Cancer
Browse by
Recent Submissions
-
Biomarkers associated with survival in patients with platinum-refractory urothelial carcinoma treated with paclitaxelBackground: Taxane- based chemotherapy is widely used in patients with platinum- and immunotherapy refractory, metastatic urothelial carcinoma (mUC). Outcomes are poor and biomarkers associated with outcome are lacking. We aim to identify cancer hallmarks associated with survival in patients receiving paclitaxel. Methods: Whole-transcriptome profiles were generated for a subset of patients enrolled in a randomised phase II study investigating paclitaxel and pazopanib in platinum refractory mUC (PLUTO, EudraCT 2011-001841-34). Estimates of gene expression were calculated and input into the Almac proprietary analysis pipeline and signature scores were calculated using ClaraT V3.0.0. Ten key gene signatures were assessed: Immuno-Oncology, Epithelial to Mesenchymal Transition, Angiogenesis, Proliferation, Cell Death, Genome Instability, Energetics, Inflammation, Immortality and Evading Growth. Hazard ratios were calculated using Cox regression model and Kaplan-Meier methods were used to estimate progression free survival (PFS) and overall survival (OS). Results: 38 and 45 patients treated with paclitaxel or pazopanib were included. Patients with high genome instability expression treated with paclitaxel had significantly improved survival with a HR of 0.29 (95% CI: 0.14-0.61, p=0.001) and HR 0.34 (95% CI: 0.17-0.69, p=0.003) for PFS and OS, respectively. Similarly, patients with high evading growth suppressor expression treated with paclitaxel had improved PFS and OS with a HR of 0.35 (95% CI: 0.19-0.77, p=0.007) and HR 0.46 (95% CI: 0.23-0.91, p=0.026), respectively. No other gene signatures had significant impact on outcome. In both paclitaxel and pazopanib cohorts, angiogenesis activation was associated with worse PFS and OS, and VEGF targeted therapy did not improve outcomes. Conclusion: High Genome-instability and Evading-growth suppressor biologies are associated with improved survival in patients with platinum refractory mUC receiving paclitaxel. These may refine mUC risk stratification and guide treatment decision in the future.
-
Dataset for reporting of the invasive carcinoma of the breast: recommendations from the International Collaboration on Cancer Reporting (ICCR)BACKGROUND AND OBJECTIVES: Current national or regional guidelines for the pathology reporting on invasive breast cancer differ in certain aspects, resulting in divergent reporting practice and a lack of comparability of data. Here we report on a new international dataset for the pathology reporting of resection specimens with invasive cancer of the breast. The dataset was produced under the auspices of the International Collaboration on Cancer Reporting (ICCR), a global alliance of major (inter-)national pathology and cancer organizations. METHODS AND RESULTS: The established ICCR process for dataset development was followed. An international expert panel consisting of breast pathologists, a surgeon, and an oncologist prepared a draft set of core and noncore data items based on a critical review and discussion of current evidence. Commentary was provided for each data item to explain the rationale for selecting it as a core or noncore element, its clinical relevance, and to highlight potential areas of disagreement or lack of evidence, in which case a consensus position was formulated. Following international public consultation, the document was finalized and ratified, and the dataset, which includes a synoptic reporting guide, was published on the ICCR website. CONCLUSIONS: This first international dataset for invasive cancer of the breast is intended to promote high-quality, standardized pathology reporting. Its widespread adoption will improve consistency of reporting, facilitate multidisciplinary communication, and enhance comparability of data, all of which will help to improve the management of invasive breast cancer patients.
