Challenges in the treatment of gastric cancer in the older patient

Gastric cancer is considered an age-related disease, with the majority of new cases in the UK diagnosed in individuals over the age of 75. At present most guidance related to the management of gastric cancer is based on trials undertaken in the fit, younger patient. Historically the elderly have been underrepresented in clinical trials, which frequently have a restricted inclusion to an upper age limit of 75. The European Society for Medical Oncology (ESMO) recommends use of a geriatric assessment to determine functional age when initiating treatment in elderly patients with gastric cancer, which has been shown to be a better predictor of treatment response than chronological age. The physiological changes that occur with age, including reduced organ function and pharmacokinetic and pharmacodynamic variability, together with impaired functional status, necessitate a more individualised approach to treatment decisions in the older patient to provide them with the same advantages from radical treatment and palliative chemotherapy as younger patients. This review summarises the current evidence extrapolated from trial data on how best to optimise treatment for elderly patients with gastric cancer

The role of aspirin in the prevention of ovarian, endometrial and cervical cancers

Drug repurposing is the application of an existing licenced drug for a new indication and potentially provides a faster and cheaper approach to developing new anti-cancer agents. Gynaecological cancers contribute significantly to the global cancer burden, highlighting the need for low cost, widely accessible therapies. A large body of evidence supports the role of aspirin as an anti-cancer agent, and a number of randomized trials are currently underway aiming to assess the potential benefit of aspirin in the treatment of cancer. This review summarizes the evidence underpinning aspirin use for the prevention of the development and recurrence of gynaecological cancers (ovarian, endometrial and cervical) and potential mechanisms of action

Statins as Potential Chemoprevention or Therapeutic Agents in Cancer: a Model for Evaluating Repurposed Drugs

Purpose of Review: Repurposing established medicines for a new therapeutic indication potentially has important global and societal impact. The high costs and slow pace of new drug development have increased interest in more cost-effective repurposed drugs, particularly in the cancer arena. The conventional drug development pathway and evidence framework are not designed for drug repurposing and there is currently no consensus on establishing the evidence base before embarking on a large, resource intensive, potential practice changing phase III randomised controlled trial (RCT). Numerous observational studies have suggested a potential role for statins as a repurposed drug for cancer chemoprevention and therapy, and we review the strength of the cumulative evidence here. Recent Findings: In the setting of cancer, a potential repurposed drug, like statins, typically goes through a cyclical history, with initial use for several years in another disease setting, prior to epidemiological research identifying a possible chemo-protective effect. However, further information is required, including review of RCT data in the initial disease setting with exploration of cancer outcomes. Additionally, more contemporary methods should be considered, such as Mendelian randomization and pharmaco-epidemiological research with “target” trial design emulation using electronic health records. Pre-clinical and traditional observational data potentially support the role of statins in the treatment of cancer; however, randomised trial evidence is not supportive. Evaluation of contemporary methods provides little added support for the use of statin therapy in cancer. Summary: We provide complementary evidence of alternative study designs to enable a robust critical appraisal from a number of sources of the go/no-go decision for a prospective phase III RCT of statins in the treatment of cancer

Multimodal Treatment in Metastatic Colorectal Cancer (mCRC) Improves Outcomes—The University College London Hospital (UCLH) Experience

