Impact of season of diagnosis on mortality among breast cancer survivors.

INTRODUCTION: There is mounting evidence that the time of breast cancer diagnosis and the start of treatment can improve survival rates. The aim of this study was to test the relationship between the season of breast cancer diagnosis and the survival of women patients receiving standard surgery treatment with radiotherapy. MATERIALS AND METHODS: The nonmetastatic breast cancer patients (n = 991) were followed from the date of diagnosis until death. Cox proportional hazards models were used to calculate multivariate hazard ratios (HRs) for all-cause mortality. HRs and 95% confidence intervals (CIs) were estimated in models adjusted for clinicopathologic and treatment factors. RESULTS: After adjusting for independent prognostic variables, we found that patients diagnosed in summer and autumn had a 40% reduced risk for 0-3-year mortality when compared to those diagnosed in spring. Among women aged <50 years, HRs comparing autumn with spring diagnosis categories were 0.53 (95% CI: 0.31-0.91) for 0-5-years and 0.68 (95% CI: 0.46-0.89) for 5-10-years after diagnosis. Diagnosis in autumn was associated with improving survival in younger patients treated with adjuvant chemotherapy (HR = 0.61, 95% CI: 0.39-0.96, P = 0.003). CONCLUSIONS: The diagnosis in summer and autumn was associated with a better overall prognosis. The effect of season of diagnosis on survival rate was most pronounced in the young age patients receiving chemotherapy.

Acute toxicity and quality of life in high risk prostate cancer patients: Updated results of randomized hypofractionation trial.

PURPOSE: The aim of our study was to perform the final analysis of acute toxicity and quality of life data obtained from 221 consecutive patients who suffered from intermediate-to-high risk prostate cancer. METHODS: In this trial, 221 patients were randomized to receive either hypofractionated (63 Gy in 20 fractions, 4 fractions/week) or conventionally fractionated (76 Gy in 38 fractions, 5 fractions/week) radiotherapy to the prostate and seminal vesicles. Elective pelvic lymph node irradiation with 46 Gy in 23 fractions sequentially and 44 Gy in 20 fractions simultaneously was also applied. RESULTS: There was no statistically significant difference in acute GU and GI toxicity in men treated with hypofractionated (SIB) (Arm 2) in comparison with patients who had conventional fractionation (Arm 1) radiation therapy. Multivariate analysis using logistic regression showed statistical significant association between acute GU ≥ 1 and PTV(LN) (p = 0.008) only. We found out that clinically relevant decrease (CRD) was significantly higher only in the urinary domain of Arm 1 at month 3 (p = 0.02). CONCLUSION: Our study demonstrated that hypofractionated radiotherapy was associated with a small but insignificant increase of acute toxicity. The reduction of overall treatment time has no significant influence on patients' QOL in any domain.

Changes of reduced glutathione and glutathione S-transferase levels in colorectal cancer patients undergoing treatment.

PURPOSE:: The available data concerning reduced glutathione (GSH) and glutathione S-transferase (GST) levels in colorectal cancer patients during the treatment process are contradictory and insufficient. METHODS:: Forty patients with metastatic colorectal cancer receiving FOLFOX4 chemotherapy with or without bevacizumab and 40 healthy volunteers were included in the study. Blood samples were taken before treatment, after 2 months and at the end of treatment in the patient group and once in the healthy volunteer group. The levels of GSH and GST in blood serum were evaluated by enzyme-linked immunosorbent assay (ELISA) according to the manufacturer's instructions. RESULTS:: The serum level of GSH was significantly lower in colorectal cancer patients before treatment than in healthy volunteers (37.84 ± 19.39 µg/mL and 52.78 ± 19.39 µg/mL, respectively; p<0.001). After treatment, the level of GSH increased significantly, while the level of GST decreased significantly. These changes were observed only in the groups of patients with partial or complete response, having metastases only in the liver, receiving FOLFOX4 chemotherapy with bevacizumab, or undergoing resection or radiofrequency ablation of liver metastases. CONCLUSIONS:: GSH and GST levels change significantly during the treatment process and these changes depend on the response to treatment, treatment type, and site of metastases. Further analysis of the changes in GSH and GST levels during treatment would allow the assessment of the predictive potential of this molecular marker.

Down-regulation of miRNA-148a and miRNA-625-3p in colorectal cancer is associated with tumor budding.

