Search

Simple Summary Several phase III randomized trials of moderate hypofractionation, including a higher proportion of high-risk prostate cancer patients treated only to the prostate, failed to demonstrate the superiority of hypofractionated regimens. There is only one randomized phase III trial, of moderately hypofractionated high-dose radiotherapy to the prostate-only versus pelvic irradiation and prostate boost, with a sufficiently long follow-up. It demonstrated better biochemical and disease-free survival when lymph nodal radiotherapy was added. Here we present the 10-year results of our experience based on an Institutional protocol adopted after a phase I–II study, on patients with unfavorable intermediate- (UIR), high- (HR), and very high-risk (VHR) prostate cancer (PCa) treated with pelvic lymph nodal irradiation (WPRT) and moderately hypofractionated high-dose (HD) simultaneous integrated boost (SIB) to the prostate. Prognostic factors for relapse, as well as acute and late gastro-intestinal (GI) and genito-urinary (GU) toxicity were also analyzed. Abstract Aims: To report 10-year outcomes of WPRT and HD moderately hypofractionated SIB to the prostate in UIR, HR, and VHR PCa. Methods: From 11/2005 to 12/2015, 224 UIR, HR, and VHR PCa patients underwent WPRT at 51.8 Gy/28 fractions and SIB at 74.2 Gy (EQD2 88 Gy) to the prostate. Androgen deprivation therapy (ADT) was prescribed in up to 86.2% of patients. Results: Median follow-up was 96.3 months (IQR: 71–124.7). Median age was 75 years (IQR: 71.3–78.1). At last follow up, G3 GI–GU toxicity was 3.1% and 8%, respectively. Ten-year biochemical relapse-free survival (bRFS) was 79.8% (95% CI: 72.3–88.1%), disease-free survival (DFS) 87.8% (95% CI: 81.7–94.3%), overall survival (OS) 65.7% (95% CI: 58.2–74.1%), and prostate cancer-specific survival (PCSS) 94.9% (95% CI: 91.0–99.0%). Only two patients presented local relapse. At univariate analysis, VHR vs. UIR was found to be a significant risk factor for biochemical relapse (HR: 2.8, 95% CI: 1.17–6.67, p = 0.021). After model selection, only Gleason Score ≥ 8 emerged as a significant factor for biochemical relapse (HR = 2.3, 95% CI: 1.12–4.9, p = 0.023). Previous TURP (HR = 3.5, 95% CI: 1.62–7.54, p = 0.001) and acute toxicity ≥ G2 (HR = 3.1, 95% CI = 1.45–6.52, p = 0.003) were significant risk factors for GU toxicity ≥ G3. Hypertension was a significant factor for GI toxicity ≥ G3 (HR = 3.63, 95% CI: 1.06–12.46, p = 0.041). ADT (HR = 0.31, 95% CI: 0.12–0.8, p = 0.015) and iPsa (HR = 0.37, 95% CI: 0.16–0.83, p = 0.0164) played a protective role. Conclusions: WPRT and HD SIB to the prostate combined with long-term ADT, in HR PCa, determine good outcomes with acceptable toxicity.

Aim We report molecular subtype impact on 1325 early breast cancer (BCa) patients treated with whole breast hypofractionated (WBH) adjuvant forward-planned intensity modulated radiotherapy (F-IMRT) without boost. Methods and materials From 02/2009-05/2017 1325 patients with pTis-pT3, pNx-N1aM0 BCa who underwent breast conservation surgery were treated with WBHF-IMRT in our institute, to a total dose of 40 Gy/15 fractions, without boost. Median age: 62 (interquartile range-IQR-:51.14–70.53) years. Histology: 8% in situ carcinoma (ISC), 92% invasive tumors. Molecular subtypes (invasive tumors): 49.9% Luminal A, 33.1% Luminal B Her2 negative (−), 6.2% Luminal B Her2 positive (+), 3.6% Hormone Receptor (HR)- Her2+, 7.1% Triple negative (TNBC), and 0.2% HR+. Chemotherapy (CT) was prescribed in 28% of patients, hormonal therapy in 80.3%, monoclonal antibodies (MAb) in 86.8% of Luminal B Her2+ and 97.7% of HR- Her2+ patients. Results Median follow up was 72.43 (IQR: 44.63–104.13) months. The 5-year Kaplan-Meier estimates of local relapse-free survival (LRFS) was 97.8%, regional-(RRFS) 98.6%, loco-regional- (LRRFS) 96.9%, distant- (DRFS) 96.6%, disease-free survival (DFS) 94.8% and overall survival (OS) 95.5%. Considering molecular subtypes, 5-year LRFS was: 99.8% for Luminal A, 96.7% for Luminal B Her2-, 94.1% for Luminal B Her2+, 87.9% for HR- Her2+, 95.1% for TNBC and 99.1% for in situ carcinoma. Conclusion While the overall estimated probability of LR within 5 years after WBHF-IMRT without boost is good (2.2%), molecular subtypes have a strong impact, despite MAb therapy in Her2+ patients, and CT for TNBC patients, and could be used as a parameter in deciding the boost prescription., Highlights • Hypofractionated three-weeks radiotherapy ensures good local control whitout boost. • In 1325 early stage breast cancers 5-year local relapse without boost was 2.2%. • Molecular subtypes have a strong impact on estimated probability of local relapse. • 5-year local control (LC) was 99.8% for Luminal A vs 87.9% for HR- Her2+. • 5-year LC was 96.7% for Luminal B Her2-, 94.1% for Luminal B Her2+, 95.1% for TNBC.

