Fabio Monari

Yttrium-90 radioembolization for unresectable/recurrent intrahepatic cholangiocarcinoma: a survival, efficacy and safety study

Background:Intrahepatic cholangiocarcinoma (ICC) is a rapidly progressing malignancy; only a minority of the tumours can be resected and the palliative regimens have shown limited success. The aim of this study was to assess overall survival (OS), tumour response and the safety of radioembolization with yttrium-90 (90Y-TARE) in patients with unresectable/recurrent ICC.Methods:Survival was calculated from the date of the 90Y-TARE procedure. Target and overall Response Evaluation Criteria in Solid Tumors (RECIST) and modified RECIST (mRECIST) and European Association for the Study of the Liver (EASL)—measuring delayed-phase contrast enhancement—treatment responses were assessed at 3 months.Results:The overall median survival was 17.9 months (95% CI: 14.3–21.4 months). Significantly longer survival was obtained in naive patients as compared with patients in whom TARE was preceded by other treatments, including surgery (52 vs 16 months, P=0.009). Significantly prolonged OS was recorded for patients with a response based on mRECIST and the EASL criteria while RECIST responses were not found to be associated with survival. Treatment was well-tolerated, and no mortality was reported within 30 days.Conclusions:In unresectable ICC, 90Y-TARE is safe and offers a survival benefit in naive patients, as well as in responders.

Efficacy of radioembolization according to tumor morphology and portal vein thrombosis in intermediate–advanced hepatocellular carcinoma

PURPOSE We analyzed overall survival (OS) following radioembolization according to macroscopic growth pattern (nodular vs infiltrative) and vascular invasion in intermediate-advanced hepatocellular carcinoma (HCC). METHODS Between September 2005 and November 2013, 104 patients (50.0% portal vein thrombosis [PVT], 29.8% infiltrative morphology) were treated. RESULTS Median OS differed significantly between patients with segmental and lobar or main PVT (p = 0.031), but was 17 months in both those with patent vessels and segmental PVT. Median OS did not differ for infiltrative and nodular HCC. Median OS was prolonged in patients with a treatment response at 3 months (p = 0.023). Prior TACE was also a significant predictor of improved OS. CONCLUSION A further indication for radioembolization might be infiltrative HCC, since OS was similar to nodular types.

Management of metastatic castration-resistant prostate cancer: A focus on radium-223: Opinions and suggestions from an expert multidisciplinary panel

Radium-223, a calcium mimetic bone-seeking radionuclide that selectively targets bone metastases with alpha particles, is approved for the treatment of men with metastatic castration-resistant prostate cancer (mCRPC) and symptomatic bone metastases. In patients with mCRPC, treatment with radium-223 has been associated with survival benefit, regardless of prior docetaxel use, and also has a positive impact on symptomatic skeletal events and quality of life. Radium-223 is best suited for patients with symptomatic mCRPC and bone-predominant disease and no visceral metastases, and may lead to better outcomes when given early in the course of the disease. An expert multidisciplinary panel convened in Milan, Italy to review the current best-evidence literature on radium-223 and to convey their personal expertise with the use of radium-223 and identify possible strategies for best practice. This article summarizes the best available evidence for the use of radium-223, discusses the essential role of the multidisciplinary team in delivering effective treatment for mCRPC, clarifies pre- and post-treatment evaluation and monitoring, and outlines future scenarios for radium-223 in the treatment of men with MCRPC.

Pretherapeutic dosimetry in patients affected by metastatic thyroid cancer using 124I PET/CT sequential scans for 131I treatment planning.

Purpose This study evaluates the use of sequential 124I PET/CT for predicting absorbed doses to metastatic lesions in patients with differentiated thyroid cancer undergoing 131I therapy. Methods From July 2011 until July 2013, 30 patients with metastatic differentiated thyroid cancer were enrolled. Each participant underwent PET/CT at 4, 24, 48, and 72 hours with 74 MBq of 124I. Blood samples and whole-body exposure measurements were obtained to calculate blood and red marrow doses. Activity concentrations and lesion volumes obtained from PET/CT were used to evaluate tumor doses with medical internal radiation dose formalism and spheres modeling. Mean administered 131I therapeutic dose was 5994 MBq (range, 1953–11,455 MBq). Results 124I PET/CT demonstrated all lesions detected by posttherapy 131I whole-body scans. Mean dose rates for blood, red marrow, and lesions were as follows: 0.07 ± 0.02 mGy/MBq, 0.05 ± 0.02 mGy/MBq, and 46.5 ± 117 mGy/MBq, respectively. Despite the high level of thyroid-stimulating hormone and CT detectable lesions, 15 of 30 patients did not show any abnormal 124I uptake. Conclusions The quantitative value of 124I PET/CT allows simple and accurate evaluation of lesion dosimetry following medical internal radiation dose formalism. Negative 124I PET/CT predicts absence of iodine avidity, potentially allowing avoidance of therapeutically ineffective 131I administration.

