Defining a role for systemic chemotherapy in local and advanced appendix adenocarcinoma.

BACKGROUND: Appendix adenocarcinomas (AAs) are rare tumours that often present late, with a propensity for peritoneal metastases (PMs). This study aimed to evaluate outcomes of AA patients undergoing cytoreductive surgery (CRS) with curative intent and determine the role of systemic chemotherapy. MATERIALS AND METHODS: Data were collected from a prospective database and classified according to World Health Organization (WHO) 2019 classification. Tumour clearance from CRS was described using a completeness of cytoreduction (CC) score ranging from 0 [no residual disease (RD)] to 3 (>2.5 cm RD). Patients with CC0-2 CRS received hyperthermic intraperitoneal chemotherapy (HIPEC). Systemic chemotherapy was categorised as 'prior' (>6 months before), 'neoadjuvant' (<6 months before), 'adjuvant' (<6 months after CC0-1 CRS) or 'palliative' (after CC2-3 CRS). Analyses used Kaplan-Meier and Cox regression methods. RESULTS: Between January 2005 and August 2021, 216 AA patients were identified for inclusion. Median age was 59 years (21-81 years). CRS/HIPEC was carried out in 182 (84%) patients, of whom 164/182 (76%) had mitomycin C HIPEC. CC0-1 was achieved in 172 (80%) patients. Systemic chemotherapy was given to 97 (45%) patients from the whole cohort and to 37/46 (80%) patients with positive nodes. Median overall survival (OS) was 122 months (95% confidence interval 61-182 months). After multivariate analysis, patients with acellular and lower-grade PM had similar OS to those with localised (M0) disease (P = 0.59 and P = 0.19). For patients with positive nodes, systemic chemotherapy was associated with reduced risk of death compared to no chemotherapy (P < 0.0019). CONCLUSION: This study identifies AA patients with positive lymph nodes derive the most benefit from systemic chemotherapy. We confirm the prognostic importance of stage and peritoneal grade, with excellent outcomes in patients with acellular mucin and lower-grade PM.

Nab-paclitaxel weekly versus dose-dense solvent-based paclitaxel followed by dose-dense epirubicin plus cyclophosphamide in high-risk HR+/HER2- early breast cancer: results from the neoadjuvant part of the WSG-ADAPT-HR+/HER2- trial.

BACKGROUND: In high-risk hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2-) early breast cancer (EBC), nanoparticle albumin-bound (nab)-paclitaxel showed promising efficacy versus solvent-based (sb)-paclitaxel in neoadjuvant trials; however, optimal patient and therapy selection remains a topic of ongoing research. Here, we investigate the potential of Oncotype DX® recurrence score (RS) and endocrine therapy (ET) response (low post-endocrine Ki67) for therapy selection. PATIENTS AND METHODS: Within the WSG-ADAPT trial (NCT01779206), high-risk HR+/HER2- EBC patients were randomized to (neo)adjuvant 4× sb-paclitaxel 175 mg/m2 q2w or 8× nab-paclitaxel 125 mg/m2 q1w, followed by 4× epirubicin + cyclophosphamide (90 mg + 600 mg) q2w; inclusion criteria: (i) cN0-1, RS 12-25, and post-ET Ki67 >10%; (ii) cN0-1 with RS >25. Patients with cN2-3 or (G3, baseline Ki67 ≥40%, and tumor size >1 cm) were allowed to be included without RS and/or ET response testing. Associations of key factors with pathological complete response (pCR) (primary) and survival (secondary) endpoints were analyzed using statistical mediation and moderation models. RESULTS: Eight hundred and sixty-four patients received neoadjuvant nab-paclitaxel (n= 437) or sb-paclitaxel (n = 427); nab-paclitaxel was superior for pCR (20.8% versus 12.9%, P = 0.002). pCR was higher for RS >25 versus RS ≤25 (16.0% versus 8.4%, P = 0.021) and for ET non-response versus ET response (15.1% versus 6.0%, P = 0.027); no factors were predictive for the relative efficacy of nab-paclitaxel versus sb-paclitaxel. Patients with pCR had longer distant disease-free survival [dDFS; hazard ratio 0.42, 95% confidence interval (CI) 0.20-0.91, P = 0.024]. Despite favorable prognostic association of RS >25 versus RS ≤25 with pCR (odds ratio 3.11, 95% CI 1.71-5.63, P ≤ 0.001), higher RS was unfavorably associated with dDFS (hazard ratio 1.03, 95% CI 1.01-1.05, P = 0.010). CONCLUSIONS: In high-risk HR+/HER2- EBC, neoadjuvant nab-paclitaxel q1w appears superior to sb-paclitaxel q2w regarding pCR. Combining RS and ET response assessment appears to select patients with highest pCR rates. The disadvantage of higher RS for dDFS is reduced in patients with pCR. These are the first results from a large neoadjuvant randomized trial supporting the use of RS to help select patients for neoadjuvant chemotherapy in high-risk HR+/HER2- EBC.

