Multi-domain neurocognitive impairment following definitive intensity-modulated radiotherapy for nasopharyngeal cancer: A cross-sectional study.

INTRODUCTION: Neurocognitive impairment from inadvertent brain irradiation is common following intensity-modulated radiotherapy (IMRT) for nasopharyngeal carcinoma (NPC). This study aimed to determine the prevalence, pattern, and radiation dose-toxicity relationship of this late complication. MATERIALS AND METHODS: We undertook a cross-sectional study of 190 post-IMRT NPC survivors. Neurocognitive function was screened using the Montreal Cognitive Assessment-Hong Kong (HK-MoCA). Detailed assessments of eight distinct neurocognitive domains were conducted: intellectual capacity (WAIS-IV), attention span (Digit Span and Visual Spatial Span), visual memory (Visual Reproduction Span), verbal memory (Auditory Verbal Learning Test), processing speed (Color Trail Test), executive function (Stroop Test), motor dexterity (Grooved Pegboard Test) and language ability (Verbal Fluency Test). The mean percentiles and Z-scores were compared with normative population data. Associations between radiation dose and brain substructures were explored using multivariable logistic regression. RESULTS: The median post-IMRT interval was 7.0 years. The prevalence of impaired HK-MoCA was 25.3 % (48/190). Among the participants, 151 (79.4 %) exhibited impairments in at least one neurocognitive domain. The predominantly impaired domains included verbal memory (short-term: mean Z-score, -0.56, p < 0.001; long-term: mean Z-score, -0.70, p < 0.001), processing speed (basic: mean Z-score, -1.04, p < 0.001; advanced: mean Z-score, -0.38, p < 0.001), executive function (mean Z-score, -1.90, p < 0.001), and motor dexterity (dominant hand: mean Z-score, -0.97, p < 0.001). Radiation dose to the whole brain, hippocampus, and temporal lobe was associated with impairments in executive function, verbal memory, processing speed, and motor dexterity. CONCLUSIONS: Neurocognitive impairment is prevalent and profound in post-IMRT NPC survivors. Cognitive assessment and rehabilitation should be considered part of survivorship care.

The prevalence of gastroesophageal reflux disease and laryngopharyngeal reflux in patients with dysphagia after radiotherapy for nasopharyngeal carcinoma.

BACKGROUND: The prevalence of gastroesophageal reflux disease (GERD) and laryngopharyngeal reflux (LPR) in post-irradiated patients with nasopharyngeal carcinoma (NPC) is unknown. MATERIALS AND METHODS: In a cross-sectional study, 31 NPC and 12 control patients completed questionnaires for GERD/LPR before esophageal manometry and 24-h pH monitoring. The DeMeester score and reflux finding score (RFS) were used to define GERD and LPR, respectively. Risk factors were identified. RESULTS: 51.6% of NPC and 8.3% of control patients, and 77.4% of NPC and 33% of control patients, were GERD-positive and LPR-positive, respectively. The GERD/LPR questionnaire failed to identify either condition in patients with NPC. No parameter differences in esophageal manometry or pneumonia incidence were noted between GERD/LPR-positive and GERD/LPR-negative patients. Post radiotherapy duration, high BMI, lack of chemotherapy, and dysphagia were positive risk factors for GERD/LPR. CONCLUSIONS: A high prevalence of GERD/LPR in patients with post-irradiated NPC exists, but reflux symptoms are inadequate for diagnosis.

Comparison of Clinical Outcomes, Pathologic Characteristics, and Immune-Related Features of Postradiation vs Sporadic Oral Cavity Squamous Cell Carcinoma.

