Publications by authors named "Giovannella Palmieri"

64 Publications

BRAF Gene and Melanoma: Back to the Future.

Int J Mol Sci 2021 Mar 27;22(7). Epub 2021 Mar 27.

Unit of Melanoma, Cancer Immunotherapy and Development Therapeutics, Istituto Nazionale Tumori IRCCS Fondazione Pascale, 80131 Naples, Italy.

As widely acknowledged, 40-50% of all melanoma patients harbour an activating BRAF mutation (mostly BRAF V600E). The identification of the RAS-RAF-MEK-ERK (MAP kinase) signalling pathway and its targeting has represented a valuable milestone for the advanced and, more recently, for the completely resected stage III and IV melanoma therapy management. However, despite progress in BRAF-mutant melanoma treatment, the two different approaches approved so far for metastatic disease, immunotherapy and BRAF+MEK inhibitors, allow a 5-year survival of no more than 60%, and most patients relapse during treatment due to acquired mechanisms of resistance. Deep insight into BRAF gene biology is fundamental to describe the acquired resistance mechanisms (primary and secondary) and to understand the molecular pathways that are now being investigated in preclinical and clinical studies with the aim of improving outcomes in BRAF-mutant patients.
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http://dx.doi.org/10.3390/ijms22073474DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8037827PMC
March 2021

A New Horizon of Liquid Biopsy in Thymic Epithelial Tumors: The Potential Utility of Circulating Cell-Free DNA.

Front Oncol 2020 4;10:602153. Epub 2021 Feb 4.

CRCTR Rare Tumors Coordinating Center of Campania Region, Naples, Italy.

Background: Thymic epithelial tumors (TETs) are rare thoracic malignancies, commonly divided into two different histopathological entities, thymoma (T) and thymic carcinoma (TC). To date, there are no specific biomarkers for monitoring the biological course of these rare tumors. We carried out a single center study aiming at the detection of circulating cell-free DNA (ccfDNA) and the correlation of its levels with metastatic dissemination and histological subtype in patients with TETs.

Methods: From July 2018 to January 2020, 5-ml blood samples from 26 patients with advanced TET (aTET) (11 patients with TC and 15 patients with T) and from six patients with completely resected TET (cr-TET), were prospectively obtained before the initiation of systemic therapy. Blood samples from 10 healthy donors were used as control. The QIAamp MinElute ccfDNA Kits was used for ccfDNA isolation from plasma; real-time PCR was used for cfDNA quantification.

Results: We found significantly higher ccfDNA amount in patients with T and TC compared to controls, with median ccfDNA level of 3.3 ng/µl, 11.4 ng/µl and 25.6 ng/µl, for healthy donors, T and TC patients, respectively (p<0.001). No significant difference was found between cr-TET and controls (p = 0.175). ccfDNA concentrations were higher in metastatic (M1a and M1b) compared to non-metastatic (M0) TETs (25.6 ng/µl versus 7.2 ng/µl; p= 0.037). No significant correlation was found either between ccfDNA and disease stage, according to both the Masaoka-Koga (p= 0.854) and the TNM 8th edition staging systems (p = 0.66), or between ccfDNA levels and overall tumor burden, estimated according RECIST 1.1 criteria (r = 0.07, p = 0.725).

Conclusions: To the best of our knowledge, this is the first study that prospectively explores detection and quantification of ccfDNA in TETs. Higher baseline cfDNA levels have been observed in both advanced T and TC comparing to the control group.
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http://dx.doi.org/10.3389/fonc.2020.602153DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7902074PMC
February 2021

In Reply.

Oncologist 2021 02 9;26(2):e350. Epub 2021 Jan 9.

University of Naples "Federico II," Department of Clinical Medicine and Surgery, CRCTR Regional Rare Tumors Reference Center, Naples, Italy.

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http://dx.doi.org/10.1002/onco.13651DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7873323PMC
February 2021

Impact of COVID-19 outbreak on cancer immunotherapy in Italy: a survey of young oncologists.

J Immunother Cancer 2020 10;8(2)

Oncology, Department of Precision Medicine, Università della Campania "L. Vanvitelli", Napoli, Campania, Italy.

Background: The coronavirus disease 2019 (COVID-19) pandemic has overwhelmed the health systems worldwide. Data regarding the impact of COVID-19 on cancer patients (CPs) undergoing or candidate for immune checkpoint inhibitors (ICIs) are lacking. We depicted the practice and adaptations in the management of patients with solid tumors eligible or receiving ICIs during the COVID-19 pandemic, with a special focus on Campania region.

Methods: This survey (25 questions), promoted by the young section of SCITO (Società Campana di ImmunoTerapia Oncologica) Group, was circulated among Italian young oncologists practicing in regions variously affected by the pandemic: high (group 1), medium (group 2) and low (group 3) prevalence of SARS-CoV-2-positive patients. For Campania region, the physician responders were split into those working in cancer centers (CC), university hospitals (UH) and general hospitals (GH). Percentages of agreement, among High (H) versus Medium (M) and versus Low (L) group for Italy and among CC, UH and GH for Campania region, were compared by using Fisher's exact tests for dichotomous answers and χ test for trends relative to the questions with 3 or more options.

Results: This is the first Italian study to investigate the COVID-19 impact on cancer immunotherapy, unique in its type and very clear in the results. The COVID-19 pandemic seemed not to affect the standard practice in the prescription and delivery of ICIs in Italy. Telemedicine was widely used. There was high consensus to interrupt immunotherapy in SARS-CoV-2-positive patients and to adopt ICIs with longer schedule interval. The majority of the responders tended not to delay the start of ICIs; there were no changes in supportive treatments, but some of the physicians opted for delaying surgeries (if part of patients' planned treatment approach). The results from responders in Campania did not differ significantly from the national ones.

Conclusion: Our study highlights the efforts of Italian oncologists to maintain high standards of care for CPs treated with ICIs, regardless the regional prevalence of COVID-19, suggesting the adoption of similar solutions. Research on patients treated with ICIs and experiencing COVID-19 will clarify the safety profile to continue the treatments, thus informing on the most appropriate clinical conducts.
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http://dx.doi.org/10.1136/jitc-2020-001154DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7565202PMC
October 2020

Thymic Epithelial Tumors as a Model of Networking: Development of a Synergistic Strategy for Clinical and Translational Research Purposes.

