Staff experiences of the use of virtual consultations in non-surgical oncology systemic anticancer therapy services.

PURPOSE: In response to the COVID-19 pandemic, virtual consultations were introduced rapidly across cancer services. This created a particular set of challenges for systemic anticancer therapy services, where patients have frequent, regular appointments to support decision-making regarding treatment. This study explores the experiences of staff who provide these consultations to understand the implications for patients, staff, and services. METHODS: A mixed-methods approach was utilized using electronic surveys containing open text and structured responses and a focus group. The survey was sent to all staff in a regional cancer center who carried out consultations with patients receiving Systemic Anticancer Therapy. Data collection took place between October 2020 and January 2021. Open text responses were analyzed using framework techniques. RESULTS: Thirty-three medical, nursing, and pharmacy staff completed the survey, and 21 attended the focus group. Staff experiences were described within a framework of risk, loss, and gain. Virtual consultations had clinical consequences for the accuracy of assessments and communication with patients. Criteria for using virtual or in-person appointments were identified along with organizational systems and processes that influenced effectiveness and safety. Concerns were raised regarding role satisfaction and use of clinical skills. CONCLUSION: The study provides new insights into the experiences and concerns of staff associated with virtual appointments. The primary purpose of consultation in systemic anticancer therapy services is to support decision-making regarding treatment, and the study identified obstacles to achieving this alongside possible criteria for determining when in-person or virtual consultations may be appropriate.

What are the competency requirements for clinical pharmacist verification of systemic anti-cancer therapy (SACT) prescribed within a clinical trial? A consensus study.

BACKGROUND: Since 2005 it has been a legal requirement in Scotland to have a suitably trained pharmacist verify SACT prescriptions. Published information for verification of SACT does not currently cover SACT prescribed within a clinical trial and the additional knowledge this requires. This poses the question of how pharmacists are deemed suitably trained to competently verify SACT prescribed within a clinical trial to ensure patient safety and service efficiency. AIM: To determine and gain consensus on the competency requirements for clinical pharmacist verification of SACT prescribed within a clinical trial. METHOD: A two stage process was adopted. Firstly, a Nominal Group Technique (NGT) was conducted with a multi-disciplinary expert panel (n = 7) from National Health Service (NHS) Lothian, part of the South East Scotland Cancer Network (SCAN). Secondly, a national survey was distributed to expert cancer care pharmacists with experience in clinical trial verification across NHS Scotland (n = 86). RESULTS: Of the 28 competencies proposed, 100% achieved consensus and were deemed important by the expert panel during the NGT. From the national survey, 26 (92.9%) of the competencies achieved national agreement and were considered transferable across Scotland. The final national competencies were split into four categories: general trial background (n = 13); calculations, laboratory results and toxicity assessments (n = 7); administration details (n = 3); prescription and patient details (n = 3). Based on the themes identified during the NGT the final national competencies were further split into two suggested complexity levels; Level 1 (core) and Level 2 (advanced). CONCLUSION: The competency requirements for clinical pharmacist verification of SACT prescribed within a clinical trial were defined for national use across Scotland. The competencies were split into four categories and two complexity levels. Further work will be required to identify training requirements, develop a training programme to support these and to determine how these competencies should be assessed. In addition, further work could be undertaken to develop a United Kingdom wide competency framework based on the results of this study.

Retrospective analysis of mortality within 30 days of systemic anticancer therapy and comparison with a previous audit at an Australian Regional Cancer Centre.

PURPOSE: To retrospectively determine the rate of death occurring within 14 and 30 days of systemic anticancer therapy (SACT), compare this against a previous audit and benchmark results against other cancer centres. Secondly, to determine if the introduction of immune checkpoint inhibitors (ICI), not available at the time of the initial audit, impacted mortality rates. METHOD: All adult solid tumour and haematology patients receiving SACT at an Australian Regional Cancer Centre (RCC) between January 2016 and July 2020 were included. RESULTS: Over a 55-month period, 1709 patients received SACT. Patients dying within 14 and 30 days of SACT were 3.3% and 7.0% respectively and is slightly higher than our previous study which was 1.89% and 5.6%. Mean time to death was 15.5 days. Males accounted for 63.9% of patients and the mean age was 66.8 years. 46.2% of the 119 patients dying in the 30 days post SACT started a new line of treatment during that time. Of 98 patients receiving ICI, 22.5% died within 30 days of commencement. Disease progression was the most common cause of death (79%). The most common place of death was the RCC (38.7%). CONCLUSION: The rate of death observed in our re-audit compares favourably with our previous audit and is still at the lower end of that seen in published studies in Australia and internationally. Cases of patients dying within 30 days of SACT should be regularly reviewed to maintain awareness of this benchmark of quality assurance and provide a feedback process for clinicians.