Importance: Postradiation oral cavity squamous cell carcinoma (OCSCC) is a common secondary malignant neoplasm affecting survivors of head and neck cancer who underwent radiotherapy. The clinical, pathologic, and immune-related features of postradiation OCSCC are poorly characterized, and treatment options are limited because of surgical difficulty and high morbidity associated with reirradiation. Objective: To determine whether postradiation OCSCC has distinctive clinical, pathologic, and immune-related features compared with demographic-matched sporadic OCSCC. Design, Setting, and Participants: This retrospective matched cohort study was conducted at a single tertiary oncology center in Hong Kong. Participants included consecutive patients with OCSCC diagnosed between 2000 and 2020. Patients with postradiation OCSCC were matched with patients with sporadic OCSCC using age, year of diagnosis, sex, and anatomic subsites. Data analysis was performed from July to December 2022. Exposure: Head and neck irradiation involving the oral cavity before the diagnosis of OCSCC. Main Outcomes and Measures: The primary outcomes were relapse pattern, survival, and causes of death. Pathologic features; immunohistochemical staining for programmed death-ligand 1, PD-1, MSH6, PMS2, FOXP3, and Ki67; and mRNA expression of 31 immune-related genes were also analyzed. Results: A total of 173 patients, 60 with postradiation OCSCC (median [IQR] age, 63.8 [53.0-71.7] years; 43 men [71.7%]) and 113 with sporadic OCSCC (median [IQR] age, 64.4 [52.8-70.6] years; 83 men [73.5%]), were included. Patients with postradiation OCSCC had a higher proportion of N0 disease than those with sporadic OCSCC (50 patients [83.3%] vs 56 patients [49.6%]). With a median (IQR) follow-up of 10.2 (1.2-20.5) years, the 10-year relapse-free survival rates were lower in patients with postradiation OCSCC than sporadic OCSCC (29.6% [95% CI, 17.1%-43.2%] vs 52.4% [95% CI, 41.8%-62.0%]; P = .04), and the same was true for overall survival (30.5% [95% CI, 17.6%-44.4%] vs 52.3% [95% CI, 41.4%-62.1%]; P = .03). All relapses in patients with postradiation OCSCC were locoregional, whereas 35.2% of relapses (12 of 34 patients) in patients with sporadic OCSCC were distant. Despite similar 10-year disease-specific survival rates between the 2 groups (68.8% [95% CI, 55.8%-81.0%] vs 67.1% [95% CI, 57.5%-76.5%]; P = .91), patients with postradiation OCSCC had excess mortality due to pneumonia and cerebrovascular events. Postradiation OCSCC exhibited more adverse pathologic features (perineural invasion, worse pattern of invasion, and tumor budding), higher PD-1 expression, and higher gene expression of CD4 and TGF-ß compared with sporadic OCSCC. Conclusions and Relevance: This retrospective matched cohort study found distinctive pathologic characteristics and relapse patterns of postradiation OCSCC compared with sporadic OCSCC, which may be attributable to the lack of adjuvant radiotherapy, aggressive biologic phenotype, and different host immune response. Further exploration of the role of immune checkpoint therapy may be justified.

Effectiveness of population-based colorectal cancer screening programme in down-staging.

BACKGROUND: This is the first evaluation study to assess the demographic characteristics of the colorectal cancer (CRC) cases detected in the prevalent round of the population-based Colorectal Cancer Screening Programme (CRCSP) in Hong Kong and to explore the effectiveness of the programme on the stage distribution of CRC. METHODS: This study covered the period between 28 September 2016 and 31 December 2018. Information on CRC diagnosis, age and stage at diagnosis were retrieved and reviewed by the Hong Kong Cancer Registry (HKCaR). The CRC detection rate among CRCSP-screened participants and incidence rate among the Hong Kong general population were calculated respectively. The odds ratio (OR) was calculated to measure the strength of association and quantify the effect of CRCSP on stage shift between CRCSP-detected CRC cases and an age-matched cohort of CRC cases diagnosed outside the programme. RESULTS: The CRC detection rate among participants of the CRCSP during the study period was 736.0/100,000, whereas the overall CRC incidence rate among general population of similar age groups was 393.7/100,000. For all ages and both sexes, the OR of stage I CRCSP-detected CRC compared to the CRC from the age-matched cohort was 3.91 (95%CI=3.41-4.48) and the OR dropped to 0.54 (95%CI=0.41-0.70) at stage IV. Meanwhile, the overall OR of CRCSP-detected CRC compared to CRC from the age-matched cohort dropped from 2.24 (95%CI=1.97-2.56) to 1.62 (95%CI=1.40-1.87) with increasing age. CONCLUSION: The present study has demonstrated the initial impact of the CRCSP on shifting the stage at diagnosis towards earlier stage. The benefit of stage-shift was similar for all ages from 60 to 77 in both sexes and seems to increase with younger age. Given the stage-dependent survival outcomes, this stage-shift could lead to a reduction in CRC-associated mortality in Hong Kong in future.