-
A systematic review and meta-analysis of diagnostic performance of fluorescein-guided sentinel lymph node biopsy in early breast cancerBACKGROUND: Evaluation of axillary lymph nodes status in cN0 axilla is performed by sentinel lymph node biopsy (SLNB) utilizing a combination of radioactive isotope and blue dye or alternative to isotope like Indocyanine green (ICG). Both are very resource-intensive; which has prompted development of low-cost technique of Fluorescein Sodium (FS)-guided SLNB. This systematic review and meta-analysis evaluate the diagnostic performance of FS-guided SLNB in early breast cancer. OBJECTIVES: The objective was to evaluate the diagnostic performance of FS for sentinel lymph node biopsy. METHODS: Eligibility criteria: Studies where SLNB was performed using FS. INFORMATION SOURCES: PubMed, EMBASE, Cochrane library and online clinical trial registers. Risk of bias: Articles were assessed for risk of bias using the QUADAS-2 tool. SYNTHESIS OF RESULTS: The main summary measures were pooled Sentinel Lymph Node Identification Rate (SLN-IR) and pooled False Negative Rate (FNR) using random-effects model. RESULTS: A total of 45 articles were retrieved by the initial systematic search. 7 out of the 45 studies comprising a total of 332 patients were included in the meta-analysis. The pooled SLN-IR was 93.2% (95% confidence interval [CI], 0.87-0.97; 87% to 97%). Five validation studies were included for pooling the false negative rate and included a total of 211 patients. The pooled FNR was 5.6% (95% confidence interval [CI], 2.9-9.07). CONCLUSION: Fluorescein-guided SLNB is a viable option for detection of lymph node metastases in clinically node negative patients with early breast cancer. It achieves a high pooled Sentinel Lymph Node Identification Rate (SLN-IR) of 93% with a false negative rate of 5.6% for the detection of axillary lymph node metastasis.
-
LymphActiv: A Digital Physical Activity Behavior Intervention for the Treatment of Lymphedema and Lipedema.Background: Lymphedema and lipedema are debilitating conditions with no proven drug or surgical therapy. Effective treatment requires self-management through movement and compression to reduce limb volume and the incidence of cellulitis. The addition of personalized everyday physical activity (PA) could be transformative, increasing the therapy window to include all waking hours per week and enabling an increased dose of PA. Aim: This service evaluation aimed to determine the feasibility of LymphActiv as a treatment option for lymphedema and lipedema patients. Methods: This service evaluation followed an open observational cohort design, including 55 patients who participated in LymphActiv over 24 weeks. Patients wore an objective PA monitor and interacted with their data in an online dashboard, alongside remote mentor support. Primary outcomes were changes to PA, body weight, limb volume and quality of life. Clinical assessments occurred at baseline and after the 24-week program. Noncompleters were used as a quasi-control group for comparison. Results: Thirty-seven patients completed, of which 81% improved PA. On average, completers reduced their right and left lower limb volumes by -1.8% and -2.1%, respectively. Completers also experienced small average weight losses of -1.2 kg. Noncompleters experienced small average increases in each of these outcome measures. Discussion: These results establish the value of LymphActiv, providing benefit to patients who might otherwise have deteriorated. For services, this could lead to substantial cost-savings through reduced admissions, greater patient independence, and less need for community health care input. The next step is to undertake a randomized, controlled trial comparing the intervention with standard care.
-
Regular follow-up with cervical cytology is of questionable value following surgical treatment of microinvasive cervical cancer.OBJECTIVES: To assess the follow-up smears and their outcomes of patients with conservatively managed early-stage cervical cancer as per UK guidelines within our service. To evaluate whether intensive follow-up can detect pre-cancer early compared to the standard 3 yearly follow-up. STUDY DESIGN: Retrospective review. METHODS: All patients treated for early stage (stage 1A1 and 1A2) with cervical cancer from 01/2002 to 01/2020 at University Hospitals of Derby and Burton were included. Patients who had initial hysterectomy were excluded from our analysis. Review conducted using electronic patient records for treatment, histology, and follow-up smears. Number of abnormal follow-up smears and number of recurrent cervical cancers were considered the main outcome measures. RESULTS: 98 cases were identified. 81 (82.65 %) were stage 1A1 and 17 (17.35 %) were stage 1A2. 74 (75.51 %) patients had squamous histology and 24 (24.49 %) had adenocarcinomas. Median follow-up was 11.08 years (4043 days). 510 follow-up smears were performed, of which 33 (6.47 %) were abnormal. 5 of these abnormal smears showed low grade dyskaryosis (0.98 %) and 2 smears showed high grade dyskaryosis (0.39 %). The positive predictive value of follow-up smears to detect pre-cancerous changes was 5.71 %. There were no recurrent cancers detected. CONCLUSIONS: Microinvasive cervical cancer is effectively managed with conservative surgery. There were no recurrent cancers detected in our cohort during follow-up and there were only 2 high grade dyskaryoses detected (n = 2/510, 0.39 %). We therefore believe that reducing the intensity of follow up of these patients should be considered.
