Allergic Contact Dermatitis Due to Methylisothiazolinone in a Young Girl's Laundry Detergent.

Methylisothiazolinone (MI) is an emerging and increasing cause of allergic contact dermatitis (ACD) in children. We present the case of a 7-year-old girl with an unusual dermatitis suspicious for contact allergy. Patch testing confirmed allergy to MI, found only in the patient's laundry detergent. This case highlights the importance of checking household product ingredients and the role of MI as an increasing cause of ACD in children.

Lung Stereotactic Body Radiation Therapy.

Lung stereotactic body radiation therapy (SBRT) is a novel and effective modality for treatment of early stage non-sail cell lung cancer (NSCLC), with expanding indications in locally advanced and metastatic disease. Herein, we will review current treatment recommendations for early stage NSCLC, detail treatment planning of SBRT, and discuss future directions.

Thermoluminescent dosimeters (TLD-100) for absorbed dose measurements in alpha-emitting radionuclides.

Early works that used thermoluminescent dosimeters (TLDs) to measure absorbed dose from alpha particles reported relatively high variation (10%) between TLDs, which is undesirable for modern dosimetry applications. This work outlines a method to increase precision for absorbed dose measured using TLDs with alpha-emitting radionuclides by applying an alpha-specific chip factor (CF) that individually characterizes the TLD sensitivity to alpha particles. Variation between TLDs was reduced from 21.8% to 6.7% for the standard TLD chips and 7.9% to 3.3% for the thin TLD chips. It has been demonstrated by this work that TLD-100 can be calibrated to precisely measure the absorbed dose to water from alpha-emitting radionuclides.

Elements in muscle tissue of three dolphin species from the east coast of South Africa.

We investigated elemental concentrations in muscle tissue of three species of dolphins incidentally bycaught off the KwaZulu-Natal coastline, South Africa. Thirty-six major, minor and trace elements were analysed in Indian Ocean humpback dolphin Sousa plumbea (n = 36), Indo-Pacific bottlenose dolphin Tursiops aduncus (n = 32) and the Common dolphin Delphinus delphis (n = 8). Significant differences in concentration between the three species were observed for 11 elements (cadmium, iron, manganese, sodium, platinum, antimony, selenium, strontium, uranium, vanadium and zinc). Mercury concentrations (maximum 29 mg/kg dry mass) were generally higher than those reported for coastal dolphin species found elsewhere. Our results reflect a combination of species differences in habitat, feeding ecology, age, and possibly species physiology and exposure to pollution levels. This study confirms the high organic pollutant concentrations documented previously for these species from the same location, and provides a well-founded case for the need to reduce pollutant sources.

A single-institution phase I feasibility study of dose-escalated IMRT for non-operative locally advanced esophageal carcinoma.

BACKGROUND AND PURPOSE: Radiation dose escalation to improve poor outcomes with chemoradiation in locally advanced esophageal carcinoma is limited in part by increased toxicity. This Phase I study investigates the use of IMRT to improve tolerability of dose escalation. MATERIALS AND METHODS: A single-institution, prospective study was conducted between 2007 and 2013 for individuals with inoperable esophageal carcinoma. Gross disease received 60 Gy in 30 fractions and at-risk sites received 54 Gy with simultaneous integrated boost. Concurrent chemotherapy primarily consisted of cisplatin/5-FU. The primary objective was to assess feasibility (<15% rate of grade 4-5 toxicity). Secondary objectives included assessment of overall survival (OS), progression free survival (PFS), and locoregional (LRR) and distant recurrence. RESULTS: Twenty-six patients were enrolled with median follow up of 17.6 months (range 0.1 to 152.0). The majority were AJCC 7th edition Stage III (54%), distal esophagus primary (81%), and adenocarcinoma histology (85%). Twenty-one patients (81%) completed their course of radiation therapy, while only 55% received 2 cycles of concurrent cisplatin/5-FU. One grade 5 and one grade 4 cardiac event occurred, both during chemoradiation and before receiving 50 Gy. The 3-year OS was 48.6% (95% CI: 32.5 to 72.2%) and PFS was 28.5% (95% CI: 14.6 to 55.5%). Half developed distant failure with LRR occurring in 10 patients (38%), isolated in 5 patients. CONCLUSION: While feasibility was demonstrated, toxicity and compliance remained limiting factors with outcomes similar to historical controls. There remains an uncertain role for dose escalation in definitive management of locally advanced esophageal cancer.

