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Purpose: Dose-dense (dd) chemotherapy regimens reduce breast cancer recurrence and mortality with no significant increase in non-cancer related mortality [1]. However, uptake is poor, probably due to concerns regarding toxicity. We aimed to quantify rates of toxicity and dose reduction in patients receiving dd epirubicin and cyclophosphamide (EC), and to identify any associated patient factors. Methods: This was a retrospective and prospective study. Patients receiving neoadjuvant or adjuvant dd EC (epirubicin 90 mg/m2 and cyclophosphamide 600 mg/m2 2-weekly) between 2018 and 2021 at two London hospitals were identified from electronic records. Baseline ECOG performance status (PS), incidence of dose delay, dose reduction and hospital admission were identified from electronic records. Results: 108 patients received dd EC, 49 (45%) in the neoadjuvant and 59 (55%) in the adjuvant setting, receiving a total of 422 cycles. Median age was 47 years (25–69 years). 105 patients (95%) had a baseline PS of 0;the other 6 (5%) a PS of 1. 99 patients (92%) received 4 cycles of dd EC as planned, of which 84 (78%) had no dose reductions. 3 patients were converted to the standard regimen due to toxicity. 5 patients had cycles omitted due to toxicity (n = 2) or other causes. One patient died due to COVID-19. 16 patients (15%) had a dose reduction. Treatment was delayed by at least 1 week in 18 patients (17%). The most common reasons for this were haematological toxicity (n = 6) and infection (n = 4). 6 patients (6%) had both delays and dose reductions. 8 patients (7%) were admitted to hospital during treatment, 4 of whom had febrile neutropenia. Conclusion: This real world data demonstrate that dd chemotherapy can be delivered in routine practice. The rates of dose reduction and delay were comparable to those found in standard regimes [1]. Patient selection by oncologists is an important factor. Reference [1] Early Breast Cancer Trialists’ Collaborative Group (EBCTCG). Increasing the dose intensity of chemotherapy by more frequent administration or sequential scheduling: a patient-level meta-analysis of 37 298 women with early breast cancer in 26 randomised trials. Lancet 2019;393(10179):1440–52.
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Social entrepreneurship is a multidimensional construct, with social value creation lying at its core. Innovativeness and venturesomeness are the prominent decision-making characteristics that facilitate value creation by social enterprises (SEs). Sustainability goals can be attained better with synergistic operations of the two entities. Both SEs and SDGs aim at creating values for overall well-being, however discrepancies in interpreting and measuring the values created, leads to problems in achieving operational integration between the two. This chapter comprehends the nature of values created by SEs. It further examines the scope and benefit of integration between SEs and SDGs for creating better value propositions. Methodology of the research included extant review of literature and relevant frameworks to comprehend concepts of SEs and SDGs. To examine practical aspects of value creation, in-depth interviews were conducted with social entrepreneurs. The chapter concludes that SDGs resonate strongly with work of many SEs due to the basic nature of their mission and objectives. However, there is ambiguity regarding how integration between the two entities can be effectively operationalized. The way forward for value creation through SEs-SDGs integration in post-COVID times is discussed. For sustenance and growth in complex times, along with emphasis on traditional values, SEs and SDGs will have to focus on creating strategic values through active collaboration and synergy. Impact reporting is critical, but additionally, core managerial and operational activities of SEs and SDGs must also orient cohesively. The chapter proposes an integrated framework for systematic alignment of SEs and SDGs missions, objectives, resource management, mobilization, networking etc. for purposeful collaborations. © 2022 by Emerald Publishing Limited.