Real-World Perspectives From Surgeons and Oncologists on Resectability Definition and Multidisciplinary Team Discussion of Stage III NSCLC in People's Republic of China, Hong Kong, and Macau: A Physician Survey.

Introduction: Decision-making in diagnosis and management of stage III NSCLC remains complex owing to disease heterogeneity and diverse treatment options, and often warrants multidisciplinary team discussion. Specifically, the selection of patients for multimodality approaches involving surgical resection presents notable challenges owing to heterogeneity in guideline definitions and the subjective, case-specific nature of evaluating resectability on the basis of preoperative assessments. Methods: An internet- and paper-based survey was conducted in 2020 among lung cancer specialists in the People's Republic of China, Hong Kong, and Macau. This survey captured perspectives on stage III NSCLC on real-world diagnosis/staging practice, definition and evaluation of resectability using case scenarios, and preferred treatment paradigms. Results: A total of 60 completed responses were obtained (60.0% surgeons; 40.0% oncologists). The surgeons' and oncologists' responses differed most in the assessment of resectability in specific case scenarios despite overall agreement on top factors determining resectability (T stage, lymph node size, and lymph node location). Of the 17 scenarios, specialists agreed (≥80%) on four "resectable" and six "unresectable" scenarios; of the seven scenarios with less than 80% agreement, surgeons and oncologists had diverging responses for six scenarios. Multidisciplinary team discussions were available in most of the respondents' institutions but usually covered only selected (<50%) stage III cases. Conclusions: This survey used a comprehensive set of stage III NSCLC case scenarios to understand how working definitions of resectability may differ between surgeons and oncologists, and thus, identify types of cases to prioritize for multidisciplinary discussions to maximize limited resources. In parallel, the development of a multidisciplinary expert consensus on treatment approaches could complement local institutional expertise as a reference for decision-making.

A practical methodology to improve the dosimetric accuracy of MR-based radiotherapy simulation for brain tumors.

PURPOSE: To investigate the dosimetric accuracy of synthetic computed tomography (sCT) images generated by a clinically-ready voxel-based MRI simulation package, and to develop a simple and feasible method to improve the accuracy. METHODS: 20 patients with brain tumor were selected to undergo CT and MRI simulation. sCT images were generated by a clinical MRI simulation package. The discrepancy between planning CT and sCT in CT number and body contour were evaluated. To resolve the discrepancies, an sCT specific CT-relative electron density (RED) calibration curve was used, and a layer of pseudo-skin was created on the sCT. The dosimetric impact of these discrepancies, and the improvement brought about by the modifications, were evaluated by a planning study. Volumetric modulated arc therapy (VMAT) treatment plans for each patient were created and optimized on the planning CT, which were then transferred to the original sCT and the modified-sCT for dose re-calculation. Dosimetric comparisons and gamma analysis between the calculated doses in different images were performed. RESULTS: The average gamma passing rate with 1%/1 mm criteria was only 70.8% for the comparison of dose distribution between planning CT and original sCT. The mean dose difference between the planning CT and the original sCT were -1.2% for PTV D95 and -1.7% for PTV Dmax, while the mean dose difference was within 0.7 Gy for all relevant OARs. After applying the modifications on the sCT, the average gamma passing rate was increased to 92.2%. Mean dose difference in PTV D95 and Dmax were reduced to -0.1% and -0.3% respectively. The mean dose difference was within 0.2 Gy for all OAR structures and no statistically significant difference were found. CONCLUSIONS: The modified-sCT demonstrated improved dosimetric agreement with the planning CT. These results indicated the overall dosimetric accuracy and practicality of this improved MR-based treatment planning method.

Integrated palliative medicine in public oncology: a 10-year review.

