Coverage of axillary lymph nodes with high tangential fields in breast radiotherapy.

The aim of this study is to evaluate the coverage of axillary nodal volumes with high tangent fields (HTF) in breast radiotherapy and to determine the utility of customised blocking. The treatment plans of 30 consecutive patients with early breast cancer were evaluated. The prescription dose was 50 Gy to the whole breast. Axillary level I-II lymph node volumes were delineated and the cranial border of the tangential fields was set just below the humeral head to create HTF. Dose-volume histograms (DVH) were used to calculate the doses received by axillary nodal volumes. In a second planning set, HTF were modified with multileaf collimators (MLC-HTF) to obtain an adequate dose coverage of axillary nodes. The mean doses of the axillary nodes, the ipsilateral lung and heart were compared between the two plans (HTF vs MLC-HTF) using a paired sample t-test. The doses received by 95% of the breast volumes were not significantly different for the two plans. The doses received by 95% of the level I and II axillary volumes were 16.79 Gy and 11.59 Gy, respectively, for HTF, increasing to 47.2 Gy and 45.03 Gy, respectively, for MLC-HTF. Mean lung doses and per cent volume of the ipsilateral lung receiving 20 Gy (V20) were also increased from 6.47 Gy and 10.47%, respectively, for HTF, to 9.56 Gy and 16.77%, respectively, for MLC-HTF. Our results suggest that HTF do not adequately cover the level I and II axillary lymph node regions. Modification of HTF with MLC is necessary to obtain an adequate coverage of axillary levels without compromising healthy tissue in the majority of the patients.

Postoperative radiotherapy in the treatment of uterine sarcomas: long-term results and analysis of prognostic factors.

PURPOSE: To evaluate the role of postoperative radiotherapy (RT) in local control and survival and to identify treatment-related prognostic factors in uterine sarcomas. METHODS: Sixty patients with uterine sarcomas treated with postoperative RT were retrospectively analyzed. Median age was 49.5 years (range 24-78). The stage distribution was as follows: stage I: 60%, II: 11.7%, and III: 28.3%. All patients were treated with pelvic irradiation (dose range 45.6-54.6 Gy). Pelvic control (PC), distant metastasis-free survival (DMFS), disease-free survival (DFS), and overall survival (OS) were calculated. Age, stage, histology, tumor size, type of surgery, residual disease, time interval between surgery and RT were selected as possible prognostic factors for PC and OS. Age, total treatment time, pelvic dose, dose per fraction, and acute side effects were analyzed as probable prognostic factors for late complications. RESULTS: Median follow-up was 84 months. The 10-year PC, DMFS, DFS and OS rates were 84, 67.3, 64 and 61.5%, respectively. Univariate analysis showed that age, residual disease, type of surgery and stage were significant factors for PC; residual disease, type of surgery and stage were significant factors for DMFS; stage was found as the only significant factor for DFS and OS. Total treatment time, pelvic dose, dose per fraction, and acute side effects were significant factors for late complications. CONCLUSION: Although our results suggest improved PC, the role of postoperative RT should be tested in prospective randomized trials.

The application of positron emission tomography/computed tomography in radiation treatment planning: effect on gross target volume definition and treatment management.

AIMS: To analyse the effect of the use of molecular imaging on gross target volume (GTV) definition and treatment management. MATERIALS AND METHODS: Fifty patients with various solid tumours who underwent positron emission tomography (PET)/computed tomography (CT) simulation for radiotherapy planning from 2006 to 2008 were enrolled in this study. First, F-18 fluorodeoxyglucose (FDG)-PET and CT scans of the treatment site in the treatment position and then a whole body scan were carried out with a dedicated PET/CT scanner and fused thereafter. FDG-avid primary tumour and lymph nodes were included into the GTV. A multidisciplinary team defined the target volume, and contouring was carried out by a radiation oncologist using visual methods. To compare the PET/CT-based volumes with CT-based volumes, contours were drawn on CT-only data with the help of site-specific radiologists who were blind to the PET/CT results after a median time of 7 months. RESULTS: In general, our PET/CT volumes were larger than our CT-based volumes. This difference was significant in patients with head and neck cancers. Major changes (> or =25%) in GTV delineation were observed in 44% of patients. In 16% of cases, PET/CT detected incidental second primaries and metastatic disease, changing the treatment strategy from curative to palliative. CONCLUSIONS: Integrating functional imaging with FDG-PET/CT into the radiotherapy planning process resulted in major changes in a significant proportion of our patients. An interdisciplinary approach between imaging and radiation oncology departments is essential in defining the target volumes.

