A randomised controlled pilot study of a Nintendo Ring Fit Adventure™ balance and strengthening exercise program in community-dwelling older adults with a history of falls.

OBJECTIVES: This pilot study examined the feasibility, acceptability, and effects of a Nintendo Ring Fit Adventure™-based balance and muscle strengthening exercise program in community-dwelling older adults with a history of falls. METHODS: Older adults who have had at least one fall in the past year were randomly assigned to an experimental (n = 21) or control group (n = 21). The experimental group performed 16 exercise sessions in total, lasting 60 min each, twice a week for 8 weeks, whereas the control group received usual care. Feasibility was evaluated based on the scores of participants in the exercises. Acceptance was evaluated using a customised questionnaire examining participants' self-perceived enjoyment, feasibility and improvements. Clinical outcomes including balance (Mini-BESTest), lower limb muscle strength (Five-Time Sit-to-Stand test), mobility (Timed-Up and Go test), dual-task ability (Timed-Up and Go test-Dual Task), fear of falling (Icon-FES) and executive function (Color Trails Test) were evaluated at baseline and 8 weeks. RESULTS: Thirty-one participants (74%) finished the 8-week assessment. The experimental group significantly improved their scores in six out of eight exercises (all p < .031). The mean scores of the self-perceived enjoyment, feasibility and improvement domains of the acceptability questionnaire were 3.46 ± .53, 3.08 ± .59, and 3.47 ± .57 respectively. A significant improvement in the anticipatory subscore of the Mini-BESTest was found in the experimental group compared to the control group (p = .02; Partial eta squared = .14). CONCLUSIONS: The Nintendo Ring Fit Adventure™-based exercise program was feasible, acceptable, and potentially effective in community-dwelling older adults with a history of falls.

Feasibility, safety, and effects of a Nintendo Ring Fit Adventure™ balance and strengthening exercise program in community-dwelling older adults with a history of falls: A feasibility randomized controlled trial.

AIM: This pilot study examined the feasibility, safety, and effects of a Nintendo Ring Fit Adventure™-based exercise program to enhance balance and lower limb muscle strength in community-dwelling older adults with a history of falls. METHODS: In total, 42 older adults who experienced at least one fall in the past year were randomly assigned to an experimental or control group. Participants in the experimental group performed 60-min sessions of the exercise program twice per week for 8 weeks. The control group received usual care. We assessed the feasibility (retention and adherence to the exercise program), safety (number of adverse events), and clinical outcomes: (1) balance (Mini-BESTest); (2) functional lower limb muscle strength (Five-Time Sit-to-Stand test); (3) mobility (Timed-Up and Go test); (4) dual-task ability (Timed-Up and Go test - Dual Task); (5) fear of falling (Icon-FES); and (6) executive function (Color Trails Test). RESULTS: Thirty-one participants (74%) completed the 8-week assessment. No adverse event associated with the exercise program was reported. There was a significant interaction in the anticipatory domain score of the Mini-BESTest between the experimental and control groups over the 8 weeks (P = 0.019). CONCLUSIONS: The Nintendo Ring Fit Adventure™-based exercise program was feasible, safe, and potentially effective in improving anticipatory balance in community-dwelling older fallers. Geriatr Gerontol Int 2024; 24: 334-341.

Consensus Statements on Precision Oncology in the China Greater Bay Area.

BACKGROUND: Next-generation sequencing comprehensive genomic panels (NGS CGPs) have enabled the delivery of tailor-made therapeutic approaches to improve survival outcomes in patients with cancer. Within the China Greater Bay Area (GBA), territorial differences in clinical practices and health care systems and strengthening collaboration warrant a regional consensus to consolidate the development and integration of precision oncology (PO). Therefore, the Precision Oncology Working Group (POWG) formulated standardized principles for the clinical application of molecular profiling, interpretation of genomic alterations, and alignment of actionable mutations with sequence-directed therapy to deliver clinical services of excellence and evidence-based care to patients with cancer in the China GBA. METHODS: Thirty experts used a modified Delphi method. The evidence extracted to support the statements was graded according to the GRADE system and reported according to the Revised Standards for Quality Improvement Reporting Excellence guidelines, version 2.0. RESULTS: The POWG reached consensus in six key statements: harmonization of reporting and quality assurance of NGS; molecular tumor board and clinical decision support systems for PO; education and training; research and real-world data collection, patient engagement, regulations, and financial reimbursement of PO treatment strategies; and clinical recommendations and implementation of PO in clinical practice. CONCLUSION: POWG consensus statements standardize the clinical application of NGS CGPs, streamline the interpretation of clinically significant genomic alterations, and align actionable mutations with sequence-directed therapies. The POWG consensus statements may harmonize the utility and delivery of PO in China's GBA.

