Effect of listening to Vedic chants and Indian classical instrumental music on patients undergoing upper gastrointestinal endoscopy: A randomized control trial.

BACKGROUND: A high level of preoperative anxiety is common among patients undergoing medical and surgical procedures. Anxiety impacts of gastroenterological procedures on psychological and physiological responses are worth consideration. AIMS AND OBJECTIVES: To analyze the effect of listening to Vedic chants and Indian classical instrumental music on anxiety levels and on blood pressure (BP), heart rate (HR), and oxygen saturation in patients undergoing upper gastrointestinal (GI) endoscopy. MATERIALS AND METHODS: A prospective, randomized controlled trial was done on 199 patients undergoing upper GI endoscopy. On arrival, their anxiety levels were assessed using state and trait scores and various physiological parameters such as HR, BP, and SpO2. Patients were randomly divided into three groups: Group I of 67 patients who were made to listen prerecorded Vedic chants for 10 min, Group II consisting of 66 patients who listened to Indian classical instrumental music for 10 min, and Group III of 66 controls who remained seated for same period in the same environment. Thereafter, their anxiety state scores and physiological parameters were reassessed. RESULTS: A significant reduction in anxiety state scores was observed in the patients in Group I (from 40.4 ± 8.9 to 38.5 ± 10.7; P < 0.05) and Group II (from 41.8 ± 9.9 to 38.0 ± 8.6; P < 0.001) while Group III controls showed no significant change in the anxiety scores. A significant decrease in systolic BP (P < 0.001), diastolic BP (P < 0.05), and SpO2 (P < 0.05 was also observed in Group II. CONCLUSION: Listening to Vedic chants and Indian classical instrumental music has beneficial effects on alleviating anxiety levels induced by apprehension of invasive procedures and can be of therapeutic use.

Preliminary results of a randomized study on therapeutic gain by concurrent chemotherapy for regionally-advanced nasopharyngeal carcinoma: NPC-9901 Trial by the Hong Kong Nasopharyngeal Cancer Study Group.

PURPOSE: This randomized study compared the results achieved by concurrent chemoradiotherapy (CRT) versus radiotherapy (RT) alone for nasopharyngeal carcinoma (NPC) with advanced nodal disease. PATIENTS AND METHODS: Patients with nonkeratinizing/undifferentiated NPC staged T1-4N2-3M0 were randomized to CRT or RT. Both arms were treated with the same RT technique and dose fractionation. The CRT patients were given cisplatin 100 mg/m2 on days 1, 22, and 43, followed by cisplatin 80 mg/m2 and fluorouracil 1,000 mg/m2/d for 96 hours starting on days 71, 99, and 127. RESULTS: From 1999 to January 2004, 348 eligible patients were randomly assigned; the median follow-up was 2.3 years. The two arms were well-balanced in all prognostic factors and RT parameters. The CRT arm achieved significantly higher failure-free survival (72% v 62% at 3-year, P = .027), mostly as a result of an improvement in locoregional control (92% v 82%, P = .005). However, distant control did not improve significantly (76% v 73%, P = .47), and the overall survival rates were almost identical (78% v 78%, P = .97). In addition, the CRT arm had significantly more acute toxicities (84% v 53%, P < .001) and late toxicities (28% v 13% at 3-year, P = .024). CONCLUSION: Preliminary results confirmed that CRT could significantly improve tumor control, particularly at locoregional sites. However, there was significant increase in the risk of toxicities and no early gain in overall survival. Longer follow-up is needed to confirm the ultimate therapeutic ratio.

Salvage radiation therapy for locally recurrent nasopharyngeal carcinoma.

