Standardisation of minimal residual disease in multiple myeloma.

The assessment of the effectiveness of chemotherapy in oncology cannot disregard the concept of minimal residual disease (MRD). In fact, the efforts of numerous scientific groups all over the world are currently focusing on this issue, with the sole purpose of defining sensitive, effective assessment criteria that are, above all, able to give acceptable, easily repeatable results worldwide. Regarding this issue, especially with the advent of new drugs, multiple myeloma is one of the haematologic malignancies for which a consensus has not yet been reached. In this review, we analyse various techniques that have been used to improve the sensitivity of response, aimed at reducing the cut-off values previously allowed, as well as serological values like serum-free light chain, or immunophenotypic tools on bone marrow or peripheral blood, like multi-parameter flow cytometry, or molecular ones such as allele-specific oligonucleotide (ASO)-qPCR and next-generation/high-throughput sequencing technologies (NGS). Moreover, our discussion makes a brief reference to promising techniques, such as mass spectrometry for identifying Ig light chain (LC) in peripheral blood, and the assessment of gene expression profile not only in defining prognostic risk at the diagnosis but also as a tool for evaluation of response.

Stereotactic Re-irradiation in Recurrent Prostate Cancer after Previous Postoperative or Definitive Radiotherapy: Long-term Results after a Median Follow-up of 4 Years.

AIMS: In 2018, we published early results from a cohort of patients treated with stereotactic body radiotherapy (SBRT) after previous radiotherapy with definitive or postoperative intent. We sought to provide extended follow-up of this cohort to confirm the safety and efficacy of this approach in a real-world scenario. MATERIALS AND METHODS: Fifty patients affected by local relapse after previous definitive or postoperative radiotherapy were treated with SBRT. Treatment provided a total dose of 30 Gy in five fractions. Data about biochemical relapse-free survival (BRFS) and metastasis-free survival (MFS), together with adverse events, were analysed. Toxicity was reported according to Common Terminology Criteria for Adverse Events (CTCAE) score v.4.03. RESULTS: After a median follow-up of 48.2 months, the median BRFS was 43 months. A Gleason score >7 and concomitant androgen deprivation therapy were shown to be predictors of the worst BRFS (hazard ratio 2.42, 95% confidence interval 1.09-5.41, P = 0.02; hazard ratio 2.83, 95% confidence interval 1.17-6.8, P = 0.02, respectively). The median MFS was not reached; concomitant androgen deprivation therapy was confirmed to be predictive of the worst MFS (hazard ratio 4.75, 95% confidence interval 1.52-14.8, P = 0.007). Late grade 1 and 2 rectal and bladder toxicity occurred in three (6%) and 13 (26%) patients, respectively. One patient experienced both grade 3 acute and chronic bladder toxicity. CONCLUSION: Salvage SBRT re-irradiation after previous postoperative or definitive radiotherapy for local prostate cancer recurrence confirmed promising results in terms of oncological outcomes and the safety of this approach.

Pattern of Recurrence After Stereotactic Radiotherapy in Prostate Cancer Patients With Nodal Pelvic Relapse. A Multi-Institutional Retrospective Analysis.

AIMS: Currently, when nodal pelvic oligorecurrent disease is detected, no standard treatment option is recommended. One possible salvage option is nodal stereotactic body radiotherapy (SBRT). Here we analysed recurrence patterns after nodal SBRT in patients affected by pelvic oligometastatic relapse after radical prostatectomy, and androgen deprivation therapy (ADT)-free survival in this population. MATERIALS AND METHODS: Data on 93 patients consecutively treated in five different institutions for pelvic oligorecurrent disease were reviewed. Inclusion criteria were biochemical recurrence after radical prostatectomy and imaging showing three or fewer metachronous lymphoadenopathies under aortic bifurcation. Patients underwent SBRT on all sites of disease. Concomitant ADT was allowed. RESULTS: After a median follow-up of 20 months (interquartile range 11-41), 57 patients had post-SBRT radiological evidence of relapse, for a median disease-free survival (DFS) of 15 months (95% confidence interval 9-24). Concomitant ADT was administered in 20 patients (21.5%). Overall, eight (8.6%), 21 (22.6%) and 28 (30.1%) patients had prostate bed only, pelvic nodal or distant relapse, respectively. The median ADT-free survival was not reached. Concomitant ADT, International Society for Urologic Pathology pattern at diagnosis < or ≥3, time to relapse ≤ or >12 months, prostate-specific antigen at recurrence < or ≥1.10 ng/ml and prostate-specific membrane antigen staging were not significantly associated with DFS. After relapse, 42 patients (45.2%) received a second SBRT course. CONCLUSION: Nodal SBRT yielded encouraging DFS and ADT-free survival in this population. Only a minority of patients developed prostate bed recurrence, suggesting that local treatment may be safely avoided. A consistent percentage of patients could be managed with a second SBRT course.

Antitumorigenic action of nelfinavir: Effects on multiple myeloma and hematologic malignancies (Review).

Protease inhibitors (PIs) inhibit HIV­1 and HIV­2 proteases, impeding virus replication and liberation of viral elements from infected cells. In human immunodeficiency virus (HIV) subjects receiving PI­based treatment, an impressive decrease in the amount of HIV­associated cancers, unconnected to viral burden or CD4 amount was observed. Research has reported that PIs have influence on cancer proliferation, spread, and survival as an effect on endoplasmic reticulum stress, proteasome, NF­κB and Akt signalling. Nelfinavir (NFV) is a nonpeptidic PI that functions by connecting to the catalytic site of the HIV protease, thus stopping the cleavage of viral polyprotein into complete, operative proteins that are fundamental for viral survival. NFV, currently not frequently employed for antiretroviral treatment, has demonstrated noteworthy off target effects in tumor patients with or without HIV disease. NFV appears to cause cell death in tumor cells by different mechanisms, which include necrosis, apoptosis and autophagy. In this review, data from preclinical research and clinical trials are reported and the mechanisms of action of NFV and their results in the treatment of hematologic malignancies, such as acute myeloid leukemia, chronic lymphoid leukemia, and diffuse large B cell lymphoma, and especially in patients with multiple myeloma are examined. In the future, experimental studies may help identify the role of NFV in cancer treatment and may promote the application of this drug into daily clinical practice.

Role of the microbiota in hematologic malignancies.

Human beings are inhabited by innumerable microorganisms that interrelate with the host in a reciprocal way, establishing a combined and efficient ecosystem - the microbiota - that can affect healthiness as well as disease. There is evidence that the conformation of the microbiota may influence, and is controlled by, the human immune system. Microbes existing in human tissues offer a multiplicity of advantages that participate in functional actions in the host through the adjustment of essential processes such as immunity, signal transduction, and metabolism. The imbalance of this microbial structure has been connected with the pathogenesis and progression of cancer. We reviewed the present knowledge of the diverse microbial ecosystems and we investigated their potential link to carcinogenesis, and the possibility of using advantageous microbes in controlling and preventing hematologic malignancies.