Introduction Significant advances in systemic therapy have improved survival for patients with advanced-stage non-small cell lung cancer (NSCLC). However, the present treatment strategies and dose-fractionation for high-dose palliative radiotherapy (RT) are based on trials from the 1990s, when RT planning was simple with less precise delivery. Contemporary lung RT uses 4D-CT, volumetric modulated arc radiotherapy, aided by online verification using cone beam CT, which enables greater accuracy and better target volume coverage, while reducing doses to normal organs at risk. The Shortened High-dose Palliative Radiotherapy for Lung Cancer study aims to evaluate the safety and feasibility of reducing the number of RT fractions and RT duration, using contemporary planning, verification and delivery techniques.Methods and analysis This single-arm, multicentre, phase-II study will test the shortened hypofractionated accelerated palliative RT regimen of 30 Gy in 6 alternate-day fractions, with strict normal tissue dose constraints. We aim to recruit 37 patients across 4 sites within the West Midlands. Quality assurance for the RT is supported by the Radiotherapy Trials Quality Assurance Group (RTTQA). Patients with locally advanced or metastatic NSCLC, who are candidates for high-dose palliative RT, before or after first-line systemic therapy, are eligible for recruitment. The primary objective of this study is to assess the safety of the proposed dose-fractionation. Secondary objectives include evaluating toxicity profiles, patient-reported outcome measures, time to progression, feasibility and the National Health Service cost-saving.Ethics and dissemination This study is conducted in accordance with the International Council for Harmonisation Good Clinical Practice (ICH GCP) guidelines and all applicable regulatory frameworks, including, but not limited to, the UK policy framework for health and social care research, as well as the Health Research Authority and Health and Care Research Wales regulations. Approval for the study was granted on 18 April 2024 (IRAS project ID: 332998; REC reference: 24/WM/0032). The chief investigator is responsible for obtaining informed consent from participants. Any individual delegated this responsibility is thoroughly authorised, trained and competent to conduct the informed consent process. On completion of the trial, the results will be shared with participants in a plain language summary and will be submitted for publication in a peer-reviewed journal. If successful, this study will inform a phase III randomised controlled trial to assess efficacy. For updates on the study, visit the study web page (https://research.mededcoventry.org/About-Us/Meet-The-Team/TMU/Ship-Rt).Trial registration number NCT06483308.

Tamoxifen's pharmacokinetics are strongly influenced by the highly polymorphic CYP2D6, while the influence of other genetic variants has been inconclusive. To further delineate this genotypic-phenotypic impact, we conducted a multi-ancestry genome-wide association study in 636 hormone-receptor-positive (HR+) breast cancer (BC) patients treated with 20 mg tamoxifen daily for ≥8 weeks and validated these genetic determinants in another 869 patients. Association with clinical outcomes was examined in 1326 non-metastatic HR+ patients receiving adjuvant tamoxifen. A genome-wide significant association with Z-endoxifen levels was observed at the CYP2D6 locus on chromosome 22 and its downstream region of TCF20 rs932376 A > G. Both CYP2D6 metabolizer status and TCF20 rs932376 A > G were independent predictors of endoxifen levels in multivariable analysis. CYP2D6 metabolizer status accounted for greater variability of mean endoxifen levels compared to TCF20 rs932376 A > G (91.2% vs 48.8%). These findings were replicated in validation cohorts. Neither TCF20 rs932376 nor CYP2D6 metabolizer status was significantly associated with BC outcomes after adjustment for known prognostic factors. Our study confirmed that CYP2D6 metabolizer status remains as the prime predictor of steady-state Z-endoxifen levels, while TCF20 rs932376 A > G has a smaller, independent effect. Both genetic factors were not associated with BC clinical outcomes.

