The need for multidisciplinarity in specialist training to optimize future patient care

Harmonious interactions between radiation, medical, interventional and surgical oncologists, as well as other members of multidisciplinary teams, are essential for the optimization of patient care in oncology. This multidisciplinary approach is particularly important in the current landscape, in which standard-of-care approaches to cancer treatment are evolving towards highly targeted treatments, precise image guidance and personalized cancer therapy. Herein, we highlight the importance of multidisciplinarity and interdisciplinarity at all levels of clinical oncology training. Potential deficits in the current career development pathways and suggested strategies to broaden clinical training and research are presented, with specific emphasis on the merits of trainee involvement in functional multidisciplinary teams. Finally, the importance of training in multidisciplinary research is discussed, with the expectation that this awareness will yield the most fertile ground for future discoveries. Our key message is for cancer professionals to fulfil their duty in ensuring that trainees appreciate the importance of multidisciplinary research and practice

The Association between Acute and Late Genitourinary and Gastrointestinal Toxicities: An Analysis of the PACE B Study

Several studies have demonstrated the association between acute and late radiotherapy toxicity in prostate cancer using older radiotherapy techniques. However, whether this association is present with newer techniques such as stereotactic body radiotherapy (SBRT), remains unclear. We use univariable and multivariable logistic regression to analyse the association between grade 2 or worse acute gastrointestinal (GI) and genitourinary (GU) toxicities with equivalent late toxicities in patients treated with SBRT and conventional or moderately fractionated radiotherapy (CRT) within the PACE-B study. 842 patients were included in this analysis. Common Terminology Criteria for Adverse Events (CTCAE) was the primary clinician reported outcome measure used in this analysis. In univariable analysis, experiencing a grade 2+ acute GU toxicity was significantly associated with developing a grade 2+ late GU toxicity after SBRT (OR 4.63, 95% CI (2.96–7.25), p < 0.0001) and CRT (OR 2.83, 95% CI (1.69–4.71), p < 0.0001). This association remained significant in multivariable analysis. In univariable analysis, experiencing a grade 2+ acute GI toxicity was also associated with developing a grade 2+ late GI toxicity after SBRT (OR 3.67, 95% CI (1.91–7.03), p < 0.0001) and CRT (OR 4.4, 95% CI (2.04–9.47), p < 0.0001). This association also remained significant in multivariable analysis. Grade 2+ baseline GU symptoms were also associated with grade 2+ late urinary toxicity in both univariable and multivariable analysis. Overall, acute toxicity is an important predictor variable for late GU/GI toxicity after localised prostate radiotherapy using SBRT and CRT. Future work should test whether optimising symptoms pre-treatment and early intervention in those with significant acute toxicities could mitigate the development late of toxicity

Stereotactic body radiotherapy for primary prostate cancer

Prostate cancer is the most common non-cutaneous cancer in males. There are a number of options for patients with localized early stage disease, including active surveillance for low-risk disease, surgery, brachytherapy, and external beam radiotherapy. Increasingly, external beam radiotherapy, in the form of dose-escalated and moderately hypofractionated regimens, is being utilized in prostate cancer, with randomized evidence to support their use. Stereotactic body radiotherapy, which is a form of extreme hypofractionation, delivered with high precision and conformality typically over 1 to 5 fractions, offers a more contemporary approach with several advantages including being non-invasive, cost-effective, convenient for patients, and potentially improving patient access. In fact, one study has estimated that if half of the patients currently eligible for conventional fractionated radiotherapy in the United States were treated instead with stereotactic body radiotherapy, this would result in a total cost savings of US$250 million per year. There is also a strong radiobiological rationale to support its use, with prostate cancer believed to have a low alpha/beta ratio and therefore being preferentially sensitive to larger fraction sizes. To date, there are no published randomized trials reporting on the comparative efficacy of stereotactic body radiotherapy compared to alternative treatment modalities, although multiple randomized trials are currently accruing. Yet, early results from the randomized phase III study of HYPOfractionated RadioTherapy of intermediate risk localized Prostate Cancer (HYPO-RT-PC) trial, as well as multiple single-arm phase I/II trials, indicate low rates of late adverse effects with this approach. In patients with low-to intermediate-risk disease, excellent biochemical relapse-free survival outcomes have been reported, albeit with relatively short median follow-up times. These promising early results, coupled with the enormous potential cost savings and implications for resource availability, suggest that stereotactic body radiotherapy will take center stage in the treatment of prostate cancer in the years to come

