Effect of Radiotherapy on the Adhesive Interface of Caries-affected Dentin and Bioactive Restorations: A Micro-CT Analysis.

PURPOSE: This study aimed to analyze the presence of defects within the adhesive interface formed with five bioactive dental materials and caries-affected dentin concerning the timing of radiotherapy (before or after the restorative procedures) by micro-CT. METHODS AND MATERIALS: A total of 96 carious human molars were randomly allocated into the following groups based on the timing of the radiotherapy sequence: radiotherapy followed by restoration (RT1) or restoration followed by radiotherapy (RT2). Then, six subgroups were established within these groups based on the type of materials used (n=8). Following cavity preparation and caries removal, a universal adhesive (G-Premio Bond) was administered in self-etch mode or accompanied by applying suitable cavity conditioners according to the manufacturers' guidelines. Subsequently, restorations were performed using five bioactive restorative materials (resin-modified glass-ionomer [Fuji II LC], high-viscosity glass-ionomer hybrid [EQUIA Forte HT], giomer [Beautifil II], alkasite [Cention N], and dual-cure bulk-fill composite [Activa Bioactive Restorative]) and a conventional microhybrid resin composite (Filtek Z250). The radiotherapy regimen encompassed 60 Grays (Gy) administered at a rate of 2 Gy/day over 6 weeks, 5 days a week. Micro-CT analysis was employed to assess adhesive defects at the interface between caries-affected dentin and the restorations. The data were analyzed using Kruskal-Wallis, Mann-Whitney U, and Dunn tests (α=0.05). RESULTS: RT2 caused significantly higher adhesive defects than RT1 for the Filtek Z250 and Activa Bioactive Restorative subgroups (p<0.05). For RT1, no significant differences were found in adhesive defects among all tested subgroups (p>0.05). By contrast, for RT2, adhesive defects were significantly higher for the Activa Bioactive Restorative and Cention N subgroups than for the EQUIA Forte HT and Beautifil II subgroups (p<0.05). CONCLUSIONS: When using most bioactive restorative materials, the timing of radiotherapy had no significant influence on the adhesive interface. Regarding restoration following a radiotherapy protocol, a favorable impact was identified with high-viscosity glass ionomer hybrid cement and giomer bioactive restorations compared with dual-cure bioactive bulk-fill composite and alkasite restorations.

The Effect of Radiotherapy on the Marginal Adaptation of Class II Direct Resin Composite Restorations: A Micro-computed Tomography Analysis.

This laboratory study was designed to evaluate the marginal adaptation of Class II mesio-occlusodistal (MOD) restorations at the cervical region with micro-computed tomography (micro-CT). Two groups of restorations were compared: 1) those that had been exposed to radiotherapy before restoration was performed using a universal adhesive in etch-and-rinse and self-etch modes; and 2) those that had previously been restored using a universal adhesive in etch-and-rinse and self-etch modes and had subsequently undergone radiotherapy. Sixty intact human molars were randomly divided into groups according to irradiation status: no radiotherapy (control group); radiotherapy followed by restoration (radiotherapy-first group); and restoration followed by radiotherapy (restoration-first group). These three groups were then subdivided into two groups each on the basis of adhesive application type (etch-and-rinse and self-etch modes), for a total of six groups (n=10/group). Standardized Class II MOD cavities were prepared. A universal adhesive (Clearfil Universal Bond Quick, Kuraray, Okayama, Japan) was applied. The teeth were restored with resin composite (Estelite Posterior Quick, Tokuyama, Tokyo, Japan). The radiotherapy protocol was conducted with 60 gray (Gy) at 2 Gy/day, five days a week for six weeks. Adhesive defects were analyzed in distal and mesial views and evaluated with micro-CT (SkyScan 1174v2, Kontich, Antwerp, Belgium) on the basis of the volume of black spaces between the cavity walls and the restorative materials (mm3). The data were analyzed using the Kruskal-Wallis, Mann Whitney U and Wilcoxon tests (p<0.05). The radiotherapy protocol did not affect the marginal adaptation of the universal adhesive at the cervical regions. Regarding the application modes, for the radiotherapy-first group, the self-etch mode caused significantly higher adhesive defects than the etch-and-rinse mode at the dentin margin. For the no-radiotherapy group, the adhesive defects at the dentin margin were significantly higher than at the enamel margin with the application of the etch-and-rinse mode.

