William Foo

Retrospective analysis of 5037 patients with nasopharyngeal carcinoma treated during 1976-1985: overall survival and patterns of failure.

This is a retrospective analysis of 5037 patients with squamous cell carcinoma of the nasopharynx treated during the years 1976-1985. The stage distribution according to Hos classification was 9% Stage I, 13% II, 50% III, 22% IV, and 6% Stage V. Only 4488 (89%) patients had a full course of megavoltage radiation therapy. The median equivalent dose to the nasopharyngeal region was 65 Gy and cervical region in node-positive patients 53 Gy. Seventy percent (906/1290) of the node-negative patients had no prophylactic neck irradiation. The overall actuarial 10-year survival rate was 43%, and the corresponding failure-free survival 34%. Altogether, 4157 (83%) patients achieved complete remission lasting more than 6 months, but 53% (2205/4157) of them relapsed after a median interval of 1.4 years. The 10-year actuarial local, regional, and distant failure-free rates were 61%, 64%, and 59%, respectively. Thirty-eight percent (338/891) of all patients with local recurrence achieved second local remission. The local complete remission rate with aggressive re-irradiation alone was 47% (333/706). But 37% (124/338) of the responders recurred the second time. The incidence of distant failure correlated significantly with both the N-stage and the T-stage, with the highest (57%) occurring in patients with N3 disease. The incidence of nodal relapse in node-negative patients was 11% (44/384) among those given prophylactic neck irradiation, but 40% (362/906) among those without. Therapeutic irradiation achieved a complete regional remission rate of 90% (306/339). However, despite successful salvage, these patients had a significantly higher distant failure rate than those without nodal relapse, even if they remained local-failure-free (21% vs 6%). Patients treated during 1981-1985 achieved significantly better treatment results than those treated during 1976-1980, especially in terms of the overall survival (57% vs 47% at 5-year), the overall failure-free survival (42% vs 35% at 5-year), and the local failure-free rate (70% vs 63% at 5-year). The possible contributing factors are discussed.

Retrospective analysis of patients with nasopharyngeal carcinoma treated during 1976-1985: Survival after local recurrence

PURPOSE To study the value of re-irradiation, the overall survival and pattern of failures for patients with nasopharyngeal recurrence. METHODS AND MATERIALS All the 891 patients with local recurrence following radiotherapy for nasopharyngeal carcinoma during 1976-1981 were retrospectively analyzed. Only 70% of them had local failure alone at the time of detection, and the T-stage distribution (by Hos system) was 31% rT1, 16% rT2, 51% rT3, and 1% rT?. Seven hundred and six (79%) patients had been re-irradiated with various techniques and doses. Among those who failed, 50 had further irradiation. RESULTS The overall 5- and 10-year actuarial cancer-specific survival rates were 14% and 9%, respectively. Patients with rT3 disease had the worst prognosis. Successful local salvage was achieved in 32% of those re-irradiated (26% of the whole series). The highest control rate was achieved by those treated with external radiotherapy to 60 Gy (equivalent) or above. Only 8/50 patients responded to the third course of radiotherapy. The cumulative incidence of late post-re-irradiation sequelae was 24%, and the treatment mortality rate 1.8%. Besides local failure, 54% had regional relapse and/or distant metastasis. Thus, only 16% of recurrent patients were totally disease-free at final assessment. CONCLUSION The overall prognosis for patients with nasopharyngeal recurrence was grave. High dose re-irradiation could achieve successful local salvage in a substantial number of patients with early recurrence, but late complications did occur. Furthermore, high incidence of failure at other sites was observed.

