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Introduction/background: For early stage medically inoperable lung cancer treated with fractionated stereotactic body radiotherapy (SBRT), higher local failure is associated with squamous carcinoma (SqC) compared to adenocarcinoma (AC). This study explored whether histology influences single-fraction SBRT local control., Materials and Methods: We surveyed our prospective data registry from 12/2009 to 12/2019 for SF-SBRT cases with biopsy-proven AC or SqC only. Outcomes of interest included local (LF), nodal (NF), distant (DF) failure rates and overall survival (OS), as well as treatment-related toxicity., Results: For the 10-year interval surveyed, 113 patients met study criteria. There was no association between histology and dose received (34 Gy or 30 Gy). Median follow up was 22.9 months. Patient characteristics were balanced between histologic cohorts. Median tumor size was 1.9 cm. Comparing total AC vs. SqC cohorts, 2-year LF rates (%) were 7.3 vs. 9.6, respectively (P = .9805). In %, 2-year LF, NF, DF and OS rates for AC for 30 Gy and 34 Gy, respectively, were 10.8 vs. 6.4; 10.5 vs. 16.2; 15.8 vs. 13.0; 77.9 vs.71.2 (all P = non-significant). In %, 2-year LF, NF, DF, and OS rates for SqC for 30 Gy and 34 Gy, respectively, were 11.8 vs. 8.1; 5.9 vs. 18.0; 23.5 vs. 9.7; 70.6 vs. 77.1 (all P = non-significant). When considering toxicities, there were no grade 4/5 toxicities and no significant differences in any other toxicity rate by histology or dose., Conclusion: SF-SBRT local control was not associated with histology, unlike fractionated schedules. This novel finding adds to the evolving understanding of this treatment schedule., (Copyright © 2022. Published by Elsevier Inc.)

Objectives: To explore the influence of treatment package time(TPT) in high-risk oral cavity squamous cell carcinoma(OCSCC) receiving adjuvant radiotherapy with concurrent chemotherapy(CRT)., Materials and Methods: We queried our multi-institutional OCSCC collaborative database for cases diagnosed between 2005 and 2015 who underwent surgery followed by adjuvant CRT. All patients had high-risk features: extranodal extension(ENE) and/or positive surgical margin(PM). TPT was days between surgery to last radiotherapy fraction. Kaplan-Meier curves, log-rank p-values and multivariate analysis(MVA) were used to investigate the impact of TPT on overall(OS), disease-free(DFS), locoregional failure-free(LRFS) and distant metastases-free(DMFS) survival., Results: We identified 187 cases: median age 58 (range, 24-87 years), males 66%, and ever smokers 69%. ENE and PM were detected in 85% and 32%, and oral tongue and floor of the mouth constituted 49% and 18%, respectively. Median radiotherapy and cisplatin doses received were 66 Gy and 200 mg/m2. Overall, median TPT was 98 (range, 63-162 days). OS was worse for TPT > 90-days (n = 134) than TPT ≤ 90 (n = 53) at two-(65% vs. 71%) and five-years (45% vs. 62%); p = 0.05, with similar results for DFS. No influence on LRFS or DMFS was noted. More lymph nodes(LN) dissected(P = 0.039), T3-4 disease(P = 0.017), and unplanned reoperations(P = 0.037) occurred with TPT > 90-days. On MVA, TPT in 10-day increments was independently detrimental for OS (Hazard Ratio: 1.14; 95 %Confidence Interval [1-1.28]; P = 0.043), perineural invasion, age and positive LN (p < 0.05 for all)., Conclusion: In one of the largest multi-institutional cohorts, TPT > 90-days predicted worse OS for high-risk OCSCC receiving adjuvant CRT. All efforts are needed to optimize perioperative care and baseline conditions for favorable outcomes., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Objectives: The importance of treating the bilateral neck in lateralized