[Treatment of recurrent glioblastoma with single-agent bevacizumab]. / Rekurrens glioblastomában szenvedo betegek kezelése bevacizumab-monoterápiával.

INTRODUCTION: The prognosis of patients with recurrent glioblastoma is poor, as the median survival does not exceed 6 months. AIM: The aim of this study was to evaluate the efficacy of bevacizumab monotherapy in patients with recurrent glioblastoma multiforme. METHOD: From April, 2012 to June, 2015, 40 patients with recurrent glioblastoma multiforme were treated with bevacizumab in a dose of 10 mg/kg every 2 weeks. RESULTS: The average progression-free survival was 6.4 months (2-22 months), and the 6-month progression-free survival was 42.5%. The six-month overall survival was 82.5%, which corresponds to those published in the literature. CONCLUSIONS: Bevacizumab monotherapy improves progression-free survival in patients with recurrent glioblastoma multiforme.

[Historical overview and the current practice of intracavitary treatment of cervical and endometrial cancer in the Oncoradiology Center of Budapest]. / A méhtest- és méhnyakrák intrakavitális kezelésének történeti áttekintése és jelen gyakorlata a Fõvárosi Onkoradiológiai Központban.

The aims of our study were to describe the history and development of intracavitary brachytherapy in the treatment of gynecological tumors, to introduce our current practice for intracavitary brachytherapy treatments based on CT planning. Gynecological intracavitary brachytherapy has been applied in our department since the early 1930s. After a long development it has been completely renewed by 2014. In our center definitive and/or preoperative gynecological HDR-AL brachytherapy treatments were given to 25 patients (13 corpus uterine cancer patients and 12 cervical cancer patients) during the period of 01. 01. 2014-31. 01. 2015. In each case, target volumes were planned by CT images, DVH (dose volume histogram) analysis was performed in order to calculate the radiation tolerance dose of rectum and urinary bladder. Evaluation was performed by the EclipseTM 11.0.47. brachytherapy treatment planning system. During the definitive treatments of the 13 uterine cancer patients the D2cc value related to rectum tolerance was 66.3 GyEQD2 (46-91 Gy). The average D2cc value of urinary bladder tolerance was 76.5 GyEQD2 (30-112 Gy). CI was 0.72 (0.6-0.95). Average value of COIN was 0.57 (0.35-0.78). Compared to the prescribed dose D100 and D90 values were given in ratios. Compared to the volume which receives 100% of reference dose V150 and V200 values were also given in ratios. D100 and D90 were calculated to be 0.66 (0.47-0.97) and 0.91 (0.8-1.25). V150 and V200 volumes were 0.11 (0.04-0.18) and 0.06 (0.02-0.1). During the definitive treatments of 12 cervical cancer patients the D2cc value related to rectum tolerance calculated by DVH was 75.2 GyEQD2 (60-82 Gy). The average D2cc value of urinary bladder tolerance was 85 GyEQD2 based on DVH. CI was 0.66 (0.42-0.76). Average value of COIN was 0.52 (0.32-0.78). Mean value of DHI was 0.46 (0.27-0.54). D100 and D90 were calculated to be 0.72 (0.57-0.89) and 0.91 (0.84-1.11). V150 and V200 volumes were 0.057 (0.02-0.13) and 0.02 (0.002-0.06). During treatments no severe side effects were found. During gynecological intracavitary HDR therapies the calculated dose of the target volume can be given safely using the EclipseTM 11.0.47. brachytherapy planning system and CT-based planning. CT-based treatment planning provides optimal safety for organs at risk, acceptable doses for rectum and urinary bladder while the target volume receives the proper prescribed dose.

Pathologic complete remission after preoperative high-dose-rate brachytherapy in patients with operable cervical cancer: preliminary results of a prospective randomized multicenter study.

