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At least 595 records · Page 33
All sourcesNASA NTRSDOE OSTI
DOE OSTI2012

Comparison of Acute and Late Toxicities for Three Modern High-Dose Radiation Treatment Techniques for Localized Prostate Cancer

Purpose: We compared acute and late genitourinary (GU) and gastrointestinal (GI) toxicities in prostate cancer patients treated with three different high-dose radiation techniques. Methods and Materials: A total of 1,903 patients with localized prostate cancer were treated with definitive RT at William Beaumont Hospital from 1992 to 2006: 22% with brachytherapy alone (BT), 55% with image-guided external beam (EB-IGRT), and 23% external beam with high-dose-rate brachytherapy boost (EBRT+HDR). Median dose with BT was 120 Gy for LDR and 38 Gy for HDR (9.5 Gy Multiplication-Sign 4). Median dose with EB-IGRT was 75.6 Gy (PTV) to prostate with or without seminal vesicles. For EBRT+HDR, the pelvis was treated to 46 Gy with an additional 19 Gy (9.5 Gy Multiplication-Sign 2) delivered via HDR. GI and GU toxicity was evaluated utilizing the NCI-CTC criteria (v.3.0). Median follow-up was 4.8 years. Results: The incidences of any acute {>=} Grade 2 GI or GU toxicities were 35%, 49%, and 55% for BT, EB-IGRT, and EBRT+HDR (p < 0.001). Any late GU toxicities {>=} Grade 2 were present in 22%, 21%, and 28% for BT, EB-IGRT, and EBRT+HDR (p = 0.01), respectively. Patients receiving EBRT+HDR had a higher incidence of urethral stricture and retention, whereas dysuria was most common in patients receiving BT. Any Grade {>=}2 late GI toxicities were 2%, 20%, and 9% for BT, EB-IGRT, and EBRT+HDR (p < 0.001). Differences were most pronounced for rectal bleeding, with 3-year rates of 0.9%, 20%, and 6% (p < 0.001) for BT, EB-IGRT, and EBRT+HDR respectively. Conclusions: Each of the three modern high-dose radiation techniques for localized prostate cancer offers a different toxicity profile. These data can help patients and physicians to make informed decisions regarding radiotherapy for prostate andenocarcinoma.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2011

High-Dose-Rate Monotherapy: Safe and Effective Brachytherapy for Patients With Localized Prostate Cancer

Purpose: High-dose-rate (HDR) brachytherapy used as the only treatment (monotherapy) for early prostate cancer is consistent with current concepts in prostate radiobiology, and the dose is reliably delivered in a prospectively defined anatomic distribution that meets all the requirements for safe and effective therapy. We report the disease control and toxicity of HDR monotherapy from California Endocurietherapy (CET) and William Beaumont Hospital (WBH) in low- and intermediate-risk prostate cancer patients. Methods and Materials: There were 298 patients with localized prostate cancer treated with HDR monotherapy between 1996 and 2005. Two biologically equivalent hypofractionation protocols were used. At CET the dose was 42 Gy in six fractions (two implantations 1 week apart) delivered to a computed tomography-defined planning treatment volume. At WBH the dose was 38 Gy in four fractions (one implantation) based on intraoperative transrectal ultrasound real-time treatment planning. The bladder, urethral, and rectal dose constraints were similar. Toxicity was scored with the National Cancer Institute Common Toxicity Criteria for Adverse Events version 3. Results: The median follow-up time was 5.2 years. The median age of the patients was 63 years, and the median value of the pretreatment prostate-specific antigen was 6.0 ng/mL. The 8-year results were 99% local control, 97% biochemical control (nadir +2), 99% distant metastasis-free survival, 99% cause-specific survival, and 95% overall survival. Toxicity was scored per event, meaning that an individual patient with more than one symptom was represented repeatedly in the morbidity data table. Genitourinary toxicity consisted of 10% transient Grade 2 urinary frequency or urgency and 3% Grade 3 episode of urinary retention. Gastrointestinal toxicity was <1%. Conclusions: High disease control rates and low morbidity demonstrate that HDR monotherapy is safe and effective for patients with localized prostate cancer.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2012

Stereotactic Irradiation of the Postoperative Resection Cavity for Brain Metastasis: A Frameless Linear Accelerator-Based Case Series and Review of the Technique

