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This study aimed to provide real-world safety and effectiveness data of everolimus (EVE) plus exemestane (EXE) in estrogen receptor positive/human epidermal growth factor receptor 2 negative (ERThis prospective observational study was conducted by 19 hospital-based oncologists in Greece. Eligible patients were treated with EVE+EXE in the first-line setting; EVE was initiated according to the approved label.Overall, 75 eligible patients (mean age: 66.9 years; visceral metastases: 49.3%; bone-only metastases: 37.3%) were included in the effectiveness analyses. Over a median (interquartile range) of 12.1 months (range=4.2-20.5 months) of EVE treatment, the median progression-free survival was 18.0 months and the overall response rate was 22.7%. Among patients that received ≥1 EVE dose (n=80), the incidence of EVE-related adverse events was 72.5% (serious: 55.0%); stomatitis (22.5%), fatigue (22.5%), pneumonitis (18.8%); and cough (18.8%) were the most common.In the routine care in Greece, EVE demonstrates clinical benefit and a predictable safety profile.

Acquired immune resistance (AIR) describes a situation in which cancer patients who initially responded clinically to immunotherapies, after a certain period of time, progress with their disease. Considering that AIR represents a feedback response of the tumor against the immune attack generated during the course of immunotherapies, it is conceivable that AIR may also occur before treatment initiation as a mechanism to escape endogenous adaptive antitumor immunity (EAAI). In the present study, we assessed the EAAI in paraffin-embedded breast primary tumor tissue samples and drew correlations with the clinical outcomes. In particular, we analyzed densities of CD8+ cells as elements mediating antitumor cytotoxicity, and of CD163+ and FoxP3+ cells as suppressor elements. We found a direct correlation between the densities of CD8+ cells and of CD163+ and/or FoxP3+ cells in the vast majority of patients’ tumors. Importantly, the vast majority of patients whose tumors were overpopulated by CD8+ cells developed AIR, which was characterized by high intratumoral CD163+ and/or FoxP3+ cell densities and reduced overall survival (OS). We also showed that AIR depends on the levels of CD8+ cell-ratios in the tumor center to the invasive margin. Our data suggest that tumors develop AIR only when under a robust endogenous immune pressure.

Background Walch B2 glenoid morphology with glenohumeral osteoarthritis is a difficult degenerative pattern to manage for shoulder surgeons. Anatomic total shoulder arthroplasty (TSA) in combination with eccentric reaming or bone grafting are the traditional methods of treatment. Newer approaches such as TSA with posteriorly augmented glenoid components and reverse shoulder arthroplasty (RSA) may offer better stability for the posteriorly subluxated biconcave B2 wear pattern. The aim of this systematic review is to compare mid-term surgical and functional outcomes of Walch B2 glenoids without significant rotator cuff pathology treated with TSA and RSA. Methods The review was performed according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines by searching the MEDLINE (PubMed) and Embase (Elsevier) databases. Inclusion criteria were clinical studies that evaluated the outcomes and complications of TSA or RSA in the setting of B2 glenoid morphology without significant rotator cuff pathology. Data relevant to TSA and RSA surgical outcomes were extracted and compiled, and outcomes were compared. A meta-analysis of proportions of complication and revision rates among TSA and RSA groups was performed. Results Overall, 16 articles were included with 414 TSAs and 78 RSAs. The average follow-up duration was 54.1 ± 14.8 months for patients undergoing TSA and 44.8 ± 10.1 months for patients undergoing RSA. The TSA group was further subdivided based on the use of eccentric reaming (135 TSAs), an augmented glenoid component (84 TSAs), or bone grafting (11 TSAs) or was unspecified (184 TSAs). Overall, patients undergoing TSA and RSA demonstrated mean improvements of 50.1 ± 8.5° and 64.7 ± 5.2° in active flexion, 58.5 ± 10.3° and 68.9 ± not reported° in active abduction, and 31.3 ± 5.7° and 29.0 ± 10.2° in active external rotation, respectively. In regard to functional outcome scores, patients undergoing TSA and RSA showed mean Constant score improvements of 38.8 ± 5.3 and 46.6 ± 3.1 points and American Shoulder and Elbow Surgeons score improvements of 48.2 ± 1.0 and 49.2 ± 25.3 points, respectively. Results of the meta-analysis with mid-term follow-up data demonstrated pooled complication rates of 9% (95% confidence interval [CI], 1%-22%) for TSA and 6% (95% CI, 0%-28%) for RSA and pooled revision rates of 2% (95% CI, 0%-8%) for TSA and 1% (95% CI, 0%-15%) for RSA. Conclusion In the setting of Walch B2 glenoid morphology, TSA with eccentric reaming or an augmented component yields comparable outcomes to RSA. Based on the patient's age, activity level, and expectations, both TSA and RSA can be considered a reasonable option to treat Walch B2 glenoid morphology.

This non-interventional, multicenter, prospective study aimed to evaluate the real-world activity of trabectedin, and its impact on symptom burden and quality of life in patients with advanced soft tissue sarcoma (aSTS) treated in routine clinical settings in Greece. Patients with histologically confirmed aSTS newly initiated on trabectedin were enrolled. The primary endpoint was progression-free survival (PFS) rate at 6 months. Secondary endpoints included PFS rate at 3 months, median PFS, objective response rate (ORR), disease control rate (DCR), overall survival (OS), and an assessment of the impact of treatment on health-related quality of life (HRQoL), cancer-related symptom burden and symptom interference with function, as well as all-cause treatment discontinuation rate. A total of 64 eligible patients from 13 Greek centers were evaluated. Patients received a median of three trabectedin cycles per patient (interquartile range [IQR]: 2.0–6.0). Median PFS was 6.6 months with 67.9% and 51.2% of patients free from progression at 3 and 6 months, respectively. ORR was 7.8% and DCR 21.9%. Median OS was 13.1 months. No significant changes from enrolment were noted in HRQoL scores. In total, 30 patients (46.9%) had at least one trabectedin-related adverse drug reaction (ADR) and 9 (14.1%) at least one serious ADR. The treatment discontinuation rate due to toxicity was 9.4%. These results suggest that trabectedin is an active treatment with clinically meaningful benefits in patients with aSTS with no new safety signals.

Pulmonary embolism (PE), along with deep vein thrombosis, are collectively known as venous thromboembolism (VTE). Predisposing factors for PE include post-operative conditions, pregnancy, cancer and an advanced age; of note, a number of genetic mutations have been found to be associated with an increased risk of PE. The association between cancer and VTE is well-established, and cancer patients present a higher risk of a thrombotic event compared to the general population. In addition, PE is a significant cause of morbidity and mortality among cancer patients. The aim of the present study was to illustrate the clinical characteristics, laboratory findings, radiology features and outcomes of cancer patients who developed PE, collected from an anticancer hospital. For this purpose, adult cancer patients diagnosed with PE by imaging with computed tomography pulmonary angiography were enrolled. The following data were recorded: Demographics, comorbidities, type of cancer, time interval between cancer diagnosis and PE occurrence, the type of therapy received and the presence of metastases, clinical signs and symptoms, predisposing factors for PE development, laboratory data, radiological findings, electrocardiography findings, and the type of therapy received for PE and outcomes in a follow-up period of 6 months. In total, 60 cancer patients were enrolled. The majority of the cancer patients were males. The most common type of cancer observed was lung cancer. The majority of cases of PE occurred within the first year from the time of cancer diagnosis, while the majority of patients had already developed metastases. In addition, the majority of cancer patients had received chemotherapy over the past month, while they were not receiving anticoagulants and had central obstruction. A large proportion of patients had asymptomatic PE. The in-hospital mortality rate was 13.3% and no relapse or mortality were observed during the follow-up period. The present study demonstrates that elevated levels of lactic acid and an increased platelet count, as well as low serum levels of carcinoembryonic antigen, albumin and D-dimer, may be potential biomarkers for asymptomatic PE among cancer patients.

