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At least 325 records · Page 18
All sourcesNASA NTRSDOE OSTI
DOE OSTI2012

Oral Mucositis Prevention By Low-Level Laser Therapy in Head-and-Neck Cancer Patients Undergoing Concurrent Chemoradiotherapy: A Phase III Randomized Study

Purpose: Oral mucositis is a major complication of concurrent chemoradiotherapy (CRT) in head-and-neck cancer patients. Low-level laser (LLL) therapy is a promising preventive therapy. We aimed to evaluate the efficacy of LLL therapy to decrease severe oral mucositis and its effect on RT interruptions. Methods and Materials: In the present randomized, double-blind, Phase III study, patients received either gallium-aluminum-arsenide LLL therapy 2.5 J/cm{sup 2} or placebo laser, before each radiation fraction. Eligible patients had to have been diagnosed with squamous cell carcinoma or undifferentiated carcinoma of the oral cavity, pharynx, larynx, or metastases to the neck with an unknown primary site. They were treated with adjuvant or definitive CRT, consisting of conventional RT 60-70 Gy (range, 1.8-2.0 Gy/d, 5 times/wk) and concurrent cisplatin. The primary endpoints were the oral mucositis severity in Weeks 2, 4, and 6 and the number of RT interruptions because of mucositis. The secondary endpoints included patient-reported pain scores. To detect a decrease in the incidence of Grade 3 or 4 oral mucositis from 80% to 50%, we planned to enroll 74 patients. Results: A total of 75 patients were included, and 37 patients received preventive LLL therapy. The mean delivered radiation dose was greater in the patients treated with LLL (69.4 vs. 67.9 Gy, p = .03). During CRT, the number of patients diagnosed with Grade 3 or 4 oral mucositis treated with LLL vs. placebo was 4 vs. 5 (Week 2, p = 1.0), 4 vs. 12 (Week 4, p = .08), and 8 vs. 9 (Week 6, p = 1.0), respectively. More of the patients treated with placebo had RT interruptions because of mucositis (6 vs. 0, p = .02). No difference was detected between the treatment arms in the incidence of severe pain. Conclusions: LLL therapy was not effective in reducing severe oral mucositis, although a marginal benefit could not be excluded. It reduced RT interruptions in these head-and-neck cancer patients, which might translate into improved CRT efficacy.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2012

Change in Pattern of Relapse After Antiangiogenic Therapy in High-Grade Glioma

Purpose: Local recurrence is the dominant pattern of relapse in high-grade glioma (HGG) after conventional therapy. The recent use of antiangiogenic therapy has shown impressive radiologic and clinical responses in adult HGG. The preclinical data suggesting increased invasiveness after angiogenic blockade have necessitated a detailed analysis of the pattern of recurrence after therapy. Methods and Materials: A total of 162 consecutive patients with HGG, either newly diagnosed (n = 58) or with recurrent disease (n = 104) underwent therapy with bevacizumab at 10 mg/kg every 2 weeks and conventional chemotherapy with or without involved field radiotherapy until disease progression. The pattern of recurrence and interval to progression were the primary aims of the present study. Diffuse invasive recurrence (DIR) was defined as the involvement of multiple lobes with or without crossing the midline. Results: At a median follow-up of 7 months (range, 1-37), 105 patients had recurrence, and 79 patients ultimately developed DIR. The interval to progression was similar in the DIR and local recurrence groups (6.5 and 6.3 months, p = .296). The hazard risk of DIR increased exponentially with time and was similar in those with newly diagnosed and recurrent HGG (R{sup 2} = 0.957). The duration of bevacizumab therapy increased the interval to recurrence (p < .0001) and improved overall survival (p < .0001). However, the pattern of relapse did not affect overall survival (p = .253). Conclusion: Along with an increase in median progression-free survival, bevacizumab therapy increased the risk of DIR in HGG patients. The risk of increased invasion with prolonged angiogenic blockade should be addressed in future clinical trials.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2011

Tolerability of Combined Modality Therapy for Rectal Cancer in Elderly Patients Aged 75 Years and Older