BACKGROUND: MiRNAs are often deregulated in colorectal cancer and might function as tumor suppressors or as oncogenes. They participate in controlling key signaling pathways involved in proliferation, invasion and apoptosis and may serve as prognostic and predictive markers. In this study we aimed to evaluate the role of miRNA-148a and miRNA-625-3p in metastatic colorectal cancer. METHODS: Fifty-four patients with a first-time diagnosed CRC receiving FOLFOX ± Bevacizumab were involved in the study. Tumor samples underwent routine pathology examination including evaluation for tumor budding and KRAS. MiRNA-148a and miRNA-625-3p expression analysis was done by RT-PCR. Associations between expression of both miRNAs and clinico-pathological factors, treatment outcomes and survival were analyzed. RESULTS: Both miRNA-148a and miRNA-625-3p were down-regulated in the tumors compared to normal colonic mucosa. Significantly lower expression of both miRNAs was noticed in tumors with budding phenomenon compared to tumors without it (median values of miRNA-148a were 0.314 and 0.753 respectively, p = 0.011, and 0.404 and 0.620 respectively for miRNA-625-3p, p = 0.036). Significantly lower expression of miRNA-625-3p was detected in rectal tumors, compared to tumors in the colon (median 0.390 and 0.665 respectively, p = 0.037). Progression free survival was significantly lower in patients with high miRNA-148a expression (6 and 9 months respectively, p = 0.033), but there were no significant differences in PFS for miRNA-625-3p and in overall survival for both miRNAs. CONCLUSIONS: There was a significant relationship between low miRNA-148a and miRNA-625-3p expression and tumor budding, which is thought to represent epithelial-mesenchymal transition. Both studied miRNAs may be associated with a more aggressive phenotype and could be the potential prognostic and predictive biomarkers in CRC. Further investigation is needed to confirm miRNAs involvement in EMT, and their prognostic and predictive value.

Microenvironment and Dose-Delivery-Dependent Response after Exposure to Ionizing Radiation in Human Colorectal Cancer Cell Lines.

A significant body of knowledge about radiobiology is based on studies of single dose cellular irradiation, despite the fact that conventional clinical applications using dose fractionation. In addition, cellular radiation response strongly depends on cell-cell and cell-extracellular matrix (ECM) interactions, which are poorly established in cancer cells grown under standard 2D cell culture conditions. In this study, we investigated the response of human colorectal carcinoma (CRC) DLD1 and HT29 cell lines, bearing distinct p53 mutations, to a single 2 or 10 Gy dose or fractionated 5 × 2 Gy doses of radiation using global transcriptomics analysis. To examine cellular response to radiation in a cell-ECM-interaction-dependent manner, CRC cells were grown under laminin-rich ECM 3D cell culture conditions. Microarray data analysis revealed that, overall, a total of 1,573 and 935 genes were differentially expressed (fold change >1.5; P < 0.05) in DLD1 and HT29 cells, respectively, at 4 h postirradiation. However, compared to a single dose of radiation, fractionated doses resulted in significantly different transcriptomic response in both CRC cell lines. Furthermore, pathway enrichment analysis indicated that p53 pathway and cell cycle/DNA damage repair or immune response functional categories were most significantly altered in DLD1 or HT29 cells, respectively, after fractionated irradiations. Novel observations of radiation-response-mediated activation of pro-survival pathways in CRC cells grown under lr-ECM 3D cell culture conditions using fractionated doses provide new directions for the development of more efficient radiotherapy strategies. Our results also indicated that cell line specific radiation response with or without activation of the conventional p53 pathway is ECM dependent, suggesting that the ECM is a key component in cellular radiation response.

Glutathione and glutathione S-transferase levels in patients with liver metastases of colorectal cancer and other hepatic disorders.