Although brain metastases from bone and soft tissue sarcoma are uncommon, advances in sarcoma treatment have led to an increasing incidence of them. We present a 23-year-old male with a history of metastatic femoral osteosarcoma, who presented with headache and unsteady gait and was diagnosed with a cerebellar metastasis. CT scan revealed a mass in the left cerebellar parenchyma with large intralesional central calcification and perilesional edema. Corticosteroid treatment led to neurological symptoms resolution, with a rapid tapering. The patient had also lung metastases and we opted to administer systemic treatment with the tyrosine kinase inhibitor cabozantinib. Given the relative radioresistance of osteosarcomas, the patient did not receive radiation therapy.

The efficacy of nab-paclitaxel in patients with metastatic breast cancer (MBC) has been demonstrated in randomized clinical trials. However, real-world evidence on effectiveness remains limited. The primary objective of this multicenter prospective study was to assess the overall response rate (ORR) of patients with MBC treated with nab-paclitaxel. Secondary objectives included progression-free survival (PFS), overall survival (OS) and quality of life, assessed with the Functional Assessment of Cancer Therapy-Breast (FACT-B) instrument. Eligible patients (N = 150; 36% with de novo MBC presentation) with a median age of 64.5 years were enrolled (86% were ER+, 33.3% (50/150) were ≥ 70 years of age and 53% were treated in the third or later line of treatment). A median of 6 cycles were administered but 26% of patients required dose reduction due to toxicity. The ORR was 26.7% [95% confidence interval (CI) 19.6–33.7], the median PFS was 6.2 months (95% CI 5.2–7.3), and the median OS 21.1 months (95% CI 17.2-not estimable). There was no statistical significant difference in the median PFS of patients

Purpose AE37 and GP2 are HER2 derived peptide vaccines. AE37 primarily elicits a CD4+ response while GP2 elicits a CD8+ response against the HER2 antigen. These peptides were tested in a large randomized trial to assess their ability to prevent recurrence in HER2 expressing breast cancer patients. The primary analyses found no difference in 5-year overall disease-free survival (DFS) but possible benefit in subgroups. Here, we present the final landmark analysis. Methods In this 4-arm, prospective, randomized, single-blinded, multi-center phase II trial, disease-free node positive and high-risk node negative breast cancer patients enrolled after standard of care therapy. Six monthly inoculations of vaccine (VG) vs. control (CG) were given as the primary vaccine series with 4 boosters at 6-month intervals. Demographic, safety, immunologic, and DFS data were evaluated. Results 456 patients were enrolled; 154 patients in the VG and 147 in CG for AE37, 89 patients in the VG and 91 in CG for GP2. The AE37 arm had no difference in DFS as compared to CG, but pre-specified exploratory subgroup analyses showed a trend towards benefit in advanced stage (p = 0.132, HR 0.573 CI 0.275–1.193), HER2 under-expression (p = 0.181, HR 0.756 CI 0.499–1.145), and triple-negative breast cancer (p = 0.266, HR 0.443 CI 0.114–1.717). In patients with both HER2 under-expression and advanced stage, there was significant benefit in the VG (p = 0.039, HR 0.375 CI 0.142–0.988) as compared to CG. The GP2 arm had no significant difference in DFS as compared to CG, but on subgroup analysis, HER2 positive patients had no recurrences with a trend toward improved DFS (p = 0.052) in VG as compared to CG. Conclusions This phase II trial reveals that AE37 and GP2 are safe and possibly associated with improved clinical outcomes of DFS in certain subgroups of breast cancer patients. With these findings, further evaluations are warranted of AE37 and GP2 vaccines given in combination and/or separately for specific subsets of breast cancer patients based on their disease biology.

We reported the alveolar bone histology prior to dental extractions in cancer patients, who received bone-targeting agents (BTA).Fifty-four patients were included. Patients underwent extractions, and bone biopsies were taken.Extractions were performed due to pain, swelling, purulence, fistula, and numbness, not responding to treatment, in 40 patients (group A); extractions due to asymptomatic, non-restorable teeth, were performed in 14 patients (group B). Complete alveolar jaw bone histological necrosis was observed in 28 of 40 (70%) patients of group A and none of group B (p .001). The development of clinical osteonecrosis (MRON) was assessed in 44 patients; 10 patients, who were also treated with Low Level Laser Treatments-LLLT, were excluded from this analysis, as the alternative therapies were a confounding factor. Twelve patients, with alveolar bone histological necrosis prior to extraction, developed medication-related osteonecrosis of the jaw (MRONJ) compared with two patients with vital or mixed vital/non-vital bone (p .0007). BTAs1 year and concurrent targeted therapy were also significantly associated with MRONJ (p = .016 and p = .050).Pain, swelling, purulence, fistula, and numbness were significantly associated with complete bone histological necrosis prior to extractions and increased MRONJ development. Research is justified to explore whether histological necrosis represents an early stage of osteonecrosis.

Introduction: Nanoparticle albumin-bound (nab)-paclitaxel (nab-P) is approved for the treatment of patients with metastatic breast cancer (MBC) who have failed first-line treatment for metastatic disease and for whom standard, anthracycline containing therapy is not indicated. Real-world evidence on the effectiveness of nab-P is sparse. From this perspective, this non-interventional study was designed to assess the impact of nab-P on the clinical outcomes and the quality of life of patients with MBC in the routine care of Greece. Materials and methods: This multicenter prospective study enrolled consented females with MBC initiated (≤7 days prior to enrollment) on nab-P according to physicians decision. Clinicopathologic parameters and patient-reported outcomes [Functional Assessment of Cancer Therapy-Breast (FACT-B)] were collected at approximately 9-week intervals during the first 12 months of study participation and approximately every 18 weeks thereafter, until the end of the study observation period (maximum 30 months). Results: Between April 2016 and October 2017, 150 eligible patients (99.3% Caucasian) were enrolled in the study in 16 oncology centers. The patients’ median age was 64.5 years (range: 30.7-84.0) and ECOG performance status was 0 in 66.4% and 1 in 26.2%. 45.3% of patients had ≥1 comorbidity (21.3% cardiovascular diseases). The median time elapsed since MBC diagnosis was 22.4 months, while 36.0% of patients were de novo metastatic. The distribution of hormone receptor (HR)/human epidermal growth factor receptor 2 (HER2) status was 74.6% HR+/HER2-, 11.9% HR-/HER2-, 11.2% HR+/HER2+, and 2.2% HR-/HER2+. Most commonly occurring metastatic sites were the bones (55.3%), lung (50.0%), and liver (40.0%). Prior taxane-based therapy was annotated in 40.0% of patients. Of the patients, 11.3% received nab-P as first, 36.0% as second, 23.3% as third, and 29.3% as fourth or further treatment line. A median of 6 cycles (range: 1-33) was administered; 42.7% of the patients completed >6 and 22.0% >8 cycles. Dose reductions were required for 26.0% of the patients, mainly due to toxicity. The objective response rate was 26.7% and the clinical benefit rate was 44.0%. After a median follow-up of 19.3 months, 92 patients had progressed and 57 had died (14 without progression). The median progression-free survival (PFS) was 6.2 months [95% confidence interval (CI): 5.2-7.3]. The 6- and 12-month PFS rates were 50.6% and 30.5%, respectively. The median overall survival was 21.1 months (95% CI: 17.2-not estimable). Liver [hazard ratio (HR): 1.81; 95% CI: 1.24-2.66] and lung (HR: 1.53; 95% CI: 1.04-2.25) metastases were associated with a higher risk of progression or death. No statistically significant change in the patients’ baseline FACT-B total score (median: 93.0) was observed. The serious and non-serious adverse event (AE) incidence rates were 12.7% and 48.0%, respectively with a total of 37 grade ≥3 AEs (not including disease progression) reported. Conclusion: This study generated real-world evidence on the effectiveness of nab-paclitaxel; no new safety signals emerged. Citation Format: Anna Koumarianou, Paris Makrantonakis, Flora Zagouri, Christos Papadimitriou, Athina Christopoulou, Epaminontas Samantas, Christos Christodoulou, Amanda Psyrri, Dimitris Bafaloukos, Gerasimos Aravantinos, Pavlos Papakotoulas, Sofia Baka, Charalampos Andreadis, Athanasios Alexopoulos, Iliada Bombolaki, Katerina Kampoli, Sofia Liori, Kiki Karvounis, Alexandros Ardavanis. Real-world multicenter, prospective study of the effects of nab-paclitaxel on clinical outcomes and quality of life of patients with metastatic breast cancer in Greece. The ‘ABReast’ study [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P2-15-07.