OBJECTIVES: The rapid ageing population of Hong Kong has a high demand on oncology and palliative care (PC) service. This study was the first territory-wide assessment in Hong Kong to assess the palliative service coverage in patients with advanced cancer in the past decade. METHODS: Cancer deaths of all 43 public hospitals of Hong Kong were screened. Randomly selected 2800 cancer deaths formed a representative cohort in all seven service clusters of Hospital Authority at 4 time points (2006, 2009, 2012, 2015). Individual patient records were thoroughly reviewed. Predictors of PC coverage was evaluated in univariable and multivariable analyses. RESULTS: From 2006 to 2015, PC coverage improved steadily from 55.4% to 68.9% (p<0.001). Median time of referral to PC service to death was 25 days (IQR: 53). For duration of inpatient PC, the median time was 22 days (IQR: 44) and it was stable over the past 10 years. Median time of referral to outpatient service to death was 74 days (IQR: 144) and there was an improvement observed (p<0.05). The current system was highly heterogeneous that PC varied between 9.8% and 84.8% in different hospitals depending on the PC service infrastructure. Multivariable Cox model identified patients associated with lower PC coverage: male, <50, rapid disease deterioration and staying in hospitals without multidisciplinary team clinic and designated palliative bed support (all p<0.01). CONCLUSION: There was concrete achievement in palliative service development in the past decade. Heterogeneity and late service provision should be addressed in future.

Docetaxel-Induced Peripheral Neuropathy in Breast Cancer Patients Treated with Adjuvant or Neo-Adjuvant Chemotherapy.

BACKGROUND: Docetaxel-induced peripheral neuropathy (PN) is typically manifested as sensory and motor neuropathy. This study aimed to investigate the incidence, duration, and risk factors of sensory and motor PN and their impact on health-related quality of life (HRQOL) among breast cancer (BC) patients during the first year since starting docetaxel-based chemotherapy. METHODS: We reported a secondary analysis of longitudinal data on docetaxel-induced PN and HRQOL among 127 BC patients. RESULTS: Cumulative incidence rates of motor and sensory PN were 31.5 and 21.3%, while the median durations of motor and sensory PN were 6 and 13 weeks. A consistently significant risk factor for both PNs was a cumulative docetaxel dose of >300 mg/m2. A significant interaction between sensory PN and time was found for physical and social functioning, while a significant motor PN and time interaction effect was identified for physical functioning only. CONCLUSIONS: Motor PN was more common than sensory PN in BC patients treated with docetaxel. Both types of PN had a significant impact on physical functioning.

Integrative Palliative Care Service Model Improved End-of-Life Care and Overall Survival of Advanced Cancer Patients in Hong Kong: A Review of Ten-Year Territory-Wide Cohort.

Background: Integrated palliative care in oncology service has been widely implemented in Hong Kong since 2006. Aim: The study aimed to review its impact on end-of-life outcomes and overall survival (OS) of cancer patients, as well as its utilization of health care resources in the past 10 years. Design: Cancer deaths of all 43 public hospitals of Hong Kong were screened. Setting/Participants: Randomly selected 2800 cancer deaths formed a representative cohort in all seven service clusters of Hospital Authority at four time points (2006, 2009, 2012, and 2015). Individual patient records were thoroughly reviewed. Propensity score-matched (PSM) analysis was employed to compare the survival of patients. Results: Palliative care provision was associated with improved palliative care outcome, including more prescription of strong opioid, fewer cardiopulmonary resuscitations and intensive care unit admissions, and less futile chemotherapy usage in the end-of-life period (all p < 0.001). In the PSM analysis, the median OS in patients with palliative service (5.10 months, 95% confidence interval [CI] 4.52-5.68 months) was significantly better than those without palliative service (1.96 months, 95% CI 1.66-2.27 months). Patients in the palliative care group had more specialist clinic visits (p < 0.001) and longer hospital stay (p < 0.001) in the last six months of life, although the duration of last admission stay at acute general ward was shortened (p < 0.001). Conclusion: Our results suggested palliative care has played a role in the remarkable improvement in end-of-life outcomes and OS. However, current palliative care model relied heavily on hospital resources. Future work is needed to strengthen community care and to build up quality monitoring systems.

Application of hypoglossal nerve constraint in definitive radiotherapy for nasopharyngeal carcinoma: A dosimetric feasibility study.

