Respiratory motion causes uncertainties in tumor edges on either computed tomography (CT) or positron emission tomography (PET) images and causes misalignment when registering PET and CT images. This phenomenon may cause radiation oncologists to delineate tumor volume inaccurately in radiotherapy treatment planning. The purpose of this study was to analyze radiology applications using interpolated average CT (IACT) as attenuation correction (AC) to diminish the occurrence of this scenario. Thirteen non-small cell lung cancer patients were recruited for the present comparison study. Each patient had full-inspiration, full-expiration CT images and free breathing PET images by an integrated PET/CT scan. IACT for AC in PETIACT was used to reduce the PET/CT misalignment. The standardized uptake value (SUV) correction with a low radiation dose was applied, and its tumor volume delineation was compared to those from HCT/PETHCT. The misalignment between the PETIACT and IACT was reduced when compared to the difference between PETHCT and HCT. The range of tumor motion was from 4 to 17 mm in the patient cohort. For HCT and PETHCT, correction was from 72% to 91%, while for IACT and PETIACT, correction was from 73% to 93% (*p<0.0001). The maximum and minimum differences in SUVmax were 0.18% and 27.27% for PETHCT and PETIACT, respectively. The largest percentage differences in the tumor volumes between HCT/PET and IACT/PET were observed in tumors located in the lowest lobe of the lung. Internal tumor volume defined by functional information using IACT/PETIACT fusion images for lung cancer would reduce the inaccuracy of tumor delineation in radiation therapy planning.

Tumor-to-tumor metastasis is a rare phenomenon, with around 150 cases being reported in the literature. Breast cancer is the second most commonly reported donor tumor after lung cancer, but thymic epithelial tumors have never been reported as recipient tumors. Furthermore, the thymus is rarely affected by metastases. To our knowledge, the present report is the first case of breast cancer metastatic to thymic epithelial tumor.

BACKGROUND:

Sagopilone (ZK219477) is a new and fully synthetic epothilone with activity against multi-drug resistant tumour cell lines. It has demonstrated clinical activity in several solid tumours like ovarian cancer and melanoma. Data about clinical efficacy of sagopilone in small-cell lung cancer are lacking. Here we report the first phase-I trial of sagopilone in combination with cisplatin in previously untreated metastatic small-cell lung cancer patients.

METHODS:

Chemonaive patients with metastatic small-cell lung cancer (SCLC) received sagopilone in four different dosing schedules ranging from 12 to 22mg/m(2) (on day 1 as 3-h infusion) followed by a fixed dose of cisplatin of 75mg/m(2) as 1-h infusion on day 1. Chemotherapy was administered every 3weeks to a maximum of six cycles. The primary objective was determination of dose-limiting toxicities (DLTs) and the maximum-tolerated dose (MTD) in this setting. Secondary objectives were assessment of objective response rates (ORR) as well as investigation of sagopilone pharmacokinetics.

RESULTS:

Twenty-six patients received a total of 107 treatment cycles of the platinum-sagopilone doublet. The recommended phase-II dose (RD) and schedule was found to be 19mg/m(2) sagopilone followed by 75mg/m(2) cisplatin. Peripheral neuropathy turned out as dose-limiting toxicity when the combination was administered over a median of four cycles. Objective responses were observed in six out of seven SCLC patients (85.7%) treated with the RD.

CONCLUSIONS:

Sagopilone and cisplatin can be safely combined in the first-line treatment of metastasised SCLC. This combination demonstrated preliminary efficacy and should be further evaluated within phase-II trials.

One of the most important pathways in non-small cell lung cancer (NSCLC) is the epidermal growth factor receptor (EGFR) pathway. This pathway affects several crucial processes in tumor development and progression, including tumor cell proliferation, apoptosis regulation, angiogenesis, and metastatic invasion. Targeting EGFR is currently being intensely explored. We are witnessing the development of a number of potential molecular-inhibiting treatments for application in clinical oncology. In the last decade, the tyrosine kinase (TK) domain of the EGFR was identified in NSCLC patients, and it has responded very well with a dramatic clinical improvement to TK inhibitors such are gefitinib and erlotinib. Unfortunately, there were primary and/or secondary resistance to these treatments, as shown by clinical trials. Subsequent molecular biology studies provided some explanations for the drug resistance phenomenon. The molecular mechanisms of resistance need to be clarified. An in-depth understanding of these targeted-therapy resistance may help us explore new strategies for overcoming or reversing the resistance to these inhibitors for the future of NSCLC treatment.

