Publications by authors named "Gabriella Macchia"

186 Publications

An Intensive Educational Intervention Significantly Improves the Adoption of Single Fractionation Radiotherapy in Uncomplicated Bone Metastases.

Clin Med Insights Oncol 2021 22;15:11795549211027148. Epub 2021 Jul 22.

Radiation Oncology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy.

Introduction: An education strategy was employed in our department to increase the rate of patients with uncomplicated painful bone metastases undergoing single fractionation radiotherapy (SFRT). The purpose of this report is to analyze the results of this strategy over a 5 year period.

Materials And Methods: In January 2015, two meetings were organized in our department. In the first, data from an audit on the current SFRT rate were shown. In the second, evidence of SFRT efficacy in the relief of pain from uncomplicated bone metastases was presented. In addition, during the weekly discussion of clinical cases, the opportunity to use the SFRT was systematically recalled. Using our institutional database, all patients treated with radiotherapy for uncomplicated painful bone metastases in the period between 2014 (year considered as a reference) and 2019 were retrieved. Data regarding treatment date (year), radiotherapy fractionation, and tumor, patients, and radiation oncologists characteristics were collected.

Results: A total of 627 patients were included in the analysis. The rate of patients undergoing SFRT increased from 4.0% in 2014 to 63.5% in 2019 ( < 0.001). At multivariable analysis, the delivery of SFRT was significantly correlated with older patients age (>80 years), lung cancer as the primary tumor, treatment prescribed by a radiation oncologist dedicated to palliative treatments, and treatment date (2014 vs 2015-2019).

Conclusions: This retrospective single-center analysis showed that a simple but intensive and prolonged departmental education strategy can increase the rate of patients treated with SFRT by nearly 16 times.
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http://dx.doi.org/10.1177/11795549211027148DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8312156PMC
July 2021

Definition of Local Recurrence Site in Resected Pancreatic Adenocarcinoma: A Multicenter Study (DOLORES-1).

Cancers (Basel) 2021 Jun 18;13(12). Epub 2021 Jun 18.

Medical Physics, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy.

The study aimed to generate a local failure (LF) risk map in resected pancreatic cancer (PC) and validate the results of previous studies, proposing new guidelines for PC postoperative radiotherapy clinical target volume (CTV) delineation. Follow-up computer tomography (CT) of resected PC was retrospectively reviewed by two radiologists identifying LFs and plotting them on a representative patient CT scan. The percentages of LF points randomly extracted based on CTV following the RTOG guidelines and based on the LF database were 70% and 30%, respectively. According to the Kernel density estimation, an LF 3D distribution map was generated and compared with the results of previous studies using a Dice index. Among the 64 resected patients, 59.4% underwent adjuvant treatment. LFs closer to the root of the celiac axis (CA) or the superior mesenteric artery (SMA) were reported in 32.8% and 67.2% cases, respectively. The mean (± standard deviation) distances of LF points to CA and SMA were 21.5 ± 17.9 mm and 21.6 ± 12.1 mm, respectively. The Dice values comparing our iso-level risk maps corresponding to 80% and 90% of the LF probabilistic density and the CTVs-80 and CTVs-90 of previous publications were 0.45-0.53 and 0.58-0.60, respectively. According to the Kernel density approach, a validated LF map was proposed, modeling a new adjuvant CTV based on a PC pattern of failure.
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http://dx.doi.org/10.3390/cancers13123051DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8234595PMC
June 2021

Non-melanoma Skin Cancer Treated by Contact High-dose-rate Radiotherapy (Brachytherapy): A Mono-institutional Series and Literature Review.

In Vivo 2021 Jul-Aug;35(4):2313-2319

U.O.C. Radioterapia Oncologica, Dipartimento di Diagnostica per Immagini, Radioterapia Oncologica ed Ematologia, Fondazione Policlinico Universitario "A. Gemelli" IRCCS, Rome, Italy.

Background/aim: Non-melanoma skin cancers (NMSC) are the most common neoplasms worldwide and their incidence has been proven to increase in recent years and their treatment should aim at cancer cure as well as cosmetic and functional results. The aim of the study was to report the results of our mono-institutional series of high-dose-rate radiotherapy (cHDR-RT) in NMSC, based on a homogenous technique and two different treatment schedules.

Patients And Methods: All patients affected by NMSC who were consecutively evaluated and treated at our Interventional Oncology Center from October 2018 to August 2020, were included. Patients underwent cHDR-RT using flap applicators and remotely afterloaded Ir-192 sources.

Results: Overall, 51 patients were treated for a total of 67 lesions. Local control (LC) and disease-specific survival (DSS) were 94.0% and 100%, respectively. Grade 1, grade 2, grade 3 and grade 4 acute toxicity rates were 24.6%, 3.5%, 3.5%, and 0.0%, respectively. The cosmetic results were graded as excellent/good, fair, and poor in 73.7%, 19.3%, and 7.0%.

Conclusion: cHDR-RT of NMSC is an effective alternative to surgery due to excellent outcomes both in terms of local control and aesthetic results especially in the face.
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http://dx.doi.org/10.21873/invivo.12505DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8286496PMC
June 2021

Efficacy and safety of stereotactic body radiotherapy (SBRT) in oligometastatic/persistent/recurrent ovarian cancer: a prospective, multicenter phase II study (MITO-RT3/RAD).

Int J Gynecol Cancer 2021 Jun 21. Epub 2021 Jun 21.

Gynecologic Oncology Unit, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Roma, Italy.

Background: Stereotactic body radiotherapy (SBRT) has shown promising results in the clinical setting of oligometastatic, persistent, or recurrent disease in several malignancies including ovarian cancer.

Primary Objective: The MITO-RT3/RAD trial is a prospective, multicenter phase II study aimed at identifying potential predictors of response and clinical outcome after SBRT treatment.

Study Hypothesis: Radiotherapy delivered by pre-defined SBRT treatment schedules and shared constraints could improve the rate of complete response.

Trial Design: All patients accrued will be treated with a radiotherapy dose in the range of 30-50 Gy by 1, 3, or 5 SBRT daily fractions to all sites of active metastatic disease according to diagnostic imaging. Schedules of treatment and dose prescription have been established before considering target sites and healthy organ dose constraints. Follow-up and monitoring of side effects will be carried out every 3 months for the first year with imaging and clinical evalutation, and every 4 months within the second year; thereafter, surveillance will be carried out every 6 months. The best response on a per lesion basis will be evaluated by computed tomographic (CT) scan, positron emission tomography/CT, or magnetic resonance imaging in case of brain lesions, every 3 months.

Major Inclusion/exclusion Criteria: The study includes patients with oligometastatic, persistent, or recurrent ovarian cancer for which salvage surgery or other local therapies are not feasible due to any relative contra-indication to further systemic therapy because of serious co-morbidities, previous severe toxicity, unavailability of potentially active systemic therapy, or patient refusal.

Primary Endpoint: The primary endpoint of the study is the clinical complete response rate to SBRT by imaging on a per lesion basis.

Sample Size: Approximately 205 lesions will be treated (90 lymph nodes and 115 parenchyma lesions).

Estimated Dates For Completing Accrual And Presenting Results: Fifty-two centers have expressed their intention to participate. Enrollment should be completed by March 2023 and analysis will be completed in September 2023.

