Exploring assessment of balance using virtual reality in patients at risk of chemotherapy-induced peripheral neuropathy.

BACKGROUND: Chemotherapy-induced peripheral neuropathy (CIPN) is a common dose-limiting toxicity for people treated for cancer. Impaired balance and falls are functional consequences of CIPN. Virtual reality (VR) technology may be able to assess balance and identify patients at risk of falls. AIMS: To assess the impact of potentially neurotoxic chemotherapy on balance using VR, and explore associations between VR balance assessment, falls and CIPN. METHODS: This prospective, repeated measures longitudinal study was conducted at two Australian cancer centres. Eligible participants were commencing adjuvant chemotherapy containing a taxane for breast cancer, or oxaliplatin for colorectal cancer (CRC), per institutional guidelines. Balance assessments using VR were conducted at baseline, end of chemotherapy and 3 and 6 months after completion of chemotherapy. Participants also completed a comprehensive CIPN assessment comprising clinical and patient-reported outcomes, and recorded falls or near falls. RESULTS: Out of 34 participants consented, 24 (71%) had breast cancer and 10 (29%) had CRC. Compared to baseline, balance threshold was reduced in 10/28 (36%) evaluable participants assessed at the end of chemotherapy, and persistent in 7/22 (32%) at 6 months. CIPN was identified in 86% at end of chemotherapy and persisted to 6 months after chemotherapy completion in 73%. Falls or near falls were reported by 12/34 (35%) participants, and were associated with impaired VR balance threshold (P = 0.002). CONCLUSIONS: While VR balance assessment was no better at identifying CIPN than existing measures, it is a potential surrogate method to assess patients at risk of falls from CIPN.

Patterns of Patient-Reported Chemotherapy-Induced Peripheral Neuropathy in Colorectal Cancer Survivors.

BACKGROUND: Chemotherapy-induced peripheral neuropathy (CIPN) can be a debilitating toxicity of oxaliplatin used for treatment of colorectal cancer (CRC). We aimed to assess CIPN symptoms and associations in our colorectal survivorship population and review the impact of neurotoxicity on dose delivery of oxaliplatin. PATIENTS AND METHODS: Patients attending their first visit to the Sydney Cancer Survivorship Centre following completion of adjuvant treatment for CRC completed comprehensive patient-reported outcome measures, including symptoms, quality of life (QoL), alcohol intake, and exercise habits. Participants scored symptoms of "numbness or pins and needles" in hands or feet from 0 (no trouble at all) to 10 (worst I can imagine). Diagnosis, treatment, and comorbidity details were obtained from medical records. A subset of patients completed serial assessments of PN symptoms at follow-up visits. RESULTS: Data were analyzed from 233 patients (52% male; mean age, 63 years) with CRC attending their first visit at the Sydney Cancer Survivorship Centre. A subset of 104 patients were included in the longitudinal analysis. The odds of patient-reported numbness were significantly higher in patients receiving oxaliplatin (odds ratio, 5.6; 95% CI, 3.2-9.8), with 72.4% of oxaliplatin-treated CRC survivors reporting numbness an average of 5.9 months after chemotherapy. Mean patient-reported numbness was significantly higher in those who received oxaliplatin-containing chemotherapy (mean, 3.31) compared with fluoropyrimidines alone (mean, 1.37) and no chemotherapy (mean, 0.66). Of the patients receiving oxaliplatin, 80% required dose reduction or early cessation, with PN the most common reason reported. QoL in physical, emotional, and functional well-being domains was lower in patients with numbness. We found a weak negative association between numbness score and age, and between (1) numbness and cardiovascular disease and (2) numbers and pain score. CONCLUSIONS: CIPN symptoms are common in CRC survivors who have received oxaliplatin and are associated with lower QoL. Neurotoxicity is underreported in clinical trials compared with real-world populations and is a major barrier to oxaliplatin treatment delivery.

Evaluating laser photobiomodulation for chemotherapy-induced peripheral neuropathy: a randomised phase II trial.