Elective bladder preservation with multimodality treatment for bladder cancer.

PURPOSE: To observe the outcome of maximal transurethral resection of bladder tumor (TURBT) followed by induction chemotherapy and concurrent chemoradiotherapy in medically inoperable patients with bladder cancer. METHODS: This study included 30 patients with stage T 2-4 bladder cancer. The patients were first treated with TURBT, and then received 2 cycles of induction chemotherapy with gemcitabine and cisplatin, followed by concurrent chemoradiotherapy with gemcitabine. RESULTS: Median follow up was 28.9 months. Radiologically, complete and partial response rates were 60 and 36.7%, while cystoscopically they were 40 and 30%, respectively. Local progression (4 cases) and distant metastasis (11 cases) were noted. Median overall survival and progressionfree survival were 32 and 21 months, respectively. One -and 2-year overall survival and progression-free survival rates were 97.60% and 83.49%, respectively. CONCLUSION: The multimodal treatment performed in this study was well tolerated and achieved a high rate of bladder preservation in selected patients with bladder cancer.

Is there a cut-off value for standardized uptake values in positron emission tomography for predicting response to treatment and survival in patients with advanced non-small cell lung cancer? Single center experience.

PURPOSE: Positron emission tomography (PET) is an important imaging technique for the diagnosis and staging of patients with non-small cell lung cancer (NSCLC). In this study, we evaluated the standardized uptake values (SUV) of PET in NSCLC patients to determine whether there was a cut-off value for predicting response to treatment and survival. METHODS: We retrospectively analyzed 149 patients with locally advanced NSCLC. All the patients were staged by PET-computerized tomography (CT) after diagnosis. 18fluoro-2-deoxyribose (FDG) was used as the PET tracer. Univariate and multivariate analyses were performed to detect whether any prognostic factors were related to response to treatment. RESULTS: The median patient age was 60 years and the median follow-up time 10.3 months. One-year progression-free survival (PFS) and overall survival (OS) rates were 31% and 58.7%, respectively. The median OS was 15.4 months. Stage, sex and response to treatment were important factors for OS and PFS. We defined a cut-off value for SUVmax (the highest standardized uptake value for all cross sectional areas) as 10.8 by using ROC analysis. Multivariate analysis identified response to treatment as the most significant (p<0.05) prognostic factor for OS. Logistic regression analysis showed that SUVmax and weight loss were important for response to treatment. CONCLUSION: Multivariate analysis indicated that whilst response to treatment was an important factor for predicting survival, the SUVmax was also significant for determining response to therapy and a cut-off value for SUVmax was defined as 10.8.

Punica granatum peel extract protects against ionizing radiation-induced enteritis and leukocyte apoptosis in rats.

Radiation-induced enteritis is a well-recognized sequel of therapeutic irradiation. Therefore we examined the radioprotective properties of Punica granatum peel extract (PPE) on the oxidative damage in the ileum. Rats were exposed to a single whole-body X-ray irradiation of 800 cGy. Irradiated rats were pretreated orally with saline or PPE (50 mg/kg/day) for 10 days before irradiation and the following 10 days, while control rats received saline or PPE but no irradiation. Then plasma and ileum samples were obtained. Irradiation caused a decrease in glutathione and total antioxidant capacity, which was accompanied by increases in malondialdehyde levels, myeloperoxidase activity, collagen content of the tissue with a concomitant increase 8-hydroxy-2'-deoxyguanosine (an index of oxidative DNA damage). Similarly, pro-inflammatory cytokines (TNF-alpha, IL-1beta and IL-6) and lactate dehydrogenase were elevated in irradiated groups as compared to control. PPE treatment reversed all these biochemical indices, as well as histopathological alterations induced by irradiation. Furthermore, flow cytometric measurements revealed that leukocyte apoptosis and cell death were increased in irradiated animals, while PPE reversed these effects. PPE supplementation reduced oxidative damage in the ileal tissues, probably by a mechanism that is associated with the decreased production of reactive oxygen metabolites and enhancement of antioxidant mechanisms. Adjuvant therapy of PPE may have a potential to support a successful radiotherapy by protecting against radiation-induced enteritis.