Purpose: Whole-brain radiation therapy (WBRT) is the standard of care after resection of a brain metastasis. However, concern regarding possible neurocognitive effects and the lack of survival benefit with this approach has led to the use of stereotactic radiosurgery (SRS) to the resection cavity in place of WBRT. We report our initial experience using an image-guided linear accelerator-based frameless stereotactic system and review the technical issues in applying this technique. Methods and Materials: We retrospectively reviewed the setup accuracy, treatment outcome, and patterns of failure of the first 18 consecutive cases treated at Brigham and Women's Hospital. The target volume was the resection cavity without a margin excluding the surgical track. Results: The median number of brain metastases per patient was 1 (range, 1-3). The median planning target volume was 3.49 mL. The median prescribed dose was 18 Gy (range, 15-18 Gy) with normalization ranging from 68% to 85%. In all cases, 99% of the planning target volume was covered by the prescribed dose. The median conformity index was 1.6 (range, 1.41-1.92). The SRS was delivered with submillimeter accuracy. At a median follow-up of 12.7 months, local control was achieved in 16/18 cavities treated. True local recurrence occurred in 2 patients. No marginal failures occurred. Distant recurrence occurred in 6/17 patients. Median time to any failure was 7.4 months. No Grade 3 or higher toxicity was recorded. A long interval between initial cancer diagnosis and the development of brain metastasis was the only factor that trended toward a significant association with the absence of recurrence (local or distant) (log-rank p = 0.097). Conclusions: Frameless stereotactic irradiation of the resection cavity after surgery for a brain metastasis is a safe and accurate technique that offers durable local control and defers the use of WBRT in select patients. This technique should be tested in larger prospective studies.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2012

Determination of Prognostic Factors for Vaginal Mucosal Toxicity Associated With Intravaginal High-Dose Rate Brachytherapy in Patients With Endometrial Cancer

Purpose: The objective of this study was to determine the patient- and treatment-related prognostic factors associated with vaginal toxicity in patients who received intravaginal high dose rate (HDR) brachytherapy alone as adjuvant treatment for endometrial cancer. Secondary goals of this study included a quantitative assessment of optimal dilator use frequency and a crude assessment of clinical predictors for compliant dilator use. Methods and Materials: We retrospectively reviewed the charts of 100 patients with histologically confirmed endometrial cancer who underwent total hysterectomy and bilateral salpingo-oophorectomy with or without lymph node dissection and adjuvant intravaginal brachytherapy between 1995 and 2009 at the Hospital of University of Pennsylvania. The most common treatment regimen used was 21 Gy in three fractions (71 patients). Symptoms of vaginal mucosal toxicity were taken from the history and physical exams noted in the patients' charts and were graded according to the Common Toxicity Criteria for Adverse Events v. 4.02. Results: The incidence of Grade 1 or asymptomatic vaginal toxicity was 33% and Grade 2-3 or symptomatic vaginal toxicity was 14%. Multivariate analysis of age, active length, and dilator use two to three times a week revealed odds ratios of 0.93 (p = 0.013), 3.96 (p = 0.008), and 0.17 (p = 0.032) respectively. Conclusion: Increasing age, vaginal dilator use of at least two to three times a week, and shorter active length were found to be significantly associated with a decreased risk of vaginal stenosis. Future prospective studies are necessary to validate our findings.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2012

Proton Radiotherapy for Parameningeal Rhabdomyosarcoma: Clinical Outcomes and Late Effects

Purpose: To report the clinical outcome and late side effect profile of proton radiotherapy in the treatment of children with parameningeal rhabdomyosarcoma (PM-RMS). Methods and Materials: Seventeen consecutive children with PM-RMS were treated with proton radiotherapy at Massachusetts General Hospital between 1996 and 2005. We reviewed the medical records of all patients and asked referring physicians to report specific side effects of interest. Results: Median patient age at diagnosis was 3.4 years (range, 0.4-17.6). Embryonal (n = 11), alveolar (n = 4), and undifferentiated (n = 2) histologies were represented. Ten patients (59%) had intracranial extension. Median prescribed dose was 50.4 cobalt gray equivalents (GyRBE) (range, 50.4-56.0 GyRBE) delivered in 1.8-2.0-GyRBE daily fractions. Median follow-up was 5.0 years for survivors. The 5-year failure-free survival estimate was 59% (95% confidence interval, 33-79%), and overall survival estimate was 64% (95% confidence interval, 37-82%). Among the 7 patients who failed, sites of first recurrence were local only (n = 2), regional only (n = 2), distant only (n = 2), and local and distant (n = 1). Late effects related to proton radiotherapy in the 10 recurrence-free patients (median follow-up, 5 years) include failure to maintain height velocity (n = 3), endocrinopathies (n = 2), mild facial hypoplasia (n = 7), failure of permanent tooth eruption (n = 3), dental caries (n = 5), and chronic nasal/sinus congestion (n = 2). Conclusions: Proton radiotherapy for patients with PM-RMS yields tumor control and survival comparable to that in historical controls with similar poor prognostic factors. Furthermore, rates of late effects from proton radiotherapy compare favorably to published reports of photon-treated cohorts.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2012

