Davide Santeufemia - Academia.edu (original) (raw)

Papers by Davide Santeufemia

This concise and handy manual provides straightforward, up-to-date guidance for cardiologists and... more This concise and handy manual provides straightforward, up-to-date guidance for cardiologists and other practitioners on the management of cancer patients with cardiac problems, whether they be due to the cancer itself or to antineoplastic treatment. Detailed attention is devoted to the various forms of cardiotoxicity associated with chemotherapy and radiotherapy. The drugs commonly responsible for each toxicity are identified and clear advice is offered on monitoring techniques and treatment approaches. In addition, the issue of cardiotoxicity due to cancer treatment in particular patient groups \\u2013 children, the elderly, and those with pre-existing cardiac disease \\u2013 is addressed separately, with guidance on when and how antineoplastic (and/or cardiological) treatments should be modified. Further sections describe the correct responses to cardiac problems secondary to the cancer itself, including thromboembolic disorders and electrolyte imbalances, and the diagnosis, treatm...

European Journal of Gynaecological Oncology, Feb 10, 2018

Additional file 1: Table S1. Sequence variations in candidate genes.

BMC Pulmonary Medicine

Background Advanced lung adenocarcinoma (LAC) is one of the most lethal malignancies worldwide. T... more Background Advanced lung adenocarcinoma (LAC) is one of the most lethal malignancies worldwide. The aim of this study was to evaluate the global survival in a real-life cohort of patients with LAC harboring driver genetic alterations. Methods A series of 1282 consecutive Sardinian LAC patients who underwent genetic testing from January 2011 through July 2016 was collected. Molecular tests were based on the clinical needs of each single case (EGFR-exon18/19/21, ALK, and, more recently, BRAF-exon15), and the availability of tissue (KRAS, MET, and presence of low-frequency EGFR-T790M mutated alleles at baseline). Results The mean follow-up time of the patients was 46 months. EGFR, KRAS, and BRAF mutations were detected in 13.7%, 21.3%, and 3% of tested cases, respectively; ALK rearrangements and MET amplifications were found respectively in 4.7% and 2% of tested cases. As expected, cases with mutations in exons 18–21 of EGFR, sensitizing to anti-EGFR tyrosine kinase inhibitors (TKIs) a...

BMC Pulmonary Medicine, 2022

Background: Advanced lung adenocarcinoma (LAC) is one of the most lethal malignancies worldwide. ... more Background: Advanced lung adenocarcinoma (LAC) is one of the most lethal malignancies worldwide. The aim of this study was to evaluate the global survival in a real-life cohort of patients with LAC harboring driver genetic alterations. Methods: A series of 1282 consecutive Sardinian LAC patients who underwent genetic testing from January 2011 through July 2016 was collected. Molecular tests were based on the clinical needs of each single case (EGFR-exon18/19/21, ALK, and, more recently, BRAF-exon15), and the availability of tissue (KRAS, MET, and presence of lowfrequency EGFR-T790M mutated alleles at baseline). Results: The mean follow-up time of the patients was 46 months. EGFR, KRAS, and BRAF mutations were detected in 13.7%, 21.3%, and 3% of tested cases, respectively; ALK rearrangements and MET amplifications were found respectively in 4.7% and 2% of tested cases. As expected, cases with mutations in exons 18-21 of EGFR, sensitizing to anti-EGFR tyrosine kinase inhibitors (TKIs)...

Anticancer research, 2013

The early diagnosis of non-small cell lung carcinoma (NSCLC) is difficult, and 30-40% of patients... more The early diagnosis of non-small cell lung carcinoma (NSCLC) is difficult, and 30-40% of patients with NSCLC develop bone metastases (BMs) during the course of their disease. Because the delayed demonstration of skeletal involvement may seriously affect survival, there is a need for early diagnosis of BMs. Unfortunately, the sensitivity of common serum tumor markers is low and they are used mainly for monitoring the efficacy of therapy and detection of recurrence. The aim of this study was to evaluate the utility of a panel of serum biomarkers in patients with NSCLC and BMs. Sixteen patients (11 males, 5 females; median age=64 years, range 54-68 years) with NSCLC and BMs (cases), and 18 age- and stage-matched patients without BMs (controls) underwent measurement of serum carboxy-terminal telopeptide of type I collagen (CTX), tartrate-resistant acid phosphatase isoform type 5b (TRAP5b) and amino-terminal propeptide of type I collagen (PINP), carcinoembryonic antigen (CEA) and fragmen...

Background: IL-2 represents yet an alternative to targeted therapy for metastatic renal cancer (m... more Background: IL-2 represents yet an alternative to targeted therapy for metastatic renal cancer (mRCC) treatment. Prior studies have suggested high dose bolus as the preferred administration modality. However, its use is limited by toxicity and the search for an alternative modality is justified. In order to reduce toxicity we evaluated feasibility, dose limiting toxicity (DLT) and activity of IL-2 chrono-infusion in mRCC. Methods: Patients (pts) with mRCC were treated with IL-2 which was administered with an escalated dose in 8 hour chrono-infusion (peak 1am, 9am, and 5pm) from 2 MUI/m 2 according to Fibonacci scale. Results: 22 pts were enrolled. 3 pts entered each Level I to V and 7 entered VI. Grade 3-4 toxicities were reported only in 4 cases (2 hypotension and renal, 1 diarrhoea) on the VI Level. DLT was 18.6 MUI/m2. Overall response rate was 14% (23% in a good-intermediate risk group). Median PFS and OS were 4.5 and 14.5 months respectively. In an univariate analysis dose leve...

Introduction to assess incidence, prognosis and obstetric outcome of patients treated for gestati... more Introduction to assess incidence, prognosis and obstetric outcome of patients treated for gestational trophoblastic disease GTD in a twenty-year period. Incidence, prognosis and obstetric outcome of gestational throphoblastic disease Methods retrospective study. Results Fifty-four cases of GTD: 46 (85.18%) cases of Hydatidiform mole (HM); 8 cases of Persistent Gestational Trophoblastic Neoplasia (GTN) (14.81%): 6/8 cases (75%) GTN not metastatic; 2/8 cases (25%) GTN metastatic. In both cases, the metastases occurred in the lungs. In 3 out of 8 GTN cases (37.5%) a histological picture of choriocarcinoma emerged. The incidence of GTD cases treated from 2000 to 2020 was 1.8 cases per 1000 deliveries and 1.3 cases per 1000 pregnancies. Of the 54 patients, 30 (55.56%) presented showed normal serum hCG levels without the need for chemotherapy. On the other hand, 24 patients (44.44%) developed a persistent trophoblastic disease and underwent adjuvant therapy. The negative prognostic factor...

