Rice Bran Arabinoxylan Compound and Quality of Life (RBAC-QoL) of Cancer Patients: An Interim Analysis of the RBAC-QoL Study.

Background The effect of rice bran arabinoxylan compound (RBAC), a plant-based immunomodulator, on the quality of life (QoL) in cancer patients and underlying physiological pathways remains unclear. Trial design The RBAC-QoL study, a double-blind, randomised, controlled pilot feasibility study, aimed to determine RBAC's effects on QoL and the associated action mechanisms. Primary outcomes were the EORTC QLQ-C30 functional, symptom, and global QoL scores with inflammatory, nutritional, and cytokine parameters as secondary and exploratory outcomes. Methods Participants were adults diagnosed with solid organ tumours (≥ stage II) undergoing active treatment in several outpatient centres in New South Wales, Australia. Interventions were RBAC or matched placebo at 3g/day for 24 weeks allocated through stratified randomisation with participants, oncologists, and data collectors blinded. Data was collected from five study visits six weeks apart. The trial remained ongoing as of December 2023. An interim intention-to-treat analysis was performed using repeated measure ANOVA with pairwise comparisons where statistical significance was observed and adjusted with covariates. Results Global QoL scores from currently available data (n = 16; RBAC = 7, placebo = 9) were statistically different between groups (F1,8 = 8.6, p = 0.019, eta2[g] = 0.267). Pairwise comparisons found significant differences at Week 6 (p = 0.032, Cohen's d = 1.454) and marginally at Week 12 (p = 0.069, d = 1.427). Age-adjusted analysis showed a continuous upward trend in QoL improvement over time with RBAC, while the placebo group did not deviate from baseline QoL. Significant elevations of serum white blood cell count (Week 18) and total protein (Weeks 12 and 18) were detected in the RBAC group compared to placebo. The total protein levels correlated highly with white blood cell count (Pearson's r = 0.539, p < 0.001) and moderately with the global QoL scores (r = 0.338, p = 0.01). No intervention-related adverse events were reported in both groups.  Conclusions RBAC improves QoL beyond placebo during active cancer treatment, possibly through the immuno-nutritional pathway - these findings, though preliminary, are valuable for future research. Funding and registration: Daiwa Pharmaceutical Co., Ltd, Japan; BioMedica Nutraceuticals Pty Ltd., Australia. ANZCTR Reg No: ACTRN12619000562178p.

Early onset pancreatic cancer-exploring contemporary treatment and outcomes using real-world data.

BACKGROUND: Pancreatic cancer incidence is increasing in younger populations. Differences between early onset pancreatic cancer (EOPC) and later onset pancreatic cancer (LOPC), and how these should inform management warrant exploration in the contemporary setting. METHODS: A prospectively collected multi-site dataset on consecutive pancreatic adenocarcinoma patients was interrogated. Patient, tumour, treatment, and outcome data were extracted for EOPC (≤50 years old) vs LOPC (>50 years old). RESULTS: Of 1683 patients diagnosed between 2016 and 2022, 112 (6.7%) were EOPC. EOPC more frequently had the tail of pancreas tumours, earlier stage disease, surgical resection, and trended towards increased receipt of chemotherapy in the curative setting compared to LOPC. EOPC more frequently received 1st line chemotherapy, 2nd line chemotherapy, and chemoradiotherapy than LOPC in the palliative setting. Recurrence-free survival was improved for the tail of pancreas EOPC vs LOPC in the resected setting; overall survival was superior for EOPC compared to LOPC across the resected, locally advanced unresectable and metastatic settings. CONCLUSIONS: EOPC remains a small proportion of pancreatic cancer diagnoses. The more favourable outcomes in EOPC suggest these younger patients are overall deriving benefits from increased treatment in the curative setting and increased therapy in the palliative setting.

Immune checkpoint inhibitor therapy for advanced cutaneous squamous cell carcinoma in Australia: a retrospective real world cohort study.

