Publications by authors named "I Rinaldi"

86 Publications

Study of relationship between dose, LET and the risk of brain necrosis after proton therapy for skull base tumors.

Radiother Oncol 2021 Aug 27;163:143-149. Epub 2021 Aug 27.

Institute of Nuclear Physics Polish Academy of Sciences, 31342 Krakow, Poland.

Purpose: We investigated the relationship between RBE-weighted dose (DRBE) calculated with constant (cRBE) and variable RBE (vRBE), dose-averaged linear energy transfer (LETd) and the risk of radiographic changes in skull base patients treated with protons.

Methods: Clinical treatment plans of 45 patients were recalculated with Monte Carlo tool FRED. Radiographic changes (i.e. edema and/or necrosis) were identified by MRI. Dosimetric parameters for cRBE and vRBE were computed. Biological margin extension and voxel-based analysis were employed looking for association of DRBE(vRBE) and LETd with brain edema and/or necrosis.

Results: When using vRBE, Dmax in the brain was above the highest dose limits for 38% of patients, while such limit was never exceeded assuming cRBE. Similar values of Dmax were observed in necrotic regions, brain and temporal lobes. Most of the brain necrosis was in proximity to the PTV. The voxel-based analysis did not show evidence of an association with high LETd values.

Conclusions: When looking at standard dosimetric parameters, the higher dose associated with vRBE seems to be responsible for an enhanced risk of radiographic changes. However, as revealed by a voxel-based analysis, the large inter-patient variability hinders the identification of a clear effect for high LETd.
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http://dx.doi.org/10.1016/j.radonc.2021.08.015DOI Listing
August 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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http://dx.doi.org/10.1016/j.radonc.2021.07.019DOI Listing
July 2021

Diagnostic Value of Neutrophil Lymphocyte Ratio and D-Dimer as Biological Markers of Deep Vein Thrombosis in Patients Presenting with Unilateral Limb Edema.

J Blood Med 2021 20;12:313-325. Epub 2021 May 20.

Department of Internal Medicine, Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia.

Introduction: Patients with deep vein thrombosis (DVT) pose high morbidity and mortality risk thus needing fast and accurate diagnosis. Wells clinical prediction scores with D-dimer testing are traditionally used to rule out patients with low probability of DVT. However, D-dimer testing has a few limitations regarding its relatively low specificity. Neutrophil-lymphocyte ratio (NLR), a marker of inflammation, was found to increase in DVT. Hence, we aimed to evaluate the role of NLR for DVT diagnosis.

Methods: Data were collected from medical records of patients with suspected DVT at Cipto Mangunkusumo National General Hospital during January-December 2014. Diagnosis of DVT was conducted using lower limb ultrasonography. Diagnostic values for NLR, D-dimer, and NLR + D-dimer were determined by receiver operating characteristic (ROC) analysis to obtain area under the curve (AUC), sensitivity, specificity, negative predictive value, and positive predictive values. Sensitivity and specificity analyses of NLR and D-dimer were also conducted based on Wells score and divided into groups of low and high probability of DVT.

Results: The AUC values for NLR, D-dimer, and NLR + D-dimer were 72.6%, 70.4%, and 76.1%, respectively. The optimal cut-off value determined for NLR was 5.12 with sensitivity of 67.7%, specificity of 67.9%, PPV of 68.85%, and NPV of 64.91% in differentiating subjects with and without DVT. This study also found that D-dimer had sensitivity of 69.4%, specificity of 71.4%, PPV of 72.88%, and NPV of 67.8%. Meanwhile, the NLR + D-dimer combination had sensitivity of 66.1% and specificity of 72.6%. Multivariate analysis showed that NLR (OR: 2.636; 95% CI: 1.144-6.076; p: 0.023) and D-dimer (OR: 4.175; 95% CI: 1.810-9.633; p: 0.001) were associated with DVT.

Conclusion: NLR value has wider AUC than D-Dimer and is relatively easier to obtain and does not require specific assay, thus enabling rapid evaluation of symptomatic patients suspected of having DVT. Adding NLR to D-dimer increased AUC to detect DVT. Therefore, NLR could serve as a complementary diagnostic tool for D-dimer to exclude DVT, especially in low clinical probability patients.
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http://dx.doi.org/10.2147/JBM.S291226DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8290850PMC
May 2021

Leukapheresis Does Not Improve Early Survival Outcome of Acute Myeloid Leukemia with Leukostasis Patients - A Dual-Center Retrospective Cohort Study.

J Blood Med 2021 14;12:623-633. Epub 2021 Jul 14.

Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia.

Introduction: Leukostasis is a medical emergency with high mortality which often occurs in acute myeloid leukemia patients with hyperleukocytosis. One of the therapies that can be used for leukostasis in acute myeloid leukemia is leukapheresis. However, whether leukapheresis can provide better survival benefit when compared with patients not receiving leukapheresis is still unclear. Hence, we aimed to evaluate the effect of chemotherapy plus leukapheresis combination versus chemotherapy only on 28-day survival of acute myeloid leukemia patients with leukostasis.

