Publications by authors named "Stefano Pergolizzi"

89 Publications

OLIGO-AIRO: a national survey on the role of radiation oncologist in the management of OLIGO-metastatic patients on the behalf of AIRO.

Med Oncol 2021 Mar 24;38(5):48. Epub 2021 Mar 24.

Advanced Radiation Oncology Department, IRCCS Sacro Cuore Don Calabria Hospital, Cancer Care Center, via Don Sempreboni 5, 37034, Negrar, Verona, Italy.

In the last years, several evidences demonstrated the role of stereotactic body radiotherapy (SBRT) in the oligometastatic disease and the possibility to increase survival in selected patients. In 2020 the study group "biology and treatment of the oligometastatic disease" of the Italian Association of Radiotherapy and Clinical Oncology (AIRO) conducted a survey evaluating the attitude of physicians in treating the oligometastatic disease and the definition of it. An electronic questionnaire was administered online to the society members. 105 questionnaires were returned. 78% responders considered as oligometastatic a disease with ≤ 5 metastases. The majority of the responders (77%) treated > 50 patients in the last year, and 89% responders agreed in considering every oligometastatic tumor susceptible to local treatments. Regarding the clinical management of the oligometastatic disease, the majority of the responders (66%) suggested an interdisciplinary discussion. When choosing a treatment option for fit patients with a single oligometastatic focus, 52% of the responders agreed in proposing only SBRT. In the case of unfit patients with a single oligometastatic lesion the agreement was in favor of the SBRT alone (89%). In the oligoprogressive setting, 41% responders opted to continue the current systemic treatment and to add SBRT, while in the case of oligoresidual disease, 70% responders was in favor of adding SBRT and continuing the current systemic treatment. In conclusions, the survey illustrated the current agreement and prescribing attitude for oligometastatic patients in Italy. The non-homogenous agreement in some clinical scenarios suggest the need of more robust evidence.
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http://dx.doi.org/10.1007/s12032-021-01493-yDOI Listing
March 2021

Dual-energy CT quantification of fractional extracellular space in cirrhotic patients: comparison between early and delayed equilibrium phases and correlation with oesophageal varices.

Radiol Med 2021 Mar 14. Epub 2021 Mar 14.

Section of Radiological Sciences, Department of Biomedical Sciences and Morphological and Functional Imaging, University of Messina, Policlinico "G. Martino", Via Consolare Valeria 1, 98100, Messina, Italy.

Objective: Fractional extracellular space has been validated as a marker of hepatic fibrotic in cirrhotic patients at CT-scan as well as on dual-energy CT, which takes advantage from iodine uptake. Since no consensus still exists between equilibrium phases performed at 3 or 10 min, the first aim of this work is to evaluate performances at the two different time points. Moreover, correlation between fractional extracellular space and oesophageal varices, directly related to liver fibrosis, has been assessed.

Materials And Methods: Dual-Energy equilibrium phases at 3 and 10 min were performed within a follow-up CT-protocol scan in cirrhotic patients. Oesophageal varices were endoscopically assessed according to their size. At the two different time points, correlation between iodine density of the right and left liver lobes and correlation between the fractional extracellular space values were assessed. Correlation between fractional extracellular space and endoscopic grade of oesophageal varices was calculated.

Results: No statistical differences were found between the iodine density values from the two liver lobes at the two time points (p = 0.8 at 3'; p = 0.5 at 10'). No statistical difference about fractional extracellular space estimation was found between the two time points (p = 0.17). Correlation between fractional extracellular space values and oesophageal varices was moderate (ρ = 0.45, IC 0.08-0.71, p < 0.05).

Conclusion: Fractional extracellular space assessed on dual-energy CT at equilibrium phases with different timing was substantially similar. The moderate correlation found between fractional extracellular space and endoscopic grade of oesophageal varices confirms that CT-scan is not currently reliable as endoscopy.
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http://dx.doi.org/10.1007/s11547-021-01341-zDOI Listing
March 2021

18F-FDG PET/CT Imaging of Prostate Stromal Tumor of Uncertain Malignant Potential.

Clin Nucl Med 2021 04;46(4):348-349

From the Department of Biomedical and Dental Sciences and Morpho-Functional Imaging, University of Messina, Messina, Italy.

Abstract: A 79-year-old man presented with dysuria and increased serum prostate-specific antigen level (21 ng/mL). MRI revealed bulky prostate enlargement but was inconclusive in revealing neoplastic lesions. Nevertheless, because of high clinical suspicion for neoplasm, transrectal biopsy revealed stromal tumor of uncertain malignant potential mixed with foci of low-grade primitive prostate stromal sarcoma. 18F-FDG PET/CT showed high FDG uptake consistent with neoplasm in the lower part of the hypertrophic prostate gland and focal areas of elevated FDG uptake, consistent with metastases in the spine, ribs, and femur.
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http://dx.doi.org/10.1097/RLU.0000000000003509DOI Listing
April 2021

Curative Radiotherapy in Elderly Patients With Muscle Invasive Bladder Cancer: The Prognostic Role of Sarcopenia.

In Vivo 2021 Jan-Feb;35(1):571-578

Radiation Oncology Unit - Papardo Hospital, Messina, Italy.

Background/aim: To evaluate the impact of sarcopenia in muscle invasive bladder cancer (MIBC) elderly patients submitted to curative radiotherapy.

Patients And Methods: Patients received radiotherapy between 2013 and 2018, and the skeletal muscle index was calculated to classify them as sarcopenic or non-sarcopenic. Primary endpoints were overall survival (OS), cancer specific survival (CSS), 90-day mortality and toxicity.

