Biomedical subjects

Lucullus H T Leung

Publications and source records attributed to Lucullus H T Leung.

12 recordsLinked to original sources

PubMed2006

Xerostomia and quality of life after intensity-modulated radiotherapy vs. conventional radiotherapy for early-stage nasopharyngeal carcinoma: initial report on a randomized controlled clinical trial.

PURPOSE: To compare directly the effect of intensity-modulated radiotherapy (IMRT) vs. conventional radiotherapy (CRT) on salivary flow and quality of life (QoL) in patients with early-stage nasopharyngeal carcinoma (NPC). METHODS AND MATERIALS: Fifty-one patients with T2, N0/N1, M0 NPC took part in a randomized controlled clinical study and received IMRT or CRT. Stimulated whole (SWS) and parotid (SPS) saliva flow were measured and Medical Outcomes Short Form 36 (SF-36), European Organization for Research and Treatment of Cancer (EORTC) core quetionnaire, and EORTC head-and-neck module (QLQ-H&N35) were completed at baseline and 2, 6, and 12 months after radiotherapy. RESULTS: Forty-six patients (88%) were in disease remission 12 months after radiotherapy. At 12 months postradiotherapy, 12 (50.0%) and 20 patients (83.3%) in the IMRT group had recovered at least 25% of preradiotherapy SWS and SPS flow respectively, compared with 1 (4.8%) and 2 patients (9.5%), respectively, in the CRT group. Global health scores showed continuous improvement in QoL after both treatments (p < 0.001). However, after 12 months subscale scores for role-physical, bodily pain, and physical function were significantly higher in the IMRT group, indicating a better condition (p < 0.05). Dry mouth and sticky saliva were problems in both groups 2 months after treatment. In the IMRT group, there was consistent improvement over time with xerostomia-related symptoms significantly less common than in the CRT group at 12 months postradiotherapy. CONCLUSIONS: IMRT was significantly better than CRT in terms of parotid sparing and improved QoL for early-stage disease. The findings support the case for assessment of health-related QoL in relation to head-and-neck cancer using a site-specific approach.

Adult↗

PubMed2006

Predictive factors of tumor control and survival after radiosurgery for local failures of nasopharyngeal carcinoma.

BACKGROUND: Stereotactic radiosurgery has been employed as a salvage treatment of local failures of nasopharyngeal carcinoma (NPC). To identify patients that would benefit from radiosurgery, we reviewed our data with emphasis on factors that predicted treatment outcome. PATIENTS AND METHODS: A total of 48 patients with local failures of NPC were treated by stereotactic radiosurgery between March 1996 and February 2005. Radiosurgery was administered using a modified linear accelerator with single or multiple isocenters to deliver a median dose of 12.5 Gy to the target periphery. Median follow-up was 54 months. RESULTS: Five-year local failure-free probability after radiosurgery was 47.2% and 5-year overall survival rate was 46.9%. Neuroendocrine complications occurred in 27% of patients but there were no treatment-related deaths. Time interval from primary radiotherapy, retreatment T stage, prior local failures and tumor volume were significant predictive factors of local control and/or survival whereas age was of marginal significance in predicting survival. A radiosurgery prognostic scoring system was designed based on these predictive factors. Five-year local failure-free probabilities in patients with good, intermediate and poor prognostic scores were 100%, 42.5%, and 9.6%. The corresponding five-year overall survival rates were 100%, 51.1%, and 0%. CONCLUSION: Important factors that predicted tumor control and survival after radiosurgery were identified. Patients with good prognostic score should be treated by radiosurgery in view of the excellent results. Patients with intermediate prognostic score may also be treated by radiosurgery but those with poor prognostic score should receive other salvage treatments.

Adult↗

PubMed2006

White matter anisotropy in post-treatment childhood cancer survivors: preliminary evidence of association with neurocognitive function.

