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Purpose: Reconstruction of the proximal femur after tumour resection can be performed with proximal femoral endopros-theses (PFE). Many studies have reported that bipolar hemiarthroplasty (BHA) reduce the risk of dislocation after oncological resections. However, progressive cotyloiditis which might require acetabular resurfacing (total hip arthroplasty [THA]) has been reported. The aim of this study is to compare the results of BHA and THA after proximal femur resection. Materials and Methods: A total of 104 consecutive patients affected by primary (n=52) and metastatic (n=52) bone tumours were included. Ninety patients underwent BHA and 14 patients underwent THA. Complications were recorded and classified according to the Henderson classification. At final follow-up, patients with the implant in site were functionally evaluated with modified Harris hip score (HHS). Results: The mean follow-up was 50 months (range, 2-171 months). Twenty-four (23.1%) patients developed major complications. Eleven (12.2%) BHA required acetabular resurfacing. Patients affected by primary bone tumours showed an increased risk of THA conversion (P=0.042). A reduced risk was observed in patients younger than 35 years (P=0.043) and in those older than 65 years (P=0.033). Dislocation occurred in four case (3.8%), in particular after THA (P=0.021). At final follow-up, 93 patients had the prosthesis in site (80 BHA and 13 THA). Mean postoperative HHS was 70 (range, 30-90). Conclusion: The risk of dislocation is lower for bipolar endoprosthesis compared to THA. However cotyloiditis and acetabular resurfacing might occurred.

Objective. Evaluate outcomes of Vancouver B2-type and B3-type proximal femur periprosthetic fractures (PPFs) in elderly patients treated with a cementless tapered modular femoral stem. Methods. 37 patients with a proximal femur PPF (34 B2-type and 5 B3-type) on primary or revision implants, with a minimum of 2-year follow-up, treated with revision of the failed stem using uncemented MP® reconstruction system stem (Waldemar Link®), were included.Results. At last follow-up, the average Harris Hip Score was 91 ± 9.8, and average Numerical Rating Score was 0.7 ± 0.8, without a significant difference between B2-type and B3-type PPFs. X-rays at last follow-up revealed bone union in all patients. According to Beals and Tower’s criteria, we found excellent radiological findings in 89.7% patients. Fourteen local surgery-related complications were reported (35.9%), and 4 patients required revision surgery (10.2%), without significant differences between B2-type and B3-type PPFs. We found involvement of both trochanters in fracture as a possible risk factor for dislocation.Conclusions. Vancouver B2-type and B3-type PPFs can be effectively treated using a cementless modular stem, even without cortical struts graft, although further studies are needed regarding B3-type PPFs.

Purpose In the current study, we evaluated whether neoadjuvant chemoradiotherapy with reduced treatment volumes due to the exclusion of elective pelvic nodal irradiation is a feasible strategy for selected patients with locally advanced rectal cancer. Methods and Materials Patients with T2 low-lying/T3, N0-N1 rectal lesions without evidence of disease in the lateral lymph nodes were prospectively recruited. All patients underwent pretreatment testing, including computed tomography imaging of the chest, abdomen, and pelvis with intravenous contrast, pelvic magnetic resonance imaging with intravenous contrast, and 18-fluorodeoxyglucose positron emission/computed tomography. The clinical target volume included the primary tumor and the mesorectum with vascular supply containing the perirectal and presacral nodes, with the upper border at the S2/S3 interspace. The total radiation dose was 50.4 Gy, and fluoropyrimidine-based chemotherapy was associated concomitantly. The primary endpoint of the study was the reduction of gastrointestinal (GI) toxicity, and the secondary endpoints were pathologic complete response, local control, overall survival, and disease-free survival. Results Fifty-two patients (30 men, 22 women) with a median age of 67 years (range, 45-85 years) were enrolled in the study. Acute grade 3 GI toxicity was 7.6%, and there were no cases of grade 4 toxicity. Three patients (5.7%) developed a local recurrence. No relapse occurred in the lateral lymph nodes. The local control rate at 5 years was 96.1%. With a median follow-up time of 72.9 months (range, 2.5-127.6 months), the 3- and 5-year overall survival rates were 89.4% and 87%, respectively. The 3- and 5-year disease-free survival rates were 82.4% and 82.4%, respectively. Conclusions De-escalation of radiation therapy target volume reduces GI side effects without compromising efficacy in patients with rectal cancer. These results cannot be clearly extended to high-risk disease and need further evaluation in future randomized trials.

Aims: We report a series of patients treated with intercalary bone graft (IBG) of the tibia diaphysis (TD) after resection of primary bone tumors. The purpose of this study was to evaluate the mid- and long-term survival of TD IBG reconstruction in children and adults, characterizing patterns of success and failure. Methods: A total of 35 patients were included in this retrospective study. Median age was 22years (range, 8–57). This series included 19 patients (54.3%) treated with homologous bone graft alone and 16 patients (45.7%) treated combining intercalary allograft with fibular autograft. Complications were recorded according to Henderson classification. Results: Median follow-up was 36months (range, 1–165). Local recurrence occurred in 2 patients (5.7%) after 12 and 60months, respectively. Major complications included graft fracture (9 cases), non-union (5 cases) and infection (4 cases). Other complications were axial deformity (2 cases), superficial infection (2 cases), compartmental syndrome (1 case). Conclusion: Intercalary bone grafts of TD have been recommended as a reliable solution with long-term success rates and good functional outcome in more than 80% of patients. However, approximately half of the patients may require further surgeries to treat major complications (deep infection, delayed or non-union and graft fracture). Additional vascularized fibula graft may ameliorate final result.