Background: Globally 43.8 million people live with cancer. A 60% increase of cancer cases is estimated by 2040, with 29.4 million patients per year requiring therapy. Optimization of cancer management, using digital innovation, is urgently needed. CureCancer is a patient-centric/driven platform, which enables patients to self-create their profile, report symptoms, and communicate with physicians. We assessed CureCancer’s feasibility and patients’ and HCPs’ satisfaction. Methods: Patients from 9 Centers were asked to register at CureCancer, upload their data and complete a questionnaire on demographics, disease and treatment characteristics, and their satisfaction. Results: 159 patients were enrolled and 144 (90.6%) registered. 114 of 144 (79.1%), 63 males and 51 females, median age 54.5 years, completed the questionnaire. 64 patients were University and 35 were high School graduates. 46 patients had metastatic disease, 87 were on active treatment and 51 received supportive care. All patients also visited non-oncology HCPs. Nineteen patients changed work status and 49 had children below 24 years. Registration was “very/very much” easy for 98 (86.0 %) patients. File uploading was “very/very much” easy for 47 (41.2%) patients. Over 80% of patients and physicians preferred the digital way. 99 patients and all HCPs will recommend CureCancer to others. Easy data access, improved communication, feeling safe, treatment adherence, interventions from distance, particularly during covid-19 pandemic and saving time and money, were highly commented by patients and HCPs. Conclusion: CureCancer was feasible, and patients and HCPs were satisfied. Patients were successful to report information on their demographics, disease and treatment characteristics. They also disclosed the need to visit non-oncology HCPs during their cancer treatment and other socioeconomic issues. Integration of CureCancer in the routine practice is expected to improve cancer care and reduce cancer costs. Patients’ self-reporting, with CureCancer, can increase the accuracy of clinical trial results and map social/work/economic issues following cancer diagnosis to assist health care policy.

Background: Current treatment recommendations for high grade non-metastatic osteosarcoma include perioperative chemotherapy and surgery. Despite this intensive protocol, approximately 40% of patients will relapse. The addition of mifamurtide to adjuvant cytotoxic chemotherapy was associated with a significant improvement in 6-year overall survival (OS) in young patients with resectable osteosarcoma, leading to its approval in Europe and other countries. Very limited real-world data are reported on its use.Methods: We retrospectively evaluated data from osteosarcoma patients who received mifamurtide in the adjuvant setting. Data were obtained from medical records in 2 high-volume bone sarcoma centers. The aim of this study was to collect real-world data on mifamurtide safety and efficacy in Greece. Results: We identified 15 patients with completely resected osteosarcoma who received mifamurtide from September 2015 to January 2020. Median age at diagnosis was 24 years old (16-76). Osteosarcoma arose in the lower extremities (n=12), in the upper extremities (n=2) or in the ilium (n=1). The majority of patients (n=13) received cisplatin/doxorubicin/methotrexate as perioperative chemotherapy and the remaining patients cisplatin/doxorubicin. After a median follow-up of 46.9 months (range, 32.8-61.1), the median recurrence-free survival was 58.7 months (range, 18.5-98.8) and the median OS 64.1 months (range, 25.6-102.6). Except for fever and chills, the only adverse event probably related to mifamurtide was pericarditis (n=1). Conclusions: Mifamurtide was well tolerated in a Greek osteosarcoma population, including patients older than 30 years. The small sample size and the non-comparative design do not allow drawing conclusions on the drug benefit in terms of survival.

Distal radius fractures are among the most common orthopaedic injuries. The volar locking plate is now the most utilized internal fixation method for these fractures. There are few reports of mechanical failure of volar locking plates within the literature. In this case report, we describe successful closed reduction of traumatic volar locking plate plastic deformation with associated fracture. In addition, we discuss existing literature regarding plastic deformation of distal radius plates.Traumatic, plastic deformation of distal radius volar locking plates with associated fracture may be managed nonoperatively with closed reduction.

Current treatment recommendations for high grade non-metastatic osteosarcoma include perioperative chemotherapy and surgery. Despite this intensive protocol, approximately 40% of patients will relapse. The addition of the immunomodulator mifamurtide to adjuvant cytotoxic chemotherapy was associated with a significant improvement in 6-year overall survival (OS) in young patients with resectable osteosarcoma, leading to its approval in Europe and other countries. Very limited real-world data are reported on its use.We retrospectively evaluated data from osteosarcoma patients who received mifamurtide in the adjuvant setting. Data were obtained from medical records in 2 high-volume bone sarcoma centers. The aim of this study was to collect real-world data on mifamurtide safety and efficacy in Greece.We identified 15 patients with completely resected osteosarcoma who received mifamurtide from September 2015 to January 2020. Median age at diagnosis was 24 years old (16-76). Osteosarcoma arose in the lower extremities (n = 12), in the upper extremities (n = 2) or in the ilium (n = 1). The majority of patients (n = 13) received cisplatin/doxorubicin/methotrexate as perioperative chemotherapy and the remaining patients cisplatin/doxorubicin. After a median follow-up of 46.9 months (range, 32.8-61.1), the median recurrence-free survival was 58.7 months (range, 18.5-98.8) and the median OS 64.1 months (range, 25.6-102.6). Except for fever and chills, the only adverse event probably related to mifamurtide was pericarditis (n = 1).Mifamurtide was well tolerated in a Greek osteosarcoma population, including patients older than 30 years. The small sample size and the non-comparative design do not allow drawing conclusions on the drug benefit in terms of survival.

Installation of jacket platforms requires simultaneous and combined operations of multiple assets. Once the whole process has to be planned, it is necessary to predict in a fast and reliable way the possible weather limitations that may occur during the operations. The paper will present the major challenges of this unusual and innovative Dynamic Positioning analysis which has been carried out for Ana Jacket installation. The obtained results show that the Dynamic Positioning system of the core vessel in intact configuration is capable to hold the position for the investigated vessels' arrangements and design operative weather conditions. Lifting, upending and installation of Ana Jacket were carried out successfully in 2021.

Background. Current treatment recommendations for high grade non-metastatic osteosarcoma include perioperative chemotherapy and surgery. Despite this intensive protocol, approximately 40% of patients will relapse. The addition of the immunomodulator mifamurtide to adjuvant cytotoxic chemotherapy was associated with a significant improvement in 6-year overall survival (OS) in young patients with resectable osteosarcoma, leading to its approval in Europe and other countries. Very limited real-world data are reported on its use. Methods. We retrospectively evaluated data from osteosarcoma patients who received mifamurtide in the adjuvant setting. Data were obtained from medical records in 2 high-volume bone sarcoma centers. The aim of this study was to collect real-world data on mifamurtide safety and efficacy in Greece. Results. We identified 15 patients with completely resected osteosarcoma who received mifamurtide from September 2015 to January 2020. Median age at diagnosis was 24 years old (16–76). Osteosarcoma arose in the lower extremities (n = 12), in the upper extremities (n = 2) or in the ilium (n = 1). The majority of patients (n = 13) received cisplatin/doxorubicin/methotrexate as perioperative chemotherapy and the remaining patients cisplatin/doxorubicin. After a median follow-up of 46.9 months (range, 32.8–61.1), the median recurrence-free survival was 58.7 months (range, 18.5–98.8) and the median OS 64.1 months (range, 25.6–102.6). Except for fever and chills, the only adverse event probably related to mifamurtide was pericarditis (n = 1). Conclusions. Mifamurtide was well tolerated in a Greek osteosarcoma population, including patients older than 30 years. The small sample size and the non-comparative design do not allow drawing conclusions on the drug benefit in terms of survival. © 2022, The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.

