Hip fractures are preventable: a proposal for osteoporosis screening and fall prevention in older people.

Osteoporosis is highly prevalent but underdiagnosed and undertreated in Hong Kong. Fragility fractures associated with osteoporosis often result in loss of independence and increased mortality for home-dwelling patients, imposing a high socio-economic burden on society. This issue requires urgent attention given the rapid growth of the elderly population in Hong Kong by approximately 4.3% each year. To address this situation, a group of experts convened to discuss practical ways to reduce the burden of fractures and formulated three recommendations: first, all men (aged ≥70 years) and women (aged ≥65 years) should receive universal dual-energy X-ray absorptiometry assessment for osteoporosis. Second, all men (aged ≥70 years) and women (aged ≥65 years) with a fracture-risk assessment-derived 10-year risk (hip fracture with bone mineral density) ≥3% should receive ≥3 years of anti-osteoporotic treatment. Third, comprehensive structured assessment (including dual-energy X-ray absorptiometry) should be conducted in older patients with a history of falling. By implementing these recommendations, we estimate that we could prevent 5234 hip fractures in 10 years, an annual incidence reduction of approximately 7%, and save HK$425 million in direct medical costs plus substantial indirect savings. Ample clinical and cost-effectiveness data support these recommendations, and studies in Hong Kong and abroad could serve as models on how to implement them. We are confident that by applying these recommendations rigorously and systematically, a significant reduction in hip fractures in Hong Kong is achievable.

The effects of lebrikizumab in patients with mild asthma following whole lung allergen challenge.

BACKGROUND: Interleukin 13 (IL13) is a T-helper type 2 (Th2) cytokine associated with inflammation and pathology in allergic diseases such as bronchial asthma. We have shown that treatment with lebrikizumab, an anti-IL13 monoclonal antibody, significantly improves prebronchodilator forced expiratory volume in 1 s (FEV(1)) in a subset of subjects with uncontrolled asthma. OBJECTIVE: To evaluate efficacy and safety of lebrikizumab in subjects with mild asthma who underwent bronchial allergen challenge. METHODS: Twenty-nine subjects were randomized 1 : 1-5 mg/kg lebrikizumab (n = 13) or placebo (n = 16) administered subcutaneously every 4 weeks over 12 weeks, a total of four doses. Primary efficacy outcome was late asthmatic response (LAR) at Week 13, defined as area under the curve of FEV1 measured 2-8 h following inhaled allergen challenge. Serum biomarkers were measured to verify IL13 pathway inhibition and identify patients with an increased response to lebrikizumab. RESULTS: At Week 13, the LAR in lebrikizumab subjects was reduced by 48% compared with placebo subjects, although this was not statistically significant (95% confidence interval, -19%, 90%). Exploratory analysis indicated that lebrikizumab-treated subjects with elevated baseline levels of peripheral blood eosinophils, serum IgE, or periostin exhibited a greater reduction in LAR compared with subjects with lower baseline levels of these biomarkers. Lebrikizumab exerted systemic effects on markers of Th2 inflammation, reducing serum immunoglobulin E (IgE), chemokine ligands 13 and 17 by approximately 25% (P < 0.01). Lebrikizumab was well tolerated. CONCLUSION AND CLINICAL RELEVANCE: Lebrikizumab reduced the LAR in subjects with mild asthma. Clinical trial number NCT00781443.

Coastal flood risk within a peri-urban area: Sussex Inlet district, SE Australia.

The peri-urban interface (PUI) exhibits characteristic qualities of both urban and rural regions, and this complexity has meant that risk assessments and long-term planning for PUI are lagging, despite these areas representing new developing settlement frontiers. This study aims to address this knowledge gap by modifying an existing approach to quantify and assess flood risk. The risk triangle framework was used to map exposure, vulnerability and biophysical variables; however, in a novel application, the risk triangle framework was adapted by presuming that there is a variation in the degree of exposure, vulnerability and biophysical variables. Within Australia and globally, PUIs are often coastal, and flood risk associated with rainfall and coastal inundation poses considerable risk to communities in the PUI; these risks will be further exacerbated should projections of increasing frequency of extreme rainfall events and accelerating sea-level rise eventuate. An indicator-based approach using the risk triangle framework that maps flood hazard, exposure and vulnerability was used to integrate the biophysical and socio-economic flooding risk for communities in PUI of the St Georges Basin and Sussex Inlet catchments of south-eastern Australia. Integrating the flood risk triangle with future scenarios of demographic and climate change, and considering factors that contribute to PUI flood risk, facilitated the identification of planning strategies that would reduce the future rate of increase in flood risk. These planning strategies are useful for natural resource managers and land use planners across Australia and globally, who are tasked with balancing socio-economic prosperity for a changing population, whilst maintaining and enhancing ecosystem services and values. The indicator-based approach used in this study provides a cost-effective first-pass risk assessment and is a valuable tool for decision makers planning for flood risk across PUIs in NSW and globally.

