Now showing items 1-20 of 96

    • Pegargiminase plus first-line chemotherapy in patients with nonepithelioid pleural mesothelioma: the ATOMIC-meso randomized clinical trial

      Fennell, Dean A (2024-02-15)
      Importance: Arginine deprivation using ADI-PEG20 (pegargiminase) combined with chemotherapy is untested in a randomized study among patients with cancer. ATOMIC-Meso (ADI-PEG20 Targeting of Malignancies Induces Cytotoxicity-Mesothelioma) is a pivotal trial comparing standard first-line chemotherapy plus pegargiminase or placebo in patients with nonepithelioid pleural mesothelioma. Objective: To determine the effect of pegargiminase-based chemotherapy on survival in nonepithelioid pleural mesothelioma, an arginine-auxotrophic tumor. Design, setting, and participants: This was a phase 2-3, double-blind randomized clinical trial conducted at 43 centers in 5 countries that included patients with chemotherapy-naive nonepithelioid pleural mesothelioma from August 1, 2017, to August 15, 2021, with at least 12 months' follow-up. Final follow-up was on August 15, 2022. Data analysis was performed from March 2018 to June 2023. Intervention: Patients were randomly assigned (1:1) to receive weekly intramuscular pegargiminase (36.8 mg/m2) or placebo. All patients received intravenous pemetrexed (500 mg/m2) and platinum (75-mg/m2 cisplatin or carboplatin area under the curve 5) chemotherapy every 3 weeks up to 6 cycles. Pegargiminase or placebo was continued until progression, toxicity, or 24 months. Main outcomes and measures: The primary end point was overall survival, and secondary end points were progression-free survival and safety. Response rate by blinded independent central review was assessed in the phase 2 portion only. Results: Among 249 randomized patients (mean [SD] age, 69.5 [7.9] years; 43 female individuals [17.3%] and 206 male individuals [82.7%]), all were included in the analysis. The median overall survival was 9.3 months (95% CI, 7.9-11.8 months) with pegargiminase-chemotherapy as compared with 7.7 months (95% CI, 6.1-9.5 months) with placebo-chemotherapy (hazard ratio [HR] for death, 0.71; 95% CI, 0.55-0.93; P = .02). The median progression-free survival was 6.2 months (95% CI, 5.8-7.4 months) with pegargiminase-chemotherapy as compared with 5.6 months (95% CI, 4.1-5.9 months) with placebo-chemotherapy (HR, 0.65; 95% CI, 0.46-0.90; P = .02). Grade 3 to 4 adverse events with pegargiminase occurred in 36 patients (28.8%) and with placebo in 21 patients (16.9%); drug hypersensitivity and skin reactions occurred in the experimental arm in 3 patients (2.4%) and 2 patients (1.6%), respectively, and none in the placebo arm. Rates of poststudy treatments were comparable in both arms (57 patients [45.6%] with pegargiminase vs 58 patients [46.8%] with placebo). Conclusions and relevance: In this randomized clinical trial of arginine depletion with pegargiminase plus chemotherapy, survival was extended beyond standard chemotherapy with a favorable safety profile in patients with nonepithelioid pleural mesothelioma. Pegargiminase-based chemotherapy as a novel antimetabolite strategy for mesothelioma validates wider clinical testing in oncology.
    • Resveratrol for the management of human health: how far have we come? A systematic review of resveratrol clinical trials to highlight gaps and opportunities

      Brown, Karen; Pepper, Coral (2024-01-06)
      Resveratrol has long been proposed as being beneficial to human health across multiple morbidities, yet there is currently no conclusive clinical evidence to advocate its recommendation in any healthcare setting. A large cohort with high-quality clinical data and clearly defined biomarkers or endpoints are required to draw meaningful conclusions. This systematic review compiles every clinical trial conducted using a defined dose of resveratrol in a purified form across multiple morbidities to highlight the current 'state-of-play' and knowledge gaps, informing future trial designs to facilitate the realisation of resveratrol's potential benefits to human health. Over the last 20 years, there have been almost 200 studies evaluating resveratrol across at least 24 indications, including cancer, menopause symptoms, diabetes, metabolic syndrome, and cardiovascular disease. There are currently no consensus treatment regimens for any given condition or endpoint, beyond the fact that resveratrol is generally well-tolerated at a dose of up to 1 g/day. Additionally, resveratrol consistently reduces inflammatory markers and improves aspects of a dysregulated metabolism. In conclusion, over the last 20 years, the increasing weight of clinical evidence suggests resveratrol can benefit human health, but more large, high-quality clinical trials are required to transition this intriguing compound from health food shops to the clinic.
    • The global landscape on the access to cancer medicines for breast cancer: the ONCOLLEGE experience

