Testing for EGFR Variants in Pleural and Pericardial Effusion Cell-Free DNA in Patients With Non-Small Cell Lung Cancer.

Importance: Molecular testing in non-small cell lung cancer (NSCLC) is commonly limited by inadequate tumor sample. Plasma cell-free DNA (cfDNA) genotyping as a complementary test is specific but only moderately sensitive. Genotyping of cfDNA in pleural and pericardial effusion (PE-cfDNA) can further optimize molecular diagnostic yield and reduce the need for repeated biopsies. Objective: To prospectively validate droplet digital polymerase chain reaction (ddPCR) for detection of sensitizing EGFR variants and acquired Thr790Met variant (T790M) from PE-cfDNA in patients with NSCLC. Design, Setting, and Participants: This prospective diagnostic validation study was conducted between September 6, 2016, and January 21, 2021 at 2 major Hong Kong cancer centers. Patients with advanced NSCLC with both wild-type and variant EGFR status and exudative PE who underwent thoracocentesis or pericardiocentesis were randomly enrolled. Patients were either EGFR-tyrosine kinase inhibitor (TKI) naive (cohort 1) or EGFR-TKI treated but osimertinib naive (cohort 2). Enrolled patients underwent pleural- or pericardial-fluid and blood sampling for ddPCR EGFR testing. EGFR status results with ddPCR testing of PE-cfDNA and blood were compared with EGFR status in matched tumor biopsy or PE cell block samples. Main Outcomes and Measures: Specificity, sensitivity, and concordance of PE-cfDNA for detection of sensitizing EGFR variants and acquired T790M variation. Results: Among 171 patients (54% female) enrolled, there were 104 in cohort 1 and 67 in cohort 2. In cohort 1, 37% (38/102) were EGFR-variant positive; PE-cfDNA showed 97% sensitivity (95% CI, 92%-100%), 97% specificity (95% CI, 93%-100%), and 97% concordance (ĸ = 0.94, P < .001) for the detection of sensitizing EGFR variants. It was more sensitive than plasma in detecting sensitizing EGFR variants (97% vs 74%, P < .001). In cohort 2, 38% (15 of 40) were positive for the EGFR T790M variant; PE-cfDNA showed 87% sensitivity (95% CI, 69%-100%), 60% specificity (95% CI, 41%-79%), and 70% concordance (ĸ = 0.42, P = .004) for acquired T790M. The EGFR T790M variant was detected in 51% of PE-cfDNA vs 25% of PE cell block samples. Conclusions and Relevance: In this diagnostic study, EGFR variants could be accurately detected from PE-cfDNA in patients with NSCLC. More EGFR T790M was detected in PE-cfDNA than in guideline-recommended PE cell block preparations. These results suggest that PE-cfDNA can complement plasma and tumor genotyping for detecting EGFR variants in patients with advanced NSCLC.

ATOM: A phase II study to assess efficacy of preemptive local ablative therapy to residual oligometastases of NSCLC after EGFR TKI.

