Recent Submissions

  • Cancer multidisciplinary team meetings: impact of logistical challenges on communication and decision-making.

    Bali, Anish; Asher, Viren
    BACKGROUND: Multidisciplinary teams (MDTs) are widely used in cancer care. Recent research points to logistical challenges impeding MDT decision-making and dissatisfaction among members. This study sought to identify different types of logistical issues and how they impacted team processes. METHODS: This was a secondary analysis of a cross-sectional observational study. Three cancer MDTs (breast, colorectal, and gynaecological) were recruited from UK hospitals. Validated observational instruments were used to measure decision-making (Metrics of Observational Decision-making, MDT-MODe), communication (Bales' Interaction Process Analysis, Bales' IPA), and case complexity (Measure of Case Discussion Complexity, MeDiC), including logistical challenges (Measure of Case Discussion Complexity, MeDiC), across 822 case discussions from 30 videoed meetings. Descriptive analysis and paired samples t tests were used to identify and compare frequency of different types of logistical challenges, along with partial correlations, controlling for clinical complexity of cases, to understand how such issues related to the MDT decision-making and communication. RESULTS: A significantly higher frequency of administrative and process issues (affecting 30 per cent of cases) was seen compared with the frequency of equipment issues (affecting 5 per cent of cases; P < 0.001) and the frequency of the attendance issues (affecting 16 per cent of cases; P < 0.001). The frequency of the attendance issues was significantly higher than the frequency of equipment issues (P < 0.001). Partial correlation analysis revealed that administrative and process issues, including attendance, were negatively correlated with quality of information (r = -0.15, P < 0.001; r = -0.11, P < 0.001), and equipment issues with the quality of contribution to meeting discussion (r = -0.14, P < 0.001). More questioning and answering by MDT members was evident with the administrative and process issues (r = 0.21, P < 0.001; r = 0.19, P < 0.001). Some differences were observed in teams' socioemotional reactions to the administrative and process issues with the gynaecological MDT showing positive correlation with positive socioemotional reactions (r = 0.20, P < 0.001), and the breast cancer MDT with negative socioemotional reactions (r = 0.17, P < 0.001). CONCLUSION: Administrative and process issues were the most frequent logistical challenges for the studied teams. Where diagnostic results were unavailable, and inadequate patient details provided, the quality of decision-making was reduced.
  • Fibroepithelial lesions of the breast: Improving the accuracy of imaging diagnosis and reducing unnecessary biopsy.

    Evans, Andrew; Jethwa, K
    Fibroadenomas and phyllodes tumours are fibroepithelial lesions of the breast. Fibroadenomas are common benign breast masses encountered both symptomatically and incidentally. Phyllodes tumours are uncommon and usually present symptomatically. Management of fibroadenomas focuses on reducing biopsies without missing cancers while radiological management of phyllodes tumours should focus on predicting the need for surgical excision with or without margins.
  • What Is the Most Effective Management of the Primary Tumor in Men with Invasive Penile Cancer: A Systematic Review of the Available Treatment Options and Their Outcomes.

    Kailavasan, Mithun
    CONTEXT: The primary lesion in penile cancer is managed by surgery or radiation. Surgical options include penile-sparing surgery, amputative surgery, laser excision, and Moh's micrographic surgery. Radiation is applied as external beam radiotherapy (EBRT) and brachytherapy. The treatment aims to completely remove the primary lesion and preserve a sufficient functional penile stump. OBJECTIVE: To assess whether the 5-yr recurrence-free rate and other outcomes, such as sexual function, quality of life, urination, and penile preserving length, vary between various treatment options. EVIDENCE ACQUISITION: The EMBASE, MEDLINE, Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials (CENTRAL; Cochrane HTA, DARE, HEED), Google Scholar, and ClinicalTrials.gov were searched for publications from 1990 through May 2021. Randomized controlled trials, nonrandomized comparative studies (NRCSs), and case series (CSs) were included. EVIDENCE SYNTHESIS: The systematic review included 88 studies, involving 9578 men from 16 NRCSs and 72 CSs. The cumulative mean 5-yr recurrence-free rates were 82.0% for penile-sparing surgery, 83.9% for amputative surgery, 78.6% for brachytherapy, 55.2% for EBRT, 69.4% for lasers, and 88.2% for Moh's micrographic surgery, as reported from CSs, and 76.7% for penile-sparing surgery and 93.3% for amputative surgery, as reported from NRCSs. Penile surgery affects sexual function, but amputative surgery causes more appearance concerns. After brachytherapy, 25% of patients reported sexual dysfunction. Both penile-sparing surgery and amputative surgery affect all aspects of psychosocial well-being. CONCLUSIONS: Despite the poor quality of evidence, data suggest that penile-sparing surgery is not inferior to amputative surgery in terms of recurrence rates in selected patients. Based on the available information, however, broadly applicable recommendations cannot be made; appropriate patient selection accounts for the relative success of all the available methods. PATIENT SUMMARY: We reviewed the evidence of various techniques to treat penile tumor and assessed their effectiveness in oncologic control and their functional outcomes. Penile-sparing as well as amputative surgery is an effective treatment option, but amputative surgery has a negative impact on sexual function. Penile-sparing surgery and radiotherapy are associated with a higher risk of local recurrence, but preserve sexual function and quality of life better. Laser and Moh's micrographic surgery could be used for smaller lesions.
  • Lactate Is a Reliable Predictor of ICU Length of Stay Following Ultra-radical Ovarian Cancer Surgery.

