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Abstract Introduction Biliary tract cancers (BTC) are rare and aggressive neoplasms. The current management of locally advanced or unresectable BTC is primarily based on chemotherapy (CHT) alone, linked to a median overall survival (OS) of approximately 12 months. However, international guidelines still consider concurrent chemoradiation (CRT) as an alternative treatment option. This study aims to review the current evidence on “modern” CRT for primary or recurrent unresectable BTC. Materials and Methods A comprehensive search was conducted on PubMed, Scopus, and Cochrane Library to identify relevant papers. Prospective or retrospective trials reporting outcomes after concurrent CRT of unresectable non‐metastatic, primary, or recurrent BTC were included. Only English‐written papers published between January 2010 and June 2022 were considered. Results Seventeen papers, comprising a total of 1961 patients, were included in the analysis. Among them, 11 papers focused solely on patients with primary unresectable BTC, while two papers included patients with isolated local recurrences and four papers encompassed both settings. In terms of tumor location, 12 papers included patients with intrahepatic, extrahepatic, and hilar BTC, as well as gallbladder cancer. The median CRT dose delivered was 50.4 Gy (range: 45.0–72.6 Gy) using conventional fractionation. Concurrent CHT primarily consisted of 5‐Fluorouracil or Gemcitabine. The pooled rates of 1‐year progression‐free survival (PFS) and OS were 40.9% and 56.2%, respectively. The median 1‐ and 2‐year OS rates were 63.1% and 29.4%, respectively. Grade ≥3 acute gastrointestinal toxicity ranged from 5.6% to 22.2% (median: 10.9%), while grade ≥3 hematological toxicity ranged from 1.6% to 50.0% (median: 21.7%). Conclusion Concurrent CRT is a viable alternative to standard CHT in patients with locally advanced BTC, offering comparable OS and PFS rates, along with an acceptable toxicity profile. However, prospective trials are needed to validate and further explore these findings.

Abstract Background Cancer-induced bone pain (CIBP), caused by bone metastases, is a common complication of cancer and strongly impairs quality of life (QoL). External beam radiotherapy (EBRT) is the current standard of care for treatment of CIBP. However, approximately 45% of patients have no adequate pain response after EBRT. Magnetic resonance image-guided high-intensity focused ultrasound (MR-HIFU) may improve pain palliation in this patient population. The main objective of this trial was to compare MR-HIFU, EBRT, and MR-HIFU + EBRT for the palliative treatment of bone metastases. Methods/design The FURTHER trial is an international multicenter, three-armed randomized controlled trial. A total of 216 patients with painful bone metastases will be randomized in a 1:1:1 ratio to receive EBRT only, MR-HIFU only, or combined treatment with EBRT followed by MR-HIFU. During a follow-up period of 6 months, patients will be contacted at eight time points to retrieve information about their level of pain, QoL, and the occurrence of (serious) adverse events. The primary outcome of the trial is pain response at 14 days after start of treatment. Secondary outcomes include pain response at 14 days after trial enrolment, pain scores (daily until the 21st day and at 4, 6, 12 and 24 weeks), toxicity, adverse events, QoL, and survival. Cost-effectiveness and cost-utility analysis will be conducted. Discussion The FURTHER trial aims to evaluate the effectiveness and cost-effectiveness of MR-HIFU—alone or in combination with EBRT—compared to EBRT to relieve CIBP. The trial will be performed in six hospitals in four European countries, all of which are partners in the FURTHER consortium. Trial registration The FURTHER trial is registered under the Netherlands Trials Register number NL71303.041.19 and ClinicalTrials.gov registration number NCT04307914. Date of trial registration is 13–01-2020.

Abstract Previous trials showed the tolerability and efficacy of a palliative radiotherapy (RT) regimen (SHARON) based on the 4 fractions delivered in 2 days in different oncological settings. In order to identify possible predictors of symptomatic response, the purpose of this study is to perform a pooled analysis of previous trials. We analyzed the impact on symptomatic response of the following parameters: tumor site, histological type, performance status (ECOG), dominant symptom, and RT dose using the Chi-square test and Fisher’s exact test. One-hundred-eighty patients were analyzed. Median RT dose was 20 Gy (range: 14–20 Gy). The overall response rate was 88.8% (95% CI 83.3–92.7%) while pre- and post-treatment mean VAS was 5.3 (± 7.7) and 2.2 (± 2.2), respectively (p 7) pain (36.0% vs 14.3%; p = 0.028). This pooled analysis showed high efficacy of the SHARON regimen in the relief of several cancer-related symptoms. The markedly and significantly higher complete pain response rate, in patients with mild-moderate pain, suggests early referral to palliative RT for patients with cancer-related pain.