Urban water metabolism indicators derived from a water mass balance - Bridging the gap between visions and performance assessment of urban water resource management.

Improving resource management in urban areas has been enshrined in visions for achieving sustainable urban areas, but to date it has been difficult to quantify performance indicators to help identify more sustainable outcomes, especially for water resources. In this work, we advance quantitative indicators for what we refer to as the 'metabolic' features of urban water management: those related to resource efficiency (for water and also water-related energy and nutrients), supply internalisation, urban hydrological performance, sustainable extraction, and recognition of the diverse functions of water. We derived indicators in consultation with stakeholders to bridge this gap between visions and performance indicators. This was done by first reviewing and categorising water-related resource management objectives for city-regions, and then deriving indicators that can gauge performance against them. The ability for these indicators to be quantified using data from an urban water mass balance was also examined. Indicators of water efficiency, supply internalisation, and hydrological performance (relative to a reference case) can be generated using existing urban water mass balance methods. In the future, indicators for water-related energy and nutrient efficiencies could be generated by overlaying the urban water balance with energy and nutrient data. Indicators of sustainable extraction and recognising diverse functions of water will require methods for defining sustainable extraction rates and a water functionality index.

Treatment outcome and prognostic factors for primary nasal lymphoma.

PURPOSE: To report our experience managing a large series of Chinese patients with primary nasal lymphoma. PATIENTS AND METHODS: From January 1975 to December 1993, 100 patients (median age, 50 years) with newly diagnosed primary nasal lymphoma were studied. There were four low-grade, 62 intermediate-grade, nine high-grade, and 25 unclassifiable lymphomas. Immunophenotyping was performed in 45 patients: eight B cell, 35 T cell, and two uncertain. All cases of angiocentric lymphoma that were typed were T cell. Fifty-two patients had stage I disease, 15 had stage II, four had stage III, and 29 had stage IV. Only 15 patients had B symptoms (weight loss, night sweats, and/or fever), and 11 had bulky disease. Thirty-nine patients with clinically localized stage I and II disease received local radiotherapy alone (before 1980), and the remaining 28 stage I and II patients received combination chemotherapy followed by local radiotherapy. The 33 patients with advanced stage III and IV disease were given combination chemotherapy, and additional radiotherapy was given to five of them who had bulky local disease. RESULTS: Significantly higher complete remission rates were observed in patients with early stages of disease and those without B symptoms. Superior disease-free survival after complete remission was observed in patients with stage I/II disease. Univariate factors associated with a better overall survival included age less than 60 years, stage I disease, and absence of B symptoms. Survival was significantly better in the subgroup of patients with stage I disease. CONCLUSION: Patients with nasal lymphoma, especially those with advanced disease, seemed to have a poor prognosis, and their clinical outcome was not improved significantly by the use of chemotherapy instead of radiotherapy or the use of doxorubicin-containing chemotherapeutic regimens.

Multicenter phase II trial of mitoxantrone in patients with advanced nasopharyngeal carcinoma in Southeast Asia: an Asian-Oceanian Clinical Oncology Association Group study.