The role of preoperative intrauterine brachytherapy (BT) in the multidisciplinary treatment of early stage cervical carcinoma (ESCC) is controversial. In 2005, a prospective randomized multicenter study was initiated in Hungary in order to explore the potential advantages of preoperative high-dose-rate (HDR) BT. In this article we evaluate the efficiency of preoperative HDR BT by the rate of pathologic complete remission (pCR) in the first 185 patients enrolled in the study at the National Institute of Oncology and at the Uzsoki Municipal Cancer Center in collaboration with the 1st Department of Gynaecology and Obstetrics of Semmelweis University, Budapest, Hungary. In arm A, patients received 2x8Gy preoperative intracavitary HDR BT, while in arm B no preoperative treatment was given. In both arms patients underwent radical Wertheim (Piver III) hysterectomy. The pCR rate was 25.7% after preoperative HDR BT, while it was only 11.2% with surgery alone (p=0.03), in these cases the tumor was eliminated during the diagnostic excision or conisation. The rate of positive surgical margins was 1.5% after preoperative BT, while it was as high as 11.4% without preoperative RT (p=0.02). There was no significant difference in the local tumor control (LTC), distant metastases free survival (DMFS) and overall survival (OS) between the two arms. According to our preliminary results preoperative intracavitary HDR BT significantly increases the rate of pCR and decreases the rate of positive surgical margins in patients with ESCC. Longer follow-up is required to establish the possible impact of pCR on the ultimate LTC and OS.

[Symptoms, diagnosis and treatment of radiation-induced enteritis]. / Sugárkezelés mellett fellépo bélgyulladások tünettana, diagnosztikája, terápiás lehetoségei.

The number of radiotherapy in the treatment of malignant diseases is increasing worldwide. During the radiotherapy of tumors in the minor pelvis and abdomen intestinal inflammation of different degree may occur even if special attention is paid. Irradiation to the minor pelvis causes in half of the cases radiation induced acute enteritis, whereas in 25% chronic enteritis and colitis will develop. Chronic enteritis following radiotherapy raises a number of diagnostic and therapeutic problems that can be solved only with cooperation of different specialties. Authors present a short review regarding therapeutical options of radiation induced enteritis.

Concomitant radiochemotherapy of cervical cancer: is it justified to reduce the dosage of cisplatin?

PURPOSE: To review the experiences regarding the therapeutic response and side effects of concomitant radiochemotherapy of cervical cancer carried out with different cisplatin doses. PATIENTS AND METHODS: At the Municipal Center for Oncoradiology, Budapest, Hungary, 92 patients with cervical cancer were treated with concomitant radiochemotherapy in the period between July 2002 and March 2007. The total dose of high-energy external radiation (megavoltage) treatment was 50.4 Gy with a fraction dose of 1.8 Gy on the small pelvis. Before irradiation, cisplatin 40 mg/m(2), 30 mg/m(2), or 20 mg/m(2) was administered once a week. RESULTS: In 17 cases, the cisplatin dose was 30 mg/m(2); during radiochemotherapy the number of cisplatin treatments was equal to or more than four in 14 patients (82%). After administering 40 mg/m(2) cisplatin to 64 patients, chemotherapy in four or more treatments could only be applied in 37 cases (58%). Eleven patients received cisplatin at the dose of 20 mg/m(2); in ten (91%) of them, the number of treatments was four or more. By comparing the side effects, it can be stated that hematologic side effects (mostly leukopenia) grade 3 occurred in 12% of the patients receiving cisplatin 30 mg/m(2), and grade G3-4 in 16% of the 40-mg/m(2) cisplatin group. For cisplatin 30 mg/m(2), 82% of hematologic side effects were in the G1 range. There was no significant difference between the 20- and 30-mg/m(2) regimens. As for the gastrointestinal toxicity, similar side effects grade 1 were detected, which occurred in 58% and 38% of the patients receiving 30 mg/m(2) and 40 mg/m(2), respectively. CONCLUSION: On the basis of a detailed analysis, the correlation between the number of treatments, the therapeutic and the side effects could be verified. In the course of dose reduction, there was no significant difference when comparing the results of therapy, however, the quality of life was better if cisplatin 30 mg/m(2) was administered instead of 40 mg/m(2). If cisplatin 20 mg/m(2) was given, the results were significantly worse. On the basis of the own results, it can be stated that the optimal weekly dose of cisplatin is 30 mg/m(2).