To evaluate the short-term outcomes of video-assisted thoracic surgery (VATS) for thoracic tumors.The data of 1,790 consecutive patients were retrospectively reviewed. These patients underwent VATS pulmonary resections, VATS esophagectomies, and VATS resections of mediastinal tumors or biopsies at the Cancer Institute & Hospital, Chinese Academy of Medical Sciences between January 2009 and January 2012.There were 33 patients converted to open thoracotomy (OT, 1.84%). The overall morbidity and mortality rate was 2.79% (50/1790) and 0.28% (5/1790), respectively. The overall hospitalization and chest tube duration were shorter in the VATS lobectomy group (n=949) than in the open thoracotomy (OT) lobectomy group (n=753). There were no significant differences in morbidity rate, mortality rate and operation time between the two groups. In the esophageal cancer patients, no significant difference was found in the number of nodal dissection, chest tube duration, morbidity rate, mortality rate, and hospital length of stay between the VATS esophagectomy group (n=81) and open esophagectomy group (n=81). However, the operation time was longer in the VATS esophagectomy group. In the thymoma patients, there was no significant difference in the chest tube duration, morbidity rate, mortality rate, and hospital length of stay between the VATS thymectomy group (n=41) and open thymectomy group (n=41). However, the operation time was longer in the VATS group. The median tumor size in the VATS thymectomy group was comparable with that in the OT group.In early-stage (I/II) non-small cell lung cancer patients who underwent lobectomies, VATS is comparable with the OT approach with similar short-term outcomes. In patients with resectable esophageal cancer, VATS esophagectomy is comparable with OT esophagectomy with similar morbidity and mortality. VATS thymectomy for Masaoka stage I and II thymoma is feasible and safe, and tumor size is not contraindicated. Longer follow-ups are needed to determine the oncologic equivalency of VATS lobectomy, esophagectomy, and thymectomy for thymoma vs. OT.

Resistance to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs), gefitinib and erlotinib, is a critical problem in the treatment of EGFR mutant lung cancer. Several mechanisms, including bypass signaling by hepatocyte growth factor (HGF)-triggered Met activation, are implicated as mediators of resistance. The mammalian target of rapamycin (mTOR), is a downstream conduit of EGFR and MET signaling, and is thus considered a therapeutically attractive target in the treatment of various types of cancers. The purpose of this study was to examine whether 2 clinically approved mTOR inhibitors, temsirolimus and everolimus, overcome HGF-dependent resistance to EGFR-TKIs in EGFR mutant lung cancer cells. Both temsirolimus and everolimus inhibited the phosphorylation of p70S6K and 4E-BP1, which are downstream targets of the mTOR pathway, and reduced the viability of EGFR mutant lung cancer cells, PC-9, and HCC827, even in the presence of HGF in vitro. In a xenograft model, temsirolimus suppressed the growth of PC-9 cells overexpressing the HGF-gene; this was associated with suppression of the mTOR signaling pathway and tumor angiogenesis. In contrast, erlotinib did not suppress this signaling pathway or tumor growth. Multiple mechanisms, including the inhibition of vascular endothelial growth factor production by tumor cells and suppression of endothelial cell viability, contribute to the anti-angiogenic effect of temsirolimus. These findings indicate that mTOR inhibitors may be useful for controlling HGF-triggered EGFR-TKI resistance in EGFR mutant lung cancer, and they provide the rationale for clinical trials of mTOR inhibitors in patients stratified by EGFR mutation and HGF expression status.

