Comparative results of preoperative chemoradiotherapy and thermochemoradiotherapy for locally advanced laryngeal cancer.

The study is based on the results of treatment of 60 patients with locally advanced laryngeal cancer (T3-4N0-3M0) exposed to combined treatment: 31 with preoperative chemoradiothera-py, 29 thermochemoradiotherapy. Radiotherapy was performed in the hyperfractionated mode: "1 Gy +1 Gy" (every 4-5 hours) 5 times a week to 30-40 Gy in total. Local hyperthermia was performed 2 times a week before the second fraction of radiotherapy in 3-4 sessions. Eight-day courses of chemotherapy were administered in the beginning of radiotherapy by scheme: vincristine (1. 4 mg/m2 per 1day), cisplatin (20 mg/m2 2, 3, 4 days), bleomycetin (10 mg/m2 5, 6 days), cyclophosphamide (200 mg/m2 7, 8 days). Surgical treatment was performed through 2,5 3 weeks after completion of radiotherapy. Local hyperthermia intensified the course of radiation reaction on the mucous of the larynx but not significant influenced on healing of surgical wounds. Thermochemoradiotherapy compared with chemoradiotherapy raised local relapse-free survival from 75 to 93% (p = 0. 07), regional, for a group of patients with stage N1-3 from 33 to 70%, N1-2 from 40 to 78% (p = 0. 1), loco -regional from 67 to 87% (p = 0. 04). Our findings suggest the necessity for further research on the use of thermochemoradiotherapy in combined treatment of patients with locally advanced laryngeal cancer.

[The results of combined treatment of patients with locally advanced laryngeal cancer using preoperative chemoradiotherapy].

The combined treatment with preoperative chemoradiotherapy (CRT) was performed in 28 patients with locally advanced laryngeal cancer (T3-4N0-3M0). Radiation therapy (RT) was carried out according to the scheme "1 + 1 Gy" (interval 4-5 hours) 5 times a week till 30-40 Gy. RT was accompanied by simultaneous polychemotherapy: vincristine (1.4 mg/m² per day), cisplatin (20 mg/m²--2-4 days) bleomicetin (10 mg/ m²--5, 6 days), cyclophosphamide (200 mg/m²--7, 8 days). Surgical treatment was carried out in 2.5-3 weeks after CRT. CRT allowed conducting organ-saving surgery on the larynx in 11 (52%) of 21 patients with T3 of primary tumor. All other patients underwent laryngectomy at a different volume. Five-year disease-free survival for the whole group in total (T3-4) was 88%. Relapses of regional metastases (MTS) occurred in 7 of 9 patients including in 4 of 5 patients after lymphadenectomy. The overall survival of patients with T3N02 was 71%, with T4N0-3--20%. Thus we have developed a method of treatment allowing to achieve high local relapse-free survival in patients with locally advanced laryngeal cancer. However organ-saving effectiveness of preoperative CRT and its effect on regional MTS remain low, which requires further research in this direction.

[Comparative results of conservative chemoradiotherapy and thermochemoradiotherapy for locally advanced laryngeal cancer].

There were analyzed results of treatment of 58 patients with laryngeal cancer T3-4N0-3M0. Chemoradiotherapy (CRT) was carried out in 27 patients, thermochemoradiotherapy (TCRT)-in 31 patients. Radiotherapy (RT) was performed in hyperfractionated mode (1 Gy + 1 Gy with an interval of 4-5 hours) 5 times a week to CTD 52-60 Gy with a 2-week break after CTD 30-40 Gy. Local hyperthermia (LHT) was carried out 2 times a week before the second fraction of RT in an amount of 3-6 sessions. The first cycle of polychemotherapy was administered at the beginning of RT and the second one-after the break. The local control under the primary tumor category T3 after CRT was equal to 58% and after TCRT--88%, at T4--72% and 25%, respectively. Late radiation damage of the larynx in the form of mucosal edema and perichondritis after CRT was in 2 patients (7%) and after TCRT--in 3 patients (10%). Thus, TCRT for locally advanced laryngeal cancer allows obtaining a higher overall survival and a local control as compared to CRT and does not lead to a significant increase of frequency of perichondritis.

[Conservative thermochemoradiation therapy of locally advanced laryngeal cancer].

