Combined adjuvant cisplatin and ifosfamide chemotherapy and radiotherapy for malignant mixed müllerian tumors of the uterus.

The role of adjuvant therapy for malignant mixed müllerian tumors of the uterus has not been established. Our aim was to review our experience with sequential adjuvant therapy using cisplatin and ifosfamide chemotherapy and radiotherapy after surgical staging. A retrospective study of 43 patients from 1995 to 2004 was undertaken. Survival was calculated using the Kaplan-Meier method and compared by the log-rank test. The Cox proportional hazard regression model was used to assess the effect of treatment on survival after adjustment for age and stage. Twenty-eight patients received adjuvant chemotherapy and 28 patients had adjuvant radiotherapy. Twenty-one patients underwent sequential adjuvant chemotherapy and radiotherapy. Tumor recurrence occurred in 14 patients at a median duration of 10 months. The overall 2- and 5-year survival was 64% and 60%, respectively. The 2- and 5-year survival for stage I and II diseases was both 95%, while the 2-year survival for stage III and IV diseases was 25%. Patients who underwent sequential adjuvant therapy had an improved survival compared with patients who did not follow the protocol (P= 0.024). Our results with sequential adjuvant therapy are encouraging and justify future randomized trials.

Tailoring the field and indication of adjuvant pelvic radiation for patients with FIGO stage Ib lymph nodes-negative cervical carcinoma following radical surgery based on the GOG score--a pilot study.

INTRODUCTION: The traditional indications for adjuvant pelvic radiotherapy (RT) for International Federation of Obstetrics and Gynecology (FIGO) stage Ib1 lymph nodes-negative cervix carcinoma following radical surgery based on histopathological factors, such as deep stromal invasion and lymphovascular space invasion (LVSI), were often inconsistently applied. The perceived risk of relapse was subjectively determined. This pilot study attempts to determine if the treatment outcome will be affected when the indication for RT is based on the Gynecologic Oncology Group (GOG) Risk Score (RS) and the field of adjuvant RT is tailored to the RS. MATERIALS AND METHODS: From 1997 to 1999, 55 patients with FIGO stage Ib1 lymph nodes-negative cervical carcinoma limited to the cervix were prescribed RT following radical surgery, based on their RS, as follows: RS <40, RT is omitted; RS >40 to <120, modified (smaller) field RT; and RS >120, standard field pelvic RT. Their incidence and site of recurrence were compared with a similar cohort of 40 patients who were treated prior to 1997. RESULTS: Prior to 1997, of the 40 patients, 10 patients were given standard field RT. There were 2 (5%) recurrent diseases. The mean duration of follow-up was 61.6 months (range, 1 to 103 months). The RS of 23 of the 30 patients who were not given RT were available. The mean RS was 22 with 5 patients having a score of >40. From 1997 onwards, of the 55 patients, 28 (51%) did not require RT, 13 (23%) were treated with modified (smaller) field RT and 14 (26%) were given standard field RT. There were 2 (3.6%) cases of relapse. The mean duration of follow-up was 36.4 months (range, 5 to 60 months). All patients with a RS of <40 did not suffer any relapse. Their survival outcomes were better when compared to patients who did not have any RT in the GOG Study. CONCLUSIONS: The results of this study indicated that postoperative adjuvant RT given to patients with a high GOG RS of >120, significantly improved their 5-year recurrence rate and disease-free survival, as compared with the similar group of patients who were without adjuvant therapy in the GOG study. Patients with a GOG risk-score of <40 may be safely spared from adjuvant pelvic RT. The current treatment protocol did not compromise the outcome in patients, compared with the use of a less precise treatment protocol in the past.

FIGO stage 1B2 cervical carcinoma--the KK Women's and Children's Hospital experience.

INTRODUCTION: The objectives of this review were to document the surgico-pathological characteristics of surgically resected FIGO stage 1B2 cervical carcinoma and to review our overall experience with this disease. MATERIALS AND METHODS: This is a retrospective review of 35 patients diagnosed and treated from September 1990 to November 2001. RESULTS: The median age was 42 years and the mean tumour diameter was 5.1 cm. Majority were squamous cell carcinomas (65.7%), 28.6% were adenocarcinomas and 5.7% were adeno-squamous carcinomas. The primary treatment comprised radical surgery in 77.1%, radiotherapy in 20% and neoadjuvant chemotherapy followed by radical surgery and adjuvant radiotherapy in 2.9%. Significant surgico-pathological features noted were deep stromal invasion (66.7%), lympho-vascular space invasion (55.6%), parametrial involvement (22.2%), positive margins (3.7%) and pelvic node metastases (33.3%). Postoperative radiation was given to 92.6% of the patients who underwent primary surgery, of whom 29% received concurrent chemotherapy. Radiation toxicity was mild with no grade 3 or 4 toxicity documented. For the patients who had surgery, the recurRence rate was 14.8% (11.1% pelvic and 3.7% distant) and the survival rate was 88.9%. For those who had primary radiation, the rate of persistent disease was 28.6%, the distant recurrence rate was 28.6% and the survival rate was 57.1%. CONCLUSION: FIGO stage 1B2 cervical carcinomas are associated with significant rates of adverse surgico-pathological features. The ideal primary treatment is yet to be established and should be determined by prospective randomised trials.

Recurrent nasopharyngeal carcinoma presenting as diffuse dermal lymphatic infiltration in the neck: three case reports.

