Surgery or radiosurgery plus whole brain radiotherapy versus surgery or radiosurgery alone for brain metastases.

BACKGROUND: The benefits of adding upfront whole-brain radiotherapy (WBRT) to surgery or stereotactic radiosurgery (SRS) when compared to surgery or SRS alone for treatment of brain metastases are unclear. OBJECTIVES: To compare the efficacy and safety of surgery or SRS plus WBRT with that of surgery or SRS alone for treatment of brain metastases in patients with systemic cancer. SEARCH METHODS: We searched MEDLINE, EMBASE and The Cochrane Central Register of Controlled Trials (CENTRAL) up to May 2013 and annual meeting proceedings of ASCO and ASTRO up to September 2012 for relevant studies. SELECTION CRITERIA: Randomised controlled trials (RCTs) comparing surgery or SRS plus WBRT with surgery or SRS alone for treatment of brain metastases. DATA COLLECTION AND ANALYSIS: Two review authors undertook the quality assessment and data extraction. The primary outcome was overall survival (OS). Secondary outcomes include progression free survival (PFS), local and distant intracranial disease progression, neurocognitive function (NF), health related quality of life (HRQL) and neurological adverse events. Hazard ratios (HR), risk ratio (RR), confidence intervals (CI), P-values (P) were estimated with random effects models using Revman 5.1 MAIN RESULTS: We identified five RCTs including 663 patients with one to four brain metastases. The risk of bias associated with lack of blinding was high and impacted to a greater or lesser extent on the quality of evidence for all of the outcomes. Adding upfront WBRT decreased the relative risk of any intracranial disease progression at one year by 53% (RR 0.47, 95% CI 0.34 to 0.66, P value < 0.0001, I(2) =34%, Chi(2) P value = 0.21, low quality evidence) but there was no clear evidence of a difference in  OS (HR 1.11, 95% CI 0.83 to 1.48, P value = 0.47, I(2) = 52%, Chi(2) P value = 0.08, low quality evidence) and PFS (HR 0.76, 95% CI 0.53 to 1.10, P value = 0.14, I(2) = 16%, Chi(2) P value = 0.28, low quality evidence). Subgroup analyses showed that the effects on overall survival were similar regardless of types of focal therapy used, number of brain metastases, dose and sequence of WBRT. The evaluation of the impact of upfront WBRT on NF, HRQL and neurological adverse events was limited by the unclear and high risk of reporting, performance and detection bias, and inconsistency in the instruments and methods used to measure and report results across studies. AUTHORS' CONCLUSIONS: There is low quality evidence that adding upfront WBRT to surgery or SRS decreases any intracranial disease progression at one year. There was no clear evidence of an effect on overall and progression free survival. The impact of upfront WBRT on neurocognitive function, health related quality of life and neurological adverse events was undetermined due to the high risk of performance and detection bias, and inconsistency in the instruments and methods used to measure and report results across studies.

Accuracy of (18)F-flurodeoxyglucose-positron emission tomography/computed tomography in the staging of newly diagnosed nasopharyngeal carcinoma: a systematic review and meta-analysis.

BACKGROUND: The specific role of 18F-flurodeoxyglucose-positron emission tomography/computed tomography (FDG-PET/CT) in staging of nasopharyngeal carcinoma (NPC) remains to be validated. A systematic review and meta-analysis were performed to assess the accuracy of staging FDG-PET/CT for newly diagnosed NPC. METHODS: We searched various biomedical databases and conference proceedings for relevant studies. We determined the pooled sensitivities and specificities, diagnostic odds ratios (DOR) and constructed summary receiver operating characteristic (SROC) curves using the hierarchical regression model. RESULTS: 15 relevant studies including 851 patients were identified. Five addressed primary tumor (T), nine addressed regional lymph nodes (N) and seven addressed distant metastasis (M). The combined sensitivity estimate for FDG-PET/CT in T classification was 0.77 (95% confidence interval [CI] 0.59-0.95). For N classification, combined sensitivity was 0.84 (95% CI 0.76-0.91), specificity was 0.90 (95% CI 0.83-0.97), DOR was 82.4 (23.2-292.6) and Q*-index was 0.90. For M classification, the combined sensitivity estimate was 0.87 (95% CI 0.74-1.00), specificity was 0.98 (95% CI 0.96-1.00), DOR was 120.9 (43.0-340.0) and Q*-index was 0.89. CONCLUSION: FDG-PET/CT showed good accuracy in N and M but not T classification for newly diagnosed NPC. FDG-PET/CT, together with Magnetic resonance imaging (MRI) of the nasopharynx, should be part of the routine staging investigations.

