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At least 1,693 records · Page 94

Regional inertia dynamics of U.S. interconnections: An event-based measurement approach

Power grid inertia plays a vital role in frequency stability following large disturbances, yet its distribution across the U.S. grid is highly uneven. While interconnection-wide inertia benchmarks are useful, they can mask regional variability driven by resource mix, network coupling, and geographic separation. This paper extends event-driven inertia estimation to the regional scale using field measurements from the Frequency Monitoring Network (FNET/GridEye). Starting from balancing authority and independent system operator footprints, candidate regions are refined using a composite coherency score that combines frequency-trajectory shape similarity, timing spread, and lead/lag behavior to ensure dynamic consistency. A filtered sliding difference method (FSDM) is then used to construct regional frequency trajectories, detect disturbance onset, and compute robust regional rate-of-change of frequency (RoCoF). Regional, local, and interconnection inertia are estimated by combining RoCoF with event power imbalance, and additional indicators (regional-to-system inertia ratio and inertial-support arrival time) quantify regional-to-interconnection coupling and relative regional contributions. The method is demonstrated on eleven regions across the Eastern Interconnection (EI) and the Western Electricity Coordinating Council (WECC), with the Electric Reliability Council of Texas (ERCOT) used for validation. In ERCOT, estimates compared against energy management system (EMS) values achieve a mean absolute percentage error of 17.94%. WECC exhibits consistently shorter inertial-support arrival times (0.15–0.3 s) than EI (0.7–1.1 s), highlighting contrasting coupling and disturbance-propagation behavior. Overall, the results reveal pronounced spatial heterogeneity in inertia and coupling, underscoring the value of regional monitoring for both operational decision-making and long-term system planning.

Disturbance events↗

Illuminating the geology: Post-injection reservoir characterisation of the CO2CRC Otway site

Proper site characterisation is essential in the planning stages of a CO 2 storage project; but we can also learn a good deal about the reservoir once the injection is underway or has been completed. During CO2CRC Otway Project Stage 2C, sources of valuable information about storage performance have been generated as a consequence of the staged injection of 15,000 t of CO 2 rich gas, as well as observations from time-lapse seismic surveys and well monitoring data. Now that injection has ceased for Stage 2C, the geological model is compared against field observations for the period spanning injection and 23 months after injection ended. The post-injection reservoir characterisation has proven critical to refine the static and dynamic models for future field development and added assurance about the long-term stabilisation of the CO 2 plume. The south-eastern progress of plume development, as seen on the time-lapse seismic data, has led to a review of the structural interpretation and horizon-fault geometry represented in the models. The developing plume has illuminated the extent of splay faults previously unresolved on the baseline seismic data. Saturation profiles interpreted from pulsed-neutron logs at the injection and observation wells show a preference for higher saturations occurring in high permeability distributary channels penetrated by each of the wells. This has reduced the uncertainty in predicting connectivity of this facies between the wells. The pressure data from numerous injection events has been used to refine the characterisation of the average horizontal permeability of the reservoir zone, and the vertical permeability of the intra-formational seal. Furthermore, it has been used to infer near-field bounding conditions of the interior splay fault, which in turn improves our understanding of containment at the site.

58 GEOSCIENCES↗

Gigaton commercial-scale carbon storage and mineralization potential in stacked Columbia River basalt reservoirs

This work presents a detailed supercritical CO 2 storage resource estimation for the stacked basalt reservoirs in the Grande Ronde Basalt of the Columbia River Basalt Group in eastern Washington and Oregon. The assessment aims to derisk the commercialization potential of geologic carbon storage in basalt by leveraging both structural and mineralization trapping of CO 2 in basalt. The structural closures formed by anticlinal ridges and synclinal valleys in Yakima Fold Belt are excellent physical traps to accommodate injected supercritical CO 2 . Rigorous hydraulic testing, well logs and simulation results from the Wallula Basalt Pilot #1 well showed the occurrence of 17 suitable permeable injection zones (up to 2,496 mD) intercalated with dense seals (~2.6E-10 mD) in the Grand Ronde Basalt. In addition, geochemical studies showed fast reactions between supercritical CO 2 and dissolved basalt minerals to form stable carbonates. In conclusion, our calculation indicates up to 40 gigatons (P90) of mineralization storage resources exist in the Grande Ronde Basalt reservoirs.

