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Search indexed NASA NTRS and DOE OSTI research on propulsion, heat transfer, battery materials and energy systems. Follow report and document links to the original sources.

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At least 1,693 records · Page 94
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DOE OSTI2016

Learning From Trials on Radiation Dose in Non-Small Cell Lung Cancer

In this issue of the International Journal of Radiation Oncology • Biology • Physics, Taylor et al present a meta-analysis of published data supporting 2 findings: (1) radiation dose escalation seems to benefit patients who receive radiation alone for non-small cell lung cancer; and (2) radiation dose escalation has a detrimental effect on overall survival in the setting of concurrent chemotherapy. The latter finding is supported by data but has perplexed the oncology community. Perhaps these findings are not perplexing at all. Perhaps it is simply another lesson in the major principle in radiation oncology, to minimize radiation dose to normal tissues.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2016

The Impact of Radiation Treatment Time on Survival in Patients With Head and Neck Cancer

Purpose: To assess the impact of radiation treatment time (RTT) in head and neck cancers on overall survival (OS) in the era of chemoradiation. Methods and Materials: Patients with diagnoses of tongue, hypopharynx, larynx, oropharynx, or tonsil cancer were identified by use of the National Cancer Database. RTT was defined as date of first radiation treatment to date of last radiation treatment. In the definitive setting, prolonged RTT was defined as >56 days, accelerated RTT was defined as <47 days, and standard RTT was defined as 47 to 56 days. In the postoperative setting, prolonged RTT was defined as >49 days, accelerated RTT was defined as <40 days, and standard RTT was defined as 40 to 49 days. We used χ{sup 2} tests to identify predictors of RTT. The Kaplan-Meier method was used to compare OS among groups. Cox proportional hazards model was used for OS analysis in patients with known comorbidity status. Results: 19,531 patients were included; 12,987 (67%) had a standard RTT, 4,369 (34%) had an accelerated RTT, and 2,165 (11%) had a prolonged RTT. On multivariable analysis, accelerated RTT (hazard ratio [HR] 0.84; 95% confidence interval [CI] 0.73-0.97) was associated with an improved OS, and prolonged RTT (HR 1.25; 95% CI 1.14-1.37) was associated with a worse OS relative to standard RTT. When the 9,200 (47%) patients receiving definitive concurrent chemoradiation were examined, prolonged RTT (HR 1.29; 95% CI 1.11-1.50) was associated with a worse OS relative to standard RTT, whereas there was no significant association between accelerated RTT and OS (HR 0.76; 95% CI 0.57-1.01). Conclusion: Prolonged RTT is associated with worse OS in patients receiving radiation therapy for head and neck cancer, even in the setting of chemoradiation. Expeditious completion of radiation should continue to be a quality metric for the management of head and neck malignancies.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2016

Salivary Cytokine Levels and Oral Mucositis in Head and Neck Cancer Patients Treated With Chemotherapy and Radiation Therapy

Purpose: We assessed the presence of salivary cytokines, their modulation during chemoradiation therapy (CTRT), and their association with oral mucositis severity in patients with head and neck cancer (HNC). Methods and Materials: The present prospective observational study enrolled 55 patients with locally advanced HNC requiring CTRT. We also studied 10 healthy volunteers and 10 patients with other cancers. The salivary levels of 13 cytokines were analyzed. We constructed a cytokine predictive score of oral mucositis severity. Results: The baseline salivary cytokine levels were not associated with the severity of treatment-induced oral mucositis. The cytokine levels overall increased during treatment, especially in patients with worse mucositis. In particular, on univariable analysis, an increase of interleukin (IL)-1β (area under the curve [AUC] 0.733; P=.009), IL-6 (AUC 0.746; P=.005), and tumor necrosis factor-α (AUC 0.710; P=.005) at the third week of treatment was significantly associated with the development of severe oral mucositis. On multivariable analysis, the predictive score based on the IL-1β and IL-6 changes from baseline to week 3 was an early strong predictor of higher grade oral mucositis. Conclusions: The treatment of HNC patients with concurrent CTRT induces a significant increase in the salivary levels of IL-1β, IL-6, and tumor necrosis factor-α, all positively associated with the severity of mucosal toxicity. A greater increase of IL-1β and IL-6 3 weeks after treatment initiation is predictive of worse oral mucositis, representing a potential tool for the early identification of patients at risk.