Discordance of epidermal growth factor receptor mutation between primary lung tumor and paired distant metastases in non-small cell lung cancer: A systematic review and meta-analysis.

PURPOSE: To evaluate the rate of discordance of epidermal growth factor receptor (EGFR) mutation between primary lung tumor and paired distant metastases in non-small-cell lung cancer (NSCLC). METHODS: We performed a meta-analysis of 17 studies (518 cases) assessing discordance rates of EGFR mutation in primary tumors and paired distant metastases. We performed subgroup analyses based on EGFR mutation status in primary tumor (mutant or wildtype), site of distant metastasis (bone, central nervous system (CNS) or lung/ pleural), methods of testing (direct sequencing or allele-specific testing) and timing of metastasis (synchronous or metachronous). RESULTS: The overall discordance rate in EGFR mutation was low at 10.36% (95% CI = 4.23% to 18.79%) and varied widely between studies (I2 = 83.18%). The EGFR discordance rate was statistically significantly higher in bone metastases (45.49%, 95% CI = 14.13 to 79.02) than CNS (17.26%, 95% CI = 7.64 to 29.74; P = 0.002) and lung/ pleural metastases (8.17%, 95% CI = 3.35 to 14.85; P < 0.001). Subgroup analyses did not demonstrate any significant effect modification on the discordance rates by the EGFR mutation status in primary lung tumor, methods of testing and timing of metastasis. CONCLUSION: The overall discordance rate in EGFR mutation between primary lung tumor and paired distant metastases in NSCLC is low, although higher discordance rates were observed in bone metastases compared with CNS and lung/pleural metastases. Future studies assessing the impact of EGFR mutation discordance on treatment outcomes are required.

Are heart doses associated with survival in patients with non-small cell lung cancer who received post-operative thoracic radiotherapy?: A national population-based study.

The aim of this retrospective national cohort study is to assess the association between various radiation heart dosimetric parameters (RHDPs), acute myocardial infarct (AMI) and overall survival (OS) outcomes in non-small cell lung cancer (NSCLC) patients treated with post-operative thoracic radiotherapy (PORT) using contemporary radiation techniques.We identified patients with stage I to III NSCLC treated with PORT at the 2 national cancer institutions from 2007 to 2014. We linked their electronic medical records to the national AMI and death registries. Univariable Cox regression was performed to assess the association between various RHDPs, AMI, and OS.We included 43 eligible patients with median follow-up of 36.6 months. Median age was 64 years. Majority of the patients had pathological stage III disease (72%). Median prescription dose was 60Gy. Median mean heart dose (MHD) was 9.4Gy. There were no AMI events. The 5-year OS was 34%. Univariable Cox regression showed that age was significantly associated with OS (hazard ratio, 1.06; 95% confidence interval, 1.01 to 1.10; P = .008). Radiation heart doses, including MHD, volume of heart receiving at least 5, 25, 30, 40, 50Gy and dose to 30% of heart volume, were not significantly associated with OS.There is insufficient evidence to conclude that RHDPs are associated with OS for patients with NSCLC treated with PORT in this study. Studies with larger sample size and longer term follow-up are needed to assess AMI outcome.

Implementation of temporal lobe contouring protocol in head and neck cancer radiotherapy planning: A quality improvement project.