OBJECTIVES: NSCLC patients harboring EGFR mutation invariably developed resistance to EGFR TKI. We postulated that oligoresidual disease (ORD) after initial TKI might harbor resistant clones. This study aimed to test if preemptive local ablative therapy (LAT) can improve progression free survival (PFS) or not compared to historic data. MATERIALS AND METHODS: Patients indicated for EGFR TKI who possessed ORD (≤ 4 PET-avid lesions) after an initial 3-month TKI therapy were enrolled. After screening PET-CT, eligible patients with PET-avid ORDs were treated by LAT, either by stereotactic ablative radiotherapy (SABR) or surgery per clinicians' discretion. TKI was continued after LAT until it was considered ineffective. PET-CT was repeated on the 3rd and 12th month post-LAT (or at progression) apart from regular imaging. Further LAT was allowed in oligoprogressive disease. Primary endpoint was PFS rate at one-year from enrollment. Overall survival (OS), PFS and treatment safety were secondary endpoints. A post hoc comparison with screen failure cohort was performed. RESULTS: Eighteen patients were enrolled from 2014-17. Recruitment was stopped before the planned number (34) due to slow accrual. Two were excluded due to consent withdrawal and significant protocol violation. Median follow up was 39.1 months. Among the 16 analyzed patients, the one-year PFS rate (i.e. 15 month post TKI) was 68.8 %. Median OS was 43.3 months. All LAT were done by SABR, and none experienced ≥ grade 3 SABR related toxicities. Compared with screen failure cohort (n = 48), pre-emptive LAT effectively reduced risk of progression (HR 0.41, p = 0.0097). CONCLUSION: Preemptive LAT in ORD appeared to be safe and feasible. The 1-year PFS rate was encouraging. However, potential biases and the limitations of the study should not be overlooked. Further randomized studies are warranted.

Food Avoidance Beliefs and Behaviors Among Chinese Cancer Patients: Validation of a New Measurement Tool.

OBJECTIVE: Restrictive food avoidance behavior among Chinese cancer patients is common. Yet, to the authors' knowledge, no study has investigated factors associated with such behavior. This study attempted to validate a new measurement tool, the Cancer Patients Food Avoidance Behaviors Scale (CPFAB), that assessed cancer patients' belief regarding 5 perceived benefits of practicing food avoidance, and to test its applicability. DESIGN: Cross-sectional face-to-face interviews. SETTING: Two outpatient oncology clinics in 2 different districts of Hong Kong. PARTICIPANTS: A total of 245 patients with nasopharyngeal and colorectal cancer. MAIN OUTCOME MEASURES: Assessment of psychometric properties of the CPFAB. ANALYSIS: Principal components method with oblique (Promax) rotations was performed to investigate the factor structure of the CPFAB. RESULTS: Psychometric properties, which included test-retest intraclass correlations (mean = 0.72; SD = 0.12), Cronbach α (.88-.94), floor (0.4% to 5.7%) and ceiling (0% to 7.3%) effects, and item-subscale (0.67-0.79) and subscale-total (0.68-0.89) correlations, were satisfactory. CONCLUSIONS AND IMPLICATIONS: The CPFAB, a new instrument used to assess food avoidance, was developed and validated. It showed satisfactory psychometric properties and can be used to evaluate interventions that seek to modify food avoidance attitudes among cancer patients.

Should all nasopharyngeal carcinoma with masticator space involvement be staged as T4?

INTRODUCTION: The prognostic significance of the involvement of anatomical masticator space (MS) in nasopharyngeal carcinoma (NPC) was retrospectively reviewed. MATERIAL AND METHODS: 1104 Patients with non-metastatic NPC treated with radical radiotherapy between 1998 and 2010 were re-staged according to the 7th edition of the American Joint Committee on Cancer (AJCC) staging system; tumors with medial pterygoid muscle (MP) and/or lateral pterygoid muscle (LP) involvement but did not fulfill the criteria for T3 or T4 were staged as TX. The tumor volume data, dosimetric data and survival endpoints of different T stage diseases were analyzed and compared to study the significance of MS involvement. RESULTS: The overall MS involvement rate was 61.0%. The median volumes of the primary gross tumor volume were 9.6ml, 15.2ml, 19.9ml, 32.6ml and 77.3ml for T1, T2, TX, T3 and T4, respectively (p<0.001). T1, T2 and TX tumors received higher minimum dose to the gross tumor volume and planning target volume than T3 and T4. Multivariate analysis showed that age, gender, T-/N-classification and the use of chemotherapy were significant prognostic factors for various survival end-points. Patients with TX disease had similar survival rates as with T1-T2; and had a significantly better 5-year overall survival rate (86.6% vs. 76.6%; p=0.013) and a trend of higher 5-year distant failure-free survival rate (91.5% vs. 81.3%; p=0.09) than patients with T3 disease. CONCLUSION: NPC with the involvement of MP and/or LP alone should be classified as T2 disease.