Sarcopenia (SP) is a syndrome characterized by age-associated loss of skeletal muscle mass and function. SP worsens both acute and late radiation-induced toxicity, prognosis, and quality of life. Myosteatosis is a pathological infiltration of muscle tissue by adipose tissue which often precedes SP and has a proven correlation with prognosis in cancer patients. Sarcopenic obesity is considered a “hidden form” of SP (due to large fat mass) and is independently related to higher mortality and worse complications after surgery and systemic treatments with worse prognostic impact compared to SP alone. The evaluation of SP is commonly based on CT images at the level of the middle of the third lumbar vertebra. On this scan, all muscle structures are contoured and then the outlined surface area is calculated. Several studies reported a negative impact of SP on overall survival in patients undergoing RT for tumors of the head and neck, esophagus, rectum, pancreas, cervix, and lung. Furthermore, several appetite-reducing side effects of RT, along with more complex radiation-induced mechanisms, can lead to SP through, but not limited to, reduced nutrition. In particular, in pediatric patients, total body irradiation was associated with the onset of SP and other changes in body composition leading to an increased risk of cardiometabolic morbidity in surviving adults. Finally, some preliminary studies showed the possibility of effectively treating SP and preventing the worsening of SP during RT. Future studies should be able to provide information on how to prevent and manage SP before, during, or after RT, in both adult and pediatric patients.

Background: The safe use of radiotherapy (RT) requires compliance with dose/volume constraints (DVCs) for organs at risk (OaRs). However, the available recommendations are sometimes conflicting and scattered across a number of different documents. Therefore, the aim of this work is to provide, in a single document, practical indications on DVCs for OaRs in external beam RT available in the literature. Material and Methods: A multidisciplinary team collected bibliographic information on the anatomical definition of OaRs, on the imaging methods needed for their definition, and on DVCs in general and in specific settings (curative RT of Hodgkin’s lymphomas, postoperative RT of breast tumors, curative RT of pediatric cancers, stereotactic ablative RT of ventricular arrythmia). The information provided in terms of DVCs was graded based on levels of evidence. Results: Over 650 papers/documents/websites were examined. The search results, together with the levels of evidence, are presented in tabular form. Conclusions: A working tool, based on collected guidelines on DVCs in different settings, is provided to help in daily clinical practice of RT departments. This could be a first step for further optimizations.

Introduction: Biliary tract cancers (BTC) are rare and aggressive neoplasms. The current management of locally advanced or unresectable BTC is primarily based on chemotherapy (CHT) alone, linked to a median overall survival (OS) of approximately 12 months. However, international guidelines still consider concurrent chemoradiation (CRT) as an alternative treatment option. This study aims to review the current evidence on "modern" CRT for primary or recurrent unresectable BTC. Materials and Methods: A comprehensive search was conducted on PubMed, Scopus, and Cochrane Library to identify relevant papers. Prospective or retrospective trials reporting outcomes after concurrent CRT of unresectable non‐metastatic, primary, or recurrent BTC were included. Only English‐written papers published between January 2010 and June 2022 were considered. Results: Seventeen papers, comprising a total of 1961 patients, were included in the analysis. Among them, 11 papers focused solely on patients with primary unresectable BTC, while two papers included patients with isolated local recurrences and four papers encompassed both settings. In terms of tumor location, 12 papers included patients with intrahepatic, extrahepatic, and hilar BTC, as well as gallbladder cancer. The median CRT dose delivered was 50.4 Gy (range: 45.0–72.6 Gy) using conventional fractionation. Concurrent CHT primarily consisted of 5‐Fluorouracil or Gemcitabine. The pooled rates of 1‐year progression‐free survival (PFS) and OS were 40.9% and 56.2%, respectively. The median 1‐ and 2‐year OS rates were 63.1% and 29.4%, respectively. Grade ≥3 acute gastrointestinal toxicity ranged from 5.6% to 22.2% (median: 10.9%), while grade ≥3 hematological toxicity ranged from 1.6% to 50.0% (median: 21.7%). Conclusion: Concurrent CRT is a viable alternative to standard CHT in patients with locally advanced BTC, offering comparable OS and PFS rates, along with an acceptable toxicity profile. However, prospective trials are needed to validate and further explore these findings. [ABSTRACT FROM AUTHOR]