PURPOSE: This study aims to evaluate the efficacy and safety of laser photobiomodulation (PBM) for treatment of established chemotherapy-induced peripheral neuropathy (CIPN) in cancer survivors. METHODS: We conducted a randomised phase II, non-comparative, sham-controlled, single-blinded clinical trial in 44 cancer survivors reporting CIPN symptoms at least 3 months following completion of neurotoxic chemotherapy. Participants were randomised 2:1 to either PBM laser or sham control delivered twice weekly for 12 sessions. Assessments were conducted at baseline, the end of intervention (6 weeks), and 6 weeks post intervention (12 weeks). Participants completed neuropathy, quality of life and function questionnaires, and a clinical neurological assessment. The primary outcome was proportion of participants with CIPN response, defined as either symptom resolution or reduction of minimally clinically important difference. RESULTS: In the laser and control groups, CIPN response rates were - 48% and 53% at 6 weeks and 45% and 33% at 12 weeks, respectively. The null hypothesis that the true response rate is 5% in the laser arm was rejected at both 6 and 12 weeks (p < 0.001 for both). Compared to baseline, patient-reported CIPN improved in both laser and control groups after the intervention. At 12 weeks, improvement was sustained in the laser group and approaching baseline in the control group. Clinical signs, quality of life, and function remained stable in both groups. Low-grade "side-effects" were observed in both arms. CONCLUSION: PBM may offer clinically meaningful symptom benefit in cancer survivors with established CIPN with improvement potentially continuing beyond completion of the intervention. A larger study is warranted to evaluate this further.

Systematic review of long-term chemotherapy-induced peripheral neuropathy (CIPN) following adjuvant oxaliplatin for colorectal cancer.

PURPOSE: Chemotherapy-induced peripheral neuropathy (CIPN) is the most common dose-limiting side effect of oxaliplatin. It often persists and can adversely affect quality of life of colorectal cancer (CRC) survivors. This systematic review explored the proportions of patients with persistent CIPN and the reporting methods used. METHODS: MEDLINE, EMBASE, Web of Science and CINAHL were searched up to March 2021 for publications reporting CIPN outcomes following adjuvant oxaliplatin-containing chemotherapy at prespecified timepoints in participants with CRC. Secondary outcomes assessed the tools used to measure CIPN. Two authors reviewed full text publications for eligibility, data extraction and appraisal. Meta-analysis was performed where Common Terminology Criteria for Adverse Events (any grade) was reported at the most frequent timepoints. RESULTS: From 7895 citations identified, 27 studies met the eligibility criteria: six were randomised control trials, and 21 were non-randomised studies. Pooled prevalence of CIPN at 6, 12, 24 and 36 months after chemotherapy were 58%, 45%, 32% and 24% respectively. The average prevalence of CIPN decreased by 26% per year after chemotherapy (pooled RR = 0.74; 95% CI 0.72-0.75). Across all studies, ten separate tools were used as the primary measure of CIPN. Quality appraisal identified open-label design and inadequate reporting of participants lost to follow-up as the main methodological limitations. CONCLUSION: Our summary of reported rates of persistent CIPN indicates substantial long-term toxicity affecting CRC survivors, and will help clinicians estimate CIPN risk and its change over time. The heterogeneity of CIPN measures identified in the review highlights the need for a standardised CIPN assessment.

Delays to diagnosis and treatment of lung cancer in Australia: healthcare professional perceptions of actual versus acceptable timeframes.

BACKGROUND: Streamlined referral to specialist care impacts lung cancer outcomes. AIM: To examine Australian healthcare professionals' (HCP) perceptions of the timeliness of pathways to diagnosis and treatment for people with lung cancer, compared against timeframe guidelines. METHODS: A 21-item survey of HCP evaluating patient waiting times to diagnosis and treatment of lung cancer was distributed through two Australian conferences, a national Multidisciplinary Team directory and email. Main outcome measures were HCP estimates of actual and acceptable waiting times in their practice and factors contributing to perceived delays. RESULTS: A total of 135 responses was obtained from HCP working in secondary healthcare who had recent clinical experience treating lung cancer patients. While 79% believed a diagnosis of lung cancer should be obtained within 14 days of first clinical suspicion, only 56% estimated that this occurred in their practice due mainly to delays in primary care. Most HCP (81%) estimated that patients receive treatment within 28 days of seeing a specialist, but 28% believed a wait of >14 days to treatment was a 'delay', generally due to resource limitations. In general, most HCP estimates of time spent in primary care were longer than those in the literature, while estimates for secondary care were shorter. CONCLUSIONS: Australian HCP treating lung cancer patients perceive a mismatch between acceptable and estimated waiting times to diagnosis and treatment of lung cancer due to patient, provider and system factors. If perceived delays are justified, it is unclear whether HCP overestimate times spent by patients in primary care or underestimate delays in secondary care. Variations in HCP expectations need to be addressed.

