Prospective Study of Stereotactic Body Radiation Therapy for Hepatocellular Carcinoma on Waitlist for Liver Transplant.

BACKGROUND AND AIMS: There are no prospective data on stereotactic body radiation therapy (SBRT) as a bridge to liver transplantation for HCC. This study aimed to evaluate the efficacy and safety of SBRT as bridging therapy, with comparison with transarterial chemoembolization (TACE) and high-intensity focused ultrasound (HIFU). APPROACH AND RESULTS: Patients were prospectively enrolled for SBRT under a standardized protocol from July 2015 and compared with a retrospective cohort of patients who underwent TACE or HIFU from 2010. The primary endpoint was tumor control rate at 1 year after bridging therapy. Secondary endpoints included cumulative incidence of dropout, toxicity, and posttransplant survival. During the study period, 150 patients were evaluated (SBRT, n = 40; TACE, n = 59; HIFU, n = 51). The tumor control rate at 1 year was significantly higher after SBRT compared with TACE and HIFU (92.3%, 43.5%, and 33.3%, respectively; P = 0.02). With competing risk analysis, the cumulative incidence of dropout at 1 and 3 years after listing was lower after SBRT (15.1% and 23.3%) compared with TACE (28.9% and 45.8%; P = 0.034) and HIFU (33.3% and 45.1%; P = 0.032). Time-to-progression at 1 and 3 years was also superior after SBRT (10.8%, 18.5% in SBRT, 45%, 54.9% in TACE, and 47.6%, 62.8% in HIFU; P < 0.001). The periprocedural toxicity was similar, without any difference in perioperative complications and patient and recurrence-free survival rates after transplant. Pathological complete response was more frequent after SBRT compared with TACE and HIFU (48.1% vs. 25% vs. 17.9%, respectively; P = 0.037). In multivariable analysis, tumor size <3 cm, listing alpha-fetoprotein <200 ng/mL, Child A, and SBRT significantly reduced the risk of dropout. CONCLUSIONS: SBRT was safe, with a significantly higher tumor control rate, reduced the risk of waitlist dropout, and should be used as an alternative to conventional bridging therapies.

Should endovascular stenting be used routinely as first-line treatment for malignant superior vena cava syndrome?-a critical review in the context of recent advances in oncological treatments.

Malignant superior vena cava syndrome (SVCS) is no longer considered a medical emergency in most cases because it rarely leads to life-threatening complications. However, it results in disturbing symptoms that can significantly affect patients' quality of life. Treating this condition effectively while minimising treatment-related morbidity is of increasing importance as cancer patients are living longer from advances in oncological treatments. This clinical practice review discusses the implications of these advances on the decision to consider stenting as the initial treatment for SVCS. Stenting is increasingly popular as it provides quick symptomatic relief with low rates of complications. Systemic treatments have evolved in the past two decades with the development of immunotherapy and targeted therapies that have different response patterns compared to conventional chemotherapy. Furthermore, major changes have also been seen in radiotherapy techniques that allow treatments to better conform to targets while sparing normal tissues. These advances have changed practice patterns for stent placement in SVCS patients in both the localised and metastatic settings. Prospective studies using standardised patient-reported outcome tools are needed to determine the optimal treatment sequence for SVCS patients, as current recommendations are mainly based on retrospective single-arm studies. An individualized approach with multidisciplinary input is therefore important to optimize patient outcomes before more robust evidence is available.

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.

A Phase II Study of Osimertinib in Patients with Advanced-Stage Non-Small Cell Lung Cancer following Prior Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor (EGFR TKI) Therapy with EGFR and T790M Mutations Detected in Plasma Circulating Tumour DNA (PLASMA Study).