Aims To report oncologic and functional outcomes in terms of tumor control and toxicity of carbon ion radiotherapy (CIRT) in reirradiation setting for recurrent salivary gland tumors at CNAO. Methods From November 2013 to September 2016, 51 consecutive patients with inoperable recurrent salivary gland tumors were retreated with CIRT in the frame of the phase II protocol CNAO S14/2012C for recurrent head and neck tumors. Results Majority of pts (74.5%) had adenoid cystic carcinoma, mainly rcT4a (51%) and rcT4b (37%). Median dose of prior photon based radiotherapy was 60 Gy. Median dose of CIRT was 60 Gy [RBE] at a mean of 3 Gy [RBE] per fraction. During reirradiation, 19 patients (37.3%) experienced grade G1 toxicity, 19 pts (37.3%) had G2 and 2 pts (3.9%) had G3. Median follow up time was 19 months. Twenty one (41.2%) patients had stable disease and 30 (58.8%) tumor progression at the time of last follow up. Furthermore, 9 (18%) patients had G1 late toxicity, 19 (37%) had G2 and 9 (17. 5%) had G3. Using the Kaplan Meier method, progression free survival (actuarial) at one and two years were 71.7% and 52.2% respectively. Estimated overall survival (actuarial) at one and two years were 90.2% and 64%, respectively. Conclusions CIRT is a good option for retreatment of inoperable recurrent salivary gland tumors with acceptable rates of acute and late toxicity. Longer follow up time is needed to assess the effectiveness of CIRT in reirradiation setting of salivary gland tumors.

INTRODUCTION: Degenerative disc disease is a major health concern in spine surgery. The aim of this systematic review was to summarize the current knowledge about injectable regenerative therapies (mesenchymal stem cells [MSC] or platelet rich plasma [PRP]) in degenerative disc disease. EVIDENCE ACQUISITION: A research and analysis of the literature on Pubmed, Medscape, Medline, Google Scholar and Cochrane databases was performed, in accordance with the Preferential Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) flowchart. Only peer-reviewed randomized controlled trials (RCTs), prospective single-arm trials, case series, and cohort studies were included. EVIDENCE SYNTHESIS: A total of 17 studies were included. All were homogeneous regarding indications to the procedure: discogenic low-back pain for at least 3-6 months, failure of conservative treatment, MRI evidence of disc degeneration. A total of 182 patients were treated with MSC and 198 patients were treated with PRP. Considering the efficacy, the studies were heterogeneous in clinical evaluation systems; however, they all reported significant improvement in clinical and functional scores. Neither major complications nor adverse effects were reported by any author. As for radiographical outcome none of the studies reported a disc height improvement after treatment. CONCLUSIONS: Degenerative disc disease is a major health concern. Regenerative therapies could play a role in the treatment of its symptoms, as they have been proven to be clinically effective, cheap, and safe. Nevertheless, further studies are needed, in order to establish evidence based standardized treatments.

Conventionally fractionated chemoradiation (CRT) or chemotherapy (CHT) are considered as standard options in locally advanced pancreatic cancer (LAPC) while stereotactic body radiotherapy (SBRT) is an emerging treatment in this setting. The aim of this study was to compare two cohorts of LAPC patients treated with SBRT ± CHT vs CRT ± CHT in terms of local control (LC), distant metastases‐free survival (DMFS), progression‐free survival (PFS), overall survival (OS), and toxicity. Eighty patients were included. Patients in the two cohorts were matched according to: age ≤/>65 years, tumor diameter (two cut‐offs, An equivalence of stereotactic body radiotherapy (SBRT) and chemoradiation (CRT) has been only suggested in some retrospective studies in pancreatic cancer (PC). This is the first matched case‐control study comparing SBRT and CRT in PC considering several endpoints. An equivalence in terms of overall survival, disease free survival, and metastasis free survival among the two treatments and an advantage of SBRT in terms of local control were recorded. Therefore, SBRT is almost comparable to standard CRT.

Simple Summary Pancreatic cancer remains a disease with a dismal outlook for patients, with high relapse rates after surgery and adjuvant treatments. Thanks to the high conformality achievable with advanced radiotherapy techniques, a more robust definition of clinical target volume (CTV) margins is mandatory. Moreover, a precise CTV definition may affect local control, minimizing radiation-related toxicity and allowing dose escalation. Contrary to two recent studies, RTOG contouring guidelines are not based on a pattern of failure analysis. We provided a local failure risk map in resected pancreatic cancer, validating the results of previous studies. Moreover, according to a new probabilistic approach, we provided new CTV contouring guidelines for the postoperative radiotherapy of pancreatic cancer, modeling targets’ margins on a combination of our validated local failure map (30% of local failures) and RTOG guidelines (70% of local failures). Abstract The study aimed to generate a local failure (LF) risk map in resected pancreatic cancer (PC) and validate the results of previous studies, proposing new guidelines for PC postoperative radiotherapy clinical target volume (CTV) delineation. Follow-up computer tomography (CT) of resected PC was retrospectively reviewed by two radiologists identifying LFs and plotting them on a representative patient CT scan. The percentages of LF points randomly extracted based on CTV following the RTOG guidelines and based on the LF database were 70% and 30%, respectively. According to the Kernel density estimation, an LF 3D distribution map was generated and compared with the results of previous studies using a Dice index. Among the 64 resected patients, 59.4% underwent adjuvant treatment. LFs closer to the root of the celiac axis (CA) or the superior mesenteric artery (SMA) were reported in 32.8% and 67.2% cases, respectively. The mean (± standard deviation) distances of LF points to CA and SMA were 21.5 ± 17.9 mm and 21.6 ± 12.1 mm, respectively. The Dice values comparing our iso-level risk maps corresponding to 80% and 90% of the LF probabilistic density and the CTVs-80 and CTVs-90 of previous publications were 0.45–0.53 and 0.58–0.60, respectively. According to the Kernel density approach, a validated LF map was proposed, modeling a new adjuvant CTV based on a PC pattern of failure.

Recent years have witnessed the rise of pathomics as a mean to describe histopathological images with quantitative biomarkers for predictive and prognostic ends, combining digital pathology, omic science and artificial intelligence. This novel research branch is the counterpart of radiomics which pursues the same aims extracting knowledge from radiological images. In this paper, we present the design of a pathomic deep learning-based system to predict the treatment outcome in non-small cell lung cancer patients. We describe the system design and optimization under the condition of limited data and limited training, with corresponding tests. The experimental results show the feasibility of the proposed scalable architecture providing also a comparison between different transfer learning strategies.