Use of drug-induced sleep endoscopy in Germany-an analysis based on claims data.

Background: Drug-induced sleep endoscopy (DISE) has recently gained relevance as a diagnostic tool for obstructive sleep apnea (OSA). However, it is unclear to what extent and in which patient cohorts DISE is used in Germany. With introduction of specific coding for this method in 2021 (Operationen- und Prozedurenschluessel, OPS code), usage can now be analyzed based on diagnosis-related groups (DRG) claims data. Methods: Aggregated data from all inpatient DISE procedures conducted in German hospitals in 2021 were obtained from the publicly available Institut fuer das Entgeltsystem im Krankenhaus (InEK) database. Patient-relevant information as well as data on hospitals providing the examinations were exported and analyzed. Results: Between January and December 2021, a total of 2765 DISE procedures were conducted and documented using the newly introduced specific code (1-611.01). Most patients were male (75.6%), in the age categories 30-39 (15.2%) and 40-49 years (17.2%), and presented with the lowest patient clinical complexity level (PCCL; class 0 = 81.88%). Pediatric use was rare (1.8%). Leading main diagnoses of patients were G47.31 (OSA) and J34.2 (deviation of nasal septum). The most common procedures conducted together with DISE were nasal surgery, and the examination was mostly provided in large public hospitals with more than 800 beds. Conclusion: Though the OSA prevalence in Germany is high, use of DISE as a diagnostic tool is low and represented only 4.4% of cases with a main diagnosis of OSA in 2021. Since specific coding was only introduced in January 2021, trends cannot yet be identified. Noticeable is the frequent combination of DISE with nasal surgery, which is not obviously related to a diagnosis of OSA. Limitations of the study are mainly related to the underlying data, which are available for the inpatient sector only, and due to potentially limited use of the OPS code, which was introduced recently and might not be known to all hospitals.

Severity of Dementia and Survival in Patients Diagnosed with Colorectal Cancer: A National Cohort Study in England and Wales.

AIMS: There is little evidence about the survival of patients with colorectal cancer (CRC) also diagnosed with dementia. We quantified dementia severity and estimated how it is associated with 2-year overall survival. MATERIALS AND METHODS: Records of patients aged 65 years or older diagnosed with CRC in England and Wales were identified. A novel proxy for dementia severity combined dementia diagnosis in administrative hospital data with Eastern Cooperative Oncology Group performance status. Cox regression was used to estimate hazard ratios with and without risk adjustment. RESULTS: In total, 4033 of 105 250 CRC patients (3.8%) had dementia recorded. Two-year survival decreased with increasing dementia severity from 65.4% without dementia, 53.5% with mild dementia, 33.0% with moderate dementia to 16.5% with severe dementia (hazard ratio comparing severe with no dementia: 2.97; 95% confidence interval 2.79, 3.16). Risk adjustment for comorbidity and cancer stage reduced this association slightly (hazard ratio 2.52; 95% confidence interval 2.37, 2.68) and additional adjustment for treatment factors reduced it further (hazard ratio 1.60; 95% confidence interval 1.50, 1.70). CONCLUSIONS: Survival of CRC patients varied strongly according to dementia severity, suggesting that a 'one-size-fits-all' policy for the care of CRC patients with dementia is not appropriate. Comprehensive assessment of cancer patients with dementia that considers dementia severity is essential in a shared decision-making process that ensures patients receive the most appropriate treatment for their individual needs and preferences.

