Stereotactic Radiation Therapy for Brain Metastases: Factors Affecting Outcomes and Radiation Necrosis.

Stereotactic radiation therapy (SRT) is a proven effective treatment for brain metastases (BM); however, symptomatic radiation necrosis (RN) is a late effect that may impact on patient's quality of life. The aim of our study was to retrospectively evaluate survival outcomes and characterize the occurrence of RN in a cohort of BM patients treated with ablative SRT at Federico II University Hospital. Clinical and dosimetric factors of 87 patients bearing a total of 220 BMs treated with SRT from 2016 to 2022 were analyzed. Among them, 46 patients with 127 BMs having clinical and MRI follow-up (FUP) ≥ 6 months were selected for RN evaluation. Dosimetric parameters of the uninvolved brain (brain without GTV) were extracted. The crude local control was 91% with neither clinical factors nor prescription dose correlating with local failure (LF). At a median FUP of 9 (1-68) months, the estimated median overall survival (OS), progression-free survival (PFS), and brain progression-free survival (bPFS) were 16, 6, and 9 months, respectively. The estimated OS rates at 1 and 3 years were 59.8% and 18.3%, respectively; bPFS at 1 and 3 years was 29.9% and 13.5%, respectively; PFS at 1 and 3 years was 15.7% and 0%, respectively; and local failure-free survival (LFFS) at 1 and 3 years was 87.2% and 83.8%, respectively. Extracranial disease status was an independent factor related to OS. Fourteen (30%) patients manifested RN. At multivariate analysis, adenocarcinoma histology, left location, and absence of chemotherapy were confirmed as independent risk factors for any-grade RN. Nine (20%) patients developed symptomatic (G2) RN, which improved or stabilized after 1-16 months of steroid therapy. With prompt recognition and, when necessary, medical therapy, RN radiological and clinical amelioration can be obtained.

Patient-specific Monte Carlo-based organ dose estimates in spiral CT via optical 3D body scanning and adaptation of a voxelized phantom dataset: proof-of-principle.

Objective. We present a method for personalized organ dose estimates obtained before the computed tomography (CT) exam, via 3D optical body scanning and Monte Carlo (MC) simulations.Approach. A voxelized phantom is derived by adapting a reference phantom to the body size and shape measured with a portable 3D optical scanner, which returns the 3D silhouette of the patient. This was used as an external rigid envelope for incorporating a tailored version of the internal body anatomy derived from a phantom dataset (National Cancer Institute, NIH, USA) matched for gender, age, weight, and height. The proof-of-principle was conducted on adult head phantoms. The Geant4 MC code provided estimates of the organ doses from 3D absorbed dose maps in the voxelized body phantom.Main results. We applied this approach for head CT scanning using an anthropomorphic voxelized head phantom derived from 3D optical scans of manikins. We compared the estimates of head organ doses with those provided by the NCICT 3.0 software (NCI, NIH, USA). Head organ doses differed up to 38% using the proposed personalized estimate and MC code, with respect to corresponding estimates calculated for the standard (non-personalized) reference head phantom. Preliminary application of the MC code to chest CT scans is shown. Real-time pre-exam personalized CT dosimetry is envisaged with adoption of a Graphics Processing Unit-based fast MC code.Significance. The developed procedure for personalized organ dose estimates before the CT exam, introduces a new approach for realistic description of size and shape of patients via voxelized phantoms specific for each patient.

Local tumor control and treatment related toxicity after plaque brachytherapy for uveal melanoma: A systematic review and a data pooled analysis.

