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Background and purpose. To study the impact of the 4DCT imaging technique on radiotherapy planning for pancreatic carcinoma. To evaluate the possibility of IMRT/IGRT to increase the dose to PTV subvolume. Material and methods. Contrast-enhanced 4DCT scans of 15 patients (PTs) with unresectable pancreatic cancer were acquired. A 4DCT based PTV (4D-PTV) was created by the convolution of contours and then expanded for geometric uncertainties; a standard PTV (STD-PTV) was derived from a single CTV plus conventional margins. Two 3D conformal treatment (3DCRT) plans and one Helical Tomotherapy (HT) plan were generated with a prescription of 60 Gy. Regarding the 3DCRT plans, the 4D-PTV was considered as the target volume for one, and the STD-PTV for the other; the HT plans were performed only for 4D-PTV. Twelve of 15 PTs were admitted to a Phase I hypofractionated study (15 fractions). The prescribed dose was 44.25 Gy to the 4D-PTV and the PTV subvolume around vascular involvement was boosted from 50 to 55 Gy; before treatment, daily patient position was corrected using MVCT. Results. 4D-PTVs were smaller than STD-PTVs with a volume reduction equal to 37%. 3DCRT plans on 4D-PTV showed a significant sparing of most OARs, the use of IMRT allowed a further significant dose reduction. In the Phase I study the PTV subvolume received up to 55 Gy with modest increase in dose to OARs. Conclusions. The 4DCT procedure decreases the overlap between PTV and OARs. HT technique, compared with 3DCRT, allows efficient dose sparing in particular for the duodenum. The IMRT/IGRT approach allows a safe dose escalation to PTV subvolume. [ABSTRACT FROM AUTHOR]

Purpose: The treatment of relapses of already irradiated primary brain tumors and metastases is difficult, given the limited effectiveness of systemic therapy and the risks of surgery or re-irradiation. Here we present the results of salvage Stereotactic Radiotherapy (SRT) for the treatment of recurrent primary brain tumors and metastases (mts) after previous radiotherapy (RT). Material/methods: From January 2018 to October 2021, 137 intracranial lesions (33 patients) were re-irradiated with robotic SRT. Primary histology was: NSCLC (n=10), breast cancer (n=9), glioblastoma (n=4), meningioma (n=2), oligodendroglioma (n=2), hemangiopericytoma (n=2), pituitary adenoma (n=2), prostate cancer (n=1), and melanoma (1). Previous RT on the same volume were performed with: GammaKnife (n=11), CyberKnife (n=8), Whole-Brain RT (n=8), post-operative IMRT/ Helical IMRT (n=8), VMAT-SRT (n=5), post-operative 3D-CRT (n=3). Eight patients had multiple previous treatments. Median time from the previous radiotherapy was 13 (3-377) months. Gross Tumor Volume (GTV) was delineated on computed tomography and contrast-enhanced T1 magnetic resonance. Median GTV was 5.24 (0.22-78.32) cc. Planning Target Volume (PTV) was obtained adding an expansion to GTV of 1 mm (for brain metastases), or 3 mm (for glioblastoma). Median PTV was 10.19 (0.43-136.9) cc. Median prescribed dose was 30 (24-37.5) Gy in 1-5 fractions (median number of fractions was 5), at a median isodose of 76% (67-80%). The patients were followed up with contrast-enhanced MRI performed every three months. Results: SRT was delivered on a median number of 2 (1-24) lesions; 7 patients were treated on ≥ 5 lesions simultaneously (from 5 to 24 lesions). Acute toxicity was G2 headache in three patients (GTV>1cc or >3 lesions), controlled by increasing the dose of steroids. Median follow-up after re-irradiation in 20 evaluable patients was 9 (1-37) months. Radionecrosis occurred in only one patient (GTV>1cc). He underwent two previous VMAT SRT (prescribed dose 30 Gy in 5 fractions and 21 Gy in 3 fractions) and presented seizures. He was treated with steroids and levetiracetam. Six-, 12-, 18-month overall survival (OS) was 79.2%, 51.7%, 37.7% respectively. Six-, 12-, 18-month local relapse free survival was 70.7%, 64.8%, 48.6% respectively (see Figure 1). Conclusions: SRT for re-irradiation is feasible, with only one case of radionecrosis registered. The treatment is effective with 12-month local control registered in 65% of pts. An accurate patient selection is warranted in order to avoid toxicity and a longer follow-up is needed to confirm the low radionecrosis rate. [ABSTRACT FROM AUTHOR]

