The current methods for improvement of the results of combined radiation therapy of the esophageal invasive cancer

Khairutdinov Rafik Vahidovich,

Republican Research Oncological Center, Tashkent, Uzbekistan.

Современные методы по улучшению результатов комбинированной лучевой терапии местнораспространенного рака пищевода

Хайруддинов Рафик Вахидович,

Республиканский онкологический научный центр МЗ РУз, г. Ташкент, Узбекистан.

В данной статье нами проанализировано течение болезни 61 больного неоперабельным раком пищевода. Из них 41 больных получили лучевую терапию и 20 больных – сочетанное лучевое лечение. Мужчин было 34 (55,74 %) и женщин -27 (44,26%). Внутрипищеводная местная гипертермия в комбинации с сочетанной лучевой терапией, а также химиотерапией и гипергликемией при раке пищевода является безопасным и относительно легко осуществимым методом лечения. Способ обеспечивает достоверное улучшение непосредственных результатов лечения больных неоперабельным местнораспространенным раком пищевода и повышается выживаемость пациентов.

Introduction

The problem of the esophageal cancer in our country, as all over the world, remains to be in the center of interests of medical science and medical clinical practice. The esophageal cancer is one the most occurrence malignant neoplasms. The number of patients with esophageal cancer primarily registered has been growing every year [1, 3, 6].

At present for treatment of esophageal cancer there were used radiation, surgical and combined methods of treatment. The radiation therapy remains to be single acceptable method of treatment in 70-80% of patients with esophageal cancer due to late referrals of the patients to medical specialists for help [2, 4, 5]. However, the results of radiation are unsatisfactory. The improvement of the results of conservative therapy as the main method of treatment for esophageal cancer is one of the actual task of the current oncology. For obtaining of the satisfactory results of the radiation therapy, form one side, it is necessary to direct maximal dose of irradiation to the focal of lesion, however occurring local and general complications prevent from full realization of the ability of radiation therapy. In this connection we consider that the development of new and improved methods of treatment directed to the defense of normal tissues from ionization and increasing harmful effect on the tumor is of great importance [4, 7, 9].

Material and methods

In our clinic in order to improve efficacy of the radiation therapy for patients with invasive forms of esophageal cancer the clinical study has been performed where there is used combination of DTGT with intracavitary irradiation associated with polyradiomodification. On the basis of the notion that tumor cells have less resistance to heat effect (40-43ºC), than healthy ones, the hyperthermia in combined and complex treatment of oncological patients has been using more frequently for present years. On our opinion the attempts to use local hyperthermia (LHT) as radiomodificator in the process of radiation therapy is one of the perspective directions (RT) [8, 9, 10].

In the Oncological Research Center of the Ministry of Health of the Republic of Uzbekistan the development of methods for use of intraesophageal hyperthermia-HT under experimental conditions and then for treatment of unresectable patients with invasive cancer of the esophagus (EIC) began in 2005 and continue till present. This report presents analysis of our accumulated experience as well as considerations concerning further development in this direction.

We analyzed development of the disease in 41 patients with unresectable esophageal cancer receiving only radiation therapy in 2006 and 20 patients receiving combined radiation therapy in 2007-2008. The males were 34(55,74%), females – 27 ( 44,26%). The mean age of patients was 59,3±3,7 years.

The technique of LHT was also used in some variants [2, 5, 7]. From 2000 there was used device based on the autonomic closed contour with circulating heat-carrier (water), and also including heat exchanger introduced in the esophageal lumen at the level of tumor and heater with pump (ultrathermostat “TC-24A” or “UT-15U”). The principle of the tumor heating is contact transmission of the heat, local contact hyperthermia (LCHT). The method of contact heat transmission is preferable now during performance of LHT.

Table 1.

The results of treatment of the esophageal cancer in relation to dose received.

During treatment of esophageal cancer we combined LHT with RT for all the patients with the exception of those which abilities have already been exhausted. Evidently LHT was sometimes performed in combination with mono- or polychemotherapy (ftoruracyl, metotrexat, cycplatin and others). Selection of one or another preparation depended from its presence in the clinic. The preparation is used in the general approved single or course doses.

