Monitoring skin dose changes during image-guided helical tomotherapy for head and neck cancer patients.

PURPOSE: An increase of skin dose during head and neck cancer (HNC) radiotherapy is potentially dangerous. Aim of this study was to quantify skin dose variation and to assess the need of planning adaptation (ART) to counteract it. METHODS: Planning CTs of 32 patients treated with helical tomotherapy (HT) according to a Simultaneous Integrated Boost (SIB) technique delivering 54/66 Gy in 30 fractions were deformably co-registered to MVCTs taken at fractions 15 and 30; in addition, the first fraction was also considered. The delivered dose-of-the-day was calculated on the corresponding deformed images. Superficial body layers (SL) were considered as a surrogate for skin, considering a layer thickness of 2 mm. Variations of SL DVH (∆SL) during therapy were quantified, focusing on ∆SL95% (i.e., 62.7 Gy). RESULTS: Small changes (within ± 1 cc for ∆SL95%) were seen in 15/32 patients. Only 2 patients experienced ∆SL95% > 1 cc in at least one of the two monitored fractions. Negative ∆SL95% > 1 cc (up to 17 cc) were much more common (15/32 patients). The trend of skin dose changes was mostly detected at the first fraction. Negative changes were correlated with the presence of any overlap between PTV and SL at planning and were explained in terms of how the planning system optimizes the PTV dose coverage near the skin. Acute toxicity was associated with planning DVH and this association was not improved if considering DVHs referring to fractions 15/30. CONCLUSION: About half of the patients treated with SIB with HT for HNC experienced a skin-sparing effect during therapy; only 6% experienced an increase. Our findings do not support skin-sparing ART, while suggesting the introduction of improved skin-sparing planning techniques.

Early volume variation of positive lymph nodes assessed by in-room mega voltage CT images predicts risk of loco-regional relapses in head and neck cancer patients treated with intensity-modulated radiotherapy.

BACKGROUND: We investigated the possibility to early identify non-responding patients based on FDG-PET positive lymph nodes (PNs) volume variation assessed with in-room images. MATERIAL AND METHODS: Twenty-seven head and neck cancer patients with at least one pre-treatment PNs were retrospectively analyzed; they received 54 Gy, 66 Gy, 69 Gy in 30 fractions on precautionary lymph nodal (N), primary (T) and PET positive (BTV) planning target volumes (PTVs), respectively with Helical TomoTherapy (SIB approach). PNs volume changes during treatment were assessed based on megavoltage computed tomography (MVCT) used for image guidance as ratio between volumes at fractions 10/20/30 and at first fraction. Data on T, N and M relapses (rT, rN, rM) were collected for all patients. The difference of PNs volume changes, during treatment, between patients with versus without relapses was tested (Mann-Whitney test). The impact of shrinkage on the corresponding survival curves (Cox proportional-hazard regression), dividing between no/moderate versus large shrinkage (based on ROC curve best cut-off value) was also investigated. RESULTS: Median follow-up was 27.4 m (3.7-108.9). The numbers for rT, rN, rM were 5, 4, 6, respectively. Differences in PNs shrinkage were found between patients with and without rT/rN at all considered timing [fr 20, rT: 0.56 vs. 1.07 (median), p = 0.06; rN: 0.57 vs. 1.25, p = 0.07]. Differences were lower for rM. Survival curves provide high hazard ratios (HR) between PNs changes and rT/rN at all considered timing [fr 20, rT: best cut-off = 0.58, HR 5.1 (95% CI 0.5-49.4), p = 0.12; rN: best cut-off = 0.98, HR 14.9 (1.6-142.9), p = 0.01]. CONCLUSION: A limited shrinkage of PNs during treatment is associated with poorer outcome in terms of T/N relapses. The early variation of PNs observed on in-room images may provide useful information about the individual response with potential application in guiding an early adaptation of the treatment.

Early changes of parotid density and volume predict modifications at the end of therapy and intensity of acute xerostomia.