Determination of exit skin dose for 192Ir intracavitary accelerated partial breast irradiation with thermoluminescent dosimeters.

PURPOSE: Intracavitary accelerated partial breast irradiation (APBI) has become a popular treatment for early stage breast cancer in recent years due to its shortened course of treatment and simplified treatment planning compared to traditional external beam breast conservation therapy. However, the exit dose to the skin is a major concern and can be a limiting factor for these treatments. Most treatment planning systems (TPSs) currently used for high dose-rate (HDR) 192Ir brachytherapy overestimate the exit skin dose because they assume a homogeneous water medium and do not account for finite patient dimensions. The purpose of this work was to quantify the TPS overestimation of the exit skin dose for a group of patients and several phantom configurations. METHODS: The TPS calculated skin dose for 59 HDR 192Ir APBI patients was compared to the skin dose measured with LiF:Mg,Ti thermoluminescent dosimeters (TLDs). Additionally, the TPS calculated dose was compared to the TLD measured dose and the Monte Carlo (MC) calculated dose for eight phantom configurations. Four of the phantom configurations simulated treatment conditions with no scattering material beyond the point of measurement and the other four configurations simulated the homogeneous scattering conditions assumed by the TPS. Since the calibration TLDs for this work were irradiated with 137Cs and the experimental irradiations were performed with 192Ir, experiments were performed to determine the intrinsic energy dependence of the TLDs. Correction factors that relate the dose at the point of measurement (center of TLD) to the dose at the point of interest (basal skin layer) were also determined and applied for each irradiation geometry. RESULTS: The TLD intrinsic energy dependence for 192Ir relative to 137Cs was 1.041 +/- 1.78%. The TPS overestimated the exit skin dose by an average of 16% for the group of 59 patients studied, and by 9%-15% for the four phantom setups simulating treatment conditions. For the four phantom setups simulating the conditions assumed by the TPS, the TPS calculated dose agreed well with the TLD and MC results (within 3% and 1%, respectively). The inverse square geometry correction factor ranged from 1.023 to 1.042, and an additional correction factor of 0.978 was applied to account for the lack of charged particle equilibrium in the TLD and basal skin layer. CONCLUSIONS: TPS calculations that assume a homogeneous water medium overestimate the exit skin dose for intracavitary APBI treatments. It is important to determine the actual skin dose received during intracavitary APBI to determine the skin dose-response relationship and establish dose limits for optimal skin sparing. This study has demonstrated that TLDs can measure the skin dose with an expanded uncertainty (k = 2) of 5.6% when the proper corrections are applied.

Effects of herbivory by Diaprepes abbreviatus (Coleoptera: Curculionidae) larvae on four woody ornamental plant species.

The hypothesis that herbivory by Diaprepes root weevil larvae reduces leaf gas exchange and biomass was tested on buttonwood (Conocarpus erectus L.), Surinam cherry (Eugenia uniflora L.), mahogany (Swietenia mahagoni Jacq.), and pond apple (Annona glabra L). For Surinam cherry, net CO2 assimilation, transpiration, and stomatal conductance, but not internal CO2 concentration (collectively referred to as leaf gas exchange values), were 7-32% higher in noninfested than infested plants. For buttonwood, all four gas exchange values were 10-54% higher for noninfested than infested plants 3 h after infestation with large, seventh-instar larvae. However, by 4 wk after this infestation, net CO2 assimilation, transpiration, and stomatal conductance, but not internal CO2 concentration, were 11-37% higher for infested than for noninfested plants. For mahogany and pond apple, there were few or no significant differences in leaf gas exchange values between infested and noninfested plants. For all species, mean shoot and root fresh and dry weights were higher for noninfested than infested plants, with the differences most significant for buttonwood (37-85% higher), followed by Surinam cherry (37-143% higher), mahogany (49-84% higher), and pond apple (24-46% higher), which had no significant differences. There were significant differences among plant species in mean head capsule widths, thus larval instars, of larvae recovered from soil with the largest larvae from Surinam cherry (2.59 +/- 0.19 mm) and the smallest from mahogany (2.29 +/- 0.06 mm). Based on differences in leaf gas exchange and plant biomass between infested and noninfested plants of the four species tested, buttonwood and Surinam cherry are the most vulnerable to feeding by Diaprepes larvae followed by mahogany then pond apple.