OBJECTIVES: To review the outcomes of immune checkpoint inhibitor (ICI) treatment of advanced cutaneous squamous cell carcinoma (CSCC) outside clinical trials. STUDY DESIGN: Retrospective observational study; review of patient records in fifteen Australian institutions. SETTING, PARTICIPANTS: All Australian adults with locally advanced or metastatic CSCC not amenable to curative surgery or radiotherapy treated with ICIs, 5 May 2017 - 23 May 2022, through a cemiplimab compassionate access scheme (Therapeutic Goods Administration Special Access Scheme) or who personally covered the cost of pembrolizumab prior to the start of the access scheme. MAIN OUTCOME MEASURES: Best overall response rate (ORR) according to standardised assessment criteria using the hierarchy: Response Evaluation Criteria in Solid Tumors (RECIST 1.1), the modified World Health Organization clinical response criteria, and the Positron Emission Tomography Response Criteria (PERCIST 1.0); overall and progression-free survival. RESULTS: A total of 286 people with advanced CSCC received ICI therapy during May 2017 - May 2022 (cemiplimab, 270; pembrolizumab, 16). Their median age was 75.2 years (range, 39.3-97.5 years) and 232 were men (81%); median follow-up time was 12.2 months (interquartile range, 5.5-20.5 months). Eighty-eight people (31%) were immunocompromised, 27 had autoimmune disease, and 59 of 277 (21%) had ECOG performance scores of 2 or 3. The ORR was 60% (166 of 278 evaluable patients): complete responses were recorded for 74 (27%) and partial responses for 92 patients (33%). Twelve-month overall survival was 78% (95% confidence interval [CI], 72-83%); progression-free survival was 65% (95% CI, 58-70%). Poorer ECOG performance status was associated with poorer overall survival (per unit: adjusted hazard ratio [aHR], 3.0; 95% CI, 2.0-4.3) and progression-free survival (aHR, 2.4; 95% CI, 1.8-3.3), as was being immunocompromised (overall: aHR, 1.8; 95% CI, 1.1-3.0; progression-free: aHR, 1.8; 95% CI, 1.2-2.7). Fifty-five people (19%) reported immune-related adverse events of grade 2 or higher; there were no treatment-related deaths. CONCLUSION: In our retrospective study, the effectiveness and toxicity of ICI therapy were similar to those determined in clinical trials. Our findings suggest that ICIs could be effective and well tolerated by people with advanced CSCC who are ineligible for clinical trials.

Feasibility and preliminary effectiveness of virtual reality as a patient education tool for people with cancer undergoing immunotherapy: a protocol for a randomised controlled pilot study in a regional setting.

INTRODUCTION: Patient education is a critical component of healthcare delivery. However, medical information and knowledge are complex and can be difficult for patients and families to comprehend when delivered verbally. The use of virtual reality (VR) to convey medical information to patients may bridge this communication gap and lead to more effective patient education. It may be of increased value to those with low health literacy and levels of patient activation, in rural and regional settings. The objective of this randomised, single-centre pilot study is to examine the feasibility and preliminary effectiveness of VR as an education tool for people with cancer. The results will provide data to inform the feasibility of a future randomised controlled trial, including sample size calculations. METHODS AND ANALYSIS: Patients with cancer undergoing immunotherapy will be recruited. A total of 36 patients will be recruited and randomised to one of three trial arms. Participants will be randomised 1:1:1 to receive VR, a two-dimensional video or standard care (ie, verbal communication and information leaflets). Feasibility will be assessed by recruitment rate, practicality, acceptability, usability and related adverse events. The potential impact of VR on patient-reported outcomes (ie, perceived information provision quality, knowledge about immunotherapy and patient activation) will be assessed and stratified by information coping style (ie, monitors vs blunters) whenever statistical analyses are significant. The patient-reported outcomes will be measured at baseline, post-intervention and 2 weeks post-intervention. In addition, semistructured interviews will be conducted with health professionals and participants randomised to the VR trial arm, to further explore acceptability and feasibility. ETHICS AND DISSEMINATION: Ethics approval was obtained from the Greater Western Human Research Ethics Committee, New South Wales Local Health District (2022/ETH01760). Informed consent will be obtained from all participants. Findings will be disseminated via relevant conference presentations and publications in peer-reviewed journals. TRIAL REGISTRATION NUMBER: ACTRN12622001473752.