PURPOSE: To quantitatively assess the predictive power of early variations of parotid gland volume and density on final changes at the end of therapy and, possibly, on acute xerostomia during IMRT for head-neck cancer. MATERIALS AND METHODS: Data of 92 parotids (46 patients) were available. Kinetics of the changes during treatment were described by the daily rate of density (rΔρ) and volume (rΔvol) variation based on weekly diagnostic kVCT images. Correlation between early and final changes was investigated as well as the correlation with prospective toxicity data (CTCAEv3.0) collected weekly during treatment for 24/46 patients. RESULTS: A higher rΔρ was observed during the first compared to last week of treatment (-0,50 vs -0,05HU, p-value = 0.0001). Based on early variations, a good estimation of the final changes may be obtained (Δρ: AUC = 0.82, p = 0.0001; Δvol: AUC = 0.77, p = 0.0001). Both early rΔρ and rΔvol predict a higher "mean" acute xerostomia score (≥ median value, 1.57; p-value = 0.01). Median early density rate changes for patients with mean xerostomia score ≥ / < 1.57 were -0.98 vs -0.22 HU/day respectively (p = 0.05). CONCLUSIONS: Early density and volume variations accurately predict final changes of parotid glands. A higher longitudinally assessed score of acute xerostomia is well predicted by higher rΔρ and rΔvol in the first two weeks of treatment: best cut-off values were -0.50 HU/day and -380 mm(3)/day for rΔρ and rΔvol respectively. Further studies are necessary to definitively assess the potential of early density/volume changes in identifying more sensitive patients at higher risk of experiencing xerostomia.

Stomach and duodenum dose-volume constraints for locally advanced pancreatic cancer patients treated in 15 fractions in combination with chemotherapy.

Purpose: To assess dosimetry predictors of gastric and duodenal toxicities for locally advanced pancreatic cancer (LAPC) patients treated with chemo-radiotherapy in 15 fractions. Methods: Data from 204 LAPC patients treated with induction+concurrent chemotherapy and radiotherapy (44.25 Gy in 15 fractions) were available. Forty-three patients received a simultaneous integrated boost of 48-58 Gy. Gastric/duodenal Common Terminology Criteria for Adverse Events v. 5 (CTCAEv5) Grade ≥2 toxicities were analyzed. Absolute/% duodenal and stomach dose-volume histograms (DVHs) of patients with/without toxicities were compared: the most predictive DVH points were identified, and their association with toxicity was tested in univariate and multivariate logistic regressions together with near-maximum dose (D0.03) and selected clinical variables. Results: Toxicity occurred in 18 patients: 3 duodenal (ulcer and duodenitis) and 10 gastric (ulcer and stomatitis); 5/18 experienced both. At univariate analysis, V44cc (duodenum: p = 0.02, OR = 1.07; stomach: p = 0.01, OR = 1.12) and D0.03 (p = 0.07, OR = 1.19; p = 0.008, OR = 1.12) were found to be the most predictive parameters. Stomach/duodenum V44Gy and stomach D0.03 were confirmed at multivariate analysis and found to be sufficiently robust at internal, bootstrap-based validation; the results regarding duodenum D0.03 were less robust. No clinical variables or %DVH was significantly associated with toxicity. The best duodenum cutoff values were V44Gy < 9.1 cc (and D0.03 < 47.6 Gy); concerning the stomach, they were V44Gy < 2 cc and D0.03 < 45 Gy. The identified predictors showed a high negative predictive value (>94%). Conclusion: In a large cohort treated with hypofractionated radiotherapy for LAPC, the risk of duodenal/gastric toxicities was associated with duodenum/stomach DVH. Constraining duodenum V44Gy < 9.1 cc, stomach V44Gy < 2 cc, and stomach D0.03 < 45 Gy should keep the toxicity rate at approximately or below 5%. The association with duodenum D0.03 was not sufficiently robust due to the limited number of events, although results suggest that a limit of 45-46 Gy should be safe.

PET-guided dose escalation tomotherapy in malignant pleural mesothelioma.

PURPOSE: To test the feasibility of salvage radiotherapy using PET-guided helical tomotherapy in patients with progressive malignant pleural mesothelioma (MPM). PATIENTS AND METHODS: A group of 12 consecutive MPM patients was treated with 56 Gy/25 fractions to the planning target volume (PTV); FDG-PET/CT simulation was always performed to include all positive lymph nodes and MPM infiltrations. Subsequently, a second group of 12 consecutive patients was treated with the same dose to the whole pleura adding a simultaneous integrated boost of 62.5 Gy to the FDG-PET/CT positive areas (BTV). RESULTS: Good dosimetric results were obtained in both groups. No grade 3 (RTOG/EORTC) acute or late toxicities were reported in the first group, while 3 cases of grade 3 late pneumonitis were registered in the second group: the duration of symptoms was 2-10 weeks. Median overall survival was 8 months (1.2-50.5 months) and 20 months (4.3-33.8 months) from the beginning of radiotherapy, for groups I and II, respectively (p=0.19). A significant impact on local relapse from radiotherapy was seen (median time to local relapse: 8 vs 17 months; 1-year local relapse-free rate: 16% vs 81%, p=0.003). CONCLUSIONS: The results of this pilot study support the planning of a phase III study of combined sequential chemoradiotherapy with dose escalation to BTV in patients not able to undergo resection.