Weekly ultra-hypofractionated radiotherapy in localised prostate cancer

Background: Moderately hypofractionated radiotherapy regimens or stereotactic body radiotherapy (SBRT) are standard of care for localised prostate cancer. However, some patients are unable or unwilling to travel daily to the radiotherapy department and do not have access to, or are not candidates for, SBRT. For many years, The Royal Marsden Hospital NHS Foundation Trust has offered a weekly ultra-hypofractionated radiotherapy regimen to the prostate (36 Gy in 6 weekly fractions) to patients unable/unwilling to travel daily. Methods: The current study is a retrospective analysis of all patients with non-metastatic localised prostate cancer receiving this treatment schedule from 2010 to 2015. Results: A total of 140 patients were included in the analysis, of whom 86 % presented with high risk disease, with 31 % having Gleason Grade Group 4 or 5 disease and 48 % T3 disease or higher. All patients received hormone treatment, and there was often a long interval between start of hormone treatment and start of radiotherapy (median of 11 months), with 34 % of all patients having progressed to non-metastatic castrate-resistant disease prior to start of radiotherapy. Median follow-up was 52 months. Median progression-free survival (PFS) and overall survival (OS) for the whole group was 70 months and 72 months, respectively. PFS and OS in patients with hormone-sensitive disease at time of radiotherapy was not reached and 75 months, respectively; and in patients with castrate-resistant disease at time of radiotherapy it was 20 months and 61 months, respectively. Conclusion: Our data shows that a weekly ultra-hypofractionated radiotherapy regimen for prostate cancer could be an option in those patients for whom daily treatment or SBRT is not an option

Is the digital rectal exam any good as a prostate cancer screening test?

© The Author(s). This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY), https://creativecommons.org/licenses/by/4.0/There is no shortage of references in popular culture to the prostate examination, with many a laugh built on the punchline of the finger up the bum. Interestingly, while cervical, breast, or bowel screening share barriers to uptake around the intimacy of the examination, ‘ick-factor’, or cultural taboos, they have never become comedy tropes — reflecting the uniquely emasculating perception of the rectal examination.Peer reviewe

Systematic Review and Meta-analysis of the Association Between Radiation Therapy Treatment Volume and Patient Outcomes

Purpose: Evidence of a volume–outcome association in cancer surgery has shaped the centralization of cancer services; however, it is unknown whether a similar association exists for radiation therapy. The objective of this study was to determine the association between radiation therapy treatment volume and patient outcomes. Methods and Materials: This systematic review and meta-analysis included studies that compared outcomes of patients who underwent definitive radiation therapy at high-volume radiation therapy facilities (HVRFs) versus low-volume facilities (LVRFs). The systematic review used Ovid MEDLINE and Embase. For the meta-analysis, a random effects model was used. Absolute effects and hazard ratios (HRs) were used to compare patient outcomes. Results: The search identified 20 studies assessing the association between radiation therapy volume and patient outcomes. Seven of the studies looked at head and neck cancers (HNCs). The remaining studies covered cervical (4), prostate (4), bladder (3), lung (2), anal (2), esophageal (1), brain (2), liver (1), and pancreatic cancer (1). The meta-analysis demonstrated that HVRFs were associated with a lower chance of death compared with LVRFs (pooled HR, 0.90; 95% CI, 0.87- 0.94). HNCs had the strongest evidence of a volume–outcome association for both nasopharyngeal cancer (pooled HR, 0.74; 95% CI, 0.62-0.89) and nonnasopharyngeal HNC subsites (pooled HR, 0.80; 95% CI, 0.75-0.84), followed by prostate cancer (pooled HR, 0.92; 95% CI, 0.86-0.98). The remaining cancer types showed weak evidence of an association. The results also demonstrate that some centers defined as HVRFs are undertaking very few procedures per annum (<5 radiation therapy cases per year). Conclusions: An association between radiation therapy treatment volume and patient outcomes exists for most cancer types. Centralization of radiation therapy services should be considered for cancer types with the strongest volume–outcome association, but the effect on equitable access to services needs to be explicitly considered

Estimates of Alpha/Beta (alpha/beta) Ratios for Individual Late Rectal Toxicity Endpoints: An Analysis of the CHHiP Trial