      Hussain, Sadaqat (2023)
      There is a growing global debate over barriers affecting the timely access to innovative anticancer therapies. Access to medicines is often traced back to the issue of costs: however, more commonly, the distance between valuable innovative treatments and the actual treatment of patients is far beyond the mere problem of financial barriers. A comprehensive approach to understand, assess to medicines should be pursued, to dissect the determinants and formulate solutions for all patients. In this chapter, we discuss drivers of access to innovation for patients with breast cancer, based on a case study of access to HER2-diagnositcs and therapeutics yielding a global landscape analysis, based on the efforts and expertise of the global collaborative group "ONCOLLEGE".
    • Attitudes and barriers to participation in window-of-opportunity trials reported by White and Asian/Asian British ethnicity patients who have undergone treatment for endometrial cancer

      Amirthanayagam, Anumithra; Moss, Esther (2023-11-23)
      Purpose: Window-of-opportunity trials (WOT) are a study design that have been used to investigate drug activity in endometrial cancer (EC). Recruitment to cancer clinical trials by patients from ethnic minority groups is reported to be lower than for patients of White ethnicity. Methods: A verbal questionnaire was conducted with White and Asian/Asian British ethnicity patients who had undergone treatment for EC. Strategic purposeful sampling was used to recruit patients from diverse social/educational backgrounds. Questions explored: background knowledge of clinical research, WOT study design, and views on medications that might be investigated. Thematic analysis was used to explore motivations for WOT participation and perceived barriers. Results: In total, 21 patients were recruited to the study (15 White and 6 Asian/Asian British). Views on optimum time to receive trial information differed, preferences ranging from 'at the time of diagnosis' to 'a few days after diagnosis'. The choice of medication under investigation had a strong influence on potential willingness to participate, with greater interest reported in medications derived from vitamins or food supplements rather than hormone-based drugs. Potential barriers to participation included concern over potential side-effects and the emotional/physical burden of a cancer diagnosis prior to major surgery. Discussion: This study provides important insights into patients' views on WOT participation in EC and raises issues that need to be considered for future trial design and participant recruitment materials. The timing and format of study information and type of substance under investigation were factors influencing potential participation. Future studies should consider using multi-lingual visual information videos to address information needs, as this may encourage participation by ethnic minority patients.
    • Anticancer actions of carnosine in cellular models of prostate cancer

      Khan, M A (2023-11-29)
      Treatments for organ-confined prostate cancer include external beam radiation therapy, radical prostatectomy, radiotherapy/brachytherapy, cryoablation and high-intensity focused ultrasound. None of these are cancer-specific and are commonly accompanied by side effects, including urinary incontinence and erectile dysfunction. Moreover, subsequent surgical treatments following biochemical recurrence after these interventions are either limited or affected by the scarring present in the surrounding tissue. Carnosine (β-alanyl-L-histidine) is a histidine-containing naturally occurring dipeptide which has been shown to have an anti-tumorigenic role without any detrimental effect on healthy cells; however, its effect on prostate cancer cells has never been investigated. In this study, we investigated the effect of carnosine on cell proliferation and metabolism in both a primary cultured androgen-resistant human prostate cancer cell line, PC346Flu1 and murine TRAMP-C1 cells. Our results show that carnosine has a significant dose-dependent inhibitory effect in vitro on the proliferation of both human (PC346Flu1) and murine (TRAMP-C1) prostate cancer cells, which was confirmed in 3D-models of the same cells. Carnosine was also shown to decrease adenosine triphosphate content and reactive species which might have been caused in part by the increase in SIRT3 also shown after carnosine treatment. These encouraging results support the need for further human in vivo work to determine the potential use of carnosine, either alone or, most likely, as an adjunct therapy to surgical or other conventional treatments.
    • Ibrutinib as first line therapy for mantle cell lymphoma: a multicentre, real-world UK study