Trial Registration: NCT04593381.
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http://dx.doi.org/10.1136/ijgc-2021-002709DOI Listing
June 2021

Personalized Treatment Planning Automation in Prostate Cancer Radiation Oncology: A Comprehensive Dosimetric Study.

Front Oncol 2021 1;11:636529. Epub 2021 Jun 1.

Radiation Oncology Unit, Gemelli Molise Hospital-Università Cattolica del Sacro Cuore, Campobasso, Italy.

Background: In radiation oncology, automation of treatment planning has reported the potential to improve plan quality and increase planning efficiency. We performed a comprehensive dosimetric evaluation of the new Personalized algorithm implemented in Pinnacle for full planning automation of VMAT prostate cancer treatments.

Material And Methods: Thirteen low-risk prostate (without lymph-nodes irradiation) and 13 high-risk prostate (with lymph-nodes irradiation) treatments were retrospectively taken from our clinical database and re-optimized using two different automated engines implemented in the Pinnacle treatment system. These two automated engines, the currently used Autoplanning and the new Personalized are both template-based algorithms that use a wish-list to formulate the planning goals and an iterative approach able to mimic the planning procedure usually adopted by experienced planners. In addition, the new Personalized module integrates a new engine, the Feasibility module, able to generate an "" DVH prediction of the achievability of planning goals. Comparison between clinically accepted manually generated (MP) and automated plans generated with both Autoplanning (AP) and Personalized engines (Pers) were performed using dose-volume histogram metrics and conformity indexes. Three different normal tissue complication probabilities (NTCPs) models were used for rectal toxicity evaluation. The planning efficiency and the accuracy of dose delivery were assessed for all plans.

Results: For similar targets coverage, Pers plans reported a significant increase of dose conformity and less irradiation of healthy tissue, with significant dose reduction for rectum, bladder, and femurs. On average, Pers plans decreased rectal mean dose by 11.3 and 8.3 Gy for low-risk and high-risk cohorts, respectively. Similarly, the Pers plans decreased the bladder mean doses by 7.3 and 7.6 Gy for low-risk and high-risk cohorts, respectively. The integral dose was reduced by 11-16% with respect to MP plans. Overall planning times were dramatically reduced to about 7 and 15 min for Pers plans. Despite the increased complexity, all plans passed the 3%/2 mm γ-analysis for dose verification.

Conclusions: The Personalized engine provided an overall increase of plan quality, in terms of dose conformity and sparing of normal tissues for prostate cancer patients. The Feasibility "" DVH prediction module provided OARs dose sparing well beyond the clinical objectives. The new Pinnacle Personalized algorithms outperformed the currently used Autoplanning ones as solution for treatment planning automation.
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http://dx.doi.org/10.3389/fonc.2021.636529DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8204695PMC
June 2021

Stereotactic radiotherapy in intrahepatic cholangiocarcinoma: A systematic review.

Mol Clin Oncol 2021 Aug 3;15(2):152. Epub 2021 Jun 3.

Radiation Oncology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, I-40138 Bologna, Italy.

Among biliary tract cancers, intrahepatic cholangiocarcinoma (ICC) has different characteristics compared with those in other sites. Current guidelines suggest several treatment options for ICC, including stereotactic body radiation therapy (SBRT). However, the role of SBRT in locally advanced ICC is unclear. The aim of the present study was to present a systematic review on the efficacy and safety of SBRT in ICC. A systematic review based on the PRISMA methodology was performed. Only papers reporting outcomes in terms of overall survival (OS) after SBRT in inoperable patients with ICC were included. Secondary aims were local control (LC), progression-free survival (PFS) and treatment-related toxicity. Six papers (145 patients) were included in the present analysis. SBRT was frequently used as a salvage treatment, since 28.6-66.7% of patients received previous systemic or local treatments. The median SBRT dose was 45 Gy delivered in 3-5 fractions. The median follow-up was 16 months, and median OS time was 14 months (range, 10-48 months). In one of the included studies, SBRT was significantly superior in terms of OS compared with both chemoradiation and trans-arterial-radio-embolization. The 1-year LC rate was 85% in one study, and 1-year PFS rates were 50 and 68% in two studies, respectively. Toxicity was generally not reported in detail or was reported including other sites of biliary cancers. Overall, limited evidence was available on the efficacy of SBRT in ICC, which should be further investigated in prospective studies with a larger number of patients. However, based on the available data, SBRT seems to produce similar results compared with other ICC treatments, with the advantage of being a very short and non-invasive therapy. Therefore, SBRT should be considered in selected patients with ICC.
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http://dx.doi.org/10.3892/mco.2021.2314DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8204140PMC
August 2021

Radiotherapy with Intensity-Modulated (IMRT) Techniques in the Treatment of Anal Carcinoma (RAINSTORM): A Multicenter Study on Behalf of AIRO (Italian Association of Radiotherapy and Clinical Oncology) Gastrointestinal Study Group.

Cancers (Basel) 2021 Apr 15;13(8). Epub 2021 Apr 15.

Laboratory of Biostatistics, Department of Medical, Oral and Biotechnological Sciences, "G. D'Annunzio" University of Chieti-Pescara, 66100 Chieti, Italy.

A multi-institutional retrospective study was conducted to evaluate the pattern of care and clinical outcomes of anal cancer patients treated with intensity-modulated radiotherapy (IMRT) techniques. In a cohort of 987 patients, the clinical complete response (CR) rate (beyond 6 months) was 90.6%. The 3-year local control (LC) rate was 85.8% (95% CI: 84.4-87.2), and the 3-year colostomy-free survival (CFS) rate was 77.9% (95% CI: 76.1-79.8). Three-year progression-free survival (PFS) and overall survival (OS) rates were 80.2% and 88.1% (95% CI: 78.8-89.4) (95% CI: 78.5-81.9), respectively. Histological grade 3 and nodal involvement were associated with lower CR ( = 0.030 and = 0.004, respectively). A statistically significant association was found between advanced stage and nodal involvement, and LC, CFS, PFS, OS and event-free survival (EFS). Overall treatment time (OTT) ≥45 days showed a trend for a lower PFS ( = 0.050) and was significantly associated with lower EFS ( = 0.030) and histological grade 3 with a lower LC ( = 0.025). No statistically significant association was found between total dose, dose/fraction and/or boost modality and clinical outcomes. This analysis reports excellent clinical results and a mild toxicity profile, confirming IMRT techniques as standard of care for the curative treatment of anal cancer patients. Lymph node involvement and histological grade have been confirmed as the most important negative prognostic factors.
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http://dx.doi.org/10.3390/cancers13081902DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8071256PMC
April 2021

Atherosclerotic Plaque Fissuration and Clinical Outcomes in Pre-Diabetics vs. Normoglycemics Patients Affected by Asymptomatic Significant Carotid Artery Stenosis at 2 Years of Follow-Up: Role of microRNAs Modulation: The ATIMIR Study.

Biomedicines 2021 Apr 8;9(4). Epub 2021 Apr 8.

Department of Advanced Medical and Surgical Sciences, University of Campania "Luigi Vanvitelli", 80100 Naples, Italy.

