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Internal target volume defined by contrast-enhanced 4D-CT scan in unresectable pancreatic tumour: Evaluation and reproducibility

We compared customized ITVs obtained with CE-4D-CT imaging (ITV(4D)) with a population-based (ITV(PBC)) in 29 patients (PTs) and evaluated the intra-observer ITV delineation reproducibility in 5 PTs with unresectable pancreatic ductal adenocarcinoma (PDA). The ITV(PBC) was quite different from the ITV(4D), with under/over estimation of volume. Intra-observer volume delineation variability on CE-4D-CT and on a single-phase CE-CT were similar (27.6% vs 24.9%).

Feasibility of an Adaptive Strategy in Preoperative Radiochemotherapy for Rectal Cancer With Image-Guided Tomotherapy: Boosting the Dose to the Shrinking Tumor

PURPOSE To investigate the feasibility of preoperative adaptive radiochemotherapy by delivering a concomitant boost to the residual tumor during the last 6 fractions of treatment. METHODS AND MATERIALS Twenty-five patients with T3/T4N0 or N+ rectal cancer were enrolled. Concomitant chemotherapy consisted of oxaliplatin 100 mg/m(2) on days -14, 0, and +14, and 5-fluorouracil 200 mg/m(2)/d from day -14 to the end of radiation therapy (day 0 is the start of radiation therapy). Radiation therapy consisted of 41.4 Gy in 18 fractions (2.3 Gy per fraction) with Tomotherapy to the tumor and regional lymph nodes (planning target volume, PTV) defined on simulation CT and MRI. After 9 fractions simulation CT and MRI were repeated for the planning of the adaptive phase: PTVadapt was generated by adding a 5-mm margin to the residual tumor. In the last 6 fractions a boost of 3.0 Gy per fraction (in total 45.6 Gy in 18 fractions) was delivered to PTVadapt while concomitantly delivering 2.3 Gy per fraction to PTV outside PTVadapt. RESULTS Three patients experienced grade 3 gastrointestinal toxicity; 2 of 3 showed toxicity before the adaptive phase. Full dose of radiation therapy, oxaliplatin, and 5-fluorouracil was delivered in 96%, 96%, and 88% of patients, respectively. Two patients with clinical complete response (cCR) refused surgery and were still cCR at 17 and 29 months. For the remaining 23 resected patients, 15 of 23 (65%) showed tumor regression grade 3 response, and 7 of 23 (30%) had pathologic complete response; 8 (35%) and 12 (52%) tumor regression grade 3 patients had ≤5% and 10% residual viable cells, respectively. CONCLUSIONS An adaptive boost strategy is feasible, with an acceptable grade 3 gastrointestinal toxicity rate and a very encouraging tumor response rate. The results suggest that there should still be room for further dose escalation of the residual tumor with the aim of increasing pathologic complete response and/or cCR rates.

Characterisation of rectal motion during neo-adjuvant radiochemotherapy for rectal cancer with image-guided tomotherapy: Implications for adaptive dose escalation strategies

Abstract Background. Interest in boosting the dose to the tumour during neo-adjuvant radiochemotherapy for rectal cancer is ever increasing, especially within the frame of adaptive radiotherapy. Rectal motion remains a potentially important obstacle to the full exploitation of this approach and needs to be carefully investigated. Material and methods. The main purposes of this work were to: a) quantify rectal motion on all fractions of a treatment course; and b) assess margins for adaptive boosting in the second part of the treatment in order to benefit of tumour reduction during treatment. Ten consecutive patients treated with image-guided tomotherapy (41.4 Gy, 18 fractions) were selected. The cranial half of the rectum (subject to motion) was contoured by a single observer on daily MVCTs. The variations of rectal volume and of the envelope of rectum positions were investigated (169 MVCTs). The impact of applying different margins to the rectum in including all its possible positions was also investigated when considering the planning kVCT, the first fraction MVCT, the half-treatment MVCT or the median rectal contours of the whole or second half of treatment as reference volumes. Results. Rectal volume reduced during treatment in all patients, with a significant time-trend in 6/10 patients. The median values of the envelope volumes were 129 cm3 and 87 cm3 in the first and second half of the treatment, respectively. On average, 95% of the rectal envelope was included by an isotropic expansion of 12 mm and 5 mm of the median contours when considering the whole or the second half of the treatment, respectively. Conclusion. A significant reduction of rectal volume was found in the second part of the treatment where rectal mobility was limited. As a consequence, relatively small margins may be used around the residual tumour volume when adaptive boost is delivered in the second half of the treatment.