      Allchin, Rebecca; Walter, Harriet Sarah; Miall, Fiona (2023-12-21)
      During the Covid-19 pandemic, ibrutinib +/- rituximab was approved in England for initial treatment of mantle cell lymphoma (MCL) instead of immunochemotherapy. As limited data are available in this setting, we conducted an observational cohort study evaluating safety and efficacy. Adults receiving ibrutinib +/- rituximab for untreated MCL were evaluated for treatment toxicity, response and survival, including outcomes in high-risk MCL (TP53 mutation/deletion/p53 overexpression, blastoid/pleomorphic, or Ki67 >/=30%). 149 patients from 43 participating centres were enrolled: 74.1% male, median age 75, 75.2% ECOG 0-1, 36.2% high-risk, 8.9% autologous transplant candidates. All patients received >/= 1 cycle ibrutinib (median 8 cycles), 39.0% with rituximab. Grade >/= 3 toxicity occurred in 20.3%, 33.8% required dose reductions/delays. At 15.6 months (mo) median follow-up, 41.6% discontinued ibrutinib; 8.1% due to toxicity. Of 104 response-assessed patients, overall (ORR) and complete response (CR) rates were 71.2% and 20.2% respectively. ORR was 77.3% (low-risk) vs. 59.0% (high-risk), p=0.05, and 78.7% (ibrutinib-rituximab) vs. 64.9% (ibrutinib), p=0.13. Median progression-free survival was 26.0mo (all patients); 13.7mo (high-risk) vs. not reached (NR) (low-risk), p=0.004. Median overall survival was NR (all); 14.8mo (high-risk) vs. NR (low-risk), p=0.005. Median post-ibrutinib survival was 1.4mo, longer in 41.9% patients receiving subsequent treatment (median 8.6 vs 0.6mo, p=0.002). Ibrutinib +/- rituximab was effective and well tolerated as first-line treatment of MCL, including older and transplant-ineligible patients. PFS and OS were significantly inferior in one-third of patients with high-risk disease and those unsuitable for post-ibrutinib treatment, highlighting the need for novel approaches in these groups.
    • Robotic-assisted surgery in high-risk surgical patients with endometrial cancer

      Moss, Esther (2023-11-04)
      Many patients diagnosed with an endometrial cancer are at high-risk for surgery due to factors such as advanced age, raised body mass index or frailty. Minimally-invasive surgery, in particular robotic-assisted, is increasingly used in the surgical management of endometrial cancer however, there are a lack of clinical trials investigating outcomes in high-risk patient populations. This article will review the current evidence and identify areas of uncertainty where future research is needed.
    • Standardized clinical annotation of digital histopathology slides at the point of diagnosis

      Hero, Emily (2023-11)
      As digital pathology replaces conventional glass slide microscopy as a means of reporting cellular pathology samples, the annotation of digital pathology whole slide images is rapidly becoming part of a pathologist's regular practice. Currently, there is no recognizable organization of these annotations, and as a result, pathologists adopt an arbitrary approach to defining regions of interest, leading to irregularity and inconsistency and limiting the downstream efficient use of this valuable effort. In this study, we propose a Standardized Annotation Reporting Style for digital whole slide images. We formed a list of 167 commonly annotated entities (under 12 specialty subcategories) based on review of Royal College of Pathologists and College of American Pathologists documents, feedback from reporting pathologists in our NHS department, and experience in developing annotation dictionaries for PathLAKE research projects. Each entity was assigned a suitable annotation shape, SNOMED CT (SNOMED International) code, and unique color. Additionally, as an example of how the approach could be expanded to specific tumor types, all lung tumors in the fifth World Health Organization of thoracic tumors 2021 were included. The proposed standardization of annotations increases their utility, making them identifiable at low power and searchable across and between cases. This would aid pathologists reporting and reviewing cases and enable annotations to be used for research. This structured approach could serve as the basis for an industry standard and be easily adopted to ensure maximum functionality and efficiency in the use of annotations made during routine clinical examination of digital slides.
    • Osimertinib with or without chemotherapy in EGFR-mutated advanced NSCLC

