Outcome after combined modality treatment for uterine papillary serous carcinoma: a study by the Rare Cancer Network (RCN).

OBJECTIVES: Uterine papillary serous carcinoma (UPSC) is a rare subtype of endometrial carcinoma, characterized by a poor outcome. We sought to better analyze the effect of surgery and adjuvant therapies on this disease. METHODS: A retrospective analysis was performed on the records of 138 women diagnosed with UPSC between 1986 and 2003 in the framework of the Rare Cancer Network. RESULTS: Median age at diagnosis was 67 years. Pure UPSC was found in 107 patients and mixed histology in 30. Fifty-four patients had stage I, 20 stage II, 41 stage III and 23 stage IV disease. Median follow-up for the surviving patients was 44 months. Surgery was performed in 129 patients, after which 122 were rendered free of gross disease and comprised the adjuvant group. Of these, 23 received platinum-based chemotherapy. Radiotherapy was applied in 52 patients and 28 underwent combined chemo-radiotherapy. At last follow-up, 57 patients were alive free of disease, 10 were alive with disease, 62 died of disease, 8 died of other causes and 1 died due to toxicity. Five-year disease-free survival (DFS), disease-specific survival (DSS) and overall survival for the 122 patients treated with curative intent were 42%, 56% and 54%, respectively. In multivariate analysis, age, stage, histology and adjuvant chemotherapy were significant for DFS; age, stage and histology were significant for DSS. Radiotherapy reduced the pelvic recurrence rate from 29% to 14% (p=0.047). CONCLUSIONS: UPSC harbours a moderate prognosis, with age, stage and histology as significant prognosticators. Conservative surgery followed by adjuvant chemotherapy and pelvic radiotherapy can be suggested as an appropriate treatment approach for patients treated with curative intent.

Effect of bladder distension on dose distribution of intracavitary brachytherapy for cervical cancer: three-dimensional computed tomography plan evaluation.

PURPOSE: To quantify the effect of bladder volume on the dose distribution during intracavitary brachytherapy for cervical cancer. METHODS AND PATIENTS: The study was performed on 10 women with cervical cancer who underwent brachytherapy treatment. After insertion of the brachytherapy applicator, the patients were transferred to the computed tomography unit. Two sets of computed tomography slices were taken, including the pelvis, one with an empty bladder and one after the bladder was filled with saline. The target and critical organs were delineated by the radiation oncologist and checked by the expert radiologist. The radiotherapy plan was run on the Plato planning system, version 14.1, to determine the dose distributions, dose-volume histograms, and maximal dose points. The doses and organ volumes were compared with the Wilcoxon signed ranks test on a personal computer using the Statistical Package for Social Sciences, version 11.0, statistical program. RESULTS: No significant difference regarding the dose distribution and target volumes between an empty or full bladder was observed. Bladder fullness significantly affected the dose to the small intestine, rectum, and bladder. The median of maximal doses to the small intestine was significantly greater with an empty bladder (493 vs. 284 cGy). Although dosimetry revealed lower doses for larger volumes of bladder, the median maximal dose to the bladder was significantly greater with a full bladder (993 vs. 925 cGy). The rectal doses were also affected by bladder distension. The median maximal dose was significantly lower in the distended bladder (481vs. 628 cGy). CONCLUSIONS: Bladder fullness changed the dose distributions to the bladder, rectum, and small intestine. The clinical importance of these changes is not known and an increase in the use of three-dimensional brachytherapy planning will highlight the answer to this question.

Concurrent gemcitabine and radiotherapy for locally advanced pancreatic cancer.

This study is designed to assess the toxicity and therapeutic effectiveness of concurrent gemcitabine and radiotherapy in patients with unresectable pancreatic cancer. Concurrent gemcitabine (400 mg/m2/wk) in six weekly cycles starting on d 1 of radiotherapy (50.4 Gy; 1.8 Gy/fraction/d; 5 d/wk) was prescribed on 22 patients with locally advanced pancreatic cancer. Patients were analyzed with regard to radiological response on computerized tomography, overall survival, and toxicity. Twelve (55%) patients completed the prescription of six gemcitabine cycles and 50.4 Gy radiotherapy; while 10 (45%) received one to five cycles of gemcitabine owing to neutropenia. All patients experienced abdominal discomfort during treatment and three patients required medical intervention. Other toxicities reported were nausea in 13 patients (60%), grade 3 vomiting in 3 (14%). Radiological response evaluations were as follows: complete, 2 (9%); partial, 9 (41%); stable, 7 (32 %); and progressive, 4 (18 %). Median survival was 8.7 mo. Combination of weekly gemcitabine (400 mg/m2) and radiotherapy provided response in 50% of the patients but was associated with severe toxicity resulting in incomplete delivery of the planned chemotherapy.

