Standard operating procedure (SOP) for immobilisation, scanning, verification and treatment of breast cancer patients undergoing proton beam therapy

Highlights

• •Standard operating procedure for breast proton beam therapy for new and existing PBT services
• •Immobilisation for breast PBT
• •Planning CT for breast PBT
• •Daily verification for breast PBT
• •Traffic light system for breast PBT daily treatment verification

Abstract

The use of proton beam therapy (PBT) for breast cancer is not currently included for standard consideration on the NHS England indication list. However, there are occasions where the use of PBT may be approved in the United Kingdom (UK), such as breast sarcoma, as part of a clinical trial or due to a photon plan meeting a threshold for significant risk of acute and late toxicities (e.g. pre-existing co-morbidities). Due to the beam characteristics, the use of PBT for breast treatment poses challenges in terms of the immobilisation, pre-treatment scanning, treatment verification and delivery. This standard operating procedure (SOP) details strategies to mitigate these that were developed as part of the implementation of breast PBT at our institution. This SOP will support existing and new PBT services when treating this patient cohort, by providing a detailed step-by-step guide to improve consistency and efficiency in the management of breast PBT.

Introduction

Proton beam therapy (PBT) facilitates high dose deposition in target tissue, with sharp distal dose fall-off, affording increased sparing of adjacent normal tissues and organs when compared to photon radiotherapy.[1] PBT can reduce dose to the heart, lung and contralateral breast, without compromising target coverage for complex breast radiotherapy.[2,3] The population that may benefit from PBT includes patients with pre-existing co-morbidities in whom a photon plan poses a significant risk of acute and late toxicities that may be reduced with this change in modality. In the breast cohort this is most likely patients that are young, those with a pre-existing cardiac or pulmonary risk factors; patients prescribed a high total dose (e.g. breast sarcoma, thus significantly increasing the incidental dose to the heart and lungs), or those defined as a teenager or young adult (TYA) with a significant risk of radiation induced second cancer.

PBT is considered and delivered as standard of care for primary breast cancer in a subset of this patient cohort within some international PBT services. However, NHS England’s current commissioning position for PBT for breast carcinoma, states that “there is not enough evidence to make treatment available”, and therefore “PBT is not recommended to be a treatment option for breast cancer”.[4] The PARABLE Trial (currently in active recruitment) aims to respond to the current lack of evidence highlighted in the NHS commissioning statement and is described elsewhere.[1,5,6].

The provision of PBT internationally is growing. University College London Hospital (UCLH) NHS Foundation Trust opened as the second of two UK PBT facilities in December 2021. UCLH accepts national referrals according to the NHS England PBT indication list.[4].

As a new PBT service, whilst establishing our breast PBT service to facilitate acceptance of PBT referrals for special indication (e.g. breast sarcoma) and trial patients (e.g. PARABLE) randomized to PBT, support and advice was sought from several international centers with extensive experience of treating this patient cohort. The absence of a published SOP was noted at that time, as such a document would have streamlined the necessary fact-finding, problem solving and training that is associated with any new technique work-up. Here we aim to present our SOP for breast PBT, that acknowledges and provides workable solutions to the PBT-specific immobilisation and verification challenges that are translational to new and existing PBT centres. We hope that this will support wider standardization and quality improvement in this potentially growing PBT patient cohort.

Patient selection and assessment

Each PBT referral is discussed during a breast multidisciplinary team (MDT) meeting. The MDT is considered quorate when there is representation from the consultant clinical oncologists, consultant radiographer, PBT physicist, PBT dosimetrists, PBT pre-treatment radiographer and PBT treatment radiographer. When the referral is approved for treatment, the patient will undergo consent and commence the PBT pathway. A photon back-up plan is not generated for this patient cohort.

Pre-planning meeting

Pre-planning meetings (members as per the MDT detailed above) are held weekly for each case to ascertain appropriate positioning, immobilisation, planning scan requirements, and diagnostic/staging datasets for image registration.