[PET/CT based radiotherapy treatment planning in head and neck cancers]. / PET/CT alapú besugárzástervezéssel szerzett tapasztalatok fej-nyaki tumorokban.

The purpose of this study was to evaluate the experiences of PET/CT based radiation planning in patients suffering from head and neck cancer. PET/CT based 3D-conformal irradiation was used in eleven patients between March 2008 and February 2009. In six of the eleven cases the therapeutic plan was modified after PET/CT examination, as the previously determined lymph node negative state proved to be lymph node positive. For that reason, the treatment needed to be completed by chemotherapy and in some cases clinical target volume and planning target volume have been also modified. PET/CT examination has a decisive influence on therapeutic planning and on the planning process in patients with head and neck cancer.

[About mastopathy]. / A mastopathiáról.

The authors review knowledge of the clinical, imaging and pathological diagnosis of mastopathy syndrome and the issues of its therapy and care. They observe that no unified nomenclature exists, all the disciplines judge the idea of mastopathy differently. Clinical and imaging diagnosis is uncertain, the correct diagnosis can be established only by the pathologist. The role of surgery is minimal. The precancerous nature of mastopathy is also discussed, the rate of malignant transformation is low. Malignant transformation of benign lesions is very rare. The most important tools are close observation, systematic care of patients by a team of professionals, possibly by the same persons, in the same institute. Further research, and more exact definitions are necessary.

[Radiochemotherapy of cervical carcinoma. (Necessity of dose reduction in chemotherapy)]. / A méhnyakrák radiokemoterápiája (a kemoterápias dózisredukció szükségessége).

INTRODUCTION: The concurrent radiochemotherapy used in the treatment of high risk and locally advanced cervical cancer therapy seems to be standard practice. Studies carried out in 1999 and 2000, reported the results of five large-scale prospective randomized investigations using radiotherapy which showed progression-free and overall survival rate increase compared to use of solely radiotherapy (Gynecology Oncology Group (GOG) 123, South West Oncology Group (SWOG) 8797, Radiotherapy Oncology Group (RTOG) 9001, Gynecology Oncology Group (GOG) 85, Gynecology Oncology Group (GOG) 120). OBJECTIVES: The aim of the investigation was to report our early findings of cervical cancer radiotherapy detailing the arising radiogen toxicity. METHOD: This is a report of a study carried out at the Oncoradiology Centre of Budapest, (between July 2002 and March 2005) on 66 cervical cancer patients. In concurrent radiotherapy the total dose of high photon energy percutaneous radiotherapy (megavolt therapy) for the pelvic region was 50.4 Gy, in 1.8 Gy fractions and with the weekly dosage of 40 mg/m2 cisplatin prior to the radiotherapy. RESULTS: The planned cytostatic treatment could be carried out on 27 patients (41%) on five treatments. At the same time, the number of treatments on the other patients had to be reduced due to haematological toxicity in the following way: 4 treatments on 16 patients (24%), 3 treatments on 7 patients (11%), 2 treatments on 10 patients (15%) and once on 6 patients (9%). Altogether it was necessary to reduce the dosage from the planned protocol, on 44 patients (67%). The optimal radiotherapy time of 56 days as reported in the literature, was exceeded in 17 cases (26%) on account of the radiogen toxicity. CONCLUSIONS: On the basis of our own results it is not advisable to raise the cisplatin weekly dosage to above 20 mg/m2.

[Evaluation of high-dose-rate brachytherapy of the preoperative treatment of stage IB (FIGO) cervical carcinoma]. / IB (FIGO) stádiumú méhnyakrák kezelésében a preoperatív magas aktivitású brachyterápia hatásosságának vizsgálata (saját eredményeink alapján).