PURPOSE: We aim to determine if the loss of white matter fractional anisotropy (FA), measured by diffusion tensor magnetic resonance imaging (DTI), in post-treatment childhood medulloblastoma (MED) and acute lymphoblastic leukemia (ALL) survivors correlate with intelligence quotient (IQ) scores. MATERIALS AND METHODS: MED and ALL survivors (n = 30; 20 male, 10 female; age range, 6.0 to 22.1 years; mean, 13.1 years) were recruited for DTI and IQ tests. In this cross-sectional study, age-matched normal control (n = 55; 32 male, 23 female; age range, 6.0 to 23 years; mean, 12.1 years) DTI was obtained to compute percentage difference in white matter FA (DeltaFA%) for each patient compared with the age-matched control group. Multivariate regression analysis was performed to determine the relationships between DeltaFA%, age at treatment, irradiation dose, time interval from treatment, and full-scale IQ (FSIQ), verbal IQ (VIQ), and performance IQ (PIQ). Receiver operating characteristics curves were used to determine the best DeltaFA% cutoffs for predicting FSIQ, VIQ, and PIQ of less than 85. RESULTS: DeltaFA% had a significant effect on FSIQ (adjusted r2 = 0.439; P < .001), VIQ (adjusted r(2) = 0.237; P = .028), and PIQ (adjusted r(2) = 0.491; P < .001) after adjusting for the effects of age at treatment, irradiation dose, and time interval from treatment. The best DeltaFA% value to predict less than 85 scores in FSIQ, VIQ, and PIQ was -3.3% with specificities of 100% and sensitivities ranging from 77.8% to 87.5%. CONCLUSION: Our preliminary findings suggest that white matter FA may be a clinically useful biomarker for the assessment of treatment-related neurotoxicity in post-treatment childhood cancer survivors.

Adolescent↗

PubMed2006

Mapping radiation dose distribution on the fractional anisotropy map: applications in the assessment of treatment-induced white matter injury.

We describe a method to map whole brain radiation dose distribution on to diffusion tensor MR (DT-MR) fractional anisotropy (FA) images and illustrate its applications for studying dose-effect relationships and regional susceptibility in two childhood medulloblastoma survivors. To determine the FA changes voxel-by-voxel in white matter, the post-treatment follow-up FA maps were coregistered to baseline pre-treatment FA maps and automatic segmentation for white matter was carried out. DeltaFA maps representing relative FA change in white matter were hence generated for visual inspection and quantitative analysis. The radiation dose distribution, calculated from radiotherapy plan and exported as images, was coregistered to baseline FA images. DT-MR imaging and processing noise was small with root mean square value of 1.49% for mean DeltaFA. We evaluated the mean DeltaFA changes of regions-of-interest according to radiation dose regions to provide an estimate of the dose-response and found increasing reduction in mean DeltaFA with increasing radiation dose up to 45 Gy after which there was a reversal in the mean FA trend and mean FA approached baseline value. We also found more severe mean FA reduction in the frontal lobes compared to the parietal lobes despite the same radiation dose, suggesting regional susceptibility in the frontal lobe, and mean FA increase in the brainstem after radiation in both patients. We conclude that the method described may be useful in estimating dose-effect relationships and studying regional susceptibility of the brain to radiation in medulloblastoma survivors.

Anisotropy↗

PubMed2006

Preservation of quality of life after intensity-modulated radiotherapy for early-stage nasopharyngeal carcinoma: results of a prospective longitudinal study.

BACKGROUND: Xerostomia is a ubiquitous complication after conventional radiotherapy for nasopharyngeal carcinoma (NPC) that seriously impairs patient quality of life (QOL). The effect on QOL of parotid-sparing intensity-modulated radiotherapy (IMRT) for early-stage NPC was assessed prospectively. METHODS: Thirty-two patients with T1-2,N0-1,M0 NPC received IMRT. Saliva flow was measured, and the Medical Outcomes Short Form 36 (SF-36), European Organization for Research and Treatment of Cancer (EORTC) core, and EORTC head and neck module (QLQ-H&N35) questionnaires were completed at baseline and 2, 6, and 12 months after IMRT. RESULTS: Saliva flow recovered to at least 25% of baseline in most cases after 1 year. Physical function, fatigue, and vitality were problems at 2 months and then resolved (p < or = .002). Global health scales showed continuous improvement in QOL after treatment (p < or = .004). Xerostomia and sticky saliva were problems 2 months after treatment; thereafter, continuous improvement occurred (p < or = .001). Xerostomia scores correlated with general aspects of QOL (p < or = .044). CONCLUSION: IMRT for early-stage disease preserved key aspects of QOL, and a reduction in xerostomia symptoms enhanced broader aspects of QOL.

Adult↗

PubMed2005

Re-irradiation of nasopharyngeal carcinoma with intensity-modulated radiotherapy.