Feasibility of safe ultra-high (EQD(2)>100 Gy) dose escalation on dominant intra-prostatic lesions (DILs) by Helical Tomotheraphy.

PURPOSE: to verify the possibility of using Helical Tomotherapy to safely escalate dose to single or multiple highly radioresistant dominant intra-prostatic lesions (DILs) as assessed by functional magnetic resonance imaging (MRI). MATERIAL: in seven intermediate/high risk patients, T2WI, T1WI and DWI MRI imaging showed evidence of one DIL in four patients and two DILs in three patients in the peripheral zone of the prostate. The planning strategy was to deliver median doses of 80, 90, 100 and 120 Gy to PTVDIL while delivering 71.4 Gy/28 fractions (EQD(2)=75 Gy) to the remaining portion of PTV. A higher priority was assigned to rectal constraints relative to DIL coverage. Rectal NTCP calculations were performed using the most recently available model data. RESULTS: the median dose to DIL could safely be escalated to at least 100 Gy (EQD(2,α/ß=10)=113 Gy) without violating safe constraints for the organs at risk. Typical rectal NTCP values were around or below 1-3% for G3 toxicity and 5-7% for G2-G3 toxicity. For the 100 Gy DIL dose boost strategy, mean D95% of DIL and PTVDIL were 98.8 Gy and 86.7 Gy, respectively. The constraints for bladder, urethra and femoral heads were always respected. CONCLUSIONS: IGRT by Helical Tomotherapy may permit the safe escalation of EQD(2,α/ß=10) to at least 113 Gy to DILs without significantly increasing rectal NTCP compared to plans without dose escalation. A Phase I-II clinical study is warranted.

Clinical Implementation of Knowledge-Based Automatic Plan Optimization for Helical Tomotherapy.

PURPOSE: To implement knowledge-based (KB) automatic planning for helical TomoTherapy (HTT). The focus of the first clinical implementation was the case of high-risk prostate cancer, including pelvic node irradiation. METHODS AND MATERIALS: One hundred two HTT clinical plans were selected to train a KB model using the RapidPlan tool incorporated in the Eclipse system (v13.6, Varian Inc). The individually optimized KB-based templates were converted into HTT-like templates and sent automatically to the HTT treatment planning system through scripting. The full dose calculation was set after 300 iterations without any additional planner intervention. Internal (20 patients in the training cohort) and external (28 new patients) validation were performed to assess the performance of the model: Automatic HTT plans (KB-TP) were compared against the original plans (TP) in terms of organs at risk and planning target volume (PTV) dose-volume parameters and by blinded clinical evaluation of 3 expert clinicians. RESULTS: KB-TP plans were generally better than or equivalent to TP plans in both validation cohorts. A significant improvement in PTVs and rectum-PTV overlap dosimetry parameters were observed for both sets. Organ-at-risk sparing for KB-TP was slightly improved, which was more evident in the external validation group and for bladder and bowel. Clinical evaluation reported KB-TP to be better in 60% of cases and worse in 10% compared with TP (P < .05). CONCLUSIONS: The fully KB-based automatic planning workflow was successfully implemented for HTT planning optimization in the case of high-risk patients with prostate cancer.

Semiautomatic technique for defining the internal gross tumor volume of lung tumors close to liver/spleen cupola by 4D-CT.

PURPOSE: It has been shown that in cases of lung tumors close to the liver cupola, the four dimensional (4D)-CT postprocessing maximum intensity projection (MIP) algorithm does not fully recover the radiotherapy internal gross tumor volume (IGTV). In this work, a semiautomatic technique was evaluated by which the residual IGTV that was not included into the IGTV by MIP algorithm was actually added. METHODS: A moving phantom and five selected patients were considered. The various IGTVs produced by the semiautomatic approach were compared to those generated by 4D-CT manual contouring. RESULTS: In all cases, the radiation oncologist qualitatively concurred with the semiautomatic IGTV. A quantitative difference in volume of 2.6% was found in the phantom study, whereas a mean difference of 0.1 +/- 4.6% was obtained in the patient studies. CONCLUSIONS: A semiautomatic technique to include the residual part of IGTV covered by liver/spleen cupola when using MIP algorithm was validated on phantom and on selected patients, revealing the possibility of defining the IGTV for patients with lesions located near liver/spleen cupola by performing only the contours on the MIP series.

Impact of sentinel lymph-node biopsy and FDG-PET in staging and radiation treatment of anal cancer patients.

