Stroke death in patients receiving radiation for head and neck cancer in the modern era.

Objectives: Head and neck cancer is a common malignancy frequently treated with chemotherapy and radiotherapy. Studies have shown an increased risk of stroke with the receipt of radiotherapy, but data on stroke-related mortality are limited, particularly in the modern era. Evaluating stroke mortality related to radiotherapy is vital given the curative nature of head and neck cancer treatment and the need to understand the risk of severe stroke in this population. Methods: We analyzed the risk of stroke death among 122,362 patients (83,651 patients who received radiation and 38,711 patients who did not) with squamous cell carcinoma of the head and neck (HNSCC) diagnosed between 1973 and 2015 in the SEER database. Patients in radiation vs. no radiation groups were matched using propensity scores. Our primary hypothesis was that radiotherapy would increase the hazard of death from stroke. We also examined other factors impacting the hazard of stroke death, including whether radiotherapy was performed during the modern era when IMRT and modern stroke care were available as well as increased HPV-mediated cancers of the head and neck. We hypothesized that the hazard of stroke death would be less in the modern era. Results: There was an increased hazard of stroke-related death in the group receiving radiation therapy (HR 1.203, p = 0.006); however, this was a very small absolute increase, and the cumulative incidence function of stroke death was significantly reduced in the modern era (p < 0.001), cohorts with chemotherapy (p=0.003), males (p=0.002), younger cohorts (p<0.001) and subsites other than nasopharynx (p=0.025). Conclusions: While radiotherapy for head and neck cancer increases the hazard of stroke death, this is reduced in the modern era and remains a very small absolute risk.

Early-Stage Primary Lung Neuroendocrine Tumors Treated With Stereotactic Body Radiation Therapy: A Multi-Institution Experience.

PURPOSE: Current guidelines recommend surgery as standard of care for primary lung neuroendocrine tumor (LNET). Given that LNET is a rare clinical entity, there is a lack of literature regarding treatment of LNET with stereotactic body radiation therapy (SBRT). We hypothesized that SBRT could lead to effective locoregional tumor control and long-term outcomes. METHODS AND MATERIALS: We retrospectively reviewed 48 tumors in 46 patients from 11 institutions with a histologically confirmed diagnosis of LNET, treated with primary radiation therapy. Data were collected for patients treated nonoperatively with primary radiation therapy between 2006 and 2020. Patient records were reviewed for lesion characteristics and clinical risk factors. Kaplan-Meier analysis, log-rank tests, and Cox multivariate models were used to compare outcomes. RESULTS: Median age at treatment was 71 years and mean tumor size was 2 cm. Thirty-two lesions were typical carcinoid histology, 7 were atypical, and 9 were indeterminate. The most common SBRT fractionation schedule was 50 to 60 Gy in 5 daily fractions. Overall survival at 3, 6, and 9 years was 64%, 43%, and 26%, respectively. Progression-free survival at 3, 6, and 9 years was 88%, 78%, and 78%, respectively. Local control at 3, 6, and 9 years was 97%, 91%, and 91%, respectively. There was 1 regional recurrence in a paraesophageal lymph node. No grade 3 or higher toxicity was identified. CONCLUSIONS: This is the largest series evaluating outcomes in patients with LNET treated with SBRT. This treatment is well tolerated, provides excellent locoregional control, and should be offered as an alternative to surgical resection for patients with early-stage LNET, particularly those who may not be ideal surgical candidates.

Patterns of recurrence after intracranial stereotactic radiosurgery for brain-only metastases from non-small cell lung cancer and the impact of upfront thoracic therapy with synchronous presentation.

