The Ki-67 proliferation index predicts recurrence-free survival in patients with dermatofibrosarcoma protuberans.

Dermatofibrosarcoma protuberans (DFSP) is an uncommon soft tissue sarcoma that originates from the dermis or subcutaneous tissue in the skin. While its prognosis is generally favorable, disease recurrence is relatively frequent. Because morbidity after repeated surgery may be significant, an optimized prediction of recurrence-free survival (RFS) has the potential to improve current management strategies. The purpose of this study was to investigate the prognostic value of the Ki-67 proliferation index with respect to RFS in patients with DFSP. We retrospectively analyzed data from 45 patients with DFSP. We calculated the Ki-67 proliferation index as the percentage of immunostained nuclei among the total number of tumor cell nuclei regardless of the intensity of immunostaining. We constructed univariate and multivariate Cox proportional hazards regression models to identify predictors of RFS. Among the 45 patients included in the study, 8 developed local recurrences and 2 had lung metastases (median follow-up: 95.0 months; range: 5.2-412.4 months). The RFS rates at 60, 120, and 240 months of follow-up were 83.8%, 76.2%, and 65.3%, respectively. The median Ki-67 proliferation index was 14%. Notably, we identified the Ki-67 proliferation index as the only independent predictor for RFS in multivariate Cox proportional hazards regression analysis (hazard ratio = 1.106, 95% confidence interval = 1.019-1.200, p = 0.016). In summary, our results highlight the potential usefulness of the Ki-67 proliferation index for facilitating the identification of patients with DFSP at higher risk of developing disease recurrences.

Enhancer of zeste homologue 2 (EZH2) expression in synovial sarcomas as a promising indicator of prognosis.

Synovial sarcoma (SS) is a type of soft-tissue sarcoma, often linked to poor survival. Although overexpression of enhancer of zeste homologue 2 (EZH2) has been associated with poor prognosis in different tumors, a few studies investigated this link in SS. Here, we analyzed the relationship between EZH2 expression and prognostic factors in SS. We included 29 patients with SS. Immunostaining of EZH2 was performed with (D2C9) XPTM Rabbit mAb antibody, and the results were classified as low EZH2 expression (negative or weak expression) and high EZH2 expression category (moderate or strong expression). Analysis of survival in relation to prognostic factors was performed with Kaplan-Meier survival curves and Cox proportional hazard regression analysis. Our sample included 19/29 female and 10/29 male patients, with age range 16-63 years. The tumor diameter ranged from 2 to 15 cm. Necrosis was observed in 15/29 cases. Sixteen cases had >10 mitoses per 50 high-power fields (HPFs). Out of 29 cases, 14 showed low and 15 had high EZH2 expression. Statistically significant results were obtained for the association between the presence of metastasis and necrosis (p = 0.042), high EZH2 expression and distant metastasis (p = 0.018), high EZH2 expression and necrosis (p = 0.016), and high EZH2 expression and the tumor size >5 cm versus tumor size ≤5 cm (p = 0.014). Patients with all of the following: the tumor size ≤5 cm, low EZH2 expression, and without necrosis and distant metastasis had significantly longer survival time. Our results are consistent with previous studies, suggesting that EZH2 overexpression is an indicator of poor prognosis in SS.

Radio-protective effect of cinnamic acid, a phenolic phytochemical, on genomic instability induced by X-rays in human blood lymphocytes in vitro.

The present study was designed to determine the protective activity of cinnamic acid against induction by X-rays of genomic instability in normal human blood lymphocytes. This radio-protective activity was assessed by use of the cytokinesis-block micronucleus test and the alkaline comet assay, with human blood lymphocytes isolated from two healthy donors. A Siemens Mevatron MD2 (Siemens AG, USA, 1994) linear accelerator was used for the irradiation with 1 or 2 Gy. Treatment of the lymphocytes with cinnamic acid prior to irradiation reduced the number of micronuclei when compared with that in control samples. Treatment with cinnamic acid without irradiation did not increase the number of micronuclei and did not show a cytostatic effect in the lymphocytes. The results of the alkaline comet assay revealed that cinnamic acid reduces the DNA damage induced by X-rays, showing a significant radio-protective effect. Cinnamic acid decreased the frequency of irradiation-induced micronuclei by 16-55% and reduced DNA breakage by 17-50%, as determined by the alkaline comet assay. Cinnamic acid may thus act as a radio-protective compound, and future studies may focus on elucidating the mechanism by which cinnamic acid offers radioprotection.

Radioprotection by two phenolic compounds: chlorogenic and quinic acid, on X-ray induced DNA damage in human blood lymphocytes in vitro.