A rather frequent problem in cardio-oncology is the imperfect comprehension between cardiologists... more A rather frequent problem in cardio-oncology is the imperfect comprehension between cardiologists and oncologist. In the daily clinical practice, the use of acronyms is common, but the acronyms used in a particular field of medicine are easily understood by the specialists of that particular field only; they may be less obvious for specialists of other fields. This chapter will help in understanding the most common oncologic and cardiologic terms.

Il carcinoma della prostata è diventato la neoplasia più frequente, a partire dai 50 anni d’età, ... more Il carcinoma della prostata è diventato la neoplasia più frequente, a partire dai 50 anni d’età, negli uomini del nostro Paese, rappresentando oltre il 20% di tutti i tumori diagnosticati1. Nel 2018, in Italia, sono state stimate circa 35.000 nuove diagnosi della malattia e circa 7200 decessi sono stati attribuibili a essa nel 20151. I pazienti affetti da malattia metastatica rappresentano una piccola, ma clinicamente significativa, percentuale di questi nuovi casi. In queste persone, generalmente, l’osso, seguito dal polmone e dal fegato, rappresenta la sede elettiva di metastatizzazione (oltre l’80% dei casi)2. Nel corso della loro storia, approssimativamente la metà di questi pazienti svilupperà complicanze, definite “skeletal-related event” (SRE), correlate al coinvolgimento secondario dell’osso. La necessità, infatti, di sottoporre l’osso a un trattamento radioterapico palliativo con finalità antalgica oppure a un intervento di chirurgia ortopedica per stabilizzarlo; la compars...

Annals of Oncology

ABSTRACT Introduction In patients with colorectal cancer (CRC), several growth factors have been ... more ABSTRACT Introduction In patients with colorectal cancer (CRC), several growth factors have been identified as regulator of angiogenesis, including vascular endothelial growth factor (VEGF), a pro-angiogenic factor which can be safely measured in the blood. Angiogenesis plays an important role in the progression of CRC, as well as in the development of regional lymph node and distant metastasis. VEGF is minimally expressed or not expressed in colorectal adenomas and in normal colonic mucosa, while it is overexpressed in inflammatory bowel diseases as well as in CRCs. It has been shown that high microvessels density, an indirect measure of the degree of angiogenesis, correlates with increased tumor aggressiveness and risk of metastasis development, and that overexpression of VEGF in cancer tissues represents a sensitive marker of angiogenesis. Because undetected metastases can contribute to the failure of primary treatment, their early identification has a substantial impact on adequate therapy. In this setting, several serum tumor markers and tissue-extracting prognostic factors have been tested, including endothelial cell growth factor, and angiogenic cytokines, such as VEGF. In several studies, preoperative serum VEGF was increased in patients with CRC compared to controls, and high VEGF serum concentration tended to occur with more advanced disease. However, these data are not confirmed, and exclusively VEGF overexpression in cancer tissues significantly correlates with tumor biology. The aim of this study was to evaluate the relationship between serum VEGF, and the expression of VEGF-1 in a group of patients with CRC. Download : Download full-size image Methods Archival paraffin-embedded tumor samples from 38 patients (26 men, 12 women, median age 64 years, range 39-76) with stage I-II colorectal adenocarcinoma who underwent intentionally curative surgical resection, were reviewed. None of the patients received preoperative adjuvant chemotherapy. Written informed consent was obtained from all the participants. Serum VEGF was measured with a commercially available human VEGF quantitative enzyme-linked immunosorbent assay (ELISA) kit, according to the manufacturer's instructions. All analyses were made in duplicate, and the mean value was used for statistical calculations. Tissue microarray blocks for immunohistochemistry staining was obtained, serial 4 µm sections were cut, and then assessed using a commercial anti-human VEGF (clone VG-1). The Pearson's correlation coefficient calculation was used to evaluate results. Results The expression of VEGF was tested using a 4-grade scoring system, according to the degree of cytoplasmic staining, ranging from negative to intense staining. Overall, the mean serum VEGF concentration was 272.7±140.5 pg/mL (range 41-670 pg/mL), while the VEGF-1 grade was 2.8±1.0. There was a significant relationship between the stage of the disease and VEGF (R=0.43, p=0.006), and between serum VEGF and VEGF-1 grade (R=0.64, t=5.06, p Conclusion Tumor growth is dependent on angiogenesis and VEGF is potent growth factor with angiogenic activity. It can safely be tested by measurements of both serum VEGF levels and grade of tumor tissue expression of VEGF-1.

