Local control of glomus tumors of the head & neck by radiation therapy and surgery.

PURPOSE: Glomus tumors are rare tumors, highly vascular and typically radiosensitive. Therapeutic options include surgery, radiation therapy (RT), embolisation or any combination of them, but the appropriate treatment still remains a challenge. The purpose of this study was to report the results of local control of 7 patients with glomus tumors treated with surgery and external beam RT (EBRT). METHODS: All of the patients underwent primary surgery and then postoperative EBRT. Follow-up was calculated from the date of initiation of EBRT and ranged from 3 to 15 years (mean 7.14, median 6.2). The likelihood of local control was analysed using the Kaplan-Meier product limit method. We also analysed the average duration of response between two groups of patients with different doses of EBRT as well as the presence of acute and late EBRT complications. RESULTS: Local control was obtained in 6/7 (85.7%) patients. Moreover, local control was achieved in 3/4 (75%) patients with recurrent glomus tumors, while in patients with postoperative residual disease local control was obtained in 3/3 (100%) of them. Patients who received <50 Gy (n=2) had shorter average duration of response compared to patients who received >50 Gy (n=5; p=0.248). There were no severe treatment complications. CONCLUSION: Surgery and RT represent an appropriate treatment approach for advanced glomus tumors with acceptable complications.

Use of high-dose cytarabine to enhance cisplatin cytotoxicity-effects on the response and overall survival rates of advanced head and neck cancer patients.

UNLABELLED: It has been reported that cytarabine, acting by at least two different mechanisms, enhances the cytotoxic effect of cisplatin in in vitro systems. The aim of this open, prospective, randomised study was to estimate the eventual benefits from the inclusion of high-dose cytarabine in the cisplatin-5-fluorouracil (5-FU) regimen as first-line treatment of patients with advanced head and neck cancer. The study recruited successive patients with unresectable grade I/II head and neck cancer who were not suitable for irradiation treatment (T any N3 or T4 N2C), metastatic or previously irradiated. All patients gave their informed consent. A joint ear, nose and throat (ENT) oncological committee performed the selection. A total of 170 patients were included in the study. Patients randomised to arm A were given 1000 mg/m(2) cytarabine on day 1 preceding for 6 h cisplatin infusion, 30 mg/m(2)/24 h cisplatin intravenous (i.v.) bolus days 1-4 and 1000 mg/m(2)/24 h 5-FU in a 4-h infusion on days 1-4. Patients in arm B were given cisplatin and 5-FU in the same dosage and schedule as in arm A. Additional irradiation+/-surgery was performed if and when feasible. Patients in both arms were well balanced with regard to clinical variables. The following results were obtained: Arm A: 84 patients were included, 74 were evaluable for activity; RESPONSE: complete response (CR) 8 (11%), partial response (PR) 40 (54%), stable disease (SD) 11 (15%), progressive disease (PD) 15 (20%). The overall response rate (RR) based on the evaluable patients was 48/74 (65%, 95% confidence interval (CI) 54-75%); The RR based on an intent-to-treat analysis was 57%, 95% CI 47-67%; Median survival was 13 months; There were 50 episodes of granulocytopenia grade IV and 15 of febrile neutropenia per 316 cycles. Arm B: 86 patients were included, 80 were evaluable for activity; RESPONSE: CR 7 (9%), PR 29 (36%), SD 10 (12.5%), PD 34 (42.5%); The overall RR based on the evaluable patients was 36/80 (45%, 95% CI 35-56%); The RR based on an intent-to-treat analysis was 42%, 95% CI 32-52%; Median survival was 8 months; There were 14 episodes of granulocytopenia grade IV and 7 febrile neutropenias per 324 cycles. The RR was significantly higher in arm A (P=0.013), power (one-sided) 80%. The proportion of patients from the appropriate subset who achieved a clinical response making additional treatment feasible was higher in arm A (P=0.00015), as well as the proportion of patients with a performance status 2+3 achieving a response (P<0.0001). Using the Log-rank test, patients from arm A achieved a significantly longer survival (P=0.009), with the probability of survival at 12 months of 0.58 for patients in arm A and 0.28 for patients in arm B. Grade IV granulocytopenia and thrombocytopenia were more frequent in arm A. Due to its haematological side-effects, cytarabine might not be the ideal drug to modulate the cytotoxicity of cisplatin. However, other modulators of its activity could be of interest for further studies in head and neck cancer patients.