Clinical diagnosis of late temporal lobe necrosis following radiation therapy for nasopharyngeal carcinoma

This is a preliminary report of 102 patients with clinical diagnosis of late temporal lobe necrosis after radical radiation therapy for nasopharyngeal carcinoma during 1964 to 1983. Histologic verification was available in 12 cases. All but three patients had been treated in our institute using schedules with doses larger than the conventional 200 cGy per fraction. The incidence rate was 1.03%. In our 80 patients with only one course of external irradiation, the doses to the temporal lobes ranged from 1665 to 2127 ret, or 1286 to 1778 brain tolerance unit (btu). The latent interval ranged from 9 months to 16 years. The median observation period is 33 months. The symptomatology, working diagnosis, treatment, and outcome are described. Surgery was hazardous because of the bilaterality of the involvement and exploration for mere verification of diagnosis was unjustified in typical cases. Treatment with corticosteroid achieved durable objective response in 25 (35%) of 72 patients. The importance of early detection and corticosteroid treatment is discussed.

Reirradiation for recurrent nasopharyngeal carcinoma: Factors affecting the therapeutic ratio and ways for improvement

PURPOSE To identify factors for maximizing local salvage and minimizing damages by reirradiation for recurrent nasopharyngeal carcinoma. METHODS AND MATERIALS 654 patients with recurrent nasopharyngeal carcinoma treated by reirradiation during 1976-1992 were retrospectively analyzed. Various fractionation schedules had been used during primary treatment with the total dose ranging from 45.6-70 Gy, fractional dose (at different phases) 1.5-4.2 Gy, and overall time 36-101 days. The gap between the two courses ranged from 0.5-10.6 years. Eighty-two percent of patients were reirradiated with teletherapy, 6% brachytherapy, and 12% with both. For those treated with teletherapy alone, the total dose ranged from 7.5-70 Gy, fractional dose 1.8-5 Gy, and overall time 3-89 days. RESULTS The 5-year actuarial local salvage and complication-free rates were 23% and 52%, respectively. Multivariate analyses showed that the extensiveness of local recurrence was the most significant factor affecting local salvage, while T-stage of primary tumor also influenced prognosis. Choice of method for reirradiation and fractional effect during both courses affected the risk of late complications. For patients treated by teletherapy alone, the hazard of local failure decreased by 1.7% per Biological Effective Dose (assuming alpha/beta ratio = 10) of the second course, while radiation factors during primary radiotherapy had no significant effect. On the other hand, the risk of late complications was predominantly affected by the primary treatment: the hazard increased by 4.2% per Biological Effective Dose (assuming alpha/beta ratio = 3) of the first course, while the corresponding impact of reirradiation failed to reach statistical significance. Length of the gap between the two courses did not affect the outcome. CONCLUSION Early detection of local recurrence and adequate total dose by reirradiation are crucial for improving the chance of local salvage. Combination of teletherapy and brachytherapy should be considered whenever feasible and large fractional dose avoided to minimize late complications. Optimization of biological dose during primary treatment is important.

Effect of Time, Dose, and Fractionation on Temporal Lobe Necrosis Following Radiotherapy for Nasopharyngeal Carcinoma