Uveal melanoma (UM) represents the most common primary intraocular tumor, and nowadays eye plaque brachytherapy (EPB) is the most frequently used visual acuity preservation treatment option for small to medium sized UMs. The excellent local tumor control (LTC) rate achieved by EPB may be associated with severe complications and adverse events. Several dosimetric and clinical risk factors for the development of EPB-related ocular morbidity can be identified. However, morbidity predictive models specifically developed for EPB are still scarce. PRISMA methodology was used for the present systematic review of articles indexed in PubMed in the last sixteen years on EPB treatment of UM which aims at determining the major factors affecting local tumor control and ocular morbidities. To our knowledge, for the first time in EPB field, local tumor control probability (TCP) and normal tissue complication probability (NTCP) modelling on pooled clinical outcomes were performed. The analyzed literature (103 studies including 21,263 UM patients) pointed out that Ru-106 EPB provided high local control outcomes while minimizing radiation induced complications. The use of treatment planning systems (TPS) was the most influencing factor for EPB outcomes such as metastasis occurrence, enucleation, and disease specific survival, irrespective of radioactive implant type. TCP and NTCP parameters were successfully extracted for 5-year LTC, cataract and optic neuropathy. In future studies, more consistent recordings of ocular morbidities along with accurate estimation of doses through routine use of TPS are needed to expand and improve the robustness of toxicity risk prediction in EPB.

The influence of basic plan parameters on calculated small field output factors - A multicenter study.

PURPOSE: The influence of basic plan parameters such as slice thickness, grid resolution, algorithm type and field size on calculated small field output factors (OFs) was evaluated in a multicentric study. METHODS AND MATERIALS: Three computational homogeneous water phantoms with slice thicknesses (ST) 1, 2 and 3 mm were shared among twenty-one centers to calculate OFs for 1x1, 2x2 and 3x3 cm2 field sizes (FSs) (normalized to 10x10 cm2 FS), with their own treatment planning system (TPS) and the energy clinically used for stereotactic body radiation therapy delivery. OFs were calculated for each combination of grid resolution (GR) (1, 2 and 3 mm) and ST and finally compared with the OFs measured for the TPS commissioning. A multivariate analysis was performed to test the effect of basic plan parameters on calculated OFs. RESULTS: A total of 509 data points were collected. Calculated OFs are slightly higher than measured ones. The multivariate analysis showed that Center, GR, algorithm type, and FS are predictive variables of the difference between calculated and measured OFs (p < 0.001). As FS decreases, the spread in the difference between calculated and measured OFs became larger when increasing the GR. Monte Carlo and Analytical Anisotropic Algorithms, presented a dependence on GR (p < 0.01), while Collapsed Cone Convolution and Acuros did not. The effect of the ST was found to be negligible. CONCLUSIONS: Modern TPSs slightly overestimate the calculated small field OFs compared with measured ones. Grid resolution, algorithm, center number and field size influence the calculation of small field OFs.

The influence of small field output factors simulated uncertainties on the calculated dose in VMAT plans for brain metastases: a multicentre study.

OBJECTIVES: This multicentric study was carried out to investigate the impact of small field output factors (OFs) inaccuracies on the calculated dose in volumetric arctherapy (VMAT) radiosurgery brain plans. METHODS: Nine centres, realised the same five VMAT plans with common planning rules and their specific clinical equipment Linac/treatment planning system commissioned with their OFs measured values (OFbaseline). In order to simulate OFs errors, two new OFs sets were generated for each centre by changing only the OFs values of the smallest field sizes (from 3.2 × 3.2 cm2 to 1 × 1 cm2) with well-defined amounts (positive and negative). Consequently, two virtual machines for each centre were recommissioned using the new OFs and the percentage dose differences ΔD (%) between the baseline plans and the same plans recalculated using the incremented (OFup) and decremented (OFdown) values were evaluated. The ΔD (%) were analysed in terms of planning target volume (PTV) coverage and organs at risk (OARs) sparing at selected dose/volume points. RESULTS: The plans recalculated with OFdown sets resulted in higher variation of doses than baseline within 1.6 and 3.4% to PTVs and OARs respectively; while the plans with OFup sets resulted in lower variation within 1.3% to both PTVs and OARs. Our analysis highlights that OFs variations affect calculated dose depending on the algorithm and on the delivery mode (field jaw/MLC-defined). The Monte Carlo (MC) algorithm resulted significantly more sensitive to OFs variations than all of the other algorithms. CONCLUSION: The aim of our study was to evaluate how small fields OFs inaccuracies can affect the dose calculation in VMAT brain radiosurgery treatments plans. It was observed that simulated OFs errors, return dosimetric calculation accuracies within the 3% between concurrent plans analysed in terms of percentage dose differences at selected dose/volume points of the PTV coverage and OARs sparing. ADVANCES IN KNOWLEDGE: First multicentre study involving different Planning/Linacs about undetectable errors in commissioning output factor for small fields.

