This project developed and validated an automated pipeline for prostate treatments to accurately determine which patients could benefit from adaptive radiotherapy (ART) using synthetic CTs (sCTs) generated from on-treatment cone-beam CT (CBCT) images.

The automated pipeline converted CBCTs to sCTs utilising deep-learning, for accurate dose recalculation. Deformable image registration mapped contours from the planning CT to the sCT, with the treatment plan recalculated. A pass/fail assessment used relevant clinical goals. A fail threshold indicated ART was required. All acquired CBCTs (230 sCTs) for 31 patients (6 who had ART) were assessed for pipeline accuracy and clinical viability, comparing clinical outcomes to pipeline outcomes.

The pipeline distinguished patients requiring ART; 74·4% of sCTs for ART patients were red (failure) results, compared to 6·4% of non-ART sCTs. The receiver operator characteristic area under curve was 0·98, demonstrating high performance. The automated pipeline was statistically significantly (p < 0·05) quicker than the current clinical assessment methods (182·5s and 556·4s, respectively), and deformed contour accuracy was acceptable, with 96·6% of deformed clinical target volumes (CTVs) clinically acceptable.

The automated pipeline identified patients who required ART with high accuracy while reducing time and resource requirements. This could reduce departmental workload and increase efficiency and personalisation of patient treatments. Further work aims to apply the pipeline to other treatment sites and investigate its potential for taking into account dose accumulation.

This study aimed to quantify the difference in setup margin in cone beam computed tomography (CBCT) setup imaging, utilising the van Herk formula for two different image registration methods. Two alternative techniques of registration, bony landmark (BL) matching and soft tissue matching (ST) for head and neck cancer patients, were investigated.

This study included 30 head and neck cancer patients who received a simultaneous integrated boost of 54–60–66 Gy in 30 fractions, using volumetric modulated arc treatment. A total of 867 CBCT images were acquired during patient setup and further analysed for setup margin calculation. A region of interest was described using a clip box between the reference and CBCT image to calculate the patient’s positional inaccuracy in three translational directions, X, Y and Z, where X was mediolateral, Y was the cranial-caudal, and Z was the anterior-posterior direction in the patient-based coordinate system, respectively. The shifts were captured by altering the BL and ST matching, and the setup margin was calculated using the van Herk formula (=2·5Σ + 0·7σ where Σ was the systematic and σ was the random error).

The difference between bony and ST matching in most cases was observed to be 1·4 mm in all translational directions at a 95% confidence interval and <1° in all rotational directions. The rotational error was found to be below the action level (±3°); hence, no corrections related to rotational error were made. The translational setup margin for bone and ST-based registration was X (BL) = 4·6 mm, X (ST) = 4·4 mm, Y (BL) = 6·3 mm, Y (ST) = 4·7 mm, Z (BL) = 3·0 mm, Z (ST) = 3·6mm.

Two distinct registration approaches for head-neck patient setup did not yield any significant difference in the setup margin calculation. A suitable approach for CBCT and reference CT registration technique was required for the setup margin calculation. Confusion in selecting the correct image registration procedure can result in incorrect treatment execution. The compatibility of the two registration approaches was established in this study. Image fusion was neutralised before the second match (ST) to avoid hysteresis. For setup verification using CBCT for the head and neck region, both bone and ST registration were compatible for setup verification.

In this study, the relation between radiation pneumonitis (RP) and a wide spectrum of clinical, radiographic and treatment-related factors was investigated. As scoring of low-grade RP can be subjective, RP grade ≥3 (RP ≥ G3) was chosen as a more objective and clinically significant endpoint for this study.

105 consecutive patients with locally advanced non-small cell lung cancer underwent conventionally fractionated radio-(chemo-)therapy to a median dose of 64 Gy. A retrospective analysis of 25 clinical (gender, race, pulmonary function, diabetes, statin use, smoking history), radiographic (emphysema, interstitial lung disease) and radiotherapy dose- and technique-related factors was performed to identify predictors of RP ≥ G3. Following testing of all variables for statistical association with RP using univariate analysis (UVA), a forward selection algorithm was implemented for building a multivariate predictive model (MVA) with limited sample size.

Median follow-up of surviving patients was 33 months (9–132 months). RP ≥ G3 was diagnosed in 10/105 (9·5%) patients. Median survival was 28·5 months. On UVA, predictors for RP ≥ G3 were diabetes, lower lobe location, planning target volume, volumetric modulated arc therapy (VMAT), lung V5 Gy (%), lung Vspared5 Gy (mL), lung V20 Gy (%) and heart V5 Gy (% and mL). On MVA, VMAT was the only significant predictor for RP ≥ G3 (p = 0·042). Lung V5 Gy and lung V20 Gy were borderline significant for RP ≥ G3. Patients with RP ≥ 3 had a median survival of 10 months compared to 29·5 months with RP < G3 (p = 0·02).

