Comparing 3-D Printed vs Standard Bolus for Breast Cancer Chest Wall Radiotherapy

1. Study Schema Intervention All subjects receive standard chest wall radiotherapy doses as follows:

• Half the days no bolus is applied to the chest wall as per the standard of care
• Half the days bolus is applied - alternating days between standard 5mm rubber bolus and the experimental 3D printed bolus. Primary and Secondary Outcomes Each subject acts as their own control comparing the standard rubber bolus with the 3D printed bolus in terms of
• The volume of air-gap between the bolus and the chest wall skin
• The time it takes the radiation therapists to set up the patient
• The calculated versus measured dose on the skin Sample size 16 patients over 4 months

1. Background and Rationale

In Canada, 25,000 women are diagnosed with breast cancer each year. Approximately 20% of these women undergo mastectomy (removal of the entire breast) as part of their curative treatment program. Radiotherapy is administered to the chest wall (where the breast was) in women whose breast cancer has spread to the lymph nodes

or in other situations in which there is a high chance there might be microscopic amounts of cancer cells left over on the chest wall. A meta-analysis of 25 randomized trials involving 8505 lymph node positive women showed post-mastectomy radiotherapy improved 10-year chest wall control rates from 73% to 92.5%. The same overview showed 15-year overall survival increased by 5.4% (60.1 vs 54.7%) in those women undergoing radiotherapy compared to those who did not.

Applying radiotherapy evenly to the chest wall during a course of 16-25 daily radiation treatments is technically challenging because, without modification, the high-energy radiotherapy machines under-dose the superficial tissue (exactly where the cancer cells might reside). To compensate for this phenomenon, a flexible polymer (rubber) "bolus" layer 3-10 mm thick is placed on the skin of the chest wall on some or all days of a radiation course. All sorts of bolus are used internationally from rubber to candle wax slabs. This standard 'bolus', typically 40 cm wide by 40 cm long, is placed on the chest wall and kept in place with tape and straps for the 15 minutes it takes to set up and administer the radiotherapy each day the bolus is applied. Because the contour of each women's chest wall is different and often include 'peaks and valleys' in the tissue, there is inevitably some 'air gaps' between the skin and the bolus material. This air gap, as seen easily on set up imaging, varies from day to day because the radiation therapists can't reproduce the exact placement of bolus, and women undergoing treatment can't get back into the exact same position on the radiotherapy bed each day. The varying air gaps can affect how much radiotherapy is getting to the skin, and can produce potential under-dosing of the cancer cells or overdosing of the normal skin.

In the Department of Radiation Oncology in Halifax the investigators have developed an innovative solution to this problem of air gap by using a 3D printing technology to create bolus that will be tailored to the exact shape of a patient's chest wall. The investigators have approximately 3 years of experience in producing 3D printed bolus for radiotherapy applications, including rigorous assessment of spatial and dosimetric accuracy of the tissues underneath the bolus. Previous research focused on medical physics validation studies, producing a 'smart bolus' to tailor electron therapy treatments at multiple treatment sites. Through this work the investigators have demonstrated that printed bolus conforms precisely even to complex patient anatomy, based on realistic phantom studies (i.e., models of patients including challenging situations e.g., treating part of a foot or ear). The bolus is designed directly from the planning CT data the patient anatomy, which is required for each patient for usual treatment planning calculations. The 3D printed bolus is typically 5 mm thick for x-ray photon beam applications and consists of polylactic acid (PLA), which is derived from starches (corn, sugar tapioca), inert, and commonly used for e.g., drinking cups and surgical pins. The average density of 3D bolus is controllable during printing and thus the investigators are able to replicate the density of the standard rubber bolus material. The investigators have shown previously that the material is accurately accounted for by the treatment planning system as confirmed in another study.

A recent in-house study of 3D printed bolus of the thickness used for this study show the calculated and measured on the machine closely correlate.

In the proposed study, producing a 3D printed bolus for each patient's chest wall could produce multiple advantages over the current technique:

1. The 3D bolus may decrease the amount of air gap between the bolus and the skin. Air gap currently limits the accuracy and uniformity of delivered radiation therapy. The 3D printed bolus would be individualized for every patient and designed and fabricated with sub-millimeter precision;
2. The time required by multiple radiation therapists to prepare the bolus setup prior to CT imaging may be reduced, particularly for challenging anatomies, given that the 3D printed bolus is produced in an automated way from CT data afterwards (without the patient and therapists present).
3. The time to set up a patient on the treatment machine (linear accelerator) may be decreased if individualized bolus 'slips' into place (compared to status-quo where bolus positioning can be iterative, error-prone and time-consuming).
4. As each patient will have their own individualized bolus, issues of infection control (contamination of bacteria from reusing the standard bolus) will be mitigated.
5. Study Objectives

To test whether 3D printed bolus produces less air gap, is faster to apply, and produces a reliable buildup of radiotherapy compared with standard rubber bolus on women undergoing chest wall radiotherapy.

1. Study Methods

This is a single-centre study accruing breast cancer patients who have already agreed to undergo chest wall radiotherapy

Study Flow for an Individual Patient

1. Accrual of patient and completion of consent process
2. CT simulation and standard bolus production (done exactly as per current standard of care)
3. Production of 3D printed bolus using the Simulation CT scan
4. Choice of location and calculation of skin dose
5. Creation of an individualized patient treatment plan

• Plan generated by dosimetrists - alternating bolus on and bolus off
• Outline of which days will be standard bolus and 3D bolus

1. Delivery of Radiotherapy on No bolus days- as per standard of care
2. Delivery of Radiotherapy on Bolus days

• Application of the Diodes to the Chest wall
• Timing of Set up time
• CBCT scan on machine for set up (allows for measurement of air gap afterwards)

1. Monitoring of patient while on and after treatment

• Air gap calculation
• Measured dose to the skin
• Skin reaction