Radiotherapy in the management of Kaposi's sarcoma: comparison of 8 Gy versus 6 Gy.

OBJECTIVE: To evaluate prospectively the efficacy of a single fraction of high-dose radiotherapy in patients with Kaposi's sarcoma. PATIENTS: Between 1994 and 2004, 47 patients with Kaposi's sarcoma were treated at Hacettepe University, Department of Radiation Oncology. Thirteen (28%) patients received chemotherapy before radiotherapy and were referred due to recurrent or progressive disease or intolerance to chemotherapy. All lesions were treated locally with a 2-3-cm safety margin with 4-6-MeV electron beams. Radiotherapy consisted of a single fraction of 8 Gy in the first four years and 6 Gy thereafter. RESULTS: The male:female ratio was 4:1. The median age was 61 years (range 18-87). Eight out of 47 patients (17%) had an underlying immunocompromised state, and one had a previous diagnosis of Hodgkin's disease. Of 203 fields treated, 51 and 152 fields were treated with 8 Gy and 6 Gy, respectively. Overall response rates (RR) at 12 months for 8- and 6 Gy were 93% and 86%, which were not statistically different. However, the difference between complete RRs at 12 months (93% and 60% for 8 Gy and 6 Gy respectively) was significant (p<0.0001). Progression-free survival and reirradiation rates were not significantly different. Side effects were tolerable in all but three patients with grade 2-3 fibrosis and edema. CONCLUSION: Radiotherapy is an effective mode of treatment for Kaposi's sarcoma, and a single dose of 8 Gy is more effective in terms of complete RR compared to 6 Gy, though overall response and progression-free survival rates were similar.

Second neoplasms in pediatric patients treated for cancer: a center's 30-year experience.

To investigate the incidence and outcome of secondary neoplasms in pediatric patients treated for childhood cancer. Between December 1971 and January 2000, a total of 5859 patients younger than age 17 were diagnosed and treated for childhood cancers in our center. Of this group, 1511 (36%) patients were followed for more than 36 months. These long-term survivors were included in this analysis. Twenty-six patients developed a secondary malignancy with an overall risk of 1.7% in this cohort. The male:female ratio was 17:10, with a median age of 7.66 at diagnosis (range, 2 to 16 y). Four patients (14.8%) with Hodgkin lymphoma; 3 each (11.1%) with retinoblastoma and rhabdomyosarcoma; 2 each (7.4%) with Wilms tumor, Ewing sarcoma, medulloblastoma, ganglioneuroblastoma, and non-Hodgkin lymphoma; and 1 each (3.7%) with ependymoma, nasopharyngeal carcinoma, osteosarcoma, astrocytoma had a secondary malignant disease during the long-term follow-up period. Secondary malignant diseases were osteosarcoma in 6 patients, acute lymphoblastic leukemia in 2, acute myelogenous leukemia in 2, and rare malignant disease in others. Four patients with osteosarcoma developed disease within the radiation field. Osteosarcoma was the most frequently occurring secondary neoplasm. Less toxic treatment modalities should be used to decrease the risk of secondary malignant diseases.

Treatment results of 84 patients with nasopharyngeal carcinoma in childhood.

