Radiosensitization of hormone-refractory prostate cancer cells by gossypol treatment.

PURPOSE: many drugs have been tested to increase the sensitivity of prostate cancer cells to radiotherapy. Gossypol, a natural polyphenolic compound extracted from the cotton plant, is one of the agents the efficacy of which has been investigated in the treatment of prostate cancer for this purpose. The main aim of this study was to investigate the best gossypol application with irradiation, when gossypol was applied either sequentially (24 h before and after irradiation) or concurrently in PC-3 hormone-refractory and radioresistant prostate cancer cells. METHODS: The XTT viability assay was used to evaluate the cytotoxicity of different concentrations of gossypol in PC- 3 cells. Irradiation was applied to PC-3 cells via 6 MV photon linear accelerator and delivered 24 h before, 24 h after radiation or at the same time with gossypol administration. RESULTS: gossypol caused radiosensitization of PC-3 cells that are known to be radioresistant, with high Bcl-2 levels. Among different applications of gossypol and irradiation (before, after and concurrent) in prostate cancer cells, the best results were observed by the application of gossypol 24 h before irradiation. CONCLUSION: our study suggests that gossypol represents a promising novel anticancer treatment for radiosensitization of human hormone-refractory prostate cancer cells.

Erythropoietin and radiotherapy in lung cancer patients.

PURPOSE: To evaluate the effectiveness of recombinant human erythropoietin (rhEPO) in relation to low hemoglobin (Hb) level, overall tumor response rates, and rhEPO adverse events in patients with lung cancer undergoing radiotherapy (RT). PATIENTS AND METHODS: Thirteen consecutive patients were included. All of them had measurable tumor before RT. 150 IU/kg of rhEPO-alpha or -beta were administered 3 times per week, 7-10 days before RT. The target Hb value was 13 g/dl. Tumor response was assessed 6 weeks after completion of RT. RESULTS: Response to rhEPO was seen 62% (n=8) of the patients. Weekly mean Hb increment was 0.69 g/dl (range 0.42-1). The mean Hb value during RT was 13.2 g/dl (range 9-14.7) in responding patients, and 10.7 g/dl (range 9.7-11.8) in non-responding patients (p=0.005). Overall response rates to RT were significantly higher in responding than in non-responding patients (p=0.034). CONCLUSION: rhEPO increased Hb levels in lung cancer patients undergoing RT. However, safety, and more importantly, indications need further clarifications.

The management of painful bone metastases with biphosphonates and palliative radiotherapy: a retrospective evaluation of 372 cases.

PURPOSE: The objective of this study was to evaluate the palliation of pain of bone metastases with biphosphonates and different radiotherapy protocols in 372 cancer patients. PATIENTS AND METHODS: Patients were treated with one of the 3 different radiotherapy protocols: 30 Gy in 10 fractions (group A), 20 Gy in 5 fractions (group B) and 8 Gy in a single fraction (group C). Two patient groups were studied: one with radiotherapy alone and the second with biphosphonates plus radiotherapy. The severity of pain was recorded before treatment. According to the pain relief, two different groups were defined: palliation rate<50% (limited palliation) and >50% (partial palliation), including complete pain relief. RESULTS: Overall limited and partial palliation rates were 20.2 and 79.8%, respectively (complete pain palliation 24.2%). In the group treated with both external radiotherapy and biphosphonates, limited and partial palliation rates were 19.5 and 80.4%, respectively (p=0.47). For 244 metastatic lesions treated with palliative radiotherapy alone, limited palliation rate was 20.4% and partial palliation rate 79.5%. No differences were detected between the groups with or without biphosphonates treatment in terms of pain palliation. According to the radiotherapy protocol, limited palliation rates in groups A, B, and C were 17.7, 20.3, and 28.5%, respectively (p=0.19, p=0.38, and p=0.26, respectively). Partial palliation rates were 82.2% in group A, 79.6% in group B and 71.4% in group C (p=0.42, p=0.21, and p=0.11, respectively). Similarly, no statistically significant differences were detected among the 3 radiotherapy schemes in terms of pain palliation. CONCLUSION: When combined with palliative radiotherapy, biphosphonates did not have any additive effects on pain palliation in the management of painful bone metastases. In addition, a single radiotherapy fraction provides equal pain palliation as multiple fractions.