-
Regular follow-up with cervical cytology is of questionable value following surgical treatment of microinvasive cervical cancer.OBJECTIVES: To assess the follow-up smears and their outcomes of patients with conservatively managed early-stage cervical cancer as per UK guidelines within our service. To evaluate whether intensive follow-up can detect pre-cancer early compared to the standard 3 yearly follow-up. STUDY DESIGN: Retrospective review. METHODS: All patients treated for early stage (stage 1A1 and 1A2) with cervical cancer from 01/2002 to 01/2020 at University Hospitals of Derby and Burton were included. Patients who had initial hysterectomy were excluded from our analysis. Review conducted using electronic patient records for treatment, histology, and follow-up smears. Number of abnormal follow-up smears and number of recurrent cervical cancers were considered the main outcome measures. RESULTS: 98 cases were identified. 81 (82.65 %) were stage 1A1 and 17 (17.35 %) were stage 1A2. 74 (75.51 %) patients had squamous histology and 24 (24.49 %) had adenocarcinomas. Median follow-up was 11.08 years (4043 days). 510 follow-up smears were performed, of which 33 (6.47 %) were abnormal. 5 of these abnormal smears showed low grade dyskaryosis (0.98 %) and 2 smears showed high grade dyskaryosis (0.39 %). The positive predictive value of follow-up smears to detect pre-cancerous changes was 5.71 %. There were no recurrent cancers detected. CONCLUSIONS: Microinvasive cervical cancer is effectively managed with conservative surgery. There were no recurrent cancers detected in our cohort during follow-up and there were only 2 high grade dyskaryoses detected (n = 2/510, 0.39 %). We therefore believe that reducing the intensity of follow up of these patients should be considered.
-
Patient characteristics, treatment patterns, and outcomes for patients with renal cell carcinoma in England: a retrospective cohort studyBackground and Objective Considering the rapidly evolving treatment landscape of renal cell carcinoma (RCC), recent descriptions of the RCC population in the UK are lacking, as are real-world data on treatment and patient outcomes. To analyse the demographic and clinical characteristics, treatment patterns, and overall survival of patients with RCC using national data sets in England. Patients and Methods This was a retrospective cohort study of patients diagnosed with RCC (all stages) between 2014-2018 using demographic, clinical, cancer registration, and treatment data. Patients were followed until death or study end (31 December 2020). Treatments administered in each line were described to understand treatment sequencing. Kaplan–Meier methods were used for time-to-event analyses. Factors associated with discontinuation and survival were identified using Cox proportional hazard models. Results and Limitations Among 32,577 included patients, the median age at diagnosis was 66 years, 63.4% were male, and 6,786 (20.8%) had metastatic RCC at diagnosis. Tyrosine kinase inhibitor (TKI) monotherapy was the most common treatment class across lines. Over three quarters of patients (78.5% [95% CI 78.0–78.9]) were alive one year after diagnosis (93.2% in the non-metastatic at diagnosis subgroup and 37.1% among patients with metastases at diagnosis). At three years post initial diagnosis, 18.0% patients were alive in the metastatic at diagnosis subgroup. Rapid evolution of the treatment landscape limits the results regarding lines of therapy. Conclusion This large-scale study provides insight on characteristics of patients with RCC, and it highlights the need for better treatment options to improve survival. MicroAbstract: Treatment pathways and survival outcomes were assessed for patients with the most common form of kidney cancer (renal cell carcinoma) in England using national data. In total, 32,577 patients were included. Over three quarters of patients were alive one year after diagnosis (93.2% in the non-metastatic subgroup and 37.1% among patients with metastases at diagnosis).