Atherosclerotic plaque instability and rupture in patients with asymptomatic carotid artery stenosis (ACAS) is a leading cause of major adverse cardiac events (MACE). This could be mainly evidenced in patients with pre-diabetes. Indeed, the altered glucose homeostasis and insulin resistance could cause over-inflammation of atherosclerotic plaque, favoring its conversion to unstable phenotype with rupture and MACE. Notably, metformin therapy reducing the metabolic distress and the inflammatory burden could reduce MACE in ACAS patients with pre-diabetes. In this setting, the microRNAs (miRs) could be used as molecular biomarkers of atherosclerosis progression, plaque rupture, and worse prognosis in normoglycemics (NG) versus pre-diabetics metformin users (PDMU) versus pre-diabetics non-metformin users (PDNMU). However, our study aimed to investigate a wide miRNA panel in peripheral blood exosomes from patients with ACAS divided in NG versus PDMU versus PDNMU, and to associate the circulating miRNA expression profiles with MACE at 2 years of follow-up after endarterectomy. The study included 234 patients with ACAS divided into NG ( = 125), PDNMU ( = 73), and PDMU ( = 36). The miRs' expression profiles of circulating exosomes were determined at baseline and at 2 years of follow-up by Affymetrix microarrays from the patients' plasma samples from any study cohort. Then we collected and analyzed MACE at 2 years of follow-up in NG versus PDMU versus PDNMU. Prediabetics versus NG had over-inflammation ( < 0.05) and over expressed miR-24 and miR-27 at baseline. At 2 years of follow-up, PDNMU versus NG, PDMU versus NG, and PDNMU versus PDMU over-expressed inflammatory markers and miR-24, miR-27, miR-100, miR-126, and miR-133 ( < 0.05). Finally, at the end of follow-up, we observed a significant difference about MACE comparing PDNMU versus NG ( = 27 (36.9%) versus = 8 (6.4%); < 0.05), PDNMU versus PDMU ( = 27 (36.9%) versus = 6 (16.6%); < 0.05); and PDMU versus NG ( = 6 (16.6%) versus = 8 (6.4%); < 0.05). Admission glucose values (HR (hazard ratio) 1.020, CI (confidence of interval) 95% (1.001-1.038), = 0.029), atheromatous carotid plaque (HR 5.373, CI 95% (1.251-11.079), = 0.024), and miR-24 (HR 3.842, CI 95% (1.768-19.222), = 0.011) predicted MACE at 2 years of follow-up. Specific circulating miRs could be over-expressed in pre-diabetics and specifically in PDNMU versus PDMU after endarterectomy. MiR24, hyperglycemia, and atheromatous plaque could predict MACE at 2 years of follow-up.
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http://dx.doi.org/10.3390/biomedicines9040401DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8068301PMC
April 2021

Challenges in lung and heart avoidance for postmastectomy breast cancer radiotherapy: Is automated planning the answer?

Med Dosim 2021 Autumn;46(3):295-303. Epub 2021 Apr 6.

Radiation Oncology Unit, Gemelli Molise Hospital, Università Cattolica del Sacro Cuore, Campobasso, Italy; Istituto di Radiologia, Università Cattolica del Sacro Cuore, Rome, Italy.

Postmastectomy radiotherapy (PMRT) has been shown to improve the overall survival for invasive breast cancer patients. However, it represents a challenging treatment geometry and individualized planning strategies with complex field arrangements are usually adopted to decrease radiotoxicity to heart and lungs. Automated treatment planning has the potential to improve plan quality consistency and planning efficiency. Herein, we describe the application of the Pinnacle Autoplanning engine as a valuable technological resource able to allow the treatment of challenging patients theoretically unfit for radiotherapy for major cardiac and pulmonary comorbidities. Treatment was planned for three left-sided chest wall and regional lymph-nodes postmastectomy breast cancer patients. A deep inspiration breath-hold (DIBH) technique was used aiming to reduce the OARs irradiation. Three manually generated plans (hybrid-IMRT (HMRT), hybrid-VMAT (HVMAT) and full VMAT (MP-VMAT) and a fully automated plan created by the Autoplanning engine (AP-VMAT) were optimized in order to ensure a safe radiation therapy to the patients. The plans were evaluated based on planning target volumes (PTVs) coverage, dose homogeneity index (HI), conformity index (CN), dose to organs at risk (OARs) and normal tissue complication probabilities (NTCPs) of pericarditis, long term mortality and pneumonitis. Despite the use of deep moderated breath-hold, all human-driven plans failed to reach the stringent dose objectives for OARs. All plans provided an optimal coverage for chest wall and lymph-nodal area. AP-VMAT delivered the lowest mean dose to the heart (3.4 to 4.9 Gy) and ipsilateral lung (7.5 to 12.5 Gy) reporting the lowest NTCP for pneumonitis (<1%), confirming the only chance to comply the dose objectives. Moreover, AP-VMAT reported a decrease of the integral dose, which was lower by about 4-8% with respect to manual plans. AP-VMAT plan resulted in up to 58% increase of MUs with respect to manual plans, suggesting a more pronounced fluence modulation and plan complexity. A major difference was found for the planning time which was reduced to less than 30 minutes by using the Auto-Planning module. With improved planning quality and efficiency, Auto-planning is an effective tool to enable high-quality plans in challenging postmastectomy breast cancer radiotherapy.
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http://dx.doi.org/10.1016/j.meddos.2021.03.002DOI Listing
April 2021

Pretreatment MRI Radiomics Based Response Prediction Model in Locally Advanced Cervical Cancer.

Diagnostics (Basel) 2021 Mar 31;11(4). Epub 2021 Mar 31.

Fondazione Policlinico Universitario "Agostino Gemelli" IRCCS, 00168 Roma, Italy.

The aim of this study was to create a radiomics model for Locally Advanced Cervical Cancer (LACC) patients to predict pathological complete response (pCR) after neoadjuvant chemoradiotherapy (NACRT) analysing T2-weighted 1.5 T magnetic resonance imaging (MRI) acquired before treatment start. Patients with LACC and an International Federation of Gynecology and Obstetrics stage from IB2 to IVA at diagnosis were retrospectively enrolled for this study. All patients underwent NACRT, followed by radical surgery; pCR-assessed on surgical specimen-was defined as absence of any residual tumour. Finally, 1889 features were extracted from MR images; features showing statistical significance in predicting pCR at the univariate analysis were selected following an iterative method, which was ad-hoc developed for this study. Based on this method, 15 different classifiers were trained considering the most significant features selected. Model selection was carried out using the area under the receiver operating characteristic curve (AUC) as target metrics. One hundred eighty-three patients from two institutions were analysed. The model, showing the highest performance with an AUC of 0.80, was the random forest method initialised with default parameters. Radiomics appeared to be a reliable tool in pCR prediction for LACC patients undergoing NACRT, supporting the identification of patient risk groups, which paves treatment pathways tailored according to the predicted outcome.
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http://dx.doi.org/10.3390/diagnostics11040631DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8066099PMC
March 2021

Post-Operative Accelerated-Hypofractionated Chemoradiation With Volumetric Modulated Arc Therapy and Simultaneous Integrated Boost in Glioblastoma: A Phase I Study (ISIDE-BT-2).

Front Oncol 2020 22;10:626400. Epub 2021 Feb 22.

Radiation Oncology Unit, Gemelli Molise Hospital - Università Cattolica del Sacro Cuore, Campobasso, Italy.

