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At least 1,225 records · Page 68
All sourcesNASA NTRSDOE OSTI
DOE OSTI2015

COSMIC: A Regimen of Intensity Modulated Radiation Therapy Plus Dose-Escalated, Raster-Scanned Carbon Ion Boost for Malignant Salivary Gland Tumors: Results of the Prospective Phase 2 Trial

Purpose: To investigate the effect of intensity modulated radiation therapy (IMRT) and dose-escalated carbon ion (C12) therapy in adenoid cystic carcinoma (ACC) and other malignant salivary gland tumors (MSGTs) of the head and neck. Patients and Methods: COSMIC (combined treatment of malignant salivary gland tumors with intensity modulated radiation therapy and carbon ions) is a prospective phase 2 trial of 24 Gy(RBE) C12 followed by 50 Gy IMRT in patients with pathologically confirmed MSGT. The primary endpoint is mucositis Common Terminology Criteria grade 3; the secondary endpoints are locoregional control (LC), progression-free survival (PFS), overall survival (OS), and toxicity. Toxicity was scored according to the Common Terminology Criteria for Adverse Events version 3; treatment response was scored according to Response Evaluation Criteria in Solid Tumors 1.1. Results: Between July 2010 and August 2011, 54 patients were accrued, and 53 were available for evaluation. The median follow-up time was 42 months; patients with microscopically incomplete resections (R1, n=20), gross residual disease (R2, n=17), and inoperable disease (n=16) were included. Eighty-nine percent of patients had ACC, and 57% had T4 tumors. The most common primary sites were paranasal sinus (34%), submandibular gland, and palate. At the completion of radiation therapy, 26% of patients experienced grade 3 mucositis, and 20 patients reported adverse events of the ear (38%). The most common observed late effects were grade 1 xerostomia (49%), hearing impairment (25%, 2% ipsilateral hearing loss), and adverse events of the eye (20%), but no visual impairment or loss of vision. Grade 1 central nervous system necrosis occurred in 6%, and 1 grade 4 ICA hemorrhage without neurologic sequelae. The best response was 54% (complete response/partial remission). At 3 years, the LC, PFS, and OS were 81.9%, 57.9%, and 78.4%, respectively. No difference was found regarding resection status. The most common site of failure was distant (55%). Local relapse was predominantly in field (79%). Conclusion: Treatment was tolerated, with moderate acute and late toxicity. The LC at 3 years was promising. No significant difference could be shown regarding resection status; hence, extensive and mutilating surgical procedures should be rediscussed. Further dose escalation may be limited in view of potential vascular adverse events.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2015

A Phase 1/2 Study of Definitive Chemoradiation Therapy Using Docetaxel, Nedaplatin, and 5-Fluorouracil (DNF-R) for Esophageal Cancer

Purpose: Patient survival in esophageal cancer (EC) remains poor. The purpose of this study was to investigate a regimen of definitive chemoradiation therapy (CRT) that exerts good local control of EC. We performed a phase 1/2 study to assess the safety and efficacy of CRT with docetaxel, nedaplatin, and 5-fluorouracil (DNF-R). Methods and Materials: Eligible patients presented with stage IB to IV EC. Patients received 2 cycles of docetaxel (20, 30, or 40 mg/m{sup 2}) and nedaplatin (50 mg/m{sup 2}) on days 1 and 8 and a continuous infusion of 5-fluorouracil (400 mg/m{sup 2}/day) on days 1 to 5 and 8 to 12, every 5 weeks, with concurrent radiation therapy (59.4 Gy/33 fractions). The recommended dose (RD) was determined using a 3 + 3 design. Results: In the phase 1 study, the dose-limiting toxicities were neutropenia and thrombocytopenia. The RD of docetaxel was determined to be 20 mg/m{sup 2}. In the phase 2 study, grade 3 to 4 acute toxicities included neutropenia (42.8%), febrile neutropenia (7.14%), thrombocytopenia (17.9%), and esophagitis (21.4%). Grade 3 to 4 late radiation toxicity included esophagostenosis (10.7%). The complete response rate was 82.1% (95% confidence interval: 67.9-96.3%). Both the median progression-free survival and overall survival were 41.2 months. Conclusions: DNF-R showed good tolerability and strong antitumor activity, suggesting that it is a potentially effective therapeutic regimen for EC.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2016

High-Dose-Rate Brachytherapy as Monotherapy for Intermediate- and High-Risk Prostate Cancer: Clinical Results for a Median 8-Year Follow-Up