Systemic therapy, survival and end-of-life costs for metastatic triple-negative breast cancer: retrospective SEER-Medicare study of women age ≥65 years.

Aim: To analyze therapy for metastatic triple-negative breast cancer (mTNBC), factors contributing to survival and costs. Patients & methods: Using 2010-2016 SEER-Medicare data, we identified women (≥65 years) with mTNBC. Results: Of 302 eligible patients, 152 (50%) received systemic therapy. In multivariable regression analyses, only age <75 years was associated with therapy receipt (odds ratio: 2.91; 95% CI: 1.79-4.74); and only systemic therapy significantly reduced risk of death (hazard ratio: 0.34; 95% CI: 0.26-0.44). Median overall survival was 13.4 (95% CI: 11.3-15.1) vs 3.3 months (95% CI: 2.7-3.9) in therapy vs no-therapy cohorts. Mean per-patient-per-month costs <30 days before end-of-life/follow-up were $14,100 and $15,600 (2019 USD), respectively. Conclusion: Poor outcomes and high costs indicate need for more effective mTNBC therapy.

Effects of molecular targeting agents and immune-checkpoint inhibitors in patients with advanced cancer who are near the end of life.

BACKGROUND: In recent years, the use of both molecular targeting agents (MTAs) and immune-checkpoint inhibitors (ICIs) tend to occupy important positions in systemic anticancer therapy (SACT). The objective of this study is to describe the predictors of SACT include both MTAs and ICIs near the end of life (EOL) and the effect on EOL care in patients with advanced cancer. METHODS: We analyzed all patients who died of advanced cancer from August 2016 to August 2019, and we analyzed the survival time of patients who underwent anticancer agents excluded due to the loss of information about the last administration of SACT. The primary endpoint of this study was to identify predictors during the last administration of SACT near EOL. RESULTS: In a multivariate analysis, the Eastern Cooperative Oncology Group performance status (ECOG-PS) (ORs 33.781) was significantly related factors within 14 days of death from the last administration of SACT. Age (ORs 0.412), ECOG-PS (ORs 11.533), primary cancer site of upper GI cancers (ORs 2.205), the number of comorbidities (ORs 0.207), MTAs (ORs 3.139), and ICIs (ORs 3.592) were significantly related factors within 30 days of death. The median survival time (MST) of patients with PS 3-4 was 29 days, while that of patients with both PS 0-2 was 76 days. The prevalence rate of delirium with MTAs was 17.5%, which was significantly lower than that of patients without it (31.8%). The prevalence rate of the mean dose of opioids in patients with ICIs was 97.9 mg/day, which was significantly higher than that of patients without it (44.9 mg/day). CONCLUSIONS: Age, ECOG-PS, primary cancer site, the number of comorbidities, MTAs, and ICIs use were significant associated with SACT near EOL. Information on these factors may aid clinical decision making in referral to palliative care institutes.

A systematic review of non-standard dosing of oral anticancer therapies.

BACKGROUND: The use of oral systemic anticancer therapies (SACT) has increased and led to improved cancer survival outcomes, particularly with the introduction of small molecule targeted agents and immunomodulators. Oral targeted SACT are, however, associated with toxicities, which might result in reduced quality of life and non-adherence. To reduce treatment-related toxicity, the practice of non-standard dosing is increasing; however guidance to govern this practice is limited. A systematic review was conducted to identify evidence of, and outcomes from, non-standard dosing of oral SACT in oncology and malignant haematology. METHODS: A comprehensive search of 78 oral SACT was conducted in the following databases: MEDLINE®, EMBASE®, Cochrane Library©, and Cumulative Index to Nursing and Allied Health Literature (CINAHL©). Studies were selected based on predefined inclusion/exclusion criteria, and were critically appraised. Extracted data were tabulated to summarise key findings. Due to diversity of study designs and heterogeneity of reported outcomes, studies were categorised and evidence was synthesised in three main themes: dose interruption; dose reduction; and other dosing strategies. RESULTS: Thirty-four studies were eligible for inclusion: four clinical trials, fifteen cohort studies and fifteen case reports. Evidence for non-standard dosing was reported for eleven oral SACT. Dose interruptions were the most commonly reported strategy (14 studies); nine studies reported dose reductions; and eleven reported other dosing strategies. Eight retrospective cohort studies reported dose interruption of sunitinib in renal cell carcinoma and showed either similar or improved responses and survival outcomes, and fewer or equivalent high grade toxicities, compared to the standard schedule. Four cohort studies retrospectively evaluated dose reductions of imatinib, gefitinib or erlotinib, for chronic myeloid leukaemia and non-small cell lung cancer, respectively. Other dosing strategies included alternate-day dosing. The quality of the evidence was limited by the small sample size in many studies, retrospective study designs, and lack of reported toxicity and/or QoL outcomes. CONCLUSIONS: This review identified limited evidence to support current non-standard dosing strategies, but some of findings, e.g. dose interruption of sunitinib, warrant further investigation in large-scale prospective clinical trials.