INTRODUCTION:Total intravenous and inhalational anaesthesia are used widely to maintain general anaesthesia for major non-cardiac surgery, yet their comparative cost-effectiveness remains uncertain. The VITAL trial evaluated clinical outcomes, showing no difference in days alive and at home at 30 days. We conducted an economic evaluation alongside VITAL to determine whether total intravenous anaesthesia offers an economic advantage within the UK NHS. METHODS:A within-trial economic evaluation was conducted from the NHS and personal social services perspective over a 6-month time horizon. Resource use was collected from trial records and questionnaires, and health-related quality of life was measured using EuroQol five-dimension five-level instrument at baseline, discharge, 30 days and 6 months. Costs were evaluated using national sources and quality-adjusted life years were calculated using the area under the curve approach. Incremental cost-effectiveness ratios were estimated using imputed datasets, with uncertainty explored through bootstrapping and the probability of cost-effectiveness illustrated using a cost-effectiveness acceptability curve across a range of willingness-to-pay thresholds. RESULTS:A total of 2507 patients were allocated randomly: 1253 (50%) received total intravenous anaesthesia; and 1254 (50%) inhalational anaesthesia. Mean costs and quality-adjusted life years were similar across groups. Incremental cost was -£145 (95%CI -£1510-£1220) and incremental quality-adjusted life years -0.001 (95%CI -0.008-0.005). Total intravenous anaesthesia showed a 56-57% probability of cost-effectiveness at standard willingness-to-pay thresholds. Sensitivity analyses, including complete-case and societal-perspective models, yielded consistent findings of equivalence. DISCUSSION:Total intravenous and inhalational anaesthesia show comparable cost-effectiveness for adults aged ≥ 50 y undergoing major non-cardiac surgery. Given clinical equipoise and equivalent economic outcomes, anaesthetic choice should continue to be guided by patient factors, clinician expertise and organisational context. Further research may be justified given the large population undergoing major surgery.

BACKGROUND:Patient-facing online triage tools potentially offer GPs a way to recognise cancer-related symptoms and features to facilitate appropriate suspected cancer referrals. Little is known about their impact on cancer diagnostic process and outcomes. AIM:To describe patterns of cancer outcome and process indicators associated with the use of online triage tools in primary care. DESIGN AND SETTING:This cross-sectional study examined the association between publicly reported practice-level data on 3053 English general practices. An online triage tool was used that linked to practice-level data and 31 233 594 triage forms completed using an online triage tool in 2022-2023. METHOD:A cross-sectional analysis (mixed-effects regression) was conducted to evaluate the association between the annual rate of eConsult forms received (weighted to practice registrations) and various cancer diagnosis process and outcome measures. RESULTS:Increased use of online triage forms was associated with higher rates of urgent suspected cancer (USC) referrals and investigations; for example, there was a 7.75% difference in colonoscopy rate (95% confidence interval [CI] = 3.83% to 8.98%) across the 90% mid-range of practices. Despite this, there was no evidence of an association with USC referrals resulting in diagnosis or emergency presentations. CONCLUSION:Greater use of online triage forms is associated with more investigations and referrals for suspected cancer, but not associated with better diagnostic outcomes. This may indicate that any additional referrals are of lower quality and overall there is an increase in inappropriate use of USC referrals. Research is needed to understand how this impacts investigations and referrals for individual patients.