Advanced osteosarcomas (OSs) and Ewing sarcomas (ESs) tend to have poor prognosis with limited therapeutic options beyond first-line therapy. Aberrant angiogenesis and MET signaling play an important role in preclinical models. The anti-angiogenic drug cabozantinib was tested in a phase 2 trial of advanced OS and ES and was associated with clinical benefits. We retrospectively analyzed the off-label use of cabozantinib in adult patients with advanced OS and ES/primitive neuroectodermal tumors (PNETs) in three centers of the Hellenic Group of Sarcoma and Rare Cancers (HGSRC). Between April 2019 and January 2022, 16 patients started taking 60 mg of cabozantinib for advanced bone sarcoma or PNET. Median age at cabozantinib initiation was 31 years (17–83). All patients had received peri-operative chemotherapy for primary sarcoma and between 0 and 4 lines of treatment (median; 2.5) for advanced disease. The most common adverse effects included fatigue, anorexia, hypertransaminasemia, weight loss, and diarrhea. One toxic death was noted (cerebral hemorrhage). Dose reduction to 40 mg was required in 31.3% of the patients. No objective response was noted, and 9/16 patients exhibited stable disease outcomes. Progression-free survival varied from 1 to 8 (median; 5) months. Our study demonstrates that cabozantinib has antitumor activity in this population. In the real-life setting, we observed similar adverse events as in the CABONE study and in other neoplasms.

Background Cancer-associated thrombosis (CAT), the second leading cause of death in patients with cancer can be treated with low molecular weight heparin (LMWH) according to guidelines. Patients and methods A multicenter prospective observational study was carried out to record anti-thrombotic treatment practice, assess thrombosis recurrence and bleeding, and identify potential risk factors. Adult patients from 18 Oncology Departments throughout Greece were followed-up for 12 months. Results A total of 120 patients with CAT receiving anticoagulant treatment were enrolled (35% incidental); 85% were treated for more than 6 months, 95.8% were treated with tinzaparin and smaller percentages with other agents. Thrombosis recurred in three patients and there was minor bleeding in four patients. Bleeding was associated with high body mass index (>35 kg/m2), trauma history, renal insufficiency and bevacizumab use. Conclusion Incidental thrombosis contributes significantly to CAT burden. Long-term use of LMWH seems to be effective and safe. Several risk factors associated with bleeding should be considered during anti-coagulation therapy planning.

Front-line bevacizumab (BEV) in combination with taxanes offers benefit in progression-free survival (PFS) in metastatic breast cancer (mBC). The medical records of mBC patients, treated with front-line BEV-based chemotherapy, were retrospectively reviewed in order to generate real life safety and efficacy data. Patients with human epidermal growth factor receptor 2 (HER2)-negative mBC treated with front-line BEV in combination with chemotherapy were eligible. Maintenance therapy with BEV and/or hormonal agents was at the physicians’ discretion. Among the 387 included patients, the most common adverse events were anemia (61.9%, mainly grade 1), grade 3/4 neutropenia (16.5%), grade 1/2 fatigue (22.3%), and grade 1/2 neuropathy (19.6%). Dose reductions were required in 164 cycles (7.1%) and toxicity led to treatment discontinuation in 21 patients (5.4%). The median PFS and the median overall survival (OS) were 13.3 (95% CI: 11.7–14.8) and 32.3 months (95% CI: 27.7–36.9), respectively. Maintenance therapy, with hormonal agents (ET) and/or BEV, was associated with longer OS versus no maintenance therapy (47.2 versus 23.6 months; p < 0.001) in patients with hormone receptor (HR)-positive disease and BEV maintenance offered longer OS versus no maintenance in patients with HR-negative disease (52.8 versus 23.3; p = 0.023). These real-life data show that front-line BEV-based chemotherapy in HER2-negative mBC patients is an effective treatment with an acceptable toxicity profile. The potential benefit of maintenance treatment, especially ET, is important and warrants further research.

Thromboprophylaxis, as a preventive measure for cancer-associated thrombosis (CAT), may be beneficial for patients with active cancer and high-risk for thrombosis. The present post hoc analysis include a total of 407 patients enrolled in the Greek Management of Thrombosis study, who received thromboprophylaxis with tinzaparin. The objectives of the present analysis were: i) To obtain sufficient evidence for the administration of prophylaxis in patients with active cancer, irrespective of Khorana risk assessment model score; ii) to identify the selection criteria for both dose and duration of tinzaparin; and iii) to evaluate the efficacy and safety of tinzaparin administered for CAT prophylaxis. The main tumor types for the patients included in the present study were as follows: Lung (25.1%), pancreatic (14.3%), breast (9.1%), stomach (8.4%), colorectal (7.9%) and ovarian (7.6%). Furthermore, metastatic disease was observed in 69.5% of the patients. High thrombotic burden agents (HTBAs) were administered to 66.3% of the patients, and 17.4% received erythropoietin. A total of 43.7% of the patients exhibited a Khorana score2. The results of the present study demonstrated that both the presence of metastatic disease and the use of HTBAs seemed to influence oncologists' decisions for the use of thromboprophylaxis in patients with active cancer, regardless of Khorana score. Tinzaparin, in dose expressed in the standard notation for heparins, i.e., anti-Xa factor international units (Anti-Xa IU), was administered at an intermediate dose (InterD; 8,000-12,000 Anti-Xa IU; once daily) to 52.4% of patients, while the remaining patients received a prophylactic dose (ProD; ≤4,500 Anti-Xa IU; once daily). The average duration of thromoprophylaxis was 5 months. Furthermore, a total of 14 (3.4%) thrombotic events and 6 (1.5%) minor bleeding events were recorded. A total of four thrombotic events were observed following an InterD treatment of tinzaparin, while 10 thrombotic events were observed following ProD treatment. The present study also demonstrated that an InterD of tinzaparin was administered more frequently to patients with a body mass index30 kg/m

Purpose: We assessed CureCancer’s feasibility and patients’ and HCPs’ satisfaction. CureCancer is a patient-centric/driven platform, which enables patients to self-create their profile, report symptoms and communicate with physicians.Methods: Patients from 18 Centers were asked to register at CureCancer, upload their data and complete a questionnaire on demographics, disease and treatment characteristics, and their satisfaction. Results: 159 patients were enrolled and 144 (90.6%) registered. 114 of 144 (79.1%), 63 males and 51 females, median age 54.5 years, completed the questionnaire. 64 patients were University and 35 were high School graduates. 46 patients had metastatic disease, 87 were on active treatment and 51 received supportive care. All patients also visited non-oncology HCPs. Nineteen patients changed work status and 49 had children below 24 years. Registration was “very/very much” easy for 98 (86.0 %) patients. File uploading was “very/very much” easy for 47 (41.2%) patients. Over 80% of patients and physicians preferred the digital way. 99 patients and all HCPs will recommend CureCancer to others. Easy data access, improved communication, feeling safe, treatment adherence, interventions from distance, particularly during covid-19 pandemic and saving time and money, were highly commented by patients and HCPs. Conclusion: CureCancer was feasible and patients and HCPs were satisfied. File uploading changed to become more user friendly. Integration of CureCancer in the routine practice is expected to improve cancer care and reduce cancer costs. Patients’ self-reporting, with CureCancer, can increase the accuracy of clinical trial results and map social/work/economic issues following cancer diagnosis to assist health care policy.

