Konstantin Lavrenkov

Effective avoidance of a functional spect-perfused lung using intensity modulated radiotherapy (IMRT) for non-small cell lung cancer (NSCLC): An update of a planning study

IMRT and 3-dimensional conformal radiotherapy (3-DCRT) plans of 25 patients with non-small cell lung (NSCLC) were compared in terms of planning target volume (PTV) coverage and sparing of functional lung (FL) defined by a SPECT perfusion scan. IMRT resulted in significant reduction of functional V(20) and mean lung dose in stage III patients with inhomogeneous hypoperfusion. If the dose to FL is shown to be the determinant of lung toxicity, IMRT would allow for effective dose escalation by specific avoidance of functional lung.

A Study of Inflammation-Based Predictors of Tumor Response to Neoadjuvant Chemoradiotherapy for Locally Advanced Rectal Cancer

Background: The ability of pretreatment laboratory markers of acute-phase inflammatory reactions like serum albumin level (SAL), hemoglobin (Hb), and absolute blood cell counts to predict complete pathological response (CPR) to neoadjuvant chemoradiotherapy (NACRT) in patients with locally advanced rectal cancer (LARC) has not yet been fully studied. Methods: We retrospectively examined the relation between SAL, Hb and absolute blood cell counts, and CPR rates in 140 LARC patients treated with NACRT. Results: Univariate analysis showed a significantly higher probability of CPR to NACRT in patients with clinical stage (CS) III LARC who had SAL >3.5 mg/dl (OR = 2.39; p = 0.04) and a neutrophil-to-lymphocyte ratio (NLR) value <5 (OR = 2.86; p = 0.03). The relation of CPR with SAL (OR = 2.11; p = 0.048) and NLR (OR = 2.54; p = 0.04) was confirmed by multivariate analysis in the same subset of patients. None of the parameters studied predicted CPR in patients with CS II disease. Patients who achieved CPR to NACRT had a higher probability of 5-year overall survival (HR 0.48; p = 0.01) and 5-year disease-free survival (HR 0.33; p = 0.003). Conclusions: Our data indicate that SAL >3.5 mg/dl and NLR <5 may be positively related to CPR after NACRT in patients with CS III LARC. Hypoalbuminemia and a high NLR may be considered an indication for a more aggressive approach to NACRT and postoperative adjuvant chemotherapy in this subset of patients. This hypothesis requires confirmation in a randomized study.

Low dose palliative radiotherapy for splenomegaly in hematologic disorders

Abstract Splenomegaly (SM) is a common complication in hematologic disorders often associated with hypersplenism, and may cause pain, epigastric discomfort and variable systemic effects due to cytopenias. We retrospectively evaluated the results of palliative splenic irradiation (PSI) in terms of symptomatic relief in patients with hematologic disorders. In 1998–2006, 32 patients with hematologic disorders (median age 57) received 52 courses of PSI for SM. Twenty-one patients (66%) were diagnosed with myeloproliferative disorders (MPD), five patients (16%) had malignant lymphoma (ML), five patients (16%) had chronic lymphocytic leukemia (CLL) and one patient (3%) had hairy cell leukemia. Splenomegaly was accompanied by pain, anemia, thrombocytopenia and cachexia. Radiation therapy to the entire spleen was delivered by two parallel opposed fields using 0.5 Gy daily fractions given 5 days per week to a total dose of 6–10 Gy. PSI resulted in splenic size reduction in 78.8%, improvement of anemia in 75% and improvement of thrombocytopenia in 63.5% of PSI courses. The median survival (MS) of patients with MPD, CLL and ML was 45, 10 and 5 months, respectively. The MS of responders to PSI versus non-responders was 45 and 16 months, respectively (hazard ratio 0.17; p = 0.03; 95% confidence interval 0.035–0.84). In our hands, low dose PSI provided effective palliation for patients with hematologic disorders with SM. Splenic re-irradiation was feasible without excessive toxicity.

Primary Malignant Lymphoma of the Prostate – A Report of Three Cases

We report the clinical, morphological and immunohistochemical findings in 3 cases of primary non-Hodgkins malignant lymphoma of the prostate. After treatment with doxorubicin-based chemotherapy, two patients achieved a complete remission, and 1 died of infective endocarditis three months after diagnosis. Until a consensus has been reached regarding the optimal treatment of prostatic lymphoma, therapy should be determined by the histologic type diagnosed and stage of the lymphoma.