PURPOSE: Patients with advanced nasopharyngeal carcinoma (NPC) have a high incidence of recurrence and often develop distant metastases despite local control. This prospective multicenter phase II trial was conducted to evaluate the safety and efficacy of Novantrone (mitoxantrone; Lederle Laboratories, Wayne, NJ) in the therapy of patients with advanced NPC. PATIENTS AND METHODS: One hundred eight patients with advanced NPC, namely, those with recurrent or persistent disease following primary radiotherapy, or newly diagnosed metastatic disease, were treated with mitoxantrone. Mitoxantrone was administered intravenously at an initial dose of 12 mg/m2 and repeated every 3 weeks, with dose escalation to a maximum of 14 mg/m2. The distribution of histologic subtypes was representative of NPC, with the majority being (61%) undifferentiated (or anaplastic) carcinoma. RESULTS: The overall response rate (complete response [CR] and partial response [PR]) was 25% (95% confidence interval, 17% to 33%). The median response duration, time to treatment failure, and survival duration were 140, 82, and 394 days, respectively. Histology (poorly differentiated squamous cell) was found to be the only important factor in predicting response (P = .04) based on a multivariate analysis of nine pretreatment characteristics. The major dose-limiting toxicity was leukopenia. The incidences of nausea/vomiting, alopecia, and stomatitis/mucositis were 34%, 6%, and 3%, respectively. None were severe. Two patients had asymptomatic, moderate Alexander-grade cardiotoxicity. CONCLUSION: This study represents a large, controlled multicenter trial of single-agent mitoxantrone in the treatment of advanced NPC. Mitoxantrone was well tolerated and produced an overall response rate comparable to that of other single-agent therapies used in the treatment of advanced head and neck cancer. Combination trials with mitoxantrone for advanced disease should be considered.

Chemoradiation and adjuvant chemotherapy in cervical cancer.

PURPOSE: Radiotherapy is the standard treatment for locally advanced cervical cancer, but treatment results remain disappointing, particularly for women with bulky central disease. We investigated the role of concurrent chemoradiation and adjuvant chemotherapy in a randomized trial. PATIENTS AND METHODS: Two hundred twenty patients with bulky stage I, II, and III cervical cancer were randomized to receive either standard pelvic radiotherapy or chemoradiation (epirubicin 60 mg/m(2)) followed by adjuvant chemotherapy with epirubicin 90 mg/m(2) administered at 4-week intervals for five additional cycles. RESULTS: Fifty-nine patients have relapsed, with a median follow-up duration of 77 months. Patients who received epirubicin radiation therapy showed a significantly longer disease-free (P =.03) and cumulative survival (P =.04). Patients who received radiation alone had significantly more distant metastasis than those who received chemoradiation (P =.012). There was no difference in long-term local tumor control (P =.99). CONCLUSION: Survival benefit has been demonstrated in patients treated with chemoradiation followed by adjuvant chemotherapy with epirubicin as compared with patients treated with standard pelvic radiotherapy alone.

A phase II study of ifosfamide, 5-fluorouracil and leucovorin in patients with recurrent nasopharyngeal carcinoma previously treated with platinum chemotherapy.

The aim of this study was to evaluate the efficacy and toxicity of ifosfamide, 5-fluorouracil (5-FU) and leucovorin (IFL) as a second-line chemotherapy regimen in patients with recurrent undifferentiated nasopharyngeal carcinoma (NPC) previously treated with platinum/5-FU. Between June 1997 and February 1999, 18 patients were entered into the study. 3 patients had loco-regional recurrence, 12 had distant metastases and 3 had both loco-regional recurrence and distant metastases. All patients had previously received platinum/5-FU as adjuvant or palliative treatments. The IFL regimen consisting of ifosfamide 1.2 g/m(2) (with mesna), 5-FU 375 mg/m(2) and leucovorin 20 mg/m(2) for 5 days and was repeated every 21 days. The dose of ifosfamide was escalated to 1.4 and 1.6 g/m(2) in subsequent cycles according to the bone marrow toxicity, and the dose of 5-FU to 450 and 525 mg/m(2) according to the severity of mucositis. Patients received a median of 3 cycles of IFL (range: 2-6), with a median total ifosfamide dose of 21 g/m(2) (range: 13-46) and a median total 5-FU dose of 6.75 g/m(2) (range: 4.1-14.7). The median follow-up was 10 months (range: 4-25). 9 patients (50%) achieved a partial response and 1 patient (6%) achieved a complete response, with an overall response rate of 56% (95% confidence interval (CI): 32-80%). For those patients who responded to IFL, 8 had subsequent disease progression on follow-up, with a median response duration of 7.1 months (95% CI: 5.3-8.9). The median time to progression for all patients was 6.5 months (95% CI: 4.2-8.7). 12 patients are still alive with an estimated 1-year survival probability rate of 51%. Treatments were well tolerated, only 1 patient had grade 3 emesis. None of the patients had grade 3/4 anaemia, leucopenia or thrombocytopenia, although IFL was discontinued in 1 patient because of persisting thrombocytopenia. IFL is an effective second-line regimen in patients with recurrent NPC and is well tolerated with mild toxicity. Combining platinum and IFL in chemonaïve patients may further improve the overall response rate and duration and is worth investigating in future trials.