Methods: This study was a dual-center retrospective cohort using secondary data from medical records collected from November 2018 to March 2019. Inclusion criteria were adult patients aged 18 years old or above, diagnosed with acute leukemia with hyperleukocytosis status defined by WBC count greater than 100,000/uL, and with symptoms of leukostasis. One-month survival analysis was conducted using Kaplan-Meier curve method. Univariate and multivariate analyses were then conducted using Cox proportional hazards model to obtain value of hazard ratio (HR) with a 95% confidence interval (CI).

Results: A total of 38 patients were obtained for analysis. The median overall survival was 25 days (95% CI: 17.001-32.999 days) in the chemotherapy only group and 20 days (95% CI: 1.497-38.503) in the chemotherapy with leukapheresis group. The use of leukapheresis did not affect 28-day survival (HR: 1.140; 95% CI: 0.396-3.283; p value: 0.809) and 7-day survival (HR: 1.073; 95% CI: 0.277-4.152; p value: 0.919). In the multivariate analysis, age ≥60 years, blast percentage ≥90%, creatinine ≥1.4 mg/dL, and presence of disseminated intravascular coagulation were associated with worse 28-day survival.

Conclusion: AML patients with leukostasis who received both chemotherapy and leukapheresis did not have better 28-day survival and 7-day survival when compared with patients receiving chemotherapy only. Old age, high blast percentage, high creatinine, and presence of disseminated intravascular coagulation were prognostic factors for worse 28-day survival.
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http://dx.doi.org/10.2147/JBM.S312140DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8286962PMC
July 2021

Treatment planning and 4D robust evaluation strategy for proton therapy of lung tumors with large motion amplitude.

Med Phys 2021 Aug 17;48(8):4425-4437. Epub 2021 Jul 17.

Department of Radiation Oncology (MAASTRO), GROW - School for Oncology, Maastricht University Medical Centre+, Maastricht, Netherlands.

Purpose: Intensity-modulated proton therapy (IMPT) for lung tumors with a large tumor movement is challenging due to loss of robustness in the target coverage. Often an upper cut-off at 5-mm tumor movement is used for proton patient selection. In this study, we propose (1) a robust and easily implementable treatment planning strategy for lung tumors with a movement larger than 5 mm, and (2) a four-dimensional computed tomography (4DCT) robust evaluation strategy for evaluating the dose distribution on the breathing phases.

Materials And Methods: We created a treatment planning strategy based on the internal target volume (ITV) concept (aim 1). The ITV was created as a union of the clinical target volumes (CTVs) on the eight 4DCT phases. The ITV expanded by 2 mm was the target during robust optimization on the average CT (avgCT). The clinical plan acceptability was judged based on a robust evaluation, computing the voxel-wise min and max (VWmin/max) doses over 28 error scenarios (range and setup errors) on the avgCT. The plans were created in RayStation (RaySearch Laboratories, Stockholm, Sweden) using a Monte Carlo dose engine, commissioned for our Mevion S250i Hyperscan system (Mevion Medical Systems, Littleton, MA, USA). We developed a new 4D robust evaluation approach (4DRobAvg; aim 2). The 28 scenario doses were computed on each individual 4DCT phase. For each scenario, the dose distributions on the individual phases were deformed to the reference phase and combined to a weighted sum, resulting in 28 weighted sum scenario dose distributions. From these 28 scenario doses, VWmin/max doses were computed. This new 4D robust evaluation was compared to two simpler 4D evaluation strategies: re-computing the nominal plan on each individual 4DCT phase (4DNom) and computing the robust VWmin/max doses on each individual phase (4DRobInd). The treatment planning and dose evaluation strategies were evaluated for 16 lung cancer patients with tumor movement of 4-26 mm.

Results: The ratio of the ITV and CTV volumes increased linearly with the tumor amplitude, with an average ratio of 1.4. Despite large ITV volumes, a clinically acceptable plan fulfilling all target and organ at risk (OAR) constraints was feasible for all patients. The 4DNom and 4DRobInd evaluation strategies were found to under- or overestimate the dosimetric effect of the tumor movement, respectively. 4DRobInd showed target underdosage for five patients, not observed in the robust evaluation on the avgCT or in 4DRobAvg. The accuracy of dose deformation used in 4DRobAvg was quantified and found acceptable, with differences for the dose-volume parameters below 1 Gy in most cases.

Conclusion: The proposed ITV-based planning strategy on the avgCT was found to be a clinically feasible approach with adequate tumor coverage and no OAR overdosage even for large tumor movement. The new proposed 4D robust evaluation, 4DRobAvg, was shown to give an easily interpretable understanding of the effect of respiratory motion dose distribution, and to give an accurate estimate of the dose delivered in the different breathing phases.
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http://dx.doi.org/10.1002/mp.15067DOI Listing
August 2021
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