[Combined treatment of rectal cancer with moderate risk of tumor progression]. / Rezul'taty primeneniya kombinirovannogo metoda lecheniya bol'nykh rakom pryamoi kishki so srednim riskom progressirovaniya opukholevogo protsessa.

OBJECTIVE: To increase the effectiveness of combined treatment in patients with rectal cancer and moderate risk of progression based on the concept of polyradiomodification (PRM). MATERIAL AND METHODS: The study included 337 patients with rectal cancer and moderate risk of tumor progression. A short course of radiotherapy (cRT) (5x5 Gy) combined with several radiomodifiers (cRT+PRM) was performed in 147 (43.6%) patients. Other 190 (56.4%) patients underwent cRT. The following radio modifiers were used: three-time application of local microwave hyperthermia (Yacht-3 or Yacht-4 devices), two-time intrarectal delivery of a biopolymer composition with Metronidazole before the 3rd and 5th irradiation sessions and two-week oral administration of Capecitabine (Xeloda) at a daily dose of 2.0 g/m2. Surgery was performed in 4-6 weeks after radiotherapy. RESULTS: CRT+PRM program increased 5-year relapse-free survival up to 81.3% compared to 60.3% after cRT alone (p=0.0003) due to significant reduction of the incidence of cancer recurrence from 8.4% to 0.7% (p=0.0013). More effective local growth control expanded the indications for sphincter-sparing surgery. These procedures were performed in 89.1% and 70.5% of patients, respectively (p=0.00001). In the cRT+PRM group, sphincter-sparing surgery reduced incidence of cancer recurrence from 13.7% to 0.8% (p=0.0110), distant metastases - from 23.9% to 13.7% (p=0.00349). CONCLUSION: Radiomodification in neoadjuvant radiotherapy is justified in patients with moderate risk of tumor progression, improves long-term results and increases the incidence of sphincter-sparing surgery.

Case Report: Education and training of RTTs for radiation oncology departments in Russia.

Modern radiotherapy is performed with sophisticated equipment that requires highly qualified professionals. In the Russian Federation the responsibilities of Radiation Therapy Technologists (RTTs) are carried out by medical nurses who receive on-the-job training. The article discusses the problems of RTT education and training, describes our own teaching experience and suggests further development for the national RTT education system in Russia.

Short-course preoperative radiotherapy combined with chemotherapy, delayed surgery and local hyperthermia for rectal cancer: a phase II study.

PURPOSE: The aim of this study was to investigate the feasibility of short-course radiotherapy with oral capecitabine, hyperthermia and delayed surgery for neoadjuvant treatment of rectal cancer. METHODS: Patients with clinically staged T2-3N0-2M0 primary rectal cancer were included. All patients received short-course 25 Gy in 5 Gy fractions radiotherapy with capecitabine, local hyperthermia and metronidazole. Capecitabine 1000 mg/m2 twice a day was given on days 1-14. Local hyperthermia, 41-45 °C for 60 min, was performed on days 3-5. Metronidazole 10 g/m2 was administered per rectum on days 3 and 5. The time interval to surgery was not less than four weeks after neoadjuvant treatment. The primary end-point was pathological complete response (pCR). Secondary end-points included neoadjuvant treatment toxicity, tumour regression, surgical and oncological outcomes. RESULTS: A total of 81 patients were included in the analysis. Ten (12.3%) patients had grade 3 toxicity and one (1.2%) patient had grade 4 toxicity. Sphincter-sparing surgery was performed for 78 (96.3%) patients. There was no postoperative mortality. Postoperative complications occurred in 11 (13.8%) patients. Sixteen (20%) patients had a pCR. The median follow-up was 40.9 months. There were no local recurrences. Nine (11.1%) patients developed distant metastases. Three-year overall survival was 97% and the three-year disease-free survival was 85%. CONCLUSIONS: Short-course radiotherapy with chemotherapy, radiosensitizers and delayed surgery is a feasible treatment for rectal cancer and may lead to tumour regression rate comparable with long-course chemoradiation.

[Primary multiple malignant lung tumors. References and a clinical observation].