BACKGROUND/AIMS: Glutathione and glutathione S-transferases (GST) are involved in cell defence against reactive oxygen species, which induces oxidative stress and are associated with different chronic diseases. The aim of the present study was to determine the differences in reduced glutathione (GSH) and GST levels in patients with different liver diseases. MATERIALS AND METHODS: Overall, 114 patients were enrolled in this study: 58 patients with colorectal cancer (18 without and 40 with liver metastases), 27 with liver steatosis, 29 with alcoholic cirrhosis and a group of 40 healthy volunteers. The levels of GSH and GST in blood serum were evaluated by enzyme-linked immunosorbent assay (ELISA) according to the manufacturer's guidelines. RESULTS: Significant differences in GSH and GST levels were observed in most of the groups compared to the healthy volunteers (GSH: 52.72 µg/mL, GST: 0.53 ng/mL): with hepatic steatosis (GSH: 17.04 µg/mL, p < 0.001; GST: 5.89 ng/mL, p < 0.001), alcoholic cirrhosis (GSH: 62.04 µg/mL, p < 0.003; GST: 0.94 ng/mL, p < 0.001) and liver metastases (GSH: 37.84 µg/mL, p < 0.001, GST: 1.25 ng/mL, p=0.747). CONCLUSION: The different GSH and GST levels in patients with colorectal cancer liver metastases, liver steatosis and alcoholic cirrhosis indicate the differences in antioxidative system damage and its compensatory possibilities and could serve as potential biomarkers for its correction.

Optimal differentiation of high- and low-grade glioma and metastasis: a meta-analysis of perfusion, diffusion, and spectroscopy metrics.

INTRODUCTION: To perform a meta-analysis of advanced magnetic resonance imaging (MRI) metrics, including relative cerebral blood volume (rCBV), normalized apparent diffusion coefficient (nADC), and spectroscopy ratios choline/creatine (Cho/Cr) and choline/N-acetyl aspartate (Cho/NAA), for the differentiation of high- and low-grade gliomas (HGG, LGG) and metastases (MTS). METHODS: For systematic review, 83 articles (dated 2000-2013) were selected from the NCBI database. Twenty-four, twenty-two, and eight articles were included respectively for spectroscopy, rCBV, and nADC meta-analysis. In the meta-analysis, we calculated overall means for rCBV, nADC, Cho/Cr (short TE-from 20 to 35 ms, medium-from 135 to 144 ms), and Cho/NAA for the HGG, LGG, and MTS groups. We used random effects model to obtain weighted averages and select thresholds. RESULTS: Overall means (with 95% CI) for rCBV, nADC, Cho/Cr (short and medium echo time, TE), and Cho/NAA were: for HGG 5.47 (4.78-6.15), 1.38 (1.16-1.60), 2.40 (1.67-3.13), 3.27 (2.78-3.77), and 4.71 (3.24-6.19); for LGG 2.00 (1.71-2.28), 1.61 (1.36-1.87), 1.46 (1.20-1.72), 1.71 (1.49-1.93), and 2.36 (1.50-3.23); for MTS 5.06 (3.85-6.27), 1.35 (1.06-1.64), 1.89 (1.72-2.06), 3.14 (1.57-4.72), (Cho/NAA was not available). LGG had significantly lower rCBV, Cho/Cr, and Cho/NAA values than HGG or MTS. No significant differences were found for nADC. CONCLUSIONS: Best differentiation between HGG and LGG is obtained from rCBV, Cho/Cr, and Cho/NAA metrics. MTS could not be reliably distinguished from HGG by the methods investigated.

Significance of KRAS, NRAS, BRAF and PIK3CA mutations in metastatic colorectal cancer patients receiving Bevacizumab: a single institution experience.

Background. KRAS mutation is an important predictive and prognostic factor for patients receiving anti-EGFR therapy. An expanded KRAS, NRAS, BRAF, PIK3CA mutation analysis provides additional prognostic information, but its role in predicting bevacizumab efficacy is unclear. The aim of our study was to evaluate the incidence of KRAS, NRAS, BRAF and PIK3CA mutations in metastatic colorectal cancer patients receiving first line oxaliplatin based chemotherapy with or without bevacizumab and to evaluate their prognostic and predictive significance. Methods. 55 patients with the first-time diagnosed CRC receiving FOLFOX ± bevacizumab were involved in the study. Tumour blocks were tested for KRAS mutations in exons 2, 3 and 4, NRAS mutations in exons 2, 3 and 4, BRAF mutation in exon 15 and PIK3CA mutations in exons 9 and 20. The association between mutations and clinico-pathological factors, treatment outcomes and survival was analyzed. Results. KRAS mutations were detected in 67.3% of the patients, BRAF in 1.8%, PIK3CA in 5.5% and there were no NRAS mutations. A significant association between the high CA 19-9 level and KRAS mutation was detected (mean CA 19-9 levels were 276 and 87 kIU/l, respectively, p = 0.019). There was a significantly higher response rate in the KRAS, NRAS, BRAF and PIK3CA wild type cohort receiving bevacizumab compared to any gene mutant type (100 and 60%, respectively, p = 0.030). The univariate Cox regression analysis did not confirm KRAS and other tested mutations as prognostic factors for PFS or OS. Conclusions. Our study revealed higher KRAS and lower NRAS, BRAF and PIK3CA mutation rates in the Lithuanian population than those reported in the literature. KRAS mutation was associated with the high CA 19-9 level and mucinous histology type, but did not show any predictive or prognostic significance. The expanded KRAS, NRAS, BRAF and PIK3CA mutation analysis provided additional significant predictive information.

