Papers by Dimitrios Ziogas
Blood, 2018
Carfilzomib (CFZ) is a non-reversible proteasome inhibitor approved for the treatment of patients... more Carfilzomib (CFZ) is a non-reversible proteasome inhibitor approved for the treatment of patients with relapsed or refractory myeloma (RRMM), either in combination with dexamethasone (Kd) or with lenalidomide and dexamethasone (KRd). CFZ has been associated with a risk of cardiovascular toxicity but although a signal of clinically significant renal complications has also been identified, renal toxicity is less extensively investigated. Thus, we analyzed the data of 114 consecutive patients who received CFZ for RRMM in our center (Department of Clinical Therapeutics, Athens, Greece) for renal outcomes and complications. Detailed baseline characteristics and medical history (demographics, history of renal and cardiovascular diseases, diabetes, medication use) and detailed data on myeloma status, proteinuria and urine electrophoresis, serum free light chains (sFLC), serum creatinine and cardiovascular complications were available in all patients for the duration of CFZ therapy. Median ...
Cancers
More than ten years after the approval of ipilimumab, immune checkpoint inhibitors (ICIs) against... more More than ten years after the approval of ipilimumab, immune checkpoint inhibitors (ICIs) against PD-1 and CTLA-4 have been established as the most effective treatment for locally advanced or metastatic melanoma, achieving durable responses either as monotherapies or in combinatorial regimens. However, a considerable proportion of patients do not respond or experience early relapse, due to multiple parameters that contribute to melanoma resistance. The expression of other immune checkpoints beyond the PD-1 and CTLA-4 molecules remains a major mechanism of immune evasion. The recent approval of anti-LAG-3 ICI, relatlimab, in combination with nivolumab for metastatic disease, has capitalized on the extensive research in the field and has highlighted the potential for further improvement of melanoma prognosis by synergistically blocking additional immune targets with new ICI-doublets, antibody–drug conjugates, or other novel modalities. Herein, we provide a comprehensive overview of pr...
Diseases of the Esophagus
Esophagectomy carries high rates of post-operative morbidity and mortality. Minimally invasive es... more Esophagectomy carries high rates of post-operative morbidity and mortality. Minimally invasive esophagectomy was introduced more than 20 years ago offering all the advantages of minimally invasive surgery and significantly reducing post-operative pulmonary and cardiac complications associated with open esophagectomy. Clinical and oncological outcomes are vastly improved standardizing this approach as inferior in the hand of experts. Herein, we aim to present our results of minimally invasive esophagectomy for esophageal and gastro-esophageal junction cancer. This is prospective analysis of consecutive patients that underwent 2-stage minimally invasive esophagectomy for esophageal and gastro-esophageal junction Siewert type I-II cancers. Operations included hybrid 2-stage esophagectomy (laparoscopic/open thoracotomic or open laparotomy/thoracoscopy) and 2-stage totally minimally invasive esophagectomy (laparoscopic/thoracoscopic). Study included adult patients with no upper age limit...
Diseases of the Esophagus
Minimally invasive esophagectomy (MIE) is a challenging procedure associated with high rate of co... more Minimally invasive esophagectomy (MIE) is a challenging procedure associated with high rate of complications and mortality. Routine lymphadenectomy includes 2-field lymphadenectomy for distal esophageal or esophago-gastric junction Siewert I-II cancers. SML refers to extended 2-field lymphadenectomy or total mediastinal lymphadenectomy. The exact benefits of superior mediastinal lymphadenectomy (SML) have long been debated with no clear evidence pertaining to improved outcomes. N=150 consecutive patients underwent totally MIE under a surgical team from September 2016 to September 2020. SML included right paratracheal nodes and lymph nodes along the right recurrent laryngeal nerve throughout its mediastinal route (including the paratracheal-retrocaval compartment) in cases of extended 2-field lymphadenectomy, as well as left paratracheal nodes and lymph nodes along the left recurrent laryngeal nerve during total mediastinal lymphadenectomy. Eligible patients underwent SML during 2-st...