Evaluation of anxiety levels during intracavitary brachytherapy applications in women with gynecological malignancies.

PURPOSE: To evaluate the anxiety levels of women treated for gynecological malignancies using intracavitary brachytherapy. METHODS: Anxiety levels prior to and after intracavitary brachytherapy application and factors influencing anxiety levels were evaluated. Women were evaluated for quality of life and psychological status before each brachytherapy application using the Hospital Anxiety and Depression Scale (HADS). Scores were grouped as follows: 0-7 = normal, 8-10 = borderline, 11-21 = abnormal. Women were also questioned about other factors which could affect anxiety levels such as marital status, education level, number of pregnancies and prior surgical history. RESULTS: Between January 2003 and August 2004, 146 women with a median age of 56 years were evaluated (range: 27-80). Eighty-six women had cervix uteri carcinoma and 63 had endometrial carcinoma. Sixty-seven women were premenopausal and 85 women were postmenopausal. The median pregnancy number was three (range = 0-10). Eighty-nine women had at least three children. Sixty-seven women had had previous operations. One hundred and twenty-five women were married and 24 women were unmarried or widowed. Before treatment, the anxiety scores were scored as normal in 49 (32%), borderline in 41 (28%), and abnormal in 59 (40%). Anxiety levels were lower in 69 women during the last application as compared with the pretreatment levels (p = 0.00). Marital status and pregnancy number showed a significant correlation with anxiety scores (p = 0.04). Age, level of education or having had a previous operation showed no significant correlation with anxiety level. CONCLUSION: These results indicate that intracavitary brachytherapy is associated with anxiety. Women need to be given detailed information before the brachytherapy application to reduce anxiety. Additional studies are needed to determine it.

Giant cell tumor of the bone with an asymptomatic huge solitary lung metastasis; case presentation and literature review.

A case concerning a man having giant cell tumor (GCT) of the leg and huge lung metastasis is presented. This case is discussed with a brief review of the relevant literature regarding detection and treatment of this care condition.

Changes of Ki-67 index in squamous cell carcinoma of the cervix during the early course of radiotherapy and prediction of prognosis.

PURPOSE: To determine whether changes in the Ki-67 index during the early course of radiotherapy could predict the prognosis in squamous cell carcinoma of the uterine cervix and be of value in clinical practice. MATERIALS AND METHODS: Biopsy specimens from 23 cases of histologically confirmed squamous cell carcinoma of the cervix were stained with anti-Ki-67 monoclonal antibody prior to radiotherapy and after 9 Gy. The correlation between the Ki-67 index, local control and distant metastasis was determined by Spearman's correlation test. RESULTS: Median age of the patients was 49. According to the FIGO staging system four patients had Stage IIA, 16 had Stage IIB, one had Stage IIIA and two had Stage IIIB disease. Among the whole group brachytherapy was applied to 17 patients (17/23) and weekly cisplatin (40 mg/m2) was applied to 15 patients (15/23). The mean Ki-67 index prior to radiotherapy and after 9 Gy for the entire group were 58.5% and 46.0%, respectively. The Ki-67 index after 9 Gy decreased in most of the patients (74%). During a median follow-up of 23 months four patients developed local recurrence and four patients developed distant metastasis. No significant correlation was detected among the local control and changes in Ki-67 index after 9 Gy, whereas there was a moderate correlation between distant metastasis and changes in Ki-67 index after 9 Gy (r = 0.51, p = 0.01). CONCLUSION: The Ki-67 index can be used safely as a proliferation marker in cervical carcinomas, and changes in the Ki-67 index during the early course of radiotherapy may predict the metastatic potential. However prospective studies including a large number of patients with long-term follow-up are necessary to confirm the clinical utility of this marker in cervical cancer.

Prognostic factors in definitive radiotherapy of uterine cervical cancer.

