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Background: Primary nasal lymphoma is a rare disease. Although most patients are initially seen in early Ann Arbor stages, their prognosis is poor. The prognostic significance of local tumor bulk has not been well studied., Methods: Twenty-one patients with nasal lymphoma treated between 1985 and 1992 were retrospectively studied. Sixteen patients (76%) below the age of 75 years received combined radiotherapy and chemotherapy. One young patient with early disease and 4 elderly patients had radiotherapy alone. Twelve cases (57%) were diagnosed as pleomorphic T-cell lymphoma based on typical histologic features alone. Immunophenotyping was performed in 10 cases; 8 were T cell and 2 were B cell. Seventeen patients (81%) had Ann Arbor clinical stage IE disease, and 4 had stage IIE disease. The local tumor extent was assessed by endoscopy in all patients and by computerized tomography (CT) in 14 patients. Eleven local tumors (52%) extended to the posterior ethmoids, sphenoid sinus, orbit, or beyond. Using a T-stage system, the prognostic significance of local tumor bulk was evaluated for stage IE patients., Results: At a median follow-up time of 16.8 months, the lymphoma recurred in 13 patients; 10 patients had systemic relapse and 10 patients, local relapse. The 5-year actuarial overall survival rate was 24%. Complete response to chemotherapy was achieved in 5 of 16 patients (31%). Four of the 6 patients who remained alive and disease-free were chemotherapy complete responders. Among stage IE patients, those with early and those with advanced local disease did not have significantly different survival., Conclusions: In view of the high systemic and local relapse rates, more-effective chemotherapy is needed to improve the survival rates, and the role of combined chemotherapy and radiotherapy should be evaluated. Further studies are required to identify patients at high risk of relapse for clinical trials with investigational treatment.

47 newly diagnosed patients with nasopharyngeal carcinoma (NPC) were studied using the proliferating cell nuclear antigen (PCNA) immunostaining technique. The results were reproducible as shown by assessment of three separate sections performed for each patient. No statistical correlation was found between PCNA labelling index (LI) and Ho's clinical staging or time required to achieve complete remission of the local disease. A higher PCNA LI was associated with a poorer disease-free survival. The literature on the use of PCNA in human tumours is reviewed.

Background: Distant metastases are common in patients with nasopharyngeal carcinoma (NPC), and their presence is the most important factor in limiting survival. We aimed to study the prognosticators determining survival subsequent to distant metastasis from NPC., Methods: A study by both mono- and multivariate analyses was carried out in 945 patients presenting between 1984 and 1989. Forty-two presented with metastases and 247 developed metastasis after primary radiotherapy., Results: Patients who presented with distant metastasis (M1-classification) had a significantly shorter survival than those who developed metastases after primary radiotherapy. The presence of hepatic metastases, short metastasis free interval, and older age at presentation significantly predicted short survival after the diagnosis of distant metastasis. Patients with metastases preceded by, and/or accompanied with, locoregional recurrence had comparable survival to those without, despite their association with a significantly longer metastasis free interval. A history of locoregional recurrence was however not compatible with long term, disease free survival, and, in its presence, advanced T-classification on presentation predicted poor survival subsequent to metastasis. Long term disease free survival (64-117 months) was attained in 4 young patients (age < 40 years) with isolated intrathoracic metastases in the absence of locoregional recurrence after achieving a complete response to aggressive treatment, with chemotherapy, radiotherapy, and/or surgery, usually multimodal., Conclusions: Some of the clinical prognosticators have been identified and an attempt was made to subclassify distant metastases according to possible differences in prognosis. A subset of metastatic NPC was identified which is compatible with long term, disease free survival. Investigations during follow-up should be directed toward the early detection of such potentially salvageable cases.

The aim of the present study was to undertake a planned interim analysis of a prospective randomized trial comparing the tumour response and the acute and subacute complications of hyperfractionated radiotherapy and conventional radiotherapy in non-metastatic nasopharyngeal carcinoma (NPC). 100 patients with newly diagnosed non-metastatic NPC were randomized to receive either conventional radiotherapy (Arm I) or hyperfractionated radiotherapy (Arm II). Stratification was done according to the T-Stage (modified Ho's T-Stage classification). The biological effective dose (10 Gy) to the primary and the upper cervical lymphatics were 75.0 and 73.1 for Arm I and 84.4 and 77.2 for Arm II, respectively. Hyperfractionated radiotherapy was associated with significant mucositis which is of higher grade than conventional radiotherapy (p = 0.0001), but the duration of mucositis was similar between the two Arms and all study patients completed radiotherapy on schedule without interruption of radiotherapy. Early survival and tumour recurrence rates were comparable between the Arms. The preliminary results indicate that the hyperfractionated radiotherapy has excellent patient compliance in Chinese patients, with acceptable acute and subacute toxicities and the local and regional complete tumour response rates being comparable with conventional radiotherapy. The significance of the time required after start of radiotherapy to achieve a complete tumour response is discussed.