Purpose: To present mature results of high-dose-rate brachytherapy (HDR-BT) as monotherapy for intermediate- and high-risk prostate cancer. Methods and Materials: From 1995 through 2012, 190 patients, 79 with intermediate-risk and 111 with high-risk prostate cancer, were treated with HDR-BT alone using 48 Gy/8 fractions, 54 Gy/9 fractions, or 45.5 Gy/7 fractions over 4 to 5 days. Neoadjuvant with or without adjuvant androgen deprivation therapy was administered to 139 patients, 35 intermediate- and 104 high-risk. Results: Median follow-up time was 92 months (range, 10-227 months), with a minimum of 2 years for surviving patients. Respective rates of cause-specific survival, overall survival, metastasis-free survival, and biochemical no evidence of disease for the intermediate-risk patients were 100%, 100%, 96%, and 93% at 5 years, and 100%, 96%, 91%, and 91% at 8 years. Corresponding rates for the high-risk patients were 97%, 93%, 84%, and 81% at 5 years, and 93%, 81%, 74%, and 77% at 8 years. The cumulative incidence of late grade 2 to 3 genitourinary toxicity was 5% at 5 years and 10% at 8 years, and that of late grade 3 was 0 at 5 years and 1% at 8 years. The cumulative incidence of late grade 2-3 gastrointestinal toxicity was 4% at 5 years and 6% at 8 years, and that of late grade 3 was 0 at 5 years and 2% at 8 years. No grade 4 or 5 toxicity was detected. Conclusions: Our single-institution study with a median 8-year follow-up showed that HDR-BT as monotherapy was safe and effective for patients with intermediate- and high-risk prostate cancer.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2016

High-Dose-Rate Monotherapy for Localized Prostate Cancer: 10-Year Results

Purpose: High-dose-rate (HDR) brachytherapy was originally used with external beam radiation therapy (EBRT) to increase the dose to the prostate without injuring the bladder or rectum. Numerous studies have reported HDR brachytherapy is safe and effective. We adapted it for use without EBRT for cases not requiring lymph node treatment. Patients and Methods: We entered the patient demographics, disease characteristics, and treatment parameters into a prospective registry and serially added follow-up data for 448 men with low-risk (n=288) and intermediate-risk (n=160) prostate cancer treated from 1996 to 2009. Their median age was 64 years (range 42-90). The median prostate-specific antigen (PSA) level was 6.0 ng/mL (range 0.2-18.2). The Gleason score was ≤6 in 76% and 7 in 24%. The median dose was 43.5 Gy in 6 fractions. The clinical and biochemical disease control and survival rates were calculated. Adverse events were graded according to the Common Toxicity Criteria of Adverse Events. Results: The median follow-up period was 6.5 years (range 0.3-15.3). The actuarial 6- and 10-year PSA progression-free survival was 98.6% (95% confidence interval [CI] 96.9%-99.4%) and 97.8% (95% CI 95.5%-98.9%). Overall survival at 10 years was 76.7% (95% CI 69.9%-82.2%). The local control, distant metastasis-free survival, and cause-specific survival were 99.7% (95% CI 97.9%-99.9%), 98.9% (95% CI 96.3%-99.7%), and 99.1% (95% CI 95.8%-99.8%). T stage, initial PSA level, Gleason score, National Comprehensive Cancer Network risk group, patient age, and androgen deprivation therapy did not significantly correlate with disease control or survival. No late grade 3 to 4 rectal toxicities developed. Late grade 3 to 4 genitourinary toxicity occurred in 4.9% (grade 3 in 4.7%). Conclusions: HDR monotherapy is a safe and highly effective treatment of low- and intermediate-risk prostate cancer.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2015

Phase 1 Dose Escalation Study of Accelerated Radiation Therapy With Concurrent Chemotherapy for Locally Advanced Lung Cancer

Purpose: To determine the maximum tolerated dose of radiation therapy (RT) given in an accelerated fashion with concurrent chemotherapy using intensity modulated RT. Methods and Materials: Patients with locally advanced lung cancer (non-small cell and small cell) with good performance status and minimal weight loss received concurrent cisplatin and etoposide with RT. Intensity modulated RT with daily image guidance was used to facilitate esophageal avoidance and delivered using 6 fractions per week (twice daily on Fridays with a 6-hour interval). The dose was escalated from 58 Gy to a planned maximum dose of 74 Gy in 4 Gy increments in a standard 3 + 3 trial design. Dose-limiting toxicity (DLT) was defined as acute grade 3-5 nonhematologic toxicity attributed to RT. Results: A total of 24 patients were enrolled, filling all dose cohorts, all completing RT and chemotherapy as prescribed. Dose-limiting toxicity occurred in 1 patient at 58 Gy (grade 3 esophagitis) and 1 patient at 70 Gy (grade 3 esophageal fistula). Both patients with DLTs had large tumors (12 cm and 10 cm, respectively) adjacent to the esophagus. Three additional patients were enrolled at both dose cohorts without further DLT. In the final 74-Gy cohort, no DLTs were observed (0 of 6). Conclusions: Dose escalation and acceleration to 74 Gy with intensity modulated RT and concurrent chemotherapy was tolerable, with a low rate of grade ≥3 acute esophageal reactions.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2016