Anatomical Adaptation-Early Clinical Evidence of Benefit and Future Needs in Lung Cancer.

Definitive treatment of locally advanced non-small-cell lung cancer with radiation is challenging. During the course of treatment, anatomical changes such as tumor regression, tumor displacement/deformation, pleural effusion, and/or atelectasis can result in a deviation of the administered radiation dose from the intended prescribed treatment and thereby worsen local control and toxicity. Adaptive radiotherapy can help correct for these changes and can be generally categorized into 3 philosophical paradigms: (1) maintenance of prescribed dose to the initially defined target volume; (2) dose reduction to healthy organs while maintaining initial prescribed dose to a regressing tumor volume; or (3) dose escalation to a regressing tumor volume with isotoxicity to healthy organs. Numerous single institution studies have investigated these methods, and results from large prospective clinical trials will hopefully provide consensus on the method, utility, and efficacy of implementing adaptive radiation therapy (ART) in a clinical setting. Additional development into standardization and automation of the ART workflow, specifically in identifying when ART is warranted and in reducing the manual clinical effort needed to produce an adaptive plan, will be paramount to making ART feasible for the broader radiation therapy community.

Defining Optimal Comorbidity Measures for Patients With Early-Stage Non-small cell lung cancer Treated With Stereotactic Body Radiation Therapy.

PURPOSE: Comparison of overall survival (OS) between stereotactic body radiation therapy (SBRT) and other treatments for early-stage non-small cell lung cancer is confounded by differences in age, performance status, and medical comorbidity. We sought to define the most robust measurement for this population among 5 indices: age, Eastern Cooperative Oncology Group performance status, Adult Comorbidity Evaluation 27, Charlson Comorbidity Index (CCI), and age-adjusted CCI (CCIa). METHODS AND MATERIALS: A total of 548 patients with stage I non-small cell lung cancer treated with SBRT were analyzed. Patients were divided into high- and low-risk groups for OS for each index using the log-rank test. Continuous and dichotomized models were compared via Akaike information criterion and the Vuong test. Multivariate Cox regression modeling was used with demographic information to determine the independent prognostic value of the continuous and dichotomized versions of the indices. The best was used to stratify the patients into as many significantly different cohorts as possible. RESULTS: Optimal cut-points between high-risk and low-risk OS groups for age, Eastern Cooperative Oncology Group status, Adult Comorbidity Evaluation 27, CCI, and CCIa were ≥75 years, ≥1, ≥3, ≥3, and ≥6 with hazard ratios for death of 1.23 (95% confidence interval, 1.00-1.50), 1.66 (1.28-2.15), 1.37 (1.12-1.67), 1.43 (1.17-1.76), and 1.47 (1.20-1.80), respectively. Dichotomizing did not result in a significant loss of prognostic power. Although there was no significant difference in prognostic power among the indices, CCIa best predicted OS. CCIa divided the patients into 3 cohorts with median OS of 42 months, 33 months, and 23 months for scores of ≤5, 6 to 7, and ≥8, respectively. CONCLUSIONS: CCIa was the best indicator of OS in every model employed with no loss of prognostic power with dichotomization. Dichotomization of CCIa (≥6) could be implemented in future comparisons of SBRT with OS. No cohort could be identified with a median survival of less than a year, for which treatment could be deemed futile.

Dispersion in the Mott insulator UO2: A comparison of photoemission spectroscopy and screened hybrid density functional theory.

We present a comparison between the screened hybrid density functional theory of Heyd, Scuseria, and Enzerhof (HSE06) and high-resolution photoemission (PES) measurement on a single crystal of UO(2). Angle-resolved photoemission data show a slight dispersion in the f-orbital derived bands in good agreement with the HSE band structure. The effect of spin-orbit coupling on the HSE band gap has also been calculated and found to be negligible.

Optimizing radiation dose and fractionation for the definitive treatment of locally advanced non-small cell lung cancer.