The Use of the Chuang's Prognostic Scale to Predict the Survival of Metastatic Colorectal Cancer Patients Receiving Palliative Systemic Anticancer Therapy.

BACKGROUND: With the increasing number of agents active against cancer, advanced cancer patients including metastatic colorectal cancer (mCRC) patients may continue receiving palliative systemic anticancer therapy (PSAT) near the end-of-life. Validated palliative prognostic models, such as the Chuang's prognostic scale (CPS), may be helpful in identifying mCRC patients with limited survival who are unlikely to benefit from PSAT. AIM: To test the ability of the CPS to predict the survival of mCRC under treatment with PSAT. METHODS: CPS was prospectively assessed in 36 mCRC patients who were receiving PSAT. The scale is based on eight items: ascites, edema, cognitive impairment, liver and lung metastases, performance status, tiredness, and weight loss. The total CPS score ranges from 0 to 8.5 with the higher score indicating worse prognosis. RESULTS: Patients were divided into two groups using a CPS cutoff score of 5, Group 1 with a CPS score ≤5 and Group 2 with a CPS score >5. Using this cutoff value, 3-month mortality was predicted with a positive predictive value of 71%, a negative predictive value of 77%, a sensitivity of 67%, a specificity of 81% and an overall accuracy of 75%. Group 1 patients had a longer median survival of 149 days (95% confidence interval [CI]: 82-216) in comparison to Group 2 patients who had a median survival of 61 days (95% CI: 35-87). The difference in survival was statistically significant (P = 0.01). CONCLUSION: CPS may be useful in identifying mCRC patients with limited survival who are unlikely to benefit from PSAT.

Aggressiveness in systemic anticancer therapy at the end of life in an oncology center.

Introduction: An increasing aggressiveness in cancer treatment at the end of life (EoL) has been reported in several, but not all, countries. This study aimed to see how aggressive cancer treatment is at the EoL in an oncology center. Methods: Retrospective study of patients 18 years or older with a solid cancer diagnosis who died in 2017. The focus was systemic anticancer therapy (SACT), excluding hormonotherapy. Results: In 2017, 2024 patients with solid tumors died. Of those patients, 1262 (62%) were male, and the median age was 69 (range 19-97) years. The most frequent primary cancer was lung cancer, followed by colorectal and stomach cancers, and 740 (37%) patients had metastatic disease. The median interval between SACT and death was 61 days. Of the patients undergoing SACT, 216 (27%) did it in the last month of life, 174 (22%) between 8 and 30 days from death, and 42 (5%) in the last week. On multivariable analysis, head and neck, colorectal, breast, and melanoma primaries; age group (older than 65 years); and metastatic disease had statistical significance associated with SACT. Of these variables, only metastatic disease is more likely to undergo SACT. Conclusion: This study confirms the relatively frequent aggressiveness in cancer treatment at the EoL. Taking into consideration previously published data, it can be tentatively concluded that the use of SACT increased in the last month and the last week of life.

Biomarkers of systemic inflammation provide additional prognostic stratification in cancers of unknown primary.

