Validation of a nomogram in the prediction of local recurrence risks after conserving surgery for Asian women with ductal carcinoma in situ of the breast.

AIMS: At our centre, ductal carcinoma in situ (DCIS) was commonly treated with breast-conservation therapy (BCT). Local recurrence after BCT is a major concern. The aims of our study were to review the outcomes of DCIS treatment in our patients and to evaluate a nomogram from Memorial Sloan Kettering Cancer Centre (MSKCC) for predicting ipsilateral breast tumour recurrence (IBTR) in our Asian population. MATERIALS AND METHODS: Chart reviews of 716 patients with pure DCIS treated from 1992 to 2011 were carried out. Univariable Cox regression analyses were used to evaluate the effects of the 10 prognostic factors of the MSKCC nomogram on IBTR. We constructed a separate National Cancer Centre Singapore (NCCS) nomogram based on multivariable Cox regression via reduced model selection by applying the stopping rule of Akaike's information criterion to predict IBTR-free survival. The abilities of the NCCS nomogram and the MSKCC nomogram to predict IBTR of individual patients were evaluated with bootstrapping of 200 sets of resamples and the NCCS dataset, respectively. Harrell's c-index was calculated for each nomogram to evaluate the concordance between predicted and observed responses of individual subjects. RESULTS: Study patients were followed up for a median of 70 months. Over 95% of patients received adjuvant radiotherapy. The 5 and 10 year actuarial IBTR-free survival rates for the cohort were 95.5 and 92.6%, respectively. In the multivariate analysis, independent prognostic factors for IBTR included use of adjuvant endocrine therapy, presence of comedonecrosis and younger age at diagnosis. These factors formed the basis of the NCCS nomogram, which had a similar c-index (NCCS: 0.696; MSKCC: 0.673) compared with the MSKCC nomogram. CONCLUSION: The MSKCC nomogram was validated in an Asian population. A simpler NCCS nomogram using a different combination of fewer prognostic factors may be sufficient for the prediction of IBTR in Asians, but requires external validation to compare for relative performance.

Paclitaxel, 5-fluorouracil and hydroxyurea concurrent with radiation in locally advanced nasopharyngeal carcinoma.

BACKGROUND: Concurrent chemoradiotherapy (CRT) is the standard treatment for locally advanced nasopharyngeal carcinoma (NPC). We conducted a phase II trial using paclitaxel, 5-fluorouracil and hydroxyurea concurrent with radiation (TFHX). PATIENTS AND METHODS: Fifty-nine patients with locally advanced NPC were treated with CRT consisting of 4-day continuous infusions of paclitaxel (20 mg/m(2)/d) and 5-fluorouracil (600 mg/m(2)/d), and oral hydroxyurea 500 mg bid for nine doses, every 3 weeks concurrent with radiotherapy (RT). RT consisted of once daily 200cGy fractions 5 times per week to a total of 7000cGy. RESULTS: Complete response was seen in 86% and 71% of patients at 4 and 12 months after CRT. The median follow-up was 34 months. Twenty-three patients experienced relapse. Sixteen deaths occurred: 13 from progressive disease. Three-year overall survival and progression-free survival were 72% and 54% respectively, with locoregional and distant control rates of 83% and 64% at 3 years respectively. Grade 3 to 4 acute toxicities included oropharyngeal mucositis in 81% of patients treated, dermatitis in 63%, weight loss in 32%, and neutropenia in 22%. Neutropenic fever was seen in 14%. There were no treatment-related deaths from acute toxicity. CONCLUSIONS: TFHX is shown to be feasible in NPC. Non-cross resistant induction chemotherapy should be further studied with this regimen.

Phase II trial of docetaxel in Asian patients with inoperable stage III non-small cell lung cancer.

Docetaxel has a response rate of greater than 30% in first-line treatment of Western patients with advanced non-small cell lung cancer (NSCLC). The goal of this open-label. phase II study was to evaluate the activity and safety profile of docetaxel in Asian patients with inoperable untreated stage III NSCLC. Docetaxel was given at 100 mg/m2 as a 1-h infusion every 3 weeks. Prophylactic dexamethasone was given to reduce hypersensitivity reactions and edema. Thirty-five patients were enrolled in the study. The response rate was 34% (95% CI, 19%-50%) according to intent-to-treat analysis. No complete response was observed. Twenty-four patients (69%) had grade 3 or 4 neutropenia in cycle 1, and febrile neutropenia was seen in 12 patients. Six patients (17%) experienced mild fluid retention. Docetaxel is an active agent in first-line treatment of Asian patients with locally advanced NSCLC, with the main toxicity being neutropenia. Fluid retention was a minor problem in this study.

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.

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.

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.

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.

Current problems in radiotherapy, chemotherapy and staging of nasopharyngeal carcinoma (NPC).