Patient immobilisation

Equipment (Fig. 1):

• •kVue™ Couch Top (QFix).
• •Armshuttle elite™ (QFix) and Access Supine Breast Board™ (QFix).
• •VacQfix Vacuum Cushions™ (QFix). Select from 70 cm x 100xcm 30L or a T Shaped 79 cm x 93 cm 20 L.
• •KneeFix™ (CIVCO Radiotherapy™) and foot support.

Fig. 1.

Immobilisation devices (QFix): (Armshuttle elite™, Access Supine Breast Board™ and VacQfix Vacuum Cushions™ at different stages; before molding to patient, and after vacuum is applied and shaped to the patient.

Pre-treatment patient Set-Up

• 1.Complete consultation with the patient to:
• 2.Confirm ID and treatment consent.
• 3.Check pregnancy status.
• 4.Explain procedure for immobilisation and scan.
• 5.Patient to approach the CT couch from the left-hand side, which is set to the minimum PBT gantry couch height to mimic treatment set up.
• 6.Position patient headfirst supine and place the unmoulded VacQfix Vacuum Cushions™ on the Armshuttle elite™ and Access Supine Breast Board (QFix). Use a KneeFix™ and foot support to aid reproducibility and comfort. Ensure the vacuum cushion valve is located at the superior aspect of the breast board to avoid the beam path.
• 7.Smooth the vacuum cushion when placed on the breast board. Place the patient’s arms up and mould around the arms to create a channel when applying the vacuum to mould the bag. Ensure the arms and shoulders are fixed into the vacuum cushion (Fig. 1), without extending under the thorax.
• 8.Ensure the vacuum cushion is kept within the limits of the arm shuttle to reduce ProBeam™ Varian Medical Systems gantry collision risk. Elbow-to-elbow measurement should not exceed 65 cm to avoid collision risk with the ProBeam™ range shifter/snout.
• 9.Position the patient so the external lasers fall on three stable positions (reference mark location), mark these with pen and place radio-opaque markers.
• 10.Advanced breast radiographer / radiation therapist (RTT) to clinically palpate and mark with radiopaque wire, the ipsilateral and contralateral breast tissue and all surgical scars.
• 11.If the patient has previous alignment tattoos, add measurements to the set-up sheet.
• 12.Document the patient’s set-up instructions, reference mark location and details that may assist RTTs. Consider photographs to aid positioning accuracy.
• 13.Cannulate the patient if intravenous contrast has been requested. Intravenous contrast is not used for primary breast cancer but may be requested for breast sarcoma.

Computed tomography (CT)

N.B. Patients are scanned and treated in free breathing due to the current technical and evidence-based limitations to deliver breast PBT in deep inspiration breath hold.

• 1.Two CT scans are acquired (if no contrast indicated) (Appendix Table 1). The first CT acquired uses a breast low dose protocol from mastoids to bottom of lungs or 4 cm inferior to breast tissue, whichever is lowest. All breast wire to be included in this scan. This scan will be used alongside the second scan to aid delineation of the breast tissue and assist with assessing ProBeam™ range shifter/snout position.
• 2.The second scan uses the breast standard protocol), from mastoids to the bottoms of lungs or 4 cm inferior to breast tissue, whichever is lowest. This scan will be used for contouring and dosimetry, therefore remove breast all wire marking, except reference markings.
• 3.For patients referred for contrast CT, a third CT scan is required, as PBT plan calculation must be performed on a non-contrast scan.
• 4.Perform the scout localiser ensuring all relevant anatomy, immobilisation and couch top is included.
• 5.Plan the helical series’ to ensure inclusion of the anatomical range required.

Table 1.

Low dose and standard breast CT scanning protocol parameters used at our institution.

	Breast Low Dose	Breast standard
Pitch (in degrees)	1.379	1
Energy (kV)	120	120
Current (mAs)	14	137
Scan thickness (mm)	2	2

After completion of all scans, apply alignment marks (Indian ink tattoos). This is not required if previous tattoos applied, instead measurements will be provided from the existing alignment tattoos to the new reference point (to be measured and marked daily on-treatment.

