Tumor pseudoprogression (lung cancer)
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At the time the article was created Bálint Botz had no recorded disclosures.View Bálint Botz's current disclosures
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Radiologic tumor pseudoprogression on imaging denotes an imaging appearance of tumor response where the tumor first exhibits findings suggestive of progression (i.e. growth, new lesions). However, during sustained therapy, response is eventually demonstrated 1.
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With the advent of novel therapeutical approaches such as immune checkpoint inhibitors, the rate of unusual tumor responses has been growing. In non-small cell lung cancer patients treated with anti-PD1 drugs, pseudoprogression was shown in about 2-5% 1,2. Pseudoprogression is not limited to primary tumors, as metastatic lung lesions may also demonstrate it 6.
Tumor pseudoprogression is most commonly encountered while using immune checkpoint inhibitors such as anti-PD1 and anti-CTLA4 drugs. Pseudoprogression is considered the result of the tumor becoming infiltrated with activated immune cells (mainly lymphocytes), thus it is indicative of therapeutic success 2. Certain serological biomarkers, such as higher neutrophil-to-lymphocyte ratio (NLR) and decreasing circulating tumor DNA (ctDNA), were suggested to aid in diagnosing pseudoprogression 5.
Radiologic pseudoprogression is typically not accompanied by specific symptoms, with patients usually appearing clinically stable or even improving 2. Unfortunately, it has been also shown that a small subset of patients with subsequently confirmed pseudoprogression will demonstrate worsening of symptoms as well, a phenomenon termed symptomatic pseudoprogression 5.
Pseudoprogression can be considered if, after beginning targeted therapy, the early follow-up study shows growth of the target lesion(s) and, occasionally, even appearance of new lesions. In some cases, transformation of the lesions to larger ground glass opacities may occur. This is mostly, but not universally, coupled with clinical stability or improvement. Thus, the diagnosis of radiologic pseudoprogression often warrants knowledge of the clinical status of the patient. Upon subsequent continued therapy patients having radiologic pseudoprogression will show stability or regression, while those with true progression will show further lesion growth and development of new lesions 1.
Recurrent pleural or pericardial effusions are sometimes seen in patients with lung cancer pseudoprogression but, unfortunately, these features are non-specific 4.
Differentiating true progression and pseudoprogression can be challenging. In one study of non-small cell lung cancer patients treated with anti-PD1 drugs, 80% of patients who were initially suspected to have pseudoprogression were subsequently found to have true progression 1.
The Response Evaluation Criteria in Solid Tumors (RECIST), version 1.1 (RECIST 1.1), was found to be insensitive in differentiating unusual response patterns from true progression. As a consequence, a multitude of immune-related response criteria (irRC) was proposed, among which iRECIST is the most widely used. The most important key difference is that progression has to be confirmed by serial imaging and new lesions can be counted toward the overall tumor burden. However, in some recent studies, neither RECIST, irRC, nor iRECIST was found to have good accuracy of differentiating true progression and pseudoprogression 1,3.
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