small oral cavity squamous cell carcinoma (OCC) is unclear. We sought to define the incidence and predictors of contralateral neck failure (CLF) in patients who underwent unilateral treatment., Materials and Methods: We performed a multi-institutional retrospective study of patients with pathologic T1-T2 (AJCC 7th edition) OCC with clinically node negative contralateral neck who underwent unilateral treatment with primary surgical resection ± adjuvant radiotherapy between 2005 and 2015. Incidence of CLF was estimated using the cumulative incidence method. Clinicopathological factors were analyzed by univariate (UVA) and multivariate analysis (MVA) for possible association with CLF. Kaplan-Meier analysis was used to estimate overall survival (OS)., Results: 176 patients were evaluated with a median of 65.9 months of follow-up. Predominant pathologic T-stage was T1 (68%), 8.5% of patients were N1, 2.8% were N2b. Adjuvant radiotherapy was delivered to 17% of patients. 5-year incidence of CLF was 4.3% (95% CI 1.2-7.4%). Depth of invasion (DOI) > 10 mm and positive ipsilateral neck node were significant predictors for CLF on UVA. DOI > 10 mm remained significant on MVA (HR = 6.7, 95% CI 1.4-32.3, p = 0.02). The 2- and 5-year OS was 90.6% (95% CI 86.2-95.0%) and 80.6% (95% CI 74.5-86.8%), respectively., Conclusion: Observation of the clinically node negative contralateral neck in small lateralized OCC can be a suitable management approach in well selected patients, however caution should be applied when DOI upstages small but deeply invasive tumors to T3 on 8th edition AJCC staging., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Purpose: Abdominal compression (COMP) and breath-hold with an active breathing coordinator (ABC) device are 2 different respiratory motion management techniques used in lung stereotactic body radiation therapy (SBRT) practice. We compared local failure (LF) results for COMP versus ABC., Methods and Materials: We surveyed our institutional review board-approved prospective registry for patients who were treated with SBRT for either a primary lung cancer (PRIME) or an oligometastatic (OLIGO) diagnosis with a minimum of 6 months' follow-up to determine their rates of local failure by motion management modality., Results: From October 2003 to July 2014, 873 patients with 931 lesions were treated. Patient characteristics included: 455 (52.1%) female; median age of 73 years (range, 37-97); median Karnofsky performance status (KPS) of 80 (range, 40-100); and median BMI of 26.2 (range, 12.1-56.3). Tumor characteristics included: median tumor size of 2.2 cm (range, 0.7-10.0); median maximum standardized uptake value from positron emission tomography PET SUVmax of 7.5 (range, 0.8-59); 234 (25.4%) were central lesions; 830 (89.2%) lesions were PRIME; and 101 (10.8%) were OLIGO. Median follow-up and SBRT dose were 16.4 months and 50 G in 5 fractions, respectively. Overall crude rate of LF was 9.9%. Use of ABC was not associated with increased LF compared with COMP: hazard ratio (HR) = 1.043 (95% CI 0.48-2.29; P = .92). Three-year actuarial rates of LF for ABC versus COMP were 13.8% and 16.5%, respectively. After stratifying by OLIGO/PRIME, neither ABC nor COMP was significantly associated with LF. Central location may be associated with LF with ABC (HR = 2.087, P = .066). On univariate analysis, BMI, tumor size, PET SUV max and central location were associated with failure, with size the most significant., Conclusions: LF rates after lung SBRT were not influenced by form of motion control overall or when stratified by tumor type. Further study on LF rates for central tumors where ABC is used is warranted., (Copyright © 2020 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved.)