Results: A total of 28 patients with a median age of 85 years met our inclusion criteria and 8 of them were sarcopenic. With a median prescribed dose of 61 Gy and a median follow-up of 24.5 months, OS rates in the sarcopenic and non-sarcopenic groups were 100% and 84.4% at 3 months, 57.1% and 56.6% at 12 months, 38.1% and 50.3% at 24 months and 38.1% and 33.5% at 48 months, respectively; the CSS rates were 100% and 94.1% at 3 months and 68.6% and 88.2% at 12, 24 and 48 months, respectively. The actuarial 90-day mortality rate was 17.9% for the whole cohort, and 20% and 12.5% for the non-sarcopenic and sarcopenic groups, respectively. The radio-induced toxicity was similar in both groups.

Conclusion: Sarcopenia cannot be considered a negative prognostic factor for MIBC elderly patients treated with external beam radiotherapy. Irradiation is therefore a feasible and effective choice for these patients, especially if unfit for surgery.
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http://dx.doi.org/10.21873/invivo.12293DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7880729PMC
October 2020

Stereotactic Radiotherapy for the Treatment of Patients With Oligo-progressive Metastatic Renal Cell Carcinoma Receiving Vascular Endothelial Growth Factor Receptor Tyrosine Kinase Inhibitor: Data From the Real World.

Anticancer Res 2020 Dec;40(12):7037-7043

Medical Oncology Unit, Policlinico, University of Palermo, Palermo, Italy.

Aim: This retrospective observational study evaluated the role of hypo-fractionated stereotactic radiotherapy (SRT) in patients with oligo-progressive metastatic renal cell carcinoma (mRCC) treated with first-line oral tyrosine kinase inhibitors (TKI). Data on local control, delay of further progression, and safety are reported.

Patients And Methods: Between January 2010 and December 2016, 28 patients with mRCC who showed oligo-progressive disease while receiving first-line pazopanib were treated with hypofractionated SRT to progressive metastatic sites to delay the change of systemic therapy. First and second progression-free survival (PFS-1 and PFS-2) were recorded, as well as objective response and toxicity.

Results: After pazopanib therapy, nine partial remissions (32%), 12 stable disease (43%) and seven progressions (25%) were recorded. The median time to progression from first-line pazopanib until oligo-progression was 9.45 months (PFS-1 range=2-30 months). Seventeen patients (61%) showed progression at pre-existing tumor sites, and 11 patients (39%) showed the appearance of new metastases. Progression-free survival after radiation therapy was 4.55 months (PFS-2 range=1-11 months). PFS-1 plus PFS-2 was 14.0 months (range=3-41 months). Severe grade 3-4 toxicities were seen only occasionally.

Conclusion: Patients with oligo-progressive mRCC treated with first-line pazopanib may benefit from hypo-fractionated high-dose SRT at progressing sites achieving a further increase in median progression-free survival. Further studies and prospective validation are required to establish if this minimally invasive approach may have a positive impact on overall survival and reported outcomes.
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http://dx.doi.org/10.21873/anticanres.14730DOI Listing
December 2020

Image-Guided Multisession Radiosurgery of Skull Base Meningiomas.

Cancers (Basel) 2020 Nov 29;12(12). Epub 2020 Nov 29.

Unit of Neurosurgery, IRCCS Istituto delle Scienze Neurologiche di Bologna, 40139 Bologna, Italy.

Background: The efficacy of single-session stereotactic radiosurgery (sSRS) for the treatment of intracranial meningioma is widely recognized. However, sSRS is not always feasible in cases of large tumors and those lying close to critically radiation-sensitive structures. When surgery is not recommended, multi-session stereotactic radiosurgery (mSRS) can be applied. Even so, the efficacy and best treatment schedule of mSRS are not yet established. The aim of this study is to validate the role of mSRS in the treatment of skull base meningiomas.

Methods: A retrospective analysis of patients with skull base meningiomas treated with mSRS (two to five fractions) at the University of Messina, Italy, from 2008 to 2018, was conducted.

Results: 156 patients met the inclusion criteria. The median follow-up period was 36.2 ± 29.3 months. Progression-free survival at 2-, 5-, and 10- years was 95%, 90%, and 80.8%, respectively. There were no new visual or motor deficits, nor cranial nerves impairments, excluding trigeminal neuralgia, which was reported by 5.7% of patients. One patient reported carotid occlusion and one developed brain edema.

Conclusion: Multisession radiosurgery is an effective approach for skull base meningiomas. The long-term control is comparable to that obtained with conventionally-fractionated radiotherapy, while the toxicity rate is very limited.
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http://dx.doi.org/10.3390/cancers12123569DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7761100PMC
November 2020

Vaginal Mucosal Melanoma: a Complete Remission after Immunotherapy and '0-7-21' Radiotherapy Regimen (24 Gy/3 fractions/21 days).

Folia Med (Plovdiv) 2020 Sep;62(3):605-609

University of Messina, Messina, Italy.