PURPOSE: Examination of stage IB (FIGO) cervical cancer patients treated with preoperative high dose rate brachytherapy (HDR BT) on the basis of specimen histology, local control and disease-free survival. MATERIAL AND METHOD: Patients with stage IB cervical cancer were treated between 01/01/1993 and 31/1/1997 as part of complex treatment with HDR BT, the dose calculated for point A 2x5.5 Gy, with one week interval in the Municipal Centre of Oncoradiology, Uzsoki Hospital, Budapest. Different types of surgery were carried out in general within two weeks after preoperative HDR BT. Depending on the specimen histology, postoperative radiation treatment varied. In case of residual tumor vaginal BT 2x5.5 Gy was applied within a week; the dose was relevant to a tissue depth of 5 mm and to the upper third of vagina. This was followed by percutaneous irradiation (telecobalt, linear accelerator) at a dose of 50 Gy, box technique. In certain cases the para-aortal region was simultaneously irradiated. In case of negative specimen no postoperative vaginal HDR BT was applied in the majority of patients. Retrospective analysis helped to determine the effectiveness of regularly followed patients, as for local control and metastasis on the basis of the time of development of dissemination, respectively. RESULT: 33.4% of 153 preoperatively treated patients had tumor-free specimen. Regular follow-up (at least 5 years) showed local relapse in 17 patients (11%), dissemination in 13 patients (8.4%), and 4 among them (2.6%) had simultaneous local relapse. CONCLUSION: On the basis of our data it can be stated that preoperative HDR BT in stage IB cervical carcinoma decreased local relapse. In spite of negative specimen histology, vaginal HDR BT can be suggested, but if there is residual tumor, both HDR BT and percutaneous irradiation is suggested on the basis of our data.

Primary radiotherapy of stage IIA/B-IIIB cervical carcinoma. A comparison of continuous versus sequential regimens.

BACKGROUND: Comprehensive literature on cervical cancer demonstrates, even today, the need for optimization of the timing of external-beam radiotherapy (EBRT) and high-dose-rate brachytherapy (HDR-BT) in the treatment of stage IIA/B-IIIB cervical carcinoma. PATIENTS AND METHODS: 210 patients with carcinoma of the cervix were treated in the Municipal Center of Oncoradiology between January 1991 and December 1996 (FIGO IIA: n = 10, FIGO IIB: n = 113, and FIGO IIIB: n = 87). Two regimens were compared: sequential radiation therapy (SRT) with 4 x 8 Gy HDR-BT to point A followed by EBRT, and continuous radiation therapy (CRT) in which 5 x 6 Gy HDR-BT to point A, one session per week, was integrated into the EBRT. A total dose of 68-70 Gy to point A and 52-54 Gy to point B was given in EBRT with SRT, five fractions per week were applied. Four fractions per week were applied in CRT, i. e., no EBRT was performed on the day of HDR-BT. Total doses to points A and B were identical in both regimens. Overall treatment time (OTT) amounted to 56 days for SRT and 35 days for CRT. Median follow-up time was 3.4 (2.5-4.2) years. RESULTS: Progression-free 5-year-survival (PFS) was 71% in the CRT and 56% in the SRT group. Nevertheless, this difference was not statistically significant (p = 1.00), and the same was found in a subgroup analysis of the different tumor stages, showing, however, an unequivocal trend. Late bladder and rectal injuries occurred in 13% and 25%, respectively. Late rectal injuries were significantly more frequent with SRT than CRT (35 patients in the SRT and 18 patients in the CRT group; p = 0.037). This was due to the higher doses per fraction of HDR-BT in the SRT group. No difference was found regarding late bladder injuries (p = 0.837). CONCLUSION: For the patients included in this study, no advantage has been found so far in using CRT, i. e., shortening the OTT by weekly integration of HDR-BT into EBRT. Nevertheless, an obvious trend exists. The dose of 8 Gy per fraction of HDR-BT in the SRT regimen was obviously too high. To achieve a significant improvement in local control and disease-free survival (DFS) as well as overall survival (OS), the combination with modern chemotherapy regimens and regional deep hyperthermia may rather be the treatment option.

Partial breast irradiation with interstitial 60CO brachytherapy results in frequent grade 3 or 4 toxicity. Evidence based on a 12-year follow-up of 70 patients.

