Rebecca M.W. Yeung

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.

Retrospective analysis on treating nasopharyngeal carcinoma with accelerated fractionation (6 fractions per week) in comparison with conventional fractionation (5 fractions per week): report on 3-year tumor control and normal tissue toxicity

BACKGROUND AND PURPOSE To assess the therapeutic gain achieved by accelerated fractionation for non-keratinizing/undifferentiated nasopharyngeal carcinoma (NPC). MATERIALS AND METHODS During January 1994 to October 1997, 325 patients were treated to a total dose of 66 Gy in 33-37 fractions: 167 (irradiated before mid-January 1996) with 5 daily fractions (CF) and subsequent 158 with 6 daily fractions (AF) per week. Their median treatment times were 46 and 39 days, respectively. Additional boost to parapharyngeal extension had been given to 181 and Cisplatin-based chemotherapy to 57 patients (24 concurrent with radiotherapy). RESULTS The AF group had significantly higher progression-free rate than the CF group (74 vs. 63% at 3 years, P=0.02 by the log-rank test). However, the difference in disease-specific survival (86 vs. 80%, P=0.39) and overall survival (81 vs. 78%, P=0.9) did not reach statistical significance. Strongly significant improvement in local failure-free rate was achieved for patients with T3-4 tumors (87 vs. 62%, P<0.01). Multivariate analyses showed that fractionation was an independent significant factor for overall progression: hazard ratio=0.63, 95% confidence interval: 0.41-0.98, P=0.04. Among the 268 patients treated with radiotherapy alone, those treated by AF had significantly higher incidence of acute reaction grade > or=3 (72 vs. 13%, P<0.01). However, all patients completed the scheduled dose without excessive prolongation, and no significant increase in late complications was observed (20 vs. 15% at 3 years, P=0.19). CONCLUSIONS The current analyses suggested that acceleration to 6 daily fractions per week could significantly improve the progression-free rate for NPC without excessive late toxicity. Improvement in local control was confined to T3-4 tumors.

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<CRT and 2.2Gy<RA plans) and NTCP of lung. Higher average MU per fraction (addition 52.4MU) was observed with a reduced treatment time compared with CRT plans. CONCLUSION The H-RA technique was superior in dosimetric outcomes for treating locally-advanced NSCLC compared to CRT and RA.

Induction chemotherapy with cisplatin and gemcitabine followed by accelerated radiotherapy and concurrent cisplatin in patients with stage IV(A-B) nasopharyngeal carcinoma

The purpose of this study was to evaluate the efficacy and toxicity of cisplatin plus gemcitabine as induction chemotherapy in advanced nasopharyngeal carcinoma (NPC).

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.

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

We aimed to develop a quality‐of‐life subscale for nasopharyngeal carcinoma (NPC) and validate the functional assessment of cancer therapy‐nasopharyngeal (FACT‐NP).

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.

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.

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

Goals of workAn 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 methodsA 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 resultsThe 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.ConclusionsThese 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.

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.