Simple Summary The therapeutic strategies employed for anaplastic thyroid cancer patients seems to be insufficient to prolong their survival, but some characteristics could predict a good prognosis, so that, starting from our experience we offer a systematic review of the literature to better understand anaplastic thyroid cancers behavior and their prognostic factors, in order to recognize and select the patients with the higher probability of better outcome even if metastatic. Moreover, we described an uncommon site of metastasis in order to improve scientific knowledge about this rare and highly aggressive pathology. Abstract Anaplastic thyroid carcinoma (ATC) is a very rare, highly aggressive malignant thyroid tumor with an overall survival from 3 to 5 months in most of the cases. Even the modern and intensive treatments seem not to be enough to provide a cure, also for the resectable ones, and the role of chemotherapy is still unclear but does not seem to prolong survival. Nevertheless, some patients survive longer and have a better outcome, even in the presence of metastasis, than what the literature reports. We present the case of a 64-year-old female affected by ATC, treated on February 2018 with surgery followed by chemoradiation. One year after surgery, the patient developed a subcutaneous recurrence that was radically resected and is still alive 29 months after the diagnosis. We propose a systematic review of the literature to deepen the knowledge of the prognostic factors of ATC with the aim to recognize and select the patients with a better outcome, even if metastatic, and to describe a very uncommon site of metastatization.

Purpose: To explore the association between planning skin dose-volume data and acute cutaneous toxicity after Radio–chemotherapy for Head and Neck (HN) cancer patients. Methods: Seventy HN patients were treated with Helical Tomotherapy (HT) with radical intent (SIB technique: 54/66 Gy to PTV1/PTV2 in 30fr) ± chemotherapy superficial body layer 2 mm thick (SL2) was delineated on planning CT. CTCAE v4.0 acute skin toxicity data were available. Absolute average Dose-Volume Histograms (DVH) of SL2 were calculated for patients with severe (G3) and severe/moderate (G3/G2) skin acute toxicities. Differences against patients with none/mild toxicity (G0/G1) were analyzed to define the most discriminative regions of SL2 DVH; univariable and multivariable logistic analyses were performed on DVH values, CTV volume, age, sex, chemotherapy. Results: Sixty-one % of patients experienced G2/G3 toxicity (rate of G3 = 19%). Differences in skin DVHs were significant in the range 53-68Gy (p-values: 0.005–0.01). V56/V64 were the most predictive parameters for G2/G3 (OR = 1.12, 95%CI = 1.03–1.21, p = 0.001) and G3 (OR = 1.13, 95%CI = 1.01–1.26, p = 0.027) with best cut-off of 7.7cc and 2.7cc respectively. The logistic model for V56 was well calibrated being both, slope and R2, close to 1. Average V64 were 2.2cc and 6cc for the two groups (G3 vs G0-G2 toxicity); the logistic model for V64 was quite well calibrated, with a slope close to 1 and R2 equal to 0.60. Conclusion: SL2 DVH is associated with the risk of acute skin toxicity. Constraining V64 < 3cc (equivalent to a 4x4cm2 skin surface) should keep the risk of G3 toxicity below or around 10%.