PURPOSE: Radiation-induced hypoglossal nerve palsy is an infrequent but debilitating late complication after definitive radiotherapy for head and neck cancers. D1cc < 74 Gy (equivalent dose in 2 Gy fractions, EQD2) has been proposed as a potential dose constraint that limits 8-year palsy risk to < 5%. This study sets to perform detailed dosimetric assessments on the applicability of this novel dose constraint in advanced nasopharyngeal carcinoma (NPC). MATERIALS AND METHODS: This is a retrospective single-institution dosimetry study. NPC radiotherapy plans were identified from an institutional database, with an aim to select 10 eligible cases. Bilateral hypoglossal nerves were retrospectively contoured following a standard atlas. Cases with either one, or both, hypoglossal nerves D1cc exceeded 74 Gy EQD2 were included. Dosimetry of hypoglossal nerves, planning target volumes (PTV) and normal structures before and after application of the new hypoglossal nerve constraint were compared and analyzed. RESULTS: Ten NPC cases were replanned. All hypoglossal nerve contours overlapped with high-dose PTV, predominantly at regions of gross nodal diseases. D1cc in 15 out of 20 hypoglossal nerves exceeded 74G y EQD2 at initial plans. All nerves fulfilled the pre-specified constraint of 74Gy EQD2 after re-plan. Median hypoglossal nerve D1cc reduced from 74.8Gy (range, 74.1 to 77.4Gy) to 73.5Gy (range, 72.4 to 74.0Gy) (p < 0.001), corresponded to a projected reduction in 8-year palsy risk from 5%-14% to 3%-5%. PTV V100 was maintained above 95% in all cases. Dose increments in near-maximum (D2) and decrements in near-minimum (D98) were < 1 Gy. Safety dosimetric parameters of standard head and neck organs-at-risk showed no significant changes. CONCLUSIONS: Hypoglossal nerve D1cc < 74 Gy EQD2 is a dosimetrically feasible constraint in definitive radiotherapy for NPC. Tumor target coverage and normal organ dosimetry were not compromised with its usage. Its routine application should be considered in definitive radiotherapy for head and neck cancers.

Psychometric testing of the Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity (FACT/GOG-Ntx) subscale in a longitudinal study of cancer patients treated with chemotherapy.

BACKGROUND: The aim of this study was to evaluate the psychometric properties of the Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity (FACT/GOG-Ntx) subscale in a longitudinal study of cancer patients treated with chemotherapy. METHODS: Patients were assessed with the FACT/GOG-Ntx subscale, European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Chemotherapy-Induced Peripheral Neuropathy Scale 20 (EORTC QLQ-CIPN20), National Cancer Institute -Common Terminology Criteria for Adverse Events (NCI-CTCAE), and light touch test using 10 g monofilament for up to ten assessment points from baseline (prior to initiation of first chemotherapy), after the end of each cycle (up to 6 cycles, 3 weeks per cycle), and at 6, 9, and 12 months after starting chemotherapy. Psychometric analyses included internal consistency reliability, convergent validity, factorial validity, sensitivity to change and responsiveness (minimal clinically important difference, MCID). RESULTS: Cronbach's alpha coefficients of the FACT/GOG-Ntx subscale were 0.82-0.89 across assessment points. The subscale strongly correlated with the EORTC QLQ-CIPN20 (r = 0.79-0.93) but low-to-moderately correlated with the NCI-CTCAE sensory (rs = 0.23-0.45) and motor items (rs = 0.15-0.50) as well as the monofilament test (rs = 0.23-0.47). The hypothesized 4-factor structure of the FACT/GOG-Ntx subscale was not confirmed at assessment points (χ2/df = 2.26-8.50; all P < 0.001). The subscale exhibited small-to-moderate sensitivity to change (r = 0.17-0.37). The MCIDs were between 1.38 and 3.68. CONCLUSION: The FACT/GOG-Ntx subscale has satisfactory reliability, validity, sensitivity to change and responsiveness to evaluate CIPN in cancer patients. Future research is needed to explore the factorial structure of the FACT/GOG-Ntx subscale as the published four-factor structure was not supported in this study.

Palliative radiation therapy for patients with orbital and ocular metastases.