Objectives: Patients with human papillomavirus (HPV) associated squamous cell carcinoma of the oropharynx (SCC-OP) have improved overall survival (OS) after distant metastasis (DM) compared to HPV negative patients. These patients may be appropriate candidates for enrollment on clinical trials evaluating the efficacy of metastasis-directed therapy (MDT). This study seeks to identify prognostic factors associated with OS after DM, which could serve as enrollment criteria for such trials., Materials and Methods: From an IRB approved multi-institutional database, we retrospectively identified patients with HPV/p16 positive SCC-OP diagnosed between 2001 and 2018. Patterns of distant failure were assessed, including number of lesions at diagnosis and sites of involvement. The primary outcome was OS after DM. Prognostic factors for OS after DM were identified with Cox proportional hazards. Stepwise approach was used for multivariable analysis., Results: We identified 621 patients with HPV-associated SCC-OP, of whom 82 (13.2%) were diagnosed with DM. Median OS after DM was 14.6 months. On multivariable analysis, smoking history and number of lesions were significantly associated with prolonged OS. Median OS after DM by smoking (never vs ever) was 37.6 vs 11.2 months (p = 0.006), and by lesion number (1 vs 2-4 vs 5 or more) was 41.2 vs 17.2 vs 10.8 months (p = 0.007)., Conclusion: Among patients with newly diagnosed metastatic HPV-associated SCC-OP, lesion number and smoking status were associated with significantly prolonged overall survival. These factors should be incorporated into the design of clinical trials investigating the utility of MDT, with or without systemic therapy, in this population., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Introduction: The objective of this study is to evaluate locoregional and distant failure for human papillomavirus-associated (HPV+) oropharyngeal squamous cell carcinoma (OPSCC) using American Joint Committee on Cancer eighth edition (AJCC 8) staging., Materials and Methods: Retrospective cohort study of 457 patients with HPV + OPSCC, treated with platinum-based chemoradiation from 2002 to 2018, followed for a median of 4.3 years. Time to locoregional failure (TTLRF) and distant failure (TTDF) were estimated by Kaplan-Meier method. Log-rank, recursive partitioning analysis (RPA), and multivariable Cox proportional hazards were used to evaluate associated factors and stratify risk., Results: Rates of five-year locoregional control (LRC) and distant control (DC) were 92% (95% CI, 90-95%) and 89% (95% CI, 85-92%), respectively. Smoking, T4, N3, and stage III were associated with significantly worse TTLRF. RPA identified three distinct locoregional failure groups: cT1-3 and <19 pack-years vs. cT1-3 with ≥19 pack-years vs. cT4 (five-year LRC: 97% vs. 90% vs. 82%, P < .0001). The only factor associated with significantly worse TTDF was smoking status, while stage was not correlated. RPA identified two prognostic groups: former or never smokers vs. current smokers (five-year DC: 92% vs. 77%, P = .0003)., Discussion: In the largest evaluation of HPV + OPSCC after platinum-based chemoradiation using AJCC 8, risk for locoregional recurrence was stratified by smoking, T category, N category, and overall stage. Risk of distant recurrence was only stratified by smoking status and not related to stage. This has implications for surveillance and clinical trial design., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Objectives: This study examines the utility of surveillance imaging in detecting locoregional failures (LRF), distant failures (DF) and second primary tumors (SPT) in patients with human papillomavirus (HPV) associated oropharyngeal cancer (OPC) after definitive chemoradiotherapy (CRT)., Methods and Materials: An institutional database identified 225 patients with biopsy proven, non- metastatic HPV+ OPC treated with definitive CRT between 2004 and 2015, whose initial post-treatment imaging was negative for disease recurrence (DR). Two groups were defined: patients with <2 scans/year Group 1 and patients with ≥2 scans/year Group 2. The Mann-Whitney test or Chi-square was used to determine differences in baseline characteristics between groups. Fine & Gray regression was used to detect an association between imaging frequency, DR and diagnosis of SPT., Results: Median follow up was 40.8 months. 