Fulminant hepatic failure in non-Hodgkin lymphoma patients treated with chemotherapy.

Chemotherapy is the mainstay of therapy for patients with non-Hodgkin lymphoma. Among side-effects associated with the use of chemotherapy, immunosuppression is one which can be potentially fatal. In hepatitis B carriers, immunosuppression permits widespread infection of the hepatocytes and its subsequent withdrawal causes an "immunological rebound" leading to massive necrosis of hepatocytes. 4 patients who died of fulminant hepatitis following chemotherapy are reported. These were patients with positive hepatitis B serology. Caution is advised when treating non-Hodgkin lymphoma in patients from hepatitis B endemic regions.

Radiotherapy of carcinoma of the uterine cervix in Singapore, 1973-1975.

The results of 322 patients with uterine cervix carcinoma treated by radiotherapy at the Singapore General Hospital in the 3-year period from 1973 to 75 are presented. Two hundred seventy-nine patients were treated with a combination of intracavitary radium, using Fletcher-Suit applicators and cobalt teletherapy; the remaining 43 patients received only cobalt teletherapy. One hundred thirty-four patients (41.6%) presented with FIGO Stage III disease. Only 46 patients (14.3%) presented with Stage I disease, showing that patients tended to present late in the disease course. Five-year actuarial (uncorrected) survival rates of 86.7% for Stage I, 65.0% for Stage II, 41.4% for Stage III and 4.9% for Stage IV were obtained with corresponding 10 year rates of 79.6%, 60.2%, 35.2% and 0%. The overall 5 and 10 year survival rates were 54.0% and 48.2%, respectively. The survival rates "flattened off" at about 7-8 years, reflecting late deaths after the fifth anniversary of treatment. Non-severe complications consisted mainly of chronic proctitis (41.3%) and vaginal stenosis (20.8%). Major complications were intestinal stricture (1.2%) and fistula formation (1.6%).

Temporal lobe necrosis following radiation therapy for nasopharyngeal carcinoma: 1H MR spectroscopic findings.

PURPOSE: To observe the patterns of radiation-induced temporal lobe necrosis (TLN) following radiation therapy for nasopharyngeal carcinoma (NPC). METHODS AND MATERIALS: Twenty-five proton magnetic resonance spectroscopic (1H MRS) examinations were acquired from 13 healthy adult volunteers for comparison with data from the patient population. There were 18 patients (28 spectra) with radiologic evidence of TLN and all patients were confirmed cases of NPC treated with radiation therapy. Six patients (33%) had a single treatment while 12 (67%) patients had two treatments. All 1H MRS examinations were performed on a 2-T whole body system (Bruker) using the point-resolved spectroscopy (PRESS) method with TE = 135 ms, TR = 3000 ms, and data processed automatically using the LCModel software package for metabolite quantification. RESULTS: The N-acetyl-aspartate (NAA) levels were reduced in all except one spectrum (96%). Choline (Cho) was increased in 3 (11%), normal in 4 (14%), and reduced in 21 (75%) spectra. The creatine (Cr) level was normal in 8 (29%) spectra and reduced in 20 (71%) spectra. In four patients with normal imaging findings 1H MRS was abnormal. CONCLUSION: 1H MRS can characterize radiation-induced TLN. Spectra with increased Cho can be mistaken for neoplasm. Spectroscopy can also identify metabolic derangement before imaging.

Concurrent chemoradiotherapy followed by adjuvant chemotherapy in Asian patients with nasopharyngeal carcinoma: toxicities and preliminary results.