Evolution of treatment for nasopharyngeal cancer--success and setback in the intensity-modulated radiotherapy era.

BACKGROUND AND PURPOSE: To assess the therapeutic gains and setbacks as we evolved from the 2-dimensional radiotherapy (2DRT) to conformal 3-dimensional (3DRT) and to intensity-modulated (IMRT) era. MATERIALS AND METHODS: 1593 consecutive patients from 1994 to 2010 were retrospectively analyzed. Evolving changes in the different era included advances in staging investigation, radiotherapy technique, dose escalation, and use of chemotherapy. RESULTS: The 3DRT era achieved significant improvement in local failure-free rate (L-FFR), disease-specific survival (DSS) and overall survival (OS). Neurological damage and bone/soft tissue necrosis were significantly reduced. However, the improvement in distant failure-free rate (D-FFR) was insignificant, and more hearing impairment occurred due to chemotherapy. Significantly higher D-FFR was achieved in the IMRT era, but L-FFR did not show further improvement. 5-Year DSS increased from 78% in the 2DRT, to 81% in the 3DRT, and 85% in the IMRT era, while the corresponding neurological toxicity rate decreased from 7.4% to 3.5% and 1.8%. CONCLUSIONS: Significant improvement in survival and reduction of serious toxicity was achieved as we evolved from 2DRT to 3DRT and IMRT era; the therapeutic ratio for all T-categories improved with more conformal techniques. Improvements in tumor control were attributed not only to advances in RT technique, but also to better imaging and increasing use of potent chemotherapy. However, it should also be noted that hearing impairment significantly increased due to chemotherapy, L-FFR reached a plateau in the 3DRT era, and it is worrisome that the result for T4 remained unsatisfactory. Besides exploring for more potent chemotherapy and innovative methods, the guideline on dose constraint should be re-visited to optimize the therapeutic ratio.

Stereotactic ablative radiotherapy for medically inoperable early stage lung cancer: early outcomes.

OBJECTIVE. To evaluate the clinical outcome and safety of stereotactic ablative radiotherapy for medically inoperable stage I non-small-cell lung carcinoma. DESIGN. Retrospective case series. SETTING. Pamela Youde Nethersole Eastern Hospital, Hong Kong. PATIENTS. All patients with medically inoperable stage I non-small-cell lung carcinoma receiving stereotactic ablative radiotherapy since its establishment in 2008. MAIN OUTCOME MEASURES. Disease control rate, overall survival, and treatment toxicities. RESULTS. Sixteen stage I non-small-cell lung carcinoma patients underwent the procedure from June 2008 to November 2011. The median patient age was 82 years and the majority (81%) had moderate-to-severe co-morbidity based on the Adult Comorbidity Evaluation 27 index. With a median follow-up of 22 months, the 2-year primary tumour control rate, disease-free survival and overall survival rates were 91%, 71% and 87%, respectively. No grade 3 (National Cancer Institute Common Terminology Criteria for Adverse Events) or higher treatment-related complications were reported. CONCLUSION. Stereotactic ablative radiotherapy can achieve a high degree of local control safely in medically inoperable patients with early lung cancer.

The superiority of hybrid-volumetric arc therapy (VMAT) technique over double arcs VMAT and 3D-conformal technique in the treatment of locally advanced non-small cell lung cancer--a planning study.

