REVIEW ONCOLOGY

Highlights in oncology 2015

Summary

This article is based on the 2016 clinical cancer advances article, published by the American Society of Clinical Oncology, and reviews the most important advances made in the different fields of oncology that are most likely to impact daily clinical practice.¹

(BELG J MED ONCOL 2016;10(2):49–57)

Early triple negative breast cancer in clinical practice

Summary

Up to 20% of breast cancers lack receptors for estradiol, progesterone and human epidermal growth factor receptor 2, triple negative breast cancer. Negativity for these receptors is not completely nor consistently defined. ImmunoHistoChemical/In Situ Hybridisation determined triple negative breast cancer is strong but incomplete compared to the molecular intrinsic basal like subtypes one and two, but also includes non-basal like subtypes. Most triple negative breast cancers are of the histological IDC-NOS type. Triple negative breast cancer in general has unfavourable clinical and prognostic characteristics and is most frequently diagnosed in young women and women with (germline) mutations in BRCA1. Therefore, triple negativity may be an indication for genetic testing of germline BRCA mutations. Lymphocytic infiltration of triple negative breast cancer correlates with a less detrimental prognosis. Triple negative breast cancers often lack mammographic micro calcifications.

Regardless of type of primary surgical treatment, patients with triple negative breast cancer are more at risk for local/regional recurrence than other types. But there is no reason for local/regional treatment or indications for (neo) adjuvant systemic therapy beyond accepted guidelines for breast cancer in general. The mainstay of (neo) adjuvant medical treatment of early triple negative breast cancer is combination (sequential) chemotherapy with anthracyclines and taxanes. Alternatives are pegylated liposomal doxorubicin or classical cyclophosphamide, methotrexate 5-fluorouracil. In triple negative breast cancer with BRCAness, platinums may replace taxanes in neoadjuvant treatment to optimise the pathologic complete response rate. Several targeted therapies proved to be effective in metastatic triple negative breast cancer, but to date there are no such validated treatments for early disease. Besides targeted therapies, immune modulatory strategies for well characterised immunogenic triple negative tumours (i.e. with different grades of lymphocytic infiltration) are promising.

(BELG J MED ONCOL 2016;10(1):7–14)

Systemic treatment for basal cell carcinoma of the skin

(BELG J MED ONCOL 2015;9(7):265–71)

Clinical application of targeted next generation sequencing for lung cancer patients

Summary

The successes of targeted agents in patients with molecularly defined tumours and improvements in genomic technology have generated enthusiasm for incorporating genomic profiling into clinical cancer practice and molecular testing has now become a standard of care for lung cancer. International guidelines recommend testing for EGFR mutations and ALK gene rearrangement to guide patient selection for therapy. However, different potentially targetable oncogenes, such as KRAS, PIK3CA, BRAF, ERBB2 or MET, for which agents are being evaluated, have been proposed as valuable for managing patients with lung cancer. Recently, the development of next generation sequencing has enabled simultaneous detection of many clinically relevant mutations in different genes in a single test. In this study, we have evaluated the clinical utility of targeted next generation sequencing, using a 22 genes panel, for patients with lung cancer on 234 samples, including cytology, biopsies and surgical resections, from two different institutions tested in routine daily practice since validation and accreditation of the method (BELAC ISO15189). On the 234 samples tested, only one case could not be sequenced due to an insufficient quantity of available tissue. Among the 233 cases tested, 223 (95.7%) samples were sequenced successfully. The median turnaround time between reception of the sample in the laboratory and report release was one week. The most frequent mutations were found in TP53 (42.1%) and KRAS (35.9%). Of successfully sequenced cases, 137 potentially actionable mutations were identified in 130 patients (58.3%), including 80 KRAS mutations, 26 EGFR mutations, fourteen BRAF mutations, eight PIK3CA mutations, three PTEN mutations, two ERBB2 insertions, two NRAS mutations and two MAP2K1 mutations. Overall, next generation sequencing can be applied in daily practice even for small samples, such as lung biopsies or cell blocks. Moreover, it provides clinically relevant information for lung cancer patients.

(BELG J MED ONCOL 2015;9(7):272–78)

Targeted therapy for the treatment of head and neck squamous cell carcinomas: hopes and pitfalls

Targeted therapy is a promising strategy for the treatment of head and neck squamous cell carcinoma and other cancers, which has been developed as a result of breakthroughs in molecular characterisation of carcinogenesis. It is thought to offer a higher therapeutic index and, therefore, to be associated with less toxicity than cytotoxic drugs. Unfortunately this kind of therapy also has weaknesses; in particular the long-term response rate is disappointing. This review will not only focus on the benefits of EGFR targeted agents in head and neck squamous cell carcinoma, but will also summarise its weaknesses.

(BELG J MED ONCOL 2015;9(5):175–78)

Heavy particle radiotherapy

Heavy ion therapy is an emerging technique in radiotherapy. It provides highly conformal dose distributions compared to those currently used with photons. These superior beam properties allow increasing the target dose without enhancing the dose to critical structures and/or offer the possibility to reduce the dose to critical structures without compromising the dose to the target. Proton therapy infrastructure is being implemented and carbon or other ion therapy, which, in addition to its physical conformity is also biologically very attractive, has become available as well.

(BELG J MED ONCOL 2015;9(3):87–94)

Thrombo-embolic events in cancer patients with impaired renal function

Venous thromboembolism is a frequent cause of mortality and morbidity in patients with malignancy. Thrombosis is one of the leading causes of death in patients with malignancy after cancer itself. As such, prompt recognition and treatment of venous thromboembolism are required in order to reduce the risk of venous thromboembolism-related mortality. This report reviews the interrelationship between cancer, renal insufficiency and venous thromboembolism. The working group behind this review article concludes that low molecular weight heparins decrease the risk of recurrent venous thrombosis in cancer patients without increasing major bleeding complications. Low molecular weight heparins are therefore recommended as first line antithrombotic treatment in cancer patients with a clear clinical benefit. In patients with renal dysfunction, who are at increased risk of bleeding and of thrombotic complications, preference should be given to unfractionated heparin or a low molecular weight heparin with a mean molecular weight such as tinzaparin, having less risk of plasma accumulation and offering the possibility to maintain full therapeutic dose.

(BELG J MED ONCOL 2015;9(2):53–60)