Concurrent hyperfractionated radiotherapy and low-dose daily carboplatin/paclitaxel in patients with early-stage (I/II) non-small-cell lung cancer: long-term results of a phase II study.

PURPOSE: Feasibility and activity of concurrent hyperfractionated radiotherapy (Hfx RT) and low-dose, daily carboplatin and paclitaxel were investigated in patients with early-stage (I/II) non-small-cell lung cancer in a phase II study. PATIENTS AND METHODS: Fifty-six patients started their treatment on day 1 with 30 mg/m2 of paclitaxel. Hfx RT using 1.3 Gy bid to a total dose of 67.6 Gy and concurrent low-dose daily carboplatin 25 mg/m2 and paclitaxel 10 mg/m2, both given Mondays through Fridays during the RT course, started from the second day. RESULTS: There were 29 complete responses (52%) and 15 partial responses (27%), and 12 patients (21%), experienced stable disease. The median survival time was 35 months, and 3- and 5-year survival rates were 50% and 36%, respectively. The median time to local progression has not been achieved, but 3- and 5-year local progression-free survival rates were 56% and 54%, respectively. The median time to distant metastasis has not been achieved, but 3- and 5- year distant metastasis-free survival rates were 61% and 61%, respectively. The median and 5-year cause-specific survivals were 39 months and 43%, respectively. Acute high-grade (> 3) toxicity was hematologic (22%), esophageal (7%), or bronchopulmonary (7%). No grade 5 toxicity was observed. Late high-grade toxicity was rarely observed (total, 10%). CONCLUSION: Hfx RT and concurrent low-dose daily carboplatin/paclitaxel was feasible with low toxicity and effective in patients with stage I/II non-small-cell lung cancer. It should continue to be investigated for this disease.

Concurrent hyperfractionated radiotherapy and low-dose daily carboplatin and paclitaxel in patients with stage III non-small-cell lung cancer: long-term results of a phase II study.

PURPOSE: To investigate the feasibility and activity of hyperfractionated radiation therapy (Hfx RT) and concurrent chemotherapy (CT) consisting of low-dose, daily carboplatin and paclitaxel in patients with stage III non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Sixty-four patients started their treatment on day 1 with 30 mg/m(2) of paclitaxel administered by 1-hour infusion. Hfx RT began on day 2 using 1.3 Gy bid to a total dose of 67.6 Gy and concurrent low-dose daily CT consisting of 25 mg/m(2) of carboplatin and 10 mg/m(2) of paclitaxel, both given Mondays to Fridays during RT course. RESULTS: Objective response rate was 83% and included complete response in 27 patients (42%) and partial response in 26 patients (41%). Ten patients (16%) had stable disease, whereas only one patient (2%) had progressive disease. The median survival time was 28 months, and 3- and 5-year survival rates were 37% and 26%, respectively. The median time to local progression was 26 months, and 3- and 5-year local progression-free survival rates were 37% and 33%, respectively. The median time to distant metastasis was 25 months, and 3- and 5- year distant metastasis-free survival rates were 37% and 31%, respectively. Acute high-grade (>/= grade 3) toxicity was hematologic (25%), esophageal (17%), bronchopulmonary (13%), and skin (9%). Late high-grade toxicity was infrequent. CONCLUSION: This combined Hfx RT/TC regimen produced results that are among the best ever reported and warrants further study in a prospective randomized fashion.

Pretreatment prognostic factors in patients with early-stage (I/II) non-small-cell lung cancer treated with hyperfractionated radiation therapy alone.

PURPOSE: To investigate influence of various pretreatment prognostic factors in patients with early stage (I/II) non-small-cell lung cancer (NSCLC) treated with hyperfractionated radiation therapy alone. PATIENTS AND METHODS: One hundred and sixteen patients were treated with tumor doses of 69.6 Gy, 1.2-Gy, twice-daily fractionation. There were 49 patients with Stage I and 67 patients with Stage II. Eighty patients had Karnofsky performance status (KPS) 90-100 and 95 patients had <5% weight loss. Peripheral tumors were observed in 57 patients. Squamous histology was observed in 70 patients and the majority of patients had concomitant disease (n=72). RESULTS: The median survival time for all patients was 29 months; 5-year survival was 29%. The median time to local progression and the distant metastasis were not achieved, whereas 5-year local progression-free and distant metastasis-free survivals were 50% and 72%, respectively. Multivariate analysis identified KPS, weight loss, location, histology, and the reason for not undergoing surgery as prognostic factors for survival. KPS, location, and histology influenced local progression-free survival, whereas only KPS and weight loss influenced distant metastasis-free survival. CONCLUSIONS: This retrospective analysis identified KPS and weight loss as the most important prognostic factors of outcome in patients with early-stage NSCLC treated with hyperfractionation radiation therapy.