Epidermal growth factor receptor (EGFR) T790M mutations drive resistance in 50% of patients with advanced non-small cell lung cancer (NSCLC) who progress on first/second generation (1G/2G) EGFR tyrosine kinase inhibitors (TKIs) and are sensitive to Osimertinib. Tissue sampling is the gold-standard modality of T790M testing, but it is invasive. We evaluated the efficacy of Osimertinib in patients with EGFR mutant NSCLC and T790M in circulating tumour DNA (ctDNA). PLASMA is a prospective, open-label, multicentre single-arm Phase II study. Patients with advanced NSCLC harbouring sensitizing EGFR and T790M mutations in plasma at progression from ≥one 1G/2G TKI were treated with 80 mg of Osimertinib daily until progression. The primary endpoint was the objective response rate (ORR); the secondary endpoints included progression-free survival (PFS), overall survival (OS), disease control rate (DCR) and toxicities. Plasma next-generation sequencing was performed to determine Osimertinib resistance mechanisms and assess serial ctDNA. A total of 110 patients from eight centres in five countries were enrolled from 2017 to 2019. The median follow-up duration was 2.64 (IQR 2.44-3.12) years. The ORR was 50.9% (95% CI 41.2-60.6) and the DCR was 84.5% (95% CI 76.4-90.7). Median PFS was 7.4 (95% CI 6.0-9.3) months; median OS was 1.63 (95% CI 1.35-2.16) years. Of all of the patients, 76% had treatment-related adverse events (TRAEs), most commonly paronychia (22.7%); 11% experienced ≥ Grade 3 TRAEs. The ctDNA baseline load and dynamics were prognostic. Osimertinib is active in NSCLC harbouring sensitizing EGFR and T790M mutations in ctDNA testing post 1G/2G TKIs.

Patterns of care and survival of Chinese glioblastoma patients in the temozolomide era: a Hong Kong population-level analysis over a 14-year period.

Background: The aim of this study is to address the paucity of epidemiological data regarding the characteristics, treatment patterns and survival outcomes of Chinese glioblastoma patients. Methods: This was a population-level study of Hong Kong adult (>18 years) Chinese patients with newly diagnosed histologically confirmed glioblastoma between 2006 and 2019. The age standardized incidence rate (ASIR), patient-, tumor- treatment-related characteristics, overall survival (OS) as well as its predictors were determined. Results: One thousand and ten patients with a median follow-up of 10.0 months were reviewed. The ASIR of glioblastoma was 1.0 per 100 000 population with no significant change during the study period. The mean age was 57 + 14 years. The median OS was 10.6 months (IQR: 5.2-18.4). Independent predictors for survival were: Karnofsky performance score >80 (adjusted OR: 0.8; 95% CI: 0.6-0.9), IDH-1 mutant (aOR: 0.7; 95% CI: 0.5-0.9) or MGMT methylated (aOR: 0.7; 95% CI: 0.5-0.8) glioblastomas, gross total resection (aOR: 0.8; 95% CI: 0.5-0.8) and temozolomide chemoradiotherapy (aOR 0.4; 95% CI: 0.3-0.6). Despite the significant increased administration of temozolomide chemoradiotherapy from 39% (127/326) of patients in 2006-2010 to 63% (227/356) in 2015-2019 (P-value < .001), median OS did not improve (2006-2010: 10.3 months vs 2015-2019: 11.8 months) (OR: 1.1; 95% CI: 0.9-1.3). Conclusions: The incidence of glioblastoma in the Chinese general population is low. We charted the development of neuro-oncological care of glioblastoma patients in Hong Kong during the temozolomide era. Although there was an increased adoption of temozolomide chemoradiotherapy, a corresponding improvement in survival was not observed.

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.

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.

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.

Delayed presentation of symptomatic breast cancers in Hong Kong: experience in a public cancer centre.

OBJECTIVE: Delayed presentation is an important obstacle to improving cancer treatment outcomes. We aimed to study the magnitude of this problem in Hong Kong and the factors associated with delayed presentation of patients with symptomatic breast cancers. DESIGN: Retrospective study using self-administered questionnaires. SETTING: Clinical Oncology Department in a regional public hospital in Hong Kong. PATIENTS: A total of 158 Chinese women with breast cancer referred to our hospital between October 2006 and December 2007 consented to participate in this study. Among these, 59 (37%) patients were referred after having surgery in private sector. RESULTS: The mean total delay (from first symptom to treatment) was 22 weeks. The mean patient delay (from first symptom to first consultation) was 13 weeks, constituting the largest component (60%) of the total delay. After symptom onset, the delay exceeded 12 weeks for consulting a doctor in 29%, and for receipt of treatment in 52% of them. Low family income (

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.

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.

Utilization of stereotactic ablative radiotherapy in oligometastatic & oligoprogressive skeletal metastases: Results and pattern of failure.

