W. Lybaert MD

Not just a ‘usual’ Li-Fraumeni syndrome

SUMMARY

The Li-Fraumeni syndrome (LFS) is characterised clinically by the appearance of tumours in multiple organs, generally at an early age. This hereditary condition is caused by germinal mutations in the TP53 gene, which codifies for the tumour suppressor gene p53.

We present here the case of a patient aged 40 with the diagnosis of LFS who presented with premenopausal breast cancer. She had a positive family history of cancer. As a consequence, she was referred to genetic counselling. Genetic analysis revealed a TP53 germline mutation, which is diagnostic for LFS. However, further genetic analysis of different tissues showed a genetic mosaicism in our patient.

Patients with LFS have a high risk for a broad spectrum of tumours. The diagnosis and management of Li-Fraumeni syndrome should be performed by a multidisciplinary team, and genetic counselling should be offered to patients and their relatives. Targeted next-generation sequencing represents an efficient approach for the identification of mutations in families with a heterogeneous phenotype. Theoretically, since mosaics do not have mutations in all of their cells, the cells that do not have mutant p53 are less likely to undergo malignant transformation or have the same risk of everyone else.

(BELG J MED ONCOL 2020;14(3):100–105)

Highlights of the Gastrointestinal Cancers Symposium 2020

SUMMARY

At the background of the Golden Gate Bridge with a view on the Pacific Ocean, the annual Gastrointestinal Cancers Symposium was held from 23^rd until 25^th January 2020 in the Moscone Congress Center in San Francisco, California. During this meeting, the potential of immunotherapy in the treatment of cancers from the upper and lower digestive tract was discussed, but no major breakthroughs were presented this year. In addition to immunotherapy, ASCO GI 2020 featured several interesting presentations on the molecular profiling of different types of gastro-intestinal cancers. These increased molecular insights will hopefully pave the way for a more biomarker-driven treatment approach for these tumours in the near future. In this report, the most important headlines will be discussed, with comments on the clinical relevance of the different studies.

(BELG J MED ONCOL 2020;14(3):116–25)

Highlights of the 2019 annual meeting of the European Neuroendocrine Tumour Society (ENETS)

MARCH 6-8TH, 2019, BARCELONA

Highlights of the Gastrointestinal Cancers Symposium 2019

SUMMARY

At the background of the Golden Gate Bridge with a view on the Pacific Ocean, the annual Gastrointestinal Cancers Symposium was held from 17–19 January 2019 in the Moscone Congress Center in San Francisco, California. The meeting further underlined the invasion of immunotherapy in the treatment landscape of gastrointestinal tumours, both in the upper and lower digestive tract. In addition to immunotherapy, lots of efforts were made in the molecular profiling of gastrointestinal cancers in every possible tumour location, which will hopefully fuel more biomarker-driven medicine in this setting in the near future. In this report, the most important headlines will be discussed, with comments on the clinical relevance of the different studies.

(BELG J MED ONCOL 2019;13(4):142–149)

Neuroendocrine neoplasms grade 3: prospective overall survival data and survival after platinum-etoposide chemotherapy within an ENETS Center of Excellence

Introduction

Overall survival (OS) and progression-free survival (PFS) data of grade 3 NENs remains limited.

Aim

The aim is to report prospective survival data in grade 3 NENs treated within NETwerk.

Methods

Patient characteristics of all grade 3 NENs treated from April 2016 to May 2018 were prospectively recorded. Median OS (mOS) from diagnosis and mOS and median PFS (mPFS) after start cisplatinum/carboplatinum-etoposide chemotherapy was calculated.

Results

Of 79 included NEN grade 3 patients, there were 46 males (58,2%). Mean age at diagnosis was 68 years [range 22-90y]. In 67% (N=53) of the cases, the primary tumor was a GEP-NEN (of which 18 unknown). In our population 44% (N=35) had metastases at diagnoses, 44% (N=35) had a Ki67 index ≥ 55%, 30% (N=24) had a Ki67 index < 55%. Platinum-etoposide chemotherapy was given in 29% (N=23) of the patients. The majority (N=41) had FDG-PET imaging of which 36 were positive and 14 had somatostatin receptor imaging (SRS) of which 11 were positive. Combined FDG-SRS positivity was seen in 5 of 11 patients (45%). Overall mOS was 10.5m (95%CI: 6.6-NR). In GEP-NEN mOS was 8.3m (95% CI: 6.0-18.7), while in NENs from other origin mOS was 12m (95% CI: 6.8-NR, p = 0.2). The mOS for patients with a Ki67 index < 55% was 14.2m (95% CI: 8.9-NA) vs 8.2m (95% CI: 5.6-NA) for patients with Ki67 index ≥ 55% (p=0.3). In multivariate analysis, age at diagnosis had significant impact on OS (HR 0.95, p=0.003), while tumor origin showed trend towards significance (HR 0.49, p= 0.056). The mPFS and mOS after chemotherapy were 6.5m (95%: 4.8 -NR) and 14.2m (95% CI: 8.3-NR). For the chemotherapy-treated group no significant effect of tumor location, metastasis at diagnosis and age at diagnosis was seen on OS and PFS.

Conclusions

In this grade 3 NEN cohort, non-GEP-NENs have a better OS survival than GEP-NENs. Our results confirm the limited PFS and OS after platinum-etoposide chemotherapy in grade 3 NENs, highlighting the need for better treatment. When performed, FDG-PET and SRS-positivity is frequent and could guide treatment.

Highlights of the 2018 Annual European Neuroendocrine Tumor Society (ENETS) Congress

March 7-9, 2018, Barcelona, Spain.

(BELG J MED ONCOL 2018:12(5):252–262)

Highlights of the Gastrointestinal Cancers Symposium 2018

With the background of the famous Golden Gate Bridge and Alcatraz, the annual Gastrointestinal Cancers Symposium was held from 18–20 January 2018 in the Moscone Congress Center in San Francisco, California. In this report, the most important headlines will be discussed, with comments on the clinical relevance of the different studies.

(BELG J MED ONCOL 2018:12(3):133–141)