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Ymittos Athens, Greece

Fragkandrea I.,The Royal Marsden Hospital | Kouloulias V.,Attikon Hospital | Mavridis P.,Hippokrateion Hospital | Zettos A.,Lung Unit | And 5 more authors.

Background: Hypofractionated Radiotherapy (RT) regimens for breast cancer, although reduce cost and time for patients and health care systems, could have a negative impact on normal underlying lung tissue. We studied and compared lung function and the post-RT radiological changes using High-Resolution Computed Tomography (HRCT) in early breast cancer patients, treated with 3-Dimentional conformal whole breast radiotherapy (WBRT) using either conventional or hypofractionated regime. Patients and Methods: Between 2008 and 2009, 61 early breast cancer patients (T1-2N0M0) were randomised into two groups. Group A (n=31) received standard radiotherapy with 50Gy/25f/5w plus boost 10Gy/5f/1w to tumour bed. Group B (n=30) received 43.2Gy/16f/22d plus boost 10Gy/5f/1w to tumour bed. Patients of both groups were subjected to dynamic lung testing, using spirometry and gas diffusion tests on Day 0 (D0, before RT), during RT and after completion of RT at 3 and 6 months. HRCT scans were performed in all patients at baseline, and 3,6,12 months after completion of RT. Respiratory symptoms were recorded at 3 and 6 months post completion of RT. Dosimetric factors, such as Central Lung Dose (CLD), lung Volume receiving more 20 Gy (V20), D25 and Mean Lung Dose (MLD) were calculated for all patients. Results: At 3 months after RT, the pulmonary changes were classified at HRCT as follows: 91.8 % were Grade 0, 8.19 % Grade 1, and 0 % Grade 2. At 6 months, 86.98 % were Grade 0, 11.47 % Grade 1, and 1.6 % Grade 2. At 12 months, 88.52 % were Grade 0, 9.19 % Grade 1 and 3.27% Grade 2. Univariate analysis showed strong association between radiation pneumonitis, age and all dosimetric parameters. There was no association between fractionation type and incidence of RN. FEV1, FVC, FEV 25, FEV 50 and DLCO showed no statistically significant reduction in both treatment groups in 3 and 6 months following completion of RT, compared to baseline. Multivariate analysis showed no relation between HRCT findings and other variables (age, smoking, chemotherapy, hormonotherapy, V20) Conclusion: Lung toxicity, as assessed with HRCT and PFTs, was minimal in both treatment arms and our results are in consistency with other published data. Hypofractionated RT was a safe modality and well tolerated by the majority of the patients. Longer follow-up is required for robust assessment of incidence of late lung fibrosis in our series. Source

Dimopoulos M.A.,National and Kapodistrian University of Athens | Kastritis E.,National and Kapodistrian University of Athens | Delimpasi S.,Evangelismos Hospital | Katodritou E.,Theagenion Cancer Center | And 15 more authors.
European Journal of Haematology

Background: Multiple myeloma (MM) affects mainly elderly persons and because the population of octogenarians increases, it is common to treat patients ≥80 years of age. These patients are often not included in clinical trials; thus, there is limited data on their characteristics and treatment outcome. Patients and methods: We retrospectively analyzed 682 consecutive, unselected patients with newly diagnosed symptomatic myeloma who started treatment between January 1, 2003 and December 31, 2010. Results: We identified 155 (23%) patients ≥ 80 years of age. Compared to patients <80 years, octogenarians had poorer performance status (P < 0.001), anemia (P = 0.006), low serum albumin (P = 0.001), and advanced ISS (P < 0.001). The median survival of patients ≥80 years was 22 months, and 14% died within 2 months from therapy initiation. The median survival of patients ≥80 years who received upfront novel agents was 26 vs. 17 months for those who did not. ECOG performance status ≤1 and frontline use of novel agents were independently associated with better survival. Response to first-line therapy was associated with improved survival (29 vs. 16 months, P = 0.017). Conclusions: Patients ≥80 years of age present with features of advanced myeloma and impaired performance status. The addition of novel agents may improve their outcome, but careful assessment and prospective clinical trials targeting the population of elderly patients are needed. © 2012 John Wiley & Sons A/S. Source

Tolia M.,National and Kapodistrian University of Athens | Zygogianni A.,National and Kapodistrian University of Athens | Kouvaris J.R.,National and Kapodistrian University of Athens | Meristoudis C.,National and Kapodistrian University of Athens | And 13 more authors.
Anticancer Research