      Ahmed, Samreen (2023-11-23)
      Background: Osimertinib is a third-generation epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) that is selective for EGFR-TKI-sensitizing and EGFR T790M resistance mutations. Evidence suggests that the addition of chemotherapy may extend the benefits of EGFR-TKI therapy. Methods: In this phase 3, international, open-label trial, we randomly assigned in a 1:1 ratio patients with EGFR-mutated (exon 19 deletion or L858R mutation) advanced non-small-cell lung cancer (NSCLC) who had not previously received treatment for advanced disease to receive osimertinib (80 mg once daily) with chemotherapy (pemetrexed [500 mg per square meter of body-surface area] plus either cisplatin [75 mg per square meter] or carboplatin [pharmacologically guided dose]) or to receive osimertinib monotherapy (80 mg once daily). The primary end point was investigator-assessed progression-free survival. Response and safety were also assessed. Results: A total of 557 patients underwent randomization. Investigator-assessed progression-free survival was significantly longer in the osimertinib-chemotherapy group than in the osimertinib group (hazard ratio for disease progression or death, 0.62; 95% confidence interval [CI], 0.49 to 0.79; P<0.001). At 24 months, 57% (95% CI, 50 to 63) of the patients in the osimertinib-chemotherapy group and 41% (95% CI, 35 to 47) of those in the osimertinib group were alive and progression-free. Progression-free survival as assessed according to blinded independent central review was consistent with the primary analysis (hazard ratio, 0.62; 95% CI, 0.48 to 0.80). An objective (complete or partial) response was observed in 83% of the patients in the osimertinib-chemotherapy group and in 76% of those in the osimertinib group; the median response duration was 24.0 months (95% CI, 20.9 to 27.8) and 15.3 months (95% CI, 12.7 to 19.4), respectively. The incidence of grade 3 or higher adverse events from any cause was higher with the combination than with monotherapy - a finding driven by known chemotherapy-related adverse events. The safety profile of osimertinib plus pemetrexed and a platinum-based agent was consistent with the established profiles of the individual agents. Conclusions: First-line treatment with osimertinib-chemotherapy led to significantly longer progression-free survival than osimertinib monotherapy among patients with EGFR-mutated advanced NSCLC. (Funded by AstraZeneca; FLAURA2 number, NCT04035486.).
    • Safety of bendamustine for the treatment of indolent non-Hodgkin lymphoma: a UK real-world experience

      Ahearne, Matthew; Miall, Fiona (2023-11-15)
      Introduction: Bendamustine is among the most effective chemotherapeutics for indolent B-cell non-Hodgkin lymphomas (iNHL), but trial reports of significant toxicity, including opportunistic infections and excess deaths, led to prescriber warnings. We conducted a multicentre observational study evaluating bendamustine toxicity in real-world practice. Methods: Patients receiving at least one dose of bendamustine (B) +/- rituximab (R) for iNHL were included. Demographics, lymphoma and treatment details and grade 3-5 adverse events (AEs) were analysed. Results: 323 patients were enrolled from 9 NHS hospitals. Most patients (96%) received BR and 46% R maintenance. 21.7% experienced serious AEs (SAE) related to treatment, including infections in 12%, with absolute risk highest during induction (63%), maintenance (20%), and follow-up (17%), and the relative risk highest during maintenance (54%), induction (34%) and follow-up (28%). Toxicity led to permanent treatment discontinuation in 13% of patients, and 2.8% died of bendamustine-related infections (n=5), myelodysplastic syndrome (n=3), and cardiac disease (n=1). More SAEs per patient were reported in patients with mantle cell lymphoma, poor pre-induction PS, poor pre-maintenance PS, abnormal pre-induction total globulins and in those receiving growth factors. Use of antimicrobial prophylaxis was variable, and 3/10 opportunistic infections occurred despite prophylaxis. Conclusion: In this real-world analysis, bendamustine-related deaths and treatment discontinuation were similar to trial populations of younger, fitter patients. Poor PS, mantle cell histology and maintenance rituximab were potential risk factors. Infections, including late onset events, were the most common treatment-related SAE and cause of death warranting extended antimicrobial prophylaxis and infectious surveillance, especially in maintenance-treated patients.
    • Outcomes and characteristics of non-melanoma skin cancers in patients with myeloproliferative neoplasms on ruxolitinib