-
Mammographic surveillance after breast cancer.Early detection of local recurrence has been shown to improve survival. What is unclear is how frequently mammography should be performed, how long surveillance should continue and how the answers to these questions vary with tumour pathology, patients age and surgery type. Many of these questions are not directly answerable from the current literature. While some of these questions will be answered by the Mammo50 study, evidence from local recurrence rates, tumour biology and the lead time of mammography can be used to guide policy. Young age is the strongest predictor of local recurrence and given the short lead time of screening in women under 50, these women require annual mammography. Women over 50 with HER-2 positive and triple negative breast cancer have higher rates of local recurrence after breast conserving surgery (BCS) than women with luminal cancers. Women with HER-2 positive and triple negative breast cancer also have a higher rate of recurrence in years 1-3 post surgery. Annual mammography in year 1-4 would appear justified. Women over 50 with luminal cancers have low rates of local recurrence and no early peak. Recurrence growth will be low due to tumour biology and hormone therapy. Biennial mammography after yr 2 would seem appropriate. Women over 50 following mastectomy have no early peak in contralateral cancers so the frequency should be determined by the lead time of screening. This would suggest 2 yearly mammography for women aged 50-60 while 3 yearly mammography may suffice for women over 60.
-
Consensus on surgical technique for sentinel lymph node dissection in cervical cancer.OBJECTIVE: The purpose of this study was to establish a consensus on the surgical technique for sentinel lymph node (SLN) dissection in cervical cancer. METHODS: A 26 question survey was emailed to international expert gynecological oncology surgeons. A two-step modified Delphi method was used to establish consensus. After a first round of online survey, the questions were amended and a second round, along with semistructured interviews was performed. Consensus was defined using a 70% cut-off for agreement. RESULTS: Twenty-five of 38 (65.8%) experts responded to the first and second rounds of the online survey. Agreement ≥70% was reached for 13 (50.0%) questions in the first round and for 15 (57.7%) in the final round. Consensus agreement identified 15 recommended, three optional, and five not recommended steps. Experts agreed on the following recommended procedures: use of indocyanine green as a tracer; superficial (with or without deep) injection at 3 and 9 o'clock; injection at the margins of uninvolved mucosa avoiding vaginal fornices; grasping the cervix with forceps only in part of the cervix is free of tumor; use of a minimally invasive approach for SLN biopsy in the case of simple trachelectomy/conization; identification of the ureter, obliterated umbilical artery, and external iliac vessels before SLN excision; commencing the dissection at the level of the uterine artery and continuing laterally; and completing dissection in one hemi-pelvis before proceeding to the contralateral side. Consensus was also reached in recommending against injection at 6 and 12 o'clock, and injection directly into the tumor in cases of the tumor completely replacing the cervix; against removal of nodes through port without protective maneuvers; absence of an ultrastaging protocol; and against modifying tracer concentration at the time of re-injection after mapping failure. CONCLUSION: Recommended, optional, and not recommended steps of SLN dissection in cervical cancer have been identified based on consensus among international experts. These represent a surgical guide that may be used by surgeons in clinical trials and for quality assurance in routine practice.
-
LymphActiv: A Digital Physical Activity Behavior Intervention for the Treatment of Lymphedema and Lipedema.Background: Lymphedema and lipedema are debilitating conditions with no proven drug or surgical therapy. Effective treatment requires self-management through movement and compression to reduce limb volume and the incidence of cellulitis. The addition of personalized everyday physical activity (PA) could be transformative, increasing the therapy window to include all waking hours per week and enabling an increased dose of PA. Aim: This service evaluation aimed to determine the feasibility of LymphActiv as a treatment option for lymphedema and lipedema patients. Methods: This service evaluation followed an open observational cohort design, including 55 patients who participated in LymphActiv over 24 weeks. Patients wore an objective PA monitor and interacted with their data in an online dashboard, alongside remote mentor support. Primary outcomes were changes to PA, body weight, limb volume and quality of life. Clinical assessments occurred at baseline and after the 24-week program. Noncompleters were used as a quasi-control group for comparison. Results: Thirty-seven patients completed, of which 81% improved PA. On average, completers reduced their right and left lower limb volumes by -1.8% and -2.1%, respectively. Completers also experienced small average weight losses of -1.2 kg. Noncompleters experienced small average increases in each of these outcome measures. Discussion: These results establish the value of LymphActiv, providing benefit to patients who might otherwise have deteriorated. For services, this could lead to substantial cost-savings through reduced admissions, greater patient independence, and less need for community health care input. The next step is to undertake a randomized, controlled trial comparing the intervention with standard care.