A Phase 2 Open Label, Single-Arm Trial to Evaluate the Combination of Cetuximab Plus Taxotere, Cisplatin, and 5-Flurouracil as an Induction Regimen in Patients With Unresectable Squamous Cell Carcinoma of the Head and Neck

Purpose: Despite treatment, prognosis of unresectable squamous cell carcinoma of the head and neck (SCCHC) is dismal. Cetuximab therapy has proven to increase the clinical activity of radiation therapy and chemotherapy in patients with locoregional advanced disease with an acceptable toxicity profile. We designed a phase 2 trial to evaluate the efficacy of docetaxel, cisplatin, and 5-fluorouracil (TPF) plus cetuximab (C-TPF) as an induction regimen in patients with unresectable SCCHN. Methods and Materials: A single-arm phase 2 trial was conducted. Eligible patients included those with untreated unresectable SCCHC, World Health Organization performance status of 0 to 1, 18 to 70 years of age. Treatment consisted of four 21-day cycles of TPF (docetaxel, 75 mg/m{sup 2} day 1; cisplatin, 75 mg/m{sup 2} day 1; 5-fluorouracil [5-FU], 750 mg/m{sup 2} day 1-5) and cetuximab, 250 mg/m{sup 2} weekly (loading dose of 400 mg/m{sup 2}). Prophylactic granulocyte colony-stimulating factor and antibiotic support were given. After induction, sequential accelerated radiation therapy with concomitant boost (69.9 Gy) and weekly cetuximab therapy were delivered in the absence of disease progression. The primary endpoint was objective response rate (ORR) to C-TPF. Results: Fifty patients were enrolled across 8 centers. Median age was 54 years; disease was stage IV; oropharynx and hypopharynx were the most common primary sites. Eighty-two percent received 4 cycles of C-TPF, and 86% started sequential treatment based on radiation therapy and cetuximab. ORR after C-TPF was 86% (95% confidence interval [CI]: 73%-94%) and 24% had complete response (CR). With a median follow-up of 40.7 months, median overall survival (OS) was 40.7 months. The 2-year actuarial locoregional control (LRC) rate was 57%. The most common drug-related grade 3 or 4 toxicities during induction were neutropenia (24%), neutropenic fever (24%), and diarrhea (20%). There were 3 treatment-related deaths (6%). Conclusions: C-TPF yields high ORR and CR as induction treatment in unresectable SCCHN. However, hematologic toxicity is too high to recommend this regimen at the current dose.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2016

Gemcitabine Plus Radiation Therapy for High-Grade Glioma: Long-Term Results of a Phase 1 Dose-Escalation Study

Purpose: To evaluate the tolerability and efficacy of gemcitabine plus radiation therapy (RT) in this phase 1 study of patients with newly diagnosed malignant glioma (HGG). Patients and Methods: Between 2004 and 2012, 29 adults with HGG were enrolled. After any extent of resection, RT (60 Gy over 6 weeks) was given concurrent with escalating doses of weekly gemcitabine. Using a time-to-event continual reassessment method, 5 dose levels were evaluated starting at 500 mg/m{sup 2} during the last 2 weeks of RT and advanced stepwise into earlier weeks. The primary objective was to determine the recommended phase 2 dose of gemcitabine plus RT. Secondary objectives included progression-free survival, overall survival (OS), and long-term toxicity. Results: Median follow-up was 38.1 months (range, 8.9-117.5 months); 24 patients were evaluable for toxicity. After 2005 when standard practice changed, patients with World Health Organization grade 4 tumors were no longer enrolled. Median progression-free survival for 22 patients with grade 3 tumors was 26.0 months (95% confidence interval [CI] 15.6-inestimable), and OS was 48.5 months (95% CI 26.8-inestimable). In 4 IDH mutated, 1p/19q codeleted patients, no failures occurred, with all but 1 alive at time of last follow-up. Seven with IDH mutated, non-codeleted tumors with ATRX loss had intermediate OS of 73.5 months (95% CI 32.8-inestimable). Six nonmutated, non-codeleted patients had a median OS of 26.5 months (95% CI 25.4-inestimable). The recommended phase 2 dose of gemcitabine plus RT was 750 mg/m{sup 2}/wk given the last 4 weeks of RT. Dose reductions were most commonly due to grade 3 neutropenia; no grade 4 or 5 toxicities were seen. Conclusions: Gemcitabine concurrent with RT is well-tolerated and yields promising outcomes, including in patients with adverse molecular features. It is a candidate for further study, particularly for poor-prognosis patient subgroups with HGG.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2016