    Addley, Susan; McGowan, Mark; Asher, Viren; Bali, Anish; Abdul, Summi; Cullimore, Victoria; Crossland, Harriet; Phillips, Andrew
    BACKGROUND/AIM: With a greater proportion of women with advanced ovarian cancer (AOC) successfully undergoing radical cytoreductive surgery, the demand on peri-operative resources - including intensive care (ICU) beds - is also on the rise. Extended post-operative ICU length of stay (LOS) confers increased patient morbidity and mortality. Several variables associated with prolonged ICU LOS following AOC surgery have been identified. We aimed to evaluate the predictive value of serum lactate levels. PATIENTS AND METHODS: All patients undergoing ultra-radical surgery for AOC in a large cancer centre over a 34-month period between 2018-2021 were identified via the institution tumour registry. Data were collected retrospectively via electronic care and operating records; biochemistry, radiology, and histopathology databases. RESULTS: In total, 63 patients were identified. Elevated intra-operative serum lactate levels were associated with significantly longer length of ICU post-operative stay. Longer time for hyperlactaemia to normalise following surgery also conferred significantly longer ICU, high dependency and total hospital LOS. Greater blood loss, higher surgical complexity and peritoneal carcinomatosis score, and longer operating time were associated with higher - and persistently elevated - peri-operative lactate levels. CONCLUSION: Serum lactate in the context of ultra-radical surgery for AOC represents an accessible and inexpensive marker with potential to not only reliably predict LOS, but also to serve as a dynamic prompt for early targeted intervention. Early recognition and correction of hyperlactaemia following AOC may reduce ICU LOS limiting both the resource pressure and patient morbidity/mortality sequelae.
  • Overview of health-related quality of life and toxicity of non-small cell lung cancer patients receiving curative-intent radiotherapy in a real-life setting (the REQUITE study).

    Ennis, Dawn
    OBJECTIVES: Radiotherapy-induced toxicity may negatively impact health-related quality of life (HRQoL). This report investigates the impact of curative-intent radiotherapy on HRQoL and toxicity in early stage and locally-advanced non-small cell lung cancer patients treated with radiotherapy or chemo-radiotherapy enrolled in the observational prospective REQUITE study. MATERIALS AND METHODS: HRQoL was assessed using the European Organisation for Research and Treatment of Cancer QLQ-C30 questionnaire up to 2 years post radiotherapy. Eleven toxicities were scored by clinicians using the Common Terminology Criteria for Adverse Events (CTCAE) version 4. Toxicity scores were calculated by subtracting baseline values. Mixed model analyses were applied to determine statistical significance (p ≤ 0.01). Meaningful clinical important differences (MCID) were determined for changes in HRQoL. Analysis was performed on the overall data, different radiotherapy techniques, multimodality treatments and disease stages. RESULTS: Data of 510 patients were analysed. There was no significant change in HRQoL or its domains, except for deterioration in cognitive functioning (p = 0.01). Radiotherapy technique had no significant impact on HRQoL. The addition of chemotherapy was significantly associated with HRQoL over time (p <.001). Overall toxicity did not significantly change over time. Acute toxicities of radiation-dermatitis (p =.003), dysphagia (p =.002) and esophagitis (p <.001) peaked at 3 months and decreased thereafter. Pneumonitis initially deteriorated but improved significantly after 12 months (p =.011). A proportion of patients experienced meaningful clinically important improvements and deteriorations in overall HRQoL and its domains. In some patients, pre-treatment symptoms improved gradually. CONCLUSIONS: While overall HRQoL and toxicity did not change over time, some patients improved, whereas others experienced acute radiotherapy-induced toxicities and deteriorated HRQoL, especially physical and cognitive functioning. Patient characteristics, more so than radiotherapy technique and treatment modality, impact post-radiotherapy toxicity and HRQoL outcomes. This stresses the importance of considering the potential impact of radiotherapy on individuals' HRQoL, symptoms and toxicity in treatment decision-making.
  • Abiraterone acetate and prednisolone with or without enzalutamide for high-risk non-metastatic prostate cancer: a meta-analysis of primary results from two randomised controlled phase 3 trials of the STAMPEDE platform protocol.