The problem of primary multiple tumors is relevant to current clinical oncology because of increasing of number of patients with multiple malignant tumors and unsolved issues of treatment. Primary multiple malignant lung tumors is a common oncological situation requires an individualized, differentiated approach to treatment. The results of treatment are associated with the prevalence of the process, stages of tumor development, spare capacity of patients. There is presented clinical example of a patient with metachronous primary multiple malignant tumors of one lung.

Prophylaxis and treatment of radiation oral cavity mucositis by hydrogel preparations in patients with oropharyngeal cancer.

Development of radiation mucositis in patients with oropharingeal cancer who are treated by radiation therapy leads to constrains breaks, decreases of the quality of life and makes the radiation dose in target insufficient. All above mentioned increases recurrence risk. Since 2010 there was developed and introduced the method of prophylaxis and treatment of radiation injuries of oral cavity in patients with oropharingeal cancer which gives an ability to improve radiation treatment outcomes and the quality of life of patients.

[Conformal radiotherapy in nasopharyngeal cancer patients].

The paper is aimed at the determination of the efficiency of various technologies of conformal radiotherapy for patients with nasopharyngeal carcinoma. The study included 56 patients with squamous cell carcinoma of the nasopharynx treated with conformal radiotherapy. 3D-CRT was performed for 28 patients, IMRT--22 patients, RapidArc--6 patients. Dosimetric parameters were determined for planned volumes and organs at risk. TD on high-risk areas was 70Gy, intermediate-risk zones 60-66Gy and low-risk areas 50-56 Gy. There were determined session duration of exposure and the number of monitor units to evaluate the efficiency of treatment. Average (Dmean), maximum (Dmax) and the minimum (Dmin) dose for RapidArc, IMRT and 3D-CRT on PTV amounted to 70.2 Gy, 69.1 Gy and 70.7 Gy; 76.2 Gy, 76.1 Gy and 77Gr; 48.8, 54.4 and 46,6Gr respectively. Compared with IMRT and 3R-CRT RapidArc reduce Dmean in the brainstem and optic nerves by 14.1% and 23%; 12.2% and 25% respectively. The average number of MU (monitor unit) with RapidArc, IMRT and 3D-CRT was 357, 1386 and 870. The average session time of irradiation was: with RapidArc, IMRT and 3D-CRT--300, 900 and 480 seconds. Compared with IMRT and 3D-CRT average treatment time and the number of monitor units in RapidArc were reduced by 74%, 42% and 67%, 47%. Thus RapidArc and IMRT technologies allow getting a better dose distribution in the irradiated volume, compared with 3 D-CRT on homogeneity and conformity. RapidArc technique reduces the pressure on the critical organs, diminishes exposure to the session and a number of MU.

[Results of complex treatment of patients with squamous cell carcinoma of the anal canal using advanced radiotherapy technologies].

During recent decades radiotherapy is the basis, on which it is built a medical complex that is the first-line treatment of patients with squamous cell carcinoma of the anal canal. An increase of overall and disease-free survival and quality of life of patients with squamous cell carcinoma of the anal canal at the present stage of development of a comprehensive medical treatment is largely due to the improvement of technical equipment of radiotherapy departments of oncology clinics. The use of modem linear electron accelerators and systems of computer dosimetric planning to create a 3D program of isodose distribution, diagnostic devices (computed tomography and magnetic resonance imaging) as well as a number of other conditions permit accurate summarizing of proposed dose, reducing of absorbed dose to critical structures, diminishing unplanned interruptions in chemoradiotherapy course by means of modern technologies of conformal radiotherapy (3D CRT, IMRT, VMAT). The paper presents the preliminary results of a comprehensive medical treatment of 14 patients with squamous cell carcinoma of the anal canal.

[The role of stereotactic radiotherapy in the treatment of patients with liver metastases].

Application of modern linear electron accelerators, equipped with precise navigation systems, maximum conformal dose delivery as well as imaging of irradiated focus significantly increased possibilities of escalating of doses of ionizing radiation in a selected volume with the necessary protection of the surrounding critical structures. These technological solutions and modern ideas about possibilities of remote beam radiation therapy resulted in a significant increase of the role of radiation therapy and, in particular, stereotactic radiotherapy in the treatment of patients with liver metastases. This technique allows creating locally in metastatic tumor site a high dose of ionizing radiation causing by that the destruction of the tumor. This promising direction in treatment of liver metastases significantly expanded possibilities of complex treatment and enabled us to provide specific assistance to those patients who have been rejected from other methods of treatment.