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.

Asian Thoracic Oncology Research Group (ATORG) Expert Consensus Statement on MET Alterations in NSCLC: Diagnostic and Therapeutic Considerations.

Non-small cell lung cancer (NSCLC) is a heterogeneous disease, with many oncogenic driver mutations, including de novo mutations in the Mesenchymal Epithelial Transition (MET) gene (specifically in Exon 14 [ex14]), that lead to tumourigenesis. Acquired alterations in the MET gene, specifically MET amplification is also associated with the development of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) resistance in patients with EGFR-mutant NSCLC. Although MET has become an actionable biomarker with the availability of MET-specific inhibitors in selected countries, there is differential accessibility to diagnostic platforms and targeted therapies across countries in Asia-Pacific (APAC). The Asian Thoracic Oncology Research Group (ATORG), an interdisciplinary group of experts from Australia, Hong Kong, Japan, Korea, Mainland China, Malaysia, the Philippines, Singapore, Taiwan, Thailand and Vietnam, discussed testing for MET alterations and considerations for using MET-specific inhibitors at a consensus meeting in January 2022, and in subsequent offline consultation. Consensus recommendations are provided by the ATORG group to address the unmet need for standardised approaches to diagnosing MET alterations in NSCLC and for using these therapies. MET inhibitors may be considered for first-line or second or subsequent lines of treatment for patients with advanced and metastatic NSCLC harbouring MET ex14 skipping mutations; MET ex14 testing is preferred within multi-gene panels for detecting targetable driver mutations in NSCLC. For patients with EGFR-mutant NSCLC and MET amplification leading to EGFR TKI resistance, enrolment in combination trials of EGFR TKIs and MET inhibitors is encouraged.

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.

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.

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.

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.

Reirradiation with intensity-modulated radiotherapy for locally recurrent T3 to T4 nasopharyngeal carcinoma.

BACKGROUND: The purpose of this study was to assess the efficacy and toxicities of reirradiation using intensity-modulated radiotherapy (IMRT) in patients with locally advanced recurrent nasopharyngeal carcinoma (NPC). METHODS: Thirty-eight patients with consecutive rT3 to rT4 NPC treated between 2005 and 2013 were retrospectively analyzed. RESULTS: The 3-year overall survival (OS), progression-free survival (PFS), and local control rate were 47.2%, 17.5%, and 44.3%, respectively. Gross target volume (GTV) D95 , GTV D50 , and age were all important prognostic factors for OS and PFS, but only GTV D95 was an important determinant for local control. A total of 73.7% patients experienced ≥1 grade 3 late toxicities and 3 patients died of massive epistaxis. Temporal lobe necrosis (TLN) developed sooner with a higher total biological equivalent dose. CONCLUSION: Adequate tumor dose coverage was important for treating rT3 to rT4 NPC. Although late complications were common, treatment-related mortality was solely vascular in nature. Dose constraints of neurologic structures for reirradiation should be revised with the latest information on late toxicities. © 2016 Wiley Periodicals, Inc. Head Neck 39: 533-540, 2017.

Comparison of Planning Quality and Efficiency Between Conventional and Knowledge-based Algorithms in Nasopharyngeal Cancer Patients Using Intensity Modulated Radiation Therapy.