BACKGROUND: To evaluate the clinical characteristics, treatment regimens, survival, and late complications in patients with nasopharyngeal carcinoma. PROCEDURE: Eighty-four patients diagnosed with nasopharyngeal carcinoma between 1972 and 2002 were retrospectively evaluated. Tumor status, lymph node involvement, metastasis, and stage were assessed according to the TNM classification. All patients were treated with radiotherapy and chemotherapy. Chemotherapeutic regimens involved cyclophosphamide from 1972 to 1982, vincristine + cyclophosphamide + epirubicine and actinomycin-D protocol from 1982 to 1999 and cisplatin + methotrexate + 5-fluorouracil with leucovorine rescue after 1999. Mean and median values were used for the demographic characteristics. Kaplan-Meier survival curves were used for survival analysis. The patient groups were compared in terms of survival duration using a log-rank test. RESULTS: There were 51 males and 33 females with a median age of 13 years (7-17) at diagnosis. At the time of diagnosis, 78.5% of the patients were at advanced stage (stages III and IV). Overall and event-free survival rates were 56.3% and 50.1%, respectively. Survival was inversely affected by advanced nodal status (P = 0.01). The survival rates (80%) were found higher with cisplatin + methotrexate + 5-fluorouracil + leucovorine rescue regimen. The most frequent late complications after therapy were hypothyroidism (9.5%), dental caries (7.1%), and trismus (7.1%). CONCLUSION: The cisplatin-based regimen was the best chemotherapeutic regimen. Less toxic regimens with better survival rates should be investigated in patients with nasopharyngeal carcinoma.

Intracranial involvement in Hodgkin's disease.

The authors report 3 cases of Hodgkin's disease with intracranial involvement. The patients were 4, 12, and 15 years old (male/female=1/2). Initially, they were treated with ABVD or COPP chemotherapies and low-dose involved field radiotherapy. Intracranial recurrences occurred 27, 40, and 42 months after initial diagnosis, respectively. Two patients experienced convulsions and the other complained of diplopia. The metastatic lesions were located supratentorially with CT or MRI. Despite initial response achieved following systemic chemotherapy and external irradiation to cranial lesions, all patients died with disseminated disease. In patients with intracranial involvement of Hodgkin's disease, prolonged disease-free survival may be achieved by combined modality treatment.

Trismus as a presenting symptom in nasopharyngeal carcinoma.

Trismus is a more common symptom in NPC patients with young age and an indicator of advanced primary tumour. Overall response rate after treatment was 88%. Trismus recovered in majority of patients at the end of treatment and patients with complete recovery of trismus may have a better survival.

A phase II study on the safety and efficacy of 5-fluorouracil, epirubicin, cyclophosphamide (FEC) followed by paclitaxel in the adjuvant treatment of breast cancer.

The incorporation of a taxane into an anthracycline-containing regimen in the adjuvant treatment of breast cancer is a promising approach. In this study, we aimed to evaluate the safety and efficacy of four cycles of FEC (fluorouracil 500 mg/m2, epirubicin 70 mg/m2, cyclophosphamide 500 mg/m2, every 3 weeks) followed by four cycles of paclitaxel (175 mg/m2 every 3 weeks) in the adjuvant treatment of node-positive and other high-risk breast cancer patients. A total of 88 female patients were enrolled. Mean age (+/- SD) of the patients was 47 +/- 10 (min: 24; max: 71). The patients were followed for a median of 48 months (min: 20; max: 64). The most common side effects were nausea-vomiting (grade I-II: 91%; grade III: 2%), as well as hematological toxicity (grade I-II: 70%; grade III: 3%). Although all patients experienced some degree of toxicity, it was severe enough to be classified as grade III or IV in only 10 (11%) of the cases. Of note, six (8%) patients had grade I and only one (1%) had grade II cardiotoxicity. No grade III or IV cardiotoxicity was observed. The full eight cycles of study treatment could be administered to 75 patients (85%). Side effects necessitated the reduction of the doses of FEC and paclitaxel in one (1%) and three patients (3%), respectively. Median overall (OS) and disease-free survival (DFS) have not yet been reached. Five-year OS and DFS have been estimated to be 78% and 61%, respectively. We conclude that FEC followed by paclitaxel is a well-tolerated and feasible regimen in the adjuvant treatment of early breast cancer. Its efficacity is comparable with other commonly used regimens and merits evaluation in a phase III study.

Radiotherapy in the management of Klippel-Trénaunay-Weber syndrome: report of two cases.