[Radiation pneumonitis in the treatment of early-stage breast cancer].

Despite of improvement of radiotherapy techniques and increasing usage of conformal radiation therapy which provides decrease of dose for normal tissues and organs, cases of radiation-induced injuries are still registrated. The aim of this study is to determine frequency and severity of lung toxicity in 513 breast cancer patients with Tis-2N0-2M0 disease after breast conserving surgery and chemotherapy depending from radiation therapy technique and irradiation volume. It is quite clear that in breast cancer patients frequency of lung toxicity after breast conserving surgery and RT increases from 20-24% when irradiating only breast to 37-41% when irradiating breast and regional lymph nodes. In our analysis the frequency of lung toxicity was quite similar for 2D conventional therapy (27,4%) and for 3D conformal therapy (28,7%). The risk of developing radiation pneumonitis increases dramatically with extension of V20 for ipsilateral lung more than 30%, mean lung dose more than 18 Gy, in patients with initial small volume of the lung (less than 110 cm3).

[Possibilities of stereotactic radiotherapy in the palliative treatment of patients with pancreatic cancer].

Morbidity and mortality from pancreatic cancer is steadily increasing. Resectable cases are not more than 20%. Conventional schemes of chemoradiation and radiation therapy are durable over the time, have toxicity and low treatment outcomes. Many foreign authors consider as promising the technique of stereotactic radiotherapy, which is often used in pancreatic cancer and permit achieving high local control. At our institution there has been developed and introduced into clinical practice a method of stereotactic radiotherapy for the palliative treatment of patients with pancreatic cancer, which improved not only the duration but also the quality of life of patients.

[The role of stereotactic radiotherapy in treatment of patients with metastatic lesion of lungs].

Since February 2012, in order to increase the effectiveness of treatment and quality of life of patients with disseminated disease, there was developed and implemented a method of stereotactic radiotherapy for metastatic lesion of lungs by tumors of different histological types. 20 patients were treated by stereotactic radiotherapy ROD 7 Gy in five sessions during 5 days. There were evaluated results of treatment and prospects of this method.

[Complex treatment of breast cancer patients with brain metastases].

Brain metastases in breast cancer develop for 24-32 months after the detection of the primary tumor. The study included patients with brain metastases who were divided into three groups: the first group--with early chemoradiotherapy (CRT) without induction chemotherapy (IC) by capecitabine; the second group--with delayed CRT with 4 or 8 courses of IC by capecitabine; the third group (a historical control) who received only whole brain radiation therapy. The median time to progression of intracranial metastases was 15.3, 12 and 5 months, respectively. The median time to the intracranial progression significantly less in the third group (5 months) compared with the first (15.3 months) (p = 0.0007) and the second (12 months) (p = 0.027) groups. The overall survival rate was 22.1, 15.1 and 6.8 months in three groups, respectively.

Phase II study of concomitant chemoradiotherapy with local hyperthermia and metronidazole for locally advanced fixed rectal cancer.

AIM: Locally advanced fixed T4 rectal cancer has a poor prognosis and no standard treatment strategy. The aim of this study was to investigate the safety and efficacy of neoadjuvant chemoradiotherapy using hypofractionated radiotherapy combined with local hyperthermia, capecitabine, oxaliplatin and metronidazole. METHOD: Radiotherapy was given to a total dose of 40 Gy in 10 fractions. Capecitabine 650 mg/m(2) twice a day was given on days 1-22 and intravenous oxaliplatin 50 mg/m(2) was administered on days 3, 10 and 17. Local hyperthermia, 41-45°C for 60 min, was performed on days 8, 10, 15 and 17. Metronidazole 10 g/m(2) was administered per rectum on days 8 and 15. Surgery was carried out within 6-8 weeks after neoadjuvant treatment. The primary end-point was R0 resection rate. Secondary end-points included 2-year disease-free survival, 2-year overall survival, local recurrence rate, grade III-IV tumour regression (Dworak) and treatment toxicity. RESULTS: From July 2006 to February 2011, 64 previously untreated patients were enrolled. R0 resection was carried out in 59 (92.2%). Five (7.8%) remained inoperable. Seven (10.9%) patients had grade IV and 30 (46.9%) had grade III regression. The main grade III toxic events included diarrhoea (15.6%, n = 10), vomiting (3.1%, n = 2), proctitis (3.1%, n = 2) and skin reaction (1.6%, n = 1). Only one (1.6%) patient had grade IV diarrhoea and vomiting. The median follow-up was 24.9 months. Two-year overall survival was 91% and 2-year disease-free survival was 83%. CONCLUSION: Hyperthermia combined with chemotherapy to produce radiosensitization for locally advanced fixed primary rectal cancer is followed by a high R0 resection rate, with toxicity comparable with standard regimens.