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

Does Unintentional Splenic Radiation Predict Outcomes After Pancreatic Cancer Radiation Therapy?

Purpose: To determine whether severity of lymphopenia is dependent on radiation dose and fractional volume of spleen irradiated unintentionally during definitive chemoradiation (CRT) in patients with locally advanced pancreatic cancer (LAPC). Methods: 177 patients with LAPC received induction chemotherapy (mainly gemcitabine-based regimens) followed by CRT (median 50.4 Gy with concurrent capecitabine) from January 2006 to December 2012. Absolute lymphocyte count (ALC) was recorded at baseline, before CRT, and 2 to 10 weeks after CRT. Splenic dose-volume histogram (DVH) parameters were reported as mean splenic dose (MSD) and percentage of splenic volume receiving at least 5- (V5), 10- (V10), 15- (V15), and 20-Gy (V20) dose. Overall survival (OS) was analyzed with use of the Cox model, and development of post-CRT severe lymphopenia (ALC <0.5 K/UL) was assessed by multivariate logistic regression with use of baseline and treatment factors. Results: The median post-CRT ALC (0.68 K/UL; range, 0.13-2.72) was significantly lower than both baseline ALC (1.42 K/UL; range, 0.34-3.97; P<.0001) and pre-CRT ALC (1.32 K/UL, range 0.36-4.82; P<.0001). Post-CRT ALC <0.5 K/UL was associated with inferior OS on univariate analysis (median, 11.1 vs 15.3 months; P=.01) and multivariate analysis (hazard ratio = 1.66, P=.01). MSD (9.8 vs 6 Gy, P=.03), median V10 (32.6 vs 16%, P=.04), V15 (23.2 vs 9.5%, P=.03), and V20 (15.4 vs 4.6%, P=.02) were significantly higher in patients with severe lymphopenia than in those without. On multivariate analysis, postinduction lymphopenia (P<.001; odds ratio [OR] = 5.25) and MSD (P=.002; OR= 3.42) were independent predictors for the development of severe post-CRT lymphopenia. Conclusion: Severe post-CRT lymphopenia is an independent predictor of poor OS in LAPC patients receiving CRT. Higher splenic doses increase the risk for the development of severe post-CRT lymphopenia. When clinically indicated, assessment of splenic DVHs before the acceptance of treatment plans may minimize the risk of severe post-CRT lymphopenia.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2017

A Randomized Phase 2 Trial of Prophylactic Manuka Honey for the Reduction of Chemoradiation Therapy–Induced Esophagitis During the Treatment of Lung Cancer: Results of NRG Oncology RTOG 1012

Purpose: Randomized trials have shown that honey is effective for the prevention of radiation-induced mucositis in head and neck cancer patients. Because there is no efficacious preventative for radiation esophagitis in lung cancer patients, this trial compared liquid honey, honey lozenges, and standard supportive care for radiation esophagitis. Methods: The patients were stratified by percentage of esophagus receiving specific radiation dose (V60 Gy esophagus <30% or ≥30%) and were then randomized between supportive care, 10 mL of liquid manuka honey 4 times a day, and 2 lozenges (10 mL of dehydrated manuka honey) 4 times a day during concurrent chemotherapy and radiation therapy. The primary endpoint was patient-reported pain on swallowing, with the use of an 11-point (0-10) scale at 4 weeks (Numerical Rating Pain Scale, NRPS). The study was designed to detect a 15% relative reduction of change in NRPS score. The secondary endpoints were trend of pain over time, opioid use, clinically graded and patient-reported adverse events, weight loss, dysphagia, nutritional status, and quality of life. Results: 53 patients were randomized to supportive care, 54 were randomized to liquid honey, and 56 were randomized to lozenge honey. There was no significant difference in the primary endpoint of change in the NRPS at 4 weeks between arms. There were no differences in any of the secondary endpoints except for opioid use at 4 weeks during treatment between the supportive care and liquid honey arms, which was found to be significant (P=.03), with more patients on the supportive care arm taking opioids. Conclusion: Honey as prescribed within this protocol was not superior to best supportive care in preventing radiation esophagitis. Further testing of other types of honey and research into the mechanisms of action are needed.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2017