PURPOSE: To determine the prognostic factors related to local control and survival in 257 patients with uterine cervical cancer treated with definitive radiotherapy (RT). MATERIALS AND METHODS: The medical records of 257 patients treated with definitive RT from January 1987 to December 1998 were reviewed retrospectively. Pretreatment and treatment parameters were analyzed to determine their prognostic value onlocal control and survival. Survival analyses were performed using the Kaplan-Meier method. The log-rank test was used for univariate analyses and the Cox regression model was used for multivariate analyses. RESULTS: Median age was 55 (range 25-82). Squamous cell carcinoma was the most common histologic type (89.1%). The distribution per FIGO Stage was IIA: 13.2%; IIB: 54.9%; IIIA: 3.9%; IIIB: 19.8%; IVA: 8.2%. Ninety-eight patients (38.1%) were treated with external RT alone; 134 (52.1%) received both external RT and intracavitary brachytherapy; 21 (8.2%) received external RT and chemotherapy and four (1.6%) received external RT, intracavitary brachytherapy and chemotherapy. Median follow-up duration was 50 months (range 24-155 months). The failure rate was 51.8% with 26.5% of patients having only local failure, 16.7% only distant failure and 8.6% both local and distant failure. Five-year local progression-free, disease-free and overall survival rates were 58.1%, 44% and 63.7%, respectively. In univariate analysis the prognostic factors identified for local progression-free survival were histology (p = 0.008), FIGO stage (p < 0.001), initial hemoglobin (Hgb) level (p = 0.001), total radiation dose (p = 0.039), use of brachytherapy (p = 0.001) and of chemotherapy (p = 0.037) and enlarged paraaortic nodes (p = 0.016). In multivariate analysis the prognostic factors were FIGO stage (p = 0.014), initial Hgb level (p = 0.040), and use of brachytherapy (p = 0.013). The prognostic factors identified for disease-free survival were histology (p = 0.011), FIGO stage (p < 0.001), initial Hgb level (p < 0.001), use of brachytherapy (p = 0.001) and of chemotherapy (p = 0.014) in univariate analysis; and FIGO stage (p < 0.001), initial Hgb level (p = 0.017), total tumor dose (p = 0.034), use of brachytherapy (p = 0.006) and of chemotherapy (p = 0.021) in multivariate analysis. Factors influencing overall survival were FIGO stage (p < 0.001), initial Hgb level (p = 0.006), overall treatment time (p = 0.028), total tumor dose (p = 0.007), use of brachytherapy (p < 0.001), enlarged paraaortic (p < 0.001) and pelvic nodes (p = 0.004) in univariate analysis; and FIGO stage (p < 0.001), overall treatment time (p = 0.031), enlarged paraaortic (p = 0.007) and pelvic lymph nodes (p = 0.043) in multivariate analysis. CONCLUSION: Definitive RT is an effective treatment for patients with uterine cervical cancer. There are many prognostic factors influencing treatment outcome. Brachytherapy and chemotherapy must be added in appropriate patients to improve the outcome. Future prospective trials should be undertaken to confirm the validity of these factors and to individualize the treatment strategy for every patient.

Radiochemotherapy for patients with locally advanced cervical cancer: early results.

