Maria Tolia

Male breast carcinoma: epidemiology, risk factors and current therapeutic approaches.

Male breast cancer is a very rare disease with an incidence of about 0.5-1% comparing with the one of female breast cancer but relatively little is known about its cause. Treatment strategies for breast cancer in males are derived from studies performed among females. The probable reasons behind the frequent, late diagnoses presented at stages III or IV might be the lack of awareness. The rarity of the disease precludes large prospective randomized clinical trials. This study reviews male breast cancer and its risk factors, recommendations for diagnosis and the management of patients with male breast cancer.

Hypofractionated Radiotherapy in Non Small Cell Lung Cancer: A Review of the Current Literature

Hypofractionated irradiation has an established role in the palliative treatment of patients with advanced medically inoperable non - small cell lung cancer (NSCLC ) and poor performance status. Also hypofractionated radiotherapy merits careful consideration in the curative treatment of patients with Stage I and II disease using contemporary technology. The biological effect of radiation on tumours is increased as the overall treatment time is shortened. Hypofractionated field radiotherapy offers acceptable palliation with minimal toxicity. The rates of palliation for hemoptysis , chest pain , cough and dyspnea reported from studies with very short regimen ( 8,5 Gy x 2 ), are comparable to those of other trials that used more protracted palliative treatment . The observed toxicity is minimal, and no cases of oesophagitis, pneumonitis, or radiation myelopathy developed. The minimal toxicity is a reflection of both the low biologic total dose and the tight RT design. Therefore the radiation side effects appear to be related to the technique of RT delivered rather than the patients PS. Hence, widely believed dogmas concerning the tolerance of critical structures to conventionally fractionated doses, such as the dose-volume effect, total dose, and time (latency) dependency, has to be re-evaluated for hypofractionated radiation therapy. As well there is data suggesting that the small stages I - II NSCLC are likely to benefit from hypofractionated regimens too. Hypofractionated stereotactic radiotherapy is a new technically complex approach to the treatment of early-stage nonsmall cell lung cancer. It is capable to deliver much higher doses to the cancer than is possible with standard techniques, and as a result, rates of tumour control are high and similar to what can be achieved by surgical resection. Refinements of technique and dose as well as randomized data are required before stereotactic radiotherapy can be endorsed as a standard of care for patients with inoperable peripherally located T1 non small cell lung cancer. A clear advantage of the very short hypofractionated palliative regimen is that it allows patients with a short expected survival time to spend more of their remaining time away from the hospital.

Evaluation of Acute Toxicity and Symptoms Palliation in a Hypofractionated Weekly Schedule of External Radiotherapy for Elderly Patients with Muscular Invasive Bladder Cancer

AIM To evaluate acute toxicity and symptoms palliation of a weekly hypofractionated 3DCRT schedule as radical treatment in elderly patients with organ confined bladder cancer cT1-2N0. MATERIALS AND METHODS Between February 2005 and June 2011, 58 prospectively selected patients diagnosed with organ confined bladder cancer were treated with external 3DCRT (4-field arrangement). All candidates were medically inoperable, with poor performance status, and with age ranged from 75 to 88 years (median 78). A dose of 36 Gy in 6 weekly fractions was prescribed. The primary study endpoints were the evaluation of haematuria, dysuria, frequency and pain palliation as well as the acute toxicity according to the RTOG/EORTC scale: an assessment was performed at baseline, during and 3 months after radiotherapy, while the maximum reported score was taken into account. RESULTS The gastrointestinal acute toxicities were 13/58 (22.4%) and 5/58 (5.6%), for grade I and II respectively. The genitourinary acute toxicities were 19/58 (32.7%) and 10/58 (17.2%), for grade I and II respectively. In terms of clinical outcome, 55/58 patients (94.8%) reported palliation of haematuria, while 19 out of 58 reported no change in frequency and dysuria. All patients reported significant improvement (P < 0.01) for pain, concerning the visual analogue score before and after radiotherapy. The median progression free survival was 14 months. CONCLUSIONS The incidence of patient-reported acute toxicity following weekly hypofractionated external 3DCRT is low while the symptom palliation compares very favorably with other reported outcomes.