PURPOSE: To study the treatment outcome in patients with locally recurrent nasopharyngeal carcinoma (NPC) and to explore whether a combination of high-dose-rate (HDR) intracavitary brachytherapy and external beam radiation therapy (ERT) could improve the therapeutic ratio. METHODS AND MATERIALS: Ninety-one patients with nonmetastatic locally recurrent NPC who were treated with curative intent during the years 1990-1999 were retrospectively analyzed. Eighty-two patients had histologically proven carcinoma. The remaining 9 had clinical and imaging features suggestive of local recurrence. The Ho's T-stage distribution at recurrence (rT) was as follows: rT1-37, rT2-14, rT3-40. Total equivalent dose (TED) was calculated by the linear-quadratic formula without a time factor correction. For those treated by combined-modality treatment (CMT), the TED was taken as the summation of the equivalent dose by ERT and the absolute dose delivered to floor of the sphenoid by brachytherapy. Eight patients were treated solely with brachytherapy, all receiving 24-45 Gy in 3-10 sessions. Forty-one patients were treated with ERT alone receiving a median TED of 57.3 Gy (range, 49.8-62.5 Gy). Forty-two patients were treated by CMT with a median equivalent dose of 50 Gy (range, 40-60 Gy) given by ERT and 14.8 Gy by brachytherapy (range, 3-29.6 Gy). Multivariate analyses were performed using the Cox regression proportional hazards model. RESULTS: The 5-year actuarial overall survival rate, disease specific survival rate and local failure-free survival (LFFS) rate for the whole group were 30%, 33. 3% and 37.8%, respectively. The 3-year LFFS rates of rT1, rT2, and rT3 diseases were 64%, 61.5%, and 18.4%, respectively (p = 0.001). Of the 8 patients treated with brachytherapy alone, 4 failed locally. Further analyses were concentrated on the ERT (41 patients) and CMT (42 patients) groups. The 3-year LFFS rates of rT1, rT2, and rT3 diseases were 66.7%, 66.7%, and 18.4%, respectively (p = 0.0008). Better local control for patients who received a TED of 60 Gy or greater was shown. The corresponding 3-year LFFS rates were 29% and 60% (p = 0.0004). Subgroup analysis on the ERT and CMT groups showed a 3-year LFFS rate of 33.5% and 57% (p = 0.003). ERT group had an excess of patients with rT3 disease. Further analysis was performed on the rT1-2 patients showing a trend toward improvement in local control in favor of the CMT group (3-year LFFS rates: CMT, 71.7%; ERT, 54%; p = 0.13). Multivariate analyses showed that rT stage (p = 0.002) and TED (p = 0.01; HR, 0.93; 95% confidence interval, 0.88-0. 98) remained significant. The 5-year major and central nervous system (CNS) complication-free rates were 26.7% and 47.8%. The following factors were found to be significant on univariate analyses for both complications in the ERT and CMT groups: (1) Modality of treatment: more complications with ERT group; and (2) rT stage. Multivariate analyses showed that the rT stage was significant for predicting the occurrence of major (p = 0.004) and CNS complications (p = 0.04). CONCLUSION: For rT1-2 local recurrences, CMT with at least 60 Gy TED is recommended. The high incidence of major late complications is of serious concern. Ways of improving the local control of Ho's rT3 disease and reducing the risk of late complications should be explored.

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.

Salvage brachytherapy for patients with locally persistent nasopharyngeal carcinoma.