This article from BJU International presents a case study of a 74-year-old patient with castration-resistant prostate cancer who underwent stereotactic body radiotherapy (SBRT) for 20 metastatic lesions. The patient had a complex treatment history involving various therapies before receiving SBRT, which served as a bridge therapy while awaiting 177Lu-PSMA-617 therapy. The SBRT treatment was delivered without reported side effects, resulting in a decrease in PSA levels and a partial or complete response at treated sites. The article discusses the efficacy and challenges of SBRT in treating multiple metastatic sites, highlighting the evolving landscape of prostate cancer therapy. [Extracted from the article]

Severe pain is frequent in patients with locally advanced pancreatic ductal adenocarcinoma (PDCA). Stereotactic body radiotherapy (SBRT) provides high local control rates in these patients. The aim of this review was to systematically analyze the available evidence on pain relief in patients with PDCA. We updated our previous systematic review through a search on PubMed of papers published from 1 January 2018 to 30 June 2021. Studies with full available text, published in English, and reporting pain relief after SBRT on PDCA were included in this analysis. Statistical analysis was carried out using the MEDCALC statistical software. All tests were two-sided. The I2 statistic was used to quantify statistical heterogeneity (high heterogeneity level: >50%). Nineteen papers were included in this updated literature review. None of them specifically aimed at assessing pain and/or quality of life. The rate of analgesics reduction or suspension ranged between 40.0 and 100.0% (median: 60.3%) in six studies. The pooled rate was 71.5% (95% CI, 61.6–80.0%), with high heterogeneity between studies (Q2 test: p < 0.0001; I2 = 83.8%). The rate of complete response of pain after SBRT ranged between 30.0 and 81.3% (median: 48.4%) in three studies. The pooled rate was 51.9% (95% CI, 39.3–64.3%), with high heterogeneity (Q2 test: p < 0.008; I2 = 79.1%). The rate of partial plus complete pain response ranged between 44.4 and 100% (median: 78.6%) in nine studies. The pooled rate was 78.3% (95% CI, 71.0–84.5%), with high heterogeneity (Q2 test: p < 0.0001; I2 = 79.4%). A linear regression with sensitivity analysis showed significantly improved overall pain response as the EQD2α/β:10 increases (p: 0.005). Eight papers did not report any side effect during and after SBRT. In three studies only transient acute effects were recorded. The results of the included studies showed high heterogeneity. However, SBRT of PDCA resulted reasonably effective in producing pain relief in these patients. Further studies are needed to assess the impact of SBRT in this setting based on Patient-Reported Outcomes.

Aldo Caporossi,1 Giovanni Alessio,2 Francesco Fasce,3 Giorgio Marchini,4 Antonio Rapisarda,5 Vincenzo Papa6 1Department of Ophthalmology, Policlinico Universitario A. Gemelli IRCSS Università Cattolica del Sacro Cuore, Roma, Italy; 2Ophthalmology Unit, Dipartimento di Scienze mediche di base, Neuroscienze e Organi di Senso Università di Bari, Azienda Ospedaliera Policlinico Consorziale, Bari, Italy; 3Ophthalmology Unit, IRCSS San Raffaele, Milano, Italy; 4Ophthalmology Unit, Ospedale Policlinico G.B. Rossi, Università di Verona, Verona, Italy; 5Ophthalmology Unit, Azienda Ospedaliera Garibaldi, Catania, Italy; 6Medical Affairs SIFI SpA, Catania, ItalyCorrespondence: Vincenzo PapaMedical Affairs SIFI SpA, Via E. Patti 36, Aci S. Antonio, Catania, ItalyEmail vincenzo.papa@sifigroup.comPurpose: To evaluate the short-term anti-inflammatory effect of dexamethasone/netilmicin fixed combination in the management of ocular inflammation after cataract surgery.Patients and Methods: Open-label, randomized, active-controlled, clinical study conducted in 6 sites in Italy; 238 patients were randomized 2:1 to dexamethasone/netilmicin (dexa/net, n=158) or betamethasone/chloramphenicol (beta/chl, n=80). Treatment started the day of surgery and continued 4 times daily for 7 days. The primary efficacy parameter was the anterior chamber (AC) flare. The percentage of patients displaying none or mild (ie, only barely detectable) AC flare was defined as “efficacy rate”, whereas the percentage of patients showing a decrease of AC flare score from baseline was defined as “percentage of responders”. Additional parameters evaluated were AC cells, conjunctival hyperaemia, corneal and lid oedema, symptoms of ocular discomfort, visual acuity, and intraocular pressure. Dexa/net was considered effective if the efficacy rate was not inferior (by means of 97.5% confidence interval) to that of beta/chl.Results: After 7 days of treatment, no AC flare was observed in 92.8% (dexa/net) and 92.3% (beta/chl) of patients, whereas no AC cells were observed in 91.5% (dexa/net) and 93.6% (beta/chl) of patients, respectively. The “efficacy rate” was 100% in both groups, whereas the “percentage of responders” was 94.1% in the dexa/net and 93.6% in the beta/chl group. The p-value to reject the null hypothesis of inferiority was < 0.001. Other efficacy parameters confirmed both treatments as highly effective, despite their difference in steroid content (2 mg/mL for beta/chl vs 1 mg/mL for dexa/net). IOP and visual acuity at the end of the study were comparable. Two cases of allergic conjunctivitis were considered adverse events and were both related to dexa/net.Conclusion: Short-term use of dexa/net fixed combination is safe and effective in the control of post-operative inflammation following uncomplicated cataract surgery.Keywords: cataract surgery, fixed combination, netilmicin, chloramphenicol