PURPOSE: Radiotherapy is the standard treatment for locally advanced cervical cancer. Recent results of the prospective randomized trials have shown an overall survival and local control advantage for cisplatin-based therapy given concurrently with radiation therapy. Thirty-nine patients who received concurrent chemoradiation between October 1999 and December 2000 were evaluated for treatment response, local control and toxicity. MATERIALS AND METHODS: Thirty-nine patients with Stage IB through IVA cervical carcinoma received weekly cisplatin (40 mg/m2) concurrent with radiotherapy. Thirty-two patients received both external and intracavitary radiotherapy and seven patients received only external radiotherapy because of insufficient tumor response for intracavitary application. Total external radiotherapy dose was 64.8 Gy with 1.8 Gy daily fractions in patients who received only external radiotherapy. Midline shielding was performed at 50.4 Gy in patients who were going to receive brachytherapy and the total external radiotherapy dose was 54-59.4 Gy. Brachytherapy was performed with a Rotterdam applicator via the microSelectron HDR machine. A total dose of 8.5-18 Gy was applied to point A. RESULTS: Median age was 55. Distribution by stages were as follows: Stage IB 5.1%, IIA 28.2%, IIB 43.6%, IIIA 7.7%, IIIB 12.8% and IVA 2.6%. Histologically 33 (84.6%) were epidermoid carcinoma, one was adenocarcinoma, two were undifferentiated carcinoma, one was malignant epithelial tumor. In two patients histological type could not be specified. The median duration of follow-up was 20 months. Four patients had local recurrence and three developed distant metastases. Thirty patients (76.9%) had complete response, eight had (20.5%) partial response and one had (2.6%) stable disease. During or after radiochemotherapy 46.2% of the patients developed toxicity due to chemotherapy. Early and late radiation morbidity rates were 66.7% and 71.8%, respectively. No grade III-IV toxicity was observed. CONCLUSION: Concurrent chemoradiation for locally advanced cervical cancer is the treatment of choice in suitable patients providing high response rates with acceptable toxicity.

Evaluation of morbidity after external radiotherapy and intracavitary brachytherapy in 771 patients with carcinoma of the uterine cervix or endometrium.

PURPOSE: The aim of the present study was to evaluate early and late radiation morbidity and to assess the factors influencing morbidity in patients with cervical or endometrial cancer treated by a combination of external radiotherapy (ERT) and intracavitary brachytherapy (IBRT). MATERIALS AND METHODS: Early and late radiation morbidity were evaluated retrospectively using RTOG/EORTC criteria and Franco-Italian glossary in 771 patients treated between November 1992 and December 1999. RESULTS: Four hundred and seven patients (52.8%) had endometrial carcinoma and 364 (47.2%) had carcinoma of the cervix. One hundred and fifty-four patients with cervical carcinoma were inoperable. In patients with endometrial carcinoma total doses at the vagina, bladder and rectum were 60.36 Gy, 56.2 Gy and 55.6 Gy respectively. Biologically equivalent doses (BED) for the same points were 79.35, 68.63 and 67.37, respectively for early effects and 123.67, 97.65 and 94.85, respectively for late effects. One hundred and sixty-nine patients (41.5%) developed acute morbidity, grade I and II bladder morbidity being the most common type and 85 patients (20.9%) developed late morbidity, grade I and II vaginal morbidity being the most common type. No grade IV morbidity was recorded. Total doses at the vagina, bladder and rectum in operated cervix cancer patients were 60.51 Gy, 56.53 Gy and 55.67 Gy, respectively. BED for the same points were 79.77, 69.36 and 67.52, respectively for early effects and 124.74, 99.3 and 95.17, respectively for late effects. Eighty patients (38.1%) developed early morbidity. Grade I and II bladder morbidity was the most common type. Sixty-five patients (30.9%) developed late morbidity, vaginal morbidity being the most common type. Total doses at the vagina, bladder and rectum in inoperable patients were 70.92 Gy, 66.71 Gy and 62.38 Gy, respectively. BED for the same points were 97.43, 89.64 and 81.63, respectively for early effects and 159.3, 143.16 and 126.56, respectively for late effects. Sixty patients (39%) developed acute morbidity which was grade I or II bladder morbidity in 95%. Ninety-five patients (61.7%) developed late morbidity which was grade I-III vaginal morbidity in 94%. CONCLUSION: Patients with cervical or endometrial cancer can be treated safely by a combination of ERT and IBRT. However the patients should be assessed before, during and after treatment and at every period of follow-up using a standard and well-defined system in order to define and predict the morbidity rate.

The impact of the haemoglobin level on the response to radiotherapy.