Introduction: The objective of this study was to present the outcomes of moderately hypofractionated helical intensity-modulated radiation therapy (HT) with/without simultaneous integrated boost (SIB) on fluorodeoxyglucose-positron emission tomography (FDG-PET) positive areas (gross tumor volume [GTV]-PET) for patients with progressive malignant pleural mesothelioma (MPM) after previous treatments. Methods and Materials: From May 2006 to April 2014, 51 patients with a median age of 68.8 years (range, 38.6-82 years) were treated. There were 41 men and 10 women; 43 epithelioid MPM and 8 sarcomatoid, involving the left pleura in 25 patients and the right pleura in 26 patients. The initial stage was: I, 11 patients; II, 14 patients; III, 17 patients; and IV, 9 patients. Chemotherapy was prescribed for 46 patients, for 6 cycles (range, 0-18 cycles). Eighteen patients had pleurectomy/decortication, and 33 had talc pleurodesis. FDG-PET was used for target identification. A median dose of 56 Gy/25 fractions was prescribed to the involved pleura, and SIB to 62.5 Gy to GTV-PET was added in 38 patients. Results: The median survival from diagnosis was 25.8 months (range, 8.4-99.0 months). One patient, treated with SIB, was alive at the October 2017 follow-up. Two cases of grade 5 radiation pneumonitis were registered. A GTV-PET ≤ 205 cc was predictive of late ≥ grade 2 lung toxicity, but also of better survival in stage III and IV disease: 5.9 versus 11.7 months (P = .04). A GTV-PET ≥ 473 cc was predictive of early death (P = .001). Conclusions: Moderately hypofractionated, FDG-PET guided salvage HT in patients with progressive MPM after previous treatments showed acceptable toxicity and outcome results similar to adjuvant radiotherapy after pleurectomy/decortication, suggesting that the delay of radiotherapy is not detrimental to survival, and has the associated benefit of postponing inherent toxicity. Fifty-one patients with malignant pleural mesothelioma treated with helical intensity-modulated radiation therapy in presence of intact lungs were analyzed. A positron emission tomography positive volume ≥ 473 cc was found predictive of early death. A positron emission tomography positive volume < 205 cc was associated with longer survival in stage III to IV patients treated with simultaneous integrated boost, and also with higher late pulmonary ≥ grade 2 toxicity.

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 with18F-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.

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. Keywords: Skin dose, DIR, MVCT, Dose of the day, Tomotherapy

Objective: To report the 3-year toxicity and outcomes of carbon 11 (11C)-choline-positron emission tomography (PET)/computed tomography (CT)-guided radiotherapy (RT), delivered via helical tomotherapy (HTT; Tomotherapy® Hi-Art II® Treatment System, Accuray Inc., Sunnyvale, CA, USA) after lymph node (LN) relapses in patients with prostate cancer. Patients and Methods: From January 2005 to March 2013, 81 patients with biochemical recurrence after surgery, with or without adjuvant/salvage RT or radical RT, and with evidence of LN 11C-choline-PET/CT pathological uptake, underwent HTT (median [range] prostate-specific antigen level 2.59 [0.61–187] ng/mL). Of the 81 patients, 72 were treated at the pelvic and/or lumbar-aortic LN chain with HTT at 51.8 Gy/28 fr and with simultaneous integrated boost to a median dose of 65.5 Gy on the pathological uptake sites detected by 11C-choline-PET/CT. Nine patients were treated without simultaneous integrated boost (50–65.5 Gy, 25–30 fr). Results: With a median (range) follow-up of 36 (9–116) months, 91.4% of the patients had a PSA reduction 3 months after HTT. The 3-year overall, local relapse-free and clinical relapse-free survival rates were 80.0, 89.8 and 61.8%, respectively. The 3-year actuarial incidences of ≥grade 2 rectal and ≥grade 2 genitourinary toxicity were 6.6% (±2.9%) and 26.3% (±5.5%), respectively. A PSA nadir of ≥0.26 ng/mL (hazard ratio [HR] 3.6, 95% confidence interval [CI] 1.7–7.7; P = 0.001), extrapelvic 11C-choline-PET/CT-positive LN location (HR 2.4, 95% CI 0.9–6.4; P = 0.07), RT previous to HTT (HR 2.7; 95% CI 1.07–6.9, P = 0.04) and number of positive LNs (HR 1.13, 95% CI 1.04–1.22; P = 0.003) were the main predictors of clinical relapse after HTT. Conclusions: 11C-choline-PET/CT-guided HTT is safe and effective in the treatment of LN relapses of prostate cancer in previously treated patients.