30% of patients had ≥T3 disease and 90% had ≥ N2 disease (AJCC 7th edition). Twenty one failures (9.3%) were observed, 7 LRF and 15 DF. Six LRF occurred within 24 months and 14 DF occurred within 36 months of treatment completion. Regression analysis showed Group 2 had increased risk of DR compared to Group1 (HR 10.3; p = 0.002) albeit with more advanced disease at baseline. Five SPT were found (2 lung, 2 esophagus, and 1 oropharynx) between 4.5 and 159 months post-CRT., Conclusion: Surveillance imaging seems most useful in the first 2-3 years post treatment, and is particularly important in detecting DF. Surveillance scans for SPT has a low yield, but should be considered for those meeting lung cancer screening guidelines., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Purpose: The toxicity profile of breast reconstruction with postmastectomy radiation therapy (PMRT) varies by technique and timing, and long-term data are limited. We compared rates of complications requiring reoperation (CRR) and reconstruction failure (RF) between immediate autologous reconstruction (I-AR), immediate tissue expander/implant reconstruction (I-TE/I), delayed autologous reconstruction (D-AR), and delayed tissue expander/implant reconstruction (D-TE/I) in patients receiving PMRT., Methods and Materials: Patients who received autologous reconstruction (AR) or tissue expander/implant reconstruction (TE/I) and PMRT between 2000 to 2008 were included. Reconstruction was immediate if performed on the same day as mastectomy followed by PMRT (I-AR or I-TE/I) or delayed if after PMRT (D-AR and D-TE/I). CRR was defined as an unplanned return to the operating room for infection, dehiscence, necrosis, hematoma, or hernia (with AR) and extrusion, leak, or contracture (with TE/I). RF was defined as unplanned conversion to another reconstruction technique or to flat chest wall. Cumulative incidence of CRR and RF was calculated using Kaplan-Meier and compared using the log-rank test. Logistic regression was used to identify variables associated with CRR and RF., Results: Two hundred four patients were included. Median follow-up was 8 years. There were 127 AR cases (63%) and 77 TE/I cases (38%). At 5 years, CRR was 18%, 38%, 34%, and 70% (P = .010) and RF was 4%, 22%, 7%, and 56% (P < .0001) for I-AR, I-TE/I, D-AR, and D-TE/I, respectively. On multivariate analysis, TE/I (hazard ratio [HR] 2.0; P = .011), body mass index ≥30 (HR 3.9; P = .002), and smoking (HR 2.7; P = .001) were significant predictors for CRR, and TE/I (HR 6.6; P < .0001), diabetes (HR 4.1; P = .044), and hypertension (HR 3.5; P = .005) were significant for RF. When excluding RF because of infection, the rate of RF was not significantly different among the 4 groups (P = .23)., Conclusions: With PMRT, TE/I reconstruction in the immediate and delayed setting is associated with higher CRR and RF compared with AR. Patient factors should guide selection of technique. Efforts to reduce rates of RF with TE/I should focus on minimizing risks for infection., (Copyright © 2019 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved.)

Purpose: Dosimetric parameters to limit chest wall toxicity (CWT) are not well defined in single-fraction (SF) stereotactic body radiation therapy (SBRT) phase 2 trials. We sought to determine the relationship of tumor location and dosimetric parameters with CWT for SF-SBRT., Methods and Materials: From a prospective registry of 1462 patients, we identified patients treated with 30 Gy or 34 Gy. Gross tumor volume was measured as abutting, ≤1 cm, 1 to 2 cm, or >2 cm from the chest wall. CWT was prospectively graded according to Common Terminology Criteria for Adverse Events version 3.0, with grade 2 requiring medical therapy, grade 3 requiring procedural intervention, and grade 4 being disabling pain. Grade 1 CWT or radiographic rib fracture was not included. Logistic regression analysis was used to identify the parameters associated with CWT and calculate the probability of CWT with dose., Results: This study included 146 lesions. The median follow-up time was 23.8 months. The 5-year local control, distant metastasis, and overall survival rates were 91.8%, 19.2%, and 28.7%, respectively. Grade 2 to 4 CWT was 30.6% for lesions abutting the chest wall, 8.2% for ≤1 cm from the chest wall, 3.8% for 1 to 2 cm from the chest wall, and 5.7% for >2 cm from the chest wall. Grade ≥3 CWT was 1.4%. Tumor abutment (odds ratio [OR]: 6.5; P = .0005), body mass index (OR: 1.1; P = .02), rib D1cc (OR: 1.01/Gy; P = .03), chest wall D1cc (OR: 1.08/Gy; P = .03), and chest wall D5cc (OR: 1.10/Gy; P = .01) were significant predictors for CWT on univariate analysis. Tumor abutment was significant for CWT (OR: 7.5; P = .007) on multivariate analysis. The probability of CWT was 15% with chest wall D5cc at 27.2 Gy and rib D1cc at 30.2 Gy., Conclusions: The rate of CWT with SF-SBRT is similar to the rates published for fractionated SBRT, with most CWT being low grade. Tumor location relative to the chest wall is not a contraindication to SF-SBRT, but the rates increase significantly with abutment. Rib D1cc and chest wall D1cc and D5cc may be used as predictors of CWT., (Copyright © 2018 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved.)

