Clinical oncology最新文献

Heterogeneity of cancer necessitates individualised cancer care as well as tailored survival endpoints-one size no longer fits all. In the past few years, apart from the standard clinical efficacy endpoints, patient reported outcomes have gathered a momentum as one among the quality indicators in the realm of practice changing oncology. These standardised and validated self-reporting instruments use a patients' viewpoint to assess the status of their health and their experience whilst receiving health care. This review explores the relevance of patient reported measures in the present clinical scenario and issues regarding its implementation amidst the barriers and challenges. These measures should be judiciously accounted as surrogate markers along with survival endpoints; for providing value based, highly comprehensive cancer care. New policy guidelines incorporating patient reported outcomes should be planned and formulated for future practice in oncology.

Aims: The recent widespread use of electronic health records (EHRs) has opened the possibility for innumerable artificial intelligence (AI) tools to aid in genomics, phenomics, and other research, as well as disease prevention, diagnosis, and therapy. Unfortunately, much of the data contained in EHRs are not optimally structured for even the most sophisticated AI approaches. There are very few published efforts investigating methods for recording discrete data in EHRs that would not slow current clinical workflows or ways to prioritise patient characteristics worth recording. Here, we propose an approach to identify and prioritise findings (phenotypes) useful for differentiating diseases, with an initial focus on relatively common small B-cell lymphomas.

Materials and methods: A website enabling crowd-sourced recording of diseases and phenotypes was developed. An expert committee in the field of B-cell lymphomas standardised phenotype terminology for use in digital resources, and select terms were included in the Human Phenotype Ontology (HPO). A total of 100 patient lymph node biopsy samples were evaluated, and phenotypes were recorded as discrete data. Bayesian networks (BNs) were developed based on these data, and their diagnostic accuracy and ability to prioritise these phenotypes for inclusion in EHRs were assessed.

Results: Out of 146 phenotypes identified from the website as potentially useful for differentiating four different lymphomas from each other and from benign lymph nodes, 70-75 were included in BNs. The diagnostic accuracy of different naïve BNs was 96.3% for non-marginal zone lymphoma cases and 50% for marginal zone lymphoma cases when all of the included phenotypes were used and 93.8% for non-marginal zone lymphoma cases and 27.5% for marginal zone lymphoma cases when only 15 phenotypes were included in the BNs.

Conclusion: This pilot provides a starting point for systematic improvement and a dataset for comparing related approaches.

Aim: Tumour-infiltrating lymphocytes (TILs) represent a promising cancer biomarker. Different TILs, including CD8+, CD4+, CD3+, and FOXP3+, have been associated with clinical outcomes. However, data are lacking regarding the value of TILs for patients receiving radiation therapy (RT). We conducted a systemic review and meta-analysis of available data evaluating TILs for patients receiving curative-intent therapy including RT.

Materials and methods: Eligible studies presented a defined cohort of patients who all received curative-intent therapy, including RT, and also reported the relationship between any TIL score and either tumour response or survival outcomes. After comprehensive search of online databases (PubMed, EMBASE, Cochrane, and Web of Science), 2 authors conducted title, abstract, and whole-text review for quality and risk of bias following Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) guidelines. Data from publications that met quality criteria were grouped via (1) TIL analysed, (2) pre- or post-RT TIL assessment, and (3) clinical outcome measured.

Results: Initial search yielded 669 unique studies. Thirty-one studies met quality criteria, of which 20 studied rectal cancer (RC), 4 oesophageal, 3 pancreas, 2 lung, cervical/uterine 1 each. We conducted systematic review and meta-analysis of the RC publications. All except 2 were single-institutional cohort studies. After meta-analysis, the pre-RT epithelial CD8+ (p = 0.04) and stromal FOXP3+ (p = 0.01) counts were associated with survival without disease, while pre-RT epithelial (p = 0.02) and stromal (p = 0.001) FOXP3+ TILs were associated with overall survival. On post-RT analysis, epithelial (p = .04) and stromal (p = 0.02) CD8+ TILs were associated with survival without disease and epithelial CD8+ TILs were associated with overall survival (p = 0.01).Preoperative CD8+ and FOXP3+ TILs were generally associated with tumour response to RT, but meta-analysis was not conducted due to heterogeneity of response measurement techniques.