Object: Lung metastases from colorectal cancer are more radioresistant, requiring higher dose to obtain a stable local control. Here we evaluate two different techniques of stereotactic body radiotherapy (SBRT) for lung metastases from colorectal cancer in patients treated in our departmed. Material and methods: From 01/2006 to 07/2020, 69 lung metastases (37 patients) from colorectal cancer were treated with SBRT in our department: 48 lesions (27 patients) with 4DCT simulation and helical/VMAT IGIMRT (4DCT) and 21 lesions (10 patients) with real time-tracking robotic radiosurgery (CK). Median ages were 71.9 years (4DCT) vs 64.1 years (CK). Median GTV were 5.16 (0.31-88.6) cc (4DCT) vs 3.98 (0.16-16) cc (CK), while median PTV were 26.3 (6.3-180) (4DCT) cc vs 16.7 (1.9 vs 45.6) cc (CK), respectively. The tighter margins used with the real-time tracking was the main factor that determined a smaller PTV volume. Central lesions were 17.1% in the 4DCT group vs 23.5% in the CK group. Median BED precribed was 102.6 Gy in the 4DCT group vs 112.5 Gy in the CK group. The tighter margins allowed us not only to prescribe a higher median BED, but also to reduce the number of fractions and the overall treatment time from 2 weeks with 6 fractions every other day to 3 consecutive daily fractions. Results: Median follow-ups were 26.4 (3-85.7) months (4DCT group) vs 16.4 (3.4-37.4) months (CK group). The treatment was well tollerated: one patient presented a grade (G) 3 pneumonitis after a treatment on 6 lesions/4 PTV’s in one month with CK. Fully recovered she died one year later for distant metastases. Five patients presented G1/G2 cough and 1 with G1 dyspnea soon after the 4DCT treatment. Four patients had persistent G1 fibrosis, and 7 G1 dyspnea after the 4DCT treatment. Local control was of 69.3% (4DCT) vs 90.5% (CK) at 12 months, 46.5% vs 81.4% at 24 months (p= 0.08) (see Fig. 1). Overall survival at 12 months was 89.5% in the CK group vs 94.7% in the 4DCT group, at 24 months 64.6 % vs 76.5 %, and at 36 months 64.6% vs 51.7%, respectively. Conclusion: SBRT in lung oligometastases from colorectal cancer have a low toxicity profile. Even a small increase of BED from 102 Gy to 112 Gy, and the higher precision allowed by the real-time tracking shows a tendency towards better local control. [ABSTRACT FROM AUTHOR]

Purpose: Tumor control probability (TCP)-based early regression index (ERITCP) is a radiobiological parameter that showed promising results in predicting pathologic complete response (pCR) on T2-weighted 1.5 T magnetic resonance (MR) images of patients with locally advanced rectal cancer. This study aims to validate the ERITCP in the context of low-tesla MR-guided radiation therapy, using images acquired with different magnetic field strength (0.35 T) and image contrast (T2/T1). Furthermore, the optimal timing for pCR prediction was estimated, calculating the ERI index at different biologically effective dose (BED) levels.Methods and Materials: Fifty-two patients with locally advanced rectal cancer treated with neoadjuvant chemoradiation therapy were enrolled in this multi-institutional retrospective study. For each patient, a 0.35 T T2/T1-weighted MR image was acquired during simulation and on each treatment day. Gross tumor volume was contoured according to International Commission on Radiation Units Report 83 guidelines. According to the original definition, ERITCP was calculated considering the residual tumor volume at BED = 25 Gy. ERI was also calculated in correspondence with several BED levels: 13, 21, 32, 40, 46, 54, 59, and 67. The predictive performance of the different ERI indices were evaluated in terms of receiver operating characteristic curve. The robustness of ERITCP with respect to the interobserver variability was also evaluated considering 2 operators and calculating the intraclass correlation index.Results: Fourteen patients showed pCR. ERITCP correctly 47 of 52 cases (accuracy = 90%), showing good results in terms of sensitivity (86%), specificity (92%), negative predictive value (95%), and positive predictive value (80%). The analysis at different BED levels shows that the best predictive performance is obtained when this parameter is calculated at BED = 25 Gy (area under the curve = 0.93). ERITCP results are robust with respect to interobserver variability (intraclass correlation index = 0.99).Conclusions: This study confirmed the validity and the robustness of ERITCP as a pCR predictor in the context of low-tesla MR-guided radiation therapy and indicate 25 Gy as the best BED level to perform predictions. [ABSTRACT FROM AUTHOR]