58 GEOSCIENCES↗

Clinical Outcomes and Patterns of Failure After Intensity-Modulated Radiotherapy for Nasopharyngeal Carcinoma

Purpose: To study and report the clinical outcomes and patterns of failure after intensity-modulated radiotherapy (IMRT) for nasopharyngeal carcinoma (NPC). Methods and Materials: The treatment outcomes of NPC patients treated with IMRT at Pamela Youde Nethersole Eastern Hospital between 2005 and 2007 were reviewed. The location and extent of locoregional failures were transferred to the pretreatment planning computed tomography for dosimetry analysis. Statistical analyses were performed on dose coverage and locoregional failures. Results: A total of 193 NPC patients were analyzed; 93% had Stage III/IV disease. Median follow-up was 30 months. Overall disease failure (at any site) developed in 35 patients. Among these, there were 23 distant metastases, 16 local failures, and 9 regional failures. Four of the locoregional failures were marginal. Dose conformity with IMRT was excellent. Patients with at least 66.5 Gy to their target volumes had significantly less locoregional failure. The 2-year local progression-free, regional progression-free, distant metastasis-free, and overall survival rates were 95%, 96%, 90%, and 92%, respectively. Conclusions: Intensity-modulated radiotherapy provides excellent locoregional control for NPC. Distant metastasis remains the most difficult challenge, and more effective systemic agents should be explored for patients presenting with advanced locoregional diseases.

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CHOD/BVAM Chemotherapy and Whole-Brain Radiotherapy for Newly Diagnosed Primary Central Nervous System Lymphoma

Purpose: To assess the efficacy and toxicity of chemotherapy consisting of cyclophosphamide, doxorubicin (Adriamycin), vincristine, and dexamethasone (CHOD) plus bis-chloronitrosourea (BCNU), cytosine arabinoside, and methotrexate (BVAM) followed by whole-brain irradiation (WBRT) for patients with primary central nervous system lymphoma (PCNSL). Methods and Materials: Patients 70 years old and younger with newly diagnosed, biopsy-proven PCNSL received one cycle of CHOD followed by two cycles of BVAM. Patients then received WBRT, 30.6 Gy, if a complete response was evoked, or 50.4 Gy if the response was less than complete; both doses were given in 1.8-Gy daily fractions. The primary efficacy endpoint was 1-year survival. Results: Thirty-six patients (19 men, 17 women) enrolled between 1995 and 2000. Median age was 60.5 years (range, 34 to 69 years). Thirty (83%) patients had baseline Eastern Cooperative Oncology Group performance scores of 0 to 1. All 36 patients were eligible for survival and response evaluations. Median time to progression was 12.3 months, and median survival was 18.5 months. The percentages of patients alive at 1, 2, and 3 years were 64%, 36%, and 33%, respectively. The best response was complete response in 10 patients and immediate progression in 7 patients. Ten (28%) patients had at least one grade 3 or higher neurologic toxicity. Conclusions: This regimen did improve the survival of PCNSL patients but also caused substantial toxicity. The improvement in survival is less than that reported with high-dose methotrexate-based therapies.

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Retrospective Study of Palliative Radiotherapy in Newly Diagnosed Head and Neck Carcinoma