BACKGROUND: Biomarkers of systemic inflammation have been shown to predict outcomes in patients with cancer of unknown primary (CUP). We sought to validate these findings in patients with confirmed CUP (cCUP) and explore their role alongside existing clinicopathological prognostic categories. PATIENTS AND METHODS: CUP oncologist from across the United Kingdom were invited to include patients with cCUP referred to their local CUP multidisciplinary team. Patient demographics, clinical, pathological and outcome data were recorded and analysed. RESULTS: Data were available for 548 patients from four CUP services. 23% (n = 124) of patients met clinicopathological criteria for favourable-risk cCUP. On multivariate analysis c-reactive protein (CRP) (p < 0.001) and the Scottish Inflammatory Prognostic Score (SIPS: combining albumin and neutrophil count) (p < 0.001) were independently predictive of survival. CRP and SIPS effectively stratified survival in patients with both favourable-risk and poor-risk cCUP based on clinicopathological features. CONCLUSIONS: Biomarkers of systemic inflammation are reliable prognostic factors in patients with cCUP, regardless of clinicopathological subgroup. We recommend that CRP or SIPS are incorporated into routine clinical assessments of patients with cCUP as a tool to aid investigation and/or treatment decision-making across all groups. Established clinicopathological factors can then be used to inform management pathways and specific systemic anticancer therapy selection.

Real-World Data Quality Framework for Oncology Time to Treatment Discontinuation Use Case: Implementation and Evaluation Study.

BACKGROUND: The importance of real-world evidence is widely recognized in observational oncology studies. However, the lack of interoperable data quality standards in the fragmented health information technology landscape represents an important challenge. Therefore, adopting validated systematic methods for evaluating data quality is important for oncology outcomes research leveraging real-world data (RWD). OBJECTIVE: This study aims to implement real-world time to treatment discontinuation (rwTTD) for a systemic anticancer therapy (SACT) as a new use case for the Use Case Specific Relevance and Quality Assessment, a framework linking data quality and relevance in fit-for-purpose RWD assessment. METHODS: To define the rwTTD use case, we mapped the operational definition of rwTTD to RWD elements commonly available from oncology electronic health record-derived data sets. We identified 20 tasks to check the completeness and plausibility of data elements concerning SACT use, line of therapy (LOT), death date, and length of follow-up. Using descriptive statistics, we illustrated how to implement the Use Case Specific Relevance and Quality Assessment on 2 oncology databases (Data sets A and B) to estimate the rwTTD of an SACT drug (target SACT) for patients with advanced head and neck cancer diagnosed on or after January 1, 2015. RESULTS: A total of 1200 (24.96%) of 4808 patients in Data set A and 237 (5.92%) of 4003 patients in Data set B received the target SACT, suggesting better relevance of the former in estimating the rwTTD of the target SACT. The 2 data sets differed with regard to the terminology used for SACT drugs, LOT format, and target SACT LOT distribution over time. Data set B appeared to have less complete SACT records, longer lags in incorporating the latest data, and incomplete mortality data, suggesting a lack of fitness for estimating rwTTD. CONCLUSIONS: The fit-for-purpose data quality assessment demonstrated substantial variability in the quality of the 2 real-world data sets. The data quality specifications applied for rwTTD estimation can be expanded to support a broad spectrum of oncology use cases.

Quality indicators for systemic anticancer therapy services: a systematic review of metrics used to compare quality across healthcare facilities.

PURPOSE: The number of systemic anticancer therapy (SACT) regimens has expanded rapidly over the last decade. There is a need to ensure quality of SACT delivery across cancer services and systems in different resource settings to reduce morbidity, mortality, and detrimental economic impact at individual and systems level. Existing literature on SACT focuses on treatment efficacy with few studies on quality or how SACT is delivered within routine care in comparison to radiation and surgical oncology. METHODS: Systematic review was conducted following PRISMA guidelines. EMBASE and MEDLINE were searched and handsearching was undertaken to identify literature on existing quality indicators (QIs) that detect meaningful variations in the quality of SACT delivery across different healthcare facilities, regions, or countries. Data extraction was undertaken by two independent reviewers. RESULTS: This review identified 63 distinct QIs from 15 papers. The majority were process QIs (n = 55, 87.3%) relating to appropriateness of treatment and guideline adherence (n = 28, 44.4%). There were few outcome QIs (n = 7, 11.1%) and only one structural QI (n = 1, 1.6%). Included studies solely focused on breast, colorectal, lung, and skin cancer. All but one studies were conducted in high-income countries. CONCLUSIONS: The results of this review highlight a significant lack of research on SACT QIs particularly those appropriate for resource-constrained settings in low- and middle-income countries. This review should form the basis for future work in transforming performance measurement of SACT provision, through context-specific QI SACT development, validation, and implementation.

Initial active surveillance for patients with metastatic renal cell carcinoma: 10 years' experience at a regional cancer Centre.