Asymptomatic primary tumour in incurable metastatic colorectal cancer: is there a role for surgical resection prior to systematic therapy or not?

INTRODUCTION: The role of the resection of asymptomatic primary colorectal cancer in patients with incurable disease is questionable. AIM: To evaluate the impact of the resection of asymptomatic primary tumour on overall survival in patients with unresectable distant metastases. MATERIAL AND METHODS: Patients treated in the National Cancer Institute, Lithuania, in the period 2008-2012, were selected retrospectively. The main inclusion criteria were: metastatic colorectal cancer (mCRC), endoscopically and histologically confirmed adenocarcinoma, without any symptoms for urgent operation, and at least one cycle of palliative chemotherapy administered. Information on patients' age, gender, tumour histology, localization of the tumour, regional lymph node involvement, number of metastatic sites, surgery and systemic treatment was collected prospectively. Eligible patients for the study were divided into two groups according to the initial treatment - surgery (patients who underwent primary tumour resection) and chemotherapy (patients who received chemotherapy without surgery). The impact of initial treatment strategy, tumour size and site, regional lymph nodes, grade of differentiation of adenocarcinoma and application of biotherapy on overall cumulative survival was estimated using the Kaplan-Meier method. To compare survival between groups the log-rank test was used. Cox regression analysis was employed to assess the effects of variables on patient survival. RESULTS: The study group consisted of 183 patients: 103 men and 80 women. The median age was 66 years (range: 37-91). There were no notable imbalances with regard to age, gender, number of metastatic sites, metastases (such as pulmonary, peritoneal, liver, metastases into non-regional lymph nodes and other metastases), the number of received cycles of chemotherapy, first line chemotherapy type or biological therapy. Only 27 (14.8%) patients received biological therapy and the majority of them (n = 25, 92.6%) were treated with bevacizumab. For surgically treated patients 1-year survival was 71.2% (95% CI: 62.1-78.5) and 5-year survival was 4.0% (95% CI: 1.0-10.5). In the chemotherapy group, survival rates were lower - 43.9% (95% CI: 31.4-55.7) and 1.7% (95% CI: 0.1-8.1), respectively. Better survival rates were in the palliative surgery group. Multivariate analysis using the Cox proportional hazards model revealed that the initial palliative surgery and the application of biological therapy were statistically significant independent prognostic factors for survival. CONCLUSIONS: Our findings suggest that palliative resectional surgery for the primary tumour in patients with incurable mCRC improves survival. Of course, one can argue that patients in the surgery group were "less problematic". Prospective randomized trials are needed to delineate precisely the role of palliative surgery of the primary tumour in these patients.

Rare types of breast carcinoma.

Breast cancer (BC) is a heterogeneous disease that encompasses several distinct entities with remarkably different characteristics. Histological type is one of important BC characteristics. Histological type is associated with differences in epidemiology, diagnostic issues, clinical course, prognosis. When we talk about BC, ductal and lobular carcinoma is usually what we have in mind. However, the other types that comprise less than 10% of BC are also very important. The rarity of many of these neoplasms does not allow large or randomized studies to define the optimal treatment. Many of the descriptions are from case reports and small series. The aim of this retrospective study was to analyze the data on rare breast cancers, to describe their main characteristics, and to calculate survival rates. We believe that the experience of our institution will contribute to the available data about these rare breast cancers and help in better understanding of this subgroup.

Guidelines for diagnostics and treatment of aromatase inhibitor-induced bone loss in women with breast cancer: a consensus of Lithuanian medical oncologists, radiation oncologists, endocrinologists, and family medicine physicians.