    Das, P
    BACKGROUND: Men with high-risk non-metastatic prostate cancer are treated with androgen-deprivation therapy (ADT) for 3 years, often combined with radiotherapy. We analysed new data from two randomised controlled phase 3 trials done in a multiarm, multistage platform protocol to assess the efficacy of adding abiraterone and prednisolone alone or with enzalutamide to ADT in this patient population. METHODS: These open-label, phase 3 trials were done at 113 sites in the UK and Switzerland. Eligible patients (no age restrictions) had high-risk (defined as node positive or, if node negative, having at least two of the following: tumour stage T3 or T4, Gleason sum score of 8-10, and prostate-specific antigen [PSA] concentration ≥40 ng/mL) or relapsing with high-risk features (≤12 months of total ADT with an interval of ≥12 months without treatment and PSA concentration ≥4 ng/mL with a doubling time of <6 months, or a PSA concentration ≥20 ng/mL, or nodal relapse) non-metastatic prostate cancer, and a WHO performance status of 0-2. Local radiotherapy (as per local guidelines, 74 Gy in 37 fractions to the prostate and seminal vesicles or the equivalent using hypofractionated schedules) was mandated for node negative and encouraged for node positive disease. In both trials, patients were randomly assigned (1:1), by use of a computerised algorithm, to ADT alone (control group), which could include surgery and luteinising-hormone-releasing hormone agonists and antagonists, or with oral abiraterone acetate (1000 mg daily) and oral prednisolone (5 mg daily; combination-therapy group). In the second trial]
  • Redefining WILD syndrome: a primary lymphatic dysplasia with congenital multisegmental lymphoedema, cutaneous lymphovascular malformation, CD4 lymphopaenia and warts.

    Keeley, Vaughan (2021-12)
    BACKGROUND: Primary lymphoedema (PL) syndromes are increasingly recognised as presentations of complex genetic disease, with at least 20 identified causative genes. Recognition of clinical patterns is key to diagnosis, research and therapeutics. The defining criteria for one such clinical syndrome, 'WILD syndrome' (Warts, Immunodeficiency, Lymphoedema and anogenital Dysplasia), have previously depended on a single case report. METHODS AND RESULTS: We present 21 patients (including the first described case) with similar clinical and immunological phenotypes. All had PL affecting multiple segments, with systemic involvement (intestinal lymphangiectasia/pleural or pericardial effusions) in 70% (n=14/20). Most (n=20, 95%) had a distinctive cutaneous lymphovascular malformation on the upper anterior chest wall. Some (n=10, 48%) also had hyperpigmented lesions resembling epidermal naevi (but probably lymphatic in origin). Warts were common (n=17, 81%) and often refractory. In contrast to the previous case report, anogenital dysplasia was uncommon-only found in two further cases (total n=3, 14%). Low CD4 counts and CD4:CD8 ratios typified the syndrome (17 of 19, 89%), but monocyte counts were universally normal, unlike GATA2 deficiency. CONCLUSION: WILD syndrome is a previously unrecognised, underdiagnosed generalised PL syndrome. Based on this case series, we redefine WILD as 'Warts, Immunodeficiency, andLymphatic Dysplasia' and suggest specific diagnostic criteria. The essential criterion is congenital multisegmental PL in a 'mosaic' distribution. The major diagnostic features are recurrent warts, cutaneous lymphovascular malformations, systemic involvement (lymphatic dysplasia), genital swelling and CD4 lymphopaenia with normal monocyte counts. The absence of family history suggests a sporadic condition, and the random distribution of swelling
  • Impact of the menstrual cycle on commercial prognostic gene signatures in oestrogen receptor-positive primary breast cancer