FOxTROT2: innovative trial design to evaluate the role of neoadjuvant chemotherapy for treating locally advanced colon cancer in older adults or those with frailty.

Treating older adults with cancer is increasingly important in modern oncology practice. However, we currently lack the high-quality evidence needed to guide optimal management of this heterogeneous group. Principally, historic under-recruitment of older adults to clinical trials limits our understanding of how existing evidence can be applied to this group. Such uncertainty is particularly prevalent in the management of colon cancer (CC). With CC being most common in older adults, many patients also suffer from frailty, which is recognised as being strongly associated with poor clinical outcomes. Conducting clinical trials in older adults presents several major challenges, many of which impact the clinical relevance of results to a real-world population. When considering this heterogeneous group, it may be difficult to define the target population, recruit participants effectively, choose an appropriate trial design, and ensure participants remain engaged with the trial during follow-up. Furthermore, after overcoming these challenges, clinical trials tend to enrol highly selected patient cohorts that comprise only the fittest older patients, which are not representative of the wider population. FOxTROT1 was the first phase III randomised controlled trial to illustrate the benefit of neoadjuvant chemotherapy (NAC) in the treatment of CC. Patients receiving NAC had greater 2-year disease-free survival compared to those proceeding straight to surgery. Outcomes for older adults in FOxTROT1 were similarly impressive when compared to their younger counterparts. Yet, this group inevitably represents a fitter subgroup of the older patient population. FOxTROT2 has been designed to investigate NAC in a full range of older adults with CC, including those with frailty. In this review, we describe the key challenges to conducting a robust clinical trial in this heterogeneous patient group, highlight our strategies for overcoming these challenges in FOxTROT2, and explain how we hope to provide clarity on the optimal treatment of CC in older adults.

Neoadjuvant durvalumab improves survival in early triple-negative breast cancer independent of pathological complete response.

BACKGROUND: Addition of immune checkpoint inhibitors to neoadjuvant chemotherapy (NACT) is a promising strategy in early breast cancer, but the optimal duration of therapy is currently unknown. In the GeparNuevo (NCT02685059) trial, addition of durvalumab to NACT as previously reported led to a moderate increase in pathological complete response (pCR) rate by an absolute 9% (P = 0.287). PATIENTS AND METHODS: Patients with cT1b-cT4a-d triple-negative breast cancer (TNBC) received durvalumab 1.5 g or placebo every 4 weeks added to nab-paclitaxel 125 mg/m2 weekly for 12 weeks, followed by durvalumab/placebo every 4 weeks plus epirubicin/cyclophosphamide every 2 weeks followed by surgery. Durvalumab was not continued after surgery. The primary objective was pCR. Secondary endpoints included invasive disease-free survival (iDFS), distant disease-free survival (DDFS) and overall survival (OS). RESULTS: A total of 174 patients were randomised between June 2016 and October 2017. After a median follow-up of 43.7 months, 34 events had occurred. Despite a non-significant increase in the pCR rate, significant differences were observed for 3-year iDFS, DDFS and OS: iDFS was 85.6% with durvalumab versus 77.2% with placebo [hazard ratio (HR) 0.48, 95% confidence interval (CI) 0.24-0.97, stratified log-rank P = 0.036]; DDFS 91.7% versus 78.4% (HR 0.31, 95% CI 0.13-0.74, P = 0.005); OS 95.2% versus 83.5% (HR 0.24, 95% CI 0.08-0.72, P = 0.006). pCR patients had 3-year iDFS of 95.5% with durvalumab and 86.1% without (HR 0.22, 95% CI 0.05-1.06). In the non-pCR cohort 3-year iDFS was 76.3% versus 69.7% (HR 0.67, 95% CI 0.29-1.54). Multivariable analysis confirmed a durvalumab effect independent of the pCR effect. No new safety signals occurred. CONCLUSIONS: Durvalumab added to NACT in TNBC significantly improved survival despite a modest pCR increase and no adjuvant component of durvalumab. Additional studies are needed to clarify the optimal duration and sequence of checkpoint inhibitors in the treatment of early TNBC.