Conclusion: TILs represent a useful parameter for tumour response and survival outcomes for patients receiving curative-intent therapy, including RT for RC. Future work should aim to standardise TIL measurement and quantification methods and to develop protocols to clarify clinical application of these findings.

Background: Isocitrate dehydrogenase [IDH]-wildtype glioblastoma is an aggressive brain cancer associated with high recurrence and poor overall survival.

Aim: Our study aims to explore the prognostic effects of radiotherapy [RT] alone versus concomitant RT with temozolomide [TMZ].

Methods: A multicentre retrospective study included a cohort of 244 patients diagnosed with IDH-wildtype glioblastoma, and it was analysed from 2013 to 2020. All patients underwent complete surgical resection of the tumour followed by standard postsurgical therapies, including RT alone [group A] or concomitant RT with TMZ chemotherapy [group B]. Intra-statistical cohort data analysis was performed.

Results: The mean age of the patients was 53.9 years [SD 16.3 years], with 87 [35.7%] females and 157 [64.3%] males. Group "A" patient [n = 67, 27.5%] received RT alone, and group "B" patient [n = 177, 72.5%] received concomitant RT with TMZ chemotherapy. All patients' mean progression-free survival [PFS] was 391.8 days (13.1 months). There was a statistically significant difference in PFS between the two treatment groups [P value<0.0001]. The hazard ratio [HR] for PFS in group "b" compared with group "a" was 0.48 [95% CI: 0.36-0.64, P < 0.001] in the univariable analysis, indicating a significant benefit of the combined treatment. This benefit was maintained in the multivariable analysis with an HR of 0.50 [95% CI: 0.37-0.67, P < 0.001]. Age was found to be a significant factor in PFS, with each additional year of age increasing HR by 2% in the univariable analysis [HR: 1.02, 95% CI: 1.01-1.03, P < 0.001] and the multivariable analysis (HR of 1.01 [95% CI: 1.01-1.02, P < 0.001)].

Conclusions: Concomitant RT with TMZ chemotherapy significantly increased PFS beyond that observed from isolated RT in patients with IDH-wildtype glioblastoma.

Aims: Oligometastatic disease describes limited metastases amenable to therapy such as stereotactic body radiotherapy (SBRT). This study aims to understand which outcomes are most important to patients when considering SBRT as a treatment option. The insights gained will help inform future patient-directed trial endpoints and provide valuable guidance to clinicians supporting patients through their decision-making process.

Materials and methods: We conducted a qualitative study with focus groups and individual interviews. Participants were recruited using a purposive-sampling matrix accounting for age, presence of metastatic disease, and previous experience with radiotherapy. Each focus group had at least two moderators, and all interviews were digitally recorded and then transcribed. Thematic analysis was performed using NVivo version 12.

Results: The study included 18 patients diagnosed with breast cancer, comprising two focus groups and four individual interviews. The median age was 54 years (range 38-74). 15/18 (83%) had prior radiotherapy experience, including 4/18 with previous SBRT experience. Three main themes were identified: 1) Participants' experience with radiotherapy; 2) patients' perceptions and considerations in relation to SBRT (including desired treatment outcomes); and 3) willingness to consider SBRT for its potential local control and durable pain control benefits, even in the absence of survival benefit. Participants prioritised extending their lives as the foremost desired outcome of SBRT, followed by quality of life. Those with prior SBRT experience were keen for repeat treatment, if available, and emphasised SBRT's minimal side effects compared to other interventions.

Conclusion: While extension of life was the primary desired treatment outcome of SBRT for oligometastatic breast cancer , all participants were willing to consider SBRT for its minimal side effects and potential benefits in local control and durable pain control, even in the absence of a survival benefit.

Aims: Determining appropriate PTV margins for SBRT of liver metastases is a non-trivial task, especially with motion management included. The widely used analytical van Herk margin recipe (van Herk et al., 2000) could break down due to (i) a low number of fractions, (ii) non-Gaussian errors, or (iii) non-homogenous dose distributions. We evaluated the validity of the analytical margin recipe in this setting for two very different guidelines for SBRT of liver metastases in three fractions - one with a relatively homogenous dose within the PTV (British) and one allowing much steeper dose gradients within the PTV (Danish).