Purpose: To determine the rate of treatment deviations during combined modality therapy for rectal cancer in elderly patients aged 75 years and older. Methods and Materials: We reviewed the records of consecutively treated patients with rectal cancer aged 75 years and older treated with combined modality therapy at Massachusetts General Hospital and Brigham and Women's Hospital from 2002 to 2007. The primary endpoint was the rate of treatment deviation, defined as a treatment break, dose reduction, early discontinuation of therapy, or hospitalization during combined modality therapy. Patient comorbidity was rated using the validated Adult Comorbidity Evaluation 27 Test (ACE-27) comorbidity index. Fisher's exact test and the Mantel-Haenszel trend test were used to identify predictors of treatment tolerability. Results: Thirty-six eligible patients had a median age of 79.0 years (range, 75-87 years); 53% (19/36) had no or mild comorbidity and 47% (17/36) had moderate or severe comorbidity. In all, 58% of patients (21/36) were treated with preoperative chemoradiotherapy (CRT) and 33% (12/36) with postoperative CRT. Although 92% patients (33/36) completed the planned radiotherapy (RT) dose, 25% (9/36) required an RT-treatment break, 11% (4/36) were hospitalized, and 33% (12/36) had a dose reduction, break, or discontinuation of concurrent chemotherapy. In all, 39% of patients (14/36) completed {>=}4 months of adjuvant chemotherapy, and 17% (6/36) completed therapy without a treatment deviation. More patients with no to mild comorbidity completed treatment than did patients with moderate to severe comorbidity (21% vs. 12%, p = 0.66). The rate of deviation did not differ between patients who had preoperative or postoperative CRT (19% vs. 17%, p = 1.0). Conclusions: The majority of elderly patients with rectal cancer in this series required early termination of treatment, treatment interruptions, or dose reductions. These data suggest that further intensification of combined modality therapy for rectal cancer should be performed with caution in elderly patients, who require aggressive supportive care to complete treatment.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2014

Dosimetric Considerations to Determine the Optimal Technique for Localized Prostate Cancer Among External Photon, Proton, or Carbon-Ion Therapy and High-Dose-Rate or Low-Dose-Rate Brachytherapy

Purpose: To assess the dosimetric differences among volumetric modulated arc therapy (VMAT), scanned proton therapy (intensity-modulated proton therapy, IMPT), scanned carbon-ion therapy (intensity-modulated carbon-ion therapy, IMIT), and low-dose-rate (LDR) and high-dose-rate (HDR) brachytherapy (BT) treatment of localized prostate cancer. Methods and Materials: Ten patients were considered for this planning study. For external beam radiation therapy (EBRT), planning target volume was created by adding a margin of 5 mm (lateral/anterior–posterior) and 8 mm (superior–inferior) to the clinical target volume. Bladder wall (BW), rectal wall (RW), femoral heads, urethra, and pelvic tissue were considered as organs at risk. For VMAT and IMPT, 78 Gy(relative biological effectiveness, RBE)/2 Gy were prescribed. The IMIT was based on 66 Gy(RBE)/20 fractions. The clinical target volume planning aims for HDR-BT ({sup 192}Ir) and LDR-BT ({sup 125}I) were D{sub 90%} ≥34 Gy in 8.5 Gy per fraction and D{sub 90%} ≥145 Gy. Both physical and RBE-weighted dose distributions for protons and carbon-ions were converted to dose distributions based on 2-Gy(IsoE) fractions. From these dose distributions various dose and dose–volume parameters were extracted. Results: Rectal wall exposure 30-70 Gy(IsoE) was reduced for IMIT, LDR-BT, and HDR-BT when compared with VMAT and IMPT. The high-dose region of the BW dose–volume histogram above 50 Gy(IsoE) of IMPT resembled the VMAT shape, whereas all other techniques showed a significantly lower high-dose region. For all 3 EBRT techniques similar urethra D{sub mean} around 74 Gy(IsoE) were obtained. The LDR-BT results were approximately 30 Gy(IsoE) higher, HDR-BT 10 Gy(IsoE) lower. Normal tissue and femoral head sparing was best with BT. Conclusion: Despite the different EBRT prescription and fractionation schemes, the high-dose regions of BW and RW expressed in Gy(IsoE) were on the same order of magnitude. Brachytherapy techniques were clearly superior in terms of BW, RW, and normal tissue sparing, with lowest values for HDR-BT.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2014

