- 64: in: Oxford Textbook of Oncology, second edition, Edited by R.L. Souhami, I. Tannock, P. Hohenberger, JC. Horiot. Oxford University Press 2002: 2477-2491
Neoplastic complications of AIDS.
Tirelli U, Spina M, Carbone A., Monfardini S.
Division of Medical Oncology A, National Cancer Institute, Via Pedemontana Occ. Le 12, (PN) 33081, Aviano, Italy
AIDS-related tumors: integrating antiviral and anticancer therapy.
Tirelli U, Bernardi D, Spina M, Vaccher E.
Division of Medical Oncology A, National Cancer Institute, Via Pedemontana Occ. Le 12, (PN) 33081, Aviano, Italy
The introduction of highly active antiretroviral therapy (HAART) has changed dramatically the landscape of HIV disease. Deaths from AIDS-related diseases have been reduced by 75% since protease inhibitor therapy and combination antiretroviral therapy came into use in late 1995. While KS is declining, the situation for non-Hodgkin's lymphoma is more complex with a reduced incidence of primary central nervous system lymphoma, but a relative stability in the number of patients developing systemic NHL. AIDS-related NHL appears not to be markedly decreased by the introduction of HAART and it is the greatest therapeutic challenge in the area of AIDS oncology. The emphasis has now shifted to cure while maintaining vigilance regarding the unique vulnerability of HIV-infected hosts. Furthermore, also for the prolongation of the survival expectancy of these patients, other non-AIDS-defining tumors, such as Hodgkin's disease, anal, head and neck, lung and testicular cancer, and melanoma have been recently reported with increased frequency in patients with HIV infection.
Relevance of intraocular involvement in the management of primary central nervous system lymphomas.
Ferreri AJ, Blay JY, Reni M, Pasini F, Gubkin A, Tirelli U, Calderoni A, Zucca E, Cortelazzo S, Chassagne C, Tinguel M, Borisch B, Berger F, Ponzoni M, Cavalli F; International Extranodal Lymphoma Study Group (IELSG).
Department of Radiochemotherapy, San Raffaele H Scientific Institute, Milan, Italy. andres.ferreri@hsr.it
BACKGROUND: Reported data regarding intraocular lymphoma (IOL) management are anecdotal. Cases of IOL included in an international multicentre series of 378 immunocompetent patients with primary central nervous system lymphomas (PCNSLs) were reviewed. PATIENTS AND METHODS: Staging included slit-lamp examination in 170 patients: IOL was diagnosed in 22 cases (13%). A concomitant brain lesion was detected in 21 cases. Planned treatment was chemotherapy followed by radiotherapy in 13 cases, chemotherapy alone in three and radiotherapy, followed by or not by chemotherapy in five; one patient was not treated. Chemotherapy included high-dose methotrexate in 12 cases. Ten patients received intrathecal chemotherapy. Radiotherapy consisted of whole brain irradiation, followed by or not by a tumour bed boost; ocular irradiation was planned in 15 cases. Irradiation in one patient without brain lesions was limited to the orbits only (50 Gy). RESULTS: IOL was positively correlated to systemic symptoms and meningeal disease. Fifteen patients (71%) achieved an objective response; 16 patients experienced a failure (2-year failure-free survival 34+/-10%). Failures involved the eyes in eight cases, with a 2-year time to ocular relapse of 59+/-11%. Ocular failure was less common in patients treated with chemotherapy plus ocular irradiation and was associated with a significantly shorter survival. Seven patients are alive [median follow-up 53 months, 2-year overall survival (OS): 39+/-11%] , five of whom were treated with ocular irradiation. The patient with isolated IOL is alive and disease-free at 14 months. OS of the entire series was similar to that of PCNSL patients with negative slit-lamp examination. CONCLUSIONS: IOL is usually associated with concomitant brain disease and shows a survival similar to that of the rest of PCNSLs. Chemotherapy combined with ocular irradiation resulted in better control of ocular disease, which seems to be associated with survival. In view of the potential role of ocular irradiation, the use of chemotherapy alone in phase II trials should be critically reconsidered in PCNSL patients with ocular disease.
