A multi-lesional analysis of diffuse idiopathic pulmonary neuroendocrine cell hyperplasia: a single-centre analysis.

AIM: To conduct a multi-lesional computed tomography (CT) analysis of diffuse idiopathic pulmonary neuroendocrine cell hyperplasia (DIPNECH) patients to determine volumetric changes in lesions over 5 years. MATERIALS AND METHODS: A retrospective case-note review was undertaken to identify 16 patients with histological and radiological features of DIPNECH between 2012-2021. Area and volume were calculated for 17 sets of lesions identified on high-resolution CT. Clinical data were extracted from electronic patient records, which included demographic data, outpatient clinic letters, histology reports, and imaging reports. RESULTS: One hundred and twenty-eight lesions were identified in 16 patients (one male, 15 female) and followed-up annually over a median 1,985 days (range 1,450-2,290). At year 1 follow-up, lesion area ranged from 1-48 mm2, and lesion volume ranged from 8-18,380 mm3; lesion area ranged from 1-45mm2 and lesion volume ranged from 11-17,800 mm3 and year 5. Half (8/16) of the patients had concomitant typical carcinoid tumours and one patient had an atypical carcinoid tumour. No statistically significant correlation (p<0.05) was found between lesion cross-sectional area or volume and duration of follow-up (years and days). No metastatic spread was observed at the time of analysis. CONCLUSIONS: No significant increase was observed in the size of over 100 lesions in patients with DIPNECH over a 5-year period and no metastasis occurred during the study period affirming the relatively indolent course of the disease.

Patterned Stimulation of the Chrimson Opsin in Glutamatergic Motor Thalamus Neurons Improves Forelimb Akinesia in Parkinsonian Rats.

Parkinson's disease (PD) is a motor disorder charactertised by altered neural activity throughout the basal ganglia-thalamocortical circuit. Electrical deep brain stimulation (DBS) is efficacious in alleviating motor symptoms, but has several notable side-effects, most likely reflecting the non-specific nature of electrical stimulation and/or the brain regions targeted. We determined whether specific optogenetic activation of glutamatergic motor thalamus (Mthal) neurons alleviated forelimb akinesia in a chronic rat model of PD. Parkinsonian rats (unilateral 6-hydroxydopamine injection) were injected with an adeno-associated viral vector (AAV5-CaMKII-Chrimson-GFP) to transduce glutamatergic Mthal neurons with the red-shifted Chrimson opsin. Optogenetic stimulation with orange light at 15 Hz tonic and a physiological pattern, previously recorded from a Mthal neuron in a control rat, significantly increased forelimb use in the reaching test (p < 0.01). Orange light theta burst stimulation, 15 Hz and control reaching patterns significantly reduced akinesia (p < 0.0001) assessed by the step test. In contrast, forelimb use in the cylinder test was unaffected by orange light stimulation with any pattern. Blue light (control) stimulation failed to alter behaviours. Activation of Chrimson using complex patterns in the Mthal may be an alternative treatment to recover movement in PD. These vector and opsin changes are important steps towards translating optogenetic stimulation to humans.

A Radiologists' Guide to En Bloc Resection of Primary Tumors in the Spine: What Does the Surgeon Want to Know?

En bloc resection in the spine is performed for both primary and metastatic bone lesions and has been proven to lengthen disease-free survival and decrease the likelihood of local recurrence. It is a complex procedure, which requires a thorough multi-disciplinary approach. This article will discuss the role of the radiologist in characterizing the underlying tumor pathology, staging the tumor and helping to predict possible intraoperative challenges for en bloc resection of primary bone lesions. The postoperative appearances and complications following en bloc resection in the spine will be considered in subsequent articles.

Well-differentiated gastroenteropancreatic G3 NET: findings from a large single centre cohort.

Neuroendocrine neoplasms are known to have heterogeneous biological behavior. G3 neuroendocrine tumours (NET G3) are characterized by well-differentiated morphology and Ki67 > 20%. The prognosis of this disease is understood to be intermediate between NET G2 and neuroendocrine carcinoma (NEC). Clinical management of NET G3 is challenging due to limited data to inform treatment strategies. We describe clinical characteristics, treatment, and outcomes in a large single centre cohort of patients with gastroenteropancreatic NET G3. Data was reviewed from 26 cases managed at Queen Elizabeth Hospital, Birmingham, UK, from 2012 to 2019. Most commonly the site of the primary tumour was unknown and majority of cases with identifiable primaries originated in the GI tract. Majority of cases demonstrated somatostatin receptor avidity. Median Ki67 was 30%, and most cases had stage IV disease at diagnosis. Treatment options included surgery, somatostatin analogs (SSA), and chemotherapy with either platinum-based or temozolomide-based regimens. Estimated progression free survival was 4 months following initiation of SSA and 3 months following initiation of chemotherapy. Disease control was observed following treatment in 5/11 patients treated with chemotherapy. Estimated median survival was 19 months; estimated 1 year survival was 60% and estimated 2 year survival was 13%. NET G3 is a heterogeneous group of tumours and patients which commonly have advanced disease at presentation. Prognosis is typically poor, though select cases may respond to treatment with SSA and/or chemotherapy. Further study is needed to compare efficacy of different treatment strategies for this disease.