Background: We characterized long-term organ-specific patterns of recurrence, time to progression (TTP) and overall survival (OS) in patients with non-small cell lung cancer (NSCLC) with brain-only metastases treated with single-fraction stereotactic radiosurgery (SRS) and analyzed the impact of upfront thoracic therapy (UTT) in those with synchronous presentation of primary NSCLC and brain metastases. Methods: The clinical records of 137 patients with brain metastases from NSCLC treated with intracranial SRS, and no other metastatic sites, were retrospectively reviewed. Patients with available follow-up imaging (n=124) were analyzed for patterns of recurrence; all were analyzed for OS. Results: The majority of first distant recurrences were in brain and thoracic sites, while extra-thoracic sites were relatively uncommon. After median follow-up of 16.0 months, 24.8% did not develop recurrence outside of brain and/or thoracic sites and 43.5% were free of distant extracranial recurrence. Whole brain radiotherapy (WBRT) and UTT, but not systemic therapy, altered patterns of recurrence and intracranial or extracranial TTP. Multivariable analysis revealed UTT, but not systemic therapy or WBRT, was associated with more favorable OS [hazard ratio (HR) 0.515, P=0.029] among 88 patients with synchronous presentation. Within the subgroup of thoracic stage III patients (n=69), those treated with UTT experienced remarkable median extracranial TTP and OS of 19.3 and 22.7 months, respectively. Conclusions: First and cumulative recurrences in patients treated with intracranial SRS for NSCLC metastases limited to brain are most often in the brain and thorax. Long-term survival is possible, regardless of thoracic stage, and is dependent on UTT among other factors.

Oligoprogression in non-small cell lung cancer: a narrative review.

Background and Objective: Non-small cell lung cancer (NSCLC) accounts for 80% of lung cancers and is the most common non-cutaneous cancer world-wide. In NSCLC, oligometastatic and oligoprogressive disease (OPD) have been recognized as separate entities within the realm of metastatic disease and are emerging concepts in the context of targeted systemic therapies. Our objectives are to discuss the current literature regarding the evolving definitions of OPD in the context of oligometastatic disease (OMD) for NSCLC. Further, to discuss current and future clinical trials that have shaped our local approach with stereotactic body radiation therapy (SBRT)/stereotactic ablative radiotherapy (SABR). Methods: Literature on OPD in NSCLC and local ablative therapy (LAT) including SBRT/SABR and stereotactic radiosurgery (SRS) was reviewed. Key Content and Findings: Oligoprogression is defined as limited (usually 3-5) metastatic areas progressing while on/off systemic therapy in the background of oligometastatic or polymetastatic disease. Prognosis in OPD with treatment (such as LAT and systemic therapy) may be more favorable. Outcomes for patients progressing on tyrosine kinase inhibitors (TKIs) with molecular mutations [such as epidermal growth factor receptor (EGFR), anaplastic lymphoma kinase (ALK)] who receive LAT are promising. Conclusions: Patients presenting with NSCLC metastasis with progression at a limited number of sites on/off a given line of systemic therapy may have favorable outcomes with aggressive LAT, which includes SBRT/SABR/SRS. Further studies need to be completed to further optimize treatment recommendations.

Squamous cell carcinoma of the head and neck with unknown primary: trends and outcomes from a hospital-based registry.

BACKGROUND: Squamous cell carcinoma of unknown primary of the head and neck region is a known entity described mainly by retrospective reports. We searched a hospital-based registry to better describe the changing incidence, and to assess diagnostic and treatment strategies. METHODS: The National Comprehensive Cancer Database was queried for head and neck cancers from oropharynx, tonsil, tongue, larynx, hypopharynx primary sites with a designation of clinical T0, representing an unknown primary. Kaplan Meier, Cox multivariate models, and propensity matched cohorts were used to assess significant factors for overall survival. RESULTS: There were 964 cases that met the criteria, and 468 cases with known treatments, staging, and survival data. The incidence increased over time, with the highest rates supported in the last 5 years. In patients who underwent HPV testing, 72% were positive. Patients with AJCC 7th clinical N2c or N3 disease had significantly worse outcomes despite the majority receiving neck dissection, radiation, and chemotherapy. Local surgery, compared to incisional or excisional biopsy, had the highest diagnostic yield of finding a primary tumor. In multivariate models, no combination of surgical approach, radiation, or systemic therapy was significantly associated with improved survival. This remained true in 1:1 propensity matched cohorts for age, comorbidities, and clinical nodal burden. In a subset of cN1 patients, combined chemoradiation therapy after excisional biopsy or local surgery was associated with (not statistically significant) improved survival compared to radiation alone (P=0.054). CONCLUSIONS: The incidence of unknown primary head and neck carcinoma is increasing, and current cases have a high proportion of HPV positivity. HPV positivity predicts strongly for a tonsil primary. Local surgery was associated with the highest diagnostic yield. Clinical nodal burden strongly predicts for overall outcome, and type of treatment facility is an important driver of survival. A subset of cN1 patients may benefit from the addition of chemotherapy to radiation.

Second Primary Non-Small-Cell Lung Cancer After Head and Neck Cancer: A Population-Based Study of Clinical and Pathologic Characteristics and Survival Outcomes in 3597 Patients.