-
Factors influencing older women's decision-making related to treatment of operable breast cancer: A qualitative systematic reviewObjective There is variation in practice in the treatment of older women with breast cancer. International guidelines highlight the importance of patient autonomy in treatment decision-making. The aim of this study is to identify factors which influence decision-making in older women with operable breast cancer, which will enable us to further understand how to support these patients. Methods Systematic review in accordance with the PRISMA guidelines was performed to identify factors which influence treatment decision-making in older women with operable breast cancer. Medline, Web of Science and SCOPUS were searched. Results The search yielded 5840 results; 13 articles met the inclusion criteria and reported on a total of 1118 women. Thematic analysis identified three key themes in which decision-making factors could be categorised. These were healthcare-related factors, patient-related factors and impact of treatment. Healthcare-related factors included communication with clinicians and provision of information. Patient-related factors were age, pre-existing knowledge, preconceptions of breast cancer and treatment, decision-making style and co-morbidities. The impact of treatment considerations included body image and effect on quality of life. Decision-making style was frequently reported; older women did not demonstrate one preferred style. Conclusions The findings have highlighted the complex interplay of factors which influence how older women make breast cancer treatment-decisions. Clinicians should have an awareness of the factors highlighted to maximise their ability to provide support and personalised care to older women with breast cancer whilst treatment decisions are made.
-
The Quality of Life after Lymphaticovenous Anastomosis in 118 Lower Limb Lymphedema Patients.Background This is a prospective study on 118 patients who underwent lymphaticovenous anastomosis (LVA) due to secondary lower limb lymphedema between January 2018 and October 2020 to evaluate patients' quality of life (QOL) using the Quality of Life Measure for Limb Lymphedema (LYMQoL) questionnaire. Methods The outcome measurement included the LYMQoL leg scoring system tool evaluating the function, appearance, symptom, mood, and overall outcome. In addition, correlation analysis was performed for three factors: based on International Society of Lymphology (ISL) stages, disease duration, and amount of volume reduction. Results The LYMQoL tool overall satisfaction score significantly increased at all intervals from 4.4 ± 0.2 preoperative to 6.5 ± 0.3 postoperative at 12 months ( p < 0.001). Significant findings were seen for each domain scores compared preoperatively and at 12 months: function score (18.6 ± 0.5 to 15.4 ± 0.6), appearance score (17.8 ± 0.5 to 16.0 ± 0.6), symptom score (11.8 ± 0.3 to 8.9 ± 0.4), and mood score (14.5 ± 0.4 to 11.4 ± 0.5; p < 0.05). The correlation analysis between improvement of the overall score and the ISL stage ( p = 0.610, correlation coefficient [ r ] = - 0.047), disease duration ( p = 0.659, r = - 0.041), and amount of limb volume reduction ( p = 0.454, r = - 0.070) showed no statistical significance. Conclusion The QOL of secondary lower limb lymphedema patients was significantly improved after LVA regardless of the severity of disease, duration of disease, and amount of volume reduction after LVA. Understanding the patient-reported outcome measurement will help the surgeons to manage and guide the expectations of the patients.
-
Nutritional interventions in prehabilitation for cancer surgery.PURPOSE OF REVIEW: Nutrition remains a key focus in the preoptimization of patients undergoing cancer surgery. Given the catabolic nature of cancer, coupled with the physiological insult of surgery, malnutrition (when assessed) is prevalent in a significant proportion of patients. Therefore, robust research on interventions to attenuate the detrimental impact of this is crucial. RECENT FINDINGS: As a unimodal prehabilitation intervention, assessment for malnutrition is the first step, as universal supplementation has not been shown to have a significant impact on outcomes. However, targeted nutritional therapy, whether that is enteral or parenteral, has been shown to improve the nutritional state of patients' presurgery, potentially reducing the rate of postoperative complications such as nosocomial infections. As part of multimodal prehabilitation, the situation is more nuanced given the difficulty in attribution of effects to the differing components, and vast heterogeneity in intervention and patient profiles. SUMMARY: Multimodal prehabilitation is proven to improve length of hospital stay and postoperative outcomes, with nutrition forming a significant part of the therapy given. Further work is required to look at not only the interplay between the optimization of nutritional status and other prehabilitation interventions, but also how to best select which patients will achieve significant benefit.