[Cryoradiation therapy of the patients presenting with locally advanced auricular skin cancer].

The objective of the present work was to improve the efficacy of treatment of locally advanced auricular skin cancer with the use of the newly proposed combined method including cryogenic and radiotherapy. The choice of the optimal temporal and thermal parameters of combined cryoradiotherapy was based on the results of previous experimental and theoretical investigations. Each radiation treatment session was immediately preceded by local cooling of the tumour down to 0°C - minus 5°C with a nitrogen vapour. Radiotherapy was performed with the use of either photon or electron radiation at a single local dose of 2 Gy-2.25 Gy (the total cumulative dose 64 Gy-68 Gy). As many as 14 patients presenting with locally advanced auricular skin cancer received combined cryogenic and radiotherapy; 10 of them had basal cell carcinoma and 4 squamous cell carcinoma. In all these cases, the treatment resulted in the complete regression of the tumours. Further observation during a follow-up period from 2 to 14 years in duration demonstrated that only two patients developed tumour relapses. These secondary neoplasms were successfully treated by cryodestruction (n=1) and surgical ablation (n=1). The proposed cryoradiotherapy made it possible to preserve the anatomical relief of the auricle and the auditory passage with good aesthetic and functional outcomes.

[Effectiveness of neoadjuvant chemoradiotherapy of locally advanced rectal cancer in conjunction with local hyperthermia and metronidazole].

Our study included 36 patients with hard fixed rectal tumors (T3, T4) who had received combined treatment at the Center's Clinics. On irrigoscopic evidence, lesions were more than 10 cm long. Radiotherapy was conducted thrice a week, STD of 4 Gy--TTD of 40 Gy; capecitabine, per os, 650 mg/m2 twice a day, days 1-22; oxaliplatin, 50 mg/m2, intravenously, days 3, 10 and 17; metronidazole in polymer composition, intrarectally, 10 mg/m2, twice, days 12 and 17 of radiotherapy; local hyperthermia (the <> installation), 460 mHz, 41-45 deg. C, 60 min, days 8, 12, 15 and 17. Diarrhea (stage III) was reported in 3 (8.3%); no toxicity (grade IV). Radical surgery was carried out in 35 (97.2%); sphincter-saving operation--20 (55.5%). Therapy-related pathomorphism (grade III-IV) was detected in 15 (42.8%). Combined neoadjuvant chemoradiotherapy plus polyradiomodification featured low toxicity and good tolerability and immediate effect.

[Advances in radiotherapy of malignant tumours].

The authors discuss changes in the equipment and technologies of radiotherapy during the past 10-15 years. These changes ensured the improvement of diagnostics and treatment of neoplasms by two other main methods, surgical and medicamental. Modifications in the combined application of radiotherapy and surgery and of radio- and pharmacotherapy are discussed.

[Docetaxel as a component in the combined therapy of locally advanced squamous cell carcinoma of the glottis and oral cavity].

Two modalities of chemoradiotherapy for locally advanced squamous cell cancer of oro-hypopharynx and oral cavity were compared in the treatment of 34 patients. Five-year survival after cisplatin, 5-FU, taxotere, and carboplatin plus irradiation with TTD of 68-72 Gy (group 1) was 59.5% versus 13.8% without taxotere (group 2). Relapse was in 9 cases (60%) (4 - group 1 and 5 - group 2). Post-therapeutic complication stage III-IV was 57.8% (group 1) and 48% (group 2).

