M.V. Maraldo

How do we move towards a personalised approach in the treatment of Early Hodgkin lymphoma

Early stage Hodgkin Lymphoma (HL) is one of the great successes in modern oncology with the vast majority of patients cured of their disease. Given the success of initial therapy, the approach towards management has therefore increasingly focused on the quality of long term survival, where a high rate of treatment-induced mortality and morbidity has been observed (Schaapveld et al, 2015). This has led to the observation in long-term follow-up that more patients are dying from the consequences of treatment than HL (Aleman et al, 2003). These late effects most often occur decades following treatment and are most well documented with higher dose extended radiation fields, which have long since been abandoned in the modern era of lower dose involved site radiotherapy (RT) (Specht et al, 2014). Current treatment protocols aim to balance the best chance of cure, using well established combined modality therapy (CMT) approaches of short course chemotherapy followed by low dose RT (Eich et al, 2010; Engert et al, 2010) against the risk of late effects, which are mostly considered to be secondary to RT. Therefore, CMT is now being challenged for a select group of patients using chemotherapy alone (CA), where the risk of adding RT is considered to outweigh the modest benefits of improvements in disease control (Radford et al, 2015). In order to quantitatively evaluate the risks and benefits with these different treatment options of CMT or CA, it is necessary to know the effect of modern treatment, integrating clinical risk and imaging biomarkers, such as F-fluorodeoxyglucose positron emission tomography/computed tomography response, to help in the assessment of benefit of improved initial HL eradication over the risks associated with late effects, which will differ between patients according to age, sex, site of disease, comorbidities and, importantly, patient preferences. The article by Parsons et al (2018) on the treatment approaches to early stage HL in the modern era using simulation modelling to help delineate long-term patient outcome is an important contribution in moving towards this personalised decision making. Here, the long-term outcomes are modelled for two patients with early stage HL treated with CMT vs. CA. The simulation aims to illustrate the differences in the individual risks and benefits associated with gender, age, and disease localization in the modern treatment era in order to better help facilitate treatment decisions for our patients. The study presents a method to move from our previous population-specific risk/benefit approach to a more personalized approach by considering the effects of primary as well as relapse treatment on an immediate and a long-time scale. A word of caution is, however, necessary in the interpretation of the results. As in all modelling studies, the model is only a reflection of the input data and when complex clinical outcome scenarios are modelled, a multitude of underlying assumption must be made. Here, it is important to know that the immediate outcome data originate from two recent adult trials, the UK-RAPID (Randomised Phase III Trial to Determine the Role of FDG– PET Imaging in Clinical Stages IA/IIA Hodgkin’s Disease) and the European Organization for Research and Treatment of Cancer (EORTC) H10 trial (Radford et al, 2015; Andre et al, 2017), whereas the paediatric data originate from the older Children’s Cancer Group (CCG) 5942 trial (Nachman et al, 2002) and the long-term outcome data originate from the updates on the CCG 5942 and the older National Cancer Institute of Canada-Eastern Cooperative Oncology Group (NCIC-ECOG) HD.6 trials (Meyer et al, 2011; Wolden et al, 2012). Certainly, only the two more recent trials reflect our current staging, treatment and evaluation standards for HL. The current study is an innovative approach to treatment optimisation and, despite the limitations in its applicability to clinical practice given the intrinsic limitations of the model itself, it should be viewed as a proof-of-concept in Correspondence: Dr Maja V. Maraldo, Department of Clinical Oncology, University of Copenhagen, Blegdamsvej 9, Copenhagen 2100, Denmark E-mail: dra.maraldo@gmail.com editorial comment

Deep inspiration breath-hold volumetric modulated arc radiotherapy decreases dose to mediastinal structures in locally advanced lung cancer

Concomitant radio-chemotherapy is the standard treatment for locally advanced non-small cell lung cancer (NSCLC), with a five-year survival of only approximately 15–20% [1]. Several clinical studies have indicated a positive dose-response relationship with an improved survival with higher dose [2,3]. However, evidence of mediastinal toxicity is accumulating: The phase III dose escalation trial RTOG 0617 [4] showed that heart dose parameters were correlated to death in a multivariate analysis and in a dose escalation trial by Cannon et al. [5] serious late toxicity from central and perihilar structures was encountered. In breast cancer radiotherapy a large population-based case-control study showed an increased risk of major cardiac events with increasing heart dose [6]. During deep inspiration breath-hold (DIBH), the lungs are inflated and the heart displaced caudally and these anatomical changes can be exploited to achieve a lower radiation dose to the intra-thoracic normal tissue. Several reports have shown that DIBH radiotherapy (RT) is a feasible alternative and has the potential of decreasing the lung dose in conventional three-dimensional conformal radiotherapy (3D-CRT) [7–9] and also with volumetric modulated arc therapy (VMAT) [10]. Furthermore, DIBH RT does not acquire a lot of time [11] or economical resources for implementation. We previously reported preliminary results from the first 10 patients included in this study and found a statistically significant reduction of mean lung dose with DIBH 3D-CRT as well as with VMAT in patients with locally advanced NSCLC [12]. The combination of DIBH and VMAT reduced these parameters further and DIBH mitigated the low dose bath induced by VMAT. Most previous studies have focused on dose to the lungs and none of them have reported on dose to bronchi and trachea. In this final report, we examine if DIBH-VMAT holds potential to decrease doses to mediastinal organs at risk (OAR) compared to free breathing (FB) VMAT.