Objective To evaluate the early toxicity of concurrent use of radiotherapy in association with CDK4/6 inhibitors (palbociclib or ribociclib) in patients with hormone-receptors positive metastatic breast cancer. Material and methods Records of patients with histologically proven metastatic or locally advanced breast cancer treated in our institution were reviewed. Patients who received radiotherapy and concurrent palbociclib or ribociclib were selected. Toxicity was assessed according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0 (NCI-CTCAE V4.0). Results Sixteen consecutive metastatic breast cancer patients with 24 radiotherapy treatments were studied. Thirteen patients (81.3%) received palbociclib, 3 (18.7%) patients received ribociclib concurrently with RT (18 and 5 radiotherapy courses respectively). The majority of patients (68.7%) received palliative radiotherapy to the bones (median dose 30 Gy, range 8–36 Gy). Five patients (31.2%) were treated in oligo-metastatic or oligo-progressive sites of disease with higher doses (median dose = 50 Gy, range 39.6–60 Gy). The most common toxicity observed was hematological toxicity. Neutropenia was common (grade 2 = 12.5%; grade 3 = 25%, grade 4 = 6.3%); 60% of patients experiencing grade ≥ 3 neutropenia had already experienced neutropenia during previous cycles of palbociclib. One patient (6.3%) completed the RT course earlier (48 Gy of 50 Gy prescribed) and another patient (6.3%) suspended RT for 2 days. Conclusion concomitant treatment of CDK4/6 and radiotherapy seems well tolerated; high grade hematological toxicity is common, but did not change treatment course in the majority of patients. Previous toxicity should be carefully evaluated as it usually reoccurs.

Aim Positron Emission Tomography with Computed Tomography (PET/CT) has been proven to be useful in the definition of Radiotherapy (RT) target volume. In this regard, the present expert review summarizes existing data for pancreas, prostate, gynecological and rectum/anal cancer. Methods A comprehensive search of published original article was made, based on SCOPUS and PubMed database, selecting the paper that evaluated the role of PET/CT in the definition of RT volume. Results FDG-PET has an important and promising role for pancreatic cancer. Choline PET/CT could be useful for identifying high-risk volumes for prostate cancer; while PSMA PET/CT is still under evaluation. FDG PET/CT in gynecological cancers has been shown to impact external-beam RT planning. The role of FDG-PET for Gross Tumor volume identification is crucial, representing a useful and powerful tool for anal and rectal cancer. Conclusion Taken together, molecular and functional imaging approaches offer a major step to individualize radiotherapeutic approach.

Over the past century, technologic advances have promoted the evolution of radiation therapy into a precise treatment modality allowing for the maximal administration of dose to tumors while sparing normal tissues. In parallel with this technological maturation, the rapid expansion in understanding the basic biology and heterogeneity of cancer has led to the development of several compounds that target specific pathways. Many of them are in advanced steps of clinical development for combination treatments with radiotherapy, and can be incorporated into radiation oncology practice for a personalized approach to maximize the therapeutic gain. This review describes the rationale for combining novel agents with radiation, and provides an overview of the current landscape focused on treatment efficacy.

Purpose Aim of the present review is to assess present data about the use of the association of Radiotherapy (RT) and targeted therapy/immunotherapy (TT/IT) in elderly people. Design PubMed database was searched for English literature published up to December 2017 using the keywords "radiotherapy" combined with "bevacizumab", "cetuximab", "trastuzumab", "erlotinib", "gefitinib", "sorafenib", "sunitinib", "vismodegib", "sonidegib", "ipilimumab", "pembrolizumab", "nivolumab". Studies performing RT and TT/IT in people aged >65-years were evaluated focusing on safety, toxicity and efficacy. Studies eligible for inclusion were: case reports, retrospective/prospective studies in which RT and new drugs were used concomitantly or sequentially, focusing on elderly sub-group. Results The systematic search identified 626 records. After exclusion of duplicates, full-text review, cross-referencing and paper that did not respect the inclusion criteria, 81 studies were included in this review. In elderly patients the combination of RT with cetuximab or bevacizumab seems feasible but with higher reported side effects. Patients’ age should not limit the association of trastuzumab and RT in HER2 positive breast cancer. The concurrent administration of TKIs and RT appears to be feasible and effective. Regarding the Immune Check Point inhibitors and RT, tolerance seems similar among older and younger people but definitive data are lacking. Instead, the association of RT and vismodegib/sonidegib remains investigational. Conclusion TT/IT in association of RT seems to be safe, but in elderly patients data concerning safety and toxicity are limited. Specific clinical trials on this population are encouraged.

Background: Bacterobilia is associated with postoperative morbidity after pancreaticoduodenectomy (PD), mostly due to infectious complications. The aim of this study was to investigate the prevalence of bacteria species isolated from intraoperative biliary cultures, and related complications after PD. Methods: An ANOVA test was used to assess the prevalence of isolated bacterial species and postoperative complications. The odds ratio was computed to evaluate the association between biliary cultures and each complication, Endoscopic Retrograde CholangioPancreatography (ERCP) and each complication, ERCP and biliary cultures, Delayed Gastric Emptying (DGE) and Postoperative Pancreatic Fistula (POPF). Results: Positive biliary cultures were found in 162/244 (66%) PDs. Different prevalences of polymicrobial biliary culture were detected in patients with postoperative complications. In SSIs, a significant prevalence of biliary culture positive for E. coli, Klebsiella pneumoniæ and Enterococcus fæcalis (p &lt, 0.001) was detected. Prevalences of polymicrobial biliary cultures with Escherichia coli, Klebsiella pneumoniæ, Enterococcus fæcalis and Enterococcus fæcium were significantly associated with POPF (p &lt, 0.001). Biliary culture positive for Escherichia coli, Enterococcus fæcalis and Enterococcus fæcium showed a higher prevalence of intra-abdominal collection and DGE (p &lt, 0.001). Notably, Escherichia coli was significantly associated with DGE as a unique complication (OR = 2.94 (1.30–6.70), p &lt, 0.01). Conclusions: Specific prevalences of polymicrobial bacterobilia are associated with major complications, while monomicrobial Escherichia coli bacterobilia is associated with DGE as a unique complication after PD.