    Sibbering, Mark (2021)
    Purpose: Changes occur in the expression of oestrogen-regulated and proliferation-associated genes in oestrogen receptor (ER)-positive breast tumours during the menstrual cycle. We investigated if Oncotype® DX recurrence score (RS), Prosigna® (ROR) and EndoPredict® (EP/EPclin) prognostic tests, which include some of these genes, vary according to the time in the menstrual cycle when they are measured. Methods: Pairs of test scores were derived from 30 ER-positive/human epidermal growth factor receptor-2-negative tumours sampled at two different points of the menstrual cycle. Menstrual cycle windows were prospectively defined as either W1 (days 1-6 and 27-35; low oestrogen and low progesterone) or W2 (days 7-26; high oestrogen and high or low progesterone). Results: The invasion module score of RS was lower (- 10.9%; p = 0.098), whereas the ER (+ 16.6%; p = 0.046) and proliferation (+ 7.3%; p = 0.13) module scores were higher in W2. PGR expression was significantly increased in W2 (+ 81.4%; p = 0.0029). Despite this, mean scores were not significantly different between W1 and W2 for any of the tests and the two measurements showed high correlation (r = 0.72-0.93). However, variability between the two measurements led to tumours being assigned to different risk categories in the following proportion of cases: RS 22.7%, ROR 27.3%, EP 13.6% and EPclin 13.6%. Conclusion: There are significant changes during the menstrual cycle in the expression of some of the genes and gene module scores comprising the RS, ROR and EP/EPclin scores. These did not affect any of the prognostic scores in a systematic fashion, but there was substantial variability in paired measurements.
  • Gastrointestinal Stromal Tumors (GISTs) as Incidental Findings in Gynecological Surgery.

    Phillips, A
    Gastrointestinal stromal tumors (GISTs) are mesenchymal tumors of the gastrointestinal tract that may be diagnosed incidentally as a part of intra-abdominal surgery for other diseases. This is a single center review to document the incidental finding of GIST at surgery for gynecological malignancies during a 10-yr period. Sixteen cases of incidental GISTs were identified in women ranging in age from 39 to 82 yr. GISTs presented as incidental secondary lesions in women undergoing surgery for other indications, typically primary debulking surgery for tubo-ovarian high-grade serous carcinoma. The GIST was located in the stomach wall in 9 cases. Other sites were cecum, omentum, and mesentery. Diagnosis of GIST was supported by immunohistochemistry in all cases and by molecular studies in 3 cases. Seventy-five percent of cases were micro-GISTs, measuring <2 cm in diameter and, where Miettinen and Lasota criteria could be applied, fitted into "no risk," "very low risk" or "low risk" prognostic groups. Seventy-five percent of women for whom survival data was available, showed disease-free survival at follow-up. The 2 women who died had concurrent high stage or high-grade gynecological malignancy at initial diagnosis.
  • The role of the Consultant Radiographer in facilitating rapid access to palliative radiotherapy.

    Fisher, S
    INTRODUCTION: The fast track pathway for palliative radiotherapy was created to facilitate rapid access to radiotherapy for symptom relief and improved quality of life. The fast track pathway has a target of 5 days from the decision to treat to starting treatment. METHODS: This study is a quantitative analysis of all patients referred and treated with palliative radiotherapy between the 1st September 2018 and 30th September 2019. The number of working days overall from referral to treatment and at each stage of the radiotherapy pathway was recorded and evaluated. The electronic referral system was amended to include the treatment priority option of 'fast track' for all patients with the selected treatment intent of 'palliative'. The data was acquired using the electronic referral system reporting tool. RESULTS: Results demonstrate a reduction in average pathway timing from 14 days to 3 days for volume planned patients, and 13 days to 2 days for virtual simulation patients referred into the fast track pathway. The routine priority palliative pathway also demonstrated a decrease in time from decision to treat to treatment, despite this not being an initial objective. CONCLUSION: Reducing pathway time from referral to treatment is achievable through the introduction of a fast track treatment priority pathway. Rapid access to treatment was facilitated through the electronic referral system fast track option, the creation of a separate fast track care path in Aria, the use of fast track alerts in Aria, and reserved planning scan and treatment appointments. IMPLICATIONS FOR PRACTICE: Rapid access to palliative radiotherapy facilitates alleviation of symptoms and improved quality of life. To improve the efficiency of the palliative radiotherapy service, a streamlined pathway and the commitment of the radiotherapy team is required.
  • Audit of uptake and user satisfaction of Attend Anywhere video consultations in Haematology outpatients QHB