Front Oncol 2020 14;10:922. Epub 2020 Jul 14.

Department of Pathology, IRCCS Regina Elena National Cancer Institute, Rome, Italy.

Among the group of thymic epithelial tumors (TET), thymomas often show either uncertain or explicit malignant biological behavior, local invasiveness, and intrathoracic relapse and are often difficult to manage. From the initial stages, thymic carcinomas tend to show aggressive behavior and extrathoracic spread. Moreover, the interplay of epithelial cells and thymocytes in thymomas causes complex immune derangement and related systemic autoimmune diseases. Due to their rare occurrence and to the limited funding opportunities available for rare tumors, it is challenging to make advances in clinical and translational research in TET. The authors of this paper are all members of a multidisciplinary clinical and research thoracic tumor team. Strong input was given to the team by long-standing expertise in TET in the Pathology Department. In addition, thanks to the collaboration between research units at our Institute as well as to national collaborations, over the last 10 years we were able to perform several tissue-based research studies. The most recent studies focused on microRNA and on functional studies on the thymic carcinoma cell line 1889c. The recent implementation of our biobank now provides us with a new tool for networking collaborative research activities. Moreover, the participation in a worldwide community such as ITMIG (International Thymic Malignancy Interest Group) has allowed us to significantly contribute toward fundamental projects/research both in tissue-based studies (The Cancer Genome Atlas) and in clinical studies (TNM staging of TET). Our achievements derive from constant commitment and long-standing experience in diagnosis and research in TET. New perspectives opened up due to the establishment of national [the Italian Collaborative Group for ThYmic MalignanciEs (TYME)] and European reference networks such as EURACAN, for an empowered joint clinical action in adult solid rare tumors. The challenge we face still lies in the advancement of clinical and basic science in thymic epithelial malignancies.
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http://dx.doi.org/10.3389/fonc.2020.00922DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7372300PMC
July 2020

Management of Germ Cell Tumors During the Outbreak of the Novel Coronavirus Disease-19 Pandemic: A Survey of International Expertise Centers.

Oncologist 2020 10 18;25(10):e1509-e1515. Epub 2020 Sep 18.

Center Hospitalier de l'Université de Montréal, Montreal, Canada.

Background: The coronavirus disease 2019 (COVID-19) pandemic has become a public health emergency affecting frail populations, including patients with cancer. This poses the question of whether cancer treatments can be postponed or modified without compromising their efficacy, especially for highly curable cancers such as germ cell tumors (GCTs).

Materials And Methods: To depict the state-of-the-art management of GCTs during the COVID-19 pandemic, a survey including 26 questions was circulated by e-mail among the physicians belonging to three cooperative groups: (a) Italian Germ Cell Cancer Group; (b) European Reference Network-Rare Adult Solid Cancers, Domain G3 (rare male genitourinary cancers); and (c) Genitourinary Medical Oncologists of Canada. Percentages of agreement between Italian respondents (I) versus Canadian respondents (C), I versus European respondents (E), and E versus C were compared by using Fisher's exact tests for dichotomous answers and chi square test for trends for the questions with three or more options.

Results: Fifty-three GCT experts responded to the survey: 20 Italian, 6 in other European countries, and 27 from Canada. Telemedicine was broadly used; there was high consensus to interrupt chemotherapy in COVID-19-positive patients (I = 75%, C = 55%, and E = 83.3%) and for use of granulocyte colony-stimulating factor primary prophylaxis for neutropenia (I = 65%, C = 62.9%, and E = 50%). The main differences emerged regarding the management of stage I and stage IIA disease, likely because of cultural and geographical differences.

Conclusion: Our study highlights the common efforts of GCT experts in Europe and Canada to maintain high standards of treatment for patients with GCT with few changes in their management during the COVID-19 pandemic.

Implications For Practice: Despite the chaos, disruptions, and fears fomented by the COVID-19 illness, oncology care teams in Italy, other European countries, and Canada are delivering the enormous promise of curative management strategies for patients with testicular cancer and other germ cell tumors. At the same time, these teams are applying safe and innovative solutions and sharing best practices to minimize frequency and intensity of patient contacts with thinly stretched health care capacity.
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http://dx.doi.org/10.1634/theoncologist.2020-0420DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7543332PMC
October 2020

Large retroperitoneal lymphadenopathy and increased risk of venous thromboembolism in patients receiving first-line chemotherapy for metastatic germ cell tumors: A study by the global germ cell cancer group (G3).

Cancer Med 2020 01 12;9(1):116-124. Epub 2019 Nov 12.

Division of Medical Oncology and Hematology, Department of Medicine, Princess Margaret Cancer Centre, University of Toronto, Toronto, ON, Canada.

Background: Metastatic germ cell tumor (mGCT) patients receiving chemotherapy have increased risk of life-threatening venous thromboembolism (VTE). Identifying VTE risk factors may guide thromboprophylaxis in this highly curable population.

Methods: Data were collected from mGCT patients receiving first-line platinum-based chemotherapy at 22 centers. Predefined variables included International Germ Cell Cancer Collaborative Group (IGCCCG) risk classification, long-axis diameter of largest retroperitoneal lymph node (RPLN), Khorana score, and use of indwelling vascular access device (VAD). VTE occurring at baseline, during chemotherapy and within 90 days, was analyzed.

Results: Data from 1135 patients were collected. Median age was 31 years (range 10-74). IGCCCG risk was 64% good, 20% intermediate, and 16% poor. VTE occurred in 150 (13%) patients. RPLN >3.5 cm demonstrated highest discriminatory accuracy for VTE (AUC 0.632, P < .001) and was associated with significantly higher risk of VTE in univariable analysis (22% vs 8%, OR 3.0, P < .001) and multivariable analysis (OR 1.8, P = .02). Other significant risk factors included, Khorana score ≥3 (OR 2.6, P = .008) and VAD use (OR 2.7, P < .001).

Conclusions: Large RPLN and VAD use are independent risk factors for VTE in mGCT patients receiving chemotherapy. VAD use should be minimized in this population and thromboprophylaxis might be considered for large RPLN.
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http://dx.doi.org/10.1002/cam4.2674DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6943085PMC
January 2020

Systemic treatment of malignant gastrointestinal neuroectodermal tumour after childhood neuroblastoma: chemotherapy in malignant gastrointestinal neuroectodermal tumour.

