Hypofractionated radiotherapy after conservative surgery may increase low-intermediate grade late fibrosis in breast cancer patients

patients Abstract Fulltext Metrics Get Permission Cite this article Authors Diges\uf9 C, Deodato F, Macchia G, Cilla S, Pieri M, Zamagni A, Farioli A, Buwenge M, Ferrandina G, Morganti AG Received 12 March 2018 Accepted for publication 23 May 2018 Published 3 October 2018 Volume 2018:10 Pages 143\u2014151 DOI https://doi.org/10.2147/BCTT.S167914 Checked for plagiarism Yes Review by Single-blind Peer reviewer comments 3 Editor who approved publication: Professor Pranela Rameshwar Article has an altmetric score of 2 Cinzia Diges\uf9,1 Francesco Deodato,1 Gabriella Macchia,1 Savino Cilla,2 Martina Pieri,3 Alice Zamagni,4 Andrea Farioli,5 Milly Buwenge,4 Gabriella Ferrandina,6,* Alessio G Morganti4,* 1Radiotherapy Unit, General Oncology Unit, Fondazione Giovanni Paolo II, Campobasso, Italy; 2Medical Physics Unit, Fondazione Giovanni Paolo II, Campobasso, Italy; 3Radiotherapy Unit, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori, Meldola, Italy; 4Radiation Oncology Center, Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna, Bologna, Italy; 5Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy; 6Department of Woman and Child Health, Gynecologic Oncology Unit, Fondazione \u201cPoliclinico Universitario A. Gemelli\u201d, IRCSS, Universita\u2019 Cattolica Sacro Cuore, Rome, Italy *These authors contributed equally to this work Aim: To compare late toxicity after postoperative hypofractionated radiotherapy (RT) and standard fractionated RT in patients with early-stage breast carcinoma. Methods: This retrospective study included 447 patients (Modulated Accelerated Radiotherapy [MARA-1]: 317 patients, and control group [CG]: 130 patients). In the CG, the whole breast received 50.4 Gy in 28 fractions (fx) using 3D-radiotherapy, plus a sequential electron boost (10 Gy in 4 fx) to tumor bed. In MARA-1 group, a forward-planned intensity-modulated radiotherapy technique with 40 Gy in 16 fx with a concomitant boost of 4 Gy to breast was used. The primary endpoint was to evaluate late toxicity, and secondary endpoints were acute toxicity, local control, and survival. ClinicalTrials.gov: NCT03461224. Results: Median follow-up was 52 months (range: 3\u2013115 months). Late skin and subcutaneous toxicity were acceptable: 5-year actuarial cumulative incidence of Grade (G) 3 late skin toxicity was 1.5% in CG and 0.0% in MARA-1. Five-year actuarial cumulative incidence of G3 late subcutaneous toxicity was 0.8% in CG and 0.3% in MARA-1. On multivariate analysis, tobacco smoking and planning target volume were associated with an increased risk of late G1 skin toxicity (HR: 2.15, 95% CI: 1.38\u20133.34 and HR: 1.12, 95% CI: 1.07\u20131.18, respectively), whereas patients with a larger planning target volume also showed an increased risk of G1 and G2 late subcutaneous toxicity (HR: 1.14, CI 95%: 1.08\u20131.20 and HR: 1.14, 95% CI: 1.01\u20131.28, respectively). MARA-1 patients also showed an increased risk of late G1 and G2 subcutaneous toxicity (HR: 2.35, 95% CI: 1.61\u20133.41 and HR: 3.07, 95% CI: 1.11\u20138.53, respectively) compared to CG. Conclusion: In this retrospective analysis, postoperative accelerated-hypofractionated RT for early-stage-breast carcinoma was associated with higher incidence of subcutaneous side effects. However, this increase was limited to G1\u2013G2 toxicity. In the future, development of predictive models could help in tailoring dose and fractionation based on the risk of toxicity

Large discrepancies between planned and actually delivered dose in IMRT of head and neck cancer. A case report