BACKGROUND AND PURPOSE: To evaluate the treatment outcome in patients with locally recurrent nasopharyngeal carcinoma (NPC) treated with intensity-modulated radiation therapy (IMRT). MATERIALS AND METHODS: Between October 2001 and May 2004, 31 patients with locally recurrent NPC received re-irradiation using IMRT. The rT classification distribution was 3 for rT1, 5 for rT2, 9 for rT3, and 14 for r T4. Median time from first course of radiotherapy to re-irradiation was 51 months. IMRT was performed using step-and-shoot method with nine 4-6 MV photon fields and median prescribed dose was 54 Gy (range: 50-60 Gy). Additional treatments included cisplatin-based induction chemotherapy in 68% and radiosurgery boost with a single dose which ranged from 8.5 to 12.5 Gy in 32%. Median follow-up time was 11 months. RESULTS: After re irradiation, 58% of patients had complete regression of primary tumor. One-year loco-regional progression-free, distant metastasis-free and overall survival rates were 56, 90, and 63%, respectively. Significantly better 1-year local progression-free rate was observed in rT1-3 than r T4 tumor (100 vs. 35%). Grade 3 late toxicities, mostly ototoxicity/cranial neuropathy, occurred in six patients (19%). One-year actuarial rates of late toxicities were 70% for all grades and 25% for Grade 3. CONCLUSION: Our preliminary results showed that good control of rT1-3 NPC can be achieved using IMRT with a dose between 50 and 60 Gy, whereas the outcome for r T4 tumor remained poor. Late toxicities were common but incidence of severe toxicities was relatively low.

Adult↗

PubMed2005

Preliminary results of radiation dose escalation for locally advanced nasopharyngeal carcinoma.

PURPOSE: To study the safety and efficacy of dose escalation in tumor for locally advanced nasopharyngeal carcinoma (NPC). METHODS AND MATERIALS: From September 2000 to June 2004, 50 patients with T3-T4 NPC were treated with intensity-modulated radiotherapy (IMRT). Fourteen patients had Stage III and 36 patients had Stage IVA-IVB disease. The prescribed dose was 76 Gy to gross tumor volume (GTV), 70 Gy to planning target volume (PTV), and 72 Gy to enlarged neck nodes (GTVn). All doses were given in 35 fractions over 7 weeks. Thirty-four patients also had concurrent cisplatin and induction or adjuvant PF (cisplatin and 5-fluorouracil). RESULTS: The average mean dose achieved in GTV, GTVn, and PTV were 79.5 Gy, 75.3 Gy, and 74.6 Gy, respectively. The median follow-up was 25 months, with 4 recurrences: 2 locoregional and 2 distant failures. All patients with recurrence had IMRT alone without chemotherapy. The 2-year locoregional control rate, distant metastases-free and disease-free survivals were 95.7%, 94.2%, and 93.1%, respectively. One treatment-related death caused by adjuvant chemotherapy occurred. The 2-year overall survival was 92.1%. CONCLUSIONS: Dose escalation to 76 Gy in tumor is feasible with T3-T4 NPC and can be combined with chemotherapy. Initial results showed good local control and survival.

Adult↗

PubMed2005

White matter anisotropy in childhood medulloblastoma survivors: association with neurotoxicity risk factors.

PURPOSE: To prospectively evaluate the relationships between change in white matter (WM) anisotropy and (a) patient age at craniospinal irradiation (CSI), (b) CSI dose, and (c) time of magnetic resonance (MR) imaging since CSI and to determine the effect of these neurotoxicity risk factors on WM anisotropy in posttreatment medulloblastoma survivors. MATERIALS AND METHODS: Informed consent was obtained from the patients, control subjects, or their parents, and the study was approved by the institutional review board. Twenty consecutive medulloblastoma survivors (14 male, six female; mean age, 11.0 years +/- 4.6 [standard deviation]) and 36 control subjects (14 male, 22 female; mean age, 10.7 years +/- 3.5) were examined. Control subjects were divided into four groups according to age: 5.0-7.9 years, 8.0-10.9 years, 11.0-13.9 years, and 14.0-18.9 years. The authors calculated the histogram-derived mean WM fractional anisotropy (FA) value for each patient and compared it with the mean WM FA value for the control subjects in the corresponding age group to evaluate the percentage change in WM FA (DeltaFA) in each patient. Spearman rank correlation analysis was used to analyze the relationships between DeltaFA and (a) age at CSI, (b) CSI dose, and (c) time of MR imaging since CSI. Then, multiple linear regression analysis was performed to study the simultaneous influence of these factors on DeltaFA. RESULTS: There were significant correlations between DeltaFA and both age at CSI (r = 0.631, P = .003) and CSI dose (r = -0.586, P = .007) but not between DeltaFA and time of MR imaging since CSI. Multiple linear regression analysis revealed age at CSI to be the only independent variable that significantly affected DeltaFA (adjusted r2= 0.391, P = .012). CONCLUSION: Loss of WM anisotropy is significantly affected by age at CSI, and there is a trend toward increasing anisotropy loss with larger CSI dose. Both age at CSI and CSI dose are known risk factors of neurotoxicity.