Use and outcomes from neoadjuvant chemotherapy in borderline resectable pancreatic ductal adenocarcinoma in an Australasian population.

BACKGROUND: Use of neoadjuvant (NA) chemotherapy is recommended when pancreatic ductal adenocarcinoma (PDAC) is borderline resectable METHOD: A retrospective analysis of consecutive patients with localized PDAC between January 2016 and March 2019 within the Australasian Pancreatic Cancer Registry (PURPLE, Pancreatic cancer: Understanding Routine Practice and Lifting End results) was performed. Clinicopathological characteristics, treatment, and outcome were analyzed. Overall survival (OS) comparison was performed using log-rank model and Kaplan-Meier analysis. RESULTS: The PURPLE database included 754 cases with localised PDAC, including 148 (20%) cases with borderline resectable pancreatic cancer (BRPC). Of the 148 BRPC patients, 44 (30%) underwent immediate surgery, 80 (54%) received NA chemotherapy, and 24 (16%) were inoperable. The median age of NA therapy patients was 63 years and FOLFIRINOX (53%) was more often used as NA therapy than gemcitabine/nab-paclitaxel (31%). Patients who received FOLFIRINOX were younger than those who received gemcitabine/nab-paclitaxel (60 years vs. 67 years, p = .01). Surgery was performed in 54% (43 of 80) of BRPC patients receiving NA chemotherapy, with 53% (16 of 30) achieving R0 resections. BRPC patients undergoing surgery had a median OS of 30 months, and 38% (9 of 24) achieved R0 resection. NA chemotherapy patients had a median OS of 20 months, improving to 24 months versus 10 months for patients receiving FOLFIRINOX compared to gemcitabine/nab-paclitaxel (Hazard Ratio (HR) .3, p < .0001). CONCLUSIONS: NA chemotherapy use in BRPC is increasing in Australia. One half of patients receiving NA chemotherapy proceed to curative resection, with 53% achieving R0 resections. Patients receiving Infusional 5-flurouracil, Irinotecan and Oxaliplatin (FOLIRINOX) had increased survival than gemcitabine/nab-paclitaxel. Treatment strategies are being explored in the MASTERPLAN and DYNAMIC-Pancreas trials.

'The best thing since sliced bread': Patient experiences of teleoncology in western NSW.

OBJECTIVE: This study explored experiences of rural cancer patients who were receiving treatments by remote video-assisted chemotherapy (RVAC) or participating in clinical trials remotely. SETTING: Participants lived in Coonabarabran or Dubbo in western NSW. PARTICIPANTS: Seven cancer patients undergoing treatment for breast, bladder or colon cancer, renal cell carcinoma or lymphoma. DESIGN: Appreciative inquiry informed this qualitative study. Semi-structured interviews were conducted between July 2018 and January 2019 and thematically analysed. RESULTS: The patient experience of teleoncology was overwhelmingly positive. Patients explained the value of relationships that developed with the local and virtual care team. Patients felt they received better care if they saw the same oncologist for the duration of their treatment and felt RVAC had accommodated this. Teleoncology allowed patients to remain independent because they were able to maintain their usual support mechanisms including family, friends and health care team. Patients described the reduced physical and emotional travel burden in addition to reduction in travel time and cost. CONCLUSIONS: These findings highlight the acceptability of teleoncology for rural patients as chemotherapy can be added to the health care and social and emotional supports, which exist in their hometown. Expansion of teleoncology should be codesigned with local communities with a focus on establishing care teams with consistent staffing to build trust between the treating team and the patient. These relationships improve the patient experience and enhance patient independence, which is a desirable attribute of cancer survivorship. Recruitment to clinical trials using teleoncology is acceptable and should be factored into trial development.

Impact of first-line FOLFIRINOX versus Gemcitabine/Nab-Paclitaxel chemotherapy on survival in advanced pancreatic cancer: Evidence from the prospective international multicentre PURPLE pancreatic cancer registry.