The aim of this article is to inform about cancer treatment-induced bone loss, to identify patients at risk and those that can benefit from bone targeted treatment as well as highlight the importance of the multidisciplinary approach in the bone health in cancer care. Patients with breast cancer treated or intended to be treated with aromatase inhibitors belong to a high-risk group because their fracture risk increases up to 30% due to a significant decrease in bone mineral density within 6-12 months after the start of hormonal treatment. To evaluate bone status and predict risk for fractures, lateral thoracic and lumbar spine X-ray imaging, bone mineral density measurement by dual energy X-ray absorptiometry at the lumbar spine L1-L4 vertebrae and/or hip and fracture risk factors assessment are mandatory tests prior to hormonal treatment. Morbidity and mortality associated with bone loss can be prevented with appropriate screening, lifestyle interventions, and therapy. Algorithm for the management of bone health in breast cancer patients was established in Lithuania to screen patients with increased risk for bone loss and to provide adequate specific osteoporosis treatment.

The significance of reduced glutathione and glutathione S-transferase during chemoradiotherapy of locally advanced cervical cancer.

BACKGROUND AND OBJECTIVE: To determine changes in reduced glutathione (GSH) and glutathione S-transferase (GST) during neoadjuvant chemotherapy followed by concurrent chemoradiation for patients with stage IIB-IIIB cervical cancer, and to evaluate their significance to the efficacy of the treatment. MATERIALS AND METHODS: According to the prospective phase II study protocol, 36 patients with stage IIB-IIIB cervical cancer were enrolled. A short course of intensive weekly neoadjuvant cisplatin and gemcitabine chemotherapy followed by concurrent weekly cisplatin and gemcitabine-based chemoradiation was administered. Blood samples for GSH, GST analysis were collected and analyzed before the start of the treatment, after neoadjuvant chemotherapy, and after the end of the chemoradiation. RESULTS: A statistically significant increase in the concentration of GSH after neoadjuvant chemotherapy was identified. After chemoradiation, values of this rate significantly decreased in contrast with GSH concentration after neoadjuvant chemotherapy in cases of stage IIB, regional metastases negative patients group, patients with a positive response to treatment, and patients who had no progression of the disease during the first 2 years after treatment. Statistically significant changes in GST during the treatment were not identified; the GST concentration after chemoradiation showed a statistically significant difference in GST concentrations in terms of the progression of the disease and disease without progression. CONCLUSIONS: The results suggest that changes in the concentration of GSH during the treatment of locally advanced cervical cancer might be important for the prediction of the efficacy of the treatment. Statistically significant changes in GST concentration levels during the treatment were not observed.

Postmastectomy internal mammary nodal irradiation: a long-term outcome.

BACKGROUND AND OBJECTIVE: The internal mammary lymph nodes (IMN) have been recognized as a potential site of regional breast cancer spread. The aim of this study was to evaluate the impact of internal mammary node radiotherapy (RT) to on clinical outcomes in breast cancer patients treated with mastectomy and postoperative radiation therapy. MATERIALS AND METHODS: This cohort study included 588 patients with breast cancers located in the central and medial quadrants. IMN RT was applied to 320 patients and 268 patients did not receive it IMN RT. Inside the IMN RT group, 165 patients received external beam IMN irradiation (IMN-EB). Mastectomy combined with using Californium-252 neutron source implantation was applied to 155 patients (IMN-BT). Cox proportional hazards modeling was used to determine the influence of IMN RT on clinical outcome. Age, tumor size, lymph nodal status, adjuvant radiotherapy, chemotherapy and hormonal therapy were assessed. RESULTS: IMN-EB resulted in a significant improvement of distant metastasis-free survival, breast cancer-specific survival and overall survival (P=0.033, P=0.037 and P=0.011, respectively). The IMN-EB radiotherapy has a significant impact on event-free survival (HR, 0.67; 95% CI, 0.46-0.91; P=0.043) and breast cancer-specific survival (HR, 0.64; 95% CI, 45-0.91; P=0.013) in patients with moderate-risk (stage T1-2N1). There was no association between IMN RT and clinical outcomes of patients with high-risk disease (stage T3-4N2-3) in any of the study end points. CONCLUSIONS: The effects of IMN-EB radiotherapy on event-free survival and breast cancer-specific survival were benefit for women with moderate-risk breast cancer.

Early prediction of response to cetuximab and radiotherapy by FDG-PET/CT for the treatment of a locoregionally advanced squamous cell carcinoma of the hypopharynx.