    Iqbal, Mariyam; Khan, Irfan; Hambleton, Harry; Aldalaq, Ahmad; Ahmad, Humayun; Razzak, Aurangzeb; Beal, Donna
    Introduction: Telemedicine clinics have historically been unpopular due to a range of clinical barriers. In March 2020 WHO declared COVID-19 as a global pandemic. This was a paradigm shift in the world of clinical medicine and initiated a rapid transition into virtual clinics as a strategy to minimise face to face (FtF) visits and limit viral spread. At Queen's Hospital Burton, Haematology patients are among the most vulnerable given the immunosuppressive effects of their conditions and treatments. Our outpatient work involves assessment of patients receiving chemotherapy which can be associated with fatal complications. It was felt that telephone consultations may be suboptimal for these assessments, and with the unclear duration of the pandemic, there has been an initiative to recruit more patients to video clinics. The Attend Anywhere' (AA) video consultation system was implemented in June. This drastically reduced the need for FtF visits to reduce infection risks. Objective(s): The primary objective of this audit was to evaluate the uptake of AA over time. We also used the data to assess whether particular patient groups were more likely to engage in video consultations. A concurrent survey was organised in order to assess patient satisfaction with AA. Method(s): A quantitative analysis of data from a consultant-led clinic was obtained from June to December 2020. The clinic letters were examined for patient demographics and to assess the type of consultation undertaken. A separate mixed-method survey of 29 patients was conducted as a part of our audit. Result(s): The results revealed a trend towards video consultations over telephone consultations during the period of time analysed, although the volume of patients undertaking telephone consultations remained higher overall. Despite the proportion of AA consultations being higher in the lower age groups, it remained popular in older age groups. The patient survey showed a high rate of patient satisfaction. A lot of the patients considered AA to be an excellent alternative to FtF and cited other significant benefits in saving time, reducing effort and minimising risk. Video consultations also felt more personal than over the phone and patients felt all their concerns were addressed with high standards of patient care. Conclusion(s): The audit showed that AA consultations are popular with patients in all demographics. They are felt to be safer than telephone consultations. As many appointments are still conducted via telephone, there is further work to be done to encourage more patients onto AA. A number of barriers to AA were noted. There were initially difficulties with staff accessing the software. There were a number of cases where patients either had no computer access, or struggled with the software. Improving communication and information booklets helped to overcome this. The older ages may have had higher representation if they had easier access to a computer, or if the software had been more straightforward. It is felt that a dedicated mobile application may provide a more user friendly system for patients. Whilst the added value of physical examination is missing in AA consultations, especially in new clinic patients, this has been a novel solution to challenges the pandemic has brought. It has helped to ensure continuity and safety in patient care.
  • Cellulitis in chronic oedema of the lower leg: an international cross-sectional study

    Keeley, Vaughan (2021-01)
    Background: Cellulitis and chronic oedema are common conditions with considerable morbidity. The number of studies designed to assess the epidemiology of cellulitis in chronic oedema are scarce. Objectives: To investigate the prevalence and risk factors of cellulitis in chronic leg oedema, including lymphoedema. Methods: A cross-sectional study, including 40 sites in nine countries, 2014-2017. Adults with clinically proven unilateral or bilateral chronic oedema (oedema >3 months) of the lower leg were included. The main outcome measures were frequency and risk factors for cellulitis within the last 12 months. Results: Out of 7477 patients, 15⋅78% had cellulitis within the last 12 months, with a life-time prevalence of 37⋅47%. The following risk factors for cellulitis were identified by multivariable analysis: wounds [odds ratio (OR) 2⋅37, 95% confidence interval (CI) 2⋅03-2⋅78], morbid obesity (OR 1⋅51, CI 95% 1⋅27-1⋅80), obesity (OR 1⋅21, CI 95% 1⋅03-1⋅41), midline swelling (OR 1⋅32, CI 95% 1⋅04-1⋅66), male sex (OR 1⋅32, CI 95% 1⋅15-1⋅52) and diabetes (OR 1⋅27, CI 95% 1⋅08-1⋅49). Controlled swelling was associated with a reduced risk (OR 0⋅59, CI 95% 0⋅51-0⋅67). In a subgroup analysis, the risk increased with the stage of oedema [International Society of Lymphology (ISL), stage II OR 2⋅04, CI 95% 1⋅23-3⋅38, and stage III OR 4⋅88, CI 95% 2⋅77-8⋅56]. Conclusions: Cellulitis in chronic leg oedema is a global problem. Several risk factors for cellulitis were identified, of which some are potentially preventable. Our findings suggest that oedema control, is one of these. We also identified that advanced stages of oedema, with hard/fibrotic tissue, might be an important clinical indicator to identify patients at particular risk.
  • Mesothelioma and Radical Surgery 2 (MARS 2): protocol for a multicentre randomised trial comparing (extended) pleurectomy decortication versus no (extended) pleurectomy decortication for patients with malignant pleural mesothelioma.