INTRODUCTION: Retrospective studies have shown an increased risk of second primary lung cancer in patients with a history of head and neck cancer (HNC). No population-based study has examined the overall survival (OS) outcomes of patients with second primary non-small-cell lung cancer (NSCLC) after HNC comparison with patients with first primary NSCLC. PATIENTS AND METHODS: Individuals with histologically confirmed NSCLC diagnosed after nonmetastatic squamous-cell carcinoma of the head and neck (HNC-NSCLC; n = 3597) were identified in Surveillance, Epidemiology, and End Results 18 registries (1988-2013). OS and baseline characteristics were compared in patients with first primary NSCLC (NSCLC-1; n = 365,551) in the same registries. RESULTS: Squamous NSCLC was more common in HNC-NSCLC (n = 745 [64.1%] localized, n = 833 [71.9%] regional, and n = 811 [63.5%] distant) than in the NSCLC-1 (n = 30,901 [38.3%] localized, n = 50,557 [48.2%] regional, and n = 53,720 [29.8%] distant; P < .001). The leading cause of death in HNC-NSCLC was NSCLC (n = 2183; 60.6%), and median OS after localized, regional, and distant NSCLC diagnosis was 2.50 years, 1.17 years, and 5 months, respectively. For NSCLC-1, median OS was 4.58 years, 1.58 years, and 6 months, respectively. These differences were significant (P < .001). In multivariable analysis, a history of HNC remained associated with worse OS for localized (hazard ratio [HR], 1.40; 95% confidence interval [CI], 1.29-1.51; P < .001), regional (HR, 1.26; 95% CI, 1.19-1.35; P < .001) and distant (HR, 1.11; 95% CI, 1.04-1.18; P < .01) stage NSCLC. CONCLUSION: A history of HNC adversely affects OS in patients who subsequently develop NSCLC. This OS decrement might have implications for NSCLC surveillance and NSCLC therapy selection in this population.

Stereotactic body radiotherapy in patients with multiple lung tumors: a focus on lung dosimetric constraints.

Introduction: Lung dosimetric constraints with stereotactic body/ablative radiotherapy (SBRT/SABR) for multiple lung lesions are not well-characterized in published literature. Classically, the lung is considered a 'parallel' organ, for which injury to functional subunits could result in partially compromised function of that organ/tissue. Therefore, with SBRT/SABR for >1 thoracic target (especially involving both lungs), lung dosimetry requires special consideration.Areas covered: Current cooperative group and multi-institutional studies of SBRT/SABR for oligometastases rely on lung constraints from expert opinion, including constraints of exposure (i.e., volume of lung receiving more than a threshold dose or mean lung dose) and/or critical volume (i.e. volume of lung receiving less than a threshold dose; also termed complementary volume). For radiation pneumonitis, which reflects inflammatory lung injury, it remains unclear which type of constraint is more predictive of toxicity risks.Expert opinion: With SBRT/SABR for multiple lung lesions, it is prudent to use both exposure and critical volume constraints. Treatment on alternate days (for radiation plans with separate treatment fields) or staging treatment may also lower lung toxicity risks. Further study on lung normal tissue complication probability in the setting of multiple lung targets is urgently needed, particularly analyses of critical volume metrics, which are relatively poorly studied.

Hypofractionated Stereotactic Radiotherapy for Non-breast or Prostate Cancer Oligometastases: A Tail of Survival Beyond 10 Years.

