REVIEW ONCOLOGY

Geriatric syndromes in oncology: what does the oncologist need to know?

SUMMARY

A ‘Geriatric Syndrome’ is characterised by its multifactorial origin. A combination of impairments leads to one specific condition that is typical for frail older patients. The rising incidence of cancer among older adults makes it interesting for the oncologist to understand common geriatric syndromes. The following geriatric syndromes are presented in this article:

Delirium: In patients with cancer, the prevalence of delirium is high. In end-stage malignant disease a prevalence near 90% has been reported. The pathophysiology is characterised by an equilibrium between predisposing and precipitating factors. The more predisposing factors, the less precipitating factors are required to develop delirium, and vice versa. Delirium is often underdiagnosed, although it leads to increased morbidity and mortality. Screening tools, such as the Confusion Assessment Method or the 4 ’A’s Test, could help the oncologist to discover delirium. Prevention and non-pharmacological therapy are the cornerstone of the approach. Pharmacological therapy is only appropriate when non-pharmacological therapy is not successful or if delirium could harm the patient.

Cognitive decline: In Belgium, the prevalence of dementia is estimated at 7.4% in adults aged 65 and over. Apart from dementia, cognitive decline in oncologic patients could also be provoked by cancer or its treatment. Cognitive decline is prognostic for overall survival in older patients with cancer. The Mini-Cog is an easy screening tool for cognitive decline, but more extensive testing, e.g. by means of a Mini Mental State Examination, can also be applied. Referral to a memory clinic should be considered, taking into account oncological diagnosis and prognosis.

Urinary incontinence: About 15 to 35% of patients older than 60 years have urinary incontinence. Urinary incontinence is associated with falls and fractures, pressure ulcers, and urinary infection. It has an emotional impact, affects quality of life and is associated with higher depression rates. In predisposed patients, precipitating factors could trigger incontinence. Prevention is of high importance and is primarily aimed at treating the precipitating factors. Pharmacological treatment blocking muscarinic receptors is associated with important side effects.

Functional decline: One third of patients receiving chemotherapy suffer from functional decline. Functional decline is prognostic for overall survival. Baseline functional assessment before initiation of treatment is important. The oncologist has to define predisposing and precipitating factors and to estimate the risk of functional decline. A multidisciplinary approach with physiotherapists, occupational therapists, nurses and social workers is warranted to achieve optimal rehabilitation.

Falls: Thirty percent of patients older than 65 years have fall incidents. Ten percent of falls lead to residual injuries. Cancer and its treatment increase the risk of falling. Bone metastases or cancer therapy can lead to more severe injuries. Falls are often preventable. Therefore, risk stratification and formulation of a multifactorial fall prevention plan by a multidisciplinary team is warranted.

(BELG J MED ONCOL 2021;15(6):270-7)

MET: another therapeutic target in non-small cell lung cancer

SUMMARY

The identification of clinically relevant driver mutations has reshaped the therapeutic landscape of non-small cell lung cancer (NSCLC). In the past year, the activation of the mesenchymal-to-epithelial transition (MET) pathway has gained importance because of the recent development of selective and effective MET inhibitors. In NSCLC, MET dysregulation may be caused either by mutation or amplification and is associated with poor prognosis. In addition, the optimal first-line treatment is currently undetermined since data from different trials suggest limited activity of immune checkpoint inhibitors, indicating a high medical need. In phase II trials, MET inhibitors have shown promising response rates (41–65%) and duration of response in MET exon 14 mutated NSCLC. First-line trials are currently ongoing. In de novo MET amplified NSCLC, the activity of these inhibitors seems limited to tumours with a high level amplification. As in other oncogene driven NSCLC, resistance mechanisms do appear ultimately and future research should focus on this in order to optimise treatment options for MET dysregulated NSCLC.

(BELG J MED ONCOL 2021;15(6):278-82)

BRCA1 and BRCA2 mutations in prostate cancer: consequences and implications

SUMMARY

BRCA mutations play an important role in prostate cancer. All patients with high-risk localised or metastatic prostate cancer should be tested for somatic mutations and, if present, for germline mutations. BRCA muta-tions translate in a more aggressive prostate cancer with a worse prognosis. If these mutations are present, PARP inhibitors may be part of the treatment strategy.

(BELG J MED ONCOL 2021;15(6):283-5)

Standard of care in 2021 for patients with ovarian cancer in Belgium

SUMMARY

Ovarian cancer is often diagnosed at an advanced stage, which is associated with worse survival outcomes and more limited therapeutic options. Over the last years, knowledge regarding the molecular features of ovarian cancer has advanced considerably, enabling the development of several options for diagnosis and treatment in a patient-tailored approach. Identification of homologous recombination deficiency (such as mutations of the BRCA1 and BRCA2 genes, or genomic instability) affecting DNA repair, has become essential in guiding treatment decisions, especially after the development of targeted agents. Therapeutic decisions take into consideration the cancer subtype, its molecular features and disease stage. Fundamental principles of good treatment for women with ovarian cancer include debulking surgery (to reduce the tumour to no residual disease whenever possible), along with appropriate systemic treatment (chemotherapy and targeted agents). To aid Belgian physicians in developing the best individual medical strategies for patients with primary and recurrent ovarian cancer, we present here standard of care applicable in Belgium, that also includes recently developed targeted agents and currently applicable reimbursement criteria.

(BELG J MED ONCOL 2021;15(6):286-91)

Genetic testing in prostate cancer in clinical practice

SUMMARY

Mutations in DNA damage repair (DDR) genes are relatively common in prostate cancer (PC), and may guide therapy selection. Approximately half of somatic DDR mutations are also present in the germline and lead to a heritable cancer predisposition syndrome (CPS), which informs on future risk, prostate cancer prognosis, and therapeutic options. In germline carriers, genetic counselling is essential to help psychosocial coping and to provide pre-symptomatic testing in relatives, who upon carrier identification can opt for intensified surveillance or – in some cases – prophylactic surgery.

(BELG J MED ONCOL 2021;15(4):156-63)

PARP inhibition and prostate cancer

SUMMARY

Deoxyribonucleic acid (DNA) recombination between homologous chromosomes is essential in the process of meiosis as it drives genetic diversity and assures accurate segregation. In somatic cells, a substantial machinery is involved in DNA damage repair (DDR). Failure to repair DNA damage has many consequences, including cancer predisposition. Insights in DDR mechanisms and the prevalence of defects in DDR in tumours has resulted in the fundamental insight of the presence of DDR defects as a chemosensitising biomarker for alkylating agents in high-grade serous ovarian cancer, non-small-cell lung cancer and glioblastoma. Increasing the DDR defect by PARP inhibition in this context of pre-existing DDR impairment, can result in catastrophic DNA damage and cancer cell death. In patients with mCRPC and demonstrated intratumoural DDR defect, PARP inhibition represents a valuable new treatment option.

(BELG J MED ONCOL 2021;15(4):164-9)

Genetic and molecular biology in pancreatobiliary cancers: Testing for pancreatobiliary cancer in the context of the Belgian NGS convention

SUMMARY

Pancreatobiliary cancers (PBC) group pancreatic and biliary tract cancers and are among the cancers with the lowest survival rate. Emerging data suggest that novel biomarker-specific targeted therapies can be proposed for selected populations with survival benefit. This review summarises the scientific evidence to test for these biomarkers in order to optimise the management of pancreatobiliary cancers, within the context of the Belgian NGS convention.

(BELG J MED ONCOL 2021;15(4):170-6)