A carboplatin and 5-fluorouracil (CF) chemotherapy protocol was designed to evaluate tumor response and toxicity in patients with metastatic nasopharyngeal carcinoma (NPC). Patients with metastatic NPC were treated with a maximum of eight courses of CF. Carboplatin was given at 300 mg/m2 by intravenous bolus on day 1 and 5-fluorouracil at 1 g/m2 per day by continuous infusion on days 1-3; cycles were repeated once every 3 weeks. A total of 42 patients were evaluable for response and toxicity. They received a median of 6 courses (range 2-8) of chemotherapy. The overall response rate was 38% (16/42), comprising 7 complete responses (CR, 17%) and 9 partial responses (PR, 21%). The median survival was 12.1 months (range 6-54.2 months). The treatment was well tolerated. Toxicity was mainly bone marrow suppression. There were four episodes of neutropenic fever, but no renal toxicity or treatment-related death was documented. The combination of carboplatin given at a fixed dose of 300 mg/m2 for 1 day and 5-fluorouracil given at 1 g/m2 per day for 3 days produced an objective response rate of 38% and tolerable side effects.

The aims of this retrospective study were to determine the role of intracavitary brachytherapy given shortly after external beam radiotherapy in the primary radical treatment of non-metastatic nasopharyngeal (NPC) cancer patients, and the prognostic factors governing local tumour control. From 1984 to 1989, 903 patients with non-disseminated NPC who had had no previous treatment were managed at the Prince of Wales Hospital, where investigation and treatment methods had been standardized according to a departmental protocol. The external radiotherapy dose of 60.0-62.5 Gy in 6 weeks was given to all patients. Parapharyngeal booster radiotherapy with a single photon beam to 20 Gy in 2 weeks was given to those with parapharyngeal tumour extension. Computed tomography of the nasopharynx and skull base, and pretreatment nasopharyngoscopy and biopsy were performed in all patients. Nasopharyngoscopy was repeated at 4 weeks after the last day of external irradiation. Local persistence in 99 patients was treated additionally by intracavitary brachytherapy to 24 Gy in three fractions over 15 days. Fifty-one patients with early stage primary disease (Ho Stage T1 and T2n (nasal)) who responded completely to external radiotherapy were given adjuvant intracavitary brachytherapy to 18 Gy in three fractions over 15 days. Intracavitary therapy was an inadequate salvage treatment for the locally persisting T3, T20 (oropharyngeal) and T2p (parapharyngeal) disease, but there was a trend towards improved local control after intracavitary brachytherapy for the locally persisting T1 tumours. Adjuvant brachytherapy did not enhance local tumour control for the early T-stage tumours that completely responded to external radiotherapy. Both forms of intracavitary brachytherapy were safe with few and acceptable complications. In the 903 non-disseminated NPCs, the patient's age and tumour involvement of the skull base and cranial nerves were significant independent prognostic factors governing local tumour control. In the 358 patients with Ho T3 disease, tumour involvement of the orbits and the laryngopharynx significantly worsened local tumour control. The presence of local persistence at 4 weeks after external radiotherapy, for which therapeutic brachytherapy was given, was marginally significant as a prognostic factor in addition to the presence of cranial nerve palsy.

A cell kinetic study of 27 newly diagnosed patients with nasopharyngeal carcinoma (NPC) using the in vitro bromodeoxyuridine (BrdU) technique was performed. The results were reproducible as demonstrated by three independent sections performed on each patient. No correlation between BrdU labelling index (LI) and Ho's clinical staging was found. A higher LI was associated with the development of distant metastases (P = 0.057). Statistically significant correlation was found between low LI and longer duration required to achieve complete remission in the primary site of disease (P = 0.026). This study suggests a potential role for in vitro BrdU labelling index as a prognosticator for NPC prior to treatment.

Nasopharyngeal carcinoma (NPC) is a highly chemo- and radiosensitive tumour, distinctive from other head and neck squamous cell carcinomas. Distant metastatic rates correlate directly with T and N stages. The prognosis of metastatic NPC is grave and long term survivors are anecdotal. We encountered an 18-year-old man with locoregionally advanced NPC, who was initially treated with neoadjuvant chemotherapy and radiotherapy, but subsequently relapsed 6 months later in the superior mediastinal and right hilar nodal regions. Further chemotherapy and consolidation radiotherapy resulted in complete remission. He is currently alive and free of disease 5 years and 6 months after the completion of salvage treatment. We recommend aggressive treatment of NPC with isolated intrathoracic nodal relapse and imaging of the mediastinum for non-metastatic Ho's Stage N3 NPC patients.