Materials and methods: We extracted sagittal motion traces for nineteen consecutive MR-guided and beam-gated treatments (57 fractions) on an MR-linac. We used these motion traces to calculate analytical van Herk GTV-to-PTV margins to account for intrafractional motion according to both British and Danish guidelines. We used the same motion traces to validate the analytical margins with motion-compensated dose accumulation in dose distributions obtained from British and Danish plans with varying PTV margins.

Results: Analytical margins for the British guidelines were 2.4 mm superior-inferiorly (SI) and 3.2 mm anterior-posteriorly (AP). For the Danish guidelines, analytical margins were 1.7 mm SI and 2.7 mm AP. Dose accumulation validation showed that a margin of 3 mm SI and 1.5 mm AP would have been sufficient for British plans to ensure 95% of the prescription dose to at least 99% of the GTV in 90% of the treatments (same criterion as used in the analytical calculation) of the patients. No PTV margin was needed to achieve the same with Danish guidelines.

Conclusion: GTV dose escalation can reduce the required motion-related PTV margins in SBRT with motion management. The van Herk margin recipe overestimates PTV margins in SBRT with inhomogeneous target dose distributions and becomes less applicable when the inhomogeneity increases.

Aims: Patient-centred radiotherapy refers to an approach where patients' needs and preferences are prioritised. Guidelines for this personalised approach are lacking. We present a multidisciplinary national consensus with the aim to provide recommendations for best practice in patient-centred radiotherapy for both clinical trials and routine practice.

Materials and methods: A multidisciplinary working group was formed, comprising of healthcare professionals and patient advocates with lived experience of radiotherapy. Three interlinking themes were identified around patient-centred radiotherapy: information, decision-making, and outcomes. Scoping reviews were carried out for each theme, considering current challenges and recommendations for best practice. Recommendations were shaped through consultation with 12 patient advocates.

Results: There is a pressing need to better support patients prior to, during, and following radiotherapy. Radiotherapy-related patient information is often complex and challenging to understand. Information resources should be cocreated with patient advocates and individualised wherever possible, including for patients from under-served groups. Shared decision-making (SDM) processes may enhance treatment satisfaction and reduce decision-regret, but these are not widely implemented. SDM requires prepared patients, trained teams, alongside adequate resources and should be offered as per patients' preferences. Healthcare system data offer complementary information to clinical trials, with the potential to provide additional insight into long-term benefits and risks of radiotherapy within 'real-world' conditions. Patient-reported outcome measures may provide greater insight regarding toxicity and impact on quality of life and should be used in synergy with clinician-reported outcomes. Outcome measures should be collected in the long term, and results should be widely disseminated to both the public and professional communities. Equity of access to radiotherapy, clinical trials, and survivorship services is a priority.

Conclusion: Patients rightly expect more from healthcare professionals, and it is important that the radiotherapy community recognises this and embraces changes which will enhance patient-centred care. Our recommendations aim to guide best practice for patient-centred radiotherapy.

Aims: Unresectable cutaneous squamous cell cancer of the head and neck (HNcSCC) poses treatment challenges in elderly and comorbid patients. Radiation therapy (RT) is often employed for locoregional control. This study aimed to determine progression-free survival (PFS) and overall survival (OS) outcomes achieved with upfront RT in unresectable HNcSCC. It also aimed to determine the impact of varying RT dose regimes on disease outcomes.

Methods: A retrospective cohort study was conducted of patients with unresectable HNcSCC treated with first-line RT at a tertiary teaching hospital in Sydney, Australia between 2015-2024. Patient, disease, treatment and follow-up data were extracted from the electronic records.

Results: Of 36 patients, 67% were male, median age was 81 years, and median Charlson Comorbidity Index was 6.5. Median follow-up was 21 months. 83% of RT courses were delivered via intensity-modulated radiation therapy (IMRT) or volumetric-modulated arc therapy (VMAT). Objective response rate was 97%. Patients were grouped into low-dose RT receiving biologically equivalent dose (BED) <60Gy (n = 18) or high-dose RT (BED ≥ 60Gy, n = 18). Infield progression-free survival (PFS) at 6 months was 56% and 78%, respectively. Overall survival at 6 months was 83% and 89%, and by 24 months 31% and 65%, respectively.