BACKGROUND: First-line palliative chemotherapy regimens in advanced pancreatic ductal adenocarcinoma (PDAC) have not been compared in head-to-head phase III randomised controlled trials (RCT). Data on optimum first-line treatment and subsequent sequencing is lacking. OBJECTIVE: To compare overall survival (OS) between first-line treatment regimens in a real-world population to determine if an optimal therapeutic sequence is associated with survival benefit. METHODS: A retrospective analysis of prospectively collated data from the Australasian PURPLE pancreatic cancer registry was undertaken. FINDINGS: From 2016 to 2020, of 1551 pancreatic cancer patients, 615 received palliative-intent chemotherapy. Patients with early-stage resected disease without recurrence (n = 369), radiotherapy alone (n = 43), received supportive care alone (n = 458) or had less than 3 months follow-up (n = 66) were excluded. Median OS was comparable between patients receiving first-line Gemcitabine/Nab-Paclitaxel (n = 376) and those receiving FOLFIRINOX (n = 73) (11.3 versus 12.3 months, P = 0.37), with 38% proceeding to second-line chemotherapy which was associated with longer mOS compared to first-line treatment alone (17.4 versus 8.2 months, P < 0.001). With second-line treatment following prior FOLFIRINOX (n = 29) or Gemcitabine/Nab-Paclitaxel (n = 101), mOS did not differ significantly (17.3 versus 15.9 months, P = 0.92), respectively, whilst median progression-free survival was longer with prior FOLFIRINOX (5.2 versus 2.9 months, P = 0.03). CONCLUSION: There was no significant difference in overall survival between either first-line chemotherapy choice, despite patients receiving FOLFIRINOX being younger, fitter, and more likely to have localised disease. However, FOLFIRINOX was associated with delayed progression. In the absence of phase III RCT data, clinicians should be comfortable using either Gemcitabine/Nab-Paclitaxel or FOLFIRINOX as first-line therapy in advanced PDAC.

Using three scenarios to explain life expectancy in advanced cancer: attitudes of patients, family members, and other healthcare professionals.

AIM: To evaluate a web-based tool for estimating and explaining three scenarios for expected survival time to people with advanced cancer (patients), their family members (FMs), and other healthcare professionals (HCPs). METHODS: Thirty-three oncologists estimated the "median survival of a group of similar patients" for patients seeking quantitative prognostic information. The web-based tool generated worst-case, most likely, and best-case scenarios for survival based on the oncologist's estimate. Oncologists presented the scenarios to each patient and provided a printed summary to patients, FMs, and HCPs. Attitudes to the information were assessed by questionnaires. Observed survival for each patient was compared with the oncologist's estimated survival and the three scenarios. RESULTS: Prognosis was discussed with 222 patients: median age 67 years; 61% male; most common primary sites pancreas 15%, non-small-cell lung 15%, and colorectal 12%. The median (range) for observed survival times was 9 months (0.5-43) and for oncologist's estimated survival times was 12 months (2-96). Ninety-one percent of patients, 91% of FMs, and 84% of HCPs agreed that it was helpful having life expectancy explained as three scenarios. The majority (77%) of patients judged the information presented about their life expectancy to be the same or better than they had expected before the consultation. The survival estimates met a priori criteria for calibration, precision, and accuracy. CONCLUSIONS: Patients, FMs, and HCPs found it helpful to receive personalized prognostic information formatted as three scenarios for survival. It was feasible, acceptable, and safe to use a web-based resource to do this.

Virtual reality as a patient education tool in healthcare: A scoping review.

OBJECTIVE: To explore what is currently known about the use of virtual reality (VR) as a patient education tool in healthcare. METHODS: Arksey and O'Malley's scoping review method and the PRISMA-ScR Checklist were employed. Four peer-reviewed databases were searched (Medline, Embase, PsychINFO, the Cochrane library). Pre-defined selection criteria identified 18 studies for inclusion. Results were synthesized using a narrative approach. RESULTS: VR as an educational tool in healthcare is feasible and acceptable, and may improve patient's knowledge about their illness and satisfaction with treatment. Most studies used the Oculus VR glasses or headset, educated patients though the use of 3D 360° VR anatomical models, and were conducted with people affected with cancer. Opportunities exist for exploring unintended consequences, and the role of VR in educating populations with lower health literacy. CONCLUSION: VR could assist in communicating medical information and knowledge to patients, but more research is needed, particularly to identify for whom and in what situations this method is most useful and to improve understanding about the potential unintended consequences. PRACTICE IMPLICATIONS: Health professionals should consider using VR to educate their patients, and researchers can use this as a road map on how to address knowledge gaps in this field.

