Alessio Giuseppe Morganti

Multimodal treatment of resectable pancreatic ductal adenocarcinoma

After a timing preoperative staging, treatment of resectable pancreatic adenocarcinoma (PDAC) includes surgery and adjuvant therapies, the former representing the initial therapeutic option and the latter aiming to reduce the incidence of both distant metastases (chemotherapy) and locoregional failures (chemoradiotherapy). Herein, we provide a critical overview on the role of multimodal treatment in PDAC and on new opportunities related to current more active poli-chemotherapy regimens, targeted therapies, and the more recent immunotherapy approaches. Moreover, an analysis of pathological markers and clinical features able to help clinicians in the selection of the best therapeutic strategy will be discussed. Lastly, the role of neoadjuvant treatment of initially resectable disease will be considered mostly in patients whose malignancy shows morphological but not clinical or biological criteria of resectability. Depending on the results of these investigational studies, today a multidisciplinary approach can offer the best address therapy for these patients.

Volumetric modulated arc therapy for treatment of solid tumors: current insights

Aim This article discusses the current use of volumetric modulated arc therapy (VMAT) techniques in clinical practice and reviews the available data from clinical outcome studies in different clinical settings. An overview of available literature about clinical outcomes with VMAT stereotactic/radiosurgical treatment is also reported. Materials and methods All published manuscripts reporting the use of VMAT in a clinical setting from 2009 to November 2016 were identified. The search was carried out in December 2016 using the National Library of Medicine (PubMed/Medline). The following words were searched: “volumetric arc therapy”[All Fields] OR “vmat”[All Fields] OR “rapidarc”[All Fields], AND “radiotherapy”[All Fields] AND “Clinical Trial”[All Fields]. Results Overall, 37 studies (21 prospective and 16 retrospective) fulfilling inclusion criteria and thus included in the review evaluated 2,029 patients treated with VMAT; of these patients, ~30.8% had genitourinary (GU) tumors (81% prostate, 19% endometrial), 26.2% head-and-neck cancer (H&NC), 13.9% oligometastases, 11.2% had anorectal cancer, 10.6% thoracic neoplasms (81% breast, 19% lung), and 7.0% brain metastases (BMs). Six different clinical scenarios for VMAT use were identified: 1) BMs, 2) H&NC, 3) thoracic neoplasms, 4) GU cancer, 5) anorectal tumor, and 6) stereotactic body radiation therapy (SBRT) performed by VMAT technique in the oligometastatic patient setting. Conclusion The literature addressing the clinical appropriateness of VMAT is scarce. Current literature suggests that VMAT, especially when used as simultaneous integrated boost or SBRT strategy, is an effective safe modality for all cancer types.

Preoperative Chemoradiation With VMAT-SIB in Rectal Cancer: A Phase II Study

Purpose The aim of this study was to investigate the efficacy and toxicity of volumetric modulated arc therapy (VMAT)–simultaneous integrated boost (SIB) in preoperative combined treatment of locally advanced rectal cancer. Methods Radiation therapy was performed using the VMAT‐SIB technique. The dose to mesorectum and pelvic lymph nodes was 45 Gy (1.8 Gy/fraction). A concomitant boost was delivered on GTV + 2‐cm margin with a total dose of 57.5 Gy (2.3 Gy/fraction). The following concomitant chemotherapy was administered: capecitabine (825 mg/m2 twice daily, 5 days per week) and oxaliplatin (130 mg/m2 on days 1, 17, and 35). Efficacy was evaluated in terms of complete pathological response (pCR). Acute toxicities were evaluated according to Common Terminology Criteria for Adverse Events version 3.0 criteria. Results A total of 18 patients (7 women; median age 62 years; clinical stage: 4 local recurrences, 6 cT4, 5 cT3, 3 cT2, 2 cN0, 7 cN1, 9 cN2) were enrolled. Sixteen patients underwent surgical resection (9 low anterior resection, 6 abdominal perineal amputations; 1 transanal excision) and 2 patients did not undergo surgery for early metastatic progression or death from acute pulmonary edema. R0 resection was achieved in all patients who underwent surgery. Overall, 4 patients had a pCR and 7 patients only a microscopic residual of disease (pT0‐Tmic: 11/18 = 61.1%; 95% CI, 36.2‐86.1). Acute grade ≥ 3 toxicity was as follows: 1 case of leukopenia, 1 skin toxicity, 1 genitourinary toxicity, and 5 gastrointestinal toxicities, with an overall incidence of 8 (44.4%) of 18 patients. One‐, 3‐, and 5‐year cumulative local control was 100%, 68.6%, and 68.6%, respectively. One‐, 3‐, and 5‐year cumulative disease‐free survival was 88.9%, 66.7%, and 66.7%, respectively. One‐, 3‐, and 5‐year cumulative overall survival was 85%, 63.8%, and 63.8%, respectively. Conclusion The regimen used in this study showed excellent results in terms of pathologic responses. However, despite the use of the VMAT technique, more than one‐third of patients had severe acute toxicity. Micro‐Abstract The efficacy and toxicity of volumetric modulated arc therapy (VMAT)–simultaneous integrated boost (SIB) in preoperative combined treatment of locally advanced rectal cancer were investigated. VMAT‐SIB with concomitant capecitabine and oxaliplatin showed a good efficacy: 11 (61.1%) of 18 patients had complete or near complete response. Severe acute toxicity was not negligible and reported in 44.4% patients.