Unusual Thyroid Carcinoma Metastases: a Case Series and Literature Review

The most common sites of metastatic differentiated thyroid cancer are the neck lymph nodes, while distant metastases typically involve the lungs, the bones, and less frequently the brain. Uncommon metastatic sites include the liver, adrenal gland, kidney, pancreas, and skin. The epidemiological aspects of thyroid metastases in rare sites are largely unknown and their identification could have a significant impact on patients management. A mini-series of unusual metastatic sites of thyroid carcinoma is proposed as a contribution to current knowledge on anatomopathological characteristics and clinical outcome. Of the six cases that were assessed, the metastases were the following: skin metastases (2), skin and pancreas metastases (1), renal metastasis (1), adrenal metastasis (1), and liver metastasis (1). In our experience, metastases in rare sites do not always represent a negative prognostic factor for disease outcome. In fact they can occur as single distant lesion and if surgically resectable, their treatment can also lead to local disease remission.

223Ra-chloride therapy in men with hormone-refractory prostate cancer and skeletal metastases: Real-world experience

Background: Radium-223 (223Ra) chloride, an alpha emitter, has been shown to improve overall survival (OS) and pain control, and to delay skeletal-related events, in patients with castration-resistant prostate cancer (CRPC) and bone metastases. Our retrospective observational study presents the first Italian experience on the efficacy and safety of 223Ra therapy in routine clinical practice. Methods: A total of 83 patients with metastatic CRPC were treated with 223Ra at 3 Italian centers between August 2013 and August 2016. 223Ra-chloride (55 kBq/kg) was administered every 4 weeks for a total of 6 cycles. Primary endpoints were OS and progression-free survival (PFS). Secondary endpoints included toxicity, pain evaluation using numeric rating scale (NRS), symptomatic skeletal-related events and biomarkers response. Results: Patients had a median age of 75 (range 53–89) years. The majority of men showed a Gleason score of 7, 8, or 9. Forty-one patients completed 6 treatment cycles; 33 stopped treatment before completing 6 cycles. Nine were still receiving therapy at the time of data collection. At the end of therapy, NRS pain scores significantly improved (p < .000001). OS was a mean of 10.1 months, while median OS had not been attained. According to Kaplan-Meier estimation, OS and PFS were 17.5 and 7.7 months, respectively. There was a significant correlation between OS and PFS with the number of 223Ra cycles; patients receiving all 6 cycles experienced the major benefit from the therapy. 223Ra was well-tolerated. Conclusions: 223Ra alpha therapy is an important therapeutic option for men with CRPC and symptomatic skeletal metastases.

Narrative medicine in metastatic prostate cancer reveals ways to improve patient awareness & quality of care

AIM To describe the journey of patients with metastatic castration-resistant prostate cancer (mCRPC) in treatment with radium-223. METHODS A multiperspective analysis was performed using narrative medicine in four Italian centers. RESULTS The substantial impact of mCRPC on quality of life through all phases of the disease was described. After an initial lack of awareness of the disease or denial of its effects, symptoms of pain, fatigue and side effects often led to sadness, fear and loneliness. The majority underwent radium-223 therapy positively, restoring their quality of life and routine activities. CONCLUSION Using narrative medicine, the importance of a patient-centered approach in the pathway of care for patients with mCRPC through all the stages of the disease was highlighted.

External beam radiotherapy in thyroid carcinoma: Clinical review and recommendations of the AIRO "Radioterapia Metabolica" Group

The therapeutic approach to thyroid carcinoma usually involves surgery as initial treatment. The use of external beam radiotherapy (EBRT) is limited to high-risk patients and depends on clinical stage and histologic type. Different behavior patterns and degrees of aggressiveness of thyroid carcinomas require different management for differentiated, medullary, and anaplastic carcinoma. However, the role of EBRT is an issue of debate. Most clinical studies are retrospective and based on single-institution experiences. In this article, we review the main literature and give recommendations for the use of EBRT in thyroid carcinoma on behalf of the “Radioterapia Metabolica” Group of the Italian Radiation Oncology Association.

18F-FDG Pet-Guided External Beam Radiotherapy in Iodine-Refractory Differentiated Thyroid Cancer: A Pilot Study

Introduction To evaluate the clinical response rate after a postoperative 18F-FDG PET/CT guided external beam radiotherapy (EBRT) in Iodine-refractory differentiated thyroid cancer. Material and Methods Patients with thyroid cancer locally recurrent after total thyroidectomy plus metabolic radiotherapy and treated with radical EBRT were included. Inclusion criteria were detectable thyroglobulin (Tg), negative postmetabolic radiotherapy whole body scintigraphy, and no surgical indications. The pretreatment 18F-FDG PET/CT resulted positive in all cases (loggia, lymph nodes, and lung). EBRT was delivered with IMRT-SIB technique. A 18F-FDG PET/CT revaluation and Tg dosage were performed 3 months after the treatment. Results Sixteen consecutive patients were included in this analysis (median follow-up: 6–44 months). Post-EBRT 18F-FDG PET/CT showed CR in 43.7%, PR in 31.2%, SD in 25.0% patients, and PD due to lung metastases in 12.5%. Overall response rate was 75.0% (CI 95%: 41.4–93.3%). Tg levels decreased in 75.0% with a median Δ of 68.0%. Two-year PFS and OS rates were 80.0% and 93.0%, respectively. Acute G3 toxicity occurred in 18.7% and late G2 toxicity in 12.5%. Conclusions   18F-FDG PET/CT was useful in target definition for radiotherapy planning, identifying positive areas not detected with 131I scintigraphy. IMRT based EBRT was feasible and our results encourage future prospective studies. This clinical trial is registered with ID: NCT03191643.

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