First dorsal interosseous muscle transfer to restore opposition of the new thumb after index pollicization: anatomical description of an original technique and case report.

Index pollicization in severe thumb hypoplasia or aplasia in children or for the reconstruction of a mutilated thumb in adults is a rare and technically demanding procedure. Weakness of the new thumb is routinely reported after index pollicization. An inappropriate position of the first dorsal interosseous muscle (FDIM) can partly explain this strength deficit. Here, we report an original anatomical study on FDIM transfer for reanimation of the new thumb's opposition function and its clinical application. An anatomical study was carried out on three upper limbs from fresh, non-embalmed adult cadavers. We demonstrated the feasibility of an FDIM transfer pedicled on the proper FDIM artery and the deep branch of the ulnar nerve. The proximal FDIM insertions were sutured to the lateral border of the flexor retinaculum to recreate the superficial thenar musculature. This procedure was performed on a 52-year-old man who was referred to us with swelling on his hand. We discovered a myxoid inflammatory fibroblastic sarcoma of the thumb that required proximal thumb amputation while preserving the base of the first metacarpal. To our knowledge, this is the first description of FDIM pedicled flap transfer during an index pollicization procedure among an adult population. However, in severe thumb hypoplasia or aplasia cases, this procedure is limited by the size and anatomical variations of the neurovascular structures among a population affected by radial longitudinal deficiency.

Outcome of breast cancer patients with low hormone receptor positivity: analysis of a 15-year population-based cohort.

BACKGROUND: Guideline recommendations for the treatment of breast cancer with low hormone receptor (HR) expression (1%-9%) are ambiguous and several studies showed more similarities with HR-negative tumors than with HR strongly positive tumors (≥10%). We used a population-based 15-year cohort to compare patient characteristics and outcome of HR low positive tumors with HR-negative and HR strongly positive tumors, respectively. PATIENTS AND METHODS: A total of 38  560 women diagnosed with early invasive breast cancer between 2004 and 2018 within the scope of the Munich Cancer Registry with 4.9 million inhabitants were included. Descriptive analyses of prognostic factors, treatment, and outcome analyses using the Kaplan-Meier method; cumulative incidence in consideration of competing risks; and multivariate analyses (Cox regression and Fine-Gray model) were conducted. Endpoints were time to local recurrence (TTLR), time to lymph node recurrence (TTLNR), time to metastasis (TTM), overall survival (OS), and relative survival (RS). RESULTS: A total of 861 patients (2%) had HR low positive, 4862 (13%) HR-negative, and 32  837 (85%) HR strongly positive tumors. Within the HER2-negative cohort (n = 33  366), survival of HR low positive tumors was significantly worse than that of HR strongly positive tumors [OS hazard ratio 0.66 (95% confidence interval 0.55-0.78)], whereas between HR low positive and HR-negative tumors no significant survival difference could be detected [OS hazard ratio 0.93 (95% confidence interval 0.78-1.11)]. TTLR, TTLNR, and TTM showed similar results. By contrast, within the HER2-positive cohort (n = 5194), no statistically significant differences between the three HR groups could be detected in multivariate analyses. CONCLUSION: Current definitions for HR positivity and its clinical relevance should be reconsidered. Patients with HR low positive/HER2-negative tumors could be regarded and treated similar to patients with triple-negative tumors.

