Clinical radiobiology of head and neck cancer: the hypothesis of stem cell activation.

PURPOSE: To estimate and reduce uncertainties of a self-consistent set of radiobiological parameters based on the outcome of head and neck cancer (HNC) patients treated with radiotherapy (RT). METHODS: Published studies comparing at least two RT schedules for HNC patients were selected. The method used to estimate the radiobiological parameters consists of three sequential steps that allow a significant reduction of uncertainties: the first, in which the intrinsic (α) and the repair (ß) radio-sensitivities were estimated together with the doubling time (T d) by an analytical/graphical method; the second, in which the kick-off time for accelerated proliferation (T k) was estimated applying the hypothesis of activation for sub-populations of stem cells during the RT; the third, in which the number of clonogens (N) was obtained by the Tumor Control Probability (TCP) model. Independent clinical data were used to validate results. RESULTS: The best estimate and the 95 % confidence intervals (95 % CIs) were: α = 0.24 Gy(-1) (0.23-0.26), ß = 0.023 Gy(-2) (0.021-0.025), α/ß = 10.6 Gy (8.4-12.6), T d = 3.5 days (3.1-3.9), T k = 19.2 days (15.1-23.3), N = 7 × 10(7) (4 × 10(7)-1 × 10(8)). From these data, the dose required to offset repopulation occurring in 1 day (D prolif) and starting after T k was also estimated as 0.69 Gy/day (0.52-0.86). CONCLUSIONS: The estimation of all the radiobiological parameters of HNC was obtained based on the hypothesis of activation for specifically tumorigenic sub-populations of stem cells. The similarity of results to those from other studies strengthens such a hypothesis that could be very useful for the predictivity of the TCP model and to design new treatment strategies for HNC.

To evaluate the accuracy of dynamic versus static IMRT delivery using portal dosimetry.

INTRODUCTION: To evaluate the delivery accuracy of dynamic (DMLC) and static (SMLC) intensity modulated radiation therapy (IMRT) techniques using portal dosimetry (PD) in Varian Eclipse Treatment Planning System. MATERIALS AND METHODS: Seven DMLC IMRT Head and Neck plans were retrospectively generated for the study using SMLC mode at 20, 10 and 5 levels of intensity (SMLC20, SMLC10, SMLC5). Dosimetric verifications performed by PD on a total of 107 fields were evaluated using the gamma index (maximum (γmax), average (γavg), percentage of points with (γ%) ≤ 1). The images were acquired at a source-detector distance of 100 cm at gantry zero degree and also at clinically planned gantry angles. RESULTS: For both modes, measurements are within acceptable criteria. (γ%) ≤ 1 improves by increasing SMLC levels (+3.4 % from SMLC5 to SMLC20, p < 0.001) and using DMLC (+3.9 % and +0.6 % compared to SMLC5 and SMLC20, respectively, p < 0.001). Also (γmax) parameter improves significantly by increasing SMLC levels (+22 % from SMLC5 to SMLC20) and using DMLC (+34 % and +16 % compared to SMLC5 and SMLC20, respectively). The effect of the gantry rotation influences the delivery accuracy by up to -7 % (p < 0.05). The effect of leaves travelling direction was almost negligible (1 %). CONCLUSIONS: A good agreement between calculated and measured fluences was obtained for DMLC and SMLC techniques at higher intensity levels; however, DMLC delivery ensures the best reproduction of computed fluence maps. The gantry rotation influences the delivery accuracy in particular for SMLC modes at lower intensity levels.

The impact of computed tomography slice thickness on the assessment of stereotactic, 3D conformal and intensity-modulated radiotherapy of brain tumors.

PURPOSE: To evaluate radiotherapy treatment planning accuracy by varying computed tomography (CT) slice thickness and tumor size. METHODS: CT datasets from patients with primary brain disease and metastatic brain disease were selected. Tumor volumes ranging from about 2.5 to 100 cc and CT scan at different slice thicknesses (1, 2, 4, 6 and 10 mm) were used to perform treatment planning (1-, 2-, 4-, 6- and 10-CT, respectively). For any slice thickness, a conformity index (CI) referring to 100, 98, 95 and 90 % isodoses and tumor size was computed. All the CI and volumes obtained were compared to evaluate the impact of CT slice thickness on treatment plans. RESULTS: The smallest volumes reduce significantly if defined on 1-CT with respect to 4- and 6-CT, while the CT slice thickness does not affect target definition for the largest volumes. The mean CI for all the considered isodoses and CT slice thickness shows no statistical differences when 1-CT is compared to 2-CT. Comparing the mean CI of 1- with 4-CT and 1- with 6-CT, statistical differences appear only for the smallest volumes with respect to 100, 98 and 95 % isodoses-the CI for 90 % isodose being not statistically significant for all the considered PTVs. CONCLUSIONS: The accuracy of radiotherapy tumor volume definition depends on CT slice thickness. To achieve a better tumor definition and dose coverage, 1- and 2-CT would be suitable for small targets, while 4- and 6-CT are suitable for the other volumes.

Clinical target volume definition for glioblastoma radiotherapy planning: magnetic resonance imaging and computed tomography.

