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Purpose: To compare, in a randomized trial, 5-fluorouracil (FU) plus leucovorin (LV) (FU+LV) vs. oral uracil and tegafur (UFT) plus LV (UFT+LV) given concomitantly with preoperative irradiation in patients with cT3-4 or N+ rectal cancer., Methods and Materials: A total of 155 patients were entered onto the trial. Patients received pelvic radiotherapy (4500-5,040 cGy in 5 to 6 weeks) and chemotherapy consisting of two 5-day courses of 20 mg/m(2)/d LV and 350 mg/m(2)/d FU in the first and fifth weeks of radiotherapy (77 patients) or one course of 25 mg/d oral LV and 300 mg/m(2)/d UFT for 4 weeks beginning in the second week of radiotherapy (78 patients). The primary endpoints were pathologic complete response (pCR) and resectability rate. Secondary endpoints included downstaging rate, toxicity, and survival., Results: Grade 3-5 acute hematologic toxicity occurred only with FU+LV (leukopenia 9%; p = 0.02). There were no differences in resectability rates (92.1% vs. 93.4%; p = 0.82). The pCR rate was 13.2% in both arms. Tumor downstaging was more frequent with UFT+LV (59.2% vs. 43.3%; p = 0.04). Three-year overall survival was 87% with FU+LV and 74% with UFT+LV (p = 0.37). The 3-year cumulative incidences of local recurrence were 7.5% and 8.9%, respectively (p = 0.619; relative risk, 1.46; 95% confidence interval 0.32-6.55)., Conclusion: Although this study lacked statistical power to exclude clinically significant differences between both groups, the outcome of patients treated with UFT+LV did not differ significantly from that of patients treated with FU+LV, and hematologic toxicity was significantly lower in the experimental arm.

Hodgkin's disease (HD) is a curable tumoral disease. However, there are groups of patients who suffer relapse and the identification of prognostic factors and the adaptation of treatments to individual risk is one the lines of investigation in this disease. A study was performed on 526 patients diagnosed of HD in our hospital between January 1967 and September 2001. An analysis was made of the most important variables in terms of both disease-free and overall survival. Overall survival in this series of patients was 94% at 2 years, 86% at 5 years, 76% at 10 years and 72% at 15 years. Median survival was 249 months. Factors influencing poor prognosis in the overall survival were: male gender (P < 0.0001), lymphocyte depletion (P < 0.0001), stages III and IV (P < 0.0001), B symptoms (P < 0.0001), spleen involvement at diagnosis (P = 0.003), no complete remission after first line treatment (P < 0.0001), and more than 30 years-of-age (P < 0.0001). Disease free survival was 83% at 2 years and 68% at 5 years although without reaching the mean follow-up. The disease free survival study revealed the following risk factors: male gender (P = 0.02), lymphocyte depletion (P < 0.0001), stages III and IV (P < 0.001), B symptoms (P < 0.001), extranodal or splenic involvement (P < 0.05), and no complete remission after first line treatment (P < 0.0001). The result of treatment optimization is that some factors that were considered to indicate a poor prognosis have disappeared, and that others which are useful have appeared and allow us to establish groups with differing risks of relapse and who could be candidates for differentiated treatments.

Purpose: To assess the impact of modality therapy on long-term outcome for infradiaphragmatic Hodgkin's disease (IDHD)., Methods and Materials: During the period 1965-1997, 847 patients with early stage Hodgkin's disease (HD) were evaluated and treated at our institution, 20 of them had IDHD (2.4%). Patients characteristics: stage I, nine patients (five pathological stage (PS), and four clinical stage (CS)) and stage II: 11 patients (six PS and five CS). Two modalities of treatment were used: combined modality (CMT), consisting of chemotherapy followed by extended field radiotherapy or radiotherapy alone (XRT). All patients with CS or PS II, except in one case, were treated with CMT. Overall, 12 patients were treated with CMT and the remaining eight patients were treated with XRT., Results: The relapse rate after initial treatment was 30%. Ten-year disease free survival (DFS) and 10-year cause-specific survival were 60% and 92%, respectively. There was a non-significant trend to a better DFS for the CMT group of patients (76% vs. 35% for the whole series and 100% vs. 24% for stage I patients). The four relapsed patients in the XRT group were inguino-femoral PS I. In four out of the six patients who relapsed (66%) the failure was located solely in the supradiaphragmatic area, outside of the radiation fields., Conclusions: In our experience, inguino-femoral stage I patients have a high relapse rate after XRT; consequently, CMT consisting of chemotherapy plus involved field radiotherapy should be recommended for early stage HD confined below diaphragm.