Annals of Oncology

ABSTRACT Introduction Despite significant advances in detection and treatment, colorectal cancer ... more ABSTRACT Introduction Despite significant advances in detection and treatment, colorectal cancer (CRC) still remains one of the most prevalent cancers, and one of the leading causes of mortality due to malignancy. In patients with stage I-II CRC surgical resection usually represents the sole treatment, while in those with metastasized tumor (stage IV) any therapy is rarely successful. Unfortunately, up to 60% of patients with CRC undergoing primary surgery with curative intention die from metastatic disease. Thus, occult tumor cells, not detected preoperatively, likely colonize and remain vital in different tissues of these patients, such as lymph nodes, blood, and bone marrow. Usually, CRC metastasizes to the liver and lungs more frequently than to bone. Isolated bone metastasis (BM) is considered truly rare, but it has been observed that the improved survival for patients with metastatic CRC following expanded treatment options is associate with an increased incidence of BMs. Because metastases in uncommon sites often indicates the terminal phase of CRC, clinicians should be more vigilant about possible BMs. For this purpose, several serum biomarkers have been tested for early detection of BMs, such as carboxy-terminal telopeptide of type I collagen (ICTP), a cross-link product of collagen I degradation, and tartrate-resistant acid phosphatase 5b (TRACP), specifically derived from osteoclasts. Recent studies showed that TRACP activity and ICTP were increased in up to 90% of patients with breast cancer and BM. The aim of this study was to evaluate the usefulness of TRACP, ICTP, and bone alkaline phosphatase (BAP) measurements in patients with CRC and BM. Methods Fourteen patients (9 men, 5 women, mean age 56.1±4.8, range 49-63 years) with CRC and confirmed BMs (cases), and a group of 15 age- and gender matched (10 men, 4 women, age 57.1±4.9 years, p=0.08) patients (controls) without BM (negative F-18 FDG PET/CT) underwent serum TRACP, ICTP, and BAP measurements. Written informed consent was obtained from all the participants. TRACP and BAP were measured by two-site enzyme-linked immunosorbent assay (ELISA), while ICTP was measured by commercially available radioimmunoassay. The sensitivity and specificity of serum TRACP, ICTP, and BAP as a marker for BM were estimated by receiver operator characteristic (ROC) curves. Results The mean levels of TRACP, ICTP, and BAP (cases vs. controls) were: 5.9±1.6 vs. 4.8±1.3 U/L (95% CI 0.11-2.11, p=0.08), 6.9±1.4 vs. 5.9±1.3 U/L (95% CI 0.94-3.04, p=0.0003), and 82.6±18.2 vs. 79.3±16.2 (95% CI 9.81-16.39, p=0.59). ROC analysis established a cutoff value for ICTP of 4.51 U/mL to identify patients with extensive BM with a specificity of 97% and a sensitivity of 92% (area under the curve=0.97; 95% CI=0.95-0.98). A strong relationship was found only between TRACP and ICTP (R=0.95, p Conclusion Serum ICTP is a useful diagnostic marker in the detection of BMs in patients with CRC, more accurate than TRACP and BAP.

Annals of Oncology

ABSTRACT Introduction Colorectal cancer (CRC) remains the third most common cancer both in men an... more ABSTRACT Introduction Colorectal cancer (CRC) remains the third most common cancer both in men and women worldwide, and its incidence rates continue to increase in the USA and Western Europe. Angiogenesis is crucial for growth of all tumors, and mature and immature endothelial cells, such as circulating endothelial cells (CECs) and endothelial progenitor cells, are present in the human blood. CECs are extremely rare in normal peripheral blood, but it has been shown that their number is significantly increased in many pathological conditions, including cancer. Some Among CECs display characteristics of terminally differentiated and mature cells, while others express specific surface antigens, suggesting a progenitor-like or stem-like phenotype. Thus, vasculogenesis is not restricted to embryonic development, and there are putative circulating endothelial progenitors which can participate in the generation of new vessels. CECs measurement is a promising biomarker to assess the efficacy of antiangiogenic therapies, and their increase may suggest the possible presence of metastatic disease, including in patients with CRC. Different cell surface markers have been tested to detect CECs, and flow cytometry represents a well suited method for their detection and quantitation. The aim of this study was to evaluate the levels of the microenvironmental cell marker CD146+CD45- phenotype, which is linked to angiogenesis, vessel damage, and disease progression, in patients with pT0-1 CRC. Methods Blood samples from 41 patients (26 men, 15 women, median age 64 years, range 39-74 years) with confirmed colorectal adenocarcinoma undergoing curative surgery were collected for analysis of CECs. Patients with distant metastases (negative F-18 FDG PET/CT) have been excluded, as well as those who had undergone adjuvant chemotherapy. Written informed consent was obtained from all the participants. All samples were stained with antihuman CD146 phycoerythrin (CD146-PE) and CD45 fluorescein isothiocyanate (CD45-FITC). Immunophenotyping was obtained using a Beckman Coulter XL-MCL flow cytometer to assess levels of CD146+CD45- CECs, using a 600 s acquisition time for each sample. According to final pathology, two groups of patients were obtained: Group A (28 patients, 68.3%) with negative lymph nodes (pN0), and Group B (13 patients, 31.7%) with regional lymph node metastasis (pN1). Results N1 patients (Group B) had a level of CD146+/CD45- cells significantly increased (19.2±9.1 vs. 12.4±8.6 CECs, 95% CI 0.72-12.88, p=0.029) in respect to N0 patients (Group B). No correlation (R=0.10, p=0.22) was found between number of the N1 and level of putative CECs. There was no difference (p=NS) between men and women. Conclusion Although CECs are a rare cell population (less than one in 1000 circulating blood cells) and their not yet completely established phenotype represent a technical challenge, our preliminary data suggest a possible increased angiogenic activity in patients with N1 CRC, which can be demonstrated using flow cytometry analysis of CECs. Further endothelial cell markers, alone or in combination, should be studied to confirm this hypothesis.

BMC Pulmonary Medicine

Background Lung cancer is one of the most incident neoplastic diseases, and a leading cause of de... more Background Lung cancer is one of the most incident neoplastic diseases, and a leading cause of death for cancer worldwide. Knowledge of the incidence of druggable genetic alterations, their correlation with clinical and pathological features of the disease, and their interplay in cases of co-occurrence is crucial for selecting the best therapeutic strategies of patients with non-small cell lung cancer. In this real-life study, we describe the molecular epidemiology of genetic alterations in five driver genes and their correlations with the demographic and clinical characteristics of Sardinian patients with lung adenocarcinoma. Methods Data from 1440 consecutive Sardinian patients with a histologically proven diagnosis of lung adenocarcinoma from January 2011 through July 2016 were prospectively investigated. EGFR mutation analysis was performed for all of them, while KRAS and BRAF mutations were searched in 1047 cases; ALK alterations were determined with fluorescence in situ hybrid...

BMC Pulmonary Medicne, 2019

Background: lung cancer is one of the most incident neoplastic diseases and a leading cause of de... more Background: lung cancer is one of the most incident neoplastic diseases and a leading cause of death for cancer worldwide. Knowledge of the incidence of druggable genetic alterations, their correlation with clinical and pathological features of the disease, and their interplay in cases of co-occurrence is crucial for selecting the best therapeutic strategies of patients with non-small cell lung cancer. In this real-life study, we describe the molecular epidemiology of genetic alterations in five driver genes and their correlations with the demographic and clinical characteristics of Sardinian patients with lung adenocarcinoma. Methods: Data from 1440 consecutive Sardinian patients with a histologically proven diagnosis of lung adenocarcinoma from January 2011 through July 2016 were prospectively investigated. EGFR mutation analysis was performed for all of them, while KRAS and BRAF mutations were searched in 1,047 cases; ALK alterations were determined with fluorescence in situ hybr...