Scoliosis in Ullrich Congenital Muscular Dystrophy (UCMD) is very common, with a reported incidence of more than 50%, and it is rapidly progressive. There are no previous studies which specifically focus on scoliosis surgery in UCMD patients. This article reports three cases of scoliosis surgery in UCMD, focusing on operative course, clinical and radiological results achieved, fusion area and complications, with a 2-year follow-up. The surgical technique adopted for vertebral arthrodesis included: High-density pedicle screw systems, asymmetric rods contouring and direct vertebral rotation. The summary results shown a significative correction of the coronal deformity, with a reduction of the mean Cobb angle from 49° to 25° post-operatively. Mean pelvic tilt remained stable, while L5-tilt showed a decrease from 10° to 6°. Mean screw density was 1.92. None of the patients required extended fixation to S2. No major complications were reported, and patients maintained their pre-operative walking ability. All the patients reported a subjective improvement in quality of life, with a better sitting comfort. In conclusion, posterior spinal fusion with high-density pedicle screw systems and direct vertebral rotation may be safe and effective in surgical correction of scoliosis in UCMD. If pelvic obliquity and L5-tilt are less than 15°, could be possible to achieve an optimal spinal and pelvic balance even without sacral or pelvic fixation.

(1) Aim: To test the performance of a deep learning algorithm in discriminating radiation therapy-related pneumonitis (RP) from COVID-19 pneumonia. (2) Methods: In this retrospective study, we enrolled three groups of subjects: pneumonia-free (control group), COVID-19 pneumonia and RP patients. CT images were analyzed by mean of an artificial intelligence (AI) algorithm based on a novel deep convolutional neural network structure. The cut-off value of risk probability of COVID-19 was 30%, values higher than 30% were classified as COVID-19 High Risk, and values below 30% as COVID-19 Low Risk. The statistical analysis included the Mann–Whitney U test (significance threshold at p &lt, 0.05) and receiver operating characteristic (ROC) curve, with fitting performed using the maximum likelihood fit of a binormal model. (3) Results: Most patients presenting RP (66.7%) were classified by the algorithm as COVID-19 Low Risk. The algorithm showed high sensitivity but low specificity in the detection of RP against COVID-19 pneumonia (sensitivity = 97.0%, specificity = 2%, area under the curve (AUC = 0.72). The specificity increased when an estimated COVID-19 risk probability cut-off of 30% was applied (sensitivity 76%, specificity 63%, AUC = 0.84). (4) Conclusions: The deep learning algorithm was able to discriminate RP from COVID-19 pneumonia, classifying most RP cases as COVID-19 Low Risk.

CASE: We describe the case of a 53-year-old man who developed acute groin pain 20 days after a posterior L4-L5 interbody fusion. Despite positioning of pedicle screws within the safe zone, an L4 right lumbar artery pseudoaneurysm was found on computer tomography angiogram. Coil embolization was successfully performed. CONCLUSION: Iatrogenic lumbar artery pseudoaneurysms are a rare complication of spinal surgery. Our case is, to the best of our knowledge, the only reported case where this lesion occurred despite good positioning of the screws: It is therefore important to always suspect and exclude this complication in case of suggestive symptoms.

Purpose The aim of this article is to present an original surgical technique for the treatment of rigid Adult Idiopathic Scoliosis (AdIS) and the results at minimum 2 years follow-up in a cohort of 40 patients. Methods We retrospectively reviewed 40 patients affected by rigid AdIS, older than 40 years and operated with a posterior one stage surgical technique summarized with the acronym Hi-PoAD, (high-density pedicle screws, Ponte osteotomies, asymmetric rods contouring, direct vertebral rotation). The demographic and surgical data were collected, and the improvement of clinical scores and radiologic parameters was obtained after surgery, at 1 and 2 years and at final follow-up, to assess deformity correction, coronal and sagittal balance and clinical outcome. Results The average follow-up was 2.9 years (range 2–3.5). Average coronal Cobb angle decreased from 65.0° ± 8.4 to 18.9° ± 3.9 (p p p Conclusions Hi-PoAD technique proved to be safe and effective in the treatment of rigid Adult Idiopathic Scoliosis. The reason for the success is related to the combined strategies adopted, that dissipates corrective forces over several levels, reducing mechanical stress at the screw–bone interface and optimizing corrective potential.

BackgroundThe choice between upfront surgery or neoadjuvant treatments (NAT) for resectable pancreatic ductal adenocarcinoma (R-PDAC) is controversial. R-PDAC with potential nodal involvement could benefit from NT. Ca (Carbohydrate antigen) 19.9 and serum albumin levels, alone or in combination, have proven their efficacy in assessing PDAC prognosis. The objective of this study was to evaluate the role of Ca 19.9 serum levels in predicting nodal status in R-PDAC.MethodsPreoperative Ca 19.9, as well as serum albumin levels, of 165 patients selected for upfront surgery have been retrospectively collected and correlated to pathological nodal status (N), resection margins status (R) and vascular resections (VR). We further performed ROC curve analysis to identify optimal Ca 19.9 cut-off for pN+, R+ and vascular resection prediction.ResultsIncreased Ca 19.9 levels in 114 PDAC patients were significantly associated with pN+ (p 418 U/ml was significantly associated with R+ (87% specificity, 36% sensitivity, p 0.014). Ca 19.9, at the cut-off >78 U/ml, indicated a significant trend to predict the need for VR (sensitivity 67%, specificity 53%; p = 0.059).ConclusionsIn R-PDAC with normal serum albumin levels, Ca 19.9 predicts pN+ and R+, thus suggesting a crucial role in deciding on NAT.

Simple Summary Many classifications to assess margins status for soft tissue sarcomas are reported in the literature. Most of the series are heterogeneous and variable in size, making it difficult to compare results from study to study. Thus, which is the best way to assess margins in order to predict the risk of local recurrence is still debated. The aim of this narrative review is to provide a comprehensive assessment of the literature on margins, and to highlight the need for a uniform description of the margin status for patients with soft tissue sarcomas (STS). Abstract Adequacy of margins must take into consideration both the resection margin width (quantity) and anatomic barrier (quality). There are several classification schemes for reporting surgical resection margin status for soft tissue sarcomas (STS). Most of the studies regarding treatment outcomes in STS included all histologic grades and histological subtypes, which include infiltrative and non-infiltrative subtypes and are very heterogeneous in terms of both histologic characteristics and treatment modalities (adjuvant treatments or not). This lack of consistency makes it difficult to compare results from study to study. Therefore, there is a great need for evidence-based standardization concerning the width of resection margins. The aim of this narrative review is to provide a comprehensive assessment of the literature on margins, and to highlight the need for a uniform description of the margin status for patients with STS. Patient cases should be discussed at multidisciplinary tumor boards and treatments should be individualized to clinical and demographic characteristics, which must include also a deep knowledge of specific histotypes behaviors, particularly infiltrative ones.