Radiation therapy is the foundation for treatment of locally advanced non-small cell lung cancer (NSCLC), a disease that is often inoperable and has limited long term survival. Local control of disease is strongly linked to patient survival and continues to be problematic despite continued attempts at changing the dose and fractionation of radiation delivered. Technological advancements such as 4-dimensional computed tomography (CT) based planning, positron emission tomography (PET) based target delineation, and daily image guidance have allowed for ever more accurate and conformal treatments. A limit to dose escalation with conventional fractions of 2 Gy once per day appears to have been reached at 60 Gy in the randomized trial Radiation Therapy Oncology Group (RTOG) 0617. Higher doses were surprisingly associated with worse overall survival. Approaches other than conventional dose escalation have been explored to better control disease including accelerating treatment to limit tumor repopulation both with hyperfractionation and its multiple small (<2 Gy) fractions each day and with hypofractionation and its single larger (>2 Gy) fraction each day. These accelerated regimens are increasingly being used with concurrent chemotherapy, and multiple institutions have reported it as tolerable. Tailoring treatment to individual patient disease and normal anatomic characteristics has been explored with isotoxic dose escalation up to the tolerance of organs at risk, with both hyperfractionation and hypofractionation. Metabolic imaging during and after treatment is increasingly being used to boost doses to residual disease. Boost doses have included moderate hypofractionation of 2-4 Gy, and more recently extreme hypofractionation with stereotactic body radiation therapy (SBRT). In spite of all these changes in dose and fractionation, lung and cardiovascular toxicity remain obstacles that limit disease control and patient survival.

Experimental investigation of GafChromic® EBT3 intrinsic energy dependence with kilovoltage x rays, 137 Cs, and 60 Co.

PURPOSE: To determine experimentally the intrinsic energy response, kbq , of EBT3 GafChromic® radiochromic film with kilovoltage x rays, 137 Cs, and 60 Co in therapeutic and diagnostic dose ranges through direct measurement with an accompanying mathematical approach to describe the physical processes involved. METHODS: The EBT3 film was irradiated with known doses using 60 Co, 137 Cs, and 13 NIST-matched kilovoltage x-ray beams. Seven dose levels, ranging from 57 to 7002 mGy, were chosen for this work. Monte Carlo methods were used to convert air-kerma rates to dose rates to the film active layer for each energy. A total of 738 film dosimeters, each measuring (1.2 × 1.2) cm2 , were cut from three film sheets out of the same lot of the latest version of EBT3 film, to allow for multiple dosimeters to be irradiated by each target dose and beam quality as well as unirradiated dosimeters to be used as controls. Net change in optical density in excess of the unirradiated controls was measured using the UWMRRC Laser Densitometry System (LDS). The dosimeter intrinsic energy response, kbq , for each dose level was determined relative to 60 Co, as the ratio of dosimeter response to each beam quality relative to the absorbed dose to the film active volume at the same dose level. A simplified, single-hit mathematical model was used to derive a single-free-parameter, ß, which is a proportionality constant that is dependent on beam quality and describes the microdosimetric interactions within the active layer of film. The response of ß for each beam quality relative to 60 Co was also determined. RESULTS: kbq was determined for a wide range of doses and energies. The results show a unique variation of kbq as a function of energy, and agree well with results from other investigations. There was no measurable dose dependence for kbq within the 500-7002 mGy range outside of the expanded measurement uncertainty of 3.65% (k = 2). For doses less than 500 mGy, the signal-to-noise ratio was too low to determine kbq accurately. The single-free-parameter, ß, fit calculations derived from the single-hit model show a correlation with kbq that suggests that ß, at least in part, characterizes the microdosimetric interactions that determine kbq . CONCLUSIONS: For the beam qualities investigated, a single energy-dependent kbq correction can be used for doses between 500 and 7002 mGy. Using the single-hit model with the single-free-parameter fit to solve for ß shows promise in the determination of the intrinsic energy response of film, with ß being the mathematical analog of the measured kbq .

Brain Metastases at Presentation in Patients With Non-Small Cell Lung Cancer.