Nasopharyngeal carcinoma (NPC) in South East Asia is almost entirely of the undifferentiated or poorly differentiated squamous cell types which are more radiosensitive and have better prospect for locoregional control. Cross-sectional imaging can now detect disease in the parapharynx which is commonly involved by this carcinoma. This has resulted in up-staging and technique modification for better local control. Poor prognostic factors include parapharyngeal, skull bone, cranial nerve or other wide-spread involvements locally. Neck nodes in the supraclavicular fossae or bulky nodes also confer poor prognoses. A simplified staging classification system is proposed. With the availability of afterloading machines, a booster dose of intracavitary radiotherapy can conveniently be given. When given shortly after the usual external radiotherapy, the desired high dose to the primary can be achieved without increasing the risk of long-term side effects. Chemotherapy given before radiotherapy helps to achieve prompt control of bulky neck nodes which distort the anatomy and pose problems in radiotherapy dosimetry. However, the eventual survival rate is still not improved. As staging and major prognostic factors are better defined, trials of adjuvant chemotherapy given after radiotherapy should be undertaken. However, the ultimate control of NPC may rest on the feasibility studies on screening for early NPC.

Bone scintigraphy in nasopharyngeal carcinoma.

One hundred and forty-three patients (Group 1) with histologically proven nasopharyngeal-carcinoma (NPC) had bone scintigraphy with 99Tcm methylenediphosphonate (MDP) or dihydroxypropanediphosphonate (DPD) within 2 months of the initial diagnosis. A further 162 patients (Group 2) had bone scans during the course of follow-up if there were symptoms of bone pain or evidence of metastases at other sites. Twenty-three per cent (33/143) of the newly diagnosed NPC patients (Group 1) had evidence of bone metastases. Of these 143 patients, 101 were T0-T2, 16 were T3 and 25 were T4. Thirty-six patients had no neck nodes (NO), 44 were N1, 25 N2 and 38 N3. Of the 162 patients in Group 2, 96 (59%) had a positive bone scan. The commonest sites for bony metastases from NPC were the spine, ribs, pelvis and lower limbs in order of frequency. There is a highly significant association with the nodal stage but no association with the UICC T staging which is not adequate in nasopharyngeal carcinoma. In our part of the world, bone metastases from NPC are a common cause of an abnormal bone scan.

Computers in radiotherapy.

Radiotherapy is one of the earliest fields in Medicine in which computers have made an inroad. The main uses of computers, which include treatment planning, dose calculations, localisation of tumours, verification of patient setups and radiation beam data acquisition, are highlighted in this paper. It is believed that a modern Radiotherapy department cannot function optimally without some form of computing facilities. With advances made in dose calculation algorithms, and in high performance computers, it is expected that the target of 3% accuracy dose calculations can be achieved in treatment planning.

Significance of tissue polypeptide antigen (TPA) levels in nasopharyngeal cancer.

Serum levels of tissue polypeptide antigen (TPA) were measured in 233 patients at the time of initial diagnosis of nasopharyngeal carcinoma (NPC). Staging of NPC was done using Ho's recommendations together with computerised tomography (CT) of skull findings. The upper limit of normal serum TPA levels in our population was noted to be 112 U/1. In 126 patients with N0 and N1 lymph node staging, the mean level of TPA was 90 U/1 +/- 9 (standard error of mean, sem), while in 107 patients with N2 and N3 nodal disease the mean was 193 U/1 +/- 25.6 (p less than 0.001). Similarly, in 162 patients with T1 and T2 disease, the average TPA level was 119 +/- 13.4 while in 71 patients with T3 disease, the mean TPA was 179 U/1 +/- 29.8 (p less than 0.03). Of 200 patients without metastases, the mean TPA level was 112 +/- 12 U/l whereas in 33 patients with known metastases in liver, lung, bone or brain, the mean TPA level was 290 +/- 51 (p less than 0.001) with liver metastases producing the highest levels. The present study indicates rising values of TPA with advancing nodal and tumour stage in NPC, with high values in metastatic disease. There is a highly significant correlation between nodal stage and TPA levels. TPA is a useful marker in the staging and follow-up of NPC patients.

A case of granulocytic sarcoma of the breast and review of the literature.

This article discusses a case of granulocytic sarcoma of the breast, presenting prior to the onset of acute myeloid leukaemia. There has only been six reported cases of such a presentation in the breast. In view of the rarity of the tumour, it is often misdiagnosed as a high grade non-Hodgkin's lymphoma. Its treatment is still controversial and includes a proposal to use anti-leukaemic drug combinations for all cases.

Conservation breast treatment: a viable option locally.

Conservation treatment in carcinoma of the breast is a viable option in the West but is still an uncommon practice locally. Many reasons have been put forth, including the late stage of the tumour we see and the small breast size. This paper presents 25 cases treated by lumpectomy and irradiation with satisfactory cosmetic results, although the follow-up period is short. The introduction of this technique may encourage women to seek treatment earlier, without the fear of losing their breasts.