Tumori Journal

al. The paper reported a rare case of primary small cell bladder carcinoma (SCCB) along with a li... more al. The paper reported a rare case of primary small cell bladder carcinoma (SCCB) along with a literature review. We appreciate the efforts of the authors to confirm the rarity of this disease and to describe in their review its clinical, diagnostic and therapeutic features. We recently observed a case of a primary SCCB and we consider it helpful to report our experience, which also describes the unusual coexistence of a primary non-small cell lung carcinoma (NSCLC). In January 2006, a 73-year-old man underwent transurethral resection of a bladder cancer. Histological examination revealed SCCB. A total-body CT scan showed the bladder tumor with pelvic lymph node involvement, as well as a lesion in the right lung of about 4 cm with ipsilateral hilar lymph node involvement. SCCB was at stage IV. A CT-guided fine-needle biopsy of the pulmonary mass performed for diagnostic refinement showed the lesion to be a NSCLC at stage IIIa. Laboratory findings showed renal insufficiency with creatinine 1.2 mg/dL and spirometry revealed a condition of chronic bronchitis related to substantial tobacco use (60 cigarettes a day since the age of 19). Considering the patient’s condition and his performance status, which precluded surgery or radiotherapy, palliative chemotherapy was started with a schedule including carboplatin AUC 4 on day 1 and gemcitabine 1000 mg/m on days 1 and 8, every 28 days. Three courses of chemotherapy were administered, the last causing severe hematological toxicity with the onset of prolonged grade 3 thrombocytopenia, which made it necessary to stop the treatment. Restaging by total-body CT scan showed stabilization of the lung cancer and a remarkable partial remission of the bladder cancer and metastatic pelvic lymph nodes. Unfortunaltely, because of the persistence of thrombocytopenia, we were unable to resume chemotherapy, and the patient’s condition declined due to pelvic progression of SCCB. Acute renal failure led to his death in June 2006. As reviewed by Zachos et al., most patients affected by SCCB have a history of smoking. In our case the concurrent development of the 2 cancers, which is very rare, was probably the result of this bad habit. Our experience confirms that SCCB has a poor prognosis. We agree with Zachos et al. that platinum-based chemotherapy provides a chance to improve the survival of patients. Recently, Shirato et al. reported the efficacy of the combination of cisplatin and gemcitabine as neoadjuvant chemotherapy in a case of SCCB. The carboplatin-gemcitabine combination may be active in both NSCLC and SCCB. We chose the carboplatin-gemcitabine regimen because of its presumed lower impact on the patient’s renal function. Our experience suggests that this regimen can lead to objective responses in SCCB and may be considered a valid treatment option in the presence of synchronous NSCLC and SCCB. However, particular attention must be paid to the management of hematological toxicity. As Zachos et al. remarked, we agree that the rareness of SCCB precludes prospective studies and the optimal therapeutic strategy is as yet undetermined. Tumori, 93: 327, 2007

Journal of Clinical Medicine

Sinonasal mucosal melanoma (SNM) is a rare and aggressive type of melanoma, and because of this, ... more Sinonasal mucosal melanoma (SNM) is a rare and aggressive type of melanoma, and because of this, we currently have a limited understanding of its genetic and molecular constitution. The incidence among SNMs of somatic mutations in the genes involved in the main molecular pathways, which have been largely associated with cutaneous melanoma, is not yet fully understood. Through a next-generation sequencing (NGS) approach using a panel of 25 genes involved in melanoma pathogenesis customized by our group, we performed a mutation analysis in a cohort of 25 SNM patients. Results showed that pathogenic mutations were found in more than 60% of SNM cases at a somatic level, with strikingly 32% of them carrying deleterious mutations in the BRAF gene. The identified mutations mostly lack the typical UV signature associated with cutaneous melanomas and showed no significant association with any histopathological parameter. Oncogenic activation of the BRAF-depending pathway, which may induce im...

Journal of Clinical Medicne, 2019

Abstract: Sinonasal mucosal melanoma (SNM) is a rare and aggressive type of melanoma, and because... more Abstract: Sinonasal mucosal melanoma (SNM) is a rare and aggressive type of melanoma, and because of this, we currently have a limited understanding of its genetic and molecular constitution. The incidence among SNMs of somatic mutations in the genes involved in the main molecular pathways, which have been largely associated with cutaneous melanoma, is not yet fully understood. Through a next generation sequencing (NGS) approach using a panel of 25 genes involved in melanoma pathogenesis customized by our group, we performed a mutation analysis in a cohort of 25 SNM patients. Results showed that pathogenic mutations were found in more than 60% of SNM cases at a somatic level, with strikingly 32% of them carrying deleterious mutations in the BRAF gene. The identified mutations mostly lack the typical UV signature associated with cutaneous melanomas and showed no significant association with any histopathological parameter. Oncogenic activation of the BRAF-depending pathway, which may...

Tumori Journal

Background Osteopetrosis or Albers-Schonberg's disease is a heterogeneous group of rare hered... more Background Osteopetrosis or Albers-Schonberg's disease is a heterogeneous group of rare hereditary troubles of the bone characterized by bone sclerosis due to an alteration of the bone reabsorption mediated by osteoclasts. The defect in the osteoclastic activity is responsible for complete or partial medullary cavities occlusion, with consequent reduced hemopoiesis, and for the excessive fragility of the affected bone segments. Case report We reported the case of a young man of 31 years affected by osteopetrosis in which a small cell lung cancer developed. Results Small cell lung cancer is a particularly rare neoplasm in the young, and even though it is highly sensitive to chemotherapeutic treatment its prognosis remains poor. The greatest clinical problem connected with chemotherapeutic treatment of patients affected by osteopetrosis is the variability of the reduction of their bone marrow reserve, which could expose them to an excessive hematological toxicity caused by the the...