Abnormal DNA methylation as a cell-free circulating DNA biomarker for colorectal cancer detection: A review of literature

Colorectal cancer (CRC) is one of the most prevalent malignancies in the world. CRC-associated morbidity and mortality is continuously increasing, in part due to a lack of early detection. The existing screening tools such as colonoscopy, are invasive and yet high cost, affecting the willingness of patients to participate in screening programs. In recent years, evidence is accumulating that the interaction of aberrant genetic and epigenetic modifications is the cornerstone for the CRC development and progression by alternating the function of tumor suppressor genes, DNA repair genes and oncogenes of colonic cells. Apart from the understanding of the underlying mechanism(s) of carcinogenesis, the aforementioned interaction has also allowed identification of clinical biomarkers, especially epigenetic, for the early detection and prognosis of cancer patients. One of the ways to detect these epigenetic biomarkers is the cell-free circulating DNA (circDNA), a blood-based cancer diagnostic test, mainly focusing in the molecular alterations found in tumor cells, such as DNA mutations and DNA methylation. In this brief review, we epitomize the current knowledge on the research in circDNA biomarkers - mainly focusing on DNA methylation - as potential blood-based tests for early detection of colorectal cancer and the challenges for validation and globally implementation of this emergent technology.

Is there any potential clinical impact of serum phosphorus and magnesium in patients with lung cancer at first diagnosis? A multi-institutional study.

BACKGROUND The aim of the study was to determine whether the expression of baseline phosphorus (P) and magnesium (Mg) levels were prognostic in terms of stage and overall survival (OS) in newly diagnosed non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC) patients. MATERIALS AND METHODS Retrospectively, 130 patients were selected at the time of diagnosis oflung cancer (100 with NSCLC and 30 with SCLC), before the initialization of any chemo-radiotherapy. The median age was 67 (range 29-92). IA, IB, IIA, IIB, IIIA, IIIB and IV stages were present in 3, 4, 19, 6, 25, 8, and 65 patients, respectively. After centrifugation, the levels of serum P and Mg were measured using the nephelometric method/ photometry and evaluated before any type of treatment. RESULTS Higher than normal levels of P were found in 127/130 patients, while only four patients had elevated Mg serum values. In terms of Spearman test, higher P serum values correlated with either stage (rho=- 0.334, p<0.001) or OS (rho=-0.212, p=0.016). Additionally, a significant negative correlation of Mg serum levels was found with stage of disease (rho=-0.135, P=0.042). On multivariate cox-regression survival analysis, only stage (p<0.01), performance status (p<0.01) and P serum (p=0.045) showed a significant prognostic value. CONCLUSIONS Our study indicated that pre-treatment P serum levels in lung cancer patients are higher than the normal range. Moreover, P and Mg serum levels are predictive of stage of disease. Along with stage and performance status, the P serum levels had also a significant impact on survival. This information may be important for stratifying patients to specific treatment protocols or intensifying their therapies. However, larger series are now needed to confirm our results.

Three-dimensional conformal radiotherapy for hepatocellular carcinoma in patients unfit for resection, ablation, or chemotherapy: a retrospective study.

Purpose. The purpose is to evaluate the feasibility, efficacy, and the toxicity of three-dimensional conformal radiotherapy (3DCRT) in patients with advanced hepatocelluar carcinoma (HCC) and inferior vena cava tumor thrombosis (IVCTT). Methods. Between 2007 and 2012, in a retrospective way, 9 patients (median age 69 years) with advanced HCC and IVCTT unfit for surgery, radiofrequency ablation, embolization, or chemotherapy were treated with three-dimensional conformal radiotherapy (3DCRT). The radiotherapy volume included both primary tumor and IVTT. The radiotherapy schedule was 50–52 Gy in 2 Gy fractions. Overall survival (OS), response to radiotherapy, visual analogue scale (VAS), and toxicity were assessed. Results. All patients demonstrated a response rate up to 60%. During radiotherapy, 3 patients experienced grade 1 nausea/vomit toxicity. All patients demonstrated an elevation of the liver enzymes (3 patients with grade 1 and 6 patients with grade 2). The mean VAS-score was decreased from 6.11 to 3.11, while the median overall survival was 24 months. Conclusion. 3DCRT achieves a very high local control rate and is suitable for patients with HCC and IVTT, while the documented radiation induced toxicity is moderate. It can be recommended for palliation in patients unable to undergo curative therapies.