Purpose: To examine the patterns of care, outcomes, and prognostic factors for patients with head-and-neck cancer (HNC) treated with palliative radiotherapy (RT). Methods and Materials: An institutional HNC anthology and electronic patient records were used to identify patients with previously untreated HNC of mucosal or salivary gland origin who underwent palliative RT at our institution between July 2003 and June 2008. Overall survival was determined from the start date of RT to either the date of death or the date of last follow-up for living patients. The data were censored if the subject was either lost to follow-up or had not been seen for follow-up at our institution for {>=}4 months. Results: We identified 148 eligible patients. The median age was 72 years (range, 19-94). Of the 148 patients, 12 had Stage II-III, 39 Stage IVA, 36 Stage IVB, and 54 Stage IVC; for 7 patients, the stage was unknown. Oropharyngeal primary cancer (40) was the most common primary site. The Eastern Cooperative Oncology Group performance status was 0 in 15, 1 in 69, 2 in 40, 3 in 19, and 4 in 5 patients. The Adult Co-morbidity Evaluation-27 scale was 0 in 33, 1 in 47, 2 in 44, and 3 in 21. The median radiation dose was 50 Gy (range, 2-70), the median fraction number was 20 (range, 1-40), and the median total treatment time (including breaks) was 29 days (range, 1-80). At analysis, 108 patients (73%) had died, 20 (13.5%) were alive, and 20 (13.5%) had been censored. The median follow-up was 4.8 months, and the median survival time was 5.2 months. Information on the treatment response was available for 103 patients (70%). On multivariate analysis, the radiation dose was an independent predictor of both overall survival (hazard ratio 0.97, 95% confidence interval 0.96-0.99, p <.01) and treatment response (odds ratio 1.05, 95% confidence interval 1.01-1.08, p <.01). Conclusion: For patients considered unsuitable for curative RT, the radiation dose might be an independent predictive factor for both overall survival and treatment response. Additional research is required to more effectively select those patients who might benefit from more aggressive treatment.

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Effect of Immobilization and Performance Status on Intrafraction Motion for Stereotactic Lung Radiotherapy: Analysis of 133 Patients

Purpose: To assess intrafractional geometric accuracy of lung stereotactic body radiation therapy (SBRT) patients treated with volumetric image guidance. Methods and Materials: Treatment setup accuracy was analyzed in 133 SBRT patients treated via research ethics board-approved protocols. For each fraction, a localization cone-beam computed tomography (CBCT) scan was acquired for soft-tissue registration to the internal target volume, followed by a couch adjustment for positional discrepancies greater than 3 mm, verified with a second CBCT scan. CBCT scans were also performed at intrafraction and end fraction. Patient positioning data from 2047 CBCT scans were recorded to determine systematic ({Sigma}) and random ({sigma}) uncertainties, as well as planning target volume margins. Data were further stratified and analyzed by immobilization method (evacuated cushion [n = 75], evacuated cushion plus abdominal compression [n = 33], or chest board [n = 25]) and by patients' Eastern Cooperative Oncology Group performance status (PS): 0 (n = 31), 1 (n = 70), or 2 (n = 32). Results: Using CBCT internal target volume was matched within {+-}3 mm in 16% of all fractions at localization, 89% at verification, 72% during treatment, and 69% after treatment. Planning target volume margins required to encompass residual setup errors after couch corrections (verification CBCT scans) were 4 mm, and they increased to 5 mm with target intrafraction motion (post-treatment CBCT scans). Small differences (<1 mm) in the cranial-caudal direction of target position were observed between the immobilization cohorts in the localization, verification, intrafraction, and post-treatment CBCT scans (p < 0.01). Positional drift varied according to patient PS, with the PS 1 and 2 cohorts drifting out of position by mid treatment more than the PS 0 cohort in the cranial-caudal direction (p = 0.04). Conclusions: Image guidance ensures high geometric accuracy for lung SBRT irrespective of immobilization method or PS. A 5-mm setup margin suffices to address intrafraction motion. This setup margin may be further reduced by strategies such as frequent image guidance or volumetric arc therapy to correct or limit intrafraction motion.

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Long-Term Results of Conformal Radiotherapy for Progressive Airway Amyloidosis

