TORPEdO: A phase III trial of intensity-modulated proton beam therapy versus intensity-modulated radiotherapy for multi-toxicity reduction in oropharyngeal cancer.

•There is a lack of prospective level I evidence for the use of PBT for most adult cancers including oropharyngeal squamous cell carcinoma (OPSCC).•TORPEdO is the UK's first PBT clinical trial and aims to determine the benefits of PBT for OPSCC.•Training and support has been provided before and during the trial to reduce variations of contouring and radiotherapy planning.•There is a strong translational component within TORPEdO. Imaging and physics data along with blood, tissue collection will inform future studies in refining patient selection for IMPT.

Digital Patient-Reported Outcome Measures for Monitoring of Patients on Cancer Treatment: Cross-sectional Questionnaire Study.

BACKGROUND: Oncology has been facing increasing outpatient activity associated with higher cancer incidence, better survival rates, and more treatment options. Innovative technological solutions could help deal with this increasing demand. Using digital patient-reported outcome measures (PROMs) to identify patients who need a face-to-face (FTF) appointment is a potential approach. OBJECTIVE: This study aims to assess the feasibility of digital PROM questionnaires to enable remote symptom monitoring for patients undergoing cancer treatment and their ability to highlight the requirement for an FTF appointment. METHODS: This study was performed at a tertiary oncology center between December 2018 and February 2019. The Common Terminology Criteria for Adverse Events were adapted into patient-friendly language to form the basis of treatment-specific digital questionnaires covering specific cancer drugs and radiotherapy treatments. These treatment-specific digital PROM questionnaires were scored by both patients and their clinicians during FTF appointments. Patients and clinicians did not see each other's scored PROMs. Agreement between patients and clinicians was assessed using descriptive statistics. Patient and staff feedback was also obtained. RESULTS: In total, 90 patients participated in the study across 10 different treatment pathways. By comparing paired patient and clinician responses, the sensitivity of the patient-completed questionnaires in correctly highlighting the need for FTF review was 94% (44/47), and all patients with severe or grade 3+ symptoms were identified (6/6, 100%). Patient-completed PROMs appropriately revealed that 29% (26/90) of the participating patients did not need FTF review based on their symptoms alone. Certain oncological treatment pathways, such as immunotherapy, were found to have a larger proportion of patients with minimal symptoms than others, such as conventional chemotherapy. Patient and staff feedback showed high approval of digital PROMs and their potential for use in remote monitoring. CONCLUSIONS: Digital PROM questionnaires can feasibly highlight the need for FTF review in oncology clinics for treatment. Their use with specific treatments could safely reduce the requirement for FTF care, and future work should evaluate their application in the remote monitoring of patients.

Use of Teleconsultations in a Regional Stereotactic Radiosurgery Service: Pilot Study.

BACKGROUND: The National Health Service Long Term Plan details plans to make digital interactions available to all patients in 5 years. Teleconsultations can improve access to specialist services; however, there is a lack of evidence for the use of teleconsultations in an oncology setting in the United Kingdom. OBJECTIVE: We aim to describe a service evaluation of teleconsultations for patients attending a regional brain metastases clinic. These patients have unique travel restrictions that prevent them from driving. METHODS: From April to October 2018, all patients attending the brain metastases clinic were offered the choice of teleconsultation in place of a face-to-face appointment. Feedback was assessed using a satisfaction questionnaire, and data of all clinic attendances were collected. RESULTS: A total of 69 individual patients had 119 appointments over the duration of the pilot, of which 36 (30.2%) were new patient appointments and 73 (61.3%) were follow-ups. Of the 69 patients, 24 (35%) took part in teleconsultations (41/119, 34.5%). User satisfaction was high, and no patients who took part in a teleconsultation reverted to face-to-face appointments. These patients avoided 2521 miles (61.6 miles per appointment) of hospital-associated travel and travel costs of £441.48 (US $599.83) to £10.78 (US $14.65) per appointment. CONCLUSIONS: Teleconsultations appear to be acceptable in this cohort of patients with brain metastases attending a regional stereotactic radiosurgery service with the potential for significant savings in travel and expenses.