To assess the role of sentinel lymph-node biopsy (SLNB) and FDG-PET in staging and radiation treatment (RT) of anal cancer patients. This retrospective study was performed on 80 patients (male: 32, female: 48) with a median age of 60 years (39-89 years) with anal squamous cell carcinoma who were treated from March 2008 to March 2018 at the IRCCS San Raffaele Hospital. Patients without clinical evidence of inguinal LNs metastases and/or with discordance between clinical evidence and imaging features were considered for SLNB. FDG-PET was performed in 69/80 patients. Patients with negative imaging in inguinal region and negative SLNB could avoid RT on groin to spare inguinal toxicity. CTV included GTV (primary tumour and positive LNs) and pelvic ± inguinal LNs. PTV1 and PTV2 corresponded to GTV and CTV, respectively, adding 0.5 cm. RT dose was 50.4 Gy/28 fractions to PTV2 and 64.8 Gy/36 fractions to PTV1, delivered with 3DCRT (n = 24) or IMRT (n = 56), concomitant to Mitomycin-C and 5-FU chemotherapy. FDG-PET showed inguinal uptake in 21/69 patients (30%) and was negative in 48/69 patients (70%). Lymphoscintigraphy was performed in 11/21 positive patients (4 patients SLNB confirmed inguinal metastases, 6 patients false positive and 1 patient SLN not found), and in 29/48 negative patients (5/29 showed metastases, 23/29 true negative and 1 SLN not found). Sensitivity, specificity, positive and negative predictive value of FDG-PET were 62%, 79%, 40% and 82%, respectively. Median follow-up time from diagnosis was 40.3 months (range: 4.6-136.4 months): 69 patients (86%) showed a complete response, 10 patients (13%) a partial response, 1 patient (1%) a stable disease. Patients treated on groin (n = 54) versus not treated (n = 26) showed more inguinal dermatitis (G1-G2: 50% vs. 12%; G3-G4: 17% vs. 0%, p < 0.05). For patients treated on groin, G3-G4 inguinal dermatitis, stomatitis and neutropenia were significantly reduced with IMRT against 3DCRT techniques (13% vs. 36%, p = 0.10; 3% vs. 36%, p = 0.003; 8% vs. 29%, p = 0.02, respectively). SLNB improves the FDG-PET inguinal LNs staging in guiding the decision to treat inguinal nodes. IMRT technique significantly reduced G3-G4 toxicities when patients are treated on groin.

Robustness of CT radiomic features against image discretization and interpolation in characterizing pancreatic neuroendocrine neoplasms.

PURPOSE: To explore the variation of the discriminative power of CT radiomic features (RF) against image discretization/interpolation in characterizing pancreatic neuro-endocrine (PanNEN) neoplasms. MATERIALS AND METHODS: Thirty-nine PanNEN patients with pre-surgical high contrast CT available were considered. Image interpolation and discretization parameters were intentionally changed, including pixel size (0.73-2.19 mm2), slice thickness (2-5 mm) and binning (32-128 grey levels) and their combination generated 27 parameter's set. The ability of 69 RF in discriminating post-surgically assessed tumor grade (>G1), positive nodes, metastases and vascular invasion was tested: AUC changes when changing the parameters were quantified for selected RF, significantly associated to each end-point. The analysis was repeated for the corresponding images with contrast medium and in a sub-group of 29/39 patients scanned on a single scanner. RESULTS: The median tumor volume was 1.57 cm3 (16%-84% percentiles: 0.62-34.58 cm3). RF variability against discretization/interpolation parameters was large: only 21/69 RF showed %COV < 20%. Despite this variability, AUC changes were limited for all end-points: with typical AUC values around 0.75-0.85, AUC ranges for the 27 parameter's set were on average 0.062 (1SD:0.037) for all end-points with maximum %COV equal to 5.5% (mean:2.3%). Performances significantly improved when excluding the 5 mm thickness case and fixing the binning to 64 (mean AUC range: 0.036, 1SD:0.019). Using contrast images or limiting the population to single-scanner patients had limited impact on AUC variability. CONCLUSIONS: The discriminative power of CT RF for panNEN is relatively invariant against image interpolation/discretization within a large range of voxel sizes and binning.

Intensity-modulated proton therapy versus helical tomotherapy in nasopharynx cancer: planning comparison and NTCP evaluation.