Purpose and Objective(s): We sought to analyze the long-term follow-up of patients treated with hypofractionated, stereotactic radiotherapy (HSRT) for oligometastases from malignancies other than breast or prostate cancer. Materials and Methods: From 2001 to 2006, 82 cancer patients with 1-5 radiographically apparent metastatic lesions (in 1-3 organs) from primary sites other than breast or prostate cancer, were enrolled on a prospective study of HSRT. Freedom from widespread metastasis (FFWM) was defined from date of enrollment until death, an event (i.e., widespread distant metastasis not amenable to local therapy), or last radiographic study. Local recurrence was scored as an event if pathologically confirmed or if a treated lesion increased by ≥20% using RECIST criteria. Prognostic variables were assessed using Cox regression analysis. Results: The mean age was 61 ± 11 years, with a male to female ratio of 46:36. The most common metastatic sites were liver (50%), lung (48%), thoracic lymph nodes (18%), and bone (5%). Sixty-one patients (74%) had 1 involved organ and 18 (22%) had 1 lesion treated. The preferred dose-fractionation scheduled was 50 Gy in 10 fractions (52 patients). The median follow-up was 1.7 years. Eleven patients lived >5 years, and 6 lived >10 years. The 5-year OS, PFS, FFWM, and LC rates were 13.4, 7.3, 18.3, and 63.4%, and the 10-years OS, PFS, FFWM, and patient LC rates were 7.3, 6.1, 13.4, and 62.2%, respectively. A greater net gross tumor volume (GTV) was significantly adverse for OS (p < 0.01) and LC (p < 0.01). For FFWM, net GTV was not a significant factor (p = 0.14). Four patients remain alive at >13 years from enrollment and treatment, without evidence of active disease. Conclusion: A small subset of select non-breast, non-prostate cancer patients with limited metastasis treated with HSRT are long-term survivors. Net GTV is a significant factor for tumor control and survival. Further research is needed to help better select patients most likely to benefit from local therapy for metastatic disease.

Comparison of Single- and Five-fraction Regimens of Stereotactic Body Radiation Therapy for Peripheral Early-stage Non-small-cell Lung Cancer: A Two-institution Propensity-matched Analysis.

PURPOSE: To evaluate differences in local control (LC), disease-specific (DC), and overall survival (OS) of patients with early-stage non-small-cell lung cancer (NSCLC) treated with single- (SF) versus 5-fraction (FF) stereotactic body radiation therapy (SBRT) at 2 institutions. PATIENTS AND METHODS: Peripheral early-stage NSCLC cases treated with a median dose of 30 Gy in SF or a median dose of 50 Gy in FF were included per institutional practice. Kaplan-Meier and Cox models were used to assess survival. A matched-pair analysis was performed to account for imbalances. Toxicities including Common Terminology Criteria for Adverse Events (CTCAE) grade 3 pneumonitis, chest wall pain requiring long-acting narcotics, and hospitalization for respiratory events 6 months posttreatment were recorded. RESULTS: A total of 163 lesions were treated between 2007 and 2015; 65 received SF SBRT and 98 received FF SBRT. Most tumors were T1 (n = 92) and T2 (n = 34) lesions and had adenocarcinoma (n = 77) and squamous cell carcinoma (n = 46) histologies, respectively. In the matched cohort, there were no differences in OS, LC, DC, or progression-free survival between the groups. LC and OS at 1 year in the matched cohort was 95% and 88%, and 87% and 84% in the SF and FF cohorts, respectively. There was 1 grade 3 pneumonitis in the FF group, and 9 total hospitalizations post-SBRT, 3 (5%) in the SF group and 6 (6%) in the FF group. CONCLUSIONS: No statistically significant differences were seen in LC or DC following SF or FF SBRT in this matched cohort of peripheral lesions. No grade 4 or higher toxicities were reported.

Stereotactic Body Radiotherapy for Lung Metastases from Colorectal Cancer: Prognostic Factors for Disease Control and Survival.

OBJECTIVES: To evaluate disease control and survival after stereotactic body radiotherapy (SBRT) for lung metastases from colorectal cancer and to identify prognostic factors after treatment. METHODS: Patients with metastatic colorectal cancer to the lungs treated with SBRT from 2002 to 2013 were identified from a prospectively maintained database. Patients may have received prior systemic therapy, radiotherapy to nonthoracic sites and/or resection of thoracic and/or nonthoracic metastases. Endpoints were timed from end of SBRT and included overall survival (OS), progression-free survival, distant metastases-free survival, and local failure-free survival. Univariate and multivariate analysis using Cox proportional hazard modeling was used to identify prognostic factors. RESULTS: Sixty-five patients were identified. Before SBRT, 69.2% and 33.8% of patients received systemic therapy and lung-directed local therapy, respectively, for metastatic disease. At the time of SBRT, 64.6% had lung-only involvement. Median survivals were: OS of 20.3 months (95% confidence intervals [CI], 15.9-27.0 mo), progression-free survival of 5.7 months (95% CI, 3.2-7.0 mo), distant metastases-free survival of 5.8 months (95% CI, 3.2-7.6 mo), and local failure-free survival of 15.4 months (95% CI, 8.5-21.1 mo). Nearly all (98%) patients developed distant progression. Extra lung and liver involvement at the time of initial metastases (hazard ratios [HR] 2.10) and extra lung involvement at SBRT (HR 2.67) were the only independent predictors of OS. Net gross target volume of >14.1 mL (HR 2.49) was the only independent predictor of local failure-free survival. CONCLUSIONS: Reasonable survival and local control can be achieved with SBRT. We identified several prognostic factors testable in future prospective trials that may help improve patient selection.

