Dimitrios Bafaloukos

• Professor of oncology
• Metropolitan Hospital

Checkpoint inhibitor myocarditis is a rare but life-threatening toxicity of immunotherapy, occasionally manifesting as persistent troponin elevation. Dual checkpoint blockade with ipilimumab and nivolumab has been found to induce immune-related myocarditis in patients with metastatic melanoma. We herein report a case of smoldering immune-related my...

The B-Raf proto-oncogene, serine/threonine kinase (BRAF)/ mitogen-activated protein kinase kinase (MEK) targeting agents have become the treatment of choice for BRAF-mutated melanoma during the last decade. However, it is possible that some long-term adverse events of these drugs have not yet been reported. A case of bilateral spontaneous, non-trau...

This study primarily aimed to generate real-world evidence (RWE) on the profile and first-line treatment (1LT) patterns of patients with advanced (unresectable Stage III/metastatic) cutaneous melanoma initiated on immuno-oncology (IO)- or targeted therapy (TT)-based 1LT between 1 January 2015 and 1 January 2018 (index period), in routine settings o...

Background/aim: Nivolumab is an FDA-approved immune checkpoint inhibitor (ICI) for patients with advanced, pre-treated non-small cell lung cancer (NSCLC). However, treatment profiles and patient outcomes often differ in routine clinical practice while the financial impact of approved therapies is largely unknown. In this study, we investigated the...

mRNA vaccines encoding tumor antigens may be able to sensitize the immune system of the host against cancer cells, enhancing antigen presentation and immune response. Since the breakout of the COVID19 pandemic, interest in mRNA vaccines has been accelerating, as vaccination against the virus served as a measure to limit disease spread. Given that i...

Simple Summary By coupling the potency of cytotoxic chemotherapy with the selectivity of targeted therapy, antibody–drug conjugates represent a unique and rapidly growing class of antitumor agents. In this review, we aim to outline the unanswered questions that have emerged after the approval of trastuzumab deruxtecan in HER2-mutant non-small cell...

Nivolumab, an anti-PD-1 check point inhibitor, is an immunotherapeutic agent, representing a major step in the treatment of melanoma. However, its use is associated with severe toxicities. Among them, gastrointestinal (GI) disorders from the lower GI tract have been widely reported. On the contrary, disorders from the upper GI tract are rare. Such...

Extrahepatic metastases of hepatocellular carcinoma (HCC) are associated with poor prognosis, while such lesions in skeletal muscles are extremely rare. A unique case of skeletal metastasis in the soleus muscle in a 76-year-old male patient with HCC is reported. The patient presented with a painful palpable mass in his left calf. Magnetic resonance...

Tumor-infiltrating lymphocytes (TILs) contribute to breast cancer (BC) prognosis. We investigated the prognostic impact of CD8+ TILs in patients with early breast cancer treated with adjuvant chemotherapy in a large observational clinical trial. Along with a 10 year follow-up, considering the efficacy and safety, we report the results of the transl...

Background: Dose-dense sequential chemotherapy with anthracyclines and taxanes achieved an 18% reduction of recurrence risk in early breast cancer (BC). The optimal chemotherapy schedule and interval between cycles remain under investigation. Methods: Overall, 990 patients were randomised to receive either three cycles of epirubicin (E, 110 mg/m...

A unique case of multiple metastatic melanoma skin nodules regression in a heavily pretreated, 72-year-old Caucasian female, after administering the second dose of the SARS-CoV-2 mRNA Pfizer-BioNTech vaccine, is presented. Two days after vaccination, all her melanoma skin nodules became painful and were significantly reduced in size. Physical exami...

Background: Dose-dense sequential chemotherapy based on anthracyclines and taxanes has achieved an 18% reduction of recurrence risk in the adjuvant setting of early breast cancer (BC). However, the optimal chemotherapy schedule and the preferable interval between cycles are still under investigation. Methods: A total of 990 eligible BC patients wer...

Background Data on the safety and efficacy of immune checkpoint inhibitors (ICI) in patients with concurrent autoimmune diseases (AID) are limited. Methods We performed a retrospective multicenter review of medical records of patients with cancer and underlying AID who received ICI. The primary endpoint was progression-free survival (PFS). Result...

Prognostic and predictive biomarkers are being studied for the diagnosis and treatment of breast cancer. The present study retrospectively assessed the mRNA expression of HER family receptor ligands and of other potential prognostic biomarkers and their association with time to progression (TTP), survival and clinicopathological characteristics in...

