Response to stereotactic ablative radiotherapy in a novel orthotopic model of non-small cell lung cancer.

Stereotactic ablative radiotherapy (SABR) is the main treatment for inoperable early-stage non-small cell lung cancer (NSCLC). Despite the widespread use of SABR, the biological determinants of response to SABR remain poorly investigated. We developed an orthotopic NSCLC animal model to study the response to clinically-relevant doses of SABR. Image-guided intra-thoracic injection of NSCLC cells was performed in the right lung of nude rats. A highly conformal dose of 34 Gy was delivered in a single fraction using clinical photon energies. Animals were sacrificed 10-60 days post treatment. Lung tumors were assessed for tumor differentiation, proliferation and invasiveness. An analysis of 770 cancer-related genes was performed on tumor-derived cell lines from treated animals at early and late time points after SABR. The majority of animals receiving SABR demonstrated complete response (67%), while 33% demonstrated local failure. 50% of animals with complete response failed distantly. Analysis of cancer-related genes revealed significant differences between tumors treated with SABR and untreated tumors. SABR significantly modulated expression of genes involved in adhesion, migration and angiogenesis. In particular, interleukin-8 (IL8) which plays a critical role in promoting tumor invasion was found to be secreted at high levels after SABR. In vitro invasion assays confirmed SABR-induced invasion and demonstrated induction of IL-8 secretion in multiple NSCLC cell lines. Our findings underscore the importance of developing targeted therapies that can circumvent the pro-invasive effects of SABR in NSCLC.

Diagnostic concordance of non-small cell lung carcinoma subtypes between biopsy and cytology specimens obtained during the same procedure.

BACKGROUND: The objectives of this study were: 1) to determine the diagnostic concordance of non-small cell lung carcinoma (NSCLC) subtypes in cytology and biopsy specimens taken during the same procedure and evaluate the causes of discordance; and 2) to determine the frequency of immunohistochemistry (IHC) use for subtyping NSCLC. METHODS: Biopsy and cytology specimens that were obtained at the same procedure and diagnosed as NSCLC between January 2011 and December 2014 at the McGill University Health Center were identified (n = 226 pairs). The diagnostic concordance between the 2 methods was evaluated. The slides from discordant cases were reviewed, and final diagnoses were made based on IHC, resection specimens, or pathologist discussion. RESULTS: Concordance in subtype diagnosis was perfect (adeno-adeno or squamous-squamous) in 66.2% of cases and was partial (adeno or squamous vs non-small cell) in 23%; discordance (adeno vs squamous) was observed in 7.8%. Although subtyping was not possible (ie, the final diagnosis was NSCLC, not otherwise specified) in 12.8% of biopsy specimens and 16.3% of cytology specimens, specific subtyping was not achieved in only 3% of cases when both modalities were considered. IHC was used in 47% of biopsy cases and 13% of cytology cases. CONCLUSIONS: Subtyping of NSCLC can be achieved in most cases (97%) by considering findings in both biopsy and cytology specimens, and concordance in subtyping between cytology and biopsy specimens can be reached in a high percentage of cases (89.2%). Cancer Cytopathol 2016;124:737-43. © 2016 American Cancer Society.

Crude and age-specific incidence rate patterns for histopathologic subtypes of ovarian cancer in Iran.

BACKGROUND: The purpose of this study was to report age-specific incidence rates of histopathological subtypes of ovarian cancer in Iran. METHODS: Data published by the pathology-based Cancer Registry, Iranian Ministry of Health and Medical Education for the year 2004, was utilized. This study included 793 new ovarian cancer cases which were analyzed by SPSS software (version 13). RESULTS: There were 45 different histologies reported in 793 new cases which were categorized into ten major groups. Epithelial tumors displayed the highest age specific incidence rate, followed by germ cell tumors. Serous epithelial tumors were the most common in the epithelial group. CONCLUSION: The age-specific incidence rate of ovarian cancer varies based on histology.

Survival of ovarian cancer in Iran: 2000-2004.

OBJECTIVE: The aim of this study was to estimate the 5-year survival of ovarian cancer in Iran between 2000 and 2004, according to age and histology. METHODS: Cancer registry of Iran, 2000-2004, was used covering nearly 80% of all ovarian cancers and 100% of all pathologically diagnosed ovarian cancers. RESULTS: Of 1,246 new ovarian cancer cases, 451 were available for further follow-up, which revealed 169 deaths and 282 live cases. The 5-year survival was 61%; 85% for germ cell tumors and 59% for epithelial tumors. Survival of serous, mucinous, endometrioid and clear cell histologic subtypes of epithelial tumors was 41%, 62%, 76% and 78%, respectively. Young patients with epithelial tumors (below 45) displayed significantly better 5-year survival rates (63% versus 53%). CONCLUSION: we found that ovarian cancer had a better survival rate in Iran in comparison to other regions. We also reviewed all probable confounding factors or real causes. In this study, age and histology affected survival.