Treatment of Head and Neck Paragangliomas With External Beam Radiation Therapy

Purpose: To retrospectively assess the outcomes of radiation therapy in patients with head and neck paragangliomas. Methods and Materials: From 1990 to 2009, 66 patients with 81 head and neck paragangliomas were treated by conventional external beam radiation therapy in 25 fractions at a median dose of 45 Gy (range, 41.4-68 Gy). One case was malignant. The median gross target volume and planning target volume were 30 cm{sup 3} (range, 0.9-243 cm{sup 3}) and 116 cm{sup 3} (range, 24-731 cm{sup 3}), respectively. Median age was 57.4 years (range, 15-84 years). Eleven patients had multicentric lesions, and 8 had family histories of paraganglioma. Paragangliomas were located in the temporal bone, the carotid body, and the glomus vagal in 51, 18, and 10 patients, respectively. Forty-six patients had exclusive radiation therapy, and 20 had salvage radiation therapy. The median follow-up was 4.1 years (range, 0.1-21.2 years). Results: One patient had a recurrence of temporal bone paraganglioma 8 years after treatment. The actuarial local control rates were 100% at 5 years and 98.7% at 10 years. Patients with multifocal tumors and family histories were significantly younger (42 years vs 58 years [P=.002] and 37 years vs 58 years [P=.0003], respectively). The association between family predisposition and multifocality was significant (P<.001). Two patients had cause-specific death within the 6 months after irradiation. During radiation therapy, 9 patients required hospitalization for weight loss, nausea, mucositis, or ophthalmic zoster. Two late vascular complications occurred (middle cerebral artery and carotid stenosis), and 2 late radiation-related meningiomas appeared 15 and 18 years after treatment. Conclusion: Conventional external beam radiation therapy is an effective and safe treatment option that achieves excellent local control; it should be considered as a first-line treatment of choice for head and neck paragangliomas.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2014

Voice Quality After Treatment of Early Vocal Cord Cancer: A Randomized Trial Comparing Laser Surgery With Radiation Therapy

Objective: Early laryngeal cancer is usually treated with either transoral laser surgery or radiation therapy. The quality of voice achieved with these treatments has not been compared in a randomized trial. Methods and Materials: Male patients with carcinoma limited to 1 mobile vocal cord (T1aN0M0) were randomly assigned to receive either laser surgery (n=32) or external beam radiation therapy (n=28). Surgery consisted of tumor excision with a CO{sub 2} laser with the patient under general anaesthesia. External beam radiation therapy to the larynx was delivered to a cumulative dose of 66 Gy in 2-Gy daily fractions over 6.5 weeks. Voice quality was assessed at baseline and 6 and 24 months after treatment. The main outcome measures were expert-rated voice quality on a grade, roughness, breathiness, asthenia, and strain (GRBAS) scale, videolaryngostroboscopic findings, and the patients' self-rated voice quality and its impact on activities of daily living. Results: Overall voice quality between the groups was rated similar, but voice was more breathy and the glottal gap was wider in patients treated with laser surgery than in those who received radiation therapy. Patients treated with radiation therapy reported less hoarseness-related inconvenience in daily living 2 years after treatment. Three patients in each group had local cancer recurrence within 2 years from randomization. Conclusions: Radiation therapy may be the treatment of choice for patients whose requirements for voice quality are demanding. Overall voice quality was similar in both treatment groups, however, indicating a need for careful consideration of patient-related factors in the choice of a treatment option.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2014

Sustained virological response with intravenous silibinin: individualized IFN-free therapy via real-time modelling of HCV kinetics