PURPOSE: To investigate the radiation-induced toxicity and cosmesis of brachytherapy (BT) alone in early stage breast cancer. METHODS AND MATERIALS: A total of 70 women diagnosed with Stage I or II breast carcinoma participated in a BT study at the Municipal Oncoradiological Center, Uzsoki Hospital, Budapest, Hungary, between November 1987 and June 1992. They had undergone breast-conserving surgery with an unknown surgical margin. The postoperative tumor bed irradiation was performed with interstitial (60)Co sources with an active length of 4 cm, with 10-mm center-to-center spacing arranged in a single plane. The median number of inserted sources was 5 (range, 2-8), with a linear activity of 133-137 MBq/cm at the beginning of the study. The 50 Gy delivered dose at 5 mm from the surface of the (60)Co sources was administered during 10-22 h to the virtual postoperative lumpectomy cavity (i.e., plane). For radiobiologic considerations, the clinical target volume (CTV) was calculated retrospectively with a 10-mm safety margin, resulting in a 72-cm(3) median CTV (range, 36-108 cm(3)) irradiated with a reference dose of 28 Gy. In the assessment of the skin and subcutaneous toxicity, the RTOG late radiation morbidity scoring system was applied. The radiosensitivity of the cultured fibroblasts was determined by clonogenic assay to check whether individual radiosensitivity played a role in the development and course of radiation-induced side-effects. RESULTS: The median follow-up was 12 years (range, 10-15 years). The population of the final study (34 cases) comprised all survivors with tumor-free breasts (27 cases) and patients with breasts erroneously ablated/excised for misinterpreted radiation-induced sequelae (7 patients). A total of 97% of the cohort (33/34) had grade > or =2, and 59% (20/34) had grade > or =3 radiation-induced toxicity. By the end of the follow-up, 85% of the patients experienced Grade > or =2 telangiectasis and 41% had Grade 3 telangiectasis. Eighty-eight percent had fibrosis of some form, and 35% had grade > or =3 fibrosis. Forty-one percent of the cohort displayed fat necrosis, which was always accompanied by Grade > or =3 fibrosis or telangiectasis. The cosmetic results were poor in 50% (17/34) of the patients. The radiosensitivity of the fibroblasts was increased in only 2/24 patients (8% of the investigated cases, in agreement with data published for the general population). Comparisons of our fibrosis prevalence data with those of others allowed an estimate of 0.47 h(-1) for the rate of recovery of DNA damage in the fibroblasts. CONCLUSIONS: Interstitial (60)Co BT of the breast tumor bed alone with a limited CTV (median, 72 cm(3)) and a total dose of 28 Gy is associated with a high rate (59%) of grade > or =3 radiation-induced toxicity and a high rate (50%) of poor cosmetic outcome at the end of a median follow-up of 12 years. A relatively high BT dose rate (1.3-2.8 Gy/h) applied during a short overall treatment time (10-22 h) and a possible geographic miss (close to skin implantation) might have contributed to the development of these sequelae.

A review on radiogenic Lhermitte's sign.

Radiation myelopathy is a rare, but extremely serious side-effect of radiotherapy. Recovery from radiation-induced motor sequelae is rare, whereas, the regeneration of sensory losses is relatively frequent. Among the sensory radiogenic injuries of the spinal cord, Lhermitte's sign (LS) is most frequent. This review describes the clinical picture and diagnostic imaging signs of radiogenic LS. There have been only a few studies on large patient groups with radiogenic LS, demonstrating a rate of occurrence of 3.6-13%, relating mainly to mantle irradiation or the radiotherapy of head and neck tumors. These cases typically manifest themselves 3 months following radiotherapy and gradually disappear within 6 months. Only 3 LS cases have been described in the English literature with extraordinarily severe symptoms lasting for more than 1 year. MRI, a sensitive tool in the detection of demyelination, failed to reveal any pathological sign accompanying radiogenic LS. However, positron emission tomography demonstrated increased [18F]fluorodeoxyglucose accumulation and [15O]butanol perfusion, but a negligible [11C]methionine uptake in the irradiated spinal cord segments in patients with long-standing LS. These imaging data are suggestive of a close direct relationship between the regional perfusion and metabolism of the spinal cord, very much like the situation in the brain. We postulate that an altered, energy-demanding conduction along the demyelinated axons of patients with chronic radiogenic LS may explain the increased metabolism and perfusion.