A Phase 2 Trial of Concurrent Chemotherapy and Proton Therapy for Stage III Non-Small Cell Lung Cancer: Results and Reflections Following Early Closure of a Single-Institution Study

Purpose: Proton therapy has been shown to reduce radiation dose to organs at risk (OAR) and could be used to safely escalate the radiation dose. We analyzed outcomes in a group of phase 2 study patients treated with dose-escalated proton therapy with concurrent chemotherapy for stage 3 non-small cell lung cancer (NSCLC). Methods and Materials: From 2009 through 2013, LU02, a phase 2 trial of proton therapy delivering 74 to 80 Gy at 2 Gy/fraction with concurrent chemotherapy for stage 3 NSCLC, was opened to accrual at our institution. Due to slow accrual and competing trials, the study was closed after just 14 patients (stage IIIA, 9 patients; stage IIIB, 5 patients) were accrued over 4 years. During that same time period, 55 additional stage III patients were treated with high-dose proton therapy, including 7 in multi-institutional proton clinical trials, 4 not enrolled due to physician preference, and 44 who were ineligible based on strict entry criteria. An unknown number of patients were ineligible for enrollment due to insurance coverage issues and thus were treated with photon radiation. Median follow-up of surviving patients was 52 months. Results: Two-year overall survival and progression-free survival rates were 57% and 25%, respectively. Median lengths of overall survival and progression-free survival were 33 months and 14 months, respectively. There were no acute grade 3 toxicities related to proton therapy. Late grade 3 gastrointestinal toxicity and pulmonary toxicity each occurred in 1 patient. Conclusions: Dose-escalated proton therapy with concurrent chemotherapy was well tolerated with encouraging results among a small cohort of patients. Unfortunately, single-institution proton studies may be difficult to accrue and consideration for pragmatic and/or multicenter trial design should be considered when developing future proton clinical trials.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2016

Prospective Study Delivering Simultaneous Integrated High-dose Tumor Boost (≤70 Gy) With Image Guided Adaptive Radiation Therapy for Radical Treatment of Localized Muscle-Invasive Bladder Cancer

Purpose: Image guided adaptive radiation therapy offers individualized solutions to improve target coverage and reduce normal tissue irradiation, allowing the opportunity to increase the radiation tumor dose and spare normal bladder tissue. Methods and Materials: A library of 3 intensity modulated radiation therapy plans were created (small, medium, and large) from planning computed tomography (CT) scans performed at 30 and 60 minutes; treating the whole bladder to 52 Gy and the tumor to 70 Gy in 32 fractions. A “plan of the day” approach was used for treatment delivery. A post-treatment cone beam CT (CBCT) scan was acquired weekly to assess intrafraction filling and coverage. Results: A total of 18 patients completed treatment to 70 Gy. The plan and treatment for 1 patient was to 68 Gy. Also, 1 patient's plan was to 70 Gy but the patient was treated to a total dose of 65.6 Gy because dose-limiting toxicity occurred before dose escalation. A total of 734 CBCT scans were evaluated. Small, medium, and large plans were used in 36%, 48%, and 16% of cases, respectively. The mean ± standard deviation rate of intrafraction filling at the start of treatment (ie, week 1) was 4.0 ± 4.8 mL/min (range 0.1-19.4) and at end of radiation therapy (ie, week 5 or 6) was 1.1 ± 1.6 mL/min (range 0.01-7.5; P=.002). The mean D{sub 98} (dose received by 98% volume) of the tumor boost and bladder as assessed on the post-treatment CBCT scan was 97.07% ± 2.10% (range 89.0%-104%) and 99.97% ± 2.62% (range 96.4%-112.0%). At a median follow-up period of 19 months (range 4-33), no muscle-invasive recurrences had developed. Two patients experienced late toxicity (both grade 3 cystitis) at 5.3 months (now resolved) and 18 months after radiation therapy. Conclusions: Image guided adaptive radiation therapy using intensity modulated radiation therapy to deliver a simultaneous integrated tumor boost to 70 Gy is feasible, with acceptable toxicity, and will be evaluated in a randomized trial.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2016

Intensity Modulated Radiation Therapy for Early-Stage Primary Gastric Diffuse Large B-Cell Lymphoma: Dosimetric Analysis, Clinical Outcome, and Quality of Life

