Background:c-MYC copy number gain (c-MYC gain) has been associated with aggressive behaviour in several cancers. However, the role of c-MYC gain has not yet been determined in lung adenocarcinomas classified by genetic alterations in epidermal growth factor receptor (EGFR), KRAS, and anaplastic lymphoma kinase (ALK) genes. We investigated the clinicopathologic and prognostic significance of c-MYC gain for disease-free survival (DFS) and overall survival (OS) according to EGFR, KRAS, and ALK gene status and stages in lung adenocarcinomas.Methods:In 255 adenocarcinomas resected in Seoul National University Bundang Hospital from 2003 to 2009, fluorescence in situ hybridisation (FISH) with c-MYC probe and centromeric enumeration probe 8 (CEP8) was analysed using tissue microarray containing single representative core per each case. EGFR (codon 18 to 21) and KRAS (codon 12, 13, and 61) mutations were analysed by polymerase chain reaction and direct sequencing method from formalin-fixed, paraffin-embedded tissue sections. ALK rearrangement was determined by FISH method. c-MYC gain was defined as >2 copies per nucleus, chromosome 8 gain as ⩾3 copies per nucleus, and gain of c-MYC:CEP8 ratio (hereafter, c-MYC amplification) as ⩾2.Results:We observed c-MYC gain in 20% (51 out of 255), chromosome 8 gain in 5.5% (14 out of 255), c-MYC amplification in 2.4% (6 out of 255), EGFR mutation in 49.4% (118 out of 239), KRAS mutation in 5.7% (7 out of 123), and ALK rearrangement in 4.9% (10 out of 205) of lung adenocarcinomas. c-MYC gain was observed in 19% (22 out of 118) of patients with lung adenocarcinomas with an EGFR mutation, but not in any patients with a KRAS mutation, or an ALK rearrangement. c-MYC gain (but not chromosome 8 gain or c-MYC amplification) was an independent poor-prognostic factor in the full cohort of lung adenocarcinoma (P=0.022, hazard ratio (HR)=1.71, 95% confidence interval (CI), 1.08–2.69 for DFS; P=0.032, HR=2.04, 95% CI, 1.06–3.91 for OS), as well as in stage I subgroup (P=0.023, HR=4.70, 95% CI, 1.24–17.78 for DFS; P=0.031, HR=4.65, 95% CI, 1.15–18.81 for OS), and in EGFR-mutant subgroup (P=0.022; HR=2.14; 95% CI, 1.11–4.10 for DFS).Conclusions:c-MYC gain (but not chromosome 8 gain or c-MYC amplification) was an independent poor-prognostic factor for DFS and OS in lung adenocarcinomas, both in full cohort and stage I cancer, and possibly for DFS in EGFR-mutant adenocarcinomas. Additional studies are required to determine if patients with lung adenocarcinoma with c-MYC gain are candidates for additional first-line treatment to mitigate their increased risk for disease progression and death.

Conventional hard or dynamic wedge systems are commonly applied to reduce the dose inhomogeneity associated with whole breast irradiation. We evaluated the dosimetric benefits of the field-in-field (FIF) technique by comparing it with the electronic compensator (EC), Varian enhanced dynamic wedge (EW) and conventional hard wedge (HW) techniques. Data were obtained from 12 patients who had undergone breast-conserving surgery (six left-sided and six right-sided). For these patients, the average breast planning target volume (PTV) was 447.4 cm(3) (range, 211.6-711.8 cm(3)). For the experiments, a 6 MV photon beam from a Varian 21 EX was used, the HW and EW angles were applied from 15 to 45 degrees, while 40-50% isodose values were chosen to achieve the best dose distribution for electronic compensation. In applying the FIF technique, we used two or three subfields for each portal. To evaluate the performance for each planning technique, we analysed a dose-volume histogram (DVH) for the PTV and organs-at-risk (OARs). To evaluate the effects of these techniques on dose inhomogeneity, we defined the PTV Dose Improvement (PDI) index, which was derived from a PTV volume between 97-103% of the differential DVHs. In addition, we compared the average monitor units (MUs) for each technique. The average PDI index with FIF is 76.4%, while the PDI indices for other treatments were 65.8, 41.8 and 50.9% for EC, EW and HW, respectively. This study demonstrated an improved performance using the FIF technique compared with the conventional HW/EW system, as well as a new modality for EC. We demonstrated that FIF is a very useful technique for improving PTV conformity, while protecting the OARs from breast tangential irradiation.

The aim of the present study was to evaluate the effect of various specific dosimetric leaf gaps on the multileaf collimator (MLC)–based small‐beam dose distribution. The dosimetric static leaf gap was determined by comparing the profiles of small MLC‐based beams with those of small collimated fields (square fields of 1, 2, 3, and 4cm). The results showed that an approximately 2‐mm gap was optimal with the Millennium 120‐leaf MLC (Varian Medical Systems, Palo Alto, CA) and a Varian 21EX 6‐MV photon beam. We also investigated how much the leaf gap affects the planning results and the actual dose distribution. A doughnut‐shaped planning target volume (PTV, 6.1 cm3) and inner organ at risk (OAR, 0.3 cm3) were delineated for delicate intensity‐modulated radiosurgery test planning. The applied leaf gaps were 0, 1, and 2 mm. The measured dose distributions were compared with the dose distribution in the treatment planning system. The maximum dose differences at inside PTV, outside PTV, and inner OAR were, respectively, 22.3%, 20.2%, and 35.2% for the 0‐mm leaf gap; 17.8%, 22.8%, and 30.8% for the 1‐mm leaf gap; and 5.5%, 8.5%, and 6.3% for the 2‐mm leaf gap. In a human head phantom (model 605: CIRS, Norfolk, VA) study, large dose differences of 1.3% – 12.7% were noted for the measurements made using the MLC files generated by the three different leaf gaps. The planned results were similar, and measurements showed a large dose difference associated with the various leaf gaps. These results strongly suggest that plans generated by a commercial inverse planning system commissioned using general collimated field data will probably demonstrate discrepancies between the planned treatments and the measured results.PACS number: 87.53.Dq

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