Radical Cystectomy Compared to Combined Modality Treatment for Muscle-Invasive Bladder Cancer: A Systematic Review and Meta-Analysis

Purpose: To perform a comprehensive comparison of overall survival (OS), disease-specific survival (DSS), progression-free survival (PFS), and treatment-related complications between radical cystectomy (RC) and combined modality treatment (CMT—radiation therapy, concurrent chemotherapy, and maximal transurethral resection of bladder tumor) in the setting of muscle-invasive bladder cancer. Methods and Materials: We searched 7 databases (PubMed, Scopus, EMBASE, Proquest, CINAHL, and (ClinicalTrials.gov)) for randomized, controlled trials and prospective and retrospective studies directly comparing RC with CMT from database inception to March 2016. We conducted meta-analyses evaluating OS, DSS, and PFS with hazard ratios (HRs) and 95% confidence intervals (CIs). Results: Nineteen studies evaluating 12,380 subjects were selected. For the 8 studies encompassing 9554 subjects eligible for meta-analyses, we found no difference in OS at 5 years (HR 0.96, favoring CMT, 95% CI 0.72-1.29; P=.778) or 10 years (HR 1.02, favoring cystectomy, 95% CI 0.73-1.42; P=.905). No difference was observed in DSS at 5 years (HR 0.83, favoring radiation, 95% CI 0.54-1.28; P=.390) or 10 years (HR 1.17, favoring cystectomy, 95% CI 0.89-1.55; P=.264), or PFS at 10 years (HR 0.85, favoring CMT, 95% CI 0.43-1.67; P=.639). The cystectomy arms had higher rates of early major complications, whereas rates of minor complications were similar between the 2 treatments. Conclusion: Current meta-analysis reveals no differences in OS, DSS, or PFS between RC and CMT. Further randomized, controlled trials are necessary to identify the optimal treatment for specific patients.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2017

Single Nucleotide Polymorphism TGFβ1 R25P Correlates with Acute Toxicity during Neoadjuvant Chemoradiotherapy in Rectal Cancer Patients

Purpose: To validate the finding of an association between single nucleotide polymorphisms (SNPs) and toxicity during chemoradiotherapy (CRT) in rectal cancer patients, in an independent population. Methods and Materials: The cohort consisted of 165 patients who received CRT for rectal cancer from 2006 to 2012. Prospectively recorded toxicity information, graded according to the Common Terminology Criteria for Adverse Events version 3.0, was retrieved from the medical record. Additionally, a subset of 52 patients recorded their gastrointestinal symptoms weekly during CRT, using the 7-item Bowel Problems Scale. Deoxyribonucleic acid was extracted from normal tissue in the proctectomy specimens and screened for 3 SNPs: XRCC1 R399Q, XPD K751Q, and TGFβ1 R25P. Univariable and multivariable logistic regression models were constructed. Results: The median radiation dose was 50.4 Gy, and all patients received concurrent chemotherapy. Toxicities measured by the Common Terminology Criteria for Adverse Events were closely associated with patient-reported outcomes for the patients who completed the 7-item Bowel Problems Scale. Grade ≥3 toxicity occurred during CRT in 14 patients (8%). All 14 patients had either XRCC1 R399Q or TGFβ1 R25P polymorphisms. The TGFβ1 R25P polymorphism was significantly associated with grade ≥3 toxicity (odds ratio [OR] 3.47, P=.04) and, in patients who completed the Bowel Problems Scale, with grade ≥4 toxicity (OR 5.61, P=.02). The latter finding persisted in a multivariable logistic regression model controlling for ethnicity, age, and sex (adjusted OR 1.83, P=.02). Conclusions: We have validated the correlation between the TGFβ1 R25P SNP and acute toxicity during CRT in an independent cohort using both clinician- and patient-reported toxicity. The information from our study could be used as a basis to formulate a prospective trial testing the utility of this SNP as a biomarker of acute toxicity during neoadjuvant treatment in locally advanced rectal cancer.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2017

The Risk of Radiation-Induced Tumors or Malignant Transformation After Single-Fraction Intracranial Radiosurgery: Results Based on a 25-Year Experience