Background:Digital pathology refers to the conversion of histopathology slides to digital image files for examination on computer workstations as opposed to conventional microscopes. Prior to adoption, it is important to demonstrate pathologists provide equivalent reports when using digital pathology in comparison to bright-field and immunofluorescent light microscopy, the current standard of care. Objective:A multicentre comparison of digital pathology with light microscopy for reporting of histopathology slides, measuring variation within and between pathologists on both modalities. Design:A blinded crossover 2000-case study estimating clinical management concordance (identical diagnoses plus differences not affecting patient management). Each sample was assessed twice by four pathologists (once using light microscopy, once using digital pathology, the order randomly assigned and a 6-week gap between viewings). Random-effects logistic regression models, including crossed random-effects terms for case and pathologist, estimated percentage clinical management concordance. Findings were interpreted with reference to 98.3% concordance (Azam AS, Miligy IM, Kimani PKU, Maqbool H, Hewitt K, Rajpoot NM, Snead DRJ. Diagnostic concordance and discordance in digital pathology: a systematic review and meta-analysis. J Clin Pathol 2021;74:448-55. https://doi.org/10.1136/jclinpath-2020-206764). Setting:Sixteen consultant pathologists, four for each specialty, from six National Health Service laboratories. Experience ranged from 3 to 35 years. Some were early adopters of digital pathology, but the majority were new to digital pathology. Interventions:Eight viewings per sample (four pathologists with light microscopy and with digital pathology), culminating in a consensus ground truth, enabling measurement of agreement within and between readers. Samples enrolled reflected routine practice, included cancer screening biopsies, and were enriched for areas of difficulty [e.g. dysplasia (7, 10, 11)]. State-of-the-art digital pathology equipment designed for diagnosis, and holding either Conformité Européene or Food and Drug Administration approval, was used. Main outcome:Intra-pathologist variation between reports issued on digital pathology and light microscopy, inter-pathologist variation against ground-truth diagnosis using light microscopy and digital pathology. Secondary outcomes:Pathologist-recorded reporting times, along with their confidence in diagnosis, analysis of eye-tracking evaluating examination techniques, and a qualitative study examining attitudes of pathologists and laboratory staff to digital pathology adoption. Results:Two thousand and twenty-four cases (608 breast, 607 gastrointestinal, 609 skin, 200 renal) were recruited, with breast and gastrointestinal including screening samples [207 (34%) breast, 250 (41%) gastrointestinal]. Overall, in light microscopy versus digital pathology comparisons, clinical management concordance levels were 99.95% (95% confidence interval 99.91 to 99.97). Similar results were observed within specialties [breast: 99.40% (95% confidence interval 99.06 to 99.62); gastrointestinal 99.96% (95% confidence interval 99.89 to 99.99); skin 99.99% (95% confidence interval 99.92 to 100.0); renal 99.99% (95% confidence interval 99.57 to 100.0)], and within screening cases [98.96% (95% confidence interval 98.42 to 99.32), breast 96.27% (94.63 to 97.43), gastrointestinal 99.93% (95% confidence interval 99.68 to 99.98)]. Reporting time between digital pathology and light microscopy was similar, but pathologists became faster on digital pathology with familiarity. Pathologists recorded high levels of confidence in their diagnosis with light microscopy, significantly higher than digital pathology. Limitations:Cytology cases and specialty groups outside those tested were not examined. The study used two digital pathology scanning systems. Other systems available on the market were not tested. Conclusions:Clinical management concordance levels between the two modalities exceed the reference 98.3% in breast, gastrointestinal, skin and renal specialties, and pooled breast and large bowel cancer screening cases. Subgroup analysis of clinically significant differences revealed a range of differences including areas where interobserver variability is known to be high, which were distributed between reads performed with both platforms and without apparent trends to either. Future work:The use of digital pathology for cytology samples remains an area for further research. Study registration:This study is registered as ISRCTN14513591. Funding:This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: 17/84/07) and is published in full in Health Technology Assessment; Vol. 29, No. 30. See the NIHR Funding and Awards website for further award information.

Residual Cancer Burden (RCB) after neoadjuvant chemotherapy (NAC) is validated to predict event-free survival (EFS) in breast cancer but has not been studied for invasive lobular carcinoma (ILC). We studied patient-level data from a pooled cohort across 12 institutions. Associations between RCB index, class, and EFS were assessed in ILC and non-ILC with mixed effect Cox models and multivariable analyses. Recursive partitioning was used in an exploratory model to stratify prognosis by RCB components. Of 5106 patients, the diagnosis was ILC in 216 and non-ILC in 4890. Increased RCB index was associated with worse EFS in both ILC and non-ILC ( p = 0.002 and p < 0.001, respectively) and remained prognostic when stratified by receptor subtype and adjusted for age, grade, T category, and nodal status. Recursive partitioning demonstrated residual invasive cancer cellularity as most prognostic in ILC. These results underscore the utility of RCB for evaluating NAC response in those with ILC.

Adjuvant trastuzumab in combination with chemotherapy has significantly improved survival in patients with HER2-positive early breast cancer but, since introduction in 2005, the 12 months duration has been questioned and trials have tested shorter durations. A systematic review and meta-analysis using individual patient data (IPD) (when available) from non-inferiority trials of reduced duration trastuzumab was carried out according to PRISMA-IPD guidelines. Primary outcome was invasive disease-free survival (IDFS); secondary outcomes were distant relapse-free survival (DRFS) and overall survival (OS). Estimated survival was calculated using random-effects and fixed-effects modelling, reported by 5 year rates and analysed using non-inferiority methods. Illustrative comparative risks were also tabled as in Cochrane Systematic Reviews. Five trials were identified: PERSEPHONE, PHARE and HORG compared 12 months (m) with 6 m; SOLD and Short-HER compared 12 m with 9 weeks. In the 5-trial analysis (11 389 patients), and in the SOLD and Short-HER (3428 patients) analysis, non-inferiority of the shorter duration was not confirmed. In contrast, for the comparison of 12 m versus 6 m (7961 patients), non-inferiority was confirmed with a 2.5% critical margin, for IDFS, DRFS and OS. The Kaplan-Meier curves demonstrated overlap of credibility intervals throughout follow-up. For every 1000 patients given 6 m trastuzumab, by 5 years, there might be 11 extra IDFS events (in addition to 141 expected for 12 m), 12 more DRFS events (in addition to 106) and nine more deaths (in addition to 73). We have demonstrated that 6 m trastuzumab in early HER2-positive breast cancer is not inferior to 12 m and is an option for patients. CRD42020172267.