    Keni, Manjusha (2020-09)
    INTRODUCTION: Mesothelioma remains a lethal cancer. To date, systemic therapy with pemetrexed and a platinum drug remains the only licensed standard of care. As the median survival for patients with mesothelioma is 12.1 months, surgery is an important consideration to improve survival and/or quality of life. Currently, only two surgical trials have been performed which found that neither extensive (extra-pleural pneumonectomy) or limited (partial pleurectomy) surgery improved survival (although there was some evidence of improved quality of life). Therefore, clinicians are now looking to evaluate pleurectomy decortication, the only radical treatment option left. METHODS AND ANALYSIS: The MARS 2 study is a UK multicentre open parallel group randomised controlled trial comparing the effectiveness and cost-effectiveness of surgery-(extended) pleurectomy decortication-versus no surgery for the treatment of pleural mesothelioma. The study will test the hypothesis that surgery and chemotherapy is superior to chemotherapy alone with respect to overall survival. Secondary outcomes include health-related quality of life, progression-free survival, measures of safety (adverse events) and resource use to 2 years. The QuinteT Recruitment Intervention is integrated into the trial to optimise recruitment. ETHICS AND DISSEMINATION: Research ethics approval was granted by London - Camberwell St. Giles Research Ethics Committee (reference 13/LO/1481) on 7 November 2013. We will submit the results for publication in a peer-reviewed journal. TRIAL REGISTRATION NUMBERS: ISRCTN-ISRCTN44351742 and ClinicalTrials.gov-NCT02040272.
  • Carcinoma of Unknown Primary (CUP) in a patient presenting with lower back pain: An Important Clinical Lesson

    Hind, Jamie; Sidhu, Gur Aziz; Powell, Chris; Lacon, Andrew; Ashwood, Neil (2020-09)
    Carcinoma of unknown primary (CUP) is associated with high rates of morbidity and mortality. We report a case of a 33-year-old female, diagnosed with CUP, after presenting with gradual onset worsening lower back pain. Immunohistochemistry, blood tests, further investigations, and Multidisciplinary team meetings failed to identify the primary malignancy. This is not an uncommon pathway for patients with CUP. This report highlights how CUP can affect the quality of life of patients and how management for CUP should be focused on enhancing Quality of Life (QOL). It also addresses the difficulty of identifying which group of patients may benefit from further investigations to identify the primary and thus receive target treatment therapy.
  • A multicentre cross-sectional observational study of cancer multidisciplinary teams: Analysis of team decision making.

    Bali, Anish; Asher, Viren (2020-08)
    BACKGROUND: Multidisciplinary teams (MDT) formulate expert informed treatment recommendations for people with cancer. We set out to examine how the factors proposed by the functional perspective of group decision making (DM), that is, interaction process, internal factors (factors emanating from within the group such as group size), external circumstances (factors coming from the outside of the team), and case-complexity affect the quality of MDT decision making. METHODS: This was a cross-sectional observational study. Three cancer MDTs were recruited with 44 members overall and 30 of their weekly meetings filmed. Validated observational instruments were used to measure quality of DM, interactions, and complexity of 822 case discussions. RESULTS: The full regression model with the variables proposed by the functional perspective was significant, R2 = 0.52, F(20, 801) = 43.47, P < .001, adjusted R2 = 0.51. Positive predictors of DM quality were asking questions (P = .001), providing answers (P = .001), team size (P = .007), gender balance (P = .003), and clinical complexity (P = .001), while negative socioemotional reactions (P = .007), gender imbalance (P = .003), logistical issues (P = .001), time-workload pressures (P = .002), and time spent in the meeting (P = .001) were negative predictors. Second half of the meetings also saw significant decrease in the DM quality (P = .001), interactions (P = .001), group size (P = .003), and clinical complexity (P = .001), and an increase in negative socioemotional reactions (P = .001) and time-workload pressures (P = .001). DISCUSSION: To the best of our knowledge, this is the first study to attempt to assess the factors proposed by the functional perspective in cancer MDTs. One novel finding is the effect of sociocognitive factors on team DM quality, while another is the cognitive-catch 22 effect: while the case discussions are significantly simpler in the second half of the meeting, there is significantly less time left to discuss the remaining cases, further adding to the cognitive taxation in teams who are now rapidly attempting to close their time-workload gap. Implications are discussed in relation to quality and safety.
  • Breast implant-associated anaplastic large cell lymphoma (BIA-ALCL): an overview of presentation and pathogenesis and guidelines for pathological diagnosis and management.