Diseases of the Esophagus
Esophagectomy is the mainstay of treatment of esophageal and gastro-esophageal junction cancer. M... more Esophagectomy is the mainstay of treatment of esophageal and gastro-esophageal junction cancer. Minimally invasive esophagectomy has been introduced in the 2000s in an effort to reduce post-operative pulmonary and cardiac complications. 2-stage totally minimally invasive esophagectomy combines laparoscopic abdominal phase followed by thoracoscopic thoracic phase. The rate limiting step of the procedure is the construction of esophago-gastric anastomosis. We aim to present our technique and results on hand-sewn thoracoscopic esophago-gastric anastomosis in prone position. This is prospective analysis of consecutive patients that underwent 2-stage totally minimally invasive esophagectomy for esophageal and gastro-esophageal junction Siewert type I-II cancers. All operations were identical in terms of patient positioning, lymphadenectomy and type of anastomosis formed. Study included adult patients with no upper age limit (>18 years); all hybrid esophagectomies, esophagectomies for ...
Diseases of the Esophagus
Totally minimally invasive 2-stage esophagectomy (TMIE) eliminates the thoracotomy associated wit... more Totally minimally invasive 2-stage esophagectomy (TMIE) eliminates the thoracotomy associated with hybrid 2-stage minimally invasive esophagectomy (hybrid-MIE). This has an important role in minimizing post-operative respiratory complications. There is ongoing growing evidence in published literature of improved clinical and oncological outcomes in totally MIE comparing to hybrid MIE, due to enhanced optics and extend of lymphadenectomy as well as to shorter length of hospital stay and surgical trauma associated to thoracoscopy. This is a retrospective analysis of consecutive patients that underwent 2-stage minimally invasive esophagectomy for esophageal and gastro-esophageal junction Siewert type I-II cancers. TMIE combines a laparoscopic and thoracoscopic approach while hybrid-MIE includes laparoscopic open thoracotomic phase. Study included adult patients with no upper age limit (>18 years). All esophagectomies for benign disease, as well as emergency operations were excluded ...
Diseases of the Esophagus
Circumferential resection margin involvement is an independent prognostic factor in patients with... more Circumferential resection margin involvement is an independent prognostic factor in patients with adenocarcinoma of the distal esophagus and esophago-gastric junction. However, there is currently no consensus on the extent and the technique of hiatal dissection. Herein, we aim to present our technique of circumferential hiatal dissection during 2-stage totally minimally invasive esophagectomy for adenocarcinoma of the distal esophagus and esophago-gastric junction with its related histopathological results. A prospective study of 200 consecutive patients undergoing 2-stage totally minimally invasive esophagectomy over a period of 60 months was conducted. Dissection of the hiatus included peri-esophageal surrounding tissues in a cylindrical fashion maximizing the distance from the esophageal wall. Crural muscle fibers and pleura bilaterally, pericardial fat anteriorly and pre-aortic tissue posteriorly were excised en bloc. Histopathological results particularly focused on involvement...
Cancer Research, 2022
Background: Breast cancer is the most frequently diagnosed cancer in women and about 10% of breas... more Background: Breast cancer is the most frequently diagnosed cancer in women and about 10% of breast cancer cases are hereditary. BRCA1 and BRCA2 are the genes most frequently associated with Hereditary Breast Cancer, although there are numerous other genes, such as PALB2, CHEK2 and ATM, that require to be considered as well. Germline Copy Number Variation (CNV) is one mutation type that is an important contributor to hereditary breast cancer. Nowadays, next-generation sequencing (NGS) technologies has contributed to multi-gene panel analysis used in clinical practice. Methods: In total, 1418 individuals were tested for breast cancer predisposition, using a solution-based capture approach. Targeted NGS was performed with a panel of 36 genes. The capture-based approach allowed for computational analysis of CNVs from NGS data. Results: We investigate the performance of the CNV module of the commercial software suite SeqPilot (JSI Medical Systems) and the non-commercial tool panelcn.MOPS...