      Laing, Heather; Garg, Mamta (2023-11-14)
      Non-melanoma skin cancers in ruxolitinib-treated MPN patients behave aggressively, with adverse features and high recurrence. In our cohort, mortality from metastatic NMSC exceeded that from myelofibrosis . Vigilant skin assessment, counselling on NMSC risks, and prospective ruxolitinib-NMSC studies are crucial.
    • Late onset toxicities associated with the use of CDK 4/6 inhibitors in hormone receptor positive (HR+), human epidermal growth factor receptor-2 negative (HER2-) metastatic breast cancer patients: a multidisciplinary, pan-EU position paper regarding their optimal management. The GIOCONDA project

      Olubukola, Ayodele; Ahmed, Samreen (2023-10-26)
      The personalization of therapies in breast cancer has favoured the introduction of new molecular-targeted therapies into clinical practice. Among them, cyclin-dependent kinases 4 and 6 (CDK4/6) inhibitors have acquired increasing importance, with the approval in recent years of palbociclib, ribociclib, and abemaciclib in combination with endocrine therapy. Currently, no guidelines are available to monitor and manage potential long-term toxicities associated with the use of these drugs. A multidisciplinary panel of European oncologists, was supported by a pharmacologist, a hematologist, a hepatologist and a pulmonologist to discuss the management of long-term toxicities, based on the literature review and their clinical experience. The panel provided detailed roadmaps to manage long-term toxicities associated with the use of CDK4/6 inhibitors in clinical practice. Knowing the frequency and characteristics of the toxicity profile associated with each CDK4/6 inhibitor is important in the decision-making process to match the right drug to the right patient.
    • Walking pace and the time between the onset of non-communicable diseases and mortality: a UK biobank prospective cohort study

      Henson, Joseph; Davies, Melanie; Zaccardi, Francesco; Goldney, Jonathan (2023-10-09)
      Purpose: To estimate trajectories of time spent in various cardiovascular disease (CVD) and cancer states, according to self-reported walking pace. Methods: 391,744 UK Biobank participants were included (median age=57 years; 54.7% women). Data was collected 2006-2010, with follow-up data collected in 2021. Usual walking pace was self-defined as slow, steady/average or brisk. Multistate modelling was used to obtain the transition rate and mean sojourn time in and across three different states (healthy, CVD/cancer, death) upon a time horizon of 10 years. Results: Those reporting an average or brisk walking pace at baseline displayed lower rates across all transitions (vs. slow walkers). The mean sojourn time in the healthy state was longer while that in the CVD/cancer state was shorter in individuals reporting an average or brisk walking pace (vs. slow). A 75-year-old woman reporting a brisk walking pace spent, on average, 8.4 years of the next 10 years in a healthy state; an additional 8.0 (95% CI: 7.3, 8.7) months longer compared to a 75-year-old woman reporting a slow walking pace. This corresponded to 4.3 (3.7, 4.9) fewer months living with CVD/ cancer. Similar results were seen in men. Conclusions: Adults reporting an average or brisk walking pace at baseline displayed a lower transition to disease development and a greater proportion of life lived without CVD/cancer. Availability of data and materials: Research was conducted using the UK Biobank Resource under Application #33266. The UK Biobank resource can be accessed by researchers on application. Variables derived for this study have been returned to the UK Biobank for future applicants to request. No additional data are available.
    • Kidney function and long-term risk of end-stage kidney disease and mortality in a multiethnic population