Providing here our aims and project background, we note that intravenous silibinin (SIL) is a potent antiviral agent against hepatitis C virus (HCV) genotype-1. In this proof of concept case-study we tested: (i) whether interferon-alfa (IFN)-free treatment with SIL plus ribavirin (RBV) can achieve sustained virological response (SVR); (ii) whether SIL is safe and feasible for prolonged duration of treatment and (iii) whether mathematical modelling of early on-treatment HCV kinetics can guide duration of therapy to achieve SVR. With our method, a 44 year-old female HCV-(genotype-1)-infected patient who developed severe psychiatric adverse events to a previous course of pegIFN+RBV, initiated combination treatment with 1200 mg/day of SIL, 1200 mg/day of RBV and 6000 u/day vitamin D. Blood samples were collected frequently till week 4, thereafter every 1-12 weeks until the end of therapy. The standard biphasic mathematical model with time-varying SIL effectiveness was used to predict the duration of therapy to achieve SVR. Our results show that, based on modelling the observed viral kinetics during the first 3 weeks of treatment, SVR was predicted to be achieved within 34 weeks of therapy. Provided with this information, the patient agreed to complete 34 weeks of treatment. IFN-free treatment with SIL+RBV was feasible, safe and achieved SVR (week-33). In conclusion, we report, for the first time, the use of real-time mathematical modelling of HCV kinetics to individualize duration of IFN-free therapy and to empower a patient to participate in shared decision making regarding length of treatment. SIL-based individualized therapy provides a treatment option for patients who do not respond to or cannot receive other HCV agents and should be further validated.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2022

225 Ac-MACROPATATE: A Novel α-Particle Peptide Receptor Radionuclide Therapy for Neuroendocrine Tumors

Neuroendocrine tumors (NETs) express somatostatin receptors (SSTRs) 2 and 5. Modified variants of somatostatin, the cognate ligand for SSTR2 and SSTR5, are used in treatment for metastatic and locoregional disease. Peptide receptor radionuclide therapy with 177 Lu-DOTATATE (DOTA-octreotate), a β-particle–emitting somatostatin derivative, has demonstrated survival benefit in patients with SSTR-positive NETs. Despite excellent results, a subset of patients has tumors that are resistant to treatment, and alternative agents are needed. Targeted α-particle therapy has been shown to kill tumors that are resistant to targeted β-particle therapy, suggesting that targeted α-particle therapy may offer a promising treatment option for patients with 177 Lu-DOTATATE–resistant disease. Although DOTATATE can chelate the clinically relevant α-particle–emitting radionuclide 225 Ac, the labeling reaction requires high temperatures, and the resulting radioconjugate has suboptimal stability. Methods: We designed and synthesized MACROPATATE (MACROPA-octreotate), a novel radioconjugate capable of chelating 225 Ac at room temperature, and assessed its in vitro and in vivo performance. Results: MACROPATATE demonstrated comparable affinity to DOTATATE (dissociation constant, 21 nM) in U2-OS-SSTR2, a SSTR2-positive transfected cell line. 225 Ac-MACROPATATE demonstrated superior serum stability at 37°C over time compared with 225 Ac-DOTATATE. Biodistribution studies demonstrated higher tumor uptake of 225 Ac-MACROPATATE than of 225 Ac-DOTATATE in mice engrafted with subcutaneous H69 NETs. Therapy studies showed that 225 Ac-MACROPATATE exhibits significant antitumor and survival benefit compared with saline control in mice engrafted with SSTR-positive tumors. However, the increased accumulation of 225 Ac-MACROPATATE in liver and kidneys and subsequent toxicity to these organs decreased its therapeutic index compared with 225 Ac-DOTATATE. Conclusion: 225 Ac-MACROPATATE and 225 Ac-DOTATATE exhibit favorable therapeutic efficacy in animal models. Because of elevated liver and kidney accumulation and lower administered activity for dose-limiting toxicity of 225 Ac-MACROPATATE, 225 Ac-DOTATATE was deemed the superior agent for targeted α-particle peptide receptor radionuclide therapy.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2015

Ceiling art in a radiation therapy department: its effect on patient treatment experience

A new initiative has been implemented at the Sunshine Hospital Radiation Therapy Centre, to provide a calming and comforting environment for patients attending radiation therapy treatment. As part of this initiative, the department's computed tomography (CT) room and radiation therapy bunkers were designed to incorporate ceiling art that replicates a number of different visual scenes. The study was undertaken to determine if ceiling art in the radiation therapy treatment CT and treatment bunkers had an effect on a patient's experience during treatment at the department. Additionally, the study aimed to identify which of the visuals in the ceiling art were most preferred by patients. Patients were requested to complete a 12-question survey. The survey solicited a patient's opinion/perception on the unit's unique ceiling display with emphasis on aesthetic appeal, patient treatment experience and the patient's engagement due to the ceiling display. The responses were dichotomised to ‘positive’ or ‘negative’. Every sixth patient who completed the survey was invited to have a general face-to-face discussion to provide further information about their thoughts on the displays. The results demonstrate that the ceiling artwork solicited a positive reaction in 89.8% of patients surveyed. This score indicates that ceiling artwork contributed positively to patients’ experiences during radiation therapy treatment. The study suggests that ceiling artwork in the department has a positive effect on patient experience during their radiation therapy treatment at the department.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2018