PURPOSE: To define the impact of preradiotherapy haemoglobin (Hb) levels on the response rate of radiotherapy in patients with head and neck, uterine cervix and lung cancer. PATIENTS AND METHODS: One hundred thirteen patients- 38 with head and neck cancer, 43 with carcinona of the uterine cervix and 32 with lung cancer- were retrospectively evaluated to determine the correlation between tumor response and preradiotherapy Hb levels. Hb level of 11 g/dl was taken as cut-off value for anemia. Patients were divided in two groups according to their objective response to radiotherapy. RESULTS: Histologically 30 of the head and neck cancers, 36 of the cervical cancers and 17 of the lung cancers were squamous-cell carcinomas. Tumor response of the epidermoid carcinomas were significantly correlated with preradiotherapy Hb levels (p < 0.001). Tumor response in patients with head and neck and cervical cancers was significantly correlated with pretreatment Hb levels while in patients with lung cancer this correlation did not reach statistical significance (p=0.059). CONCLUSION: Preradiotherapy Hb level is an important factor in determining the efficacy of radiotherapy. Raising the Hb level before radiotherapy may have a beneficial impact on the response to radiotherapy.

Primary osteosarcoma of the sphenoid bone with multiple recurrences: a case report and review of the literature.

In this paper a patient with primary osteosarcoma of the sphenoid bone, which recurred twice following surgery and was managed with re-excision, irradiation and chemotherapy is presented due to its extremely rare presentation and atypical course. The relevant literature is also reviewed.

High-dose epirubicin and cisplatin in locally advanced undifferentiated nasopharyngeal carcinoma.

AIM: Undifferentiated nasopharyngeal carcinoma (UNPC) is a chemosensitive tumour; a randomized study evaluating neoadjuvant chemotherapy with bleomycin/epidoxorubicin/cisplatin (BEC) in addition to conventional radiotherapy has resulted in a better disease-free survival in the chemotherapy arm. The bleomycin infusion in the BEC regimen has necessitated hospitalization for the infusion, and resulted in serious pulmonary toxicity. This study has aimed to omit the bleomycin, and test the efficacy and toxicity of cisplatin (C) and a higher dose of epidoxorubicin (EPI) in patients with locally advanced UNPC. METHODS: Seventy-one patients with locally advanced UNPC were treated with three cycles of C 100 mg/m2 day 1, and EPI 100 mg/m2 day 1 every 3 weeks followed by conventional radiotherapy of 70 Gy. RESULTS: Neoadjuvant chemotherapy was well tolerated. There was only 1-week delay in 14.3% of the patients and no dose modification. Grade III-IV neutropenia occurred in 18.9% of the cycles: none of the patients developed neutropenic fever. No patient progressed during chemotherapy, the complete response rate was 26.8% (95% CI = 16.9-38.6) and the partial response rate was 59.1% (95% CI = 46.8-70.7) for an objective response rate of 85.9% (95% CI = 75.6-93.0) at the end of the three cycles of chemotherapy. After the completion of radiotherapy, the complete response rate increased to 81.7% (95% CI = 70.7-89.9) and the objective response increased to 91.5% (95% CI = 82.5-96.8). The median disease-free interval and the median survival have not been reached. The 5-year disease-free and overall survival rates are 53.0% (95% CI = 43.7-62.0) and 57.2% (95% CI = 48.3-65.2), respectively. CONCLUSION: Neoadjuvant C and EPI, easily administered in the outpatient setting, is an effective and well-tolerated regimen in the treatment of locally advanced UNPC.

High dose rate endobronchial brachytherapy in combination with external beam radiotherapy for stage III non-small cell lung cancer.

INTRODUCTION: A phase-II study was planned to test the effect of external beam radiotherapy in combination with endobronchial brachytherapy on the local control and survival of stage-III non-small cell lung cancer patients. MATERIALS AND METHODS: Thirty patients with stage-III non-small cell lung cancer have been treated with 60 Gy external beam radiotherapy and 3 x 5 Gy HDR endobronchial brachytherapy to control tumor and to prolong survival. RESULTS: Therapy regimen was found to be very effective for the palliation of major symptoms, palliation rates were 42.8% for cough, 95.2% for hemoptysis, 88.2% for chest pain and 80.0% for dyspnea. There was a 76.7% tumor response (53.3% complete, 23.3% partial) verified by chest CT scans and bronchoscopy. However, median locoregional disease free survival was 9+/-4 months (95% CI: 1-17) and it was only 9.6% at 5 years. Major side effects were radiation bronchitis (70.0%), esophagitis (6.6%) in the acute period and bronchial fibrosis (25%), esophagial fibrosis (12.5%) and fatal hemoptysis (10.5%) in the late period. Median survival was 11+/-4 months (95% CI: 4-18),and 5-year actuarial survival was 10%. Locoregional disease free survival (P=0.008) and the overall survival was longer (P<0.001) in the patients younger than 60, survival was also improved in the patients with complete response (P=0.019). There were no major complications during catheterisation; early side effects were quite tolerable but severe late complications were around 10%. CONCLUSIONS: It is concluded that endobronchial brachytherapy in combination with external irradiation provides a good rate of response, however does not eradicate locoregional disease and does not prolong survival except for some subgroups such as younger patients.