PURPOSE: Locally persistent nasopharyngeal carcinoma (NPC) carries an increased risk of local failure if additional treatment is not given. This study was conducted to evaluate the outcomes of patients with locally persistent NPC as treated by high-dose-rate (HDR) intracavitary brachytherapy, and to explore whether routine brachytherapy boost could improve the local control. METHODS AND MATERIALS: Eighty-seven patients with locally persistent NPC treated during 1990-1998 with HDR intracavitary brachytherapy were retrospectively analyzed. Fibreoptic nasopharyngoscopy was performed 3-6 weeks after completion of the primary external radiation therapy (ERT). Biopsies were only taken from suspicious areas. Those with complete regression of local disease were put on observation. Eighty-seven patients were shown to have persistent viable disease at a median time of 6 weeks post-RT. The distribution according to Ho's staging system at initial diagnosis was as follows: Stage I-8, II-33, III-41, IV-5; T1-19, T2-48, T3-20; N0-32, N1-22, N2-28, N3-5. CT scan for restaging was not performed after the documentation of persistent disease. Our policy was to treat all patients with persistent disease with brachytherapy irrespective of the extent of disease just prior to brachytherapy. They were treated with HDR intracavitary brachytherapy, with either cobalt sources or an iridium source, giving 22.5-24 Gy in 3 weekly sessions in all but 4 patients. This dose was prescribed at a distance of 1.5 cm from the center of the surface as defined by the sources in the first six patients and subsequently reduced to 1 cm for the others. Twelve patients were treated with neoadjuvant chemotherapy. To compare the efficacy of brachytherapy, another 383 consecutive nonmetastatic patients, treated with curative intent by ERT, during the years 1990-1993, were evaluated. Multivariate analysis was performed using the Cox regression proportional hazards model. RESULTS: The 5-year actuarial local failure-free survival (LFFS) rates and disease-specific survival rates for the brachytherapy group and ERT group were 85% and 76.6% (p = 0.15), and 72% and 67.8% (p = 0.2), respectively. The corresponding 5-year actuarial LFFS rates for T1, T2, and T3 disease were 94.7%, 88.2%, 67.4%, and 84.1%, 79.8%, 62.6%. In assessing the local control, only the T staging was significant on multivariate analysis (p = 0.0004). Other parameters such as age, sex, and persistence of disease (giving brachytherapy) were all nonsignificant. Complications were comparable between the two groups. In the persistent group, the local failure rates of the patients treated with and without neoadjuvant chemotherapy were 17% (2/12) and 13% (10/75) respectively. When analyzed according to different brachytherapy sources, the 5-year LFFS rates of the T1, T2, and T3 patients treated with iridium and cobalt sources were 100% vs. 85.7 (p = 0.19), 93.6% vs. 70% (p = 0.04), and 67.7% vs. 60% (p = 0.72). The difference was statistically significant for the T2 groups. When early T-stage (T1 and T2) patients were grouped together for analysis, the iridium group again showed a statistically significant improvement in 5-year LFFS rate when it was compared with the cobalt group (95.3% vs. 76.5%, p = 0.03) and the ERT alone group (95.3% vs. 81.5%, p = 0.03). The improvement of local control is attributed to a higher nasopharyngeal mucosal dose that is achieved by using small-size flexible applicators with an iridium source. It is interesting to note that the 5-year LFFS rates for the ERT alone group (T1: 84.1%, T2: 79.8%, T3: 62.6%) are comparable to the corresponding rates of the cobalt group. This information supports our speculation that an adequate booster treatment could compensate for inadequate primary treatment. The prognosis of patients with locally recurrent NPC is grave. Maximizing the local control is therefore crucial for the survival of the patients. (ABSTRACT TRUNCATED)

High dose rate brachytherapy for carcinoma of the oral tongue.

PURPOSE: The purpose of this study is to assess the feasibility of treating early-staged tongue cancer with high dose rate (HDR) remote afterloading technique. Furthermore, a new figure of merit, the Geometry Index (GI), is introduced to quantify the quality of the implants. METHODS AND MATERIALS: Between 1994 and 1995, eight patients with carcinoma of the oral tongue were treated solely with interstitial implant using the HDR remote afterloading technique. Five patients had T1 N0 disease and the remaining three had T2 N0 disease. Elective neck treatment was withheld. The male-to-female ratio was 1:1, and the mean age 60 years (range: 32-72 years). The median follow-up time was 26 months (range: 6-30 months). The afterloading catheters were positioned through the submandibular approach with the assistance of templates. Six patients had single planar implant and the remaining two had double planar implant. The median number of catheters inserted was 5 (range: 4-9). The median dose given was 60 Gy in 10 fractions over 6 days. The interfraction interval was 7 h. Mandibular and maxillary shields were inserted prior to treatment. Thomadsen et al. introduced the use of Implant Quality Index (QI). We introduce a new parameter, GI, which is defined as ratio of the QI of the nonoptimized executed implant to the corresponding QI value of the nonoptimized idealized implant. RESULTS: The mucositis lasted for 6 to 20 weeks (median: 10 weeks). There was no local failure up to a median follow-up of 26 months. Two patients developed ipsilateral neck node metastases at 2 and 4 months following implant, respectively. One patient had involvement at level II and the other failed at level I to III. Both patients were salvaged by neck node dissection and regionally remained in control. One patient with multiple nodal metastases and extracapsular spread developed biopsy-proven liver metastases and succumbed 6 months following implant. One patient treated with double planar implant developed Grade 3 necrosis of the soft tissue and bone. This complication is largely preventable now, as we have acquired more technical expertise. The mean GI values for the single and double planar implants were 0.88 (range: 0.84-0.91) and 0.8, respectively. This correlates with our practical experience that it is more difficult to maintain a good geometry as double planar implant is required. The GI gives a better view of the geometry of implant as it compares the nonoptimized QI of the executed implant with its ideal counterpart. The failure to achieve a high GI in double planar implants is presumed to relate to technical difficulties rather than variation in individual performance. CONCLUSION: Our preliminary experience in treating early-staged tongue cancer with the HDR remote afterloading technique is inspiring, as it gives a local control rate of 100% with acceptable morbidity. Further studies are eagerly awaited to delineate the optimum schedule for this modality of treatment. It is hoped that the GI values, which represents the skills of insertion, could be routinely reported so that treatment results between different centers could be compared in a more precise manner.