This concise and handy manual provides straightforward, up-to-date guidance for cardiologists and... more This concise and handy manual provides straightforward, up-to-date guidance for cardiologists and other practitioners on the management of cancer patients with cardiac problems, whether they be due to the cancer itself or to antineoplastic treatment. Detailed attention is devoted to the various forms of cardiotoxicity associated with chemotherapy and radiotherapy. The drugs commonly responsible for each toxicity are identified and clear advice is offered on monitoring techniques and treatment approaches. In addition, the issue of cardiotoxicity due to cancer treatment in particular patient groups \\u2013 children, the elderly, and those with pre-existing cardiac disease \\u2013 is addressed separately, with guidance on when and how antineoplastic (and/or cardiological) treatments should be modified. Further sections describe the correct responses to cardiac problems secondary to the cancer itself, including thromboembolic disorders and electrolyte imbalances, and the diagnosis, treatm...

European Journal of Gynaecological Oncology, Feb 10, 2018

Additional file 1: Table S1. Sequence variations in candidate genes.

BMC Pulmonary Medicine

Background Advanced lung adenocarcinoma (LAC) is one of the most lethal malignancies worldwide. T... more Background Advanced lung adenocarcinoma (LAC) is one of the most lethal malignancies worldwide. The aim of this study was to evaluate the global survival in a real-life cohort of patients with LAC harboring driver genetic alterations. Methods A series of 1282 consecutive Sardinian LAC patients who underwent genetic testing from January 2011 through July 2016 was collected. Molecular tests were based on the clinical needs of each single case (EGFR-exon18/19/21, ALK, and, more recently, BRAF-exon15), and the availability of tissue (KRAS, MET, and presence of low-frequency EGFR-T790M mutated alleles at baseline). Results The mean follow-up time of the patients was 46 months. EGFR, KRAS, and BRAF mutations were detected in 13.7%, 21.3%, and 3% of tested cases, respectively; ALK rearrangements and MET amplifications were found respectively in 4.7% and 2% of tested cases. As expected, cases with mutations in exons 18–21 of EGFR, sensitizing to anti-EGFR tyrosine kinase inhibitors (TKIs) a...

BMC Pulmonary Medicine, 2022

Background: Advanced lung adenocarcinoma (LAC) is one of the most lethal malignancies worldwide. ... more Background: Advanced lung adenocarcinoma (LAC) is one of the most lethal malignancies worldwide. The aim of this study was to evaluate the global survival in a real-life cohort of patients with LAC harboring driver genetic alterations. Methods: A series of 1282 consecutive Sardinian LAC patients who underwent genetic testing from January 2011 through July 2016 was collected. Molecular tests were based on the clinical needs of each single case (EGFR-exon18/19/21, ALK, and, more recently, BRAF-exon15), and the availability of tissue (KRAS, MET, and presence of lowfrequency EGFR-T790M mutated alleles at baseline). Results: The mean follow-up time of the patients was 46 months. EGFR, KRAS, and BRAF mutations were detected in 13.7%, 21.3%, and 3% of tested cases, respectively; ALK rearrangements and MET amplifications were found respectively in 4.7% and 2% of tested cases. As expected, cases with mutations in exons 18-21 of EGFR, sensitizing to anti-EGFR tyrosine kinase inhibitors (TKIs)...

Anticancer research, 2013

The early diagnosis of non-small cell lung carcinoma (NSCLC) is difficult, and 30-40% of patients... more The early diagnosis of non-small cell lung carcinoma (NSCLC) is difficult, and 30-40% of patients with NSCLC develop bone metastases (BMs) during the course of their disease. Because the delayed demonstration of skeletal involvement may seriously affect survival, there is a need for early diagnosis of BMs. Unfortunately, the sensitivity of common serum tumor markers is low and they are used mainly for monitoring the efficacy of therapy and detection of recurrence. The aim of this study was to evaluate the utility of a panel of serum biomarkers in patients with NSCLC and BMs. Sixteen patients (11 males, 5 females; median age=64 years, range 54-68 years) with NSCLC and BMs (cases), and 18 age- and stage-matched patients without BMs (controls) underwent measurement of serum carboxy-terminal telopeptide of type I collagen (CTX), tartrate-resistant acid phosphatase isoform type 5b (TRAP5b) and amino-terminal propeptide of type I collagen (PINP), carcinoembryonic antigen (CEA) and fragmen...

Background: IL-2 represents yet an alternative to targeted therapy for metastatic renal cancer (m... more Background: IL-2 represents yet an alternative to targeted therapy for metastatic renal cancer (mRCC) treatment. Prior studies have suggested high dose bolus as the preferred administration modality. However, its use is limited by toxicity and the search for an alternative modality is justified. In order to reduce toxicity we evaluated feasibility, dose limiting toxicity (DLT) and activity of IL-2 chrono-infusion in mRCC. Methods: Patients (pts) with mRCC were treated with IL-2 which was administered with an escalated dose in 8 hour chrono-infusion (peak 1am, 9am, and 5pm) from 2 MUI/m 2 according to Fibonacci scale. Results: 22 pts were enrolled. 3 pts entered each Level I to V and 7 entered VI. Grade 3-4 toxicities were reported only in 4 cases (2 hypotension and renal, 1 diarrhoea) on the VI Level. DLT was 18.6 MUI/m2. Overall response rate was 14% (23% in a good-intermediate risk group). Median PFS and OS were 4.5 and 14.5 months respectively. In an univariate analysis dose leve...

Introduction to assess incidence, prognosis and obstetric outcome of patients treated for gestati... more Introduction to assess incidence, prognosis and obstetric outcome of patients treated for gestational trophoblastic disease GTD in a twenty-year period. Incidence, prognosis and obstetric outcome of gestational throphoblastic disease Methods retrospective study. Results Fifty-four cases of GTD: 46 (85.18%) cases of Hydatidiform mole (HM); 8 cases of Persistent Gestational Trophoblastic Neoplasia (GTN) (14.81%): 6/8 cases (75%) GTN not metastatic; 2/8 cases (25%) GTN metastatic. In both cases, the metastases occurred in the lungs. In 3 out of 8 GTN cases (37.5%) a histological picture of choriocarcinoma emerged. The incidence of GTD cases treated from 2000 to 2020 was 1.8 cases per 1000 deliveries and 1.3 cases per 1000 pregnancies. Of the 54 patients, 30 (55.56%) presented showed normal serum hCG levels without the need for chemotherapy. On the other hand, 24 patients (44.44%) developed a persistent trophoblastic disease and underwent adjuvant therapy. The negative prognostic factor...