OBJECTIVE: We used brain radiotherapy as a surrogate for the presence of brain metastases in patients with non-small cell lung cancer (NSCLC) to determine the prevalence of brain metastases using the Surveillance Epidemiology and End Results database. METHODS: Patients with NSCLC diagnosed between 1988 and 1997 were subdivided according to brain radiotherapy status at presentation into: "none" or "radiation therapy indicated." We calculated the frequency of brain radiotherapy use in all patients. Odds ratios (ORs) for the indication of brain radiotherapy were calculated for individual prespecified covariates of interest. All statistical tests were 2-sided and P<0.05 were considered significant. RESULTS: At presentation, brain radiotherapy was indicated in 10,963 (8.3%) of the 131,456 patients diagnosed with NSCLC between 1988 and 1997. On multivariable analysis the following were significantly associated with brain radiotherapy use: age (OR, 0.653 per 10 y increase in age; 95% confidence interval [CI]: 0.642, 0.665); female sex (OR, 1.05; 95% CI: 1.01, 1.10]); adenocarcinoma histology (HR, 1.67; 95% CI: 1.58, 1.76) or large cell or other histology (OR, 1.67; 95% CI: 1.57, 1.77); tumor size>3 cm (3.1 to 5 cm OR, 1.22; 95% CI: 1.14, 1.30 and >5 cm OR, 1.25; 95% CI: 1.17, 1.33); tumor grade >II (grade III OR, 1.82; 95% CI: 1.69, 1.95 and grade IV OR, 1.91; 95% CI: 1.73, 2.11); and nodal involvement N1 (OR, 1.33; 95% CI: 1.20, 1.47), N2 (OR, 2.24; 95% CI: 2.10, 2.40), and N3 (OR, 2.39; 95% CI: 2.19, 2.60). CONCLUSIONS: Brain radiotherapy is indicated in over 8% of patients with NSCLC at presentation. We demonstrated that the risk of brain metastasis at presentation may be stratified with the use of 6 clinical factors.

Functional properties of stellate cells in medial entorhinal cortex layer II.

Layer II of the medial entorhinal cortex (MEC) contains two principal cell types: pyramidal cells and stellate cells. Accumulating evidence suggests that these two cell types have distinct molecular profiles, physiological properties, and connectivity. The observations hint at a fundamental functional difference between the two cell populations but conclusions have been mixed. Here, we used a tTA-based transgenic mouse line to drive expression of ArchT, an optogenetic silencer, specifically in stellate cells. We were able to optogenetically identify stellate cells and characterize their firing properties in freely moving mice. The stellate cell population included cells from a range of functional cell classes. Roughly one in four of the tagged cells were grid cells, suggesting that stellate cells contribute not only to path-integration-based representation of self-location but also have other functions. The data support observations suggesting that grid cells are not the sole determinant of place cell firing.

Non-small-cell Lung Cancer With Brain Metastasis at Presentation.

BACKGROUND: Data on the prevalence of brain metastases at presentation in patients with non-small-cell lung cancer (NSCLC) are limited. We queried the National Cancer Data Base to determine prevalence, clinical risk factors, and outcomes of patients with NSCLC presenting with brain metastases. PATIENTS AND METHODS: Patients with NSCLC diagnosed between 2010 and 2012 were identified using the National Cancer Data Base. The risk of brain metastases for individual variables was summarized by odds ratios and calculated using logistic regression analysis. The Kaplan-Meier product limit method was used to calculate the median and 1-, 2-, and 3-year overall survival (OS). RESULTS: Brain metastases were observed in 47,546 (10.4%) of the 457,481 patients with NSCLC overall. The prevalence of brain metastases was much higher (26%) in patients with stage IV disease at presentation. On multivariate analysis, younger age, adenocarcinoma or large cell histology, tumor size > 3 cm, tumor grade ≥ II, and node-positive disease were associated with brain metastases. The prevalence of brain metastases ranged from as low as 0.57% in patients with only 1 risk factor to as high as 22% in patients with all 5 risk factors. The median and 1-, 2-, and 3-year OS for patients with brain metastases were 6 months and 29.9%, 14.3%, and 8.4%, respectively, with the 3-year OS increasing to 36.2% in those with T1/2 and N0/1 undergoing surgery for the primary site. CONCLUSIONS: In patients with NSCLC, the risk of brain metastases at presentation may be calculated based on 5 clinical variables. Selected patients with brain metastases at presentation may achieve prolonged benefit.

Stereotactic Body Radiation Therapy for Central Early-Stage NSCLC: Results of a Prospective Phase I/II Trial.