Thermochemoradiation therapy was performed in 31 patients with laryngeal cancer (T3-4N0-3M0). Radiotherapy was performed in 2 stages 1+1 Gy (every 4-5 hours), 5 times a week to SOD 52-60 Gy with a 2-week break after SOD 30-32 Gy. Local hyperthermia was carried out two times a week before the second fraction in an amount of radiation therapy sessions 3-6. In the days of local hyperthermia second fraction of radiotherapy increased to 3 Gy. Courses of chemotherapy were combined with radiation therapy and local hyperthermia at the beginning of each stage of treatment. For the whole group a complete response of the primary tumor was diagnosed in 25 (80.6%) patients, partial - in 6 (19.3%). Of the 12 patients with N1-3 complete regression of metastases occurred in 5 (41.7%), partial - also in 5 (41.7%). Five-year overall survival was 88.2% T3N0, T4N1 in 3 - 62.1%. Local control of the primary tumor in these terms in the group T3 was detected in 88.2%, in the group T4 - 77.8%, regional control of metastases with N1-3 - 33.3%. Late swelling of the mucous membrane of the larynx developed in 4 (12.9%) patients, perichondritis - in 3 (9.7%). Thermochemoradiation therapy of locally advanced cancer of the larynx provides a fairly good results comparable with those of the combined treatment.

[Prognostic value of markers for proliferative activity and apoptotic regulation in laryngeal squamous cell carcinoma].

Prognosis for patients with laryngeal squamous cell carcinoma depends on many factors, among which molecular biological markers receive ever increasing attention. The purpose of this study was to determine the prognostic value of the expression of the proteins p53 and bcl-2 and the proliferation markers Ki-67 and cyclin D1 in laryngeal squamous cell carcinoma. Biopsy specimens from 64 patients aged 34 to 77 years (mean age 56+1.2 years) with invasive laryngeal squamous cell carcinoma, who received combination therapy at the Medical Radiology Research Center, Russian Academy of Medical Sciences, were studied. The level of Ki-67 and the expression of cyclin D1, p53, and bcl-2 were compared with clinical and anatomic parameters (T stage, tumor grade, and the presence of regional metastases), using Student's t-test and fourfold table analysis (X2 or Fisher's exact test). Survival rates were analyzed by the Kaplan-Meier method; the significance of differences between survival curves was confirmed by Cox's F-test. The value p0.05 was taken to be significant. Ki-67 is an important prognostic marker for the N status (p=0.03) and recurrence (p=0.04) and a marker for tumor grading (p<0.01). Cyclin D1 expression is associated with low overall and relapse-free survival rates (p=0.05 and 0.03, respectively). The prognostic marker for a recurrence is p53 (p=0.01) that is related to the N status at the trend level (p=0.08). The marker bcl-2 is associated with high overall survival (p=0.01) and N status at the trend level (p=0.08).

[Results of combined treatment in locally advanced cancer of the larynx using preoperative thermochemoradiotherapy].

This paper analyzes the results of combined treatment with preoperative thermochemoradiotherapy in 28 patients with locally advanced laryngeal cancer (T3-4N0-3M0). Radiation therapy (RT) 32 Gy was carried out 5 times a week with splitting the daily dose of radiation on the 2 factions (interval 4 hours) on a "1 Gy + 1 Gy," in the days of the local hyperthermia (LGT)--on a "1 Gy + 3 Gy". LGT in an amount of 3-4 sessions was performed two times a week before the 2nd fraction of RT. The course of polychemotherapy was administered concurrently with RT and LGT. In 2-3 weeks after completion of the course thermochemoradiotherapy patients were operated. Organ-saving operations were performed 10 (56%) of 18 patients with primary tumors categories T3 and 2 (20%) of 10 with T4. Postoperative wounds healed by first intention in 21 (75%) patients. The cumulative 5-year overall survival in the whole group (T3-4N0-3) was 89%, for patients without regional metastases (T3-4N0)--100%. Relapse-free survival time for those patients with a primary tumor T3 equaled 94%, T4--90%. Relapse metastases occurred in 20% of patients. Thus, preoperative thermochemoradiotherapy is a highly effective method of treatment for locally advanced cancer of the larynx and does not lead to the development of severe postoperative complications.

[Angiogenesis in laryngeal squamous carcinoma and its prognostic significance].