Dosimetric comparison of intensity modulated pelvic radiotherapy with 3D conformal radiotherapy in patients with gynecologic malignancies.

PURPOSE: Before initiating an intensity modulated radiotherapy (IMRT) program for gynecologic malignancies we prospectively evaluated the potential benefits of IMRT by dose volume histogram comparison of IMRT and 3D conformal radiotherapy plans. METHODS: Plans of ten consecutive patients with cervical and endometrial cancer were evaluated. For each patient a 4-field box technique was compared to an IMRT plan. Both plans were normalized to deliver 50.4 Gy to the PTV in six patients and 45 Gy in the remaining four. Isodose distributions and dose volume histograms were compared in seven dose levels. RESULTS: IMRT reduced the volume of small bowel receiving more than 45 Gy in all patients. The average absolute volume of small bowel receiving 45 Gy was significantly reduced from 318 cc to 33 cc. No significant increase in the volume of small bowel receiving less than 20 Gy was observed. Rectum, bladder and bone marrow volumes receiving high doses were also significantly reduced with IMRT. CONCLUSIONS: IMRT significantly reduces the volume of normal tissues irradiated to high doses without compromising the target coverage. This may potentially lead to a reduction in treatment related toxicities.

Implantation of fiducial markers for image guidance in prostate radiotherapy: patient-reported toxicity.

The purpose of this study was to evaluate patient-reported morbidity of implanted fiducial markers used for image guidance in prostate radiotherapy. Three fiducial markers were implanted under transrectal ultrasound guidance to 177 patients who were referred to our department for definitive radiotherapy between June 2005 and January 2008. No local anaesthesia was administered. Patients were asked to complete a questionnaire about the possible side effects of this invasive procedure. 135 patients completed the questionnaire at a median of 57 weeks after the procedure. Pain during the procedure was assessed with the Wong-Baker Faces Pain Rating Scale. Patients were also asked to compare the pain with the diagnostic biopsy. Although haematuria, rectal bleeding and fever were reported by 15%, 4% and 2% of the 135 patients, respectively, no major toxicity necessitating any intervention was observed. The mean pain score reported by the patients was 1.7 (range, 0-5). 87% of patients reported less (or comparable) pain than the diagnostic biopsy. In conclusion, implantation of fiducial markers for image guidance in prostate radiotherapy is a safe and well-tolerated procedure.

Impact of percent positive random biopsies on biochemical outcome in prostate cancer patients treated with external beam radiotherapy with or without androgen deprivation.

PURPOSE: To identify the prognostic factors for biochemical outcome in patients with localized prostatic adenocarcinoma treated with external beam radiotherapy (EBRT) with or without androgen deprivation (AD) and to investigate the impact of percent positive prostate core biopsies (PCB%). METHODS: From 1998 through 2003, 333 patients with newly diagnosed localized prostate cancer were retrospectively analyzed. The patients were treated in two institutions with definitive EBRT to a median dose of 72 Gy and 80% of them received short- or long-term AD. Biochemical failure was defined using ASTRO criteria with 3 consecutive rises in prostate specific antigen (PSA). RESULTS: Median follow up was 36 months. Gleason score, initial PSA, risk grouping, PCB%, AD and total duration of AD were found to be significant predictors for biochemical outcome in univariate analysis. Independent predictors for PSA failure on multivariate analysis were PCB% and duration of AD. Among 3 risk groups, in the intermediate risk group the biochemical control was significantly better in patients with < 67% positive core biopsies. In the subgroup analysis of patients who received a prostatic dose or= 67% positive core biopsies. These significant differences did not exist in patients receiving > 70.2 Gy and long-term hormonal therapy. CONCLUSION: Our results suggest that high PCB% could be a predictor of biochemical relapse, especially in the intermediate risk group. The role of PCB% in prostate cancer should be investigated in further trials.

Cervical cancer coexisting with small lymphocytic lymphoma detected during positron emission tomography/computed tomography simulation: a case report.

