveolar translocation t(2;13). Staging studies revealed no evidence of disseminated disease. He was treated with stereotactic radiotherapy with concurrent temozolamide to be followed by vincristine, actinomycin-D, and cyclophosphamide (VAC) systemic therapy.
<div>AbstractPurpose:<p>In this prospective trial, we sought to assess the feasibility of concurrent administration of ipilimumab and radiation as adjuvant, neoadjuvant, or definitive therapy in patients with regionally advanced melanoma.</p>Patients and Methods:<p>Twenty-four patients in two cohorts were enrolled and received ipilimumab at 3 mg/kg every 3 weeks for four doses in conjunction with radiation; median dose was 4,000 cGy (interquartile range, 3,550–4,800 cGy). Patients in cohort 1 were treated adjuvantly; patients in cohort 2 were treated either neoadjuvantly or as definitive therapy.</p>Results:<p>Adverse event profiles were consistent with those previously reported with checkpoint inhibition and radiation. For the neoadjuvant/definitive cohort, the objective response rate was 64% (80% confidence interval, 40%–83%), with 4 of 10 evaluable patients achieving a radiographic complete response. An additional 3 patients in this cohort had a partial response and went on to surgical resection. With 2 years of follow-up, the 6-, 12-, and 24-month relapse-free survival for the adjuvant cohort was 85%, 69%, and 62%, respectively. At 2 years, all patients in the neoadjuvant/definitive cohort and 10/13 patients in the adjuvant cohort were still alive. Correlative studies suggested that response in some patients were associated with specific CD4<sup>+</sup> T-cell subsets.</p>Conclusions:<p>Overall, concurrent administration of ipilimumab and radiation was feasible, and resulted in a high response rate, converting some patients with unresectable disease into surgical candidates. Additional studies to investigate the combination of radiation and checkpoint inhibitor therapy are warranted.</p></div>
In this prospective trial, we sought to assess the feasibility of concurrent administration of ipilimumab and radiation as adjuvant, neoadjuvant, or definitive therapy in patients with regionally advanced melanoma.
254 Background: Ampullary carcinoma is a rare malignancy. Despite radical resection, survival rates remain low with high rates of local failure. To define the role of radiation therapy and chemotherapy with surgery, we performed a single institution analysis of treatment- related outcomes. Methods: A retrospective analysis was performed of all patients undergoing potentially curative therapy for adenocarcinoma of the ampulla of Vater at Duke University Hospitals between 1975 and 2009. Local control (LC), overall survival (OS), disease-free survival (DFS), and metastases-free survival (MFS) were estimated using the Kaplan-Meier Method. Results: One hundred thirty-seven patients with ampullary carcinoma underwent potentially curative pancreaticoduodenectomy. Sixty-one patients undergoing resection received adjuvant (n= 43) or neoadjuvant (n=18) radiation therapy with concurrent chemotherapy (CRT). Patients receiving radiotherapy were more likely to have poorly differentiated tumors. Median radiation dose was 50 Gy. Median follow up was 8.8 years. Of patients receiving neoadjuvant therapy, 67% were downstaged on final pathology with 28% achieving pathologic complete response. Three-year local control was significantly improved in patients receiving CRT (88% vs. 55% p= 0.001) with trend toward a 3-year OS benefit in patients receiving CRT (62% vs. 46% p=0.074). Despite this, there was no significant difference in 3-year DFS (66% CRT vs 48% surgery alone p=0.09) or MFS (69% CRT vs 63% surgery alone p=0.337). Conclusions: Long term survival rates are low. Local failure rates are high following radical resection alone and improved with CRT. Despite more adverse pathologic features in patients receiving CRT, survival outcomes were at least equivalent with a trend toward statistical significance. Given the patterns of relapse with surgery alone and local control benefit in patients receiving CRT, the use of chemoradiotherapy in selected patients should be considered. No significant financial relationships to disclose.