Introduction: The conformality of modern intensity modulated radiation therapy (IMRT) allows avoidance of the submandibular glands (SMG) in select patients, potentially improving late xerostomia. This study explores the safety and efficacy of this approach in select oropharyngeal carcinoma (OPC) patients., Methods: Patients with T1-2N+ human papillomavirus (HPV)-associated OPC treated with definitive IMRT at one institution from 2009 to 2014 were identified. Patients were divided into 3 groups: bilateral level IB targeted (A, n = 16), a single level IB targeted (B, n = 61), and bilateral IB spared (C, n = 9). Outcomes were reviewed to identify the rate of level IB regional recurrence. Odds ratios were calculated for xerostomia between groups., Results: Level Ib was targeted in 93 instances (54.1%) and avoided in 79 instances (45.9%). Mean SMG doses were significantly lower when level IB was spared compared to when targeted (37.5 Gy vs 67.5 Gy; P < 0.0001). Median doses to oral cavity decreased with increasing level Ib sparing (40.7 Gy [A] vs 35.4 Gy [B] vs 30.7 [C]; P = 0.002). The rate of late grade ≥2 xerostomia was significantly lower in patients with bilateral 1b sparing (53% in A vs 0% in C; P = 0.007). Sparing 1b unilaterally resulted in a non-significant decrease in late grade ≥2 xerostomia (P = 0.181). No regional failures were identified in levels IB (median follow up = 59.3 months)., Conclusion: Sparing level IB is safe in T1-2N+ HPV+ OPC. Avoiding level Ib translates into significantly lower SMG and oral cavity doses. Larger studies are needed to validate these findings and the impact of this technique., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Background: Submandibular gland (SMG) metastases are extremely rare in head and neck cancer, even in the presence of level Ib lymph node (LN) involvement. In recent years, we have contoured the SMG and specifically attempted to limit its dose exposure even in patients in whom the level Ib LN station is targeted. This study reports our preliminary feasibility and safety experience with selective submandibular gland sparing., Methods: Patients with squamous cell cancer (SCC) of the oral cavity or oropharynx with T1-2, N0-3, M0 disease in whom at least a single level Ib lymph node region was included in the target volume were identified. All patients were treated from 2009 to 2014 with definitive or postoperative IMRT with or without chemotherapy. Patients with recurrent disease, previous radiation or treated palliatively were excluded., Results: A total of 174 patients met criteria for inclusion. Among the 185 level Ib LN stations that were deliberately targeted in the clinical treatment volume, 32 submandibular glands were contoured, excluded from the target volume and avoided during treatment planning. Mean dose to the spared SMG were reduced by 12% (66.6 Gy vs. 58.9 Gy, p < .001). None of these patients experienced any level 1b LN failures., Conclusion: Selective sparing of the submandibular gland when targeting the level 1b nodes in oral cavity and oropharynx cancer is feasible, reduces the mean dose to submandibular glands and does not result in increased level 1b nodal failure rates. Additional studies with larger cohorts are needed to validate this preliminary observation., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Background: The disease-specific graded prognostic assessment (DS-GPA) for brain metastases is a powerful prognostic tool but has not been validated for patients with synchronous brain metastases (SBM) in newly diagnosed non-small-cell lung cancer (NSCLC)., Patients and Methods: We identified patients with newly diagnosed NSCLC with 1 to 3 SBM treated with stereotactic radiosurgery (SRS) between 1997 and 2012. We included patients whose brain metastases were treated with SRS alone or combined SRS and whole-brain radiotherapy (WBRT). Patients were stratified according to NSCLC DS-GPA to evaluate the accuracy of survival estimates., Results: One hundred sixty-four patients were treated with either SRS alone (n = 85; 52%) or SRS and WBRT (n = 79; 48%). Median overall survival (OS) stratified according to DS-GPA of 0 to 1, 1.5 to 2, 2.5 to 3, and 3.5 to 4 were 2.8, 6.7, 9.8, and 13.2 months, respectively, consistent with OS reported for brain metastases in NSCLC DS-GPA (3.0, 6.5, 11.3, and 14.8 months, respectively). No difference in median progression-free survival or OS was noted with combined use of SRS and WBRT: 6.0 versus 6.1 