PURPOSE: To compare intensity-modulated proton therapy (IMPT) and helical tomotherapy (HT) treatment plans for nasopharynx cancer using a simultaneous integrated boost approach. METHODS AND MATERIALS: The data from 6 patients who had previously been treated with HT were used. A three-beam IMPT technique was optimized in the Hyperion treatment planning system, simulating a "beam scanning" technique. HT was planned using the tomotherapy treatment planning system. Both techniques were optimized to simultaneously deliver 66 Gy in 30 fractions to planning target volume (PTV1; GTV and enlarged nodes) and 54 Gy to PTV2 subclinical, electively treated nodes. Normal tissue complication probability calculation was performed for the parotids and larynx. RESULTS: Very similar PTVs coverage and homogeneity of the target dose distribution for IMPT and HT were found. The conformity index was significantly lower for protons than for photons (1.19 vs. 1.42, respectively). The mean dose to the ipsilateral and contralateral parotid glands decreased by 6.4 Gy and 5.6 Gy, respectively, with IMPT. The volume of mucosa and esophagus receiving > or =20 Gy and > or =30 Gy with IMPT was significantly lower than with HT. The average volume of larynx receiving > or =50 Gy was significantly lower with HT, while for thyroid, it was comparable. The volume receiving > or =30, > or =20, and > or =10 Gy in total body volume decreased with IMPT by 14.5%, 19.4%, and 23.1%, respectively. The normal tissue complication probability for the parotid glands was significantly lower with IMPT for all sets of parameters; however, we also estimated an almost full recovery of the contralateral parotid with HT. The normal tissue complication probability for the larynx was not significantly different between the two irradiation techniques. CONCLUSION: Excellent target coverage, homogeneity within the PTVs, and sparing of the organs at risk were reached with both modalities. IMPT allows for better sparing of most organs at risk at medium-to-low doses.

Dose-volume and biological-model based comparison between helical tomotherapy and (inverse-planned) IMAT for prostate tumours.

BACKGROUND AND PURPOSE: Helical tomotherapy (HT) and intensity-modulated arc therapy (IMAT) are two arc-based approaches to the delivery of intensity-modulated radiotherapy (IMRT). Through plan comparisons we have investigated the potential of IMAT, both with constant (conventional or IMAT-C) and variable (non-conventional or IMAT-NC, a theoretical exercise) dose-rate, to serve as an alternative to helical tomotherapy. MATERIALS AND METHODS: Six patients with prostate tumours treated by HT with a moderately hypo-fractionated protocol, involving a simultaneous integrated boost, were re-planned as IMAT treatments. A method for IMAT inverse-planning using a commercial module for static IMRT combined with a multi-leaf collimator (MLC) arc-sequencing was developed. IMAT plans were compared to HT plans in terms of dose statistics and radiobiological indices. RESULTS: Concerning the planning target volume (PTV), the mean doses for all PTVs were similar for HT and IMAT-C plans with minimum dose, target coverage, equivalent uniform dose (EUD) and tumour control probability (TCP) values being generally higher for HT; maximum dose and degree of heterogeneity were instead higher for IMAT-C. In relation to organs at risk, mean doses and normal tissue complication probability (NTCP) values were similar between the two modalities, except for the penile bulb where IMAT was significantly better. Re-normalizing all plans to the same rectal toxicity (NTCP=5%), the HT modality yielded higher TCP than IMAT-C but there was no significant difference between HT and IMAT-NC. The integral dose with HT was higher than that for IMAT. CONCLUSIONS: with regards to the plan analysis, the HT is superior to IMAT-C in terms of target coverage and dose homogeneity within the PTV. Introducing dose-rate variation during arc-rotation, not deliverable with current linac technology, the simulations result in comparable plan indices between (IMAT-NC) and HT.

Treatment planning comparison between conformal radiotherapy and helical tomotherapy in the case of locally advanced-stage NSCLC.

BACKGROUND AND PURPOSE: To investigate the impact of Helical Tomotherapy (HT) upon the dose distribution when compared to our routinely delivered 3D conformal radiotherapy (CRT) in the case of patients affected by stage III non-small-cell lung cancer (NSCLC). MATERIAL AND METHODS: Thirteen stage III inoperable NSCLC patients were scheduled to receive 61.2-70.2Gy, 1.8Gy/fraction. Two treatment techniques (HT and CRT) were considered, and in the case of CRT the dose calculation was performed using both the pencil beam (PB) and Anisotropic Analytical Algorithm (AAA) available on the Varian Eclipse planning system. Dose volume constraints for PTV coverage and OAR sparing were assessed for the HT inverse planning with the highest priority upon PTV coverage and spinal cord sparing. The three plans were compared in terms of dose-volume histograms (DVHs) and normal tissue complication probability (NTCP). A statistical analysis was performed using non-parametric Wilcoxon matched pairs tests. RESULTS: In CRT the use of a less accurate algorithm (PB) decreased the monitor unit number by 2.4%. HT significantly improved dose homogeneity within PTV compared with CRT_AAA. For lung parenchyma V20-V40 were lower with HT, corresponding to a decrease of 7% in the risk of radiation pneumonitis. The volume of the heart and esophagus irradiated to >45-60Gy were reduced using HT plans. For eight PTs with an esophagus-PTV overlap >5%, HT significantly reduced both late and acute esophageal complication probability. CONCLUSIONS: Our findings obtained in stage III NSCLC patients underline that HT guarantees an important sparing of lungs and esophagus, thus HT has the potential to improve therapeutic ratio, when compared with CRT, by means of dose escalation and/or combined treatment strategy. In CRT of locally advanced lung cancers, the use of a more advanced algorithm would give significantly better modeling of target dose and coverage.

