Risk of radiation-induced second malignant neoplasms from photon and proton radiotherapy in paediatric abdominal neuroblastoma.

BACKGROUND AND PURPOSE: State-of-the-art radiotherapy modalities have the potential of reducing late effects of treatment in childhood cancer survivors. Our aim was to investigate the carcinogenic risk associated with 3D conformal (photon) radiation (3D-CRT), intensity modulated arc therapy (IMAT) and pencil beam scanning proton therapy (PBS-PT) in the treatment of paediatric abdominal neuroblastoma. MATERIALS AND METHODS: The risk of radiation-induced second malignant neoplasm (SMN) was estimated using the concept of organ equivalent dose (OED) for eleven organs (lungs, rectum, colon, stomach, small intestine, liver, bladder, skin, central nervous system (CNS), bone, and soft tissues). The risk ratio (RR) between radiotherapy modalities and lifetime absolute risks (LAR) were reported for twenty abdominal neuroblastoma patients (median, 4y; range, 1-9y) historically treated with 3D-CRT that were also retrospectively replanned for IMAT and PBS-PT. RESULTS: The risk of SMN due to primary radiation was reduced in PBS-PT against 3D-CRT and IMAT for most patients and organs. The RR across all organs ranged from 0.38 ± 0.22 (bladder) to 0.98 ± 0.04 (CNS) between PBS-PT and IMAT, and 0.12 ± 0.06 (rectum and bladder) to 1.06 ± 0.43 (bone) between PBS-PT and 3D-CRT. The LAR for most organs was within 0.01-1% (except the colon) with a cumulative risk of 21 ± 13%, 35 ± 14% and 35 ± 16% for PBS-PT, IMAT and 3D-CRT, respectively. CONCLUSIONS: PBS-PT was associated with the lowest risk of radiation-induced SMN compared to IMAT and 3D-CRT in abdominal neuroblastoma treatment. Other clinical endpoints and plan robustness should also be considered for optimal plan selection.

Experimental assessment of inter-centre variation in stopping-power and range prediction in particle therapy.

PURPOSE: Experimental assessment of inter-centre variation and absolute accuracy of stopping-power-ratio (SPR) prediction within 17 particle therapy centres of the European Particle Therapy Network. MATERIAL AND METHODS: A head and body phantom with seventeen tissue-equivalent materials were scanned consecutively at the participating centres using their individual clinical CT scan protocol and translated into SPR with their in-house CT-number-to-SPR conversion. Inter-centre variation and absolute accuracy in SPR prediction were quantified for three tissue groups: lung, soft tissues and bones. The integral effect on range prediction for typical clinical beams traversing different tissues was determined for representative beam paths for the treatment of primary brain tumours as well as lung and prostate cancer. RESULTS: An inter-centre variation in SPR prediction (2σ) of 8.7%, 6.3% and 1.5% relative to water was determined for bone, lung and soft-tissue surrogates in the head setup, respectively. Slightly smaller variations were observed in the body phantom (6.2%, 3.1%, 1.3%). This translated into inter-centre variation of integral range prediction (2σ) of 2.9%, 2.6% and 1.3% for typical beam paths of prostate-, lung- and primary brain-tumour treatments, respectively. The absolute error in range exceeded 2% in every fourth participating centre. The consideration of beam hardening and the execution of an independent HLUT validation had a positive effect, on average. CONCLUSION: The large inter-centre variations in SPR and range prediction justify the currently clinically used margins accounting for range uncertainty, which are of the same magnitude as the inter-centre variation. This study underlines the necessity of higher standardisation in CT-number-to-SPR conversion.

Assessment of the impact of CT calibration procedures for proton therapy planning on pediatric treatments.