Dose-Response of TLD-100 in the Dose Range Useful for Hypofractionated Radiotherapy.

PURPOSE: The aim of the study was to exploit the feasibility of thermoluminescent dosimeters (TLDs) in radiation therapy techniques in which high dose per fraction is involved. METHODS: Dose-response of TLD-100 (LiF: Mg, Ti) was investigated in both 6-MV photon and 6-MeV electron beams. The element correction factor (ECF) generation method was applied to check the variability of the TLDs response. Two batches of 50 TLDs were divided into groups and exposed in the dose range 0 to 30 Gy. Regression analysis was performed with both linear and quadratic models. For each irradiation beam, the calibration curves were obtained in 3 dose range 0 to 8 Gy, 0 to 10 Gy, and 0 to 30 Gy. The best-fitting model was assessed by the Akaike Information Criterion test. RESULTS: The ECF process resulted a useful tool to reduce the coefficients of variation from original values higher than 5% to about 3.5%, for all the batches exposed. The results confirm the linearity of dose-response curve below the dose level of 10 Gy for photon and electron beam and the supralinear trend above. CONCLUSION: The TLDs are suitable dosimeters for dose monitoring and verification in radiation treatment involving dose up to 30 Gy in a single fraction.

Technological evolution of radiation treatment: Implications for clinical applications.

The contemporary approach to the management of a cancer patient requires an "ab initio" involvement of different medical domains in order to correctly design an individual patient's pathway toward cure. With new therapeutic tools in every medical field developing faster than ever before the patient care outcomes can be achieved if all surgical, drug, and radiation options are considered in the design of the appropriate therapeutic strategy for a given patient. Radiation therapy (RT) is a clinical discipline in which experts from different fields continuously interact in order to manage the multistep process of the radiation treatment. RT is found to be an appropriate intervention for diverse indications in about 50% of cancer patients during the course of their disease. Technologies are essential in dealing with the complexity of RT treatments and for driving the increasingly sophisticated RT approaches becoming available for the treatment of Cancer. High conformal techniques, namely intensity modulated or volumetric modulated arc techniques, ablative techniques (Stereotactic Radiotherapy and Stereotactic Radiosurgery), particle therapy (proton or carbon ion therapy) allow for success in treating irregularly shaped or critically located targets and for the sharpness of the dose fall-off outside the target. The advanced on-board imaging, including real-time position management systems, makes possible image-guided radiation treatment that results in substantial margin reduction and, in select cases, implementation of an adaptive approach. The therapeutic gains of modern RT are also due in part to the enhanced anticancer activity obtained by coadministering RT with chemotherapy, targeted molecules, and currently immune checkpoints inhibitors. These main clinically relevant steps forward in Radiation Oncology represent a change of gear in the field that may have a profound impact on the management of cancer patients.

SBRT planning for spinal metastasis: indications from a large multicentric study.

BACKGROUND: The dosimetric variability in spine stereotactic body radiation therapy (SBRT) planning was investigated in a large number of centres to identify crowd knowledge-based solutions. METHODS: Two spinal cases were planned by 48 planners (38 centres). The required prescription dose (PD) was 3â€¯× 10 Gy and the planning target volume (PTV) coverage request was: VPD > 90% (minimum request: VPD > 80%). The dose constraints were: planning risk volume (PRV) spinal cord: V18Gy < 0.35 cm3, V21.9 Gy < 0.03 cm3; oesophagus: V17.7 Gy < 5 cm3, V25.2 Gy < 0.03 cm3. Planners who did not fulfil the protocol requirements were asked to re-optimize the plans, using the results of planners with the same technology. Statistical analysis was performed to assess correlations between dosimetric results and planning parameters. A quality index (QI) was defined for scoring plans. RESULTS: In all, 12.5% of plans did not meet the protocol requirements. After re-optimization, 98% of plans fulfilled the constraints, showing the positive impact of knowledge sharing. Statistical analysis showed a significant correlation (p < 0.05) between the homogeneity index (HI) and PTV coverage for both cases, while the correlation between HI and spinal cord sparing was significant only for the single dorsal PTV case. Moreover, the multileaf collimator leaf thickness correlated with the spinal cord sparing. Planners using comparable delivery/planning system techniques produced different QI, highlighting the impact of the planner's skills in the optimization process. CONCLUSION: Both the technology and the planner's skills are fundamentally important in spine SBRT planning optimization. Knowledge sharing helped to follow the plan objectives.