Purpose: To evaluate the efficacy of conformal external beam radiotherapy (RT) for local control of progressive airway amyloidosis. Methods and Materials: We conducted a retrospective review of patients with biopsy-proven progressive airway amyloidosis treated with conformal RT between 2000 and 2006 at Boston Medical Center. The patients were evaluated for performance status and pulmonary function, with computed tomography and endoscopy after RT compared with the pretreatment studies. Local control was defined as the lack of progression of airway wall thickening on computed tomography imaging and stable endobronchial deposits by endoscopy. Results: A total of 10 symptomatic airway amyloidosis patients (3 laryngeal and 7 tracheobronchial) received RT to a median total dose of 20 Gy in 10 fractions within 2 weeks. At a median follow-up of 6.7 years (range, 1.5-10.3), 8 of the 10 patients had local control. The remaining 2 patients underwent repeat RT 6 and 8.4 months after initial RT, 1 for persistent bronchial obstruction and 1 for progression of subglottic amyloid disease with subsequent disease control. The Eastern Cooperative Oncology Group performance status improved at a median of 18 months after RT compared with the baseline values, from a median score of 2 to a median of 1 (p = .035). Airflow (forced expiratory volume in 1 second) measurements increased compared with the baseline values at each follow-up evaluation, reaching a 10.7% increase (p = .087) at the last testing (median duration, 64.8 months). Acute toxicity was limited to Grade 1-2 esophagitis, occurring in 40% of patients. No late toxicity was observed. Conclusions: RT prevented progressive amyloid deposition in 8 of 10 patients, resulting in a marginally increased forced expiratory volume in 1 second, and improved functional capacity, without late morbidity.

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Radioembolization for Neuroendocrine Liver Metastases: Safety, Imaging, and Long-Term Outcomes

Purpose: To present long-term outcomes on the safety and efficacy of Yttrium-90 radioembolization in the treatment of unresectable hepatic neuroendocrine metastases refractory to standard-of-care therapy. Methods and Materials: This study was approved by our institutional review board and was compliant with the Health Insurance Portability and Accountability Act. Forty patients with hepatic neuroendocrine metastases were treated with {sup 90}Y radioembolization at a single center. Toxicity was assessed using National Cancer Institute Common Terminology Criteria v3.0. Response to therapy was assessed by World Health Organization (WHO) guidelines for size and European Association for the Study of the Liver disease (EASL) guidelines for necrosis. Time to response and overall survival were calculated using the Kaplan-Meier method. Univariate and multivariate analyses were performed. Results: The median dose was 113 Gy (29-299 Gy). Clinical toxicities included fatigue (63%), nausea/vomiting (40%), abdominal pain (18%), fever (8%), diarrhea and weight loss (5%); Grade 3 and 4 bilirubin toxicities were experienced by 2 patients and 1 patient, respectively. Different responses were noted by WHO (complete response, 1.2%; partial response, 62.7%) and EASL (complete response, 20.5%; partial response, 43.4%). Median time to response was 4 and 4.9 months by lesion and patient, respectively. The 1-, 2-, and 3-year overall survival rates were 72.5%, 62.5%, and 45%, respectively. Eastern Cooperative Oncology Group (ECOG) performance score 0 (p < 0.0001), tumor burden {<=}25% (p = 0.0019), albumin {>=}3.5 g/dL (p = 0.017), and bilirubin {<=}1.2 mg/dL (p = 0.002) prognosticated survival on univariate analysis; only ECOG performance score 0 and bilirubin {<=}1.2 mg/dL prognosticated better survival outcome on multivariate analysis (p = 0.0001 and p = 0.02). Conclusion: Yttrium-90 therapy for hepatic neuroendocrine metastases leads to satisfactory tumor response and patient survival with low toxicity, in line with published national guidelines recommending radioembolization as a potential option for unresectable hepatic neuroendocrine metastases.

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Short-Course Accelerated Radiotherapy in Palliative Treatment of Advanced Pelvic Malignancies: A Phase I Study