Purpose: To determine the risk of radiation-induced tumors or malignant transformation after single-fraction intracranial stereotactic radiosurgery (SRS). Methods and Materials: We performed a retrospective review of 1837 patients who received single-fraction SRS for arteriovenous malformation or benign tumor (meningioma, vestibular schwannoma, pituitary adenoma, glomus tumor) at a single center between 1990 and 2009. Patients were excluded if they refused research authorization (n=31), had a genetic predisposition to tumor development (n=84), received prior or concurrent radiation therapy (n=79), or had less than 5 years of imaging follow-up after SRS (n=501). The median imaging follow-up period for the remaining 1142 patients was 9.0 years (range, 5-24.9 years). Results: No radiation-induced tumors were identified in 11,264 patient-years of follow-up after SRS. The risk of a radiation-induced tumor developing after SRS was 0.0% at 5 years (95% confidence interval [CI], 0.0%-0.4%), 0.0% at 10 years (95% CI, 0.0%-0.9%), and 0.0% at 15 years (95% CI, 0.0%-2.8%). Malignant transformation occurred in 7 of 316 meningioma patients (2.2%) and 1 of 358 vestibular schwannoma patients (0.3%) at a median of 4.9 years (range, 2.8-13.8 years) after SRS. No cases of malignant transformation were noted in patients with pituitary adenomas (n=188) or glomus tumors (n=47). The 5-, 10-, and 15-year risk of malignant transformation was 0.5% (95% CI, 0.0%-0.9%), 0.8% (95% CI, 0.0%-1.8%), and 2.4% (95% CI, 0.0%-5.5%), respectively. Patients who underwent prior resection (hazard ratio, 14.56; 95% CI, 1.79-118.33; P=.01) and who had meningioma pathology (hazard ratio, 11.72; 95% CI, 1.44-96.15; P=.02) were at increased risk of malignant transformation. Conclusions: The risk of radiation-induced tumors or malignant transformation after SRS is very low and should not be used as a justification for choosing alternative treatment approaches (surgical resection, observation) over SRS for appropriate patients.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2017

Multicenter Evaluation of the Tolerability of Combined Treatment With PD-1 and CTLA-4 Immune Checkpoint Inhibitors and Palliative Radiation Therapy

Purpose: To analyze immune-related adverse events (ir-AEs) in patients treated with radiation and immune checkpoint blockade. Methods and Materials: We retrospectively reviewed records from patients with metastatic non-small cell lung cancer, melanoma, or renal cell cancer who received at least 1 cycle of a CTLA-4 or PD-1 inhibitor and radiation. Immune-related adverse events, defined using Common Terminology Criteria for Adverse Events version 4.0, were tabulated in relation to treatment variables, and associations with sequencing and timing were assessed. Results: We identified 133 patients, of whom 28 received a CTLA-4 inhibitor alone, 88 received a PD-1 inhibitor alone, and 17 received both classes of inhibitors either sequentially (n=13) or concurrently (n=4). Fifty-six patients received radiation within 14 days of an immune checkpoint inhibitor. Forty-six patients experienced at least 1 ir-AE (34.6%). Patients receiving both CTLA-4 and PD-1 inhibitors experienced more any-grade ir-AEs as compared with either individually (71% vs 29%, P=.0008). Any-grade ir-AEs occurred in 39% of patients in whom radiation was administered within 14 days of immunotherapy, compared with 23% of other patients (P=.06) and more often in patients who received higher equivalent dose in 2-Gy fractions (EQD2) EQD2 (P=.01). However, most toxicities were mild. There were no associations between site irradiated and specific ir-AEs. Conclusions: Our data suggest the combination of focal palliative radiation and CTLA-4 and/or PD-1 inhibitors is well tolerated, with manageable ir-AEs that did not seem to be associated with the particular site irradiated. Although conclusions are limited by the heterogeneity of patients and treatments, and future confirmatory studies are needed, this information can help guide clinical practice for patients receiving immune checkpoint therapy who require palliative radiation therapy.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2017

The Older Adult With Locoregionally Advanced Head and Neck Squamous Cell Carcinoma: Knowledge Gaps and Future Direction in Assessment and Treatment