-
Comparison of add-on medications for persistent storage symptoms after α-blocker treatment in BPH patients - a network meta-analysis.BACKGROUND: Patients with benign prostatic hyperplasia (BPH) receive α-blockers as first-line therapy to treat lower urinary tract symptoms; however, some individuals still experience residual storage symptoms. Antimuscarinics, β3-agonists, and desmopressin are effective add-on medications. Nevertheless, there is currently no evidence for the appropriate choice of the first add-on medication. This systematic review aimed to investigate the clinical benefits of antimuscarinics, β3-agonists, and desmopressin, in addition to α-blockers, for persistent storage symptoms in BPH patients. METHODS: A comprehensive literature search of randomized controlled trials (RCTs) comparing the efficacy of different add-on medications in BPH patients with persistent storage symptoms despite α-blocker treatment was conducted. Clinical outcomes included the International Prostate Symptom Score (IPSS), IPSS storage subscore, nocturia, micturition, and urgency. A network meta-analysis was performed to estimate the effect size. Surface under cumulative ranking curves (SUCRAs) were used to rank the included treatments for each outcome. RESULTS: A total of 15 RCTs were identified. Add-on imidafenacin and mirabegron resulted in significant improvement in all outcomes assessed. Other add-on medications such as desmopressin, tolterodine, solifenacin, fesoterodine, and propiverine showed positive benefits for most, but not all, outcomes. Based on the SUCRA rankings, add-on desmopressin was the best-ranked treatment for IPSS and nocturia, and add-on imidafenacin was the best for the IPSS storage subscore and micturition. CONCLUSIONS: BPH patients presenting with persistent storage symptoms despite α-blocker administration are recommended to include additional treatment. Desmopressin and imidafenacin may be considered high-priority add-on treatments because of their superior efficacy compared with other medications.
-
A systematic review and meta-analysis of miRNAs for the detection of cervical cancer.Aim: This study aimed to critically appraise the evidence of the diagnostic effectiveness of miRNAs for the detection of cervical cancer. Methods & materials: A systematic review and meta-analysis was performed, searching PubMed, EMBASE and Web of Science. An umbrella meta-analysis of meta-analyses of individual biomarkers was performed. A Grading of Recommendations, Assessment, Development and Evaluations (GRADE) assessment of evidence was also performed. Results: A total of 52 miRNAs were included. Umbrella meta-analysis revealed significant heterogeneity in terms of sensitivity, specificity, receiver operating characteristic (ROC), positive predictive value and/or negative predictive value. Umbrella effects were 0.76 (95% CI: 0.73-0.78), 0.78 (95% CI: 0.75-0.81), 0.77 (95% CI: 0.75-0.80), 0.75 (95% CI: 0.71-0.79) and 0.76 (95% CI: 0.74-0.79), respectively. Conclusion: Moderate quality evidence suggested miR199a-5p, miR21-5p and miR-141a had excellent diagnostic performance. Plain Language Summary: miRNAs are small chemical messengers that play a role in the regulation of protein produced inside the cytoplasm of cells, including cancer cells. In cervical cancer cells, miRNAs become dysregulated – that is, their levels become increased or decreased – and therefore detecting their relative abundance or absence in test samples may enable identification of cervical cancer. This study aimed to systematically collect and appraise the evidence for the diagnostic ability of miRNAs for detection of cervical cancer. A systematic appraisal of the evidence was conducted by searching three research databases (PubMed, EMBASE and Web of Science) to collect evidence published up to 13 November 2022. Results for diagnostic performance of 52 miRNAs were extracted from 20 relevant studies. An assessment of risk of bias for each study was performed using a standardized checklist, which identified one high-quality study, 18 moderate-quality studies and one low-quality study. Results for each individual biomarker were assessed by meta-analytic methods, which generated weighted averages for 38 of 52 miRNAs. All 52 miRNAs were then compared using an umbrella meta-analysis (a weighted average of all miRNA biomarkers), which identified significant differences in diagnostic ability between miRNAs. Sensitivity analyses suggested that these differences were partly explained by differences in grades of cervical cancer and differences in types of sample used for testing. A GRADE assessment of the overall evidence quality suggested that moderate-quality evidence supported further investigation of three miRNA biomarkers (miR-199a-5p, miR-21-5p and miR-141a), which performed excellently (i.e., better than the umbrella weighted average) across five performance parameters, including sensitivity, specificity, receiver operator characteristic, positive predictive value and negative predictive value. In summary, this study suggested miR-199a-5p, miR-21-5p and miR-141a had excellent diagnostic performance for detection of cervical cancer and recommends further investigation of these miRNAs in randomized controlled trials.
