Publications by authors named "S Molinelli"

60 Publications

How LEM-based RBE and dose-averaged LET affected clinical outcomes of sacral chordoma patients treated with carbon ion radiotherapy.

Radiother Oncol 2021 Sep 17;163:209-214. Epub 2021 Sep 17.

Fondazione CNAO, Pavia, Italy.

Purpose/objective: To understand the role of relative biological effectiveness (RBE) and dose-averaged linear energy transfer (LET) distributions in the treatment of sacral chordoma (SC) patients with carbon ion radiotherapy (CIRT).

Material/methods: Clinical plans of 50 SC patients consecutively treated before August 2018 with a local effect model-based optimization were recalculated with the modified microdosimetric kinetic RBE model (mMKM). Twenty-six patients were classified as progressive disease and the relapse volume was contoured on the corresponding follow-up diagnostic sequence. The remaining 24 patients populated the control group. Target prescription dose (D), near-to-minimum- (D) and near-to-maximum- (D) doses were compared between the two cohorts in both RBE systems. LET distribution was evaluated for in-field relapsed cases with respect to the control group.

Results: Target D and D were respectively 10% and 18% lower than what we aimed at. Dosimetric evaluators showed no significant difference, in neither of the RBE frameworks, between relapsed and control sets. Half of the relapse volumes were located in a well-covered high dose region. On average, over these cases, median target LET was significantly lower than the control cohort mean value (27 vs 30 keV/μm). Most notably, the volume receiving dose from high-LET particles (>50 keV/μm) lay substantially below recently reported data in the literature.

Conclusion: A combined multi model RBE- and LET-based optimization could play a key role in the enhancement of the therapeutic ratio of CIRT for large radioresistant tumors such as sacral chordomas.
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September 2021

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

Radiother Oncol 2021 Jul 27;163:7-13. Epub 2021 Jul 27.

OncoRay - National Center for Radiation Research in Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Helmholtz-Zentrum Dresden - Rossendorf, Dresden, Germany; Helmholtz-Zentrum Dresden - Rossendorf, Institute of Radiooncology - OncoRay, Dresden, Germany; Department of Radiotherapy and Radiation Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Germany; German Cancer Consortium (DKTK), partner site Dresden, and German Cancer Research Center (DKFZ), Heidelberg, Germany.

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.
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July 2021

High-dose hypofractionated pencil beam scanning carbon ion radiotherapy for lung tumors: Dosimetric impact of different spot sizes and robustness to interfractional uncertainties.

Phys Med 2021 May 10;85:79-86. Epub 2021 May 10.

CNAO, National Center for Oncological Hadrontherapy, Strada Campeggi 53, I-27100 Pavia, Italy.

Purpose: The robustness against setup and motion uncertainties of gated four-dimensional restricted robust optimization (4DRRO) was investigated for hypofractionated carbon ion radiotherapy (CIRT) of lung tumors.

Methods: CIRT plans of 9 patients were optimized using 4DRRO strategy with 3 mm setup errors, 3% density errors and 3 breathing phases related to the gate window. The prescription was 60 Gy(RBE) in 4 fractions. Standard spots (SS) were compared to big spots (BS). Plans were recalculated on multiple 4DCTs acquired within 3 weeks from treatment simulation and rigidly registered with planning images using bone matching. Warped dose distributions were generated using deformable image registration and accumulated on the planning 4DCTs. Target coverage (D98%, D95% and V95%) and dose to lung were evaluated in the recalculated and accumulated dose distributions.

Results: Comparable target coverage was obtained with both spot sizes (p = 0.53 for D95%). The mean lung dose increased of 0.6 Gy(RBE) with BS (p = 0.0078), still respecting the dose constraint of a 4-fraction stereotactic treatment for the risk of radiation pneumonitis. Statistically significant differences were found in the recalculated and accumulated D95% (p = 0.048 and p = 0.024), with BS showing to be more robust. Using BS, the average degradations of the D98%, D95% and V95% in the accumulated doses were -2.7%, -1.6% and -1.5%.