Purpose: To define the maximum tolerated dose of a conformal short-course accelerated radiotherapy in patients with symptomatic advanced pelvic cancer. Methods and Materials: A phase I trial in 3 dose-escalation steps was designed: 14 Gy (3.5-Gy fractions), 16 Gy (4-Gy fractions), and 18 Gy (4.5-Gy fractions). The eligibility criteria included locally advanced and/or metastatic pelvic cancer and Eastern Cooperative Oncology Group performance status of {<=}3. Treatment was delivered in 2 days with twice-daily fractionation and at least an 8-hour interval. Patients were treated in cohorts of 6-12 to define the maximum tolerated dose. The dose-limiting toxicity was defined as any acute toxicity of grade 3 or greater, using the Radiation Therapy Oncology Group scale. Pain was recorded using a visual analog scale. The effect on quality of life was evaluated according to Cancer Linear Analog Scale (CLAS). Results: Of the 27 enrolled patients, 11 were male and 16 were female, with a median age of 72 years (range 47-86). The primary tumor sites were gynecologic (48%), colorectal (33.5%), and genitourinary (18.5%). The most frequent baseline symptoms were bleeding (48%) and pain (33%). Only grade 1-2 acute toxicities were recorded. No patients experienced dose-limiting toxicity. With a median follow-up time of 6 months (range 3-28), no late toxicities were observed. The overall (complete plus partial) symptom remission was 88.9% (95% confidence interval 66.0%-97.8%). Five patients (41.7%) had complete pain relief, and six (50%) showed >30% visual analog scale reduction. The overall response rate for pain was 91.67% (95% confidence interval 52.4%-99.9%). Conclusions: Conformal short course radiotherapy in twice-daily fractions for 2 consecutive days was well tolerated up to a total dose of 18 Gy. A phase II study is ongoing to confirm the efficacy on symptom control and quality of life indexes.

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Can Locoregional Treatment of the Primary Tumor Improve Outcomes for Women With Stage IV Breast Cancer at Diagnosis?

Purpose: To examine the effect of locoregional treatment (LRT) of the primary tumor on survival in patients with Stage IV breast cancer at diagnosis. Methods and Materials: The study cohort comprised 733 women referred to the British Columbia Cancer Agency between 1996 and 2005 with newly diagnosed clinical or pathologic M1 breast cancer. Tumor and treatment characteristics, overall survival (OS), and locoregional progression-free survival were compared between patients treated with (n = 378) and without (n = 355) LRT of the primary disease. Multivariable analysis was performed with Cox regression modeling. Results: The median follow-up time was 1.9 years. LRT consisted of surgery alone in 67% of patients, radiotherapy alone in 22%, and both in 11%. LRT was used more commonly in women with age <50 years, Eastern Cooperative Oncology Group (ECOG) performance status 0-1, Stage T1-2 tumors, N0-1 disease, limited M1 burden, and asymptomatic M1 disease (all p < 0.05). Systemic therapy was used in 92% of patients who underwent LRT and 85% of patients who did not. In patients treated with LRT compared with those without LRT, the 5-year OS rates were 21% vs. 14% (p < 0.001), and the rates of locoregional progression-free survival were 72% vs. 46% (p < 0.001). Among 378 patients treated with LRT, the rates of 5-year OS were higher in patients with age <50, ECOG performance status 0-1, estrogen receptor-positive disease, clear surgical margins, single subsite, bone-only metastasis, and one to four metastatic lesions (all p < 0.003). On multivariable analysis, LRT was associated with improved OS (hazard ratio, 0.78; 95% confidence interval, 0.64-0.94, p = 0.009). Conclusion: Locoregional treatment of the primary disease is associated with improved survival in some women with Stage IV breast cancer at diagnosis. Among those treated with LRT, the most favorable rates of survival were observed in subsets with young age, good performance status, estrogen receptor-positive disease, clear margins, and distant disease limited to one subsite, bone-only involvement, or fewer than five metastatic lesions.

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Predicting Radiation Pneumonitis After Stereotactic Ablative Radiation Therapy in Patients Previously Treated With Conventional Thoracic Radiation Therapy