A rather frequent problem in cardio-oncology is the imperfect comprehension between cardiologists... more A rather frequent problem in cardio-oncology is the imperfect comprehension between cardiologists and oncologist. In the daily clinical practice, the use of acronyms is common, but the acronyms used in a particular field of medicine are easily understood by the specialists of that particular field only; they may be less obvious for specialists of other fields. This chapter will help in understanding the most common oncologic and cardiologic terms.

Il carcinoma della prostata è diventato la neoplasia più frequente, a partire dai 50 anni d’età, ... more Il carcinoma della prostata è diventato la neoplasia più frequente, a partire dai 50 anni d’età, negli uomini del nostro Paese, rappresentando oltre il 20% di tutti i tumori diagnosticati1. Nel 2018, in Italia, sono state stimate circa 35.000 nuove diagnosi della malattia e circa 7200 decessi sono stati attribuibili a essa nel 20151. I pazienti affetti da malattia metastatica rappresentano una piccola, ma clinicamente significativa, percentuale di questi nuovi casi. In queste persone, generalmente, l’osso, seguito dal polmone e dal fegato, rappresenta la sede elettiva di metastatizzazione (oltre l’80% dei casi)2. Nel corso della loro storia, approssimativamente la metà di questi pazienti svilupperà complicanze, definite “skeletal-related event” (SRE), correlate al coinvolgimento secondario dell’osso. La necessità, infatti, di sottoporre l’osso a un trattamento radioterapico palliativo con finalità antalgica oppure a un intervento di chirurgia ortopedica per stabilizzarlo; la compars...

Annals of Oncology

ABSTRACT Introduction In patients with colorectal cancer (CRC), several growth factors have been ... more ABSTRACT Introduction In patients with colorectal cancer (CRC), several growth factors have been identified as regulator of angiogenesis, including vascular endothelial growth factor (VEGF), a pro-angiogenic factor which can be safely measured in the blood. Angiogenesis plays an important role in the progression of CRC, as well as in the development of regional lymph node and distant metastasis. VEGF is minimally expressed or not expressed in colorectal adenomas and in normal colonic mucosa, while it is overexpressed in inflammatory bowel diseases as well as in CRCs. It has been shown that high microvessels density, an indirect measure of the degree of angiogenesis, correlates with increased tumor aggressiveness and risk of metastasis development, and that overexpression of VEGF in cancer tissues represents a sensitive marker of angiogenesis. Because undetected metastases can contribute to the failure of primary treatment, their early identification has a substantial impact on adequate therapy. In this setting, several serum tumor markers and tissue-extracting prognostic factors have been tested, including endothelial cell growth factor, and angiogenic cytokines, such as VEGF. In several studies, preoperative serum VEGF was increased in patients with CRC compared to controls, and high VEGF serum concentration tended to occur with more advanced disease. However, these data are not confirmed, and exclusively VEGF overexpression in cancer tissues significantly correlates with tumor biology. The aim of this study was to evaluate the relationship between serum VEGF, and the expression of VEGF-1 in a group of patients with CRC. Download : Download full-size image Methods Archival paraffin-embedded tumor samples from 38 patients (26 men, 12 women, median age 64 years, range 39-76) with stage I-II colorectal adenocarcinoma who underwent intentionally curative surgical resection, were reviewed. None of the patients received preoperative adjuvant chemotherapy. Written informed consent was obtained from all the participants. Serum VEGF was measured with a commercially available human VEGF quantitative enzyme-linked immunosorbent assay (ELISA) kit, according to the manufacturer's instructions. All analyses were made in duplicate, and the mean value was used for statistical calculations. Tissue microarray blocks for immunohistochemistry staining was obtained, serial 4 µm sections were cut, and then assessed using a commercial anti-human VEGF (clone VG-1). The Pearson's correlation coefficient calculation was used to evaluate results. Results The expression of VEGF was tested using a 4-grade scoring system, according to the degree of cytoplasmic staining, ranging from negative to intense staining. Overall, the mean serum VEGF concentration was 272.7±140.5 pg/mL (range 41-670 pg/mL), while the VEGF-1 grade was 2.8±1.0. There was a significant relationship between the stage of the disease and VEGF (R=0.43, p=0.006), and between serum VEGF and VEGF-1 grade (R=0.64, t=5.06, p Conclusion Tumor growth is dependent on angiogenesis and VEGF is potent growth factor with angiogenic activity. It can safely be tested by measurements of both serum VEGF levels and grade of tumor tissue expression of VEGF-1.