Anticancer Drugs 2019 10;30(9):959-963

Oncology Unit, CRTR Rare Tumors Reference Center, AOU Federico II of Naples.

Malignant gastrointestinal neuroectodermal tumour is an extremely rare neoplasm that arises in the wall of the small bowel, stomach or large bowel in young-aged and middle-aged adults. Histologically, it is generally characterized by monomorphic cells with clear cytoplasma, S-100 protein expression, and EWSR1 gene translocation. To the best of our knowledge, we describe for the first time, the case of a young woman with a diagnosis of metastatic gastrointestinal neuroectodermal tumour arising from ileum, who had a childhood adrenal neuroblastoma with liver, bone and lymph nodes metastasis, treated with four cycles of chemotherapy with the schedule CADO-CVP (CADO: cyclophosphamide 300 mg/m/day on days 1-5, vincristine 1,5 mg/m/day on days 1 and 5, and doxorubicin 60 mg/m/day on day 5; CVP: cisplatin 40 mg/m/day on days 1-5 and etoposide 100 mg/m/day on days 1-5) followed by right adrenal, kidney, lymph nodes and liver lesion resection, conditioning chemotherapy (melphalan-carmustine-teniposide), stem cells autologous transplantation and consecutively radiotherapy on the spine (T9 to L3) for a total of 30 Gy. For the second diagnosis of gastrointestinal neuroectodermal tumour with liver metastasis, she underwent ileal tumour resection and platinum-anthracycline based chemotherapy with initial shrinkage of liver metastasis. Unfortunately, despite the initial response and the following delivered therapies, she died for rapid progressive disease. Taking into account the late effects of past therapeutic modalities, a long-term surveillance of young child treated for neuroblastoma, is required to appreciate their overall risks of second malignancies.
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http://dx.doi.org/10.1097/CAD.0000000000000806DOI Listing
October 2019

Recommendations for surveillance and follow-up of men with testicular germ cell tumors: a multidisciplinary consensus conference by the Italian Germ cell cancer Group and the Associazione Italiana di Oncologia Medica.

Crit Rev Oncol Hematol 2019 May 20;137:154-164. Epub 2019 Mar 20.

IGG Italian Germ cell cancer Group, Italy.

Background: No compelling evidence is available about surveillance and follow-up of patients with testicular germ cell tumour (TGCT).

Methods: In the light of the best clinical evidence, the Italian Germ cell cancer Group (IGG) and the Associazione Italiana di Oncologia Medica (AIOM) set up a multidisciplinary national consensus conference, involving 42 leading experts and 3 TGCT survivors. A minimum of 50% of votes was required in order to achieve a consensus recommendation on 29 questions.

Results: Recommendations have been summarized in three tables, divided by stage I seminoma, stage I nonseminoma and the advanced disease, which may be useful for clinicians to appropriately choose the clinical investigation and its timing during the surveillance and follow-up of TGCT patients based on an accurate estimation of their risk of disease relapse.

Conclusions: The IGG-AIOM consensus recommendations may help clinicians to choose appropriate clinical investigations for the surveillance and follow-up of TGCT patients.
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http://dx.doi.org/10.1016/j.critrevonc.2019.03.006DOI Listing
May 2019

Therapeutic sequences in patients with grade 1-2 neuroendocrine tumors (NET): an observational multicenter study from the ELIOS group.

Endocrine 2019 11 14;66(2):417-424. Epub 2019 Mar 14.

Division of Endocrinology, Department of Clinical Medicine and Surgery, Federico II University of Naples, Naples, Italy.

Purpose: Many different treatments are suggested by guidelines to treat grade 1-2 (G1-G2) neuroendocrine tumors (NET). However, a precise therapeutic algorithm has not yet been established. This study aims at identifying and comparing the main therapeutic sequences in G1-G2 NET.

Methods: A retrospective observational Italian multicenter study was designed to collect data on therapeutic sequences in NET. Median progression-free survival (PFS) was compared between therapeutic sequences, as well as the number and grade of side effects and the rate of dose reduction/treatment discontinuation.

Results: Among 1182 patients with neuroendocrine neoplasia included in the ELIOS database, 131 G1-G2 gastroenteropancreatic, lung and unknown primary NET, unresectable or persistent/relapsing after surgery, treated with ≥2 systemic treatments, were included. Four main therapeutic sequences were identified in 99 patients: (A) somatostatin analogs (SSA) standard dose to SSA high dose (n = 36), (B) SSA to everolimus (n = 31), (C) SSA to chemotherapy (n = 17), (D) SSA to peptide receptor radionuclide therapy (PRRT) (n = 15). Median PFS of the second-line treatment was not reached in sequence A, 33 months in sequence B, 20 months in sequence C, 30 months in sequence D (p = 0.16). Both total number and severity of side effects were significantly higher in sequences B and C than A and D (p = 0.04), as well as the rate of dose reduction/discontinuation (p = 0.03).

Conclusions: SSA followed by SSA high dose, everolimus, chemotherapy or PRRT represent the main therapeutic sequences in G1-G2 NET. Median PFS was not significantly different between sequences. However, the sequences with SSA high dose or PRRT seem to be better tolerated than sequences with everolimus or chemotherapy.
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http://dx.doi.org/10.1007/s12020-019-01894-0DOI Listing
November 2019

Best practices for the management of thymic epithelial tumors: A position paper by the Italian collaborative group for ThYmic MalignanciEs (TYME).

Cancer Treat Rev 2018 Dec 5;71:76-87. Epub 2018 Oct 5.

Rare Tumors Reference Center, Department of Clinical Medicine and Surgery, University Federico II, Naples, Italy.

Thymic epithelial tumors (TETs) are a heterogenous group of rare tumors, with a complex histopatological classification. Furthermore, the recent introduction of the first TNM staging system, that is scheduled to replace the Masaoka-Koga system, may create further difficulties in TET management, that remains challenging. Several guidelines for treatment of TETs are available and provide recommendations based mainly on non randomized trials and retrospective or limited series. Often the lack of evidence leads to formulation of indications based on expert opinions. As for other rare cancers it is crucial to create networks to coordinate the work among centres involved in treatment of these diseases in order to offer the best diagnostic and therapeutic tools. For this purpose, in 2014 a network named TYME (ThYmic MalignanciEs), was founded in Italy with the aim of improving care and research in TETs. In September 2017 a panel of multidisciplinary experts from TYME network and from other Italian centres strongly involved in TET diagnosis and treatment convened a first Italian Expert meeting together with representatives of association for patients affected by rare thoracic cancers Tu.To.R, to explore how these tumors are managed in the different centres of Italy compared to ESMO guidelines. In this paper we summarize the issues discussed during that meeting and we propose recommandations based on Masaoka Koga and the new TNM staging system.
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http://dx.doi.org/10.1016/j.ctrv.2018.10.001DOI Listing
December 2018

RELEVENT Trial: Phase II Trial of Ramucirumab, Carboplatin, and Paclitaxel in Previously Untreated Thymic Carcinoma/B3 Thymoma With Area of Carcinoma.