BACKGROUND: Patients with cancer may develop metastases to the orbit causing distressing symptoms. External beam radiation therapy (RT) is an effective palliative treatment for patients with orbital and ocular metastases. The aim of treatment is to preserve vision and to reduce pain. Delivery of 30 to 40 Gy in 2 Fr fractions is a practice in many oncology centres. The aim of this study is to evaluate the outcome of shortcourse palliative radiotherapy in the management of orbital and ocular metastases. METHODS: A retrospective study to review all patients with orbital metastases treated in 2016 to 2018 were performed. The primary outcomes were a change in visual acuity and tumor response. Secondary outcomes included toxicities of radiotherapy, symptomatic response and survival. RESULTS: Fifteen patients with 19 eyes were included. The most common presenting symptoms were decreased vision, periorbital swelling, and pain. The median follow-up period was 8 months. Visual acuity improved in 11 out of 13 (84.6%) of patients and remained stable in the remaining 2 patients. Partial and complete response (CR) of tumor was observed in 14 out of 15 (93.3%) of patients while one (6.6%) patient had stable disease. The overall response rate (ORR) was 100%. Two (13.3%) patients had grade 2 conjunctivitis. There were no grade 3-4 toxicities and no long-term toxicities observed. The median survival was 9.1 months from diagnosis of choroidal metastases. CONCLUSIONS: Short course palliative RT is effective and well tolerated in patients with orbital and ocular metastases. The current review showed that it effectively preserves vision and improves orbital symptoms with minimal radiation-induced toxicity. Short course radiotherapy will help to minimize the traveling time to the hospital and relieve the burden of a long treatment course in this palliative patient population.

Radiation-induced hypoglossal nerve palsy after definitive radiotherapy for nasopharyngeal carcinoma: Clinical predictors and dose-toxicity relationship.

BACKGROUND AND PURPOSE: Radiation-induced hypoglossal nerve palsy is a debilitating and irreversible late complication after definitive radiotherapy for nasopharyngeal carcinoma (NPC) and other skull base tumors. This study sets to evaluate its incidence and clinical predictive factors, and to propose relevant dosimetric constraints for this structure to guide radiotherapy planning. MATERIALS AND METHODS: We undertook a retrospective review of 797 NPC patients who underwent definitive intensity-modulated radiotherapy (IMRT) between 2003 and 2011. Cumulative incidence and clinical predictors for radiation-induced hypoglossal nerve palsy were evaluated. Archived radiotherapy plans were retrieved and 330 independent hypoglossal nerves were retrospectively contoured following standardized atlas. Optimal threshold analyses of dosimetric parameters (Dmax, D0.5cc, D1cc, D2cc, Dmean) were conducted using receiver operating characteristic curves. Normal tissue complication probability was generated with logistic regression modeling. RESULTS: With a median follow-up of 8.1 years, sixty-nine (8.7%) patients developed radiation-induced hypoglossal nerve palsy. High radiotherapy dose, premorbid diabetes, advanced T-stage and radiological hypoglossal canal involvement were independent clinical risk factors. Maximum dose received by 1 cc volume (D1cc) was the best predictor for the development of radiation-induced nerve palsy (AUC = 0.826) at 8 years after IMRT. Hypoglossal nerves with D1cc of 74 Gy EQD2 had an estimated palsy risk of 4.7%. Nerves with D1cc <74 Gy EQD2 had significantly lower risk of palsy than those ≥74 Gy EQD2 (2.4% vs 20.8%, p <0.001). CONCLUSION: Incidence of radiation-induced hypoglossal nerve palsy was high after definitive IMRT for NPC. D1cc <74 Gy EQD2 can serve as a useful dose constraint to adopt during radiotherapy planning to limit palsy risk to <5% at 8 years after IMRT.

Risk factors for chemotherapy-induced peripheral neuropathy in patients receiving taxane- and platinum-based chemotherapy.