Purpose The aim of this study was to test the feasibility and dosimetric accuracy of a method that employs planning CT-to-MVCT deformable image registration (DIR) for calculation of the daily dose for head and neck (HN) patients treated with Helical Tomotherapy (HT). Methods For each patient, the planning kVCT (CTplan) was deformably registered to the MVCT acquired at the 15th therapy session (MV15) with a B-Spline Free Form algorithm using Mattes mutual information (open-source software 3D Slicer), resulting in a deformed CT (CTdef). On the same day as MVCT15, a kVCT was acquired with the patient in the same treatment position (CT15). The original HT plans were recalculated both on CTdef and CT15, and the corresponding dose distributions were compared; local dose differences

Purpose: Characterizing the changes of PET-positive lymphnodes (PNs) of head-neck cancer patients during image-guided Tomotherapy in order to verify if our clinical margin for PTV boost are adequate. Material and methods: Weekly MVCTs of 30 patients were matched with the planning kVCT (kVCT_pl) on bony anatomy: 42 visible PNs were contoured on kVCT_pl/MVCTs. Intra/inter-observer and inter-modality variability in contouring PNs was evaluated by blind re-delineation. Shrinkage of PNs and center-of-mass (CM) shifts were measured and Van Herk margins for the residual error were estimated. In addition, due to the PNs' shrinkage during therapy, probability coverage maps were considered to estimate the fraction of the high probability contours missed by the clinical PTV (5mm margin); larger margins were tried for PNs showing some missing. Results: MVCTs were adequate for PNs' delineation (DICE=0.85; range=0.79–0.91). Twenty-seven PNs showed a significant volume shrinkage at the end of therapy (median: 71%, range: 27–94%, ρ =−0.93). Time–trend of 3D-CM shift was significant for 38% of PNs (median: 5.1mm at the end of treatment, range: 1.0–8.9). The clinical PTV included 95% of the 90%/100% probability contours in 40/36 (95%/86%) PNs respectively. Van Herk margins (not considering shrinkage) were approximately 7mm for all three main axes. The clinical PTV included 95% of the 90%/100% probability contours in 40/36 (95%/86%) PNs respectively. Conclusions: The residual error relative to PNs after bone match is relatively small; the impact of CM shifts is partially counterbalanced by shrinkage. Our results do not seem to support an extensive use of adaptive re-planning to avoid the missing of PNs in dose-escalated protocols, although more information about the dosimetry impact of the reported changes is warranted.

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.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.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].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.

Images taken during and after RT for head and neck cancer have the potential to quantitatively assess xerostomia. Image information may be used as biomarkers of RT effects on parotid glands with significant potential to support adaptive treatment strategies. We investigated the possibility to extract information based on in-room CT images (kVCT, MVCT), acquired for daily image-guided radiotherapy treatment of head-and-neck cancer patients, in order to predict individual response in terms of toxicity. Follow-up MRI images were also used in order to investigate long term parotid gland deformation.

Nasopharyngeal carcinoma is rare in western countries, accounting for less than 1% of all malignancies. Despite prognosis is satisfactory for newly diagnosed, non-metastatic disease, management of recurrent disease is challenging, with a survival expectancy of approximately 6 mo with the use of chemotherapy as the sole salvage treatment. We report a case of recurrent nasopharyngeal carcinoma treated with a combination of chemotherapy, radiotherapy and surgery in the context of a multidisciplinary approach. A durable complete response was achieved.

Purpose To compare helical Tomotherapy (HT), two volumetric-modulated arc techniques and conventional fixed-field intensity modulated techniques (S-IMRT) for head-neck (HN) cancers. Methods and materials Eighteen HN patients were considered. Four treatment plans were generated for each patient: HT, S-IMRT optimised with Eclipse treatment planning system and two volumetric techniques using Elekta–Oncentra approach (VMAT) and Varian-RapidArc (RA), using two full arcs. All techniques were optimised to simultaneously deliver 66Gy to PTV1 (GTV and enlarged nodes) and 54Gy to PTV2 (subclinical and electively treated nodes). Comparisons were assessed on several dosimetric parameters and, secondarily, on planned MUs and delivery time. Results Concerning PTV coverage, significantly better results were found for HT and RA. HT significantly improved the target coverage both compared to S-IMRT and VMAT. No significant differences were found between S-IMRT and volumetric techniques in terms of dose homogeneity. For OARs, all the techniques were able to satisfy all hard constraints; significantly better results were found for HT, especially in the intermediate dose range (15–30 Gy). S-IMRT reached a significantly better OARs sparing with respect to VMAT and RA. No significant differences were found for body mean dose, excepting higher values of V5–V10 for HT. A reduction of planned MUs and delivery treatment time was found with volumetric techniques. Conclusions The objectives of satisfying target coverage and sparing of critical structures were reached with all techniques. S-IMRT techniques were found more advantageous compared to RA and VMAT for OARs sparing. HT reached the best overall treatment plan quality.