Background: Glioblastoma Multiforme (GBM) is the most common primary brain cancer and one of the most lethal tumors. Theoretically, modern radiotherapy (RT) techniques allow dose-escalation due to the reduced irradiation of healthy tissues. This study aimed to define the adjuvant maximum tolerated dose (MTD) using volumetric modulated arc RT with simultaneous integrated boost (VMAT-SIB) plus standard dose temozolomide (TMZ) in GBM.

Methods: A Phase I clinical trial was performed in operated GBM patients using VMAT-SIB technique with progressively increased total dose. RT was delivered in 25 fractions (5 weeks) to two planning target volumes (PTVs) defined by adding a 5-mm margin to the clinical target volumes (CTVs). The CTV was the tumor bed plus the MRI enhancing residual lesion with 10-mm margin. The CTV was the CTV plus 20-mm margin. Only PTV dose was escalated (planned dose levels: 72.5, 75, 77.5, 80, 82.5, 85 Gy), while PTV dose remained unchanged (45 Gy/1.8 Gy). Concurrent and sequential TMZ was prescribed according to the EORTC/NCIC protocol. Dose-limiting toxicities (DLTs) were defined as any G ≥ 3 non-hematological acute toxicity or any G ≥ 4 acute hematological toxicities (RTOG scale) or any G ≥ 2 late toxicities (RTOG-EORTC scale).

Results: Thirty-seven patients (M/F: 21/16; median age: 59 years; median follow-up: 12 months) were enrolled and treated as follows: 6 patients (72.5 Gy), 10 patients (75 Gy), 10 patients (77.5 Gy), 9 patients (80 Gy), 2 patients (82.5 Gy), and 0 patients (85 Gy). Eleven patients (29.7%) had G1-2 acute neurological toxicity, while 3 patients (8.1%) showed G ≥ 3 acute neurological toxicities at 77.5 Gy, 80 Gy, and 82.5 Gy levels, respectively. Since two DLTs (G3 neurological: 1 patient and G5 hematological toxicity: 1 patient) were observed at 82.5 Gy level, the trial was closed and the 80 Gy dose-level was defined as the MTD. Two asymptomatic histologically proven radionecrosis were recorded.

Conclusions: According to the results of this Phase I trial, 80 Gy in 25 fractions accelerated hypofractionated RT is the MTD using VMAT-SIB plus standard dose TMZ in resected GBM.
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http://dx.doi.org/10.3389/fonc.2020.626400DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7937791PMC
February 2021

Electrochemotherapy in Kaposi sarcoma: A systematic review.

Mol Clin Oncol 2021 Apr 8;14(4):64. Epub 2021 Feb 8.

Radiation Oncology Center, Department of Experimental, Diagnostic and Specialty Medicine-DIMES, University of Bologna, I-40138 Bologna, Italy.

Kaposi sarcoma (KS) is a rare angioproliferative disorder, which is usually associated with human herpesvirus-8 infection. Electrochemotherapy (ECT) may be an option in the treatment of KS skin lesions due to the high response rate noted in neoplastic lesions of different histological types. The aim of the present systematic review was to analyse the available evidence on using ECT in the treatment of KS skin lesions. Tumor response, local control and toxicity were analyzed. In the three included studies, the complete response rate was 65-100% and the overall response rate in all studies was 100%. The treatment was well tolerated with mild and transient toxicity. However, further studies are required to fully analyze long-term disease control and to compare ECT with other local therapies used for KS.
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http://dx.doi.org/10.3892/mco.2021.2226DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7890459PMC
April 2021

Brachytherapy or external beam radiotherapy as a boost in locally advanced cervical cancer: a Gynaecology Study Group in the Italian Association of Radiation and Clinical Oncology (AIRO) review.

Int J Gynecol Cancer 2021 09 25;31(9):1278-1286. Epub 2021 Feb 25.

Radiation Oncology Section, University of Perugia and Perugia General Hospital, Perugia, Umbria, Italy.

This review analyzes the experience and trends in external beam radiotherapy for delivering a boost in locally advanced cervical cancer, identifying whether radiation therapy modalities impact clinical outcomes with the ultimate aim of evaluating alternatives to brachytherapy. Three independent Italian radiation oncologists conducted a literature search on different external beam radiotherapy boost modalities in locally advanced cervical cancer. The search yielded 30 studies. Eight dosimetric studies, evaluating target coverage and dose to organs at risk, and nine clinical investigations, reporting clinical outcomes, were analyzed. Dosimetric studies comparing external beam radiotherapy boost with brachytherapy produced divergent results, while clinical studies were limited by their retrospective nature, heterogeneous doses, radiation schedules, volumes and techniques, diverse follow-up times, and small cohorts of patients. Evidence emerged that high-tech external beam radiotherapy seemed no better than image-guided brachytherapy for delivering a boost in locally advanced cervical cancer. Prospective clinical studies comparing high-tech external beam radiotherapy and image-guided brachytherapy should be encouraged.
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http://dx.doi.org/10.1136/ijgc-2020-002310DOI Listing
September 2021

Personalized automation of treatment planning in head-neck cancer: A step forward for quality in radiation therapy?

Phys Med 2021 Feb 25;82:7-16. Epub 2021 Jan 25.

Radiation Oncology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Italy; DIMES, Alma Mater Studiorum Bologna University, Italy.

Purpose: To perform a comprehensive dosimetric and clinical evaluation of the new Pinnacle Personalized automated planning system for complex head-and-neck treatments.

Methods: Fifteen consecutive head-neck patients were enrolled. Radiotherapy was prescribed using VMAT with simultaneous integrated boost strategy. Personalized planning integrates the Feasibility engine able to supply an "a priori" DVH prediction of the achievability of planning goals. Comparison between clinically accepted manually-generated (MP) and automated (AP) plans was performed using dose-volume histograms and a blinded clinical evaluation by two radiation oncologists. Planning time between MP and AP was compared. Dose accuracy was validated using the PTW Octavius-4D phantom together with the 1500 2D-array.

Results: For similar targets coverage, AP plans reported less irradiation of healthy tissue, with significant dose reduction for spinal cord, brainstem and parotids. On average, the mean dose to parotids and maximal doses to spinal cord and brainstem were reduced by 13-15% (p < 0.001), 9% (p < 0.001) and 16% (p < 0.001), respectively. The integral dose was reduced by 16% (p < 0.001). The dose conformity for the three PTVs was significantly higher with AP plans (p < 0.001). The two oncologists chose AP plans in more than 80% of cases. Overall planning times were reduced to <30 min for automated optimization. All AP plans passed the 3%/2 mm γ-analysis by more than 95%.

Conclusion: Complex head-neck plans created using Personalized automated engine provided an overall increase of plan quality, in terms of dose conformity and sparing of normal tissues. The Feasibility module allowed OARs dose sparing well beyond the clinical objectives.
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http://dx.doi.org/10.1016/j.ejmp.2020.12.015DOI Listing
February 2021

Systematic review of stereotactic body radiotherapy for nodal metastases.

Clin Exp Metastasis 2021 02 16;38(1):11-29. Epub 2021 Jan 16.

Radiotherapy Department, IRCCS Azienda Ospedaliero-Universitaria Di Bologna, via Giuseppe Massarenti 9, 40138, Bologna, Italy.