Outcome of metastatic non-small cell lung carcinoma patients receiving docetaxelcisplatin combination chemotherapy: single institution experience.

PURPOSE: Despite advances in the detection and treatment, the long-term survival of patients with advanced nonsmall cell lung cancer (NSCLC) remains poor, with a 5-year overall survival (OS) of less than 5%. We conducted this observational study to determine the influence of docetaxel plus cisplatin combination chemotherapy on response, time to progression (TTP) and OS, and to evaluate its tolerability in chemotherapy-naïve patients with metastatic NSCLC. PATIENTS AND METHODS: Patients with histologically or cytologically confirmed stage IV NSCLC who met the following criteria were eligible for the study: no previous chemotherapy, Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-2, objectively measurable disease, adequate bone marrow reserve, normal hepatic and renal function. Patients received docetaxel 75 mg/m(2) and cisplatin 75 mg/m(2), both given on day 1. Cycles were repeated every 3 weeks and a total of 4-6 cycles were scheduled to be administered. RESULTS: 50 consecutive eligible patients were enrolled into the study. Median follow-up time was 6 months (range 1-21). Median age was 61.5 years (range 39-75). Forty-eight (96%) patients were male. Histological type was squamous cell carcinoma in 21 (42%) patients, adenocarcinoma in 11 (22%) and undifferentiated carcinoma in 18 (36%). The median OS time was 16 months (range 7.1-24.9; 95% CI: 8-24). One-year OS was 56.3%. Overall response rate was 44% with 40% partial (PR) and 4% complete responses (CR). Twenty-eight percent of patients had stable disease (SD) and 28% progressive disease (PD). The median TTP was 4 months (range 2-13; 95% CI: 2.4-5.5). CONCLUSION: Docetaxel/cisplatin combination demonstrated efficacy comparable to other platinum-containing doublets.

Concomitant administration of uracil-tegafur and leucovorin during adjuvant radiotherapy for locally advanced rectal cancer.

PURPOSE: We report the feasibility and toxicity profile, and the impact on local control, disease-free survival and overall survival rates of our study which consisted of postoperative concurrent chemoradiotherapy, followed by adjuvant chemotherapy using uracil-tegafur (UFT)/leukovorin (LV) in locally advanced rectal cancer patients. PATIENTS AND METHODS: Thirty-one patients operated for rectal adenocarcinoma (pT3/4 or N+) were enrolled onto the study. Twenty-three patients were males and 8 females with median age 62 years (range 21-85). Radiotherapy (RT) to the pelvis with conformal technique and individual blocks was delivered within 8 weeks following surgery. Total RT dose was 50.4 Gy and was given in a conventional single fraction of 1.8 Gy per day. Chemotherapy was administered concomitantly and consisted of UFT (300 mg/m(2)/day) and LV (30 mg/day) during RT-days. Following chemoradiotherapy, chemotherapy alone was administered for 4 cycles in the same dose for 28 days every 35 days. RESULTS: No lethal toxicity occurred. All patients completed the scheduled RT. Concurrent chemotherapy continued in 22 (70.9%) patients until the end of RT. Seventeen (54.8%) patients completed the whole concurrent chemoradiotherapy and adjuvant chemotherapy as planned. No grade 3-4 stomatitis/mucositis or haematological toxicities were observed during the whole treatment period. During concomitant therapy grade 1-2 toxicities were: nausea/vomiting 60%, dyspepsia/gastric pain 39%, diarrhea 39% and dysuria 10%, whereas grade 3 nausea and diarrhea occurred in 6% and 19%, respectively. Median follow-up was 22 months. Two-year local control, disease-free survival and overall survival rates were 96.3%, 72.3% and 83.2%, respectively. CONCLUSION: The acute toxicity profile of UFT/LV, local control, disease-free survival and overall survival in the concurrent chemoradiotherapy setting for operated, locally advanced rectal cancer seem comparable with the standard 5-fluorouracil (5-FU)-based therapies.

