Assessment of the Implementation of Lung Cancer Consensus Statements From the Royal College of Radiologists in 2021; Progress and Barriers.

BACKGROUND: Lung cancer outcomes in the UK are worse than those in many similar countries. The RCR developed a series of 43 consensus statements (CS) to facilitate improvements in care for patients treated with radiotherapy. METHODS: We asked all 61 UK radiotherapy centres to self-assess the implementation of the CS and to describe their departmental key strengths and weaknesses in September 2021. RESULTS: 87% of centres returned their assessments. Whilst developmental activity was seen in most areas for most centres, 24 of the statements were felt to be difficult to implement within the next 2 years by at least one centre. The most frequently reported strengths were in the implementation of SABR (stereotactic body radiotherapy), concurrent chemoradiation for non-small cell lung cancer and technological aspects of treatment planning. The most frequently described departmental weaknesses were in pre-habilitation, timeliness of PET/CT scans and prophylaxis for Pneumocystis jiroveci Pneumonia (PJP). Barriers to implementation were often due to insufficient resource, a requirement for organisations to work together, and a perceived lack of evidence base. Strengths were often attributed to good team working, a local champion and being an early adopter. CONCLUSIONS: This work confirms the commitment of lung cancer radiotherapy teams across the UK to improve outcomes for their patients. Most of the statements have been implemented at least partially. Themes have been identified to aid further progress, one of which is a requirement for significant investment.

The Elderly are Less Likely to Receive Recommended Radical Radiotherapy for Non-small Cell Lung Cancer.

AIMS: The National Institute for Healthcare Excellence recommends continuous hyperfractionated, accelerated radiotherapy (CHART), concurrent chemoradiation (cCRT) and stereotactic ablative radiotherapy (SABR) for appropriate patients with non-small cell lung cancer (NSCLC), but these are not universally available in all UK radiotherapy centres. Reduced access to these treatments may be contributing to reduced survival, with the concern that elderly patients are less likely to receive guideline-recommended therapy (GRT). MATERIALS AND METHODS: We report a prospective, UK national study of patients treated with curative-intent radiotherapy for NSCLC over a 2 month period. Clinical oncologists in all UK radiotherapy centres were contacted and asked to complete a proforma on all patients treated with curative-intent radiotherapy. RESULTS: Three hundred and seventeen records were returned from 82% of centres. Only 49% (95% confidence interval 43-55%) of patients received the GRT for their tumour type. Patients aged 70 years or over were less likely to access GRT than those under 70 years (40% compared with 60%, P = 0.001), both as a result of clinicians offering therapy less frequently (52% compared with 65%, P = 0.03) and a higher refusal of therapy (22% versus 8%, P = 0.02). A reluctance to travel to a different centre was a key component of these decisions. SABR was delivered to only 52% of suitable patients, mainly because it was not available in the local centre. CONCLUSIONS: In this study of UK curative-intent radiotherapy practice, a lack of local access seems to limit uptake of advanced radiotherapy techniques such as SABR, especially for patients aged over 70 years.

The Quality of Curative-intent Radiotherapy for Non-small Cell Lung Cancer in the UK.

AIMS: Lung cancer is the leading cause of cancer-related death in the UK. The quality of curative-intent radiotherapy is associated with better outcomes. National quality standards from the National Institute for Health and Care Excellence (NICE) on patient work-up and treatment selection were used, with guidance from the Royal College of Radiologists on the technical delivery of radiotherapy, to assess the quality of curative-intent non-small cell lung cancer radiotherapy and to describe current UK practice. MATERIALS AND METHODS: Radiotherapy departments completed one questionnaire for each patient started on curative-intent radiotherapy for 8 weeks in 2013. RESULTS: Eighty-two per cent of centres returned a total of 317 proformas. Patient selection with positron emission tomography/computed tomography, performance status and Forced Expiratory Volume in 1 second (FEV1) was usually undertaken. Fifty-six per cent had pathological confirmation of mediastinal lymph nodes and 22% staging brain scans; 20% were treated with concurrent chemoradiation, 12% with Stereotactic Ablative Radiotherapy (SABR) and 8% with Continuous Hyperfractionated Accelerated Radiotherapy (CHART). Sixty-three per cent of patients received 55 Gy/20 fractions. Although respiratory compensation was routinely undertaken, only 33% used four-dimensional computed tomography. Seventy per cent of patients were verified with cone beam computed tomography. There was consistency of practice in dosimetric constraints for organs at risk and follow-up. CONCLUSIONS: This audit has described current UK practice. The latest recommendations for patient selection with pathological confirmation of mediastinal lymph nodes, brain staging and respiratory function testing are not universally followed. Although there is evidence of increasing use of newer techniques such as four-dimensional computed tomography and cone beam image-guided radiotherapy, there is still variability in access. Efforts should be made to improve access to modern technologies and quality assurance of radiotherapy plans.