months (P = .81) and 8.5 versus 9.1 months (P = .093), respectively. In multivariable analysis, Karnofsky performance status (hazard ratio [HR], 0.98; P = .008), extracranial metastases (HR, 0.498; P = .0003), squamous histology (HR, 1.81; P = .02), and number of brain metastases (2 vs. 1; HR, 1.504; P = .04, and 3 vs. 1; HR, 1.66; P = .05) were significant predictors of OS., Conclusion: The DS-GPA accurately estimates the prognosis of patients with SBM in newly diagnosed NSCLC. Patients with synchronous brain metastasis in newly diagnosed NSCLC should be carefully stratified for consideration of aggressive therapy., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Purpose: To report on the patient, tumor, and treatment characteristics of patients aged 90 years or older who were treated with lung stereotactic body radiation therapy (SBRT) for early stage lung cancer and the resulting clinical outcomes., Methods and Materials: We surveyed our institutional review board-approved prospective lung SBRT data registry for patients aged 90 years or older who were treated for early stage lung cancer to determine the rates of local failure, progression-free survival, and overall survival as well as treatment-related toxicity., Results: For the 2004 to 2016 time period, 19 patients (of a total of 1268 lung SBRT cases) were identified. The median age at treatment was 91.6 years (range, 90-97 years). Most patients were female (52.6%) and former smokers (78.9%). The median tumor size was 2.1 cm (range, 1.5-5.4 cm). Tissue was obtained for diagnosis in 68.4% of patients, with the predominant histology being adenocarcinoma (42.2%). Six patients (31.6%) had central lesions. The median follow-up for all patients was 17.3 months. The median SBRT schedule was 50 Gy in 5 fractions over 5 consecutive days and was used in 9 cases (47.4%). The median pre-SBRT and 6-month post-SBRT pulmonary testing showed that the forced expiratory volume in one second, as the percent predicted, was 81.9 and 84.5 and the diffusing capacity of the lungs for carbon monoxide, as the percent predicted, was 66.5 and 67, respectively. No grade 3 or higher toxicities were observed. The 2-year rates of local failure, progression-free survival, and overall survival were 5.6%, 48.6%, and 47.8%, respectively., Conclusions: Lung SBRT appears to be safe and effective in nonagenarians with stage I lung cancer. The absence of high-grade toxicities and mortality warrants its consideration as the primary curative modality in this population., (Copyright © 2017 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved.)

Purpose: Stereotactic body radiation therapy (SBRT) is the standard of care for medically inoperable patients with early-stage NSCLC. However, NSCLC is composed of several histological subtypes and the impact of this heterogeneity on SBRT treatments has yet to be established., Methods: We analyzed 740 patients with early-stage NSCLC treated definitively with SBRT from 2003 through 2015. We calculated cumulative incidence curves using the competing risk method and identified predictors of local failure using Fine and Gray regression., Results: Overall, 72 patients had a local failure, with a cumulative incidence of local failure at 3 years of 11.8%. On univariate analysis, squamous histological subtype, younger age, fewer medical comorbidities, higher body mass index, higher positron emission tomography standardized uptake value, central tumors, and lower radiation dose were associated with an increased risk for local failure. On multivariable analysis, squamous histological subtype (hazard ratio = 2.4 p = 0.008) was the strongest predictor of local failure. Patients with squamous cancers fail SBRT at a significantly higher rate than do those with adenocarcinomas or NSCLC not otherwise specified, with 3-year cumulative rates of local failure of 18.9% (95% confidence interval [CI]: 12.7-25.1), 8.7% (95% CI: 4.6-12.8), and 4.1% (95% CI: 0-9.6), respectively., Conclusion: Our results demonstrate an increased rate of local failure in patients with squamous cell carcinoma. Standard approaches for radiotherapy that demonstrate efficacy for a population may not achieve optimal results for individual patients. Establishing the differential dose effect of SBRT across histological groups is likely to improve efficacy and inform ongoing and future studies that aim to expand indications for SBRT., (Copyright © 2016 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.)