Congruence and trajectories of device-measured and self-reported physical activity during therapy for early breast cancer.

PURPOSE: This study examines congruence between self-reported and device-measured physical activity data in women with early breast cancer and compares trajectories under different treatments. METHODS: Women with non-metastatic breast cancer were recruited before primary therapy. In four weeks distributed over six months after treatment start, patients reported time spent on work, transport, chores and sports via diary and wore Garmin® vivofit 3 accelerometers to assess steps taken. Associations between these measures and agreement regarding guideline adherence were tested with Spearman's Correlation Coefficient and Weighted Kappa statistic. Effects of time and treatment were evaluated using mixed analyses of variance. RESULTS: Ninety-nine participants (median age = 50) were treated with adjuvant (N = 23), neoadjuvant (N = 21) or without chemotherapy (N = 55). Coherence between self-report and device data was strong (r = 0.566). Agreement about reaching recommendations was only "fair" (kappa coefficient = 0.321 and 0.249, resp.). Neither treatment or week nor their interaction had effects on step counts (all p > 0.05). Self-reported activity time was lower for patients with chemotherapy than for those without (adjuvant: ∆ = 69min, p = 0.006, neoadjuvant: ∆ = 45min, p = 0.038) and lower in week 18 than in week 3 (∆ = 43min, p = 0.010). CONCLUSION: Results show that consumer-grade activity monitors and self-reports correlate but show different perspectives on physical activity in breast cancer patients. In general, patients perceive some decline regardless of primary treatment regimen. Those affected should be offered assistance to gain the benefits of activity. Accelerometers may help professionals to identify these individuals and patients to verify appraisal of their activity levels.

Concordance of the molecular subtype classification between core needle biopsy and surgical specimen in primary breast cancer.

BACKGROUND: Molecular profiling of breast cancer (BC) classifies several intrinsic subtypes based on different patterns of gene expression. Multigene assays estimate the risk of recurrence and help to select high-risk patients for adjuvant chemotherapy. However, these tests are associated with significant costs. Immunohistochemistry (IHC) offers a surrogate classification for molecular subtypes by determining estrogen (ER) and progesterone receptors (PR), human epidermal growth factor (Her2neu), as well as the proliferation marker Ki67. Core needle biopsy (CNB) is well established in BC diagnosis and allows a pre-operative assessment of biomarkers. The aim of this study was to analyze the concordance of these markers between CNB and surgical specimens to assess whether re-testing of the surgical specimen is mandatory. MATERIALS AND METHODS: Within a 3-year period, patients with primary BC and paired samples of CNB and surgical specimens were analyzed retrospectively. Concordance rates of ER, PR, Her2neu, Ki67, and the surrogate classification for molecular subtypes were calculated using the Landis and Koch agreement grades. RESULTS: Out of 2254 patients with primary breast cancer, 1307 paired specimens without pre-operative treatment were available for analysis Concordance rates for ER, PR, Her2neu, and Ki67 status showed substantial-to-almost perfect agreement grades (κ = 0.91, 0.75, 0.89, and 0.61, respectively). Though substantial concordance was also found for the subtype classification (κ = 0.70), the molecular subtype changed in 18.5% of patients based on the testing of the surgical specimen, mainly from luminal A-like to luminal B-like. CONCLUSIONS: Though the concordance rates for single markers were convincing, a significant proportion of the molecular subtypes differed between CNB and the surgical specimen. Re-testing of PR and Ki67 is mandatory to ensure optimal treatment decisions. Further research is necessary to define safe, efficient, and cost-effective predictive models in adjuvant breast cancer therapy.

[Results of the Dry Eye Research Grant Award 2016]. / Ergebnisse der Sicca-Forschungsförderung 2016.