The management of patients with central nervous system germ-cell tumours is evolving, and a definitive standard has not been achieved. A large amount of data indicate that radiotherapy alone results in long-term relapse free survival rates of about 90% in patients with germinoma. Various prospective trials evaluated the results of combinations of chemotherapy and reduced dose and/or volume radiotherapy. The survival rates of combined treatment approaches were similar to the rates achieved with craniospinal radiotherapy alone. Nevertheless, the relapse rates were probably higher due to the significant number of relapses that arouse outside the volume treated with radiotherapy. Additional studies are necessary to determine the appropriate radiotherapy volumes and the role of combined treatments. Chemotherapy alone results in high relapse rates and can not be recommended. Mature teratomas are benign germ cell tumours that can be controlled with complete surgical resection in over 90% of cases. Non-germinoma germ cell tumours are a heterogeneous group of tumours that includes very aggressive tumours such as mixed and pure choriocarcinomas, yolk sac tumours, and embryonal carcinomas; and tumours with intermediate aggressiveness such as mixed tumours with germinoma and teratoma, immature teratomas and teratomas with malignant transformation. Both radiotherapy alone and chemotherapy alone result in quite low rates of tumour control and current treatment approaches include chemotherapy and radiotherapy, with surgical removal of the tumour in some patients. Pineocytomas are benign tumours that are controlled in most cases by complete surgical resection or partial surgical resection and local field irradiation. Current treatment approaches for pineoblastomas include surgery, chemotherapy, and craniospinal irradiation with a local boost. Chemotherapy alone was used to delay irradiation in infants with very little success.

We reviewed the outcome of the 10 patients (13 eyes) with localized, biopsy-proven, low-grade lymphoma of the conjunctiva treated at our Department between 1988 and 1997. All patients were treated by beta-ray brachytherapy using a bidirectional 90Sr-90Y ophthalmic applicator (Applicator SIA 2, Amersham plc). Total doses, prescribed at the surface of the applicator, varied between 40 Gy and 80 Gy. With a median follow-up of 78 months (range: 14 to 146 months), seven patients remained with no evidence of relapse (67.5% 10 year disease free survival). Local control was achieved in 10 out of 13 eyes (76.9%). Two of the three local relapses were marginal. One of these three patients also developed a metachronous lymphoma in the contralateral conjunctiva. These three patients underwent a second course of brachytherapy with 90Sr/90Y and remained free of second relapse 109, 68 and 33 months after salvage therapy. No cases of systemic relapse were observed. Late (LENT-SOMA) complications were of grade 2 in five eyes, of grade 3 in one eye and of grade 4 in one eye. Late complications of grade 2 or higher were observed in one out of five patients (20%) treated with doses lower or equal to 50 Gy and in six out of eight patients (75%) treated with doses higher than 50 Gy (P=0.086). Our data indicates that beta-ray brachytherapy was ultimately able to control most conjunctival lymphomas but carried a risk of late complications and marginal relapses that was possibly higher than the rates reported for other radiotherapy techniques.

Use of CSF shunt devices is a common practice in neurosurgery, and infection of the shunt is the most frequent complication. In spite of the fact that bacteria are the most widely implicated pathogens, reports of fungal infections, especially due to Candida sp., have increased in recent years. Their reported frequency ranges between 6% and 17%. Many factors have been implicated in the pathogenesis of Candida meningitis, such as broad spectrum antibiotics used in the treatment of a bacterial meningitis, steroids and indwelling bladder and intravenous catheters. The treatment of Candida meningitis still consists of systemic antifungal agents and removal of the shunt.

Purpose: To determine the activity and evaluate the toxicity of uracil and tegafur in a 4:1 molar concentration (UFT) plus low-dose leucovorin administered concomitantly with pelvic irradiation in patients with unresectable or recurrent rectal cancer., Methods and Materials: Thirty-five patients (22 with primary unresectable tumors and 13 with locally recurrent tumors) were enrolled in the trial. Thirty-five patients were evaluable for toxicity and 32 of these were evaluable for clinical response. Patients received 300 mg/m2/day UFT and 30 mg/day leucovorin on days 8-35 concomitantly with pelvic radiotherapy, to a total dose of 45 Gy., Results: Eight of the 35 (23%) patients developed Grade 3 diarrhea and were treated with radiotherapy alone after this event. Of the 22 patients with unresectable primary tumors, 17 underwent surgery, and resection was feasible in 15 cases (88%). Of the 32 patients evaluable for clinical response, 4 (13%) had a complete clinical response (CR) and 22 (69%) a partial response (PR). A complete pathologic response was observed in 3 cases (18%) and, a PR in 11 cases (65%)., Conclusion: The response rates achieved with this schedule seem comparable to those obtained with 5-FU and radiotherapy. These results warrant further evaluation of this combination in patients with unresectable or locally advanced tumors.

We report on a case of the so-called sarcoidosis-lymphoma syndrome in a 65-years-old man diagnosed as having sarcoidosis and, four years later, neurosarcoidosis. The diagnoses of epidermoid carcinoma of the skin and of stage IV monocytoid, small cell lymphocytic lymphoma were made five and seven years, respectively, after the initial diagnosis of sarcoidosis. It has been suggested that the increased mitotic activity of lymphocytes observed in sarcoidosis, favours their malignant transformation. Hypothetically, sarcoidosis might also influence the development of epidermoid carcinomas by depletion of circulating T4 lymphocytes and decreased resistance to oncogenic viruses that could lead to decreased tumour rejection in the epithelia exposed to carcinogenic stimuli.

