Ernesto Zanet

AIDS-related Kaposi's sarcoma: state of the art and therapeutic strategies.

In the HAART era Kaposis sarcoma (KS) remains the second most frequent tumor in HIV-infected patients worldwide, and it has become the most common cancer in Sub-Saharan Africa. In western countries the risk for KS in men having sex with men (MSM) is 5 to 10 times higher compared to other groups of individuals practicing other HIV-risk behaviors. Patients with KS in Sub-Saharan Africa have very high tumor burdens and rapid disease progression with a diminished life expectancy of less than 6 months. KS lesions are comprised of both distinctive spindle cells of endothelial origin and a variable inflammatory infiltrate, which suggests that KS may result from reactive hyperproliferation induced by chronic inflammation, and therefore it is not a true neoplasm. KS has a variable clinical course ranging from very indolent forms, requiring no or minimal therapy, to a rapidly progressive disease. Treatment decisions must take into consideration the extent and the rate of tumor growth, patients symptoms, immune system conditions and concurrent HIV-related complications. Several different therapeutic options are available but the optimal therapy is still unclear. Highly Active Antiretroviral Therapy (HAART) including protease inhibitors (PI) may represent the first treatment step for slowly progressive disease; chemotherapy (CT) plus HAART is indicated for visceral and/or rapidly progressive disease, whereas maintenance (M)-HAART after systemic chemotherapy may be an effective anti-KS measure after debulking CT. The angiogenic nature of KS makes it particularly suitable for therapies based on targeted agents such as metalloproteinase inhibitors, angiogenesis inhibitors and tyrosine kinase inhibitors. The aim of this article is to provide an up-to-date review of the current status and perspectives of AIDS-related KS in the HAART era.

Glioblastoma in elderly patients: Safety and efficacy of adjuvant radiotherapy with concomitant temozolomide

The aim of this study was to evaluate the impact of radiotherapy plus concomitant and adjuvant temozolomide (TMZ), in terms of feasibility and activity, in elderly patients with glioblastoma. From January 2002 to December 2007, 42 consecutive patients with glioblastoma (27 men and 15 women) aged 65 years or more (median age 71.3 years), received radiotherapy plus concomitant and adjuvant TMZ. Nineteen patients (45.2%) had a Karnofsky index >or=80. Thirty-six patients (85.8%) underwent complete or subtotal resection, while 6 patients (14.2%) were only biopsied. All patients received adjuvant radiotherapy within 4 weeks from surgery. Twenty-two patients (54.8%) underwent adjuvant TMZ. Early discontinuation of concomitant TMZ program due to toxicity was observed in 8 patients. Considered variables were: age, Karnofsky index, surgery versus no surgery, radiation dose, and chemotherapy. At a median follow-up of 10.2 months, the 6- and 12-month overall survival rates were 81.9% and 27.8%, respectively. There was a significantly better survival for patients with a performance status according to Karnofsky >80 (p<0.0001). Actuarial progression-free survival at 6- and 12-month was 46.4% and 9.8%, respectively. Globally, the treatment was well tolerated with no treatment-related toxicity in 69% of patients. In conclusion, in elderly patients, the adjuvant chemo-radiotherapy was well tolerated with an acceptable rate of toxicity, and patients with a good performance status had a significantly better survival. However, further prospective trials are needed to confirm these results.

Pancreatic cancer in HIV-positive patients: a clinical case-control study.

Objectives Pancreatic cancer (PC) is the fourth and fifth most common cause of cancer-related death among men in United States and in Europe, respectively. No data are available for HIV-positive patients. The aim of this study was to investigate and to compare clinical presentation and outcome between HIV-positive and HIV-negative PC patients. Methods From April 1988 to June 2010, the Italian Cooperative Group on AIDS and Tumors identified 16 cases of HIV-positive PC patients. Each HIV-positive patient from our institution was randomly matched (ratio 1:2) with HIV-negative patients (32 controls) based on sex and year of PC diagnosis. Differences in clinical presentation, treatment, and overall survival were assessed. Results At multivariate analysis, HIV-positive patients compared with HIV-negative patients had a higher risk of an unfavorable performance status (PS ≥2) and a younger age (<50 years) at cancer diagnosis. At multivariate analysis, HIV-positive status and PS of 2 or greater were the only 2 features that significantly reduced PC patients’ survival. Conclusions Our data show, for the first time, that HIV-positive PC patients, compared with HIV-negative patients, are younger at cancer diagnosis. Furthermore, they share a more unfavorable PS and a shorter survival.