Annals of Oncology

ABSTRACT Introduction Despite significant advances in detection and treatment, colorectal cancer ... more ABSTRACT Introduction Despite significant advances in detection and treatment, colorectal cancer (CRC) still remains one of the most prevalent cancers, and one of the leading causes of mortality due to malignancy. In patients with stage I-II CRC surgical resection usually represents the sole treatment, while in those with metastasized tumor (stage IV) any therapy is rarely successful. Unfortunately, up to 60% of patients with CRC undergoing primary surgery with curative intention die from metastatic disease. Thus, occult tumor cells, not detected preoperatively, likely colonize and remain vital in different tissues of these patients, such as lymph nodes, blood, and bone marrow. Usually, CRC metastasizes to the liver and lungs more frequently than to bone. Isolated bone metastasis (BM) is considered truly rare, but it has been observed that the improved survival for patients with metastatic CRC following expanded treatment options is associate with an increased incidence of BMs. Because metastases in uncommon sites often indicates the terminal phase of CRC, clinicians should be more vigilant about possible BMs. For this purpose, several serum biomarkers have been tested for early detection of BMs, such as carboxy-terminal telopeptide of type I collagen (ICTP), a cross-link product of collagen I degradation, and tartrate-resistant acid phosphatase 5b (TRACP), specifically derived from osteoclasts. Recent studies showed that TRACP activity and ICTP were increased in up to 90% of patients with breast cancer and BM. The aim of this study was to evaluate the usefulness of TRACP, ICTP, and bone alkaline phosphatase (BAP) measurements in patients with CRC and BM. Methods Fourteen patients (9 men, 5 women, mean age 56.1±4.8, range 49-63 years) with CRC and confirmed BMs (cases), and a group of 15 age- and gender matched (10 men, 4 women, age 57.1±4.9 years, p=0.08) patients (controls) without BM (negative F-18 FDG PET/CT) underwent serum TRACP, ICTP, and BAP measurements. Written informed consent was obtained from all the participants. TRACP and BAP were measured by two-site enzyme-linked immunosorbent assay (ELISA), while ICTP was measured by commercially available radioimmunoassay. The sensitivity and specificity of serum TRACP, ICTP, and BAP as a marker for BM were estimated by receiver operator characteristic (ROC) curves. Results The mean levels of TRACP, ICTP, and BAP (cases vs. controls) were: 5.9±1.6 vs. 4.8±1.3 U/L (95% CI 0.11-2.11, p=0.08), 6.9±1.4 vs. 5.9±1.3 U/L (95% CI 0.94-3.04, p=0.0003), and 82.6±18.2 vs. 79.3±16.2 (95% CI 9.81-16.39, p=0.59). ROC analysis established a cutoff value for ICTP of 4.51 U/mL to identify patients with extensive BM with a specificity of 97% and a sensitivity of 92% (area under the curve=0.97; 95% CI=0.95-0.98). A strong relationship was found only between TRACP and ICTP (R=0.95, p Conclusion Serum ICTP is a useful diagnostic marker in the detection of BMs in patients with CRC, more accurate than TRACP and BAP.

Annals of Oncology

ABSTRACT Introduction Colorectal cancer (CRC) remains the third most common cancer both in men an... more ABSTRACT Introduction Colorectal cancer (CRC) remains the third most common cancer both in men and women worldwide, and its incidence rates continue to increase in the USA and Western Europe. Angiogenesis is crucial for growth of all tumors, and mature and immature endothelial cells, such as circulating endothelial cells (CECs) and endothelial progenitor cells, are present in the human blood. CECs are extremely rare in normal peripheral blood, but it has been shown that their number is significantly increased in many pathological conditions, including cancer. Some Among CECs display characteristics of terminally differentiated and mature cells, while others express specific surface antigens, suggesting a progenitor-like or stem-like phenotype. Thus, vasculogenesis is not restricted to embryonic development, and there are putative circulating endothelial progenitors which can participate in the generation of new vessels. CECs measurement is a promising biomarker to assess the efficacy of antiangiogenic therapies, and their increase may suggest the possible presence of metastatic disease, including in patients with CRC. Different cell surface markers have been tested to detect CECs, and flow cytometry represents a well suited method for their detection and quantitation. The aim of this study was to evaluate the levels of the microenvironmental cell marker CD146+CD45- phenotype, which is linked to angiogenesis, vessel damage, and disease progression, in patients with pT0-1 CRC. Methods Blood samples from 41 patients (26 men, 15 women, median age 64 years, range 39-74 years) with confirmed colorectal adenocarcinoma undergoing curative surgery were collected for analysis of CECs. Patients with distant metastases (negative F-18 FDG PET/CT) have been excluded, as well as those who had undergone adjuvant chemotherapy. Written informed consent was obtained from all the participants. All samples were stained with antihuman CD146 phycoerythrin (CD146-PE) and CD45 fluorescein isothiocyanate (CD45-FITC). Immunophenotyping was obtained using a Beckman Coulter XL-MCL flow cytometer to assess levels of CD146+CD45- CECs, using a 600 s acquisition time for each sample. According to final pathology, two groups of patients were obtained: Group A (28 patients, 68.3%) with negative lymph nodes (pN0), and Group B (13 patients, 31.7%) with regional lymph node metastasis (pN1). Results N1 patients (Group B) had a level of CD146+/CD45- cells significantly increased (19.2±9.1 vs. 12.4±8.6 CECs, 95% CI 0.72-12.88, p=0.029) in respect to N0 patients (Group B). No correlation (R=0.10, p=0.22) was found between number of the N1 and level of putative CECs. There was no difference (p=NS) between men and women. Conclusion Although CECs are a rare cell population (less than one in 1000 circulating blood cells) and their not yet completely established phenotype represent a technical challenge, our preliminary data suggest a possible increased angiogenic activity in patients with N1 CRC, which can be demonstrated using flow cytometry analysis of CECs. Further endothelial cell markers, alone or in combination, should be studied to confirm this hypothesis.

BMC Pulmonary Medicine

Background Lung cancer is one of the most incident neoplastic diseases, and a leading cause of de... more Background Lung cancer is one of the most incident neoplastic diseases, and a leading cause of death for cancer worldwide. Knowledge of the incidence of druggable genetic alterations, their correlation with clinical and pathological features of the disease, and their interplay in cases of co-occurrence is crucial for selecting the best therapeutic strategies of patients with non-small cell lung cancer. In this real-life study, we describe the molecular epidemiology of genetic alterations in five driver genes and their correlations with the demographic and clinical characteristics of Sardinian patients with lung adenocarcinoma. Methods Data from 1440 consecutive Sardinian patients with a histologically proven diagnosis of lung adenocarcinoma from January 2011 through July 2016 were prospectively investigated. EGFR mutation analysis was performed for all of them, while KRAS and BRAF mutations were searched in 1047 cases; ALK alterations were determined with fluorescence in situ hybrid...

BMC Pulmonary Medicne, 2019

Background: lung cancer is one of the most incident neoplastic diseases and a leading cause of de... more Background: lung cancer is one of the most incident neoplastic diseases and a leading cause of death for cancer worldwide. Knowledge of the incidence of druggable genetic alterations, their correlation with clinical and pathological features of the disease, and their interplay in cases of co-occurrence is crucial for selecting the best therapeutic strategies of patients with non-small cell lung cancer. In this real-life study, we describe the molecular epidemiology of genetic alterations in five driver genes and their correlations with the demographic and clinical characteristics of Sardinian patients with lung adenocarcinoma. Methods: Data from 1440 consecutive Sardinian patients with a histologically proven diagnosis of lung adenocarcinoma from January 2011 through July 2016 were prospectively investigated. EGFR mutation analysis was performed for all of them, while KRAS and BRAF mutations were searched in 1,047 cases; ALK alterations were determined with fluorescence in situ hybr...