The Sicca-Förderpreis (Dry Eye Award) supports the development of scientific research on the pathogenesis, diagnostics, and treatment of dry eye and ocular surface diseases. It is awarded after a limited call for proposals in German-speaking countries, written application and selection of the award winner after evaluation by a jury of ophthalmologists working in basic and clinical science. In this article examples of the results of funded projects of the Sicca-Förderpreis 2016 are cursorily described, which were presented at the Ophthalmological Academy of Germany 2019 (Augenärztliche Akademie Deutschland 2019) and therefore provide an insight into current scientific developments. The role of muscarinic receptors and those of urea in the pathogenesis of dry eye as well as the (missing) correlation of tear film stability, viscosity and surface tension are highlighted. A project on the early detection of ocular involvement in graft versus host disease and the idea of treating meibomian gland dysfunction with eyelid surgery techniques are also groundbreaking. The outlined projects represent the potential for further substantial developments in the understanding, diagnostics and treatment of dry eye; however, their long-term clinical relevance still needs to be established.

Sentinel lymph node mapping with indocyanine green compared to blue dye tracer in gynecologic malignancies-A single center experience of 218 patients.

BACKGROUND AND OBJECTIVES: To compare the detection rates of sentinel lymph nodes after converting the tracer technique from blue dye to indocyanine green (ICG). METHODS: Patients with uterine or cervical cancer were enrolled for sentinel lymph node (SLN) dissection. A total of 109 consecutive patients were analyzed and compared to a historical cohort of 109 consecutive patients with the sentinel blue dye technique. SLNs were analyzed by ultrastaging. RESULTS: The bilateral mapping rate of sentinel nodes was significantly higher with the ICG (78%; n = 85) compared to the blue dye tracer (61%; n = 67; p = .006). Neither the mean number of SLN nor the rate of low volume metastases showed significant differences between both cohorts. In the subgroup of endometrial cancer patients, the number of systematic lymph node dissection (LND) was significantly lower in the ICG cohort compared to the blue dye cohort (9% vs. 28%, p = .001). CONCLUSIONS: ICG improved the detection rate of pelvic SLN compared to blue dye and may be considered as the superior technique. In clinical practice, the rate of systematic LND further decreased after incorporating SLN mapping with ICG. Reliable safety data are still pending.

A new capsulotomy-based dorsal approach to the wrist: A cadaver study.

Using a cadaver study, we described a new dorsal approach to the wrist joint using a "U-shaped with proximal base" capsulotomy. Six fresh adult cadaveric wrists were dissected after intra-arterial silicone injection. We did a dorsal approach to expose the dorsal joint capsule. It was then possible to identify the dorsal radiocarpal and intercarpal ligaments, the dorsal radiocarpal and intercarpal arterial arches, the dorsal branch of the anterior interosseous artery and the terminal branch of the posterior interosseous nerve. Wrist arthrotomy was done using our capsulotomy. In each dissected capsular flap, we always found the individual ligament, vascular, and nerve structures, implying they were intact over their trajectories. The mean surface area of the articular exposure was 945 mm2 (range 725-1102 mm2) allowing easy access to the carpal bones and the radiocarpal and midcarpal joint spaces. This surgical approach to the wrist is technically feasible and avoids damaging the dorsal extrinsic ligaments fibers. Keeping the vascularization intact could improve capsular healing, while preserving innervation could maintain wrist proprioception.

Preparative field flow fractionation for complex environmental samples: online detection by inductively coupled plasma mass spectrometry and offline detection by gas chromatography with flame ionization.