The impact of tobacco smoking and alcohol drinking on survival of patients with non‐Hodgkin lymphoma

Tobacco smoking and alcohol consumption have not been clearly related to the risk of non‐Hodgkin lymphoma (NHL), and the impact of these two factors on survival of NHL patients has received little attention. Cases were 268 subjects with incident histologically‐confirmed NHL, admitted as inpatients to the Division of Medical Oncology, between 1983 and 2002. These individuals were enrolled as cases in case‐control studies conducted at the same institution over the same period. For all patients clinical (histological subtype, major prognostic factors and treatment) and epidemiological data (smoking and drinking habits) were available. Survival analysis was performed using Kaplan‐Meier methods. Hazard ratio (HR) was estimated by Cox proportional hazard model. Compared to never smokers, patients who smoked ≥20 cigarettes/day had higher risks of death (HR = 1.70, 95% confidence interval (CI): 1.06–2.73) and lower survivals at 5 years (60 and 46%, respectively). Likewise, patients who drunk ≥4 drinks/day showed 1.69‐fold higher probability of death (95% CI: 1.04–2.76) in comparison to drinkers of <2 drinks/day (5‐year survival: 47 and 67%, respectively). When combining exposure to alcohol and tobacco, no excess of death emerged in light drinkers (<4 drinks/day), irrespective of their smoking habits, but higher risks of death emerged among heavy drinkers. In the present study, heavy tobacco smoking, and particularly, heavy alcohol drinking were associated with poor survival in NHL patients. Our findings strongly encourage physicians to advice NHL patients to stop smoking and diminish alcohol consumption to obtain improvements in the course of NHL.

Clinical Presentation and Outcome of Colorectal Cancer in HIV-Positive Patients: A Clinical Case-Control Study

Background: Data on colorectal cancer (CRC) in HIV-positive patients are limited. The study objective was to investigate and compare clinical presentation and outcome between HIV-positive and HIV-negative CRC patients. Patients and Methods: Between September 1985 and November 2003 we identified 27 cases of HIV-positive CRC patients from the cancer registry database – Italian Cooperative Group AIDS and Tumours (GICAT); the clinical presentation/outcome information was retrieved. Each HIV-positive patient from our institution was randomly matched (ratio 1:2) with HIV-negative patients (54 controls) based on age, sex, and year of diagnosis in the same time period. Differences in clinical presentation, treatment, and overall survival were assessed. Results: Of 1130 HIV-negative CRC patients, 54 were identified and matched with 27 HIV-positive patients. Compared with the HIV-negative patients, the HIV-positive patients had a higher risk of lower performance status (PS: ≥2) (odds ratio (OR) = 14.4; 95% confidence interval (CI): 3.6–57.7), a higher risk of unfavorable Dukes’ stage (D) (OR = 4.9; 95% CI: 1.8–13.5), and a higher risk of poor grading (G3–G4) (OR = 5.0; 95% CI: 1.9–13.4). Median overall follow-up was 27 months (range: 2–212). At multivariate analysis, the only characteristics that significantly reduced the survival of the CRC patients were: HIV-positive status (hazard ratio (HR): 2.4; 95% CI: 1.1–5.2) and Dukes’ stage D (HR: 3.7; 95% CI: 1.9–7.1). Conclusion: Our data show that HIV-positive CRC patients compared to HIV-negative patients have a poorer PS, an unfavorable Dukes’ stage, higher grading and shorter survival.