Annals of Hematology, 2020
Introduction: MGUS-a premalignancy with a risk of 1% per year transformation into MM or other lym... more Introduction: MGUS-a premalignancy with a risk of 1% per year transformation into MM or other lymphoid proliferation. Immunophenotyping is one of the modern methods used in MGUS and MM diagnosis. Objective: Identify immunophenotypic markers, significant in MM and MGUS. Materials and Methods: The study included 126 patients for 2014-2017, Gomel (Belarus). Antigen expression was determined by flow cytometry. The results were estimated at the diagnosis time. MGUS and MM were more common in women (64,3 % and 60 %, respectively). The median age was 63 years. Results: At the time of MGUS diagnosis there was revealed a significant increase in CD56 expression in 21 (75%) patients. In 16 patients (53,3%), the loss of marker CD19 was observed. In 15 patients (50%), a negative phenotype by CD45 was detected. During the three-year follow-up, 11 of 30 (36,6%) patients with MGUS (IgG, BJ protein in urine, increased expression of CD56, lack of expression of CD19, CD45 and CD27) progressed to MM. In two patients, along with a high level of pathological M-protein (>20 g/l) significant increase in CD117 expression was detected (p ¼0,05). In one patient, the disease was transformed into Waldenström's disease. At the first time diagnosed MM in the bone marrow, there was most often found expression of tumor marker CD56 (in 74,1% of cases). In a smaller amount, there were detected CD117 expression (44% of cases), CD33 (28% of cases), CD20 (35,3% of cases). The lowest overall survival was found in patients with high expression CD56 (p¼0,057). In patients with high CD20 expression, overall survival was lower than in patients without this marker and the presence of multiple soft-tissue components was present in the clinic. At the same time, the frequency of remission after 3 courses of VAD did not depend on the immunophenotypic markers CD56 (p ¼0,418), CD33 (p ¼0,471), CD20 (p ¼0,151), CD117 (p ¼0,689). Conclusion: Immunophenotype features of tumor cells can provide additional information on the nature of tumor clone in a patient, which can be considered as an additional factor for individualizing therapy.
Blood, 2015
The diagnosis of MM that requires therapy in elderly individuals is increasing. The management of... more The diagnosis of MM that requires therapy in elderly individuals is increasing. The management of such patients is challenging due to several factors, besides disease characteristics and age that affect outcome. Geriatric assessment (GA) is a multidimensional diagnostic approach that collects data on the medical, psychosocial and functional capabilities and limitations of elderly patients to develop treatment and care decisions and improve the use of health care resources. The IMWG has proposed a simplified GA…
Blood, 2015
The prognosis of patients with AL amyloidosis depends on the degree of cardiac dysfunction. Eleva... more The prognosis of patients with AL amyloidosis depends on the degree of cardiac dysfunction. Elevated cardiac troponin levels and of NTproBNP identify patients at high risk (stage 3 per Mayo stage); very high levels of NTproBNP are further associated with quite poor outcomes. Low blood pressure (BP) is associated with poor prognosis in patients with Mayo stage-3 disease (Wechalekar et al Blood 2013). BP depends on cardiac output and is tightly regulated by the autonomic nervous system (ANS), which is also commonly affected and deregulated in AL amyloidosis. However, the prognostic role of BP has not been evaluated prospectively and the measurement of BP in patients with AL has not been standardized as a prognostic factor. In addition, the importance of the deregulation of ANS in AL amyloidosis as a determinant of BP has not been evaluated. Baroreceptor reflex sensitivity (BRS) is implicated in the homeostatic regulation of the cardiovascular system and can be measured as a surrogate ...