Impact of treatment interruptions due to toxicity on outcome of patients with early stage (I/II) non-small-cell lung cancer (NSCLC) treated with hyperfractionated radiation therapy alone.

We investigated the effect of treatment interruptions due to high-grade (> or =3) toxicity on outcome of patients with early stage (I/II) non-small-cell lung cancer treated with hyperfractionated radiation therapy (Hfx RT). Of 116 patients treated with total tumour doses of 69.6 Gy, 1.2 Gy b.i.d. fractionation, 44 patients refused surgery while 72 patients were medically inoperable due to existing co-morbid states. Patients who were medically inoperable had worse KPS (P=0.0059) and more pronounced weight loss (P=0.0005). Among them, 12 patients experienced high-grade toxicity and 11 of them with either acute (n=6) or "consequential" late (n=5) high-grade toxicity requested interruption in the Hfx RT course (range, 12-25 days; median, 17 days). Superior survival (OS) was observed in patients who refused surgery when compared to those who were medically inoperable (P=0.0041), as well as superior local recurrence-free survival (LRFS) (P=0.011), but not different distant metastasis-free survival (P=0.14). Cause-specific survival (CSS) also favoured patients who refused surgery (P=0.004). Multivariate analysis showed independent influence of the reason for not undergoing surgery on OS (P=0.035), but not on LRFS (P=0.084) or CSS (P=0.068). Patients who refused surgery did not experience high-grade toxicity (0/44), whereas 11 of 72 patients with medical inoperability and co-morbid states experienced high-grade toxicity and had treatment interruptions to manage toxicity (P=0.0064). Patients without treatment interruptions had significantly better OS (P=0.00000), LRFS (P=0.00000) and CSS (P=0.00000) than those with treatment interruptions. When corrected for treatment interruptions, the reason for not undergoing surgery independently influenced OS (P=0.040), but not LRFS (P=0.092) or CSS (P=0.068). In contrast to this, treatment interruption was independent prognosticator of all three endpoints used (P=0.00031, P=0.0075 and P=0.00033, respectively). When 11 patients with treatment interruptions were excluded, the reason for not undergoing surgery still affected OS (P=0.037) and CSS (P=0.039) but not LRFS (P=0.11). Multivariate analyses using OS, CSS and LRFS showed that the reason for not undergoing surgery affected OS (P=0.0436), but neither CSS (P=0.083) nor LRFS (P=0.080).

[Significance of pathohistological findings and the expression of Bcl-2 in diagnosis and treatment of oral planocellular carcinoma].

BACKGROUND/AIM: Numerous studies were aimed to detect and characterize various tumor markers in patients with oral planocellular carcinoma in order to reduce moratlity and mobidity rates of these patients, as well as to establish the correlation between the expression of specific tumor marker and prognostic outcome. The aim of this study was to determine patohistological characteristics of tumor and peritumor tissue in patients with oral planocellular carcinoma, with special regard to the expression of Bcl-2, as well as to point out the significance of clinicomorphological correlations for clinical use. METHODS: Sixty-two patients with oral planocellular carcinoma, stage II and III, were examined. The patients were surgically treated for this condition at the Clinic for Maxillofacial Surgery, Military Medical Academy, Belgrade. Surgical specimens were obtained from both tumor and peritumoral tissues. Patohistologic degree of tumor differentiation and the immunohistochemical expression of Bcl-2 were determinated for each specimens. RESULTS: Twenty-four (39%) patients had tumor dimension T1, while six (9%) and thirty-two (52%) patients had tumor dimension T2 and T3, respectively. Patohistologic analysis of peritumor connective, fat, muscle and bone tissue samples confirmed the presence of tumor infiltration. The expression of Bcl-2 in peritumor tissue samples correlated significantly with tumor's histologic grade (rho = 0.468; p < 0.001), nuclear grade (rho = 0.430; p < 0.001) and nucleocytoplasmic ratio (rho = 0.410; p = 0.001). CONCLUSION: This results suggest that the expression of Bcl-2 in combination with patohistologic findings could have a prognostic value in patients with oral planocellular carcinoma.