Pre-treatment haemoglobin concentration is a prognostic factor in patients with early-stage breast cancer.

We investigated the prevalence of anaemia (haemoglobin concentration < 12 g/dl) in 336 women with early-stage breast cancer and its association with other known prognostic factors. The median follow-up period was 60.5 months (range 9 - 123 months). Seventy-nine women (23.5%) had a low pre-treatment haemoglobin concentration, but anaemia was not correlated with age, tumour size, nodal status, histological grade or hormone receptor status. Univariate analysis revealed that disease-free survival and overall survival were shorter in patients with anaemia at the time of diagnosis than in patients with normal haemoglobin concentrations. Anaemia remained a significant prognostic factor for disease-free survival and overall survival in the multivariate analysis (relative risk, 1.884 and 1.785, respectively). These results suggest that pre-treatment haemoglobin concentration is an independent prognostic factor in patients with early-stage breast cancer.

Prognostic significance of thrombocytosis in node-negative colon cancer.

Several clinical studies have shown that thrombocytosis is a poor prognostic factor in some types of cancer, but data about the impact of thrombocytosis on prognosis in patients with colon cancer are very limited. We investigated the prevalence and prognostic effect of pre-operative thrombocytosis, defined as a platelet count > 400 x 10(9)/l, retrospectively in patients with node-negative colon cancer. Out of 198 patients, 24 (12.1%) had thrombocytosis, and its presence correlated with tumour depth and lymphatic invasion. Univariate analysis revealed that disease-free survival and overall survival were shorter in patients with pre-operative thrombocytosis than those without thrombocytosis. On multivariate analysis, thrombocytosis alone retained significance as a poor prognostic factor for both disease-free survival and overall survival. In conclusion, this study shows an association between thrombocytosis and poor survival in patients with node-negative colon cancer. The preoperative platelet count may help to identify patients with an unfavourable prognosis in this subgroup.

Evaluation of pulmonary complications of radiotherapy in breast cancer patients.

PURPOSE: To study the early and late pulmonary complications of radiotherapy (RT) in patients with operated breast cancer who received postoperative RT. PATIENTS AND METHODS: Radiation pneumonia (RP) and radiation fibrosis (RF) rates were evaluated after 3 and 18 months from the end of RT, using the Radiation Therapy Oncology Group and the European Organization for the Research and Treatment of Cancer (RTOG/ EORTC) combined toxicity classification scale. Evaluation included physical examination, high resolution computed tomography (HRCT) of the thorax, and pulmonary function tests (PFTs). The incidence of RP and RF, the relationship between RP and RF and possible predisposing factors and the impact of RT on the PFTs were analyzed. RESULTS: Between December 2000 and March 2001 35 patients were included in the study. Due to several reasons 29 patients were evaluable for RP and 25 for RF. On the 3rd month post-RT, 17 (59%) patients developed RP. Three (18%) of the cases were grade 1, 13 (76%) grade 2 and 1 (6%) grade 3. One patient was radiologically diagnosed with early RF. When evaluated for RF, 9 (36%) of 25 patients were found to have RF. Four (45%) of them were grade 1, and 5 (55%) grade 2. FEV1, FEV1/FVC, VC, FVC values showed different degrees of decline on the 3rd month. The most prominent change occurred with DLCO/ VA ratio which decreased by 20%. On the 18th month, all values returned to at least the pretreatment levels. CONCLUSION: RT-induced RP and RF are quite frequent. As clinical findings are generally nonspesific, radiological findings of RP and RF should be known. Early and late effects on PFTs are generally mild and transient.