We present the case of a patient with vaginal mucosal melanoma who underwent complete remission after immunotherapy and '0-7-21' radiotherapy regimen (24 Gy/3 fractions/21 days). An 80-year-old woman had a biopsy of a voluminous vaginal lesion and received a histological diagnosis of melanoma with angiomatoid aspects. The patient underwent immunotherapy with pembrolizumab 2 mg/kg every 3 weeks and was sent to our attention for planning radiotherapy as the extent of the lesion did not make it susceptible to surgery.Considering the concomitant administration of pembrolizumab, we chose to treat this patient with a modulated intensity radiation therapy technique delivering a hypofractionated dose of 24 Gy in 3 fractions delivered on days 0, 7, and 21. We observed a complete clinical remission of the melanoma 12 months after radiotherapy and she has been alive for 18 months with no clinical signs of local recurrence.
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http://dx.doi.org/10.3897/folmed.62.e49926DOI Listing
September 2020

High-dose Radiotherapy for Oligo-progressive NSCLC Receiving EGFR Tyrosine Kinase Inhibitors: Real World Data.

In Vivo 2020 Jul-Aug;34(4):2009-2014

Medical Oncology and Supportive Care Unit, La Maddalena Cancer Center, Palermo, Italy

Background/aim: Local ablative treatments for oligo-progressive, EGFR mutated non-small cell lung cancer (mut-NCSLC) may improve long-term disease control and survival. We analyzed the efficacy of hypo-fractionated, high-dose radiation therapy (HDRT), in association with prolonged EGFR tyrosine kinase inhibitors (TKI) in oligo-progressive, EGFR mutant-NSCLC.

Patients And Methods: Progression-free survival-1 (PFS-1, date from initiation of TKI therapy until oligo-progression or death), and progression-free survival-2 (PFS-2, date of focal progression until further progression or death) were evaluated.

Results: Thirty-six patients were analyzed. The median PFS 1 was 12.5 months. HDHRT consisted of intensity-modulated RT and stereotactic RT in 23 (64%) and 13 (36%) patients respectively. The median PFS 2 was 6.3 months. Overall survival was 38.7 months.

Conclusion: Hypo-fractionated HDRT plus TKI therapy, is associated with a significant prolongation of disease control (overall PFS: 18.8 months), with manageable side effects. These real-world data support the use of local ablative approaches in oligo-progressive EGFR mut-NSCLC.
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http://dx.doi.org/10.21873/invivo.11999DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7439904PMC
April 2020

Factors affecting outcome in frameless non-isocentric stereotactic radiosurgery for trigeminal neuralgia: a multicentric cohort study.

Radiat Oncol 2020 May 22;15(1):115. Epub 2020 May 22.

Brain Radiosurgery, CDI Centro Diagnostico Italiano, Milan, Italy.

Background: Stereotactic radiosurgery (SRS) is an effective treatment for trigeminal neuralgia (TN). Nevertheless, a proportion of patients will experience recurrence and treatment-related sensory disturbances. In order to evaluate the predictors of efficacy and safety of image-guided non-isocentric radiosurgery, we analyzed the impact of trigeminal nerve volume and the nerve dose/volume relationship, together with relevant clinical characteristics.

Methods: Two-hundred and ninety-six procedures were performed on 262 patients at three centers. In 17 patients the TN was secondary to multiple sclerosis (MS). Trigeminal pain and sensory disturbances were classified according to the Barrow Neurological Institute (BNI) scale. Pain-free-intervals were investigated using Kaplan Meier analyses. Univariate and multivariate Cox regression analyses were performed to identify predictors.

Results: The median follow-up period was 38 months, median maximal dose 72.4 Gy, median target nerve volume 25 mm, and median prescription dose 60 Gy. Pain control rate (BNI I-III) at 6, 12, 24, 36, 48, and 60 months were 96.8, 90.9, 84.2, 81.4, 74.2, and 71.2%, respectively. Overall, 18% of patients developed sensory disturbances. Patients with volume ≥ 30 mm were more likely to maintain pain relief (p = 0.031), and low integral dose (< 1.4 mJ) tended to be associated with more pain recurrence than intermediate (1.4-2.7 mJ) or high integral dose (> 2.7 mJ; low vs. intermediate: log-rank test, χ = 5.02, p = 0.019; low vs. high: log-rank test, χ = 6.026, p = 0.014). MS, integral dose, and mean dose were the factors associated with pain recurrence, while re-irradiation and MS were predictors for sensory disturbance in the multivariate analysis.

Conclusions: The dose to nerve volume ratio is predictive of pain recurrence in TN, and re-irradiation has a major impact on the development of sensory disturbances after non-isocentric SRS. Interestingly, the integral dose may differ significantly in treatments using apparently similar dose and volume constraints.
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http://dx.doi.org/10.1186/s13014-020-01535-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7243318PMC
May 2020

COVID-19 outbreak and cancer radiotherapy disruption in Italy: Survey endorsed by the Italian Association of Radiotherapy and Clinical Oncology (AIRO).

Radiother Oncol 2020 08 12;149:89-93. Epub 2020 May 12.

Radiation Oncology Division, Oncology and Speciality Medicine Department, San Camillo-Forlanini Hospital, Roma, Italy; President of AIRO (Italian Association of Radiotherapy and Clinical Oncology), Italy.

Italy experienced one of the world's deadliest COVID-19 outbreaks and healthcare systems had to instantly reorganise activity. The Italian Radiation Oncology Departments adapted numerous solutions to minimize the disruptions. Information technologies, treatment prioritization and implementation of hypofractionation and protection procedures allowed balancing between cancer patient care and patient/healthcare workers safety.
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http://dx.doi.org/10.1016/j.radonc.2020.04.061DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7215158PMC
August 2020

Simultaneous Integrated Boost Radiotherapy in Unresectable Stage IV (M0) Head and Neck Squamous Cell Cancer Patients: Daily Clinical Practice.

Rep Pract Oncol Radiother 2020 May-Jun;25(3):399-404. Epub 2020 Apr 13.