The case is reported of a patient with locally recurrent carcinoma of the tongue treated with intensity-modulated radiotherapy (IMRT) (simultaneous integrated boost) plus concurrent chemotherapy, who during the third week of radiotherapy developed grade 3 mucositis. Treatment was interrupted for 10 days until significant resolution of the symptoms. At the time of treatment resumption the patient showed 8% weight loss, and in vivo portal dose verification revealed large discrepancies between the computed and measured doses. A new CT scan showed marked tumor shrinkage and modifications to the critical structures. The comparison between the original plan and the hybrid IMRT showed a minimal dose increase in the new target volumes and a marked dose increase in the organs at risk. This case confirms the need for a robust quality assurance program when using IMRT, the feasibility and efficacy of in vivo dosimetry to detect significant discrepancies between planned and delivered dose, and the need to combine IMRT with 4-dimensional radiotherapy, at least for head and neck cancer

Squamous cell carcinoma antigen in patients with locally advanced cervical carcinoma undergoing preoperative radiochemotherapy: Association with pathological response to treatment and clinical outcome

Objective: We investigated the role of squamous cell carcinoma (SCC) at presentation (pre-SCC) and after treatment (post-SCC) as predictor of pathological response and outcome in locally advanced cervical cancer (LACC) patients undergoing preoperative chemoradiation. Methods: One hundred and twenty-three consecutive LACC patients underwent preoperative chemoradiation including cisplatin and 5-fluorouracil plus external radiotherapy to the whole pelvic region. Clinical responders underwent radical surgery. SCC levels were expressed in nanograms/milliliter. Results: Ninety-five of 123 (77.2%) and 15/113 (13.3%) cases were classified as having high pre-SCC and high post-SCC levels. Complete pathological response was documented in 51 cases (41.5%), while persistence of microscopic foci was shown in 40 cases (32.5%). In the univariate analysis, FIGO (International Federation of Gynecology and Obstetrics) stage, clinical response to treatment and post-SCC levels were associated with pathological response to chemoradiation. In the multivariate analysis, only clinical response to treatment and post-SCC levels retained an independent role as predictors of pathological response to treatment. Cases with high post-SCC status had a shorter disease-free survival than cases with low post-SCC levels (p = 0.028). In the multivariate analysis, lack of a pathological complete response/persistence of microscopic foci to treatment retained an independent negative prognostic role for disease-free survival. Conclusions: Post-SCC identifies LACC patients with a poor chance of pathological response to chemoradiation and an unfavorable outcome. Copyright \ua9 2008 S. Karger AG

Optimal beam margins in linac-based VMAT stereotactic ablative body radiotherapy: A Pareto front analysis for liver metastases

We explored the Pareto fronts mathematical strategy to determine the optimal block margin and prescription isodose for stereotactic body radiotherapy (SBRT) treatments of liver metastases using the volumetric-modulated arc therapy (VMAT) technique. Three targets (planning target volumes [PTVs] = 20, 55, and 101 cc) were selected. A single fraction dose of 26 Gy was prescribed (prescription dose [PD]). VMAT plans were generated for 3 different beam energies. Pareto fronts based on (1) different multileaf collimator (MLC) block margin around PTV and (2) different prescription isodose lines (IDL) were produced. For each block margin, the greatest IDL fulfilling the criteria (95% of PTV reached 100%) was considered as providing the optimal clinical plan for PTV coverage. Liver Dmean, V7Gy, and V12Gy were used against the PTV coverage to generate the fronts. Gradient indexes (GI and mGI), homogeneity index (HI), and healthy liver irradiation in terms of Dmean, V7Gy, and V12Gy were calculated to compare different plans. In addition, each target was also optimized with a full-inverse planning engine to obtain a direct comparison with anatomy-based treatment planning system (TPS) results. About 900 plans were calculated to generate the fronts. GI and mGI show a U-shaped behavior as a function of beam margin with minimal values obtained with a +1 mm MLC margin. For these plans, the IDL ranges from 74% to 86%. GI and mGI show also a V-shaped behavior with respect to HI index, with minimum values at 1 mm for all metrics, independent of tumor dimensions and beam energy. Full-inversed optimized plans reported worse results with respect to Pareto plans. In conclusion, Pareto fronts provide a rigorous strategy to choose clinical optimal plans in SBRT treatments. We show that a 1-mm MLC block margin provides the best results with regard to healthy liver tissue irradiation and steepness of dose fallout