Older adults with head and neck squamous cell carcinoma (HNSCC) pose unique treatment and supportive care challenges to oncologists and other cancer care providers. The majority of patients with HNSCC present with locoregionally advanced disease, for which combined-modality treatment integrating chemotherapy and radiation therapy is often necessary to maximize tumor control. However, applying these approaches to an older population with concomitant comorbidities and a higher risk of functional impairments remains challenging and is exacerbated by the paucity of studies involving older adults. The purpose of this article is to identify knowledge gaps in the evaluation and management of older adults with HNSCC—particularly those undergoing concurrent chemoradiation therapy—and their caregivers through a review of the literature conducted by clinicians, researchers, and patient advocates. The findings highlight the importance of a geriatric assessment and the therapeutic paradigms and challenges relevant to this population. Furthermore, we identify the need for additional research and interventions related to key supportive care issues that arise during and after treatment in older adults with locoregionally advanced HNSCC. On the basis of our findings, we prioritize these issues to guide future patient-oriented research endeavors to address these knowledge gaps and thus better serve this growing patient population.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2017

Dosimetric Predictors of Patient-Reported Xerostomia and Dysphagia With Deintensified Chemoradiation Therapy for HPV-Associated Oropharyngeal Squamous Cell Carcinoma

Purpose/Objective(s): To estimate the association between different dose-volume metrics of the salivary glands and pharyngeal constrictors with patient reported severity of xerostomia/dysphagia in the setting of deintensified chemoradiation therapy (CRT). Methods and Materials: Forty-five patients were treated on a phase 2 study assessing the efficacy of deintensified CRT for favorable-risk, HPV-associated oropharyngeal squamous cell carcinoma. Patients received 60 Gy intensity modulated radiation therapy with concurrent weekly cisplatin (30 mg/m{sup 2}), and reported the severity of their xerostomia/dysphagia (before and after treatment) using the patient-reported outcome version of the Common Terminology Criteria for Adverse Events (CTCAE) (PRO-CTCAE). Individual patient dosimetric data of the contralateral parotid and submandibular glands and pharyngeal constrictors were correlated with changes in PRO-CTCAE severity. A change in severity (from baseline) of ≥2 was considered clinically meaningful. Associations between dose-volume metrics and patient outcomes were assessed with receiver operating characteristic (ROC) curve and logistic regression model. Results: Six months after CRT, patients reporting <2 change in xerostomia severity (n=14) had an average D{sub mean} = 22 ± 9 Gy to the sum of the contralateral glands (parotid + submandibular) compared with the patients reporting ≥2 change (n=21), who had an average D{sub mean} = 34 ± 8 Gy. V15 to V55 for the combined contralateral glands showed the strongest association with xerostomia (area under the curve [AUC] = 0.83-0.86). Based on the regression analysis, a 20% risk of toxicity was associated with V15 = 48%, V25 = 30%, and D{sub mean}=21 Gy. Six months after CRT, patients reporting <2 change in dysphagia severity (n=26) had an average V55 = 76 ± 13 (%) to the superior pharyngeal constrictor compared with the patients reporting ≥2 change in severity (n=9), who had average V55 = 89 ± 13 (%). V55to V60 had the strongest association with dysphagia (AUC = 0.70-0.75). Based on the regression analysis, a 20% risk of toxicity was associated with V55 = 78%, V60 = 40%. The findings at 12 months were similar. Conclusions: After deintensified CRT, the rate of patient-reported xerostomia/dysphagia appears to be associated with the V15 of the combined contralateral salivary glands and V55 to V60 of the superior pharyngeal constrictors.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2017

Prognostic Relevance of Treatment Failure Patterns in Pediatric High-Grade Glioma: Is There a Role for a Revised Failure Classification System?

