The rates of second lung cancers and the survival of surgically-resected second primary lung cancers in patients undergoing resection of an initial primary lung cancer.

BACKGROUND: The Lung Cancer Screening Trial demonstrated improved overall survival (OS) and lung cancer specific survival (LCSS), likely due to finding early-stage NSCLC. The purpose of our investigation is to evaluate whether long-term surveillance strategies (4+ years after surgical resection of the initial lung cancer(1LC)) would be beneficial in NSCLC patients by assessing the rates of second lung cancers(2LC) and the OS/LCSS in patients undergoing definitive surgery in 1LC as compared to 2LC (>48 months after 1LC) populations. METHODS: SEER13/18 database was reviewed for patients during 1998-2013. Log-rank tests were used to determine the OS/LCSS differences between the 1LC and 2LC in the entire surgical group(EG) and in those having an early-stage resectable tumors (ESR, tumors <4 cm, node negative). Joinpoint analysis was used to determine rates of second cancers 4-10 year after 1LC using SEER-9 during years 1985-2014. RESULTS: The rate of 2LCs was significantly less than all other second cancers until 2001 when the incidence of 2LCs increased sharply and became significantly greater than all other second cancers in females starting in year 2005 and in men starting in year 2010. OS/LCSS, adjusted for propensity score by using inverse probability weighting, demonstrated similar OS, but worse LCSS for 2LCs in the EG, but similar OS/LCSSs in the ESR group. CONCLUSION: Because the rate of 2LCs are increasing and because the OS/LCSS of the 1LC and 2LC are similar in early-stage lesions, we feel that continued surveillance of patients in order to find early-stage disease may be beneficial.

SU-E-T-511: Dose Variations Related to Tumor Size and Location for Pencil Beam and Anisotropic Analytical Algorithms.

PURPOSE: To investigate the tumor geometric relationship to the dose variations of Anisotropic Analytical Algorithm (AAA), pencil beam convolution algorithm with/without modified Bath Power Law(PBMPL)/PB in stereotactic body radiation therapy(SBRT) treatment plans of patients presenting with a solitary primary lung cancer. MATERIALS/METHODS: Treatment plans of 14 patients (7 upper lobe, 7 lower lobe) were used for this study. The planning target volume (PTV) size ranges from 3.9c.c. to 156.7c.c. The SBRT treatment plans were composed of 10-12 non- coplanar photon beams as per RTOG guidelines. The prescription dose for this study were (i) 4×12Gy, (ii) 5×10Gy, and (iii) 5×11Gy. The Varian Eclipse treatment planning system Eclipse v. 8.9 (Palo Alto, CA) was used for this study. Four-dimensional CT (4D CT) data were used to define the integral target volume (ITV) on maximum intensity projection. An 5mm circumferential margin was used to create PTV from ITV. Plans were generated with three algorithms. RESULTS: a). For small lesions (PTV occupy less than 1% of the ipsilateral lung volume), the PBMPL plans had overestimated the dose by average 10% compared to AAA. But the PB without any heterogeneity correction agrees well with AAA. b). For big lesions (PTV occupy more than 1% of the ipsilateral lung volume), the PBMPL plans had agreed well with AAA. But the PB without any heterogeneity correction underestimate the dose by average 15% compared to AAA. c). The tumor location (Group1: within 1cm from the lung wall;Group2: 2cm away from the lung wall Group3: in between zone of 1 and 2cm from the lung wall; Group 4:Spread from the lung wall to the 2cm away zone) seems to relate with dose calculation variations among different algorithms. CONCLUSIONS: Prescription adjustment is not necessary for PTV less than 1% of ipsilateral lung volume as the recent suggestion by the quality assurance working group of phase III Rosel study of prescription dose reduction of 10% from 60Gy to 54Gy when utilizing AAA instead of PBC.

Confirmation of the role of diabetes in the local recurrence of surgically resected non-small cell lung cancer.

PURPOSE: We recently demonstrated that diabetes mellitus was an independent risk factor for local recurrence (LR) for patients undergoing resection of non-small cell lung cancer (NSCLC). This investigation was performed to confirm or refute this finding in a different patient cohort. MATERIALS AND METHODS: Patients were eligible if they did not have a second primary cancer within 5 years of the original diagnosis, had at least 3-month follow-up, and did not receive radiotherapy. There were 373 and 168 patients in the original (P1) and confirmatory (P2) cohorts, respectively, with 66 and 30 patients with diabetes. RESULTS: The median follow-up was 33 months (range, 3-98 months). Diabetes was an independent risk factor for LR in a Cox model in both the P2 (p=0.05, hazard ratio [HR] 2.15) and P1 (p=0.008, HR 1.90) cohorts, separately from BMI, glucose control, and the presence of the metabolic syndrome. The rates of LR in the patients with diabetes after combining the cohorts at 2, 3, and 5 years were 23%, 33%, and 56%, respectively; these rates were 15%, 19%, and 26% in non-diabetics. In multivariate Cox regression and competing risk analysis of the combined cohorts, the HRs for LR in patients with diabetes exceeded those of more established risk factors for LR including a 1-cm increase in tumor size and lymphovascular invasion. CONCLUSIONS: Diabetes was confirmed to be an independent predictor of the risk of LR following resection of NSCLC.

Fractionated stereotactic radiotherapy for the treatment of acoustic neuromas: preliminary results.