[Conformal radiotherapy for prostate cancer].

Data are presented on a retrospective comparison of the results of remote radiotherapy and combined treatment of prostate cancer (T2T4NxM0) (88) at the Center's Clinics (1999-2003). Diagnosis was confirmed by morphological evidence: T2NxM0 (group 1)--18.2%, T3aNx M0 (group 2)--53.4%, T3bNx M0 (group 3)--18.2%, T4NxM0--10.2% (group 4). In group 1 (n=37), contemporary radiotherapy was administered--TTD--up to 44 Gy (stage I) and up to 66-70 Gy (stage II). In group 2 (n=51), contemporary radiotherapy was supplemented with inhalation of radioprotector GGS-9--TTD--up to 44 Gy plus GGS-9 (stage I) and up to 72-76 Gy plus conformaton radiotherapy (3D CRT) (stage II). When GGS-9 was used at stage I the rate of acute radiation injury dropped from 56.7% in group 1 to 11.7% in group 2, (p=0.0001). The frequency of late-onset injury was also lower in patients receiving 3D CRT (13.5 and 3.9%, respectively) (p=0.01). Local and biological relapse occurred frequently after contemporary radiotherapy (27%) as compared with conformation one (5.8%). The latter treatment was followed by higher 5-year recurrence-free survival (94.2%) as compared with contemporary radiotherapy (73%), (p=0.0001). Owing to use of 3D CRT, dose distribution was improved as volume and dosage for organs at risk of irradiation decreased, while TTD increased up to 72-76 Gy unaccompanied by a rise in early-onset injuries. On the contrary, late-onset radiation damage fell down.

[Polyradiomodification as component of combined treatment of rectal cancer: rationale and results].

The report discusses our 30-year experience with surgical and combined treatment of rectal cancer. In cases of preoperative radiotherapy, loco-regional frequency of relapse dropped to 9.6% as compared with surgery (16.3%). After preoperative thermoradiotherapy it fell to 4.6%; polyradiomodification - 0.5% (3-year follow-up). Distant metastasis formation rates were: after polyradiomodification--1.5%, radiotherapy--9.6%, and thermo-radiotherapy--6%. Recurrence-free survival rates (3 years) were: polyradiomodification--97.3%, thermo-radiotherapy--75.9%, radiotherapy--71.1%, and surgery--58%. Data on regimens and dosage of polyradiomodification alongside radiation damage for different combinations of treatment are presented.

[Results of surgical and radiotherapy of prostatic cancer T1-4N0-1M0].

To compare the results of radical prostatectomy and conformal radiotherapy in prostatic cancer T1-4N0-1M0, we made a retrospective study of 306 patients with prostatic cancer T1-4N0-1M0 of whom 144 (47.1%) were treated surgically (radical prostatectomy) while 162 (52.9%) were exposed to extracorporeal conformic radiotherapy. Follow-up median was 30.7 +/- 29.8 months. Five and 10-year overall, specific and PSA recurrence free survival in 306 patients was 94.0% and 90.1% (median was not achieved), 96.6% and 94.3% (median was not achieved), 66.1 and 49.2% (median was 84.0 +/- 4.4 months). In multifactorial analysis significant prognostic factors of PSA recurrence free survival were T category (p = 0.021) and Glison's sum (p = 0.002). In the subgroup of patients with local prostatic cancer there was a significant superiority of the operated patients by PSA recurrence free survival over irradiated group in baseline PSA < 10 ng/ ml (p = 0.015), Glison's index < 7 (p = 0.071) and combination of these factors (p = 0.018). A favourable prognosis factor of PSA recurrence free survival in operated patients was operative Glison's index < 7 (p = 0.001), among operated patients--nadir PSA < 1 ng/ ml (p = 0.003). Surgical and radiation treatment of local and locally advanced prostatic cancer provided satisfactory results. In the group of good prognosis (cT1-2N0, PSA < 10 ng/ml, Glison's sum < 7) radical prostatectomy gives advantage of PSA recurrence free survival. In patients with prostatic cancer cT > T2, N+, Glison's index > 7 and PSA > 10 ng/ml surgical treatment and remote radiotherapy are equally effective in respect to survival free of biochemical recurrence.