INTRODUCTION: We report results from a prospective phase I/II trial for patients with centrally located, early-stage NSCLC receiving stereotactic body radiation therapy. METHODS: Eligible patients were medically inoperable with biopsy-proven NSCLC within 2 cm of the proximal bronchial tree or 5 mm of the mediastinal pleura or parietal pericardium. Phase I had four dose levels using 5 fractions: 9, 10, 11, and 12 Gy per fraction. The primary phase II objective was to determine if the maximum tolerated dose in phase I achieved local control greater than 80% at 2 years. RESULTS: Seventy-four patients were enrolled; 23 to phase I and 51 to phase II. Two phase I patients treated with 10 Gy × 5 fractions developed unrelated acute grade 3 lung toxicities which resolved. The phase II dose level selected was 11 Gy × 5 fractions. The median follow-up for living phase II patients was 27 months (range, 9 to 58 months). Two-year local control using 11 Gy × 5 fractions was 85% (95% confidence interval [CI]: 62%-95%). Two-year overall survival was 43% (95% CI: 28%-57%). Three patients (6%, 95% CI: 1%-17%) experienced acute grade 3 and 4 cardiac or pulmonary toxicities. Of the 41 patients evaluable for late cardiac and pulmonary toxicity, 11 (27%, 95% CI: 14%-43%) developed grade 3, 5 (12%, 95% CI: 4%-26%) developed grade 4, and 1 (4%, 95% CI: 0%-13%) died of grade 5 toxicity. CONCLUSION: Stereotactic body radiation therapy for central NSCLC using 11 Gy × 5 fractions is tolerable and has excellent local control, but is associated severe late toxicity in some patients.

Short delay in initiation of radiotherapy for patients with glioblastoma-effect of concurrent chemotherapy: a secondary analysis from the NRG Oncology/Radiation Therapy Oncology Group database.

Background: We previously reported the unexpected finding of significantly improved survival for newly diagnosed glioblastoma in patients when radiation therapy (RT) was initiated later (>4 wk post-op) compared with earlier (≤2 wk post-op). In that analysis, data were analyzed from 2855 patients from 16 NRG Oncology/Radiotherapy Oncology Group (RTOG) trials conducted prior to the era of concurrent temozolomide (TMZ) with RT. We now report on 1395 newly diagnosed glioblastomas from 2 studies, treated with RT and concurrent TMZ followed by adjuvant TMZ. Our hypothesis was that concurrent TMZ has a synergistic/radiosensitizing mechanism, making RT timing less significant. Methods: Data from patients treated with TMZ-based chemoradiation from NRG Oncology/RTOG 0525 and 0825 were analyzed. An analysis comparable to our prior study was performed to determine whether there was still an impact on survival by delaying RT. Overall survival (OS) was investigated using the Kaplan-Meier method and Cox proportional hazards model. Early progression (during time of diagnosis to 30 days after RT completion) was analyzed using the chi-square test. Results: Given the small number of patients who started RT early following surgery, comparisons were made between >4 and ≤4 weeks delay of radiation from time of operation. There was no statistically significant difference in OS (hazard ratio = 0.93; P = 0.29; 95% CI: 0.80-1.07) after adjusting for known prognostic factors (recursive partitioning analysis and O6-methylguanine-DNA methyltransferase methylation status). Similarly, the rate of early progression did not differ significantly (P = 0.63). Conclusions: We did not observe a significant prognostic influence of delaying radiation when given concurrently with TMZ for newly diagnosed glioblastoma. The effects of early (1-3 wk post-op) or late (>5 wk) initiation of radiation tested in our prior study could not be replicated.

Stereotactic Body Radiation Therapy for Operable Early-Stage Lung Cancer: Findings From the NRG Oncology RTOG 0618 Trial.