Purpose: To determine the incidence of and risk factors for radiation pneumonitis (RP) after stereotactic ablative radiation therapy (SABR) to the lung in patients who had previously undergone conventional thoracic radiation therapy. Methods and Materials: Seventy-two patients who had previously received conventionally fractionated radiation therapy to the thorax were treated with SABR (50 Gy in 4 fractions) for recurrent disease or secondary parenchymal lung cancer (T <4 cm, N0, M0, or Mx). Severe (grade {>=}3) RP and potential predictive factors were analyzed by univariate and multivariate logistic regression analyses. A scoring system was established to predict the risk of RP. Results: At a median follow-up time of 16 months after SABR (range, 4-56 months), 15 patients had severe RP (14 [18.9%] grade 3 and 1 [1.4%] grade 5) and 1 patient (1.4%) had a local recurrence. In univariate analyses, Eastern Cooperative Oncology Group performance status (ECOG PS) before SABR, forced expiratory volume in 1 second (FEV1), and previous planning target volume (PTV) location were associated with the incidence of severe RP. The V{sub 10} and mean lung dose (MLD) of the previous plan and the V{sub 10}-V{sub 40} and MLD of the composite plan were also related to RP. Multivariate analysis revealed that ECOG PS scores of 2-3 before SABR (P=.009), FEV1 {<=}65% before SABR (P=.012), V{sub 20} {>=}30% of the composite plan (P=.021), and an initial PTV in the bilateral mediastinum (P=.025) were all associated with RP. Conclusions: We found that severe RP was relatively common, occurring in 20.8% of patients, and could be predicted by an ECOG PS score of 2-3, an FEV1 {<=}65%, a previous PTV spanning the bilateral mediastinum, and V{sub 20} {>=}30% on composite (previous RT+SABR) plans. Prospective studies are needed to validate these predictors and the scoring system on which they are based.

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A Phase I Study of Short-Course Accelerated Whole Brain Radiation Therapy for Multiple Brain Metastases

Purpose: To define the maximum tolerated dose (MTD) of a SHort-course Accelerated whole brain RadiatiON therapy (SHARON) in the treatment of patients with multiple brain metastases. Methods and Materials: A phase 1 trial in 4 dose-escalation steps was designed: 12 Gy (3 Gy per fraction), 14 Gy (3.5 Gy per fraction), 16 Gy (4 Gy per fraction), and 18 Gy (4.5 Gy per fraction). Eligibility criteria included patients with unfavorable recursive partitioning analysis (RPA) class > or =2 with at least 3 brain metastases or metastatic disease in more than 3 organ systems, and Eastern Cooperative Oncology Group (ECOG) performance status {<=}3. Treatment was delivered in 2 days with twice-daily fractionation. Patients were treated in cohorts of 6-12 to define the MTD. The dose-limiting toxicity (DLT) was defined as any acute toxicity {>=}grade 3, according to the Radiation Therapy Oncology Group scale. Information on the status of the main neurologic symptoms and quality of life were recorded. Results: Characteristics of the 49 enrolled patients were as follows: male/female, 30/19; median age, 66 years (range, 23-83 years). ECOG performance status was <3 in 46 patients (94%). Fourteen patients (29%) were considered to be in recursive partitioning analysis (RPA) class 3. Grade 1-2 acute neurologic (26.4%) and skin (18.3%) toxicities were recorded. Only 1 patient experienced DLT (neurologic grade 3 acute toxicity). With a median follow-up time of 5 months (range, 1-23 months), no late toxicities have been observed. Three weeks after treatment, 16 of 21 symptomatic patients showed an improvement or resolution of presenting symptoms (overall symptom response rate, 76.2%; confidence interval 0.95: 60.3-95.9%). Conclusions: Short-course accelerated radiation therapy in twice-daily fractions for 2 consecutive days is tolerated up to a total dose of 18 Gy. A phase 2 study has been planned to evaluate the efficacy on overall survival, symptom control, and quality of life indices.

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Nonendemic HPV-Positive Nasopharyngeal Carcinoma: Association With Poor Prognosis