Temporal lobe necrosis as result of radiation for nasopharyngeal cancer (NPC) occurs up to 28% of NPC patients. The only effective mitigation is by strict adherence to temporal lobe dose tolerances during radiotherapy planning, which in turn hinges on accurate temporal lobe delineation. We aim to improve the accuracy and to standardize temporal lobe contouring for patients receiving head and neck radiotherapy for NPC in a tertiary teaching hospital in Singapore.The baseline data were obtained from 10 patients in the diagnostic phase and the effect of interventions were measured in 37 patients who underwent head and neck radiotherapy over a 6-month period.We conducted the project based on the Clinical Practice Improvement Program methodology. The baseline pooled mean percentage variation in temporal lobe contouring was 39.9% (0.8%-60.2%). There was a low level of temporal lobe contouring concordance and this provided the impetus for implementation of strategies to improve the accuracy and reproducibility of temporal lobe contouring. The interventions included supervision and training of radiation therapists and residents in temporal lobe contouring, and standardization of temporal lobe contouring with a protocol and contouring atlas.Thirty-seven patients were treated during the study period from June to November 2014. Following implementation of the first set of interventions, the pooled mean percentage variation in temporal lobe contouring decreased but was not sustained. The implementation of the second set of interventions resulted in a decrease from 39.9% (January to September 2014) to 17.3% (October to November 2014) where P = .004 using t test. Weekly variation was seen throughout the study period but the decrease was sustained after standardizing and providing a contouring atlas for temporal lobe contouring.Temporal lobe contouring can be standardized through effective implementation of a temporal lobe contouring protocol and atlas.

Long-term outcomes after reirradiation in nasopharyngeal carcinoma with intensity-modulated radiotherapy: A meta-analysis.

BACKGROUND: The purpose of this clinical review was to summate the published data for the long-term outcomes of reirradiation with intensity-modulated radiotherapy (IMRT) for locally recurrent nasopharyngeal carcinoma (NPC). METHODS: We searched biomedical literature databases for eligible studies published from January 2005 to September 2016. Outcomes of interests were 5-year local failure-free survival, distant failure-free survival, overall survival (OS), and toxicities. Meta-analysis was performed using a random effects model. RESULTS: We found 4 comparative and 8 noncomparative studies (n = 1768). Reirradiation was associated with pooled event rates of 72% (95% confidence interval [CI] 66%-78%; I2 = 84%), 85% (95% CI 82%-88%; I2 = 69%), and 41% (95% CI 36%-47%; I2 = 80%) for 5-year local failure-free survival, distant failure-free survival, and OS, respectively, with significant heterogeneity among the study results. The pooled event rate for grade 5 toxicities was 33% (95% CI 30%-35%; I2 = 0%) with minimal heterogeneity. CONCLUSION: Reirradiation with IMRT for locally recurrent NPC could confer long-term disease control and survival but is associated with significant mortality.

Association between radiation heart dosimetric parameters, myocardial infarct and overall survival in stage 3 non-small cell lung cancer treated with definitive thoracic radiotherapy.

OBJECTIVES: The aim of this retrospective observational study is to assess the association between various radiation heart dosimetric parameters (RHDPs) and acute myocardial infarct (AMI) and overall survival (OS) outcomes in stage III non-small cell lung cancer (NSCLC) treated with definitive radiotherapy with or without chemotherapy. MATERIALS AND METHODS: We identified eligible patients treated at two institutions from 2007 to 2014. We linked their electronic medical records to the national AMI and death registries. We performed univariable and multivariable Cox regressions analysis to assess the association between various RHDPs, AMI and OS. RESULTS: 120 eligible patients were included with a median follow-up of 17.6 months. Median age was 65.5 years. Median prescription dose was 60 Gy. Median mean heart dose (MHD) was 12.6 Gy. Univariable analysis showed that higher MHD (hazard ratio (HR), 1.03; 95% confidence interval (CI), 1.01-1.06; P = .008) and volume of heart receiving at least 5 Gy (V5) (HR, 1.01; 95% CI, 1.00-1.03; P = .042) were associated with increased hazards for AMI. Univariable analysis showed that higher MHD, V5, V25, V30, V40, V50 and dose to 30% of heart volume were associated with increased hazards for death. Multivariable analysis showed that there was no statistically significant association between various RHDPs and OS. CONCLUSION: The incidence of AMI is low among stage III NSCLC treated with definitive radiotherapy with or without chemotherapy. There is insufficient evidence to conclude that RHDPs are associated with AMI or OS in our study.