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We sought to determine parameters of the acute phase response, a feature of innate immunity activated by infectious noxae and cancer, deranged by Covid-19 and establish oncological indices' prognostic potential for patients with concomitant cancer and Covid-19. Between 27/02 and 23/06/2020, OnCovid retrospectively accrued 1,318 consecutive referrals of patients with cancer and Covid-19 aged 18 from the U.K., Spain, Italy, Belgium, and Germany. Patients with myeloma, leukemia, or insufficient data were excluded. The neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), prognostic nutritional index (PNI), modified Glasgow prognostic score (mGPS), and prognostic index (PI) were evaluated for their prognostic potential, with the NLR, PLR, and PNI risk stratifications dichotomized around median values and the pre-established risk categorizations from literature utilized for the mGPS and PI. 1,071 eligible patients were randomly assorted into a training set (TS, n=529) and validation set (VS, n=542) matched for age (67.9±13.3 TS, 68.5±13.5 VS), presence of 1 comorbidity (52.1% TS, 49.8% VS), development of 1 Covid-19 complication (27% TS, 25.9% VS), and active malignancy at Covid-19 diagnosis (66.7% TS, 61.6% VS). Among all 1,071 patients, deceased patients tended to categorize into poor risk groups for the NLR, PNI, mGPS, and PI (P<0.0001) with a return to pre-Covid-19 diagnosis NLR, PNI, and mGPS categorizations following recovery (P<0.01). In the TS, higher mortality rates were associated with NLR>6 (44.6% vs 28%, P<0.0001), PNI<40 (46.6% vs 20.9%, P<0.0001), mGPS (50.6% for mGPS2 vs 30.4% and 11.4% for mGPS1 and 0, P<0.0001), and PI (50% for PI2 vs 40% for PI1 and 9.1% for PI0, P<0.0001). Findings were confirmed in the VS (P<0.001 for all comparisons). Patients in poor risk categories had shorter median overall survival [OS], (NLR>6 30 days 95%CI 1-63, PNI<40 23 days 95%CI 10-35, mGPS2 20 days 95%CI 8-32, PI2 23 days 95%CI 1-56) compared to patients in good risk categories, for whom median OS was not reached (P<0.001 for all comparisons). The PLR was not associated with survival. Analyses of survival in the VS confirmed the NLR (P<0.0001), PNI (P<0.0001), PI (P<0.01), and mGPS (P<0.001) as predictors of survival. In a multivariable Cox regression model including all inflammatory indices and pre-established prognostic factors for severe Covid-19 including sex, age, comorbid burden, malignancy status, and receipt of anti-cancer therapy at Covid-19 diagnosis, the PNI was the only factor to emerge with a significant hazard ratio [HR] in both TS and VS analysis (TS HR 1.97, 95%CI 1.19-3.26, P=0.008;VS HR 2.48, 95%CI 1.47- 4.20, P=0.001). We conclude that systemic inflammation drives mortality from Covid-19 through hypoalbuminemia and lymphocytopenia as measured by the PNI and propose the PNI as the OnCovid Inflammatory Score (OIS) in this context.
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Molecular communications essentially analyze the transmission of the information at the nano level in cells, the smart devices that constitute our bodies. This emerging field uses traditional communication systems elements and maps them to molecular signaling and communication found inside and outside the body. Hence, molecular communications’ fundamental importance denotes the necessity to develop a new technology framework that provides a novel perspective to fight human diseases (the COVID-19 pandemic has highlighted this challenge). Thus, the architecture for molecular communications can be explored from the perspective of computer networks, i.e., the TCP/IP reference model and the basic model of MC can also be represented using Shannon’s communication model (i.e., transmitter, communication channel, and receiver). In this field, IEEE impulses the 1906.1 and 1906.1.1 standards that establish definitions, terminology, and a conceptual model for ad hoc network communication at the nanoscale. With these ICT perspectives, we appropriately have analyzed gene expression in eukaryotes organisms as a layered stack (network, link, and physical layer) of a nano communication network. In this biological communication process, the cellular nucleus behaves as the DTE, the ribosomes, and Endoplasmic Reticulum represent the DCE, the Golgi Apparatus represents a border router. The proteins secreted by the cell move through the bloodstream (physical transmission medium) and reaching the receiver (DCE-DTE), which processes the information through ligands and their receptors. © 2021, ICST Institute for Computer Sciences, Social Informatics and Telecommunications Engineering.
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Objectives: The limited access to addiction services pre-COVID-19 and the increase in substance use disorder support required during COVID has led to a heightened need for virtual addictions care capacity building interventions. We describe the evaluation of Project Extension for Community Healthcare Outcomes (TM)-Ontario Addiction Medicine and Psychosocial Interventions (ECHO-AMPI), a Canadian virtual tele-mentoring program focused on building capacity in community-based addiction care during COVID-19. Methods: We used Moore's multi-level evaluation framework for continuing education. Participants rated their satisfaction on a five-point Likert scale. A pre-post 10-item scale was used to measure self-efficacy. Participants used a binary scale to self-report post-participation whether ECHO changed their practice. Participants also responded to an open-text question around how participation in ECHO has impacted challenges experienced during the pandemic. Results: Seventy-nine healthcare professionals from 62 organizations across Ontario participated in ECHO-AMPI. Mean satisfaction ratings were high (>4.27/5), and a 12% improvement in participants' addictions care mean self-efficacy scores was observed (P < 0.001). Post-ECHO participation, 77% of participants reported practice change. Analysis of open-text responses highlighted participants felt ECHO fostered an open and supportive community, improved knowledge and skills via the acquisition of new resources, enhanced participants' interaction with their clients, and reduced professional isolation. Conclusions: ECHO-AMPI demonstrated the ability to engage providers and build addictions care capacity during COVID-19, specifically by improving learning outcomes and supporting practice change. Our data also suggests that this virtual tele-mentoring model can provide a supportive community of practice for addictions care providers during COVID-19.