Workforce shortages in medical oncology: a looming threat to quality cancer care.

Supply must meet demand to maintain our high standards of cancer care.

The shortage of medical oncologists: the Australian Medical Oncologist Workforce Study.

OBJECTIVE: To determine current and projected supply, demand and shortfall of medical oncologists (MOs) and the Australian chemotherapy utilisation rate. DESIGN, SETTING AND PARTICIPANTS: A 2009 cross-sectional observational study of Australian adult medical oncology practice work patterns. INSTRUMENT: Electronic or paper self-administered questionnaire. MAIN OUTCOME MEASURES: The 2009 and projected (2014) supply, demand and shortfall of full-time equivalent (FTE) MOs, and the chemotherapy utilisation rate. RESULTS: 476 medical oncology positions comprising 234 FTE MOs were identified. Of the 150 medical oncology practices, 117 (78%) were in metropolitan locations and 33 (22%) were in rural locations. The average number of new patients seen per FTE MO was 270 patients (ranging by state from 191 to 343). The demand for FTE MOs was estimated at 326 to 391 in 2009 and 361 to 432 in 2014. The shortfall of FTE MOs was estimated at 92 to 157 in 2009 and 84 to 156 in 2014. The chemotherapy utilisation rate was 19%. CONCLUSIONS: The current shortage of MOs is expected to persist in the future. National strategies are needed to increase the capacity of the medical oncology workforce and the chemotherapy utilisation rate.

Why do delays to diagnosis and treatment of lung cancer occur? A mixed methods study of insights from Australian clinicians.

AIMS: Delays in lung cancer diagnosis and treatment can impact survival. We explored reasons for delays experienced by patients with lung cancer to identify themes and strategies for improvement. METHODS: We used national timeframe recommendations and standardized definitions to identify General Practitioners and specialists caring for 34 patients who experienced delays in our previous Medicare data linkage study. Clinicians participated in a survey and interview, including qualitative (exploratory, open-ended questions) and quantitative (rating scales) components. Exploratory content analysis, cross-case triangulation, and descriptive statistics were performed. Krippendorff's coefficient was used to assess level of agreement between clinicians and patients, and among clinicians, on perceived delays. RESULTS: Overall, 27 out of 50 (54%) eligible clinicians participated (including 11 respiratory physicians and seven medical oncologists). Dominant themes for perceived causes of delay included referral barriers, limited General Practitioner (GP) awareness of subtle clinical presentations, insufficient radiology interpretation, and lack of cancer coordinators. "Unavoidable" delays may occur due to clinical circumstances. Awareness and uptake of referral and timeframe guidelines were low, with clinicians using professional networks over guidelines. There was no consistent agreement on perceived delays between patients and clinicians, and among clinicians (Krippendorff's coefficient .03 [P = .8]). CONCLUSIONS: Strategies for minimizing avoidable delays include efficient GP to specialist referral and more lung cancer coordinators to assist with patient expectations and waitlist management. Clinicians' reliance on experience, rather than guidelines, indicates need to review guideline utility. Raising awareness of benchmarks and unavoidable barriers may recalibrate perceptions of "delays" to diagnosis and treatment of lung cancer.

Ibudilast for prevention of oxaliplatin-induced acute neurotoxicity: a pilot study assessing preliminary efficacy, tolerability and pharmacokinetic interactions in patients with metastatic gastrointestinal cancer.