The radiation therapy was performed in relation to standard anatomic cross-section on the border of the upper, middle and low thirds of the esophagus. The contour of anatomic—topographic scheme was closed to the oval with sizes along the main axes 20 [ 30 cm. The conditions of the irradiation were resource - gamma-apparatus Rocus, Agat. The sizes of the field at the level of focal center – 16 [ 15 cm, distance between resource and focus was 75 cm. the doses from the fields in static irradiation were selected so that every field of the studied plan gave similar contribution in dose in the center of the focus.

In the control group the distational telegammatherapy was performed with single dose (SD) 2 Gr five times a week, the planned summary focal dose (SFD) 60 Gr, used in graduated prolonged method, divided course with interval after 36-40 Gr 3-4 weeks.

Results and discussion

The patients were selected individually for use of one or other scheme of treatment in the majority of studies. The motive for change of the scheme of treatment was the search of optimal variant of the regimen for our used factors and their consecutive application. The evaluation of the direct results of treatment was performed in accordance to the WHO recommendations (2000), and the patients’ survival was assessed with use of direct method.

There were not found signs of tumor growth acceleration or metastatic spreading in our patients who received LHT in complex with RT or CT. Practically in all the patients even after some séances of LHT the esophageal patency had been improved.

The main group included 14 patients who received combined radiation therapy consisted of DTHT in regimen of multifractioned SD 1,5 Gr two times a day with interval 4 hours, SFD 60 Gr and intracavitary radiation therapy with SD 5 Gr on the middle and lower thirds, on the upper third esophagus in dose 3 Gr two times a week, SFD 25-30 Gr.

The abovementioned data showed that the full effect in the control group observed only in the patients receiving DTHT with SFD more than 60 Gr, and was 26,7%. Out of the patients receiving DTHT with SFD less than 60 Gr the full effect was not observed in any case.

Table 2.

Results of the associated radiation therapy of the esophageal cancer.

The full effect (Table 2) in the main group was achieved in 12 (60%) patients, and partial effect in 6(30%) patients and no effect was in two patients 910%).

The long-term results were found in 23 patients of control group and in 14 patients of the main group. In the control group the recurrent development during the first 6 months occurred in 9 patients, to 12 months in one patient, to 18 months there were survived 6 patients , and one patient was observed during 20 months (then he was lost for us). In the main group during observation (to 9 months) the recurrence was noted in one patients during the first 7 months, and continued growth was noted after 3 months in 3 patients.

In our clinic for improvement of the results of radiation therapy for the patients with invasive esophageal cancer the clinical examination was performed with use of combination of DTGT with intracavitary irradiation additionally to polyradiomodification. Our observations were directed to the maximal irradiation of the tumor cells in minimal lesion of the surrounding normal tissues and organs.

At present there has been formed group of patients who receive DTHT in regimen of multifractioning in SD-1,5 Gr, two times a day, interval between séances 4 hours, SFD 60 Gr. Two times a week the patients will be given intraesophageal radiation therapy – brachiotherapy with single dose (SD) in tumors in the upper third 2 Gr, in middle and lower thirds in dose 3 Gr, SFD – 25-30 Gr. The glucose will be administered intravenously 20%-400 ml two hours before the first séance of irradiation with blood sugar indicator more 12 moll. Before onset of the DTHT 5-ftoruracyl in dose 500-750 ml will be introduced intravenously. Before brachiotherapy there will be introduced intravenously cysplatin 30 mg, summary dose 90 mg, and séances of local hyperthermia.

At present time during treatment of the patients with LHT we use the scheme including associated RT, brachoiotherapy, LHT, Hgl and CT. However, in this case during séances of brachiotherapy and LHT the ischemization of the tumor occurred, at least in the layers adjusted to the heat changer at the expense of rising pressure in it up to 180-200 mm Hg. The results obtained indicated about increase in efficacy of the treatment. The investigation is continuing, and its results will be the subject of the special report.

Conclusions

From the studied regimens of irradiation the round rotation, technique of the three-field irradiation allowing achievement of high even irradiation of the focus is recommended for treatment of invasive esophageal cancer.

The further improvement of the combined use of combined radiation therapy with radiochemomodificators (local hyperthermia and hyperglycemia) for treatment of esophageal cancer is justified.

Intraesophageal local hyperthermia in combination with associated radiation therapy as well as with chemotherapy and hyperglycemia in esophageal cancer appeared to be safe and relatively feasible method of treatment. The method provides reliable improvement of the direct results of treatment for patients with unresectable invasive esophageal cancer and improves survival period of the patients treated at all the terms of observation.

References

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Поступила в редакцию 19.03.2010 г.