Elderly head and neck (H-N) cancer patients: a monoinstitutional series.
Vaccher E, Talamini R, Franchin G, Tirelli U, Barzan L.
Division of Medical Oncology A, National Cancer Institute, Aviano.
Publication Types:
Lectures
Non Hodgkin's lymphoma in the elderly.
Tirelli U, Bernardi D.
Centro di Riferimento Oncologico, Divisione di Oncologia Medica A, Aviano (PN).
Hodgkin's disease in the elderly: current status and future directions.
Proctor SJ, Rueffer JU, Angus B, Breuer K, Flechtner H, Jarret R, Levis A, Taylor P, Tirelli U.
University Department of Haematology, School of Clinical and Laboratory Sciences, Royal Victoria Infirmary, Newcastle-upon-Tyne, UK.
A multicenter study of treatment of primary CNS lymphoma.
Ferreri AJ, Reni M, Pasini F, Calderoni A, Tirelli U, Pivnik A, Aondio GM, Ferrarese F, Gomez H, Ponzoni M, Borisch B, Berger F, Chassagne C, Iuzzolino P, Carbone A, Weis J, Pedrinis E, Motta T, Jouvet A, Barbui T, Cavalli F, Blay JY.
Department of Radiochemotherapy, San Raffaele H. Scientific Institute, Milan, Italy. andres.ferreri@hsr.it
OBJECTIVE: To characterize the therapeutic variables correlated to outcome in 370 patients with primary CNS lymphoma. METHODS: Planned treatment was radiotherapy (RT) in 98 patients, chemotherapy (CHT) in 32, RT followed by CHT in 36, and CHT followed by RT in 197 patients. High-dose methotrexate (HD-MTX; 1 to 8 g/m2) was used in 169 patients and intrathecal CHT in 109. RESULTS: One hundred sixteen patients are alive (median follow-up 24 months), with a 2-year overall survival of 37%. Patients treated with CHT followed by RT had improved survival with respect to patients treated with RT alone. Patients receiving HD-MTX-based primary CHT survived longer than those treated with other drugs. HD-MTX associated with other cytostatics, in particular HD-cytarabine, produced better results than HD-MTX alone. No correlation between MTX dose and survival was found. In patients receiving HD-MTX, consolidation RT or intrathecal CHT did not improve survival. Age, performance status, lactate dehydrogenase serum level, CSF protein level, site of disease, and use of HD-MTX were all predictors of survival. CONCLUSIONS: Combination CHT-RT is superior to RT alone. Patients treated with primary CHT containing HD-MTX exhibited improved survival. In these patients, the addition of HD-cytarabine was associated with a better survival, whereas intrathecal CHT was not correlated to outcome. RT may be unnecessary in patients achieving complete remission after receiving HD-MTX-based primary CHT.
Intensified CHOP regimen in aggressive lymphomas: maximal dose intensity and dose density of doxorubicin and cyclophosphamide.
Balzarotti M, Spina M, Sarina B, Magagnoli M, Castagna L, Milan I, Ripa C, Latteri F, Bernardi D, Bertuzzi A, Nozza A, Roncalli M, Morenghi E, Tirelli U, Santoro A.
Department of Medical Oncology and Hematology, and Division of Pathology, Istituto Clinico Humanitas, Rozzano (Milano).