Purpose: To evaluate the dosimetric superiority, efficacy, toxicity, and quality of life (QOL) data of intensity modulated radiation therapy (IMRT) in patients with primary gastric diffuse large B-cell lymphoma (PG-DLBCL). Methods and Materials: Forty-six consecutive patients with early-stage PG-DLBCL underwent IMRT after chemotherapy. The majority of patients (61.5%) were subclassified as the non-germinal center B cell–like subtype. Dosimetric parameters of the planning target volume (PTV) and organs at risk were assessed. Survival rates were depicted with the Kaplan-Meier method and compared with the log-rank test. Quality of life was evaluated using the QLQ-C30-STO22 questionnaires at the last follow-up contact. Results: The median PTV mean dose was 41.6 Gy. Only 0.73% of the PTV received <95% of the prescribed dose, indicating excellent target coverage. The median kidney V20 and liver V30 were 14.1% and 16.1%, respectively. The 5-year overall survival (OS), progression-free survival, and locoregional control rates for all patients were 80.4%, 75.0%, and 93.2%, respectively. Stage, lactate dehydrogenase level, and immunophenotype were significant prognostic factors for OS, and only stage was a significant factor for locoregional control. Consolidation IMRT in patients with complete response after chemotherapy resulted in significantly better OS and progression-free survival than salvage IMRT in patients with non-complete response. Two of 8 patients who had chronic liver disease experienced grade 4 or grade 5 acute hepatic failure after 4 to 5 cycles of rituximab-based chemotherapy and IMRT (40 Gy). No other serious acute or late toxicity was observed. The long-term global and functional QOL scales were excellent, with negligible symptom scales. Conclusions: Intensity modulated radiation therapy yielded excellent target coverage and critical tissue sparing and achieved favorable outcomes with acceptable toxicity and good long-term QOL in early-stage PG-DLBCL.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2016

Stereotactic Radiosurgery: Treatment of Brain Metastasis Without Interruption of Systemic Therapy

Purpose: To evaluate the prevalence, outcomes, and toxicities of concurrent delivery of systemic therapy with stereotactic radiosurgery (SRS) for treatment of brain metastases. Methods and Materials: We conducted a retrospective review of 193 patients treated at our institution with SRS without prior whole-brain radiation therapy (WBRT) for brain metastases between 2009 and 2014. Outcome metrics included administration of concurrent systemic therapy, myelosuppression, neurotoxicity, and survival. Results: One hundred ninety-three patients with a median age of 61 years underwent a total of 291 SRS treatments. Thirty-seven percent of SRS treatments were delivered concurrently with systemic therapy, of which 46% were with conventional myelosuppressive chemotherapy, and 54% with targeted and immune therapy agents. Myelosuppression was minimal after treatment with both systemic therapy and SRS, with 14% grade 3-4 toxicity for lymphopenia and 4-9% for leukopenia, neutropenia, anemia, and thrombocytopenia. Neurotoxicity was also minimal after combined therapy, with no grade 4 and <5% grade 3 toxicity, 34% dexamethasone requirement, and 4% radiation necrosis, all similar to treatments with SRS alone. Median overall survival was similar after SRS alone (14.4 months) versus SRS with systemic therapy (12.9 months). In patients with a new diagnosis of primary cancer with brain metastasis, early treatment with concurrent systemic therapy and SRS correlated with improved survival versus SRS alone (41.6 vs 21.5 months, P<.05). Conclusions: Systemic therapy can be safely given concurrently with SRS for brain metastases: our results suggest minimal myelosuppression and neurotoxicity. Concurrent therapy is an attractive option for patients who have both intracranial and extracranial metastatic disease and may be particularly beneficial in patients with a new diagnosis of primary cancer with brain metastasis.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2016

Stereotactic Body Radiation Therapy for Spinal Metastases in the Postoperative Setting: A Secondary Analysis of Mature Phase 1-2 Trials

Purpose: To evaluate the outcomes in patients treated on prospective phase 1-2 protocols with postoperative stereotactic body radiation therapy (SBRT) and identify the associated prognostic variables. Methods and Materials: Sixty-six patients with 69 tumors were treated with SBRT on prospective phase 1-2 studies for spinal metastases between 2002 and 2010. All patients underwent SBRT after spine surgery, which included laminectomy, vertebrectomy, or a combination of these techniques. Renal cell carcinoma was the most common histology represented (n=35, 53%) followed by sarcomas (n=13, 20%). Thirty-one patients (47%) were treated with prior conventional radiation to the spine (median dose 30 Gy). Patients were followed up with spinal magnetic resonance imaging (MRI) studies to determine the treated tumor control (TC). Pain and other symptom data were collected prospectively to determine treatment response and toxicity. Results: The median follow-up time was 30 months (range, 1-145 months) for all patients and 75 months for living patients (range, 6-145 months). The actuarial 1-year rate of TC was 85%, adjacent vertebral body control was 85%, and overall survival (OS) was 74% (median 29 months). On multivariate competing-risks analysis, sarcoma histology (subhazard ratio [SHR] = 2.38, 95% confidence interval [CI] 1.05-5.6, P=.04) and larger preoperative tumor volumes (SHR=1.01, 95% CI 1.0-1.01, P=.006) were significantly associated with worse TC. Karnofsky performance status was the only significant predictor for OS on multivariate analysis. There were no differences in TC between patients treated with different surgical techniques or different preoperative or postoperative Bilsky grades. There were no grade 3 or higher neurologic toxicities. Conclusion: This study represents a large series of prospective data available on patients treated with SBRT in the postoperative setting. The combination of surgery with SBRT can offer patients with metastatic disease to the spine the chance of durable tumor control with minimal toxicity.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2016