Post-operative pulmonary complications (PPCs) are an important source of morbidity and mortality after major abdominal and thoracic surgery. The use of neuromuscular blocking drugs in general anaesthesia is an important risk factor for PPCs. The incomplete reversal of this neuromuscular blockade at the end of surgery leads to residual weakness of respiratory muscles and predisposes to aspiration of pharyngeal contents, hypoventilation, and thus to PPCs such as atelectasis and pneumonia. Two reversal drugs for neuromuscular blocking agents are available: neostigmine and sugammadex. Compared with neostigmine, sugammadex use results in more rapid reversal of neuromuscular blockade, and small clinical efficacy studies have suggested an associated lower incidence of PPCs. The comparative clinical effectiveness of the two drugs in reducing length of hospital stay or mortality is uncertain. Moreover, a potential safety concern with sugammadex is the relatively high incidence of life-threatening allergic reactions in countries where this drug has been widely used over the last decade. SINFONIA is a pragmatic, randomised, open-label, parallel group, superiority trial with an internal pilot which aims to compare the clinical and cost effectiveness of the two available drugs for reversal of neuromuscular blockade, sugammadex and neostigmine, in patients aged 50 years or older undergoing major abdominal or non-cardiac thoracic surgery. The trial will randomise 2500 patients from approximately 40 centres in the UK. The primary outcome will be days alive and out of hospital at 30 days (DAH-30), with key secondary outcomes of PPC incidence, quality of life, and mortality up to 180 days. An embedded observational study will investigate the rate of allergic sensitisation following exposure to sugammadex. The SINFONIA trial addresses an important question for anaesthetists and for patients undergoing major abdominal and thoracic surgery. The choice of reversal agent for neuromuscular blockade between sugammadex and neostigmine is currently largely a matter of anaesthetist preference. A growing body of evidence suggests that sugammadex may reduce the incidence of post-operative pulmonary complications relative to neostigmine. This pragmatic clinical effectiveness trial will provide robust evidence as to the effects of the two drugs on patient-centred outcomes such as DAH-30, as well as on cost effectiveness and the incidence of allergic sensitisation. The trial was registered on the ISRCTN database ( https://www.isrctn.com ) prior to opening to recruitment (registration no 15109717).

Background: Hyperglycaemia after noncardiac surgery occurs commonly and is associated with complications. The choice of maintenance anaesthesia may promote hyperglycaemia and increase glucose variability, both of which exacerbate inflammation and organ dysfunction. We hypothesise that total intravenous anaesthesia reduces glucose variability, particularly in individuals with insulin resistance or diabetes mellitus, and hence may reduce postoperative complications. Methods: This multicentre, randomised controlled parallel group trial will recruit 450 participants ≥50 yr undergoing elective noncardiac surgery. Participants will be randomly allocated in a 1:1 ratio (with minimisation) to receive either total intravenous anaesthesia or inhalation agents (typically sevoflurane) for maintenance of anaesthesia. The primary outcome is blood glucose, measured at prespecified timepoints (before, immediately after, and the morning after surgery). Continuous glucose monitoring (CGM; Dexcom G7) will commence at induction of anaesthesia for up to 10 days after surgery (or hospital discharge) to establish the reliability and accuracy of CGM compared with blood glucose measurements. Secondary outcomes include days alive and out of hospital within 30 days of surgery and postoperative complications (Clavien–Dindo grade ≥2). Absolute glucose and CGM-derived measures of glucose variability will be compared between participants who sustain, or remain free of, myocardial injury within 24 h of surgery, infectious complications within 30 days of surgery, and vasopressor use persisting >4 h after surgery. Conclusions: GlucoVITAL will establish whether the mode of anaesthesia may alter glucose control in susceptible individuals and also explore the role of glucose variability in organ injury after noncardiac surgery using CGM. Clinical trial registration: ISRCTN46862025.