A subset of patients with metastatic renal cell carcinoma (mRCC) follow an indolent disease course and may benefit from initial active surveillance (AS). However, selecting patients suitable for this approach is challenging. To investigate this we sought to define outcomes of patients with mRCC suitable for initial AS. All patients with mRCC clinically selected for initial AS at the Edinburgh Cancer Centre between January 2010 and December 2020 were identified. Key inflammatory biomarkers (haemoglobin, white cell count, neutrophil count, platelets, C-reactive protein [CRP], albumin, corrected calcium) and the International Metastatic RCC Database Consortium (IMDC) risk score were measured. The relationship between these and time to systemic anticancer therapy (tSACT) and overall survival (OS) was analysed. Data were available for 160 patients. Estimated median overall survival was 88.0 (interquartile range [IQR] 34.0-127.0) months. Median tSACT was 31.8 (IQR 12.0-76.3) months. On multivariate analysis, only CRP was predictive of tSACT (HR 2.47 [95% CI:1.59-3.85] p < 0.001) and OS (HR 3.89 [95% CI:2.15-6.83] p < 0.001). Patients with CRP > 10 mg/L were more likely to commence SACT within 1 year than those with CRP≤10 mg/L (41% vs. 18%, Relative Risk 2.16 (95% CI:1.18-3.96) (p = 0.012)). IMDC risk score was not predictive of tSACT or OS. Active surveillance is an appropriate initial management option for selected patients with mRCC. CRP, a biomarker of systemic inflammation, may provide additional objective information to assist clinical decision-making in patients with mRCC being considered for initial AS. Although this is a retrospective observational study, the cohort is well defined and includes all patients managed with initial AS in an inclusive real-world setting.

The effect of comprehensive geriatric assessment on care received, treatment completion, toxicity, cancer-related and geriatric assessment outcomes, and quality of life for older adults receiving systemic anti-cancer treatment: A systematic review.

INTRODUCTION: This systematic review aims to summarise the available literature on the effect of geriatric assessment (multidimensional health assessment across medical, social, and functional domains; "GA") or comprehensive geriatric assessment (geriatric assessment with intervention or management recommendations; "CGA") compared to usual care for older adults with cancer on care received, treatment completion, adverse treatment effects, survival and health-related quality of life. MATERIALS AND METHODS: A systematic search of MEDLINE, EMBASE, CINAHL, and PubMed was conducted to identify randomised controlled trials or prospective cohort comparison studies on the effect of GA/CGA on care received, treatment, and cancer outcomes for older adults with cancer. RESULTS: Ten studies were included: seven randomised controlled trials (RCTs), two phase II randomised pilot studies, and one prospective cohort comparison study. All studies included older adults receiving systemic therapy, mostly chemotherapy, for mixed cancer types (eight studies), colorectal cancer (one study), and non-small cell lung cancer (one study). Integrating GA/CGA into oncological care increased treatment completion (three of nine studies), reduced grade 3+ chemotherapy toxicity (two of five studies), and improved quality of life scores (four of five studies). No studies found significant differences in survival between GA/CGA and usual care. GA/CGA incorporated into care decisions prompted less intensive treatment and greater non-oncological interventions, including supportive care strategies. DISCUSSION: GA/CGA integrated into the care of an older adult with cancer has the potential to optimise care decisions, which may lead to reduced treatment toxicity, increased treatment completion, and improved health-related quality of life scores.

Assessing the Acceptability of Home Blood Monitoring for Patients With Cancer Who Are Receiving Systemic Anticancer Therapy From a Patient, Caregiver, and Clinician Perspective: Focus Group and Interview Study.