-
Diagnostic accuracy of intraoperative margin assessment techniques in surgery for head and neck squamous cell carcinoma: A meta-analysisBACKGROUND: Positive margins following head and neck squamous cell carcinoma (HNSCC) surgery lead to significant morbidity and mortality. Existing Intraoperative Margin Assessment (IMA) techniques are not widely used due to limitations in sampling technique, time constraints and resource requirements. We performed a meta-analysis of the diagnostic performance of existing IMA techniques in HNSCC, providing a benchmark against which emerging techniques may be judged. METHODS: The study was conducted according to Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guidelines. Studies were included if they reported diagnostic metrics of techniques used during HNSCC surgery, compared with permanent histopathology. Screening, manuscript review and data extraction was performed by multiple independent observers. Pooled sensitivity and specificity were estimated using the bivariate random effects model. RESULTS: From an initial 2344 references, 35 studies were included for meta-analysis. Sensitivity (Sens), specificity (Spec), diagnostic odds ratio (DOR) and area under the receiver operating characteristic curve (AUROC) were calculated for each group (n, Sens, Spec, DOR, AUROC): frozen section = 13, 0.798, 0.991, 309.8, 0.976; tumour-targeted fluorescence (TTF) = 5, 0.957, 0.827, 66.4, 0.944; optical techniques = 10, 0.919, 0.855, 58.9, 0.925; touch imprint cytology = 3, 0.925, 0.988, 51.1, 0.919; topical staining = 4, 0.918, 0.759, 16.4, 0.833. CONCLUSIONS: Frozen section and TTF had the best diagnostic performance. Frozen section is limited by sampling error. TTF shows promise but involves administration of a systemic agent. Neither is currently in widespread clinical use. Emerging techniques must demonstrate competitive diagnostic accuracy whilst allowing rapid, reliable, cost-effective results.
-
Abiraterone acetate plus prednisolone with or without enzalutamide for patients with metastatic prostate cancer starting androgen deprivation therapy: final results from two randomised phase 3 trials of the STAMPEDE platform protocolBACKGROUND: Abiraterone acetate plus prednisolone (herein referred to as abiraterone) or enzalutamide added at the start of androgen deprivation therapy improves outcomes for patients with metastatic prostate cancer. Here, we aimed to evaluate long-term outcomes and test whether combining enzalutamide with abiraterone and androgen deprivation therapy improves survival. METHODS: We analysed two open-label, randomised, controlled, phase 3 trials of the STAMPEDE platform protocol, with no overlapping controls, conducted at 117 sites in the UK and Switzerland. Eligible patients (no age restriction) had metastatic, histologically-confirmed prostate adenocarcinoma; a WHO performance status of 0-2; and adequate haematological, renal, and liver function. Patients were randomly assigned (1:1) using a computerised algorithm and a minimisation technique to either standard of care (androgen deprivation therapy; docetaxel 75 mg/m2 intravenously for six cycles with prednisolone 10 mg orally once per day allowed from Dec 17, 2015) or standard of care plus abiraterone acetate 1000 mg and prednisolone 5 mg (in the abiraterone trial) orally or abiraterone acetate and prednisolone plus enzalutamide 160 mg orally once a day (in the abiraterone and enzalutamide trial). Patients were stratified by centre, age, WHO performance status, type of androgen deprivation therapy, use of aspirin or non-steroidal anti-inflammatory drugs, pelvic nodal status, planned radiotherapy, and planned docetaxel use. The primary outcome was overall survival assessed in the intention-to-treat population. Safety was assessed in all patients who started treatment. A fixed-effects meta-analysis of individual patient data was used to compare differences in survival between the two trials. STAMPEDE is registered with ClinicalTrials.gov (NCT00268476) and ISRCTN (ISRCTN78818544). FINDINGS: Between Nov 15, 2011, and Jan 17, 2014, 1003 patients were randomly assigned to standard of care (n=502) or standard of