BACKGROUND: Positron emission tomography (PET)/computed tomography (CT) simulation in cervical cancer may help radiation oncologists to better define the target volumes. It may also detect extrapelvic lesions and incidental second malignancies, leading to significant changes in treatment management. CASE: A 63-year-old woman who was deemed inoperable due to carcinoma of the cervical stump extending to the parametria and paraaortic lymph nodes detected on MR images presented for extended field radiotherapy. PET/CT simulation revealed an FDG avid mass in the cervical stump, and an enlarged axillary lymphadenopathy showing moderate FDG uptake. The excisional biopsy was consistent with small lymphocytic lymphoma (SLL). CONCLUSION: In our case, PET/CT simulation not only led to changes in treatment management, but also revealed a very rare coexistence of SLL and invasive squamous cell carcinoma of the cervix.

Radiotherapy for benign diseases: a retrospective analysis.

PURPOSE: Radiotherapy of benign diseases has become a frequently discussed subject while there are neither generally accepted guidelines about the indications of radiotherapy, doses and fractionation schedules nor adequate data about the risks and the effectiveness of irradiation. We have retrospectively analyzed the patients who were irradiated for benign diseases in our department. PATIENTS AND METHODS: During the period 1978-1997, a total of 262 patients were irradiated for benign diseases. Megavoltage equipment was used for irradiation of 253 patients, while the remaining 9 patients were irradiated by orthovoltage equipments. The diseases were grouped in 5 categories, and the distribution of the patients referred and irradiated per year was analyzed. Radiotherapy doses, fractionation, response rates and follow-up were evaluated. RESULTS: The number of irradiated patients has been increasing since the 1990's. The most common indication for irradiation was Graves' ophthalmopathy and the incidence of this group has increased after 1992. On the other hand, the number of patients irradiated for soft tissue, bone and skin diseases, except aggressive fibromatosis, has declined in the past 15 years. Response rates were more than 60% for most of the diseases. The patients' follow-up ranged between 1 and 156 months (median 4 months), but it was rather short for most of them. CONCLUSION: We observed common problems about the irradiation of benign diseases such as variations on the accepted indications, the treatment schedules and followup.

Endometrial carcinoma and an unusual presentation of bone metastasis: a case report.

BACKGROUND: Although metastasis to bone is common in solid tumors, it seldom occurs in endometrial carcinoma. It is usually seen together with abdominopelvic recurrences and/or other organ metastases. Furthermore, bone metastases involving only the lower limbs are seen extremely rare. CASE: 67-year-old woman was referred for a vaginal recurrence from endometrial carcinoma. Pelvic irradiation and intracavitary brachytherapy failed to control the disease. Subsequently, she was presented with swelling of her left foot resembling an abscess, and bone scan revealed an increased uptake in both lower extremities below the knees. Furthermore, biopsy showed metastatic disease. She died 2 months after palliative irradiation with progressive disease. CONCLUSION: It should be remembered that bone metastasis at unusual sites might be seen in endometrial carcinoma.

Nasopharyngeal carcinoma in childhood: long-term results of 32 patients.

PURPOSE: To evaluate treatment results and prognostic factors, pediatric patients with nasopharyngeal carcinoma were reviewed. MATERIALS AND METHODS: Thirty-two patients at the age of 16 and younger were treated for nasopharyngeal carcinoma. One patient had WHO type I, 15 had WHO type II, and 14 had WHO type III histology. All patients were treated with radiotherapy, median dose to nasopharynx and involved nodes was 70 Gy (range 60-70.4 Gy), three patients received intracavitary booster dose of 24 Gy in three fractions, 12 patients were also given from two to four courses of platinum based neo-adjuvant chemotherapy. RESULTS: Twenty-three patients are alive and well with a median follow-up of 107 months. Ten and 15 years loco-regional control (LRC) and overall survival (OS) rates were 82.5, 68.7 and 72.7, 62.4%, respectively. Patient age, size of the lymph node and prolongation of overall external radiotherapy time were found to be the prognostic factors in univariate analysis, however the only factor remained significant after multivariate analysis was the size of the lymph node on LRC. Almost all long-term survivors experienced moderate to severe complications yielding complication free survival rate of 10.9% at 15 years.

Multidisciplinary approach to Wilms' tumor: 18 years of experience.

