Sait Okkan

Multivariate analysis of prognostic factors in 75 patients with soft tissue sarcoma

The results of 75 patients with soft-tissue sarcomas treated by the combination of local surgical excision plus postoperative radiotherapy are reported. Thirty-five tumors were situated in the extremities, 32 in the trunk, and eight in the head and neck. Twenty-eight tumors were high grade, 33 intermediate and 14 low grade. Sixty-two patients had complete resections (wide or marginal) and 13 incomplete resections (intralesional). Radiation was administered with a shrinking-field technique (median total dose, 64 Gy; range, 50-78). Twenty-five patients developed local recurrence (33%). The 5-year local control rate was 67%. On univariate analysis, a tumor site other than extremity (p < 0.05), unfavorable histology (p < 0.01), and incomplete resection (p < 0.01) were poor risk factors for local recurrence. When multivariate analysis were performed, only incomplete resection (relative risk (RR) 7.2) remained a poor risk factor. The 5-year overall survival rate was 50.5% for the entire group. Following a univariate analysis of host tumor and treatment-related factors, a tumor site other than extremity (p < 0.05), high tumor grade (p < 0.01) unfavorable histology (p < 0.05), and incomplete tumor resection (p < 0.01) were found to significantly increase the risk of further tumor death. Multivariate analysis found high tumor grade (RR 5.6), and incomplete resection (RR 7) to be independent poor risk factors for survival.

Nasopharyngeal carcinoma in childhood: long-term results of 32 patients

PURPOSE To evaluate treatment results and prognostic factors, pediatric patients with nasopharyngeal carcinoma were reviewed. MATERIALS AND METHODS Thirty-two patients at the age of 16 and younger were treated for nasopharyngeal carcinoma. One patient had WHO type I, 15 had WHO type II, and 14 had WHO type III histology. All patients were treated with radiotherapy, median dose to nasopharynx and involved nodes was 70 Gy (range 60-70.4 Gy), three patients received intracavitary booster dose of 24 Gy in three fractions, 12 patients were also given from two to four courses of platinum based neo-adjuvant chemotherapy. RESULTS Twenty-three patients are alive and well with a median follow-up of 107 months. Ten and 15 years loco-regional control (LRC) and overall survival (OS) rates were 82.5, 68.7 and 72.7, 62.4%, respectively. Patient age, size of the lymph node and prolongation of overall external radiotherapy time were found to be the prognostic factors in univariate analysis, however the only factor remained significant after multivariate analysis was the size of the lymph node on LRC. Almost all long-term survivors experienced moderate to severe complications yielding complication free survival rate of 10.9% at 15 years.

Postoperative radiotherapy in carcinoma of the cervix: treatment results and prognostic factors

In order to assess the role of postoperative radiotherapy and prognostic factors, 126 patients who were treated with radiotherapy after surgery for clinical early-stage carcinoma of the cervix were reviewed. All patients received external pelvic radiotherapy and 37 patients were treated with additional vaginal cuff irradiation. The 5-year overall survival, disease-free survival and locoregional control rates were 71.1, 69.9 and 78.1%, respectively. The 5-year disease-free survival rates were 40% for grade 3 vs. 75.4% for grade 1 tumours (p = 0.05), 76.5% for pathological stage IB versus 54.1% for pathological stage IIA (p = 0.04), 36.6% for node-positive patients versus 82.5% for node-negative patients (p = 0.0017), 54% for full thickness cervical invasion versus 100% superficial cervical invasion (p = 0.01), 34.8% for positive margins versus 78.1 for negative margins (p < 0.0001). After a multivariate analysis, tumour grade (p = 0.026) and presence of positive margins (p = 0.006) were found to independently influence the outcome. Grade II and III complication rate was 5.5% in all patients. In conclusion, postoperative radiotherapy should be used in patients treated with simple hysterectomy as well as those treated with radical hysterectomy with unfavorable pathological findings.