Purpose: To evaluate the efficacy of pre-operative low-dose radiation computed tomography (CT) in optimizing screw placement in patients with adolescent idiopathic scoliosis (AIS). Methods: 49 patients with AIS who required correction and posterior fusion between January 2018 and December 2019 were included in this retrospective study. All patients underwent surgery performed by the same team of experienced surgeons. Patients were divided in two groups. The study group received a pre-operative low-dose CT scan (CT group, n = 25), differently from the control group (CG, n = 24). Patients of both groups received a post-operative low-dose CT scan. The primary outcome measure was the accuracy of screw placement on the Gertzbein–Robbins scale (grades A and B were considered acceptable). Secondary outcome measures included a comparison of perioperative complications. Results: A total of 1045 screws were placed. In CT group (n = 25, screws = 528) and CG (n = 24, screws = 517), trajectories were grade A or B in 94.5% and 93.6% of screws, respectively. Two screws (one for each group) were removed because of intra-operative-evoked potentials alteration and one screw required revision after post-operative imaging. No correlation was found between the malpositioning rate and the proximity to the apex of the curve, conversely a significative peak of misplacements was observed at T3 (p < 0.01). No neurological and vascular complications related to screw placement were recorded. There was not intergroup difference neither in screw accuracy (Chi-Square, 2-tailed Fisher’s exact, p = 0.63), nor in complications rate. Conclusion: Pre-operative low-dose CT scan as surgical plan does not contribute in reducing pedicle screw misplacement rate. Study design: Retrospective comparative cohort study. Level of evidence: III.

Purpose: Allograft reconstruction with or without vascularized fibula can be a valuable solution to treat childhood intercalary tumours of the distal femur. We aimed to assess the oncological status, complication rate and survival of distal femur intercalary reconstruction after trans-metaphyseal (TMR) and trans-epiphyseal resection (TER). We also evaluated the impact of distal temporary graft fixation on skeletal growth after TMR. Methods: We retrospectively reviewed 23 skeletally immature patients affected by distal femur osteosarcoma (18) and Ewing sarcoma (5). Mean patients age was 10.3years. In 11 cases, TMR was performed with physis preservation and temporary distal graft fixation. In 9 patients, TER was performed with growth plate sacrifice. The last 3 cases were treated with TMR and sliding plate fixation. Results: Mean follow-up was 8.4years. No deaths occurred, but 3 patients presented lung metastasis and 2 cases presented local recurrence in soft tissues. 10 implant-related complications occurred, all surgically treated. At skeletal maturity, mean femoral dysmetria was 2.3cm after TMR and temporary epiphysiodesis, and 3.1cm after TER. In TMR group, a strong trend towards physeal recovery was observed after epiphyseal screws removal (p = 0.061), but valgus deformity in distal femur was more frequent (p = 0.049). MSTS score was good or excellent in all patients, with no statistically significant difference between TMR and TER. Conclusions: Intercalary graft reconstruction after TMR and TER allows good local disease control and excellent functional results with long-term follow-up. Temporary distal fixation might reduce the final limb discrepancy after TMR, but valgus deformity could develop. Level of evidence: Level IV.

Background Adolescent idiopathic scoliosis (AIS) is a frequent disorder. Since patients with AIS are typically as active as age-matched controls and post-operative reduction in physical activity has detrimental effects on their well-being, return to sport (RTS) is an important perioperative concern. Aim of the present study is to review the literature concerning return to sport after spinal fusion for AIS. Methods This work was carried out in accordance with Preferential Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. The search was carried out in December 2020. Only peer-reviewed randomized controlled trials (RCTs), retrospective studies (RS), retrospective case series (RCS) and perspective cohort studies (PCS) were considered for inclusion. Results Six studies were included; only one of them was prospective. All the authors reported a time to RTS ranging between 6 and 18 months. Between 28 and 36.6% of all patients changed sport, choosing lower impact activities, mostly due to loss of flexibility of the spine. No complications due to return to play were noted. Conclusion According to current evidence, patients who received spinal arthrodesis for AIS can safely return to any sport, even those that require extreme levels of spinal and pelvic movements such as gymnastics and golf. As there is little evidence, however, of the spinal loading that occurs during such movements, there is a lack of scientific evidence-based recommendations or guidelines surgeons and other health care providers can follow. Prospective comparative studies are needed to investigate these biomechanical and clinical issues. Level of evidence Level III.

Opinion statement New molecular insights are being achieved in synovial sarcoma (SS) that can provide new potential diagnostic and prognostic markers as well as therapeutic targets. In particular, the advancement of research on epigenomics and gene regulation is promising. The concrete hypothesis that the pathogenesis of SS might mainly depend on the disruption of the balance of the complex interaction between epigenomic regulatory complexes and the consequences on gene expression opens interesting new perspectives. The standard of care for primary SS is wide surgical resection combined with radiation in selected cases. The role of chemotherapy is still under refinement and can be considered in patients at high risk of metastasis or in those with advanced disease. Cytotoxic chemotherapy (anthracyclines, ifosfamide, trabectedin, and pazopanib) is the treatment of choice, despite several possible side effects. Many possible drug-able targets have been identified. However, the impact of these strategies in improving SS outcome is still limited, thus making current and future research strongly needed to improve the survival of patients with SS.