Psychosocial well-being and supportive care needs of cancer patients and survivors living in rural or regional areas: a systematic review from 2010 to 2021.

PURPOSE: To summarise what is currently known about the psychosocial morbidity, experiences, and needs of people with cancer and their informal caregivers, who live in rural or regional areas of developed countries. METHODS: Eligible studies dating from August 2010 until May 2021 were identified through several online databases, including MEDLINE, EMBASE, PsychINFO, and RURAL (Rural and Remote Health Database). Results were reported according to the PRISMA guidelines and the protocol was registered on PROSPERO (CRD42020171764). RESULTS: Sixty-five studies were included in this review, including 20 qualitative studies, 41 quantitative studies, and 4 mixed methods studies. Qualitative research demonstrated that many unique psychosocial needs of rural people remain unmet, particularly relating to finances, travel, and accessing care. However, most (9/19) quantitative studies that compared rural and urban groups reported no significant differences in psychosocial needs, morbidity, or quality of life (QOL). Five quantitative studies reported poorer psychosocial outcomes (social and emotional functioning) in urban cancer survivors, while three highlighted poorer outcomes (physical functioning, role functioning, and self-reported mental health outcomes) in the rural group. CONCLUSION: Recent research shows that rural people affected by cancer have unique unmet psychosocial needs relating to rurality. However, there was little evidence that rural cancer survivors report greater unmet needs than their urban counterparts. This contrasts to the findings from a 2011 systematic review that found rural survivors consistently reported worse psychosocial outcomes. More population-based research is needed to establish whether uniquely rural unmet needs are due to general or cancer-specific factors.

Systematic Review of Neoadjuvant Immunotherapy for Patients With Non-Small Cell Lung Cancer.

There is a paucity of robust clinical evidence for the role of neoadjuvant immunotherapy in patients with resectable non-small cell lung cancer. The primary aim of the study was to identify the available data on the feasibility, safety and efficacy of neoadjuvant immunotherapy. A systematic review was conducted using electronic databases. Relevant studies were identified according to predefined selection criteria. Five relevant publications on 4 completed trials were identified. In most studies, >90% of patients were able to undergo surgery within the planned timeframe after neoadjuvant immunotherapy. There was a high incidence of open thoracotomy procedures, either planned or converted from a planned minimally invasive approach. Mortality ranged from 0 to 5%, but none of the reported deaths were considered directly treatment-related. Morbidities were reported according to adverse events related to neoadjuvant systemic therapy, and postoperative surgical complications. Survival outcomes were limited due to short follow-up periods. Major pathologic response ranged from 40.5 to 56.7%, whilst complete pathologic response of the primary tumor ranged from 15 to 33%. Radiological responses were reported according to RECIST criteria and fluorodeoxyglucose-avidity. This systematic review reported safe perioperative outcomes of patients who underwent resection following neoadjuvant immunotherapy. However, there was a relatively high incidence of open thoracotomy procedures, partly due to the technical challenges associated with increased fibrosis and inflammation of tissue, as well as the more advanced stages of disease in patients enrolled in the studies. Future studies should focus on identifying predictors of pathological response.

Impact of COVID-19 on cancer service delivery: results from an international survey of oncology clinicians.