The Use of Patient-Facing Teleconsultations in the National Health Service: Scoping Review.

BACKGROUND: The National Health Service (NHS) Long-Term Plan has set out a vision of enabling patients to access digital interactions with health care professionals within 5 years, including by video link. OBJECTIVE: This review aimed to examine the extent and nature of the use of patient-facing teleconsultations within a health care setting in the United Kingdom and what outcome measures have been assessed. METHODS: We conducted a systematic scoping review of teleconsultation studies following the Joanna Briggs Institute methodology. PubMed, Scopus, the Cochrane Library, and the Cumulative Index to Nursing and Allied Health Literature were searched up to the end of December 2018 for publications that reported on the use of patient-facing teleconsultations in a UK health care setting. RESULTS: The search retrieved 3132 publications, of which 101 were included for a full review. Overall, the studies were heterogeneous in design, in the specialty assessed, and reported outcome measures. The technology used for teleconsultations changed over time with earlier studies employing bespoke, often expensive, solutions. Two-thirds of the studies, conducted between 1995 and 2005, used this method. Later studies transitioned to Web-based commercial solutions such as Skype. There were five outcome measures that were assessed: (1) technical feasibility, (2) user satisfaction, (3) clinical effectiveness, (4) cost, (5) logistical and operational considerations. Due to the changing nature of technology over time, there were differing technical issues across the studies. Generally, teleconsultations were acceptable to patients, but this was less consistent among health care professionals. However, among both groups, face-to-face consultations were still seen as the gold standard. A wide range of clinical scenarios found teleconsultations to be clinically useful but potentially limited to more straightforward clinical interactions. Due to the wide array of study types and changes in technology over time, it is difficult to draw definitive conclusions on the cost involved. However, cost savings for health care providers have been demonstrated by the goal-directed implementation of teleconsultations. The integration of technology into routine practice represents a complex problem with barriers identified in funding and hospital reimbursement, information technologies infrastructure, and integration into clinicians' workflow. CONCLUSIONS: Teleconsultations appear to be safe and effective in the correct clinical situations. Where offered, it is likely that patients will be keen to engage, although teleconsultations should only be offered as an option to support traditional care models rather than replace them outright. Health care staff should be encouraged and supported in using teleconsultations to diversify their practice. Health care organizations need to consider developing a digital technology strategy and implementation groups to assist health care staff to integrate digitally enabled care into routine practice. The introduction of new technologies should be assessed after a set period with service evaluations, including feedback from key stakeholders.

Defining patterns of care in the management of patients with brain metastases in a large oncology centre: A single-centre retrospective audit of 236 cases.

AIMS: The role of selected treatments for brain metastases (BM) is well documented; however, the prevalence of these is not. We report on the patterns of care in the management of BM in a large oncology centre. MATERIALS AND METHODS: We retrospectively audited 236 cases of newly diagnosed BM from January 2016 to December 2017 by looking at 2 years of radiology reports and gathered data on primary site, survival, treatment received, palliative care input and brain metastases-related admissions. RESULTS: Eighty-two per cent of cases were related to lung, breast and melanoma primaries. Half of patients received a form of treatment with the other half receiving best supportive care. Of these, whole-brain radiotherapy (39%) and stereotactic radiosurgery (40%) were the most common treatment modalities. Most common reasons for admissions were headaches, seizures, weakness and confusion. CONCLUSION: This is the first study in the UK that gives an in-depth overview of the real-world management of brain metastases. We have demonstrated the prevalence of treatment across the spectrum of brain metastases patients. Radiotherapy is the mainstay of treatment in nearly 80% of cases; however, care needs to be taken in ensuring that SRS is offered to those who are suitable.

Hypoxia imaging with [18F]HX4 PET in squamous cell head and neck cancers: a pilot study for integration into treatment planning.