PURPOSE: Nasopharyngeal carcinoma (NPC) is endemic in Singapore. Nearly 60% of the patients diagnosed with NPC will present with locally advanced disease. The North American Intergroup study 0099 reported improved survival outcome in patients with locally advanced NPC who received combined chemoradiotherapy when compared to radiotherapy alone. Hence we explored the feasibility and efficacy of a similar protocol in our patients. METHODS AND MATERIALS: Between June 1996 and December 1997, 57 patients were treated with the following schedule as described. Radical radiotherapy (RT) of 66-70 Gy to the primary and neck with cisplatin (CDDP) 25 mg/m2 on days 1-4 given by infusion over 6-8 hours daily on weeks 1, 4, and 7 of the RT. This is followed by a further 3 cycles of adjuvant chemotherapy starting from week 11 from the first dose of radiation (CDDP 20 mg/m2/d and 5-fluorouracil [5-FU] 1 gm/m2/d on days 1-4 every 28 days). RESULTS: The majority of patients (68%) had Stage IV disease. About 54% of patients received all the intended treatment; 75% received all 3 cycles of CDDP during the RT phase and 63% received all three cycles of adjuvant chemotherapy. The received dose intensity of CDDP and 5-FU of greater than 0.8 was achieved in 58% and 60% of the patients respectively. Two treatment-related deaths due to reactivation of hepatitis B and neutropenic sepsis respectively, were encountered. At median follow-up of 16 months, 14 patients had relapsed, 12 systemically and 2 loco-regionally. CONCLUSION: Due to the acceptable tolerability of such a protocol in our cohort of patients, we have embarked on a Phase III study to confirm the results of the 0099 Intergroup study in the Asian context.

MACOP-B in advanced non-Hodgkin's lymphoma.

Between May 1986 and March 1991, 38 patients with previously untreated advanced intermediate and high-grade non-Hodgkin's lymphoma were treated with methotrexate, doxorubicin, cyclophosphamide, vincristine, prednisone, and bleomycin (MACOP-B): 73% of the patients had stages III and IV disease, 55% had "B" symptoms, and 55% had bulky disease (nodal masses > 10 cm). Histologic subtypes included diffuse large-cell and immunoblastic lymphoma. In 96% of patients clinical response was achieved (69% complete response and 27% partial response). Acturial disease-free survival and overall survival were 55% and 60%, respectively, at 2 years. Treatment-related mortality was 16%: 3 patients died from neutropenic sepsis and 3 (hepatitis B carriers) from fulminant hepatitis at the time of steroid withdrawal. The incidence of nonfatal neutropenic fever was 24% and mucocutaneous toxicity was common. The poorer overall results may be attributed to more advanced disease. Caution is advised in the use of MACOP-B among hepatitis B carriers.

Nasopharyngeal cancer treated in Singapore.

With effect from July 1987 CT-scans of the nasopharynx became routinely available in the staging of nasopharyngeal cancer (NPC) in our department. Eighty-four evaluable cases during these first six months were studied and the results at a median follow-up period of 34 months revealed that 74% were alive at 2 years. The local relapse rate were 4% for T1; 10% for T2 and 35% for T3 tumours.

Intracranial germ cell tumour: experience of a Singaporean institution over 11-year period.

BACKGROUND: Intracranial germ cell tumours (IGCT) are rare. We present our experience in Therapeutic Radiology Department, National Cancer Centre, Singapore. METHODS: A retrospective study was conducted through case notes review on 25 patients with IGCT referred between January 1988 and January 1999. RESULTS: The median age at diagnosis was 13 years (range 6-22). The tumours were mainly pineal germinoma (72%). Median follow-up for living patients was 2.57 years (range 0.12-10.8). Median radiotherapy (RT) dose to whole brain, primary site and spine was 35.3,54 and 30 Gys respectively. Four to six cycles of BEP or JEB chemotherapy (CM) were given in 10 patients. As for the whole study group, the seven-year overall survival (OS) and recurrence-free survival (RFS) were 86% (95% CI 72-100) and 78% (95% CI 60-100) respectively. The 10-year OS and RFS were 65% (95% CI 36-100) and 78% (95% CI 60-100) respectively. The germinoma group had 75% 10-year OS and 86% 10-year RFS. Mixed germinoma and non-germinoma germ cell tumours (NGGCT) group had 50% one-year RFS and 44% two-year OS. Acute side-effects of RT and CM were minimal. There was no statistically significant difference in side-effects when treatment modalities were compared. CONCLUSION: In the treatment of intracranial germinoma, we recommend biopsy and CSRT. Primary chemotherapy (+/- low-dose cranial RT) should be used in the protocol or clinical trial settings. Chemo-radiotherapy is recommended for mixed germinoma and NGGCT. A multicentre trial is needed to address various controversial issues.

