I. Lale Atahan

Conventional external radiotherapy in the management of clivus chordomas with overt residual disease.

Abstract Cranial chordomas are uncommon tumors accounting for less than 1% of all intracranial neoplasms. Although they are slowly growing, rarely metastasising tumors, cranial chordomas are challenging to treat due to their critical location, invasive nature and aggressive recurrence. The aim of this retrospective study was to evaluate the role of conventional irradiation in the treatment of clival chordomas with overt residual disease after incomplete surgery.Between January 1979 and December 1997, 18 patients with histologically confirmed clival chordoma were treated with radiotherapy. Median age at the time of diagnosis was 32 years. The mean duration of the symptoms before diagnosis was 33.9 months. Median tumor diameter at initial presentation was 5 cm (range, 3–7 cm). The type of surgical procedure was subtotal excision in 11 patients and biopsy in 7. Radiation treatment was delivered with megavoltage units, and total doses between 50 Gy and 64 Gy (median, 60 Gy) were administered with conventional daily fractions. One patient received additional 12.50 Gy with linear accelerator-based stereotactic radiosurgery after subtotal excision and external irradiation.The mean follow-up time was 43.2 months. Overall survival at 5 years was 35%. Eleven patients showed progression after radiotherapy. The median time to progression after radiotherapy was 40.8 months (38.4–43.2) with a 5-year progression-free survival of 23%. Five patients (29.4%) showed symptomatic relief after radiotherapy while persistent symptoms were recorded for 6 patients. Incomplete surgery and conventional external radiotherapy with a dose of around 60 Gy seem to be inadequate in the treatment of clival chordomas.

Comparison of AJCC 1988 and 1997 classifications for nasopharyngeal carcinoma

PURPOSE A comparison of American Joint Committee on Cancer (AJCC) 1988 and 1997 nasopharyngeal carcinoma (NPC) classifications was made in terms of patient distribution and efficacy in predicting prognosis. METHODS AND MATERIALS Between 1993-1997, 90 patients (64 M, 26 F) with non-metastatic NPC were treated. The mean age was 42.02 (range: 9-82) years old. Histopathological diagnosis was WHO 2 and 3 in 83 (92.2%) patients. All patients were prospectively staged using AJCC 1988 and modified Hos classifications (1989) and these data were stored in a computer database. Retrieval of this information enabled us to restage patients according to the AJCC 1997. Median follow-up was 38 months. RESULTS According to the AJCC 1988 there were 2 (2.2%), 6 (6.7%), 13 (14.4%), and 69 (76.7%) patients in Stage I, II, III and IV, respectively. Same figures were 8 (8.8%), 21 (23.3%), 26 (28.9%), and 35 (38.8%), according to AJCC 1997. Three year overall survival (OS) rates were 100%, 100%, 67%, and 62% for patients Stage I, II, III, and IV according to the AJCC 1988 and 100%, 72%, 65%, and 55%, (I vs. IV; p = 0.03, I vs. III; p = 0.05) respectively, according to the AJCC 1997. Three year loco-regional relapse free survival (LRRFS) rates were 50%, 100%, 100%, and 83% (I vs. III; p = 0.03) for patients in Stage I, II, III, and IV according to the AJCC 1988. Same figures were 88%, 90%, 89%, and 85% according to the AJCC 1997. Three year distant metastasis free survival (DMFS) rates were 100%, 100%, 82%, and 67% for patients in Stage I, II, III, and IV according to the AJCC 1988. Same figures were 100%, 74%, 80%, and 57% (I vs. IV; p = 0.03) according to the AJCC 1997. We did not observe any significant difference in LRRFS among T stages for both staging system and the N stage was the primary determinant for DMFS in both systems. CONCLUSIONS We observed a better patient distribution with AJCC 1997 comparing to AJCC 1988. The new classification also attained better statistical significances among stages in the OS and DMFS rates.