Conclusion: RT is an efficacious treatment that can be tailored to individual patient contexts with unresectable HNcSCC. It has a high response rate overall, with higher doses producing longer disease control. Some patients with poorer functional status receiving low-dose RT can still achieve a sustained response. Future comparisons of outcomes and cost-effectiveness with emerging treatments such as immunotherapy will be important in guiding management for frail patients with unresectable disease.

Aims: Ductal Carcinoma In Situ (DCIS) treated by breast-conserving surgery followed by radiotherapy aims to decrease the probability of locally recurrent disease. The role of whole breast irradiation, specifically in DCIS having low recurrence risk and low risk of becoming invasive, is increasingly debated. Also, the added value of applying boost irradiation in DCIS has been questioned. Hence, we evaluated the nationwide radiotherapy use in DCIS treatment in the Netherlands.

Materials and methods: Women diagnosed with DCIS in 2008-2022 were identified in the Netherlands Cancer Registry. Their primary treatment was presented over time and for age groups, stratified for DCIS grade I-II and III. Factors associated with radiotherapy use after breast-conserving surgery and boost irradiation use in whole breast irradiation after breast-conserving surgery were identified.

Results: In women with DCIS grade I-II (N = 16,653), the use of breast-conserving surgery without radiotherapy increased from ∼11% in 2008-2013 to ∼26% in 2017-2022. Furthermore, post-breast-conserving surgery radiotherapy increasingly concerned whole breast irradiation without a boost or partial breast irradiation. Moreover, surgery was omitted more often in recent years (30% in 2022). In DCIS grade III (N = 13,534), the use of breast-conserving surgery without radiotherapy only slightly increased in the most recent years in older patients, while boost irradiation was increasingly omitted. Whole breast irradiation and boost irradiation following breast-conserving surgery were more often applied in case of a higher risk of recurrences: young age, larger lesions, or irradical resection. Variation was observed for hospital-characteristics but not for regions.

Conclusion: In DCIS, the process of omitting breast irradiation after breast-conserving surgery is clearly ongoing. Boost irradiation was administered less frequently. Furthermore, the use of partial breast irradiation was introduced in recent years. These effects are more prominent in older women and those with grade I-II DCIS.

Aims: The SCOPE2 trial evaluates radiotherapy (RT) dose escalation for oesophageal cancer. We report findings from the accompanying RT quality assurance (RTQA) programme and identify recommendations for PROTIEUS, the next UK trial in oesophageal RT.

Maetrials and methods: SCOPE2's RTQA programme consisted of a pre-accrual and on-trial component. RTQA pre-accrual requirements included acceptable submission of 3D ± 4D benchmark contouring exercise(s) and a high-dose planning case. On-trial requirements for contouring and planning included prospective reviews (PRs) of each centre's first 3D ± 4D patient and all high-dose cases prior to formal safety review. Further PRs were at the RTQA team's discretion. Timely retrospective reviews (TRRs) were also undertaken for a random 10%. Submissions were assessed against pre-defined criteria and RT planning guidance document (RPGD). This study includes initial submissions only; subsequent resubmissions are not included in this analysis.

Results: For contouring, 30/64 (47%) pre-accrual submissions were approved. 38/64 (59%) contained ≥1 target volume (TV) unacceptable variation from protocol (UV), most commonly in CTVB and ITV. Organ-at-risk (OAR) contour review was undertaken in 28/64 (44%); 6/28 (21%) contained ≥1 UV, most commonly in heart and spinal cord. 82/126 (65%) on-trial submissions were approved. 47/126 (37%) contained ≥1 TV UV, most commonly in CTVB, GTV and ITV. For OARs, 30/126 (24%) contained ≥1 UV, most commonly in heart and lungs. On-trial contour submissions were significantly more likely to be approved than pre-accrual (p = 0.016). For planning, 32/43 (79%) pre-accrual plans were approved, those unacceptable were due to PTV coverage/conformity. 118/120 (98%) on-trial plans were approved, the remaining unacceptable were due to PTV coverage/conformity. No UVs in OAR dose constraints were observed. All on-trial submissions were approved following resubmission where necessary.

Conclusion: Despite an RPGD, contouring atlas, and similar contouring protocols from preceding trials, the SCOPE2 RTQA programme demonstrates a high frequency of UVs. Our findings inform recommendations for future oesophageal RT trials.