Radical radiotherapy for carcinoma of the uterine cervix using high dose rate brachytherapy--a preliminary report.

From April 1992 to December 1994, a total of 61 patients with carcinoma of the cervix were treated with curative intent using initially external beam therapy followed by high dose rate brachytherapy. On reviewing 57 patients with adequate follow-up data, the local failure rate was found to be 12.3% and metastatic failure rate was 15.8%. Local pelvic failure rates for stage II and III patients were 10% and 13.6% respectively, but for stage I disease, there was one local failure out of 5 patients, at a rate of 20%. This is probably due to the small number in this subgroup. Complication rate was low with only one patient with grade IV problems, giving a serious complication rate of 1.7% only. Overall actuarial rate in this group was 50.1%. These results are encouraging but further review on achieving adequate follow-up is needed before firm conclusions can be drawn.

Half body irradiation for palliation of widespread metastatic bone disease.

An analysis is made of 134 patients treated by a single dose half body irradiation at the Department of Therapeutic Radiology, Singapore General Hospital. A total of 149 fields were treated with 15 patients receiving both upper and lower half treatments. This technique achieved a more than 70% subjective pain relief in the patients who had widespread bony metastases. Side effects were minimal and this technique has been used on an outpatient basis since the first preliminary study in 1986. There was a dose response, more than 75% (75 out of 97 patients) with pain relief using doses of 700 cGy and above. Sensitive tumours also produced better results with nasopharyngeal carcinoma, prostate and breast having pain relief in more than 70% of patients. The largest group of patients (51 cases) treated was nasopharyngeal carcinoma, as this tumour is fairly common locally and often presents with bony metastases as the first site of spread.

Intraluminal brachytherapy in the treatment of oesophageal cancers--some preliminary results.

Cancer of the oesophagus is the sixth commonest cancer in males in Singapore. The majority occur in the elderly and patients are often debilitated at presentation. Treatment is often aimed at palliation only. In this article, the preliminary results of 15 patients treated solely on a high dose rate remote afterloading Gammamed brachytherapy machine with an Iridium 192 (Ir192) source are reported. The patients were given 15 Gray (Gy) in a single or two 7.5 Gray fractions. All the patients treated had some improvement of their dysphagia, and seven out of 11 (63%) evaluable patients had symptom improvement lasting at least 11 weeks.

Adjuvant combination chemotherapy for osteosarcoma.

The management of patients with osteosarcoma in Singapore has for many years been an unrewarding task for the attending physicians. Encouraged by reports of long-term survivals with adjuvant cytotoxic chemotherapy appearing in 1975, orthopaedic surgeons and radiation therapists at the Singapore General Hospital undertook a program of combination chemotherapy in moderate doses for osteosarcoma patients with localised disease treated by ablative surgery. A few who refused surgery had irradiation of the primary tumour.

Testicular seminoma--the results of treatment by radiotherapy in Singapore.

A retrospective analysis was done of 49 patients treated for testicular seminoma over a 15-year period between January 1980 and April 1995 at the Department of Therapeutic Radiology, Singapore General Hospital. Their mean age was 39 years and their median period of follow-up was 67 months. Using the Royal Marsden Staging classification, 35 (71.4%) were stage I, 10 (20.4%) were stage II, I (2%) was stage III, and 3 (6.1%) were stage IV. Five (10.2%) arose in undescended testes. Thirty-six patients were treated with inguinal orchidectomy and postoperative radiotherapy to the para-aortic and ipsilateral iliac nodes. Eight had para-aortic and bilateral iliac irradiation, and 2 had ipsilateral pelvic, para-aortic, mediastinal and supraclavicular lymph node irradiation. Six of the patients had, in addition, irradiation of the inguinal-scrotal area. Nine received both chemotherapy as well as radiotherapy. The median dose of radiation given was 30.67 Gy and where a boost was required, the median total tumour dose was 35.75 Gy. The actuarial relapse-free survival at 10 years was 88.9% and the actuarial overall survival at 10 years was also 88.9%. Long-term treatment toxicities were uncommon.