Auto- versus human-driven plan in mediastinal Hodgkin lymphoma radiation treatment.

BACKGROUND: Technological advances in Hodgkin lymphoma (HL) radiation therapy (RT) by high conformal treatments potentially increase control over organs-at-risk (OARs) dose distribution. However, plan optimization remains a time-consuming task with great operator dependent variability. Purpose of the present study was to devise a fully automated pipeline based on the Pinnacle3 Auto-Planning (AP) algorithm for treating female supradiaphragmatic HL (SHL) patients. METHODS: CT-scans of 10 female patients with SHL were considered. A "butterfly" (BF) volumetric modulated arc therapy was optimized using SmartArc module integrated in Pinnacle3 v. 9.10 using Collapsed Cone Convolution Superposition algorithm (30 Gy in 20 fractions). Human-driven (Manual-BF) and AP-BF optimization plans were generated. For AP, an optimization objective list of Planning Target Volume (PTV)/OAR clinical goals was first implemented, starting from a subset of 5 patients used for algorithm training. This list was then tested on the remaining 5 patients (validation set). In addition to the BF technique, the AP engine was applied to a 2 coplanar disjointed arc (AP-ARC) technique using the same objective list. For plan evaluation, dose-volume-histograms of PTVs and OARs were extracted; homogeneity and conformity indices (HI and CI), OARs dose-volume metrics and odds for different toxicity endpoints were computed. Non-parametric Friedman and Dunn tests were used to identify significant differences between groups. RESULTS: A single AP objective list for SHL was obtained. Compared to the manual plan, both AP-plans offer comparable CIs while AP-ARC also achieved comparable HIs. All plans fulfilled the clinical dose criteria set for OARs: both AP solutions performed at least as good as Manual-BF plan. In particular, AP-ARC outperformed AP-BF in terms of heart sparing involving a lower risk of coronary events and radiation-induced lung fibrosis. Hands-on planning time decreased by a factor of 10 using AP on average. CONCLUSIONS: Despite the high interpatient PTV (size and position) variability, it was possible to set a standard SHL AP optimization list with a high level of generalizability. Using the implemented list, the AP module was able to limit OAR doses, producing clinically acceptable plans with stable quality without additional user input. Overall, the AP engine associated to the arc technique represents the best option for SHL.

A multi-center output factor intercomparison to uncover systematic inaccuracies in small field dosimetry.

Large uncertainties in output factor (OF) small fields dosimetry motivated multicentric studies. The focus of the study was the determination of the OFs, for different linacs and radiosurgery units, using new-generation detectors. Intercomparison studies between radiotherapy centers improved quality dosimetry practices. Results confirmed the effectiveness of the studies to uncover large systematic inaccuracies in small field dosimetry.

Frontiers in planning optimization for lung SBRT.

Emerging data are showing the safety and the efficacy of Stereotactic Body Radiation therapy (SBRT) in lung cancer management. In this context, the very high doses delivered to the Planning Target Volume, make the planning phase essential for achieving high dose levels conformed to the shape of the target in order to have a good prognosis for tumor control and to avoid an overdose in relevant healthy adjacent tissue. In this non-systematic review we analyzed the technological and the physics aspects of SBRT planning for lung cancer. In particular, the aims of the study were: (i) to evaluate prescription strategies (homogeneous or inhomogeneous), (ii) to outline possible geometrical solutions by comparing the dosimetric results (iii) to describe the technological possibilities for a safe and effective treatment, (iv) to present the issues concerning radiobiological planning and the automation of the planning process.

Small field output factors evaluation with a microDiamond detector over 30 Italian centers.