BACKGROUND: The aim was to evaluate the characteristics of Wilms' tumor and the results of combined modality treatment obtained in our center in Turkey. METHODS: From January 1978 to December 1996, 106 patients with Wilms' tumor were diagnosed. Of these 106 patients, 61 were male and 45 were female (M/F = 1,35); the median age at diagnosis was 39 months. The distribution of the 106 patients according to clinical stage was stage I 10%, stage II 42%, stage III 35%, stage IV 9% and stage V 4%. Histologically, 102 of the cases could be evaluated: favorable histology was diagnosed in 88.2% and unfavorable histology in 11.8% of the patients. Ninety-eight patients were treated according to NWTS and eight patients according to SIOP protocols. RESULTS: The EFS and overall survival rates at 2 years were 74.2 and 79.5% respectively, and at 5 years 72.4 and 76.6% respectively. CONCLUSION: As a developing country we evaluated our survival rates and report an improvement in treatment in recent years.

Continuous hyperfractionated accelerated radiotherapy in the treatment of high-grade astrocytomas.

Between May 1993 and January 1995, 36 patients with high-grade astrocytomas were treated with 1.05 Gy continuous hyperfractionated accelerated radiotherapy three times daily to a total target dose of 59.85 Gy in 19 days with 6-h intervals. The median age of the patients was 51 years and the median follow-up was 58 weeks. The median survival rate was 58 weeks and the cumulative survival rate was 22% at 2 years. No severe toxicity occurred in patients treated with this fractionation scheme. These results suggest that continuous hyperfractionated accelerated radiotherapy is an altered fractionation schedule for high-grade astrocytomas with tolerable acute toxicity and survival rates comparable to conventional fractionation and to other altered fractionation schedules.

A randomised study of ornidazole as a radiosensitiser in carcinoma of the cervix: long term results.

This paper presents long-term results of a randomised study of ornidazole as a radiosensitiser in locally advanced carcinoma of the cervix. A total of 76 patients were randomised and followed-up with a median of 85 months. All patients were treated with external and intracavitary irradiation. The 10 year actuarial local control rate was 61% in patients receiving ornidazole, compared with 50% for placebo group. This difference was not statistically significant. Ten year actuarial overall and disease-free survival rates were also similar in the two treatment groups. Although, when analysed by stage, there was a significant advantage in the local control (54% vs 15%; P = 0.044) and disease-free survival rates (37% vs 8%; P = 0.047) in ornidazole group for stage IIIB cases, its implication is obscure because of the small number of patients. In this study moderate and severe complication rates were found to be 30%. These results suggest that ornidazole seems to have relatively weak sensitisation and it may show a possibility of a marginal benefit with unconventional irradiation using relatively large radiation doses. However, the results are insufficient for a real gain in the probability of local tumour control and survival.

Multivariate analysis of prognostic factors in 75 patients with soft tissue sarcoma.

The results of 75 patients with soft-tissue sarcomas treated by the combination of local surgical excision plus postoperative radiotherapy are reported. Thirty-five tumors were situated in the extremities, 32 in the trunk, and eight in the head and neck. Twenty-eight tumors were high grade, 33 intermediate and 14 low grade. Sixty-two patients had complete resections (wide or marginal) and 13 incomplete resections (intralesional). Radiation was administered with a shrinking-field technique (median total dose, 64 Gy; range, 50-78). Twenty-five patients developed local recurrence (33%). The 5-year local control rate was 67%. On univariate analysis, a tumor site other than extremity (p < 0.05), unfavorable histology (p < 0.01), and incomplete resection (p < 0.01) were poor risk factors for local recurrence. When multivariate analysis were performed, only incomplete resection (relative risk (RR) 7.2) remained a poor risk factor. The 5-year overall survival rate was 50.5% for the entire group. Following a univariate analysis of host tumor and treatment-related factors, a tumor site other than extremity (p < 0.05), high tumor grade (p < 0.01) unfavorable histology (p < 0.05), and incomplete tumor resection (p < 0.01) were found to significantly increase the risk of further tumor death. Multivariate analysis found high tumor grade (RR 5.6), and incomplete resection (RR 7) to be independent poor risk factors for survival.

Postoperative radiotherapy in carcinoma of the cervix: treatment results and prognostic factors.