The present study was designed to determine the radioprotective effect of two phytochemicals, namely, quinic acid and chlorogenic acid, against X-ray irradiation-induced genomic instability in non-tumorigenic human blood lymphocytes. The protective ability of two phenolic acids against radiation-induced DNA damage was assessed using the alkaline comet assay in human blood lymphocytes isolated from two healthy human donors. A Siemens Mevatron MD2 (Siemens AG, USA, 1994) linear accelerator was used for irradiation. The results of the alkaline comet assay revealed that quinic acid and chlorogenic acid decreased the DNA damage induced by X-ray irradiation and provided a significant radioprotective effect. Quinic acid decreased the presence of irradiation-induced DNA damage by 5.99-53.57% and chlorogenic acid by 4.49-48.15%, as determined by the alkaline comet assay. The results show that quinic acid and chlorogenic acid may act as radioprotective compounds. Future studies should focus on determining the mechanism by which these phenolic acids provide radioprotection.

Comparison of protracted infusion 5-fluorouracil and capecitabine in adjuvant chemoradiotherapy for rectal cancer.

BACKGROUND/AIMS: 5-Fluorouracil-based chemoradiotherapy is the most widely used treatment modality in the adjuvant treatment of rectal cancer. Capecitabine represents a valuable alternative to 5-Fluorouracil in this situation. METHODOLOGY: Patients with stage II and stage III rectal adenocarcinoma, who were included in this analysis, received adjuvant chemoradiotherapy consisting of external-beam radiotherapy (50.4-54Gy) either with 5-Fluorouracil at a median dose of 300 mg/m2/day by protracted venous infusion for 5 days a week, or capecitabine at a median dose of 1650 mg/m2/day for 5 days a week after surgery. The data concerning the toxicity and the efficacy of the treatments were compared in patients treated with 5-Fluorouracil- and capecitabine-based chemoradiotherapy. RESULTS: Forty-three patients received 5-Fluorouracil, and 24 patients received capecitabine during adjuvant radiotherapy. Although there were no differences between the groups in terms of toxicity rates, distant metastasis-free survival, disease-free survival, and overall survival rates; a trend for improved loco-regional recurrence-free survival rate was observed in the capecitabine arm (p = 0.063). CONCLUSIONS: Capecitabine is at least as effective as 5-Fluorouracil in the postoperative treatment of rectal adenocarcinoma. Considering the trend for improved loco-regional recurrence-free survival rate in the capecitabine arm, it seems that the drug exerts better synergy with radiotherapy in this situation.

Factors influencing axillary node metastasis in breast cancer.

AIMS AND BACKGROUND: The status of the axillary lymph nodes at the time of diagnosis has been accepted as one of the most important prognostic factors for the overall and disease-free survival of patients with breast cancer. The aim of our study was to determine which factors influence axillary node involvement in invasive breast cancer. METHODS: The data presented here were obtained from 344 patients who were treated for invasive breast cancer at the Department of Radiation Oncology, Uludag University Medical College, Bursa, Turkey. Possible prognostic factors were categorized as patient related and tumor related. The Mann-Whitney U test was used for univariate analysis and logistic regression was used for multivariate analysis. RESULTS: In univariate analysis, a familial cancer history (P = 0.0042), age < 40 years (P = 0.0276), higher T stage (P < 0.0000), nipple involvement (P = 0.0345), skin involvement (P = 0.0270), perineural invasion (P = 0.0231), and lymphatic vessel invasion (P < 0.0000) were correlated with increased axillary node involvement. A higher incidence of > or = 4 involved lymph nodes was associated with higher T stage (P = 0.0004), nipple involvement (P = 0.0292), presence of an extensive intraductal component (P = 0.0023), skin involvement (P = 0.0008), perineural invasion (P = 0.0523), and lymphatic vessel invasion (P < 0.0000) in univariate analysis. In multivariate analysis, age < 40 years (P = 0.0454), cancer history within the family (P = 0.0024), higher T stage (P = 0.0339), lymphatic vessel invasion (P = 0.0003), and perineural invasion (P = 0.0408) were found to be independent factors for axillary lymph node positivity. Age < 40 years (P = 0.0221), perineural invasion (P = 0.0408), and an extensive intraductal component (P = 0.0132) were associated with an increased incidence of > or = 4 involved nodes in the logistic regression analysis. In patients with breast cancer, the incidence of axillary lymph node involvement was independently influenced by age < 40 years, presence of cancer history within the family, higher T stage, lymphatic vessel invasion, and perineural invasion. CONCLUSIONS: In conclusion, absence of familial cancer history, presence of lymphatic vessel invasion, higher T stage, and age below 40 years independently increased the risk of axillary node involvement. Presence of perineural invasion and lymphatic vessel invasion, age below 40, and an extensive intraductal component of more than 25% independently affected the risk of having > or = 4 nodes involved. Patients characterized by these factors may be classified into a higher risk group for nodal involvement, but more data are needed to define factors that can help in the decision-making regarding the omission of axillary treatment.