Blood, 2016
Pomalidomide with low dose dexamethasone (Pd) is a standard treatment for patients who have faile... more Pomalidomide with low dose dexamethasone (Pd) is a standard treatment for patients who have failed both lenalidomide (Len) & bortezomib (Bor). Phase III studies showed that Pd is active irrespective of the number of prior therapies and whether Len or Bor were the last therapies prior to Pd. However, it remains unclear what is the activity of Pd when administered immediately after refractoriness to Len or when is administered following secondary resistance. Furthermore, the importance of the time elapsed from the administration of Len to Pd has not been explored. We analyzed the outcomes of 116 consecutive patients with MM after failure of both Len & Bor that were treated in the Department of Clinical Therapeutics, National and Kapodistrian University of Athens, and who all received pomalidomide 4 mg with weekly dexamethasone. Median age was 62 years (range 38-86 years); median number of prior treatments was 4 (range 1-9), 58% had received ASCT, 73% were refractory to the last Bor-ba...
Clinical Lymphoma Myeloma and Leukemia, 2019
BACKGROUND Waldenström's macroglobulinemia (WM) is a rare malignancy characterized by bone ma... more BACKGROUND Waldenström's macroglobulinemia (WM) is a rare malignancy characterized by bone marrow infiltration by lymphoplasmacytic cells and the presence of a monoclonal IgM paraprotein. The interactions of lymphoplasmacytic cells with other cells in their microenvironment, including mast cells and endothelial cells, support their survival and proliferation and can induce resistance to therapy. von Willebrand factor (vWF) plays a key role in primary hemostasis but is also a marker of endothelial "stimulation." High levels of vWF have been associated with an adverse prognosis in patients with symptomatic WM and might reflect the interactions between lymphoplasmacytic cells and other cells of their microenvironment. MATERIALS AND METHODS Considering vWF and ADAMTS-13 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13) as markers of endothelial dysfunction and activation, we evaluated the prognostic importance of vWF and ADAMTS-13 antigen levels in the serum of patients with previously untreated symptomatic WM to validate vWF as a possible prognostic marker for progression-free and overall survival. We also validated the measurement of vWF in the serum instead of citrated plasma and investigated the possible correlations of ADAMTS-13 antigen levels with disease characteristics. The analysis included 42 patients with symptomatic WM and 19 matched healthy controls. RESULTS The serum levels of vWF antigen provided significant prognostic information, and patients with levels ≥ 200 IU/dL had a very poor prognosis compared with patients with lower levels. The ADAMTS-13 antigen levels were decreased in WM patients and correlated with the IgM levels, β2-microglobulin, and extent of bone marrow infiltration. CONCLUSION vWF levels measured in the serum could become an important prognostic marker in patients with WM and requires further investigation.
Clinical Lymphoma Myeloma and Leukemia, 2017
we analyzed the characteristics of patients in whom serum sSLAMF7 was detected and the correlatio... more we analyzed the characteristics of patients in whom serum sSLAMF7 was detected and the correlation with SLAMF7 expression levels in CD138+ myeloma cells. Finally, NK cell-mediated antibody-mediated antibody-dependent cytotoxic (ADCC) activity against the SLAM7-expressing MM cell line U266 was assessed in the lactate dehydrogenase (LDH)-based cytotoxicity assay using NK cell line NK-92MI. Results: 33% of MM patients (n¼34), but no MGUS patients or controls, had detectable sSLAMF7 in serum (range: 0.011e14.7 ng/mL). sSLAMF7 levels in symptomatic MM patients were significantly higher than those in asymptomatic ones (P¼0.0316). Furthermore, sSLAMF7 levels in patients with International Staging System (ISS) and revised ISS (R-ISS) stage 2/3 were markedly increased in comparison with ISS and R-ISS stage 1 (P¼0.0007 and 0.0177, respectively). Serum sSLAMF7 concentrations were not correlated with the percentage of plasma cells or SLAMF7 mRNA expression levels in CD138+ plasma cells in BM obtained from patients. When comparing the clinical characteristics between sSLAMF7-positive (n¼34) and-negative groups (n¼69), plasma cell percentage and LDH levels, and corrected calcium,
Leukemia & lymphoma, Jan 7, 2017