PURPOSE: To compare the dosimetric performance of three different treatment techniques - conformal radiotherapy (CRT), double arcs volumetric modulated arc therapy (RapidArc, RA) and Hybrid-RapidArc (H-RA) for locally-advanced non-small cell lung cancer (NSCLC). MATERIAL AND METHODS: CRT, RA and H-RA plans were optimized for 24 stage III NSCLC patients. The target prescription dose was 60Gy. CRT consisted of 5-7 coplanar fields, while RA comprised of two 204(o) arcs. H-RA referred to two 204(o) arcs plus 2 static fields, which accounted for approximately half of the total dose. The plans were optimized to fulfill the departmental plan acceptance criteria. RESULTS: RA and H-RA yielded a 20% better conformity compared with CRT. Lung volume receiving >20Gy (V20) and mean lung dose (MLD) were the lowest in H-RA (V20 1.7% and 2.1% lower, MLD 0.59Gy and 0.41Gy lower than CRT & RA respectively) without jeopardizing the low-dose lung volume (V5). H-RA plans gave the lowest mean maximum spinal cord dose (34.4Gy, 3.9Gy

Use of Rasch analysis in the evaluation of the Oropharyngeal Mucositis Quality Of Life Scale.

BACKGROUND: Oropharyngeal mucositis (OM) is a significant clinical problem causing profound impairment of health-related quality of life (HQoL) for patients undergoing cancer therapy. The Oropharyngeal Mucositis-Specific Health-Related Quality of Life Measure (OMQoL) was developed using classical test theory to measure the self-perceived HQoL of patients with mucositis. OBJECTIVES: The aim of this study was to analyze the OMQoL according to the Rasch model and, on the basis of results, determine whether improvements could be made. METHOD: A multicenter approach was used, and 210 patients treated with stomatotoxic chemotherapy (36%), high-dose myeloablative chemotherapy ± total body irradiation (10%), or head and neck irradiation ± chemotherapy (54%) completed the OMQoL. The Partial Credit Model of Rasch analysis was applied to evaluate the 31-item OMQoL using WINSTEPS and R software. Unidimensionality (measurement of a single construct), item fit, response category performance, person separation reliability, targeting of item difficulty to person ability, and differential item functioning (DIF) were examined. RESULTS: Of 31 items, 5 were removed due to misfit; the OMQoL was reduced to 26 items with acceptable information weighted fit/outlier-sensitive fit indices (within 0.7-1.3) and eigenvalue units (≤2.0), confirming the unidimensionality of the reduced OMQoL. The OMQoL and its four subscales showed ordered category thresholds, and the person separation reliability was high (person separation index >0.2 with reliability >.8). Nevertheless, some of the items in the OMQoL might not be targeted effectively to patients with low levels of OM. Significant uniform and nonuniform DIFs were not found for gender (uniform DIF, p = .26; nonuniform DIF, p= .24) and age (uniform DIF, p = .95; nonuniform DIF, p = .65). DISCUSSION: Rasch analysis reveals that the reduced 26-item OMQoL is unidimensional and is adequate to measure HQoL for patients with OM regardless of gender and age group. This improved version can provide a common platform for nurses to use in their assessment, caring, and treatment of patients with OM.

Relationships between explanatory style, posttraumatic growth and posttraumatic stress disorder symptoms among Chinese breast cancer patients.

Many existing models posit that cognitive processing style is an important factor affecting self-perceived positive changes. In this study, the effects of explanatory style (the manner in which people cognitively process and explain why they experience good and bad events) on both posttraumatic growth (PTG) and posttraumatic stress disorder (PTSD) symptoms were examined among 90 Chinese women with breast cancer. It was found that explanatory style for good events, but not for bad events, was significantly associated with self-reported PTG. Women who attributed the causes of positive events to internal, global and stable factors tended to report more posttraumatic growth. In contrast, explanatory style for bad events, as opposed to good events, was significantly and positively correlated with PTSD symptoms. Among the three dimensions of explanatory style (internal, stable and global), the tendency to globalise the causes of good and bad events were the most important predictors of self-reported PTG and PTSD symptoms, respectively. While enhancing an optimistic explanatory style for bad events might reduce posttraumatic stress symptoms, cultivating an optimistic explanatory style for good events is likely to increase self-perceived positive changes after breast cancer diagnosis and treatment.

