Breath-Hold in Abdominal & Lung Cancer Radiotherapy - Tumour Reproducibility, Tumour Stability & Patient Experience

1. Breathing Assessment: It is our department policy to deliver SABR and some standard fractionated radiotherapy to upper abdominal tumours in EBH using the Elekta ABC device. DIBH may be used if a patient is unable to comply with EBH requirements. It is our department policy to deliver SABR to lung tumours in DIBH using the ABC device, for select patients. Standard pre-treatment management in our department for patients assessed as suitable for a breath-hold technique is to undergo a breathing assessment to confirm eligibility. The breathing assessment involves a training session to confirm the patient is able to perform breath-hold with the ABC device, for a minimum time of 15 seconds. The breathing assessment also involves a 4DCT (lung) or 4D- CBCT (upper abdominal) to confirm a breath-hold technique is required. For this study, all consenting patients planned for radiotherapy to liver, pancreas, adrenal and kidney cancers will be assessed for eligibility for each of EBH, DIBH and IBH techniques. Patients planned for radiotherapy to lung cancer will only be assessed for DIBH technique (i.e. no change to usual care). Two radiation therapists perform the breathing assessment. At the breathing assessment, patients are determined to be eligible for proceeding with a breath-hold technique if they are able to comply with all ABC requirements (use mouth-piece, nose-peg and operate control switch) and breath-hold in at least one technique (of IBH, DIBH and/or EBH) for greater than 15 seconds. With the exception of patients planned for radiotherapy to the lung, patients will be screened for eligibility in all three techniques (IBH, DIBH & EBH). During the breathing assessment, the patient’s maximum tolerable breath-hold time in each technique will be determined. This is the maximum amount of time, measured in seconds that the patient is able to hold their breath comfortably, and repeatedly. This time will be recorded for each technique (IBH, DIBH & EBH). The patient’s recovery time between consecutive breath holds will also be recorded. Recovery is determined by the patient as the time from completing one breath hold to the patient indicating they are ready to perform the next breath hold. Patients indicate when they are ready by depressing the ABC control switch. 2. Stability & Reproducibility Assessment: To assess the stability and reproducibility of the tumour position during each breath-hold, and between consecutive breath holds, a series of kV x-ray fluoroscopy images will be acquired. It is our department policy for patients undergoing lung SABR to perform three breath-holds whilst kV fluoroscopy images are acquired. For this study, all consenting patients undergoing lung SABR will perform five breath-holds, under kV fluoroscopy imaging in DIBH. There is an additional two kV images acquired, compared to usual care of lung SABR patients in this study. It is our department policy for patients undergoing upper abdominal SABR to perform three breath-hold kV fluoroscopy images are acquired in either EBH or DIBH. For this study, all consenting patients undergoing upper abdominal radiotherapy will perform five breath-holds, under kV fluoroscopy imaging for each eligible technique (EBH, IBH, DIBH). This is up to twelve additional kV fluoroscopy images for patients in this study, compared to usual care. The kV fluoroscopy is performed on an Elekta™ linear accelerator, using the XVI™ software “MotionView” function. The position of the tumour will be tracked under kV fluoroscopy by assessment of the tumour (if directly visible) or via an appropriate tumour surrogate (diaphragm or fiducial marker) position. Each kV fluoroscopy image is acquired as an Antero-Posterior (AP) image, with the x-ray tube located anterior to the patient. The order in which the breath-hold techniques (EBH, IBH, & DIBH) will be assessed will be randomized for each patient, to reduce risk of bias. Stability: The stability of the breath-hold is defined as the range of cranio-caudal motion, of the tumour, or its surrogate, during a breath-hold. Reproducibility: The reproducibility is defined as the cranio-caudal displacement of the tumour/surrogate position between consecutive breath-holds. Patient Experience Questionnaire: Immediately following this assessment, patients will be asked to complete a questionnaire to assess their experience of each technique. The questionnaire will ask patients to rate their experience of each of the attempted breath-hold methods. Patients who were assessed for all three breath-hold methods will also be asked to rank the breath-hold methods in order of their preference. The order of the questions provided to the patient will match the order in which the breathing assessment was randomized. This questionnaire has been developed specifically for this study, as no validated questionnaire tools were able to be identified. Statistical advice was sought in the development of this questionnaire. As required, a staff member involved in the breathing and/or reproducibility & stability assessment will conduct a semi-structured interview with the patient to elicit responses to all applicable questions. 3. Determination of Treatment Technique: Following the Breathing Assessment and Stability & Reproducibility Assessment, selection of a breath-hold technique will be made, which will be used for the patient’s radiotherapy treatment. For upper abdominal patients who were deemed eligible for more than one technique, selection of treatment technique is made by prioritizing: a. Reproducibility assessment: Selection of the most reproducible technique should be prioritized highest. If two or more techniques have the same reproducibility, then; b. Stability assessment: Selection of the most stable technique should be prioritized second. If two or more techniques have the same reproducibility and stability, then; c. Breath-hold time: Selection of the technique with the longest maximum tolerable breath-hold time should be prioritized third. For lung patients, the selection of the DIBH is indicated if: a) Tumour motion exceeds 10mm on free-breathing radiotherapy planning 4DCT OR b) If otherwise deemed to require DIBH based on Radiation Oncologist assessment. Reasons may include: previous radiotherapy in the area; organ at risk in close proximity to tumour. 4. Radiotherapy Planning Patients will have all subsequent planning and treatment imaging performed using the chosen breath-hold technique. There is no change to usual care for radiotherapy planning procedures. The Gross Tumour Volume (GTV) will be delineated on each planning CT by the treating Radiation Oncologist. The tumour surrogates will be delineated on each planning CT by a Radiation Therapist or Radiation Oncologist. The inter-breath hold displacement of the tumour or tumour surrogate will be measured as change in GTV centroid location in three planes. The measurements will be recorded in the patient’s Mosaiq electronic record. 5. Radiotherapy Treatment – Inter-fraction & Intra-fraction reproducibility Usual care radiotherapy treatment will be delivered for all patients. There is no change to standard patient management. For all treatment fractions, Cone Beam Computed Tomography (CBCT) images are acquired before radiotherapy treatment delivery. For patients undergoing Stereotactic Ablative Radiotherapy (SABR), images may also be acquired during and after treatment delivery. At each treatment fraction, a minimum of one breath-hold CBCT will be acquired as per standard practice. Each CBCT will be acquired over several breath-holds. The displacement of the tumour or its surrogate will be measured and used to assess the intra-fraction and inter-fraction reproducibility. Each CBCT will be automatically fused to the planning CT using a two-step registration. Step one, a bone algorithm fusion is used to correct any gross patient misalignment. Step two, a tumour or tumour surrogate (grey value) or fiducial marker (seed) fusion is used to correct any misalignment of the tumour position. For this study, the tumour displacement will be measured as the correction applied from step one to step two. The measurements will be recorded in the patient’s Mosaiq electronic record. 6. Radiotherapy Treatment – Efficiency Total treatment time (measured as total “beam on” time, in seconds, including “beam-hold” recovery time, where patient is between consecutive breath-holds but excluding time to reposition gantry between treatment beams), breath-hold time, and number of breath-holds required to deliver treatment will be recorded for the first three fractions for all patients. From this, an estimate of treatment efficiency will be determined as: (breath hold time (sec) x number of breath holds)/total treatment time (sec) e.g. 17 seconds x 12 breath-holds / 540 seconds total = 17 x 12 / 540 = 0.378 The measurements will be recorded in the patient’s Mosaiq electronic record.