Klippel-Trénaunay-Weber syndrome (KTWS) is characterized by combined vascular malformations of capillary, venous, and lymphatic types usually observed during infancy or childhood. In this report, we describe two KTWS patients treated with radiotherapy after long-term conservative treatment or multiple surgical interventions. The first patient, a 15-year-old female, presented with vascular masses located on the right upper extremity. She was treated conservatively for 14 years, and amputation was offered at the age of 14 due to cardiac failure. A course of radiotherapy to a total dose of 40 Gy with conventional daily fractionation was administered as an alternative to the mutilating surgery, and prominent improvement both subjectively and objectively was detected 1 year after radiotherapy. The second patient, a 40-year-old male, suffered from huge vascular masses of both the trunk and lower extremities. Despite multiple surgical interventions and conservative treatment, disease progressed and neurological symptoms occurred due to compression of vertebral structures. He was administered a course of 30 Gy radiotherapy with 1.5 Gy daily fractions to the lower thoracic region and whole abdominal cavity. Six months after radiotherapy, subjective relief described by the patient but without any objective response was detected. Though considered as a benign disease, KTWS can cause life-threatening complications. The response of one of our patients is a hopeful finding for considering radiotherapy as an alternative treatment modality for these patients.

Treatment results of 59 young patients with nasopharyngeal carcinoma.

PURPOSE: To evaluate the outcome of patients 17 (90.5% versus 64.7%; p=0.02). Patients aged <16 years had longer 5 year DMFS (90.5% versus 67.7%; p=0.05) with a borderline significance. DMFS is significantly shorter in patients initially presented with N3 disease compared to N0-2 disease (58.8% versus 84.4%; p=0.04). CONCLUSIONS: We suggest that RT combined with multiagent chemotherapy is effective in achieving satisfactory DFS and comparable OS in young patients with NPC. Results of both previous series and ours are evoking the necessity of early administration of efficient chemotherapeutic agents in addition to radiotherapy, but indistinct is the precise regimen and the intensity along the radiotherapy. All efforts towards decreasing late side effects of treatment should be encouraged in this long life expected group.

Prognostic role of Ebstein-Barr virus latent membrane protein-1 and interleukin-10 expression in patients with nasopharyngeal carcinoma.

PURPOSE: We aimed to investigate Ebstein-Barr virus (EBV) latent membrane protein-1 (LMP-1) and Interleukine-10 (IL-10) expression in nasopharyngeal carcinoma (NPC) patients and to evaluate their prognostic significance. MATERIAL AND METHODS: Between 1993 and 1999, 166 patients were treated with the diagnosis of nonmetastatic NPC at our department. The expression of LMP-1 and IL-10 was investigated by using an immunohistochemical approach in 74 (53 male, 21 female) patients whose paraffin embedded tissue samples were available. A detailed histopathological analysis including degree of apoptosis and lymphocyte infiltration was made and all patients were reclassified according to the World Health Organization (WHO) classification. Univariate, multivariate, and logistic regression analyses were performed using all clinical and pathological prognostic factors. All patients were treated with radiotherapy +/- chemotherapy. Follow-up ranged between 12 and 80 months (median: 32). RESULTS: The histopathological diagnosis was WHO-I in 1 (1.3%), WHO-II in 15 (20.2%), and WHO-III in 58 (79.5%) patients. There were 38 (51%) patients with IL-10 expression and 44 (61%) patients with LMP-1 expression. Twenty-seven (36.4%) patients were found to be both IL-10 and LMP-1 positive. There were significantly more N0 disease in patients without LMP-1 expression compared to LMP-1 positive patients (65% vs. 35%, p = 0.01). The logistic regression analysis showed advanced nodal involvement to be the major parameter affecting the expression of IL-10 (p = 0.03). Three-year overall survival (OS), locoregional relapse free survival (LRRFS), and distant metastasis free survival (DMFS) rates were 67.8%, 84.4%, and 74.3%, respectively, for the whole group. On univariate analysis, LRRFS was significantly lower in WHO-III patients, DMFS was significantly lower in advanced nodal disease and IL-10 negative patients, and OS was significantly lower in WHO-III patients. Multivariate analysis showed that WHO-III and T2 patients were significantly associated with lower OS and N3 patients were significantly associated with lower DMFS. CONCLUSION: We observed a high rate (61%) of EBV (LMP-1 positive) and NPC association in our patients. LMP-1 positive tumors were found to be more prone to invade lymph nodes. Patients with negative IL-10 expression had more advanced N disease. We did not find a prognostic significant role of IL-10 and EBV LMP-1 on survival in multivariate analysis.

Prospective study of combined modality treatment or radiotherapy alone in the management of early-stage adult Hodgkin's disease.