BACKGROUND:Hyperglycaemia after noncardiac surgery is rarely detected outside of the critical care environment, yet occurs commonly and is associated with excess complications including infections and myocardial injury. Systematic, prospectively collected data regarding the accuracy of continuous glucose monitoring commenced immediately before surgery and throughout the early perioperative period are lacking. METHODS:We prospectively enrolled patients aged >50 yr undergoing noncardiac surgery who required at least 24 h of hospital stay. We used real-time continuous glucose monitoring (Dexcom G7 sensor, placed in the upper outer arm) (Dexcom, San Diego, CA, USA) with reference values from arterial blood glucose measurements by amperometry. The primary outcome was the overall mean difference (bias) before surgery, at end of surgery, and 24 h after surgery (Bland-Altman analysis). Secondary outcomes included the mean absolute relative difference and surveillance error grid analyses. RESULTS:We compared paired blood (73% arterial) and continuous glucose monitoring glucose values at each prespecified timepoint in 118 participants (64/118 [54%] female; mean age: 66 [range: 51-89] yr; 25% with diabetes mellitus). The overall bias between continuous glucose monitoring and blood glucose from measurements at each of the three timepoints in the first 24 h after induction of anaesthesia was 0.38 mM (95% confidence interval [95% CI]: 0.23-0.53; n=340 paired readings). Bias decreased from before the start of surgery (1.08 mM [95% CI: 0.87-1.29]; n=116) to 0.15 mM at the end of surgery (95% CI: -0.15 to 0.46; n=113). Mean absolute relative difference ranged from 12.0% to 18.3%. Error grid analyses found that >98% continuous glucose monitoring values were within acceptable risk ranges. CONCLUSIONS:The accuracy of state-of-the-art continuous glucose monitoring is sufficient for perioperative use and could enhance perioperative surveillance of dysglycaemia. CLINICAL TRIAL REGISTRATION:ISRCTN46862025.

At least 5 years of adjuvant endocrine therapy substantially reduces risks of recurrence and mortality in oestrogen-receptor positive early breast cancer. However, adherence to endocrine therapy is sub-optimal; poor adherence is associated with higher risks of recurrence and death from breast cancer, worse cancer-specific health-related quality-of-life, and increased healthcare costs. The SWEET randomised control trial aims to evaluate effectiveness and cost-effectiveness of the HT Me intervention in reducing poor adherence to adjuvant endocrine therapy and improve cancer-specific health-related quality-of-life in women with oestrogen-receptor positive early breast cancer. This is a UK based, pragmatic, open label randomised control trial. Participants (stages 1–3 oestrogen-receptor positive breast cancer, completed surgery, within 14 weeks of first endocrine therapy prescription; n = 1460) complete a baseline questionnaire, and are randomised to the HT Me intervention plus usual care, or usual care alone. The HT Me intervention is evidence-based, theory-informed and patient-centred. It consists of viewing an animation, two consultations with a SWEET study practitioner (a health care professional trained in delivering the intervention) approximately 3 months apart, access to the interactive HT Me web-app for the 18 months, and regular monthly nudges. All participants complete follow-up questionnaires at 6, 12, and 18 months. A multi-method process evaluation will be conducted involving quantitative analysis exploring mechanisms of action of the intervention, and qualitative interviews with a sample of participants and health care professionals involved in the trial. Primary endpoints are adjuvant endocrine therapy adherence (combined self-report (Medication Adherence Report Scale) and Proportion of Days Covered calculated from prescription encashment records) and cancer-specific health-related quality-of-life (Functional Assessment of Cancer Therapy Scale- General). Secondary endpoints are adjuvant endocrine therapy-specific health-related quality-of-life and within-trial cost-utility analysis which will evaluate cost-effectiveness. The SWEET trial seeks to address a significant issue affecting the growing population of breast cancer survivors: poor adherence to adjuvant endocrine therapy. Challenges addressed and resolved within the protocol include the following: capacity at sites to deliver the intervention; variations in breast cancer services nationally; and measuring adherence. This trial has potential to improve quality of life and adherence to endocrine therapy; reducing numbers of recurrences and breast cancer deaths, benefiting women, their families and the health service. ISRCTN Number: ISRCTN24852890 registered on 02.08.2023.