Clearance check (Pre-treatment)

For each patient a clearance check appointment is scheduled, approximately 1 week prior to start date. The patient is not required to attend.

All equipment is placed on the couch as per the set-up instructions. The patient’s VacQfix™ cushion provides a surrogate for the patients elbows position.

The couch is positioned at the isocentre, provided by the planner for each individual patient’s plan. The isocentre height above the couch is set using the ruler function and table vertical scale. The Access Supine Breast Board™ has a ruler scale along its edge and the position of the reference marks is recorded at pre-treatment scanning. A longitudinal shift is applied from this point. Laterally, the shift is applied from couch zero.

A clearance check of all proposed treatment angles, with snout extension, range shifter and gantry angles for imaging acquisition is undertaken.

If the clearance check fails, parameters to achieve collision-free delivery are provided to the dosimetry team.

Treatment set-up and imaging acquisition (Day 1)

Treatment is delivered on a Varian ProBeam™ gantry with 360° rotation and integrated Cone-Beam CT (CBCT).

Patient approaches the treatment couch from the left-hand side (in parked position). Seated, they are positioned centrally on the Access™ supine breast board with customised vacuum cushion, before lying back. RTTs use integrated lasers to align the patient according to anatomical landmarks and reference marks.

The isocentre position is achieved by applying the couch translational shifts, according to the plan.

A CBCT is acquired using the ‘Thorax’ anatomy template (Field-of-view 52 cm, length 20.7 cm, 2 mm reconstruction slice thickness) (Appendix Table 2)

Table 2.

CBCT scanning thorax scanning protocol.

	Thorax CBCT protocol
Energy (kV)	125
Current (mAs)	1525
Focal spot	Large

During the planning stage, the isocentre is positioned cranio-caudally to optimise the visualisation of clinical target volume (CTV) within the CBCT range. If the CTV is > 21 cm long, the visualisation of nodal volumes superiorly is prioritised, unless the patient has undergone breast conserving surgery (BCS) and has a lower quadrant tumour bed. For all patients (BCS) the tumour bed must be within the CBCT.

Image review (Daily)

Once acquired, CBCT’s are reviewed online by RTTs, utilising the ProBeam™ software A 3D-3D auto-match is carried out using 4 degrees of freedom (DoF). Pitch and roll are excluded due to potentially causing a discrepancy in the patients’ contour, which can have a larger impact on beam path. [7] If individual patient setup and verification suggests that these positional corrections will facilitate optimal treatment delivery, this must be discussed with the senior RTT before applying the shifts.

An auto-match is applied using a region of interest (ROI) (Fig. 2) which includes:

• •Superiorly – CTV (exclude head of humerus where not excluding CTV)
• •Inferiorly – CTV and 1 cm inferior to inframammary fold, if applicable (BCS)
• •Medially − Width of sternum
• •Laterally − Entire patient contour (ipsilateral side)
• •Anteriorly – Entire patient contour
• •Posteriorly − CTV.

Fig. 2.

ROI used for the CBCT match (right breast/chestwall CTV = red contour; nodal CTVs = green, blue and yellow contours; orange contour = 20 % isodose contour). (For interpretation of the references to colour in this figure legend, the reader is referred to the web version of this article.)

The 20 % isodose is converted to a contour during plan preparation prior to fraction 1 (Fig. 2). This contour is used as the volume of interest (VOI) for the auto-match. The intensity is set to bones.

The CBCT match is assessed ranking by priorities, where applicable

• 1.Simultaneous integrated boost (SIB) CTV
• 2.Whole breast/chest wall CTV
• 3.Nodal level I-IV + interpectoral CTV
• 4.IMN CTV

External body contour changes of > 3 mm within the 20 % isodose contour are evaluated with respect to the impact on the plan dosimetry. This includes: consideration of the number of slices where the body contour change is present; whether the body contour change is at the level of the tumour bed/SIB volume; whether the body contour change can be corrected by repositioning the patient, amendment of the match, or if a dosimetric evaluation is required (discussion between dosimetry and senior RTT).