A retrospective study on 422 nasopharyngeal carcinoma (NPC) patients with cervical nodal metastases treated between 1984 and 1987 was performed. 169 received neoadjuvant chemotherapy (CHEMO) with cisplatinum and 5-fluorouracil for two or three courses prior to definitive radiotherapy and 253 were treated by radical radiotherapy alone (NCHEMO). While the primary tumour (T-stage) prognosticators had been comparable between the two groups, CHEMO had significantly more advanced cervical nodal metastases with bulkier nodes and more low-cervical and supraclavicular nodes (P < 0.05) which could account for its overall worse survival, poorer regional tumour control and a trend towards worse systemic tumour control. The worse regional control in CHEMO for Ho's N1 could be the result of more bulky nodes and more tumours infiltrating the skull base and/or causing cranial nerve(s) palsy. There was no statistical or apparent difference between CHEMO and NCHEMO for the same Ho's overall stages of NPC with comparable nodal and primary tumour characteristics for the clinical endpoints of actuarial survival rate (ASR), disease-free survival rate (DFS), free of local failure survival rate (FLF), and free from distant metastases survival rate (FDM), despite the presence of significantly more fixed nodes and bulky nodes. This suggests a possible beneficial effect of the neoadjuvant chemotherapy. However, multivariate analysis has not shown the administration of the neoadjuvant chemotherapy to be of prognostic significance. Even though the chemotherapy was well tolerated with little toxicity, we recommend against the routine use of neoadjuvant chemotherapy in cervical-node-positive NPC outside the context of a prospective randomised clinical trial.

Purpose: A prospective randomized trial was conducted to compare chemoradiotherapy against radiotherapy alone in the treatment of locoregionally advanced nasopharyngeal carcinoma., Methods and Materials: Eighty-two patients with histologically proven nasopharyngeal carcinoma who had either Ho's N3 staging or any N stage with a nodal diameter of > or = 4 cm were entered. Seventy-seven patients were evaluated for tumor response and survival. The patients were randomized to receive two cycles of cisplatin 100 mg/m2 Day 1,5-fluorouracil 1000 mg/m2 24-h infusion Days 2, 3, and 4 before radical radiotherapy, and four cycles of postradiotherapy chemotherapy (37 patients) or radiotherapy alone (40 patients). All patients received radical radiotherapy to the nasopharynx and neck. The nasopharynx and upper neck were treated to 66 Gy by conventional fractionation and the lower neck to 58 Gy. Booster radiotherapy (7.5 Gy/two fractions/week) was given to any residual nodes after standard radiotherapy., Results: The patient characteristics, including staging, were similar in both arms. The overall response rate to neoadjuvant chemotherapy was 81% (19% complete response, 62% partial response). The rates of radiotherapy for boosting parapharyngeal disease or residual lymph nodes were not significantly different in the two arms. The overall complete response rate to chemoradiotherapy was 100%, and to radiotherapy alone, 95%. Toxicities in the chemoradiotherapy arm were mainly myelosuppression, nephrotoxicity, and nausea and vomiting. The degree of mucositis was not significantly different in the two arms. There was no treatment-related death. The median follow up was 28.5 months. The 2-year overall survival was 80% in the chemoradiotherapy arm and 80.5% in the radiotherapy arm. The 2-year disease-free survival was 68% in the chemoradiotherapy arm and 72% in the radiotherapy arm, without significant difference between the two arms. The locoregional relapse rate, distant metastatic rate, and median time to relapse were also not significantly different between the two arms., Conclusion: Despite promising tumor response rates from Phase II trials, this prospective randomized trial has demonstrated no benefit from adjunctive chemotherapy to radiotherapy in the treatment of locoregionally advanced nasopharyngeal carcinoma.

A patient with perineal extramammary Paget's disease is described. He was treated successfully with fractionated high dose rate brachytherapy.

Six hundred and twenty-eight patients with non-metastatic nasopharyngeal carcinoma were staged by CT scanning and treated with radical locoregional radiotherapy. Parapharyngeal boost radiation for bulky parapharyngeal involvement, neoadjuvant chemotherapy for bulky nodal metastases, and intracavitary 192Ir treatment for local persistence of tumour after external radiotherapy were also used as appropriate. Forty-eight patients had Ho's (1978) Stage I disease (7.6%), 167 Stage II (26.6%), 312 Stage III (49.7%) and 101 Stage IV (16.1%). At 2 years after treatment, 185 patients (29.5%) had developed recurrence; 112 had distant metastases (60.5%), and 75 had local failure (40.5%). Eighty-three patients had developed distant metastases alone, 73 patients locoregional failure alone and 29 patients had both locoregional and metastatic failure. The overall 2-year actuarial distant and local failure rates were 18.4% and 12.7% respectively. Distant metastasis is the major form of treatment failure which limits early survival. Seventy-four per cent of distant metastases were not associated with locoregional recurrence and had probably arisen from pre-existing occult foci. Our data also suggest that the advent of CT scanning has improved local tumour delineation and radiotherapy planning, and hence local control.