PURPOSE: To determine the efficacy and toxicity of combined modality treatment (CMT) or radiotherapy (RT) alone in the management of clinical Stage I-IIA adult Hodgkin's disease patients. METHODS AND MATERIALS: Forty-seven patients with supradiaphragmatic clinical Stage I-IIA Hodgkin's disease without bulky mediastinal lymphadenopathy were enrolled into this prospective study between September 1997 and February 2002. Patients with very favorable criteria presenting with one or two nonbulky nodal areas involved, an erythrocyte sedimentation rate of <50 mm/h, age <40 years, and either lymphocyte predominant or nodular sclerosing histologic findings were treated by RT alone. Patients missing any of these favorable criteria were classified as the other favorable group and were treated with three courses of doxorubicin, bleomycin, vinblastine, and dacarbazine chemotherapy followed by involved-field RT. The median age was 36 years (range, 19-53 years). Of the 47 patients, 15 were women and 32 were men. Only 3 patients were classified as the most favorable group and treated with mantle RT alone; the remaining 44 were treated with CMT. RESULTS: The median follow-up was 51 months (range, 20-74 months). Only 2 patients developed recurrence, both out of the irradiated field, one in the contralateral neck and the other in the abdomen. The 5-year relapse-free and overall survival rate was 95.4% and 97.8%, respectively. Although none of the prognostic factors were statistically significant for relapse-free survival, a trend was noted for the response to chemotherapy (p = 0.06). Only 2 patients developed treatment-related complications. One patient treated with mantle RT alone developed severe ischemic heart disease and one in the CMT arm developed subclinical hypothyroidism. CONCLUSION: Despite the short follow-up, CMT or RT alone tailored according to the clinical prognostic factors were successful in terms of disease control in clinical Stage I-IIA Hodgkin's disease. Longer follow-up is required to make definitive conclusions.

Non-metastatic stage IV nasopharyngeal carcinoma patients: analysis of the pattern of relapse and survival.

BACKGROUND AND PURPOSE: The objective of this study is to analyze the mode of recurrence patterns and survival of our 96 non-metastatic stage IVA and IVB nasopharyngeal carcinoma (NPC) patients. PATIENTS AND METHODS: A total of 234 previously untreated, histologically confirmed non-metastatic NPC patients were treated in our department between 1993 and 2001. Among them 96 patients (41%) were staged as IVA or B disease. All patients were uniformly staged using the fifth edition of AJCC/UICC staging system. There were 76 male and 20 female patients. Their ages ranged from 9 to 72 years (median age: 43.5). Histopathological diagnosis was WHO 2 and 3 in 89 (93%) patients. All patients were treated with external radiotherapy and 77 out of 96 patients (80%) with stage IV disease received either concomitant or neoadjuvant cisplatin based combined chemotherapy regimens. Median follow-up time was 30 months (range: 4-101 months). RESULTS: At the time of this analysis, 60 (62%) patients were alive and 48 of them were free of disease. Local recurrence rate was found to be significantly higher in stage IVA patients (28 vs. 11%, P=0.02) and distant metastasis rate was significantly higher in stage IVB patients (40 vs. %8, P=0.0001). The 3 year overall (OS), disease free (DFS), loco regional relapse free (LRRFS) and distant metastasis free survival (DMFS) rates were 71, 74, 77 and 94% for stage IVA and 60, 46, 77 and 58% for stage IVB patients, respectively. Three year LRFS rates for stage IVA and IVB were 77 and 89%, respectively (P=0.1). Age older than 40 years was found to be statistically significant adverse prognostic factor both for OS (P=0.01) and LRRFS (P=0.005) in univariate analysis. Advanced N status was an unfavorable prognostic factor both for OS (P=0.03), DFS (P=0.0004) and DMFS (P=0.0003). DMFS was adversely affected by the presence of cranial nerve palsy at diagnosis (P=0.01), advanced T status (P=0.03) and advanced N status (P=0.0003). In univariate analysis treatment with chemotherapy was found to be an unfavorable prognostic factor for DMFS (P=0.02). According to the multivariate analysis, older age (>40 year of age) was a significant independent prognostic factor for OS (P=0.02), DFS (P=0.05) and LRRFS (P=0.01). Patients with advanced N status had worse OS (P=0.03), DFS (P<0.0001) and DMFS (P=0.07). Patients treated with chemotherapy as an adjuvant to radiotherapy had tended to have a better DFS (P=0.04). CONCLUSIONS: The local relapse was the major cause of failure in patients with stage IVA disease, and distant metastasis was the predominant treatment failure in stage IVB patients. While stage IVA patients may benefit more intensive local treatment strategies, stage IVB patients definitely need more systemic treatment.

