Introduction and Background
It has been recognized for some time that human cancers demonstrate remarkable heterogeneity, not only between patients and tissues of origin but even between subpopulations of different cells within a single primary neoplasm or among the metastatic lesions within a single individual . As overall cancer survivorship continues to increase , and patients are exposed to more and more lines of therapy, it is inevitable that selection for aggressive phenotypes among cancer cells will occur and this can lead to seemingly contradictory progression of one or a few sites of disease in spite of an overall tumor burden response to therapy (ie, “oligoprogression”).
We have previously discussed the important role of the radiologist in defining the oligometastatic state of cancer, in which patients can harbor a small number (generally less than five) of metastases and yet may still be candidates for targeted therapy (surgical resection, ablation, cryotherapy, or radiation) and potential cure . In a similar vein, radiologists must be aware of oligoprogression as an emerging concept in modern oncology. The key distinction from oligometastases is that a patient with oligoprogression can have any number of systemic metastases, but only one or a small number are progressing, whereas the remainder are stable or responding to systemic therapy .
Multiple recent publications reviewed in this manuscript have studied the role of focal therapy for oligoprogressive lesions. Ablative radiation is the most commonly employed method in the literature for focal therapy in oligoprogression. Stereotactic radiosurgery refers to the process of using multiple radiation beams at different angles relative to an intracranial site to be treated and delivering large doses of conformal radiation in one or a few fractions . Stereotactic ablative radiotherapy (SABR) and stereotactic body radiation therapy (SBRT) both refer to a similar process that is carried out with extracranial sites of disease . The use of multiple beams generally allows the radiation oncologist to avoid undue toxicity to nearby normal tissues, although if SABR or SBRT is being considered the radiologist may wish to emphasize in the report the degree of nearness or contact between a metastatic deposit and any radiosensitive organs such as the spinal cord or bowel. Outside of ablative radiation, other modalities such as traditional fractionated radiation, radiofrequency ablation, cryotherapy, and surgery may have roles in certain circumstances.
Lung Cancer
The malignancy for which the role of focal therapy for oligoprogression has been most extensively studied is non–small cell lung cancer (NSCLC). An overarching goal of many of the studies in NSCLC has been to continue patients on otherwise effective systemic therapies, reserving later line therapies for more widespread progression . The radiologist should carefully examine NSCLC patients on systemic therapy for evidence of new, enlarging, or morphologically more suspicious sites of disease, with particular attention paid to the common areas of disease involvement such as locoregional lymph nodes, ipsilateral or contralateral lung parenchyma, adrenal glands, liver, skeletal structures, and central nervous system. Just as important as identifying the sites of progression in these patients is assuring that the progression is truly limited to one or a few sites.
Cheung has recently provided an outstanding review of oligoprogression with an emphasis on NSCLC given the preponderance of the literature. Herein are highlighted some of the findings of a subset of the studies that were also included in his review. For example, an important study involving 65 patients with anaplastic lymphoma kinase-positive or epidermal growth factor receptor (EGFR)-mutant NSCLC found that 25 of 51 patients who progressed on systemic therapy (crizotinib or erlotinib) were oligoprogressive and suitable for focal therapy with stereotactic radiosurgery, whole brain radiation therapy, SABR or SBRT, or surgery . An additional progression-free survival period of 6.2 months was achieved in a subset of patients, although those patients again progressed after focal therapy. Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1), a set of criteria that is certainly familiar to many oncology imagers, was one of the metrics by which progression could be determined.
Yu et al also looked at the role of focal therapy in oligoprogression of EGFR-mutant metastatic NSCLCs that were progressing through treatment with EGFR tyrosine kinase inhibitors . The authors excluded patients with oligoprogression confined to the brain. The determination of oligoprogression was based on routine or symptom-based imaging evaluation. The median time to further progression after focal therapy was 10 months, with a median time of 22 months before a change in systemic therapy, suggesting that the treatments targeted to the oligoprogressive sites provided substantive local control of the disease.
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Other Malignancies
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Conclusions
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