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Background: Data from the first wave of COVID-19 infection demonstrated that a history of cancer and SACT was associated with poorer outcomes. Our study compares outcomes for cancer patients matched to non-cancer patients between the two waves in order to explore further how cancer and its treatment may impact COVID-19 mortality. Methods: Data was collected for patients with positive PCR and history of cancer between 1 Mar to 20 May 2020 and 1 Dec to 8 Feb 2021 for wave 1 and 2, respectively. A contemporaneous cohort of patients without cancer were age- and sex-matched for comparison. Results: The total number of patients presenting with COVID-19 was higher in wave two (1135 vs 626). 207 of these patients had cancer, and were matched to 452 patients without cancer from both waves. There was a significantly improved chance of mortality in wave 2 (HR 0.41, p < 0.0001). When adjusting for age, sex and co-morbidities, cancer was an independent risk factor for mortality amongst patients hospitalised with COVID-19 in wave 1 (HR 1.62, p = 0.02), but not in wave 2. There was a trend towards improved survival for hospitalised patients in wave 2 receiving COVID-19 specific treatment including dexamethasone, remdesivir, tocilizumab (HR 0.75, p = 0.086). For the combined cancer cohort, SACT was an independent predictor of mortality, as was metastatic disease. [Formula presented] Conclusions: The mortality for both cancer and non-cancer patients improved between waves of the pandemic. Advances in detection, prevention and treatment may account for this. Cancer was no longer a risk factor for mortality in the second wave, however SACT and metastatic cancer remained risk factors for mortality within the cancer cohort. This emphasises the need for ongoing protection of patients with advanced cancer and those on SACT, including through their prioritisation for COVID-19 vaccination globally. Legal entity responsible for the study: The authors. Funding: Has not received any funding. Disclosure: H. Shaw: Financial Interests, Personal, Invited Speaker, Advisory/Consultancy: Novartis;Financial Interests, Personal, Invited Speaker, Advisory/Consultancy: BMS;Financial Interests, Personal, Invited Speaker, Advisory/Consultancy: MSD;Financial Interests, Personal, Invited Speaker, Advisory/Consultancy: Immunocore;Financial Interests, Personal, Invited Speaker, Advisory/Consultancy: Idera;Financial Interests, Personal, Invited Speaker, Advisory/Consultancy: Iovance;Financial Interests, Personal, Invited Speaker, Advisory/Consultancy: Sanofi Genzyme/Regeneron;Financial Interests, Personal, Invited Speaker, Advisory/Consultancy: Macrogenics;Financi Interests, Personal, Invited Speaker, Advisory/Consultancy: Roche. R. Roylance: Financial Interests, Personal, Other, Personal Fees: Novartis;Financial Interests, Personal, Other, Personal Fees & None-financial support: Daiichi Sankyo;Financial Interests, Personal, Other, Personal Fees: Eli-Lilly;Financial Interests, Personal, Other, Personal Fees: Pfizer;Financial Interests, Personal, Other, Personal Fees & None-financial support: G1 Therapeutics;Non-Financial Interests, Personal, Other, None-financial support: Roche;Non-Financial Interests, Personal, Other, None-financial support: AstraZeneca. All other authors have declared no conflicts of interest.