BACKGROUND: Regular blood testing is an integral part of systemic anticancer therapy delivery. Blood tests are required before every administration of treatment to ensure that a patient is sufficiently well to receive it. Blood testing is burdensome for patients as they require either an extra visit within 48 hours of planned administration of treatment or a significantly long visit if performed on the day of treatment. The additional time for appointments can have a significant impact on the quality of life of someone who is living with cancer. In the United Kingdom, the COVID-19 pandemic created unprecedented disruption to the delivery of cancer care. Face-to-face hospital visits were reduced, resulting in the need to develop more innovative ways of working to minimize treatment interruptions. This led to significant uptake of digital technologies, with new models of care rapidly deployed across the UK health service to meet these challenges. OBJECTIVE: This study aimed to explore the acceptability of a point-of-care home blood monitoring device for people with cancer who are receiving systemic anticancer therapy, which is being developed in response to the increased need for remote care for patients with cancer. METHODS: Qualitative focus groups and semistructured interviews were conducted with patients (23/47, 49%), caregivers (6/47, 13%), and health care professionals (18/47, 38%) over a 19-month time frame from May 2019 to December 2020. Data were analyzed using framework analysis guided by the Unified Theory of Acceptance and Use of Technology model. RESULTS: Analysis identified 4 overarching themes: performance expectancy, effort expectancy, social influence, and facilitating conditions. CONCLUSIONS: This study found that patients with cancer, their caregivers, and health care professionals had positive perceptions about home blood monitoring. Although they are often considered synonymously, self-testing and self-management are not mutually exclusive, and this study illustrated some disparity in opinions regarding patient self-management. Home blood monitoring has the potential to provide patients with cancer with a convenient option for blood monitoring. It would minimize hospital attendances, decrease late treatment deferrals, and provide prompt recognition of cancer treatment toxicities, thus enhancing the existing nurse-led protocols and clinical pathways. Home blood monitoring would create a long-term sustainable transformation for the delivery of cancer care, using digital health to act as a facilitator to address a pertinent issue regarding improving the efficiency of hospital resources and increasing the delivery of personalized patient care. Further studies are needed to determine how and where home blood monitoring would fit within clinical pathways, in a way that is robust and equitable.

Impact of Bevacizumab on Visual Function, Tumor Size, and Toxicity in Pediatric Progressive Optic Pathway Glioma: A Retrospective Nationwide Multicentre Study.

BACKGROUNDS: Bevacizumab (BVZ) is used as a subsequent line of treatment for pediatric optic pathway glioma (OPG) in the case of progression. Data on the treatment effect concerning tumor progression and visual function are scarce and nationwide studies are lacking. METHODS: We performed a retrospective, nationwide, multicentre cohort study including all pediatric patients with OPG treated with BVZ in the Netherlands (2009-2021). Progression-free survival, change in visual acuity and visual field, MRI-based radiologic response, and toxicity were evaluated. RESULTS: In total, 33 pediatric patients with OPG were treated with BVZ (median 12 months). Visual acuity improved in 20.5%, remained stable in 74.4%, and decreased in 5.1% of 39 of all analysed eyes. The monocular visual field improved in 73.1%, remained stable in 15.4%, and decreased in 7.7% of 25 analysed eyes. Radiologic response at the end of therapy showed a partial response in 7 patients (21.9%), minor response in 7 (21.9%), stable disease in 15 (46.9%), and progressive disease in 3 (9.3%). Progression-free survival at 18 and 36 months after the start of BVZ reduced from 70.9% to 38.0%. Toxicity (≥grade 3 CTCAE) during treatment was observed in five patients (15.2%). CONCLUSION: Treatment of BVZ in pediatric patients with OPG revealed stabilisation in the majority of patients, but was followed by progression at a later time point in more than 60% of patients. This profile seems relatively acceptable given the benefits of visual field improvement in more than 70% of analysed eyes and visual acuity improvement in more than 20% of eyes at the cessation of BVZ.

Treatment patterns and outcomes for patients with malignant pleural mesothelioma in England in 2013-2017: A nationwide CAS registry analysis from the I-O Optimise initiative.

OBJECTIVES: Malignant pleural mesothelioma (MPM) is a rare and aggressive cancer with a poor prognosis and limited treatment options. This study assessed the characteristics, treatment patterns, and outcomes for patients diagnosed with MPM in England. MATERIALS AND METHODS: As part of I-O Optimise, this retrospective cohort study analyzed data recorded in the Cancer Analysis System in England for all adult patients newly diagnosed with MPM between 2013 and 2017, with follow-up to March 2018 or death, whichever occurred first. Overall survival (OS) was estimated using Kaplan-Meier methods. A Cox regression model was used to describe the impact of sociodemographic and clinical characteristics at diagnosis on OS. RESULTS: 9458 patients diagnosed with MPM were analyzed. Median age at diagnosis was 75 years; 83.4% were male. Eastern Cooperative Oncology Group performance status (ECOG PS) was 0-1 for 44.5%; 2 for 11.5%; >2 for 9.1%; and missing for 34.9% of patients. TNM stage was missing for 60.4%. A majority of patients had epithelioid histology (36.4%) or not otherwise specified (NOS) MPM (43.3%). After diagnosis, 48.7% of all patients received best supportive care (BSC; no surgery, radiotherapy, SACT); 11.4% received palliative radiotherapy alone; 6.5% underwent surgery; 33.4% received systemic anticancer therapy (SACT) as initial treatment. Platinum plus pemetrexed was the main SACT regimen used in both first and second line. Median OS (8.3 months) varied by histopathology and ranged from 4.3 to 13.3 months for sarcomatoid and epithelioid MPM, respectively. After adjusting for age, sex, and ECOG PS, sarcomatoid, biphasic, and NOS MPM remained significantly associated with worse OS than epithelioid MPM (all p < 0.001). Median OS varied from 4.6 to 17.0 months for patients receiving BSC/palliative radiotherapy, and patients receiving surgery, respectively. CONCLUSION: Outcomes for patients with MPM in England remain poor. Future studies will investigate the impact of newer therapies on the treatment patterns and survival of MPM patients.