Results and complications of high dose rate and low dose rate brachytherapy in carcinoma of the cervix: Cerrahpaşa experience

PURPOSE To evaluate the results and complications of treatment with high dose rate (HDR) compared to low dose rate (LDR) brachytherapy in cervical carcinoma. METHODS Three hundred and seventy patients who were treated with external irradiation and intracavitary brachytherapy and followed for more than 2 years between 1978 and 1998 have been recently updated. The low dose rate group consisted of 77 cases treated between 1978 and 1982 and HDR group consisted of 293 cases treated between 1982 and 1998. All patients first received external irradiation with 60Co or 9-18 MV photons and a median dose of 54 Gy was given in 6 weeks. In the LDR group, intracavitary treatment was given with Manchester applicators loaded with radium (30 mg) in an intrauterine tube and 20 mg in vaginal ovoids. The dose delivered to point A was on average 32 Gy in one application. In the HDR group, a total dose of 24 Gy was given to point A in three insertions 1 week apart. The dose rate was 0.62 Gy at point A. RESULTS The 5-year pelvic control rate was found to be 73% in the HDR group, compared with 86% in the radium group for stage I cases. In stage IIB and IIIB cases, the rates were 68% and 45% for HDR and 65% and 53% for LDR, respectively. In all stages, there was no statistical difference in pelvic control and survival rates between the two groups. Overall incidence of late complications was found as 31.1% and 31.9% in HDR and LDR groups, respectively. The grade 2-4 late complication rate was 14% in the HDR group compared to 19% in the LDR group (P>0.05). CONCLUSION HDR brachytherapy in the management of the cervix appears to be a safe and efficacious approach. Pelvic control, survival and complications rates are quite similar when compared with LDR.

Continuous hyperfractionated accelerated radiotherapy in the treatment of high-grade astrocytomas

Between May 1993 and January 1995, 36 patients with high-grade astrocytomas were treated with 1.05 Gy continuous hyperfractionated accelerated radiotherapy three times daily to a total target dose of 59.85 Gy in 19 days with 6-h intervals. The median age of the patients was 51 years and the median follow-up was 58 weeks. The median survival rate was 58 weeks and the cumulative survival rate was 22% at 2 years. No severe toxicity occurred in patients treated with this fractionation scheme. These results suggest that continuous hyperfractionated accelerated radiotherapy is an altered fractionation schedule for high-grade astrocytomas with tolerable acute toxicity and survival rates comparable to conventional fractionation and to other altered fractionation schedules.

Use of ornidazole in fractionated radiotherapy: dose tolerance, serum and tumour tissue concentration.

Sensitizing and neurotoxic effect of ornidazole, was tested in a double-blind randomized study in patients with carcinoma of the cervix and larynx. Ornidazole or placebo were given orally, two times weekly, for 3 weeks. Dose was 2.5 g/m2 for each administration. Total dose given was 15 g/m2. Radiation therapy was given 3 h after the drug administration. Ornidazole was well tolerated in the majority of the patients. No neurotoxic side effects, such as peripheral neuropathy or convulsion, were observed with a total dose of up to 30 g. Dizziness, somnolence and nausea were the prominent acute side effects, seen mostly (70%) in women. In the placebo group this rate was 17% (p less than 0.01). No important side effect was observed in men receiving ornidazole. Serum concentration of ornidazole reached the maximum level in 2-4 h after oral administration and ranged (23 patients) from 65.1 to 139.8 micrograms/ml. Mean half-life was 15.6 +/- 2.8 h. Peak concentration in tumour tissue was achieved 1-3 h after the administration, ranging from 13.0 to 78.0 micrograms/g. Tumour concentration of ornidazole ranged from 14 to 93% of the serum concentration at the time of irradiation.

The radiosensitizing effect of ornidazole in hypoxic mammalian tissue: An in vivo study

In this study the sensitizing effect of ornidazole is investigated in vivo. The selected test system is the acute killing effect of radiation within 4-6 days after abdominal irradiation ranging from 9 to 24 Gy, in groups of C57 black mice. Ornidazole is given intraperitoneally in 500 mg/kg, 100 mg/kg, 20 mg/kg doses prior to irradiation of animals breathing air, oxygen or nitrogen. A decrease of LD50 dose is observed from 24.39 +/- 5.66 to 16.38 +/- 1.86 and 18.04 +/- 2.48 Gy, respectively, in nitrogen breathing animals. No sensitizing effect was observed in doses of 20 mg/kg. Enhancement Ratio (ER) was found to be 1.48 +/- 0.25 and 1.35 +/- 0.27; relative sensitizing efficiency (RSE) was 40% and 29% respectively. No sensitizing effect was observed in animals irradiated in oxic conditions. These results showed that ornidazole (Ro-7-0207) has a sensitizing effect on hypoxic cells in vivo. It is worthwhile to try this drug in a clinical study.