Cetuximab (CTX) is used for the concurrent treatment with radiotherapy (RT) in squamous cell carcinoma of head and neck (HNSCC). There are no reliable clinical predictive markers of effectiveness of CTX at yet. We describe the clinical case of patient who received a CTX/RT to cure locoregionally advanced hypopharyngeal SCC. 2-Deoxy-2-[(18)F]fluoro-d-glucose positron emission tomography and computed tomography ((18)FDG-PET/CT) was performed before the treatment and repeated 10 days after CTX induction dose. A repeated (18)FDG-PET/CT scan showed dramatic decrease of metabolic parameters. Patient had a complete response after treatment and is still alive and cured after 5 years.

A randomized hypofractionation dose escalation trial for high risk prostate cancer patients: interim analysis of acute toxicity and quality of life in 124 patients.

BACKGROUND: The α/ß ratio for prostate cancer is postulated being in the range of 0.8 to 2.2 Gy, giving rise to the hypothesis that there may be a therapeutic advantage to hypofractionation. To do so, we carried out a randomized trial comparing hypofractionated and conventionally fractionated image-guided intensity modulated radiotherapy (IG-IMRT) in high-risk prostate cancer. Here, we report on acute toxicity and quality of life (QOL) for the first 124 randomized patients. METHODS: The trial compares 76 Gy in 38 fractions (5 fractions/week) (Arm 1) to 63 Gy in 20 fractions (4 fractions/week) (Arm 2) (IG-IMRT). Prophylactic pelvic lymph node irradiation with 46 Gy in 23 fractions sequentially (Arm 1) and 44 Gy in 20 fractions simultaneously (Arm 2) was applied. All patients had long term androgen deprivation therapy (ADT) started before RT. Both physician-rated acute toxicity and patient-reported QOL using EPIC questionnaire are described. RESULTS: There were no differences in overall maximum acute gastrointestinal (GI) or genitourinary (GU) toxicity. Compared to conventional fractionation (Arm 1), GI and GU toxicity both developed significantly earlier but also disappeared earlier in the Arm 2, reaching significant differences from Arm 1 at week 8 and 9. In multivariate analyses, only parameter shown to be related to increased acute Grade ≥1 GU toxicity was the study Arm 2 (p = 0.049). There were no statistically significant differences of mean EPIC scores in any domain and sub-scales. The clinically relevant decrease (CRD) in EPIC urinary domain was significantly higher in Arm 2 at month 1 with a faster recovery at month 3 as compared to Arm 1. CONCLUSIONS: Hypofractionation at 3.15 Gy per fraction to 63 Gy within 5 weeks was well tolerated. The GI and GU physician-rated acute toxicity both developed earlier but recovered faster using hypofractionation. There was a correlation between acute toxicity and bowel and urinary QOL outcomes. Longer follow-up is needed to determine the significance of these associations with late toxicity.

Second malignancies following conventional or combined ²5²Cf neutron brachytherapy with external beam radiotherapy for breast cancer.

We retrospectively evaluated the risk of second malignancies among 832 patients with inner or central breast cancer treated with conventional external beam schedule (CRT group), or neutron brachytherapy using Californium-252 (²5²Cf) sources and hypofractionated external beam radiotherapy (HRTC group), between 1987 and 1996 at the Institute of Oncology, Vilnius University. Patients were observed until the occurrences of death or development of a second malignancy, or until 31 December 2009, whichever was earlier. Median follow-up time was 10.4 years (range, 1.2-24.1 years). Risk of second primary cancers was quantified using standardized incidence ratios (SIRs). Cox proportional hazards regression models were used to estimate hazard ratios (HRs). There was a significant increase in the risk of second primary cancers compared with the general population (SIR 1.3, 95% CI 1.1-1.5). The observed number of second primary cancers was also higher than expected for breast (SIR 1.8, 95% CI 1.3-2.4) and lung cancer (SIR 3.8, 95% CI 2.0-6.7). For second breast cancer, no raised relative risk was observed during the period ≥10 or more years after radiotherapy. Compared with the CRT group, HRTC patients had a not statistically significant higher risk of breast cancer. Increased relative risks were observed specifically for age at initial diagnosis of <50 years (HR 2.9, 95% CI 1.6-5.2) and for obesity (HR 2.8, 95% CI 1.1-7.2).