Importance: Stereotactic body radiation therapy (SBRT) has become a standard treatment for patients with medically inoperable early-stage lung cancer. However, its effectiveness in patients medically suitable for surgery is unclear. Objective: To evaluate whether noninvasive SBRT delivered on an outpatient basis can safely eradicate lung cancer and cure selected patients with operable lung cancer, obviating the need for surgical resection. Design, Setting, and Participants: Single-arm phase 2 NRG Oncology Radiation Therapy Oncology Group 0618 study enrolled patients from December 2007 to May 2010 with median follow-up of 48.1 months (range, 15.4-73.7 months). The setting was a multicenter North American academic and community practice cancer center consortium. Patients had operable biopsy-proven peripheral T1 to T2, N0, M0 non-small cell tumors no more than 5 cm in diameter, forced expiratory volume in 1 second (FEV1) and diffusing capacity greater than 35% predicted, arterial oxygen tension greater than 60 mm Hg, arterial carbon dioxide tension less than 50 mm Hg, and no severe medical problems. The data analysis was performed in October 2014. Interventions: The SBRT prescription dose was 54 Gy delivered in 3 18-Gy fractions over 1.5 to 2.0 weeks. Main Outcomes and Measures: Primary end point was primary tumor control, with survival, adverse events, and the incidence and outcome of surgical salvage as secondary end points. Results: Of 33 patients accrued, 26 were evaluable (23 T1 and 3 T2 tumors; 15 [58%] male; median age, 72.5 [range, 54-88] years). Median FEV1 and diffusing capacity of the lung for carbon monoxide at enrollment were 72.5% (range, 38%-136%) and 68% (range, 22%-96%) of predicted, respectively. Only 1 patient had a primary tumor recurrence. Involved lobe failure, the other component defining local failure, did not occur in any patient, so the estimated 4-year primary tumor control and local control rate were both 96% (95% CI, 83%-100%). As per protocol guidelines, the single patient with local recurrence underwent salvage lobectomy 1.2 years after SBRT, complicated by a grade 4 cardiac arrhythmia. The 4-year estimates of disease-free and overall survival were 57% (95% CI, 36%-74%) and 56% (95% CI, 35%-73%), respectively. Median overall survival was 55.2 months (95% CI, 37.7 months to not reached). Protocol-specified treatment-related grade 3, 4, and 5 adverse events were reported in 2 (8%; 95% CI, 0.1%-25%), 0, and 0 patients, respectively. Conclusions and Relevance: As given, SBRT appears to be associated with a high rate of primary tumor control, low treatment-related morbidity, and infrequent need for surgical salvage in patients with operable early-stage lung cancer. Trial Registration: ClinicalTrials.gov Identifier: NCT00551369.

The influence of shark liver oils on normal and transformed mammalian cells in culture.

n3 polyunsaturated fatty acids have been reported to have anti-carcinogenic effects on mammalian carcinomas. n3 fatty acids occur in high concentrations in marine oils, especially shark liver oils. Several reports have indicated an extremely low incidence of cancer in sharks, although other reports indicate carcinogenesis in some shark species. It has been hypothesised that n3 fatty acids and other components of shark liver oil may exert anti-carcinogenic effects. The aim of this study was to assess whether shark liver oil, from four Indian Ocean shark species, exerted anti-proliferative effects on transformed and normal mammalian cells in culture, and to assess whether the ratio of n3 to n6 polyunsaturates influenced the results. Neither the shark liver oils themselves, nor the ratio of n3 to n6, showed any consistently significant effects with either transformed or normal cells.

Radiation Treatment Time and Overall Survival in Locally Advanced Non-small Cell Lung Cancer.

PURPOSE: Prolonged radiation treatment (RT) time (RTT) has been associated with worse survival in several malignancies. The present study investigated whether delays during RT are associated with overall survival (OS) in non-small cell lung cancer (NSCLC). METHODS AND MATERIALS: The National Cancer Database was queried for patients with stage III NSCLC who had received definitive concurrent chemotherapy and fractionated RT to standard doses (59.4-70.0 Gy) and fractionation from 2004 to 2013. The RTT was classified as standard or prolonged for each treatment regimen according to the radiation dose and number of fractions. Cox proportional hazards models were used to evaluate the association between the following factors and OS: RTT, RT fractionation, demographic and pathologic factors, and chemotherapeutic agents. RESULTS: Of 14,154 patients, the RTT was prolonged in 6262 (44.2%). Factors associated with prolonged RTT included female sex (odds ratio [OR] 1.21, P<.0001), black race (OR 1.20, P=.001), nonprivate health insurance (OR 1.30, P<.0001), and lower income (<$63,000 annually, OR 1.20, P<.0001). The median OS was significantly worse for patients with prolonged RTT than that for those with standard RTT (18.6 vs 22.7 months, P<.0001). Furthermore, the OS worsened with each cumulative interval of delay (standard RTT vs prolonged 1-2 days, 20.5 months, P=.009; prolonged 3-5 days, 17.9 months, P<.0001; prolonged 6-9 days, 17.7 months, P<.0001; prolonged >9 days, 17.1 months, P<.0001). On multivariable analysis, prolonged RTT was independently associated with inferior OS (hazard ratio 1.21, P<.0001). Prolonged RTT as a continuous variable was also significantly associated with worse OS (hazard ratio 1.001, P=.0007). CONCLUSIONS: Delays during RT appear to negatively affect survival for patients with locally advanced NSCLC. We have detailed the demographic and socioeconomic barriers influencing prolonged RTT as a method to address the health disparities in this regard. Cumulative interruptions of RT should be minimized.