      Zaccardi, Francesco; Khunti, Kamlesh; Brunskill, Nigel; Xu, Gang (2023-06-19)
      Introduction: Contemporary differences between South Asian and White ethnicities in the incidence of end-stage kidney disease (ESKD) and mortality are poorly described. Methods: Data for all South Asian patients who had an estimated glomerular filtration rate (eGFR) measure after January 1, 2006, and 1 million randomly selected participants of other ethnicities were extracted from the Clinical Practice Research Datalink (CPRD). All participants were followed-up with from index date until ESKD, all-cause mortality, or end of study. All-cause mortality rate and ESKD incidence rate by age were described among Whites and South Asians, and adjusted hazard ratios (HRs) of these 2 outcomes by baseline eGFR estimated using Cox proportional hazard model. Results: A total of 40,888 South Asians and 236,634 Whites were followed for a median of 5.3 and 9.4 years for ESKD incidence and mortality outcomes, respectively. All-cause mortality rates were higher among Whites than South Asians; South Asian women aged between 70 and 85 years had a slightly higher ESKD incidence rate compared to their White counterparts. Compared to Whites with a baseline eGFR of 90 ml/min per 1.73 m2, adjusted HRs for all-cause mortality were significantly lower among South Asians than Whites; however, adjusted HRs for ESKD incidence by baseline eGFR were similar in both ethnicities. Calculating South Asian eGFRs using an ethnicity-specific equation had no impact on the results. Conclusions: South Asians experience lower mortality than Whites but not substantially higher rates of ESKD. Further research is warranted to better understand the reasons for these ethnic differences and possible impacts on chronic kidney disease (CKD) service delivery and patient outcomes.
    • The British Orthopaedic Oncology Management (BOOM) audit

      Ashford, Robert; Sharma, Vivek; Rai, Paul; Mitchell, Lara; Hutchings, Steffan; Nichols, Jennifer; Singh, Harvinder; Armstrong, Alison; Brown, Andrew (01/10/2023)
      Aims: Most patients with advanced malignancy suffer bone metastases, which pose a significant challenge to orthopaedic services and burden to the health economy. This study aimed to assess adherence to the British Orthopaedic Oncology Society (BOOS)/British Orthopaedic Association (BOA) guidelines on patients with metastatic bone disease (MBD) in the UK. Methods: A prospective, multicentre, national collaborative audit was designed and delivered by a trainee-led collaborative group. Data were collected over three months (1 April 2021 to 30 June 2021) for all patients presenting with MBD. A data collection tool allowed investigators at each hospital to compare practice against guidelines. Data were collated and analyzed centrally to quantify compliance from 84 hospitals in the UK for a total of 1,137 patients who were eligible for inclusion. Results: A total of 846 patients with pelvic and appendicular MBD were analyzed, after excluding those with only spinal metastatic disease. A designated MBD lead was not present in 39% of centres (33/84). Adequate radiographs were not performed in 19% of patients (160/846), and 29% (247/846) did not have an up-to-date CT of thorax, abdomen, and pelvis to stage their disease. Compliance was low obtaining an oncological opinion (69%; 584/846) and prognosis estimations (38%; 223/846). Surgery was performed in 38% of patients (319/846), with the rates of up-to-date radiological investigations and oncology input with prognosis below the expected standard. Of the 25% (215/846) presenting with a solitary metastasis, a tertiary opinion from a MBD centre and biopsy was sought in 60% (130/215). Conclusion: Current practice in the UK does not comply with national guidelines, especially regarding investigations prior to surgery and for patients with solitary metastases. This study highlights the need for investment and improvement in care. The recent publication of British Orthopaedic Association Standards for Trauma (BOAST) defines auditable standards to drive these improvements for this vulnerable patient group.
    • Navigating thyroid dysfunction and comorbidities among university students in Abbottabad, Pakistan - a cross-sectional evaluation of screening tool for thyroid dysfunction

      Iqbal, Muhammad (2023-09-15)
      Background: Thyroid dysfunction has a direct role in diagnosing, and assessment and indicates the development of thyroid carcinoma. This study aimed to assess thyroid dysfunction through medical camps in different age and sex groups in students of Comsats University Abbottabad Pakistan. Methods: In this study, a cross-sectional survey design was used. For data collection, a two-day medical camp was set in the Comsats University Abbottabad campus. The students were examined physically for symptoms of thyroid dysfunction using the survey questionnaire specifically designed for this study. Results: The current research revealed that 78 out of 1032 students, or 7.6% of the population, had thyroid disease. Although 39.3% (=406) were found to have low risk, followed by 36.7% (n=379) had moderate risk and 23.9% (n=247) had high risk of thyroid dysfunction. Altogether, 6.1% (n=63) of the students had high blood pressure (BP), 3.2% (n=33) had high cholesterolemia, 3.4% (n=33) had angina, and 0.9% (n=9) had diabetes mellitus (DM). In relation, students who exhibit signs and symptoms that last longer than five weeks include 42.2% (n=435) who felt the need for excessive sleep, 35.3% (n=364) who felt tired, 36.8% (n=380) who had trouble concentrating and 30.1% (n=311) who had palpitations. The high risk of thyroid being seen predominantly in students between the ages of 15-20 years (31.2%, n=148), as opposed to other age groups (p=0.001). Similar to this, women having a higher risk of thyroid disease (26.5%) than men (22.8%) (p =0.001). Conclusion: In conclusion, few students suffer with thyroid found to have high risk of thyroid disease. This method of questionnaire-based screening for thyroid dysfunction is cost-effective, with no additive risk of adverse effects from excessive screening, and could help in the early detection of thyroid and help avoid excess costs related to thyroid dysfunction and cancer screening.
    • NICE 2022 guidelines on the management of melanoma: Update and implications

