Barbara Rombi

Spot-scanning proton radiation therapy for pediatric chordoma and chondrosarcoma: clinical outcome of 26 patients treated at paul scherrer institute.

PURPOSE To evaluate the clinical results of fractionated spot-scanning proton radiation therapy (PT) in 26 pediatric patients treated at Paul Scherrer Institute for chordoma (CH) or chondrosarcoma (CS) of the skull base or axial skeleton. METHODS AND MATERIALS Between June 2000 and June 2010, 19 CH and 7 CS patients with tumors originating from the skull base (17) and the axial skeleton (9) were treated with PT. Mean age at the time of PT was 13.2 years. The mean prescribed dose was 74 Gy (relative biological effectiveness [RBE]) for CH and 66 Gy (RBE) for CS, at a dose of 1.8-2.0 Gy (RBE) per fraction. RESULTS Mean follow-up was 46 months. Actuarial 5-year local control (LC) rates were 81% for CH and 80% for CS. Actuarial 5-year overall survival (OS) was 89% for CH and 75% for CS. Two CH patients had local failures: one is alive with evidence of disease, while the other patient succumbed to local recurrence in the surgical pathway. One CS patient died of local progression of the disease. No high-grade late toxicities were observed. CONCLUSIONS Spot-scanning PT for pediatric CH and CS patients resulted in excellent clinical outcomes with acceptable rates of late toxicity. Longer follow-up time and larger cohort are needed to fully assess tumor control and late effects of treatment.

Experimental verification of IMPT treatment plans in an anthropomorphic phantom in the presence of delivery uncertainties

Clinically relevant intensity modulated proton therapy (IMPT) treatment plans were measured in a newly developed anthropomorphic phantom (i) to assess plan accuracy in the presence of high heterogeneity and (ii) to measure plan robustness in the case of treatment uncertainties (range and spatial). The new phantom consists of five different tissue substitute materials simulating different tissue types and was cut into sagittal planes so as to facilitate the verification of co-planar proton fields. GafChromic films were positioned in the different planes of the phantom, and 3D-IMPT and distal edge tracking (DET) plans were delivered to a volume simulating a skull base chordoma. In addition, treatments planned on CTs of the phantom with HU units modified were delivered to simulate systematic range uncertainties (range-error treatments). Finally, plans were delivered with the phantom rotated to simulate spatial errors. Results show excellent agreement between the calculated and the measured dose distribution: >99% and 98% of points with a gamma value <1 (3%/3 mm) for the 3D-IMPT and the DET plan, respectively. For both range and spatial errors, the 3D-IMPT plan was more robust than the DET plan. Both plans were more robust to range than to the spatial uncertainties. Finally, for range error treatments, measured distributions were compared to a model for predicting delivery errors in the treatment planning system. Good agreement has been found between the model and the measurements for both types of IMPT plan.

Supine craniospinal irradiation in pediatric patients by proton pencil beam scanning

BACKGROUND AND PURPOSE Proton therapy is the emerging treatment modality for craniospinal irradiation (CSI) in pediatric patients. Herein, special methods adopted for CSI at proton Therapy Center of Trento by pencil beam scanning (PBS) are comprehensively described. MATERIALS AND METHODS Twelve pediatric patients were treated by proton PBS using two/three isocenters. Special methods refer to: (i) patient positioning in supine position on immobilization devices crossed by the beams; (ii) planning field-junctions via the ancillary-beam technique; (iii) achieving lens-sparing by three-beams whole-brain-irradiation; (iv) applying a movable-snout and beam-splitting technique to reduce the lateral penumbra. Patient-specific quality assurance (QA) program was performed using two-dimensional ion chamber array and γ-analysis. Daily kilovoltage alignment was performed. RESULTS PBS allowed to obtain optimal target coverage (mean D98%>98%) with reduced dose to organs-at-risk. Lens sparing was obtained (mean D1∼730cGyE). Reducing lateral penumbra decreased the dose to the kidneys (mean Dmean<600cGyE). After kilovoltage alignment, potential dose deviations in the upper and lower junctions were small (average 0.8% and 1.2% respectively). Due to imperfect modeling of range shifter, QA showed better agreements between measurements and calculations at depths >4cm (mean γ>95%) than at depths<4cm. CONCLUSIONS The reported methods allowed to effectively perform proton PBS CSI.