PURPOSE: The aim of the study was a multicenter evaluation of MLC&jaws-defined small field output factors (OF) for different linear accelerator manufacturers and for different beam energies using the latest synthetic single crystal diamond detector commercially available. The feasibility of providing an experimental OF data set, useful for on-site measurements validation, was also evaluated. METHODS: This work was performed in the framework of the Italian Association of Medical Physics (AIFM) SBRT working group. The project was subdivided in two phases: in the first phase each center measured OFs using their own routine detector for nominal field sizes ranging from 10×10cm2 to 0.6×0.6cm2. In the second phase, the measurements were repeated in all centers using the PTW 60019 microDiamond detector. RESULTS: The project enrolled 30 Italian centers. Micro-ion chambers and silicon diodes were used for OF measurements in 24 and 6 centers respectively. Gafchromic films and TLDs were used for very small field OFs in 3 and 1 centers. Regarding the measurements performed with the user's detectors, OF standard deviations (SD) for field sizes down to 2×2cm2 were in all cases <2.7%. In the second phase, a reduction of around 50% of the SD was obtained using the microDiamond detector. CONCLUSIONS: The measured values presented in this multicenter study provide a consistent dataset for OFs that could be a useful tool for improving dosimetric procedures in centers. The microDiamond data present a small variation among the centers confirming that this detector can contribute to improve overall accuracy in radiotherapy.

Low dose rate brachytherapy (LDR-BT) as monotherapy for early stage prostate cancer in Italy: practice and outcome analysis in a series of 2237 patients from 11 institutions.

OBJECTIVE: Low-dose-rate brachytherapy (LDR-BT) in localized prostate cancer is available since 15 years in Italy. We realized the first national multicentre and multidisciplinary data collection to evaluate LDR-BT practice, given as monotherapy, and outcome in terms of biochemical failure. METHODS: Between May 1998 and December 2011, 2237 patients with early-stage prostate cancer from 11 Italian community and academic hospitals were treated with iodine-125 ((125)I) or palladium-103 LDR-BT as monotherapy and followed up for at least 2 years. (125)I seeds were implanted in 97.7% of the patients: the mean dose received by 90% of target volume was 145 Gy; the mean target volume receiving 100% of prescribed dose (V100) was 91.1%. Biochemical failure-free survival (BFFS), disease-specific survival (DSS) and overall survival (OS) were estimated using Kaplan-Meier method. Log-rank test and multivariable Cox regression were used to evaluate the relationship of covariates with outcomes. RESULTS: Median follow-up time was 65 months. 5- and 7-year DSS, OS and BFFS were 99 and 98%, 94 and 89%, and 92 and 88%, respectively. At multivariate analysis, the National Comprehensive Cancer Network score (p < 0.0001) and V100 (p = 0.09) were correlated with BFFS, with V100 effect significantly different between patients at low risk and those at intermediate/high risk (p = 0.04). Short follow-up and lack of toxicity data represent the main limitations for a global evaluation of LDR-BT. CONCLUSION: This first multicentre Italian report confirms LDR-BT as an excellent curative modality for low-/intermediate-risk prostate cancer. ADVANCES IN KNOWLEDGE: Multidisciplinary teams may help to select adequately patients to be treated with brachytherapy, with a direct impact on the implant quality and, possibly, on outcome.

SBRT for prostate cancer: Challenges and features from a physicist prospective.

Emerging data are showing the safety and the efficacy of Stereotactic Body Radiation Therapy (SBRT) in prostate cancer management. In this context, the medical physicists are regularly involved to review the appropriateness of the adopted technology and to proactively study new solutions. From the physics point of view there are two major challenges in prostate SBRT: (1) mitigation of geometrical uncertainty and (2) generation of highly conformal dose distributions that maximally spare the OARs. Geometrical uncertainties have to be limited as much as possible in order to avoid the use of large PTV margins. Furthermore, advanced planning and delivery techniques are needed to generate maximally conformal dose distributions. In this non-systematic review the technology and the physics aspects of SBRT for prostate cancer were analyzed. In details, the aims were: (i) to describe the rationale of reducing the number of fractions (i.e. increasing the dose per fraction), (ii) to analyze the features to be accounted for performing an extreme hypo-fractionation scheme (>6-7Gy), and (iii) to describe technological solutions for treating in a safe way. The analysis of outcomes, toxicities, and other clinical aspects are not object of the present evaluation.