Preoperative chemoradiation and intra-operative radiotherapy for pancreatic carcinoma

In recent years, preoperative chemoradiation has received growing interest for the treatment of locally advanced pancreatic cancer. In an attempt to improve resectability and disease control, we used preoperative radiation therapy and concomitant 5-fluorouracil in a combined modality therapy protocol. The aim of the study was to evaluate definitive results in terms of toxicity, response and clinical outcome

Postoperative Intensity-Modulated Radiotherapy in Low-Risk Endometrial Cancers: Final Results of a Phase I Study

Purpose: To determine the maximum tolerated dose of short-course radiotherapy (intensity-modulated radiotherapy technique) to the upper two thirds of the vagina in endometrial cancers with low risk of local recurrence. Patients and Methods: A Phase I clinical trial was performed. Eligible patients had low-risk resected primary endometrial adenocarcinomas. Radiotherapy was delivered in 5 fractions over 1 week. The planning target volume was the clinical target volume plus 5 mm. The clinical target volume was defined as the upper two thirds of the vagina as evidenced at CT simulation by a vaginal radio-opaque device. The planning target volume was irradiated by a seven-field intensity-modulated radiotherapy technique, planned by the Plato Sunrise inverse planning system. A first cohort of 6 patients received 25 Gy (5-Gy fractions), and a subsequent cohort received 30 Gy (6-Gy fractions). The Common Toxicity Criteria scale, version 3.0, was used to score toxicity. Results: Twelve patients with endometrial cancer were enrolled. Median age was 58 years (range, 49-74 years). Pathologic stage was IB (83.3%) and IC (16.7%). Median tumor size was 30 mm (range, 15-50 mm). All patients completed the prescribed radiotherapy. No patient experienced a dose-limiting toxicity at the first level, and the radiotherapy dose was escalated from 25 to 30 Gy. No patients at the second dose level experienced dose-limiting toxicity. The most common Grade 2 toxicity was gastrointestinal, which was tolerable and manageable. Conclusions: The maximum tolerated dose of short-course radiotherapy was 30 Gy at 6 Gy per fraction. On the basis of this result, we are conducting a Phase II study with radiotherapy delivered at 30 Gy. \ua9 2010 Elsevier Inc. All rights reserved

Phase I-II studies on accelerated IMRT in breast carcinoma: technical comparison and acute toxicity in 332 patients.

BACKGROUND AND PURPOSE: To evaluate the results in terms of dosimetric parameters and acute toxicity of two clinical studies (MARA-1 and MARA-2) on accelerated IMRT-based postoperative radiotherapy. These results are compared with historical control group (CG) of patients treated with "standard" 3D postoperative radiotherapy. MATERIALS AND METHODS: Prescribed dose to the breast was 50.4Gy in the CG, 40Gy in MARA-1 (low risk of local recurrence), and 50Gy in MARA-2 (medium-high risk of recurrence). The tumor bed total dose was 60.4Gy (sequential 10Gy electron boost), 44Gy (concomitant 4Gy boost), and 60Gy (concomitant 10Gy boost) in CG, MARA-1 and MARA-2 studies, respectively. Overall treatment time was of 32 fractions for CG (6.4weeks); 16 fractions for MARA-1 study (3.2weeks) and 25 fractions for MARA-2 study (5weeks). RESULTS: Three hundred and thirty two patients were included in the analysis. Dosimetric analysis showed D(max) and V(107%) reduction (p<0.001) and D(min) improvement (p<0.001) in the PTV in patients treated with IMRT. Grade 2 acute skin toxicity was 33.6%, 13.1%, and 45.1% in the CG, MARA-1, and MARA-2, respectively (p<0.001), and grade 3 acute skin toxicity was 3.1%, 1.0%, and 2.0%, respectively. Similarly, larger PTV and use of chemotherapy with anthracyclines and taxanes were associated with a greater acute toxicity. With a median follow-up of 31 months, no patients showed local or nodal relapse. CONCLUSIONS: A simplified step and shoot IMRT technique allowed better PTV coverage and reduced overall treatment time (CG, 6.6weeks; MARA-1, 3.2weeks; MARA-2, 5weeks) with acceptable short-term toxicity