PURPOSE: Intensity modulated radiation therapy (IMRT) is widely used to achieve a highly conformal dose and improve treatment outcome. However, plan quality and planning time are institute and planner dependent, and no standardized tool exists to recognize an optimal plan. RapidPlan, a knowledge-based algorithm, can generate constraints to assist optimization and produce high-quality IMRT plans. This report evaluated the quality and efficiency of using RapidPlan in nasopharyngeal carcinoma (NPC) IMRT planning. METHODS AND MATERIALS: RapidPlan was configured using 79 radical IMRT plans for NPC; 20 consecutive NPC patients indicated for radical radiation therapy between October 2014 and May 2015 were then recruited to assess its performance. The ability of RapidPlan to produce acceptable plans was evaluated. For plans that could not achieve clinical acceptance, manual touch-up was performed. The IMRT plans produced without RapidPlan (manual plans) and with RapidPlan (RP-2 plans, including those with manual touch-up) were compared in terms of dosimetric quality and planning efficiency. RESULTS: RapidPlan by itself could produce clinically acceptable plans for 9 of the 20 patients; manual touch-up increased the number of acceptable plans (RP-2 plans) to 19. The target dose coverage and conformity were very similar. No difference was found in the maximum dose to the brainstem and optic chiasm. RP-2 plans delivered a higher maximum dose to the spinal cord (46.4 Gy vs 43.9 Gy, P=.002) but a lower dose to the parotid (mean dose to right parotid, 37.3 Gy vs 45.4 Gy; left, 34.4 Gy vs 43.1 Gy; P<.001) and the right cochlea (mean dose, 48.6 Gy vs 52.6 Gy; P=.02). The total planning time for RP-2 plans was significantly less than that for manual plans (64 minutes vs 295 minutes, P<.001). CONCLUSIONS: This study shows that RapidPlan can significantly improve planning efficiency and produce quality IMRT plans for NPC patients.

Development and Validation of the McMaster Prescribing Competency Assessment for Medical Trainees (MacPCA).

BACKGROUND: Prescribing is an essential skill for all physicians, built on knowledge of clinical pharmacology, therapeutics and toxicology across the life cycle. The decline in organized clinical pharmacology training in medical schools, combined with an expanding pharmacopeia and increasing complexity of patient care, makes prescribing competency difficult for medical students to master. OBJECTIVES: To develop and validate the McMaster Prescribing Competency Assessment (MacPCA), an online tool suitable for evaluating clinical pharmacology knowledge and prescribing skills of medical trainees in Canada. METHODS: The MacPCA was developed using an online examination platform scalable to multiple sites across Canada. Questions represented 8 domains of safe and effective prescribing with level of difficulty aimed at a final year medical student. Validation assessment concentrated on face and construct validity. RESULTS: 58 participants (7, 12 and 21 medical students in Years 1, 2, and 3, respectively and 8 undergraduate controls) were recruited. Mean scores were 31% (SD 13.6), 46% (SD 14.9), 75% (SD 8.3) and 81% (SD 10.5) for the controls, Year 1, Year 2, and Year 3 (final year) students, respectively. Combined Year 2/Year 3 scores were significantly better than control/Year 1 scores (p<0.0001). Final year student feedback indicated the test was fair, clear and unambiguous, aimed at the right level, with sufficient time for completion. CONCLUSIONS: The MacPCA demonstrated good face validity and successfully discriminated between upper year medical students and their junior colleagues. Further expansion of testing and validation is warranted.

Preliminary results of trial NPC-0501 evaluating the therapeutic gain by changing from concurrent-adjuvant to induction-concurrent chemoradiotherapy, changing from fluorouracil to capecitabine, and changing from conventional to accelerated radiotherapy fractionation in patients with locoregionally advanced nasopharyngeal carcinoma.