Introduction: The role of stereotactic body radiotherapy (SBRT) for tumors involving the chest wall (CW) remains ill-defined. The Radiation Therapy Oncology Group 0236 trial allowed inclusion of T3N0 non-small-cell lung cancer (NSCLC) < 5 cm, although ultimately none were enrolled. No published data set investigating this population is available., Materials and Methods: We queried an institutional review board-approved prospective SBRT registry to identify patients with tumors involving the CW, defined as radiographic evidence of frank soft tissue invasion or bony destruction. All patients underwent SBRT to a median dose of 50 Gy in 5 fractions and were followed up for tumor control, pain response, and toxicity., Results: Of 820 NSCLC patients reviewed, 13 with CW involvement were identified. Of these 13 patients, 10 had primary T3N0 NSCLC and 3 had recurrent NSCLC. Their median age was 78 years, the Karnofsky performance status was 80, the Charlson score was 3, and the tumor diameter was 4.0 cm. The 1-year local, locoregional, and distant control rates were 89%, 62%, 80%, respectively. Of 9 patients with pretreatment tumor-related CW pain, 7 (78%) reported improvement after treatment. Regarding toxicity, 2 of 13 (15%) experienced new or worsening CW pain (both grade ≤ 2); 3 cases (23%) of grade 1-2 radiation pneumonitis developed. No patient exhibited late skin changes or fibrosis., Conclusion: SBRT for NSCLC involving the CW was well tolerated, with promising early rates of tumor control and no grade ≥ 3 toxicity. Tumor-related CW pain was relieved in most patients, and the treatment-related toxicity rates appeared acceptable. Further investigation in this subset of patients with NSCLC is warranted., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Introduction: Isolated nodal failure (INF) without synchronous local or distant failure is an uncommon occurrence after stereotactic body radiation therapy (SBRT) for lung cancer. Here we review the natural history and patterns of failure after post-SBRT INF with or without salvage mediastinal radiotherapy (SvRT)., Methods: Patients treated with SBRT for non-small cell lung cancer with definitive intent were identified. Patients who experienced hilar or mediastinal INF without synchronous distant, lobar, or local failure were included and grouped according to the use of SvRT. The rates of subsequent locoregional control, distant metastases, progression-free survival (PFS), and overall survival were assessed., Results: Of 797 patients treated with definitive SBRT, 24 (3%) experienced INF and 15 (63%) received SvRT. The most common SvRT regimen (53%) was 45 Gy in 15 fractions. The median follow-up after INF was 11.3 months for survivors. There were no grade 3 or higher toxicities after SvRT. The 1-year Kaplan-Meier PFS and overall survival estimates were 33% and 56% for patients not receiving radiotherapy and 75% and 73% with SvRT. After SvRT, the rate of locoregional control at 1 year was 84.4%. Crude rates of distant failure were 20.0% with SvRT and 22.2% with no radiotherapy. Of the 13 deaths observed, five (38%) were related to distant progression of lung cancer, four (31%) to comorbidities, three (23%) to mediastinal progression, and one (8%) to an unknown cause., Conclusions: INF is uncommon after SBRT. Despite the significant comorbidities of this population, intrathoracic progression remains a contributor to morbidity and mortality. SVRT for INF is well tolerated and may improve PFS., (Copyright © 2016 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.)

Objectives: To analyze a cohort of patients with HPV positive, oropharyngeal squamous cell carcinoma (OPSCC) treated with lower radiation dose to clinically involved lymph nodes., Materials and Methods: We retrospectively identified patients with HPV positive, OPSCC treated with definitive chemoradiotherapy (70-74.4Gy) to the primary site and, since a post-radiation neck dissection was planned, 54Gy to the involved nodal areas. Neck dissection was ultimately omitted in all cases due to complete response. All patients were treated with a 3 field approach with sequential boost plans. Composite plans were generated retrospectively and primary tumor and lymph node GTVs were contoured and nodes were expanded by 5mm to form a CTV. Mean dose, dose to 95% (D95) and dose to 99% (D99) were determined., Results: Fifty patients treated from 2008 to 2010 with 113 involved nodes were identified. The median age was 57years, and 6%, 46%, and 48% were current, former, and never smokers. Ninety percent of patients received concurrent cisplatin based chemotherapy. Median D95 and D99 to involved nodes were 59.8Gy and 55.9Gy respectively. At a median follow up of 54.1months, two patients developed nodal failure and four developed metastatic disease. Five year loco-regional control, disease free survival and overall survival were 96%, 81% and 86% respectively., Conclusion: In this exploratory analysis, regional lymph node control in HPV positive oropharyngeal cancer was not compromised by dose de-escalated radiotherapy to involved nodes in the setting of concurrent cisplatin based chemotherapy., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Introduction: To examine regional nodal failure patterns with respect to lesion size in medically inoperable early-stage non-small cell lung cancer (NSCLC) patients treated with definitive lung stereotactic body radiation therapy (SBRT)., Methods: Between 2004 and 2012, 342 medically inoperable early-stage NSCLC patients treated with definitive SBRT were identified in our institutional review board-approved prospective registry. All patients were treated on a Novalis/BrainLAB system using ExacTrac for image guidance. Kaplan-Meier analysis was performed with the log-rank test used to detect differences between lesion size and nodal failure patterns. Cox-proportional hazard regression analysis was performed to identify predictors of nodal failure., Results: Median follow-up was 17.6 months (range, 0-84 months). Median tumor size, positron emission tomography maximum standardized uptake value, and dose/fractionation were 2.2 cm (range, 0.8-7.2 cm), 6.7 (range, 1-59), and 50 Gray (Gy)/five fractions, respectively. Of the 342 lesions evaluated, 14.6% (50 of 342) experienced nodal failure. Nodal failure rates were 17.45% (26 of 149), 10.3% (11 of 107), 14.1% (10 of 71), and 20% (3 of 15) for lesions less than or equal to 2 cm, 2.1 to 3 cm, 3.1 to 5 cm, and greater than 5 cm, respectively. Rates of nodal failure were not significantly different between the four different size groups (p = 0.15). On univariate analysis, 2.1 to 3 cm lesions versus less than or equal to 2 cm exhibited less nodal failure after SBRT (hazard ratio = 0.406; 95% confidence interval = 0.189-0.87; p = 0.0205). No other patient, tumor, or treatment factor significantly affected nodal failure., Conclusion: For early-stage NSCLC treated with SBRT, tumor size does not influence the rates of regional nodal failure. This finding warrants further investigation on the possible mechanisms of SBRT by which loco-regional control is improved.