Unit of Radiation Oncology - University Hospital "G. Martino", Via Consolare Valeria, 1 - 98125 Messina, Italy.

Aim: To evaluate clinical outcome in locally-advanced stage IV (M0) head and neck cancer patients treated using intensity-modulated radiotherapy (IMRT) with simultaneous integrated boost (SIB) in daily clinical practice.

Background: Despite SIB-IMRT has been reported as a feasible and effective advanced head and neck cancer treatment, there are few data about its concurrent use with systemic therapies.

Material And Methods: We reviewed 41 staged IV (M0) head and neck cancer patients treated in two radiotherapy units in the city of Messina (Italy) during the last six years, using intensity modulated techniques-SIB. 22/41 patients had concomitant chemotherapy or cetuximab. Acute and late toxicities, objective response (OR) rate, local control (LC) and overall survival (OS) have been evaluated.

Results: 37/41 patients received the planned doses of radiotherapy, 2 patients died during the therapy. The major acute regional toxicities were skin reaction and mucositis. A case of mandibular osteoradionecrosis was recorded. At completion of treatment, OR was evaluated in 38 patients: 32/38 patients (84.2%) had complete (55.3%) and partial (28.9%) response. The 1- and 5-year LC rates were 73.4% and 69.73%, respectively. The 1-, 3-, and 5-year OS rates were 85.93%, 51.49% and 44.14%, respectively. No statistically significant differences in outcomes have been observed in patients treated with radiotherapy alone vs. irradiation concomitant to chemo/biotherapy. The median OS was 45 months.

Conclusion: SIB-IMRT is safeand can be used with concomitant chemotherapy/biotherapy in real-life daily clinical practice. SIB-IMRT alone is a valid alternative in patients unfit for systemic therapies.
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http://dx.doi.org/10.1016/j.rpor.2020.04.006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7190747PMC
April 2020

Stereotactic Body Radiation Therapy With Simultaneous Integrated Boost in Patients With Spinal Metastases.

Technol Cancer Res Treat 2020 Jan-Dec;19:1533033820904447

Radiation Oncology Unit, Department of Biomedical, Dental Sciences and of Morphological and Functional Images, University of Messina, Italy.

Stereotactic body radiation therapy in patients with spine metastases maximizes local tumor control and preserves neurologic function. A novel approach could be the use of stereotactic body radiation therapy with simultaneous integrated boost delivering modality. The aim of the present study is to report our experience in the treatment of spine metastases using a frameless radiosurgery system delivering stereotactic body radiation therapy-simultaneous integrated boost technique. The primary endpoints were the pain control and the time to local progression; the secondary ones were the overall survival and toxicity. A total of 20 patients with spine metastases and 22 metastatic sites were treated in our center with stereotactic body radiation therapy-simultaneous integrated boost between December 2007 and July 2018. Stereotactic body radiation therapy-simultaneous integrated boost treatments were delivered doses of 8 to 10 Gy in 1 fraction to isodose line of 50%. The median follow-up was 35 months (range: 12-110). The median time to local progression for all patients was not reached and the actuarial 1-, 2-, and 3-years local free progression rate was 86.36%. In 17 of 20 patients, a complete pain remission was observed and 3 of 20 patients had a partial pain remission (complete pain remission + partial pain remission: 100%). The median overall survival was 38 months (range 12-83). None of the patients experienced neither radiation adverse events (grade 1-4) nor reported pain flair reaction. None of the patients included in our series experienced vertebral compression fracture. Spine radiosurgery with stereotactic body radiation therapy-simultaneous integrated boost is safe. The use of this modality in spine metastases patients provides an excellent local control.
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http://dx.doi.org/10.1177/1533033820904447DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7225842PMC
September 2020

Stereotactic body radiation therapy and radiofrequency ablation for the treatment of liver metastases: How and when?

Rep Pract Oncol Radiother 2020 May-Jun;25(3):299-306. Epub 2020 Feb 21.

Radiation Oncology Unit - Department of Biomedical, Dental Science and Morphological and Functional Images, University of Messina, Messina, Italy.

Limited liver metastases represent a clinical challenge. Surgical approach is the most frequently reported treatment option, however, some patients are not eligible for surgical interventions. Relatively recent technologic advances have permitted the safe use of ablative techniques employed in the cure of hepatic metastases. Among these, radiofrequency ablation (RFA) and stereotactic body radiotherapy (SBRT) have emerged as valid treatments in a significant proportion of patients with intrahepatic oligometastatic disease. This review offers an up-to-date of current available literature on this issue focusing on the use and outcomes of RFA and SBRT, according to the PICO (Population, Intervention, Comparison and Outcomes) criteria.
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http://dx.doi.org/10.1016/j.rpor.2020.02.010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7078501PMC
February 2020

Collision and composition tumors: rare conditions to remember in differential diagnosis of adrenal glands lesions.

Quant Imaging Med Surg 2019 Nov;9(11):1902-1903

Section of Radiological Sciences, Department of Biomedical Sciences and Morphological and Functional Imaging, University of Messina, Messina, Italy.

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http://dx.doi.org/10.21037/qims.2019.05.11DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6902145PMC
November 2019

Effect of granulocyte colony-stimulating factor on bone marrow: evaluation by intravoxel incoherent motion and dynamic contrast-enhanced magnetic resonance imaging.

Radiol Med 2020 Mar 10;125(3):280-287. Epub 2019 Dec 10.

Department of Biomedical and Dental Sciences and of Morphofunctional Imaging, University of Messina, Messina, Italy.