Tumori Journal

al. The paper reported a rare case of primary small cell bladder carcinoma (SCCB) along with a li... more al. The paper reported a rare case of primary small cell bladder carcinoma (SCCB) along with a literature review. We appreciate the efforts of the authors to confirm the rarity of this disease and to describe in their review its clinical, diagnostic and therapeutic features. We recently observed a case of a primary SCCB and we consider it helpful to report our experience, which also describes the unusual coexistence of a primary non-small cell lung carcinoma (NSCLC). In January 2006, a 73-year-old man underwent transurethral resection of a bladder cancer. Histological examination revealed SCCB. A total-body CT scan showed the bladder tumor with pelvic lymph node involvement, as well as a lesion in the right lung of about 4 cm with ipsilateral hilar lymph node involvement. SCCB was at stage IV. A CT-guided fine-needle biopsy of the pulmonary mass performed for diagnostic refinement showed the lesion to be a NSCLC at stage IIIa. Laboratory findings showed renal insufficiency with creatinine 1.2 mg/dL and spirometry revealed a condition of chronic bronchitis related to substantial tobacco use (60 cigarettes a day since the age of 19). Considering the patient’s condition and his performance status, which precluded surgery or radiotherapy, palliative chemotherapy was started with a schedule including carboplatin AUC 4 on day 1 and gemcitabine 1000 mg/m on days 1 and 8, every 28 days. Three courses of chemotherapy were administered, the last causing severe hematological toxicity with the onset of prolonged grade 3 thrombocytopenia, which made it necessary to stop the treatment. Restaging by total-body CT scan showed stabilization of the lung cancer and a remarkable partial remission of the bladder cancer and metastatic pelvic lymph nodes. Unfortunaltely, because of the persistence of thrombocytopenia, we were unable to resume chemotherapy, and the patient’s condition declined due to pelvic progression of SCCB. Acute renal failure led to his death in June 2006. As reviewed by Zachos et al., most patients affected by SCCB have a history of smoking. In our case the concurrent development of the 2 cancers, which is very rare, was probably the result of this bad habit. Our experience confirms that SCCB has a poor prognosis. We agree with Zachos et al. that platinum-based chemotherapy provides a chance to improve the survival of patients. Recently, Shirato et al. reported the efficacy of the combination of cisplatin and gemcitabine as neoadjuvant chemotherapy in a case of SCCB. The carboplatin-gemcitabine combination may be active in both NSCLC and SCCB. We chose the carboplatin-gemcitabine regimen because of its presumed lower impact on the patient’s renal function. Our experience suggests that this regimen can lead to objective responses in SCCB and may be considered a valid treatment option in the presence of synchronous NSCLC and SCCB. However, particular attention must be paid to the management of hematological toxicity. As Zachos et al. remarked, we agree that the rareness of SCCB precludes prospective studies and the optimal therapeutic strategy is as yet undetermined. Tumori, 93: 327, 2007

Journal of Clinical Medicine

Sinonasal mucosal melanoma (SNM) is a rare and aggressive type of melanoma, and because of this, ... more Sinonasal mucosal melanoma (SNM) is a rare and aggressive type of melanoma, and because of this, we currently have a limited understanding of its genetic and molecular constitution. The incidence among SNMs of somatic mutations in the genes involved in the main molecular pathways, which have been largely associated with cutaneous melanoma, is not yet fully understood. Through a next-generation sequencing (NGS) approach using a panel of 25 genes involved in melanoma pathogenesis customized by our group, we performed a mutation analysis in a cohort of 25 SNM patients. Results showed that pathogenic mutations were found in more than 60% of SNM cases at a somatic level, with strikingly 32% of them carrying deleterious mutations in the BRAF gene. The identified mutations mostly lack the typical UV signature associated with cutaneous melanomas and showed no significant association with any histopathological parameter. Oncogenic activation of the BRAF-depending pathway, which may induce im...

Journal of Clinical Medicne, 2019

Abstract: Sinonasal mucosal melanoma (SNM) is a rare and aggressive type of melanoma, and because... more Abstract: Sinonasal mucosal melanoma (SNM) is a rare and aggressive type of melanoma, and because of this, we currently have a limited understanding of its genetic and molecular constitution. The incidence among SNMs of somatic mutations in the genes involved in the main molecular pathways, which have been largely associated with cutaneous melanoma, is not yet fully understood. Through a next generation sequencing (NGS) approach using a panel of 25 genes involved in melanoma pathogenesis customized by our group, we performed a mutation analysis in a cohort of 25 SNM patients. Results showed that pathogenic mutations were found in more than 60% of SNM cases at a somatic level, with strikingly 32% of them carrying deleterious mutations in the BRAF gene. The identified mutations mostly lack the typical UV signature associated with cutaneous melanomas and showed no significant association with any histopathological parameter. Oncogenic activation of the BRAF-depending pathway, which may...

Tumori Journal

Background Osteopetrosis or Albers-Schonberg's disease is a heterogeneous group of rare hered... more Background Osteopetrosis or Albers-Schonberg's disease is a heterogeneous group of rare hereditary troubles of the bone characterized by bone sclerosis due to an alteration of the bone reabsorption mediated by osteoclasts. The defect in the osteoclastic activity is responsible for complete or partial medullary cavities occlusion, with consequent reduced hemopoiesis, and for the excessive fragility of the affected bone segments. Case report We reported the case of a young man of 31 years affected by osteopetrosis in which a small cell lung cancer developed. Results Small cell lung cancer is a particularly rare neoplasm in the young, and even though it is highly sensitive to chemotherapeutic treatment its prognosis remains poor. The greatest clinical problem connected with chemotherapeutic treatment of patients affected by osteopetrosis is the variability of the reduction of their bone marrow reserve, which could expose them to an excessive hematological toxicity caused by the the...