Objectives: To evaluate the predictive role of primary tumor and lymph-node uptake for disease-free survival (DFS) in head and neck cancer (HNC) patients (pts) candidates to radical RT. Methods: 25 HNC pts (median age 59.3 yrs, range: 23-81 yrs) treated with FDG PET/CT guided radical radiotherapy (2005-2011,simultaneous integrated boost (SIB) on PET positive sub-volume intensity-modulated radiotherapy (IMRT), 69Gy, 30 fractions),were retrospectively included. SUV,with and without Partial Volume Effect correction (PVC) and Biological Target Volume (BTV) (60% SUVmax) were calculated for both primary tumor and nodes (SUVT, SUVL and BTVT, BTVL, respectively) on pre-therapy FDG PET/CT, to identify SUV patient clusters.Two-year DFS was calculated for each cluster. Results: FDG PET/CT detected primary tumor in all 25 cases and cervical nodes in 17/25 pts (1 FP and 2 FN). SUVT correlated with SUVL, both with and without PVC (r=0.82, 0.76 respectively). Pts with negative nodes(G1) had SUVT17 and SUVL>13 (SUVT>14.6 and SUVL>13 without PVC). DFS was 55.5%,45.8% and 75% for G1,G2 and G3 when PVC was applied,while 55.5%,50.3%and 66.7% without PVC. Conclusions: Pretreatment SUV has a prognostic value for DFS in HNC pts candidates to RT. PVC is essential for accurate SUV measurement.A high primary tumor uptake (SUVT >17) is always associated with the presence of positive nodes

PURPOSE: Measuring parotid density changes in patients treated with IMRT for head-neck cancer (HNC) and assessing correlation with treatment-related parameters. PATIENTS AND MATERIALS: Data of 84 patients treated with IMRT for different HNC were pooled from three institutions. Parotid deformation and average Hounsfield number changes (?HU) were evaluated through MVCT (with Helical Tomotherapy) or diagnostic kVCT images taken at the treatment start/end. Parotids were delineated in the first image and propagated to the last using a previously validated algorithm based on elastic registration. The correlation between ?HU and several treatment-related parameters was tested; then, logistic uni- and multi-variate analyses taking "large" ?HU as end-point were carried out. Due to the better image quality, analyses were repeated considering only kVCT data. RESULTS: ?HU was negative in 116/168 parotids (69%; for kVCT patients: 72/92, 78%). The average ?HU was significantly different from zero (-7.3, 0.20-0.25HU/fraction, p

Purpose To assess anatomical, clinical and dosimetric pre-treatment parameters, possibly predictors of parotid shrinkage during radiotherapy of head and neck cancer (HNC). Materials Data of 174 parotids from four institutions were analysed; patients were treated with IMRT, with radical and adjuvant intent. Parotid shrinkage was evaluated by the volumetric difference (Δ V ) between parotid volumes at the end and those at the start of the therapy, as assessed by CT images (MVCT for 40 patients, KVCT for 47 patients). Correlation between Δ V cc/% and a number of dosimetric, clinical and geometrical parameters was assessed. Univariate as well as stepwise logistic multivariate (MVA) analyses were performed by considering as an end-point a Δ V cc/% larger than the median value. Linear models of Δ V (continuous variable) based on the most predictive variables found at the MVA were developed. Results Median Δ V cc/% were 6.95cc and 26%, respectively. The most predictive independent variables of Δ V cc at MVA were the initial parotid volume (IPV, OR: 1.100; p =0.0002) and D mean (OR: 1.059; p =0.038). The main independent predictors of Δ V % at MVA were age (OR: 0.968; p =0.041) and V 40 (OR: 1.0338; p =0.013). Δ V cc and Δ V % may be well described by the equations: Δ V cc=−2.44+0.076 D mean (Gy)+0.279 IPV (cc) and Δ V %=34.23+0.192 V 40 (%)−0.2203 age (year). The predictive power of the Δ V cc model is higher than that of the Δ V % model. Conclusions IPV/age and D mean/ V 40 are the major dosimetric and clinical/anatomic predictors of Δ V cc and Δ V %. Δ V cc and Δ V % may be well described by bi-linear models including the above-mentioned variables.