Asymmetric flow field flow fractionation (AF4) in particular online with elemental detection via inductively coupled plasma mass spectrometry (ICP-MS) has been developed as powerful and flexible separation technique for suspensions of nano- and micro-particles covering a broad range of applications including environmental water samples and soil extracts. However, for challenging applications, such as particulate phosphorus determination in non-contaminated water samples at levels close to the limit of detection the throughput of the analytical field flow fractionation (FFF) is not sufficient. The same holds true for more specific identification and quantification of black carbon (BC) which needs a subsequent complex multi-step analysis using the well-established benzene polycarboxylic acids (BPCA) method. To overcome these limitations, the performance of a commercially available preparative AF4 channel, which has rarely been applied, yet, was investigated in this study. Using the example of an extract from charcoal spiked soil, method development for the preparative channel was performed and the results from six replicate fractionations with multi-element online detection by ICP-MS were compared to the results from the analytical channel for the same extracts. A similar fractionation pattern was achieved and the quantitative results agreed well for most of the particulate fractions (ratio 1.7 with standard deviation (SD) 0.2 for fraction 1, ratio 0.81 with SD 0.14 for fraction 2 and ratio 1.1 with SD 0.2 for fraction 3). Relative standard deviations were in the range of 9% to 18% for the preparative channel and between 3% and 17% for the analytical channel. Transferability of the separation parameters between both channels is discussed as well as the operational challenges of the preparative channel. As proof of principle, preparative fractionation of an extract from charcoal spiked soil was performed with fraction collection and subsequent quantification of BC via the BPCA method including derivatization, cation exchange pre-cleaning and finally gas chromatographic separation and quantification via flame ionization detection. The results indicated the majority of detected BC in the often so-called dissolved fraction was bound to nanoparticles (48%) and colloids (27%). Only 25% was detected in the cross flow (truly dissolved fraction). This successful example opens new possibilities for hyphenation of FFF separation with multiple detection techniques for improved characterization of particulate matter in challenging applications.

Determinants of Variation in the Use of Adjuvant Chemotherapy for Stage III Colon Cancer in England.

AIMS: Adjuvant chemotherapy (ACT) for stage III colon cancer is well-established. This study aimed to explore the determinants of ACT use and between-hospital variation within the English National Health Service (NHS). MATERIALS AND METHODS: In total, 11 932 patients (diagnosed 2014-2017) with pathological stage III colon cancer in the English NHS were identified from the National Bowel Cancer Audit. Records were linked to Systemic Anti-Cancer Therapy and Hospital Episode Statistics databases. Multi-level logistic regression analyses were carried out to estimate independent factors for ACT use, including age, sex, deprivation, comorbidities, performance status, American Society of Anaesthesiologists (ASA) grade, surgical urgency, surgical access, TNM staging, readmission and hospital-level factors (university teaching hospital, on-site chemotherapy and high-volume centre). A random intercept was modelled for each English NHS hospital (n = 142). Between-hospital variation was explored using funnel plot methodology. Fully adjusted random-intercept models were fitted separately in young (<70 years) and elderly (≥70 years) patients and intra-class correlation coefficients estimated. RESULTS: 60.7% of patients received ACT. Age was the strongest determinant. Compared with patients aged <60 years, those aged 60-64 (adjusted odds ratio [aOR] 0.76, 95% confidence interval 0.63-0.93), 65-69 (aOR 0.63, 95% confidence interval 0.54-0.74), 70-74 (aOR 0.53, 95% confidence interval 0.44-0.62), 75-79 (aOR 0.23, 95% confidence interval 0.19-0.27) and ≥80 years (aOR 0.05, 95% confidence interval 0.04-0.06) were significantly less likely to receive ACT. With adjustment for other factors, ACT use was more likely in patients with higher socioeconomic status, fewer comorbidities, better performance status, lower ASA grade, advanced disease, elective resections, laparoscopic procedures and no unplanned readmissions. Hospital-level factors were non-significant. The observed proportions of ACT administration in the young and elderly were 46-100% (80% of hospitals 74-90%) and 10-81% (80% of hospitals 33-65%), respectively. Risk adjustment did not reduce between-hospital variation. Despite adjustment, age accounted for 9.9% (7.2-13.4%) of between-hospital variation in the elderly compared with 2.7% (1.2-5.7%) in the young. CONCLUSIONS: There is significant between-hospital variation in ACT use for stage III colon cancer, especially for older patients. Advanced age alone seems to be a greater barrier to ACT use in some hospitals.