Anaemia in cardiac surgery - a retrospective review of a centre's experience with a pre-operative intravenous iron clinic.

Pre-operative anaemia is associated with higher rates of transfusion and worse outcomes, including prolonged hospital stay, morbidity and mortality. Iron deficiency is associated with significantly lower haemoglobin levels throughout the peri-operative period and more frequent blood transfusion. Correction of iron stores before surgery forms part of the first pillar of patient blood management. We established a pre-operative anaemia clinic to aid identification and treatment of patients with iron deficiency anaemia scheduled for elective cardiac surgery. We present a retrospective observational review of our experience from January 2017 to December 2019. One-hundred and ninety patients received treatment with intravenous iron, a median of 21 days before cardiac surgery. Of these, 179 had a formal laboratory haemoglobin level measured before surgery, demonstrating a median rise in haemoglobin of 8.0 g.l-1 . Patients treated with i.v. iron demonstrated a significantly higher incidence of transfusion (60%) compared with the non-anaemic cohort (22%) during the same time period, p < 0.001. Significantly higher rates of new requirement for renal replacement therapy (6.7% vs. 0.6%, p < 0.001) and of stroke (3.7% vs. 1.2%, p = 0.010) were also seen in this group compared with those without anaemia, although there was no significant difference in in-hospital mortality (1.6% vs. 0.8%, p = 0.230). In patients where the presenting haemoglobin was less than 130 g.l-1 , but there was no intervention or treatment, there was no difference in rates of transfusion or of complications compared with the anaemic group treated with iron. In patients with proven iron deficiency anaemia, supplementation with intravenous iron showed only a modest effect on haemoglobin and this group still had a significantly higher transfusion requirement than the non-anaemic cohort. Supplementation with intravenous iron did not improve outcomes compared with patients with anaemia who did not receive intravenous iron and did not reduce peri-operative risk to non-anaemic levels. Questions remain regarding identification of patients who will receive most benefit, the use of concomitant treatment with other agents, and the optimum time frames for treatment in order to produce benefit in the real-world setting.

Early data on long-term efficacy and safety of inotersen in patients with hereditary transthyretin amyloidosis: a 2-year update from the open-label extension of the NEURO-TTR trial.

BACKGROUND AND PURPOSE: Hereditary transthyretin (hATTR) amyloidosis causes progressive polyneuropathy resulting from transthyretin (TTR) amyloid deposition throughout the body, including the peripheral nerves. The efficacy and safety of inotersen, an antisense oligonucleotide inhibitor of TTR protein production, were demonstrated in the pivotal NEURO-TTR study in patients with hATTR polyneuropathy. Here, the long-term efficacy and safety of inotersen are assessed in an ongoing open-label extension (OLE) study. METHODS: Patients who completed NEURO-TTR were eligible to enroll in the OLE (NCT02175004). Efficacy assessments included the modified Neuropathy Impairment Score plus seven neurophysiological tests composite score (mNIS + 7), the Norfolk Quality of Life - Diabetic Neuropathy (Norfolk QOL-DN) questionnaire total score and the Short-Form 36 Health Survey (SF-36) Physical Component Summary (PCS) score. Safety and tolerability were also assessed. RESULTS: Overall, 97% (135/139) of patients who completed NEURO-TTR enrolled in the OLE. Patients who received inotersen for 39 cumulative months in NEURO-TTR and the OLE continued to show benefit; patients who switched from placebo to inotersen in the OLE demonstrated improvement or stabilization of neurological disease progression by mNIS + 7, Norfolk QOL-DN and SF-36 PCS. No new safety concerns were identified. There was no evidence of increased risk for grade 4 thrombocytopenia or severe renal events with increased duration of inotersen exposure. CONCLUSION: Inotersen slowed disease progression and reduced deterioration of quality of life in patients with hATTR polyneuropathy. Early treatment with inotersen resulted in greater long-term disease stabilization than delayed initiation. Routine platelet and renal safety monitoring were effective; no new safety signals were observed.