Purpose: To investigate the relationship between human papillomavirus (HPV) and Epstein-Barr virus (EBV) in nonendemic nasopharyngeal carcinoma (NPC) and assess the prognostic implications of viral status. Methods and Materials: Paraffin-embedded tumor specimens from 62 patients with primary NPC diagnosed between 1985 and 2011 were analyzed for EBV and high-risk HPV. EBV status was determined by the use of in situ hybridization for EBV encoded RNA. HPV status was assessed with p16 immunohistochemistry and multiplex polymerase chain reaction MassArray for determination of HPV type. Proportional hazards models were used to compare the risk of death among patients as stratified by viral status. Results: Of 61 evaluable tumors, 26 (43%) were EBV-positive/HPV-negative, 18 (30%) were HPV-positive/EBV-negative, and 17 (28%) were EBV/HPV-negative. EBV and HPV infection was mutually exclusive. HPV positivity was significantly correlated with World Health Organization grade 2 tumors, older age, and smoking (all P<.001). The racial distribution of the study population was 74% white, 15% African American, and 11% Asian/Middle Eastern. Among HPV-positive patients, 94% were white. At a median follow-up time of 7 years, HPV-positive and EBV/HPV-negative tumors exhibited worse outcomes than did EBV-positive tumors, including decreased overall survival (hazard ratio [HR] 2.98, P=.01; and HR 3.89, P=.002), progression-free survival (HR 2.55, P=.02; and HR 4.04, P<.001), and locoregional control (HR 4.01, P=.03; and HR 6.87, P=.001). Conclusion: In our Midwestern population, high-risk HPV infection may play an etiologic role in the development of nonendemic, EBV-negative NPC. Compared with EBV-positive NPC, HPV-positive and EBV/HPV-negative NPC are associated with worse outcomes. A larger confirmatory study is needed to validate these findings.

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Outcomes of Low-Risk Ductal Carcinoma In Situ in Southeast Asian Women Treated With Breast Conservation Therapy

Purpose: To examine the outcomes of Southeast Asian (SEA) women with low-risk ductal carcinoma in situ (DCIS) treated with breast-conserving surgery (BCS) and adjuvant radiation therapy. Methods and Materials: Retrospective chart reviews of patients treated with BCS for DCIS from 1995 to 2011 were performed. Patients meeting the selection criteria from Eastern Cooperative Oncology Group 5194 were included. Most patients received adjuvant radiation therapy (RT) consisting of whole-breast RT delivered to 50 Gy followed by a 10-Gy boost to the tumor bed. Results: Of 744 patients with pathologic diagnosis of pure DCIS identified, 273 met the selection criteria: low-intermediate grade (LIG), n=219; high grade (HG), n=54. Median follow-up for these patients was 60 months. There were 8 ipsilateral breast tumor recurrences (IBTRs) in total, 7 of which were DCIS. The estimated actuarial IBTR rates at 5 and 10 years for the entire cohort are 1.8% and 4.3%, respectively. Of the 219 patients with LIG DCIS, 210 received RT and 9 did not. There were 7 IBTRs in LIG DCIS, 2 among the 9 patients who did not receive RT. The IBTR rates in LIG DCIS at 5 and 10 years are 2.3% and 4.2%, respectively. All patients with HG DCIS received RT. There was only 1 IBTR occurring beyond 5 years, giving an estimated IBTR rate of 4.5% at 10 years. Conclusions: SEA women with screen-detected DCIS have exceedingly low rates of IBTR after BCS, comparable to that observed in reports of similar patients with low-risk DCIS treated with adjuvant radiation.

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Impact of Pretreatment Tumor Growth Rate on Outcome of Early-Stage Lung Cancer Treated With Stereotactic Body Radiation Therapy

Purpose: To determine the influence of pretreatment tumor growth rate on outcomes in patients with early-stage non-small cell lung cancer (NSCLC) treated with stereotactic body radiation therapy (SBRT). Methods and Materials: A review was conducted on 160 patients with T1-T2N0M0 NSCLC treated with SBRT at single institution. The patient's demographic and clinical data, time interval (t) between diagnostic and planning computed tomography (CT), vital status, disease status, and cause of death were extracted from a prospectively kept database. Differences in gross tumor volume between diagnostic CT (GTV1) and planning CT (GTV2) were recorded, and growth rate was calculated by use of specific growth rate (SGR). Kaplan-Meier curves were constructed for overall survival (OS). Differences between groups were compared with a log-rank test. Multivariate analyses were performed by use of the Cox proportional hazard model with SGR and other relevant clinical factors. Cumulative incidence was calculated for local, regional, and distant failures by use of the competing risk approach and was compared with Gray's test. Results: The median time interval between diagnostic and planning CT was 82 days. The patients were divided into 2 groups, and the median SGR was used as a cut-off. The median survival times were 38.6 and 27.7 months for the low and high SGR groups, respectively (P=.03). Eastern Cooperative Oncology Group performance status (P=.01), sex (P=.04), SGR (P=.03), and GTV2 (P=.002) were predictive for OS in multivariable Cox regression analysis and, except sex, were similarly predictive for failure-free survival (FFS). The 3-year cumulative incidences of regional failure were 19.2% and 6.0% for the high and low SGR groups, respectively (P=.047). Conclusion: High SGR was correlated with both poorer OS and FFS in patients with early-stage NSCLC treated with SBRT. If validated, this measurement may be useful in identifying patients most likely to benefit from adjuvant therapy after SBRT.