Combination therapy with BH3 mimetic and hyperthermia tends to be more effective on anti-melanoma treatment

Highlights: • The anti-melanoma ability of ch282-5 is synergistically amplified by hyperthermia. • Combination therapy with ch282-5 and hyperthermia activates pro-apoptotic signaling and inhibits pro-survival signaling. • Ch282-5 combining with microwave hyperthermia remits pulmonary colonization of melanoma cells. Malignant melanoma has shown increased incidence and high mortality rate in the last three decades. In this study, we investigated whether combination therapy with ch282-5 (a novel BH3 mimetic) and microwave hyperthermia could display synergistic antitumor effects against melanoma. Our results indicated that combination therapy reduced the viability and proliferation of melanoma cells. Through inhibiting the expression of anti-apoptotic proteins of Bcl-2 and IAP family and activating MAPK proteins, combined hyperthermia enhanced ch282-5-induced apoptosis. Combination therapy also synergistically disturbed the mTOR/p70S6k signaling pathway, which is important for cell survival and migration. Moreover, our results showed that combination therapy remarkably suppressed melanoma cell migration in vitro and significantly reduced experimental pulmonary metastasis in vivo. In conclusion, our results indicate that combination therapy with ch282-5 and hyperthermia has synergistic antitumor effects and provides a possible therapeutic strategy for advanced melanoma.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2012

On the Benefits and Risks of Proton Therapy in Pediatric Craniopharyngioma

Purpose: Craniopharyngioma is a pediatric brain tumor whose volume is prone to change during radiation therapy. We compared photon- and proton-based irradiation methods to determine the effect of tumor volume change on target coverage and normal tissue irradiation in these patients. Methods and Materials: For this retrospective study, we acquired imaging and treatment-planning data from 14 children with craniopharyngioma (mean age, 5.1 years) irradiated with photons (54 Gy) and monitored by weekly magnetic resonance imaging (MRI) examinations during radiation therapy. Photon intensity-modulated radiation therapy (IMRT), double-scatter proton (DSP) therapy, and intensity-modulated proton therapy (IMPT) plans were created for each patient based on his or her pre-irradiation MRI. Target volumes were contoured on each weekly MRI scan for adaptive modeling. The measured differences in conformity index (CI) and normal tissue doses, including functional sub-volumes of the brain, were compared across the planning methods, as was target coverage based on changes in target volumes during treatment. Results: CI and normal tissue dose values of IMPT plans were significantly better than those of the IMRT and DSP plans (p < 0.01). Although IMRT plans had a higher CI and lower optic nerve doses (p < 0.01) than did DSP plans, DSP plans had lower cochlear, optic chiasm, brain, and scanned body doses (p < 0.01). The mean planning target volume (PTV) at baseline was 54.8 cm{sup 3}, and the mean increase in PTV was 11.3% over the course of treatment. The dose to 95% of the PTV was correlated with a change in the PTV; the R{sup 2} values for all models, 0.73 (IMRT), 0.38 (DSP), and 0.62 (IMPT), were significant (p < 0.01). Conclusions: Compared with photon IMRT, proton therapy has the potential to significantly reduce whole-brain and -body irradiation in pediatric patients with craniopharyngioma. IMPT is the most conformal method and spares the most normal tissue; however, it is highly sensitive to target volume changes, whereas the DSP method is not.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2012

Radiation Therapy With Full-Dose Gemcitabine and Oxaliplatin for Unresectable Pancreatic Cancer