Proton Beam Therapy for Pediatric Chordomas: State of the Art

Chordomas are a rare form of primary bone tumors arising from clivus, vertebra, and sacrum. Although it usually occurs in adults, children can be affected too. Multidisciplinary treatment is required and is particularly challenging because the chordoma’s proximity to critical structures creates a high risk for significant adverse events. Standard procedure consists of extensive surgery followed by high-dose radiation therapy in excess of 70 Gy. Proton beam therapy has become one of the standard procedures to achieve high, local intensity while maximally sparing normal tissue in adults and children. Results achieved so far are promising and are superior to what has been achieved with surgery alone or conventional radiation therapy. When compared with modern photon radiation techniques, such as intensity-modulated radiation therapy, proton beam therapy may be of particular interest for children to provide high conformality while reducing the irradiated volume and therefore potentially minimizing the risk for secondary cancer induction. The role of chemotherapy remains to be defined.

Universal field matching in craniospinal irradiation by a background‐dose gradient‐optimized method

Abstract Purpose The gradient‐optimized methods are overcoming the traditional feathering methods to plan field junctions in craniospinal irradiation. In this note, a new gradient‐optimized technique, based on the use of a background dose, is described. Methods Treatment planning was performed by RayStation (RaySearch Laboratories, Stockholm, Sweden) on the CT scans of a pediatric patient. Both proton (by pencil beam scanning) and photon (by volumetric modulated arc therapy) treatments were planned with three isocenters. An ‘in silico’ ideal background dose was created first to cover the upper‐spinal target and to produce a perfect dose gradient along the upper and lower junction regions. Using it as background, the cranial and the lower‐spinal beams were planned by inverse optimization to obtain dose coverage of their relevant targets and of the junction volumes. Finally, the upper‐spinal beam was inversely planned after removal of the background dose and with the previously optimized beams switched on. Results In both proton and photon plans, the optimized cranial and the lower‐spinal beams produced a perfect linear gradient in the junction regions, complementary to that produced by the optimized upper‐spinal beam. The final dose distributions showed a homogeneous coverage of the targets. Discussion Our simple technique allowed to obtain high‐quality gradients in the junction region. Such technique universally works for photons as well as protons and could be applicable to the TPSs that allow to manage a background dose.

SIOPE – Brain tumor group consensus guideline on craniospinal target volume delineation for high-precision radiotherapy

OBJECTIVE To develop a consensus guideline for craniospinal target volume (TV) delineation in children and young adults participating in SIOPE studies in the era of high-precision radiotherapy. METHODS AND MATERIALS During four consensus meetings (Cambridge, Essen, Liverpool, and Marseille), conventional field-based TV has been translated into image-guided high-precision craniospinal TV by a group of expert paediatric radiation oncologists and enhanced by MRI images of liquor distribution. RESULTS The CTVcranial should include the whole brain, cribriform plate, most inferior part of the temporal lobes, and the pituitary fossa. If the full length of both optic nerves is not included, the dose received by different volumes of optic nerve should be recorded to correlate with future patterns of relapse (no consensus). The CTVcranial should be modified to include the dural cuffs of cranial nerves as they pass through the skull base foramina. Attempts to spare the cochlea by excluding CSF within the internal auditory canal should be avoided. The CTVspinal should include the entire subarachnoid space, including nerve roots laterally. The lower limit of the spinal CTV is at the lower limit of the thecal sac, best visible on MRI scan. There is no need to include sacral root canals in the spinal CTV. CONCLUSION This consensus guideline has the potential to improve consistency of craniospinal TV delineation in an era of high-precision radiotherapy. This proposal will be incorporated in the RTQA guidelines of future SIOPE-BTG trials using CSI.