The aim of this analysis was to assess the efficacy of stereotactic body radiotherapy (SBRT) in terms of local control (LC) and progression-free survival (PFS) in patients with lymph node metastases (NMs) from solid tumors. A systematic literature search from the earliest date to July 25th, 2019 was performed following PRISMA guidelines. Papers reporting LC and/or PFS of NMs using SBRT (< 10 fractions) were selected. The clinical outcomes rates were pooled by means of a random or fixed-effect model. Twenty-nine studies were eligible (969 patients: 938 (LC) and 698 (PFS)). LC and PFS results were reported in 28 and 18 papers, respectively. Heterogeneity was observed in terms of patient and treatment characteristics. Pooled 2-year LC reported in 11 studies was 79.3% (95%CI, 72.8%-85.7%) with substantial heterogeneity between studies (Q2 test: p = 0.0083; I2 = 57.9%), while pooled 2-year PFS reported in 8 studies was 35.9% (95%CI, 22.1%-49.7%) with very high heterogeneity between studies (Q2 test: p < 0.0001; I2 = 86.1%). Grade ≥ 3 and Grade 5 toxicity rates were 2.0% and 0.2%, respectively. SBRT of NMs seems to be safe and effective in terms of LC. However, due to the marked heterogeneity of the included series, prospective studies are required.
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http://dx.doi.org/10.1007/s10585-020-10071-xDOI Listing
February 2021

Hippocampal-sparing radiotherapy and neurocognitive impairment: A systematic literature review.

J Cancer Res Ther 2020 Oct-Dec;16(6):1215-1222

Department of Experimental, Radiation Oncology Center, Diagnostic and Specialty Medicine - DIMES, University of Bologna, Bologna, Italy.

Introduction: Whole-brain radiation therapy (WBRT) is an effective therapeutic modality in patients with brain metastases. However, nearly 90% of patients undergoing WBRT suffer from a neurocognitive function (NCF) impairment at diagnosis, and up to two-thirds will experience a further decline within 2-6 months after WBRT. Focal-dose reduction on bilateral hippocampus is thought to improve NCF preservation. The aim was to present a systematic review of clinical results on NCF after hippocampal-sparing (HS) WBRT.

Materials And Methods: A systematic review of published literature was performed on PubMed and the Cochrane Library. Only prospective clinical trials reporting NCF outcome in patients treated with HS-WBRT have been analyzed.

Results: A total of 165 patients from three studies were included. These studies are characterized by small sample size and different methods in terms of WBRT technique but with similar planning analysis and NCF assessment tests. No significant changes in NCF (i.e., verbal and nonverbal learning memory, executive functions, and psychomotor speed) between baseline and 4-month follow-up after RT and only a mean relative decline in delayed recall at 4 months (7% compared to 30% of historical control) were observed.

Conclusions: Considering preliminary results on NCF preservation, further studies seem justified in patients undergoing brain irradiation for brain metastases or referred for prophylactic cranial irradiation to evaluate long-term effects on NCF and quality of life.
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http://dx.doi.org/10.4103/jcrt.JCRT_573_17DOI Listing
February 2021

Intensity-Modulated Radiotherapy with Concomitant Boost After Breast Conserving Surgery: A Phase I-II Trial.

Breast Cancer (Dove Med Press) 2020 12;12:243-249. Epub 2020 Nov 12.

Radiation Oncology Center, Department of Experimental, Diagnostic and Specialty Medicine ‑ DIMES, University of Bologna, S. Orsola-Malpighi Hospital, Bologna, Italy.

Purpose: A concomitant boost (CB) in patients treated with postoperative radiotherapy after conservative surgery of invasive breast cancer (BC) has been suggested for treatment time reduction and therapy intensification. The aim of this analysis was to assess long-term tolerability of a CB in patients treated with postoperative intensity Modulated Accelerated RAdiotherapy (MARA).

Patients And Methods: In this phase I-II trial, 321 patients with intermediate-high risk BC (pT1-4 with at least one of the following characteristics: pre or perimenopausal status, pN2-3, positive or close margins) were enrolled. Patients were treated with forward-planned intensity modulated radiotherapy (IMRT) and CB. A total dose of 50 Gy (2 Gy/fraction) and 60 Gy (2.4 Gy/fraction) was prescribed to the whole breast and the tumor bed, respectively. The potential impact of hypertension, diabetes, smoking habit, alcohol consumption, chemotherapy, and hormone therapy on both skin and subcutaneous late toxicity-free survival (LTFS) was evaluated. Survival curves were calculated using the Kaplan-Meier method.

Results: Median follow-up was 52 months (range: 3-115). Regional node irradiation, adjuvant chemotherapy and hormonal therapy were prescribed to 29.3%, 65.4% and 81.0% of patients, respectively. Five-year G2 and G3 skin LTFS were 95.6% and 100.0%, respectively. Five-year G2 and G3 subcutaneous LTFS were 80.0% and 98.6%, respectively. Only diabetes showed a significant correlation with worse G3 subcutaneous LTFS (p: 0.024). Five-year loco-regional control, metastasis-free survival, disease-free survival, and overall survival were 98.0%, 91.8%, 89.7% and 96.3%, respectively.

Conclusion: IMRT combined with CB was associated with a low risk of > G2 late toxicities (0.0% and 1.4% for skin and subcutaneous tissue, respectively). The cumulative actuarial incidence of local recurrences was 2.0% despite the exclusion of low-risk patients. Our results suggest that CB is safe and effective in patients with intermediate-high risk BC.

Trial Registration: ClinicalTrials.gov: NCT03471741.
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http://dx.doi.org/10.2147/BCTT.S261587DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7670173PMC
November 2020

Electrochemotherapy of skin metastases from breast cancer: a systematic review.

Clin Exp Metastasis 2021 02 12;38(1):1-10. Epub 2020 Nov 12.

Radiation Oncology Center, Department of Experimental, Diagnostic and Specialty Medicine - DIMES, University of Bologna S. Orsola-Malpighi Hospital, Via Massarenti 9, 40138, Bologna, Italy.

Skin metastases occur in 5-30% of breast cancer (BC) patients. Standard treatments include systemic therapies (chemotherapy, endocrine therapy, and immunotherapy) and local treatments (surgery and radiotherapy). Electrochemotherapy (ECT) could be another option in this setting based on preclinical and clinical studies. Aim of this review was to analyze the available evidence on ECT in skin metastases from BC. Studies reporting on ECT in skin metastases from BC were included in this review. Studies not reporting toxicity or tumor response or not reporting results separately from other primary cancers were excluded. The search was based on Medline, Scopus, and The Cochrane Library databases. Eleven studies including 464 patients were analyzed. ECT was performed using intravenous/intratumoral bleomycin (10 studies) or intratumoral cisplatin (one study). Complete and overall pooled response rates were 46.2% (CI 33.2-59.4 and 74.6% (CI 60.6-86.4) in studies reporting results on a per patient basis and 61.9% (CI 53.8-69.6) and 86.9% (CI 80.0-92.6) in studies reporting results on a per lesion basis, respectively. Worse response rates in larger lesions were observed in three studies. The incidence of toxicity was heterogeneous but adverse events were mild and manageable in all studies. One- and 3-year local progression-free survival was 86.2% and 81.0% in two studies, respectively. ECT is tolerable and effective in terms of response in BC skin metastases especially in less advanced lesions. Further studies are justified to compare ECT with other treatments in this setting.
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http://dx.doi.org/10.1007/s10585-020-10063-xDOI Listing
February 2021

Simultaneous Integrated Radiotherapy Boost to the Dominant Intraprostatic Lesion: Final Results of a Phase I/II Trial.