Adoption of prophylactic cranial irradiation (PCI) for extensive stage small cell lung cancer (ES-SCLC): a population based outcome study.

BACKGROUND: The survival benefit of PCI in ES-SCLC reported by a European randomized trial (RCT) in 2007 was not replicated by a Japanese RCT published in 2017. This study aimed to evaluate the uptake of PCI before and after publication of the European RCT and its association with survival in ES-SCLC. METHODS: We identified eligible patients in the only two Singapore national cancer centres from 2003 to 2010. We linked their electronic medical records to the national death registry. We described the utilization of PCI in patients diagnosed from 2003 to 2006 (pre-adoption cohort) with patients diagnosed from 2007 to 2010 (post-adoption cohort). We performed univariable and multivariable Cox regression analysis to assess the association between PCI and survival. RESULTS: We identified 224 patients with ES-SCLC with no brain metastases. Among the 71 patients who had at least stable disease after first line chemotherapy, there was an increase in the use of PCI from the period 2007 to 2010 compared with 2003 to 2006 (32% versus 10%, P = 0.044). PCI was associated with improved OS (hazard ratio 0.22, 95% CI 0.10 to 0.47, P < 0.001) compared to no PCI in the multivariable analysis. CONCLUSION: There was an increase in the adoption of PCI for ES-SCLC since 2007. PCI was associated with improved survival in patients who did not have mandatory MRI brain imaging prior to PCI and had stable disease or better after first line chemotherapy, suggesting that the results of the European RCT are reproducible in the real-world practice.

A phase II trial of preoperative concurrent chemotherapy and dose escalated intensity modulated radiotherapy (IMRT) for locally advanced rectal cancer.

Objectives: To determine the pathological response rates and toxicity and in patients with locally advanced rectal cancer treated with concurrent capecitabine and dose escalated intensity modulated radiotherapy (IMRT) Methods: Patients with stage II or III adenocarcinoma of the rectum were treated with preoperative concurrent capecitabine and IMRT. Dose of capecitabine was 825mg/m2, 5 days a week for 5 weeks. IMRT was used to deliver a dose of 45Gy in 25 fractions (1.8Gy per fraction daily, 5 days a week over 5 weeks) to the regional lymphatics and areas at risk of harbouring microscopic disease. A concomitant synchronous integrated boost (SIB) to the gross tumour with a margin to a total dose of 55Gy in 25 fractions was also delivered in the same period. TME surgery was performed 8 weeks after preoperative therapy. The primary endpoint is pathological complete response rate (pCR) and the secondary endpoint was downstaging rates, Sphincter preservation rates (SPR), disease free survival (DFS) at 2 years and toxicity graded using the CTCAE v3.0. Results: Twenty three patients were enrolled. Three were not evaluable; one did not complete treatment due to logistic issues and two declined surgery. The remaining 20 patients completed preoperative chemoIMRT followed by TME surgery. At a median follow-up of 38.2 months (17.5-53.2 months), 90% (18 of 20) patients were alive. The 2 year overall survival and DFS were 90% and 90% respectively. 35%(7/20) of patients had a pCR. 65% (13 of 20) patients had successful downstaging of their rectal tumours. There was no local recurrence. Sphincter preservation rate was 85%. Treatment was well tolerated with only one patient (5%) having Grade 3 radiation proctitis. Conclusions: Preoperative concurrent capecitabine and dose escalated IMRT is well tolerated and results in high rates of pCR. A randomized trial comparing this regimen with standard 3D conformal chemoradiotherapy is warranted.

Impact of epidermal growth factor receptor sensitizing mutations on outcomes of patients with non-small cell lung cancer treated with definitive thoracic radiation therapy: a systematic review and meta-analysis.