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 61.2–70.2 Gy, 1.8 Gy/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 >45–60 Gy 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.

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.

Purpose In order to explore the potential of helical Tomotherapy in the treatment of head and neck cancers (HNC), a planning study comparing our routinely delivered IMRT technique (dynamic MLC Varian 600CD Linac, inversely optimised by the Helios/Eclipse system) against two different Tomotherapy planning approaches was performed. Materials and methods In the first Tomotherapy plan (TOMO-a), we merely applied the same constraints used for the IMRT-Linac technique; in the second one (TOMO-b), we tried to stress the sparing of parotids and mandible while keeping PTV coverage and spinal cord Dmax similar to their values in the TOMO-a plan. Five patients with locally advanced oropharinx (n=3), hypopharinx (n=1) and larynx (n=1) cancer were considered. For each patient, CTV1 including neck nodes and the tumour was defined and was expanded with a margin of 0.5 cm (PTV1); then, CTV2 including high risk nodes and CTV3 including only T were defined and the corresponding PTV2/PTV3 were defined by a 0.5 cm expansion. IMRT and Tomotherapy planning were optimised to deliver 54 Gy in 30 fractions on PTV1 and 16.2 Gy in 9 fractions on PTV3; in the case a PTV2 was defined, 15 Gy were concomitantly delivered while delivering 16.2 Gy on PTV3. Separated plans for the two phases (Phase 1: first 30 fractions; Phase 2: last 9 fractions) were compared in terms of dose–volume histograms (DVH) and dose statistics on PTVs and OARs. Results When considering Phase 1, Tomotherapy improved the homogeneity of the dose distribution within PTV1 while delivering the same prescribed dose (assessed to be the median dose to PTV): the fraction of PTV1 receiving more than 95% of the prescribed dose (V95%) increased from 90% (IMRT) to 96–97% for Tomotherapy plans. Dmax within PTV1 decreased from 60.3 Gy (IMRT) to 57.4 Gy (TOMO-a) and 58.7 Gy (TOMO-b). Spinal cord Dmax decreased from 31.6 Gy (IMRT) to 26.5 Gy (TOMO-a) and 24.6 Gy (TOMO-b). No attempts to further reduce spinal cord Dmax were done. Mean dose to the parotids decreased from 26.1 Gy (IMRT) to 25.1 Gy (TOMO-a) and 20.8 Gy (TOMO-b). Mandible was significantly better spared with Tomotherapy: mean dose decreased from 34.9 Gy (IMRT) to 34.0 Gy (TOMO-a) and 30.7 Gy (TOMO-b).When considering phase 2, the average gains (TOMO-b vs IMRT) were more modest and depended on the location of PTV2/PTV3. Conclusions Preliminary findings obtained in a sequential approach for HNC suggest that Tomotherapy has the potential to significantly improve the therapeutic ratio with respect to a conventional IMRT delivery method.

Background The study of lung parenchyma anatomical modification is useful to estimate dose discrepancies during the radiation treatment of Non-Small-Cell Lung Cancer (NSCLC) patients. We propose and validate a method, based on free-form deformation and mutual information, to elastically register planning kVCT with daily MVCT images, to estimate lung parenchyma modification during Tomotherapy. Methods We analyzed 15 registrations between the planning kVCT and 3 MVCT images for each of the 5 NSCLC patients. Image registration accuracy was evaluated by visual inspection and, quantitatively, by Correlation Coefficients (CC) and Target Registration Errors (TRE). Finally, a lung volume correspondence analysis was performed to specifically evaluate registration accuracy in lungs. Results Results showed that elastic registration was always satisfactory, both qualitatively and quantitatively: TRE after elastic registration (average value of 3.6 mm) remained comparable and often smaller than voxel resolution. Lung volume variations were well estimated by elastic registration (average volume and centroid errors of 1.78% and 0.87 mm, respectively). Conclusions Our results demonstrate that this method is able to estimate lung deformations in thorax MVCT, with an accuracy within 3.6 mm comparable or smaller than the voxel dimension of the kVCT and MVCT images. It could be used to estimate lung parenchyma dose variations in thoracic Tomotherapy.