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Background: Primary granulocyte-colony stimulating factor (GSCF) prophylaxis with dose-dense chemotherapy for early stage breast cancer is routine practice to prevent febrile neutropenia (FN). Our current practice administers 7 days of GCSF, which reduces the FN risk but is associated with extra toxicity and costs. We reviewed the rates of FN, neutropenia, hospital admissions and GCSF-related toxicity in early stage breast cancer patients receiving 7 days of GCSF with dose-dense epirubicin and cyclophosphamide (EC). Methods: Between 2018 and 2021, patients treated for early stage breast cancer with dose-dense epirubicin (90mg/m2) and cyclophosphamide (600mg/m2) given every 2 weeks at two London hospitals were identified from chemotherapy prescribing records. Treatment delays, dose reductions, hospital admissions and GCSF-related toxicity were assessed from medical records. Results: Ninety-seven patients were identified, receiving 373 cycles of dose-dense EC. Median age was 46 years (25 – 60 yrs). GCSF was prescribed for 7 days (days 3-10) at 300mcg and 480mcg for 82 and 15 patients respectively according to baseline weight. Three patients had dose delays due to neutropenia, one of whom was non-compliant with GCSF. Risk of hospital admission for any reason was 5.2% per patient (1.3% /cycle). Two patients were admitted with neutropenic sepsis (risk 2.1%/patient, 0.5%/cycle). One was admitted on day 7 and the other on day 10 of the cycle. Both had a neutrophil count of 0.26 x 10ˆ9 /L. One subsequently died of COVID pneumonitis. Toxicity to GCSF was recorded in 41% of patients (16.4%/cycle). Musculoskeletal pain was the most common toxicity (95%), others included headache and injection site pain. Thirty-three patients had neutrophilia (> 7.5 x 10ˆ9/L) prior to a cycle (event rate 17.4%/cycle). Duration of GCSF was reduced in 16 patients;12 due to toxicity, 1 due to neutrophilia, 1 due to raised neutrophil precursors and 2 not recorded. Of these, no patients had any further treatment delays or dose reductions. Conclusions: The optimal duration of GCSF prophylaxis to reduce the FN risk with dose-dense regimens is unclear. Seven days of GCSF is associated with toxicity - a reduction to 5 days should be considered. Legal entity responsible for the study: Royal Free London NHS Foundation Trust. Funding: Has not received any funding. Disclosure: All authors have declared no conflicts of interest.
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Background: One of the major challenges with COVID-19 has been the changes to cancer services, including changes to the type of systemic anti-cancer treatment being delivered to patients. There needs to be a better understanding of which cancer patients are at the greatest amount of risk to make informed decisions on how cancer treatment can be altered to protect patients from COVID-19 infection. The CAPITOL (COVID-19 CAncer PatIenT Outcomes in North London) study investigated the outcomes of patients receiving systemic anti-cancer therapies (SACT) with regards to COVID-19 infection, as patients with cancer are hypothesised to be at higher risk. Methods: CAPITOL collected data from all patients receiving SACT at two cancer centres. The effect of clinical characteristics on the incidence and severity of COVID-19 infection in patients on SACT was the primary outcome, and we used univariable and multivariable models in our analysis, adjusting for age, gender and comorbidities. Results: 2871 patients were analysed from 2nd March to 31st May 2020, all of whom received SACT;during this time period 68 (2.4%) were diagnosed with COVID-19. Receiving SACT increased the risk of death when contracting COVID-19 (adjusted (adj.) OR 9.84;95% CI 5.73 - 16.9). The risk of contracting COVID-19 was increased by receiving chemotherapy (adj. OR 2.99;95% CI = 1.72 - 5.21), with the risk significantly increased by high dose chemotherapy (adj. OR 2.36, 95% CI 1.35 - 6.48). Patients with comorbidities (adjusted OR 2.29;95% CI 1.19 - 4.38), or with a respiratory or intrathoracic neoplasm (adj. OR 2.12;95% CI 1.04 - 4.36) were also at increased risk of contracting COVID-19. Cancer patients who received targeted treatment had a reduced risk of contracting COVID-19 (adj. OR 0.53;95% CI 0.30 - 0.95), while there was no significant change in risk caused by treatment intent (curative versus palliative), hormonal- or immunotherapy and solid versus haematological cancers. Conclusions: To the best of our knowledge, this is one of the first investigations into the risk of contracting COVID-19 in a cohort of all cancer patients on SACT. We found that patients on SACT are more likely to die if they contract COVID-19. The type of SACT received by cancer patients can affect their likelihood of contacting COVID-19, with chemotherapy increasing risk, targeted therapy decreasing risk and a potential protective effect for hormonal and immunotherapy.