Late radiation effects to the rectum and bladder in gynecologic cancer patients: the comparison of LENT/SOMA and RTOG/EORTC late-effects scoring systems.

PURPOSE: To test the correlation of LENT/SOMA and RTOG/EORTC late-effect scales for rectum and bladder, 116 cases with gynecologic malignancies that were treated with radiotherapy were assessed with both scales. METHODS AND MATERIALS: All cases had been treated at least 6 months before the date of assessment with external beam radiotherapy (50--54 Gy to midline) and 1--2 fractions of HDR brachytherapy (2 x 8.5 Gy to point-A for 32 inoperable cases; 1 x 9.25 Gy to 5--9 mm from the ovoid surface for 84 postoperative cases). The patients were questioned with both scales, and the correlation between the two scales was analyzed by Spearman's rho (rank correlation) test. RESULTS: There were 64 cases with uterine cervix carcinoma and 52 cases with endometrium carcinoma, The overall (external + brachy) doses to ICRU points were 57.8 +/- 3.8 Gy for rectum and 59.3 +/- 4.9 Gy for bladder. The statistical analysis of LENT/SOMA and RTOG/EORTC scales revealed a very good correlation for rectum (r = 0.81; p < 0.01) and a good correlation for bladder (r = 0.72; p < 0.01). CONCLUSION: The LENT/SOMA system is a further step on the reporting of late radiation effects. Some modifications will improve its precision, and multicentric randomized studies are needed to test its validity.

Postoperative radiotherapy in endometrial carcinoma: analysis of prognostic factors in 440 cases.

PURPOSE: The aim of this study was to determine the prognostic factors influencing overall, disease-free and local recurrence-free survival in patients treated postoperatively with adjuvant radiotherapy for endometrial carcinoma. METHODS: The records of 440 patients with endometrial carcinoma treated by postoperative radiotherapy between January 1985 and June 1997 were reviewed retrospectively. All patients received postoperative external radiotherapy with 1.8-2.0 Gy daily fractions up to 36-68 Gy (median 54 Gy). Intracavitary brachytherapy was applied to 61.8% of the cases. Survival analysis was performed using the Kaplan-Meier method. The log-rank test was used for univariate analysis and the Cox regression model for multivariate analysis. RESULTS: Median age of the patients was 57 (range: 35-83). Histologically 80.2% were adenocarcinoma, 5.7% adenosquamous carcinoma, 5.2% clear-cell carcinoma and 4.3% serous papillary carcinoma. The distribution by stages were: 62.2% Stage I, 20.0% Stage II, 14.9% Stage III, 2.8% Stage IV. Median follow-up time was 53 months (7-173 months). Total failure rate was 15.2% with 2.7% of patients having only local failure, 2.0% local and distant failure and 10.5% distant failure only. Five-year overall, disease-free and local recurrence-free survival rates were 81.6%, 80.7% and 94.6%, respectively. According to univariate analysis prognostic factors influencing disease-free survival were histologic type (p=0.0067), histologic grade (p=0.0015), stage (p<0.0001), myometrial invasion (p<0.0001), peritoneal cytology (p=0.0013) and cervical involvement (p=0.0106) while the prognostic factors affecting local recurrence-free survival were stage (p=0.0277), myometrial invasion (p=0.0054), peritoneal cytology (p=0.0427). According to multivariate analysis prognostic factors influencing disease-free survival were histologic type (p=0.0194), myometrial invasion (p=0.0021), and histologic grade (p=0.0303) while the only prognostic factor influencing local recurrence-free survival was myometrial invasion (p=0.0241). CONCLUSION: Radiotherapy is a highly effective adjuvant treatment providing an excellent locoregional control rate and it should be continued for patients with unfavorable prognostic factors.