Electrochemotherapy (ECT) is an emerging therapeutic approach gaining growing interest for its potential immunomodulatory effects in cancer treatment. This narrative review systematically examines the current state of knowledge regarding the interplay between ECT and the immune system. Through an analysis of preclinical and clinical studies, the review highlights ECT capacity to induce immunogenic cell death, activate dendritic cells, release tumor antigens, trigger inflammatory responses, and occasionally manifest systemic effects—the abscopal phenomenon. These mechanisms collectively suggest the ECT potential to influence both local tumor control and immune responses. While implications for clinical practice appear promising, warranting the consideration of ECT as a complementary treatment to immunotherapy, the evidence remains preliminary. Consequently, further research is needed to elucidate the underlying mechanisms, optimize treatment protocols, explore potential synergies, and decipher the parameters influencing the abscopal effect. As the field advances, the integration of ECT's potential immunomodulatory aspects into clinical practice will need careful evaluation and collaboration among clinical practitioners, researchers, and policymakers. [ABSTRACT FROM AUTHOR]

Purpose: This systematic review aimed to assess the feasibility, safety, and efficacy of using modern external beam radiotherapy (EBRT) techniques, such as intensity-modulated radiotherapy (IMRT), volumetric modulated arc therapy (VMAT), and stereotactic body radiotherapy (SBRT) as alternative approaches to brachytherapy (BRT) in adjuvant treatment of endometrial cancer (EC). Material and methods: A systematic review was conducted following PRISMA guidelines. The research question was framed using the PICO method, focusing on patients with EC [P] and comparing modern EBRT techniques (IMRT, VMAT, SBRT) [I] vs. BRT [C], to evaluate their feasibility, safety, and effectiveness, particularly in terms of tumor local control (LC) [O]. Both planning and clinical outcomes, including acute toxicity, late side effects, and LC were analyzed with quality assessments performed using the GRADE framework and ROBINS-I tool. Results: Planning studies revealed that while IMRT and VMAT provided comparable or improved target coverage and dose homogeneity compared with BRT, brachytherapy was associated with lower doses to critical organs. Post-operative SBRT and SIB-VMAT studies reported high LC rates (up to 100%) with minimal acute toxicity. However, the overall quality of evidence was low to very low, with significant risks of bias, mainly related to participant selection. Conclusions: This review highlights that, although modern EBRT techniques, such as IMRT and VMAT are feasible alternative approaches to BRT for post-operative vaginal cuff irradiation, the current evidence does not support their superiority over BRT. Brachytherapy remains a highly effective treatment modality with well-established benefits. Future research should focus on more robust comparisons between EBRT and BRT, considering not only local control and toxicity, but also psychological impact and quality of life, especially in low-resource settings, where access to BRT may be limited. [ABSTRACT FROM AUTHOR]