Planning design of locally advanced pancreatic carcinoma using 4DCT and IMRT/IGRT technologies

Abstract 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.

Hypofractionated Image-Guided IMRT in Advanced Pancreatic Cancer With Simultaneous Integrated Boost to Infiltrated Vessels Concomitant With Capecitabine: A Phase I Study

PURPOSE To determine the maximum tolerated radiation dose (MTD) of an integrated boost to the tumor subvolume infiltrating vessels, delivered simultaneously with radical dose to the whole tumor and concomitant capecitabine in patients with pretreated advanced pancreatic adenocarcinoma. METHODS AND MATERIALS Patients with stage III or IV pancreatic adenocarcinoma without progressive disease after induction chemotherapy were eligible. Patients underwent simulated contrast-enhanced four-dimensional computed tomography and fluorodeoxyglucose-labeled positron emission tomography. Gross tumor volume 1 (GTV1), the tumor, and GTV2, the tumor subvolume 1 cm around the infiltrated vessels, were contoured. GTVs were fused to generate Internal Target Volume (ITV)1 and ITV2. Biological tumor volume (BTV) was fused with ITV1 to create the BTV+Internal Target Volume (ITV) 1. A margin of 5/5/7 mm (7 mm in cranium-caudal) was added to BTV+ITV1 and to ITV2 to create Planning Target Volume (PTV) 1 and PTV2, respectively. Radiation therapy was delivered with tomotherapy. PTV1 received a fixed dose of 44.25 Gy in 15 fractions, and PTV2 received a dose escalation from 48 to 58 Gy as simultaneous integrated boost (SIB) in consecutive groups of at least 3 patients. Concomitant chemotherapy was capecitabine, 1250 mg/m(2) daily. Dose-limiting toxicity (DLT) was defined as any treatment-related G3 nonhematological or G4 hematological toxicity occurring during the treatment or within 90 days from its completion. RESULTS From June 2005 to February 2010, 25 patients were enrolled. The dose escalation on the SIB was stopped at 58 Gy without reaching the MTD. One patient in the 2(nd) dose level (50 Gy) had a DLT: G3 acute gastric ulcer. Three patients had G3 late adverse effects associated with gastric and/or duodenal mucosal damage. All patients received the planned dose of radiation. CONCLUSIONS A dose of 44.25 Gy in 15 fractions to the whole tumor with an SIB of 58 Gy to small tumor subvolumes concomitant with capecitabine is feasible in chemotherapy-pretreated patients with advanced pancreatic cancer.

Assessment and clinical validation of margins for adaptive simultaneous integrated boost in neo-adjuvant radiochemotherapy for rectal cancer.

PURPOSE An adaptive concomitant boost (ACB) for the neo-adjuvant treatment of rectal cancer was clinically implemented. In this study population margins M(90,90) considering rectal deformation were derived for 10 consecutive patients treated at 18 × 2.3Gy with Helical Tomotherapy (HT) and prospectively validated on 20 additional patients treated with HT, delivering ACB in the last 6 fractions. METHODS Sectorial margins M(90,90) of the whole and second treatment parts were assessed for 90% population through a method combining the 90% coverage probability maps of rectal positions (CPC90%) with 3D local distance measurements between the CPC90% and a reference rectal contour. M(90,90) were compared with the margins M(90,90)(95%/99%), ensuring CPC90% coverage with 95%/99% confidence level. M(90,90) of the treatment second part were chosen as ACB margins which were clinically validated for each patient by means of %volume missing of CPC5/6 excluded by the ACB margins. RESULTS The whole treatment M(90,90) ranged between 1.9 mm and 9 mm in the lower-posterior and upper-anterior sectors, respectively. Regarding ACB, M(90,90) were 7 mm in the anterior direction and <5 mm elsewhere. M(90,90)(95%/99%) did not significantly differ from M(90,90). The %volume excluded by the ACB margin was<2% for all male and <5% for 9/10 female patients. The dosimetry impact on R_adapt for the patients with the largest residual error was negligible. CONCLUSIONS Local deformation measurements confirm an anisotropic motion of rectum once set-up error is rigidly corrected. Margins of 7 mm anterior and 5 mm elsewhere are adequate for ACB. Female patients show a slightly larger residual error.