BACKGROUND: A current recommendation for locoregionally advanced nasopharyngeal carcinoma (NPC) is conventional fractionated radiotherapy with concurrent cisplatin plus adjuvant cisplatin and fluorouracil (PF). In this randomized trial, the authors evaluated the potential therapeutic benefit from changing to an induction-concurrent chemotherapy sequence, replacing fluorouracil with oral capecitabine, and/or using accelerated rather than conventional radiotherapy fractionation. METHODS: Patients with stage III through IVB, nonkeratinizing NPC were randomly allocated to 1 of 6 treatment arms. The protocol was amended in 2009 to permit confining randomization to the conventional fractionation arms. The primary endpoint was progression-free survival. Secondary endpoints included overall survival and safety. RESULTS: In total, 803 patients were accrued, and 706 patients were randomly allocated to all 6 treatment arms. Comparisons of induction PF versus adjuvant PF did not indicate a significant improvement. Unadjusted comparisons of induction cisplatin and capecitabine (PX) versus adjuvant PF indicated a favorable trend in progression-free survival for the conventional fractionation arm (P = .045); analyses that were adjusted for other significant factors and fractionation reflected a significant reduction in the hazards of disease progression (hazard ratio [HR], 0.54; 95% confidence interval [CI], 0.36-0.80) and death (HR, 0.42; 95% CI, 0.25-0.70). Unadjusted comparisons of induction sequences versus adjuvant sequences did not reach statistical significance, but adjusted comparisons indicated favorable improvements by induction sequence. Comparisons of induction PX versus induction PF revealed fewer toxicities (neutropenia and electrolyte disturbance), unadjusted comparisons of efficacy were statistically insignificant, but adjusted analyses indicated that induction PX had a lower hazard of death (HR, 0.57; 95% CI, 0.34-0.97). Changing the fractionation from conventional to accelerated did not achieve any benefit but incurred higher toxicities (acute mucositis and dehydration). CONCLUSIONS: Preliminary results indicate that the benefit of changing to an induction-concurrent sequence remains uncertain; replacing fluorouracil with oral capecitabine warrants further validation in view of its convenience, favorable toxicity profile, and favorable trends in efficacy; and accelerated fractionation is not recommended for patients with locoregionally advanced NPC who receive chemoradiotherapy.

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.

Individualized treatment in stage IVC nasopharyngeal carcinoma.

The stage IVC nasopharyngeal carcinoma is a catch-all entity covering minute solitary metastasis to bulky disseminated disease. Prognosis varies greatly within this stage group. A subset of patients with oligometastases may benefit from aggressive local ablative therapy. Meanwhile, in multiple metastatic diseases, customizing conventional cytotoxics basing on individual tumor characteristics and previous chemotherapy responses can be a new direction to improve therapeutic results. Prognostic models built on clinical features and genomic profiles can be utilized to stratify different risk groups and tailor therapy schemes.

The impact of dosimetric inadequacy on treatment outcome of nasopharyngeal carcinoma with IMRT.

BACKGROUND AND PURPOSE: This study aims to address the relationship between tumor size and dosimetric inadequacy in treating nasopharyngeal carcinoma (NPC), and how it subsequently affects the local control. MATERIAL AND METHODS: 444 NPC patients treated with IMRT from 2005 to 2010 were included in the study. The planning aim was to deliver at least 66.5 Gy (i.e. 95% of 70 Gy) to 95% of the primary gross tumor volume (GTV_P) while keeping all the critical neurological organs at risk (OAR) within dose tolerance. Treatment outcome were analyzed according to T stage, GTV_P volume and the degree of under-dosing. RESULTS: Disease outcome was related to T stage, GTV_P volume and the degree of under-dosing. The 5-year local failure free survival (LFFS), disease free survival (DFS) and overall survival (OS) for T4 disease were 74%, 50.4% and 63.6% respectively. 48 cm(3) was identified as the critical cut-off GTV_P volume, the large volume group (GTV_P ≥ 48 cm(3)) had lower 5-year DFS (50.4% vs. 76.6%) and OS (65.2% vs. 86.3%, p < 0.001). Most T4 diseases (and some T3) were under-dosed (<66.5 Gy) and an under-dosed GTV_P volume of 3.4 cm(3) was found to be prognostically important. Multivariate analyses showed that the effect of GTV_P volume on LFFR and DFS was outweighed by the degree of under-dosing. CONCLUSIONS: Treatment outcome of locally advanced NPC was significantly affected by the volume of under-dosed (<66.5 Gy) GTV_P due to the neighboring neurological structures. A new set of OAR dose constraint and specification is proposed.

Staging of nasopharyngeal carcinoma--the past, the present and the future.

This article reviews the evolution of the International Union Against Cancer/American Joint Committee on Cancer staging system for nasopharyngeal carcinoma. With the increasing availability of newer imaging methods, more sophisticated radiotherapy techniques and rapidly evolving molecular assays, we also examine newer clinical features that might have impact on staging. A new version of the staging system taking into account of some of these factors is also proposed.

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.