OBJECTIVES: To report clinician-perceived changes to cancer service delivery in response to COVID-19. DESIGN: Multidisciplinary Australasian cancer clinician survey in collaboration with the European Society of Medical Oncology. SETTING: Between May and June 2020 clinicians from 70 countries were surveyed; majority from Europe (n=196; 39%) with 1846 COVID-19 cases per million people, Australia (AUS)/New Zealand (NZ) (n=188; 38%) with 267/236 per million and Asia (n=75; 15%) with 121 per million at time of survey distribution. PARTICIPANTS: Medical oncologists (n=372; 74%), radiation oncologists (n=91; 18%) and surgical oncologists (n=38; 8%). RESULTS: Eighty-nine per cent of clinicians reported altering clinical practices; more commonly among those with versus without patients diagnosed with COVID-19 (n=142; 93% vs n=225; 86%, p=0.03) but regardless of community transmission levels (p=0.26). More European clinicians (n=111; 66.1%) had treated patients diagnosed with COVID-19 compared with Asia (n=20; 27.8%) and AUS/NZ (n=8; 4.8%), p<0.001. Many clinicians (n=307; 71.4%) reported concerns that reduced access to standard treatments during the pandemic would negatively impact patient survival. The reported proportion of consultations using telehealth increased by 7.7-fold, with 25.1% (n=108) of clinicians concerned that patient survival would be worse due to this increase. Clinicians reviewed a median of 10 fewer outpatients/week (including non-face to face) compared with prior to the pandemic, translating to 5010 fewer specialist oncology visits per week among the surveyed group. Mental health was negatively impacted for 52.6% (n=190) of clinicians. CONCLUSION: Clinicians reported widespread changes to oncology services, in regions of both high and low COVID-19 case numbers. Clinician concerns of potential negative impacts on patient outcomes warrant objective assessment, with system and policy implications for healthcare delivery at large.

Rice bran arabinoxylan compound and quality of life of cancer patients (RBAC-QoL): Study protocol for a randomized pilot feasibility trial.

INTRODUCTION: Rice bran arabinoxylan compound (RBAC) is a nutraceutical for enhancing a depleted immune system during and after cancer treatment. This pilot feasibility trial aims to evaluate the effects of RBAC on cancer patients' quality of life during active treatment, compared to placebo, using a validated questionnaire. Other outcome measures include changes in inflammatory and nutritional status, cytokine profile, and gut microbiota. METHODS/DESIGN: The study will recruit 50 participants from a regional cancer center in Australia. Patients aged 18-70, diagnosed with solid organ cancers stage II and above, and currently undergoing active systemic therapies, are eligible. Random allocation of participants into two groups is stratified based on metastatic status and treatment type. The dosage is either 3 g/day of RBAC or placebo in identical packaging. The participants, study coordinator, and treating oncologists are blinded to the interventions. Data collections are at baseline and at four follow-up sessions, which are six weeks apart (24 weeks). Statistical analysis will involve a protected p-value with multiple dependent values and analyzed by ANOVA with repeated measures on the occasion of testing and with both a full Bonferroni or Sidak corrections applied to protect against Type I errors. Any observed significance warrants further analysis with pairwise comparisons. Analysis of covariance will also be performed to assess any influence of the demographic data, cancer diagnosis, as well as changes in physical activity, dietary habits, and complementary medicine usage. Comparisons of gut microbiota will be based on the analysis of the fecal microbiome using 16S ribosomal ribonucleic acid amplicon sequencing. The proposed research timeline is from October 2018 to May 2022. TRIAL REGISTRATION: ANZCTR. Reg No: ACTRN12619000562178p.

Older adults' preferred and perceived roles in decision-making about palliative chemotherapy, decision priorities and information preferences.

AIM: Patients with cancer have varied preferences for involvement in decision-making. We sought older adults' preferred and perceived roles in decision-making about palliative chemotherapy; priorities; and information received and desired. METHODS: Patients ≥65y who had made a decision about palliative chemotherapy with an oncologist completed a written questionnaire. Preferred and perceived decision-making roles were assessed by the Control Preferences Scale. Wilcoxon rank-sum tests evaluated associations with preferred role. Factors important in decision-making were rated and ranked, and receipt of, and desire for information was described. RESULTS: Characteristics of the 179 respondents: median age 74y, male (64%), having chemotherapy (83%), vulnerable (Vulnerable Elders Survey-13 score ≥ 3) (52%). Preferred decision-making roles (n = 173) were active in 39%, collaborative in 27%, and passive in 35%. Perceived decision-making roles (n = 172) were active in 42%, collaborative in 22%, and passive in 36% and matched the preferred role for 63% of patients. Associated with preference for an active role: being single/widowed (p = .004, OR = 1.49), having declined chemotherapy (p = .02, OR = 2.00). Ranked most important (n = 159) were "doing everything possible" (30%), "my doctor's recommendation" (26%), "my quality of life" (20%), and "living longer" (15%). A minority expected chemotherapy to cure their cancer (14%). Most had discussed expectations of cure (70%), side effects (88%) and benefits (82%) of chemotherapy. Fewer had received quantitative prognostic information (49%) than desired this information (67%). CONCLUSION: Older adults exhibited a range of preferences for involvement in decision-making about palliative chemotherapy. Oncologists should seek patients' decision-making preferences, priorities, and information needs when discussing palliative chemotherapy.