care plus abiraterone (n=501) in the abiraterone trial. Between July 29, 2014, and March 31, 2016, 916 patients were randomly assigned to standard of care (n=454) or standard of care plus abiraterone and enzalutamide (n=462) in the abiraterone and enzalutamide trial. Median follow-up was 96 months (IQR 86-107) in the abiraterone trial and 72 months (61-74) in the abiraterone and enzalutamide trial. In the abiraterone trial, median overall survival was 76·6 months (95% CI 67·8-86·9) in the abiraterone group versus 45·7 months (41·6-52·0) in the standard of care group (hazard ratio [HR] 0·62 [95% CI 0·53-0·73]; p<0·0001). In the abiraterone and enzalutamide trial, median overall survival was 73·1 months (61·9-81·3) in the abiraterone and enzalutamide group versus 51·8 months (45·3-59·0) in the standard of care group (HR 0·65 [0·55-0·77]; p<0·0001). We found no difference in the treatment effect between these two trials (interaction HR 1·05 [0·83-1·32]; pinteraction=0·71) or between-trial heterogeneity (I2 p=0·70). In the first 5 years of treatment, grade 3-5 toxic effects were higher when abiraterone was added to standard of care (271 [54%] of 498 vs 192 [38%] of 502 with standard of care) and the highest toxic effects were seen when abiraterone and enzalutamide were added to standard of care (302 [68%] of 445 vs 204 [45%] of 454 with standard of care). Cardiac causes were the most common cause of death due to adverse events (five [1%] with standard of care plus abiraterone and enzalutamide [two attributed to treatment] and one (<1%) with standard of care in the abiraterone trial). INTERPRETATION: Enzalutamide and abiraterone should not be combined for patients with prostate cancer starting long-term androgen deprivation therapy. Clinically important improvements in survival from addition of abiraterone to androgen deprivation therapy are maintained for longer than 7 years. FUNDING: Cancer Research UK, UK Medical Research Council, Swiss Group for Clinical Cancer Research, Janssen, and Astellas.
-
Email alerts allow more rapid assessment by palliative care service and decrease length of hospital stay for those discharged homeThe Hospital Palliative Care Team (HPCT) at Royal Derby Hospital, part of Derby Teaching Hospitals NHS Foundation Trust, is a team of Medics and Clinical Nurse Specialists who review in-patients with specialist palliative care needs. Our team identified a number of circumstances where patients were readmitted, but not promptly re-referred, to HPCT. Through analysis of our statistics, we found that the average length of time between admission to hospital and referral to HPCT was 8 days. It was felt that earlier HPCT intervention may have facilitated better patient outcomes through more timely assessment and symptom review; and that through early review there was potential to reduce length of stay and improve rates of discharge to a preferred place of care. We therefore introduced an electronic alert (e-alert) system
-
The Prognostic Value of Neutrophil-to-Lymphocyte Ratio and Platelet-to-Lymphocyte Ratio for Small Renal Cell Carcinomas after Image-Guided Cryoablation or Radio-Frequency Ablation.There is a lack of cheap and effective biomarkers for the prediction of renal cancer outcomes post-image-guided ablation. This is a retrospective study of patients with localised small renal cell cancer (T1a or T1b) undergoing cryoablation or radiofrequency ablation (RFA) at our institution from 2003 to 2016. A total of 203 patients were included in the analysis. In the multivariable analysis, patients with raised neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) pre-operatively, post-operatively and peri-operatively are associated with significantly worsened cancer-specific survival, overall survival and metastasis-free survival. Furthermore, an increased PLR pre-operatively is also associated with increased odds of a larger than 25% drop in renal function post-operatively. In conclusion, NLR and PLR are effective prognostic factors in predicting oncological outcomes and peri-operative outcomes; however, larger external datasets should be used to validate the findings prior to clinical application.