Anticancer Res 2020 Nov;40(11):6499-6503

Radiotherapy Unit, Gemelli Molise Hospital, Campobasso, Italy.

Background/aim: Late toxicity and long-term outcomes of a phase I-II trial on patients with prostate cancer treated with an integrated boost to the dominant intraprostatic lesion (DIL) are reported.

Patients And Methods: Patients were treated using intensity-modulated radiotherapy, with a simultaneous integrated boost to the DIL, defined on staging magnetic resonance imaging, delivering 72 Gy in 1.8 Gy/fraction to prostate/seminal vesicles and 80 Gy in 2 Gy/fraction to the DIL. The primary endpoint was acute toxicity and secondary endpoints were late toxicity and biochemical disease-free survival.

Results: Forty-four patients were enrolled. The median follow-up was 120 (range=25-150) months. Five-year rates of grade 3 late gastrointestinal and genitourinary toxicity were 2.3% and 4.5%, respectively; only one grade 4 late genitourinary toxicity was recorded. Five-year biochemical relapse-free and overall survival rates were 95.3% and 95.5%, respectively.

Conclusion: The treatment was well tolerated and achieved excellent results in terms of outcome in patients with low-intermediate Gleason's score and low risk of nodal metastasis.
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http://dx.doi.org/10.21873/anticanres.14672DOI Listing
November 2020

Advanced head and neck cancer in older adults: Results of a short course accelerated radiotherapy trial.

J Geriatr Oncol 2021 04 21;12(3):441-445. Epub 2020 Oct 21.

Radiation Oncology Unit, Gemelli Molise Hospital, Catholic University of Sacred Heart, Largo A. Gemelli 1, 86100 Campobasso, Italy; Istituto di Radiologia, Catholic University of Sacred Heart, 00168 Rome, Italy.

Objectives: To assess the feasibility and safety of a repeated SHort course Accelerated RadiatiON therapy (SHARON) regimen in the palliative setting of Head and Neck (H&N) cancer in older adults.

Material And Methods: Patients with histological confirmed H&N cancers, age ≥ 80 years, expected survival >3 months, and Eastern Cooperative Oncology Group (ECOG) performance status of ≤3 were enrolled. Patients were treated in cohorts of six patients: a total dose of 20 Gy was delivered in 2 consecutive days with a twice-daily fractionation (5 Gy per fraction) and at least 8-h interval. If no Grade 3 toxicity was registered, a second enrollment started with another cohort of six patients to whom were administered two cycles (total dose of 40 Gy). The primary endpoint was to evaluate the feasibility of the two cycles of treatment. Secondary endpoints were evaluation of symptoms control rate, symptoms-free survival (SFS), and Quality of Life (QoL) scores.

Results: Seventeen consecutive patients (median age: 85 years) were treated. Nine patients were treated with one cycle and 8 patients with two cycles. No G3 toxicity was reported in either cohort. With a median follow-up time of 4 months, 3-month SFS in the first and second cohorts was 83.3%, and 87.5%, respectively. The overall palliative response rate was 88%. Among 13 patients reporting pain, 8 (61.5%) showed an improvement or resolution of their pain.

Conclusion: Repeated short course accelerated radiotherapy in a palliative setting of H&N cancers is safe and well-tolerated in older adults.
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http://dx.doi.org/10.1016/j.jgo.2020.10.006DOI Listing
April 2021

Automated treatment planning as a dose escalation strategy for stereotactic radiation therapy in pancreatic cancer.

J Appl Clin Med Phys 2020 Nov 16;21(11):48-57. Epub 2020 Oct 16.

Radiation Oncology Department, DIMES Università di Bologna - Ospedale S.Orsola Malpighi, Bologna, Italy.

Purpose: To assess the feasibility of automated stereotactic volumetric modulated arc therapy (SBRT-VMAT) planning using a simultaneous integrated boost (SIB) approach as a dose escalation strategy for SBRT in pancreatic cancer.

Methods: Twelve patients with pancreatic cancer were retrospectively replanned. Dose prescription was 30 Gy to the planning target volume (PTV) and was escalated up to 50 Gy to the boost target volume (BTV) using a SIB technique in 5 fractions. All plans were generated by Pinnacle Autoplanning using 6MV dual-arc VMAT technique for flattened (FF) and flattening filter-free beams (FFF). An overlap volume (OLV) between the PRV duodenum and the PTV was defined to correlate with the ability to boost the BTV. Dosimetric metrics for BTV and PTV coverage, maximal doses for serial OARs, integral dose, conformation numbers, and dose contrast indexes were used to analyze the dosimetric results. Dose accuracy was validated using the PTW Octavius-4D phantom together with the 1500 2D-array. Differences between FF and FFF plans were quantified using the Wilcoxon matched-pair signed rank.

Results: Full prescription doses to the 95% of PTV and BTV can be delivered to patients with no OLV. BTV mean dose was >90% of the prescribed doses for all patients at all dose levels. Compared to FF plans, FFF plans showed significant reduced integral doses, larger number of MUs, and reduced beam-on-times up to 51% for the highest dose level. Despite plan complexity, pre-treatment verification reported a gamma pass-rate greater than the acceptance threshold of 95% for all FF and FFF plans for 3%-2 mm criteria.

Conclusions: The SIB-SBRT strategy with Autoplanning was dosimetrically feasible. Ablative doses up to 50 Gy in 5 fractions can be delivered to the BTV for almost all patients respecting all the normal tissue constraints. A prospective clinical trial based on SBRT strategy using SIB-VMAT technique with FFF beams seems to be justified.
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http://dx.doi.org/10.1002/acm2.13025DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7700933PMC
November 2020

Skin toxicity following radiotherapy in patients with breast carcinoma: is anthocyanin supplementation beneficial?

Clin Nutr 2021 04 6;40(4):2068-2077. Epub 2020 Oct 6.

Department of Epidemiology and Prevention, IRCCS Neuromed, Pozzilli, IS, Italy. Electronic address:

Background: The EU-supported ATHENA project stems from a previous study suggesting that moderate wine consumption reduced the side-effects of radiotherapy (RT) in breast cancer patients, an effect possibly due to non-alcoholic anthocyanin fractions of wine.

Objective: To evaluate the role of anthocyanins on RT skin side effects in breast cancer patients.

Methods: Randomized, controlled, double-blind clinical trial. Patients were assigned to an intensity modulated radiation therapy (IMRT) either for three or five weeks, then randomized to receive three times a day a water-soluble anthocyanin (125 mg)-rich extract of corn cob or a placebo. Supplementation started one week before till the end of RT. Skin characteristics were detected by a standardized, non-invasive Cutometer® dual-MPA580, providing quantitative indices of skin maximal distensibility (R0), elasticity (R2, R5, R7) and viscoelasticity (R6); a Mexameter® MX18 probe evaluated the skin erythema (Er) and melanin (M). Measures were performed before (T0), at the end of RT and of supplementation (T1), and 1, 6 and 12 months after RT (T2-T4). Acute and late skin toxicity were scored according to the RTOG/EORTG scale. Selected biomarkers were measured at T0 and T1.