Severe oral mucositis associated with cancer therapy: impact on oral functional status and quality of life.

GOALS OF WORK: This study determined the incidence of severe oral mucositis (OM), patients' self-reported moderate and severe oral symptoms, and change of quality of life (QoL), as well as examined whether OM severity and pain scores predicted the impairment of oral function and QoL. PATIENTS AND METHODS: A multicenter approach was used and 137 patients treated with stomatotoxic chemotherapy (45%), high-dose myeloablative chemotherapy with or without concomitant total body irradiation (12%), head and neck irradiation with or without concomitant chemotherapy (44%) completed the OM-specific QoL measure (OMQoL) once or twice weekly over a 4- or 10-week period, along with concurrent measures of OM using WHO Mucositis Grading System and oral symptoms using 10 cm visual analog scale. MAIN RESULTS: The incidence of severe OM was 50% (n = 68). About 77-80% of patients with severe OM reported moderate or severe mouth or throat pain, and 66-78% reported moderate or severe oral functional problems. The oral symptoms peak and area-under-the-curve (AUC) scores of patients with severe OM (peak 5.6 to 6.8; AUC 3.8 to 5.2) were significantly higher than those without OM and those with mild OM (p < 0.01). The OMQoL subscales peak and AUC scores of patients with severe OM (peak 47.9 to 62.1; AUC -40.1 to -25.8) were significantly lower than those without OM and those with mild OM (p < 0.01). Of those with severe OM, 88-94% had a drop in the OMQoL subscale scores to at least 10 points from the baseline. Pain resulting from OM, in particular throat pain, is most predictive of oral functional impairment (standardized ß = 0.53-0.83). CONCLUSIONS: Severe OM can cause profound pain and oral functional incapability and clinical significant impairment of QoL.

Development and validation of the functional assessment of cancer therapy nasopharyngeal cancer subscale.

BACKGROUND: We aimed to develop a quality-of-life subscale for nasopharyngeal carcinoma (NPC) and validate the functional assessment of cancer therapy-nasopharyngeal (FACT-NP). METHODS: The FACT-NP was tested cross-sectionally in survivors of postirradiated NPC (n = 357) and was administered to newly diagnosed patients (n = 160) before, at the end of, and 3 months after radiotherapy (RT). RESULTS: Each FACT-NP domain was internally consistent (Cronbach's alpha = 0.87-0.90). The test-retest reliability for each subscale was satisfactory (intraclass correlation coefficient = .73-.88). Concurrent validity was suggested by the moderate to strong correlations between the FACT-NP and the Quality of Life-Radiation Therapy Instrument-Head and Neck (QOL-RTI-H&N) subscales (Pearson r = .39-.84). The FACT-NP was responsive to clinical changes from pretreatment to 3 months after RT (effect sizes > 0.6 for clinically relevant subscales). The pooled data for multitrait scaling analysis showed satisfactory item internal consistency and item discriminant validity (100% and 90% scaling success, respectively). CONCLUSION: The FACT-NP is a reliable and valid instrument for measuring QOL in patients with NPC.

A patient-reported outcome instrument to assess the impact of oropharyngeal mucositis on health-related quality of life: a longitudinal psychometric evaluation.