Pretreatment neck node biopsy had been performed on 50 of 422 patients who had cervical node metastases from nasopharyngeal carcinoma when initially seen. Multivariate analysis using the Cox proportional hazards model shows that pretreatment node biopsy is not a significant determinant of distant metastases, survival, or recurrence in the neck. Results of similar studies are reviewed and the role of pretreatment node biopsy in nasopharyngeal carcinoma discussed.

Radical neck dissection (RND) for recurrent nasopharyngeal carcinoma (NPC) after radiotherapy was retrospectively evaluated in 38 patients treated between April 1986 and December 1991. Thirty patients (79%) had advanced-stage disease. Four patients required nasopharyngectomy as well as RND. The mortality was 0%, and the morbidity was 13%. The actuarial survival rates at 5 years from the time of initial radiotherapy and RND were 50% and 25%, respectively. Of the 21 patients with relapses after surgical salvage, 5 had recurrences in the nasopharynx, 3 had recurrences in the neck, and 13 had distant metastases. We conclude that RND for recurrent NPC is safe and efficacious; however, it is associated with a significant (34%) incidence of distant metastases. These results can be improved by evaluating patients for distant metastases and excluding those with distant metastases. Improvement in the treatment of distant metastases is also needed.

Sixty Chinese breast cancer patients underwent ovarian irradiation with one of two dose schedules: 12 Gy/4 fractions/4-6 days or 14 Gy/4 fractions/4-6 days. The ovarian ablation failure rates were 14% and 0% respectively in patients above 40 years of age. The overall ablation failure rate in younger patients was unacceptably high at 35%. The significance of the findings is discussed.

Based on the clinical data of a retrospective study of 659 NPC patients with routine computed tomography of the nasopharyngeal region, a refinement of Ho's stage-classification for NPC is proposed with reduction in the number of overall stages without sacrificing the accuracy in predicting prognosis in the short term. Classifying the cervical lymph nodal metastasis into supraclavicular (Ho's N3) and above supraclavicular (Ho's N1 + N2) and the nasopharyngeal primary into early (Ho's T1 + T2n + T20) and advanced (Ho's T2p + T3 + T3p) forms the conceptual backbone of the present proposed modification of the original Ho stage-classification. Power in predicting the occurrence of distant metastases and the local failures has been enhanced by the proposed T-stage and N-stage re-grouping. Retrospective comparison between Ho's and the UICC stage-classifications showed a more even patients number distribution among the overall stages and a greater power in predicting NPC prognosis for the former. Prospective studies to compare the value of the different stage-classifications are required for recommendation of a single classification for general acceptance to facilitate comparison of treatment results between centres.

This is a retrospective study of 90 patients who developed distant metastases after radical radiotherapy for nasopharyngeal carcinoma. The skeleton was the commonest site of distant metastases. Clubbing, hypercalcemia and malignant fever occurred in about 10% of patients with pulmonary, skeletal and hepatic metastases respectively. An effective chemotherapeutic regimen for palliation of pulmonary and hepatic metastases was cisplatinum/carboplatin-5FU which gave a complete response rate of 29% and partial response rate of 21%. This was considered superior to some non-cisplatinum-containing regimens. One patient with hepatic metastases had good palliation by hepatic irradiation. The median survival of all patients with distant metastases was eight months. Five (6%) patients survived more than two years with one surviving free of disease at 31 months. Hepatic metastases and spinal cord compression were associated with short survivals.

Five hundred sixty-four nasopharyngeal carcinomas (NPC), mostly of undifferentiated histologic type, were studied for survival, distant metastasis, and local recurrence. All had computerized tomography of the nasopharynx and skull base (CT-NP) and fiberoptic nasopharyngoscopy for evaluation of the primary tumor. Regional disease was assessed by palpation. A computer data base was formed on presentation, containing all information required for staging according to Ho's, the International Union Against Cancer (UICC), and the American Joint Committee (AJC) classifications. The three were compared for their efficacy in predicting prognosis. Ho's classification was superior to the other two because its overall stages differed from one another more significantly in the actuarial survival (ASR), disease-free survival (DFS), and freedom from distant metastasis (FDM) rates, and its N staging was more accurate in predicting FDM. Stages T1 and T2 of UICC/AJC were similar in the freedom from local recurrence rate (FLR) and should be grouped together, equivalent to Ho's T1. A more even patients number distribution among the stages also favored the use of Ho's classification.