BACKGROUND: Radical chemoradiotherapy is the primary treatment for head and neck cancers in many hospitals. Tumour hypoxia causes radiotherapy resistance and is an indicator of poor prognosis for patients. Identifying hypoxia to select patients for intensified or hypoxia-modified treatment regimens is therefore of high clinical importance. PATIENTS AND METHODS: We evaluated hypoxia in a group of patients with newly diagnosed squamous cell head and neck cancer using the hypoxia-selective radiotracer [F]HX4. Patients underwent a single [F]HX4 PET/computed tomography scan prior to beginning chemoradiotherapy. RESULTS: Three out of eight patients recruited were scanned with [F]HX4. Two out of three had pretreatment [F]FDG PET/computed tomography scans available for review. [F]HX4 tumour uptake varied between patients, with tumour to mediastinal ratios ranging from 1 to 3.5. CONCLUSION: The spectrum of [F]HX4 uptake in this small series of patients exemplifies the difference in oxygenation profiles between histologically similar tumours. Performing an additional PET scan with [F]HX4 prior to chemoradiotherapy treatment was logistically challenging in a routine setting, and therefore validation of its clinical impact should be the focus of future studies [EudraCT number 2013-003563-58].

Effective avoidance of a functional spect-perfused lung using intensity modulated radiotherapy (IMRT) for non-small cell lung cancer (NSCLC): an update of a planning study.

IMRT and 3-dimensional conformal radiotherapy (3-DCRT) plans of 25 patients with non-small cell lung (NSCLC) were compared in terms of planning target volume (PTV) coverage and sparing of functional lung (FL) defined by a SPECT perfusion scan. IMRT resulted in significant reduction of functional V(20) and mean lung dose in stage III patients with inhomogeneous hypoperfusion. If the dose to FL is shown to be the determinant of lung toxicity, IMRT would allow for effective dose escalation by specific avoidance of functional lung.

Defining the margins in the radical radiotherapy of non-small cell lung cancer (NSCLC) with active breathing control (ABC) and the effect on physical lung parameters.

BACKGROUND: The effectiveness of ABC has been traditionally measured as the reduction in internal margin (IM) within the planning target volume (PTV). Not to overestimate the benefit of ABC, the effect of patient movement during treatment also needs to be taken into account. We determined the IM and set-up error with ABC and the effect on physical lung parameters compared to standard margins used with free breathing. We also assessed interfraction oesophageal movement to determine a planning organ at risk volume (PRV). MATERIALS AND METHODS: Two sequential studies were performed using ABC in NSCLC patients suitable for radical radiotherapy (RT). Twelve out of 14 patients in Study 1 had tumours visible fluoroscopically and had intrafraction tumour movement assessed with and without ABC. Sixteen patients were recruited to Study 2 and had interfraction tumour movement measured using ABC in a moderate deep inspiration breath-hold, of these 7 patients also had interfraction oesophageal movement recorded. Interfraction movement was assessed by CT scan prior to and in the middle and final week of RT. Displacement of the tumour centre of mass and oesophageal borders relative to the first scan provided a measure of movement. Set-up error was measured in 9 patients treated with an in-house lung board adapted for the ABC device. Combining movement and set-up errors determined PTV and PRV margins with ABC. The effect of ABC on mean lung dose (MLD), lung V20 and V13 was calculated. RESULTS: ABC in a moderate deep inspiration breath-hold was tolerated in 25 out of 30 patients (83%) in Study 1 and 2. The random contribution of periodic tumour motion was reduced by 90% in the y direction with ABC compared to free-breathing. The magnitude of motion reduction was less in the x and z direction. Combining the systematic and random set-up error in quadrature with the systematic and random intrafraction and interfraction tumour variations with ABC results in a PTV margin of 8.3mm in the x direction, 12.0mm in the y direction and 9.8mm in the z direction. There was a relative mean reduction in MLD, lung V20 and V13 of 25%, 21% and 18% with the ABC PTV compared to a free-breathing PTV. Oesophageal movement combined with set-up error resulted in an isotropic PRV of 4.7 mm. CONCLUSIONS: The reduction in PTV size with ABC resulted in an 18-25% relative reduction in physical lung parameters. PTV margin reduction has the potential to spare normal lung and allow dose-escalation if coupled with image-guided RT. The oesophageal PRV needs to be considered when irradiating central disease and is of increasing importance with altered RT fractionation and concomitant chemoradiation schedules. Further reductions in PTV and PRV may be possible if patient set-up error was minimised, confirming that attention to patient immobilisation is as important as attempts to control tumour motion.