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Definitive Primary Therapy in Patients Presenting With Oligometastatic Non-Small Cell Lung Cancer

Purpose: Although palliative chemotherapy is the standard of care for patients with diagnoses of stage IV non-small cell lung cancer (NSCLC), patients with a small metastatic burden, “oligometastatic” disease, may benefit from more aggressive local therapy. Methods and Materials: We identified 186 patients (26% of stage IV patients) prospectively enrolled in our institutional database from 2002 to 2012 with oligometastatic disease, which we defined as 5 or fewer distant metastatic lesions at diagnosis. Univariate and multivariable Cox proportional hazards models were used to identify patient and disease factors associated with improved survival. Using propensity score methods, we investigated the effect of definitive local therapy to the primary tumor on overall survival. Results: Median age at diagnosis was 61 years of age; 51% of patients were female; 12% had squamous histology; and 33% had N0-1 disease. On multivariable analysis, Eastern Cooperate Oncology Group performance status ≥2 (hazard ratio [HR], 2.43), nodal status, N2-3 (HR, 2.16), squamous pathology, and metastases to multiple organs (HR, 2.11) were associated with a greater hazard of death (all P<.01). The number of metastatic lesions and radiologic size of the primary tumor were not significantly associated with overall survival. Definitive local therapy to the primary tumor was associated with prolonged survival (HR, 0.65, P=.043). Conclusions: Definitive local therapy to the primary tumor appears to be associated with improved survival in patients with oligometastatic NSCLC. Select patient and tumor characteristics, including good performance status, nonsquamous histology, and limited nodal disease, may predict for improved survival in these patients.

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Phase 2 Study of Concurrent Cetuximab Plus Definitive Thoracic Radiation Therapy Followed by Consolidation Docetaxel Plus Cetuximab in Poor Prognosis or Elderly Patients With Locally Advanced Non-Small Cell Lung Cancer

Background: Recursive partitioning analysis has shown that Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) ≥2, male sex, and age ≥70 years are prognostic of poor outcome in locally advanced non-small cell lung cancer (LA-NSCLC) patients. Concurrent chemoradiation therapy (CRT) improves survival, but toxicity is a concern in this frail patient cohort. We therefore opened this trial of concurrent definitive thoracic radiation therapy (XRT) and cetuximab, followed by consolidation docetaxel plus cetuximab. Methods and Materials: Eligible patients had pathologically proven, unresectable LA-NSCLC (stage IIA-“dry” IIIB). They had ECOG PS 2 or weight loss ≥5% in 3 months or were aged ≥70 years. The primary objective was progression-free survival (PFS). Secondary objectives included overall survival (OS) and overall response rate (ORR). Results: From May 2008 to November 2010, a total of 32 patients were evaluated in our single-institution, institutional review board–approved prospective clinical trial. Three patients were screen failures and 2 more withdrew consent before treatment, leaving 27 evaluable patients. One was removed because of poor therapy compliance, and 2 were taken off trial because of grade 3 cetuximab-related toxicities but were followed up under intent-to-treat analysis. The median follow-up and OS were 10.5 months. The median PFS was 7.5 months. The ORR was 59.3%. Eight early/sudden deaths were reported. Upon review, 6 patients developed severe pulmonary complications. Conclusions: Patients enrolled in this trial had improved OS compared with poor-PS historical controls (10.5 vs 6.4 months) and comparable OS to good-PS historical controls (10.5 vs 11.9 months) treated with XRT alone. However, pulmonary toxicity is a concern. Consolidative cetuximab/docetaxel, in conjunction with high-dose radiation therapy, is a putative cause.

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