Background In the military, return-to-duty status has commonly been used as a functional outcome measure after orthopaedic surgery. This is sometimes regarded similarly to return to sports or as an indicator of return to full function. However, there is variability in how return-to-duty data are reported in clinical research studies, and it is unclear whether return-to-duty status alone can be used as a surrogate for return to sport or whether it is a useful marker for return to full function. Questions/purposes (1) What proportion of military patients who reported return to duty also returned to athletic participation as defined by self-reported level of physical activity? (2) What proportion of military patients who reported return to duty reported other indicators of decreased function (such as nondeployability, change in work type or level, or medical evaluation board)? Methods Preoperative and postoperative self-reported physical profile status (mandated physical limitation), physical activity status, work status, deployment status, military occupation specialty changes, and medical evaluation board status were retrospectively reviewed for all active-duty soldiers who underwent orthopaedic surgery at Madigan Army Medical Center, Joint Base Lewis-McChord from February 2017 to October 2018. Survey data were collected on patients preoperatively and 6, 12, and 24 months postoperatively in all subspecialty and general orthopaedic clinics. Patients were considered potentially eligible if they were on active-duty status at the time of their surgery and consented to the survey (1319 patients). A total of 89% (1175) were excluded since they did not have survey data at the 1 year mark. Of the remaining 144 patients, 9% (13) were excluded due to the same patient having undergone multiple procedures, and 2% (3) were excluded for incomplete data. This left 10% (128) of the original group available for analysis. Ninety-eight patients reported not having a physical profile at their latest postoperative visit; however, 14 of these patients also stated they were retired from the military, leaving 84 patients in the return-to-duty group. Self-reported "full-time duty with no restrictions" was originally used as the indicator for return to duty; however, the authors felt this to be too vague and instead used soldiers' self-reported profile status as a more specific indicator of return to duty. Mean length of follow-up was 13 ± 3 months. Eighty-three percent (70 of 84) of patients were men. Mean age at the preoperative visit was 35 ± 8 years. The most common surgery types were sports shoulder (n = 22) and sports knee (n = 14). The subgroups were too small to analyze by orthopaedic procedure. Based on active-duty status and requirements of the military profession, all patients were considered physically active before their injury or surgery. Return to sport was determined by asking patients how their level of physical activity compared with their level before their injury (higher, same, or lower). We identified the number of other indicators that may suggest decreased function by investigating change in work type/level, self-reported nondeployability, or medical evaluation board. This was performed with a simple survey. Results Of the 84 patients reporting return to duty at the final follow-up, 67% (56) reported an overall lower level of physical activity. Twenty-seven percent (23) reported not returning to the same work level, 32% (27) reported being nondeployable, 23% (19) reported undergoing a medical evaluation board (evaluation for medical separation from the military), and 11% (9) reported a change in military occupation specialty (change of job description). Conclusion Return to duty is commonly reported in military orthopaedics to describe postoperative functional outcome. Although self-reported return to duty may have value for military study populations, based on the findings of this investigation, surgeons should not consider return to duty a marker of return to sport or return to full function. However, further investigation is required to see to what degree this general conclusion applies to the various orthopaedic subspecialties and to ascertain how self-reported return to duty compares with specific outcome measures used for particular procedures and subspecialties. Level of evidence Level IV, therapeutic study.

Introduction: Coexistance of pancreatic carcinoma and Leriche syndrome is an extremely rare pathological condition. Leriche syndrome is defined as occlusion of the distal aorta at the bifurcation into the common iliac arteries. Case Report: We report the case of a 57-year old male patient with a locally advanced pancreatic tumor that during chemotherapy presented Leriche syndrome. Four months after the diagnosis and although the initial staging by MRI had only revealed a few atheromatic lesions of the abdominal aorta, the patient complained about claudication of the legs and hypoesthesia. Angiography with multi-detector computed tomography (MDCTA) was performed using aortography protocol and three-dimensional reconstruction of the images followed, deCmonstrating the relationship between pancreatic carcinoma and Leriche syndrome. : Review of the literature revealed that acute abdominal thrombosis is rare in cancer patients. To our knowledge, complete occlusion of the aorta in a patient with pancreatic cancer has not been reported yet.

Background Current chemotherapy regimens for the treatment of colorectal cancer (CRC) include oxaliplatin, irinotecan, and fluorouracil along with leucovorin. Cytotoxicity involves the induction of programmed cell death. Objective The purpose of this study was to assess the molecular effects of doxorubicin (a 14-OH derivative of the natural product daunorubicin) and common chemotherapeutic drugs (used in the clinical practice to treat CRC) on the expression of the most prominent members of the BCL2 family, namely BCL2, BAX, BCLX, and MCL1. Moreover, we sought to define the role of BCL2L12, another member of the BCL2 family, the apoptotic role of which is ambiguous. Methods The MTT cell proliferation assay was used to determine the IC50 of each chemotherapeutic drug at 72 hours of treatment of Caco-2 and DLD-1 colorectal adenocarcinoma cell lines. Real-time PCR was used to quantify the antiapoptotic BCL2-α, BLCX-L, and MCL1-L transcripts, the proapoptotic BAX, BLCX-S, BLCX-ES, MCL1-S, and MCL1-ES transcripts, and BCL2L12 expression in relation to GAPDH mRNA levels. Results We constructed growth curves of Caco-2 and DLD-1 cells and determined the IC50 of each drug at 72 hours of treatment. Significant alterations in the expression levels of the studied BCL2 family genes and/or particular transcripts were observed. Conclusion The intrinsic apoptotic pathway is activated during treatment of CRC cells with common chemotherapeutic drugs. Moreover, BCL2L12 mRNA expression increases progressively during treatment, similarly to the expression of other BCL2 family genes favoring apoptosis and/or particular proapoptotic transcripts, thus suggesting a proapoptotic role for BCL2L12 in chemotherapy-treated CRC cells.

Background The “EMERGE” study, aimed to capture real-life management patterns and outcomes in metastatic breast cancer (MBC) in Greece, also accounting for hormone (HR) and human epidermal growth factor receptor 2 (HER2) status. Methods “EMERGE” was a multicenter, retrospective cohort study of adult MBC patients diagnosed between 01-Janaury-2010 and 30-June-2012, either de novo or having progressed from a non-metastatic state. Patient data, including treatment patterns and outcomes, were mainly abstracted through medical chart review. Results 386 patients were enrolled by 16 hospital-based oncologists between 12-March-2013 and 31-March-2015. The median look-back period was 29.1 months. At MBC diagnosis, 56.1% of the patients were HR+/HER2−, 16.6% HR+/HER2+, 14.5% HR−/HER2−, and 12.8% HR−/HER2+. In the first line setting, chemotherapy, targeted therapy and endocrine therapy were received by 76.7, 52.4, and 28.3% of the overall population, and by 66.5/36.2/42.0%, 80.4/80.4/28.6%, 88.4/90.7/0.0, and 95.6%/56.5/6.5% of the HR+/HER2−, HR+/HER2+, HR−/HER2+, HR−/HER2− subpopulations, respectively. In the overall population, the disease progression incidence rate was 0.57 [95% confidence interval (CI): 0.48–0.67] per person-year; median progression-free survival (PFS) was 22.4 (95% CI: 20.4–24.7) and overall survival (OS) was 45.0 (95% CI: 40.9–55.0) months. Median PFS was 24.6 (95% CI: 21.3–27.9) in HR+/HER2−, 19.7 (95% CI: 12.9–25.9) in HR+/HER2+, 23.0 (95% CI: 16.6–29.7) in HR−/HER2+ and 18.3 (95% CI: 10.0–24.7) months in HR−/HER2− subpopulations. A multivariable Cox proportional hazards model, adjusted among other factors for age and duration of diagnosis, HR and HER2 status, demonstrated that in the overall population PFS was better among those receiving first line endocrine therapy (hazard ratio: 0.70; 95%CI: 0.51–0.95; p = 0.024). Conclusions “EMERGE” demonstrates differences between HR/HER2 subtypes in clinical outcomes and divergence from evidence-based guideline recommendations for MBC management, especially as it pertains to the HR+/HER2− patients in which chemotherapy was favored over endocrine therapy in the first line setting. Study registration The study has been registered on the electronic Registry of Non-Interventional Studies (RNIS) posted on the website of the Hellenic Association of Pharmaceutical Companies (SFEE): https://www.dilon.sfee.gr/studiesp_d.php?meleti_id=NIS-OGR-XXX-2012/1

Background: Angiogenesis is a hallmark of breast cancer (BC) and is mediated by the vascular endothelial growth factor (VEGF) signaling axis. It is regulated by different proangiogenic factors, including platelet-derived growth factor-CC (PDGF-CC) and heparin-binding EGF-like growth factor (HB-EGF), as well as co-receptors, such as neuropilin-1, which could have prognostic implications in BC patients. Patients and methods: We assessed the serum levels of VEGF, HB-EGF, PDGF-CC and neuropilin-1 in 205 patients with early BC (invasive, n = 187; in situ, n = 18) and in 31 healthy donors (HD) and investigated the potential associations with clinical and histopathological parameters. Results: VEGF serum levels were significantly higher in patients with invasive versus ductal carcinomas in situ. PDGF-CC serum concentrations varied among BC molecular subtypes. Furthermore, we observed a differential expression of most biomarkers between overweight/obese (body mass index (BMI) ≥ 25 kg/m2) and non-obese patients among the BC molecular subtypes. Finally, the classification of subjects according to menopausal status revealed a significant difference in specific biomarker levels between patients and HD. Conclusion: The serum concentrations of angiogenic molecules differ among breast cancer molecular subtypes and are affected by the BMI and menopausal status, which could have possible clinical or prognostic implications.