Effective treatment for smoking cessation.

An effective method of cigarette smoking cessation using acupuncture is described. From May 1976 to December 1982, 514 patients were treated. Of 339 evaluable patients, 297 stopped smoking, for a success rate of 88 percent. In a two-year follow-up, the rate of relapse was 31 percent. The possible mechanisms by which this technique works are discussed.

The effect of loco-regional control on distant metastatic dissemination in carcinoma of the nasopharynx: an analysis of 1301 patients.

PURPOSE: This study evaluated the effect of loco-regional control on incidence of distant metastases in patients with nasopharyngeal carcinoma. METHODS AND MATERIALS: Retrospective analysis was performed on 1301 patients with nasopharyngeal carcinoma treated from 1976-1989 in our hospital. The effect of different prognostic indicators on distant metastases free survival (DMFS) was analyzed, including T stage, N stage, sex, and loco-regional control. The significance of loco-regional control in distant metastatic dissemination was further studied with period and subgroup analysis. Cox regression was performed to identify the independent prognostic variables. RESULTS: Patients with loco-regional relapse had significantly higher distant metastases rate than patients with loco-regional control (time-adjusted distant metastases rate at 5 years was 40.7% vs. 29.4%, p = 0.0012). By period analysis, the effect of loco-regional control on distant metastases was found to be significant in the first 2 years from diagnosis. Subgroup analysis showed that loco-regional relapse was associated with significantly higher distant metastases rate in patients with T1, N0, and N1 disease (p = 0.001, 0.001, 0.0226, respectively). The Cox regression model also confirmed loco-regional control as an independent prognostic indicator of distant metastases (p = 0.0001) besides T stage (p = 0.0006) and N stage (p = 0.0001). CONCLUSION: Loco-regional relapse is a significant risk factor for development of distant metastases. Further effort should be made to improve loco-regional control and to eradicate distant metastases.

Nasopharyngeal carcinoma: orderly neck node spread.

A prospective study of 271 consecutive patients with newly diagnosed nasopharyngeal carcinoma was undertaken to assess the pattern of cervical nodal involvement with reference to 10 cervical nodal groups and three levels of neck; 204 (75.3%) patients were found to have cervical lymphadenopathy at presentation. Fifty-four (26.5%) of these patients had right cervical lymphadenopathy, 70 (34.3%) had left cervical lymphadenopathy, and 80 (39.2%) had bilateral cervical lymphadenopathy. The occurrence of lymphadenopathy in the 10 cervical nodal groups and the mean size of nodes in these nodal groups were computed. The subdigastric and upper jugular group was involved in more than 95% of cases. The lower the position in the neck, the less frequently the nodal group was involved. The mean size of nodes was largest in the subdigastric and upper jugular region compared with the other groups. The nodes in the upper neck were generally larger than those in the lower neck. The lower two levels of neck were involved without involvement of the upper level of the ipsilateral neck in fewer than 4% of cases. The present study indicates that neck node involvement by nasopharyngeal carcinoma is by orderly spread down the neck, which explains the adverse prognostic significance of neck node involvement in the lower neck. The orderly involvement of the neck nodes suggests that prophylactic irradiation of the neck should be given at least one level beyond the clinical extent of disease, which for patients with no clinically palpable node would mean prophylactic irradiation of the upper neck.

Nasopharyngeal carcinoma with dermatomyositis.

From 1976 to 1986, ten out of 1154 consecutive nasopharyngeal carcinoma (NPC) patients were found to have dermatomyositis (DM). Their clinical features and treatment results were analyzed. The skin manifestation was typical of DM and myopathy occurred in seven patients. All the tumor on presentation were early stage and locoregional control after radiotherapy was satisfactory. All but one patient had DM prior to diagnosis of NPC. The prognosis of NPC was not affected by DM with survival being comparable to contemporary controls. The complication of radiotherapy were unusually severe. Chronic radiation skin ulceration occurred in 2 patients and subcutaneous indurated fibrosis affecting both sides of neck occurred in all patients. Acute radiation mucositis was also prominent.