A Novel Form of Breast Intraoperative Radiation Therapy With CT-Guided High-Dose-Rate Brachytherapy: Results of a Prospective Phase 1 Clinical Trial

Purpose: Existing intraoperative radiation therapy (IORT) techniques are criticized for the lack of image guided treatment planning and energy deposition with, at times, poor resultant dosimetry and low radiation dose. We pioneered a novel method of IORT that incorporates customized, computed tomography (CT)-based treatment planning and high-dose-rate (HDR) brachytherapy to overcome these drawbacks: CT-HDR-IORT. Methods and Materials: A phase 1 study was conducted to demonstrate the feasibility and safety of CT-HDR-IORT. Eligibility criteria included age ≥50 years, invasive or in situ breast cancer, tumor size <3 cm, and N0 disease. Patients were eligible before or within 30 days of breast-conserving surgery (BCS). BCS was performed, and a multilumen balloon catheter was placed. CT images were obtained, a customized HDR brachytherapy plan was created, and a dose of 12.5 Gy was delivered to 1-cm depth from the balloon surface. The catheter was removed, and the skin was closed. The primary endpoints were feasibility and acute toxicity. Feasibility was defined as IORT treatment interval (time from CT acquisition until IORT completion) ≤90 minutes. The secondary endpoints included dosimetry, cosmetic outcome, quality of life, and late toxicity. Results: Twenty-eight patients were enrolled. The 6-month follow-up assessments were completed by 93% of enrollees. The median IORT treatment interval was 67.2 minutes (range, 50-108 minutes). The treatment met feasibility criteria in 26 women (93%). The dosimetric goals were met in 22 patients (79%). There were no Radiation Therapy Oncology Group grade 3+ toxicities; 6 patients (21%) experienced grade 2 events. Most patients (93%) had good/excellent cosmetic outcomes at the last follow-up visit. Conclusions: CT-HDR-IORT is feasible and safe. This promising approach for a conformal, image-based, higher-dose breast IORT is being evaluated in a phase 2 trial.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2016

The Outcome for Patients With Pathologic Node-Positive Prostate Cancer Treated With Intensity Modulated Radiation Therapy and Androgen Deprivation Therapy: A Case-Matched Analysis of pN1 and pN0 Patients

Purpose: Improved outcome is reported after surgery or external beam radiation therapy (EBRT) plus androgen deprivation therapy (ADT) for patients with lymph node (LN) positive (N1) prostate cancer (PC). Surgical series have shown that pathologic (p)N1 PC does not behave the same in all patients. The aim of this study was to perform a matched-case analysis to compare the outcome of pN1 and pN0 PC after high-dose EBRT plus ADT. Methods and Materials: Radiation therapy up to 80 Gy was delivered to the prostate with a minimal dose of 45 Gy to the pelvis for pN1 patients. After matching, Kaplan-Meier statistics were used to compare the 5-year biochemical and clinical relapse-free survival (bRFS and cRFS), prostate cancer–specific survival (PCSS), and overall survival (OS). Acute and late rectal and urinary toxicity was evaluated. Results: Sixty-nine pN1 PC patients were matched 1:1 with pN0 PC patients. The median follow-up time was 60 months. The 5-year bRFS and cRFS for pN1 versus pN0 PC patients were 65% ± 7% versus 79% ± 5% (P=.08) and 70% ± 6% versus 83% ± 5% (P=.04) respectively. No significant difference was found in bRFS or cRFS rates between low volume pN1 (≤2 positive LNs) and pN0 patients. The 5-year PCSS and OS were comparable between pN1 and pN0 PC patients: PCSS: 92% ± 4% versus 93% ± 3% (P=.66); OS: 82% ± 5% versus 80% ± 5% (P=.58). Severe toxicity was rare for both groups, although pN1 patients experienced significantly more acute grade 2 rectal toxicity. Conclusion: Primary EBRT plus 2 to 3 years of ADT is a legitimate treatment option for pN1 PC patients, especially those with ≤2 positive LNs, and this with bRFS and cRFS rates comparable to those in pN0 PC patients. For pN1 PC patients with >2 positive LNs, bRFS and cRFS are worse than in pN0 patients, but even in this subgroup, long-term disease control is obtained.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2016