Guy's cancer cohort - real world evidence for cancer pathways.

BACKGROUND: The burden of disease due to cancer remains substantial. Since the value of real-world evidence has also been recognised by regulatory agencies, we established a Research Ethics Committee (REC) approved research database for cancer patients (Reference: 18/NW/0297). CONSTRUCTION AND CONTENT: Guy's Cancer Cohort introduces the concept of opt-out consent processes for research in a subset of oncology patients diagnosed and treated at a large NHS Trust in the UK. From April 2016 until March 2017, 1388 eligible patients visited Guy's and St Thomas' NHS Foundation Trust (GSTT) for breast cancer management. For urological cancers this number was 1757 and for lung cancer 677. The Cohort consists of a large repository of routinely collected clinical data recorded both retrospectively and prospectively. The database contains detailed clinical information collected at various timepoints across the treatment pathway inclusive of diagnostic data, and data on disease progression, recurrence and survival. CONCLUSIONS: Guy's Cancer Cohort provides a valuable infrastructure to answer a wide variety of research questions of a clinical, mechanistic, and supportive care nature. Clinical research using this database will result in improved patient safety and experience. Guy's Cancer Cohort promotes collaborative research and will accept applications for the release of anonymised datasets for research purposes.

Experiences of breast cancer in Arab countries. A thematic synthesis.

BACKGROUND: Breast cancer is the most common cancer in women globally. Its negative effects on a woman's quality of life are related to the individual and socio-cultural factors. This review aimed to identify and synthesise the reported experiences and quality of life of women with breast cancer in Arab countries. METHODS: PubMed, Embase, Web of Science, SCOPUS, PsychInfo, CINAHL, Allied and Complementary Medicine Database, and Index Medicus for the Eastern Mediterranean Region were searched for articles published from start to March 2019 using PRISMA guidelines. These searches were complimented by citation tracking and  hand searching of relevant journals. A thematic synthesis was carried out on the 'findings/results' sections from the identified papers. RESULTS: Of 5228 records identified, 19 were included in the review which represented 401 women from 11 Arab countries. All used qualitative methods of data collection to produce rich descriptions of experiences. Thematic synthesis of the extracted data identified three major themes, Perceptions and reactions, Coping or enduring and Changing roles. CONCLUSIONS: This review provides a rich description of the reported quality of life and experiences of women with breast cancer in Arab countries. These are influenced by the women's and society's views of cancer, the women's role in society and family, religious faith and the healthcare context and access to treatment choices and information.

Patient-reported outcome measures for facial skin cancer: a systematic review and evaluation of the quality of their measurement properties.

BACKGROUND: Skin cancer is the commonest malignancy worldwide, often occurring on the face. Both the condition and treatment can lead to scarring and facial disfigurement, affecting a patient's health-related quality of life (HRQoL), which can be measured using patient-reported outcome measures (PROMs). OBJECTIVES: This systematic review identifies PROMs for facial skin cancer and appraises their methodological quality and psychometric properties using up-to-date methods. METHODS: MEDLINE, Embase, PsycINFO, Cochrane and CINAHL were searched systematically in accordance with PRISMA guidelines, identifying all PROMs designed for or validated in facial skin cancer. Methodological quality and evidence of psychometric properties were assessed using the COnsensus-based Standards for the Selection of Health Measurement INstruments (COSMIN) checklist and criteria proposed by Terwee and colleagues. A best-evidence synthesis and assessment of instrument focus on post-resection reconstruction was also performed. RESULTS: We included 24 studies on 11 PROMs. Methodological quality and psychometric evidence was variable, with the Patient Outcome of Surgery - Head/Neck (POS-H/N), Skin Cancer Index (SCI), Skin Cancer Quality of Life Impact Tool (SCQOLIT) and Essers and colleagues demonstrating the greatest level of validation. None scored well in their relevance to post-skin cancer reconstruction of the face. CONCLUSIONS: This systematic review critically appraises PROMs for facial skin cancer using internationally accepted criteria. The identified PROMs demonstrate a variation in the quality of validation performed, with a need to improve this across all PROMs in the field. Only through improving the quality of available PROMs and their focus on the post-treatment aesthetic and functional outcome will we be able to truly appreciate the concerns of our patients and improve the management of facial skin cancer.