[Correlation between p53 expression and clinical-pathological characteristics of gastric cancer].

UNLABELLED: BACKGRAUND/AIM: Gene p53, or "cell genome keeper", has a preventive effect on the occurrence of genetic aberrations and prevents abnormal expansion of (tumor) cells. In gastric cancer cells in most cases we register high expression of mutated p53 gene, which correlates with prognosis and specific clinical-pathological characteristics of gastric cancer. METHODS: Using the imunohistochemical method we determined the level of expression of p53 protein in 62 gastric cancers and 30 precancerous conditions (intestinal metaplasia of the stomach). We analyzed the relationship of the level of p53 expression and clinical pathological characteristics of gastric cancer. RESULTS: Expression of p53 was positive in 42 (67.7%) tumor cases and in 7 (14.3%) cases of intestinal metaplasia. Expression of P53 and stomach cancer were in direct correlation (p = 0.000). Sensitivity for p53 in stomach cancer cases was 67.7% (42/62), and specifility was 76.7% (23/30). Expression of mutated p53 protein was in direct correlation with the invasion of lymph nodes (p = 0.034) and with invasion of blood vessels by carcinoma cells (p = 0.042). CONCLUSION: There is a direct correlation between p53 expression and gastric cancer and it indicates the ability of carcinoma cells to invade blood vessels.

[High, open wedge tibial osteotomy: finite element analysis of five internal fixation modalities].

BACKGROUND/AIM: Medial open wedge tibial osteotomy is one of the most widely accepted method of treatment for varus knee deformity in younger patient population. Its success depends on the quality of fixation and preservation of the outer cortex of the tibia. The aim of the study was to evaluate stress distribution in five numerically designed plate configurations which can be used in open wedge tibial osteotomy. METHODS: The paper describes the 3D numerical model of the tibia with 10 degrees varus deformity correction obtained by an optical scanner ATOS. The simulation anticipated axial compressive loads of 700 N, 1 400 N and 2 100 N. We used a modification of the standard T-plate in all of the five tested models. Modalities were tested with and without a metal block, and with and without a stable angle fixation plates and screws. Software PAK was used in the analysis of stress distribution. RESULTS: With exception for the standard T-plate configuration without the supporting block, the loads up to 1400 N did not result in critical stresses on the outer cortex of the tibia in the remaining four models. There is an objective risk of possible failure of the outer cortex and loss of correction at a load of 2100 N in all configurations. The plate model with the angle stable fixation and the supporting metal block showed the most optimal distribution of stresses on the plate-bone composite compared to other models. CONCLUSION: The standard T-plate configuration without supporting metal block is not sufficient to stabilize the open wedge osteotomy of the tibia. Numerical models of the angle stable T-plate and the supporting metal block achieved a favorable distribution of stresses on the bone and implant which require further biomechanical testing.

Elevated serum level of IL-23 correlates with expression of VEGF in human colorectal carcinoma.

BACKGROUND AND AIMS: Interleukin-23 (IL-23) has a role in inflammatory bowel diseases (IBD) as a condition of higher risk of colorectal carcinogenesis. Vascular endothelial growth factor (VEGF) is overexpressed in IBD and colorectal carcinoma. Therefore, we aimed at uncovering the relationship between serum level of IL-23 and expression of VEGF in colorectal cancer (CRC) patients and to establish the relationship between VEGF and p53 and serum levels of IL-23, as well as its possible role in carcinogenesis of colorectal carcinomas. METHODS: Levels of IL-23 from serum samples of patients with colorectal carcinoma (n = 40) and healthy control samples (n = 37) were examined for IL-23-Ab using an ELISA assay. We also determined the expression of VEGF and p53 by immunohistochemistry in 59 cases of CRC. RESULTS: We found significantly higher serum levels of IL-23 in patients with CRC compared to control subjects (IL-23; mean 189.46 pg/mL vs. mean 34.77 pg/mL, p = 0.033). We also detected higher serum levels of IL-23 in patients with overexpressed VEGF (p = 0.028). Our results also showed that concomitant expression of VEGF and increased serum levels of IL-23 are in positive correlation with histological grade 2 (p <0.05). CONCLUSIONS: Our data indicate that serum IL-23 levels are significantly elevated in CRC vs. control patients and are strongly associated with overexpression of VEGF, thus they may play an important role in carcinogenesis of CRC.