A report of 21 cases of malignant lymphoma treated by radiotherapy.

In 1971, 21 new patients with malignant lymphoma were treated at the Therapeutic Radiology Department, Singapore General Hospital. 17 patients completed their courses of radiotherapy. Of the 17 patients given radical treatment, 5 were of Hodgkin's disease and 12 of Non-Hodgkin's disease. The 5-year survival for the group with Hodgkin's disease is 80% (4/5). The 5-year survival for the group with Non-Hodgkin's disease in 41.6% (5/12).

A review of patients with high-risk carcinoma of the cervix treated with combined surgery and postoperative radiotherapy.

From May 1992 to October 1995, 57 patients with early stage cervical carcinoma were treated with hysterectomy and postoperative pelvic radiotherapy because of the presence of adverse histopathologic features. On prospective follow-up and analysis, the clinical outcome for 50 of these patients showed a pelvic disease control rate of 90.9%, a disease-free survival of 80.6% and an overall survival of 86.3%. Of the 8 relapses, half occurred in the pelvis i.e., 2 in the vaginal vault and 2 in the pelvic side walls. No severe complications were observed, but there was a 20% long-term Radiation Therapy and Oncology Group (RTOG) grade 1 to 2 urinary bladder dysfunctional problem and 28% incidence of suprapubic and/or leg oedema.

Radiotherapy as local adjuvant treatment for endometrial carcinoma--a review of 45 patients.

Forty-five patients with endometrial carcinoma were treated with local postoperative adjuvant radiotherapy during the period 1992 to 1995. Radiotherapy technique comprised both external beam irradiation as well as high-dose-rate vaginal vault brachytherapy. The 5-year overall survival and relapse-free survival rates were 74% and 73%, respectively and poorly differentiated histology grade was associated with poorer prognosis. Only 1 patient developed an isolated vaginal vault recurrence and another 9 patients relapsed mainly at the distal anatomical sites. The main radiotherapy-related complications were vaginal adhesion and stenosis. Radiotherapy is therefore effective as local adjuvant treatment in reducing risk of local-regional relapse in endometrial carcinoma.

Localised nodal non-Hodgkin's lymphoma--a study of 42 cases treated by radiotherapy.

The records of 42 patients with stage I and II nodal non-Hodgkin's lymphoma treated by radiotherapy with and without chemotherapy were analysed with regards to clinical presentation, investigations, treatment, radiotherapy techniques and results. The 5-year overall survival rates for all, low grade, intermediate grade and high grade histology types are 69.5%, 100%, 64.4% and 46.9% respectively. The 5-year relapse-free survival rates of those treated by initial radiotherapy alone for all, low grade and intermediate-high grade histology types are 54.8%, 46.9% and 59.4% respectively.

Orbital lymphoma: results of radiation therapy.

Orbital lymphoma is a rare presentation of non-Hodgkin's lymphoma. Treatment with radiotherapy is well-established. Twenty cases of orbital lymphoma treated at the Singapore General Hospital with radiation therapy were reviewed. All patients had improvement of their initial presenting symptoms and complete remission after radiation. Long-term local control was achieved in 17 of 20 (85%) of the treated orbits.

Adriamycin in the treatment of resectible and irresectible primary hepatocellular carcinoma.