Application of the Target Lipid Model and Passive Samplers to Characterize the Toxicity of Bioavailable Organics in Oil Sands Process-Affected Water.

Oil sand operations in Alberta, Canada will eventually include returning treated process-affected waters to the environment. Organic constituents in oil sand process-affected water (OSPW) represent complex mixtures of nonionic and ionic (e.g., naphthenic acids) compounds, and compositions can vary spatially and temporally, which has impeded development of water quality benchmarks. To address this challenge, it was hypothesized that solid phase microextraction fibers coated with polydimethylsiloxane (PDMS) could be used as a biomimetic extraction (BE) to measure bioavailable organics in OSPW. Organic constituents of OSPW were assumed to contribute additively to toxicity, and partitioning to PDMS was assumed to be predictive of accumulation in target lipids, which were the presumed site of action. This method was tested using toxicity data for individual model compounds, defined mixtures, and organic mixtures extracted from OSPW. Toxicity was correlated with BE data, which supports the use of this method in hazard assessments of acute lethality to aquatic organisms. A species sensitivity distribution (SSD), based on target lipid model and BE values, was similar to SSDs based on residues in tissues for both nonionic and ionic organics. BE was shown to be an analytical tool that accounts for bioaccumulation of organic compound mixtures from which toxicity can be predicted, with the potential to aid in the development of water quality guidelines.

Pancreatic and gastric heterotopic tissue presenting as a symptomatic gallbladder mass: A case report and literature review.

Pancreatic and gastric heterotopia is an uncommon congenital anomaly in which gastric and/or pancreatic tissue is found outside of its anatomic location. In the majority of patients, lesions are found incidentally because they tend to be asymptomatic. However, lesions may become symptomatic when inflammation, obstruction, and bleeding occurs. Depending on tissue size and location they can harvest a landscape of nonspecific symptoms, causing a delay in diagnosis. Heterotopic tissue of either gastric or pancreatic origin have been reported in literature, however the presence of combined gastric and pancreatic heterotopic tissue is exceedingly rare. We report a case of an 18-year-old female with polypoid gastric and pancreatic heterotopia and focal intestinal metaplasia of the gallbladder with clinical findings of acute cholecystitis. In this literature review, we synthesize the clinical significance, histopathological features, diagnosis and management of pancreatic and gastric heterotopic tissue.

RUNX in Invertebrates.

Runx genes have been identified in all metazoans and considerable conservation of function observed across a wide range of phyla. Thus, insight gained from studying simple model organisms is invaluable in understanding RUNX biology in higher animals. Consequently, this chapter will focus on the Runx genes in the diploblasts, which includes sea anemones and sponges, as well as the lower triploblasts, including the sea urchin, nematode, planaria and insect. Due to the high degree of functional redundancy amongst vertebrate Runx genes, simpler model organisms with a solo Runx gene, like C. elegans, are invaluable systems in which to probe the molecular basis of RUNX function within a whole organism. Additionally, comparative analyses of Runx sequence and function allows for the development of novel evolutionary insights. Strikingly, recent data has emerged that reveals the presence of a Runx gene in a protist, demonstrating even more widespread occurrence of Runx genes than was previously thought. This review will summarize recent progress in using invertebrate organisms to investigate RUNX function during development and regeneration, highlighting emerging unifying themes.

Cefepime plasma concentrations and clinical toxicity: a retrospective cohort study.

OBJECTIVES: Cefepime remains an important antibiotic for severe bacterial infections, yet some meta-analyses have shown elevated mortality among patients randomized to it. Therapeutic drug monitoring (TDM) of ß-lactam antibiotics is increasing, but optimal plasma concentrations remain unknown. We examined clinical outcomes of patients undergoing cefepime TDM in an initial effort to define the drug's toxicity threshold. METHODS: In this single-centre retrospective cohort study, we enrolled all adult hospitalized patients receiving cefepime and undergoing TDM from January 2013 through July 2016. The primary outcome was the incidence of clinical toxicity; a secondary outcome was clinical failure. Plasma samples were analysed via high-performance liquid chromatography with ultraviolet detection. RESULTS: A total of 161 cefepime concentrations were drawn from 93 patients. Roughly half (82/161, 51%) and one-third (49/161, 30%) were trough and steady-state levels from patients receiving intermittent and continuous infusions, respectively; median concentrations were 17.6 mg/L (IQR 9.7-35.2) and 29.2 mg/L (IQR 18.9-45.9). Ten patients (11%) experienced a neurologic event considered at least possibly related to cefepime; neurotoxicity was associated with poorer renal function (median creatinine clearance 54 (IQR 39-97) vs. 75 mL/min/1.732 (IQR 44-104)) and longer cefepime durations (mean 8.3 (SD±6.7) vs. 13.3 days (± 14.2), p = 0.071). Patients with trough levels >20 mg/L had a fivefold higher risk for neurologic events (OR 5.05, 95% CI 1.3-19.8). CONCLUSIONS: Neurotoxicity potentially related to cefepime occurred at plasma concentrations >35 mg/L. For those receiving intermittent infusions, trough concentrations >20 mg/L should be avoided until further information is available from prospective studies.