Effect of geometrical optimization on the treatment volumes and the dose homogeneity of biplane interstitial brachytherapy implants.

BACKGROUND AND PURPOSE: The isodose distributions of HDR stepping source brachytherapy implants can be modified by changing dwell times and this procedure is called optimization. The purpose of this study is to evaluate the effect of geometrical optimization on the brachytherapy volumes and the dose homogeneity inside the implant and to compare them with non-optimized counterparts. MATERIAL AND METHODS: A set of biplane breast implants consisting of 84 different configurations have been digitized by the planning computer and volumetric analysis was performed for both non-optimized and geometrically optimized implants. Treated length (TL), treated volume (V100), irradiated volume (V50), overdose volume (V200) and quality index (QI) have been calculated for every non-optimized implant and compared to its corresponding geometrically optimized implant having a similar configuration and covering the same target length. RESULTS: The mean TL was 74.48% of the active length (AL) for non-optimized implants and was 91.87% for optimized implants (P < 0.001). The mean QI was 1.83 for non-optimized implants and 2.17 for optimized implants (P < 0.001). The mean V50/V100 value was 2.71 for non-optimized implants and 2.65 for optimized implants (P < 0.001) and the mean V200/V100 value was 0.09 for non-optimized implants and 0.10 for optimized implants (P < 0.001). CONCLUSIONS: By performing geometrical optimization it is possible to implant shorter needles for a given tumour to adequately cover the target volume with the reference isodose and thus surgical damage is reduced. The amount of healthy tissues outside the target receiving considerable radiation is significantly reduced due to the decrease in irradiated volume. Dose homogeneity inside the implant is significantly improved. Although there is a slight increase of overdose volume inside the implant, this increase is considered to be negligible in clinical applications.

Hyperfractionated radiotherapy combined with simultaneous chemotherapy in inoperable non-small cell lung cancer: a pilot study.

Between March 1992 and February 1993, hyperfractionated radiotherapy (HRT) (1.2 Gy.fraction-1, twice a day, total dosage of 69.6 Gy) and simultaneous cisplatin (70 mg.m-2, 3rd and 23rd days of HRT) and etoposide (70 mg.m-2, 1-3rd and 20-23rd days of HRT) were applied to 27 patients with inoperable non-small cell lung cancer (NSCLC). Their Karnofsky performance statuses were 70-90%, and mean age was 52 (36-63). Two cases were stage II (one of the patients refused the operation and the other was medically inoperable because of insufficient ventilation), eight were stage IIIA and 17 were stage IIIB. No severe life-threatening grade IV acute toxicity findings were observed. Generally, acute side-effects were transient and did not require discontinuation of treatment. Tumour responses were as follows: complete response in six cases (23%); partial response in 19 cases (70%); and stable disease in two (7%). When complete response rates were compared according to stage, histological type, age group and weight loss, no statistically significant difference was found. Median overall and disease-free survival times were 14 months (95% confidence interval) (95% CI) 11-17 months and 10 months (95% CI 7-13 months), respectively. Twelve and 24 months overall and disease-free survival rates were 56 and 30%, and 36 and 24% respectively. No statistically significant difference was found in overall survival rates among epidermoid and nonepidermoid types, while the difference in disease-free survival was statistically significant. The acute and late complications of our HRT and simultaneous chemotherapy protocol were tolerable and the survival rates were encouraging.

Lipid secreting breast carcinoma in childhood: a case report.

A ten-year-old girl was admitted to our hospital with a mass in the left breast after a local recurrence following a resection done in a district hospital three months earlier. A modified radical mastectomy with axillary lymph node dissection was performed in our department. Histological examination revealed a lipid secreting carcinoma (lipid-rich carcinoma) of the breast. To our knowledge she is the first case in childhood in the literature and is therefore reported.