PURPOSE To study the relative effects of different radiation factors on temporal lobe necrosis (TLN) and predictive accuracy of different biological equivalent models. METHODS AND MATERIALS Consecutive patients (1008) treated radically with four different fractionation schedules during 1976-1985 for T1 nasopharyngeal carcinoma were retrospectively analyzed. All were irradiated by megavoltage photons using the same technique. Their age ranged from 18-84 years, and 92% of patients had complete follow-up. The fractional dose to inferomedial parts of both temporal lobes ranged from 2.5-4.2 Gy, total dose 45.6-60 Gy, and overall time 38-75 days. RESULTS Despite a lower total dose of 50.4 Gy, the 621 patients irradiated with 4.2 Gy per fraction had a significantly higher incidence of temporal lobe necrosis than the 320 patients treated to 60 Gy with 2.5 Gy per fraction: the 10-year actuarial incidence being 18.6% vs. 4.6%, p < 0.001. Multivariate survival analysis showed that fractional effect (product of total dose and fractional dose) was the most significant factor: p = 0.0022, hazard ratio (HR) = 1.044 per Gy2. Overall time and age were both insignificant. The alpha/beta ratio calculated from our data was 2.9 Gy (95% CI: -1.8, 7.6 Gy). Biological effective dose (BED(Gy3)), neuret, and brain tolerance unit all showed strongly significant correlation with the necrotic rate (p < 0.001), and gave similar predictions. The hazard of TLN increased by 14% per Gy3, and it was estimated that 64 Gy (at conventional fractionation of 2 Gy daily) would lead to a 5% necrotic rate at 10 years. Not only did the nominal standard dose (NSD) show the lowest value in terms of log likelihood and standardized HR, but its predictions on TLN deviated markedly from clinically observed rates. CONCLUSION Fractional effect is the most significant factor affecting cerebral necrosis, and overall time has little protective effect. The BED formula, assuming an alpha/beta ratio of 3 Gy, is an appropriate model for predicting late effects on the temporal lobe, and NSD could give seriously misleading predictions.

Changing epidemiology of nasopharyngeal carcinoma in Hong Kong over a 20‐year period (1980–99): An encouraging reduction in both incidence and mortality

Epidemiological data from the Hong Kong Cancer Registry for the period 1980–99 were analyzed. Altogether 21,768 new cases of nasopharyngeal carcinoma (NPC) and 8,664 related deaths were registered. In both genders, the peak incidence occurred in the 50–59 years age group, and this age distribution pattern remained similar throughout. The age‐standardized incidence rate steadily decreased from 28.5 in 1980–84 to 20.2 in 1995–99 per 100,000 males, and from 11.2–7.8 per 100,000 females, resulting in a total decrease of 29% for males and 30% for females over this 20‐year period. The magnitude of total decrease in NPC mortality amounted to 43% and 50%, respectively, as the age‐standardized mortality rate steadily decreased from 13.7 in 1980–84 to 7.8 in 1995–99 per 100,000 males, and from 4.5–2.2 per 100,000 females. The age‐standardized mortality/incidence ratio also decreased from the peak of 0.48 in 1980–84 to 0.39 in 1995–99 for males, and from 0.40–0.29 for females. Females had significantly lower age‐standardized incidence (male/female ratio 2.5–2.6, p < 0.01) and mortality (male/female ratio 3.0–3.5, p< 0.01) throughout the whole period. Furthermore, females had consistently lower mortality/incidence ratio: 0.29 vs. 0.39 in 1995–99. These data are highly suggestive of significant improvement in prevention and control of NPC in Hong Kong. Closer scrutiny of the differences in intrinsic and extrinsic factors between the genders might help to show important factors affecting oncogenesis and prognosis. Possible ways for further reduction of incidence and mortality are discussed.

Staging of nasopharyngeal carcinoma: From Ho's to the new UICC system †

The independent significance of different tumor factors in 4,514 patients with undifferentiated or non‐keratinizing carcinoma of the nasopharynx irradiated at the Queen Elizabeth Hospital during 1976–1985 were analyzed retrospectively. Multivariate analyses showed that the most significant primary factors included cranial nerve palsy, erosion of base of skull and oropharynx. For tumors within the nasopharynx, there was no difference in survival between those with involvement of 1 site vs. more than 1 sites. Patients with cranial nerve palsy had significantly worse prognosis than those with bony erosion alone. Although the nodal characteristics (size, level of extension, fixation, laterality and multiplicity) were inter‐related, their independent impact all reached statistical significance. However, the criteria used currently could be simplified: laterality should be revised to unilateral vs. bilateral, level to upper‐mid vs. lower neck, and size to ≤6 cm vs. >6 cm. Grouping of N2 together with N3 into Stage IV was inappropriate as the former had significantly better prognosis. Our findings, together with review of the publications, provided clinical data for developing the current UICC staging system for nasopharyngeal carcinoma. Such major revision resulted not only in better distinction of hazards, but also more even distribution of cases between different stages. Int. J. Cancer (Pred. Oncol.): 84:179–187, 1999.