BACKGROUND: Any malignancy has the propensity to metastasize to skin. The frequency of skin metastases vary in different tumors and occur in about 0.7% to 10% of all patients diagnosed with cancer. It is rare in nasopharyngeal carcinoma. METHOD: Three cases of relapsed nasopharyngeal carcinoma with diffuse dermal involvement were described. Their clinical presentation, results of investigations, and response to treatment were reviewed. Literature review of similar forms of presentation was done by means of a MEDLINE search. RESULTS: At the time of dermal relapse, all three patients had a uniform clinical picture of facial, periorbital, and lip swelling associated with stridor and dysphagia. Histologic findings showed dermal infiltrates of malignant cells, and CT scan showed diffuse infiltration of the subcutaneous tissue. Despite chemotherapy, the clinical course was relentless. CONCLUSION: This report describes a presentation of disease that is underdiagnosed and heightens awareness of oncologists to this form of recurrence in nasopharyngeal carcinoma.

Prognostic factors in 677 patients in Singapore with nondisseminated nasopharyngeal carcinoma.

BACKGROUND: The objective of the current study was to describe the survival of nasopharyngeal carcinoma (NPC) patients in Singapore, verify the prognostic value of the revised 1997 TNM staging system, and develop a multivariate prognostic model for NPC. In addition, the authors also examined the prognostic value of characteristics of lymph node spread and parapharyngeal involvement. METHODS: A prospectively maintained database containing clinical and computed tomography scan data was used to reclassify 677 NPC patients treated between 1992 and 1994 according to the new staging system. Records were linked with the death registry to ascertain the patient's vital status and date of death. Overall and stage specific survival were analyzed using the Kaplan-Meier method and the log rank test. Univariate and multivariate Cox proportional hazards regression analysis were used to obtain prognostic models. RESULTS: Two hundred seventy-four deaths (40.5%) occurred. The 5-year survival rate was 56.6% (95% confidence interval [95% CI], 52.3%, 60.7%). The stage specific 5-year survival rates were: Stage I, 88%; Stage IIA, 75%; Stage IIB, 74%; Stage III, 60%; Stage IVA, 35%; and Stage IVB, 28%. TNM stage was found to be a statistically significant prognostic factor (P < 0.0001). Cranial nerve (hazard ratio [HR]: 2.77), orbit (HR: 5.71), and intracranial involvement (HR: 2.46) conferred a particularly bad prognosis in univariate analysis. Independently significant prognostic factors were age; lymph node status; and paraoropharyngeal, cranial nerve, orbit, and nasal involvement. Among lymph node positive patients, independently significant prognostic lymph node characteristics were Ho level and laterality. Although parapharyngeal involvement appeared to be prognostically unimportant, paraoropharyngeal involvement distinguished a subgroup with a poorer prognosis (HR: 1.84; 95% CI, 1.45, 2.34; P < 0.0001). Lateral spread to the medial infratemporal fossa and beyond also was found to confer a poorer prognosis. CONCLUSIONS: The results of the current study show that the revised 1997 TNM staging system is prognostically useful. Subdivision into paraoropharyngeal involvement and using the medial infratemporal fossa to delineate prognostically significant lateral spread should be considered in future revisions.

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.

Phase II trial of a paclitaxel and carboplatin combination in Asian patients with metastatic nasopharyngeal carcinoma.

PURPOSE: An earlier phase II trial of paclitaxel in patients with metastatic nasopharyngeal carcinoma (NPC) demonstrated a response rate of 22%. Hence we proceeded to study the combination of paclitaxel and carboplatin in these patients. PATIENTS AND METHODS: The 21-day regimen was as follows: i.v. paclitaxel 175 mg/m2 over three hours preceded by standard premedications, followed by i.v. carboplatin dosed at AUC of six infused over one hour. Only chemotherapy-naive patients with histological diagnoses of undifferentiated carcinoma of the nasopharynx, systemic metastases and radiologically measurable lesions were eligible. RESULTS: Thirty-two patients were accrued to this study. Twenty patients (62%) had at least two sites of metastasis. The main grade 3-4 toxicity was neutropenia (31%). Nine patients (28%) developed neutropenic sepsis, which caused the demise of one of them. Twenty-four patients (75%) responded to treatment, with one (3%) attaining a complete response. The median time to progression of disease was seven months and the median survival was 12 months. At one year, 52% of the patients were alive. CONCLUSIONS: The combination of paclitaxel and carboplatin is an active regimen in NPC. Its convenience of administration and good tolerability make it an attractive alternative regimen to consider for patients with metastatic disease.

Patient profile and survival in 270 computer tomography-staged patients with nasopharyngeal cancer treated at the Singapore General Hospital.

This is a report analysing the patient profile and survival results in 270 patients with nasopharyngeal carcinoma treated with radiation therapy between July 1987 and December 1988. The patients had a median age of 52.6 months, and a male-female ratio of 2.5:1. Ninety-four percent of patients were Chinese. The commonest presentation was that of a neck mass (found in approximately 65% of patients). Approximately two-thirds presented with disease more advanced than Ho's stage II. At a median follow-up of 52.6 months, the 5-year actuarial survival rate was 53% and the freedom from relapse rate was 57%. One hundred and seven patients died within the observation period. Of these, 46 patients had disease in the post nasal space, 41 in the neck and 60 in sites outside the head and neck.

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.