Purpose: Angiogenesis is a crucial phenomenon in the development and progression of breast cancer (BC), but the clinical significance of angiogenesis-related proteins in metastatic BC remains unknown. This study investigates the prognostic value of vascular endothelial growth factor receptors 1, 2, 3 (VEGFR1, VEGFR2, VEGFR3) as well as vascular en...

Purpose Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) are the preferred first-line option for patients with advanced, EGFR-mutant non-small cell lung cancer (NSCLC). Afatinib, a second-generation irreversible EGFR-TKI, has been extensively used in Greece in this setting; however, real-world data regarding molecular epide...

The dabrafenib plus trametinib (dab + tram) combination has demonstrated durable long-term efficacy in patients with BRAF V600–mutant metastatic melanoma. However, real-world data characterizing patients with long-term benefit are limited. DESCRIBE III was a global, observational, retrospective, chart review study in patients with unresectable or m...

Background/aim: Human epidermal growth factor receptor 2 (HER2) P95-isoform could be involved in trastuzumab resistance in HER2 metastatic breast cancer. Materials and methods: A total of 114 metastatic breast cancer patients treated with trastuzumab were evaluated retrospectively. HER2 was centrally reviewed. P95 was evaluated along with other...

Objective: Melanoma is one of the most aggressive cancers and is responsible for the majority of skin cancer deaths, with the presence of metastases prognostic for poor survival. At a time when most cancer incidences are falling, the annual incidence of melanoma has risen as rapidly as 4-6% in many European countries, with a substantial economic bu...

Our aim was to determine the prevalence, prognostic and predictive role of germline pathogenic/likely pathogenic variants (P/LPVs) in cancer predisposing genes in patients with pancreatic ductal adenocarcinoma (PDAC). Germline testing of 62 cancer susceptibility genes was performed on unselected patients diagnosed from 02/2003 to 01/2020 with PDAC,...

Background Tumor-infiltrating lymphocytes (TILs) and their subsets contribute to breast cancer prognosis. We investigated the prognostic impact of CD3+, CD8+ and FOXP3+ TILs in patients with early intermediate/high-risk breast cancer treated with adjuvant anthracycline-based chemotherapy within two randomized trials conducted by our Group.Methods W...

Background We evaluated real-world clinical outcomes and toxicity data and assessed treatment-related costs in patients with advanced breast cancer who received treatment with cyclin-dependent kinase inhibitors (CDKi). Patients and methods We conducted a prospective–retrospective analysis of patients with advanced hormone receptor-positive, human...

PurposeThe 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 methodsThe primary objective of this multicenter prospective study was to assess the overall response rate (ORR) of patients with MBC tr...

Background: Approximately one third of women who develop melanoma at childbearing age are diagnosed during gestation or the postpartum period, facing pregnancy-associated melanoma (PAM). However, only some retrospective studies with heterogeneous data have analyzed the impact of pregnancy on melanoma development, and no evidence exists about the b...

Introduction: Nanoparticle albumin-bound ()-paclitaxel (-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 -P is sparse. From this perspectiv...

Background: We evaluated the association between pathogenic mutations and overall survival (OS) in patients with cancer referred to Hellenic Cooperative Oncology Group–affiliated Departments. Patients and methods: Patients referred from 12/1980 to 1/2017 had molecular testing (for research) of archival tumor tissue collected at the time of first di...

Purpose Crevicular fluid was used to assess interleukin-17 (IL-17) and vascular endothelial growth factor (VEGF) in cancer patients receiving zoledronic acid and/or bevacizumab. The markers were also assessed in the serum. Methods Twenty-five patients were included and comprised three groups: patients who received zoledronic acid (n = 9), patients...

Background The principles of dose-dense (dd) and sequential (s) chemotherapy (CT) were introduced in the adjuvant setting by HeCOG in 1997. We aimed to explore the long-term clinical benefit and safety of treatment of adjuvant dds-CT in patients (pts) with high-risk BC. Methods We performed a pooled analysis from 6 HeCOG-initiated clinical trials...

Background: Limited data are available on nivolumab in challenging subgroups with advanced melanoma. We report outcomes of nivolumab after prior ipilimumab in patients who are typically excluded from clinical trials. Patients and methods: In this phase II, single-arm, open-label, multicentre study (CheckMate 172), patients with advanced melanoma...

Background: Nivolumab has been widely studied in non-acral cutaneous melanoma; however, limited data are available in other melanoma subtypes. We report outcomes by melanoma subtype in patients who received nivolumab after progression on prior ipilimumab. Patients and methods: CheckMate 172 was a phase II, single-arm, open-label, multicentre stu...