T1 nasopharyngeal carcinoma: the effect of waiting time on tumor control.

PURPOSE: To study the effect of unperturbed tumor growth on the control of nasopharyngeal carcinoma. METHODS AND MATERIALS: This is a retrospective analysis of 290 patients with T1N0-3M0 disease (Ho's classification) treated by the same technique and dose schedule to the nasopharyngeal region. The median interval from diagnosis to commencement of irradiation was 26 days (range: 8-68 days). Cox proportional hazards analyses were performed to study the independent effect of waiting time on the probability of failure at various sites. Actuarial failure-free survival of patients with delay < 22 days, 22-28 days and > 28 days were also compared to illustrate the clinical observation. RESULTS: Both tests showed that waiting time had no significant impact on local failure: The N-stage stratified hazard ratio was 0.985 per day, and the 10-year local failure-free survival for the three groups was 76%, 80%, and 82%, respectively. A similar result was obtained for nodal control in patients with our scheduled neck irradiation. Although the p value of all tests failed to reach statistical significance, the N-stage stratified hazard ratio for distant failure was 1.020 per day, and the corresponding metastasis-free survival in patients with N2-3 disease was 70%, 65%, and 52%, respectively. For node-negative patients without elective neck irradiation, the hazard ratio was 1.019 per day, with the corresponding regional failure-free rates at 57%, 62%, and 33%, respectively. CONCLUSION: Delay in initiation of treatment to the primary target (within the range observed) did not affect the control rate at irradiated sites, but there was a trend (though statistically insignificant) towards increase in failures at untreated sites that were clinically too serious to be ignored.

Recurrent nasopharyngeal carcinoma: the puzzles of long latency.

PURPOSE: To study the peculiar characteristics of relapses with long latency following radical treatment for nasopharyngeal carcinoma. METHODS AND MATERIALS: 847 patients with nasopharyngeal recurrence were retrospectively studied, focusing on the independent effects of latency on different outcome aspects and its relationship with other prognostic factors. RESULTS: The proportion of recurrence with latency <2 years (Group A), 2-<5 years (Group B), and 25 years (Group C) were 52%, 39%, and 9%, respectively. A higher proportion of Group C originated from patients with node-negative early primary, but fewer of them were still confined within the nasopharynx at detection of recurrence. There was no significant difference in the choice of salvage modality, but among those reirradiated, more of Group C were treated with external beams to a higher dose. The difference in local salvage rate was not statistically significant, but the 5-year distant failure-free rates of the 3 groups were 57%, 67%, and 83%, respectively; and the corresponding disease-specific survival (DSS) were 14%, 20%, and 35%. Multivariate analysis confirmed the independent significance of latency in predicting distant failure (hazard ratio = 0.81 per year, p < 0.01) and cancer deaths (hazard ratio = 0.90 per year, p < 0.01). CONCLUSIONS: Nasopharyngeal recurrence with long latency showed different natural behavior: the prognosis was significantly better due to lower risk of distant failure.

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.

p53 inactivating mutations in Chinese nasopharyngeal carcinomas.

Previously a low frequency of p53 mutations was detected in nasopharyngeal carcinoma (NPC) using molecular techniques to screen for mutations, yet immunohistochemical staining revealed a high frequency of p53 aberrant proteins. These findings might be attributed to the occurrence of p53 mutations outside the common hot spots and/or the inactivation of the protein through interactions with cellular or viral proteins. Using a previously established simple and sensitive p53 yeast functional assay, we blindly screened 25 nasopharyngeal biopsies for p53 mutations from exons 4 to 11. p53 was mutated in 27.3% of NPC specimens and in 0% of the nasopharyngeal biopsies from patients with non-malignant diseases. Two p53 mutations were detected in exon 7 and two were detected in exon 8. Interestingly, the exon 8 mutations observed in NPC lie in codons which appear to be hot spots for mutations in other head and neck cancers.