e18677 Background: Venous ThromboEmbolism (VTE), might be a challenge with a lot of negative consequences for patients with active cancer. VTE affects ongoing anticancer treatment, worsening morbidity and mortality, increases economic burden and escalates psychological distress. Incidence of VTE in patients with cancer reported 20%. Current guidelines recommend pharmacologic prophylaxis in ambulatory cancer patients with Khorana score ≥2. Methods: ACT4CAT is a prospective observational phase IV study conducted by HeSMO Greece, aiming to record the clinical practice of VTE prophylaxis in active cancer patients. Ambulatory patients who received thromboprophylaxis enrolled after signing informed consent. Study was approved by bioethics committee. Results: 691 patients from 19 oncology departments received thromboprophylaxis in 1st line 57.6%, 2nd line 14.8%, adjuvant 9.0% and neoadjuvant 7.5%. Age ≥65 found 55%, BMI≥30 17.5% and males 63%. Tumor types: gastrointestinal 45.4%, lung 25.8%, urological 11.6%, gynecological 6.0%, breast 4.2% and others 7.0%. High-Risk for Thrombosis Agents (HRTAs) received 87.2%, specifically: platinum agents (56.3%), antimetabolites (54.2%) and immunotherapy (12.1%). 54,5% of the anticancer agents had potential drug-drug interaction (DDI) with anticoagulation treatment. Thromboprophylaxis duration lasted 5.3±3.5 months. Main agents were: tinzaparin 89.6%, fondaparinux 6.0%, bemiparin 2.2%, enoxaparin 1.6%, apixaban 0.3% and rivaroxaban 0.3%. Intermediate thromboprophylaxis dose received 68% of patients, lower in adjuvant setting (45.2%), with a preference in metastatic cases (OR: 1.5 95% CI: 1.02-2.3, p = 0.026). 14 thrombotic events reported (efficacy: 98.0%, 95%CI: 96.6-98.8%) and 12 grade 1 bleeding (1.7%, 95%CI: 1.0-3.0%). Conclusions: Prevention of VTE in ambulatory patients with active cancer found effective and safe. Apart from the Khorana score, specific patient characteristics, metastasis, HRTAs and DDIs seemed that affect clinical decision for thromboprophylaxis mainly with LMWHs and often on intermediate dose regardless the clinical setting. Oncologists appeared informed that CAT is not negligible risk. Clinical trial information: NCT03909399. [Table: see text]

Pulmonary embolism (PE), along with deep vein thrombosis, are collectively known as venous thromboembo- lism (VTE). Predisposing factors for PE include post-operative conditions, pregnancy, cancer and an advanced age; of note, a number of genetic mutations have been found to be associ- ated with an increased risk of PE. The association between cancer and VTE is well-established, and cancer patients present a higher risk of a thrombotic event compared to the general population. In addition, PE is a significant cause of morbidity and mortality among cancer patients. The aim of the present study was to illustrate the clinical characteristics, laboratory findings, radiology features and outcomes of cancer patients who developed PE, collected from an anticancer hospital. For this purpose, adult cancer patients diagnosed with PE by imaging with computed tomography pulmonary angiography were enrolled. The following data were recorded: Demographics, comorbidities, type of cancer, time interval between cancer diagnosis and PE occurrence, the type of therapy received and the presence of metastases, clinical signs and symptoms, predisposing factors for PE development, laboratory data, radiological findings, electrocardiography findings, and the type of therapy received for PE and outcomes in a follow-up period of 6 months. In total, 60 cancer patients were enrolled. The majority of the cancer patients were males. The most common type of cancer observed was lung cancer. The majority of cases of PE occurred within the first year from the time of cancer diagnosis, while the majority of patients had already developed metastases. In addition, the majority of cancer patients had received chemotherapy over the past month, while they were not receiving anticoagulants and had central obstruction. A large proportion of patients had asymptomatic PE. The in-hospital mortality rate was 13.3% and no relapse or mortality were observed during the follow-up period. The present study demonstrates that elevated levels of lactic acid and an increased platelet count, as well as low serum levels of carcinoembryonic antigen, albumin and D-dimer, may be potential biomarkers for asymptomatic PE among cancer patients. © 2021 Spandidos Publications. All rights reserved.

Simple Summary Therapeutic cancer vaccines have failed to demonstrate clinical improvements in phase III clinical trials over the past two decades. This has led to a rather discouraging view regarding their role in the field of cancer immunotherapy. Herein, we critically examine important issues for improving cancer vaccination strategies in an attempt to rekindle interest for this type of immunotherapy. We highlight the importance of proper clinical design in terms of selected groups of patients, taking into consideration (a) changes in initially established standard-of-care treatments; (b) the appropriate follow-up period necessary to achieve meaningful results; (c) statistical considerations for the delay of treatment effects (i.e., time for development of an effective immune response), thus excluding irrelevant early events; and (d) appropriate biomarkers that could guide vaccinations with clinical benefits to patients. Tackling the aforementioned challenges, therapeutic vaccines could take their rightful place in the immunotherapy hall of fame. Abstract Therapeutic cancer vaccines have been at the forefront of cancer immunotherapy for more than 20 years, with promising results in phase I and—in some cases—phase II clinical trials, but with failures in large phase III studies. After dozens of clinical studies, only Dendreon’s dendritic cell vaccine Sipuleucel-T has succeeded in receiving US FDA approval for the treatment of metastatic castrate-resistant prostate cancer. Although scientists working on cancer immunotherapy feel that this is an essential breakthrough for the field, they still expect that new vaccine regimens will yield better clinical benefits compared to the four months prolonged median overall survival (OS) Sipuleucel-T demonstrated in the IMPACT phase III clinical trial. Clinical development of cancer vaccines has been unsuccessful due to failures either in randomized phase II or—even worse—phase III trials. Thus, rigorous re-evaluation of these trials is urgently required in order to redefine aspects and optimize the benefits offered by therapeutic cancer vaccines. The scope of this review is to provide to the reader our thoughts on the key challenges in maximizing the therapeutic potentials of cancer vaccines, with a special focus on issues that touch upon clinical trial design.

Background: Cancer patients are at high risk for cancer-associated thrombosis (CAT). CAT is the second leading cause of death in these patients but it can be preventable with thromboprophylaxis. Patients and Methods: An observational, prospective, multicenter study aiming to record CAT management in clinical practice was conducted by the Hellenic Society of Medical Oncology (HeSMO). Results: A total of 426 active cancer patients (mean age 65.3 years, mean BMI: 26.1 kg/m2) who received thromboprophylaxis, were included from 18 oncology units. Tumor types were lung 25.1%, pancreas 13.9%, breast 8.7%, stomach 8.5%, ovarian 7.8%, and others 36%, while 69% had metastases. A total of 71% had a Khorana score &le, 2 and 61% received High Thrombotic Risk Chemotherapy Agents (HTRCAs, e.g., platinum). For thromboprophylaxis patients received mainly Low Molecular Weight Heparins (LMWHs), on higher than prophylactic doses in 50% of cases. Overall, 16 (3.8%) thrombotic events and 6 (1.4%) bleeding events were recorded. Notably, patients on higher doses of LMWHs compared to patients who received standard prophylactic doses had 70% lower odds to develop thrombotic events (OR: 0.3, 95% CI: 0.10&ndash, 1.0, p = 0.04). Conclusion: CAT is an important issue in oncology. Along with the Khorana score, factors as metastasis and use of HTRCAs should also be taken into consideration. Thromboprophylaxis for active cancer patients with LMWHs, even on higher doses is safe and efficient.