Adolescent↗

PubMed2004

Intensity-modulated radiotherapy for early-stage nasopharyngeal carcinoma: a prospective study on disease control and preservation of salivary function.

BACKGROUND: Xerostomia is a uniform complication after radiotherapy (RT) for nasopharyngeal carcinoma (NPC). Dosimetric studies suggested that intensity-modulated RT (IMRT) can spare part of the parotid glands from high-dose radiation. Disease control and salivary function after IMRT for early-stage NPC was studied prospectively. METHODS: Thirty-three patients with T1,N0-N1,M0 NPC were treated with IMRT from 2000 to 2002. The prescribed dose was 68-70 grays (Gy) in 34 fractions to gross tumor volume, 64-68 Gy to the planning target volume, and 70 Gy to enlarged cervical lymph nodes. Nineteen patients had stimulated whole salivary (SWS) flow assessment and stimulated parotid salivary (SPS) flow assessment at baseline and at 2 months, 6 months, 12 months, 18 months, and 24 months after the completion of IMRT. RESULTS: At a median follow-up of 2 years, only 1 neck failure was observed. The 2-year and 3-year local control, distant metastases-free, and overall survival rates all were 100%. The lymph node control and progression-free survival rates were 100% at 2 years and 92.3% at 3 years, respectively. The average mean dose to the parotid gland was 38.8 Gy. The SWS and SPS flow showed continuous recovery: 60% and 47.1% of patients recovered at least 25% of their baseline SPS flow and SWS flow, respectively, at 1 year after completion of IMRT, and the proportions rose to 85.7% and 71.4%, respectively, by 2 years. The pH and buffering capacity of saliva also improved with time. CONCLUSIONS: Parotid-sparing IMRT achieved good locoregional control, and there was continuous recovery of salivary flow, pH, and buffering capacity in the first 2 years after IMRT in patients with NPC.

Adult↗

PubMed2004

Tumor volume is not an independent prognostic factor in early-stage nasopharyngeal carcinoma treated by radiotherapy alone.

PURPOSE: To determine whether the tumor volume can predict the treatment outcome in early-stage nasopharyngeal carcinoma (NPC) treated by radiotherapy alone. METHODS AND MATERIALS: The pretreatment CT scans of 116 patients with American Joint Committee on Cancer Stage I-II NPC treated by radiotherapy alone were retrospectively reviewed. The clinician outlined the tumor extent. The primary tumor volume (PTV) and nodal volume (NV) were then calculated by a summation-of-areas technique. The PTV and NV were correlated with locoregional control, distant failure, and survival. The median follow-up time was 105 months. RESULTS: Patients with Stage I disease had a 5-year locoregional control rate of 95% and a disease-specific survival (DSS) rate of 97%; for Stage II disease, the corresponding rates were 81% and 79%. The PTV ranged from 1.3 to 75.5 cm3 (median, 12.6 cm3), with substantial overlap between T1 and T2 disease. The NV ranged from 0 to 35.4 cm(3). Patients with a PTV >15 cm3 had significantly worse local control (5-year control rate, 82% vs. 93%; p = 0.033), but no statistically significant difference was noted in survival (5-year DSS rate, 83% vs. 89%; p = 0.30). The difference in local control was mainly seen in those with T2 disease. Patients with NV >4 cm3 had a greater distant failure rate (5-year distant metastasis-free rate, 72% vs. 90%; p = 0.011) and worse survival (5-year DSS rate, 76% vs. 94%; p = 0.0038). Nodal control was excellent with no difference between a NV of < or =4 cm3 and a NV of >4 cm3 (5-year control rate, 97% vs. 100%). The survival rate was worst in patients with a PTV >15 cm3 and a NV >4 cm3 (5-year DSS rate, 68%) and best in those with a PTV of < or =15 cm3 and a NV of < or =4 cm3 (5-year DSS rate, 92%). Multivariate analysis, however, showed that only parapharyngeal extension (T2b) and N1 stage were independent factors that predicted locoregional control and survival, and N1 stage was the only factor that predicted distant failure. CONCLUSION: The pretreatment tumor volume has a limited prognostic value in early-stage NPC compared with the usual T and N classification, with Stage T2b and N1 as independent factors that predicted treatment outcome. Within T2 disease, the estimation of tumor volume may identify a subgroup of patients with a greater risk of local failure that warrants more aggressive treatment.

Adult↗

PubMed2004

White-matter diffusion anisotropy after chemo-irradiation: a statistical parametric mapping study and histogram analysis.