BACKGROUND: To determine if the presence of epidermal growth factor receptor (EGFR) sensitizing mutations improves tumor control and survival outcomes in patients with non-metastatic non-small cell lung cancer (NSCLC) who received definitive thoracic radiation therapy (TRT) with or without chemotherapy. MATERIALS AND METHODS: We searched MEDLINE for eligible comparative studies which compared the outcomes of patients treated with definitive TRT according to EGFR mutation status. Meta-analysis was performed using random effects model. Outcomes of interest were tumor overall response rate (ORR), loco-regional (LRR), distant recurrence rates (DRR), relapse-free survival (RFS), overall survival (OS) and adverse events (AE). RESULTS: We found seven studies including 537 patients with stage III NSCLC. Up to 45% of patients in the studies had mutations in exon 19 and 21. Patients harbouring EGFR sensitizing mutations had a trend towards improvement in ORR (risk ratio 1.17, 95% confidence interval 0.99-1.37, P = 0.06) compared to EGFR wild type status. There were no significant differences in LRR, DRR, RFS, OS and AE outcomes between the EGFR mutant and EGFR wild type groups. CONCLUSIONS: The presence of EGFR sensitizing mutations may improve tumour response rate but not survival in patients with localized NSCLC treated with definitive thoracic radiation therapy with or without chemotherapy.

EGFR tyrosine kinase inhibitors versus cranial radiation therapy for EGFR mutant non-small cell lung cancer with brain metastases: a systematic review and meta-analysis.

BACKGROUND AND PURPOSE: EGFR TKIs alone have demonstrated activity against intracranial disease in EGFR mutant non-small cell lung cancer (NSCLC). This study aimed to determine if upfront cranial radiotherapy improves intracranial disease control and survival outcomes in EGFR mutant NSCLC with brain metastases relative to TKIs alone. MATERIALS AND METHODS: We searched MEDLINE and various conference proceedings from 2008 to July 2014 for eligible studies where patients received upfront cranial radiotherapy or TKIs alone. Outcomes of interest were overall intracranial disease response rate (ORR), four-month intracranial disease progression-free survival (PFS), two-year overall survival (OS) and neurological adverse events (AE). We used random effects models to pool outcomes across studies and compared them using interaction tests. RESULTS: We found 12 non-comparative observational studies (n=363) with severe methodological limitations. Upfront cranial radiotherapy results in similar intracranial disease ORR (relative risk (RR) 0.93, 95% confidence interval (CI) 0.82-1.06; interaction p value (p)=0.53), improved four-month intracranial disease PFS (RR 1.06, 95% CI 1.00-1.12; p=0.03), improved two-year OS (RR 1.33, 95% CI 1.00-1.77; p=0.05) but caused more neurological AEs than TKIs alone. CONCLUSION: There is evidence, albeit of low quality, that upfront cranial radiotherapy may improve intracranial disease control and survival outcomes compared with TKI alone.

Postoperative chemo-radiotherapy versus chemotherapy for resected gastric cancer: a systematic review and meta-analysis.

INTRODUCTION: This study conducted a systematic review and meta-analysis (direct and indirect) of published randomised controlled trials (RCTs) to compare the effects of postoperative chemo-radiotherapy (ChRT) with chemotherapy (Ch) on overall and disease-free survival (DFS) for patients with resectable gastric cancer. METHODS: We searched MEDLINE and CENTRAL from the date of inception and annual meeting proceedings of American Society of Clinical Oncology and American Society for Radiation Oncology from 1999 to November 2012 for RCTs comparing postoperative ChRT with Ch, postoperative ChRT with surgery alone and postoperative Ch with surgery alone. The primary outcome was overall survival (OS); secondary outcomes included DFS and toxicity. Hazard ratios (HRs), confidence intervals (CIs) and P values (P) were estimated with fixed effects models using Revman 5.1. RESULTS: We found six trials comparing postoperative ChRT with Ch (n = 1171). Meta-analysis of direct comparison trials showed that postoperative ChRT significantly improved both OS (HR 0.80, 95% CI 0.65-0.98, P = 0.03) and DFS (HR 0.76, 95% CI 0.63-0.91, P = 0.003) when compared with Ch. There were no significant differences in toxicity between the two groups. CONCLUSIONS: This study suggests a survival benefit of postoperative ChRT over Ch in patients with resected gastric cancer.

Late toxicities after conventional radiation therapy alone for nasopharyngeal carcinoma.