Improved Planning Time and Plan Quality Through Multicriteria Optimization for Intensity-Modulated Radiotherapy

Purpose: To test whether multicriteria optimization (MCO) can reduce treatment planning time and improve plan quality in intensity-modulated radiotherapy (IMRT). Methods and Materials: Ten IMRT patients (5 with glioblastoma and 5 with locally advanced pancreatic cancers) were logged during the standard treatment planning procedure currently in use at Massachusetts General Hospital (MGH). Planning durations and other relevant planning information were recorded. In parallel, the patients were planned using an MCO planning system, and similar planning time data were collected. The patients were treated with the standard plan, but each MCO plan was also approved by the physicians. Plans were then blindly reviewed 3 weeks after planning by the treating physician. Results: In all cases, the treatment planning time was vastly shorter for the MCO planning (average MCO treatment planning time was 12 min; average standard planning time was 135 min). The physician involvement time in the planning process increased from an average of 4.8 min for the standard process to 8.6 min for the MCO process. In all cases, the MCO plan was blindly identified as the superior plan. Conclusions: This provides the first concrete evidence that MCO-based planning is superior in terms of both planning efficiency and dose distribution quality compared with the current trial and error-based IMRT planning approach.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2011

Outcome and Prognostic Factors of Radiation Therapy for Medulloblastoma

Purpose: To investigate treatment outcome and prognostic factors after radiation therapy in patients with medulloblastomas (MB). Methods and Materials: Sixty-six patients with histologically confirmed MB were treated at University Hospital of Heidelberg between 1985 and 2009. Forty-two patients (64%) were pediatric ({<=}18 years), and 24 patients (36%) were adults. Tumor resection was performed in all patients and was complete in 47%. All patients underwent postoperative craniospinal irradiation (CSI) delivering a median craniospinal dose of 35.5 Gy with additional boosts to the posterior fossa up to 54.0 Gy. Forty-seven patients received chemotherapy, including 21 in whom chemotherapy was administered before CSI. Statistical analysis was performed using the log-rank test and the Kaplan-Meier method. Results: Median follow-up was 93 months. Overall survival (OS) and local and distant progression-free survival (LPFS and DPFS) were 73%, 62%, and 77% at 60 months. Both local and distant recurrence predisposed for significantly reduced OS. Macroscopic complete tumor resection, desmoplastic histology and early initiation of postoperative radiation therapy within 28 days were associated with improved outcome. The addition of chemotherapy did not improve survival rates. Toxicity was moderate. Conclusions: Complete resection of MB followed by CSI yields long survival rates in both children and adults. Delayed initiation of CSI is associated with poor outcome. Desmoplastic histology is associated with improved survival. The role of chemotherapy, especially in the adult population, must be further investigated in clinical studies.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2011

Patterns and Risk Factors of Locoregional Recurrence in T1-T2 Node Negative Breast Cancer Patients Treated With Mastectomy: Implications for Postmastectomy Radiotherapy