Efficacy of dual-specific Bcr-Abl and Src-family kinase inhibitors in cells sensitive and resistant to imatinib mesylate.

Monotherapy of chronic myeloid leukemia (CML) with imatinib mesylate has been cast into shadow by the evolution of clinical resistance during therapy. Resistance to imatinib can arise by multiple mechanisms including amplification or mutation of Bcr-Abl, and continuity of imatinib therapy is probably a poor option for either of these patient groups. Recently, however, a structurally distinct new class of drugs, the pyrido[2,3-d]pyrimidines, has been described, and these compounds are predicted to make different molecular contacts in the Abl kinase domain. These drugs potently target both the Bcr-Abl and Src-family kinase activities, both of which are thought to be relevant to survival of the leukemic cell. We asked whether these drugs could selectively induce cell death in murine cell line models of CML cells sensitive and resistant to imatinib by different mechanisms. We show that whereas the pyrido[2,3-d] pyrimidines are indeed highly potent in suppressing proliferation of Bcr-Abl-overexpressing imatinib-resistant cells, they are almost completely ineffective against cells expressing the T315I mutant. This implies that despite structural differences from imatinib, these drugs are unlikely to be useful in patients expressing this mutant Bcr-Abl protein, but may be effective in cases where selection of cells overexpressing the oncoprotein leads to refractoriness to imatinib.

Pattern recognition of 31P magnetic resonance spectroscopy tumour spectra obtained in vivo.

Pattern recognition has been applied to the analysis of in vivo 31P NMR spectra. Using four different classes of tumour and three types of normal tissue, cluster analysis and artificial neural networks were successful in separating and classifying the majority of samples analysed. Although the phosphomonoester and P(i) regions appeared to be the most important spectral features, data representing the entire 31P spectrum were required for best separation of the tumour and tissue classes.

The effect of oestrogen ablation on the phospholipid metabolite content of primary and transplanted rat mammary tumours.

The concentration of phospholipid metabolites was determined in chemical extracts from two types of rat mammary tumours and compared with proliferation data (S-phase fraction). One of the tumours was an oestrogen-sensitive transplanted tumour. In this tumour the concentration of phosphocholine (PC) and glycerophosphorylcholine (GPC) correlated strongly with the S-phase fraction but not with the number of cells actively synthesizing DNA. Oestrogen ablation resulted in tumour regression. Regressing tumours contained less PC and more GPC than those actively growing. The other tumour was induced in rats by intravenous administration of N-methyl N-nitrosourea. Phosphoethanolamine (PE), PC and GPC levels were not associated with the S-phase fraction in this tumour. Oestrogen ablation resulted in tumour regression. There was no significant difference between the regressing and growing tumours in PE, PC or GPC content.

Monitoring therapeutic response to tamoxifen in NMU-induced rat mammary tumours by 31P MRS.

Tamoxifen injections were given once a week for 4 weeks to 19 rats bearing N-methyl-N-nitrosourea (NMU)-induced mammary carcinomas. NMR spectra were collected on days 2, 7, 14, 21 and 28. Only 42% of the tumours responded to the tamoxifen in that they regressed significantly; another 21% did not change in size and 37% grew significantly. In the ones that did subsequently regress there were significant changes in the NTP/Pi ratio as early as 2 days after treatment, before any detectable change in volume was recorded, and continuing up to 21 days. The significance of these findings and the possible mechanisms underlying the changes are discussed.