Stage I testicular seminoma: para-aortic and iliac irradiation with reduced dose after orchiectomy.

BACKGROUND AND PURPOSE: Radiotherapy remains the treatment of choice for patients with stage I seminoma. The aim of this study is to report preliminary results of reduced dose radiotherapy to ipsilateral pelvic and para-aortic lymph nodes. MATERIALS AND METHODS: Between February 1996 and December 2001, 53 patients with stage I testicular seminoma were treated with adjuvant radiotherapy after orchiectomy. The median age was 34 years (19-59 years). Four (7.5%) patients had a history of cryptorchidism. Eleven (20.8%) patients showed elevated beta-human chorionic gonadotropin. All patients had a radical inguinal orchiectomy and histopathological analysis yielded classic seminoma in 47 (88.7%), spermatocytic in 5 (9.4%) and anaplastic in 1 (1.9%) patients. A total of 19.6-20 Gy in 1.8- to 2-Gy daily fractions was administered to the para-aortic and ipsilateral iliac lymphatics. RESULTS: Median follow-up time was 42 months (12-77 months). One patient developed para-aortic lymph node recurrence at month 28 of the follow-up. Five-year overall and disease-free survivals were 100 and 98%, respectively. Only grade I-II of the Radiation Therapy Oncology Group acute gastrointestinal complications without any severe late toxicity was detected. CONCLUSION: Reduced dose radiotherapy seems to be as effective as higher doses in the management of stage I seminoma with an acceptable toxicity.

Waldeyer's ring lymphomas: treatment results and prognostic factors.

Optimal management of patients with localized Waldeyer's ring (WR) lymphoma remains controversial due to the lack of randomized studies and heterogenous grouping of most reported series. In this retrospective study, we have evaluated the possible prognostic factors and treatment outcome of WR non-Hodgkin's lymphoma. Between December 1993 and February 2000, 32 patients with WR lymphoma, stage I (11 patients) and stage II (21 patients) were treated. There were 17 male patients and 15 female patients with a median age of 47 years. The distribution among different anatomical sites were as follows: tonsils in 16 (50%), nasopharynx in 10 (31%), base of tongue in 6 (19%). According to Working Formulation, 10 had high-grade, 17 intermediate grade, 3 low-grade, and 2 had unclassified lymphomas. Combined chemotherapy and radiotherapy was the primary modality of therapy for intermediate or high-grade lymphoma. Radiotherapy alone was employed only in low-grade WR lymphomas. Chemotherapy was median 6 courses of CHOP (cyclophosphamide, doxorubicin (Adriamycin), vincristine, and prednisolone) in 26 patients and CEOP (cyclophosphamide, doxorubicin, etoposide, and prednisone). Radiotherapy volume was involved field and the median dose was 40 Gy. Median follow-up is 40 months (ranged from 6-82 months). Overall survival and disease-free survival (DFS) rates at 3 years are 100% and 92%, respectively. Two patients developed recurrence, both salvaged with further chemotherapy. Only one patient died because of other reasons. International Prognostic Index score (2) is found to be an important prognostic factor for DFS. The other significant prognostic factors for DFS are performance status and serum levels of alkaline phosphatase and lactate dehydrogenase. Our results suggest that combined chemotherapy and involved field radiotherapy is appropriate treatment for stage I-II WR lymphoma. International Prognostic Index is the strongest predictor for DFS.

Tissue trace element change after total body irradiation.