EP-1691: A planning approach for lens sparing proton craniospinal irradiation in pediatric patients

S789 ________________________________________________________________________________ majority of cases surpassed all optimal dose constraints demonstrating the high quality of the planning technique. The incorporation of deep inspiration breath hold (DIBH) ensured doses to the heart were exceptionally low; mean heart dose for left breast cases averaged 1.4Gy for both treatment options. As neither technique has proven superior, the significantly reduced treatment times associated with VMAT make this a more desirable option to implement clinically.

Radiosurgery and Hypofractionated Stereotactic Irradiation with Photons or Protons for Tumours of the Skull Base

Recent technological advances in photon-RT have allowed an improvement in targeting accuracy, dose escalation, delivery of multiple large fractions (hypofractionated stereotactic radiation therapy HSRT) or single fraction stereotactic ablative radiation therapy (radiosur‐ gery SRS). Radiosurgery delivers a single large dose with very steep dose fall-off outside the lesion to very small volumes in order to be tumouricidal through DNA damage or ablative causing necrosis via a vascular endothelial damage [1]. Furthermore, it has been shown that molecular responses to radiation differ based on dose per fraction. More recently, HSRT in two to five sessions has been employed to deliver extremely hypofractionated regimens. Prelimi‐ nary data suggest that HSRT may represent an effective treatment associated with lower risk of radiation-related adverse effects in patients with perioptic or large benign tumours as compared with single fraction SRS, although potential benefits remain to be demonstrated.

The Role of Irradiation in the Treatment of Chordoma of the Base of Skull and Spine

Chordoma is an uncommon neoplasm of the bone arising from embryonic remnants of the notochord. The overall age-adjusted incidence is about 8 per 10 million, but this figure is dependent on age, sex, and race (Jemal et al., 2007). This tumor typically occurs in the axial skeleton mainly involving the sacrococcygeal region and the base of the skull (Mirra et al., 2002). The natural history of such malignancy is of a slow but progressive growth ultimately translating into a local aggressive behaviour. Overall, five-year survival rates are near 60% to 70%, although 10-year survival drops to 35% to 40% (Dorfman, 1998). The rate of distant metastases (to lung, bone, soft tissue, lymph nodes, liver, and skin) varies in a range between 0% and 40% (Chambers et al., 1979) even though usually late detected with most patients succumbing to their local disease. Based on these considerations the control of primary disease remains the major therapeutic challenge. Given the rarity of this tumor, data on efficacy and safety of the treatments are limited and mainly based on few, small sized, retrospective series. The standard of care is considered surgery, when feasible, with the aim of establishing a definitive diagnosis and obtaining the maximal debulking of the lesion. Surgical outcomes depend on tumor location and size at diagnosis. Considering the large size of most sacral lesions and the proximity to critical healthy structures of skull base and vertebral chordomas, maximal resection usually entails a relevant morbidity with poor functional outcome in a significant proportion of patients. Therefore, even if local control and survival rates strictly depend on the achievement of negative margins, radical surgery can be rarely obtained (Cotler et al., 1983). In such scenario recurrence rates can approach 70%. This situation clearly supports the interest for radiation therapy as an adjuvant modality after residual disease even though the irregular and infiltrative nature of this tumor makes it difficult to be targeted. The role of irradiation either as a postoperative treatment or as a curative measure in inoperable lesions is widely debated. Chordomas have been historically considered radio resistant tumors requiring high doses of radiation (> 60 Gy) to respond best. However, a dose–response relationship has not been clearly reported across all series (Tai et al., 1995) and the doses needed to control the tumor in general exceed the tolerance dose levels of nearby normal structures (Pai, 2001; Slater, 1988). Several irradiation modalities have been proposed (particle therapy, intensity-modulated radiation therapy, stereotactic irradiation) without a clearly established superiority of one