Time to surgery and pathologic complete response after neoadjuvant chemoradiation in rectal cancer: A population study on 2094 patients

Highlights • A large population based analysis to evaluate pathologic response according to time of surgery.• LARC patients were treated with modern techniques of radiotherapy and surgery.• The rate of pCR increased according to time interval from 12.6% to 31.1%.• The pCR increasing was 1.5% (about 0.2%/die) per each week of waiting.• Lengthening the interval (>13 weeks) significantly improved the pathological response.

Radiological differential diagnosis between fibrosis and recurrence after stereotactic body radiation therapy (SBRT) in early stage non-small cell lung cancer (NSCLC)

BackgroundnParenchymal changes after stereotactic body radiation therapy (SBRT) make differential diagnosis between treatment outcomes and disease recurrence often difficult. The purpose of our study was to identify the radiographic features detectable at computed tomography (CT) scan [high-risk features (HRFs)] that allow enough specificity and sensitivity for early detection of recurrence.nnnMethodsnWe retrospectively evaluated patients who underwent SBRT for inoperable early stage non-small cell lung cancer (NSCLC). The median delivered dose performed was 50 Gy in 5 fractions prescribed to 80% isodose. All patients underwent chest CT scan before SBRT and at 3, 6, 12, 18, 24 months after, and then annually. Each CT scan was evaluated and benign and HRFs were recorded. 18F-fluorodeoxyglucose-CT was not used routinely.nnnResultsnForty-five patients were included (34 males, 11 females; median age: 77 years; stage IA: 77.8%, stage IB: 22.2%; median follow-up: 21.7 months). Two year and actuarial local control was 77%. HRFs were identified in 20 patients. The most significant predictor of relapse was an enlarging opacity at 12 months (P<0.001) with 84.6% sensitivity and 71.8% specificity. The presence of ≥2 HRFs demonstrated a high sensibility (92.3%) and specificity (71.9%) (P<0.0001).nnnConclusionsnDetection of HRFs is predictive of relapse with a sensibility that increases with the number of HRFs observed. This observation may allow to better define the diagnostic follow algorithm up suggesting to performing further exams only in patients with >2 HRFs.

Predictive factors of late-onset rectal mucosal changes after radiotherapy of prostate cancer

BACKGROUND/AIMnThe Vienna Rectoscopy Score (VRS; from 0, absence of rectal mucosal changes, to 5) assessed 1 year after radiotherapy is a surrogate end-point of late rectal toxicity. The aim of this study was to investigate the association between treatment-related factors and 1-year VRS.nnnPATIENTS AND METHODSnWe performed a retrospective analysis of prospectively collected data. Patients with prostate adenocarcinoma treated with definitive or postoperative radiotherapy (RT) underwent endoscopy 1 year after RT. Relationships between VRS of 2 or more and treatment parameters were investigated by univariate and multivariate logistic analyses.nnnRESULTSnOne hundred and ninety-five patients (mean age=69 years; range=43-81 years) were considered eligible for the study. At univariate analysis, patients treated with hypofractionation plus radiosurgery boost (p<0.001) and an equivalent dose in 2 Gy per fraction (EQD2) (α/β=3) ≥75 Gy (p<0.001) was associated with a significantly higher incidence of VRS ≥2 after 1 year of follow-up. At multivariate analysis, radiosurgery boost was an independent risk factor for developing rectal mucosal lesions (VRS ≥2), yielding an odds ratio (OR) of 4.14 (95% confidence interval (CI)=1.2-13.8), while pelvic surgery was inversely associated with VRS ≥2 (OR=0.39; 95% CI=0.17-0.94).nnnCONCLUSIONnHypofractionation followed by radiosurgery boost significantly increased the risk of developing late-onset rectal mucosal changes. Therefore, special care and preventative treatment strategies are needed when using radiosurgery boost after hypofractionated RT.