PR (PRDI-BF1 and RIZ) domain containing proteins (PRDM) have been indicated to play important roles in several human cancers. The objectives of this study were to determine the frequency and prognostic significance of PRDM1 and PRDM14 expression in a cohort of surgically resected non-small cell lung cancer (NSCLC) patients. Immunohistochemistry and Western blotting was used to detect the expression status of PRDM1 in primary tumors and PRDM14 for both primary lung cancers and matched lymph node metastases. Univariate and multivariate analysis were performed to determine the association between PRDM expression and prognosis. PRDM1 expression was observed in all NSCLC patients' tumor samples. PRDM14 was found to be increased expression in 35.65 % cases (46/129) for primary tumors and 39.68 % cases (25/63) for paired metastatic lymph nodes. Increased expression of PRDM14 correlated with differentiation of tumor cells significantly (P = 0.008). Western blotting analysis verified that PRDM14 associated with cell differentiation in NSCLC. The overall survival rates of patients with high PRDM14 expression and low PRDM14 expression were 41.30 and 65.06 %, respectively (hazard ratio: 3.051, 95 % CI: 1.752, 5.312, P < 0.0001). The progression-free survival rates were 34.78 % for patients in the high expression group and 59.03 % for patients in the low OLC1 expression group (hazard ratio: 2.775, 95 % CI: 1.648, 4.675, P < 0.0001). Thus, our study showed that increased expression of PRDM14 correlated with cell differentiation of NSCLC cells. PRDM14 was a potential biomarker for predicting unfavorable prognosis in NSCLC.

BACKGROUND::

Angiosarcoma (AS) is a rare soft tissue sarcoma showing endothelial differentiation as indicated by morphology and expression of CD31 (blood), D2-40 (lymphatic), factor VIII, and CD34 (both). We sought to examine the pattern of immunohistochemical markers of differentiation in AS and correlate these with outcome.

DESIGN:

: An AS tissue microarray (n = 70 specimens) was constructed for immunohistochemical analysis of CD31, CD34, factor VIII, D2-40, and pan-cytokeratin. Samples on this array were linked to clinicopathologic and outcome data for these patients. Univariate analyses were used to explore disease-specific survival (DSS) factors.

RESULTS::

Nine metastatic, 23 localized, and 4 recurrent cases were included. Information about the tissue status (ie, primary or metastasis) was unavailable in 4 patients. Primary sites for the tumor included bone (n = 1), breast parenchyma (n = 11), breast skin (n = 4), heart (n = 5), skin (n = 8), soft tissue (n = 7), and unknown (n = 3). Three patients presented with multifocal disease (primary sites in these patients included breast, skin, and soft tissue). Metastatic sites included lung, bone, lymph nodes, brain, liver, and parotid. Of the 40 cases, 8 (20%) showed a pure or predominant epithelioid histology. Of the biomarkers evaluated by tissue microarray, 92% of tumors expressed at least one endothelial marker (factor VIII = 83%, CD31 = 80%, CD34 = 63%, and D2-40 = 43%) with 88% expressing 2 or more markers. Eighty-eight percent of tumors expressing D2-40 coexpressed CD31, an unusual combination in normal vessels. No endothelial marker clearly associated with disease-specific survival. Fifty percent (4/8) of epithelioid cases and 9% (3/32) of nonepithelioid cases showed keratin expression.

CONCLUSIONS::

Unusual patterns and loss of endothelial markers are common in AS, suggesting use of multiple markers in challenging cases and perhaps indicating important biologic characteristics.

Patients with advanced-stage bronchial cancer benefit from systemic cytostatic therapy, in particular from regimens integrating cisplatin and taxanes. However, eventual disease progression leads to a fatal outcome in most cases, originating from tumor cells resisting chemotherapy. We here show that the intracellular ATP-binding cassette transporter A3 (ABCA3), previously recognized as critical for the secretion of surfactant components from type 2 pneumocytes, is expressed in non-small-cell lung cancer (NSCLC) cells. With some heterogeneity in a given specimen, expression levels detected immunohistochemically in primary cancer tissue were highest in adenocarcinomas and lowest in small cell lung cancers. Genetic silencing of ABCA3 in the NSCLC cell line models A549, NCI-H1650 and NCI-H1975 significantly increased tumor cell susceptibility to the cytostatic effects of both cisplatin (in all cell lines) and paclitaxel (in two of three cell lines). Taken together, ABCA3 emerges as a modulator of NSCLC cell susceptibility to cytostatic therapy.

Collision tumors are rare in nature. We report a case of a 70-year-old woman who was found to have a new mass in the right lung. Right upper and middle lobectomies with a mediastinal lymph node sampling were performed. Pathological examination of the mass revealed a collision tumor composed of micropapillary adenocarcinoma and typical carcinoid. The neoplastic cells were not intimately admixed with one another. To the best of our knowledge, this case is the first report in the English medical literature of a primary pulmonary collision tumor consisting of micropapillary adenocarcinoma and typical carcinoid.