A comprehensive geriatric assessment screening questionnaire (CGA-GOLD) for older people undergoing treatment for cancer.

Oncology services do not routinely assess broader needs of older people with cancer. This study evaluates a comprehensive geriatric assessment and comorbidity screening questionnaire (CGA-GOLD) covering evidence-based domains and quality of life (EORTC-QLQ-C30). Patients aged 65+ attending oncology services were recruited into (1) Observational cohort (completed CGA-GOLD, received standard oncology care), (2) Intervention cohort (responses categorised 'low-risk', 'high-risk', 'possible need' by geriatricians). N = 417 observational patients (1002 invited by post, 418 consented, age 73.9 ± 5.4) completed CGA-GOLD in 11.7 ± 7.9 min, 86.3% required no assistance, 3.1% overall missing responses. Multiple problems reported: hypertension (18.1%), diabetes (16.9%), dyspnoea on flat surfaces (27.6%), polypharmacy (46%), difficulty walking (14.9%), fatigue (40.5%), living alone (30.9%), social isolation (11.2%), recent functional dependence (27.8%), urinary incontinence (21.4%), falls (13.3%). 237/239 intervention patients completed CGA-GOLD and consecutive subsets examined. The doctor and nurse specialist independently identified same need level in 87.3% (high inter-rater reliability kappa = 0.80), taking 1-2 min per questionnaire. Need level remained unchanged following hospital notes review against responses in 90% (75/83). 'Possible need' patients were telephoned with change in 29% (16/55) to low-risk and none to high-risk, confirming high need was not being missed. CGA-GOLD screening questionnaire was acceptable to older patients, feasibly administered in NHS cancer services, described comorbidities, CGA and QOL needs, and reliably identified higher risk patients requiring further input for optimal cancer treatment.

Proximal Resection Margin in Ivor-Lewis Oesophagectomy for Cancer.

OBJECTIVE: The purpose of this study was to investigate whether a long proximal oesophageal resection margin (PRM) is associated with improved survival after oesophagectomy for cancer and to identify the optimal margin to aim for in this patient group. METHODS: A prospectively maintained database identified 174 patients who underwent Ivor-Lewis oesophagectomy for cancer. Demographic, clinical, and pathological data were collected. X-tile software was used to identify the optimal resection point. Two models were analysed: single point resection with comparison of two groups (short and long), and two resection points with three groups (short, medium, and long) to provide a range. RESULTS: The median PRM was 4.0 cm (interquartile range: 2.5-6.0 cm). After adjustment for significant confounders, multivariable Cox PH analysis demonstrated that the optimal resection margin was 1.7 cm, and in the three-group analysis the optimum PRM was between 1.7 and 3 cm. In the two-group analysis, the long margin had no effect on DFS (p = 0.37), but carried a significantly improved overall survival (hazard ratio [HR] = 0.46, 95 % confidence interval [CI] 0.25-0.87, p = 0.02). In the three-group analysis, the medium and long groups had improved OS compared with the short group (on average 54 %, HR ≥ 0.45, p ≤ 0.04). The 5-year disease-free and overall survival rates were highest in the medium PRM group (48 and 57 % respectively). CONCLUSIONS: Optimal survival following oesophagectomy for cancer is achieved with a PRM > 1.7 cm, but a PRM > 3 cm does not yield a further survival advantage. Thus, the optimal PRM is likely to be between 1.7 and 3 cm.

Integrated palliative care in Europe: a qualitative systematic literature review of empirically-tested models in cancer and chronic disease.