BACKGROUND: Following our previous study of CHOP (cyclophosphamide, doxorubicin, vincristine and prednisone) intensification in non-Hodgkin's lymphoma (NHL), in the present report we attempted to further increase dose intensity by shortening the between-course intervals with the support of growth factors. PATIENTS AND METHODS: A total of 67 patients were enrolled. With a fixed dose of doxorubicin 75 mg/m(2), cyclophosphamide (CTX) was started at a dose of 1750 mg/m(2) and increased by 250 mg/m(2) in consecutive cohorts of patients provided that no dose-limiting toxicity occurred. After the maximal tolerated dose (MTD) had been identified, this was used to treat more patients in order to confirm the feasibility of the regimen on a large scale, with the number of cycles being varied on the basis of disease extension. RESULTS: Twenty-three cases were enrolled in the CTX dose finding phase. Dose-limiting non-hematological toxicity occurred at 2250 mg/m(2). As the intermediate level of 2000 mg/m(2) had a borderline toxicity profile, a CTX dose of 1750 mg/m(2) was defined as the MTD. A total of 53 patients then received the MTD during the course of the study as a whole. At the MTD, toxicity was acceptable. Only 10 of 189 cycles (4%) required hospitalization due to infection or febrile neutropenia. Seventy-four percent of the patients achieved complete remission. Freedom from progression and overall survival at 12 months were 71% and 86% in the whole series, and 58% and 71% for high-risk cases, respectively. CONCLUSIONS: This intensified CHOP regimen is feasible on an outpatient basis. It can be safely considered a definitive treatment in patients at low and intermediate risk, and as induction before high-dose consolidation in high-risk cases.
Differentiation between non-Hodgkin's lymphoma recurrence and second primary lymphoma by VDJ rearrangement analysis.
Libra M, De Re V, Gasparotto D, Gloghini A, Marzotto A, Milan I, Tirelli U, Stivala F, Carbone A, Boiocchi M.
Division of Experimental Oncology 1, Centro di Riferimento Oncologico Aviano, Department of Biomedical Science, Clinical Pathology and Molecular Oncology Section, University of Catania, Division of Pathology, and Division of Medical Oncology A, Centro di Riferimento Oncologico Aviano, Italy.
Relapses in non-Hodgkin's lymphomas (NHL) could be due to the reappearance of the initial neoplasm or new primary tumours. Discrimination between the two events would allow a more targeted therapeutic approach. VDJ rearrangement was used as marker of clonality in metachronous biopsy specimens from 10 patients with relapsed B-NHL. Complimentarity determining region 3 was amplified and sequenced. D-JH was identical in eight matched primary/secondary tumours, confirming the diagnosis of recurrence. In contrast, primary and secondary tumours in two patients were of different clonal origin. Our data indicate that VDJ analysis is a fundamental tool for identificaton of relapses in NHL.
Expression of cyclin-dependent kinase inhibitor p27(Kip1) in AIDS-related diffuse large-cell lymphomas is associated with Epstein-Barr virus-encoded latent membrane protein 1.
Gloghini A, Gaidano G, Larocca LM, Pierconti F, Cingolani A, Dal Maso L, Capello D, Franceschi S, Tirelli U, Libra M, Niu H, Dalla-Favera R, Carbone A.
Division of Pathology, Centro di Riferimento Oncologico, Istituto Nazionale Tumori, IRCCS, Aviano, Italy.
Knowledge of the role of cell-cycle regulators in the pathogenesis of acquired immune deficiency syndrome-related non-Hodgkin's lymphomas (AIDS-NHLs) is scarce. Here we analyzed 86 systemic AIDS-NHLs and 20 AIDS-primary central nervous system lymphomas for expression of p27(Kip1), a negative regulator of cell-cycle progression belonging to the Kip family of cyclin-dependent kinase inhibitors. In parallel, we investigated the relationship between p27(Kip1), the lymphoma proliferation index, Epstein-Barr virus status, expression of cellular cyclin D3 and cyclin D1, and B-cell differentiation stage. We report that AIDS-immunoblastic lymphomas (AIDS-IBLs), either systemic or primarily localized to the central nervous system, consistently express p27(Kip1) protein (19 of 24 and 10 of 14, respectively) despite the high proliferative rate of the lymphoma clone, suggesting a failure of p27(Kip1) to inhibit the cell cycle in AIDS-IBL. Conversely, the remaining systemic AIDS-NHLs and AIDS-primary central nervous system lymphomas preferentially fail to express p27(Kip1). Expression of p27(Kip1) in Epstein-Barr virus-positive AIDS-NHLs generally associates with latent membrane protein 1 (LMP1) expression and is related to a late stage of B-cell differentiation, characterized by the BCL-6-/MUM1+/syn-1+/- phenotypic profile, whereas it seems to be unrelated to the expression of cellular cyclins. In B cells in vitro, induction of LMP-1 expression under the control of inducible promoters up-regulates expression of p27(Kip1), thus providing a putative mechanistic explanation for the association between LMP1 and p27(Kip1) observed in vivo. Overall, these data show that AIDS-IBL pathogenesis is characterized by loss of the inverse relationship between p27(Kip1) positivity and tumor growth fraction that is otherwise generally observed in normal lymphoid tissues and in most other types of NHLs.