Long-Term Update of NRG Oncology RTOG 0319: A Phase 1 and 2 Trial to Evaluate 3-Dimensional Conformal Radiation Therapy Confined to the Region of the Lumpectomy Cavity for Stage I and II Breast Carcinoma

Purpose: NRG Oncology RTOG 0319 was the first cooperative group trial in the United States to evaluate 3-dimensional conformal radiation therapy (3D-CRT) accelerated partial breast irradiation (APBI). This report updates secondary endpoints of toxicity and efficacy. Methods and Materials: Patients with stage I or II invasive breast cancer (tumor size ≤3 cm, ≤3 positive lymph nodes, negative margins) were eligible for 3D-CRT APBI: 38.5 Gy in 10 twice-daily fractions. Patient characteristics and treatment details have previously been reported. Adverse events were graded with CTCAE v3.0 (National Cancer Institute Common Terminology Criteria for Adverse Events version 3.0). This analysis updates the rates of ipsilateral breast recurrence (IBR), contralateral breast recurrence, ipsilateral node recurrence (INR), metastatic sites (distant metastases [DM]), mastectomy, disease-free survival, mastectomy-free survival, and overall survival. Results: Of 58 enrolled patients, 52 were eligible, with a median age of 61 years; 94% had stage I cancer and 83% had estrogen receptor positive disease. The median follow-up period was 8 years (minimum-maximum, 1.7-9.0 years). The 7-year estimate of isolated IBR (no DM) was 5.9%. The 7-year estimates of all IBRs, INR, mastectomy rate, and DM were 7.7%, 5.8%, 7.7%, and 7.7%, respectively. All 4 IBRs were invasive, of which 3 had a component within the planning target volume. The patterns of failure were as follows: 3 IBRs, 1 INR, 2 DM, 1 INR plus DM, and 1 IBR plus INR plus DM. The 7-year estimates of mastectomy-free survival, disease-free survival, and overall survival were 71.2%, 71.2%, and 78.8%, respectively. Thirteen patients died: 3 of breast cancer and 10 of other causes. Grade 3 (G3) treatment-related adverse events were reported by 4 patients (7.7%). No G3 pain or pulmonary or cardiac toxicities were reported. Conclusions: This phase 1 and 2 trial of 3D-CRT APBI continues to show durable tumor control and minimal G3 toxicity, comparable to other APBI techniques. Mature phase 3 results will determine the appropriateness and limitations of this noninvasive APBI technique.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2017

Genetic Variants in CD44 and MAT1A Confer Susceptibility to Acute Skin Reaction in Breast Cancer Patients Undergoing Radiation Therapy

Purpose: Heterogeneity in radiation therapy (RT)-induced normal tissue toxicity is observed in 10% of cancer patients, limiting the therapeutic outcomes. In addition to treatment-related factors, normal tissue adverse reactions also manifest from genetic alterations in distinct pathways majorly involving DNA damage–repair genes, inflammatory cytokine genes, cell cycle regulation, and antioxidant response. Therefore, the common sequence variants in these radioresponsive genes might modify the severity of normal tissue toxicity, and the identification of the same could have clinical relevance as a predictive biomarker. Methods and Materials: The present study was conducted in a cohort of patients with breast cancer to evaluate the possible associations between genetic variants in radioresponsive genes described previously and the risk of developing RT-induced acute skin adverse reactions. We tested 22 genetic variants reported in 18 genes (ie, NFE2L2, OGG1, NEIL3, RAD17, PTTG1, REV3L, ALAD, CD44, RAD9A, TGFβR3, MAD2L2, MAP3K7, MAT1A, RPS6KB2, ZNF830, SH3GL1, BAX, and XRCC1) using TaqMan assay-based real-time polymerase chain reaction. At the end of RT, the severity of skin damage was scored, and the subjects were dichotomized as nonoverresponders (Radiation Therapy Oncology Group grade <2) and overresponders (Radiation Therapy Oncology Group grade ≥2) for analysis. Results: Of the 22 single nucleotide polymorphisms studied, the rs8193 polymorphism lying in the micro-RNA binding site of 3′-UTR of CD44 was significantly (P=.0270) associated with RT-induced adverse skin reactions. Generalized multifactor dimensionality reduction analysis showed significant (P=.0107) gene–gene interactions between MAT1A and CD44. Furthermore, an increase in the total number of risk alleles was associated with increasing occurrence of overresponses (P=.0302). Conclusions: The genetic polymorphisms in radioresponsive genes act as genetic modifiers of acute normal tissue toxicity outcomes after RT by acting individually (rs8193), by gene–gene interactions (MAT1A and CD44), and/or by the additive effects of risk alleles.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2017