Objective: To report our experience with the use of intravoxel incoherent motion (IVIM) magnetic resonance imaging (MRI) and dynamic contrast-enhanced (DCE)-MRI in bone marrow before and after administration of granulocyte colony-stimulating factor (GCSF). Moreover, a small series of patients with bone metastases from breast cancer have been evaluated by IVIM DW-MRI and DCE-MRI before and after GCSF administration.

Materials And Methods: We studied with IVIM-MRI and DCE-MRI 14 patients with rectal or uterine cervix cancer studied before and 4-18 days after administration of GCSF; the second MR examination was obtained after three chemotherapy courses. IVIM perfusion fraction (f), pseudo-diffusion coefficient (D*), true diffusion coefficient (D) and apparent diffusion coefficient (ADC) as well area under the curve at 60 s (AUC60) were calculated for bone marrow before and after GCSF administration. Moreover, two different IVIM parametric maps (i.e., ADC and ADC) were generated by selecting two different intervals of b values (0-1000 and 0-80, respectively). Furthermore, four patients affected by pelvic bone metastases from breast adenocarcinoma who received GCSF administration were also qualitatively evaluated for evidence of lesions on ADC maps, ADC maps and DCE-MRI.

Results: ADC, D, D*, f and AUC60 values were significantly higher in hyperplastic bone marrow than in untreated bone marrow (p values < 0.0001, < 0.0001, < 0.001, < 0.001, < 0.0001, respectively). All bone metastases were clearly differentiable from hyperplastic bone marrow on ADC maps, but not on ADC maps and DCE-MRI.

Conclusion: MR functional imaging techniques, such as DW-, IVIM DW- and DCE-MRI are effective tools in assessing the response of bone marrow to the administration of growth factors. Although an overlap between signal of hyperplastic bone marrow and lytic bone metastases can occur on ADC maps and DCE-MRI, evaluation of ADCl maps by IVIM DW-MRI could permit to differentiate hyperplastic bone marrow from lytic bone metastases. Further studies are needed to confirm our data.
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http://dx.doi.org/10.1007/s11547-019-01115-8DOI Listing
March 2020

Adenoid cystic carcinoma of trachea: long-term disease control after endoscopic surgery and radiotherapy.

Future Oncol 2020 Jun 3;16(16s):33-39. Epub 2019 Dec 3.

UOC Radioterapia AOOE Cannizzaro di Catania 95100, Italy.

Adenoid cystic carcinoma is a rare tumor of head and neck region and its development in the thoracic region is even less frequent. This implies the absence of guidelines for therapeutic management and a consequent case-by-case approach. The role of radiotherapy is not yet clearly defined, but intensity-modulated radiotherapy allows for improved organ-at-risk sparing. We have collected the cases of four patients treated at our institutions by the means of intensity-modulated radiotherapy, after endoscopic resection. Patients treated achieved long-term disease control of about 5 years, with a minimal acute toxicity. Longer follow-up is needed to drain conclusion on the impact of this treatment on overall survival.
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http://dx.doi.org/10.2217/fon-2018-0685DOI Listing
June 2020

Normofractionated stereotactic radiotherapy versus CyberKnife-based hypofractionation in skull base meningioma: a German and Italian pooled cohort analysis.

Radiat Oncol 2019 Nov 12;14(1):201. Epub 2019 Nov 12.

Department of Radiation Oncology, Charité Universitätsmedizin Berlin, Berlin, Germany.

Background: This retrospective German and Italian multicenter analysis aimed to compare the role of normofractionated stereotactic radiotherapy (nFSRT) to CyberKnife-based hypofractionated stereotactic radiotherapy (CK-hFSRT) for skull base meningiomas.

Methods: Overall, 341 patients across three centers were treated with either nFSRT or CK-hFSRT for skull base meningioma. Treatment planning was based on computed tomography (CT) and magnetic resonance imaging (MRI) following institutional guidelines. Most nFSRT patients received 33 × 1.8 Gy, and most CK-hFSRT patients received 5 × 5 Gy. The median follow-up time was 36 months (range: 1-232 months).

Results: In the CK-hFSRT group, the 1-, 3-, and 10-year local control (LC) rates were 99.4, 96.8, and 80.3%, respectively. In the nFSRT group, the 1-, 3-, and 10-year LC rates were 100, 99, and 79.1%, respectively. There were no significant differences in LC rates between the nFSRT and CK-hFSRT groups (p = 0.56, hazard ratio = 0.76, 95% confidence interval, 0.3-1.9). In the CK-hFSRT group, only one case (0.49%) of severe toxicity (CTCAE 4.0 ≥ 3) was observed. In the nFSRT group, three cases (2.1%) of grade III toxicity were observed.

Conclusion: This analysis of pooled data from three centers showed excellent LC and low side effect rates for patients treated with CK-hFSRT or nFSRT. The efficacy, safety, and convenience of a shortened treatment period provide a compelling case for the use of CK-hFSRT in patients with moderate size skull base meningioma and provided that OAR constraints are met.
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http://dx.doi.org/10.1186/s13014-019-1397-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6852939PMC
November 2019

Pain REduction with bone metastases STereotactic radiotherapy (PREST): A phase III randomized multicentric trial.

Trials 2019 Oct 28;20(1):609. Epub 2019 Oct 28.

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

Background: Palliative antalgic treatments represent an issue for clinical management and a challenge for scientific research. Radiotherapy (RT) plays a central role. Techniques such as stereotactic body radiotherapy (SBRT) were largely investigated in several phase 2 studies with good symptom response, becoming widely adopted. However, evidence from randomized, direct comparison of RT and SBRT is still lacking.