Clin Lung Cancer 2018 09 3;19(5):e811-e814. Epub 2018 Jul 3.

Unit of Thoracic Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.

Thymic epithelial tumors are rare malignancies. Thymic carcinoma represents about 20% of all thymic epithelial tumors and has aggressive behavior, with a greater tendency to metastatic spread. Thymic carcinoma is often diagnosed in advanced stages for which systemic treatment is the main therapeutic option. The association of chemotherapy and antiangiogenic agents in the first-line setting has never been investigated in this very rare cancer. However, preclinical and clinical evidence has suggested that inhibition of angiogenesis could be beneficial. The RELEVENT trial is a multicenter, open-label, single-arm, phase II study aimed at investigating the activity and safety of ramucirumab combined with paclitaxel and carboplatin in chemotherapy-naive patients affected by thymic carcinoma or B3 thymoma with area of carcinoma. The primary endpoint of the trial is the overall response rate. Progression-free survival, overall survival, and safety are secondary endpoints. Patient-reported outcomes will be collected at each visit. The mutational status of a subset of genes, polymorphisms, and selected micro-RNA expression will be evaluated.
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http://dx.doi.org/10.1016/j.cllc.2018.06.005DOI Listing
September 2018

Clinical features and psychological aspects of the decision-making process in stage I testicular germ cell tumors.

Future Oncol 2018 Jul 29;14(16):1591-1599. Epub 2018 Jun 29.

CRTR Rare Tumors Reference Center, University of Naples Federico II, Naples, Italy.

Testicular germ cell tumors (TGCTs) are the most prevalent malignancies in young Caucasian men. Clinical stage I (CSI) TGCTs present the highest cure rate and treatment options after orchiectomy depend on histology and risk factors. Nevertheless, the management of CSI TGCTs is controversial due to the availability of multiple treatments and the lack of randomized trials. An integrated multidisciplinary approach that includes clinicians (surgeons, radiotherapists and oncologists) and psychologists is crucial to maximize the patients' compliance and must be acknowledged with appropriate tools. The aim of our work is to review the oncological and psychological aspects of the decision-making process, discussing the fundamental role of the patient involvement in the personalized management of CSI TGCTs.
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http://dx.doi.org/10.2217/fon-2017-0670DOI Listing
July 2018

Long term deficiency of vitamin D in germ cell testicular cancer survivors.

Oncotarget 2018 Apr 20;9(30):21078-21085. Epub 2018 Apr 20.

Department of Medicine and Surgery, Division of Medical Oncology, Centro di Riferimento Tumori Rari Regione Campania, University of Naples "Federico II", Napoli, Italy.

Background: Cisplatin-based chemotherapy significantly improved the survival of patients with germ cell testicular cancer. However, long term side effects of chemotherapy have non-negligible impact on the quality of life of these young patients, who have a long life expectancy after being successfully treated.

Materials And Methods: 25-OH vitamin D, testosterone, FSH and LH of patients with testicular cancer were retrospectively evaluated and for each patient clinical information were collected. The tissue of 52 patients with germ cell tumors was analyzed for VDR expression by immunohistochemistry. The serum 25-OH vitamin D and VDR expression were correlated to the patients 'clinical characteristics.

Results: 25-OH vitamin D was analyzed in 82 patients. Insufficient (< 30 ng/ml) levels were detected in 65%-85%, mild deficient (< 20 ng/ml) in 25%-36% and severe deficient (< 10 ng/ml) in 6%-18% of the patients over a median follow-up of 48 months. No difference in serum 25-OH vitamin D was detected over the follow-up time points. No correlation with histology, stage and type of treatment was found. The 25-OH vitamin D levels were not correlated to testosterone, FSH and LH levels. Interestingly, the expression of VDR was much higher in non seminoma than in seminoma tissue.

Conclusions: Patients with testicular cancer have reduced vitamin D levels after the treatment of the primary cancer. Since long term hypovitaminosis D leads to high risk of fractures, infertility and cardiovascular diseases, we envision that vitamin D should be regularly checked in patients with testicular cancer and replaced if needed.
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http://dx.doi.org/10.18632/oncotarget.24925DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5940414PMC
April 2018

Phase II Study of Everolimus in Patients With Thymoma and Thymic Carcinoma Previously Treated With Cisplatin-Based Chemotherapy.

J Clin Oncol 2018 02 14;36(4):342-349. Epub 2017 Dec 14.

Paolo Andrea Zucali, Matteo Simonelli, Matteo Perrino, Fabio De Vincenzo, Laura Giordano, Monica Bertossi, Annarita Destro, Luca Di Tommaso, and Armando Santoro¸ Humanitas Clinical and Research Hospital; Tommaso De Pas, Francesca Toffalorio, Fabio Conforti, and Angela Cioffi, European Institute of Oncology; Paolo Andrea Zucali, Matteo Simonelli, Luca Di Tommaso, and Armando Santoro, Humanitas University, Milan; Giovannella Palmieri, Vincenzo Damiano, Margaret Ottaviano, and Sabino De Placido, Università Federico II, Naples; Adolfo Favaretto and Giulia Pasello, Istituto Oncologico Veneto, Padua; Antonio Chella and Erika Garbella, University Hospital, Pisa; Marcello Tiseo, Azienda Ospedaliero-Universitaria of Parma, Parma; and Michele Caruso and Marco Ali, Humanitas Centro Catanese di Oncologia, Catania, Italy.