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Background: The COVID-19 (C19) pandemic has prompted alterations to systemic anti-cancer therapy (SACT) due to concerns of immunosuppression and healthcare exposure. However, the effects of SACT on mortality in patients who acquire C19 are not well understood. As a national cancer centre within a major C19 hotspot, we seek to address these risks at scale. Method(s): Patients with a history of solid cancers and laboratory confirmed C19 (1 Mar to 31 May 2020) were included. Haematological malignancies were excluded. The primary outcome was time from C19 diagnosis to death. The last follow-up date was 22 Jun 2020. Result(s): We identified 94 cancer patients;62 males (median age 73, BMI 24.9), and 32 females (median age 68.5, BMI 25.7). Genitourinary (n = 24) cancers were the most common, followed by gastrointestinal (n = 23), thoracic (n = 15), and gynaecological (n = 9) cancers. 25 patients received SACT: chemotherapy (n = 15), endocrine therapy (n = 8), immunotherapy (n = 4), and targeted anti-cancer therapy (n = 2). 16 patients received SACT with palliative intent. Patients on SACT had a greater incidence of metastatic disease (48.0% vs 10.6%, p 0.001) and were younger (median age 62.5 vs 73.0, p = 0.01). They were also more likely to have renal impairment (p = 0.02), lymphopaenia (p = 0.01) and anaemia (p = 0.04) compared to those not on SACT. The univariate analysis showed age and co-morbidities were associated with mortality (Table). Adjusting for age, ethnicity, co-morbidities and the presence of metastatic cancer, SACT was an independent risk factor for C19 mortality (HR 2.46, 1.09 - 5.5, p = 0.03). Age, South Asian ethnicity, hypertension and cerebrovascular disease were also independent risk factors for C19 mortality. [Formula presented] Conclusion(s): C19 infection poses a substantial risk to cancer patients and our data suggests that SACT is an independent risk factor for mortality in C19 infection. These findings call for a nuanced approach to C19 risk, focusing on established risk factors such as age and co-morbidities to guide treatment decisions. Legal entity responsible for the study: University College London Hospital. Funding(s): Has not received any funding. Disclosure: All authors have declared no conflicts of interest. Copyright © 2020
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Background: The COVID-19 pandemic remains of pressing concern for patients with cancer. Mortality from COVID-19 is predicted by age and co-morbidities, but the relative contribution of cancer is poorly understood. As a tertiary academic hospital serving a large general and cancer population in a COVID-19 epicentre, we are uniquely placed to investigate this. We report data from our study, comparing cancer patients to an age- and sex-matched non-cancer cohort. Methods: Patients with laboratory confirmed COVID-19 from 1 March to 31 May 2020 were included. Patients with a history of solid cancer were compared to an age- and sex-matched non-cancer cohort. Patients with haematological malignancies were excluded. Results: We identified 94 patients with cancer and 226 patients without cancer. In univariate analysis, age, South Asian ethnicity and co-morbidities predicted mortality (see table). More in the cancer cohort had died compared to the non-cancer cohort (43.6% vs 34.1%). The higher mortality among cancer patients was statistically significant among those aged 70 years and above (OR 2.28, 1.14-4.50, p = 0.02). After adjusting for age, ethnicity and co-morbidities, a history of cancer was an independent predictor of mortality following COVID-19 (HR 1.57, 95% CI:1.04-2.4, p = 0.03). Patients with active malignancy also had similarly increased adjusted mortality (HR 1.64, 95% CI: 1.03 – 2.6, p = 0.04). Increasing age (HR 1.49 every 10 years, 95% CI:1.25-1.8, p <0.001), South Asian ethnicity (HR 2.92, 95% CI:1.73-4.9, p <0.001) and cerebrovascular disease (HR 1.93, 95% CI:1.18-3.2, p = 0.008) were also confirmed as independent predictors of mortality. [Formula presented] Conclusions: Along with known risk factors, cancer confers an independent risk for mortality in COVID-19. Taken together, our findings support the need to continue ‘shielding’ patients with cancer from exposure to COVID-19 infection. Increasing age and co-morbidity should take precedence when weighing up risk factors for severe COVID-19 infection in cancer patients. Legal entity responsible for the study: University College London Hospitals NHS Foundation Trust. Funding: Has not received any funding. Disclosure: H.M. Shaw: Advisory/Consultancy, Speaker Bureau/Expert testimony: Novartis, BMS, MSD;Advisory/Consultancy: Immunocore, Idera, Iovance, Genmab, Sanofi Genzyme/Regeneron, Macrogenics, Roche;Speaker Bureau/Expert testimony: Sanofi Genzyme. All other authors have declared no conflicts of interest.