The present review aims at providing an assessment of the clinical significance of Biphosphonates (BPs) in the treatment of patients with cancer. Materials and Methods: A systematic literature review was performed based on database search in PubMed/Medline and included articles up to August 2013. Results: BPs can reduce, delay, and prevent complications related to bone metastases. They improve mobility, functionality, pain, and quality of life. They limit survival of any inactive cancer cells in the microenvironment of the bone marrow, contributing to their death from anti-neoplastic treatments. Moreover, they limit and delay bone morbidity due to osteoporosis related to hormonotherapy in breast and prostate cancer. Finally, benefits can be derived from the combination of BPs with radiotherapy in bone density, recalcification, opioid use, and patient's quality of life and performance status. Conclusion: The contribution of BPs in the course of certain neoplasms is preventive and synergistic to other treatments. © 2014, International Institute of Anticancer Research. All rights reserved. Source

Terpos E.,National and Kapodistrian University of Athens | Christoulas D.,251 General Air Force Hospital | Kastritis E.,National and Kapodistrian University of Athens | Katodritou E.,Theagenio Cancer Hospital | And 10 more authors.
American Journal of Hematology

The combination of lenalidomide plus dexamethasone (RD) is very effective for patients with relapsed/refractory myeloma. However, the effect of RD on bone metabolism has not been previously evaluated in these patients. To address this issue, we initially performed a retrospective study in 106 consecutive patients with relapsed or refractory myeloma who received RD. We measured the following bone indices on Cycle 1/Day 1 and then on Cycles 3 and 6/Day 28: dickkopf-1 (Dkk-1), sRANKL, osteoprotegerin (OPG), bone resorption markers (C-telopeptide of collagen type-I, CTX and TRACP-5b) and bone formation markers (bone-specific alkaline phosphatase-bALP and osteocalcin). RD produced a reduction of CTX only in responders, with no effect on bone formation. To validate these results, we then evaluated prospectively 99 patients who received either RD (n=50) or VRD (bortezomib + RD, n=49). RD reduced CTX, mainly in responders but showed no effect on bone formation, confirming the result of the retrospective study. However, the addition of bortezomib to RD (VRD arm) reduced Dkk-1, sRANKL/OPG, and CTX, while it increased bALP and OC after six cycles of therapy. These changes were irrespective of treatment response, which was similar between treatment arms. No skeletal-related events were observed in the VRD arm while two, nonresponding patients treated with RD developed a vertebral fracture. We conclude that RD reduces bone resorption only in responding patients with relapsed/refractory myeloma but has no effect on bone formation. Combination with bortezomib, which enhances bone formation, seems to be preferred for the management of myeloma patients with osteolytic disease. © 2013 Wiley Periodicals, Inc. Source

Kastritis E.,National and Kapodistrian University of Athens | Zagouri F.,National and Kapodistrian University of Athens | Symeonidis A.,University of Patras | Roussou M.,National and Kapodistrian University of Athens | And 19 more authors.

Suppression of uninvolved immunoglobulins is common in multiple myeloma (MM) but the prognostic significance of this phenomenon has not been assessed. We evaluated the prognostic significance of the preservation of uninvolved immunoglobulins in 1755 consecutive, unselected, patients with newly diagnosed, symptomatic MM with pre-therapy immunoglobulin levels measured by nephelometry. Suppression of at least one uninvolved immunoglobulin was observed in 87% of patients and was more common in patients with immunoglobulin A myeloma, those aged over 65 years, in patients with advanced-International Staging System (ISS) stage, extensive-bone marrow infiltration, anemia, low platelet counts, high levels of serum M-monoclonal protein or renal dysfunction. Patients with preserved immunoglobulins had a better survival than patients with suppressed immunoglobulins (median survival 55 vs 41.5 months, P<0.001). In multivariate analysis, preservation of uninvolved immunoglobulins was independently associated with better survival (hazard ratio: 0.781, 95% confidence interval: 0.618-0.987, P=0.039); irrespective of the treatment. In a subset of 500 patients, which were strictly followed for disease progression, preservation of uninvolved immunoglobulins was associated with a significantly longer progression-free survival (60 vs 25 months, P<0.001), independently of other common prognostic factors. In conclusion, preservation of uninvolved immunoglobulins in newly diagnosed patients with symptomatic MM was independently associated with long term disease control and improved survival.Leukemia advance online publication, 11 April 2014; doi:10.1038/leu.2014.110. Source

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