Purpose No effective salvage treatments are available for patients with advanced/recurrent thymoma (T) or thymic carcinoma (TC) who have progressed after platinum-based chemotherapy. This study evaluated the activity of everolimus in patients with advanced/recurrent T or TC previously treated with cisplatin-containing chemotherapy. Patients and Methods This was a single-arm, single-stage, open-label, multicenter, phase II trial. Patients received oral everolimus 10 mg/d until disease progression, unacceptable toxicity, or patient refusal. A Fleming phase II trial was designed. The null hypothesis of a true disease control rate (DCR) of 40% was tested against a one-sided alternative of a true DCR of 60% (α = β = 0.10): If disease control were achieved in ≥ 21 of the first 41 evaluable patients, everolimus could be recommended for further evaluation. Progression-free survival, overall survival, and safety were also evaluated. Results From 2011 to 2013, 51 patients were enrolled (T, n = 32; TC, n = 19). Complete remission was observed in one patient with TC, partial response in five patients (T, n = 3; TC, n = 2), and stable disease in 38 patients (T, n = 27; TC, n= 11), with a DCR of 88% (T,: 93.8%; TC, 77.8%). With a median follow up of 25.7 months, median progression-free survival was 10.1 months (T,: 16.6 months; TC, 5.6 months), and median overall survival was 25.7 months (T, not reached; TC, 14.7 months). Fourteen patients had a serious drug-related adverse event; of these patients, nine permanently discontinued treatment. Three patients died of pneumonitis while in the study. Immunohistochemical positivity for p4E-BP1 or insulin-like growth factor-1 receptor was statistically significantly related to a shorter survival. Conclusion Everolimus may induce durable disease control in a high percentage of patients with T or TC, albeit with a potential high risk of fatal pneumonitis.
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http://dx.doi.org/10.1200/JCO.2017.74.4078DOI Listing
February 2018

Evaluation of metabolic response with F-FDG PET-CT in patients with advanced or recurrent thymic epithelial tumors.

Cancer Imaging 2017 Mar 7;17(1):10. Epub 2017 Mar 7.

Department of Advanced Biomedical Sciences, University of Naples Federico II, Via Pansini 5, Edificio 10, 80131, Naples, Italy.

Background: Patients with advanced or recurrent thymic epithelial tumors (TETs) often need several consecutive lines of chemotherapy. The aim of this retrospective monocentric study was to test whether F-Fluorodeoxyglucose positron emission tomography-computed tomography (F-FDG PET-CT) is able to monitor standard chemotherapy efficacy in those patients and whether metabolic response correlates with morphovolumetric response as assessed by Response Evaluation Criteria in Solid Tumor (RECIST).

Methods: We evaluated 27 consecutive patients with advanced (16 patients) or recurrent (11 patients) TETs. All patients underwent F-FDG PET-CT before and after at least 3 cycles of chemotherapy. Maximum standardized uptake value (SUV) of all detected lesions was recorded and the most F-FDG avid lesion in each patient was selected for determination of percentage change of SUV (ΔSUV) in pre- and post-treatment scans. Tumor response was assessed by contrast-enhanced computed tomography (CE-CT) using RECIST criteria. Receiver operating characteristic (ROC) curve analysis was performed to define the optimal threshold of ΔSUV discriminating responders from non-responders.

Results: Metabolic response expressed as ΔSUV was significantly correlated with morphovolumetric response (Spearman's rank correlation, r = 0.64, p = 0.001). ROC curve analysis showed that a ΔSUV value of -25% could discriminate responders from non-responders with a sensitivity of 88% and a specificity of 80%. Conversely, basal SUV values were not predictive of morphovolumetric tumor response.

Conclusions: Our findings indicate that metabolic response assessed by F-FDG PET-CT, through evaluation of ΔSUV, may allow identification of responders and non-responders thus guiding adaptation of therapy in patients with advanced or recurrent TETs.
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http://dx.doi.org/10.1186/s40644-017-0112-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5339950PMC
March 2017

Thymic epithelial tumors in a worldwide perspective: lessons from observational studies.

J Thorac Dis 2016 Aug;8(8):1851-5

Rare Tumors Reference Center, Department of Clinical Medicine and Surgery, University Federico II, Naples, Italy.

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http://dx.doi.org/10.21037/jtd.2016.06.57DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4999657PMC
August 2016

Hepatocellular carcinoma: Will novel targeted drugs really impact the next future?

World J Gastroenterol 2016 Jul;22(27):6114-26

Liliana Montella, Raffaele Addeo, Salvatore Del Prete, Medical Oncology Unit, "San Giovanni di Dio" Hospital, Frattamaggiore, 80027 Naples, Italy.

Cancer treatment has been revolutionized by the advent of new molecular targeted and immunotherapeutic agents. Identification of the role of tumor angiogenesis changed the understanding of many tumors. After the unsuccessful results with chemotherapy, sorafenib, by interfering with angiogenic pathways, has become pivotal in the treatment of hepatocellular carcinoma. Sorafenib is the only systemic treatment to show a modest but statistically significant survival benefit. All novel drugs and strategies for treatment of advanced hepatocellular carcinoma must be compared with the results obtained with sorafenib, but no new drug or drug combination has yet achieved better results. In our opinion, the efforts to impact the natural history of the disease will be directed not only to drug development but also to understanding the underlying liver disease (usually hepatitis B virus- or hepatitis C virus-related) and to interrupting the progression of cirrhosis. It will be important to define the role and amount of mutations in the complex pathogenesis of hepatocellular carcinoma and to better integrate locoregional and systemic therapies. It will be important also to optimize the therapeutic strategies with existing chemotherapeutic drugs and new targeted agents.
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http://dx.doi.org/10.3748/wjg.v22.i27.6114DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4945973PMC
July 2016

Molecular genetic alterations in egfr CA-SSR-1 microsatellite and egfr copy number changes are associated with aggressiveness in thymoma.

J Thorac Dis 2016 Mar;8(3):386-95

1 Department of Pathology, Regina Elena National Cancer Institute, Rome, Italy ; 2 Thoracic Surgery, Regina Elena National Cancer Institute, Rome, Italy ; 3 Rare Tumors Reference Center, Department of Clinical Medicine and Surgery, University Federico II, Naples, Italy ; 4 Pathology, Catholic University, Rome, Italy ; 5 Department of Neurosciences, Catholic University, Rome, Italy ; 6 Division of Health Technologies-ENEA C.R. Casaccia, Rome, Italy ; 7 Biostatistic Unit, Regina Elena National Cancer Institute, Rome, Italy ; 8 Thoracic Surgery, Catholic University, Rome, Italy ; 9 Department of Oncology, Faculty of Health Science, McMaster University, Hamilton, Canada.