Three- Versus Five-Fraction Regimens of Stereotactic Body Radiotherapy for Peripheral Early-Stage Non-Small-Cell Lung Cancer: A Two-Institution Propensity Score-Matched Analysis.

PURPOSE: To evaluate differences in outcomes of early-stage peripheral non-small-cell lung cancer (NSCLC) treated with either 3- or 5-fraction stereotactic body radiotherapy (SBRT) at 2 institutions. PATIENTS AND METHODS: Patients diagnosed with peripherally located early-stage NSCLC who received either a median dose of 60 Gy (interquartile range [IQR], 60-60, biologically effective dose, 151-151) in 3 fractions or a median dose of 50 Gy (IQR, 50-50, biologically effective dose, 94-94) in 5 fractions were included in this study. All data were retrospectively collected and reviewed in an institutional review board-approved database. RESULTS: A total of 192 lesions in 192 patients were identified: 94 received 3-fraction SBRT and 98 received 5-fraction SBRT. Patients in the 5-fraction cohort had significantly smaller tumors (P = .0021). Larger tumor size was associated with worse overall survival (hazard ratio, 1.40, P = .0013) for all patients. A single grade 3 toxicity was reported in each cohort. A propensity score-matched cohort of 94 patients was constructed with a median follow-up of 29.3 months (IQR, 17.3-44.6) for the 3-fraction cohort and 31.0 months (IQR, 17.0-48.5) for the 5-fraction cohort (P = .84). There were no statistically significant differences between these 2 cohorts in overall survival (P = .33), progression-free survival (P = .40), local failure (P = .86), and nodal or distant failure (P = .57) at 2 years. CONCLUSION: The 3- and 5-fraction SBRT regimens for early-stage peripheral NSCLC had comparable clinical outcomes. Both regimens were well tolerated. A large tumor size was an adverse prognostic factor for worse survival.

Radiotherapy for Oligometastatic Lung Cancer.

Non-small cell lung cancer (NSCLC) typically presents at an advanced stage, which is often felt to be incurable, and such patients are usually treated with a palliative approach. Accumulating retrospective and prospective clinical evidence, including a recently completed randomized trial, support the existence of an oligometastatic disease state wherein select individuals with advanced NSCLC may experience historically unprecedented prolonged survival with aggressive local treatments, consisting of radiotherapy and/or surgery, to limited sites of metastatic disease. This is reflected in the most recent AJCC staging subcategorizing metastatic disease into intra-thoracic (M1a), a single extra thoracic site (M1b), and more diffuse metastases (M1c). In the field of radiation oncology, recent technological advances have allowed for the delivery of very high, potentially ablative, doses of radiotherapy to both intra- and extra-cranial disease sites, referred to as stereotactic radiosurgery and stereotactic body radiotherapy (or SABR), in much shorter time periods compared to conventional radiation and with minimal associated toxicity. At the same time, significant improvements in systemic therapy, including platinum-based doublet chemotherapy, molecular agents targeting oncogene-addicted NSCLC, and immunotherapy in the form of checkpoint inhibitors, have led to improved control of micro-metastatic disease and extended survival sparking newfound interest in combining these agents with ablative local therapies to provide additive, and in the case of radiation and immunotherapy, potentially synergistic, effects in order to further improve progression-free and overall survival. Currently, despite the tantalizing potential associated with aggressive local therapy in the setting of oligometastatic NSCLC, well-designed prospective randomized controlled trials sufficiently powered to detect and measure the possible added benefit afforded by this approach are desperately needed.

The evolving role of radiotherapy in treatment of oligometastatic NSCLC.