Methods/design: The PREST trial was designed as an interventional study without medicinal treatment. It is a phase 3, open-label, multicentric trial randomized 1:1. Inclusion criteria include painful spinal bone metastases presenting with a pain level > 4 (or > 1 if being treated with an analgesic) on the Numeric Rating Scale (NRS); expected intermediate/high prognosis (greater than 6 months) according to the Mizumoto prognostic score; low spine instability neoplastic score (SINS) sores (< 7); magnetic resonance imaging (MRI) assessment of the bulky lesion. Patients will be assigned to either standard conventional radiotherapy involving 4 Gy × 5 fractions (fx) to the whole involved vertebra or SBRT by intensity modulated radiotherapy with simultaneous integrated boost (IMRT-SIB) involving 7 Gy × 3 fx to the whole involved vertebra + 10 Gy × 3 fx on the macroscopic lesion (gross tumor volume (GTV)). In the experimental arm, the GTV will be contoured by registration with baseline MRI.

Discussion: The primary endpoint is overall pain reduction, defined in terms of variation between baseline and 3-month evaluation; pain will be measured using the NRS. Secondary endpoints include pain control duration; retreatment rates (after a minimum interval of 1 month); local control assessed with RECIST criteria; symptom progression free survival; progression-free survival; overall survival; and quality of life (at 0, 30, and 90 days). Accrual of 330 lesions is planned. The experimental arm is expected to have an improvement in overall pain response rates of 15% with respect to the standard arm (60% according to Chow et al. (Int J Radiat Oncol Biol Phys. 82(5):1730-7, 2012)).

Trial Registration: ClinicalTrials.gov, NCT03597984 . Registered on July 2018.
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http://dx.doi.org/10.1186/s13063-019-3676-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6816218PMC
October 2019

Modern Treatment of Brain Arteriovenous Malformations Using Preoperative Planning Based on Navigated Transcranial Magnetic Stimulation: A Revisitation of the Concept of Eloquence.

World Neurosurg 2019 Nov 24;131:371-384. Epub 2019 Jun 24.

Division of Neurosurgery, BIOMORF Department, University of Messina, Messina, Italy.

Background: Navigated transcranial magnetic stimulation (nTMS) provides a reliable identification of "eloquent" cortical brain areas. Moreover, it can be used for diffusion tensor imaging fiber tracking of eloquent subcortical tracts. We describe the use of nTMS-based cortical mapping and diffusion tensor imaging fiber tracking for defining the "eloquence" of areas surrounding brain arteriovenous malformations (BAVMs), aiming to improve patient stratification and treatment.

Methods: We collected data of BAVMs suspected to be in eloquent areas treated between 2017 and 2019, and submitted to nTMS-based reconstruction of motor, language, and visual pathways for the definition of the eloquence of the surrounding brain areas. We describe the nTMS-based approach and analyze its impact on patient stratification and allocation to treatment in comparison with the standard assessment of eloquence based on anatomical landmarks.

Results: Ten patients were included in the study. Preliminarily, 9 BAVMs were suspected to be located in an eloquent area. After nTMS-based mapping, only 5 BAVMs were confirmed to be close to eloquent structures, thus leading to a change of the score for eloquence and of the final BAVMs grading in 60% of patients. Treatment was customized according to nTMS information, and no cases of neurological worsening were observed. Radiological obliteration was complete in 7 cases microsurgically treated, and accounted for about 70% in the remaining 3 patients 1 year after radiosurgical treatment.

Conclusions: The nTMS-based information allows an accurate stratification and allocation of patients with BAVMs to the most effective treatment according to a modern, customized, neurophysiological identification of the adjacent eloquent brain networks.
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http://dx.doi.org/10.1016/j.wneu.2019.06.119DOI Listing
November 2019

Multisession radiosurgery for perioptic meningiomas: medium-to-long term results from a CyberKnife cooperative study.

J Neurooncol 2019 Jul 22;143(3):597-604. Epub 2019 May 22.

Radiotherapy Unit, Dept. of Neurosurgery, Fondazione IRCCS Istituto Neurologico C. Besta, Via Celoria 11, 20133, Milan, Italy.

Purpose: Most recent literature has confirmed the efficacy of single-session radiosurgery (sRS) in the treatment of intracranial meningioma. Unfortunately, sRS is not always applicable due to large tumor volume and the proximity of the tumor to critical structures. When sRS is not recommended, multi-session radiosurgery (mRS) can be the solution. The best treatment schedule for mRS, however, is not well established. The aim of the present retrospective study is to validate the effectiveness of one approach, 25 Gy delivered in 5 fractions in 5 consecutive days, to treat skull base meningiomas.

Methods: This is a retrospective multicenter study. Patients with an anterior or a medium skull base meningioma that could not be treated by sRS due to large volume or proximity to the anterior optic pathways (AOPs) underwent 5-fraction mRS. Only patients with at least 36 months follow-up were included in the analysis. Local control and visual outcomes were investigated.

Results: One-hundred-sixty-seven patients were included in the analysis. One-hundred-one patients underwent RS as a primary indication and 66 were treated after a previous surgery. The median follow-up period was 51 months (range 36-129 months). Progression-free survival at 3, 5 and 8 years were, respectively, 98%, 94% and 90%. Excluding the progressive disease patients, the visual worsening rate was 3.7%. The 42% of the patients with a pre-treatment visual deficit experienced improvement in vision.