PURPOSE: In this study, we examined the changes of tissue contents of trace elements and iron after total body irradiation (TBI) and their possible impact on late toxicities. MATERIAL AND METHODS: 20 female Wistar rats were randomly assigned to two groups - either radiation (n = 10) or control (n = 10). Rats in the radiation group received TBI of 5 Gy in a single fraction. Rats were sacrificed and tissue samples of heart, lung and kidney were taken 8 weeks after radiation. Tissue levels of zinc, copper, magnesium, manganese and iron analysis were performed with an atomic absorption spectrophotometer and suprapure grade standard solutions. One kidney of each animal was taken for electron microscopic analysis. Blood samples were collected from all animals and the blood chemistry related to kidney function was studied. RESULTS: The kidney levels of Fe and Cu significantly increased 8 weeks after irradiation (p < 0.05). The Cu/Zn ratio did not reach statistical significance in any tissue, however in kidney, there was a tendency to rise (p = 0.08). Myocardium and lung content of trace elements and iron did not show any significant change 8 weeks after irradiation. Electron microscopic analysis showed significant injury in glomerular endothelial cells, renal tubules and thickening of basement membrane. Blood chemistry showed a significant rise in serum creatinine (p = 0.008) and calcium (p = 0.01) in the TBI group. Serum creatinine levels were 0.73 and 0.84 mg/dl, and serum calcium levels were 10.1 and 11.3 mg/dl in control and TBI groups, respectively. CONCLUSION: A sublethal dose of TBI causes deposition of Cu and Fe within the kidney after TBI. Deposition of these elements may have some additional role on the toxicity caused by direct radiation on the kidney.

Adjuvant high-dose-rate brachytherapy after external beam radiotherapy in nasopharyngeal carcinoma.

PURPOSE: To compare the local control and survival rates obtained with either external beam radiation therapy (ERT) and adjuvant high-dose-rate (HDR) brachytherapy (BRT) or ERT alone in patients with nasopharyngeal cancer. METHODS AND MATERIALS: Between December 1993 and December 1999, 144 patients (106 male, 38 female) with the diagnosis of nasopharyngeal cancer were treated with either ERT and adjuvant HDR BRT (Group A) or ERT alone (Group B) at our department. BRT was not applied in 38 patients for the following reasons: (1) Unit was unavailable (n = 13), (2) Patient was younger than 18 years (n = 17), (3) Patient received accelerated hyperfractionated ERT (n = 6), and (4) Patient refused BRT (n = 2). The median age for whole group was 43 (range: 9-82 years). According to the AJCC-1997 staging system, there were 11 (7.6%), 35 (24.3%), 38 (26.4%), and 60 (41.7%) patients in Stage I, II, III, and IV, respectively. There were 57 (39.6%) patients with T1, 41 (28.5%) with T2, 20 (13.9%) with T3, and 26 (18.1%) with T4 tumors. Histopathologic diagnosis was WHO 2-3 in 137 (95.2%) patients. ERT doses ranged between 58.8 and 74 Gy (median: 66 Gy). There were significantly more patients with young age, N2 status, and Stage III disease in Group B and with Stage II disease in Group A. Significantly more patients received chemotherapy in Group B. BRT with an HDR 192Ir microSelectron afterloading unit was delivered in 106 patients at the conclusion of ERT using a single-channel nasal applicator. Dose was prescribed at 1 cm from the source, and total dose of 12 Gy in 3 fractions on 3 consecutive days was given immediately after ERT. Besides radiotherapy, 82 (56.9%) patients received cisplatin-based chemotherapy, as well. Follow-up time ranged between 12 and 80 months (median: 32 months). RESULTS: The two groups were comparable in terms of local recurrence, locoregional failure, regional failure, and rate of distant metastasis. Local failure was observed in 11 (10.3%) out of 106 patients in Group A and in 2 (5.2%) out of 38 patients in Group B (p > 0.05). Three-year disease-free survival rate was 67% and 80% (p = 0.07), respectively, and 3-year local recurrence-free survival rate was 86% and 94% (p = 0.23) for Group A and B, respectively. Multivariate analysis showed that advanced nodal status and male gender were significantly unfavorable factors for disease-free survival, and Stage II disease was unfavorable for local recurrence-free survival. The administration of adjuvant HDR BRT was not an independent prognostic factor in multivariate analysis. Out of 106 patients, 42 (39.7%) experienced nasal congestion, transient nasal obstruction, and/or fibrinous exudate in response to antihistaminic treatment. Only three (2.8%) patients experienced nasal synechy related, most probably, to the BRT. Five patients developed severe neural complications; only one out of five was observed in Group A. No severe complication attributed directly to BRT was detected. CONCLUSION: The acute and late morbidity of adjuvant HDR BRT is acceptable with our treatment scheme, but we did not find any local control difference between our patients treated with adjuvant BRT after ERT and ERT alone. We believe that the exact role of adjuvant HDR BRT can be elucidated only by prospective randomized studies.