Non-small cell lung cancer (NSCLC) patients with metastases limited in site and number, termed oligometastases, may represent a unique subpopulation of advanced NSCLC with improved prognosis. The optimal management of these patients remains unclear with the treatment approach currently undergoing a paradigm shift. The potential benefit of aggressive metastasis directed local treatment with surgery and/or radiotherapy (RT) in combination with systemic therapy is bolstered predominantly by retrospective analyses but also by a growing number of non-randomized prospective studies regarding the use of ablative RT techniques including stereotactic body radiotherapy (SBRT), alternatively termed stereotactic ablative radiotherapy (SABR), directed at the primary tumor (if present) and all metastatic sites. Long-term survival is possible in a subset of patients treated aggressively in this manner. The challenge for the clinical oncology community moving forward is appropriately selecting patients for this treatment approach based on clinical, imaging, and molecular features and increasing enrollment of patients to prospective clinical trials to more definitively determine the added benefit and appropriate timing of aggressive metastasis directed therapy in the oligometastatic setting.

Is there a subset of patients with recurrent cancer in the vagina who are not candidates for interstitial brachytherapy that can be treated with multichannel vaginal brachytherapy using graphic optimization?

PURPOSE: To evaluate recurrent vaginal cancer treated with vaginal brachytherapy (VBT) using graphic optimization in patients not amenable to surgery and interstitial brachytherapy (ISBT). MATERIAL AND METHODS: We retrospectively reviewed the records of 5 patients with recurrent cancer in the vagina that were deemed not to be good candidates for ISBT implant because of medical reasons. All patients received computed tomography/magnetic resonance imaging (CT/MRI) based evaluation in addition to a detailed clinical examination, and were noted to have recurrent nodules in the vagina with size ranging from 10-25 mm. Four of the 5 patients had recurrent disease in the vaginal apex, whereas one patient had recurrence in the lateral vaginal wall. Subsequently, all patients were treated with external beam radiation therapy (EBRT) followed by multichannel vaginal cylinder (MVC)-based VBT using graphic optimization for shaping the isodose to improve the clinical target volume (CTV) coverage, as well as to spare the organs at risk (OAR). The dose to the bladder and rectum with regard to 0.1 cc, 1 cc, and 2 cc were recorded. RESULTS: Median age of the patients was 78 years (range 58-86 years). Thickness of the lesions before VBT ranged from 6-15 mm. All patients were followed up with MRI at 3 months. All patients but one demonstrated complete clinical/ radiological response of the tumor. No patient had any grade III/IV toxicity at 24 months. CONCLUSIONS: MVC-based VBT using graphic optimization is safe and yields favorable results if used judiciously.

Definitive radiotherapy for stage I nonsmall cell lung cancer: a population-based study of survival.

BACKGROUND: The current study characterizes the overall survival (OS) and cause-specific survival (CSS) of patients with stage I nonsmall cell lung cancer (NSCLC) who were treated with radiotherapy alone, and analyzes the variables potentially affecting survival outcomes. METHODS: A total of 8524 patients with stage I NSCLC (according to the sixth edition of the American Joint Committee on Cancer staging manual) who were diagnosed between 1988 and 2008 were retrospectively analyzed using the population-based Surveillance, Epidemiology, and End Results database. Cox regression analysis was used to calculate hazard ratios (HR) from multivariate analyses. RESULTS: The 1-year, 2-year, and 5-year OS rates were 62%, 37%, and 11%, respectively; the corresponding lung cancer CSS survival rates were 68%, 45%, and 20%, respectively. Approximately 77% of deaths were from lung cancer (5292 of 6891 total deaths). Cardiac (n = 477 deaths) and pulmonary (other than lung cancer deaths; n = 475 deaths) deaths accounted for 14% of deaths. From Cox proportional hazards analyses, male sex (HR, 1.2) and squamous cell carcinoma histology (HR, > 1.1) were found to be significantly (P < .0001) adverse prognostic factors for both OS and lung cancer CSS. A more recent calendar year of diagnosis was associated with significantly (P < .0001) improved OS (HR, 0.84 per decade) and lung cancer CSS. This trend was also significant (P < 0.0001) when restricting analyses to those patients with tumors measuring ≤ 5 cm (n = 5402 patients). T1 classification (vs T2 or T unknown) and smaller tumor size were found to be significantly (P < .0001) favorable factors. CONCLUSIONS: From a population-based registry analysis of patients with stage I NSCLC, significant (albeit modest) improvements in survival in more recent years were appreciated, which likely reflect technologic advances in the diagnosis of, staging of, and radiotherapy for NSCLC.

Second primary lung cancer after head and neck squamous cell cancer: population-based study of risk factors.