      Ramachandran, Sanjeev; Begaj, Ardit; Morgan, Bruno; Faust, Guy; Patel, Nakul; Jayarajan, Rajshree (2023-07-20)
      Aims: In July 2022, NICE updated the guidelines on the management of melanoma by lowering the number of follow-up appointments and sentinel lymph node biopsy (SLNB) but increasing the number of scans. This study aims to evaluate the implications of executing the new guidelines in terms of cost-effectiveness and personnel. Methods: All patients newly diagnosed with melanoma in 2019 at a regional skin cancer specialist center were reviewed. Data were analyzed for their journey on an idealized pathway modeled over a 5-year follow-up period when adhering to both the previous and new guidelines. Differences in the management of melanoma were elucidated by comparing these changes. The cost was quantified on a perpatient basis and the financial implication on each department was considered. Results: One hundred and ten patients were diagnosed with melanoma in 2019, stages I-III. The changes ease the burden on plastic surgery and dermatology; however, increased pressure is faced by radiologists and histopathologists. An overall cost benefit of £141.85 perpatient was calculated, resulting in a decrease of 1.22 hospital visits on average and an increase in the time spent there (19.55 min). The additional expenses of implementing the new guidelines due to the added BRAF tests, CT, and ultrasound scans are outweighed by savings from the reduction in follow-up appointments and SLNB. Conclusion: The focus has shifted to less invasive procedures for lower melanoma stages and fewer follow-up appointments, at the expense of more genetic testing and imaging. This paper serves as a useful baseline for other centers to plan their service provision and resource allocation to adhere to the updated guidelines.
    • Changes in lung cancer staging and emergency presentations during the first year of the COVID-19 pandemic

      Vella, Claire; Ashraf, Asif; Ajmal, Syed; Sudhir, Rajini; Agrawal, Sanjay; Tufail, Muhammad; Bennett, Jonathan (2023-01)
      Aim: This study retrospectively analyses the impact of the 1st year of the COVID-19 pandemic on route of presentation and staging in lung cancer compared to the 2 years before and after implementation of the Leicester Optimal Lung Cancer Pathway (LOLCP) in Leicester, United Kingdom. Method: Electronic databases and hospital records were used to identify all patients diagnosed with lung cancer in 2018 (pre-LOLCP), 2019 (post-LOLCP), and March 2020-2021 (post-COVID-19 lockdown). Information regarding patient characteristics, performance status, stage, and route of diagnosis was documented and analysed. Emergency presentation was defined as diagnosis of new lung cancer being made after unscheduled attendance to urgent or emergency care facility. Results: Following implementation of the LOLCP pathway, there was a significant decrease in emergency presentations from 26.8 to 19.6% (p = 0.002) with a stage shift from 33.9% early stage disease to 40.3%. These improved outcomes were annulled during the COVID-19 pandemic, with emergency presentations increasing to 38.9% (p < 0.001) and a reduction in early-stage lung cancer diagnoses to 31.5%. There was a 61% decline in 2 week wait referrals but no significant decline in the LOLCP direct-to-CT referrals. Conclusion: We have demonstrated a significant increase in late-stage lung cancer diagnoses and emergency presentations during the first year of the COVID-19 pandemic. The causes for these changes are likely to be multifactorial. The long-term effect on lung cancer mortality remains to be seen and is an important focus of future study.