Conclusions: Gated 4DRRO was highly robust against setup and motion uncertainties. BS increased the dose to healthy tissues but were more robust than SS. The selected optimization settings guaranteed adequate target coverage during the simulated treatment course with acceptable risk of toxicity.
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May 2021

Ultrahypofractionated radiotherapy for localized prostate cancer with simultaneous boost to the dominant intraprostatic lesion: a plan comparison.

Tumori 2021 Apr 25:3008916211011667. Epub 2021 Apr 25.

Department of Radiation Oncology, Istituto Europeo di Oncologia IRCCS, Milan, Italy.

Objective: To compare different stereotactic body techniques-intensity-modulated radiotherapy with photons and protons, applied to radiotherapy of prostatic cancer-with simultaneous integrated boost (SIB) on the dominant intraprostatic lesion (DIL).

Methods: Ten patients were selected for this planning study. Dosimetric results were compared between volumetric modulated arc therapy, intensity-modulated radiation therapy (IMRT), and intensity-modulated proton therapy both with two (IMPT 2F) and five fields (IMPT 5F) planning while applying the prescription schemes of 7.25 Gy/fraction to the prostate gland and 7.5 Gy/fraction to the DIL in 5 fractions.

Results: Comparison of the coverages of the planning target volumes showed that small differences exist. The IMPT-2F-5F techniques allowed higher doses in the targets; conformal indexes resulted similar; homogeneity was better in the photon techniques (2%-5%). Regarding the organs at risk, all the techniques were able to maintain the dose well below the prescribed constraints: in the rectum, the IMPT-2F-5F and IMRT were more efficient in lowering the intermediate doses; in the bladder, the median dose was significantly better in the case of IMPT (2F-5F). In the urethra, the best sparing was achieved only by IMPT-5F.

Conclusions: Stereotactic radiotherapy with SIB for localized prostate cancer is feasible with all the investigated techniques. Concerning IMPT, the two-beam technique does not seem to have a greater advantage compared to the standard techniques; the 5-beam technique seems more promising also accounting for the range uncertainty.
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April 2021

Investigating DWI changes in white matter of meningioma patients treated with proton therapy.

Phys Med 2021 Apr 16;84:72-79. Epub 2021 Apr 16.

Department of Electronics, Information and Bioengineering, Politecnico di Milano, Piazza Leonardo da Vinci 32, 20133 Milan, Italy. Electronic address:

Purpose: To evaluate changes in diffusion and perfusion-related properties of white matter (WM) induced by proton therapy, which is capable of a greater dose sparing to organs at risk with respect to conventional X-ray radiotherapy, and to eventually expose early manifestations of delayed neuro-toxicities.

Methods: Apparent diffusion coefficient (ADC) and IVIM parameters (D, D* and f) were estimated from diffusion-weighted MRI (DWI) in 46 patients affected by meningioma and treated with proton therapy. The impact on changes in diffusion and perfusion-related WM properties of dose and time, as well as the influence of demographic and pre-treatment clinical information, were investigated through linear mixed-effects models.

Results: Decreasing trends in ADC and D were found for WM regions hit by medium-high (30-40 Gy(RBE)) and high (>40 Gy(RBE)) doses, which are compatible with diffusion restriction due to radiation-induced cellular injury. Significant influence of dose and time on median ADC changes were observed. Also, D* showed a significant dependency on dose, whereas f consistently showed no dependency on dose and time. Age, gender and surgery extent were also found to affect changes in ADC.

Conclusions: These results overall agree with those from studies conducted on cohorts of mixed proton and X-ray radiotherapy patients. Future work should focus on relating our findings with clinical information of co-morbidities and thus exploiting such or more advanced imaging data to build normal tissue complication probability models to better integrate clinical and dose information.
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April 2021