Effect of time, dose and fractionation on local control of nasopharyngeal carcinoma.

To study the effect of radiation factors on local control of nasopharyngeal carcinoma, 1008 patients with similarly staged T1N03M0 disease (Ho's classification) were retrospectively analyzed. All patients were treated by megavoltage irradiation alone using the same technique. Four different fractionation schedules had been used sequentially during 1976-1985: with total dose ranging from 45.6 to 60 Gy and fractional dose from 2.5 to 4.2 Gy. The median overall time was 39 days (range = 38-75 days). Both for the whole series and 763 patients with nodal control, total dose was the most important radiation factor. The hazard of local failure decreased by 9% per additional Gy (p < 0.01). Biological equivalents expressed in terms of Biologically Effective Dose or Nominal Standard Dose also showed strong correlation. Fractional dose had no significant impact. The effect of overall treatment time was insignificant for the whole series, but almost reached statistical significance for those with nodal control (p = 0.06). Further study is required for elucidation, as 85% of patients completed treatment within a very narrow range (38-42 days), and the possible hazard is clinically too significant to be ignored.

Improved local control for early T-stage nasopharyngeal carcinoma--a tale of two hospitals.

PURPOSE: To study the efficacy of intracavitary brachytherapy (ICT) in early T-stage nasopharyngeal carcinoma (NPC). METHODS AND MATERIALS: All early T-stage (T1 and T2 nasal cavity tumour) NPC treated with a curative intent up to 1996 were analyzed (n=743), 163 from the Prince of Wales Hospital (PWH) and 25 from Tuen Mun Hospital (TMH) were given ICT after radical external radiotherapy (ERT; group A). They were compared with 555 patients treated with ERT alone (group B). The radiotherapy techniques were identical between the two hospitals. The ERT delivered the tumoricidal dose (uncorrected biological equivalent dose (BED)-10, > or = 75 Gy) to the primary tumour, and this did not differ in technique or dosage between the two groups. The ICT delivered a dose of 18-24 Gy in three fractions over 15 days to a point 1 cm perpendicular to the midpoint of the plane of the sources. RESULTS: The local failure was significantly less (crude rates, 6.9 vs. 13.0%; 5-year actuarial rates, 5.8 vs. 11.7%) and the disease-specific mortality was significantly lower (crude rates, 13.8 vs. 18.9%; 5-year actuarial rates, 12.2 vs. 15.2%) in group A compared with group B. ICT was the only significant independent prognostic factor predictive of fewer local failures. When ICT was excluded from the Cox regression model, the total physical dose or the total BED-10 uncorrected for tumour repopulation became significant in predicting the ultimate local failure rate. The two groups were comparable in the rate of the chronic radiation complications. A significant dose-tumour-control relationship existed, plotting the local failure as a function of the total physical dose or the total BED. CONCLUSIONS: Supplementing ERT, which delivered the tumoricidal dose (uncorrected BED-10, > or = 75 Gy), with ICT significantly enhanced ultimate local control in early T-stage (T1/T2 nasal infiltration) NPC. A significant dose-tumour-control relationship exists above the conventional tumoricidal dose level.

Nasopharyngeal carcinoma: local control by megavoltage irradiation.

This is a retrospective analysis of the long-term local control in 4128 patients with non-disseminated nasopharyngeal carcinoma treated solely by megavoltage irradiation during the years 1976-1985. The T-stage distribution according to Ho's classification was T1 37%, T2 14% and T3 49%. Different fractionation schedules had been employed at different periods, and the median dose to the primary target was equivalent to 65 Gy by time dose fractionation calculation. In 8% (344) of patients the tumour failed to regress completely after the basic course, but 89% (148/167) of those suitable for salvage with additional irradiation eventually attained complete local remission. The cumulative incidence of local failure was 24% (5% persistence, 19% recurrence). The 10-year actuarial local failure-free survival was 67%. While patients with T2 and T3a tumours achieved local control comparable to T1, those with T3c-d had the poorest control (with highest incidence of persistence and advanced recurrence). T-stage adjusted analyses suggested a significant trend of dose-response: the odds ratios for local failure were 1.16 and 1.86, respectively, when patients given 60-63 Gy and 55-59 Gy were compared with those given 64 Gy or above (p value = 0.0018). Patients treated during 1981-1985 achieved higher local failure-free survival than those treated during 1976-1980 (75% versus 70% at 5 years, p value = 0.0013). The possible attributes are studied, and ways for future optimization of treatment discussed.