Background: The key role of egfr in thymoma pathogenesis has been questioned following the failure in identifying recurrent genetic alterations of egfr coding sequences and relevant egfr amplification rate. We investigated the role of the non-coding egfr CA simple sequence repeat 1 (CA-SSR-1) in a thymoma case series.

Methods: We used sequencing and egfr-fluorescence in situ hybridization (FISH) to genotype 43 thymomas; (I) for polymorphisms and somatic loss of heterozygosity of the non-coding egfr CA-SSR-1 microsatellite and (II) for egfr gene copy number changes.

Results: We found two prevalent CA-SSR-1 genotypes: a homozygous 16 CA repeat and a heterozygous genotype, bearing alleles with 16 and 20 CA repeats. The average combined allele length was correlated with tumor subtype: shorter sequences were significantly associated with the more aggressive WHO thymoma subtype group including B2/B3, B3 and B3/C histotypes. Four out of 29 informative cases analysed for somatic CA-SSR-1 loss of heterozygosity showed allelic imbalance (AI), 3/4 with loss of the longer allele. By egfr-FISH analysis, 9 out of 33 cases were FISH positive. Moreover, the two integrated techniques demonstrated that 3 out of 4 CA-SSR-1-AI positive cases with short allele relative prevalence showed significantly low or high chromosome 7 "polysomy"/increased gene copy number by egfr-FISH.

Conclusions: Our molecular and genetic and follow up data indicated that CA-SSR-1-allelic imbalance with short allele relative prevalence significantly correlated with EGFR 3+ immunohistochemical score, increased egfr Gene Copy Number, advanced stage and with relapsing/metastatic behaviour in thymomas.
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http://dx.doi.org/10.21037/jtd.2016.02.40DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4805790PMC
March 2016

Somatostatin analogues according to Ki67 index in neuroendocrine tumours: an observational retrospective-prospective analysis from real life.

Oncotarget 2016 Feb;7(5):5538-47

Endocrinology Unit, Department of Clinical Medicine and Surgery, Università di Napoli Federico II, Napoli, Italy.

Somatostatin analogues (SSAs) have shown limited and variable antiproliferative effects in neuroendocrine tumours (NETs). Whether tumour control by SSAs depends on grading based on the 2010 WHO NET classification is still unclear. The aim of this study is to evaluate the efficacy of long-acting SSAs in NETs according to Ki67 index. An observational Italian multicentre study was designed to collect data in patients with gastro-entero-pancreatic or thoracic NETs under SSA treatment. Both retrospective and prospective data were included and they were analysed in line with Ki67 index, immunohistochemically evaluated in tumour samples and graded according to WHO classification (G1 = Ki67 index 0-2%, G2 = Ki67 index 3-20%, G3 = Ki67 index > 20%). Among 601 patients with NET, 140 with a histologically confirmed gastro-entero-pancreatic or thoracic NET or NET with unknown primary were treated with lanreotide autogel or octreotide LAR. An objective tumour response was observed in 11%, stability in 58% and progression in 31%. Objective response and tumour stability were not significantly different between G1 and G2 NETs. Progression free survival was longer but not significantly different in G1 than G2 NETs (median: 89 vs 43 months, p = 0.15). The median PFS was significantly longer in NETs showing Ki67 < 5% than in those showing Ki67 ≥ 5% (89 vs 35 months, p = 0.005). SSA therapy shows significant antiproliferative effects in well differentiated low/intermediate-proliferating NETs, not only G1 but also in G2 type. A Ki67 index of 5% seems to work better than 3% to select the best candidates for SSA therapy.
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http://dx.doi.org/10.18632/oncotarget.6686DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4868704PMC
February 2016

Correlative Imaging in a Patient with Cystic Thymoma: CT, MR and PET/CT Comparison.

Pol J Radiol 2015 13;80:22-6. Epub 2015 Jan 13.

Department of Diagnostic Imaging, University Federico II, Fondazione SDN (IRCCS), Naples, Italy.

Background: Cystic thymoma is a rare variant of thymic neoplasm characterized by almost complete cystic degeneration with mixed internal structure. We describe a case of a 60 year-old woman with a cystic thymoma studied with advanced tomographic imaging stydies. CT, MRI and PET/CT with (18)F-FDG were performed; volumetric CT and MRI images provided better anatomic evaluation for pre-operative assessment, while PET/CT was helpful for lesion characterization based on (18)F-FDG uptake. Although imaging studies are mandatory for pre-operative evaluation of cystic thymoma, final diagnosis still remains surgical.

Case Report: A 60-year-old woman with recent chest pain and no history of previous disease was admitted to our departement to investigate the result of a previous chest X-ray that showed bilateral mediastinal enlargement; for this purpose, enhanced chest CT scan was performed using a 64-rows scanner (Toshiba, Aquilion 64, Japan) before and after intravenous bolus administration of iodinated non ionic contrast agent; CT images demonstrated the presence of a large mediastinal mass (11×8 cm) located in the anterior mediastinum who extended from the anonymous vein to the cardio-phrenic space, compressing the left atrium and causing medium lobe atelectasis; bilateral pleural effusion was also present.

Conclusions: In conclusion, correlative imaging plays a foundamental role for the diagnostic evaluation of patient with cystic thymoma. In particular, volumetric CT and MRI studies can provide better anatomic informations regarding internal structure and local tumor spread for pre-operative assessment. Conversely, metabolic imaging using (18)F-FDG PET/CT is helpful for lesion characterization differentiating benign from malignant lesion on the basis of intense tracer uptake. The role of PET/MRI is still under investigation. However, final diagnosis still remains surgical even though imaging studies are mandatory for pre-operative patient management.
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http://dx.doi.org/10.12659/PJR.892105DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4294593PMC
January 2015

Capecitabine plus gemcitabine in thymic epithelial tumors: final analysis of a Phase II trial.

Future Oncol 2014 Nov;10(14):2141-7

Cancer Center for Rare Tumors of Campania & Medical Oncology Division, University Federico II of Naples, Naples, Italy.

Background: A multi-institutional Phase II trial was initiated in 2005 to test the combination gemcitabine and capecitabine in patients with thymic epithelial malignancies (TETs).

Patients & Methods: Patients with histologic confirmation of TET diagnosis by central review who had received >1 systemic chemotherapy treatment were included. Patients received oral capecitabine (650 mg/mq twice daily on days 1-14) and intravenous gemcitabine (1000 mg/mq on days 1 and 8 every 3 weeks).