A randomized study on palliative radiation therapy for inoperable non small cell carcinoma of the lung.

Between October 1981 and November 1984, 291 patients with inoperable advanced non-small cell carcinoma of the lung (NSCLC) were randomized to a two-arm study. Eighteen of 291 defaulted treatment and were excluded from the study. Twenty-seven of 273 died during treatment; they were invaluable for treatment response but were included in survival analysis. Without correction for lung attenuation 45 Gy/18 fractions/4 1/2 weeks were given in arm 1 and 31.2 Gy/4 fractions/4 weeks were given in arm 2. One hundred twenty-eight of 273 were included in arm 1 and 145/273 in arm 2. The two arms were comparable in patient age, sex, performance status and symptoms, primary tumor site, histology, stage of the disease, and distribution of metastases and radiation portal size used. Prognosis was poor with an overall median survival of 20 weeks and was similar in both arms. Radiological tumor response was also similar: 53% in arm 1 and 50% in arm 2. However arm 1 was superior than arm 2 in achieving symptom palliation, 71% vs 54%, p less than 0.02. Treatment complications were mild and included mainly radiation oesophagitis and pneumonitis and pulmonary fibrosis. Treatments in both arms were equally well tolerated.

Adjunctive chemotherapy to radical radiation therapy in the treatment of advanced nasopharyngeal carcinoma.

Sixty-eight consecutive patients with previously untreated nasopharyngeal carcinoma (NPC) with advanced cervical lymph nodal metastases were studied retrospectively for the effectiveness of combining chemotherapy with radical radiation therapy (RT). In 1981 and 1982, 36 patients were treated with radical radiation therapy alone (arm 1). In 1983, 13 patients were given 2 courses of VBMF prior to RT (arm 2). In 1984, 19 patients were given radical RT sandwiched between 2 courses of PVBMF before and 2 after (arm 3). The three arms were comparable in patient characteristics with similar stages of the disease, sex, age distribution, and rates of completion of the prescribed treatments. There was no significant difference in actuarial or disease-free survival between arm 1 and 3 or arm 2 and 3, but arm 1 compared favorably with arm 2 in actuarial survival (X2 = 9.533, p = 0.002). The distant relapses in arms 2 and 3 occurred at significantly shorter times after diagnosis than those in arm 1 (t = 4.1083, p = 0.0001). Postponement of radiation therapy by chemotherapy might have accounted for the earlier distant relapses in arm 2 and 3. Radiation therapy alone given in radical dose had been demonstrated to achieve significantly more complete responses in cervical nodal metastases than either forms of chemotherapy (VBMF or PVBMF) given just two courses prior to radiation therapy (p less than 0.00003). More controlled clinical trials must be completed before acceptance of chemotherapy as part of a standard radical treatment for advanced nasopharyngeal carcinoma with advanced cervical lymph nodal metastases. In all future trials, closer integration in time sequence between the two treatment modalities is indicated. Meanwhile cervical nodal status (CR vs, PR plus NR) at the end of any treatment was shown to be of paramount prognostic significance.

Transpalatal insertion of radioactive gold grain for the treatment of persistent and recurrent nasopharyngeal carcinoma.

PURPOSE: To evaluate the efficacy of radioactive gold grain implant via the split palate approach in the control of locally recurrent or persistent nasopharyngeal carcinoma. METHODS AND MATERIAL: Forty-three patients, 10 for persistent NPC, 28 for first relapse in the nasopharynx, and five for second relapse in the nasopharynx, were treated. The diameter of the tumors at the time of gold grain implant ranged from 0.5 to 5 cm, the number of gold grains inserted varied from 4 to 14, the median number was seven. RESULTS: There was no significant difference in the control of the primary tumor for persistent disease (80% at 5 years), first relapse (61% at 5 years) and second relapse (80% at 3 years), p = 0.8845. The difference in survival between the three subgroups of patients, however, was highly significant (p = 0.0040). Thirty patients had CT evaluation before gold grain implant and the tumor was found confined to the nasopharynx in 21, in the remaining nine patients erosion of the sphenoid sinus or other parts of the base of skull was noted. The difference in the control between those patients with tumors confined to the nasopharynx and those patients with extranasopharyngeal extension of tumor almost reached statistical significance (81% and 44% respectively at 5 years, p = 0.0554). For the six patients who developed local recurrence after gold grain implant and were evaluable for the pattern of failure, the recurrent tumors were considered originating from another region of the nasopharynx in four, and in-field failure in the other two cases. CONCLUSION: Radioactive gold grain implant as salvage treatment provides satisfactory control of persistent and recurrent nasopharyngeal carcinoma. The local control was better when the tumor was localized to the nasopharynx, thus underlines the importance of close follow-up for early recognition of relapse and persistent tumor. However, such patients still suffered from high incidence of regional and distant failure, the pathophysiology and management of which require further investigation.

