Eduardas Aleknavičius

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

BackgroundThe α/β ratio for prostate cancer is postulated being in the range of 0.8 to 2.2xa0Gy, 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.MethodsThe trial compares 76xa0Gy in 38 fractions (5 fractions/week) (Arm 1) to 63xa0Gy in 20 fractions (4 fractions/week) (Arm 2) (IG-IMRT). Prophylactic pelvic lymph node irradiation with 46xa0Gy in 23 fractions sequentially (Arm 1) and 44xa0Gy 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.ResultsThere 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 (pu2009=u20090.049). 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.ConclusionsHypofractionation at 3.15xa0Gy per fraction to 63xa0Gy within 5xa0weeks 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.

The value of prognostic factors for uterine cervical cancer patients treated with irradiation alone

BackgroundThe aim of our study was to investigate and evaluate the prognostic value of and correlations between preclinical and clinical factors such as the stage of the disease, blood Hb level before treatment, size of cervix and lymph nodes evaluated by CT, age, dose of irradiation and duration of radiotherapy related to overall survival, disease-free survival, local control and metastases-free survival in cervical cancer patients receiving radiotherapy alone.Methods162 patients with International Federation of Gynecology and Obstetrics (FIGO) stage IIA-IIIB cervical carcinoma treated with irradiation were analysed. Univariate and multivariate analyses using the Cox regression model were performed to determine statistical significance of some tumor-related factors.ResultsThe Hb level before treatment showed significant influence on overall survival (p = 0.001), desease free survival (p = 0.040) and local control (p = 0.038). The lymph node status (>10 mm) assessed on CT had impact on overall survival (p = 0,030) and local control (p = 0,036). The dose at point A had impact on disease free survival (p = 0,028) and local control (p = 0,021) and the radiotherapy duration had showed significant influence on overall survival (p = 0,045), disease free survival (p = 0,006) and local control (p = 0,033).ConclusionAnemia is a significant and independent prognostic factor of overall survival, disease-free survival and local control in cervical cancer patients treated with irradiation. The size of lymph nodes in CT is an independent prognostic factor for overall survival and local control in cervical cancer patients. The size of cervix uteri evaluated by CT has no prognostic significance in cervical cancer patients treated with radiotherapy. The prognostic value of FIGO stage of cervical cancer is influenced by other factors, analyzed in this study and is not an independent prognostic factor.

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

Introduction nTo 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).

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, Raynauds 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 Raynauds 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 Raynauds 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 Raynauds to Raynauds phenomenon, male preponderance in the paraneoplastic Raynauds 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 Raynauds 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 Raynauds differential diagnosis.

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.

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.

Triple negative breast cancer: adjuvant chemotherapy effect on survival

PURPOSEnThe purpose of this study was to evaluate the overall survival of patients with triple negative breast cancer and the impact of different adjuvant chemotherapy regimens on survival.nnnMATERIAL/METHODSnThe study group consisted of 99 breast cancer patients with immunohistochemically confirmed triple negative breast cancer. The impact of various factors as well as the impact of different chemotherapy regimens on survival was evaluated.nnnRESULTSnThe overall survival of breast cancer patients was 97.0% (95% CI 90.9-99.0), 84.9% (95% CI 76.1-90.6) and 66.5% (95% CI 55.5-75.3) 10, 30 and 60 months after diagnosis, respectively. Univariate analysis demonstrated that the following were significant risk factors for breast cancer patients survival: patients age, stage of disease, tumour size, lymph node status, type of surgery and chemotherapy. Better survival was related to younger patients age, smaller tumour size, lower stage of disease, no lymph nodes involvement. Survival rates were higher among patients who received adjuvant chemotherapy and underwent quadrantectomy. In the multivariate statistical analysis the significant independent prognostic variables influencing survival were lymph node status and adjuvant chemotherapy. Survival rates of the patients, who received adjuvant anthracycline containing chemotherapy were higher, than those in non-anthracycline containing treatment group, but the difference was not statistically significant.nnnCONCLUSIONnPatients who had lymph node status N2-3 and those who did not receive adjuvant chemotherapy showed worse prognosis and survival than other patients. The impact of chemotherapy type (anthracycline containing or non-anthracycline containing) on patients survival was not statistically significant.

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

BACKGROUND AND OBJECTIVEnTo 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.nnnMATERIALS AND METHODSnAccording 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.nnnRESULTSnA 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.nnnCONCLUSIONSnThe 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.

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

BackgroundMiRNAs 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.MethodsFifty-four patients with a first-time diagnosed CRC receiving FOLFOXxa0±xa0Bevacizumab 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.ResultsBoth 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, pxa0=xa00.011, and 0.404 and 0.620 respectively for miRNA-625-3p, pxa0=xa00.036). 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, pxa0=xa00.037). Progression free survival was significantly lower in patients with high miRNA-148a expression (6 and 9xa0months respectively, pxa0=xa00.033), but there were no significant differences in PFS for miRNA-625-3p and in overall survival for both miRNAs.ConclusionsThere 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.

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.