GOALS OF WORK: An oropharyngeal mucositis (OM)-specific health-related quality of life measure (OMQoL) has been developed to assess the impact of OM from the perspective of patients. The current paper describes the convergent, concurrent, and known-group validities and responsiveness in relation to clinical and health outcomes. MATERIALS AND METHODS: A multicenter approach was used, and 137 patients treated with different cancer therapies completed the OMQoL and the European Organization for Research and Treatment of Cancer Quality of Life questionnaire [EORTC QLQ-C30 (Ch)] twice over a 4-week period or weekly over a 7-week period, along with concurrent measures of OM and its related symptoms. MAIN RESULTS: The OM-related symptom scores correlated highly with the OMQoL, confirming its convergent validity (r = -0.724--0.971, p < 0.01). Moderate correlations between the subscales of the OMQoL and EORTC QLQ-C30 (Ch) were indicative of good concurrent validity (r = 0.450-0.724, p < 0.01). The OMQoL was able to distinguish between patients with different severities of OM (p < 0.01) and types of cancer therapy (p < 0.01), providing evidence of good known-group validity. The changes in effects sizes corresponding to changes in OM curves indicate that the OMQoL is responsive to changes in OM status. CONCLUSIONS: These findings suggest that the OMQoL has very good psychometric properties and can be used as a health-related quality of life assessment for cancer patients with OM. Much work is still needed in strengthening the psychometric qualities and interpretability of the OMQoL by demonstrating its ability to detect outcome changes over time.

New measure of health-related quality of life for patients with oropharyngeal mucositis: development and preliminary psychometric evaluation.

BACKGROUND: Oropharyngeal mucositis (OM) causes profound impairment of patients' health-related quality of life (HQoL). The aim of the article is to describe the development and preliminary validation of an HQoL instrument, OMQoL, specifically for patients with OM. METHODS: First, a qualitative phase was conducted to generate items (n = 23). Face validity was assessed by focus group interviews (n = 13). Expert content review (n = 7) was used to ensure content validity. The second step was a quantitative validation phase comprised a multicenter study (n = 210) to help identify subscales of the instrument addressing different dimensions of OM and to measure reliability. RESULTS: The qualitative interview generated 171 items. Using focus group discussion and expert content review, items were reduced to 41 items. Factor and scaling analyses of these 41 items resulted in 4 subscales, contributed by 31 items, depicting problems with symptoms, diet, social function, and swallowing. The floor effect was modest. The factorial structure was satisfactory with loading >0.40 on each subscale for all items. All corrected item-total corrections were higher than 0.40 (r = 0.457-0.874). The internal consistency reliability of each subscale was high, with Cronbach alpha coefficients ranging from 0.906 to 0.934. The test-retest reliability of the individual items using weighted kappa was good (kappa values 0.610-0.895). The intraclass correlation results for the subscale totals were all in excess of 0.70 (0.864-0.934). CONCLUSIONS: An initial psychometric analysis of the OMQoL was encouraging. The OMQoL could provide a valuable tool for the assessment of HQoL of patients with OM.

Treatment of Stage IV(A-B) nasopharyngeal carcinoma by induction-concurrent chemoradiotherapy and accelerated fractionation: impact of chemotherapy schemes.

PURPOSE: The aim of this study was to evaluate the impact of different chemotherapy regimens in patients with advanced nasopharyngeal carcinoma (NPC) treated by induction-concurrent chemoradiotherapy. METHODS AND MATERIALS: Between 1998 and 2003, 75 Stage IV(A-B) NPC patients were treated with 3 cycles of induction chemotherapy with cisplatin plus 5-fluorouracil (PF) (n = 41) or cisplatin plus gemcitabine (PG) (n = 34), followed by accelerated radiotherapy in concurrence with 2 cycles of cisplatin. In 18 (24%) patients, cisplatin was completely replaced by carboplatin in both concurrent cycles, mainly because of borderline renal functions. RESULTS: The median follow-up was 3.6 years. The 3-year locoregional failure-free survival, progression-free survival, and overall survival of the whole group were 80%, 68%, and 80% respectively. No significant difference was found between patients treated with either induction regimens. However, patients with only carboplatin in the 2 concurrent cycles had significantly inferior 3-year locoregional failure-free survival (56% vs. 86%, p = 0.014), progression-free survival (39% vs. 72%, p = 0.001), and overall survival (61% vs. 87%, p = 0.046) when compared with the rest of the group. In multivariate analysis, the complete replacement of cisplatin by carboplatin during concurrent chemoradiotherapy was still an independent adverse factor in locoregional failure-free survival (hazard ratio, 3.662; 95% CI, 1.145-11.765; p = 0.029) and progression-free survival (hazard ratio, 3.390; 95% CI, 1.443-7.937; p = 0.005). CONCLUSIONS: The more convenient PG regimen is as effective as the PF regimen as induction chemotherapy for patients with advanced NPC. Replacing cisplatin with carboplatin in the concurrent phase carries a poor prognosis.