Could early tumour volume changes assessed on morphological MRI predict the response to chemoradiation therapy in locally-advanced rectal cancer?

AIM To investigate the potential role of an additional magnetic resonance imaging (MRI) examination performed during neoadjuvant chemoradiation therapy (CRT) in the prediction of pathological response in locally advanced rectal cancer (LARC). MATERIAL AND METHODS Forty-eight consecutive patients with LARC underwent neoadjuvant CRT. MRI studies at 1.5 T, including high-resolution T2-weighted sequences that were acquired parallel and perpendicular to the main axis of the tumour were performed before (preMRI), during (midMRI), and 6-8 weeks after the end of CRT (postMRI). Cancer volumes (Vpre, Vmid, Vpost) were drawn manually and the reduction rate calculated (ΔVmid, ΔVpost). According to Rödels pathological tumour regression grade (TRG), patients were considered non-responders (NR; TRG0-2), partial responders (PR; TRG3), and complete responders (CR; TRG4). Multivariate regression analysis was performed to identify the best MRI predictors of NR, PR, and CR. RESULTS Twenty-five patients were considered PR (52%), 13 CR (27%), and 10 NR (22%). Tumour shrinkage mainly occurred shortly after CRT (ΔVmid: CR: 80±10% versus PR: 56±19% versus NR: 28±22%, p=2.2×10-16). Vmid, Vpost, ΔVmid, and ΔVpost correlated with TRG (p<0.001). At multivariate analysis, the combined assessment of Vmid and ΔVmid was selected as the best predictor of response to CRT, in that it distinguishes CR, PR, and NR early and accurately (81.5%). CONCLUSION MidMRI allows final response assessment to neoadjuvant CRT earlier and better than the MRI performed after the end of CRT. MRI findings at midMRI may be useful to tailor patient treatment.

EP-1300: Preoperative, Adaptive Radiotherapy with Tomotherapy concomitant with chemotherapy in rectal cancer

ESTRO 35 2016 _____________________________________________________________________________________________________ Morphologic and/or metabolic imaging re-assessment was performed between 12 and 26 weeks after treatment. Disease-free survival (DFS) was calculated from the end of treatment to the date of first event of disease recurrence. Overall survival (OS) was calculated from the end of treatment to the date of death from any cause or of last follow-up.

PO-0749: Factors predicting late severe urinary incontinence after postprostatectomy RT: a longitudinal study

Results: Finally 550 patients with prostate cancer were included, with median age of 70 years old (47-85), Mean follow-up time was 136.8 months, between 5,6 and 245,8 months. D’Amico risk classification distribution was for low risk, mediun and high 20.4%, 36,5% and 43,1% respectively. RCI distribution categories was as follows 61,5%, 21,8 and 16,7%. Survival analysis showed significant differences (p<0.001) between RCI groups at 5 and 10 years. Survival probability was 98,2 and 88,5% ; 95% and 79,6% ; and 52,2% and 8,9% was respectively for each RCI category.

A.189 - Early prediction of individual response in neo-adjuvant adaptive radiochemotherapy for rectal cancer

Radboud University Medical Center, Department of Radiology and Nuclear Medicine, Nijmegen, The Netherlands University Hospital Poitiers-, Department of Nuclear Medicine-, Poitiers, France Leiden University Medical Center, Department of Radiology and Nuclear Medicine, Leiden, The Netherlands University Hospital Poitiers-, Department of Nuclear Medicine, Poitiers, France University of Brest, INSERMUMR1101LaTIM, Brest, France