Introduction: Periacetabular reconstruction after resection of primary bone tumour is a very demanding procedure. They are frequently associated with scarce functional results and a high rate of complications. We report a series of patients with periacetabular resections for primary bone tumours and reconstruction with a porous tantalum (PT) acetabular cup (AC). Materials and methods: 27 patients (median age 30 years) were included, being affected by primary bone tumours of the pelvis and treated with peri-acetabular resection and reconstruction with a PT AC. The diagnoses were 13 osteosarcomas, 7 chondrosarcomas and 7 Ewing sarcomas. Function was assessed with the Harris Hip Score and complications were classified according to Zeifang. Results: The median follow-up was 70 months. 1 patient required removal of the PT AC because of implant associated infection 55 months after surgery. There was 1 hip dislocation and no case of aseptic loosening. At final follow-up, the median HHS was 81 points (range 48–92). Conclusions: The used PT AC had good medium-term survival rates and good functional results. This technique is a viable reconstructive option after resections of periacetabular primary bone sarcomas.

Background and purpose To identify anatomical and/or preplanning characteristics correlated with left descending artery (LAD) dose and therefore provide guidance in the selection of patients with left-breast cancer that could benefit the most from the use of deep inspiration breath hold radiotherapy (DIBH-RT). Materials and methods We retrospectively identified patients with left-sided breast cancer who underwent whole breast radiotherapy in DIBH and extracted data from treatment plans in free-breathing (FB) and DIBH. The following anatomical parameters were obtained from the planning CTs in FB: lung volume, heart volume, breast separation, minimum distance from LAD to tangent open field. Receiving operating characteristics was also performed to define the cut-off point of parameters to use in LAD dosimetry prediction. Areas under the curve (AUCs) were calculated for all variables. Post-test probability has been calculated to evaluate advantage for parameters combination. Results One hundred ninety-seven patients were identified. The strongest predictor at FB CT scan of LAD maximum dose > 10 Gy and a LAD mean dose > 4 Gy was the minimum distance of LAD from tangent open fields. Adding consecutively other preplanning anatomic parameters, the positive predictive value (PPV) to identify patients at risk of higher dose to LAD was > 90%. Conclusions The dosimetric benefit of DIBH is valid for all patients and DIBH should be preferred for all left sided patients; however we can identify a subgroup of patients who benefit the least from DIBH. This is the group with favorable anatomy: limited breast separation, well expanded lungs, LAD distant from open tangent fields.

The use of a navigation system allows precise resection of a tumor and accurate reconstruction of the resultant defect thereby sparing important anatomical structures and preserving function. It is an “image-based” system where the imaging (computed tomography and magnetic resonance imaging) is required to supply the software with data. The fusion of the preoperative imaging provides pre-operative information about local anatomy and extent of the tumor, so that it allows an accurate preoperative planning. Accurate pre-operative imaging is mandatory in order to minimize CATS errors, thus performing accurate tumor resections.

Lung cancer accounts for the largest amount of deaths worldwide with respect to the other oncological pathologies. To guarantee the most effective cure to patients for such aggressive tumours, radiomics is increasing as a novel and promising research field that aims at extracting knowledge from data in terms of quantitative measures that are computed from diagnostic images, with prognostic and predictive ends. This knowledge could be used to optimize current treatments and to maximize their efficacy. To this end, we hereby study the use of such quantitative biomarkers computed from CT images of patients affected by Non-Small Cell Lung Cancer to predict Overall Survival. The main contributions of this work are two: first, we consider different volumes of interest for the same patient to find out whether the volume surrounding the visible lesions can provide useful information, second, we introduce 3D Local Binary Patterns, which are texture measures scarcely explored in radiomics. As further validation, we show that the proposed signature outperforms not only the features automatically computed by a deep learning-based approach, but also another signature at the state-of-the-art using other handcrafted features.

BackgroundSymptoms of SARS-CoV-2 infection in children are nonspecific and shared with other common acute viral illnesses (fever, respiratory or gastrointestinal symptoms, and cutaneous signs), thus making clinical differential diagnosis tricky. In Italy, first line management of pediatric care is handed over to Primary Care Pediatricians (PCPs), who were not allowed to directly perform diagnostic tests during the recent COVID-19 outbreak. Without a confirmatory diagnosis, PCPs could only collect information on “COVID-19 like symptoms” rather than identify typical COVID-19 symptoms.AimTo evaluate the prevalence of COVID-19 like symptoms in outpatient children, during Italian lockdown. To provide PCPs a risk score to be used in clinical practice during the differential diagnosis process.MethodsA survey was submitted to 50 PCPs (assisting 47,500 children) from 7 different Italian regions between the 4th of March and the 23rd of May 2020 (total and partial lockdown period). COVID-19 like symptoms in the assisted children were recorded, as well as presence of confirmed/suspected cases in children’s families, which was taken as proxy of COVID-19. Multivariable logistic regression was accomplished to estimate the risk of having suspected/confirmed cases in families, considering symptoms as potential determinants.Results2,300 children (4.8% of overall survey population) fell ill with COVID-19 like symptoms, 3.1% and 1.7% during total and partial lockdown period respectively. The concurrent presence of fatigue, cough, and diarrhea in children, in absence of sore throat/earache and abnormal skin signs, represents the maximum risk level of having a suspected/confirmed case of COVID-19 at home.ConclusionsThe percentage of children presenting COVID-19 like symptoms at home has been remarkable also during the total lockdown period. The present study identified a pattern of symptoms which could help, in a cost-effective perspective, PCPs in daily clinical practice to define priorities in addressing children to the proper diagnostic procedure.

Prosthetic joint infection (PJI) is a common complication following orthopedic megaprosthetic implantations (EPR), estimated up to 50%. Silver coatings were introduced in order to reduce the incidence of PJI, by using the antibacterial activity of silver. Three different silver coatings are available: MUTARS® (Implantcast), Agluna® (Accentus Medical), PorAg® (Waldemar Link). The aim of this review is to provide an overview on efficacy and safety of silver-coated EPR both in primary and revision surgery, comparing infection rate according to the type of implant. Through an electronic systematic search, we reviewed the articles concerning silver-coated EPRs. Infection rate, silver-related complications, local and blood concentrations of the silver were evaluated. Meta-analyses were performed to compare results from each study included. Nineteen studies were included. The overall infection rate in patients with silver-coated implants was 17.6% (133/755). Overall infection rate in primary silver-coated EPR was been 9.2% (44/445), compared to 11.2% (57/507) of non-silver-coated implants. The overall infection rate after revisions was 13.7% (25/183) in patients with silver-coated EPR and 29.2% (47/161) when uncoated EPR were used, revealing a strength statistically significative utility of silver coatings in preventing infections in this group (p: 0.019). Generally, the use of MUTARS® EPR had produced an almost constant decrease in the incidence of primary PJI but there are few data on the effectiveness in revisions. The results from the use of Agluna® in both primary and revisions implants are inconstant. Conversely, PorAg® had proven to be effective both in PJI prevention but, especially, when used in PJI revision settings. Local argyria was reported in 8 out of 357 patients (2.2%), while no systemic complications were described. Local and blood concentrations of silver were always reported very far to the threshold of toxicity, with the lowest concentration found using PorAg®. Silver-coated EPRs are safe and effective in reduction in PJI and re-infection rate, in particular when used in higher risk patients and after two-stage revisions to fight PJI.

