Chiara Dellepiane

Pharmacotherapy to protect ovarian function and fertility during cancer treatment

In recent years, modern anticancer treatments have led to significant survival improvements; however, in premenopausal women, the administration of these therapies is also associated with potential unwanted side effects such as treatment-related premature ovarian failure (POF) and subsequent reduced fertility [1]. At the time of cancer diagnosis, the maintenance of gonadal function and fertility has crucial importance for many patients. As recommended by international guidelines, all patients of reproductive age should be counseled about the potential treatment-related loss of ovarian function and fertility and helped with informed fertility preservation decisions [2,3]. For young female cancer patients, embryo/oocyte cryopreservation are standard strategies to preserve fertility [2,3]; however, they require a period of controlled ovarian stimulation with subsequent delay in the initiation of anticancer treatments and they cannot preserve gonadal function during cytotoxic therapy. Pharmacological protection of the ovaries with the use of temporary ovarian suppression with gonadotropin-releasing hormone analogs (GnRHa) during chemotherapy is a widely available option requiring no delay in the initiation of treatment. However, taking into account the controversial data available up to 2013, it was considered an experimental strategy in cancer patients [2,3]. Over the past few years, several important news have become available on the potential efficacy and safety of temporary ovarian suppression with GnRHa during chemotherapy as a strategy to preserve ovarian function and fertility in young patients with breast cancer and lymphoma.

A Case of Plasmacytoid Variant of Bladder Cancer with a Single Penile Metastasis and a Complete Response to Carboplatin-Based Chemotherapy and Review of the Literature

The plasmacytoid variant of urothelial carcinoma is considered a rare variant of urothelial carcinoma, accounting for 3% of all malignant primary tumors. The histologic and morphologic features are characterized by medium-size and dyshesive tumor cells with abundant eosinophilic cytoplasm, small hyperchromatic nuclei, and frequent mitotic figures, resembling plasma cells. We describe the case of a patient who underwent radical cystectomy, bilateral lymphadenectomy, and adjuvant chemotherapy for locally advanced plasmacytoid variant of urothelial carcinoma. After metastatic spread of the disease to the penis, the patient underwent 4 cycles of a carboplatin and paclitaxel regimen, experiencing a 12-month diseasefree interval. Currently, no role for chemotherapy has been defined, given the absence of data from clinical randomized trials supporting their use. Therefore, we aimed to provide a comprehensive review of the published data focusing on the pathologic diagnosis and therapeutic management of this rare neoplasm.

Intradermal influenza vaccination in complete remission cancer patients: molecular insights

We previously showed that long-lasting complete remission (CR) non-Hodgkin lymphoma (NHL) patients treated with rituximab-containing chemotherapy have an attenuated antibody response to virosomal (Bedognetti et al, J. Immunology, 2011) or MF-59 adjuvanted (Bedognetti et al, Blood, 2012) seasonal (or pandemic) influenza vaccine (as compared with healthy controls), associated with persistent CD27+ Memory B cell depletion and hypogammaglobulinemia. Here, we evaluated humoral and innate response to trivalent intradermal vaccination in NHL in CR previously treated with rituximab-containing chemotherapy (at least one year before vaccine administration), RIT group, and in CR cancer patients treated with chemotherapy without rituximab (at least one year before vaccine administration), Non-RIT group. Intradermal administration was chosen considering its promising data, compared to conventional intramuscular route, in terms of immunogenicity and safety. Humoral response was assessed by hemagglutinin inhibition assay on sera collected at time 0 (just before vaccination) and at time 28 (four weeks after vaccination). Innate response was assessed by whole-genome gene expression analysis (Affymetrix Humane Gene ST 1.0) on PBMC collected at time 0 and at time 1 (24 hours after vaccine administration). Patients treated with rituximab-containing chemotherapy had, overall, a lower antibody response, compared to patients treated with chemotherapy alone. Overall, intradermal vaccination induced dramatic changes in gene-expression profile already one day after vaccination. These changes underline the activation of IFN stimulated genes (eg, STAT1, STAT2, CXCL10, IDO1, GBP1) and modulation of NK-associated transcripts. In addition, pathway and gene-enrichment analysis show that RIT and non-RIT groups have different quantitative and qualitative transcriptomic changes 24 hours after vaccination administration. Concordantly with antibody-titer, the innate response was more intense in Non-RIT group compared with RIT group.