Results of a two-year quality control program for a helical tomotherapy unit.

BACKGROUND AND PURPOSE: Image-guided helical tomotherapy (HT) is a new modality for delivering intensity modulated radiation therapy (IMRT) with helical irradiation: the slip ring continuously rotates while the couch moves into the bore. The radiation source (Linac, 6 MV) is collimated into a fan beam and modulated by means of a binary multileaf collimator (MLC). A xenon detector array, opposite the radiation source, allows a megavoltage-CT (MVCT) acquisition of patient images for set-up verification. The aim of this paper is to report the results of a two-year quality control (QC) program for the physical and dosimetric characterization of an HT unit installed at our Institute and clinically activated in November 2004, in order to monitor and verify the stability and the reliability of this promising radiation treatment unit. MATERIALS AND METHODS: Conventional Linac acceptance protocols (ATP) and QC protocols were adapted to HT with the addition of specific items reflecting important differences between the two irradiation modalities. QC tests can be summarized as: (a) mechanical and geometrical characterization of the system's components: evaluation of alignment among radiation source-gantry rotation plan-jaws-MLC-MVCT; (b) treatment beam configuration in static condition: depth dose curves (PDD) and profiles, output factors, output reproducibility and linearity; (c) dynamic component characterization: accuracy and reproducibility of MLC positioning; rotational output reproducibility and linearity, leaf latency, couch movement constancy; (d) gantry-couch and MLC-gantry synchronization; and (e) MVCT image quality. Peculiar periodicity specific tolerance and action levels were defined. Ionization chambers (Exradin A1SL 0.056 cc), films (XOmat-V/EDR2), water and solid water phantoms were used to perform quality assurance measurements. RESULTS: Over a two-year period the final average output variation after possible beam output adjustment was -0.2+/-1% for the static condition and equal to 0+/-1% for the rotational condition: around 98% of the collected output data was within the action level compared to 94% if no beam output adjustment was considered. An average energy variation of -0.4+/-0.4% was found. The daily absolute dose verification of IMRT plans showed a dose reproducibility of -0.5+/-1.2% and -0.4+/-2.2%, for low and high dose gradient regions, respectively. Source-jaws-MLC and MVCT alignment results and jaw and leaf positioning accuracy were +/-1mm. Couch-gantry-MLC synchrony tests showed good stability level (

Physics aspects of prostate tomotherapy: planning optimization and image-guidance issues.

PURPOSE: To review planning and image-guidance aspects of more than 3 years experience in the treatment of prostate cancer with Helical Tomotherapy (HT). METHODS AND MATERIALS: Planning issues concerning two Phase I-II clinical studies were addressed: in the first one, 58 Gy in 20 fractions were delivered to the prostatic bed for post-prostatectomy patients: in the second one, a simultaneous integrated boost (SIB) approach was applied for radical treatment, delivering 71.4-74.2 Gy to the prostate in 28 fractions. On-line daily MVCT image guidance was applied: bone match was used for post-operative patients while prostate match was applied for radically treated patients. MVCT data of a large sample of both categories of patients were reviewed. RESULTS: At now, more than 250 patients were treated. Planning data show the ability of HT in creating highly homogeneous dose distributions within PTVs. Organs at risk (OAR) sparing also showed to be excellent. HT was also found to favorably compare to inversely-optimized IMAT in terms of PTVs coverage and dose distribution homogeneity. In the case of pelvic nodes irradiation, a large sparing of bowel was evident compared to 3DCRT and conventional 5-fields IMRT. The analysis of MVCT data showed a limited motion of the prostate (about 5% of the fractions show a deviation > or =3 mm in posterior-anterior direction), due to the careful application of rectal emptying procedures. Based on phantom measurements and on the comparison with intra-prostatic calcification-based match, direct visualization prostate match seems to be sufficiently reliable in assessing shifts > or =3 mm. CONCLUSIONS: HT offers excellent planning solutions for prostate cancer, showing to be highly efficient in a SIB scenario. Daily MVCT information showed evidence of a limited motion of the prostate in the context of rectal filling control obtained by instructing patients in self-administrating a rectal enema.