Retrospective Evaluation of the Use of Pembrolizumab in Malignant Mesothelioma in a Real-World Australian Population.

INTRODUCTION: We investigated the efficacy and toxicity of pembrolizumab in patients with mesothelioma from a real-world Australian population. We aimed to determine clinical factors and predictive biomarkers that could help select patients who are likely to benefit from pembrolizumab. METHOD: Patients with mesothelioma who were treated with pembrolizumab as part of the Insurance and Care New South Wales compensation scheme were included. Clinical information was collected retrospectively. Tumor biomarkers such as programmed death-ligand 1 (PD-L1), BAP1, and CD3-positive (CD3+) tumor-infiltrating lymphocytes (TILs) were examined using archival formalin-fixed paraffin-embedded tumor samples. RESULTS: A total of 98 patients were included with a median age of 70 years (range, 46-91 y); 92% were men; 76% had epithelioid subtype; 21% had an Eastern Cooperative Oncology Group (ECOG) performance status of 0. Pembrolizumab was used as second-line or subsequent-line treatment in 94 patients and as first-line treatment in four patients. The overall response rate was 18%, and the disease control rate was 56%. The median progression-free survival (PFS) was 4.8 months (95% confidence interval: 3.6-6.2), and the median overall survival (OS) was 9.5 months (95% confidence interval: 6.6-13.7). Immune-related adverse events occurred in 27% of patients, of which nine (9%) were of grade 3 or higher. In the multivariable analysis, factors independently associated with longer PFS included baseline ECOG status of 0 (median PFS: 12 mo versus 4 mo, p < 0.01) and PD-L1 tumor proportion score of greater than or equal to 1% (median PFS: 6 mo versus 4 mo, p < 0.01). Baseline platelet count of less than or equal to 400 × 109/liter was independently associated with longer PFS and OS (median PFS: 6 mo versus 2 mo, p = 0.05; median OS: 10 mo versus 4 mo, p = 0.01), whereas lack of pretreatment dexamethasone was independently associated with OS but not PFS (median OS: 10 mo versus 3 mo, p = 0.01). The odds of response were higher for patients with baseline ECOG status of 0 (p = 0.02) and with greater than or equal to 5% CD3+ TILs in the tumor (p < 0.01). PD-L1 expression, BAP1 loss, and CD3+ TILs in the stroma were not significantly associated with the overall response rate. CONCLUSIONS: Immunotherapy is a reasonable treatment option for patients with mesothelioma. Our results are comparable to other clinical trials investigating pembrolizumab in mesothelioma in terms of response. Good performance status assessment remains the most robust predictor for patient outcomes. CD3+ TILs in the tumor may help select patients that are likely to respond to pembrolizumab, whereas factors such as PD-L1 expression, baseline platelet count, and lack of pretreatment dexamethasone may help predict survival outcomes from pembrolizumab treatment.

Patterns of immunotherapy use and management of toxicities in regional and tertiary settings.