A potential to reduce pulmonary toxicity: the use of perfusion SPECT with IMRT for functional lung avoidance in radiotherapy of non-small cell lung cancer.

BACKGROUND AND PURPOSE: The study aimed to examine specific avoidance of functional lung (FL) defined by a single photon emission computerized tomography (SPECT) lung perfusion scan, using intensity modulated radiotherapy (IMRT) and three-dimensional conformal radiotherapy (3-DCRT) in patients with non-small cell lung cancer (NSCLC). MATERIALS AND METHODS: Patients with NSCLC underwent planning computerized tomography (CT) and lung perfusion SPECT scan in the treatment position using fiducial markers to allow co-registration in the treatment planning system. Radiotherapy (RT) volumes were delineated on the CT scan. FL was defined using co-registered SPECT images. Two inverse coplanar RT plans were generated for each patient: 4-field 3-DCRT and 5-field step-and-shoot IMRT. 3-DCRT plans were created using automated AutoPlan optimisation software, and IMRT plans were generated employing Pinnacle(3) treatment planning system (Philips Radiation Oncology Systems). All plans were prescribed to 64 Gy in 32 fractions using data for the 6 MV beam from an Elekta linear accelerator. The objectives for both plans were to minimize the volume of FL irradiated to 20 Gy (fV(20)) and dose variation within the planning target volume (PTV). A spinal cord dose was constrained to 46 Gy. Volume of PTV receiving 90% of the prescribed dose (PTV(90)), fV(20), and functional mean lung dose (fMLD) were recorded. The PTV(90)/fV(20) ratio was used to account for variations in both measures, where a higher value represented a better plan. RESULTS: Thirty-four RT plans of 17 patients with stage I-IIIB NSCLC suitable for radical RT were analysed. In 6 patients with stage I-II disease there was no improvement in PTV(90), fV(20), PTV/fV(20) ratio and fMLD using IMRT compared to 3-DCRT. In 11 patients with stage IIIA-B disease, the PTV was equally well covered with IMRT and 3-DCRT plans, with IMRT producing better PTV(90)/fV(20) ratio (mean ratio - 7.2 vs. 5.3, respectively, p=0.001) and reduced fMLD figures compared to 3-DCRT (mean value - 11.5 vs. 14.3 Gy, p=0.001). This was due to reduction in fV(20) while maintaining PTV coverage. CONCLUSION: The use of IMRT compared to 3-DCRT improves the avoidance of FL defined by perfusion SPECT scan in selected patients with locally advanced NSCLC. If the dose to FL is shown to be the primary determinant of lung toxicity, IMRT would allow for effective dose escalation by specific avoidance of FL.

Comparison of inverse-planned three-dimensional conformal radiotherapy and intensity-modulated radiotherapy for non-small-cell lung cancer.