Multiple myeloma (MM) patients are considered severely immune-compromised and at high risk of opp... more Multiple myeloma (MM) patients are considered severely immune-compromised and at high risk of opportunistic infections, independently of the therapeutic approach and the response status. Leishmaniasis seems to behave as such an opportunistic infection; the incubation time of initial infection ranges between 2 and 6 months, while a recurrence of latent infection is possible [1]. It is a rare vector-borne infection that is caused by more than 20 species of an intramacrophage protozoon, which is transmitted to humans by more than 30 different species of phlebotomus sandflies (or less often by contaminated blood products transfusion) [1–3]. Although leishmaniasis is an endemic disease with 90% of cases occurring in tropical and subtropical areas (e.g. Brazil, India but also South and Mediterranean Europe) [2,4], more recently with the growth of international travel, its frequency is also increasing in western countries. This predominantly occurs in immune-compromised patients, including patients with HIV-acquired immunodeficiency [5,6], patients who underwent an organ or hematopoietic stem cell transplantation [4,7–11] and patients with lymphoproliferative disorders who were treated with anti-CD52 and anti-CD20 monoclonal antibodies [12,13]. Recent epidemiological data have shown that novel antimyeloma agents and their combinations have contributed significantly to the increased risk of conventional bacterial and viral infections in MM patients observed in the last decades [14]. However, limited data are available on the incidence of opportunistic fungal and parasitic infections in MM patients who are treated with novel agents. Currently, the approval of monoclonal antibodies (mAbs)-containing triplets, including daratumumab (a human IgGj mAb-targeting surface protein CD38) or elotuzumab (a humanized G1 mAb-targeting surface glycoprotein SLAMF7) in combination with lenalidomide and dexamethasone for relapsed MM has increased the therapeutic options for myeloma patients and has intensified the immune-mediated management [15,16]. In this letter, we present two ‘real-world’ MM patients who developed leishmania infection, which recurred during antimyeloma treatment with a triplet of a mAb with lenalidomide and dexamethasone. In addition, we describe our therapeutic decisions for both diseases and our considerations about the interaction of mAb-triplets and the immune background of underlying leishmania infection.
Journal of Clinical Oncology, 2015
389 Background: HCC is the second leading cause of cancer related mortality worldwide. Standard t... more 389 Background: HCC is the second leading cause of cancer related mortality worldwide. Standard treatment for advanced disease is sorafenib, which is associated with a modest improvement in overall survival. We hypothesized that patients with oligometastatic disease treated with sorafenib have improved outcomes over those with extensive metastases. Methods: A retrospective analysis of all patients with advanced HCC treated with sorafenib at a large HCC centre. 190 patients were identified (177 patients with sorafenib alone, 13 patients treated with a combination of sorafenib and erlotinib/placebo as part of the SEARCH trial). Disease distribution was defined as intra-hepatic, oligometastatic (3 or fewer extra-hepatic metastases) and extensive (more than 3 metastases) at the time of starting sorafenib. Overall survival (OS), progression free survival (PFS) and toxicities were recorded. Results: The median age for all patients was 66 years (26-87), 157 male and 33 female. Underlying l...
Journal of Clinical Oncology, 2015
435 Background: HCC is the third commonest malignancy worldwide, with the highest incidence rates... more 435 Background: HCC is the third commonest malignancy worldwide, with the highest incidence rates in patients over 75 years of age. Although sorafenib is used for patients with advanced HCC, there are concerns about the outcomes and tolerability in this age group. Methods: We conducted a retrospective study of 190 patients treated with sorafenib (177 with sorafenib alone, 17 patients with a combination of sorafenib and erlotinib/placebo within the SEARCH trial). Patient demographics and outcomes were recorded. Results: 190 patients were identified with a median age of 66 (26-87). 151 patients were <75 years old (yrs) and 39 patients were >75. 157 patients were male and 33 female. Underlying liver disease in the over 75 group were: non-alcoholic fatty liver disease (N=14, 35.9%), unknown aetiology (N=14, 35.9%), alcoholic liver disease (N=7, 17.9%), hepatitis C (N=2, 5.1%), hepatitis B (N=1, 2.56%,) and autoimmune hepatitis (N=1, 2.56%). 33 patients were Child-Pugh A status whe...