BACKGROUND: The introduction of the cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) and programmed cell death protein 1 (PD-1) immune checkpoint inhibitors and their subsequent listing on the Pharmaceutical Benefits Scheme for use in metastatic melanomas, renal cell carcinomas and non-small-cell lung cancers has resulted in routine use of these agents in oncology practices, including in regional areas. Although immunotherapeutic agents generally have a favourable toxicity profile compared to chemotherapy, they can provoke immune-related adverse effects (irAE) caused by an unregulated and hyperstimulated immune response. Some of these effects can be serious and life-threatening. AIMS: To compare the utilisation of immunotherapy and the rates, management and outcomes of irAE between a regional oncology service and a tertiary service. METHODS: We reviewed the medical records for all patients treated with immunotherapy in the participating services for the 5-year period from 31 July 2012 to 31 July 2017. RESULTS: Data demonstrated that rates of immunotherapy use are both similar and increasing across the tertiary and regional services. The rates, types and severity of irAE are equivalent and in concordance with pre-existing literature. Immune-related adverse events appear to be identified and treated earlier in the regional service with the corresponding reduction in the duration of immunosuppression and requirement for inpatient management. CONCLUSION: The use of immunotherapy in a regional setting is safe and equivalent to that of a tertiary centre.

A multicentre analysis of abiraterone acetate in Canadian patients with metastatic castration-resistant prostate cancer.

INTRODUCTON: The COU-AA-301 trial showed that abiraterone acetate (abiraterone), an oral cytochrome p450 CYP17 inhibitor, improved survival for men with metastatic castration-resistant prostate cancer (mCRPC) progressing after docetaxel. To better understand the non-clinical trial experience with abiraterone, we undertook a multicentre retrospective analysis of Canadian mCRPC patients treated with abiraterone. METHODS: Consecutive patients with mCRPC who received abiraterone post-docetaxel were identified using centralized pharmacy records. These patients came from 5 Canadian tertiary cancer centres. Patients who received abiraterone for approved indications were included. Demographics, prognostic factors, treatment outcomes and adverse events were abstracted. RESULTS: We included 187 patients who initiated abiraterone between January 2011 and June 2012. The median age at diagnosis and abiraterone start was 65 and 73 years, respectively. Seventy-three (39%) patients had metastatic disease at diagnosis. The Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, 2 and 3 was noted in 17, 96, 39 and 8 patients, respectively. The median prostate-specific antigen (PSA) at abiraterone start was 132, with a median PSA doubling time of 2.8 months. The median follow-up of patients still on active follow-up was 13 months. The proportion of patients achieving a ≥50% PSA reduction was 64/177 (36%). PSA progression-free survival was 3.5 months (95% confidence interval [CI], 3.0, 4.0). Median overall survival from start of abiraterone was 11 months (95% CI, 8.0, 13) and 38 months (95% CI, 31, 41) from date of mCRPC. Anemia and fatigue were the most commonly reported adverse events. CONCLUSIONS: This study carries the inherent limitations of a retrospective chart review. The outcomes in this series of men treated with abiraterone in a non-trial setting were expected, considering previous clinical trials. Our results, therefore, support the generalizability of the COU-AA-301 study results.

NT-proBNP Changes in Patients with Ascites during Large Volume Paracentesis.

Background. N-terminal probrain natriuretic peptide (NT-proBNP) is a hormone involved in the regulation of cardiovascular homeostasis. Changes in serum NT-proBNP during large volume paracentesis (LVP) in patients with ascites have never before been examined. Aims. To determine if significant changes in serum NT-proBNP occur in patients undergoing LVP and the associated clinical correlates in patients with cirrhosis. Method. A total of 45 patients with ascites were prospectively recruited. Serum NT-proBNP, biochemistry, and haemodynamics were determined at baseline and at key time points during and after paracentesis. Results. 34 patients were analysed; 19 had ascites due to cirrhosis and 15 from malignancy. In those with cirrhosis, NT-proBNP decreased by 77.3 pg/mL at 2 L of drainage and 94.3 pg/mL at the end of paracentesis, compared with an increase of 10.5 pg/mL and 77.2 pg/mL in cancer patients at the same time points (P = 0.05 and P = 0.03). Only congestive cardiac failure (CCF) was an independent predictor of significant NT-proBNP changes at the end of drainage in cirrhotic patients (P < 0.01). There were no significant changes in haemodynamics or renal biochemistry for either group. Conclusion. Significant reductions in serum NT-proBNP during LVP occur in patients with cirrhosis but not malignancy, and only comorbid CCF appeared to predict such changes.