The treatment of 205 patients with primary hepatocellular carcinoma in Singapore from 1975 to 1980 is reviewed. Adriamycin given at a dose of 40 mg/m(2) intravenously every 4 weeks for irresectible tumours achieved a response rate of 32% alone and has significantly prolonged the median survival time to 4 1/2 months (135 days) in these individuals. Despite this response only 1/34 (3%) patient showed complete remission and is alive at 2 1/2 years. Use of other combinations with Adriamycin e.g. 5 Fluorouracil and Vincristine produced a significant response in the first 16 weeks (p < 0.005) but not thereafter, when completed with the historical group. To improve the response and to consolidate this response, split doses of total hepatic irradiation (to a maximum of 3,150 rads) and alternate day administration of intravenous Adriamycin 10 mg (to a maximum of 90 mg) were given. 12/23 patients (50%) responded. This was followed by a four weekly Adriamycin, 5 F.U. and Vincristine. Median survival time was 5 1/2 months (165 days). Relapse occurred in all patients. Similarly in 5 patients who had resections, early recurrences occurred in 3/5 (60%) within 3 months, inspite of postoperative chemotherapy with Adriamycin, 5 F.U., Vincristine and Cyclophosphamide given every four weeks. In view of the high recurrence rate following effective treatment, further studies on the biological behaviour of these abnormal livers is required.

Gastrointestinal lymphoma--a review of 54 patients in Singapore.

Primary gastrointestinal (GI) lymphoma accounts for 2% to 5% of all GI malignancies. Primary therapy in uncomplicated GI lymphoma remains controversial. Fifty-four patients (male to female ratio of 4:3, median age 56 years) with GI lymphoma were studied to evaluate complications and results of therapy. The sites involved were the stomach (31), small bowel (12), large bowel (4), gallbladder (1) and multifocal (6). Distribution by stage and grade (Working Formulation or Kiel) were: IE-30%, IIE-43%, IIIE-6%, IV-20% and unknown-1%; low grade-33%, intermediate grade-59% and high grade-8%. Majority (54%) had diffuse large cell lymphoma. Twenty-three patients (43%) underwent primary resection of the tumour followed by chemotherapy in 14 or radiotherapy in 3. Seventeen patients (31%) had primary chemotherapy and 3 (6%) had primary radiotherapy. Of the 48 patients who underwent therapy, 52% had complete response. At the last follow-up (median 21 months), 25 patients were disease-free. Overall survival was 67% at two years. Treatment strategies employing surgery, radiotherapy and chemotherapy, alone or in combination, do not appear to influence outcome. Surgical resection plus chemotherapy appear to be effective in the control of local and distant disease.

Concurrent chemoradiotherapy in patients with locally advanced nasopharyngeal carcinoma of the undifferentiated type.

The result with radiotherapy alone in patients with locally advanced nasopharyngeal carcinoma (NPC) was disappointing. Encouraging results have been reported with the use of concurrent chemoradiotherapy in patients with locally advanced squamous cell carcinoma of the head and neck. Hence, we decided to explore the use of this treatment schedule in patients who presented with locally advanced disease (UICC/AJCC classification system). Between July 1995 and March 1996, 14 patients with locally advanced NPC were treated with the following schedule: radiation therapy was given conventionally to a total of 66 to 70 Gy to both the nasopharynx and neck with or without parapharyngeal/intracavitary boost; chemotherapy consisted of intravenous cisplatin at 20 mg/m2/day and intravenous 5-flurouracil 1000 mg/m2/day, infused over 8 hours on days 1 to 4 during the first and fifth week of radiation therapy. Depending on the patient's tolerability and clinical assessment of toxicity, a third cycle of chemotherapy was planned 4 to 5 weeks after the second cycle, upon the completion of the radiotherapy. Twelve patients completed all intended treatment. Two patients failed to do so due to treatment-related mortality. The median follow-up duration was 30 months. Limiting toxicities were myelosuppression and oropharyngeal mucositis. The overall response rate was a 100% at both the primary and nodal sites of disease. The median disease-free survival was 21 months. Forty per cent of the patients were alive at 3 years. This treatment schedule was associated with an unacceptable treatment-related death rate. As a result, this protocol was terminated.