BACKGROUND AND PURPOSE: We sought to evaluate the nature and frequency of late toxicities in a cohort of nasopharyngeal cancer (NPC) patients treated with conventional radiotherapy alone. METHODS AND MATERIALS: Seven-hundred and ninety-six consecutive NPC patients treated using conventional radiotherapy at a single center from 1992 to 1995 were retrospectively analyzed. Patients with histology proven, completely staged, Stage I-IVB World Health Organization Type I-III NPC and completed radical radiotherapy were included. Patients with incomplete staging investigations, distant metastases at diagnosis, previous treatment, and incomplete radiotherapy were excluded. Radiotherapy-related complications were categorized using the RTOG Late Radiation Morbidity Scoring Criteria. RESULTS: Median follow-up was 7.2 years. The 5-year overall survival and disease free survival were 69% and 56%, respectively, and the corresponding 10-year rates were 52% and 44%. Among 771 patients with at least 3 months of follow-up post treatment, 565 (73%) developed RT-related complications. Diagnosed neurological complications were cranial nerve palsies (n=70; 9%), temporal lobe necrosis (n=37; 5%), Lhermitte's syndrome (n=7; 1%), and brachial plexopathy (n=2; 0.3%). Non-neurological complications included xerostomia (n=353; 46%), neck fibrosis (n=169; 22%), hypo-pituitarism (n=48; 6%), hearing loss (n=120; 16%), dysphagia (n=116; 15%), otorrhea (n=101; 13%), tinnitus (n=94; 12%), permanent tube feeding (n=61; 8%), trismus (n=45; 6%), second malignancies within treatment field (n=17; 2%), and osteo-radionecrosis (n=13; 2%). CONCLUSIONS: While radiotherapy is curative in NPC, many patients suffer significant late treatment morbidities with conventional radiotherapy techniques.

Controversies and challenges in the current management of nasopharyngeal cancer.

Nasopharyngeal carcinoma is uncommon worldwide, but poses a significant public health burden in endemic regions. Primary treatment for nonmetastatic disease is by radiation therapy, which has evolved from simple 2D-planning techniques to intensity-modulated radiation therapy. The role of systemic therapy has also become more prominent, with concurrent cisplatin-based chemoradiation the current standard of care for locally advanced disease based on multiple Phase III studies. Based on these advances, the prognosis of nasopharyngeal carcinoma appears to have improved significantly over the past two decades. Nevertheless, there are areas of substantial uncertainty and divergent views in the optimal treatment strategy. Distant metastases have become the dominant mode of treatment failure with the excellent local control provided by intensity-modulated radiation therapy. Recent studies have focused on this challenge of treating micrometastases while keeping toxicities manageable. Radiation therapy techniques continue to be refined to maintain consistently high locoregional tumor control while decreasing the probability of acute and late toxicities. This article discusses some of the current issues confronting the multidisciplinary team managing this disease.

Intensity-modulated radiation therapy without concurrent chemotherapy for stage IIb nasopharyngeal cancer.

OBJECTIVES: To evaluate the treatment outcome of patients with stage IIB nasopharyngeal carcinoma (NPC) after definitive intensity-modulated radiotherapy (IMRT) without concurrent chemotherapy. METHODS: Between August 2003 and December 2006, 107 patients with T1N1M0 (8%), T2N0M0 (13%), or T2N1M0 (79%) NPC were definitively treated with IMRT. Sixty-one received IMRT only, and 46 patients had various strategies of systemic treatment, consisting of abbreviated neoadjuvant (38 patients), concurrent (8 patients), or adjuvant (16 patients) chemotherapy. Radiation doses prescribed to the planning tumor volume of the gross disease, high-risk clinical tumor volume, and low-risk clinical tumor volume were 66 to 70 Gy, 54 to 60 Gy, and 50-54 Gy, respectively. RESULTS: With a median follow-up of 39 months (range, 7-77 months), 6 patients had locoregional relapse: 1 local only, 1 locoregional, and 4 regional only. Five patients had distant failure. Five of 6 total deaths were cancer related. The 3-year estimated local control, regional control, metastasis-free survival, disease-free survival, and overall survival were 96.5%, 98%, 94.8%, 90.7%, and 95.8%, respectively. No significant difference in treatment outcome was demonstrated in patients treated with or without chemotherapy of any schedule. CONCLUSIONS: IMRT without concurrent chemotherapy provides good outcome for patients with stage IIB NPC with acceptable toxicity. Neoadjuvant chemotherapy did not appear to provide significant additional benefit for this patient subgroup. Further investigation in the prospective setting is warranted to explore the role of systemic agents in the treatment of NPC with limited primary disease and cervical lymphadenopathy when IMRT is used.