Prognosis for laryngeal squamous carcinoma patients depends on numerous factors, and tumor-related angiogenesis is one of them. Our study was concerned with prognostic significance of intra-tumor vascular bed in such patients. Bioptic material was sampled from 61 patients, aged 34-77, after combined treatment at the Center's Clinic. Microvascular density, overall perimeter of vascular wall and overall vascular area were compared with such clinical characteristics as T stage, tumor cell differentiation and presence of regional metastases using t-test (Student) and contingency tables (2x2) (chi2, Fisher's accuracy criterion). The Caplan-Meyer method was used to evaluate survival and Cox F-test--to assess survival curve difference significance (p < or = 0.05). The angiogenesis pattern proved a significant prognosticator for relapse, relapse-free and specific survival.

[Ki-67 and p53 expression as prognosticators of clinical course aggressiveness of squamous cell cancer of the larynx].

The study used bioptic sampling material from 64 patients with invasive squamous cell cancer of the larynx, aged 34-77 (mean age--56 +/- 1.2), receiving combined treatment at the Center's Clinic, Obninsk. Ki-67 and p53 levels were assayed vs. such clinico-anatomical parameters as tumor size, cell differentiation grade and presence of regional metastasis. The study revealed a significant direct correlation between Ki-67 index, on the one hand, and tumor size, tumor cell differentiation and relapse, on the other. p53 expression in tumor tissue was associated with a relatively high incidence of relapse (p = 0.01). Both markers may be used as prognosticators of survival in laryngeal cancer.

[Results of combined therapy for malignant tumors of the nasal cavity and accessory nasal sinus depending on the fractionation of preoperative radiotherapy].

Data on the treatment of 215 patients with locally advanced malignancies of the nasal cavity and accessory nasal sinus are presented. All patients received preoperative radiotherapy using different fractionation schemes under a total target dose (TTD) of 32-40 Gy. Surgery was carried out two weeks later. Whenever radicality of surgery was in doubt, postoperative gamma therapy included exposure to 2 Gy 5 times a week (TTD--30-40 Gy) (n=121). Group I (n-57) received radiation at standard fractionated dosage. In group II (n=66), fractionation, tentatively considered "dynamic" was used while, in group III, fractionation was dynamic in actual fact. In group IV (n=10), superfractionation (1+1 Gy) was employed in group V (n=6),--gamma-neutron therapy. Patients in group VI (n=51) were operated on as scheduled and received 5 Gy, twice a week (TTD--20 Gy). According to 5-year follow-up, the best results were obtained with the use of larger doses of preoperative radiation (groups II, III, VI). Postoperative radiotherapy proved ineffective and it would be useless unless ablative procedures were definitely faulty during surgery.

[Chemoradiation therapy in conjunction with physical means of radiomodification for locally advanced laryngeal cancer].

The study deals with the results of examination and treatment of 1040 patients with cancer (T3-4N0-3M0) of larynx and laryngopharynx. Radiotherapy was given to 358 patients concurrently with systemic polychemotherapy and different means of radiomodification. The remaining patients (682) receiving the same treatment minus systemic polychemotherapy were in control. Relapse-free (72.6%) and overall survival (82.7%) in the study group was significantly higher than in controls (54.7% and 63.4%, respectively) (p < 0.001). Moreover, an organ's function was preserved in 57.1% compared with 28.5% in control (p < 0.001).

[Combined therapy of malignant tumors of the upper jaw and nasal cavity using pre- and post-operative radiation with metronidazol radiomodification]. / Kombinirovannye lechenie zlokachestvennykh opukholei verkhnei cheliusti i polosti nosa s ispol'zovaniem pred- i posleoperatsionnogo kyrsov oblucheniia v sochetanii s radiomodifikatsiei metronidazolom.

Seventy-five patients with malignant tumors of the upper jaw and nasal cavity have received combination therapy. Administration of metronidasol (5-8 g/m2 body surface) in combination with large doses of preoperative radiation was shown to significantly improve 3-year total and recurrence-free survival-from 50 to 60% and 32 to 57%, respectively. As a result, no postoperative radiotherapy was required. Postoperative radiation treatment is indicated when means of radiosensibilization are not used. The use of radiomodifiers is mandatory in combination therapy of non-differentiated cell carcinoma, cylindroma, transitory-cell papilloma and non-epithelial neoplasms.