BackgroundImproving outcomes after surgery is a major public health research priority for patients, clinicians and the NHS. The greatest burden of perioperative complications, mortality and healthcare costs lies amongst the population of patients aged over 50 years who undergo major non-cardiac surgery. The Volatile vs Total Intravenous Anaesthesia for major non-cardiac surgery (VITAL) trial specifically examines the effect of anaesthetic technique on key patient outcomes: quality of recovery after surgery (quality of recovery after anaesthesia, patient satisfaction and major post-operative complications), survival and patient safety.MethodsA multi-centre pragmatic efficient randomised trial with health economic evaluation comparing total intravenous anaesthesia with volatile-based anaesthesia in adults (aged 50 and over) undergoing elective major non-cardiac surgery under general anaesthesia.DiscussionGiven the very large number of patients exposed to general anaesthesia every year, even small differences in outcome between the two techniques could result in substantial excess harm. Results from the VITAL trial will ensure patients can benefit from the very safest anaesthesia care, promoting an early return home, reducing healthcare costs and maximising the health benefits of surgical treatments.Trial registrationISRCTN62903453. September 09, 2021.

Aims To conduct a definitive multicentre comparison of digital pathology (DP) with light microscopy (LM) for reporting histopathology slides including breast and bowel cancer screening samples. Methods A total of 2024 cases (608 breast, 607 GI, 609 skin, 200 renal) were studied, including 207 breast and 250 bowel cancer screening samples. Cases were examined by four pathologists (16 study pathologists across the four speciality groups), using both LM and DP, with the order randomly assigned and 6 weeks between viewings. Reports were compared for clinical management concordance (CMC), meaning identical diagnoses plus differences which do not affect patient management. Percentage CMCs were computed using logistic regression models with crossed random‐effects terms for case and pathologist. The obtained percentage CMCs were referenced to 98.3% calculated from previous studies. Results For all cases LM versus DP comparisons showed the CMC rates were 99.95% [95% confidence interval (CI) = 99.90–99.97] and 98.96 (95% CI = 98.42–99.32) for cancer screening samples. In speciality groups CMC for LM versus DP showed: breast 99.40% (99.06–99.62) overall and 96.27% (94.63–97.43) for cancer screening samples; [gastrointestinal (GI) = 99.96% (99.89–99.99)] overall and 99.93% (99.68–99.98) for bowel cancer screening samples; skin 99.99% (99.92–100.0); renal 99.99% (99.57–100.0). Analysis of clinically significant differences revealed discrepancies in areas where interobserver variability is known to be high, in reads performed with both modalities and without apparent trends to either. Conclusions Comparing LM and DP CMC, overall rates exceed the reference 98.3%, providing compelling evidence that pathologists provide equivalent results for both routine and cancer screening samples irrespective of the modality used.

Histopathology is a challenging interpretive discipline, and the level of confidence a pathologist has in their diagnosis is known to vary, which is conveyed descriptively in pathology reports. There has been little study to accurately quantify pathologists’ diagnostic confidence or the factors that influence it. In this study involving sixteen pathologists from six NHS trusts, we assessed diagnostic confidence across multiple variables and four specialties. Each case was reported by four pathologists, with each pathologist reporting each case twice (on light microscopy (LM) and digital pathology (DP)). For each diagnosis, pathologists recorded their confidence on a 7-point Likert scale. This provided 16,187 diagnoses and associated confidence scores for analysis. All variables investigated were found to be significantly predictive of diagnostic confidence, except level of pathologist experience. Confidence was lower for difficult to report cases, cases where there was inter- and intra-pathologist variation in the diagnosis, and cases where the pathologist made an incorrect diagnosis. Confidence was higher, although nominally, for LM diagnoses than DP (rate ratio 1.09 (95

PDF file - 237KB, Supplementary Table 1: Published Studies of Putative Functional SNPs Supplementary Table 2a: Drug Regimens and Doses of Taxanes by Study Supplementary Table 2b: Comparison of Toxicity grades/rates by recruiting trial in PGSNPS included in Taxane Related Sensory Neuropathy Study Supplementary Table 3: PGSNPS Taxane Treated Patient Characteristics Supplementary Table 4: All Putative Functional SNPs Replicated in the PGSNPS dataset (phenotype: cumulative dose to TRSN) Supplementary Table 5: All Putative Functional SNPs Replicated in the PGSNPS dataset (phenotype: maximum TRSN) Supplementary Figure 1: Percentage of Patients with TRSN ≥ grade 2 by genotype, for three statistically significant SNPs that were genotyped in PGSNPS (maximum TRSN) Supplementary Figures 2a-c: Kaplan-Meier curves Kaplan-Meier curves: Shows for each SNP, by genotype, the probability of TRSN grade 0-1 (i.e., the probability of not experiencing moderate/severe TRSN) as the cumulative dose increases.