Results: Of the 30 patients included (18 men, 12 women; median age: 57 years, range: 48-61 years), the majority (73%) had thymoma, and the remaining thymic carcinoma. Eight patients developed grade 3-4 neutropenia. A total of 12 patients had a response. Median progression-free survival was 11 months (range: 6.5-16.5).

Conclusion: Capecitabine and gemcitabine is highly active in TETs.
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http://dx.doi.org/10.2217/fon.14.144DOI Listing
November 2014

The role of immunotherapy in solid tumors: report from the Campania Society of Oncology Immunotherapy (SCITO) meeting, Naples 2014.

J Transl Med 2014 Oct 21;12:291. Epub 2014 Oct 21.

Unit of Oncology, A.O.R.N. dei COLLI "Ospedali Monaldi-Cotugno-CTO", Naples, Italy.

The therapeutic approach to advanced or metastatic solid tumors, either with chemotherapy or targeted therapies, is mainly palliative. Resistance to chemotherapy occurs very frequently and is one of the most important reasons for disease progression. Immunotherapy has the potential to mount an ongoing, dynamic immune response that can kill tumor cells for an extended time after the conventional therapy has been administered. Such a long-lasting response is potentially able to completely eradicate tumor cells, rather than producing only a temporary killing of cells. The most promising immune-based treatments are monoclonal antibodies that act as checkpoint inhibitors (e.g. ipilimumab and nivolumab), adoptive cell therapy (e.g. T-cells expressing chimeric antigen receptors) and vaccines (e.g. sipuleucel-T). Ipilimumab is currently approved for the treatment of metastatic melanoma and sipuleucel-T is approved for advanced prostate cancer. There is great interest in immunotherapy in other solid tumors, potentially used alone or in a multimodal fashion with chemotherapy and/or biological drugs. In this paper, we review recent advances in immuno-oncology in solid malignancies (except melanoma) as were discussed at the inaugural meeting of the Campania Society of Oncology Immunotherapy (SCITO).
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http://dx.doi.org/10.1186/s12967-014-0291-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4209076PMC
October 2014

Diagnostic features and subtyping of thymoma lymph node metastases.

Biomed Res Int 2014 8;2014:546149. Epub 2014 Jul 8.

Department of Pathology, Regina Elena National Cancer Institute, Via Elio Chianesi 53, 00144 Rome, Italy.

Aim: The purpose of the present study was to characterize the morphological features of thymoma metastases in lymph nodes and to evaluate the possibility of their subtyping according to the 2004 WHO classification of thymus tumors.

Materials And Methods: We reviewed 210 thymoma cases in our series of thymic epithelial tumors (TET), including their recurrences and lymphogenous metastases. Three cases of lymph node metastases, one case occurring synchronously with the primary tumor and one synchronously with the first relapse (both in intrathoracic location) and one case of metastasis observed in a laterocervical lymph node subsequently to two thymoma relapses were found.

Results: The metastatic nodes were variably but extensively involved in all cases. The histological features were similar in both primary tumors and metastases. Thymoma metastases were subtyped according to the WHO classification as B3 (one case) and B2 (two cases), and distinctive features in comparison to metastatic epithelial neoplasias from other sites were observed.

Conclusion: Thymoma lymph node metastases, although rare, can be subtyped according to the WHO classification on the basis of their morphological and immunohistochemical features. Clinically, the presence of nodal metastases may herald subsequent relapses and further metastases even in extrathoracic sites.
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http://dx.doi.org/10.1155/2014/546149DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4109419PMC
April 2015

Thymic epithelial tumors express vascular endothelial growth factors and their receptors as potential targets of antiangiogenic therapy: a tissue micro array-based multicenter study.

Lung Cancer 2014 Aug 22;85(2):191-6. Epub 2014 May 22.

Thoracic Surgery, Regina Elena National Cancer Institute, Rome, Italy.

Objectives: Tumor angiogenesis is an essential and complex process necessary for the growth of all tumors which represents a potential therapeutic target. Angiogenesis inhibitors targeting vascular endothelial growth factor (VEGF) or their receptor tyrosine kinases have been approved by the FDA. In thymic epithelial tumors (TET), targeted therapies have been sporadically applied due to their rarity. To ascertain the presence of potential therapeutic targets, we analyzed by immunohistochemistry the expression of angiogenesis-related biomarkers in a large series of TET arranged in Tissue Micro Arrays (TMA).

Materials And Methods: We assessed by immunohistochemistry the expression of the possible molecular target of anti-angiogenic therapy, i.e. VEGFA, VEGFC, VEGFD, VEGFR1, VEGFR2, VEGFR3, and PDGFRβ, in a TMA series of 200 TET collected in the framework of a multi-institutional collaborative project for Rare Diseases.

Results: When compared to the low-risk tumors, high-risk TET (B2, B3, carcinomas) contained higher proportion of cancer cells expressing VEGFA, VEGFC and VEGFD (P<0.001, P<0.001, and P<0.001) growth factors, and their receptors VEGFR1 (P=0.002), VEGFR2 (P=0.013), and VEGFR3 (P=0.041). No differences were observed in terms of PDGFRβ expression.

Conclusions: According to our data, it is possible to hypothesize the existence of multiple paracrine and/or autocrine loops in TET, particularly in the high-risk ones, involved in TET growth and progression. Anti-angiogenic agents, directed to inhibit these loops, are therefore to be considered as potential tools in advanced TET therapy.
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http://dx.doi.org/10.1016/j.lungcan.2014.05.010DOI Listing
August 2014

Potential value of Gleason score in predicting the benefit of cabazitaxel in metastatic castration-resistant prostate cancer.

Future Oncol 2013 Jun;9(6):889-97

Genitourinary Cancer Section, Medical Oncology Division, Department of Endocrinology & Oncology, University Federico II, Napoli, Italy.

Aim: This study aimed to identify predictive/prognostic factors in castration-resistant prostate cancer patients treated with cabazitaxel.

Patients & Methods: Patients were enrolled from March 2011 to December 2011 in an international expanded access program. In January 2012, when cabazitaxel became commercially available, a prospective study was initiated at University Federico II of Naples and at Rionero in Vulture Hospital.