Background: Despite notable advances in the management of metastatic colorectal cancer (mCRC) over the last two decades, treatment intent in the vast majority of patients remains palliative due to technically unresectable disease, extensive disease, or co-morbidities precluding major surgery. Up to 30% of individuals with mCRC are considered potentially suitable for primary or metastasis-directed multimodal therapy, including surgical resection, ablative techniques, or stereotactic radiotherapy (RT), with the aim of improving survival outcomes. We reviewed the potential benefits of multimodal therapy on the survival of patients with mCRC treated at the UCLH. Methods: Clinical data on baseline characteristics, multimodal treatments, and survival outcomes were retrospectively collected from all patients with mCRC receiving systemic chemotherapy between January 2013 and April 2017. Primary outcome was the impact of multimodal therapy on overall survival, compared to systemic therapy alone, and the effect of different types of multimodal therapy on survival outcome, and was assessed using the Kaplan–Meier approach. All analyses were adjusted for age, gender, and side of primary tumour. Results: One-hundred and twenty-five patients with mCRC were treated during the study period (median age: 62 years (range 19–89). The liver was the most frequent metastatic site (78%; 97/125). A total of 52% (65/125) had ≥2 lines of systemic chemotherapy. Of the 125 patients having systemic chemotherapy, 74 (59%) underwent multimodal treatment to the primary tumour or metastasis. Median overall survival (OS) was 25.7 months [95% Confidence Interval (CI) 21.5–29.0], and 3-year survival, 26%. Univariate analysis demonstrated that patients who had additional procedures (surgery/ablation/RT) were significantly less likely to die (Hazard Ratio (HR) 0.18, 95% CI 0.12–0.29, p < 0.0001) compared to those receiving systemic chemotherapy alone. Increasing number of multimodal procedures was associated with an incremental increase in survival—with median OS 28.4 m, 35.7 m, and 64.8 m, respectively, for 1, 2, or ≥3 procedures (log-rank p < 0.0001). After exclusion of those who received systemic chemotherapy only (n = 51), metastatic resections were associated with improved survival (adjusted HR 0.36, 95% CI 0.20–0.63, p < 0.0001), confirmed in multivariate analysis. Multiple single-organ procedures did not improve survival. Conclusion: Multimodal therapy for metastatic bowel cancer is associated with significant survival benefit. Resection/radical RT of the primary and resection of metastatic disease should be considered to improve survival outcomes following multidisciplinary team (MDT) discussion and individual assessment of fitness

COVID-19 in cancer patients on systemic anti-cancer therapies: outcomes from the CAPITOL (COVID-19 Cancer PatIenT Outcomes in North London) cohort study

Background: Patients with cancer are hypothesised to be at increased risk of contracting COVID-19, leading to changes in treatment pathways in those treated with systemic anti-cancer treatments (SACT). This study investigated the outcomes of patients receiving SACT to assess whether they were at greater risk of contracting COVID-19 or having more severe outcomes. / Methods: Data was collected from all patients receiving SACT in two cancer centres as part of CAPITOL (COVID-19 Cancer PatIenT Outcomes in North London). The primary outcome was the effect of clinical characteristics on the incidence and severity of COVID-19 infection in patients on SACT. We used univariable and multivariable models to analyse outcomes, adjusting for age, gender and comorbidities. / Results: A total of 2871 patients receiving SACT from 2 March to 31 May 2020 were analysed; 68 (2.4%) were diagnosed with COVID-19. Cancer patients receiving SACT were more likely to die if they contracted COVID-19 than those who did not [adjusted (adj.) odds ratio (OR) 9.84; 95% confidence interval (CI) 5.73–16.9]. Receiving chemotherapy increased the risk of developing COVID-19 (adj. OR 2.99; 95% CI = 1.72–5.21), with high dose chemotherapy significantly increasing risk (adj. OR 2.36, 95% CI 1.35–6.48), as did the presence of comorbidities (adj. OR 2.29; 95% CI 1.19–4.38), and having a respiratory or intrathoracic neoplasm (adj. OR 2.12; 95% CI 1.04–4.36). Receiving targeted treatment had a protective effect (adj. OR 0.53; 95% CI 0.30–0.95). Treatment intent (curative versus palliative), hormonal- or immunotherapy and solid versus haematological cancers had no significant effect on risk. / Conclusion: Patients on SACT are more likely to die if they contract COVID-19. Those on chemotherapy, particularly high dose chemotherapy, are more likely to contract COVID-19, while targeted treatment appears to be protective

Outcomes of the 2019 Novel Coronavirus in patients with or without a history of cancer - a multi-centre North London experience