Aims and Background: The role of radiotherapy in the management of patients with optic pathway tumors remains controversial. This study analyzes the outcome of patients treated with radiotherapy and attempts to identify the groups of patients that may require early therapy., Methods: We retrospectively reviewed 36 patients with optic pathway tumors treated with radiotherapy alone (26 patients) or with postoperative radiotherapy (10 patients). Seven patients had optic nerve tumors and 29 patients had chiasmal tumors. The actuarial progression free survival and observed survival probabilities were calculated using the Kaplan-Meier method and differences between curves were evaluated by the Mantel-Cox test. The obtained significant variables in the univariate analysis were analyzed using the Cox proportional hazards model., Results: The 10-year actuarial progression-free survival (10-y PFS) rate was 86% for patients with optic nerve gliomas and 47% for patients with chiasmal tumors. The 10-year actuarial observed survival (10-y OS) rate was 75% for patients with optic nerve gliomas and 53% for patients with chiasmal gliomas. In the group of patients with chiasmal tumors, progression-free survival and observed survival rates were significantly lower in infants (10-y PFS: 30%; 10-y OS: 37%), in patients with neurological deficits (10-y PFS and 10-y OS: 23%), in patients with signs of elevated intracranial pressure (10-y PFS and 10-y OS: 9%), with hydrocephalus (10-y PFS and 10-y OS: 0%), or with impairment of consciousness (10-y PFS and 10-y OS: 17%). Evaluation by computed tomography scanning was associated with a significantly higher probability of PFS. Radiation doses lower than 50 Gy were associated with significantly lower PFS and OS rates. In the Cox multivariate analysis, presence of neurological deficits and radiation dose significantly influenced observed survival. Presence of hydrocephalus significantly influenced progression-free survival., Conclusions: The prognosis of patients with chiasmal gliomas presenting with neurologic deficits is poor and should be treated at diagnosis. A minimum tumor dose of 50 Gy is recommended.

We reviewed 90 patients with squamous cell carcinoma of the base of the tongue. Fifty-three patients were treated with external beam radiotherapy alone (3 T1, 11 T2, 21 T3, and 18 T4 tumors) and thirty-seven patients were treated with external beam radiotherapy plus brachytherapy boost (4 T1, 15 T2, 11 T3, and 7 T4 tumors). For patients with T1, T2 and T3 primaries, the actuarial 3-year local relapse-free survival was 42% following external beam radiotherapy alone and 67% following external beam radiotherapy plus brachytherapy (p < 0.05). The actuarial 3-year cause specific survival for these T-stages was 37% for patients treated with external beam radiotherapy alone and 53% for patients treated with external beam radiotherapy plus brachytherapy (p = 0.1). In the Cox multivariate analyses restricted patients with T1, T2 and T3 staged tumors, treatment modality was the only predictor for local control but no influence on specific survival was found. The trend towards significant differences in specific survival found in the univariate comparison of both treatment modalities was probably due to the significantly higher number of N-positive patients treated with external beam radiotherapy alone. When all stages were included in the Cox analysis, low hemoglobin level, invasion of deep muscle, number of palpable nodes, and history of weight loss significantly influenced the outcome. Soft tissue necrosis occurred more frequently in patients treated with external beam radiotherapy plus brachytherapy (33% vs. 10%, p = 0.52).

We reviewed 21 patients who underwent salvage treatment after a biopsy of proven locally recurrent carcinoma of the oropharynx. Two of these patients underwent a second salvage treatment after failure of the first. Treatment was performed with Ir192 interstitial implant in 17 cases (13 rT1 and 4 rT2); by surgery in five cases (3 rT1, 1 rT2, 1 rTx), including two patients who had relapsed after salvage treatment with Ir192 implant; and by hyperfractionated external beam irradiation plus concomitant Tegafur chemotherapy in one case (rT3). The primary tumour was controlled in four of the 17 cases (23 per cent) treated with Ir192 implant. Of these four patients, two remained disease-free 42 and 59 months after treatment, one died of nodal metastases eight months after treatment and another of distant metastases 19 months after treatment. Four of the five cases (80 per cent) treated with surgery, including two patients who relapsed after salvage brachytherapy, remained free from local, regional and distant relapse 21, 25, 31 and 56 months after treatment.

We have performed univariate and multivariate analysis to identify the clinical and treatment-related prognostic factors in a series of 254 patients with newly diagnosed, histologically proven, oropharyngeal squamous cell carcinoma treated with radical radiation therapy. The probabilities of local control, regional control, disease-free survival (DFS) and adjusted survival (AS) were calculated using the Kaplan-Meier method and differences between curves were evaluated by the Mantel-Cox test. The obtained significant variables in the univariate analysis were analysed using the Cox proportional hazards model. In the Cox multivariate analysis, four variables significantly influenced local control probability in the following order: tumour diameter, N stage, alcohol intake and weight loss. N stage significantly influenced the probability of regional control. Five variables influenced both DFS and AS: N stage, tumour diameter, weight loss, alcohol intake and tumour origin within the posterior oropharyngeal wall.