Estimating the Prevalence of a True Oligometastatic Disease.

To delineate a patient group with few distant metastases that could possibly benefit from a curative therapeutic strategy employing a local approach, the term oligometastatic disease (OMD) was introduced into the clinical practice almost 30 years ago [...]

Oligometastatic Disease Management: Finding the Sweet Spot.

Hematogenous dissemination represents a common manifestation of squamous cell carcinoma of the head and neck, and the recommended therapeutic options usually consist of systemically administered drugs with palliative intent. However, mounting evidence suggests that patients with few and slowly progressive distant lesions of small size may benefit from various local ablation techniques, which have already been established as standard-of-care modalities for example in colorectal and renal cell carcinomas and in sarcomas. In principle, serving as radical approaches to eradicate cancer, these interventions can be curative. Their impact on local control and overall survival has been shown in numerous retrospective and prospective studies. The term oligometastatic refers to the number of distant lesions which should generally not surpass five in total, ideally in one organ. Currently, surgical resection remains the method of choice supported by the majority of published data. More recently, stereotactic (ablative) body radiotherapy (SABR/SBRT) has emerged as a viable alternative. In cases technically amenable to such local interventions, several other clinical variables need to be taken into account also, including patient-related factors (general health status, patient preferences, socioeconomic background) and disease-related factors (primary tumor site, growth kinetics, synchronous or metachronous metastases). In head and neck cancer, patients presenting with late development of slowly progressive oligometastatic lesions in the lungs secondary to human papillomavirus (HPV)-positive oropharyngeal cancer are the ideal candidates for metastasectomy or other local therapies. However, literature data are still limited to say whether there are other subgroups benefiting from this approach. One of the plausible explanations is that radiological follow-up after primary curative therapy is usually not recommended because its impact on survival has not been unequivocal, which is also due to the rarity of oligometastatic manifestations in this disease. At the same time, aggressive treatment of synchronous metastases early in the disease course should be weighed against the risk of futile interventions in a disease with already multimetastatic microscopic dissemination. Therefore, attentive treatment sequencing, meticulous appraisal of cancer extension, refinement of post-treatment surveillance, and understanding of tumor biology and kinetics are crucial in the management of oligometastases

Change Is in the Air: The Hypoxic Induction of Phenotype Switching in Melanoma

Melanoma cells can switch from a highly proliferative, less invasive state to a highly invasive, less proliferative state, a phenomenon termed phenotype switching. This results in a highly heterogenous tumor, where a slow-growing, aggressive population of cells may resist tumor therapy, and it predicts tumor recurrence. Here we discuss the observation made by Widmer et al. that hypoxia may drive phenotype switching

PIK3CA mutations, phosphatase and tensin homolog, human epidermal growth factor receptor 2, and insulin-like growth factor 1 receptor and adjuvant tamoxifen resistance in postmenopausal breast cancer patients

Introduction: Inhibitors of the phosphatidylinositol-3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/AKT/mTOR) pathway can overcome endocrine resistance in estrogen receptor (ER) α-positive breast cancer, but companion diagnostics indicating PI3K/AKT/mTOR activation and consequently endocrine resistance are lacking. PIK3CA mutations frequently occur in ERα-positive breast cancer and result in PI3K/AKT/mTOR activation in vitro. Nevertheless, the prognostic and treatment-predictive value of these mutations in ERα-positive breast cancer is contradictive. We tested the clinical validity of PIK3CA mutations and other canonic pathway drivers to predict intrinsic resistance to adjuvant tamoxifen. In addition, we tested the association between these drivers and downstream activated proteins.Methods: Primary tumors from 563 ERα-positive postmenopausal patients, randomized between adjuvant tamoxifen (1 to 3 years) versus observation were recollected. PIK3CA hotspot mutations in exon 9 and exon 20 were assessed with Sequenom Mass Spectometry. Immunohistochemistry was performed for human epidermal growth factor receptor 2 (HER2), phosphatase and tensin homolog (PTEN), and insulin-like growth factor 1 receptor (IGF-1R). We tested the association between these molecular alterations and downstream activated proteins (like phospho-protein kinase B (p-AKT), phospho-mammalian target of rapamycin (p-mTOR), p-ERK1/2, and p-p70S6K). Recurrence-free interval improvement with tamoxifen versus control was assessed according to the presence or absence of canonic pathway drivers, by using Cox proportional hazard models, including a test for interaction.Results: PIK3CA mutations (both exon 9 and exon 20) were associated with low tumor grade. An enrichment of PIK3CA exon 20 mutations was observed in progesterone receptor- positive tumors. PIK3CA exon 20 mutations were not associated with downstream-activated proteins. No significant interaction between PIK3CA mutations or any of the other canonic pathway drivers and tamoxifen-treatment benefit was found.Conclusion: PIK3CA mutations do not have clinical validity to predict intrinsic resistance to adjuvant tamoxifen and may therefore be unsuitable as companion diagnostic for PI3K/AKT/mTOR inhibitors in ERα- positive, postmenopausal, early breast cancer patients