Purpose: We completed a Phase I trial of gemcitabine and oxaliplatin with concurrent radiotherapy in patients with previously untreated pancreatic cancer. The results of a subset of patients with unresectable disease who went on to receive planned additional therapy are reported here. Methods and Materials: All patients received two 28-day cycles of gemcitabine (1,000 mg/m{sup 2} on Days 1, 8, and 15) and oxaliplatin (40-85 mg/m{sup 2} on Days 1 and 15, per a dose-escalation schema). Radiation therapy was delivered concurrently with Cycle 1 (27 Gy in 1.8-Gy fractions). At 9 weeks, patients were reassessed for resectability. Those deemed to have unresectable disease were offered a second round of treatment consisting of 2 cycles of gemcitabine and oxaliplatin and 27 Gy of radiation therapy (total, 54 Gy). Radiation was delivered to the gross tumor volume plus 1 cm by use of a three-dimensional conformal technique. We used the Common Terminology Criteria for Adverse Events to assess acute toxicity. Late toxicity was scored per the Radiation Therapy Oncology Group scale. Computed tomography scans were reviewed to determine pattern of failure, local response, and disease progression. Kaplan-Meier methodology and Cox regression models were used to evaluate survival and freedom from failure. Results: Thirty-two patients from the Phase I dose-escalation study had unresectable disease, three of whom had low-volume metastatic disease. Of this group, 16 patients went on to receive additional therapy to complete a total of 4 cycles of chemotherapy and 54 Gy of concurrent radiation. For this subset, 38% had at least a partial tumor response at a median of 3.2 months. Median survival was 11.8 months (range, 4.4-26.3 months). The 1-year freedom from local progression rate was 93.8% (95% confidence interval, 63.2-99.1). Conclusions: Radiation therapy to 54 Gy with concurrent full-dose gemcitabine and oxaliplatin is well tolerated and results in favorable rates of local tumor response and 1-year freedom from local progression.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2012

Brachial Plexus-Associated Neuropathy After High-Dose Radiation Therapy for Head-and-Neck Cancer

Purpose: To identify clinical and treatment-related predictors of brachial plexus-associated neuropathies after radiation therapy for head-and-neck cancer. Methods and Materials: Three hundred thirty patients who had previously completed radiation therapy for head-and-neck cancer were prospectively screened using a standardized instrument for symptoms of neuropathy thought to be related to brachial plexus injury. All patients were disease-free at the time of screening. The median time from completion of radiation therapy was 56 months (range, 6-135 months). One-hundred fifty-five patients (47%) were treated by definitive radiation therapy, and 175 (53%) were treated postoperatively. Radiation doses ranged from 50 to 74 Gy (median, 66 Gy). Intensity-modulated radiation therapy was used in 62% of cases, and 133 patients (40%) received concurrent chemotherapy. Results: Forty patients (12%) reported neuropathic symptoms, with the most common being ipsilateral pain (50%), numbness/tingling (40%), motor weakness, and/or muscle atrophy (25%). When patients with <5 years of follow-up were excluded, the rate of positive symptoms increased to 22%. On univariate analysis, the following factors were significantly associated with brachial plexus symptoms: prior neck dissection (p = 0.01), concurrent chemotherapy (p = 0.01), and radiation maximum dose (p < 0.001). Cox regression analysis confirmed that both neck dissection (p < 0.001) and radiation maximum dose (p < 0.001) were independently predictive of symptoms. Conclusion: The incidence of brachial plexus-associated neuropathies after radiation therapy for head-and-neck cancer may be underreported. In view of the dose-response relationship identified, limiting radiation dose to the brachial plexus should be considered when possible.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2012

Long-Term Follow-Up of Preoperative Pelvic Radiation Therapy and Concomitant Boost Irradiation in Locally Advanced Rectal Cancer Patients: A Multi-Institutional Phase II Study (KROG 04-01)