Radiotherapy for the Primary Tumor in Patients with Metastatic Rectal Cancer

Patients with metastatic rectal cancer (mRC) have a poor prognosis and suffer from several symptoms like bleeding, pain, and obstruction. Radiation therapy (RT) has been used both for palliation and improvement of overall survival (OS) in potentially curable patients. However, treatment in this setting is debated and a recent literature review included only studies published before 2000. Therefore, an analysis of literature was performed including only studies published in recent years (2010–2016) to better evaluate the effect of modern RT in these patients.The analysis of nine reviewed studies (six retrospective and three phase II) showed that RT is able to achieve pain, bleeding, and obstruction response rate of 79, 87, and 78%, respectively. Moreover, in patients receiving radio-chemo-surgical combined modality treatment, median survivals ranging between 30 and 38xa0months were recorded, with 5-year survival up to 55% of patients. RT was generally well tolerated with the most common reported side effect being diarrhea/proctitis.Further studies in this field are needed to establish the best therapeutic sequences, to define the optimal RT dose and fractionation, and to evaluate the clinical results in terms of quality of life (QoL).

Unusual case of spindle cell sarcoma metastases to right ventricle: a case report and a literature review

Cardiac metastases from sarcoma are uncommon. Due to their rarity there is not a standard of care. However, complete cardiac metastases resection is the best option but most of patients has widespread disease. In these patients palliative radiotherapy (RT) might improve symptoms and prevent further cardiac function decline. Here we present the case of a symptomatic 30-year-old woman with spindle cell sarcoma metastasis of right ventriculum and widespread disease. The patient received radiotherapy to the heart with palliative intent. Cardiac metastases represent a challenging clinic problem. Treatment should be individualized in a multidisciplinary setting, when possible surgery seems to be the best options. However, radiotherapy even in case of widespread disease can improve clinical control symptoms by reducing the mass effect.

A surgical multi-layer technique for pelvic reconstruction after total exenteration using a combination of pedicled omental flap, human acellular dermal matrix and autologous adipose derived cells

Highlights • A multi-layer technique for reconstruction after pelvic exenteration is proposed.• Human acellular dermal matrix used in reconstruction after total pelvic exenteration.• A reconstructive technique based on human dermis, omental flap and fat is proposed.

Complete pathological response after chemo-radiation in anaplastic thyroid cancer: A report of two cases

Giuseppe Zanirato Rambaldi, Fabio Monari, Michelangelo Fiorentino, Silvia Cammelli, Andrea Repaci, Nadia Cremonini, Ottavio Cavicchi, Umberto Caliceti, Eleonora Farina, Francesco Deodato, Francesca Di Fabio, Livio Presutti, Stefano Fanti, Giovanni P. Frezza and Alessio G. Morganti Radiation Oncology Unit, Department of Experimental, Diagnostic and Specialty Medicine – DIMES, University of Bologna, S. Orsola-Malpighi Hospital, Bologna; Italy; Pathology Unit, Department of Experimental, Diagnostic and Specialty Medicine – DIMES, University of Bologna, S. Orsola-Malpighi Hospital, Bologna, Italy; Endocrinology Unit, University of Bologna, S. Orsola-Malpighi Hospital, Bologna, Italy; Endocrinology Unit, Maggiore Hospital, Bologna, Italy; Otolaringology Unit, University of Bologna, S. Orsola-Malpighi Hospital, Bologna, Italy; Radiotherapy Unit, General Oncology Unit, Fondazione Giovanni Paolo II, Campobasso, Italy; Oncology Unit, University of Bologna, S. Orsola-Malpighi Hospital, Bologna, Italy; Otolaringology Unit, University of Modena, Modena, Italy; Nuclear Medicine Unit, Department of Experimental, Diagnostic and Specialty Medicine – DIMES, University of Bologna, S. Orsola-Malpighi Hospital, Bologna, Italy; Radiation Oncology Unit, Bellaria Hospital, Bologna, Italy