BACKGROUND: Patients with head and neck squamous cell cancer (HNSCC) are at risk of developing second primary lung cancer (SPLC). METHODS: Among 61,883 patients with HNSCC from the Surveillance, Epidemiology and End Results (SEER) database, 4522 developed SPLC (any histology) ≥2 months after HNSCC. We correlated risk with demographic and tumor-related parameters. RESULTS: The risk of SPLC after HNSCC was 5.8%, 11.4%, and 16.4% at 5, 10, and 15 years, respectively. From Cox regression, significantly adverse (p < .0001) risk factors for SPLC included: regional versus localized HNSCC stage (hazard ratio [HR] = 1.16), hypopharyngeal or supraglottic laryngeal site (HR = 1.57), increased age (HR = 1.26/decade), black race (HR = 1.27), and male sex (HR = 1.26). Glottic (HR = 0.75) and tonsillar or oral cavity sites (HR = 0.80) were associated with significantly (p < .0001) lower risks of SPLC. CONCLUSION: From population-based actuarial analyses, HNSCCs with more aggressive clinicopathologic features were more apt to develop SPLC, suggestive of similar environmental and/or host factors for these cancers.

Thoracic malignant solitary fibrous tumors: A population-based study of survival.

INTRODUCTION: This study characterizes the overall survival (OS) and cause specific survival (CSS) of patients with thoracic malignant solitary fibrous tumors. METHODS: Eighty-two patients with malignant solitary fibrous tumors of the lung, pleura or mediastinum, diagnosed from 2001-2007, were retrospectively analyzed using the population-based Surveillance, Epidemiology, and End Results database. RESULTS: Among 77 patients with available staging information, 42% (n=32) had localized disease, 31% (n=24) had regional disease extension (without nodal involvement) and 27% had regional-nodal (n=2) or distant (n=19) metastases. Cancer-directed surgery was performed in 85%; radiation was performed in 16%. The 1-year, 5-year and median OS were 87%, 49% and 4.6 years respectively. The 1-year, 5-year and median CSS were 89%, 61% and 5.7 years respectively. Less advanced stage and undergoing cancer-directed surgery were favorable prognostic factors. For localized, regional and distant stage the median OS was: not reached at 6.3 years, 4.4 years and 2.0 years respectively (P=0.021); the median CSS was not reached at 6.3 years, 5.0 years and 2.4 years (P=0.068). For patients undergoing versus not undergoing surgery, the median OS was 4.9 vs 0.9 years (P=0.053) and median CSS was 5.7 vs 0.9 years (P=0.011). Tumor size was not significant. CONCLUSIONS: From a population-based analysis of patients with thoracic malignant solitary fibrous tumors, stage and cancer-directed surgery had the greatest impact on OS and CSS. While being amenable to surgery likely reflects more indolent disease and/or better performance status and cardiopulmonary function, the significantly favorable impact of surgery also likely reflects a therapeutic benefit.

Low-dose radiosurgery for benign intracranial lesions.

This study assesses the efficacy and neurotoxicity of radiosurgical treatment of benign intracranial tumors using a linear accelerator, with relatively low dose and homogeneous dosimetry. Between June 1998 and July 2000, 27 patients were treated for benign lesions with radiosurgery using a 6-MV linear accelerator-based X-knife system and circular collimators. The lesions included schwannoma, meningioma, papillary cyst adenoma, and hemangioblastoma. Five patients had tissue diagnosis. The mean peripheral dose to the tumor margin was 12.8 Gy. The mean dose to the isocenter was 16.3 Gy. One to five isocenters were used to treat these lesions, with a mean of 10 arcs per isocenter and mean collimator size of 1.25 cm. Follow-up information was available on all patients, with a mean follow-up duration of 33 months. Six patients (22%) had improved symptoms and 21 (78%) had stable symptoms. Eight patients (30%) had regression of tumor and 19 had stable disease (70%). No patient had tumor progression, and Radiation Therapy Oncology Group (RTOG) grade III or IV toxicity did not occur in any patients. In 3 patients (11%), RTOG grade I or grade II neurotoxicity developed. Of these, one patient had worsening of a preexisting VIIth nerve deficit that required temporary oral methylprednisolone, and in two patients a mild trigeminal deficit developed that did not require any medical intervention. Low-dose homogeneous radiosurgery using a linear accelerator is an effective treatment for benign intracranial tumors. If lower, more homogeneous radiation doses produce responses as durable as higher doses, then toxicity might be further reduced.