Purpose: Postmastectomy radiation therapy (PMRT) can reduce locoregional recurrences (LRR) in high-risk patients, but its role in the treatment of lymph node negative (LN-) breast cancer remains unclear. The aim of this study was to identify a subgroup of T1-T2 breast cancer patients with LN- who might benefit from PMRT. Methods and Materials: We retrospectively reviewed 1,136 node-negative T1-T2 breast cancer cases treated with mastectomy without PMRT at the Massachusetts General Hospital between 1980 and 2004. We estimated cumulative incidence rates for LRR overall and in specific subgroups, and used Cox proportional hazards models to identify potential risk factors. Results: Median follow-up was 9 years. The 10-year cumulative incidence of LRR was 5.2% (95% CI: 3.9-6.7%). Chest wall was the most common (73%) site of LRR. Tumor size, margin, patient age, systemic therapy, and lymphovascular invasion (LVI) were significantly associated with LRR on multivariate analysis. These five variables were subsequently used as risk factors for stratified analysis. The 10-year cumulative incidence of LRR for patients with no risk factors was 2.0% (95% CI: 0.5-5.2%), whereas the incidence for patients with three or more risk factors was 19.7% (95% CI: 12.2-28.6%). Conclusion: It has been suggested that patients with T1-T2N0 breast cancer who undergo mastectomy represent a favorable group for which PMRT renders little benefit. However, this study suggests that select patients with multiple risk factors including LVI, tumor size {>=}2 cm, close or positive margin, age {<=}50, and no systemic therapy are at higher risk of LRR and may benefit from PMRT.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2012

Esophageal Stenosis Associated With Tumor Regression in Radiotherapy for Esophageal Cancer: Frequency and Prediction

Purpose: To determine clinical factors for predicting the frequency and severity of esophageal stenosis associated with tumor regression in radiotherapy for esophageal cancer. Methods and Materials: The study group consisted of 109 patients with esophageal cancer of T1-4 and Stage I-III who were treated with definitive radiotherapy and achieved a complete response of their primary lesion at Kyushu University Hospital between January 1998 and December 2007. Esophageal stenosis was evaluated using esophagographic images within 3 months after completion of radiotherapy. We investigated the correlation between esophageal stenosis after radiotherapy and each of the clinical factors with regard to tumors and therapy. For validation of the correlative factors for esophageal stenosis, an artificial neural network was used to predict the esophageal stenotic ratio. Results: Esophageal stenosis tended to be more severe and more frequent in T3-4 cases than in T1-2 cases. Esophageal stenosis in cases with full circumference involvement tended to be more severe and more frequent than that in cases without full circumference involvement. Increases in wall thickness tended to be associated with increases in esophageal stenosis severity and frequency. In the multivariate analysis, T stage, extent of involved circumference, and wall thickness of the tumor region were significantly correlated to esophageal stenosis (p = 0.031, p < 0.0001, and p = 0.0011, respectively). The esophageal stenotic ratio predicted by the artificial neural network, which learned these three factors, was significantly correlated to the actual observed stenotic ratio, with a correlation coefficient of 0.864 (p < 0.001). Conclusion: Our study suggested that T stage, extent of involved circumference, and esophageal wall thickness of the tumor region were useful to predict the frequency and severity of esophageal stenosis associated with tumor regression in radiotherapy for esophageal cancer.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2011

Comparison of Clinical Outcomes of Surgery Followed by Local Brain Radiotherapy and Surgery Followed by Whole Brain Radiotherapy in Patients With Single Brain Metastasis: Single-Center Retrospective Analysis

Purpose: Data comparing the clinical outcomes of local brain radiotherapy (LBRT) and whole brain RT (WBRT) in patients with a single brain metastasis after tumor removal are limited. Patients and Methods: A retrospective analysis was performed to compare the patterns of treatment failure, cause of death, progression-free survival, median survival time, and Karnofsky performance status for long-term survivors among patients who underwent surgery followed by either LBRT or WBRT between 1990 and 2008 at the National Cancer Center Hospital. Results: A total of 130 consecutive patients were identified. The median progression-free survival period among the patients who received postoperative LBRT (n = 64) and WBRT (n = 66) was 9.7 and 11.5 months, respectively (p = .75). The local recurrence rates (LBRT, 9.4% vs. WBRT, 12.1%) and intracranial new metastasis rate (LBRT, 42.2% vs. WBRT, 33.3%) were similar in each arm. The incidence of leptomeningeal metastasis was also equivalent (LBRT, 9.4% vs. WBRT, 10.6%). The median survival time for the LBRT and WBRT patients was 13.9 and 16.7 months, respectively (p = .88). A neurologic cause of death was noted in 35.6% of the patients in the LBRT group and 36.7% of the WBRT group (p = .99). The Karnofsky performance status at 2 years was comparable between the two groups. Conclusions: The clinical outcomes of LBRT and WBRT were similar. A prospective evaluation is warranted.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2012

Use of Germline Polymorphisms in Predicting Concurrent Chemoradiotherapy Response in Esophageal Cancer