Purpose: We sought to investigate the pattern of treatment failure with respect to anatomic extent, radiation dose, and criteria for failure according to the Response Assessment in Neuro-Oncology (RANO). We evaluated the corresponding prognostic significance of these factors in patients with pediatric high-grade glioma (pHGG). Methods and Materials: Fifty-six patients with pHGG were enrolled in an institutional phase 1 to 2 prospective trial that included maximal safe resection and radiation therapy with concurrent and adjuvant erlotinib. The radiation therapy dose administered was 54 to 59.4 Gy at 1.8 Gy/d. Tumor progression was defined according to clinical symptoms and imaging features and was classified in relation to the original extent of the tumor, radiation prescription target volume coverage, and RANO criteria (RANOc). Results: With a median follow-up period of 90 months (range, 70-124 months), progression occurred in 48 patients (85.7%) while 8 (14.3%) were without progression. Central failure represented 42.6% of the total cohort, while in-field, marginal, and distant failures occurred in 7.4%, 9.3%, and 22.2%, respectively. Patients with biopsy or subtotal resection had increased rates of central failure and represented 14.81% and 16.67% of the total cohort, respectively. Tumor progression was classified as local, local plus distant, or distant. Among patients with local failure as a component of failure, 5 were considered to have marginal failure. Patients with frontal, temporal, and parietal disease had the highest rates of multifocal failure. A comparison between responses defined by RANOc demonstrated varied time to death (TTD) from progression. Conclusions: Pediatric high-grade glioma was shown to have high rates of central failure, particularly in cases with limited resection. Patients with central failure had a trend toward more prolonged TTD from failure relative to other failure patterns. The low marginal failure rates seen in this group suggest that less conservative radiation target margins may be possible. TTD from failure varied according to RANO type, suggesting that adult RANOc require modification before being applied to pHGG.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2017

Phase 1 Study of Ipilimumab Combined With Whole Brain Radiation Therapy or Radiosurgery for Melanoma Patients With Brain Metastases

Purpose: We performed a phase 1 study to determine the maximum tolerable dose and safety of ipilimumab with stereotactic radiosurgery (SRS) or whole brain radiation therapy (WBRT) in patients with brain metastases from melanoma. Methods and Materials: Based on the intracranial disease burden, patients underwent WBRT (arm A) or SRS (arm B). The ipilimumab starting dose was 3 mg/kg every 3 weeks, starting on day 3 of WBRT or 2 days after SRS. The ipilimumab dose was escalated to 10 mg/kg using a 2-stage, 3+3 design. The primary endpoint was to determine the maximum tolerable dose of ipilimumab combined with radiation therapy. The secondary endpoints were overall survival, intracranial and extracranial control, progression-free survival, and toxicity. The (ClinicalTrials.gov) registration number is (NCT01703507). Results: The characteristics of the 16 patients enrolled between 2011 and 2014 were mean age, 60 years; median number of brain metastases, 2 (range 1->10); and number with EC disease, 13 (81%). Treatment included WBRT (n=5), SRS (n=11), and ipilimumab 3 mg/kg (n=7) or 10 mg/kg (n=9). The median follow-up was 8 months (arm A) and 10.5 months (arm B). A total of 21 grade 1 to 2 neurotoxic effects occurred, with no dose-limiting toxicities. One patient experienced grade 3 neurotoxicity before ipilimumab administration. Ten additional grade 3 toxicities were reported, with gastrointestinal toxicities (n=5; 31%) the most common. No patient developed grade 4 or 5 toxicity. The median progression-free survival and overall survival in arm A was 2.5 months and 8 months and in arm B was 2.1 months and not reached, respectively. Conclusions: Concurrent ipilimumab 10 mg/kg with SRS is safe. The WBRT arm was closed early because of slow accrual but demonstrated safety with ipilimumab 3 mg/kg. No patient experienced dose-limiting toxicity. Larger studies, including those with combination checkpoint inhibitor therapy and SRS, are warranted.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2018

Prospective, Multicenter, Phase 2 Trial of Induction Chemotherapy Followed by Bio-Chemoradiotherapy for Locally Advanced Recurrent Nasopharyngeal Carcinoma

To evaluate, in a phase 2 study, whether induction docetaxel, cisplatin, and fluorouracil (TPF) followed by weekly docetaxel and cetuximab in concurrence with intensity modulated radiation therapy can improve the treatment outcome for patients with advanced locally recurrent nasopharyngeal carcinoma (rNPC).

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2021

Phase 1 Study of Low-Dose Fractionated Whole Abdominal Radiation Therapy in Combination With Weekly Paclitaxel for Platinum-Resistant Ovarian Cancer (GCGS-01)

Low-dose fractionated whole abdominal radiation therapy (LDFWART) has synergistic activity with paclitaxel in preclinical models. The aim of this phase 1 trial was to determine the recommended phase 2 dose and preliminary activity of weekly paclitaxel (wP) concurrent with LDFWART in patients with platinum-resistant ovarian cancer (PROC).

62 RADIOLOGY AND NUCLEAR MEDICINE↗