Computed tomography evaluation of neck node metastases from nasopharyngeal carcinoma.

PURPOSE: To study the role of computed tomography in the pre-therapy evaluation of nasopharyngeal carcinoma. METHODS AND MATERIALS: The computed tomography of 119 new patients of nasopharyngeal carcinoma were evaluated independent of clinical findings for neck node metastases, and then compared with clinical findings. Contrast enhanced axial scans were obtained at 5 mm intervals with the infraorbitomeatal line parallel to the gantry. Scans were obtained from the supra-sellar cistern to the C5 or C6 vertebra for the evaluation of the base of skull, nasopharynx, paranasopharyngeal space and the upper and mid neck. RESULT: The present study confirmed the disparity of nodal extent documented by clinical palpation and computed tomography. Of the 37 patients who have no clinically palpable node (N0), computed tomography showed nodal involvement in 11 (29.7%) of them, and they were up-staged from N0 to N1. Computed tomography showed multiple or bilateral nodes in seven (58.3%) of the 12 patients with AJC N1 disease and they were hence up-staged to N2. All together, there were 28 (23.5%) patients who have no computed tomography evidence of nodal involvement by tumor. In agreement with clinical experience, the most commonly involved nodal groups were the upper internal jugular and upper spinoaccessary, followed by the lateral retropharyngeal. The percentage of nodes which were not clinically palpable was roughly the same for different regions (15-30%), except, as expected, that all the retropharyngeal nodes were not palpable. The risk of harboring retropharyngeal node was proportional to the size of the largest node in the ipsilateral neck. CONCLUSION: A significant proportion of patients with clinically negative neck (N0) or AJC N1 disease will be upstaged by computed tomography, thus supporting its routine use in pre-therapy evaluation of nasopharyngeal carcinoma.

Radiotherapy for nasopharyngeal carcinoma: shielding the pituitary may improve therapeutic ratio.

PURPOSE: Nasopharyngeal carcinoma (NPC) is well known for its invasiveness and erosion of the base of the skull is not uncommon. Before the advent of computed tomography, the evaluation of the base of the skull was by plain radiography. Because of the low sensitivity of these investigations, traditional teaching has included the sphenoid sinus in the volume of irradiation. Increase in longevity of patients allows the manifestation and documentation of the long-term sequelae of irradiating the hypothalamic-pituitary axis and the temporal lobes. This study is an attempt to evaluate whether the hypothalamic-pituitary axis can be shielded from the target volume in a proportion of NPC patients. METHODS AND MATERIALS: One hundred fifty-two NPC patients with no evidence of erosion of the base of the skull and sphenoid, nor extension to the nasal fossa and ethmoid sinuses were randomized to receive standard radiotherapy covering the whole sphenoid sinus or radiotherapy using a modified technique that shields the pituitary and the anterior part of the hypothalamus. This modified technique also shields a large part of the lower temporal lobes that are otherwise covered by standard treatment portals. The characteristics and treatment of the two subgroups of patients were otherwise comparable. RESULTS: At a median follow-up of 31.5 months, the tumor control between the two subgroups of patients were comparable (p = 0.3928). However, 8 of the 71 patients in the unshielded group had developed symptomatic neuroendocrine complications, while none of the other group did (p = 0.0061). Two patients developed secondary hypothyroidism, one patient developed oligomenorrhoea associated with raised prolactin, and five patients developed temporal lobe necrosis. CONCLUSIONS: The protective effect on neuroendocrine complication of this shield was demonstrated at median follow-up of 31.5 months, and the local control was not jeopardized. Modification of treatment technique as presently described, which is applicable to one-third of NPC patients to improve the therapeutic ratio, is recommended for general use.