Anal Cancer: Focus on HIV-Positive Patients in the HAART Era

Anal cancer represents an increasing health problem, especially in immune-compromised patients, as HIV-positive patients. Notably, a significant higher incidence rate is reported among HIV infected patients with the advent of highly active antiretroviral therapy (HAART). To date, no randomised trial supports the correlation between existing screening strategies and reduced progression of anal intraepithelial neoplasia (AIN) to anal cancer or improved survival. Nevertheless, screening and treatment of AIN by topical agents should be implemented in high risk population. Data on invasive anal cancer treatment show that combined modality treatment (CMT) is the treatment of choice. Early reports on HIV-positive patients describe higher treatment toxicity and a relation with lower CD4 count and higher HIV viral load. More recently, reported outcomes seem to be similar in HIV-positive population and general population. Reports on a rise in local recurrence rates and in acute side effects along with a correlation with pre-treatment CD4 counts in HIV-positive patients, are not confirmed by all authors. The development of the first approved vaccine is a milestone in the field of anogenital cancers. However, many questions are still unresolved especially as concerns immunization in the setting of HIV infection.

HIV-Positive Patients with Liver Metastases from Colorectal Cancer Deserve the Same Therapeutic Approach as the General Population

a Division of Medical Oncology A, National Cancer Institute, Aviano, b Department of Surgery, University of Catania, c Department of Clinical Sciences, Section of Infectious Diseases and Immunopathology, ‘L.Sacco’ Hospital, University of Milan, d Liver and Multivisceral Transplant Centre, University of Modena and Reggio Emilia, e Division of Medical Oncology, Colorectal Department, National Cancer Institute Pascale, Naples, Italy

Phase 2 study of intrathecal, long-acting liposomal cytarabine in the prophylaxis of lymphomatous meningitis in human immunodeficiency virus-related non-Hodgkin lymphoma.

Patients with aggressive non‐Hodgkin lymphoma (NHL) develop central nervous system (CNS) progression or recurrence during the course of their disease. Patients with human immunodeficiency virus (HIV)‐NHL often develop CNS progression despite the use of prophylaxis. Liposomal cytarabine (DepoCyte) has shown activity in lymphomatous meningitis, but there are limited data for prophylaxis.

Unusual presentation of metastatic hepatocellular carcinoma in an HIV/HCV coinfected patient: Case report and review of the literature

Hepatocellular carcinoma (HCC) is an increasing cause of mortality in human immunodeficiency virus (HIV) seropositive patients. Concurrent infection with HIV may accelerate the progression from cirrhosis to HCC. Viral hepatitis and alcohol abuse are the main risk factors for HCC in developed countries. Exposure to these risk factors is common among HIV-infected patients. We report the case of a 43-year-old woman affected by HCC, with unusual soft tissue metastases (left masseter muscle) and HIV/HCV coinfection. The usual route of metastatic spread from classic HCC is hematogenous, with the most common extrahepatic site being the lung. Our case, besides the unusual distant metastatic site, showed very rapid clinical progression, as has been commonly observed in HIV-infected patients with HCC. The case series of HCC in HIV-positive individuals published to date does not cumulatively exceed 70 subjects.

Bevacizumab plus irinotecan-, fluorouracil-, and leucovorin-based chemotherapy with concomitant HAART in an HIV-positive patient with metastatic colorectal cancer.

Background: In the era of highly active antiretroviral therapy (HAART), malignancies are the primary cause of increased mortality in patients with human immunodeficiency virus (HIV) infection, hence representing a new challenge for oncologists. To date, there is little evidence in the English literature about chemotherapy treatment in HIV-positive patients with metastatic colorectal cancer. Case Report: We describe the case of an HIV-positive 48-year-old male patient with metastatic colorectal cancer, treated with a bevacizumab, irinotecan, fluorouracil, and leucovorin regimen, with concomitant HAART. No opportunistic infections and grade 3–4 haematological and non-haematological toxicity were reported. The HIV infection was kept under control during the bevacizumab chemotherapy treatment. Conclusions: This case suggests that, in the HAART era, the best multidisciplinary approaches can be offered to HIV-positive patients with metastatic colorectal cancer, who have a good performance status and a well controlled HIV infection. An HIV infection should not preclude the use of the best available chemotherapy treatment in this particular group of patients, including targeted/biological drugs.