Skin dose calculation during radiotherapy of head and neck cancer using deformable image registration of planning and mega-voltage computed tomography scans.

BACKGROUND AND PURPOSE: Head-Neck (HN) patients may experience severe acute skin complications that can cause treatment interruption and increase the risk of late fibrosis. This study assessed a method for accurately monitoring skin dose changes during helical tomotherapy for HN cancer based on deformable image registration of planning computed tomography (CT) and mega-voltage CT (MVCT). MATERIALS AND METHODS: Planning CTs of nine patients were deformably registered to mid-treatment MVCT (MV15) images resulting in CTdef images. The original plans were recalculated on both CTdef and mid-treatment kilo-voltage CT (CT15) taken as ground truth. Superficial layers (SL) of the body with thicknesses of 2, 3 and 5 mm (SL2, SL3, SL5) were considered as derma surrogates. SL V95%, V97%, V98%, V100%, V102%, V105% and V107% of the prescribed PTV dose were extracted for CT15/CTdef and compared (considering patients with skin dose > 95%). For comparison, doses were calculated directly on the calibrated MVCT and analyzed in the same way. RESULTS: Differences between SL2/SL3/SL5 V95%-V107% in CT15/CTdef were very small: for eight of nine patients the difference between the considered SL2 Vd% computed on CTdef and CT15 was less than 1.4 cm3 for all d%. A larger value was found when using MVCT for skin dose calculation (4.8 cm3 for SL2), although CTdef body contour matched CT15 body with accuracy similar to that of MV15. CONCLUSIONS: Deforming the planning CT-to-MVCT was shown to be accurate considering external body contours and skin DVHs. The method was able to accurately identify superficial overdosing.

Quantifying the robustness of [18F]FDG-PET/CT radiomic features with respect to tumor delineation in head and neck and pancreatic cancer patients.

PURPOSE: To investigate the robustness of PET radiomic features (RF) against tumour delineation uncertainty in two clinically relevant situations. METHODS: Twenty-five head-and-neck (HN) and 25 pancreatic cancer patients previously treated with 18F-Fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT)-based planning optimization were considered. Seven FDG-based contours were delineated for tumour (T) and positive lymph nodes (N, for HN patients only) following manual (2 observers), semi-automatic (based on SUV maximum gradient: PET_Edge) and automatic (40%, 50%, 60%, 70% SUV_max thresholds) methods. Seventy-three RF (14 of first order and 59 of higher order) were extracted using the CGITA software (v.1.4). The impact of delineation on volume agreement and RF was assessed by DICE and Intra-class Correlation Coefficients (ICC). RESULTS: A large disagreement between manual and SUV_max method was found for thresholds  ≥50%. Inter-observer variability showed median DICE values between 0.81 (HN-T) and 0.73 (pancreas). Volumes defined by PET_Edge were better consistent with the manual ones compared to SUV40%. Regarding RF, 19%/19%/47% of the features showed ICC < 0.80 between observers for HN-N/HN-T/pancreas, mostly in the Voxel-alignment matrix and in the intensity-size zone matrix families. RFs with ICC < 0.80 against manual delineation (taking the worst value) increased to 44%/36%/61% for PET_Edge and to 69%/53%/75% for SUV40%. CONCLUSIONS: About 80%/50% of 72 RF were consistent between observers for HN/pancreas patients. PET_edge was sufficiently robust against manual delineation while SUV40% showed a worse performance. This result suggests the possibility to replace manual with semi-automatic delineation of HN and pancreas tumours in studies including PET radiomic analyses.

Agreement criteria between expected and measured field fluences in IMRT of head and neck cancer: the importance and use of the gamma histograms statistical analysis.