PURPOSE: Relative stopping powers (RSPs) for proton therapy are estimated using single-energy computed tomography (SECT), calibrated with standardized tissues of the adult male. It is assumed that those tissues are representative of tissues of all age and sex. Female, male, and pediatric tissues differ from one another in density and composition. In this study, we use tabulated pediatric tissues and computational phantoms to investigate the impact of this assumption on pediatric proton therapy. The potential of dual-energy CT (DECT) to improve the accuracy of these calculations is explored. METHODS: We study 51 human body tissues, categorized into male/female for the age groups newborn, 1-, 5-, 10-, and 15-year-old children, and adult, with given compositions and densities. CT numbers are simulated and RSPs are estimated using SECT and DECT methods. Estimated tissue RSPs from each method are compared to theoretical RSPs. The dose and range errors of each approach are evaluated on three computational phantoms (Ewing's sarcoma, salivary sarcoma, and glioma) derived from pediatric proton therapy patients. RESULTS: With SECT, soft tissues have mean estimation errors and standard deviation up to (1.96 ± 4.18)% observed in newborns, compared to (0.20 ± 1.15)% in adult males. Mean estimation errors for bones are up to (-3.35 ± 4.76)% in pediatrics as opposed to (0.10 ± 0.66)% in adult males. With DECT, mean errors reduce to (0.17 ± 0.13)% and (0.23 ± 0.22)% in newborns (soft tissues/bones). With SECT, dose errors in a Ewing's sarcoma phantom are exceeding 5 Gy (10% of prescribed dose) at the distal end of the treatment field, with volumes of dose errors >5 Gy of V diff > 5 = 4630.7  mm3 . Similar observations are made in the head and neck phantoms, with overdoses to healthy tissue exceeding 2 Gy (4%). A systematic Bragg peak shift resulting in either over- or underdosage of healthy tissues and target volumes depending on the crossed tissues RSP prediction errors is observed. Water equivalent range errors of single beams are between -1.53 and 5.50 mm (min, max) (Ewing's sarcoma phantom), -0.78 and 3.62 mm (salivary sarcoma phantom), and -0.43 and 1.41 mm (glioma phantom). DECT can reduce dose errors to <1 Gy and range errors to <1 mm. CONCLUSION: Single-energy computed tomography estimates RSPs for pediatric tissues with systematic shifts. DECT improves the accuracy of RSPs and dose distributions in pediatric tissues compared to the SECT calibration curve based on adult male tissues.

Understanding the impact of pelvic organ motion on dose delivered to target volumes during IMRT for cervical cancer.

BACKGROUND: Advanced radiotherapy techniques reduce normal tissue dose by conforming closely to target volumes. In cervical cancer radiotherapy, organ filling affects clinical target volume (CTV; cervix, uterus) position. This study estimates the dosimetric effect of this primary CTV position variation during chemoradiation. METHODS/MATERIALS: Twice weekly cone-beam computed tomography (CBCT) images of ten patients undergoing cervical chemoradiation were retrospectively analysed. Primary CTV, bladder and rectum were delineated. RapidArc plans were created using 10-15mm CTV-PTV margins and dose delivered to CTV based on each CBCT position was calculated using a novel vector approach. Dose delivered along the central uterine, mid-uterus and cervix vectors were analysed as well as dose delivered to points at uterine tip, anterior mid-uterus and anterior cervix. Additional RapidArc plans were created for large planning bladder volume cases using the CTV acquired with bladder volume at 150-300cc. RESULTS: 105 scans for 10 patients were analysed. Vector analysis revealed CTV underdosing in certain cases. Below 95% average vector coverage was found for all three vectors in 2 cases and one vector in 1 case. Volumetric analysis revealed D99<95% in 48% of fractions. Patients with large planning bladder volumes (>300cc) demonstrated the largest variation. Replanning improved this coverage. The anterior mid-uterus point was least well-covered; median 98.7% dose, reducing to 91.4% in cases with large planning bladder volumes. Again, replanning significantly improved this. D99>95% was maintained in 93% of fractions when bladder volume was 50cc below to 150cc above planning volume compared to 24% of fractions if bladder volume was outside this range. Similarly, D95>95% was 100% versus 84%. CONCLUSION: Organ position variation detrimentally affected dose delivered to CTV including cervix. Large planning bladder volumes (>300cc) led to more variation. We recommend bladder volumes of 150-300cc at planning and a range of 50cc below to 150cc above planning for treatment.

The dosimetric impact of target volume delineation variation for cervical cancer radiotherapy.

BACKGROUND: Cervical cancer inter-observer delineation variation has been demonstrated. This article addresses its dosimetric impact. METHODS: 21 centres outlined two INTERLACE trial quality assurance test cases. A gold standard clinical target volume (GSCTV) was created from a consensus and STAPLE outline. RapidArc plans were created for all centres' planning target volumes (PTVs; PTV1+2). Gold standard PTVs (GSPTVs) were created for each plan by applying each centre's CTV-PTV margins to GSCTV. DVH parameters including D95% and Dmean for each PTV1+2 and GSPTV were compared, representing planned versus GSPTV delivered dose. PTV1+2 and GSPTV V95% was also calculated. RESULTS: Reviewing all parameters, no plans achieved acceptable GSPTV coverage. GSPTV V95%⩾95% was not achieved for any plan. GSPTV V95%<90% in 15/21 (case 1) and 14/22 (case 2) and <80% in 2 plans from both cases. GSPTV V95% is on average 10-15% lower than planned and GSPTV D95% is 10-20% lower than planned. Most common GSCTV anatomical areas not receiving 95% dose were vagina, obturator and external iliac nodes and, in case 1, the superior nodal aspect. CONCLUSION: Cervical cancer CTV delineation variation leads to significant reductions in dose delivered to GSPTV. This highlights the ongoing importance of standardising delineation in the IMRT era.