In order to assess the role of postoperative radiotherapy and prognostic factors, 126 patients who were treated with radiotherapy after surgery for clinical early-stage carcinoma of the cervix were reviewed. All patients received external pelvic radiotherapy and 37 patients were treated with additional vaginal cuff irradiation. The 5-year overall survival, disease-free survival and locoregional control rates were 71.1, 69.9 and 78.1%, respectively. The 5-year disease-free survival rates were 40% for grade 3 vs. 75.4% for grade 1 tumours (p = 0.05), 76.5% for pathological stage IB versus 54.1% for pathological stage IIA (p = 0.04), 36.6% for node-positive patients versus 82.5% for node-negative patients (p = 0.0017), 54% for full thickness cervical invasion versus 100% superficial cervical invasion (p = 0.01), 34.8% for positive margins versus 78.1 for negative margins (p < 0.0001). After a multivariate analysis, tumour grade (p = 0.026) and presence of positive margins (p = 0.006) were found to independently influence the outcome. Grade II and III complication rate was 5.5% in all patients. In conclusion, postoperative radiotherapy should be used in patients treated with simple hysterectomy as well as those treated with radical hysterectomy with unfavorable pathological findings.

Wilms' tumor: prognostic factors and survival.

A statistical analysis of 38 cases of Wilms' tumor treated and followed by the Pediatric Oncology Group of Cerrahpasa Medical Faculty, from 1977 to 1984, is presented. The two-year survival rate was 67% and the five-year survival rate was found to be 63%. There was a strong correlation between the stage and age of the patients and prognosis. The median age was 16 months in stages I and II of the disease and the two-year survival rate was 87%. The median age was found to be 5 years in advanced stages and the survival rate at 2 years was 43%. No correlation was found between survival and initial symptoms of the tumor or its localization. The effects of histological grade on prognosis of disease were also investigated.

Use of ornidazole in fractionated radiotherapy: dose tolerance, serum and tumour tissue concentration.

Sensitizing and neurotoxic effect of ornidazole, was tested in a double-blind randomized study in patients with carcinoma of the cervix and larynx. Ornidazole or placebo were given orally, two times weekly, for 3 weeks. Dose was 2.5 g/m2 for each administration. Total dose given was 15 g/m2. Radiation therapy was given 3 h after the drug administration. Ornidazole was well tolerated in the majority of the patients. No neurotoxic side effects, such as peripheral neuropathy or convulsion, were observed with a total dose of up to 30 g. Dizziness, somnolence and nausea were the prominent acute side effects, seen mostly (70%) in women. In the placebo group this rate was 17% (p less than 0.01). No important side effect was observed in men receiving ornidazole. Serum concentration of ornidazole reached the maximum level in 2-4 h after oral administration and ranged (23 patients) from 65.1 to 139.8 micrograms/ml. Mean half-life was 15.6 +/- 2.8 h. Peak concentration in tumour tissue was achieved 1-3 h after the administration, ranging from 13.0 to 78.0 micrograms/g. Tumour concentration of ornidazole ranged from 14 to 93% of the serum concentration at the time of irradiation.

The radiosensitizing effect of ornidazole in hypoxic mammalian tissue: an in vivo study.

In this study the sensitizing effect of ornidazole is investigated in vivo. The selected test system is the acute killing effect of radiation within 4-6 days after abdominal irradiation ranging from 9 to 24 Gy, in groups of C57 black mice. Ornidazole is given intraperitoneally in 500 mg/kg, 100 mg/kg, 20 mg/kg doses prior to irradiation of animals breathing air, oxygen or nitrogen. A decrease of LD50 dose is observed from 24.39 +/- 5.66 to 16.38 +/- 1.86 and 18.04 +/- 2.48 Gy, respectively, in nitrogen breathing animals. No sensitizing effect was observed in doses of 20 mg/kg. Enhancement Ratio (ER) was found to be 1.48 +/- 0.25 and 1.35 +/- 0.27; relative sensitizing efficiency (RSE) was 40% and 29% respectively. No sensitizing effect was observed in animals irradiated in oxic conditions. These results showed that ornidazole (Ro-7-0207) has a sensitizing effect on hypoxic cells in vivo. It is worthwhile to try this drug in a clinical study.