Prognostic Significance of Serum Inflammatory Response Markers in Newly Diagnosed Non-Small Cell Lung Cancer before Chemoirradiation

Purpose. To identify whether the serums baseline C-reactive protein (CRP) and albumin (Alb) levels related to clinicopathological parameters and overall survival (OS) in non-small cell lung cancer (NSCLC). Methods. In total, 100 consecutive patients (mean age = 68.38 ± 10.85 years) that underwent chemoradiotherapy were studied. Measurements of CRP and Alb were performed before any treatment. Results. Serum CRP levels were significantly associated with histological grade (P < 0.001), TNM stage (P < 0.001), PS (P = 0.009), and Alb (P < 0.001). Additionally CRP and Alb levels were found significantly associated with overall survival in univariate analysis (log-rank test, P < 0.001 and P = 0.002, resp.) and CRP remained significant after controlling for age, alcohol, performance status, and TNM stage, whereas albumin showed a borderline effect on the hazard rate (P = 0.052). Conclusions. CRP and Alb are both promising biomarkers in identification of NSCLC patients with poor prognosis and form a possible target for intensifying their therapies.

Malignant central nervous system tumors among adolescents and young adults (15‐39 years old) in 14 Southern‐Eastern European registries and the US Surveillance, Epidemiology, and End Results program: Mortality and survival patterns

Unique features and worse outcomes have been reported for cancers among adolescents and young adults (AYAs; 15‐39 years old). The aim of this study was to explore the mortality and survival patterns of malignant central nervous system (CNS) tumors among AYAs in Southern‐Eastern Europe (SEE) in comparison with the US Surveillance, Epidemiology, and End Results (SEER) program.

Prognostic Value of MRS Metabolites in Postoperative Irradiated High Grade Gliomas

Purpose. We studied the prognostic significance of Magnetic Resonance Spectroscopy (MRS) in operated high grade gliomas. Materials and Methods. Twelve patients were treated with radiotherapy and Temozolomide. The MRS data were taken four weeks after operation (before radiotherapy) and every six months after the completion of RT. The N-acetyl aspartate, choline, creatine, and myo-inositol parameters were quantified, analyzed, and correlated to recurrence-free survival (RFS). Results. The median RFS was 26.06 months. RFS was significantly worse in elderly patients (P = 0.001) along with the higher choline/creatine ratios at either baseline (P = 0.003) or six months post Radiotherapy (P = 0.042). Median RFS was 23 months in high choline/creatine levels ≥2 at 6 months after radiotherapy and 11 months for those with <2 choline/creatine levels. There was a significant correlation of maximum difference of choline/creatine ratio with RFS (rho = 0.64, P = 0.045). Conclusion. Age and choline/creatine ratio are strong independent prognostic factors in high grade gliomas.

Adjuvant chemotherapy and acute toxicity in hypofractionated radiotherapy for early breast cancer

AIM To evaluate the effect of chemotherapy to the acute toxicity of a hypofractionated radiotherapy (HFRT) schedule for breast cancer. METHODS We retrospectively analyzed 116 breast cancer patients with T1, 2N0Mx. The patients received 3-D conformal radiotherapy with a total physical dose of 50.54 Gy or 53.2 Gy in 19 or 20 fractions according to stage, over 23-24 d. The last three to four fractions were delivered as a sequential tumor boost. All patients were monitored for acute skin toxicity according to the European Organization for Research and Treatment of Cancer/Radiation Therapy Oncology Group criteria. The maximum monitored value was taken as the final grading score. Multivariate analysis was performed for the contribution of age, chemotherapy and 19 vs 20 fractions to the radiation acute skin toxicity. RESULTS The acute radiation induced skin toxicity was as following: grade I 27.6%, grade II 7.8% and grade III 2.6%. No significant correlation was noted between toxicity grading and chemotherapy (P = 0.154, χ(2) test). The mean values of acute toxicity score in terms of chemotherapy or not, were 0.64 and 0.46 respectively (P = 0.109, Mann Whitney test). No significant correlation was also noted between acute skin toxicity and radiotherapy fractions (P = 0.47, χ(2) test). According to univariate analysis, only chemotherapy contributed significantly to the development of acute skin toxicity but with a critical value of P = 0.05. However, in multivariate analysis, chemotherapy lost its statistical significance. None of the patients during the 2-years of follow-up presented any locoregional relapse. CONCLUSION There is no clear evidence that chemotherapy has an impact to acute skin toxicity after an HFRT schedule. A randomized trial is needed for definite conclusions.