Purpose: Changes in fraction size of external beam radiation therapy exert nonlinear effects on subsequent toxicity. Commonly described by the linear-quadratic model, fraction size sensitivity of normal tissues is expressed by the α/β ratio. We sought to study individual α/β ratios for different late rectal effects after prostate external beam radiation therapy. Methods and Materials: The CHHiP trial (ISRCTN97182923) randomized men with nonmetastatic prostate cancer 1:1:1 to 74 Gy/37 fractions (Fr), 60 Gy/20 Fr, or 57 Gy/19 Fr. Patients in the study had full dosimetric data and zero baseline toxicity. Toxicity scales were amalgamated to 6 bowel endpoints: bleeding, diarrhea, pain, proctitis, sphincter control, and stricture. Lyman-Kutcher-Burman models with or without equivalent dose in 2 Gy/Fr correction were log-likelihood fitted by endpoint, estimating α/β ratios. The α/β ratio estimate sensitivity was assessed using sequential inclusion of dose modifying factors (DMFs): age, diabetes, hypertension, inflammatory bowel or diverticular disease (IBD/diverticular), and hemorrhoids. 95% confidence intervals (CIs) were bootstrapped. Likelihood ratio testing of 632 estimator log-likelihoods compared the models. Results: Late rectal α/β ratio estimates (without DMF) ranged from bleeding (G1 + α/β = 1.6 Gy; 95% CI, 0.9-2.5 Gy) to sphincter control (G1 + α/β = 3.1 Gy; 95% CI, 1.4-9.1 Gy). Bowel pain modelled poorly (α/β, 3.6 Gy; 95% CI, 0.0-840 Gy). Inclusion of IBD/diverticular disease as a DMF significantly improved fits for stool frequency G2+ (P = .00041) and proctitis G1+ (P = .00046). However, the α/β ratios were similar in these no-DMF versus DMF models for both stool frequency G2+ (α/β 2.7 Gy vs 2.5 Gy) and proctitis G1+ (α/β 2.7 Gy vs 2.6 Gy). Frequency-weighted averaging of endpoint α/β ratios produced: G1 + α/β ratio = 2.4 Gy; G2 + α/β ratio = 2.3 Gy. Conclusions: We estimated α/β ratios for several common late adverse effects of rectal radiation therapy. When comparing dose-fractionation schedules, we suggest using late a rectal α/β ratio ≤ 3 Gy

Improving performance in radiation oncology: An international systematic review of quality improvement interventions.

National cancer audits and registers have highlighted significant national and international variation in patient care and outcomes. Quality Improvement (QI) is mandated in radiation oncology but the interventions designed to support QI in this field remain poorly understood. This paper seeks to assess the types of QI interventions in radiation oncology, the QI evaluation design and their impact on process of care measures and patient-related outcomes. MEDLINE and EMBASE were searched systematically for studies of QI interventions in radiation oncology between 2000 and 2024. The studies needed to identify the quantitative or qualitative impact of the QI intervention on process of care measures or patient-related outcomes. Study results were summarised using narrative synthesis and appraised using the Quality Improvement Minimum Quality Criteria Set (QI-MQCS). 26 papers were included in the analysis. The majority of studies were conducted in the USA (n = 13) and in Europe (n = 7), with only two studies conducted at a national level. Ten studies covered all tumour types, with six specifically focusing on head and neck cancers, two each on prostate and nasopharyngeal cancers, and one study each examining lung, cervical, rectal, and breast cancers. The aspects of care evaluated most frequently were those relating to reducing waiting times or increasing utilisation of radiotherapy as per guidelines (n = 15), followed by those seeking to reduce radiotherapy contouring variability (n = 5) and those involving the management of symptoms during or after radiotherapy treatment (n = 6). Only 42 % of studies reported funding, with the most frequent funding source being national, government or federal (n = 6). All QI interventions across the 26 studies were successful as they resulted in an improvement in a process or patient-related outcome measure. The studies scored between 10 and 15 out of 16, according to the QI-MQCS criteria. Despite substantial investments in cancer research and development, there is a scarcity of information on how to enhance the quality of care in radiation oncology. While there are examples of national cancer audits and registers in a number of countries, much of the research in QI interventions is being conducted in the USA. This situation underscores the need for more comprehensive, well-funded studies and improved training for clinicians to conduct high-quality improvement activities and research. There should be a greater emphasis on the substantial gains that can be achieved by improving existing care in terms of access and outcomes, rather than solely focusing on innovation

Stereotactic body radiotherapy for Ultra-Central lung Tumors: A systematic review and Meta-Analysis and International Stereotactic Radiosurgery Society practice guidelines