    Deb, Rahul (2019-12)
    AIMS: Breast implant-associated anaplastic large cell lymphoma (BIA-ALCL) is an uncommon complication associated largely with textured implants. It is important that the symptoms associated with BIA-ALCL are recognised and that robust pathways are in place to establish the diagnosis. The aim of this paper is to review what is known of the incidence of the disease, current thoughts on pathogenesis, patterns of presentation and pathological features to provide standard guidelines for its diagnosis. METHODS AND RESULTS: Systematic review of the literature via PubMed covering cases series, modes of presentation, cytological, histological and immunohistochemical features and disease outcome. Since 1997, 518 cases throughout 25 countries have been registered on the American Society of Plastic Surgeons PROFILE registry, with an estimated risk for women with an implant of one to three per million per year. It most frequently presents as a late-onset accumulation of seroma fluid, sometimes as a mass lesion. The neoplastic cells are highly atypical, consistently strongly positive for CD30, with 43-90% also positive for EMA, and all are ALK-negative. Behaviour is best predicted using a staging system for solid tumours. CONCLUSION: BIA-ALCL is a rare but important complication of breast implants. While characterised by CD30-positive neoplastic cells this must be interpreted with care, and we provide pathological guidelines for the robust diagnosis of this lesion as well as the most appropriate staging system and management strategies. Finally, in order to generate more accurate data on incidence, we recommend mechanisms for the routine central reporting of all cases.
  • Prolonged interruption of chemotherapy in patients undergoing delayed debulking surgery for advanced high grade serous ovarian cancer is associated with a worse prognosis.

    Phillips, A (2020-04)
    INTRODUCTION: The current standard of care for advanced high grade serous ovarian cancer (HGSC) comprises a combination of debulking surgery and platinum-based chemotherapy given in the neoadjuvant or adjuvant setting. In the neoadjuvant setting, patients usually undergo 3 cycles of chemotherapy followed by interval cytoreductive surgery (ICS), then 3 further cycles of chemotherapy. However, the optimum timeframe to administer chemotherapy before and after ICS remains unclear. We therefore examine the survival impact of the interval between pre- and post-operative chemotherapy in patients undergoing ICS in a well-established patient cohort. Factors leading to "delays" in recommencing post-operative chemotherapy were also examined. METHODS: The study comprises of a retrospective cohort of 205 cases with FIGO stage III and IV HGSC undergoing ICS. The duration of the interval between pre-operative and post-operative chemotherapy was correlated with progression-free (PFS) and overall survival (OS). Univariate and multivariate analyses were constructed to identify factors associated with survival and prolonged chemotherapy interruption. RESULTS: The median interval between pre-operative and post-operative chemotherapy was 63 days. Multivariate analyses revealed macroscopic residual disease (HR:2.280, 95% CI:1.635-3.177, p ≤ 0.001) and interruption of chemotherapy >10 weeks (HR:1.65, 95%CI:1.201-2.290, p = 0.002) were associated with poorer OS. Existing medical comorbidities and longer hospital stay were independent prognostic factors for prolonging the chemotherapy interruption. CONCLUSION: Our study recommends that interruption to chemotherapy to allow patients to undergo ICS should be ≤10 weeks; otherwise, OS is significantly impacted. Patients with pre-existing medical comorbidities should receive additional support pre- and post-operatively to keep the chemotherapy interruption to a minimum.
  • Update and audit of the St George's classification algorithm of primary lymphatic anomalies: a clinical and molecular approach to diagnosis.

    Keeley, Vaughan; Riches, Katie (2020-05)
    Primary lymphatic anomalies may present in a myriad of ways and are highly heterogenous. Careful consideration of the presentation can lead to an accurate clinical and/or molecular diagnosis which will assist with management. The most common presentation is lymphoedema, swelling resulting from failure of the peripheral lymphatic system. However, there may be internal lymphatic dysfunction, for example, chylous reflux, or lymphatic malformations, including the thorax or abdomen. A number of causal germline or postzygotic gene mutations have been discovered. Some through careful phenotyping and categorisation of the patients based on the St George's classification pathway/algorithm. The St George's classification algorithm is aimed at providing an accurate diagnosis for patients with lymphoedema based on age of onset, areas affected by swelling and associated clinical features. This has enabled the identification of new causative genes. This update brings the classification of primary lymphatic disorders in line with the International Society for the Study of Vascular Anomalies 2018 classification for vascular anomalies. The St George's algorithm considers combined vascular malformations and primary lymphatic anomalies. It divides the types of primary lymphatic anomalies into lymphatic malformations and primary lymphoedema. It further divides the primary lymphoedema into syndromic, generalised lymphatic dysplasia with internal/systemic involvement, congenital-onset lymphoedema and late-onset lymphoedema. An audit and update of the algorithm has revealed where new genes have been discovered and that a molecular diagnosis was possible in 26% of all patients overall and 41% of those tested.
  • Adjuvant chemotherapy in upper tract urothelial carcinoma (the POUT trial): a phase 3, open-label, randomised controlled trial.