PURPOSE: To evaluate the efficacy and toxicity of fractionated, stereotactic radiotherapy (SRT) for acoustic neuromas. METHODS AND MATERIALS: Twelve patients with acoustic neuroma were treated with SRT between June 1992 and October 1994. Follow-up ranged from 16-44 months. Patient age ranged from 27-70 (median: 45). Eight patients were treated with primary SRT and four patients were treated after primary surgical intervention for recurrent [3] or persistent [1] disease. Tumor volumes were 1.2-18.4 cm3 (median: 10.1 cm3). Collimator sizes ranged from 30-50 mm (median: 37.5). Tumors received 1.8 Gy/day normalized to the 95% isodose line. Patients received a minimum prescribed dose of 54 Gy in 27-30 fractions over a 6-week period. RESULTS: After a median follow-up of 26.5 months, local control was obtained in 12 out of 12 lesions. Tumor regression was noted in three patients, and tumor stabilization was found in the remaining nine patients. No patient developed a new cranial nerve deficit. One patients developed worsening of preexisting Vth cranial neuropathy and another experienced a decrease in hearing. However, all nine patients with useful hearing prior to SRT maintained useful hearing at last follow-up. CONCLUSIONS: Stereotactic radiotherapy provided excellent local control without new cranial nerve deficits. These results must be viewed as tentative in nature because of the small number of patients and the short median follow-up period.

Hypertonic treatment during premature chromosome condensation allows visualization of interphase chromosome breaks repaired with fast kinetics in irradiated CHO cells.

A class of interphase chromosome breaks was visualized in irradiated (10 Gy) plateau-phase CHO cells after treatment (2-30 min) in hypertonic (500 mM NaCl) growth medium during the period normally allowed for chromosome condensation, in the premature chromosome condensation (PCC) assay. Rejoining of this class of interphase chromosome breaks was fast (t1/2 = 1.5 min) compared to the rejoining of interphase chromosome breaks normally observed in the absence of hypertonic treatment (t1/2 = 76 min), suggesting that they are formed from a different subset of precursor DNA lesions. A fast (t1/2fast = 12 min) and a slow (t1/2slow = 71 min) component were also observed in the rejoining of radiation-induced (50 Gy) DNA double-strand breaks (DSBs), as measured by pulsed-field gel electrophoresis. We propose that fast-repairing DSBs are the precursor lesions underlying the fast-repairing interphase chromosome breaks observed in these experiments. Slowly repairing DSBs are postulated to be the precursor lesions underlying the slowly repairing interphase chromosome breaks visualized using regular protocols for PCC. The visualization of fast-repairing interphase chromosome breaks achieved in these experiments is assumed to be due to a destabilization of chromatin by the hypertonic medium. This chromatin destabilization may cause either an inhibition of the rejoining of the fast component of DSBs during the period allowed for PCC or a transformation of a defined subset of fast-repairing DSBs into chromosome breaks. The latter hypothesis allows a more consistent interpretation of the available results. Transformation of a defined subset of fast-repairing DSBs to interphase chromosome breaks may be equivalent to damage fixation, and may correspond to the fixation of a form of PLD (beta-PLD) sensitive to treatment in hypertonic medium.

Hypertonic treatment does not affect the radiation yield of interphase chromosome breaks in DNA double-strand break repair-deficient xrs-5 cells.

A DNA double-strand break (DSB) repair-deficient CHO cell line, xrs-5, was used to evaluate the effect of hypertonic treatment on the radiation yield of interphase chromosome breaks, as visualized by means of premature chromosome condensation (PCC). For this purpose, interphase chromosome breaks were measured in plateau-phase G1 cells after exposure to 10 Gy X rays using either the standard protocol for PCC induction or a revised protocol that includes a brief (20 min) treatment in hypertonic medium (500 mM NaCl) during chromosome condensation. Experiments at the chromosome level were complemented by experiments at the DNA and the cellular level performed under similar postirradiation conditions. The results obtained were compared to those reported previously for CHO cells. Radiation yields of interphase chromosome breaks, as measured using standard protocols for PCC induction, were higher in xrs-5 than in CHO cells. However, the yields became similar between the two cell lines when a 20-min incubation in hypertonic medium was introduced immediately after fusion with mitotic cells. This equalization was due to the fact that incubation in hypertonic medium did not affect the radiation yield of interphase chromosome breaks in xrs-5 cells but increased it in CHO cells to levels similar to those measured in xrs-5 cells. This result suggests that xrs-5 cells constitutively express as interphase chromosome breaks a subset of DSBs which in repair-proficient CHO cells requires incubation in hypertonic medium for transformation to interphase chromosome breaks. Rejoining of DSBs, when measured in isotonic medium, was incomplete in xrs-5 cells compared to CHO cells. Rejoining of DSBs normally repaired in xrs-5 cells was completely inhibited during treatment in hypertonic medium. Postirradiation treatment in hypertonic medium affected the survival of xrs-5 cells only modestly, suggesting that the sector of PLD (beta-PLD) which required treatment in hypertonic medium for fixation in repair-proficient CHO cells is fixed constitutively in xrs-5 cells. These results are in agreement with a model developed to interpret results obtained in similar experiments with CHO cells (Iliakis et al., Radiat. Res 135, 160-170, 1993). The model postulates that potentiation in CHO cell killing induced by hypertonic treatment is caused by the transformation of a subset of fast-repairing DSBs to irreparable interphase chromosome breaks and assumes that this transformation is equivalent to fixation of beta-PLD.(ABSTRACT TRUNCATED AT 400 WORDS)