BACKGROUND: Integrated Palliative Care (PC) strategies are often implemented following models, namely standardized designs that provide frameworks for the organization of care for people with a progressive life-threatening illness and/or for their (in)formal caregivers. The aim of this qualitative systematic review is to identify empirically-evaluated models of PC in cancer and chronic disease in Europe. Further, develop a generic framework that will consist of the basis for the design of future models for integrated PC in Europe. METHODS: Cochrane, PubMed, EMBASE, CINAHL, AMED, BNI, Web of Science, NHS Evidence. Five journals and references from included studies were hand-searched. Two reviewers screened the search results. Studies with adult patients with advanced cancer/chronic disease from 1995 to 2013 in Europe, in English, French, German, Dutch, Hungarian or Spanish were included. A narrative synthesis was used. RESULTS: 14 studies were included, 7 models for chronic disease, 4 for integrated care in oncology, 2 for both cancer and chronic disease and 2 for end-of-life pathways. The results show a strong agreement on the benefits of the involvement of a PC multidisciplinary team: better symptom control, less caregiver burden, improvement in continuity and coordination of care, fewer admissions, cost effectiveness and patients dying in their preferred place. CONCLUSION: Based on our findings, a generic framework for integrated PC in cancer and chronic disease is proposed. This framework fosters integration of PC in the disease trajectory concurrently with treatment and identifies the importance of employing a PC-trained multidisciplinary team with a threefold focus: treatment, consulting and training.

Chemotherapy at First Diagnosis of Advanced Prostate Cancer - Revolution or Evolution? Findings from a British Uro-oncology Group UK Survey to Evaluate Oncologists' Views on First-line Docetaxel in Combination with Androgen Deprivation Therapy in Castrate-sensitive Metastatic and High-risk/Locally Advanced Prostate Cancer.

AIMS: There have been three randomised trials investigating docetaxel in combination with androgen deprivation therapy as first-line therapy for hormone-sensitive metastatic and locally advanced/high-risk prostate cancer. The largest of these studies, UK STAMPEDE trial, recently presented in June 2015. The aim of this survey was to evaluate if oncologists' practice has changed as a result of these studies, or if their practice is likely to change in different clinical settings in the future. MATERIALS AND METHODS: The British Uro-oncology Group issued a semi-structured online questionnaire to its membership of 160 specialist urological oncologists practising in the UK. Links to the abstracts of GETUG-AFU-15, E3805 CHAARTED and STAMPEDE were attached with the survey for respondents to review before completing the survey. RESULTS: In total, 111 participants completed the survey; 87% stated that STAMPEDE will influence their clinical practice in the future. Almost all (96%) would offer docetaxel with androgen deprivation therapy to men presenting with high volume metastatic prostate cancer. Fewer oncologists would offer this treatment to men with low volume metastatic prostate cancer, locally advanced or relapsed disease. Various patient- and disease-related factors were considered in decision making, as well as resource implications. CONCLUSIONS: This survey reports oncologists' attitudes towards a major change in practice in the standard of care for men with newly diagnosed advanced prostate cancer in the UK. The survey highlighted the complexities surrounding the clinical implementation of the data from these studies, including changes in referral pathways, with the early involvement of oncologists in such patients' care, increases in workloads for oncologists and chemotherapy units and the need for national approval for re-imbursement of these treatments.

The impact of comprehensive geriatric assessment interventions on tolerance to chemotherapy in older people.

BACKGROUND: Although comorbidities are identified in routine oncology practice, intervention plans for the coexisting needs of older people receiving chemotherapy are rarely made. This study evaluates the impact of geriatrician-delivered comprehensive geriatric assessment (CGA) interventions on chemotherapy toxicity and tolerance for older people with cancer. METHODS: Comparative study of two cohorts of older patients (aged 70+ years) undergoing chemotherapy in a London Hospital. The observational control group (N=70, October 2010-July 2012) received standard oncology care. The intervention group (N=65, September 2011-February 2013) underwent risk stratification using a patient-completed screening questionnaire and high-risk patients received CGA. Impact of CGA interventions on chemotherapy tolerance outcomes and grade 3+ toxicity rate were evaluated. Outcomes were adjusted for age, comorbidity, metastatic disease and initial dose reductions. RESULTS: Intervention participants undergoing CGA received mean of 6.2±2.6 (range 0-15) CGA intervention plans each. They were more likely to complete cancer treatment as planned (odds ratio (OR) 4.14 (95% CI: 1.50-11.42), P=0.006) and fewer required treatment modifications (OR 0.34 (95% CI: 0.16-0.73), P=0.006). Overall grade 3+ toxicity rate was 43.8% in the intervention group and 52.9% in the control (P=0.292). CONCLUSIONS: Geriatrician-led CGA interventions were associated with improved chemotherapy tolerance. Standard oncology care should shift towards modifying coexisting conditions to optimise chemotherapy outcomes for older people.