REVIEW ONCOLOGY

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)

The androgen receptor in prostate cancer

The androgen receptor plays a role as a nuclear transcription factor after activation by its ligands. It is an essential component in the development and progression of prostate cancer. The different factors that play a role in relation to the androgen receptor and prostate cancer are discussed. The different treatment strategies in relation to prostate cancer are addressed.

(BELG J MED ONCOL 2015;9(2):61–4)

Isolated lung perfusion as additional treatment for lung metastases

The golden standard for the treatment of lung metastases remains complete surgical resection. Prognostic factors for patients with lung metastases are histology, number of metastases and disease-free interval. However, the chance of recurrent disease in the treated lung remains high after complete resection, even in combination with systemic chemotherapy. Systemic toxicity limits the dose of the latter, resulting in only limited local pulmonary control. Therefore, new techniques are developed to deliver a high-dose of chemotherapy selectively into the lung, reducing the risk of systemic toxicity. One of these techniques is isolated lung perfusion, which is comparable with isolated limb perfusion. This experimental surgical technique allows delivery of a very high-dose of chemotherapy with or without biological response modifiers to the lung, without the risk of systemic exposure. Experimental studies with this technique have shown its superiority in achieving higher tissue concentrations of chemotherapy in the target organ as well as improved survival in comparison with systemic chemotherapy. As shown in several phase I studies, this technique is technically feasible with minimal morbidity and minimal impact on pulmonary function. In a recent phase II study, an improved local pulmonary control was found in comparison with the literature. This review discusses the current status of isolated lung perfusion as well as newer, less invasive techniques to deliver high-dose chemotherapy selectively to the lung.

(BELG J MED ONCOL 2015;9(1):5–10)