Samuele Gigliola,1 Giancarlo Sborgia,1 Alfredo Niro,2 Carmela Palmisano,1 Pasquale Puzo,1 Gianluigi Giuliani,1 Luigi Sborgia,1 Valentina Pastore,1 Alessandra Sborgia,2 Giovanni Alessio1 1Eye Clinic, Depatment of Medical Science, Neuroscience and Sense Organs, University of Bari, Bari, Italy; 2Eye Clinic, Hospital “S. G. MOSCATI”, ASL TA, Taranto, ItalyCorrespondence: Alfredo NiroEye Clinic, Hospital “S. G. MOSCATI,” ASL TA, Via per Martina Franca, Statte, Taranto, 74010, ItalyEmail alfred.nir@tiscali.itIntroduction: We described a one-handed rotational phacoemulsification technique to decrease phaco time and power, and surgical stress on the cornea in eyes with different types of cataract.Methods: In this technique a single sutureless corneal incision was made without any side-port incision. After hydrodissection and hydrodelamination were performed, a phaco tip was positioned in contact with the nucleus beside the capsulorhexis edge. By using a peristaltic pump, phacoemulsification was started with high levels of vacuum to keep the probe tip on the edge of the lens and to ensure the rotation of the nucleus, and with low ultrasound energy. The torsional mode used required less occlusion time and volume of fluid. The inclination of the tip was modified to 45-degree, directing it toward the lens center. So the nucleus was aspirated from the periphery toward the center by a rotational movement.Results: The eye in the technical video had a NC4-NO4 cataract. The preoperative vision in this eye was 20/100 with no improvement with refraction. On postoperative day 1, visual acuity had improved to 20/20. We recorded low intraoperative parameters including ultrasound time (21.4 sec), phacoemulsification power (73%), balanced salt solution used (31 mL) and cumulative dissipated energy (7.27) at the conclusion of the case. After 1 month, Central Corneal Thickness changed from 504 μm to 516 μm, and Endothelial Cell Loss was 1.15%.Conclusion: This technique uses a single clear corneal incision, high vacuum and low ultrasound power to reduce the exposition to excessive surgical maneuvers, fluid turbulence and ultrasound energy.Keywords: cataract surgery, single corneal incision, one-handed phacoemulsification, phaco-rolling

Cervical cancer is a common female cancer, with nearly 600,000 cases and more than 300,000 deaths worldwide every year. From a clinical point of view, surgery plays a key role in early cancer management, whereas advanced stages are treated with chemotherapy and/or radiation as adjuvant therapies. Nevertheless, predicting the degree of cancer response to chemotherapy or radiation therapy at diagnosis in order to personalize the clinical approach represents the biggest challenge in locally advanced cancers. The feasibility of such predictive models has been repeatedly assessed using histopathological factors, imaging and nuclear methods, tissue and fluid scans, however with poor results. In this context, the identification of novel potential biomarkers remains an unmet clinical need, and microRNAs (miRNAs) represent an interesting opportunity. With this in mind, the aim of this systematic review was to map the current literature on tumor and circulating miRNAs identified as significantly associated with the therapeutic response in cervical cancer; finally, a perspective point of view sheds light on the challenges ahead in this tumor.Systematic Review RegistrationPROSPERO (CRD42021277980).

BackgroundSarcopenia (SP) is defined as the quantitative and functional impairment of skeletal muscles. SP is commonly related to older age and is frequent in patients with cancer. To provide an overview of SP in patients treated with radiotherapy (RT) and to evaluate the current evidence, we analyzed the available systematic reviews and meta-analyses.MethodsReviews were identified using PubMed, Scopus, and Cochrane library databases, without date restriction. Only systematic reviews and meta-analyses on the prognostic impact of SP and on any treatments aimed at reducing SP effect, in patients undergoing RT, were included in this review. The analyses not separately reporting the results in patients treated with RT were excluded. The quality assessment was performed using AMSTAR-2 (A MeaSurement Tool to Assess systematic Reviews).ResultsFrom the 84 papers identified, five reviews met the inclusion criteria with four reports mainly including non-randomized trials. Three reviews on the effect of SP showed a significantly negative impact on overall survival in patients undergoing RT and/or chemoradiation for H&N cancers (HR: 1.63-2.07). Two reviews on interventional studies showed the possibility of 1) improving physical functions through nutritional and physical interventions and 2) avoiding muscle wasting by means of sufficient protein intake. The quality assessment of the included review showed that two and three analyses are classifiable as having low and moderate overall confidence rating, respectively.ConclusionsThe analyzed reviews uniformly confirmed the negative impact of SP in patients with H&N tumors undergoing RT and the possibility of improving muscle mass and function through nutritional and physical interventions. These results justify further research on this topic based on a more uniform SP definition and on a complete evaluation of the potentially confounding parameters.