AIM: To evaluate the outcome and toxicities of stereotactic ablative radiotherapy (SABR) for skeletal metastasis in a tertiary cancer center. METHODS: This is a retrospective review of 22 patients treated with SABR for skeletal metastases for oligometastases (OM) or oligoprogression (OP) since October 2012. There are a total of 27 treatments with 20 spinal and seven non-spinal metastases. Treatment outcome including local control (LC), progression-free survival (PFS), overall survival (OS), pain control, treatment-related toxicity and failure pattern are described. Patients are assessed by interval computed tomography (CT), positron emission tomography-CT, magnetic resonance imaging or bone scintigraphy by physicians' discretion. Toxicities are graded by common toxicities criteria version 4.03. RESULT: The median age of the patients is 64 years. Primary sites include lung (50%), breast (32%), nasopharynx (9%), prostate (4.5%) and colon (4.5%). Twelve patients with OM and 10 with OP are included. Dose to most spinal and non-spinal metastases is 35 and 50 Gy, respectively, in five fractions. With a median follow up of 15.6 months, there are three local failures (1-year LC 91.2%). The median PFS and OS are 10.1 and 37.3 months, while PFS of OP and OM group is 6.6 and 10.6 months, respectively. Two-third of symptomatic patients have at least 1-year complete pain control. There are two vertebral fractures and one grade 3 esophagitis. CONCLUSION: Our series shows excellent LC of SABR to skeletal metastases with limited toxicities in OM and OP diseases. However, its benefit of survival warrants further studies.

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.

Sustained response to standard dose osimertinib in a patient with plasma T790M-positive leptomeningeal metastases from primary lung adenocarcinoma.

A 44-year-old male, never smoker, suffers from stage IV adenocarcinoma of the right lung with epidermal growth factor receptor (EGFR) exon-21 L858R point mutation on initial presentation. After 23 months of treatment with gefitinib, intercalated with multiple courses of radiotherapy, leptomeningeal metastases (LMs) developed. Acquired T790M mutation was confirmed by the droplet digital polymerase chain reaction plasma EGFR test. After switching to osimertinib at the standard dose, his neurocognitive function improved clinically, coupled with sustained radiological improvement. As this clinical entity is underrepresented in clinical trials, the practicability of plasma EGFR testing and the optimal dose-response relationship of osimertinib in T790M-positive lung cancer complicated with LM deserves further exploration.

Characterization of PD-L1 expression and immune cell infiltration in nasopharyngeal cancer.

OBJECTIVES: Locally recurrent or metastatic nasopharyngeal cancer (NPC) remains an important challenge, with more effective and durable therapeutic options needed. Cancer immunotherapy, and in particular therapies that target the PD-L1/PD-1 immune checkpoint pathway, may provide new options to treat NPC patients. This study evaluated PD-L1 and CD8 expression levels and the respective associations with clinical and histopathological characteristics of patients with NPC. MATERIALS AND METHODS: Diagnostic tumour biopsies were obtained before radical radiotherapy with or without chemotherapy from 161 patients with NPC. These biopsies were analysed for PD-L1 expression levels on tumour cells (TC) and tumour-infiltrating immune cells (IC), and for CD8 T-cell infiltration. Results were correlated with baseline characteristics and clinical outcomes with standard-of-care treatment regimens. Additionally, pre- and post-treatment-paired tumour samples were analysed (n=146). RESULTS: 75% of tumours expressed PD-L1 on IC and 24% on TC. Baseline clinical characteristics of stage, sex and age did not correlate with PD-L1 expression. Additionally, overall survival and progression-free survival of standard-of-care treatment did not correlate with baseline PD-L1 expression. CD8 levels did correlate with clinical outcomes; however, results were confounded by other baseline characteristics. After treatment, PD-L1 expression dropped a median of 1.5% on IC and a median of 2.75% on TC. Median CD8 expression dropped 1.9%. CONCLUSIONS: Majority of NPC biopsy samples demonstrated PD-L1 expression on ⩾1% of IC, with fewer expressing PD-L1 on TC. In contrast to previous smaller studies, no prognostic value was observed for PD-L1 expression levels in patients with NPC.

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.

Clinical oncology and palliative medicine as a combined specialty--a unique model in Hong Kong.

The importance of early integration of palliative care (PC) into oncology treatment is increasingly being recognized. However, there is no consensus on what is the optimal way of integration. This article describes a unique model in Hong Kong where clinical oncology and palliative medicine (PM) is integrated through the development of PM as a subspecialty under clinical oncology.

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.

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.