Results: 193 patients previously assigned to 3- or 5-week RT schedules were randomized to either anthocyanin (97) or placebo (96) supplementation. RT induced changes in skin parameters: R0, R2, R5 and R7 decreased, while R6 increased; the changes in R0 and R6 continued in the same direction up to one year, while the others recovered towards basal values; Er and M peaked at T1 and T2, respectively, and returned to basal values at T4. Comparable skin changes were apparent in anthocyanin and placebo groups. A moderate RT-induced increase in total and HDL cholesterol and triglycerides was prevented by anthocyanins.

Conclusions: Anthocyanin supplementation did not prevent RT-induced local skin toxicity. The supplementation was well tolerated and safe.
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http://dx.doi.org/10.1016/j.clnu.2020.09.030DOI Listing
April 2021

Hypofractionated sequential radiotherapy boost: a promising strategy in inoperable locally advanced pancreatic cancer patients.

J Cancer Res Clin Oncol 2021 Mar 1;147(3):661-667. Epub 2020 Oct 1.

Università Cattolica del Sacro Cuore, Roma, Italy.

Purpose: To investigate the potential benefits of a hypofractionated radiotherapy boost (HRB) after chemotherapy (CT) and concomitant chemoradiotherapy (CRT) in locally advanced pancreatic cancer (LAPC) patients. Primary endpoints were early and late toxicity, local control (LC) and pain-free progression (PFP) assessment. Two-years overall survival (OS), metastasis-free survival (MFS) and disease-free survival (DFS) were secondary endpoints.

Materials And Methods: Patients (pts) affected by unresectable non-metastatic LAPC, previously treated with CT and CRT in upfront or sandwich setting, were selected for sequential HRB. Total prescribed dose was 30 Gy in 5 fractions (fr) to pancreatic primary lesion. Dose de-escalation was allowed in case of failure in respecting organs at risk constraints. Early and late toxicity were assessed according to CTCAE v.4.0 classification. The Kersh-Hazra scale was used for pain assessment. Local Control, PFP, MFS and DFS were calculated from the date of HRB to the date of relapse or the date of the last follow-up.

Results: Thirty-one pts affected by unresectable, non-metastatic LAPC were consecutively enrolled from November 2004 to October 2019. All pts completed the planned HRB. Total delivered dose varied according to duodenal dose constraint: 20 Gy in 5 fr (N: 6; 19.4%), 20 Gy in 4 fr (N: 5; 16.2%), 25 Gy in 5 fr (N: 18; 58.0%) and 30 Gy in 6 fr (N: 2; 6.4%). Early and late toxicity were assessed in all pts: no Grade 3 or 4 acute gastrointestinal toxicity and no late gastrointestinal complications occurred. Median LC was 19 months (range 1-156) and 1- and 2-year PFP were 85% and 62.7%, respectively (median 28 months; range 2-139). According to the Kersh-Hazra scale, four pts had a Grade 3 and four pts had a Grade 1 abdominal pain before HRB. At the last follow-up only 3/31 pts had residual Grade 1 abdominal pain.Median MFS was 18 months (range 1-139). The 2-year OS after HRB was 57.4%, while 2-year OS from diagnosis was 77.3%.

Conclusion: Treatment intensification with hypofractionated radiotherapy boost is well tolerated in pts affected by unresectable LAPC previously treated with CT/CRT. Its rates of local and pain control are encouraging, supporting its introduction in clinical practice. Timing, schedule and dose of HRB need to be further investigated to personalize therapy and optimize clinical advantages.
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http://dx.doi.org/10.1007/s00432-020-03411-7DOI Listing
March 2021

Timing to achieve the highest rate of pCR after preoperative radiochemotherapy in rectal cancer: a pooled analysis of 3085 patients from 7 randomized trials.

Radiother Oncol 2021 01 20;154:154-160. Epub 2020 Sep 20.

UOC Radioterapia Oncologica, Dipartimento di Diagnostica per Immagini, Radioterapia Oncologica ed Ematologia, Fondazione Policlinico Universitario "A. Gemelli" IRCCS - Roma, Italy; Istituto di Radiologia, Università Cattolica del Sacro Cuore - Roma, Italy.

Purpose: Optimal timing of surgery after neoadjuvant chemoradiotherapy (Nad-CRT) is still controversial in locally advanced rectal cancer (LARC). The primary goal of this study was to determine the best surgical interval (SI) to achieve the highest rate of pathological complete response (pCR) and secondly to evaluate the effect on survival outcomes according to the SI.

Patients And Methods: Patients data were extracted from the international randomized trials: Accord12/0405, EORTC22921, FFCD9203, CAO/ARO/AIO-94, CAO-ARO-AIO-04, INTERACT and TROG01.04. Inclusion criteria were: age≥ 18, cT3-T4 and cN0-2, no clinical evidence of distant metastasis at diagnosis, Nad-CRT followed by surgery. Pearson's Chi-squared test with Yates' continuity correction for categorical variables, the Mann-Whitney test for continuous variables, Mann-Kendall test, Kaplan-Meier curves with log-rank test, univariate and multivariate logistic regression model was used for data analysis.

Results: 3085 patients met the inclusion criteria. Overall, the pCR rate was 14% at a median SI of 6 weeks (range 1-31). The cumulative pCR rate increased significantly when SI lengthened, with 95% of pCR events within 10 weeks from Nad-CRT. At univariate and multivariate logistic regression analysis, lengthening of SI (p< 0.01), radiotherapy dose (p< 0.01), and the addition of oxaliplatin to Nad-CRT (p< 0.01) had a favorable impact on pCR. Furthermore, lengthening of SI was not impact on local recurrences, distance metastases, and overall survival.

Conclusion: This pooled analysis suggests that the best time to achieve pCR in LARC is at 10 weeks, considering that the lengthening of SI is not detrimental concerning survival outcomes.
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http://dx.doi.org/10.1016/j.radonc.2020.09.026DOI Listing
January 2021

Stereotactic body radiotherapy vs conventionally fractionated chemoradiation in locally advanced pancreatic cancer: A multicenter case-control study (PAULA-1).

Cancer Med 2020 11 10;9(21):7879-7887. Epub 2020 Sep 10.

Radiation Oncology Center, Department of Experimental, Diagnostic and Specialty Medicine - DIMES, University of Bologna, S. Orsola-Malpighi Hospital, Bologna, Italy.

Conventionally fractionated chemoradiation (CRT) or chemotherapy (CHT) are considered as standard options in locally advanced pancreatic cancer (LAPC) while stereotactic body radiotherapy (SBRT) is an emerging treatment in this setting. The aim of this study was to compare two cohorts of LAPC patients treated with SBRT ± CHT vs CRT ± CHT in terms of local control (LC), distant metastases-free survival (DMFS), progression-free survival (PFS), overall survival (OS), and toxicity. Eighty patients were included. Patients in the two cohorts were matched according to: age ≤/>65 years, tumor diameter (two cut-offs:
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http://dx.doi.org/10.1002/cam4.3330DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7643643PMC
November 2020

Radiotherapy of Prostate Carcinoma: A Comparison of the Predictive Role of EAU NCCN Risk Stratification Systems.

Anticancer Res 2020 Aug;40(8):4413-4418

Radiation Oncology Center, Department of Experimental, Diagnostic and Specialty Medicine - DIMES, University of Bologna, S. Orsola-Malpighi Hospital, Bologna, Italy.

Background/aim: To compare the predictive efficacy of National Comprehensive Cancer Network (NCCN) and European Association of Urology (EAU) risk stratification systems in radiotherapy of prostate cancer.