Background: Alternative splicing of vascular endothelial growth factor A (VEGFA) results in VEGFAxxxb antiangiogenic isoforms that fail to activate angiogenesis. Bevacizumab, widely used in patients with metastatic colorectal cancer (CRC), binds both VEGFA and VEGFAxxxb isoforms. Patients and methods: Formalin-fixed, paraffin-embedded primary tu...

Background: Src, CDKN1B, and JAK2 play a crucial role in the coordination of cell signaling pathways. In the present study, we aim to investigate the prognostic significance of these biomarkers in HER2-positive metastatic breast cancer (MBC) patients treated with trastuzumab (T). Methods: Formalin-fixed paraffin-embedded tumor tissue samples fro...

Renal cell carcinoma (RCC) is the most frequent cancer of the kidney and it accounts for 3% of all solid malignancies. Although rare, cutaneous metastases can be an important manifestation of RCC. We present a case of a 56-year-old male with a history of RCC, followed by the development of cutaneous metastases 4 years later with an uncommon clinica...

Background-aim: SRC, CDKN1B and JAK2 play a crucial role in the coordination and facilitation of cell-signaling pathways controlling a wide range of cellular functions. In the present study, we investigated the prognostic significance and clinical utlity of these biomarkers in metastatic breast cancer (MBC) patients treated with trastuzumab (T). Me...

In the current study, we performed a complete analysis, with four different methods, of all four HER family receptors, in a series of patients with metastatic breast cancer treated with trastuzumab-based regimens and evaluated their prognostic value. Formalin-fixed paraffin-embedded tumor tissue samples were collected from 227 patients, considered...

Associations of EGFR, HER2, HER3 and HER4 protein expression with mRNA expression. (DOCX)

This retrospective cohort study assessed the prognostic significance of distant metastasis-free interval (DMFI) in patients with relapsed BRAF-mutant melanoma treated with BRAF with or without MEK inhibitors (BRAFi±MEKi). Patients with a DMFI of up to 24 months were compared with those with DMFI of more than 24 months, with regard to their postrela...

BACKGROUND: Trastuzumab is a monoclonal antibody against HER2-positive breast cancer. Despite improving the natural history of the disease, there is a number of patients who are resistant to it, whereas all patients will eventually develop resistance and disease will progress. Inconsistent preclinical data show that the IGF-R pathway may contribute...

Skin imaging is crucial for the early detection of melanoma. There are many different techniques that are in use in the clinic, such as dermoscopy, confocal laser scanning microscopy, ultrasound, PET scan, and MRI. Following diagnosis, accurate disease staging is appropriate for treatment planning, and the detection of distant metastases is very im...

Background Tumor‐infiltrating lymphocytes (TILs) have been shown to be of prognostic value in several cancer types. In early breast cancer, TILs have a prognostic utility, as well, especially in HER2‐positive and triple‐negative breast cancer. TILs presence is broadly associated with improved survival; however, there is controversy regarding TILs s...

Several studies support an important role of angiogenesis in breast cancer growth and metastasis. The main objectives of the study were to investigate the immunohistochemical expression of vascular endothelial growth factor (VEGF) family ligands (VEGF-A and VEGF-C) and receptors (VEGFR1, VEGFR2 and VEGFR3) in breast cancer and their associations wi...

Hazard ratios (95% CIs) estimated from univariate Cox regression for selected clinicopathological parameters. (PDF)

Descriptive statistics for the five angiogenesis-related proteins (calculated as the percentage of tumor stained cells). (PDF)

Associations between the angiogenesis-related proteins (using 5-years ROC curve cut-offs) and selected clinicopathological parameters. Data presented as N (%). p-values of the chi-square test are shown. (PDF)

Associations among the angiogenesis-related proteins (using 5-years ROC curve cut-offs). Data presented as N (%). p-values of the chi-square test are shown. (PDF)

Background: The efficacy and safety of the FOLFIRI (leucovorin, 5-fluorouracil, irinotecan, and oxaliplatin) regimen combined with aflibercept has not been studied in the first-line management of patients with metastatic colorectal cancer (mCRC). Patients and methods: In the context of a prospective single-arm trial (NCT02129257), patients with...

Background-aim: Metastatic breast cancer (MBC) is an incurable disease. Trastuzumab, a recombinant humanized monoclonal antibody, was found to significantly prolongsurvival of patients with metastatic HER2 over-expressing and/or amplified breast cancer. In the current study, we performed a complete analysis, with four different methods, of all four...