Stanford V regimen and concomitant HAART in 59 patients with Hodgkin disease and HIV infection.
Spina M, Gabarre J, Rossi G, Fasan M, Schiantarelli C, Nigra E, Mena M, Antinori A, Ammassari A, Talamini R, Vaccher E, di Gennaro G, Tirelli U.
Division of Medical Oncology A, National Cancer Institute, Via Pedemontana Occidentale 12, 33081 Aviano (PN), Italy.
A phase 2 prospective study was performed to evaluate the feasibility and activity of a short, dose-intensive chemotherapy regimen and radiotherapy (the Stanford V regimen) plus highly active antiretroviral therapy (HAART) and granulocyte colony-stimulating factor (G-CSF) support in patients with Hodgkin disease and HIV infection. Fifty-nine patients were enrolled. Stanford V was well tolerated and 69% of the patients completed treatment with no dose reduction or delayed chemotherapy administration. The most important dose-limiting side effects were bone marrow toxicity and neurotoxicity. Complete remission was achieved by 81% of the patients, and after a median follow-up of 17 months 33 patients (56%) were alive and disease-free. The estimated 3-year overall survival (OS), disease-free survival (DFS), and freedom from progression (FFP) were 51%, 68%, and 60%, respectively. Probability of FFP was significantly (P =.02) higher among patients with an International Prognostic Score (IPS) of 2 or lower than in those with an IPS higher than 2, and the percentages of FFP at 2 years in these groups were 83% and 41%, respectively. Similarly, the probability of OS was significantly (P =.0004) different in the 2 groups, and the percentages of OS at 3 years were 76% and 33%, respectively. Our data confirm that the Stanford V regimen with concomitant HAART is feasible and active in an HIV setting. However, a more intensive approach should be considered in patients with high IPSs.
Cancer-related fatigue (review).
Tavio M, Milan I, Tirelli U.
Division of Medical Oncology A, National Cancer Institute, Via Pedemontana Occidentale 12, I-33081 Aviano (PN), Italy.
Fatigue is one of the most common complaints of people with cancer. It affects the majority of patients actively undergoing cancer related therapies, but also a meaningful number of those who successfully completed therapy and are disease-free and potentially cured at the end of the treatments. In cancer setting, fatigue is to be defined as a chronic form of tiredness, which is perceived by the patient as being unusual or abnormal, and absolutely disproportionate with respect to the amount of exercise or activity he/she has carried out and which is not removed by resting or sleeping. The exact cause of fatigue is not known. In cancer setting there are many contributing or associated factors, such as cancer itself, cancer treatment (chemotherapy, radiation therapy, immunotherapy and surgery), depression or anxiety, some medications, pain, nausea, vomiting or diarrhea, poor nutrition, anemia, infections, insomnia. There is no standard of care for the assessment or treatment of fatigue in patients with cancer. The evaluation of fatigue is intrinsically multidimensional, even though the lack of objective measurement methods makes it difficult to draw up worldwide-accepted guidelines; nonetheless, a number of methods have been developed to assess it. Treatment of fatigue should depend on its cause, but presently it is still addressed against the associated symptoms rather than fatigue itself. Useful approaches includes erythropoietin alpha, psychostimulants, medications to treat pain, depression, nausea and difficult sleeping, physical therapy for reconditioning exercises or energy saving techniques, health education. In this report some of the crucial issues related to fatigue in people with cancer are reviewed.