Impact of Radiation Therapy in Surgically Resected Limited-Stage Small Cell Lung Carcinoma.

PURPOSE: To elucidate the role of radiation therapy (RT) in the treatment of surgically resected limited-stage small cell lung carcinoma (LSCLC). METHODS: We queried the SEER database from 1998 to 2012 to identify patients who were diagnosed with LSCLC as their only primary tumor. Kaplan-Meier analysis was utilized to determine disease-specific survival (DSS) and overall survival (OS), while multivariate analysis was used to compare survival in terms of patients and treatment characteristics. RESULTS: Eight hundred twenty-three LSCLC patients were identified for inclusion within the study. 12-month DSS for patients who did not receive surgery or RT was 31.9% (95% CI 27.7-36.3), 93.3% (95% CI 71.6-90.5) for surgery alone, and 81.0% (95% CI 69.3-88.6) for surgery + RT. 12-month OS was 27.2% (95% CI 23.4-31.1), 74.7% (95% CI 62.6-83.4), and 78.3% (95% CI 66.4-86.4) for no surgery or RT, for surgery alone, and for surgery + RT, respectively. In terms of multivariate analysis, patients receiving surgery alone and patients receiving surgery + RT had a better DSS and OS than those who received neither treatment. However, OS (HR 1.60; 95% CI 0.93-2.75, p = 0.09) and DSS (HR 1.34; 95% CI 0.72-2.51, p = 0.37) were not significantly associated with patients receiving surgery alone compared to surgery + RT. CONCLUSIONS: Surgery alone and surgery + RT were positively associated with DSS and OS compared to patients who did not receive surgery or RT. However, the addition of RT to surgery did not significantly predict DSS or OS compared to surgery alone.

Adjuvant radiation therapy in uterine carcinosarcoma: A population-based analysis of patient demographic and clinical characteristics, patterns of care and outcomes.

OBJECTIVE: To examine clinical and demographic characteristics of a population-based cohort of patients with uterine carcinosarcoma (UCS), to assess access to treatment and survival patterns. METHODS: Surveillance, Epidemiology and End Results database was queried for patients diagnosed in 1999-2010 and treated with surgery with or without adjuvant radiation therapy (aRT). The Kaplan-Meier method was used to estimate survival functions, and Cox proportional hazards regression - to analyze the effect of covariates on survival. RESULTS: 2342 patients were eligible. African Americans presented with more advanced AJCC stages than other races (35.4% vs. 29.1%; p<0.01). African Americans vs. others, and women diagnosed in 1999-2004 vs. in 2005-2010, received aRT at a similar rate: 36.5% vs. 39.9% (p=NS), and 39.5% vs. 38.9% (p=NS), respectively. There was a trend towards higher aRT utilization among patients younger than 65 vs. older (41.4% vs. 37.5%; p<0.06). We observed better overall and cause-specific survival in the aRT group: 42 vs. 22 (p<0.0001) and 57 vs. 28months (p<0.0001), respectively. Black race, diagnosis in 1999-2004, advanced stage and age≥65years carried a higher risk of UCS death. CONCLUSIONS: We observed greater survival rate in the aRT group. African Americans were more likely to present with later stage disease and die of UCS than non-African Americans. Age and stage, but not race, influenced receipt of aRT. Patients treated more recently survived longer.

First Clinical Report on Comparative Treatment and Survival Outcomes in Second Cancers after Primary Head and Neck Cancer: A Population-Based Study.

INTRODUCTION: To compare patients' survival of second primary malignancy (SPM) after head and neck squamous cell carcinoma (HNSCC). METHODS: The Surveillance, Epidemiology, and End Results (SEER) database was utilized (1973-2011). The Kaplan-Meier method with log-rank test was used to compare the overall survival (OS) and cause-specific survival (CSS) among treatment methods from the time of diagnosis of SPMs. Cox proportional regression models were used to adjust the impact for risk factors on CSS. RESULTS: A total of 3,038 patients were identified (5-yr OS 22.6% (21.0-24.3%)). For head and neck (HN) SPMs, the patients who received 'conservative surgery with radiation' had the best 5-yr OS (65.2% (48.9-86.9%)); and the 'conservative surgery' group had the best 5-yr CSS (89.9% (85.6-94.5%)). For lung SPMs, the 'radical surgery' group showed the best survival (2-yr OS 60.8% (56.0-66.1%), 2-yr CSS 70.6% (65.8-75.8%), respectively). Esophagus SPMs had poor prognosis, with no difference among the treatment groups. In lung SPMs, younger age (p<0.001) and black race (p<0.05) were most favorable CSS predictors. CONCLUSIONS: The prognosis of SPMs after HNSCC is worse compared with corresponding primary tumor. Conservative surgery with or without radiation showed the most favorable outcomes in HN SPMs.​.

Investigating the intermediates in the reaction of ribonucleoside triphosphate reductase from Lactobacillus leichmannii: An application of HF EPR-RFQ technology.

In this investigation high-frequency electron paramagnetic resonance spectroscopy (HFEPR) in conjunction with innovative rapid freeze-quench (RFQ) technology is employed to study the exchange-coupled thiyl radical-cob(II)alamin system in ribonucleotide reductase from a prokaryote Lactobacillus leichmannii. The size of the exchange coupling (Jex) and the values of the thiyl radical g tensor are refined, while confirming the previously determined (Gerfen et al. (1996) [20]) distance between the paramagnets. Conclusions relevant to ribonucleotide reductase catalysis and the architecture of the active site are presented. A key part of this work has been the development of a unique RFQ apparatus for the preparation of millisecond quench time RFQ samples which can be packed into small (0.5 mm ID) sample tubes used for CW and pulsed HFEPR--lack of this ability has heretofore precluded such studies. The technology is compatible with a broad range of spectroscopic techniques and can be readily adopted by other laboratories.

An oxyferrous heme/protein-based radical intermediate is catalytically competent in the catalase reaction of Mycobacterium tuberculosis catalase-peroxidase (KatG).

A mechanism accounting for the robust catalase activity in catalase-peroxidases (KatG) presents a new challenge in heme protein enzymology. In Mycobacterium tuberculosis, KatG is the sole catalase and is also responsible for peroxidative activation of isoniazid, an anti-tuberculosis pro-drug. Here, optical stopped-flow spectrophotometry, rapid freeze-quench EPR spectroscopy both at the X-band and at the D-band, and mutagenesis are used to identify catalase reaction intermediates in M. tuberculosis KatG. In the presence of millimolar H2O2 at neutral pH, oxyferrous heme is formed within milliseconds from ferric (resting) KatG, whereas at pH 8.5, low spin ferric heme is formed. Using rapid freeze-quench EPR at X-band under both of these conditions, a narrow doublet radical signal with an 11 G principal hyperfine splitting was detected within the first milliseconds of turnover. The radical and the unique heme intermediates persist in wild-type KatG only during the time course of turnover of excess H2O2 (1000-fold or more). Mutation of Met255, Tyr229, or Trp107, which have covalently linked side chains in a unique distal side adduct (MYW) in wild-type KatG, abolishes this radical and the catalase activity. The D-band EPR spectrum of the radical exhibits a rhombic g tensor with dual gx values (2.00550 and 2.00606) and unique gy (2.00344) and gz values (2.00186) similar to but not typical of native tyrosyl radicals. Density functional theory calculations based on a model of an MYW adduct radical built from x-ray coordinates predict experimentally observed hyperfine interactions and a shift in g values away from the native tyrosyl radical. A catalytic role for an MYW adduct radical in the catalase mechanism of KatG is proposed.