Study design: Systematic review of the literature. Purpose: To systematically review the literature to assess the efficacy of night-time bracing in controlling curve progression with respect to traditional full-time thoraco-lumbo-sacral orthoses (TLSOs) in patient with adolescent idiopathic scoliosis. Methods: PubMed, Ovid, Cochrane Reviews and Google Scholar were all accessed and a combination of terms and keywords pertaining to the core concept was used in the research. Case reports, technical notes, instructional courses, literature reviews, biomechanical and/or in vitro studies were all excluded, as well as case series (level IV studies). The methodological quality of the selected articles was assessed using the MINORS methodology score. Given the overall level and quality of the available evidence, conclusions were drawn based on a summary of the evidence. Results: Seven studies were included. Five papers reported no differences in curve progression between traditional TLSOs and night-time braces and the remaining two studies reported TLSO to be superior. Conclusion: The current available literature does not permit us to draw conclusions about night-time braces. The low methodological quality of the studies examined makes it impossible to compare the effectiveness of the night-time braces with that of traditional TLSOs. Prospective well-designed clinical trials applying SRS inclusion and evaluation criteria are mandatory to better define the role of night-time orthosis in the treatment of adolescent idiopathic scoliosis.

Pancreatic ductal adenocarcinoma (PDAC) is the fourth leading cause of cancer-related death in women (7%) and the sixth in men (5%) in Italy, with a life expectancy of around 5% at 5 years. From 2010, the Italian Association of Medical Oncology (AIOM) developed national guidelines for several cancers. In this report, we report a summary of clinical recommendations of diagnosis, treatment and follow-up of PDAC, which may guide physicians in their current practice. A panel of AIOM experts in upper gastrointestinal cancer malignancies discussed the available scientific evidence supporting the clinical recommendations.

Aim: Anatomic (AN) Endoprosthesis (EPR) reconstructions of the shoulder after intra-articular proximal humerus (Malawer type 1) resections are characterized by early recovery and low complications rate. However, shoulder instability and limited mobility can occur. Reverse shoulder (RS) EPR has been introduced to improve functional outcome. The aim of this systematic review is to evaluate shoulder reconstructions with AN or RS EPR after Malawer type 1 resection, comparing complications and functional results. Methods: Through an electronic systematic search of PubMed, articles concerning EPR after shoulder Malawer type 1 resections were reviewed. Complications rate, range of motion (ROM) and functional outcome (Musculoskeletal Society Tumor Society—MSTS score) of AN and RS EPR were evaluated. Results: Sixteen studies were included. A similar complication rate was observed between AN and RS EPR rate (26.4% and 22.4%, respectively, p = 0.37). Soft tissue failure was the most frequent complication and cause of revision in both groups. Mean post-operative flexion and abduction ROM and MSTS scores were significantly higher in RS EPR, particularly among patients with preserved deltoid function (p = 0.013, p = 0.025 and p = 0.005, respectively). Conclusions: Anatomic and reverse shoulder EPR represent safe and effective implants for shoulder reconstruction, with similar implant stability and complication rates. RS EPR significantly improves post-operative ROM and functional outcomes, especially when at least a partial function of the abductor apparatus is preserved.

Aim Aim of this analysis is to review the role of RT in the management of several rare tumors for adult patients. Methods Collection data regarding RT and rare tumors was made by Pubmed. Results For mucosal melanomas, RT is prescribed, being associated with lower local recurrence rate. For trachea tumors, RT was used as adjuvant or salvage treatment for unresectable disease. For pNET, RT can be a suitable option for post-surgical or unresectable/borderline. For bronchopulmonary neuroendocrine tumors the role of adjuvant treatments is uncertain. For hepatobiliary and ovarian malignancy, stereotactic body RT (SBRT) is a promising approach. For soft tissue sarcoma, perioperative treatments are indicated, and a growing role of SBRT in oligometastatic disease is recognized. For endocrine tumors, adjuvant RT has demonstrated benefits through reducing recurrence risk. Conclusion The radiotherapy is a frequent indication in adult rare cancers; thus the role of Radiation Oncologist must not be neglected.

New RT techniques and data emerging from follow-up for several tumor sites suggest that treatment volume de-escalation may permit to minimize therapy-related side effects and/or obtain better clinical outcomes. Here, we summarize the main evidence about volume de-escalation in RT. The relevant literature from PubMed was reviewed in this article. The ClinicalTrials.gov database was searched for clinical trials related to the specific topic. In Lymphoma, large-volume techniques (extended- and involved-field RT) are being successfully replaced by involved-site RT and involved-node RT. In head and neck carcinoma, spare a part of elective neck is controversial. In early breast cancer, partial breast irradiation has been established as a treatment option in low-risk patients. In pancreatic cancer stereotactic body radiotherapy may be used to dose escalation. Stereotactic radiosurgery should be the treatment choice for patients with oligometastatic brain disease and a life expectancy of more than 3 months, and it should be considered an alternative to WBRT for patients with multiple brain metastases. Further clinical trials are necessary to improve the identification of suitable patient cohorts and the extent of possible volume de-escalation that does not compromise tumor control.