Acute phase response during radiotherapy

Abstract Purpose: The acute phase response is characterized by changes in the plasma concentrations of a number of liver-synthesized proteins, one of which is C-reactive protein (CRP). The existence of these changes in the plasma profile underlies the change in erythrocyte sedimentation rate (ESR). Acute phase response itself is an illness and may result from immunologic reactions and inflammatory processes. This study is designed to determine whether the CRP level and ESR increase during radiotherapy and whether their rise correlates with acute and late radiation morbidity. Methods and Materials: Between April 1997 and October 1998, 51 patients with the diagnosis of endometrium and cervical cancer were treated with surgery and postoperative radiotherapy. Median age at the time of radiotherapy was 52 (range, 26–73) years. Thirty patients received pelvic radiotherapy, and 21 patients were treated by pelvic–paraaortic irradiation. A total dose of 50.4 Gy to the pelvis and 45 Gy to the paraaortic field were delivered in conventional fraction. Erythrocyte sedimentation rates and CRP levels were studied before, during, and at the end of radiotherapy. Results: The mean ESR measurements before and after radiotherapy were 40 (8–100) and 52 (10–120), and mean CRP levels were 1.4 (0.12–9.8) and 2.7 (0.12–32.2), respectively. The statistical analysis yielded significant rise in ESR and CRP levels at the end of radiotherapy ( p p = 0.005 and 0.028 respectively). Conclusion: Acute phase response was present during radiotherapy. Radiotherapy should be considered as a cause of increase in CRP level and ESR especially in clinical conditions where acute phase response is important.

Treatment results of 84 patients with nasopharyngeal carcinoma in childhood

To evaluate the clinical characteristics, treatment regimens, survival, and late complications in patients with nasopharyngeal carcinoma.

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.

BASAL CELL CARCINOMAS DEVELOPING IN A CASE OF MEDULLOBLASTOMA ASSOCIATED WITH GORLIN'S SYNDROME

We report a case of a 20-year-old male with Gorlins syndrome (nevoid basal cell carcinoma syndrome), developing multiple basal cell carcinomas within irradiation fields 10 years after the treatment of medulloblastoma.

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.

Intracranial involvement in Hodgkin's disease.

The authors report 3 cases of Hodgkins 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 Hodgkins disease, prolonged disease-free survival may be achieved by combined modality treatment.

High dose rate mold brachytherapy of early gingival carcinoma: A clinical report

Two elderly edentulous patients with the diagnosis of early stage cancer of the upper gingiva were treated by customized dental mold brachytherapy. Locoregional tumor control was achieved in both patients. One patient is alive without any evidence of disease 36 months after treatment, the other patient died of distant metastasis shortly after brachytherapy. Brachytherapy, being easy to apply with short treatment time and good acute tolerance, is a good choice and effective modality for the management of early stage gingival cancer, particularly in elderly patients.

THE EFFECT OF VERAPAMIL IN THE PREVENTION OF RADIATION-INDUCED CATARACT

PURPOSE Cataract is an unavoidable complication when radiation therapy includes the lens, even in small doses. Alterations in the ion content of the lens were considered to play an essential role in cataract formation. In this experimental study, the effect of verapamil on ion concentrations within the irradiated lenses was investigated in rats. METHODS AND MATERIALS Forty female Wistar albino rats, each weighing 180-250 g, were divided into three groups: (a) radiation treated (n = 10); (b) no treatment (n = 10); (c) or a combination of radiation and verapamil (n = 20). Both the radiation group and verapamil-treated group received 5 Gy radiation to the cranium in a single fraction, including the eyes, within the irradiation volume. All animals were sacrificed by bleeding, 7.5 weeks posttreatment. Calcium, sodium, and potassium levels were measured in blood and in lens homogenates. However, for technical reasons, magnesium levels could only be studied in lens homogenates. RESULTS Potassium and sodium concentrations in lens homogenates did not differ in the control and radiation groups, but both were significantly lower in the verapamil-treated group (p = 0.001, p = 0.009, respectively). Calcium levels were higher in the radiation group and lower in the verapamil-treated group compared to the controls (p < 0.0001); magnesium levels did not differ (p = 0.37). CONCLUSION Verapamil effectively decreased the lens calcium concentration, which is accepted as the key element in radiation cataractogenesis. It is therefore concluded that verapamil may reduce the risk of radiation-induced cataract formation.