Ongoing clinical trials on axillary management.

INTRODUCTION: Within the last 50 years the management of patients with breast cancer has changed dramatically with a significant de-escalation of the role and magnitude of surgery, both for the management of the primary tumor and for the management of the axilla. In the management of the axilla of patients with early stage breast cancer (EBC) and clinically uninvolved axilla (cN0), axillary lymph node dissection (ALND) was gradually replaced by sentinel lymph node biopsy (SLNB) saving more than 60-70% of patients from an unnecessary dissection. Further studies confirmed that isolated tumor cells or micrometastases found on the SLN had no further benefit from ALND sparing even more patients from an unnecessary ALND. Eventually, the Z0011 and other studies showed that even patients with 1-2 positive SLN can be spared from ALND provided they fulfill certain criteria. Still though there were many flaws in these studies and further research was necessary to generalize the results of these studies to a wider target group. Meanwhile, there is a clear view that many low risk patients if they have their axilla evaluated via US and are not found to have suspicious nodes, it is highly unlikely to have involved axilla. This let to studies evaluating the non-surgical management of the axilla. Finally, in the post neoadjuvant setting 3 randomized controlled trials showed that under certain circumstances SLNB can be done after the NAC even in patients who initially had involved axilla and was converted to clinically uninvolved (cN1→cN0). EVIDENCE ACQUISITION: PubMed, Medline, the Cochrane Library Controlled Trials Register as well as National Institutes of Health ClinicalTrials.Gov database have been consulted up to May 2020. EVIDENCE SYNTHESIS: We studied and described the ongoing trials on patients not undergoing neoadjuvant chemotherapy and we discussed the eligibility criteria, the comparison arms and the expected outcomes. We further examined the ongoing trials on patients undergoing neoadjuvant chemotherapy in the same manner. CONCLUSIONS: Although we have covered a long way in the journey of eliminating axillary surgery, there are still lots of questions to be answered and trials to be conducted. We anticipate the results of the ongoing trials to provide the necessary evidence to safely de-escalate more the axillary surgery, both in the non-neoadjuvant as well as in the neoadjuvant setting, hoping that in the not so far future the axillary surgery will eventually perish.

Longitudinal assessment of immunological status and rate of immune recovery following treatment in children with ALL.

BACKGROUND: We prospectively evaluated the immunological status, immune recovery and risk of infection in pediatric ALL patients treated on the BFM 95 protocol. PROCEDURE: Humoral and cellular immunity were evaluated in 72 children with ALL at the end of intensive therapy and values were compared to those at the completion of therapy and 6-monthly. Parameters investigated included lymphocyte subpopulation by flow cytometry, immunoglobulin levels by nephelometry, antibody titers to previous immunizations and delayed hypersensitivity with skin testing. Immune responses were correlated to duration of therapy, CNS radiotherapy, age and sex. RESULTS: Humoral immunity was severely depressed by the end of intensive therapy with low immunoglobulin levels and CD19, improved after therapy cessation. Cellular immune responses were normal at the end of intensive treatment but declined significantly by the end of therapy and both CD4 and CD8 remained low at later evaluation points whereas CD4/CD8 ratio was increasing. Duration of therapy and CNS radiotherapy did not affect the rate of immune recovery whereas female had higher CD19, CD45RO, and IgM and children >7 years had higher CD19 and lower CD16 and CD3DR. Among immunized children, 86.7% maintained protective antibodies to MMR and 63% to polio. Despite impairment of immunity, infections outside the neutropenic periods were common viral illnesses. CONCLUSION: Humoral immunity was depressed in children with ALL at the end of intensive therapy but began to recover after cessation of therapy. In contrast, cellular immunity declined significantly by the end of therapy and remained abnormal for at least 1 year post-therapy.

Central nervous system tumours among adolescents and young adults (15-39 years) in Southern and Eastern Europe: Registration improvements reveal higher incidence rates compared to the US.

AIM: To present incidence of central nervous system (CNS) tumours among adolescents and young adults (AYAs; 15-39 years) derived from registries of Southern and Eastern Europe (SEE) in comparison to the Surveillance, Epidemiology and End Results (SEER), US and explore changes due to etiological parameters or registration improvement via evaluating time trends. METHODS: Diagnoses of 11,438 incident malignant CNS tumours in AYAs (1990-2014) were retrieved from 14 collaborating SEE cancer registries and 13,573 from the publicly available SEER database (1990-2012). Age-adjusted incidence rates (AIRs) were calculated; Poisson and joinpoint regression analyses were performed for temporal trends. RESULTS: The overall AIR of malignant CNS tumours among AYAs was higher in SEE (28.1/million) compared to SEER (24.7/million). Astrocytomas comprised almost half of the cases in both regions, albeit the higher proportion of unspecified cases in SEE registries (30% versus 2.5% in SEER). Similar were the age and gender distributions across SEE and SEER with a male-to-female ratio of 1.3 and an overall increase of incidence by age. Increasing temporal trends in incidence were documented in four SEE registries (Greater Poland, Portugal North, Turkey-Izmir and Ukraine) versus an annual decrease in Croatia (-2.5%) and a rather stable rate in SEER (-0.3%). CONCLUSION: This first report on descriptive epidemiology of AYAs malignant CNS tumours in the SEE area shows higher incidence rates as compared to the United States of America and variable temporal trends that may be linked to registration improvements. Hence, it emphasises the need for optimisation of cancer registration processes, as to enable the in-depth evaluation of the observed patterns by disease subtype.