Purpose: To evaluate the predictive value of 18F-FDG PET/CT semiquantitative parameters of the primary tumour and CA 19-9 levels assessed before treatment in patients with locally advanced pancreatic cancer (LAPC). Methods: Among one-hundred twenty patients with LAPC treated at our institution with initial chemotherapy followed by curative chemoradiotherapy (CRT) from July 2013 to January 2019, a secondary analysis with baseline 18F-FDG PET/CT was conducted in fifty-eight patients. Pre-treatment CA 19-9 level and the maximum standardized uptake value (SUVmax), metabolic tumour volume (MTV) and total lesion glycolysis (TLG) of primary tumour were measured. The receiving operating characteristics (ROC) analysis was performed to define the cut-off point of SUVmax, MTV, TLG and CA 19-9 values to use in prediction of early progression (EP), local progression (LP) and overall survival (OS). Areas under the curve (AUCs) were assessed for all variables. Post-test probability was calculated to evaluate the advantage for parameters combination. Results: For EP, CA 19-9 level &gt, 698 U/mL resulted the best marker to identify patient at higher risk with OR of 5.96 (95% CI, 1.66&ndash, 19.47, p = 0.005) and a Positive Predictive Value (PPV) of 61%. For LP, the most significant parameter was TLG (OR 9.75, 95% CI, 1.64&ndash, 57.87, p = 0.012), with PPV of 83%. For OS, the most significant parameter was MTV (OR 3.12, 95% CI, 0.9&ndash, 10.83, p = 0.07) with PPV of 88%. Adding consecutively each of the other parameters, PPV to identify patients at risk resulted further increased (&gt, 90%). Conclusions: Pre-treatment CA 19-9 level, as well as MTV and TLG values of primary tumour at baseline 18F-FDG PET/CT and their combination, may represent significant predictors of EP, LP and OS in LAPC patients.

Background: The aim of this retrospective study is to verify whether preoperative systemic inflammatory markers (serum C-reactive protein [CRP] and neutrophil-lymphocyte ratio [NLR]) can help in predicting the disease-specific survival (DSS) and local recurrence (LR) rate in adult patients affected by localized myxofibrosarcoma (MFS) of the extremities. Methods: We reviewed 126 adult patients with primary, localized MFS of the limbs. We analyzed DSS and LR. Results: Median age at the time of surgery was 68 years (range 19–92). Median CRP was 0.4 mg/dL and median NLR was 2.8. A worse DSS was found in patients who had preoperative CRP >0.5 mg/dL (p = 0.002) and in those with NLR >3.5 (p < 0.001). In multivariate analysis, tumor size and grade as well as preoperative CRP values and NLR were confirmed to be prognostic factors in terms of DSS. An increased risk of LR was found in multivariate analysis in patients with a tail sign and with high gadolinium enhancement at preoperative MRI. Conclusions: Patients with high preoperative CRP and NLR levels, as well as large and high-grade tumors, might be considered as candidates for additional, more aggressive treatment approaches or more stringent follow-up schedules.

The difficulty in conducting meaningful clinical research is a multifactorial issue, involving political, financial and cultural problems, which can lead to unexpected negative long-term consequences, in terms of knowledge advancement and impact on patient care. The aims of the present review were to evaluate the publications of Italian radiotherapy (RT) groups during a 20-year period and to verify whether research is still appealing to young radiation oncologists (ROs) in Italy. PubMed database was searched for English-language articles published by Italian groups from January 1985 to December 2005. Analyzed variables were: publication/year, kind of study, geographical area and age of the first author. The systematic review identified 3291 articles: 1207 papers fulfilled the inclusion criteria. The number of Italian published papers increased during the examined period. Retrospective analyses, prospective phase I–II trials and literature reviews were 44, 20 and 14.5% of all published manuscripts, respectively. Randomized trials showed a mild increase from 2000 to 2005, but their absolute number remained low respect to other types of studies (4%). Northern Italy produced the very most of Italian research papers (58.7%). The age of the first/second author was evaluated on 716 papers: In more than 50% of cases, the first author was younger than 40. Despite a general gradual improvement, RT clinical research suffers in Italy (as elsewhere) from insufficient funding, with a negative impact on evidence production. It is worth noting that clinical research is still appealing and accessible to junior Italian RO.

Ideal time interval between end of neoadjuvant radio-chemotherapy (NRCT) and surgery for rectal cancer is debated. Effect that different time intervals have on postoperative complications with particular regard to anastomotic dehiscence (AD) was evaluated on 167 patients who underwent surgery after long-course NRCT. Three different time intervals were considered: (0–42; 43–56; > 57 days). A time interval > 57 days was significantly protective for AD (p = 0.04, Odds ratio = 0.35; 95% CI 0.1254–0.9585) without influence on early oncological outcomes. Optimal time interval after end of NRCT and surgery may help achieving the best pathological response with lowest postoperative morbidity. Trial registration number: Clinical Trial. Gov NCT04013347. https://clinicaltrials.gov/ct2/results?cond=&term=NCT04013347&cntry=&state=&city=&dist= ).

Aim: To evaluate the efficacy of a propolis-based syrup, FARINGEL®, in preventing radiation-induced esophagitis in locally advanced lung cancer patients. Methods. Patients were treated with concurrent chemoradiotherapy (CRT) using involved-field radiotherapy (RT). Every patient received FARINGEL at the beginning of CRT until the first follow-up. The data of the study group were compared with the data of a control group treated without the administration of the syrup. Results: Forty-five patients were enrolled. Forty-one (91.1%) completed the protocol and were evaluable for esophagitis. Grade ≥2 toxicity occurred in 9/41 patients (22%). No differences in overall toxicity were detected between the study group and the control group (n = 55, 60.9 vs. 54.5%; p = ns). Grade 2–3 esophagitis was lower in the study group in comparison with the control group (22 and 38%, respectively), but statistical significance was not reached (p = 0.09). However, the onset of grade ≥2 esophagitis was delayed in the study group compared to the control group, occurring at higher doses of RT (41.8 vs. 25.4 Gy; p < 0.001). Furthermore, the mean number of interruption days for esophagitis was lower in the study group than in the control group (0.6 ± 2.0 vs. 2.1 ± 3.6; p = 0.025). Conclusion: FARINGEL was well-tolerated and delayed esophagitis that was induced by CRT for locally advanced lung cancer.