Purpose: To report on medically inoperable stage I small cell lung cancer (SCLC) patients for whom stereotactic body radiation therapy (SBRT) was employed to manage the primary tumor., Methods and Materials: Review of our institutional review board approved SBRT registry revealed 6 cases of stage I SCLC out of 430 patients over a 6-year interval (2004-2010). All patients had biopsy proven disease and deemed medically inoperable by a thoracic surgeon. Our institutional approach was to treat with a combination of SBRT, platinum-etoposide chemotherapy (CHT) and prophylactic cranial irradiation (PCI). SBRT was delivered using a Novalis/BrainLAB platform and ExacTrac (BrainLab, Westchester, IL) for image guidance., Results: Patient characteristics included a median Karnofsky performance scale of 80, a median age of 68 years, 4 females, and 1 patient still smoking at presentation. Impaired pulmonary function caused inoperability in 50% of cases. Tumor characteristics included median tumor size of 2.6 cm and median positron emission tomography-standard uptake valuemax of 9. The SBRT was 60 Gy/3 fractions (3 patients), 50 Gy/5 fractions (2 patients), 30 Gy/1 fraction (1 patient). Median follow-up was 11.9 months. There was no grade 3 or higher, and 1 grade 2, toxicity. Three patients were alive at analysis and 3 patients had died of non-cancer causes. At 1 year, local control was 100%, there was no regional nodal failure, and 1 patient had distant failure (liver). Overall and disease-free survivals at 1 year were 63% and 75%, respectively., Conclusions: Employing SBRT for stage I medically inoperable SCLC is rational, with excellent local control and encouraging disease-specific survival. The absence of regional nodal failure supports positron emission tomography for mediastinal staging. Platinum-based CHT may be feasible in vulnerable populations., (Copyright © 2013 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved.)

Leukocyte-derived microparticles (MPs) are markers of cardiovascular diseases and contribute to pathogenesis by their interaction with various cell types. The presence and activation state of a multifunctional leukocyte receptor, integrin alpha(M)beta(2) (CD11b/18), on MPs derived from human neutrophils (PMNs) were examined. alpha(M)beta(2) expression was significantly enhanced on MPs derived from stimulated compared with resting PMNs. Furthermore, alpha(M)beta(2) on MPs from stimulated but not resting PMNs was in an activated conformation because it was capable of binding activation-specific monoclonal antibodies (CBRM1/5 and mAb24) and soluble fibrinogen. MPs expressing active alpha(M)beta(2) interacted with and were potent activators of resting platelets as assessed by induction of P-selectin expression and activation of alpha(IIb)beta(3). With the use of function-blocking antibodies and MPs obtained from alpha(M)(-/-)-deficient mice, we found that engagement of GPIbalpha on platelets by alpha(M)beta(2) on MPs plays a pivotal role in MP binding. Platelet activation by MPs occurs by a pathway dependent on Akt phosphorylation. PSGL-1/P-selectin interaction also is involved in the conjugation of MPs to platelets, and the combination of blocking reagents to both alpha(M)beta(2)/GPIbalpha and to PSGL-1/P-selectin completely abrogates MP-induced platelet activation. Thus, cooperation of these 2 receptor/counterreceptor systems regulates the prothrombotic properties of PMN-derived MPs.