Conclusion: 25 Gy delivered in 5 fractions is an effective modality for meningiomas that are near the AOP or are too large to be treated by sRS. The treatment schedule controlled the tumors while sparing visual function.
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http://dx.doi.org/10.1007/s11060-019-03196-xDOI Listing
July 2019

Consensus statements on ablative radiotherapy for oligometastatic prostate cancer: A position paper of Italian Association of Radiotherapy and Clinical Oncology (AIRO).

Crit Rev Oncol Hematol 2019 Jun 1;138:24-28. Epub 2019 Apr 1.

Department of Radiation Oncology, University and Spedali Civili Hospital, Brescia, Italy.

Oligometastatic prostate cancer comprises a wide spectrum of conditions, ranging from de novo oligometastatic cancer at diagnosis to oligometastatic castration-resistant disease, which are distinct entities in terms of biology and prognosis. In order to clarify and standardize the clinical role of ablative radiotherapy in oligometastatic prostate cancer, the Italian Association of Radiotherapy and Clinical Oncology (AIRO) formed an expert panel to review the current literature and develop a formal consensus. Oligometastatic prostate cancer was defined as the presence of up to three metastatic lesions involving bones or nodes outside pelvis. Thereafter, four clinical scenarios were explored: metastatic castration-sensitive disease at diagnosis and after primary treatment, and metastatic castration-resistant disease at diagnosis and during treatment, where the role of ablative radiotherapy was defined either in conjunction with systemic therapy or as the only treatment in selected cases. This paper summarizes the current literature about these issues and the proposed recommendations.
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http://dx.doi.org/10.1016/j.critrevonc.2019.03.014DOI Listing
June 2019

DCE and DSC perfusion MRI diagnostic accuracy in the follow-up of primary and metastatic intra-axial brain tumors treated by radiosurgery with cyberknife.

Radiat Oncol 2019 Apr 15;14(1):65. Epub 2019 Apr 15.

Neuroradiology Unit, Department of Biomedical, Dental Science and Morphological and Functional Images, University of Messina, Messina, Italy.

Background: The differential diagnosis between radiation necrosis, tumor recurrence and tumor progression is crucial for the evaluation of treatment response and treatment planning. The appearance of treatment-induced tissue necrosis on conventional Magnetic Resonance Imaging (MRI) is similar to brain tumor recurrence and it could be difficult to differentiate the two entities on follow-up MRI examinations. Dynamic Susceptibility Contrast-enhanced (DSC) and Dynamic Contrast-Enhanced (DCE) are MRI perfusion techniques that use an exogenous, intravascular, non-diffusible gadolinium-based contrast agent. The aim of this study was to compare the diagnostic accuracy of DSC and DCE perfusion MRI in the differential diagnosis between radiation necrosis and tumor recurrence, in the follow-up of primary and metastatic intra-axial brain tumors after Stereotactic RadioSurgery (SRS) performed with CyberKnife.

Methods: A total of 72 enhancing lesions (57 brain metastases and 15 primary brain tumors) were analyzed with DCE and DSC, by means of MRI acquisition performed by 1,5 Tesla MR scanner. The statistical relationship between the diagnosis of tumor recurrence or radiation necrosis, decided according to clinicoradiologically criteria, rCBV and Ktrans was evaluated by the point-biserial correlation coefficient respectively.

Results: The statistical analysis showed a correlation between the diagnosis of radiation necrosis or recurrent tumor with Ktrans (rpb = 0.54, p < 0.001) and with rCBV (rpb = 0.37, p = 0.002). The ROC analysis of rCBV values demonstrated a good classification ability in differentiating radiation necrosis from tumour recurrence as well as the Ktrans. The optimal cut-off value for rCBV was k = 1.23 with 0.88 of sensitivity and 0.75 of specificity while for Ktrans was k = 28.76 with 0.89 of sensitivity and 0.97 of specificity.

Conclusions: MRI perfusion techniques, particularly DCE, help in the differential diagnosis by tumor recurrence and radiation necrosis during the follow-up after radiosurgery.
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http://dx.doi.org/10.1186/s13014-019-1271-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6466652PMC
April 2019

Posterior perineal hernia long after surgery: Our experience.

J Med Imaging Radiat Oncol 2019 06 29;63(3):356-357. Epub 2019 Mar 29.

Department of Biomedical Sciences and Morphological and Functional Imaging, University of Messina, Messina, Italy.

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http://dx.doi.org/10.1111/1754-9485.12883DOI Listing
June 2019

Clinical Evaluation of Low-Molecular-Weight Hyaluronic Acid-Based Treatment on Onset of Acute Side Effects in Women Receiving Adjuvant Radiotherapy after Cervical Surgery: A Randomized Clinical Trial.

Oncol Res Treat 2019 12;42(4):217-223. Epub 2019 Mar 12.

Operative Unit of Radiation Oncology, Department of Image Diagnostics, University Hospital "G. Martino", Messina, Italy.

Background: Radiotherapy treatment for cervical cancer (CC) often induces side effects, including inflammation, dryness, dyspareunia. Considering its key role in the healing process, hyaluronic acid (HA) could be useful for the completion of radiotherapy.

Objectives: The aim of this work was to evaluate the ability of HA to reduce the onset of side effects due to radiotherapy.

Materials And Methods: In total, 180 women undergoing radiotherapy were randomized into two arms: controls and those treated with vaginal suppositories containing low-molecular-weight HA from day 1 of radiotherapy. The study lasted 5 weeks and was characterized by three visits: at baseline (T0), 15 days later (T1), and at the end of the radiotherapy cycle (T2). The onset of side effects, pain, safety, efficacy, acceptability of treatment, and compliance to the therapy were evaluated.