PURPOSE: This prospective, open-label, sequential 'before vs. after' pilot study was conducted to provide preliminary efficacy and tolerability data for ibudilast in the prevention of oxaliplatin-induced neurotoxicity in patients with metastatic upper gastrointestinal or colorectal cancer. Any potential impact of ibudilast on oxaliplatin and 5-fluorouracil pharmacokinetics was also explored. METHODS: Participants were administered a chemotherapy cycle (FOLFOX or CapeOx), followed by a chemotherapy cycle with co-administration of ibudilast 30 mg b.i.d. p.o. Efficacy was assessed on Day 3 and end of cycle using the Oxaliplatin-Specific Neurotoxicity Scale (OSNS) and additional clinical/patient-reported neurotoxicity measures. A population pharmacokinetic approach was used to determine oxaliplatin and 5-fluorouracil pharmacokinetics with and without ibudilast. RESULTS: Sixteen participants consented; 14 completed both chemotherapy cycles. Across all measures, the majority of participants experienced either an improvement or no worsening of neurotoxicity with ibudilast treatment. Based on OSNS assessments, acute neurotoxicity was unchanged in 12/14 participants and improved in 2/14 participants. The 90% confidence interval (CI) of the dose-normalised ratio of oxaliplatin AUC (90% CI 95.0-109%) and 5-fluorouracil AUC (90% CI 66.5-173%) indicated no significant impact of ibudilast on systemic exposure. CONCLUSION: This pilot study indicated ibudilast co-administration may improve or stabilise oxaliplatin-induced neurotoxicity. Given the expected worsening of symptoms in patients with continued chemotherapy, this represents a signal of effect that warrants further investigation. Pharmacokinetic analysis indicates ibudilast has no significant effect on oxaliplatin pharmacokinetics, and is unlikely to influence pharmacokinetics of 5-fluorouracil. CLINICAL TRIAL REGISTRATION: Trial registration number: UTN U1111-1209-0075 and ANZCTRN12618000232235 (registered 13/02/2018).

How long is too long? A scoping review of health system delays in lung cancer.

Earlier access to lung cancer specialist (LCS) care improves survival, highlighting the need for streamlined patient referral. International guidelines recommend 14-day maximum time intervals from general practitioner (GP) referral to first LCS appointment ("GP-LCS interval"), and diagnosis to treatment ("treatment interval"). We compared time intervals in lung cancer care against timeframe benchmarks, and explored barriers and facilitators to timely care.We conducted a scoping review of literature from MEDLINE, Embase, Scopus and hand searches. Primary end-points were GP-LCS and treatment intervals. Performance against guidelines and factors responsible for delays were explored. We used descriptive statistics and nonparametric Wilcoxon rank sum tests to compare intervals in studies reporting fast-track interventions.Of 1343 identified studies, 128 full-text articles were eligible. Only 33 (26%) studies reported GP-LCS intervals, with an overall median of 7 days and distributions largely meeting guidelines. Overall, 52 (41%) studies reported treatment intervals, with a median of 27 days, and distributions of times falling short of guidelines. There was no effect of fast-track interventions on reducing time intervals. Lack of symptoms and multiple procedures or specialist visits were suggested causes for delay.Although most patients with lung cancer see a specialist within a reasonable timeframe, treatment commencement is often delayed. There is regional variation in establishing timeliness of care.

Times to Diagnosis and Treatment of Lung Cancer in New South Wales, Australia: A Multicenter, Medicare Data Linkage Study.

INTRODUCTION: Earlier access to lung cancer specialist (LCS) care improves survival. We examined times to diagnosis and treatment of patients with lung cancer in rural and metropolitan New South Wales (NSW) Australia, benchmarked against recent timeframe recommendations. MATERIALS AND METHODS: Semistructured interviews of recently diagnosed patients with lung cancer from five NSW cancer centers were used to determine standardized time intervals to diagnosis and treatment, triangulated with Medicare data linkage and medical records. We used descriptive statistics to evaluate the primary end points of median time intervals from general practitioner (GP) referral to first LCS visit (GP-LCS interval) and to treatment start (Secondary Care interval). Univariable and multivariable analyses were used to study associations with delays in end points. Post hoc survival analyses were performed. RESULTS: Data linkage was performed for 125 patients (68% stage IV; 69% metropolitan), with 108 interviewed. The median GP-LCS interval was 4 days, with 83% of patients seeing an LCS within the recommended 14 days. The median Secondary Care interval was 42 days (52% within 42 days). There were no significant differences between time intervals faced by rural and metropolitan patients overall, although metropolitan patients took 18 days less than rural counterparts to commence radiation/chemoradiation (95% CI, -33.2 to -2.54; P = .02). One third of patients perceived delays. Delays did not affect survival. CONCLUSION: Rural and metropolitan NSW patients face comparable time lines to diagnosis and treatment of lung cancer. Most patients are seen by an LCS within recommended timeframes, but transition through Secondary Care and addressing patient expectations could be improved.