Patients And Methods: One-thousand-nine-hundred-nine patients treated with definitive (1,074), adjuvant (381), and salvage radiotherapy (454) were analysed.

Results: Both systems significantly predicted biochemical-relapse-free-survival, metastasis-free-survival, and disease-free-survival, while only the NCCN system correlated with local-control in the definitive radiotherapy group. In the adjuvant setting, both systems failed to predict all outcomes. In the salvage setting, only the NCCN system significantly predicted biochemical-relapse-free-survival, metastasis-free-survival and disease-free-survival.

Conclusion: This analysis confirms the efficacy of both systems in definitive radiotherapy and suggests the utility of the NCCN also in salvage radiotherapy.
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http://dx.doi.org/10.21873/anticanres.14446DOI Listing
August 2020

Personalizing vulvar cancer workflow in COVID-19 era: a proposal from Vul.Can MDT.

J Cancer Res Clin Oncol 2020 Oct 12;146(10):2535-2545. Epub 2020 Jul 12.

UOC Ginecologia Oncologica, Dipartimento Scienze della Salute della Donna, del Bambino e di Sanità Pubblica, Fondazione Policlinico Universitario A. Gemelli IRCCS, Largo A. Gemelli 8, 00168, Rome, Italy.

Introduction: Since the community spread of Coronavirus disease 2019 (COVID-19), the practice of oncologic care at our comprehensive cancer center has changed. Postponing cancer treatment without consideration of its implications could cost more lives than can be saved. In this special situation, we must continue to provide our cancer patients with the highest quality of medical services assuring the safety. This article provides general guidance on supporting curative treatment strategies in vulvar cancer patients.

Methods: At our institution, a vulvar cancer multidisciplinary team (Vul.Can MDT) of specialists is responsible for personalized treatment of this disease. The phase 2 period necessarily requires specific procedures for both outpatient and inpatient pathways and to provide strategies concerning the management of vulvar cancer patients even in case of an eventually concomitant SARS-CoV-2 infection. In brief, an accurate remote and in person triage must be provided routinely and patients submitted to specific diagnostic tests prior to every major treatment or procedure (surgery, RT, and CT) or in case of suspicion for COVID-19 syndrome. The decisional workflow for these women often old and frail, have been rapidly adjusted by our Vul.Can MDT to mitigate the potential risks of COVID-19.

Results: The team produced two types of recommendations concerning: (1) safety regulations of care pathways, patients and health care providers, (2) personalized treatment strategies. We present a protocol that can be applied in clinical practice: the flowcharts provided, include the modulation of treatment intensity designed for surgical procedures and radiation, stratified for FIGO stage of disease and intention.

Conclusion: We suggest that our proposals are applicable in this setting of patients, considering anyway current international recommendations and guidelines.
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http://dx.doi.org/10.1007/s00432-020-03312-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7354358PMC
October 2020

Optimized stereotactic volumetric modulated arc therapy as an alternative to brachytherapy for vaginal cuff boost. A dosimetric study.

Med Dosim 2020 Winter;45(4):352-358. Epub 2020 Jun 19.

Radiation Oncology Department, DIMES University of Bologna - S.Orsola Malpighi Hospital, Bologna, Italy.

We evaluate the role of stereotactic body radiotherapy using volumetric modulated arc therapy (VMAT) technique as an alternative to high-dose rate brachytherapy (HDR-BT) in the treatment of vaginal cuff in postoperative endometrial cancer. CT scans of 8 patients were used in this study. The clinical target volume (CTV) was defined as the 0.5 cm tissue around the applicator (then subtracting the applicator). Total dose was 30Gy delivered in 5 fractions. In HDR-BT, dose was prescribed at a distance of 0.5 cm from the surface applicator. For VMAT irradiation, a planning target volume (PTV) was obtained from CTV by an expansion of 3 mm. Two VMAT plans were generated using a full arc rotation. The first plan was optimized with an anatomy-based optimization module (PO-VMAT) using a 1mm multileaf collimator beam margin to enhance dose heterogeneity and dose fallout outside the target. The second plan was generated with a full-inverse planning module (FI-VMAT). Conformity (CI100, CI50, CI25), gradient (GI) indexes, and integral doses were calculated. To account for various dose heterogeneity distributions we calculated the equivalent uniform dose (EUD) using the Niemerko model. A Kruskal-Wallis analysis of variance followed by Dunn's-type multiple comparisons was performed. Dose distributions were more heterogeneous with HDR-BT: Dmean was 144.2% of prescription dose for CTV in HDR-BT and 118.5 and 108.6% for PTV in PO-VMAT and FI-VMAT, respectively. The mean values of EUD for CTV were 136.9%, 130.0 %, and 111.0% of prescription dose in HDR-BT, PO-VMAT, and FI-VMAT plans, respectively. GI indexes were 2.81, 3.41, and 4.14 for HDR-BT, PO-VMAT, and FI-VMAT, respectively. Near-maximal doses (D0.1cc) for rectum and bladder were significantly higher in HDR-BT plans compared to PO-VMAT and FI-VMAT plans (rectum: 131.2% vs112.8% vs 112.0%, respectively; bladder: 129.2% vs 108.7%, and 109.8%, respectively). PO-VMAT plans were able to mimic the HDR-BT dose distribution, showing a successful capability of highly conformal dose distribution, EUD values similar to HDR-BT, and steep dose-gradient outside PTV, then providing a reasonable alternative to brachytherapy.
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http://dx.doi.org/10.1016/j.meddos.2020.05.003DOI Listing
June 2020

Stereobody radiotherapy for nodal recurrences in oligometastatic patients: a pooled analysis from two phase I clinical trials.

Clin Exp Metastasis 2020 08 3;37(4):519-529. Epub 2020 Jun 3.

Radiotherapy Unit, Gemelli Molise Hospital, Campobasso, Italy.

Stereotactic body radiotherapy (SBRT) has been shown to achieve high local control rates in limited metastatic burden of disease. Few papers reported on the efficacy of SBRT in nodal oligometastases. The primary aim of the present paper was to analyze the treatment outcome in this setting. Data from DESTROY-1 and SRS-DESTROY-2 phase I clinical trials were reviewed and analyzed. These trials were based on a 5 fractions and a single fraction regimens, respectively. End-points of this analysis were toxicity rates, overall response rate (ORR), and local control (LC). Patients treated between December 2003 and January 2018, with any metastatic site, and primary tumor type and histology were included. One hundred-eighty-one patients (M/F: 93/88; median age: 67, range 37-88) treated with SBRT on 253 nodal lesions were analyzed. Initially, the used technique was 3D-CRT (20.9%), while subsequently treatments were delivered by VMAT (79.1%). The total dose to the PTV ranged between 12 Gy/single fraction to 50 Gy/5 fractions. With a median follow-up of 21 months (2-124), no grade 3 acute or late toxicity was recorded. ORR based on functional imaging was 92.5% with a complete response rate of 76%. Two- and three-year actuarial LC were 81.6% and 76.0%, respectively. Our large pooled analysis confirms the efficacy and safety of SBRT/SRS in patients with nodal metastases and identifies clinical and treatment variables able to predict complete response and local control rate.
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http://dx.doi.org/10.1007/s10585-020-10039-xDOI Listing
August 2020
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