Purpose: The efficacy of nab-paclitaxel in patients with metastatic breast cancer (MBC) has been demonstrated in randomized clinical trials. However, real-world evidence on effectiveness remains limited. Patients and methods: The primary objective of this multicenter prospective study was to assess the overall response rate (ORR) of patients with MBC treated with nab-paclitaxel. Secondary objectives included progression-free survival (PFS), overall survival (OS) and quality of life, assessed with the Functional Assessment of Cancer Therapy-Breast (FACT-B) instrument. Results: Eligible patients (N = 150; 36% with de novo MBC presentation) with a median age of 64.5 years were enrolled (86% were ER+, 33.3% (50/150) were ≥ 70 years of age and 53% were treated in the third or later line of treatment). A median of 6 cycles were administered but 26% of patients required dose reduction due to toxicity. The ORR was 26.7% [95% confidence interval (CI) 19.6–33.7], the median PFS was 6.2 months (95% CI 5.2–7.3), and the median OS 21.1 months (95% CI 17.2-not estimable). There was no statistical significant difference in the median PFS of patients < and ≥ 70 years of age. The patients’ baseline FACT-B total score remained unchanged. The serious and non-serious adverse event incidence rates were 13% and 48%, respectively. Conclusions: This prospective study provides further evidence on quality of life, efficacy, and safety of nab-paclitaxel in patients with MBC and sheds more light in special subpopulations such as the elderly and those treated beyond the second line. © 2020, Springer Science+Business Media, LLC, part of Springer Nature.

Objective: We reported the alveolar bone histology prior to dental extractions in cancer patients, who received bone-targeting agents (BTA). Subjects and Methods: Fifty-four patients were included. Patients underwent extractions, and bone biopsies were taken. Results: Extractions were performed due to pain, swelling, purulence, fistula, and numbness, not responding to treatment, in 40 patients (group A); extractions due to asymptomatic, non-restorable teeth, were performed in 14 patients (group B). Complete alveolar jaw bone histological necrosis was observed in 28 of 40 (70%) patients of group A and none of group B (p 1 year and concurrent targeted therapy were also significantly associated with MRONJ (p =.016 and p =.050). Conclusion: Pain, swelling, purulence, fistula, and numbness were significantly associated with complete bone histological necrosis prior to extractions and increased MRONJ development. Research is justified to explore whether histological necrosis represents an early stage of osteonecrosis. © 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd. All rights reserved

Background Bladder cancer (BlCa) heterogeneity and the lack of personalised prognosis lead to patients’ highly variable treatment outcomes. Here, we have analysed the utility of the GAS5 tumour-suppressor lncRNA in improving BlCa prognosis. Methods GAS5 was quantified in a screening cohort of 176 patients. Hedegaard et al. (2016) (n = 476) and TCGA provisional (n = 413) were used as validation cohorts. Survival analysis was performed using recurrence and progression for NMIBC, or death for MIBC. Internal validation was performed by bootstrap analysis, and decision curve analysis was used to evaluate the clinical benefit on disease prognosis. Results GAS5 levels were significantly downregulated in BlCa and associated with invasive high-grade tumours, and high EORTC-risk NMIBC patients. GAS5 loss was strongly and independently correlated with higher risk for NMIBC early relapse (HR = 2.680, p = 0.011) and progression (HR = 6.362, p = 0.035). Hedegaard et al. and TCGA validation cohorts’ analysis clearly confirmed the association of GAS5 loss with NMIBC worse prognosis. Finally, multivariate models incorporating GAS5 with disease established markers resulted in higher clinical benefit for NMIBC prognosis. Conclusions GAS5 loss is associated with adverse outcome of NMIBC and results in improved positive prediction of NMIBC patients at higher risk for short-term relapse and progression, supporting personalised prognosis and treatment decisions.

Objective MicroRNA-331 (miR-331) has shown regulatory activity against several genes whose expression has been claimed to be deregulated in breast tumors, including that of epidermal growth factor receptor 2 (HER2). Herein, the clinical value of miR-331 expression was investigated by analyzing its levels in breast benign and malignant tumors. Methods The expression levels of miR-331 were quantified via real-time PCR in 130 malignant and 66 benign breast tissue specimens collected after surgical resection of primary tumors. The generated data were analyzed by applying several statistical tests in order to examine the relationship of miR-331 expression with various established clinicopathological features and survival data of patients. Results Our data showed that miR-331 was overexpressed in malignant breast tumors compared to their benign counterparts both overall (P = 0.026) and individually when the subgroups of fibroadenoma and invasive ductal carcinoma were analyzed with each other (P = 0.001). ROC curve analysis confirmed the diagnostic value of these variations, providing an AUC value equal to 0.597 (P = 0.026) and 0.663 (P = 0.001), respectively. Furthermore, miR-331 levels were elevated (P = 0.026) in ductal cancerous specimens compared to the lobular ones but failed to correlate with other clinicopathological features or survival data of the breast cancer patients. Conclusions Our results provide evidence that miR-331 levels might provide valuable information regarding the differential diagnosis of benign and malignant breast tumors but present no prognostic value for breast cancer.

Primary squamous cell carcinoma (SCC) of the ovary is rare. Most cases arise from a cystic teratoma or less frequently from Brenner tumor or endometriosis. We reviewed 36 cases of primary ovarian SCC reported in the literature including a case diagnosed and treated in our institution.Data was collected by using the key-words "primary squamous cell carcinoma" and "ovary" on Google Scholar and PubMed in April 2018. All reviewed cases were analyzed according to diagnosis, surgical approach, adjuvant therapy and outcome.To date 23 articles presenting 36 cases of primary ovarian SCC are reported. Nine patients had stage I, 8 stage II, 11 stage III and 5 stage IV disease, whereas 3 patients had in situ carcinoma. All patients underwent surgery (mainly hysterectomy with bilateral salpingo-oophorectomy). Adjuvant therapy was reported in 24 patients, 15 of which received chemotherapy, 6 radiotherapy and 3 a combination of both. Chemotherapy regimens were similar to the ones used in ovarian carcinoma (more often platinum plus paclitaxel). Follow-up period was in general short and survival varied between 9 days and 14 years, depending on the stage at diagnosis.Primary ovarian SCC is a rare entity with poor prognosis, compared to serous carcinoma. Treatment is usually extrapolated from classical ovarian carcinoma algorithms, including surgical management combined with adjuvant chemotherapy with or without radiotherapy. Further investigations are needed to define optimal treatment, such as chemotherapy regimens and the role of radiotherapy and lymph node dissection.

The current state of the SARS-CoV-2 pandemic is an equilibrium between expanding vaccine coverage on the one hand, and emergence of variants of concern which compromise vaccine effectiveness and enhance viral transmission on the other. Inequity in vaccine distribution, primarily an ethical issue, challenges this equilibrium, as industrialized countries prepare to administer a third booster dose to their population. Solid tumor cancer patients typically respond well to initial full vaccination and someone could argue that they should not be prioritized for an adjuvant third dose, since protection from severe disease has largely been achieved with the two-dose regimen. Nevertheless, their immune status is dynamic and not all of them exhibit an adequate immune response. A booster third dose is necessary for the inadequate responders, while it will result in better protection of all patients from mild disease as well, which if presented could have ominous consequences due to their overall frailty, and their need to adhere to strict therapeutic schemes. International scientific and public health communities should develop approaches that allow for wide immediate vaccination coverage of the developing world, in parallel with administration of adjuvant doses to solid tumor cancer patients (and other at-risk categories) of the developed nations, in order to avoid prolonging the pandemic, which will be prospectively against cancer patients' best interest.

Introduction/Background Breast cancer (BC), depending on molecular subtype, usually metastasize to the liver, lungs, bone and brain. We report an interesting case of a patient, previously treated for hormone receptor-positive, HER2-negative early BC, who presented 7 years later with HER2-positive metastatic disease. Finally she developed an intramedullary spinal metastasis. Methodology A 61 year-old woman underwent left mastectomy in 2010 for BC hormone receptor-positive, HER2-negative, with lymph node involvement. She also received adjuvant chemotherapy, radiation therapy and hormonal treatment until 2017. In 2017 she received Paclitaxel/Bevacizumab followed by Bevacizumab maintenance for recurrence in the lungs, liver and bones. In February 2018 she underwent rebiopsy in the liver due to progressive disease, which revealed metastasis from hormone receptor-negative, HER2-positive BC. She received Trastuzumab/Pertuzumab/Docetaxel until August 2018. In the meanwhile she receive whole-brain radiation therapy in June 2018 for multiple brain metastases. In August 2018 she started Trastuzumab-Emtansine due to progressive disease. On January 2019 she presented in our department with paraplegia. Results Spine MRI was performed ad revealed an intramedullary lesion on level T12-L1 of 3.6×1.5×1.4 cm with contrast enhancement. Differential diagnosis included metastasis from breast cancer and ependymoma. Blood tests indicated thrombopenia and hepatic disturbances. After discussion with the neurosurgeons and radiation oncologists we did not offer any treatment to our patient, because of the established paralysis of the lower extremities. Conclusion BC can rarely give intramedullary spinal lesions. Their treatment is quite challenging. Disclosure Nothing to disclose.