BACKGROUND: Chemotherapy-induced peripheral neuropathy (CIPN) is a significant and difficult to manage side effect of neurotoxic chemotherapies. Several risk factors for CIPN have been identified to date, but inconsistencies and methodological limitations exist in past research. Also, a limited number of potential risk factors has been investigated in the past. AIM: The objective of this study was to assess the relative contribution of a wider range of risk factors in the development of CIPN. METHODS: This analysis used the 6-month data after starting chemotherapy from a larger prospective observational study on CIPN risk, prevalence, and quality of life. Patients were assessed at recruitment for possible CIPN risk factors, including prior history of neuropathies, current/past infectious diseases; neurotoxic medication history; personal and treatment characteristics; smoking history, alcohol use, and vegetable/fruit intake. Neuropathy was assessed at 6-months after starting chemotherapy with the neuropathy (motor/sensory) items of the NCI-CTCAE scale and the WHO criterion for neuropathy. Data on symptom burden were also collected. RESULTS: Data were available from 255 patients from three cancer centers in Hong Kong, Singapore, and UK. The use of different scales did not always identify the same predictor variables. Key risk factors in multivariate regression models included older age (highest OR = 1.08, p < 0.01 with the WHO scale), chemotherapy (platinum-based chemotherapy had OR = 0.20-0.27 in developing CIPN compared to taxane-based chemotherapy), history of neuropathy (for motor CIPN only, OR = 8.36, p < 0.01), symptom burden (OR = 1.06, p < 0.05), number of chemotherapy cycles received (OR = 1.19-1.24, p < 0.01), and alcohol intake (OR = 0.32, p < 0.05). In univariate analysis, the use of statins was implicated with CIPN (p = 0.03-0.04 with different assessments) and diabetes showed a trend (p = 0.09) in the development of CIPN. CONCLUSION: This study confirmed the CIPN risk related to certain variables and identified new ones. This knowledge can assist with treatment decisions and patient education.

Minimal clinically important difference of the EORTC QLQ-CIPN20 for worsening peripheral neuropathy in patients receiving neurotoxic chemotherapy.

CONTEXT/OBJECTIVES: This is the first study to determine the minimal clinically important difference (MCID) of the European Organisation of Research and Treatment of Cancer Quality of Life Questionnaire-CIPN twenty-item scale (EORTC QLQ-CIPN20), a validated instrument designed to elicit cancer patients' experience of symptoms and functional limitations related to chemotherapy-induced peripheral neuropathy. METHODS: Cancer patients receiving neurotoxic chemotherapy completed EORTC QLQ-CIPN20 and the Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity [FACT/GOG-NTX] at baseline, second cycle of chemotherapy (T2, n = 287), and 12 months after chemotherapy (T3, n = 191). Anchor-based approach used the validated FACT/GOG-NTX neurotoxicity (Ntx) subscale to identify optimal MCID cutoff for deterioration. Distribution-based approach used one-third standard deviation (SD), half SD, and one standard error of measurement of the total EORTC QLQ-CIPN20 score. RESULTS: There was a moderate correlation between the change scores of the Ntx subscale and sensory and motor subscales of QLQ-CIPN20 (T2: r = - 0.722, p < 0.001 and r = - 0.518, p < 0.001, respectively; T3: r = - 0.699; p < 0.001 and r = - 0.523, p < 0.001, respectively). The correlation between the change scores of the Ntx subscale and the QLQ-CIPN20 autonomic subscale was poor (T2: r = - 0.354, p < 0.001; T3: r = 0.286, p < 0.001). Based on the MCID derived using distribution-based method, the MCID for the QLQ-CIPN20 sensory subscale was 2.5-5.9 (6.9% to 16.4% of the subdomain score) and for motor subscale was 2.6-5.0 (8.1%-15.6% of the subdomain score). CONCLUSION: The MCID for the EORTC QLQ-CIPN20 established using distribution-based approaches was 2.5-5.9 for the sensory subscale and 2.6-5.0 for the motor subscale. When noted in assessments even with small change in scores, clinicians can be alerted for appropriate intervention.

Living with chemotherapy-induced peripheral neuropathy: Uncovering the symptom experience and self-management of neuropathic symptoms among cancer survivors.

PURPOSE: The study aimed at uncovering the symptom experience of neurotoxicity, self-adopted approaches and perspectives in managing chemotherapy-induced peripheral neuropathic (CIPN) symptoms in a sample of Chinese cancer survivors. METHODS: A qualitative descriptive study was used to explore individual experiences. A purposive sample of 12 female participants experiencing CIPN was invited to semi-structured interviews who were part of a larger prospective observational study investigating the natural progression and risk factors of CIPN. Textual interview data were managed in NVivo. Content analysis was used. RESULTS: Participants were aged 41-64 years and experienced moderate to severe neuropathic symptoms from 5 to 23 months after completion of a six-cycle chemotherapy regimens at reported during the interviews. Four categories emerged from the qualitative data, namely, (1) experience come to reality: characteristics of CIPN symptoms, (2) disruptions and perceived threat: ability to perform activities and resume work, (3) re-establishing an 'at least satisfactory level of well-being', and (4) views of and approaches in managing neuropathic symptoms. CONCLUSIONS: The characteristics of CIPN symptoms causing disruptions in functional and/or psychosocial well-being from the patients' perspectives and the self-help strategies used to manage symptoms showed a need to provide quality multidisciplinary supportive care, focusing on restoring functional and psychosocial well-being, and enhancing knowledge about symptom assessment and evidence-based strategies for empowering cancer survivors to cope with this complex symptom.