Background: Tumor-infiltrating lymphocytes (TILs) have been shown to be of prognostic value in several cancer types. In early breast cancer, TILs have a prognostic utility, as well, especially in HER2-positive and triple-negative breast cancer (TNBC). TILs presence is broadly associated with improved survival, however there is controversy regarding...

Please check the hierarchy of the section headings and confirm if correct.

Background-Aim To evaluate the prognostic role of elaborate molecular clusters encompassing cyclin D1, cyclin E1, p21, p27 and p53 in the context of various breast cancer subtypes. Methods Cyclin E1, cyclin D1, p53, p21 and p27 were evaluated with immunohistochemistry in 1077 formalin-fixed paraffin-embedded tissues from breast cancer patients who...

Associations among the examined markers—N (%). (DOC)

Associations of the examined markers with patient and tumor characteristics—N (%). Bold cells indicate p-values lower than 0.05. (DOC)

Clinical trial characteristics. (DOC)

Background: The Notch pathway has been implicated in triple-negative breast cancer (TNBC). Herein, we studied the subcellular localization of the less investigated Notch2 and Notch3 and that of the Jagged1 (Jag1) ligand in patients with operable TNBC. Patients and methods: We applied immunohistochemistry for Notch2, Notch3 and Jag1 in 333 tumors...

Background: Epidermal growth factor receptor (EGFR) aberrations have been implicated in the pathogenesis of triple-negative breast cancer (TNBC) but their impact on prognosis and, therefore, druggability, remain controversial. Herein, we studied EGFR aberrations at different molecular levels and assessed their prognostic impact in patients with op...

The preservation of pathogenic BRCA1/2 germline mutations in tumor tissues is usually not questioned, while it remains unknown whether these interact with somatic genotypes for patient outcome. Herein we compared germline and tumor genotypes in operable triple-negative breast cancer (TNBC) and evaluated their combined effects on prognosis. We analy...

Background: There is an unmet need for more efficient patient stratification for receiving trastuzumab in the metastatic breast cancer (mBC) setting, since only part of such patients benefit from the addition of this agent to chemotherapy. The aim of this study was to investigate the prognostic value of biomarkers including MYC and MET in mBC pati...

Background: We investigated the impact of PIK3CA and TP53 mutations and p53 protein status on the outcome of patients who had been treated with adjuvant anthracycline-taxane chemotherapy within clinical trials in the pre- and post-trastuzumab era. Results: TP53 and PIK3CA mutations were found in 380 (21.5%) and 458 (25.9%) cases, respectively, i...

Background-Aim: There is an unmet need for de-selecting HER2-positive patients with advanced breast cancer (ABC), since only some of those patients benefit from the addition of anti-HER2 agents to chemotherapy. The aim of this study was to investigate candidate biomarkers, including MYC and MET, in parallel with an extended array of biomarkers prev...

Resected stage IIB-IIIC malignant melanoma has a poor prognosis with a high risk of relapse and death. Treatment with adjuvant interferon alfa-2b (IFN-α-2b) is associated with improved relapse-free and overall survivals (OS), but the most appropriate dose and duration of treatment are unknown. In this article, we present an individual patient data...

Prophylactic erythropoiesis-stimulating agent (ESA) administration for chemotherapy-induced anemia (CIA) is not supported by current guidelines. Long-term follow-up of patients WHO had been treated with ESA for CIA in the past may provide useful information. In 2002, we undertook a prospective, randomized phase III trial of prophylactic vs. hemoglo...

Background: Intensive chemotherapy confers benefit to patients with high-risk early breast cancer (BC). We characterized the feasibility and toxicity profile of anthracycline-containing adjuvant chemotherapy (ACAC) in older women with early BC. Patients and methods: Available data from women who received ACAC for BC in 3 randomized trials were r...

Purpose: Local recurrence is considered a major concern in patients diagnosed with ductal carcinoma in situ (DCIS), as its invasive occurrence is associated with high rates of distant disease and mortality. This study aims to assess the possible correlation of hormonal receptor status, Ki-67 and HER2 expression with recurrence rates in women with...

Background: The PI3K-AKT pathway is frequently activated in breast cancer. PIK3CA mutations are most frequently found in the helical (exon 9) and kinase (exon 20) domains of this protein. The aim of the present study was to examine the role of different types of PIK3CA mutations in combination with molecular biomarkers related to PI3K-AKT signalin...

Vascular endothelial growth factor C (VEGFC) and vascular endothelial growth factor receptor 1 (VEGFR1) mRNA overexpression has recently been shown to have strong predictive and prognostic value in patients with high-risk early breast cancer undergoing adjuvant chemotherapy. The present study evaluated associations of VEGFC and VEGFR1 with human ep...