Background The International Duration Evaluation of Adjuvant Chemotherapy (IDEA) aimed to investigate whether a 3 months (3M) of oxaliplatin/fluoropyrimidine-based adjuvant chemotherapy (CT) is non-inferior to the 6-month (6M) administration in 3-year disease-free survival (3yDFS) in high-risk (HR) stage II or stage III colon cancer (CC). Methods Hellenic Oncology Research Group (HORG)-IDEA randomized patients between 3M and 6M of CT with FOLFOX4 or CAPOX. Results In total 1115 patients, 413 with HR stage II and 702 with stage III CC, were randomized. The median follow-up was 67.0 (38.3–126.0) months. Overall, 394 DFS events (202 in 3M arm and 192 in 6M arm) where recorded. The 3yDFS rate was 77.2% [95% confidence interval (CI) 72.1% to 82.3%] for 3M and 77.9% (72.6% to 82.5%) for 6M of treatment [hazard ratio (HR) 1.05 (95% CI 0.61–1.55); P=0.647]. Eighty DFS events (3M N=41; 6M N=39) were observed in HR stage II patients for a 3yDFS rate of 82.7% and 83.4%, respectively (HR 1.05; 95% CI 0.68–1.63, P=0.829). For stage III patients, 314 DFS events (3M N=161 and 6M N=153) were observed, for a 3yDFS rate of 72.9% for 3M versus 74.1% for 6M (HR 1.06; 95% CI 0.81–1.42, P=0.622). For HR stage II patients receiving FOLFOX4, 3yDFS rate was 76.7% for 3M and 79.3% for 6M (HR 1.21; 95% CI 0.54–2.70). For HR stage II patients receiving CAPOX the 3yDFS rate was 85.4% for 3M and 83.8% for 6M (HR 0.99; 95% CI 0.59–1.67). For stage III patients receiving FOLFOX4, the 3yDFS rate was 71.5% for 3M and 77.3% for 6M (HR 1.18; 95% CI 0.74–1.86). For stage III patients receiving CAPOX, the 3yDFS rate was 74.5% for 3M and 74.7% for 6M (HR 0.99; 95% CI 0.70–1.44). Conclusions The results of the HORG-IDEA study are in line with those of the global IDEA project, indicating that the 3yDFS is dependent on the administered adjuvant regimen and the choice and duration of regimen should be personalized. ClinicalTrials.gov Registration Number NCT01308086.

Ewing Sarcoma/Primitive Neuroectodermal Tumor (ES/PNET) is a malignant small round cell tumor belonging to the Ewing Sarcoma Family of Tumors. It occurs more commonly in children and young adults. Its localization in the adrenal gland is extremely rare. We reviewed 35 cases of ES/PNET of the adrenal gland reported in the literature and presented our case.Data were collected by searching for ES/PNET and adrenal gland key words on Google Scholar and PubMed in March 2018, including a case diagnosed in our department. We analyzed all reviewed cases for diagnosis, surgical and systemic therapy and outcome.To date 24 articles presenting cases of ES/PNET of the adrenal gland are reported in the literature. We included in our review 35 cases previously described and one new case. Histologically all cases consisted of sheets of small round cells. Immunohistochemistry was also performed in all cases. Most cases stained positive for CD99 and negative for lymphocytic markers. Markers of epithelial differentiation displayed variable results. In all cases tested, characteristic translocations were displayed supporting the diagnosis. All patients but four were treated surgically and the majority received adjuvant therapy. Only very few cases received neoadjuvant chemotherapy.Primary ES/PNET of the adrenal gland is a rare tumor, showing specific morphological, immunohistochemical and cytogenetic characteristics. Treatment consists of surgery, chemotherapy and radiotherapy. Further investigations paired with long term follow-up are necessary to define prognosis for this rare entity.

Immunotherapy (IO) with anti-PD1 inhibitors is available for the treatment of recurrent/metastatic squamous cell carcinomas of the head and neck (SCCHD) since 2016. Both nivolumab and pembrolizumab were tested in phase 3 randomized trials in adults progressing on or after platinum-based therapy and were found to confer an overall survival benefit compared to investigator’s choice. However, very limited data exist concerning IO use in rare subtypes of head and neck carcinoma, like salivary gland carcinoma. We retrospectively collected clinical data of all patients diagnosed with rare subtypes of head and neck carcinoma, who were treated with immune checkpoint inhibitors in our department during the last 5 years. We analyzed safety and efficacy of these therapies. We identified six patients who received nivolumab for recurrent or metastatic head and neck carcinomas, between 31 and 57 years old. All patients had received at least one line of platinum-chemotherapy, as well as radiation therapy. Treatment was administered every 2 weeks, at a dose of 3 mg per kilogram of body weight. Number of nivolumab cycles varied between 2 and 18. Progression-free survival varied from 1 to 12 months and overall survival from 4 to 24 months. Tolerance was very good, except for one case of diabetes and hypothyroidism requiring medication. There is currently insufficient evidence regarding the optimal treatment of the rare non-squamous cell carcinoma of the head and neck. Our case series supports a role for immunotherapy in these patients. However, larger collaborative studies are needed to evaluate this treatment.

// Zafar Malik 1 , Axel Heidenreich 1 , 2 , Sergio Bracarda 3 , Alexandros Ardavanis 4 , Philip Parente 5 , Hans-Joerg Scholz 6 , Ayse Ozatilgan 7 , Evelyne Ecstein-Fraisse 8 , Simon Hitier 9 and Giuseppe Di Lorenzo 10 1 The Clatterbridge Cancer Centre NHS Foundation Trust, Wirral, UK 2 Department of Urology, Uro-Oncology, Robot-Assisted and Specialized Urologic Surgery, University Hospital Cologne, Cologne, Germany 3 Azienda USL Toscana Sud-Est, Istituto Toscana Tumori (ITT), Ospedale San Donato, Arezzo, Italy 4 Oncology Hospital AGIOS SAVVAS Oncology Clinic, Athens, Greece 5 ECRU-Oncology, Victoria, Australia 6 Asklepios Klink GmbH Weissenfels, Weissenfels, Germany 7 Sanofi, Cambridge, Massachusetts, USA 8 Sanofi, Paris, France 9 Sanofi, Chilly-Mazarin, France 10 Department of Clinical Medicine and Surgery, University of Naples Federico II, Napoli, Italy Correspondence to: Zafar Malik, email: zaf.malik@nhs.net Keywords: mCRPC; cabazitaxel; CUP; EAP; real-world Received: January 08, 2019 Accepted: April 29, 2019 Published: June 25, 2019 ABSTRACT Background Cabazitaxel is a second-generation taxane approved for use in patients with metastatic castration-resistant prostate cancer (mCRPC) previously treated with docetaxel. Early access programmes were established to allow eligible patients with mCRPC access to cabazitaxel before regulatory approval. Materials and Methods The primary objective was to allow access to cabazitaxel before commercial availability for patients with mCRPC whose disease had progressed during or after chemotherapy with docetaxel; the secondary objective was overall safety. Patients received cabazitaxel 25 mg/m 2 on Day 1 of a 21-day cycle, with daily oral 10 mg prednisone/prednisolone. G-CSF was administered per ASCO guidelines. Results In total, 1432 patients received cabazitaxel across 41 countries between 2010 and 2014 (median 6.0 treatment cycles [range 1–49]). The most frequently occurring treatment-emergent adverse events (TEAEs) possibly related to treatment were diarrhoea (33.3%), fatigue (25.4%) and anaemia (23.7%); the most frequently occurring possibly related Grade 3/4 TEAEs were neutropenia (18.7%) and febrile neutropenia (6.9%). G-CSF was administered in ≥ 1 cycle in 64% of patients (10.1% therapeutic use; 57.8% prophylactic use; 9.7% both uses). Conclusion The safety profile of cabazitaxel in this pooled analysis of two cabazitaxel early access programmes was manageable and consistent with previous Phase III trials (TROPIC, PROSELICA).