Purpose: To perform a prospective phase II study to investigate the efficacy and safety of preoperative pelvic radiation therapy and concomitant small-field boost irradiation with 5-fluorouracil and leucovorin for 5 weeks in locally advanced rectal cancer patients. Methods and Materials: Sixty-nine patients with locally advanced, nonmetastatic, mid-to-lower rectal cancer were prospectively enrolled. They had received preoperative chemoradiation therapy and total mesorectal excision. Pelvic radiation therapy of 43.2 Gy in 24 fractions plus concomitant boost radiation therapy of 7.2 Gy in 12 fractions was delivered to the pelvis and tumor bed for 5 weeks. Two cycles of 5-fluorouracil and leucovorin were administered for 3 days in the first and fifth week of radiation therapy. The pathologic response, survival outcome, and treatment toxicity were evaluated for the study endpoints. Results: Of 69 patients, 8 (11.6%) had a pathologically complete response. Downstaging rates were 40.5% for T classification and 68.1% for N classification. At the median follow-up of 69 months, 36 patients have been followed up for more than 5 years. The 5-year disease-free survival (DFS) and overall survival rates were 66.0% and 75.3%, respectively. Higher pathologic T (P = .045) and N (P = .032) classification were significant adverse prognostic factors for DFS, and high-grade histology was an adverse prognostic factor for both DFS (P = .025) and overall survival (P = .031) on the multivariate analysis. Fifteen patients (21.7%) experienced grade 3 or 4 acute toxicity, and 7 patients (10.1%) had long-term toxicity. Conclusion: Preoperative pelvic radiation therapy with concomitant boost irradiation with 5-fluorouracil and leucovorin for 5 weeks showed acceptable acute and long-term toxicities. However, the benefit of concomitant small-field boost irradiation for 5 weeks in rectal cancer patients was not demonstrated beyond conventional irradiation for 6 weeks in terms of tumor response and survival.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2013

A Multicenter Phase II Trial of S-1 With Concurrent Radiation Therapy for Locally Advanced Pancreatic Cancer

Purpose: The aim of this trial was to evaluate the efficacy and toxicity of S-1 and concurrent radiation therapy for locally advanced pancreatic cancer (PC). Methods and Materials: Locally advanced PC patients with histologically or cytologically confirmed adenocarcinoma or adenosquamous carcinoma, who had no previous therapy were enrolled. Radiation therapy was delivered through 3 or more fields at a total dose of 50.4 Gy in 28 fractions over 5.5 weeks. S-1 was administered orally at a dose of 80 mg/m{sup 2} twice daily on the day of irradiation during radiation therapy. After a 2- to 8-week break, patients received a maintenance dose of S-1 (80 mg/m{sup 2}/day for 28 consecutive days, followed by a 14-day rest period) was then administered until the appearance of disease progression or unacceptable toxicity. The primary efficacy endpoint was survival, and the secondary efficacy endpoints were progression-free survival, response rate, and serum carbohydrate antigen 19-9 (CA19-9) response; the safety endpoint was toxicity. Results: Of the 60 evaluable patients, 16 patients achieved a partial response (27%; 95% confidence interval [CI], 16%-40%). The median progression-free survival period, overall survival period, and 1-year survival rate of the evaluable patients were 9.7 months (95% CI, 6.9-11.6 months), 16.2 months (95% CI, 13.5-21.3 months), and 72% (95%CI, 59%-82%), respectively. Of the 42 patients with a pretreatment serum CA19-9 level of {>=}100 U/ml, 34 (81%) patients showed a decrease of greater than 50%. Leukopenia (6 patients, 10%) and anorexia (4 patients, 7%) were the major grade 3-4 toxicities with chemoradiation therapy. Conclusions: The effect of S-1 with concurrent radiation therapy in patients with locally advanced PC was found to be very favorable, with only mild toxicity.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2013

Results of a Quality Assurance Review of External Beam Radiation Therapy in the International Society of Paediatric Oncology (Europe) Neuroblastoma Group's High-risk Neuroblastoma Trial: A SIOPEN Study

Purpose: Radiation therapy is important for local control in neuroblastoma. This study reviewed the compliance of plans with the radiation therapy guidelines of the International Society of Paediatric Oncology (Europe) Neuroblastoma Group (SIOPEN) High-Risk Trial protocol. Methods and Materials: The SIOPEN trial central electronic database has sections to record diagnostic imaging and radiation therapy planning data. Individual centers may upload data remotely, but not all centers involved in the trial chose to use this system. A quality scoring system was devised based on how well the radiation therapy plan matched the protocol guidelines, to what extent deviations were justified, and whether adverse effects may result. Central review of radiation therapy planning was undertaken retrospectively in 100 patients for whom complete diagnostic and treatment sets were available. Data were reviewed and compared against protocol guidelines by an international team of radiation oncologists and radiologists. For each patient in the sample, the central review team assigned a quality assurance score. Results: It was found that in 48% of patients there was full compliance with protocol requirements. In 29%, there were deviations for justifiable reasons with no likely long-term adverse effects resulting. In 5%, deviations had occurred for justifiable reasons, but that might result in adverse effects. In 1%, there was a deviation with no discernible justification, which would not lead to long-term adverse events. In 17%, unjustified deviations were noted, with a risk of an adverse outcome resulting. Conclusions: Owing to concern over the proportion of patients in whom unjustified deviations were observed, a protocol amendment has been issued. This offers the opportunity for central review of radiation therapy plans before the start of treatment and the treating clinician a chance to modify plans.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2013