Results: Forty-seven patients were enrolled in this study. Patients received a median of nine cycles of cabazitaxel. Median progression-free survival was 7.0 months (95% CI: 5.7-8.0). Seventeen patients were still alive at the time of the analysis, with a median overall survival of 14 months (95% CI: 11-16). At multivariate analysis, a higher Gleason score (≥ 8) appeared to be associated with prolonged progression-free survival (hazard ratio: 0.36; 95% CI: 0.18-0.72); however, the higher Gleason score showed no statistical impact on overall survival.

Conclusion: We hypothesize that the Gleason score has the potential to be incorporated in the clinical decision-making process for definition of treatment strategy in docetaxel-pretreated castration-resistant prostate cancer patients. We encourage further experimentation in this setting.
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http://dx.doi.org/10.2217/fon.13.39DOI Listing
June 2013

Non-AIDS-related Kaposi's sarcoma: A single-institution experience.

World J Clin Oncol 2013 May;4(2):52-7

Pasquale Rescigno, Rossella Di Trolio, Carlo Buonerba, Piera Federico, Davide Bosso, Antonella Virtuoso, Michela Izzo, Tania Policastro, Luca Vaccaro, Francesco Perri, Elide Matano, Sabino De Placido, Giovannella Palmieri, Giuseppe Di Lorenzo, Genitourinary Cancer Section and Rare-Cancer Center, Medical Oncology Division, University Federico II, 80131 Napoli, Italy.

Aim: To evaluate the outcomes and potential prognostic factors in patients with non-acquired immunodeficiency syndrome (AIDS)-related Kaposi's sarcoma (KS).

Methods: Patients with histologically proven non-AIDS-related KS treated with systemic chemotherapy were included in this retrospective analysis. In some cases, the human herpes virus 8 status was assessed by immunohistochemistry. The patients were staged according to the Mediterranean KS staging system. A multivariable model was constructed using a forward stepwise selection procedure. A P value < 0.05 was considered statistically significant, and all tests were two-sided.

Results: Thirty-two cases were included in this analysis. The average age at diagnosis was 70 years, with a male/female ratio of approximately 2:1. Eighty-four percent of the cases had classic KS. All patients received systemic chemotherapy containing one of the following agents: vinca alkaloid, taxane, and pegylated liposomal doxorubicin. Ten patients (31.5%) experienced a partial response, and a complete response was achieved in four patients (12.4%) and stable disease in sixteen cases (50%). Two patients (6.2%) were refractory to the systemic treatment. The median progression-free survival (PFS) was 11.7 mo, whereas the median overall survival was 28.5 mo. At multivariate analysis, the presence of nodular lesions (vs macular lesions only) was significantly related to a lower PFS (hazard ratio: 3.09; 95%CI: 1.18-8.13, P = 0.0133).

Conclusion: Non-AIDS-related KS appears mostly limited to the skin and is well-responsive to systemic therapies. Our data show that nodular lesions may be associated with a shorter PFS in patients receiving chemotherapy.
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http://dx.doi.org/10.5306/wjco.v4.i2.52DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3659264PMC
May 2013

Tumor-to-tumor metastasis: breast cancer metastatic to thymic epithelial tumor.

Anticancer Drugs 2013 Aug;24(7):759-64

Department of Molecular and Clinical Endocrinology and Oncology, Federico II University of Naples School of Medicine, Division of Medical Oncology, Naples, Italy.

Tumor-to-tumor metastasis is a rare phenomenon, with around 150 cases being reported in the literature. Breast cancer is the second most commonly reported donor tumor after lung cancer, but thymic epithelial tumors have never been reported as recipient tumors. Furthermore, the thymus is rarely affected by metastases. To our knowledge, the present report is the first case of breast cancer metastatic to thymic epithelial tumor.
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http://dx.doi.org/10.1097/CAD.0b013e328362a68bDOI Listing
August 2013

Combined imaging with 18F-FDG-PET/CT and 111In-labeled octreotide SPECT for evaluation of thymic epithelial tumors.

Clin Nucl Med 2013 May;38(5):354-8

Department of Biomorphological and Functional Sciences, University of Naples Federico II, Naples, Italy.

Purpose: This study aimed to test the role of combined imaging with 18F-FDG-PET/CT and 111In-octreotide SPECT in characterizing thymic epithelial tumors (TETs).

Methods: We evaluated 20 patients with newly diagnosed TETs who had undergone concomitant 18F-FDG-PET/CT and 111In-octreotide SPECT. Thymic epithelial tumors were classified by World Health Organization (WHO) as low-risk thymomas (5), high-risk thymomas (4), and thymic carcinomas (11, among which 6 neuroendocrine tumors). Patients were staged according to Masaoka system. 18F-FDG-PET/CT was performed and SUV(max) of primary tumors was recorded. 111In-octreotide SPECT of the thorax was performed, and tumor-to-background ratio was determined on the 24-hour coronal sections.

Results: All patients showed increased 18F-FDG uptake in mediastinal lesions. SUV(max) were significantly correlated with WHO classification (r = 0.66, P < 0.01) and with Masaoka stage (r = 0.60, P < 0.01). SUV(max) of low-risk thymomas (mean [SD], 2.87 [0.83]) were significantly lower than those of high-risk thymomas (mean [SD], 7.21 [1.73], P < 0.01) and of thymic carcinomas (mean [SD], 9.39 [5.80], P < 0.05), whereas no significant difference was found between high-risk thymomas and thymic carcinomas. SUV(max) of all high-risk thymomas and thymic carcinomas was 4.5 or greater. All primary tumors were detected by In-octreotide SPECT, and tumor-to-background ratios ranged between 1.67 and 10.10. No statistically significant correlation was found between tumor-to-background ratios and WHO classification (r = 0.24, P = 0.36) and Masaoka stages (r = 0.31, P = 0.23). However tumor-to-background ratios of thymic neuroendocrine tumors (mean [SD], 5.71 [3.09]) were significantly higher than those of all other TETs with SUV(max) of 4.5 or greater (mean [SD], 2.41 [0.56]; P < 0.05).

Conclusions: 18F-FDG-PET/CT scan allows to differentiate high-risk epithelial tumors and thymic carcinomas from low-risk thymomas, whereas 111In-octreotide SPECT may identify neuroendocrine tumors among those showing high 18F-FDG uptake.
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http://dx.doi.org/10.1097/RLU.0b013e318286bd84DOI Listing
May 2013