BACKGROUND Stereotactic body radiotherapy (SBRT) is an effective and safe modality for early-stage lung cancer and lung metastases. However, tumors in an ultra-central location pose unique safety considerations. We performed a systematic review and meta-analysis to summarize the current safety and efficacy data and provide practice recommendations on behalf of the International Stereotactic Radiosurgery Society (ISRS). METHODS We performed a systematic review using PubMed and EMBASE databases of patients with ultra-central lung tumors treated with SBRT. Studies reporting local control (LC) and/or toxicity were included. Studies with <5 treated lesions, non-English language, re-irradiation, nodal tumors, or mixed outcomes in which ultra-central tumors could not be discerned were excluded. Random-effects meta-analysis was performed for studies reporting relevant endpoints. Meta-regression was conducted to determine the effect of various covariates on the primary outcomes. RESULTS 602 unique studies were identified of which 27 (one prospective observational, the remainder retrospective) were included, representing 1183 treated targets. All studies defined ultra-central as the planning target volume (PTV) overlapping the proximal bronchial tree (PBT). The most common dose fractionations were 50 Gy/5, 60 Gy/8, and 60 Gy/12 fractions. The pooled 1- and 2-year LC estimates were 92 % and 89 %, respectively. Meta-regression identified biological effective dose (BED10) as a significant predictor of 1-year LC. A total of 109 grade 3-4 toxicity events, with a pooled incidence of 6 %, were reported, most commonly pneumonitis. There were 73 treatment related deaths, with a pooled incidence of 4 %, with the most common being hemoptysis. Anticoagulation, interstitial lung disease, endobronchial tumor, and concomitant targeted therapies were observed risk factors for fatal toxicity events. CONCLUSION SBRT for ultra-central lung tumors results in acceptable rates of local control, albeit with risks of severe toxicity. Caution should be taken for appropriate patient selection, consideration of concomitant therapies, and radiotherapy plan design

Genitourinary α/β Ratios in the CHHiP Trial the Fraction Size Sensitivity of Late Genitourinary Toxicity: Analysis of Alpha/Beta (α/β) Ratios in the CHHiP Trial

PURPOSE: Moderately hypofractionated external beam intensity-modulated radiotherapy (IMRT) for prostate cancer is now standard-of-care. Normal tissue toxicity responses to fraction size alteration are non-linear: the linear-quadratic model is a widely-used framework accounting for this, through the α/β ratio. Few α/β ratio estimates exist for human late genitourinary endpoints; here we provide estimates derived from a hypofractionation trial. METHODS AND MATERIALS: The XXXXXX trial randomised 3216 men with localised prostate cancer 1:1:1 between conventionally fractionated IMRT (74Gy/37 fractions (Fr)) and two moderately hypofractionated regimens (60Gy/20Fr & 57Gy/19Fr). Radiotherapy plan and suitable follow-up assessment was available for 2206 men. Three prospectively assessed clinician-reported toxicity scales were amalgamated for common genitourinary endpoints: Dysuria, Haematuria, Incontinence, Reduced flow/Stricture, Urine Frequency. Per endpoint, only patients with baseline zero toxicity were included. Three models for endpoint grade ≥1 (G1+) and G2+ toxicity were fitted: Lyman Kutcher-Burman (LKB) without equivalent dose in 2Gy/Fr (EQD2) correction [LKB-NoEQD2]; LKB with EQD2-correction [LKB-EQD2]; LKB-EQD2 with dose-modifying-factor (DMF) inclusion [LKB-EQD2-DMF]. DMFs were: age, diabetes, hypertension, pelvic surgery, prior transurethral resection of prostate (TURP), overall treatment time and acute genitourinary toxicity (G2+). Bootstrapping generated 95% confidence intervals and unbiased performance estimates. Models were compared by likelihood ratio test. RESULTS: The LKB-EQD2 model significantly improved performance over LKB-NoEQD2 for just three endpoints: Dysuria G1+ (α/β=2.0 Gy, 95%CI 1.2-3.2Gy), Haematuria G1+ (α/β=0.9 Gy, 95%CI 0.1-2.2Gy) and Haematuria G2+ (α/β=0.6Gy, 95%CI 0.1-1.7Gy). For these three endpoints, further incorporation of two DMFs improved on LKB-EQD2: acute genitourinary toxicity and Prior TURP (Haematuria G1+ only), but α/β ratio estimates remained stable. CONCLUSIONS: Inclusion of EQD2-correction significantly improved model fitting for Dysuria and Haematuria endpoints, where fitted α/β ratio estimates were low: 0.6-2 Gy. This suggests therapeutic gain for clinician-reported GU toxicity, through hypofractionation, might be lower than expected by typical late α/β ratio assumptions of 3-5 Gy