Results: Patients in the control arm reported the onset and worsening of all symptoms with a moderate or severe grade at T2, whereas in the treatment arm almost 90% of patients reported the absence of symptoms or a mild grade. All patients in the treatment arm referred a lower intensity of pain on a visual analog scale compared with the control arm at T2 (6.85 ± 0.94 vs. 1.88 ± 1.02).

Conclusions: HA was able to help vaginal mucosa healing during radiotherapy in patients with CC.
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http://dx.doi.org/10.1159/000496036DOI Listing
September 2019

Trends in combined radio-chemotherapy for locally advanced rectal cancer: a survey among radiation oncology centers of Sicily region on behalf of AIRO.

Radiol Med 2019 Jul 26;124(7):671-681. Epub 2019 Feb 26.

Dipartimento di Scienze Biomediche, Odontoiatriche e delle Immagini Morfologiche e Funzionali, Università degli Studi di Messina, Messina, Italy.

Aim: To conduct a survey among Sicilian centers of radiation oncology belonging to Associazione Italiana di Radioterapia ed Oncologia Clinica (AIRO), to record the different methods of integration of radio-chemotherapy both in neoadjuvant and adjuvant settings, to evaluate surgical procedures in relation to the sphincter preservation and to report the different toxicity profiles of the treatment strategies.

Methods: A questionnaire was sent at the end of 2017 to all the radiation oncology centers of Sicily region in order to collect the data from individual centers and the treatment characteristics retrospectively over the previous 5 years, from 2012 to 2016. The required data were collected from 13 centers out of 17 which, in relation to the single catchment areas, correspond to approximately 85% of the Sicilian population. The requested data concerned the type of integrated treatment (neoadjuvant vs adjuvant vs radical), combination with chemotherapy (induction, concomitant, adjuvant), type of surgical intervention (sphincter-saving vs abdomino-perineal resection), disease stage, schedule and radiotherapy technique adopted, as well as toxicity detected over the treatment period.

Results: A total of 784 pts (M/F: 509/275) were treated between 2012 and 2016, with a median age of 67 years (range 25-92). The majority of patients was treated in the neoadjuvant phase (62% of the total) compared to the adjuvant phase (31%) and to those treated radically (7%). Twenty-five percent of patients did not receive combination chemotherapy mainly for cardiovascular problems. Chemotherapy used concomitantly to radiotherapy was single-agent capecitabine (73% of patients) or 5-fluorouracil (27%). The use of chemotherapy alone before concomitant treatment is more common for patients treated in the adjuvant phase (64% of this subgroup), while 14% of patients treated in the neoadjuvant phase received induction chemotherapy before the concomitant phase; in both cases of chemotherapy alone, the majority of patients (91%) received oxaliplatin-based protocols (FOLFOX/XELOX/CAPOX). Few patients (3%) received chemotherapy alone after the concomitant phase. Information on the surgical treatment received is available for 88% of the sample. Of these, 93% received a surgical treatment. The overall rate of sphincter-saving surgery (anterior resection) was 72%, but the contribution of neoadjuvant treatment allowed to reach a rate of 83% in this subgroup (against 65% found in the subgroup of patients treated in adjuvant phase). Traditional radiotherapy schedule (45-50 Gy in 25-28 fractions) was used in 90% of patients, of which an intensified treatment in neoadjuvant phase (45 Gy + boost of 9-10 Gy) was used in 11% of patients. A short-course regimen (25 Gy in 5 fraction) in neoadjuvant setting was opted rarely (7%). Three-dimensional conformal technique was preferred over intensity-modulated ones (73% vs 27%). Toxicity was mainly of grade I-II CTCAE (skin 23%, gastrointestinal 39%, genitourinary 14%) compared to grade III (gastrointestinal 4%, genitourinary and hematological < 1%). Interestingly, the toxicity rates were significantly higher in the adjuvant group compared to the neoadjuvant (GI: 58% vs 31%, GU: 21% vs 10%).

Conclusion: The present survey shows that in the Sicily region integrated therapies for rectal cancer have allowed a neoadjuvant approach in the majority of patients, thus resulting in a greater use of sphincter conservative surgery. The toxicity has also been reported to be significantly less in this treatment setting.
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http://dx.doi.org/10.1007/s11547-019-01007-xDOI Listing
July 2019

Combination of novel systemic agents and radiotherapy for solid tumors - Part II: An AIRO (Italian association of radiotherapy and clinical oncology) overview focused on treatment toxicity.

Crit Rev Oncol Hematol 2019 Feb 30;134:104-119. Epub 2018 Nov 30.

Department of Radiation Oncology, Ospedale Policlinico San Martino and University of Genoa, Genoa, Italy.

Clinical development and use of novel systemic agents in combination with radiotherapy (RT) is at nowadays most advanced in the field of treatment of solid tumors. Although for many of these substances preclinical studies provide sufficient evidences on their principal capability to enhance radiation effects, the majority of them have not been investigated in even phase I clinical trials for safety in the context of RT. In clinical practice, unexpected acute and late side effects may emerge especially in combination with RT. As a matter of fact, despite combined modality treatment holds potential for enhancing the therapeutic ratio, some concerns are raised from the lack of high-quality clinical data to guide the care of patients who are treated with novel compounds in conjunction with RT. The aim of this review is to provide, from a radio-oncological point of view, an overview of the most advanced combined treatment concepts for solid tumors focusing on treatment toxicity.
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http://dx.doi.org/10.1016/j.critrevonc.2018.11.006DOI Listing
February 2019