Rosanna Dammacco,1 Giovanni Alessio,1 Ermete Giancipoli,2 Patrizia Leone,3 Anna Cirulli,3 Leonardo Resta,4 Angelo Vacca,3 Franco Dammacco3 1Department of Ophthalmology and Neuroscience, University of Bari “Aldo Moro”, Medical School, Bari, Italy; 2Department of Biomedical Sciences, Ophthalmology Unit, University of Sassari, Sassari, Italy; 3Department of Biomedical Sciences and Human Oncology, University of Bari “Aldo Moro”, Medical School, Bari, Italy; 4Department of Emergency and Organ Transplantation, University of Bari “Aldo Moro”, Medical School, Bari, ItalyCorrespondence: Franco DammaccoDepartment of Biomedical Sciences and Human Oncology, University of Bari “Aldo Moro”, Medical School, Polyclinic, Piazza Giulio Cesare, 11, Bari 70124, ItalyTel +39 080 5478 863Fax +39 080 5478 820Email francesco.dammacco@uniba.itPurpose: Giant cell arteritis (GCA), a chronic vasculitis of the large and medium-sized arteries, affects people > 50 years of age. This study assessed the prevalence of visual manifestations and other clinical features at presentation in an Italian cohort of GCA patients. Recent advances in the pathophysiology, diagnosis, and therapy of GCA are also reviewed.Methods: This retrospective, single-center study conducted by the ophthalmology and internal medicine clinics of one university recruited 56 patients from 2005 to 2016 and followed them for 11– 54 months.Results: Ocular involvement was diagnosed in 19 patients (33.9%), with permanent vision loss in 19.6% (7.1% of the cohort with bilateral vision loss). Arteritic anterior and posterior ischemic optic neuropathy were diagnosed in 11 patients (57.9%) and 1 patient (5.3%), respectively, cotton wool spots in 3 patients (15.8%), central retinal artery occlusion in 2 patients (10.5%), and anterior segment ischemia and multifocal choroidal ischemia in 1 patient each (5.3%). Polymyalgia rheumatica was associated with GCA in 44.6% of the patients. The most common extra-ocular manifestation was constitutional symptoms (82.1% of the patients). Large-vessel involvement, including of the ascending aorta, aortic arch, and left axillary artery, was diagnosed by magnetic resonance or computed tomography (CT) angiography and 18FDG positron emission/CT. Glucocorticoids (GCs) remain the standard-of-care worldwide, but methotrexate, provided as a steroid-sparing drug in 41% of the patients, resulted in earlier tapering, a lower cumulative dose of GCs, and a lower rate of relapse. Among the combinations of GCs and immunosuppressive drugs proposed to treat GCA, only tocilizumab has effectively induced and maintained disease remission.Conclusion: According to our data and literature reports: a) GCA is a systemic disease; b) its diagnosis is expedited by the adjunct use of imaging techniques; c) insights into the pathogenesis of GCA may allow an improved, differentiated therapeutic approach.Keywords: giant cell arteritis, ocular manifestations, diagnostic imaging, glucocorticoids, pathogenetic advances, tocilizumab

Abstract Background It has been hypothesized that radiotherapy (RT) techniques delivering radiations to larger volumes (IMRT, VMAT) are potentially associated with a higher risk of second primary tumors. The aim of this study was to analyse the impact of RT technique (3D-CRT vs IMRT/VMAT) on the incidence of second tumors in prostate cancer (PCa) patients. Methods A retrospective study on 2526 previously irradiated PCa patients was performed. Patients were treated with 3D-CRT (21.3%), IMRT (68.1%), or VMAT (10.6%). Second tumors incidence was analysed in 3 categories: pelvic, pelvic and abdominal, and “any site”. The correlation with RT technique was analysed using log-rank test and Cox’s proportional hazard method. Results With a median follow-up of 72 months (range: 9–185), 92 (3.6%) cases of second tumors were recorded with 48 months (range: 9–152) median interval from RT. Actuarial 10-year second tumor free survival (STFS) was 87.3%. Ten-year STFS in patients treated with 3D-CRT and IMRT/VMAT was 85.8 and 84.5%, respectively (p: .627). A significantly higher 10-year cumulative incidence of second tumors in the pelvis was registered in patients treated with IMRT/VMAT compared to 3D-CRT (10.7% vs 6.0%; p: .033). The lower incidence of second pelvic cancers in patients treated with 3D-CRT was confirmed at multivariable analysis (HR: 2.42, 95%CI: 1.07–5.47, p: .034). Conclusions The incidence of second pelvic tumors after RT of PCa showed a significant correlation with treatment technique. Further analyses in larger series with prolonged follow-up are needed to confirm these results.