Giant dumbbell tumor of the posterior mediastinum.

BACKGROUND: Giant dumbbell-shaped tumors are very rare and characterized by intra- and extraspinal propagation of different dimensions. In thoracal localization, invasive growth can lead up to rib and vertebra erosion. CASE REPORT: We presented a 54-year-old woman with a giant dumbbell schwannoma in the posterior mediastinum. The tumor was removed by the posterior approach with hemilaminectomy and costotransversectomy. By microscopic examination the diagnosis of benign schwannoma was made. A year after the surgery, the patient was without neurological deficiency and without radiological signs of illness relapse. CONCLUSION: Treatment of dumbbell schwannoma is surgical, dilemmas of the optimal surgical approach. When it is thoracally located the posterior approach with hemilaminectomy and costotransversectomy is safe and effective for its removal.

[The phagocytic activity of monocytes in different stages of breast cancer]. / Fagocitna aktivnost monocita u razlicitim stadijumima karcinoma dojke.

INTRODUCTION: Defective monocyte function has been associated with a variety of human malignancies. However, the diagnostic and/or prognostic significance of this disturbance remains unclear. MATERIAL AND METHODS: The number of leukocytes, proportion and absolute number of granulocytes, lymphocytes and monocytes, and monocyte phagocytic function were determined in a group of 30 patients with invasive ductal breast cancers. Cancer patients were divided into 3 groups on the basis of clinical stage of the disease: group A--patients with localized disease; group B--patients with regional lymph node metastases; group C--patients with distant metastases. The control group consisted of 10 age-matched healthy women. RESULTS: This study demonstrates that patients with breast cancer have a significant decrease in the absolute number of monocytes and phagocytic activity. Moreover, compared to healthy individuals, the absolute number of monocytes decreases in cancer patients, reaching the lowest value in patients with distant metastases (group C). Similarly, phagocytic activity of peripheral blood monocytes was significantly lower in patients with tumors. Index of phagocytosis showed a two-fold, and capacity of phagocytosis a seven-fold decrease in advanced-stage patients (C). DISCUSSION AND CONCLUSION: The phagocytic activity reveals the dynamics of the host tumor interface. This method is used alone or combined with other methods as an indicator of the extent or activity of the disease. We conclude that monocyte phagocytic function can be used as an additional prognostic factor in breast cancer monitoring.

Phagocytic activity and nitric oxide production of circulating polymorphonuclear leukocytes from patients with peritoneal carcinomatosis.

Many studies have demonstrated an increase of neutrophils in patients with advanced cancer. However, the possible role of increased neutrophils in various neoplasms studied to date varies considerably. The authors examined the changes in white blood cell counts in patients with peritoneal carcinomatosis. Malonildialdehyde and nitric oxide (NO) plasma and ascitic fluid levels, phagocitic activity and the ability of the polymorphonuclear cells (PMNCs) to produce nitric oxide were also measured. An increase in PMNCs and decrease in lymphocytes was found in cancer patients. Compared with healthy controls, cancer PMNCs showed significant enhancement of phagocytosis Similarly, pretreatment of healthy PMNCs with crude supernatants from short-term cultures of the peritoneal cells from ascitic fluid of patients with peritoneal carcinomatosis caused marked stimulation of PMNC phagocytosis. In addition, plasma and ascitic fluid nitric oxide levels in cancer patients were significantly higher than those found in control one. Most importantly, it was found that PMNCs from cancer patients release significantly more nitric oxide than corresponding normal controls. Therefore, considering the fact that neutrophils make up more than 50% of total leukocytes, these cells can play one of the most important roles in tumor biology.