Purpose: The proximity or overlap of planning target volume (PTV) and organs-at-risk (OARs) poses a major challenge in stereotactic body radiation therapy (SBRT) of pancreatic cancer (PACA). This international treatment planning benchmark study investigates whether simultaneous integrated boost (SIB) and simultaneous integrated protection (SIP) concepts in PACA SBRT can lead to improved and harmonized plan quality., Methods and Materials: A multiparametric specification of desired target doses (gross target volume [GTV] D50% , GTV D99% , PTV D95% , and PTV 0.5cc ) with 2 prescription doses of GTV D50% = 5 × 9.2Gy (46 Gy) and GTV D50% = 8 × 8.25 Gy (66 Gy) and OAR limits were distributed with planning computed tomography and contours from 3 PACA patients. In phase 1, plans were ranked using a scoring system for comparison of trade-offs between GTV/PTV and OAR. In phase 2, replanning was performed for the most challenging case and prescription with dedicated SIB and SIP contours provided for optimization after group discussion., Results: For all 3 cases and both phases combined, 292 plans were generated from 42 institutions in 5 countries using commonly available treatment planning systems. The GTV D50% prescription was performed by only 76% and 74% of planners within 2% for 5 and 8 fractions, respectively. The GTV D99% goal was mostly reached, while the balance between OAR and target dose showed initial SIB/SIP-like optimization strategies in about 50% of plans. For plan ranking, 149 and 217 score penalties were given for 5 and 8 fractions, pointing to improvement possibilities. For phase 2, the GTV D50% prescription was performed by 95% of planners within 2%, and GTV D99% as well as OAR doses were better harmonized with notable less score penalties. Fourteen of 19 planners improved their plan rank, 9 of them by at least 2 ranks., Conclusions: Dedicated SIB/SIP concepts in combination with multiparametric prescriptions and constraints can lead to overall harmonized and high treatment plan quality for PACA SBRT. Standardized SIB/SIP treatment planning in multicenter clinical trials appears feasible after group consensus and training., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Purpose: Tumor control probability (TCP)-based early regression index (ERI TCP ) is a radiobiological parameter that showed promising results in predicting pathologic complete response (pCR) on T2-weighted 1.5 T magnetic resonance (MR) images of patients with locally advanced rectal cancer. This study aims to validate the ERI TCP in the context of low-tesla MR-guided radiation therapy, using images acquired with different magnetic field strength (0.35 T) and image contrast (T2/T1). Furthermore, the optimal timing for pCR prediction was estimated, calculating the ERI index at different biologically effective dose (BED) levels., Methods and Materials: Fifty-two patients with locally advanced rectal cancer treated with neoadjuvant chemoradiation therapy were enrolled in this multi-institutional retrospective study. For each patient, a 0.35 T T2/T1-weighted MR image was acquired during simulation and on each treatment day. Gross tumor volume was contoured according to International Commission on Radiation Units Report 83 guidelines. According to the original definition, ERI TCP was calculated considering the residual tumor volume at BED = 25 Gy. ERI was also calculated in correspondence with several BED levels: 13, 21, 32, 40, 46, 54, 59, and 67. The predictive performance of the different ERI indices were evaluated in terms of receiver operating characteristic curve. The robustness of ERI TCP with respect to the interobserver variability was also evaluated considering 2 operators and calculating the intraclass correlation index., Results: Fourteen patients showed pCR. ERI TCP correctly 47 of 52 cases (accuracy = 90%), showing good results in terms of sensitivity (86%), specificity (92%), negative predictive value (95%), and positive predictive value (80%). The analysis at different BED levels shows that the best predictive performance is obtained when this parameter is calculated at BED = 25 Gy (area under the curve = 0.93). ERI TCP results are robust with respect to interobserver variability (intraclass correlation index = 0.99)., Conclusions: This study confirmed the validity and the robustness of ERI TCP as a pCR predictor in the context of low-tesla MR-guided radiation therapy and indicate 25 Gy as the best BED level to perform predictions., (Copyright © 2020 Elsevier Inc. All rights reserved.)

We investigated the dose-response of the external beam therapy 3 (EBT3) films for proton and carbon ion clinical beams, in comparison with conventional radiotherapy beams; we also measured the film response along the energy deposition-curve in water. We performed measurements at three hadrontherapy centres by delivering monoenergetic pencil beams (protons: 63-230 MeV; carbon ions: 115-400 MeV/u), at 0.4-20 Gy dose to water, in the plateau of the depth-dose curve. We also irradiated the films to clinical MV-photon and electron beams. We placed the EBT3 films in water along the whole depth-dose curve for 148.8 MeV protons and 398.9 MeV/u carbon ions, in comparison with measurements provided by a plane-parallel ionization chamber. For protons, the response of EBT3 in the plateau of the depth-dose curve is not different from that of photons, within experimental uncertainties. For carbon ions, we observed an energy dependent under-response of EBT3 film, from 16% to 29% with respect to photon beams. Moreover, we observed an under-response in the Bragg peak region of about 10% for 148.8 MeV protons and of about 42% for 398.9 MeV/u carbon ions. For proton and carbon ion clinical beams, an under-response occurs at the Bragg peak. For carbon ions, we also observed an under-response of the EBT3 in the plateau of the depth-dose curve. This effect is the highest at the lowest initial energy of the clinical beams, a phenomenon related to the corresponding higher LET in the film sensitive layer. This behavior should be properly modeled when using EBT3 films for accurate 3D dosimetry.

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.

The aim of this study is to provide a method to track the anatomical alterations of parotid glands during radiation treatment. The method we implemented is based on an intensity-based free-form deformable registration to realign the planning kilo-Voltage CT (kVCT) and the daily Mega-Voltage (MVCT) image sets and on an automatic contour propagation algorithm based on surface construction by triangular mesh. The accuracy of the method was evaluated through visual inspection and comparison with manual contours drawn by expert physicians. The uncertainties of automatic contours were similar to those of manual contours, in terms of parotid volumes and center-of-mass distances. The parotid volumes decreased with a median total loss of 21.7%. We observed an average medial shift of parotid center-of-mass of 3.1 mm from the external part toward the midline. The deformable registration method presented in this work provides an accurate tool for the automatic evaluation of parotid changes occurring during a radiotherapy treatment period.