ROI: Region of Interest. SIB: Simultaneous Integrated Boost. SCF: Supraclavicular Fossa. IMN: Internal Mammary Nodes. CBCT: Cone Beam CT. * = excluding pitch and roll unless discussed and confirmed with senior treatment and physics/dosimetry team.

A traffic light system (Table 3) and flow chart (Fig. 3) is used to guide RTTs in their decision to deliver the fraction and assist in identifying changes which require a dosimetric evaluation.

Table 3.

Traffic light assessment criteria for PBT imaging matching.

Recommended action	Assessment Criteria
Green Continue	• Chest wall/lung interface as planned • Breast CTV < 5 mm • Clips < 5 mm • Nodal level I-IV + interpect CTV < 5 mm • IMN CTV < 5 mm
Amber Highlight to Senior RTT for urgent review before the next treatment fraction	• Chest wall/lung interface > 3 mm • Breast CTV ≥ 5 mm • Clips ≥ 5 mm • Nodal level I-IV + interpect CTV ≥ 5 mm • IMN CTV ≥ 5 mm • If pitch and/or roll are required • External contour > 3 mm (within the 20 % isodose).
Red **Do not treat** Consult senior RTT/physicist/clinician	• Chest wall/lung interface ≥ 10 mm • Breast CTV ≥ 10 mm • Clips ≥ 10 mm • Nodal level I-IV + interpect CTV ≥ 10 mm • IMN CTV ≥ 10 mm

Fig. 3.

Flowchart for breast CBCT acquisition and matching.

Manual adjustment of the match, including the addition of pitch and roll, may be required to improve adherence to the match priorities. This is discussed with the senior RTT. Experience to date suggests that when a manual adjustment is required, this may be due to poor patient set-up rather than internal anatomical changes, therefore RTTs are to consider re-positioning and re-imaging the patient.

Bilateral breast treatment (additional steps and considerations)

For bilateral breast treatment the dosimetrist will assign the same vertical and longitudinal isocentre for both treatment sides. Due to the requirement of the ProBeam to deliver beams in a counter-clockwise direction, the left-side will be treated first unless the right-side is more complex, e.g. more CTVs.

A CBCT is acquired at the left-side isocentre. A 3DoF auto match is undertaken with the ROI for the left-side, using the ipsilateral match priorities as per 8.4 to 8.6. 3DoF is used (not 4DoF) as the impact of rotation on the dose cannot be quantified. The right-side CTVs are visually assessed to confirm they are within tolerance following the left-side correction. Corrective shifts for the left-side are applied and treatment is delivered to this isocentre.

The planned lateral shift to the right-side is applied and a second CBCT is acquired. This is assessed as per 8.4 to 8.6 (3DoF).

If any correction > 5 mm for the right-side is required, consideration of the field match/gap between treatment sides is discussed with a senior RTT and dosimetrist. This situation is not expected to arise because the position of the right CTVs has been visually evaluated during the first CBCT. Lateral corrective shifts are of particular concern due to the impact of the dose already delivered to the first side on this fraction. A limited corrective shift may be considered preferable to repositioning the patient.

Corrective shifts are applied, and treatment is delivered to the right-side.

Discussion & Conclusions

This SOP has been developed and implemented by our PBT centre in response to patient's being referred and accepted for PBT to the breast/anterior chest wall +/- locoregional nodal targets.This SOP contains specific novel measures and considerations when treating this anatomical site with PBT, with regard to immobilisation, positioning and verification. The measures employed acknowledge the unique challenges posed by this patient cohort, associated with deformative set-up errors due to large target volumes and the anatomical location and extent, that cannot simply be corrected with couch shifts.[6] Establishing this standardised protocol has supported our centre to safely and efficiently position, scan, plan, verify, and treat this patient cohort. With new centres opening internationally, and the potential role of PBT for this anatomical site being acknowledged, this SOP provides a supportive resource to centres when implementing similar techniques.

Declaration of competing interest

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.