Objective: The Cancer and Aging Research Group (CARG) score was developed to predict severe chemotherapy-induced toxicity risk in older adults; validation study results have varied. The Tolerance of Anti-cancer Systemic Therapy in the Elderly study sought to evaluate the CARG score prospectively in a chemotherapy-naïve UK population. Methods and analysis: This multicentre, prospective, observational study recruited patients aged ≥65 years commencing first-line chemotherapy for any solid organ malignancy or setting. Baseline demographics and established frailty measures were recorded. Follow-up data including toxicity and hospital admissions were collected retrospectively. Baseline CARG score predictive ability was assessed. Results: 339 patients were recruited from 19 centres; median age 73 years (range 65–92), 51.9% male and 54.9% gastrointestinal primary. At baseline, 85% of patients were of Eastern Cooperative Oncology Group Performance Status (ECOG PS) 0–1, with median Rockwood Clinical Frailty Scale (CFS) 3 (range 0–8). 314 (92.6%) patients had follow-up data; 69 (22.3%) patients experienced Common Terminology for Cancer Adverse Events grade ≥3 toxicity and 84 (27%) required hospital admission during treatment. Increasing CARG risk groups had increased grade ≥3 toxicity (low 19.6%, medium 22.2%, high 28.2%); however, this was non-significant with no evidence of robust predictive performance. Predictive performance of CFS and ECOG PS was superior to CARG. Importantly, patient and clinician perceptions of toxicity risk differed significantly. Conclusions: In older UK patients with cancer commencing chemotherapy, baseline frailty was prevalent. CARG score did not robustly discriminate or predict high-grade toxicity risk. ECOG and CFS showed superior, although limited, ability to predict and discriminate. This study highlights the need for the development of tools that better predict toxicity in this population.

Purpose: The current approach for molecular subtyping of colon cancer relies on gene expression profiling, which is invasive and has limited ability to reveal dynamics and spatial heterogeneity. Molecular imaging techniques, such as PET, present a noninvasive alternative for visualizing biological information from tumors. However, the factors influencing PET imaging phenotype, the suitable PET radiotracers for differentiating tumor subtypes, and the relationship between PET phenotypes and tumor genotype or gene expression–based subtyping remain unknown. Experimental Design: In this study, we conducted 126 PET scans using four different metabolic PET tracers, [18F]fluorodeoxy-D-glucose ([18F]FDG), O-(2-[18F]fluoroethyl)-l-tyrosine ([18F]FET), 3′-deoxy-3′-[18F]fluorothymidine ([18F]FLT), and [11C]acetate ([11C]ACE), using a spectrum of five preclinical colon cancer models with varying genetics (BMT, AKPN, AK, AKPT, KPN), at three sites (subcutaneous, orthograft, autochthonous) and at two tumor stages (primary vs. metastatic). Results: The results demonstrate that imaging signatures are influenced by genotype, tumor environment, and stage. PET imaging signatures exhibited significant heterogeneity, with each cancer model displaying distinct radiotracer profiles. Oncogenic Kras and Apc loss showed the most distinctive imaging features, with [18F]FLT and [18F]FET being particularly effective, respectively. The tissue environment notably impacted [18F]FDG uptake, and in a metastatic model, [18F]FET demonstrated higher uptake. Conclusions: By examining factors contributing to PET-imaging phenotype, this study establishes the feasibility of noninvasive molecular stratification using multiplex radiotracer PET. It lays the foundation for further exploration of PET-based subtyping in human cancer, thereby facilitating noninvasive molecular diagnosis.

The Oncotype DX Breast RS test has been adopted in Scotland and has been the subject of a large population-based study by a Scottish Consensus Group to assess the uptake of the recurrence score (RS), evaluate co-variates associated with the RS and to analyse the effect it may have had on clinical practice. Pan-Scotland study between August 2018-August 2021 evaluating 833 patients who had a RS test performed as part of their diagnostic pathway. Data was extracted retrospectively from electronic records and analysis conducted to describe change in chemotherapy administration (by direct comparison with conventional risk assessment tools), and univariate/multivariate analysis to assess relationship between covariates and the RS. Chemotherapy treatment was strongly influenced by the RS (p < 0.001). Only 30 % of patients received chemotherapy treatment in the intermediate and high risk PREDICT groups, where chemotherapy is considered. Additionally, 55.5 % of patients with a high risk PREDICT had a low RS and did not receive chemotherapy. There were 17 % of patients with a low risk PREDICT but high RS who received chemotherapy. Multivariate regression analysis showed the progesterone receptor Allred score (PR score) to be a strong independent predictor of the RS, with a negative PR score being associated with high RS (OR 4.49, p < 0.001). Increasing grade was also associated with high RS (OR 3.81, p < 0.001). Classic lobular pathology was associated with a low RS in comparison to other tumour pathology (p < 0.01). Nodal disease was associated with a lower RS (p = 0.012) on univariate analysis, with menopausal status (p = 0.43) not influencing the RS on univariate or multivariate analysis. Genomic assays offer the potential for risk-stratified decision making regarding the use of chemotherapy. They can help reduce unnecessary chemotherapy treatment and identify a subgroup of patients with more adverse genomic tumour biology. A recent publication by Health Improvement Scotland (HIS) has updated guidance on use of the RS test for NHS Scotland. It suggests to limit its use to the intermediate risk PREDICT group. Our study shows the impact of the RS test in the low and high risk PREDICT groups. The implementation across Scotland has resulted in a notable shift in practice, leading to a significant reduction in chemotherapy administration in the setting of high risk PREDICT scores returning low risk RS. There has also been utility for the test in the low risk PREDICT group to detect a small subgroup with a high RS. We have found the PR score to have a strong independent association with high risk RS. This finding was not evaluated by the key RS test papers, and the potential prognostic information provided by the PR score as a surrogate biomarker is an outstanding question that requires more research to validate.

Background Although rare, uterine sarcomas account for a high proportion of uterine cancer mortality. Treatment options and robust trial data are limited. Objectives The TOURISM study (Treatment Outcomes in UteRIne SarcoMa) is a UK-wide study by the National Oncology Trainees Collaborative for Healthcare Research which aimed to characterise this patient cohort. Design A retrospective descriptive cohort study. Patients with carcinosarcomas/mixed Mullerian tumours, non-uterine gynaecological sarcomas and uterine metastases were excluded. Routine clinical data, including general patient demographics, diagnosis, treatment and outcomes, were collated and pseudonymised. Setting Patients diagnosed with uterine sarcoma in the UK National Health Service between 1 January 2008 and 31 December 2017 were identified from electronic records. Participants A total of 406 patients from eight centres were eligible for inclusion. Results The median age at diagnosis was 56 years, with leiomyosarcoma the most common diagnosis (54.4%). The majority (57.9%) were diagnosed at the International Federation of Gynecology and Obstetrics stage I, with 19.7% diagnosed at stage IV. Nearly half (45.2%) of the patients received at least one line of chemotherapy, of which most (81.0%) received doxorubicin first-line. In the stage I group 7.4% received adjuvant chemotherapy and 15.0% received adjuvant radiotherapy. Median overall survival was 37 months; however, survival varied significantly by stage at diagnosis (stage I: 105 months; stage II: 33 months; stage III: 19 months; stage IV: 14 months). Conclusions Our data highlight the diversity in patient management in uterine sarcoma and a marked survival advantage for patients diagnosed with stage I disease. These data highlight the importance of a multidisciplinary approach and describe real-world trends in systemic therapies, radiotherapy and surgical treatment in this rare cancer type.