Phase II study of induction chemotherapy with gemcitabine plus 5-fluorouracil followed by gemcitabine-based concurrent chemoradiotherapy for unresectable locally advanced pancreatic cancer.

AIMS AND BACKGROUND: To evaluate the efficacy and tolerability of a new treatment approach including induction chemotherapy (CT) and concurrent chemoradiotherapy (CRT) in unresectable, locally advanced pancreatic cancer (LAPC). PATIENTS AND METHODS: Twenty-four patients with LAPC were enrolled in the study. They first received induction CT consisting of 5-fluorouracil (5FU) (500 mg/m2) and gemcitabine (1000 mg/m2), which were given weekly for 3 weeks of every 4. Patients showing a response or disease stabilization after 2 cycles of induction CT received CRT consisting of external beam radiotherapy (50.4-54 Gy in fractions of 1.8 Gy/day) and gemcitabine (350 mg/m2, weekly for 6 weeks). Patients without disease progression received 2 additional cycles of CT consisting of 5FU plus gemcitabine with the same doses and schedule as given in the induction CT. RESULTS: After the end of the study, 2 (8%) and 5 (21%) patients showed complete and partial responses, respectively. Five patients (21%) had disease stabilization. The grade 3 and 4 toxicities associated with CT were neutropenia (21%) and thrombocytopenia (4%). The grade 3 and 4 toxicities occurring in patients who received CRT were neutropenia (24%), thrombocytopenia (24%), diarrhea (18%), and nausea (12%). The median progression-free survival for all patients was 6 months (95% CI, 3.6-8.4), and the median overall survival was 11 months (95% CI, 8.16-13.84). CONCLUSIONS: The CRT approach of this study is moderately active and has an acceptable toxicity profile. However, the incorporation of combination CT into CRT at the present schedule could not produce any additional benefit over CRT alone. Newer agents with more systemic activity are clearly warranted.

Evaluation of infections in non-small cell lung cancer patients treated with radiotherapy.

PURPOSE: We aim to determine infections occurring in patients with non-small cell lung cancer during radiotherapy (RT). METHODS AND MATERIALS: A total of 181 patients had been treated with thoracic radiotherapy between October 1995 and December 1999. Radiotherapy was given using 1.8-3Gray (Gy) fraction daily, five fractions a week for a total dose of 59.4Gy (30-70.2Gy). A complete history was collected retrospectively for each patient. All microbiological examinations were performed according to the routine procedures of the hospital laboratory. Numeric and categoric variables were employed such as sex, age, performance status, histology, stage, chemotherapy, usage of corticosteroids, neutropenia, surgery, hospitalization, associated diseases, smoking during treatment, package per year of cigarette smoking, dose of radiotherapy, and response rates. RESULTS: Infections developed in 84 patients (46%, 84/181) during thoracic radiotherapy. A 101 episodes of infections developed in these patients. Most patients suffered from sputum production (65%), cough (59%), auscultation findings (31%) and fever (31%). Gram-negative bacteria were the most frequently isolated pathogens in the cultures of specimens (70%, 16/23 samples). Neoadjuvant chemotherapy (OR=4.81; 95% CI, 1.57-9.12; p=0.003) and neutropenia (OR=4.25; 95% CI, 1.44-6.89; p=0.009) were found as risk factors for influencing infection based on logistic regression analyses. Package per year of cigarette smoking was found statistically significantly higher in patients with infections than patients without infections (p=0.001). A slight increase in infections, which was of borderline statistical significance (p=0.07), was observed in patients age over 70. Ciprofloxacin and clarithromycin were the most frequently used agents in treatment. Median survival was 9 months in the patients with infection and 13 months in the 97 patients without infection. Overall survival seemed to be statistically significantly better in patients without infection than patients with infection (p=0.042) calculated using Kaplan-Meier method. Based on Cox regression analyses; overall survival was not correlated to presence of infection but associated with poor performance status (5940 cGy (OR=2.06; 95% CI, 0.72-7.18; p=0.007) and the absence of response to treatment (OR=2.45; 95% CI, 0.89-14.23; p<0.001) were also found to be risk factors for survival. CONCLUSIONS: Infections are important causes of morbidity and mortality in lung cancer patients. The control of infection in these patients may improve the survival. Predisposing factors and treatment management approaches in non-small cell lung cancer should be defined carefully.

Acquired lymphangiectasis after breast conservation treatment for breast cancer: report of a case.

Acquired lymphangiectasis is a dilatation of lymphatic vessels that can result as a complication of surgical intervention and radiation therapy for malignancy. Acquired lymphangiectasis shares clinical and histological features with the congenital lesion, lymphangioma circumscriptum. Diagnosis and treatment of these vesiculobullous lesions is important because they may be associated with pain, chronic drainage, and cellulitis. We describe patient who had these lesions after treatment for cancer. Although a number of treatment options are available, we have found cryosurgery and electrocautery to be particularly effective.