Neck dissection in the management of regional metastases in patients with undifferentiated nasopharyngeal carcinomas.

Residual regional disease after the primary treatment of nasopharyngeal carcinoma is still considered to be a therapeutic problem. The limitations of prophylactic radical radiation, further doses of irradiation as a useful salvage procedure, and the effects on vital structures were the reasons that we employed a therapeutic protocol consisting of radical neck dissection after 40 Gy of radiotherapy and a full tumor dose after surgery. The initial treatment consisted of chemotherapy. Between 1977 and 1991 surgical removal of residual neck metastases was performed in 44 patients with undifferentiated nasopharyngeal carcinomas who had regional metastases at the time of diagnosis. Fourteen patients (group A) had radical neck dissections after initial chemotherapy (using doxorubicin, etoposide, bleomycin and/or 5-fluouracil) and between two courses of locoregional radiotherapy. The remaining 30 patients (group B) were operated on after finishing chemotherapy and locoregional radiotherapy (group B 1) or receiving only full-dose locoregional radiotherapy (group B 2). All patients had histopathologically proven complete remission of primary tumors before neck surgery. The five-year survival rates for group A were 78%, 40% for group B 1 and 27% for group B 2. There were statistically significant differences between groups A and B (P < 0. 01), but not between groups B 1 and B 2. In group A one patient died from subsequent distant metastases and two from local tumor recurrences. Twenty patients died in group B, regional relapses occurred in 40% of the patients in group B 1 and 33% in group B 2, while distant metastases developed in 40% of group B 2. These findings again showed that radical neck dissection was an effective approach for controlling neck disease. When performed after initial chemotherapy and between two courses of radiotherapy, surgery significantly improves the prognosis of patients with positive regional lymph nodes at the time of diagnosis.

A comparative study of undifferentiated nasopharyngeal carcinoma treated with radiotherapy or combined treatment with zorubicin-cisplatin and radiotherapy.

Undifferentiated nasopharyngeal carcinoma has been related to the Epstein-Barr virus. These tumors are known to be radiosensitive and chemosensitive. While radiotherapy (RT) allows for a high rate of local control, 80% of all patients die from or with metastatic spread. This study analyzed 61 patients treated with RT alone and 28 treated with zorubicin (ZRB)-cisplatin (CDDP) and RT between 1977 and 1990. All patients treated with RT received 60-74 Gy in 6-7 weeks. Patients treated with combined therapy received ZRB 250 mg/m2 on the 1st day and CDDP 30 mg/m2 from the 2nd to 5th day. The interval between cycles was 4 weeks. Following treatment with chemotherapy patients were then given RT. The 5-year survival rate was 20% for patients with T1 and T2 tumors when treated with RT alone and 54% when treated with chemotherapy (CT). This was 25% for T3 and T4 lesions with RT only and 27% for RT with CT. Survival of patients with N0 and N1 lesions was 41% after RT and 60% after RT with CT. This decreased to 10% for N2 and N3 lesions treated with RT and 30% with RT and CT.

[Treatment of locally advanced esophageal cancer by combined intralumenal brachytherapy and external beam radiotherapy]. / Lecenje lokalno uznapredovalog karcinoma jednjaka kombinovanom endoluminalnom i transkutanom radioterapijom.

The prognosis of patients with esophageal cancer is poor, due to frequent local recurrence and distant metastasis. The last decade has also seen that brachytherapy as a treatment with real potential to improve the therapeutic ratio of external irradiation. From March 1993 to October 1994 at the Institute of oncology and radiology in Belgrade, 18 patients with locally advanced esophageal cancer were treated by combined intralumenal brachytherapywith external beam irradiation. Median age was 59.6 years (range 43-70) and male/female ratio 2.6:1. Biopsy via endoscopy showed squamous cell carcinoma in 17 patients and adenocarcinoma in one case. External beam radiotherapywas applied on linear accelerator by locoregional texhnique with tumor dose of 30-60 Gy in 10-30 fractions. Intralumenal brachytherapy was eprformed on microselectron with tumor dose 5-20 Gy in 1-4 fractions. Response rate (complete response rate + partial response rate) was registrated in 13/18 (72%) patients. The good paliative effect for dysphagia, continuated passage for any food and increase body weight was shown in 16/18 (88%) patients. Six months after treatment, 7/13 patients were free of disease. Acute complications as irradiation pesophagitis occured in majority of patients.