The effect of interruptions and prolonged treatment time in radiotherapy for nasopharyngeal carcinoma.

PURPOSE: The effect of interruptions and prolonged overall treatment time in radiotherapy for nasopharyngeal carcinoma and the significance of timing of interruption was investigated. METHODS AND MATERIALS: Treatment records of 229 patients treated with continuous course (CC) and 567 patients treated with split course (SC) radiotherapy for nonmetastatic NPC were reviewed. Overall treatment time without inclusion of time for boost was calculated. Treatment that extended 1 week beyond scheduled time was considered prolonged. Outcome in patients who completed treatment "per schedule" were compared with those who had "prolonged" treatment. Because of known patient selection bias between CC and SC, patients on the two schedules were analyzed separately. Multivariate analysis was performed for patients on SC. Total number of days of interruption, age, sex, T and N stage, and the use of boost were tested for the whole SC group. Analysis on the effect of timing of interruption was performed in a subgroup of 223 patients on SC who had a single unplanned interruption. Timing of interruption, either before or after the fourth week for the unplanned interruption, was tested in addition to the other variables in multivariate analysis for this subgroup of SC. RESULTS: Twenty-seven (11.8%) patients on CC and 96 (16.9%) patients on SC had prolonged treatment. Patients on SC who had prolonged treatment had significantly poorer loco-regional control rate and disease free survival when compared with those who completed radiotherapy per schedule (p = 0.0063 and 0.001, respectively, with adjustment for stage). For CC, the effect of prolonged treatment on outcome was not significant. The small number of events for patients on CC probably account for the insignificant finding. The number of days of interruption was confirmed as prognostic factor, independent of T and N stages, for loco-regional control and disease-free survival in multivariate analysis for SC. The hazard rate for loco-regional failure increased by 3.3% for each day of interruption. The timing of interruption, at the beginning or towards end of treatment, did not significantly alter outcome. CONCLUSION: Interruptions and prolonged treatment adversely affect outcome in radiotherapy for NPC and the effect of repopulation was confirmed. Every effort should be made to keep treatment on schedule and interruptions for whatever reasons should be minimized.

Volumetric analysis of tumor extent in nasopharyngeal carcinoma and correlation with treatment outcome.

PURPOSE: To investigate the variability of tumor volume in nasopharyngeal carcinoma using quantitative measurements of tumor bulk derived from computed tomography, and to study the prognostic value of tumor volume in comparison with other variables. METHODS AND MATERIALS: Two hundred ninety patients with newly diagnosed nasopharyngeal carcinoma were included in the study. The primary tumor volume (PTV) and nodal tumor volume (NTV) were obtained by outlining the tumor contour followed by summation of areas in sequential pretreatment computed tomography axial scans. Total tumor volume (TTV) was obtained by adding the PTV and NTV. All patients had radiotherapy as the primary treatment, 67 patients also received cisplatin-based neoadjuvant chemotheraphy. RESULTS: A large variation in tumor volume was observed, especially in advanced stage disease. The median PTV (cc) in Ho's T1, T2, and T3 disease were: 6.9 (range: 0.9-42.7), 18.8 (1.6-127.9), and 52.4 (3.3-166.8). The median TTV (cc) in Ho's stage I to IV disease were: 7.6 (range: 1.3-42.7), 19.8 (3.2-55.7), 40.7 (4.1-222.7), and 51.1 (3.1-274.7). Patients with a large PTV (>60 cc) were associated with significantly poorer local control (5-year local control rate: 56%) and disease-specific survival (5-year survival rate: 53%). In patients with a small PTV (< or =20 cc), there were no significant differences in local control among different T stages. Large NTV (>30 cc) was associated with significantly higher distant failure rate (5-year distant relapse-free survival rate: 54%) and lower disease-specific survival (5-year survival rate: 40%). In multivariate analysis, only PTV was found to be an independent factor in predicting local control. CONCLUSION: A large variation of tumor volume was present in different T stage disease of nasopharyngeal carcinoma, and PTV represents an independent prognostic factor of local control that appears to be more predictive than Ho's T stage classification.