High-dose-rate remote afterloading irradiation of carcinoma of the cervix in Hong Kong: unexpectedly high complication rate.

One hundred and thirty-six patients with biopsy-proven carcinoma of cervix were treated with external beam irradiation to the whole pelvis (46 Gy in 23 fractions) and three weekly applications of high-dose-rate (HDR) intracavitary brachytherapy of 7 or 8 Gy per fraction to point A (2 cm above and 2 cm lateral to the cervical os). The actuarial 5-year survival rate was 72% (Stage IB 85%; IIA 64%; IIB 70%; IIIA 25%; IIIB 53%). Patient age above 61 years and Stage III disease were adverse determinants for survival as shown by multivariate analysis. Late complications developed in 47% (65/137) of patients. Grade 3 or above complications occurred in the bladder, small bowel and sigmoid colon/rectum in 5%, 3% and 7% of patients, respectively. The most significant determinant of severe rectal complications was the addition of a lower vaginal tandem (P less than 0.01); the other determinants of rectal complications included a uterine length greater than 5 cm, a total biologically effective dose to the rectum of more than 120 Gy3 and Stage III disease.

The importance of three-dimensional brachytherapy treatment planning for nasopharyngeal carcinoma.

High dose rate (HDR) intracavitary brachytherapy is now more frequently incorporated into treatment programmes for patients with persistent and recurrent nasopharyngeal carcinoma (NPC). However, many centres still employ two-dimensional (2-D) image reconstruction for applicators with a three-dimensional (3-D) orientation. In this study, we introduced the use of a mobile modified Nucletron reconstruction box inside the brachytherapy suite for image reconstruction and quality assurance. Three-dimensional reconstruction of the applicators' configurations proved possible and the dose distributions generated by the 2-D and 3-D image reconstructions could be compared. Thirty-one applications were included in this part of the analysis. The results showed that, based on the 2-D planning method, the reference doses were under-prescribed by 1%-10% in all except one patient, whose dose was over-prescribed by 3%. The evaluated doses to the floor of the sphenoid, which was shown to be significant for subsequent local control, was shown to be underestimated by up to 19% or overestimated by 18%, with an average of 5.9% dose underestimation. With this system, the reliability of the anchoring techniques was verified by posttherapy radiographs. Any catheter displacement of more than 1 mm was counted as a failure. Nine of the 43 verified applications were classified as failures, although six of nine catheter displacements measured < or = 2.5 mm. We recommend the routine use of a modified reconstruction box for 3-D image reconstruction for dose calculation and prescription in the treatment of NPC with HDR intracavitary brachytherapy. Quality assurance programmes should be included as an integral part of any HDR treatment; their importance cannot be overemphasized.

Staging of nasopharyngeal carcinoma: evaluation of N-staging by Ho and UICC/AJCC systems. Union Internationale Contre le Cancer. American Joint Committee for Cancer.

To evaluate the prognostic accuracy of N-staging by Ho's and the UICC/AJCC systems, 5020 patients with undifferentiated or poorly differentiated squamous cell carcinoma of the nasopharynx treated at the Queen Elizabeth Hospital, Hong Kong in the period 1976-1985 were analysed retrospectively. They were initially staged with Ho's system, but detailed records of nodal involvement allowed accurate retrospective restaging with the UICC/ AJCC (1988) system. Staging assessment depended almost entirely on physical examination; only 14% of patients had additional investigations with computed tomography. To evaluate the independent significance of different nodal parameters, T-stage adjusted analyses of the 4730 patients presenting without distant metastases were performed. Both N-staging systems showed a strongly significant overall correlation with distant failures and cancer-specific deaths. A significant trend was also shown for nodal failures in node-positive patients. Ho's system was superior in predicting distant failures, while the UICC/AJCC system was superior for nodal failures. However, even with due adjustment for level, the independent significance of nodal size, laterality and fixity could be demonstrated. After adjustment for UICC/AJCC N-stage, both level and fixity were also significant. Furthermore, when adjusted for all other meaningful parameters, there were no significant differences between ipsilateral and contralateral involvement, upper and mid-level extent, and nodal size < or = 3 cm or > 3- < or = 6 cm. N-staging can be further optimized by a newly proposed system incorporating fixity (movable versus fixed), level (upper-mid versus lower), size (greatest diameter < or = 6 cm versus > 6 cm), and laterality (unilateral versus bilateral) as staging criteria.