Hematologic Nadirs During Chemoradiation for Anal Cancer: Temporal Characterization and Dosimetric Predictors

Purpose: Pelvic bone marrow (BM) constraints may offer a means to reduce the toxicity commonly associated with chemoradiation for anal cancer. We conducted a bi-institutional analysis of dose-volume metrics in a time-sensitive fashion to devise practical metrics to minimize hematologic toxicity. Methods and Materials: Fifty-six anal cancer patients from 2 institutions received definitive radiation therapy (median primary dose of 54 Gy) using intensity modulated radiation therapy (IMRT, n=49) or 3-dimensional (3D) conformal therapy (n=7) with concurrent 5-fluorouracil (5-FU) and mitomycin C. Weekly blood counts were retrospectively plotted to characterize the time course of cytopenias. Dose-volume parameters were correlated with blood counts at a standardized time point to identify predictors of initial blood count nadirs. Results: Leukocytes, neutrophils, and platelets reached a nadir at week 3 of treatment. Smaller volumes of the pelvic BM correlated most strongly with lower week 3 blood counts, more so than age, sex, body mass index (BMI), or dose metrics. Patients who had ≥750 cc of pelvic BM spared from doses of ≥30 Gy had 0% grade 3+ leukopenia or neutropenia at week 3. Higher V40 Gy to the lower pelvic BM (LP V40) also correlated with cytopenia. Patients with an LP V40 >23% had higher rates of grade 3+ leukopenia (29% vs 4%, P=.02), grade 3+ neutropenia (33% vs 8%, P=.04), and grade 2+ thrombocytopenia (32% vs 7%, P=.04) at week 3. On multivariate analysis, pelvic BM volume and LP V40 remained associated with leukocyte count, and all marrow subsite volumes remained associated with neutrophil counts at week 3 (P<.1). Conclusions: Larger pelvic BM volumes correlate with less severe leukocyte and neutrophil nadirs, suggesting that larger total “marrow reserve” can mitigate cytopenias. Sparing a critical marrow reserve and limiting the V40 Gy to the lower pelvis may reduce the risk of hematologic toxicity.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2017

Nationwide, Multicenter, Retrospective Study on High-Dose-Rate Brachytherapy as Monotherapy for Prostate Cancer

Purpose: To present, analyze, and discuss results of a nationwide, multicenter, retrospective study on high-dose-rate brachytherapy (HDR-BT) as monotherapy for low-, intermediate-, and high-risk prostate cancer. Methods and Materials: From 1995 through 2013, 524 patients, 73 (14%) with low-risk, 207 (40%) with intermediate-risk, and 244 (47%) with high-risk prostate cancer, were treated with HDR-BT as monotherapy at 5 institutions in Japan. Dose fractionations were 27 Gy/2 fractions for 69 patients (13%), 45.5 Gy/7 fractions for 168 (32%), 49 Gy/7 fractions for 149 (28%), 54 Gy/9 fractions for 130 (25%), and others for 8 (2%). Of these patients, 156 (30%) did not receive androgen deprivation therapy, and 202 patients (39%) did receive androgen deprivation therapy <1 year, 112 (21%) for 1-3 years, and 54 (10%) for >3 years. Median follow-up time was 5.9 years (range, 0.4-18.1 years), with a minimum of 2 years for surviving patients. Results: After 5 years, respective actuarial rates of no biochemical evidence of disease, overall survival, cause-specific survival, and metastasis-free survival for all patients were 92%, 97%, 99%, and 94%. For low/intermediate/high-risk patients, the 5-year no biochemical evidence of disease rates were 95%/94%/89%, the 5-year overall survival rates were 98%/98%/94%, the 5-year cause-specific survival rates were 98%/100%/98%, and the 5-year metastasis-free survival rates were 98%/95%/90%, respectively. The cumulative incidence of late grade 2 to 3 genitourinary toxicity at 5 years was 19%, and that of late grade 3 was 1%. The corresponding incidences of gastrointestinal toxicity were 3% and 0% (0.2%). No grade 4 or 5 of either type of toxicity was detected. Conclusions: The findings of this nationwide, multicenter, retrospective study demonstrate that HDR-BT as monotherapy was safe and effective for all patients with low-, intermediate-, and high-risk prostate cancer.

62 RADIOLOGY AND NUCLEAR MEDICINE↗