PURPOSE: Lungs are the major dose-limiting organ during radiotherapy (RT) for non-small-cell lung cancer owing to the development of pneumonitis. This study compared intensity-modulated RT (IMRT) with three-dimensional conformal RT (3D-CRT) in reducing the dose to the lungs. METHODS: Ten patients with localized non-small-cell lung cancer underwent computed tomography (CT). The planning target volume (PTV) was defined and the organs at risk were outlined. An inverse-planning program, AutoPlan, was used to design the beam angle-optimized six-field noncoplanar 3D-CRT plans. Each 3D-CRT plan was compared with a series of five IMRT plans per patient. The IMRT plans were created using a commercial algorithm and consisted of a series of three, five, seven, and nine equidistant coplanar field arrangements and one six-field noncoplanar plan. The planning objectives were to minimize the lung dose while maintaining the dose to the PTV. The percentage of lung volume receiving >20 Gy (V20) and the percentage of the PTV covered by the 90% isodose (PTV90) were the primary endpoints. The PTV90/V20 ratio was used as the parameter accounting for both the reduction in lung volume treated and the PTV coverage. RESULTS: All IMRT plans, except for the three-field coplanar plans, improved the PTV90/V20 ratio significantly compared with the optimized 3D-CRT plan. Nine coplanar IMRT beams were significantly better than five or seven coplanar IMRT beams, with an improved PTV90/V20 ratio. CONCLUSION: The results of our study have shown that IMRT can reduce the dose to the lungs compared with 3D-CRT by improving the conformity of the plan.

The incorporation of SPECT functional lung imaging into inverse radiotherapy planning for non-small cell lung cancer.

BACKGROUND AND PURPOSE: Patients with non-small cell lung cancer (NSCLC) often have inhomogeneous lung perfusion. Radiotherapy planning computed tomography (CT) scans have been accurately co-registered with lung perfusion single photon emission computed tomography (SPECT) scans to design radiotherapy treatments which limit dose to healthy 'perfused' lung. PATIENTS AND METHODS: Patients with localised NSCLC had CT and SPECT scans accurately co-registered in the planning system. The SPECT images were used to define a volume of perfused 'functioning' lung (FL). Inverse planning software was used to create 3D-conformal plans, the planning objective being either to minimise the dose to whole lungs (WL) or to minimise the dose to FL. RESULTS: Four plans were created for each of six patients. The mean difference in volume between WL and FL was 1011.7 cm(3) (range 596.2-1581.1cm(3)). One patient with bilateral upper lobe perfusion deficits had a 16% reduction in FLV(20) (the percentage volume of functioning lung receiving >or=20 Gy). The remaining patients had inhomogeneous perfusion deficits such that inverse planning was not able to sufficiently optimise beam angles to avoid functioning lung. CONCLUSION: SPECT perfusion images can be accurately co-registered with radiotherapy planning CT scans and may be helpful in creating treatment plans for patients with large perfusion deficits.

Segmentation of IMRT plans for radical lung radiotherapy delivery with the step-and-shoot technique.

The purpose of this work was to determine a segmentation protocol for the treatment of localized non-small-cell lung cancer (NSCLC) with intensity-modulated radiotherapy (IMRT) that is as effective as possible while practically simple and hence robust to known practical inaccuracies. This study focused on the stratification of continuous profiles into a discrete number of intensity levels. The selection of the segmentation parameters for the delivery of the fluence profiles using multiple static fields has been considered. Five-field equispaced IMRT treatment plans of five patients with NSCLC were selected. The study comprised nine treatment plans for each patient, starting from a conformal plan, optimizing it for IMRT and then segmenting it utilizing different numbers of segments in each case and optimizing for segment weights separately. A conformal plan, optimized for beam directions, collimator and wedge angles, was also used for comparison with the IMRT plans, so as to consider the best coplanar conformal case. A dose objective for the PTV and the organs-at-risk plus a constraint for the spinal cord were set for all inverse plans. All stages were compared with the aid of dose-volume histograms, dose distributions at the plane of the isocenter, intensity maps for key beams and plots of PTV homogeneity and overall conformality versus complexity. The unsegmented IMRT plans gave the best results but cannot be realized in practice with an MLC. They were best approximated by plans that needed 106-167 segments to deliver, but did not deteriorate significantly when approximated by plans which required 26-40 segments in total. All segmented IMRT plans gave a better lung sparing than the conformal plans, indicating that the deterioration of IMRT plans following segmentation is not equivalent to that of unmodulated, conformal plans. However, optimized conformal plans have the potential to approach the lung sparing achieved by segmented IMRT plans. Among the IMRT situations examined, five-field treatment plans for the lung, utilizing a maximum of 40 segments in total, have proven to give a good approximation of the IMRT plans with continuous modulation.