In this study, VMAT was the only factor that was significantly correlated with RP ≥ G3. Avoiding RP ≥ G3 is important as a toxicity per se and as a risk factor for poor survival. To reduce RP, caution needs to be taken to reduce low-dose lung volumes in addition to other well-established dose constraints.

To evaluate the dosimetric effect of modelling a non-homogeneous couch on patients’ quality assurance (QA) gamma pass rates for intensity-modulated radiotherapy (IMRT) and volumetric modulated arc therapy (VMAT) techniques.

A non-homogeneous treatment couch (TxT 550 TTM, CIVCO, USA) was imaged using the LINAC mounted cone-beam computer tomography (CBCT) system. Modelling this couch in different situations, including incomplete (homogeneous model), correct model and not defined situations in the treatment planning system (TPS), was performed based on the geometrical and material densities data extracted from the CBCT images. Calculated gamma pass rates between TPS dose calculations and the measurements in a phantom for different couch models were obtained and compared at two gamma criteria (2%-2 mm and 3%-3 mm).

Comparing TPS calculations for the correct modelled couch and the measurements showed high gamma pass rates for both the IMRT and VMAT techniques (96·5 ±  0·9%, 99·2 ±  0·5% for IMRT in 2%-2 mm and 3%-3 mm criteria; 97·5 ±  0·8%, 99·4 ±  0·5% for VMAT). The overall gamma pass rate of the IMRT plan QAs was reduced by about 2% and 3% on average for incomplete and no couch modelling, respectively. These reductions for VMAT techniques were 2·5% and 4·3%, respectively.

Non-homogeneous couches have different parts with different attenuations, which can be correctly defined using LINAC CBCT. Modelling of treatment couch has a significant effect on patient QA results for VMAT and IMRT plans, especially in radiation fields/subfield transmitting from the couch. We suggest using LINAC CBCTs as an appropriate device for couch modelling in modulated radiotherapy techniques.

Radiation therapy has historically used margins for target volume to ensure dosimetric planning criteria. The size of margin for a given treatment site is still uncertain particularly for moving targets along with set-up variations leading to a fuzziness of target volume. In this study, we have estimated the dosimetric benefit of normal structures using biological-based optimal margins. The treatment margins are derived by knowledge-based fuzzy logic technique which is considering the radiotherapy uncertainties in treatment planning.

All treatment plans were performed using stepped increments of asymmetric margins to estimate prostate radiobiological indices such as tumour control probability (TCP) and normal tissue complication probability (NTCP). An absolute NTCP of 5% was considered to be the maximum acceptable value while TCP of 85% was considered to be the minimal acceptable limit for each volumetric modulated arc therapy (VMAT) plan of localised prostate cancer radiotherapy. Results were used to formulate rules and membership functions for Mamdani-type fuzzy inference system (FIS). In implementing the rules for the fuzzy system for ΔNTCP values above 10%, the PTV margin was not permitted to exceed 5 mm to avoid rectal complications due to margin selection. The new margins were applied in VMAT planning of prostate cancer for standard displacement errors. The dosimetric results of normal tissue predictors were estimated such as organ mean doses, rectum V60 (volume receiving 60 Gy), bladder V65 (volume receiving 65 Gy) and other clinically significant dose–volume indicators and compared with VMAT plans using current margin formulations.

Dosimetric results compared well to the results obtained by current techniques. Good agreement was obtained between proposed fuzzy model margins and currently used margins in lower error magnitude, but significant results were observed at higher error magnitude when organ toxicity concerned without compromising the target volumes.

The new margins may be helpful to estimate possible outcomes of normal tissue complications and thus may improve complication free survival particularly when organ motion errors are inevitable, case by case.

The dosimetric impact of volumetric modulated arc therapy (VMAT) in lung cancer compared with 3D conformal radiotherapy (3DCRT) is well known. However, this improvement is often associated with an increase in low doses. The aim of this study is to quantify these results more accurately.

For each patient treated with 3DCRT, a second VMAT treatment plan was calculated. Usual dosimetric parameters such as target coverage or dose to the organs at risk were used to achieve the comparisons.

For planning target volume, homogeneity and conformity indices showed superiority of VMAT (respectively 0·07 and 0·87) compared to 3DCRT (0·11 and 0·57). For spinal cord planning organ at risk volume, the median maximum dose was 45·6 Gy in 3DCRT against 19·3 Gy in VMAT. Heart volume receiving at least 35 Gy (V35) decreased from 15·64% in 3DCRT to 8·28% in VMAT. Oesophagus V50 was higher in 3DCRT (25·45%) than in VMAT (14·03%). The mean lung dose was 17·9 Gy in 3DCRT versus 15·5 Gy in VMAT. Moreover, volumes receiving 5, 10 and 15 Gy were not significantly different between the two techniques when VMAT was performed with partial arcs.