Rhabdoid carcinoma of the rectum.

Rhabdoid colonic tumors are very rare lesions with just a few publications describing such neoplasms. Even more unusual for these lesions are their primary rectal locations, with only two brief case reports having been published on that subject to date. We present a case of a composite rhabdoid rectal carcinoma in a 49-year-old male. The tumor behaved very aggressively, with rapid patient demise despite radical surgery and intensive postoperative chemotherapy (FOLFIRI [folinic acid {leucovorin}, fluorouracil {5-fluorouracil}, and irinotecan] and FOLFOX4 [folinic acid {leucovorin}, fluorouraci {5-fluorouracil}, and oxaliplatin]). Pathologic examination was supportive of a rhabdoid carcinoma, with a compatible immunohistochemical profile, demonstrating synchronous expression of vimentin and epithelial markers in the tumor cells. In addition, BRAF V600E gene mutation, together with a wild-type KRAS gene, was identified, and no evidence of microsatellite instability based on MLH1, MSH2, MSH6, and PMS2 immunophenotypes, i.e., no loss of expression for all 4 markers, was observed. Our reported case confirms previously published observations of the clinical aggressiveness and the poor therapeutic response for rhabdoid tumors.

Targeted therapy in patients with non-small cell lung cancer previously treated with chemotherapy.

A case of successful and prolonged treatment of metastatic non-small cell lung cancer with the epidermal growth factor receptor antagonist erlotinib is presented. A never-smoker female was diagnosed with stage IV lung cancer in December 2005. A chest CT scan showed soft tissue mass 35×34 mm in size in the right lung with metastases in the lymph nodes and in the left lung. A biopsy revealed a poorly differentiated adenocarcinoma. The disease showed poor response to the first-line and second-line chemotherapy. Targeted therapy with erlotinib was started in February 2007. The most severe adverse event observed was grade 3 skin rash. The disease was stable until February 2009 when brain metastases were detected. Erlotinib was continued until May 2009 when disease progression in the lungs was confirmed. The patient died due to ongoing disease progression in December 2009. Retrospective genetic analysis of a tumor specimen was performed, and no mutations in EGFR exons 18-21 were detected. The patient had a significant clinical benefit for the period of 24 months. These results are consistent with previous reports in literature that clinical characteristics such as female gender, nonsmoker, adenocarcinoma histology, and severe cutaneous toxicity seem to predict good response to erlotinib. In the present case, erlotinib proved to be effective even in heavily pretreated, chemotherapy-resistant lung adenocarcinoma. So far, no exact predictive biomarkers of erlotinib effectiveness have been determined; and their further analyses are essential.

Prevalence of paraneoplastic rheumatic syndromes and their antibody profile among patients with solid tumours.

The aims of this study were to assess the prevalence of paraneoplastic rheumatic syndromes in a cohort of patients with newly diagnosed solid tumours and to describe their autoimmune profile, comparing it to the controls. Screening questionnaires (3,770) were distributed, and during a three-step study, 94 patients were confirmed to have both paraneoplastic syndrome and oncology diagnoses. Three control groups-patients with undifferentiated arthritis, Raynaud's phenomenon for non-malignant causes and solid tumours only-were designed to compare with the paraneoplastic cases and their immunology profile. The prevalence of paraneoplastic rheumatic syndromes was 2.65% (95% CI 0.21-3.20). The group of patients with arthritis and the group of patients with Raynaud's syndrome were found to prevail among other clinical presentations of paraneoplastic rheumatic syndromes. Both paraneoplastic syndromes were linked to malignancies of the urogenital system. Antinuclear antibodies were found to be similarly frequent in the paraneoplastic arthritis, paraneoplastic Raynaud's phenomenon and the solid tumour groups. No differences were observed when comparing paraneoplastic arthritis and undifferentiated arthritis, except that the patients with paraneoplastic arthritis were older. Comparing paraneoplastic Raynaud's to Raynaud's phenomenon, male preponderance in the paraneoplastic Raynaud's phenomenon group was observed, and the patients were obviously older. Paraneoplastic rheumatic syndromes are rare and more often occur in older patients. Among them, paraneoplastic arthritis and Raynaud's syndrome were the most frequent. The immunology profile does not help in discriminating between arthritis and paraneoplastic arthritis patients and is of limited use in Raynaud's differential diagnosis.