Leukemia & lymphoma, 2017
In the current evolving landscape of myeloma therapies, no recommended salvage strategy exists fo... more In the current evolving landscape of myeloma therapies, no recommended salvage strategy exists for patients with relapsed multiple myeloma (MM) after initial successful autologous stem cell transplantation (ASCT) and therapeutic options extend from conventional chemotherapy and novel agents to second autologous and allogeneic transplants. In this article, we summarize the documented evidence about the utilization of second ASCT in patients with relapsed MM after a primary auto-graft and discuss the correct timing for such a salvage approach, the individual characteristics of patients who will benefit more, as well as the therapeutic role of second ASCT in the modern era of forthcoming anti-myeloma treatments.
Leukemia & Lymphoma, 2016
Monoclonal immunoglobulin deposition disease (MIDD) is characterized by non-organized immunoglobu... more Monoclonal immunoglobulin deposition disease (MIDD) is characterized by non-organized immunoglobulin-fragments along renal basement membranes with subsequent organ deterioration. Treatment is directed against the immunoglobulin-producing clone. We treated 18 MIDD patients with bortezomib-based regimens (12 received bortezomib-dexamethasone, 6 bortezomib-dexamethasone with cyclophosphamide). Eleven (61%) patients achieved a hematologic response, but only 6 (33.3%) reached to a complete (CR) or very good partial response (VGPR). Regarding renal outcomes 77.8 and 55.6% had !30 and !50% reduction of proteinuria, respectively, but 33.3% ended up in end-stage renal disease (ESRD). Among patients with CR or VGPR, median eGFR improvement was 7.7 ml/min/1.73 m 2 and none progressed to ESRD, but no significant renal recovery was observed in patients achieving a partial response or less, with 50% progressing to dialysis. Pretreatment eGFR seems to influence renal prognosis. Bortezomib-based treatment is considered an effective approach in MIDD and reaching to a deep hematologic response (!VGPR) conditionally controls further renal declining.
European Journal of Gastroenterology & Hepatology, 2017
Sorafenib is the standard of care for patients with advanced hepatocellular carcinoma (HCC), but ... more Sorafenib is the standard of care for patients with advanced hepatocellular carcinoma (HCC), but data on its use in the elderly are inconclusive. All consecutive HCC patients who were treated in our institution with sorafenib since its licensing were included in the analysis. Patients were divided into two groups: (A) up to 75 and (B) older than 75 years old. Our endpoints were overall survival (OS) and time to treatment failure (TTF) because of disease progression or toxicity. Safety parameters and the prognostic effect of HCC characteristics were also investigated. Data from 190 patients (157 men), median age 66 (26-87) years, were studied (A=151 and B=39). No significant difference in OS and TTF was detected between the two groups [7.1 (5.5-8.7) vs. 10.4 (6.5-14.3) months, P=0.360 and 4.2 (2.3-6.2) vs. 5.6 (3.1-8.1) months, P=0.369, respectively]. Incidence of toxicities at all grades and dose reductions were comparable between groups A and B. In a multivariate setting, patients with Child-Pugh B score at baseline were associated with a higher risk of death (adjusted hazard ratio=2.17, 95% confidence interval:1.24-3.79, P=0.007) and treatment failure (adjusted hazard ratio=4.64, 95% confidence interval: 2.55-8.42, P=0.001) and had shorter OS and TTF compared with patients with a Child-Pugh A (P=0.004 and P&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.001, respectively). Elderly patients with advanced HCC, when treated with sorafenib, have an equivalent clinical outcome with similar toxicity rates as their younger counterparts. Age alone should not be a discriminating factor for the management of advanced HCC with sorafenib.
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Papers by Dimitrios Ziogas