Purpose: To identify germline polymorphisms to predict concurrent chemoradiation therapy (CCRT) response in esophageal cancer patients. Materials and Methods: A total of 139 esophageal cancer patients treated with CCRT (cisplatin-based chemotherapy combined with 40 Gy of irradiation) and subsequent esophagectomy were recruited at the National Taiwan University Hospital between 1997 and 2008. After excluding confounding factors (i.e., females and patients aged {>=}70 years), 116 patients were enrolled to identify single nucleotide polymorphisms (SNPs) associated with specific CCRT responses. Genotyping arrays and mass spectrometry were used sequentially to determine germline polymorphisms from blood samples. These polymorphisms remain stable throughout disease progression, unlike somatic mutations from tumor tissues. Two-stage design and additive genetic models were adopted in this study. Results: From the 26 SNPs identified in the first stage, 2 SNPs were found to be significantly associated with CCRT response in the second stage. Single nucleotide polymorphism rs16863886, located between SGPP2 and FARSB on chromosome 2q36.1, was significantly associated with a 3.93-fold increase in pathologic complete response to CCRT (95% confidence interval 1.62-10.30) under additive models. Single nucleotide polymorphism rs4954256, located in ZRANB3 on chromosome 2q21.3, was associated with a 3.93-fold increase in pathologic complete response to CCRT (95% confidence interval 1.57-10.87). The predictive accuracy for CCRT response was 71.59% with these two SNPs combined. Conclusions: This is the first study to identify germline polymorphisms with a high accuracy for predicting CCRT response in the treatment of esophageal cancer.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2012

Standardized Total Average Toxicity Score: A Scale- and Grade-Independent Measure of Late Radiotherapy Toxicity to Facilitate Pooling of Data From Different Studies

Purpose: The search for clinical and biologic biomarkers associated with late radiotherapy toxicity is hindered by the use of multiple and different endpoints from a variety of scoring systems, hampering comparisons across studies and pooling of data. We propose a novel metric, the Standardized Total Average Toxicity (STAT) score, to try to overcome these difficulties. Methods and Materials: STAT scores were derived for 1010 patients from the Cambridge breast intensity-modulated radiotherapy trial and 493 women from University Hospitals of Leicester. The sensitivity of the STAT score to detect differences between patient groups, stratified by factors known to influence late toxicity, was compared with that of individual endpoints. Analysis of residuals was used to quantify the effect of these covariates. Results: In the Cambridge cohort, STAT scores detected differences (p < 0.00005) between patients attributable to breast volume, surgical specimen weight, dosimetry, acute toxicity, radiation boost to tumor bed, postoperative infection, and smoking (p < 0.0002), with no loss of sensitivity over individual toxicity endpoints. Diabetes (p = 0.017), poor postoperative surgical cosmesis (p = 0.0036), use of chemotherapy (p = 0.0054), and increasing age (p = 0.041) were also associated with increased STAT score. When the Cambridge and Leicester datasets were combined, STAT was associated with smoking status (p < 0.00005), diabetes (p = 0.041), chemotherapy (p = 0.0008), and radiotherapy boost (p = 0.0001). STAT was independent of the toxicity scale used and was able to deal with missing data. There were correlations between residuals of the STAT score obtained using different toxicity scales (r > 0.86, p < 0.00005 for both datasets). Conclusions: The STAT score may be used to facilitate the analysis of overall late radiation toxicity, from multiple trials or centers, in studies of possible genetic and nongenetic determinants of radiotherapy toxicity.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2011

Delineation of Gross Tumor Volume (GTV) for Radiation Treatment Planning of Locally Advanced Rectal Cancer Using Information From MRI or FDG-PET/CT: A Prospective Study