PURPOSE: To assess the differences between the target delineation using computed tomography (CT) and imaging fusion CT/magnetic resonance imaging (MRI) for the radiotherapy planning of glioblastoma. METHODS: One hundred-twenty gross tumor volume and clinical target volume on CT and MRI (GTVCT/CTVCT, GTVMRI/CTVMRI, respectively) were contoured and evaluated. The treatments planning (total dose 60 Gy) based on CTVCT were analysed in terms of percentage of CTVCT and CTVMRI receiving 95 % of the prescribed dose (V95-CTVCT, V95-CTVMRI). RESULTS: GTVs and CTVs contoured on MRI were significantly larger than those delineated on CT (p = 0.0003, p = 0.0006, respectively). Nighty-two percent of CTVCT was coincident with the CTVMRI and 8 % was normal tissue; 20 % of CTVMRI, considered as tumor volume, was not included on CTVCT. The V95-CTVMRI was significantly lower than the V95-CTVCT (p = 0.0005). CONCLUSIONS: In the delineation of glioblastoma target volume, fusion CT/MRI was preferred. The CT only is insufficient for the CTV dose coverage.

Planning target volume assessment in lung tumors during 3D conformal radiotherapy by means of an aSi electronic portal imaging device in cine mode.

PURPOSE: The major uncertainties in treating lung cancer are the repositioning errors and respiratory lung tumor motion. Typically, margins are added to the clinical target volume (CTV) to obtain a planning target volume (PTV) allowing the accommodation of such uncertainties. We want to test a new technique to assess the adequacy of the chosen PTV using an aSi electronic portal imaging device (EPID). METHODS: Four patients affected by lung cancer and treated by radical 3D conformal radiotherapy (3DRT) were studied. During treatment the EPID was used in cine mode acquisition: acquired images were used to the aim. RESULTS AND CONCLUSIONS: Treatment monitoring with an EPID in cine mode is shown to be a clinically feasible and useful tool.

Cone-beam computed tomography dose monitoring during intensity-modulated radiotherapy in head and neck cancer: parotid glands.

PURPOSE: To evaluate the dosimetric changes of parotid glands (PG) during a course of intensity-modulated radiotherapy (IMRT) in head and neck (H&N) cancer patients. METHODS: Ten patients with H&N cancer treated by IMRT were analyzed. The original treatment plan (CT(plan)) was transferred to cone-beam computed tomography (CBCT) acquired at the 15th and 20th treatment day (CBCT(plan) I and II, respectively). The PG mean dose (D(mean)), the dose to 50 % of the volume, and the percent of volume receiving 30 and 50 Gy were measured by the dose volume histogram. RESULTS: 30 IMRT plans were evaluated (3 plans/patient). All dosimetric end points increased significantly for both PG only when CT(plan) was compared to CBCT(plan) I. The D(mean) increased significantly only for ipsilateral PG (p = 0.02) at week 3. CONCLUSION: During a course of IMRT, CBCT is a feasible method to check the PG dosimetric variations. Perhaps, the 3rd week of radiotherapy could be considered as the time-check-point.

Apresentações incomuns do hemangioma hepático: ensaio iconográfico / Unusual presentations of hepatic hemangioma: an iconographic essay

O nosso objetivo foi descrever e ilustrar aspectos incomuns do hemangioma hepático na ultra-sonografia (US), tomografia computadorizada (TC) e ressonância magnética (RM). A partir da análise retrospectiva de 300 casos de pacientes com diagnósticos de hemangioma hepático, por meio da análise combinada de exames de imagem, biópsia ou acompanhamento clínico, selecionamos aqueles com apresentação atípica em um ou mais métodos de imagem ou aqueles com evolução não usual, ilustrando os seus principais aspectos de imagem. Entre os casos apresentados, escolhemos pacientes com hemangiomas: hipoecogênicos na US; hipovasculares ou avasculares na TC e RM; com calcificações grosseiras; gigantes e medindo mais de 20 cm de diâmetro; predominantemente exofíticos; hipointensos em T2; promovendo defeito de perfusão; com cicatriz central e simulando hiperplasia nodular focal; com crescimento evolutivo. O hemangioma hepático é o tumor mais comum do fígado e geralmente tem apresentação típica. Porém, os seus diversos aspectos não usuais precisam ser conhecidos para auxiliar na orientação diagnóstica e conduta.

In order to evaluate atypical aspects of hepatic hemangiomas at ultrasound (US), computed tomography (CT) and magnetic resonance imaging (MRI), we have retrospectively analyzed 300 cases of patients diagnosed with hepatic hemangiomas by means of combined imaging studies, clinical follow-up and/or biopsy results. Based on this analysis we have selected those cases with atypical findings at one or more imaging methods or those presenting an unusual evolution such as: hypoechoic nodules at US; giant, heterogeneous hemangiomas; rapidly filling hemangiomas; calcified hemangiomas; pedunculated hemangiomas; hypointense hemangiomas at T2-weighted images; causing perfusion defect; with central scar simulating focal nodular hyperplasia; hemangiomas with adjacent abnormalities such as arterial-portal venous shunt and capsular retraction as well as hemangiomas enlarging over time. The hepatic hemangioma is the most common benign tumor affecting the liver and usually presents typical aspect. However, atypical findings should be known aiming at supporting diagnosis guidance and clinical decisions.