In-depth evaluation of the AJCC/UICC 1997 staging system of nasopharyngeal carcinoma: prognostic homogeneity and proposed refinements.

PURPOSE To critically evaluate the American Joint Commission on Cancer (AJCC)/International Union Against Cancer (UICC) 1997 staging system and look back on its achievements by comparing it with the AJCC/UICC 1992 and Ho 1978 staging systems. To identify areas for additional refinement, we analyzed the prognostic heterogeneity within each stage in depth, which provided important clues for the addition or better categorization of the different defining criteria. METHODS AND MATERIALS We performed a retrospective review of the data from 1294 consecutive biopsy-proven nonmetastatic nasopharyngeal carcinoma patients and staged the extent of disease according to the defining criteria of the three staging systems. All patients had undergone detailed pretreatment assessment by fiberoptic endoscopy and CT. Radical-intent radiotherapy was given using the Ho technique according to our standard protocol. RESULTS The AJCC/UICC 1997 staging system was superior to the other two staging systems, because it assigned patients to more uniform-size stage groupings and correlated better with prognosis. Parapharyngeal space involvement was not an independent predictor for survival, local control, or metastasis. On the other hand, carotid space involvement correlated with a greater likelihood of metastasis. Prognostic heterogeneity was found. Those with orbit, cranial nerve, or intracranial involvement fared worse within Stage T4; those with a maximal lymph node size >3 cm fared worse within Stage N2; and those with bilateral lymph node metastasis fared worse within Stage N3. CONCLUSION The prognostic accuracy of the AJCC/UICC 1997 staging system can be improved further by recategorization of the T, N, and group stage criteria.

Total biological effect on late reactive tissues following reirradiation for recurrent nasopharyngeal carcinoma

PURPOSE To assess the additional damage of normal tissues attributable to reirradiation and the magnitude of partial recovery following the initial course. METHODS AND MATERIALS Symptomatic late complication rates (excluding xerostomia) in 3635 patients receiving one course (Group 1) and 487 patients receiving two courses of external radiotherapy (Group 2) for nasopharyngeal carcinoma were retrospectively analyzed and compared. RESULTS Group 2 had significantly lower actuarial complication-free survival rates than Group 1: 48% versus 81% at 5 years. The post-retreatment incidence was significantly affected by biologically effective dose (BED) (assuming an alpha/beta ratio of 3 Gy) of the first course: hazard ratio (HR) = 1.04 per Gy(3) (p = 0.01), but only marginally by that of the second course: HR = 1.01 per Gy(3) (p = 0.06). If the summated BED was taken as the dose unit, it was estimated that a total BED of 143 Gy(3) would induce a 20% incidence at 5 years, while the corresponding dose projected from Group 1 was 111 Gy(3). The gap effect was insignificant in the overall analyses, but a trend of decreasing risk with increasing interval was observed in patients with gap > or = 2 years: HR = 0.86 per year (p = 0.07). CONCLUSION The major determinant of post-retreatment complication is the severity of damage during the initial course. The sum of total doses tolerated is higher than that expected with a single-course treatment, suggesting occurrence of partial recovery (particularly in those reirradiated after an interval of 2 years or more).

Short-term, medium-term, long-term, and lifetime risks of developing and dying of breast carcinoma in a Westernized Chinese Population: Evidence from Hong Kong between 1976 and 2000

Estimates of lifetime and shorter‐term risks of developing and dying of breast carcinoma are useful translational statistics for risk communication; however, these statistics are unknown for Chinese women, who account for one‐fifth of the worlds female population. In the current study, the authors examined age‐specific 5‐year, 10‐year, 20‐year, and lifetime risks of breast carcinoma incidence and disease‐related mortality among Hong Kong women.