Silvana Guerriero,1 Francesco D’Oria,1 Giacomo Rossetti,2 Rosa Anna Favale,1 Stefano Zoccolella,1 Giovanni Alessio,1 Vittoria Petruzzella1 1Department of Medical Science, Neuroscience and Sense Organs, University of Bari Aldo Moro, Bari, Italy; 2Department of Molecular Biology, University of Geneva, Geneva, SwitzerlandCorrespondence: Vittoria PetruzzellaDipartimento di Scienze Mediche di Base, Neuroscienze e, Organi di Senso - Università degli Studi Aldo Moro, Piazza G. Cesare, Bari 70124, ItalyTel +39 080 5448530Fax +39 080 5448538Email vittoria.petruzzella@uniba.itAbstract: Charcot-Marie-Tooth (CMT) constitutes a group of heterogeneous hereditary motor and sensor neuropathies. Mutations in mitofusin-2 (MFN2) cause CMT type 2A by altering mitochondrial fusion and trafficking along with the axonal microtubule system. In literature patients presenting with CMT2A are reported as having a subacute onset of optic atrophy associated with central scotoma and color vision defects. We report on the clinical and genetic findings in a 40 years-old Caucasian woman presenting with CMT type 2A and MFN 2 mutation (c.2258duplT/p.Leu753fs) who presented bilateral progressive optic atrophy with bilateral severe concentric narrowing of the visual field but normal visual acuity and color vision. This is the first report that describes such phenotypical manifestation of an MFN 2 mutation suggesting that the molecular mechanisms underlying the mitofusin-2 function alteration at optic nerve need to be investigated further.Keywords: Charcot-Marie-Tooth type 2A, mitofusin2, optic atrophy, mitochondria, visual field

Purpose/Objective(s)Stereotactic ablative body radiotherapy (SBRT) for vertebral metastases is a challenging treatment process. Planning automation has recently reported the potential to improve plan quality and increase planning efficiency. We performed a dosimetric evaluation of the new Personalized engine implemented in Pinnacle3 for full planning automation of SBRT spine treatments in terms of plan quality, treatment efficiency, and delivery accuracy.Materials/MethodsThe Pinnacle3 treatment planning system was used to reoptimize six patients with spinal metastases, employing two separate automated engines. These two automated engines, the existing Autoplanning and the new Personalized, are both template-based algorithms that employ a wishlist to construct planning goals and an iterative technique to replicate the planning procedure performed by skilled planners. The boost tumor volume (BTV) was defined as the macroscopically visible lesion on RM examination, and the planning target volume (PTV) corresponds with the entire vertebra. Dose was prescribed according to simultaneous integrated boost strategy with BTV and PTV irradiated simultaneously over 3 fractions with a dose of 30 and 21 Gy, respectively. Dose-volume histogram (DVH) metrics and conformance indices were used to compare clinically accepted manual plans (MP) with automated plans developed using both Autoplanning (AP) and Personalized engines (Pers). All plans were evaluated for planning efficiency and dose delivery accuracy.ResultsFor similar spinal cord sparing, automated plans reported a significant improvement of target coverage and dose conformity. On average, Pers plans increased near-minimal dose D98% by 10.4% and 8.9% and target coverage D95% by 8.0% and by 4.6% for BTV and PTV, respectively. Automated plans provided significantly superior dose conformity and dose contrast by 37%–47% and by 4.6%–5.7% compared with manual plans. Overall planning times were dramatically reduced to about 15 and 23 min for Pers and AP plans, respectively. The average beam-on times were found to be within 3 min for all plans. Despite the increased complexity, all plans passed the 2%/2 mm γ-analysis for dose verification.ConclusionAutomated planning for spine SBRT through the new Pinnacle3 Personalized engine provided an overall increase of plan quality in terms of dose conformity and a major increase in efficiency. In this complex anatomical site, Personalized strongly reduce the tradeoff between optimal accurate dosimetry and planning time.