© The Author(s) 2020. This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 License (https://creativecommons.org/licenses/by-nc/4.0/) which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access pages (https://us.sagepub.com/en-us/nam/open-access-at-sage).Background Four months after the first known case of the 2019 novel coronavirus disease (COVID-19), on the 11th March 2020, the WHO declared the outbreak a pandemic and acknowledged the potential to overwhelm national healthcare systems. The high prevalence and associated healthcare, social and economic challenges of COVID-19 suggest this pandemic is likely to have a major impact on cancer management, and has been shown to potentially have worse outcomes in this cohort of vulnerable patients (1). This study aims to compare the outcomes of reverse transcriptase polymerase chain reaction (RT-PCR) confirmed COVID-19 positive disease in patients with or without a history of cancer. Method: We retrospectively collected clinical, pathological and radiological characteristics and outcomes of COVID-19 RT-PCR positive cancer patients treated consecutively in four different North London hospitals (cohort A). Outcomes recorded included morbidity, mortality and length of hospital stay. All clinically relevant outcomes were then compared to consecutively admitted COVID-19 positive patients, without a history of cancer (cohort B), treated at the primary centre during the same time period (12th March- 7th April 2020). Results: A total of 52 electronic patient records during the study time period were reviewed. Cohort A (median age 76 years, 56% males) and cohort B (median age 58 years, 62% male) comprised of 26 patients each. With the exclusion of cancer, both had a median of 2 comorbidities. Within cohort A, the most frequent underlying cancer was colorectal (5/26) and prostate cancer (5/26), and 77% of patients in Cohort A had received previous anti-cancer therapy. The most common presenting symptoms were cough and pyrexia in both cohorts. Frequent laboratory findings included lymphopenia, anaemia and elevated CRP in both cohorts, whilst hypokalaemia, hypoalbuminaemia and hypoproteinaemia was predominantly seen amongst patients with cancer. Median duration of admission was 7 days in both cohorts. The mortality rate was the same in both cohorts (23%), with median age of mortality of 80 years. Of cancer patients who died, all were advanced stage, had been treated with palliative intent and had received anti-cancer therapy within 13 days of admission. Conclusion: Old age, late stage of cancer diagnosis and multiple co-morbidities adversely influence the outcome of patients with COVID-19 positive patients. Whilst extra caution is warranted in the administration of anti-cancer therapies pertaining to the risk of immune-suppression, this data does not demonstrate a higher risk to cancer patients compared to their non-cancer counterparts.Peer reviewedFinal Published versio

A guideline for the outpatient management of glycaemic control in people with cancer

Individuals with cancer are at increased risk of developing new onset diabetes mellitus and hyperglycaemia, and an estimated 20% of people with cancer already have an underlying diagnosis of diabetes mellitus. People with both cancer and diabetes may have an increased risk of toxicities, hospital admissions and morbidity, with hyperglycaemia potentially attenuating the efficacy of chemotherapy often secondary to dose reductions and early cessation. Numerous studies have demonstrated that hyperglycaemia is prognostic of worse overall survival and risk of cancer recurrence. These guidelines aim to provide the oncology/haemato-oncology and diabetes multidisciplinary teams with the tools to manage people with diabetes commencing anti-cancer/ glucocorticoid therapy, as well as identifying individuals without a known diagnosis of diabetes who are at risk of developing hyperglycaemia and new onset diabetes

Interpretation of DAS28 and its components in the assessment of inflammatory and non-inflammatory aspects of rheumatoid arthritis

Background: DAS28 is interpreted as the inflammatory disease activity of RA. Non-inflammatory pain mechanisms can confound assessment. We aimed to examine the use of DAS28 components or DAS28-derived measures that have been published as indices of non-inflammatory pain mechanisms, to inform interpretation of disease activity. Methods: Data were used from multiple observational epidemiology studies of people with RA. Statistical characteristics of DAS28 components and derived indices were assessed using baseline and follow up data from British Society for Rheumatology Biologics Registry participants [1] commencing anti-TNF therapy (n = 10813), or [2] changing between non-biologic DMARDs (n=2992), [3] Early Rheumatoid Arthritis Network participants (n=813), and [4] participants in a cross-sectional study exploring fibromyalgia and pain thresholds (n=45). Repeatability was tested in 34 patients with active RA. Derived indices were the proportion of DAS28 attributable to patient-reported components (DAS28-P), tender-swollen difference and tender:swollen ratio. Pressure pain detection threshold (PPT) was used as an index of pain sensitisation. Results: DAS28, tender joint count, visual analogue scale, DAS28-P, tender-swollen difference and tender:swollen ratio were more strongly associated with pain, PPT and fibromyalgia status than were swollen joint count or erythrocyte sedimentation rate. DAS28-P, tender-swollen difference and tender:swollen ratio better predicted pain over 1 year than did DAS28 or its individual components. Conclusions: DAS28 is strongly associated both with inflammation and with patient-reported outcomes. DAS28-derived indices such as tender-swollen difference are associated with non-inflammatory pain mechanisms, can predict future pain and should inform how DAS28 is interpreted as an index of inflammatory disease activity in RA