The aim of the study was to evaluate white-matter (WM) diffusion anisotropy in medulloblastoma survivors after cranial irradiation and chemotherapy using voxel-based analysis with SPM99 and fractional anisotropy (FA) histogram-derived indices, and to identify quantitative indices for detecting and monitoring children with treatment-induced white-matter injury. Familywise error rate (FWE) that corrects for multiple comparisons was used to locate statistically significant regions of P < 0.05 in voxel-based analysis. Subsequently, the false discovery rate (FDR) controlling procedure (corrected P < 0.05) was used. FA map histogram analysis of histogram-derived indices, mean FA, mean FA peak height, and peak location was performed. Two-sample t test was used in all analyses. Using FWE-corrected P < 0.05, there was a cluster of reduced anisotropy in the periventricular white matter lateral to the left ventricular atrium. When FDR-corrected P < 0.05 was used, there were multiple clusters of reduced anisotropy in the periventricular white matter, the corpus callosum, and corona radiata. Simplified voxel-based morphometry (VBM)-like analysis of cerebrospinal fluid (CSF) did not show significant differences between patient and control subjects. 'White-matter FA map' histogram showed significant reduction in mean FA and mean FA peak location and significant increase in mean FA peak height in the patient group compared to control subjects (P = 0.003, P = 0.003, and P = 0.014, respectively). This approach of quantifying FA can be applied to characterize anisotropy in the white matter after cranial irradiation and chemotherapy and can potentially be used to detect and monitor treatment-induced neurotoxicity.

Adolescent↗

PubMed2003

Linear accelerator-based stereotactic radiosurgery for limited, locally persistent, and recurrent nasopharyngeal carcinoma: efficacy and complications.

PURPOSE: To evaluate the efficacy and complication of linear accelerator-based stereotactic radiosurgery (SRS) when used as salvage treatment for early-stage persistent and recurrent nasopharyngeal carcinoma (NPC) after primary radiotherapy (RT). MATERIALS AND METHODS: Between March 1998 and June 2001, 18 patients (15 men and 3 women; median age 46 years, range 32-84) with locally persistent or recurrent NPC confined to the nasopharynx (rT1) or with limited extension to the nasal fossa or parapharyngeal space (rT2) were treated by SRS. Thirteen patients had rT1 disease and 5 had rT2 disease. Most patients had disease not amenable to surgery or brachytherapy. All patients had undergone previous radical RT. Persistent disease was defined as tumor relapse within 4 months of completion of primary RT, and recurrence as tumor relapse beyond 4 months. Seven patients were treated for persistent disease, eight for a first recurrence, and three for a second recurrence. SRS was performed using multiple noncoplanar arcs of photons delivered to the target volume, which was defined by axial CT at a 3 mm thickness, supplemented by MRI in selected patients (67%). The median target volume was 5.3 cm(3) (range 2.2-16.9). The median SRS dose was 12.5 Gy (range 11-14) delivered to the 80% isodose line. All patients underwent serial nasopharyngoscopy and imaging after SRS. The median follow-up was 26 months (range 11-48). RESULTS: After SRS, 16 (89%) of 18 patients had complete regression of tumor as assessed by nasopharyngoscopy and biopsy. Four patients with an initial complete response to SRS subsequently developed local relapse again, with one recurrence developing outside the target volume 8 months after SRS and three within the target volume at 6-26 months after SRS. Two patients with local disease controlled by SRS developed relapse in other sites (neck node and liver metastases). The actuarial 2-year local control rate after SRS was 72%. Patients treated for persistent disease had a better local control rate (100%; 7 of 7) than those treated for recurrent disease (46%; 5 of 11). Patients with rT1 disease also had a better outcome after SRS compared with those with rT2 disease, with a control rate of 77% (10 of 13) for rT1 disease and 40% (2 of 5) for rT2 disease. Treatments were well tolerated, with no acute side effects. One patient had radiologic evidence of temporal lobe necrosis, although the right temporal lobe had already received a high dose during prior RT. That patient also developed additional local recurrence and liver metastases and died. The actuarial 2-year survival rate was 86%. CONCLUSIONS: Our preliminary results indicate that SRS is an effective treatment modality for persistent and recurrent early-stage NPC, with early control rates comparable to other salvage treatments such as brachytherapy and nasopharyngectomy. A modest SRS dose at 12.5 Gy also appears to be effective and is associated with minimal morbidities. More clinical experience and longer follow-up are needed to validate our results and to address fully the role of SRS in salvaging local failures of NPC.

Adult↗