Purpose: Accurate delineation of target volumes is important to maximize radiation dose to the tumor and minimize it to nontumor tissue. Computed tomography (CT) and magnetic resonance imaging (MRI) are standard imaging modalities in rectal cancer. The aim was to explore whether functional imaging with F-18 fluorodeoxyglucose (FDG) positron emission tomography (PET), combined with CT (FDG-PET/CT) gives additional information to standard pretreatment evaluation and changes the shape and size of the gross tumor volume (GTV). Methods and Materials: From 2007 to 2009, 77 consecutive patients with locally advanced rectal cancer were prospectively screened for inclusion in the study at two university hospitals in Sweden, and 68 patients were eligible. Standard GTV was delineated using information from clinical examination, CT, and MRI (GTV-MRI). Thereafter, a GTV-PET was defined in the fused PET-CT, and the target volume delineations were compared for total volume, overlap, and mismatch. Pathologic uptake suspect of metastases was also registered. Results: The median volume of GTV-MRI was larger than that of GTV-PET: 111 cm{sup 3} vs. 87 cm{sup 3} (p < 0.001). In many cases, the GTV-MRI contained the GTV defined on the PET/CT images as subvolumes, but when a GTV total was calculated after the addition of GTV-PET to GTV-MRI, the volume increased, with median 11% (range, 0.5-72%). New lesions were seen in 15% of the patients for whom PET/CT was used. Conclusions: FDG-PET/CT facilitates and adds important information to the standard delineation procedure of locally advanced rectal cancer, mostly resulting in a smaller GTV, but a larger total GTV using the union of GTV-MRI and GTV-PET. New lesions were sometimes seen, potentially changing the treatment strategy.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2012

Proton Radiotherapy for Pediatric Ewing's Sarcoma: Initial Clinical Outcomes

Purpose: Proton radiotherapy (PT) has been prescribed similarly to photon radiotherapy to achieve comparable disease control rates at comparable doses. The chief advantage of protons in this setting is to reduce acute and late toxicities by decreasing the amount of normal tissue irradiated. We report the preliminary clinical outcomes including late effects on our pediatric Ewing's sarcoma patients treated with PT at the Francis H. Burr Proton Therapy Center at Massachusetts General Hospital (Boston, MA). Methods and Materials: This was a retrospective review of the medical records of 30 children with Ewing's sarcoma who were treated with PT between April 2003 and April 2009. Results: A total of 14 male and 16 female patients with tumors in several anatomic sites were treated with PT at a median age of 10 years. The median dose was 54 Gy (relative biological effectiveness) with a median follow-up of 38.4 months. The 3-year actuarial rates of event-free survival, local control, and overall survival were 60%, 86%, and 89%, respectively. PT was acutely well tolerated, with mostly mild-to-moderate skin reactions. At the time of writing, the only serious late effects have been four hematologic malignancies, which are known risks of topoisomerase and anthracyline exposure. Conclusions: Proton radiotherapy was well tolerated, with few adverse events. Longer follow-up is needed to more fully assess tumor control and late effects, but the preliminary results are encouraging.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2012

Long-Term Outcome and Patterns of Failure in Primary Ocular Adnexal Mucosa-Associated Lymphoid Tissue Lymphoma Treated With Radiotherapy

Purpose: To evaluate the long-term treatment outcome and disease behavior of primary ocular adnexal MALT (mucosa-associated lymphoid tissue) lymphoma (POAML) after treatment with radiotherapy. Methods and Materials: Seventy-eight patients (42 male, 36 female) diagnosed with stage I POAML between 1991 and 2010 at Kobe University Hospital were included. The median age was 60 years (range, 22-85 years). The median radiation dose administered was 30.6 Gy. Rituximab-based targeted therapy and/or chemotherapy was performed in 20 patients (25.6%). Local control (LC), recurrence-free survival (RFS), and overall survival (OS) rates were calculated using the Kaplan-Meier method. Results: The median follow-up duration was 66 months. Major tumor sites were conjunctiva in 37 patients (47.4%), orbita in 29 (37.2%), and lacrimal glands in 12 (15.4%). The 5- and 10-year OS rates were 98.1% and 95.3%, respectively. The 5- and 10-year LC rates were both 100%, and the 5- and 10-year RFS rates were 88.5% and 75.9%, respectively. Patients treated with a combination of radiotherapy and targeted therapy and/or chemotherapy had a trend for a better RFS compared with those treated with radiotherapy alone (p = 0.114). None developed greater than Grade 2 acute morbidity. There were 14 patients who experienced Grade 2 morbidities (cataract: 14; retinal disorders: 7; dry eye: 3), 23 patients who had Grade 3 morbidities (cataract: 23; dry eye: 1), and 1 patient who had Grade 4 glaucoma. Conclusions: Radiotherapy for POAML was shown to be highly effective and safe for LC and OS on the basis of long-term observation. The absence of systemic relapse in patients with combined-modality treatment suggests that lower doses of radiation combined with targeted therapy may be worth further study.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2012

Stereotactic Radiosurgery for Acoustic Neuromas: What Happens Long Term?