BACKGROUND AND PURPOSE: The aim of this study was to analyse our pre-treatment QA data in order to establish uniquely defined agreement criteria between planned and delivered dose distribution for clinical QA practice in IMRT of head and neck (HN) patients. MATERIALS AND METHODS: Pre-treatment QA dosimetry using films in combination with ionisation chambers is routinely evaluated for each patient. This evaluation is performed by comparing planned and measured dose distributions in terms of absolute point dose measurements, planar dose verification and gamma function analysis using 4%/3mm values as acceptance criteria. In the current investigation, gamma histograms, calculated on dose levels higher than 10% of the prescription dose (1.8Gy/fraction), were further analysed by considering mean values, gamma values corresponding to Delta=mean+1.5 SD (named as gamma(Delta)) and the % of points with gamma<1, gamma<1.5 and gamma>2. When considering the patient population, the average values of all these parameters and their confidence limits (mean value+1.5 SD) were calculated. The results here presented refer to 57 HN patients treated in the period September 04-April 06. RESULTS: Better results were found for treatments performed with our newly installed linac (e.g. average gamma(Delta): 0.8 vs. 1.1 for the preexisting one, p<0.001), due to a more accurate dosimetric configuration. Also, confidence limits for the percentage of points with gamma<1, gamma<1.5 and gamma>2 were found to be quite different for the two linacs (95.3%, 98.9% and 0.4% for the newly installed unit, 87.6%, 95.2% and 2.0% for the preexisting one). CONCLUSIONS: Statistical analyses of gamma evaluation of QA pre-treatment dosimetry are useful to properly define confidence limits of the agreement between expected and measured fluences based on our institutional experience. Our results confirm that the dosimetry configuration of the beam may significantly affect the agreement between planned and measured IMRT beam fluences.

Role of computed tomography and [18F] fluorodeoxyglucose positron emission tomography image fusion in conformal radiotherapy of non-small cell lung cancer: a comparison with standard techniques with and without elective nodal irradiation.

AIMS AND BACKGROUND: Mediastinal elective node irradiation (ENI) in patients with non-small cell lung cancer candidate to radical radiotherapy is controversial. In this study, the impact of co-registered [18F]fluorodeoxyglucose-positron emission tomography (PET) and standard computed tomography (CT) on definition of target volumes and toxicity parameters was evaluated, by comparison with standard CT-based simulation with and without ENI. METHODS: CT-based gross tumor volume (GTVCT) was first contoured by a single observer without knowledge of PET results. Subsequently, the integrated GTV based on PET/CT coregistered images (GTVPET/CT) was defined. Each patient was planned according to three different treatment techniques: 1) radiotherapy with ENI using the CT data set alone (ENI plan); 2) radiotherapy without ENI using the CT data set alone (no ENI plan); 3) radiotherapy without ENI using PET/CT fusion data set (PET plan). Rival plans were compared for each patient with respect to dose to the normal tissues (spinal cord, healthy lungs, heart and esophagus). RESULTS: The addition of PET-modified TNM staging in 10/21 enrolled patients (48%); 3/21 were shifted to palliative treatment due to detection of metastatic disease or large tumor not amenable to high-dose radiotherapy. In 7/18 (39%) patients treated with radical radiotherapy, a significant (> or =25%) change in volume between GTVCT and GTVPET/CT was observed. For all the organs at risk, ENI plans had dose values significantly greater than no-ENI and PET plans. Comparing no ENI and PET plans, no statistically significant difference was observed, except for maximum point dose to the spinal cord Dmax, which was significantly lower in PET plans. Notably, even in patients in whom PET/CT planning resulted in an increased GTV, toxicity parameters were fairly acceptable, and always more favorable than with ENI plans. CONCLUSIONS: Our study suggests that [18F]-fluorodeoxyglucose-PET should be integrated in no-ENI techniques, as it improves target volume delineation without a major increase in predicted toxicity.

Geometrical and dosimetrical uncertainties in hypofractionated radiotherapy of the lung: A review.

The application of high precision hypofractionated regimes (a.k.a. stereotactic body radiotherapy (SBRT)) to the treatment of lung cancer is a 'success story' of radiotherapy. From the technical perspective, lung SBRT is a challenging technique as all aspects of the treatment workflow, from imaging to dose calculation to treatment delivery, should be carefully handled in order to ensure consistency between planned and delivered dose. In this review such technical aspects are presented and discussed, looking at what has been developed over the years. The use of imaging techniques such as slow-CT, breath-hold CT, four-dimensional CT and mid-ventilation is reviewed, presenting the main characteristics of each approach but not necessarily to single out 'the best' solution. Concerning dose calculation, a number of studies clearly separate dose algorithms that should be considered inadequate for lung SBRT (e.g. simple pencil beam algorithms) from approaches such as convolution algorithms, Monte Carlo, and solution of the transport equation, that are much better at handling the combination of small fields and heterogenenous geometries that make dose calculation not trivial. Patient positioning and management of intrafraction motion have been two areas of significant developments, to the point where it is difficult to identify which solution represents the best compromise between technical complexity and clinical effectiveness. The review analyses several of these methods, outlining the residual uncertainties associated with each of them. Last but not least, two subjects are discussed, adaptive therapy and particle therapy, that may represent in the near future additional tools for the technical improvement of lung SBRT.