A combined pretreatment of 1,25-dihydroxyvitamin D3 and sodium valproate enhances the damaging effect of ionizing radiation on prostate cancer cells ☆

Radiotherapy is one of the curative treatment options for prostate cancer (PCa). However, effective doses of ionizing radiation (IR) have a high risk of side effects. To increase sensitivity of PCa to IR we pretreated human androgen-refractory DU145 PCa cells with a combination of sodium valproate (VPA), a well-tolerated drug with histone deacetylases inhibiting activity, and 1,25-dihydroxyvitamin D3, 1,25(OH)2D3, the active metabolite of vitamin D, a well known anticancer agent. The results show that irradiation (4Gy) of DU145 PCa cells pretreated with a combination of 1 mM VPA and 100 nM 1,25(OH)2D3 efficiently suppressed (87.9%) PCa cell proliferation. IR after combined pretreatment resulted in increased DNA double-strand breaks expressed as levels of phosphorylated histone H2A.X, compared with non-treated cells the increase was 58.1% in pretreated cells and 11.8% in non-pretreated cells (p<0.002). Combined pretreatment enhanced IR-induced activation of DNA damage checkpoint kinase Chk2, 39.0% in pretreated cells compared to 23.8% in non-pretreated cells (p<0.05). These molecular changes led to DNA replication blockade, S-phase cell-cycle arrest and enhanced apoptosis. Cumulatively, the results indicate that combined pretreatment with VPA and 1,25(OH)2D3 followed by IR is a highly effective treatment for human PCa cells. This observation may have important implications for reducing doses of radiation administered to cancer patients thus limiting the severity of side effects.

Prospective study of empiric monotherapy with ceftazidime for low-risk grade IV febrile neutropenia after cytotoxic chemotherapy in cancer patients

Purpose: It was the aim of this study to evaluate the results of a prospective study in a single medical center using ceftazidime monotherapy in cancer patients with chemotherapy-induced grade IV febrile neutropenia and a low risk for gram-negative bacteremia. Subjects and Methods: Thirty-eight patients were admitted with low-risk grade IV febrile neutropenia after chemotherapy for solid tumors. The median patient age was 57 years (range 18–74). Sixteen patients (42%) developed febrile neutropenia after the first cycle of current chemotherapy line, 9 patients (24%) received 2–3 cycles and 13 patients (34%) received more than 3 chemotherapy cycles before manifesting febrile neutropenia. Five patients were treated with prophylactic granulocyte colony-stimulating factor commenced 24 h after completion of the chemotherapy cycle. Empiric monotherapy with intravenous ceftazidime was started on admission and administered 2 g every 8 h. Results: The mean polymorphic nuclear cell count on admission was 231 cells/mm3. Ceftazidime therapy was well tolerated. Twenty-five (66%) patients responded with clinical improvement and complete resolution of fever within 48 h after initiation of ceftazidime therapy. Thirty-two (84%) patients were afebrile after 72 h of therapy. Thirty-three patients (87%) remained on unmodified ceftazidime therapy throughout their hospitalization. Five patients (13%) subsequently required modification of the treatment regimen for various reasons. Mean duration of fever and neutropenia were 2 (1–10) days and 4 (1–11) days, respectively. None of the patients discontinued therapy because of adverse effects. No positive blood cultures were obtained. No events of septic shock were observed. Mean duration of hospitalization was 6 days (range 3–12). Conclusion: In our series, monotherapy with intravenous ceftazidime appears safe and effective in cancer patients with low-risk grade IV febrile neutropenia after cytotoxic chemotherapy and may appreciably reduce antibiotics costs.

Pulmonary Sarcoidosis Mimicking Metastases in Breast Cancer Patients

Accessible online at: www.karger.com/onk Fax +49 761 4 52 07 14 E-mail Information@Karger.de www.karger.com of right breast (T1b, N0/27, M0). Adjuvant therapy consisted of 4 cycles of intravenous doxorubicin 60 mg/m2 and cyclophosphamide 600 mg/m2 repeated every 4 weeks, followed by lumpectomy, 50.4 Gy radiotherapy to the breast and daily tamoxifen 20 mg planned for 5 years. 4 years after initial diagnosis she presented with weight loss of 7 kg within 3 months. Diagnostic CT scan showed mediastinal lymphoadenopathy and bilateral pulmonary interstitial lesions. Trans-bronchial biopsy was performed and pathologic examination was consistent with sarcoidosis. The patient was not treated because of allergy to steroids. CT scans repeated in 4-months intervals for the last 2 years demonstrated stable appearance of mediastinal and pulmonary lesions. Introduction