    Chakraborti, Prabir (2020-04)
    BACKGROUND: Urothelial carcinomas of the upper urinary tract (UTUCs) are rare, with poorer stage-for-stage prognosis than urothelial carcinomas of the urinary bladder. No international consensus exists on the benefit of adjuvant chemotherapy for patients with UTUCs after nephroureterectomy with curative intent. The POUT (Peri-Operative chemotherapy versus sUrveillance in upper Tract urothelial cancer) trial aimed to assess the efficacy of systemic platinum-based chemotherapy in patients with UTUCs. METHODS: We did a phase 3, open-label, randomised controlled trial at 71 hospitals in the UK. We recruited patients with UTUC after nephroureterectomy staged as either pT2-T4 pN0-N3 M0 or pTany N1-3 M0. We randomly allocated participants centrally (1:1) to either surveillance or four 21-day cycles of chemotherapy, using a minimisation algorithm with a random element. Chemotherapy was either cisplatin (70 mg/m2) or carboplatin (area under the curve [AUC]4•5/AUC5, for glomerular filtration rate <50 mL/min only) administered intravenously on day 1 and gemcitabine (1000 mg/m2) administered intravenously on days 1 and 8; chemotherapy was initiated within 90 days of surgery. Follow-up included standard cystoscopic, radiological, and clinical assessments. The primary endpoint was disease-free survival analysed by intention to treat with a Peto-Haybittle stopping rule for (in)efficacy. The trial is registered with ClinicalTrials.gov, NCT01993979. A preplanned interim analysis met the efficacy criterion for early closure after recruitment of 261 participants. FINDINGS: Between June 19, 2012, and Nov 8, 2017, we enrolled 261 participants from 57 of 71 open study sites. 132 patients were assigned chemotherapy and 129 surveillance. One participant allocated chemotherapy withdrew consent for data use after randomisation and was excluded from analyses. Adjuvant chemotherapy significantly improved disease-free survival (hazard ratio 0•45, 95% CI 0•30-0•68; p=0•0001) at a median follow-up of 30•3 months (IQR 18•0-47•5). 3-year event-free estimates were 71% (95% CI 61-78) and 46% (36-56) for chemotherapy and surveillance, respectively. 55 (44%) of 126 participants who started chemotherapy had acute grade 3 or worse treatment-emergent adverse events, which accorded with frequently reported events for the chemotherapy regimen. Five (4%) of 129 patients managed by surveillance had acute grade 3 or worse emergent adverse events. No treatment-related deaths were reported. INTERPRETATION: Gemcitabine-platinum combination chemotherapy initiated within 90 days after nephroureterectomy significantly improved disease-free survival in patients with locally advanced UTUC. Adjuvant platinum-based chemotherapy should be considered a new standard of care after nephroureterectomy for this patient population. FUNDING: Cancer Research UK.
  • Patient-Reported Outcome Results From the Open-Label, Randomized Phase III Myeloma X Trial Evaluating Salvage Autologous Stem-Cell Transplantation in Relapsed Multiple Myeloma.

    Allotey, D (2019-07)
    PURPOSE: Salvage autologous stem-cell transplantation (sASCT) in patients with multiple myeloma (MM) relapsing after a prior autologous stem-cell transplantation leads to increased remission duration and overall survival. We report a comprehensive study on patient-reported outcomes, including quality of life (QoL) and pain in sASCT. METHODS: Patients were randomly assigned to either sASCT or nontransplantation consolidation (NTC). Pain and QoL were assessed as secondary outcomes using validated QoL instruments (European Organisation for Research and Treatment of Cancer QLQ-C30 and myeloma-specific module, QLQ-MY20; the Brief Pain Inventory [Short Form]; and the Leeds Assessment of Neuropathic Symptoms and Signs [Self-Assessment] scale). RESULTS: A total of 288 patients (> 96%) consented to the QoL substudy. The median follow-up was 52 months. The European Organisation for Research and Treatment of Cancer QLQ-C30 Global health status scores were higher (better) in the NTC group at 100 days after random assignment (P = .0496), but not at later time points. Pain interference was higher (worse) in the sASCT group than in the NTC group at 6 months after random assignment (P = .0267), with patients with sASCT reporting higher scores for Pain interference with daily living for up to 2 years after random assignment. Patients reporting lower concerns about adverse effects of treatment after sASCT had a time to progression advantage. CONCLUSION: Patients with sASCT with relapsed MM demonstrated a comparative reduction in QoL and greater impact of treatment adverse effects lasting for 6 months and up to 2 years for pain, after which patients who had received sASCT reported better outcomes. Patients who experienced lower adverse effects after sASCT had longer time to progression and overall survival, showing the need to improve symptom management peritransplantation. To our knowledge, this study provides the most comprehensive picture of QoL before and after sASCT in patients with relapsed MM.

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