Survival Advantage With the Addition of Radiation Therapy to Chemotherapy in Early Stage Peripheral T-Cell Lymphoma, Not Otherwise Specified

Purpose: Early stage peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS) is rare. The purpose of this study was to evaluate the outcome of treatment as well as the potential role of radiation therapy in PTCL-NOS. Methods and Materials: Thirty-five patients with early stage PTCL-NOS were included. There were 13 patients with stage I disease and 22 with stage II. All patients except 1 received doxorubicin-based chemotherapy alone (n=13) or a combination of chemotherapy and radiation therapy (CMT) (n=21). Results: The 3-year overall survival (OS) and progression-free survival (PFS) rates for the entire group were 41.3% and 25.7%, respectively. The addition of radiation therapy to chemotherapy significantly improved OS and PFS in early stage PTCL-NOS. The 3-year OS and PFS rates were 49.7% and 33.3% for CMT, compared with 23.1% (P=.042) and 15.4% (P=.035) for chemotherapy alone, respectively. The prognosis for patients who achieved a complete response (CR) was significantly better than that observed in those who did not achieve a CR. Conclusions: Despite the aggressive clinical course of early stage PTCL-NOS, additional radiation therapy has a significant impact on outcome. The integration of local radiation therapy into more effective systemic therapies may further improve survival.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2013

Image Guided Hypofractionated 3-Dimensional Radiation Therapy in Patients With Inoperable Advanced Stage Non-Small Cell Lung Cancer

Purpose: Hypofractionated radiation therapy (HypoRT) can potentially improve local control with a higher biological effect and shorter overall treatment time. Response, local control, toxicity rates, and survival rates were evaluated in patients affected by inoperable advanced stage non-small cell lung cancer (NSCLC) who received HypoRT. Methods and Materials: Thirty patients with advanced NSCLC were enrolled; 27% had stage IIIA, 50% had stage IIIB, and 23% had stage IV disease. All patients underwent HypoRT with a prescribed total dose of 60 Gy in 20 fractions of 3 Gy each. Radiation treatment was delivered using an image guided radiation therapy technique to verify correct position. Toxicities were graded according to Radiation Therapy Oncology Group morbidity score. Survival rates were estimated using the Kaplan-Meier method. Results: The median follow-up was 13 months (range, 4-56 months). All patients completed radiation therapy and received the total dose of 60 Gy to the primary tumor and positive lymph nodes. The overall response rate after radiation therapy was 83% (3 patients with complete response and 22 patients with partial response). The 2-year overall survival and progression-free survival rates were 38.1% and 36%, respectively. Locoregional recurrence/persistence occurred in 11 (37%) patients. Distant metastasis occurred in 17 (57%) patients. Acute toxicities occurred consisting of grade 1 to 2 hematological toxicity in 5 patients (17%) and grade 3 in 1 patient; grade 1 to 2 esophagitis in 12 patients (40%) and grade 3 in 1 patient; and grade 1 to 2 pneumonitis in 6 patients (20%) and grade 3 in 2 patients (7%). Thirty-three percent of patients developed grade 1 to 2 late toxicities. Only 3 patients developed grade 3 late adverse effects: esophagitis in 1 patient and pneumonitis in 2 patients. Conclusions: Hypofractionated curative radiation therapy is a feasible and well-tolerated treatment for patients with locally advanced NSCLC. Randomized studies are needed to compare HypoRT to conventional treatment.

62 RADIOLOGY AND NUCLEAR MEDICINE↗