All the dosimetric parameters were improved with VMAT compared to the 3DCRT without increasing low doses when using partial arcs.

The aim of the current study was to (i) to calculate organ equivalent dose (OED) and (ii) to estimate excess absolute risks (EARs), lifetime attributable risks (LARs) and relative risks (RRs) from stereotactic ablative radiotherapy (SABR) for lung cancer to in-field, close to field, and out of field structures.

A total of five patients with T1, T2 (≤4 cm), N0, M0 medically inoperable non-small cell lung cancer were selected for treatment planning. Patient selection criteria were based on RTOG 0236. Five treatment deliveries were investigated: (i) three-dimensional conformal radiotherapy (3DCRT), (ii) intensity-modulated radiotherapy (IMRT), (iii) intensity-modulated radiotherapy with flattening filter free beam (IMRTF), (iv) volumetric modulated arc therapy (VMAT) and (v) volumetric modulated arc therapy with flattening filter free arcs (VMATF). Delineated normal structures included chest wall, left and right lung, trachea, small and large airways, spinal cord, oesophagus and involved ribs. All plans were prescribed to 60 Gy in five fractions to primary planning target volume (PTV) volume so that ≥98% of the PTV received ≥98% of the prescription dose and internal tumour volume received 100% of the prescription dose. The OED for all delineated normal structures was calculated using differential dose volume histograms. Using risk models, the age-dependent LAR’s and RR were calculated. Additionally, the secondary cancer risk for organs inside primary radiation was analysed using sarcoma and carcinoma risk models.

For all patients, the mean V20 volumes from the SABR plans were 4·1% (3DRT), 11·8% (IMRT), and 12·7% (VMAT), respectively. The EAR (combining all organs EAR) for all the organs studied, ranged from 8·5 to 10·6/10,000 persons/year for VMATF and 3DCRT, respectively. The EAR (combining all organs EAR) for all the organs studied, ranged from 8·5 to 10·6/10,000 persons/year for VMATF and 3DCRT, respectively. The absolute EAR difference between IMRT and IMRTF was low ranging from 0·2 to 0·4/10,000 persons-year, whereas delivery difference (IMRT and VMAT) had a significant impact on EAR with absolute difference ranging from 0·5 to 1·0/10,000 persons-year for IMRT and VMAT and 1·1–1·5/10,000 persons-year for IMRTF, VMATF, respectively. The LAR data showed a strong dependence on age at exposure and the LAR decreased as a function of age at exposure. The absolute attributable risk of bone sarcoma was lower with the VMAT plan and was significantly higher with the 3DCRT plan.

From a clinical perspective, it should be concluded that all five solutions investigated in the study can offer high quality of patient treatments and only estimates of radiation-induced malignancies can truly differentiate among them. The results suggested it would be reasonable to use the cumulative LAR difference when needed to select between treatment techniques. In conclusion, the LAR of radiation-induced secondary cancer was significantly lower when using VMATF than when using IMRT for SABR lung patients. VMATF would be the right choice for the treatment of SABR lung patients in terms of LAR. However, more work is required for the specific estimation and long-term validation and updating of the models behind LAR estimation.

The aim of this paper is to compare neural induced changes in three-dimensional conformal radiotherapy (3D-CRT) versus intensity modulated radiation therapy (IMRT) and volumetric modulated arc therapy (VMAT) for nasopharyngeal cancers.

Radiotherapy plans for 10 patients with nasopharyngeal cancer stages III and IV were prospectively developed for 3D-CRT, IMRT and VMAT using Varian Eclipse planning system. The same radiation therapist carried out all planning and the same clinical dosimetric constraints were used. Normal tissue complication probabilities were calculated.

The mean planning target volume’s (PTVs) conformity index (CI) for 3D-CRT was 1·424, for IMRT 1·1, and for VMAT 1·081. The PTV homogeneity (HI) index was 0·204 for 3D-CRT, 0·124 for IMRT and 0·153 for VMAT. Normal tissue complication probabilities gave complex results for 3D-CRT, IMRT and VMAT and are analysed in detail in this paper. The mean monitor units were 95 (range 9–180) for 3D-CRT; 165 (range 52–277) for IMRT; and 331 (range 167–494) for VMAT (p<0·05).

VMAT is associated with similar dosimetric advantages as IMRT over 3D-CRT for nasopharyngeal cancer. VMAT is associated with faster delivery times and greater number of mean monitor units than IMRT. Brain radionecrosis severity and risk, in the past, have been underestimated. By improving the life expectancy of patients with nasopharyngeal cancer to ensure maintenance of the neural structures, recommended dose limits should be considered as a first degree priority (as the spinal cord, brainstem, etc.) when IMRT and VMAT plans are implemented.