Purpose: To determine the clinical outcomes for acoustic neuroma treated with low-dose linear accelerator stereotactic radiosurgery (SRS) >10 years earlier at the Royal Adelaide Hospital using data collected prospectively at a dedicated SRS clinic. Methods and Materials: Between November 1993 and December 2000, 51 patients underwent SRS for acoustic neuroma. For the 44 patients with primary SRS for sporadic (unilateral) lesions, the median age was 63 years, the median of the maximal tumor diameter was 21 mm (range, 11-34), and the marginal dose was 14 Gy for the first 4 patients and 12 Gy for the other 40. Results: The crude tumor control rate was 97.7% (1 patient required salvage surgery for progression at 9.75 years). Only 8 (29%) of 28 patients ultimately retained useful hearing (interaural pure tone average {<=}50 dB). Also, although the Kaplan-Meier estimated rate of hearing preservation at 5 years was 57% (95% confidence interval, 38-74%), this decreased to 24% (95% confidence interval, 11-44%) at 10 years. New or worsened V and VII cranial neuropathy occurred in 11% and 2% of patients, respectively; all cases were transient. No case of radiation oncogenesis developed. Conclusions: The long-term follow-up data of low-dose (12-14 Gy) linear accelerator SRS for acoustic neuroma have confirmed excellent tumor control and acceptable cranial neuropathy rates but a continual decrease in hearing preservation out to {>=}10 years.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2012

Preliminary Results of Fractionated Stereotactic Radiotherapy After Cyst Drainage for Craniopharyngioma in Adults

Purpose: To retrospectively evaluate the effectiveness of fractionated stereotactic radiotherapy (FSRT) for craniopharyngioma. Methods and Materials: Between 1999 and 2005, 16 patients with craniopharyngioma were referred to Tokyo Medical University Hospital. They received FSRT alone after histologic confirmation by needle biopsy and underwent cyst drainage via endoscopy. The median prescription dose fraction was 30 Gy in six fractions. All patients except 1 were followed up until December 2009 or death. Results: The median follow-up period was 52 months (range, 4-117 months). Of the 17 patients, 3 experienced recurrence 4 to 71 months after FSRT. The 3-year local control rate was 82.4%. One patient died of thyroid cancer, and the 3-year survival rate was 94.1%. Eight patients had improved visual fields at a median of 2.5 months after FSRT, but hormonal functions did not improve in any patient. Conclusions: FSRT after cyst drainage seems to be safe and effective for patients with craniopharyngiomas, and it may be a safe alternative to surgery.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2012

DNA Repair Biomarkers Predict Response to Neoadjuvant Chemoradiotherapy in Esophageal Cancer

Purpose: The addition of neoadjuvant chemoradiotherapy prior to surgical resection for esophageal cancer has improved clinical outcomes in some trials. Pathologic complete response (pCR) following neoadjuvant therapy is associated with better clinical outcome in these patients, but only 22% to 40% of patients achieve pCR. Because both chemotherapy and radiotherapy act by inducing DNA damage, we analyzed proteins selected from multiple DNA repair pathways, using quantitative immunohistochemistry coupled with a digital pathology platform, as possible biomarkers of treatment response and clinical outcome. Methods and Materials: We identified 79 patients diagnosed with esophageal cancer between October 1994 and September 2002, with biopsy tissue available, who underwent neoadjuvant chemoradiotherapy prior to surgery at the Massachusetts General Hospital and used their archived, formalin-fixed, paraffin-embedded biopsy samples to create tissue microarrays (TMA). TMA sections were stained using antibodies against proteins in various DNA repair pathways including XPF, FANCD2, PAR, MLH1, PARP1, and phosphorylated MAPKAP kinase 2 (pMK2). Stained TMA slides were evaluated using machine-based image analysis, and scoring incorporated both the intensity and the quantity of positive tumor nuclei. Biomarker scores and clinical data were assessed for correlations with clinical outcome. Results: Higher scores for MLH1 (p = 0.018) and lower scores for FANCD2 (p = 0.037) were associated with pathologic response to neoadjuvant chemoradiation on multivariable analysis. Staining of MLH1, PARP1, XPF, and PAR was associated with recurrence-free survival, and staining of PARP1 and FANCD2 was associated with overall survival on multivariable analysis. Conclusions: DNA repair proteins analyzed by immunohistochemistry may be useful as predictive markers for response to neoadjuvant chemoradiotherapy in patients with esophageal cancer. These results are hypothesis generating and need confirmation in an independent data set.

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