Hypoalbuminaemia as a Prognostic Biomarker of First-Line Treatment Resistance in Metastatic Non-small Cell Lung Cancer.

Introduction: Despite significant advances in systemic anticancer therapy (SACT) for non-small cell lung cancer (NSCLC), many patients still fail to respond to treatment or develop treatment resistance. Albumin, a biomarker of systemic inflammation and malnutrition, predicts survival in many cancers. We evaluated the prognostic significance of albumin in patients receiving first-line targeted therapy or immunotherapy-based SACT for metastatic NSCLC. Methods: All patients treated with first-line targeted therapy or immunotherapy-based SACT for metastatic NSCLC at a regional Scottish cancer centre were identified. Serum albumin at pre-treatment, after 12-weeks of treatment, and at the time of progressive disease were recorded. The relationship between albumin (≥ 35g/L v <35g/L) and overall survival (OS) was examined. Results: Data were available for 389 patients of both targeted therapy cohort (n = 159) and immunotherapy-based therapy cohort (n = 230). Pre-treatment albumin was predictive of OS in each cohort at HR1.82 (95%CI 1.23-2.7) (p =0.003) and HR2.55 (95%CI 1.78-3.65) (p < 0.001), respectively. Pre-treatment albumin <35 g/L was associated with a significantly higher relative risk of death within 12 weeks in each cohort at RR9.58 (95%CI 2.20-41.72, p = 0.003) and RR3.60 (95%CI 1.74-6.57, p < 0.001), respectively. The 12-week albumin was predictive of OS in each cohort at HR1.88 (95%CI 1.86-4.46) (p < 0.001) and HR2.67 (95%CI 1.74-4.08) (p < 0.001), respectively. 46 out of 133 (35%) evaluable patients treated with targeted therapy and 43 out of 169 (25%) treated with immunotherapy-based therapy crossed over albumin prognostic groups between pre-treatment and 12-week. The prognostic value of 12-week albumin was independent of pre-treatment albumin status. A majority of patients had albumin <35g/L at the time of progressive disease when it was also predictive of survival following progressive disease at HR2.48 (95%CI 1.61-3.82) (p < 0.001) and HR2.87 (95%CI 1.91-4.31) (p < 0.001) respectively). Conclusions: Albumin is a reliable prognostic factor in patients with metastatic NSCLC, predicting survival independent of the class of drug treatment at various time points during the patient journey. Tracking albumin concentrations during systemic therapy may indicate disease activity or treatment response over time.

An Automated Line-of-Therapy Algorithm for Adults With Metastatic Non-Small Cell Lung Cancer: Validation Study Using Blinded Manual Chart Review.

BACKGROUND: Extraction of line-of-therapy (LOT) information from electronic health record and claims data is essential for determining longitudinal changes in systemic anticancer therapy in real-world clinical settings. OBJECTIVE: The aim of this retrospective cohort analysis is to validate and refine our previously described open-source LOT algorithm by comparing the output of the algorithm with results obtained through blinded manual chart review. METHODS: We used structured electronic health record data and clinical documents to identify 500 adult patients treated for metastatic non-small cell lung cancer with systemic anticancer therapy from 2011 to mid-2018; we assigned patients to training (n=350) and test (n=150) cohorts, randomly divided proportional to the overall ratio of simple:complex cases (n=254:246). Simple cases were patients who received one LOT and no maintenance therapy; complex cases were patients who received more than one LOT and/or maintenance therapy. Algorithmic changes were performed using the training cohort data, after which the refined algorithm was evaluated against the test cohort. RESULTS: For simple cases, 16 instances of discordance between the LOT algorithm and chart review prerefinement were reduced to 8 instances postrefinement; in the test cohort, there was no discordance between algorithm and chart review. For complex cases, algorithm refinement reduced the discordance from 68 to 62 instances, with 37 instances in the test cohort. The percentage agreement between LOT algorithm output and chart review for patients who received one LOT was 89% prerefinement, 93% postrefinement, and 93% for the test cohort, whereas the likelihood of precise matching between algorithm output and chart review decreased with an increasing number of unique regimens. Several areas of discordance that arose from differing definitions of LOTs and maintenance therapy could not be objectively resolved because of a lack of precise definitions in the medical literature. CONCLUSIONS: Our findings identify common sources of discordance between the LOT algorithm and clinician documentation, providing the possibility of targeted algorithm refinement.