N-staging of nasopharyngeal carcinoma: discrepancy between UICC/AJCC and Ho systems. Union Internationale Contre le Cancer. American Joint Committee for Cancer.

To enable clinicians to have a better understanding of the limitations of the UICC/AJCC and Ho N-staging systems for nasopharyngeal carcinoma, 4730 patients without distant metastases at diagnosis were retrospectively analysed. The two systems agreed in 54% (1867/3451) of node-positive patients, and their treatment results were taken as the reference for comparison. To identify the most appropriate N-stage for the discrepant groups, their outcomes were measured against the respective reference. All patients with single, ipsilateral and small nodes, irrespective of their relative position in the upper-mid neck should be classified as N1, while those with multiple, bilateral/contralateral or medium-sized node(s) are effectively N2, even if nodal involvement is confined to the upper neck. All patients with extension to the supraclavicular fossa (irrespective of size) and those with nodes larger than 6 cm at the greatest diameter (irrespective of level) should be classified and treated as N3, especially as, in this group, half of the patients died of distant metastases and trials of adjuvant systemic therapy have to be considered. Areas of inaccurate prognostication by the respective system should be noted to avoid misguiding treatment strategy. The present analyses support our previous suggestions that both the level of extent and the bulk of nodal deposits are important prognostic factors. While supraclavicular involvement is a significant demarcation, there is little justification for further division into upper and mid-levels. The merits of both systems should be duly recognized and combined for the further improvement of prognostic accuracy.

Primary non-Hodgkin's lymphoma of the prostate.

We report the results of treating a patient with stage IIBE primary large B-cell non-Hodgkin's lymphoma of the prostate. Complete remission was achieved following aggressive chemotherapy and consolidation radiotherapy. The patient remains in clinical remission 2 years after presentation.

Small cell carcinoma of the cervix complicated by pregnancy.

We report the results of treatment in a 26-year old patient with stage IB2 small cell carcinoma of the cervix complicated by pregnancy. A pathological complete remission was achieved following sandwich chemotherapy and radiotherapy. The patient remains in clinical remission 14 months after presentation.

Technical hints for high dose rate interstitial tongue brachytherapy.

High dose rate (HDR) interstitial tongue brachytherapy is a new treatment modality. This study describes important technical details required for its successful use. Thirteen patients with carcinoma of the oral tongue were treated solely with interstitial brachytherapy using HDR remote afterloading techniques during the years 1994-1997. The afterloading catheters were positioned by the submandibular approach with the assistance of a template set. Custom-made mandibular lead shields were inserted prior to treatment. Special reusable Tuen Mun Hospital (TMH) lead buttons were made for improved radiation protection. The median dose given was 55 Gy in ten fractions over 6 days. The interfraction interval was 7 hours for the first seven patients treated and was extended to 8 hours for the other six. Shrinking field techniques were employed and the treatment length of the last fraction was reduced by 5 mm. Commencing with the second patient treated with double planar implants, the medial plane was treated with eight fractions while the lateral plane received ten fractions. To reduce further the potential risk of tract seeding, additional coverage to the implantation tracts was given for the last four patients, with the resultant isodose curves resembling a 'comb rake/brush'. The mean and median measured doses on the inner face of the mandibular shields were 113% and 93% of the reference dose respectively (range 77-247). The dose to the corresponding sites on the gingival surface can be reduced by 75% if the 3 mm thick lead shield is placed successfully. With the use of the TMH button, the transmitted dose to the tissue in direct contact can be reduced by one-third. With the 'comb rake/brush' dose distribution, the high dose volume of the single planar implants could be reduced by 44%, compared with the low dose rate technique, if loading to just 5 mm short of the submandibular skin was required. The mean doses for the combination of eight double planar plus two single planar implants, and ten double planar implants, are on average 29% and 37% greater than the reference dose respectively. An 8% reduction in absolute dose in the region between the planes of the catheters would lead to an even greater magnitude of reduction in morbidity to late responding tissue. The prerequisite for the success of HDR interstitial implants is to develop a good technique in positioning the afterloading catheters and protection of the normal tissue. Its importance merits special attention if HDR remote afterloading interstitial tongue brachytherapy is to realize its full potential.