Pre- and post-surgery treatments in rectal cancer: a long-term single-centre experience.

BACKGROUND: Our study evaluated long-term survival outcomes in rectal cancer patients treated with preoperative radiotherapy, and the impact on survival of concomitant and postoperative adjuvant chemotherapy (ctx), among other prognostic factors. METHODS: The study included 196 patients [median age: 58 years (range: 20-86 years); 63.0% men] with locally advanced rectal carcinoma and, in some cases, resectable liver metastasis. Rates of distant metastasis and local recurrence and of 5-year distant metastasis-free survival (dmfs) and overall survival (os) were determined. RESULTS: The 5-year os rate was 57.0%, with a median duration of 81.5 months (95% confidence interval: 73.7 months to 89.4 months), and the 5-year dmfs rate was 54.1%, with a median duration of 68.4 months (95% confidence interval: 40.4 months to 96.4 months). Prognostic factors for higher os and dmfs rates were downstaging (p = 0.013 and p = 0.005 respectively), radiotherapy dose (50 Gy vs. 56 Gy or 45-46 Gy, both p = 0.002), and concomitant ctx use (p = 0.004 and p = 0.001) and type (5-fluorouracil-leucovorin-folinic acid vs. tegafur-folinic acid, p = 0.034 and p = 0.043). Adjuvant ctx after neoadjuvant long-term concomitant chemoradiotherapy (ccrt) and surgery was associated with better 5-year os rates for postoperative T0-T3 disease (p = 0.003) and disease at all lymph node stages (p = 0.001). CONCLUSIONS: Our findings revealed a favourable survival outcome with long-term fractionated irradiation and concomitant 5-fluorouracil-based ctx, achieving 5-year os and dmfs rates of 57.0% and 54.1% respectively. Preoperative administration of radiotherapy (50 Gy) and postoperative adjuvant ctx were associated with a significant survival benefit. Radiation doses above 50 Gy and the interval between ccrt and surgery had no significant effect on survival.

Quercetin protects radiation-induced DNA damage and apoptosis in kidney and bladder tissues of rats.

Ionizing radiation (IR) can induce cell damage and cell death through the reactive oxygen species generated by radiolytic hydrolysis. The present study was aimed to determine the possible protective effects of quercetin, a well-known antioxidant agent, against IR-induced bladder and kidney damage in rats. Sprague-Dawley rats were exposed to 8-Gy whole-abdominal IR and given either vehicle or quercetin (20 mg/kg, ip). Rats were decapitated at either 36 h or 10 days following IR, where quercetin or vehicle injections were repeated once daily, and kidney and bladder samples were obtained for the determination of myeloperoxidase and caspase-3 activities, an index of tissue neutrophil infiltration and apoptosis, respectively. Radiation-induced inflammation was evaluated through tissue cytokine, TNF-α levels. In order to examine oxidative DNA damage, tissue 8-hydroxydeoxyguanosine (8-OHdG) levels were measured. All tissues were also examined microscopically. In the saline-treated irradiation groups, myeloperoxidase and caspase-3 activities, 8-OHdG and TNF-α levels were found to be increased in both tissues (p < 0.05). In the quercetin-treated-IR groups, all these oxidant responses were prevented significantly (p < 0.05). The present data demonstrate that quercetin, through its free radical scavenging and antioxidant properties, attenuates irradiation-induced oxidative organ injury, suggesting that quercetin may have a potential benefit in radiotherapy by minimizing the adverse effects and will improve patient care.

Concurrent chemoradiotherapy with low dose weekly gemcitabine in medically inoperable muscle-invasive bladder cancer patients

PURPOSE: We aimed to determine the efficacy and the toxicity of low dose weekly gemcitabine with radiation therapy in medically unfit muscle-invasive bladder cancer patients. METHODS: Twenty-six patients were included into the retrospective analysis. Weekly gemcitabine was administered 75 mg/m(2) with a median dose of 63 Gy radiation therapy. Clinical target volume was defined as the urinary bladder only in conformal treatment planning. RESULTS: Median follow-up was 51 months (range 14-118 months). Complete response rate was 62.5 %. The 5-year local progression-free survival, disease-specific survival and overall survival rates were 40.6, 59.5 and 58.5 %, respectively. Concurrent chemotherapy was continued in 80.7 % of patients without any interruption. Gemcitabine was stopped due to grade 3 thrombocytopenia (n = 1), cardiac angina (n = 1), chronic obstructive pulmonary disease exacerbation (n = 1) or patients' reluctance (n = 2). CONCLUSIONS: Low dose weekly gemcitabine with concurrent radiotherapy is a tolerable regimen and have comparable outcomes with platinum-based combined treatments in muscle-invasive bladder cancer. Prospective randomized trials can help in understanding the safety and efficacy of this treatment specially in medically unfit patients (AU)

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Concurrent chemoradiotherapy with low dose weekly gemcitabine in medically inoperable muscle-invasive bladder cancer patients.

PURPOSE: We aimed to determine the efficacy and the toxicity of low dose weekly gemcitabine with radiation therapy in medically unfit muscle-invasive bladder cancer patients. METHODS: Twenty-six patients were included into the retrospective analysis. Weekly gemcitabine was administered 75 mg/m(2) with a median dose of 63 Gy radiation therapy. Clinical target volume was defined as the urinary bladder only in conformal treatment planning. RESULTS: Median follow-up was 51 months (range 14-118 months). Complete response rate was 62.5 %. The 5-year local progression-free survival, disease-specific survival and overall survival rates were 40.6, 59.5 and 58.5 %, respectively. Concurrent chemotherapy was continued in 80.7 % of patients without any interruption. Gemcitabine was stopped due to grade 3 thrombocytopenia (n = 1), cardiac angina (n = 1), chronic obstructive pulmonary disease exacerbation (n = 1) or patients' reluctance (n = 2). CONCLUSIONS: Low dose weekly gemcitabine with concurrent radiotherapy is a tolerable regimen and have comparable outcomes with platinum-based combined treatments in muscle-invasive bladder cancer. Prospective randomized trials can help in understanding the safety and efficacy of this treatment specially in medically unfit patients.

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.