Treatment of stage IV(A-B) nasopharyngeal carcinoma by induction-concurrent chemoradiotherapy and accelerated fractionation.

PURPOSE: To explore a more effective strategy for treating nasopharyngeal carcinoma with extensive locoregional disease. METHODS AND MATERIALS: Between October 1998 and January 2003, 49 patients with Stage IV(A-B) disease infiltrating or abutting neurologic structures were treated with induction-concurrent chemotherapy and accelerated radiotherapy (RT). A combination of cisplatin and 5-fluorouracil was used in the induction phase and single-agent cisplatin in the concurrent phase. All patients were irradiated with conformal techniques at 2 Gy/fraction, six daily fractions weekly, to a total dose of 70 Gy. RESULTS: Although 92% of patients had one or more acute toxicities Grade 3 or worse, 96% completed the whole course of RT, and 92% had five or more cycles of chemotherapy. The great majority of toxicities were uneventful, but 1 patient died of neutropenic sepsis. With a median follow-up of 3.1 years, 20 patients had failure at one or more sites and 15 patients died. The 3-year locoregional and distant failure-free rate was 77% and 75%, respectively, and the overall survival rate was 71%. At last follow-up, 27% of patients had developed late Grade 3 or worse toxicity (24% were hearing impairments), but none had radiation-induced neurologic damage. CONCLUSION: The current strategy achieved encouraging results for this poor prognostic group, and confirmation of the therapeutic gain by a prospective randomized trial is warranted.

Primary tumor volume of nasopharyngeal carcinoma: prognostic significance for local control.

PURPOSE: To study the prognostic significance of primary tumor volume on local control of nasopharyngeal carcinoma. METHODS AND MATERIALS: Between 1998 and 2001, 308 consecutive patients with nasopharyngeal carcinoma treated with radical intent were staged with MRI. On the basis of the extent of tumor infiltration outlined by a diagnostic radiologist, the gross tumor volume of the primary and involved retropharyngeal nodes (GTV-P) was delineated by a radiation oncologist for three-dimensional conformal radiotherapy to the nasopharyngeal region using the Helax-TMS Planning System. All patients were treated with 2 Gy daily to a total dose of 70 Gy in 6-7 weeks. Additionally, chemotherapy was given to 128 patients (42%). RESULTS: The median GTV-P for the whole series was 22 cm(3) (range, 1.4-218 cm(3)). Although the GTV-P varied substantially within each T stage, the overall correlation between these two parameters was strongly significant (p <0.01), with the median GTV-P 2.7 cm(3) for T1, 13.2 cm(3) for T2, 28.1 cm(3) for T3, and 65.5 cm(3) for T4. With a median follow-up of 1.9 years (range, 0.1-3.9 years), the 3-year local failure-free rate was 87%. The 3-year local failure-free rate was 97% for patients with a GTV-P <15 cm(3) compared with 82% for those with a GTV-P > or =15 cm(3) (p <0.01). On multivariate analysis (with T stage as a covariate), GTV-P remained an independent prognostic factor for the local failure-free rate (hazard ratio, 1.01; 95% confidence interval, 1.00-1.02; p <0.01). CONCLUSION: Our data suggested that GTV-P is a strongly significant factor for predicting local control of nasopharyngeal carcinoma. The risk of local failure was estimated to increase by 1% for every 1 cm(3) increase in primary tumor volume.