Defining the true impact of coronavirus disease 2019 in the at-risk population of patients with cancer.

BACKGROUND: In light of the coronavirus disease 2019 (COVID-19) pandemic, cancer centres in the United Kingdom and Europe re-organised their services at an unprecedented pace, and many patients with cancer have had their treatments severely disrupted. Patients with cancer were considered at high risk on sparse evidence, and despite a small number of emerging observational studies, the true incidence and impact of COVID-19 in the 'at-risk' population of patients with cancer is yet to be defined. METHODS: Epidemiological and clinical data were collected prospectively for patients attending the Royal Marsden Hospital and three network hospitals between March 1st and April 30th 2020 that were confirmed to have Severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) infection. Significance of clinical and pathological characteristics was assessed using the Fisher's exact test and Wilcoxon rank sum test, whilst univariate and multivariate logistic regression models were used to further assess risk. The number of patients attending in March/April 2020 for face-to-face attendances was also extracted. FINDINGS: During the 2-month study period, 867 of 13,489 (6.4%) patients met the criteria leading to swab testing. Of the total at-risk population, only 113 of 13,489 (0.84%) were swab positive, 101 of 13,489 (0.75%) required hospital admission and 29 of 13,489 (0.21%) died of COVID-19. Of the patients that attended the hospital to receive cytotoxic chemotherapy alone or in combination with other therapy, 59 of 2001 (2.9%) were admitted to the hospital for COVID-19-related issues and 20 of 2001 (1%) died. Of the patients that collected targeted treatments, 16 of 1126 (1.4%) were admitted and 1 of 1126 (0.1%) died. Of the 11 patients that had received radiotherapy, 6 of 1042 (0.6%) required inpatient admission and 2 of 1042 (0.2%) died. INTERPRETATIONS: Administration of systemic anticancer therapy appears to be associated with a modest risk of severe COVID-19 infection. Based on this snapshot taken as the first wave of COVID-19 hit our practice, we conclude that continuation of active cancer treatment, even in the palliative setting, is appropriate.

Survival in melanoma brain metastases in the era of novel systemic therapies.

BACKGROUND: Melanoma brain metastases (MBMs) have historically poor overall survival (OS). Recently introduced systemic anticancer therapies (SACTs), namely targeted therapies such as BRAF inhibitors and immunotherapy, to control advanced disease have shown improved survival. Today, increasingly aggressive strategies are sought for MBM. We review outcomes in MBM after surgery or stereotactic radiosurgery (SRS) and the survival impact in advanced systemic disease when combined with novel anticancer therapies. METHODS: A retrospective cohort study of patients referred to a regional neuro-oncology multidisciplinary team (MDT) meeting with MBM. Demographic data, extent of systemic disease, and data on surgical and oncological management were collected, plus the use of SACT. The primary outcomes were median OS, 12- and 24-month survival, and progression-free survival. RESULTS: Between 2010 and 2018, 142 patients with MBM were referred. Following the introduction of SACT, the rate of referrals to MDT more than doubled from 11.6 to 25.7 patients per year. Focal brain metastasis was treated surgically in 23 (16.2%) patients and by SRS in 29 (20.4%). Fifty-six (39.4%) patients underwent palliative whole-brain radiotherapy and 34 (23.9%) did not receive treatment. Median OS was 11 months for the surgical cohort, 9 months for the SRS cohort, and increased when treatment with or without SACT was considered to 23 and 12 months, respectively. CONCLUSION: In the setting of SACTs, survival in MBM is significantly improved after surgery or SRS even in patients with advanced and uncontrolled systemic disease at the time of presentation, supporting an aggressive approach to MBM management.