Retropharyngeal nodal metastasis related to higher rate of distant metastasis in patients with N0 and N1 nasopharyngeal cancer.

BACKGROUND: Retropharyngeal lymph node (RLN) staging in nasopharyngeal carcinoma (NPC) can be controversial. METHODS: We retrospectively reviewed all patients with T(2-4), N(0-1) NPC treated between 1992 and 1994 to examine if RLN metastasis resulted in an increased incidence of distant metastases. RESULTS: Of the 667 patients with NPC, 395 had T(2-4), N(0-1) disease, 140 had N(0), and 255 had N(1). All had staging CT scans and were treated with radiotherapy. Median follow-up was 8.3 years. Seventy-four percent showed undifferentiated histology. In this cohort, 187 (47%) had RLN metastases. Multivariate analysis showed that RLN conferred a higher hazard for distant metastasis (p = .04). Using the Kaplan-Meier method, patients with N(0) disease and RLN had a similar hazard for distant metastases as patients with N(1) disease when compared with patients with N(0) disease and without RLN. CONCLUSION: Patients with N(0) disease and RLN appear to share a similar prognosis to patients with N(1) disease.

Treatment of nasopharyngeal carcinoma using intensity-modulated radiotherapy-the national cancer centre singapore experience.

PURPOSE: The aim of this study was to determine the efficacy and acute toxicity of our early experience with treating nasopharyngeal carcinoma (NPC) patients with intensity-modulated radiotherapy (IMRT). METHODS AND MATERIALS: A review was conducted on case records of 195 patients with histologically proven, nonmetastatic NPC treated with IMRT between 2002 and 2005. MRI of the head and neck was fused with CT simulation images. All plans had target volumes at three dose levels, with a prescribed dose of 70 Gy to the gross disease, in 2.0-2.12 Gy/fraction over 33-35 fractions. Cisplatin-based chemotherapy was offered to Stage III/IV patients. RESULTS: Median patient age was 52 years, and 69% were male. Median follow-up was 36.5 months. One hundred and twenty-three patients had Stage III/IV disease (63%); 50 (26%) had T4 disease. One hundred and eighty-eight (96%) had complete response; 7 (4%) had partial response. Of the complete responders, 10 (5.3%) had local recurrence, giving a 3-year local recurrence-free survival estimate of 93.1% and a 3-year disease-free survival of 82.1%. Fifty-one patients (26%) had at least one Grade 3 toxicity. CONCLUSIONS: Results from our series are comparable to those reported by other centers. Acute toxicity is common. Local failure or persistent disease, especially in patients with bulky T4 disease, are issues that must be addressed in future trials.

Outcome of patients with nasal natural killer (NK)/T-cell lymphoma treated with radiotherapy, with or without chemotherapy.

BACKGROUND: This study reviews the outcome of patients with nasal natural killer (NK)/T-cell lymphoma treated at the Therapeutic Radiology Department, National Cancer Centre, Singapore, from 1997 to 2003. METHODS: Twenty-one consecutive patients treated with radiotherapy, with or without chemotherapy, were retrospectively reviewed. RESULTS: The median age was 44 years (range, 27-86 years). Thirteen patients had stage I disease, five had stage II disease, and three had stage IV disease. Immunophenotyping was CD 56+ in 18 patients. Median follow-up for patients still alive was 23.4 months (range, 8.9-78.5 months). A median dose of 50 Gy (range, 35-56 Gy) was delivered. Sixteen patients also received chemotherapy. Two-year overall survival was 52.8%. Five patients had rapidly progressive disease, with a median survival of 89 days from diagnosis. The other 16 patients had complete remission, after which four relapsed. There were two local relapses. CONCLUSIONS: This disease often carries a poor prognosis, despite multimodality treatment. Radiotherapy may contribute to local control in some patients.