T790M mutant copy number quantified via ddPCR predicts outcome after osimertinib treatment in lung cancer.

Osimertinib prolongs progression-free survival (PFS) in patients with metastatic, epidermal growth factor receptor (EGFR) T790M-mutated, non-small cell lung cancer (NSCLC) after failure of EGFR tyrosine kinase inhibitor (TKI) therapy. We investigated the utility of T790M mutant copy number quantification in a plasma cell-free DNA (cfDNA) assay for predicting clinical outcomes of osimertinib treatment. We retrospectively examined 161 patients who underwent plasma EGFR testing using a digital droplet polymerase chain reaction (ddPCR) technique after EGFR-TKI failure. Of the 74 (46%) patients with detectable T790M mutations in plasma, 55 received osimertinib treatment. Patients who achieved partial response had a higher plasma mutant copy levels than those with progressive disease. Patients who achieved stable disease also tended to have higher plasma mutant copy levels than those with progressive disease. High mutant copy number (≥ 105 per mL of plasma) was associated with shorter PFS (median: 5.5 months vs. not reached) and overall survival (median: 9.1 months vs. NR). Quantitative measurements of T790M mutant copy number in plasma cfDNA by ddPCR thus predicted treatment response and survival outcomes after osimertinib in NSCLC patients resistant to EGFR TKI.

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.

International radiation oncology trainee decision making in the management of radiotherapy-induced nausea and vomiting.

PURPOSE: This study explored international radiation oncology trainee decision making in the management of radiotherapy-induced nausea and vomiting (RINV). METHODS: Radiation oncology trainees who were members of the national radiation oncology associations of the USA, Canada, Netherlands, Australia, New Zealand, France, Spain and Singapore completed a Web-based survey. Respondents estimated the risks of nausea and vomiting associated with six standardised radiotherapy-only clinical case vignettes modelled after international anti-emetic guidelines and then committed to prophylactic, rescue or no therapy as an initial management approach for each case. RESULTS: One hundred and seventy-six trainees from 11 countries responded. Only 28 % were aware of any anti-emetic guideline. In general, risk estimates and management approaches for the high-risk and minimal risk cases varied less and were more in line with guideline standards than were estimates and approaches for the moderate- and low-risk cases. Prophylactic therapy was the most common approach for the high-risk and a moderate-risk case (83 and 71 % of respondents respectively), while rescue therapy was the most common approach for a second moderate-risk case (69 %), two low-risk cases (69 and 76 %) and a minimal risk case (68 %). A serotonin receptor antagonist was the most commonly recommended prophylactic agent. On multivariate analysis, a higher estimated risk of nausea predicted for recommending prophylactic therapy, and a lower estimated risk of nausea predicted for recommending rescue therapy. CONCLUSIONS: Radiation oncology trainee risk estimates and recommended management approaches for RINV clinical case vignettes varied and matched guideline standards more often for high-risk and minimal risk cases than for moderate- and low-risk cases. Risk estimates of nausea specifically were strong predictors of management decisions.

'Who', 'when' and 'how' in re-irradiation of recurrent painful bone metastases.

Re-irradiation of painful bony metastases is increasingly performed since patients are receiving better systemic treatments and having longer life expectancy, and may also be due to the increase use of initial single fraction radiotherapy. However, randomized control trial on the efficacy of re-irradiation is lacking. A recent meta-analysis concluded with a 58% response rate for pain relief by re-irradiation of symptomatic bone metastases. In this review, the effectiveness of re-irradiation in terms of clinical and economical aspects, and clinical questions on who, when, and how to re-irradiate would be discussed. A brief review of other treatment options and comparison with re-irradiation of bone metastases would be performed.