Lung stereotactic ablative body radiotherapy: A large scale multi-institutional planning comparison for interpreting results of multi-institutional studies.

PURPOSE: A large-scale multi-institutional planning comparison on lung cancer SABR is presented with the aim of investigating possible criticism in carrying out retrospective multicentre data analysis from a dosimetric perspective. METHODS: Five CT series were sent to the participants. The dose prescription to PTV was 54Gy in 3 fractions of 18Gy. The plans were compared in terms of PTV-gEUD2 (generalized Equivalent Uniform Dose equivalent to 2Gy), mean dose to PTV, Homogeneity Index (PTV-HI), Conformity Index (PTV-CI) and Gradient Index (PTV-GI). We calculated the maximum dose for each OAR (organ at risk) considered as well as the MLD2 (mean lung dose equivalent to 2Gy). The data were stratified according to expertise and technology. RESULTS: Twenty-six centers equipped with Linacs, 3DCRT (4% - 1 center), static IMRT (8% - 2 centers), VMAT (76% - 20 centers), CyberKnife (4% - 1 center), and Tomotherapy (8% - 2 centers) collaborated. Significant PTV-gEUD2 differences were observed (range: 105-161Gy); mean-PTV dose, PTV-HI, PTV-CI, and PTV-GI were, respectively, 56.8±3.4Gy, 14.2±10.1%, 0.70±0.15, and 4.9±1.9. Significant correlations for PTV-gEUD2 versus PTV-HI, and MLD2 versus PTV-GI, were observed. CONCLUSIONS: The differences in terms of PTV-gEUD2 may suggest the inclusion of PTV-gEUD2 calculation for retrospective data inter-comparison.

Multicentre treatment planning inter-comparison in a national context: The liver stereotactic ablative radiotherapy case.

PURPOSE: To compare five liver metastasis stereotactic ablative radiotherapy (SABR) plans optimised in fourteen centres with 3D-Conformal-RT, IMRT, VMAT, CyberKnife and Tomotherapy and identify possible dosimetric differences. METHODS: Dose prescription was 75 Gy in 3 fractions, normalised at 67%-95% isodose. RESULTS: Excluding few cases, all institutions achieved the planning objectives. Differences up to 40% and 25% in mean dose to liver and PTV were found. No significant correlations between technological factors and DVH for target and OARs were observed; the optimisation strategies selected by the planners played a key role in the planning procedure. CONCLUSIONS: The human factor and the constraints imposed to the target volume have a greater dosimetric impact than treatment planning and radiation delivery technology in stereotactic treatment of liver metastases. Significant differences found both in terms of dosimetric target coverage and OAR sparing should be taken into consideration before starting a multi-institutional SARB clinical trial.

Role of the technical aspects of hypofractionated radiation therapy treatment of prostate cancer: a review.

The increasing use of moderate (<35 fractions) and extreme (<5 fractions) hypofractionated radiation therapy in prostate cancer is yielding favorable results, both in terms of maintained biochemical response and toxicity. Several hypofractionation (HF) schemes for the treatment of prostate cancer are available, although there is considerable variability in the techniques used to manage intra-/interfraction motion and deliver radiation doses. We performed a review of the published studies on HF regimens as a topic of interest for the Stereotactic Ablative Radiotherapy working group, which is part of the Italian Association of Medical Physics. Aspects of organ motion management (imaging for contouring, target volume definition, and rectum/bladder preparation) and treatment delivery (prostate localization, image guided radiation therapy strategy and frequency) were evaluated and categorized to assess outcome relative to disease control and toxicity. Despite the heterogeneity of the data, some interesting trends that emerged from the review might be useful in identifying an optimum HF strategy.

A feasibility dosimetric study on prostate cancer : are we ready for a multicenter clinical trial on SBRT?

PURPOSE: The Italian Association of Medical Physics (AIFM) started a working group dedicated to stereotactic body radiotherapy (SBRT) treatment. In this work, we performed a multicenter planning study on patients who were candidates for SBRT in the treatment of prostate cancer with the aim of evaluating the dosimetric consistency among the different hospitals. METHODS AND MATERIALS: Fourteen centers were provided the contours of 5 patients. Plans were performed following the dose prescription and constraints for organs at risk (OARs) of a reference paper. The dose prescription was 35 Gy in five fractions for the planning target volume (PTV). Different techniques were used (3D-CRT, fixed-Field IMRT, VMAT, CyberKnife). Plans were compared in terms of dose-volume histogram (DVH) parameters. Furthermore, the median DVH was calculated and one patient was re-planned. RESULTS: A total of 70 plans were compared. The maximum dose to the body was 107.9 ± 4.5 % (range 101.5-116.3 %). Dose at 98 % (D98 %) and mean dose to the clinical target volume (CTV) were 102.0 ± 0.9 % (global range 101.1-102.9 %) and 105.1 ± 0.6 % (range 98.6-124.6 %). Similar trends were found for D95 % and mean dose to the PTV. Important differences were found in terms of the homogeneity index. Doses to OARs were heterogeneous. The subgroups with the same treatment planning system showed differences comparable to the differences of the whole group. In the re-optimized plans, DVH differences among institutes were reduced and OAR sparing improved. CONCLUSION: Important dosimetric differences with possible clinical implications, in particular related to OARs, were found. Replanning allowed a reduction in the OAR dose and decreased standard deviations. Multicenter clinical trials on SBRT should require a preplanning study to standardize the optimization procedure.

HPV-related oropharyngeal carcinoma with Overt Level II and/or III metastases at presentation: The risk of subclinical disease in ipsilateral levels IB, IV and V.

BACKGROUND: To assess the risk of subclinical neck nodal involvement of levels IB, IV and V for early T-stage, node positive, human papilloma virus (HPV)-related oropharyngeal carcinoma. MATERIAL AND METHODS: We retrospectively identified the patients with clinically positive and un-violated neck that underwent upfront ipsilateral neck dissection for HPV-related oropharyngeal cancer between 1998 and 2010. From the pathology report we extracted the prevalence rate of involvement of each selected level and then estimated the risk that a level that does not contain any node larger than 10 mm at computed tomography (CT) harbors subclinical disease. Predictors of involvement were investigated as well. RESULTS: Ninety-one patients were analyzed. The risk of subclinical disease in both levels IB and V is < 5%, while it is 6.5% (95% CI 3.1-9.9%) for level IV. Level IB subclinical involvement slightly exceeds 5% when 2 + ipsilateral levels besides IB are involved. The risk of occult disease in level IV tends to be < 5% when level III is not involved. CONCLUSION: These data support the exclusion from the elective nodal volume of level V and level IB but when 2 + other levels are involved. Level IV might also be spared when level III is negative. Clinical implementation within a prospective study is justified.

Head and neck intensity modulated radiotherapy parotid glands: time of re-planning.

PURPOSE: To investigate the correct time point for re-planning by evaluating dosimetric changes in the parotid glands (PGs) during intensity-modulated radiotherapy (IMRT) in head and neck cancer patients. MATERIALS AND METHODS: Patients with head and neck cancer treated with IMRT were enrolled. During treatment all patients underwent cone-beam computed tomography (CBCT) scans to verify the set-up. CBCT scans at treatment days 10, 15, 20 and 25 were used to transfer the original plan (CBCTplan I, II, III, IV, respectively) using rigid registration between the two. The PGs were retrospectively contoured and evaluated with the dose-volume histogram. The mean dose, the dose to 50 % of volume, and the percentage of volume receiving 30 and 50 Gy were evaluated for each PG. The Wilcoxon sign ranked test was used to evaluate the effects of dosimetric variations and values <0.05 were taken to be significant. RESULTS: From February to June 2011, ten patients were enrolled and five IMRT plans were evaluated for each patient. All the dosimetric parameters increased throughout the treatment course. However, this increase was statistically significant at treatment days 10 and 15 (CBCTplan I, II; p = 0.02, p = 0.03, respectively). CONCLUSION: CBCT is a feasible method to assess the dosimetric changes in the PGs. Our data showed that checking the PG volume and dose could be indicated during the third week of treatment.