Objective: Update the last known review, and summarize the definitions, diagnostic criteria, reported risk factors, possible mechanisms and potential biomarkers of hyperprogressive disease (HPD) under immunotherapy.Background: Immunotherapy is a relatively new systemic therapy adding a new method of treatment of especially advanced cancer patients. In a variety of immunotherapies, however, an unexpected acceleration of tumor growth, known as HPD, is observed in approximately 30% of patients after immune checkpoint inhibitor (ICI) treatment. HPD has a deleterious survival effect on patients and represents an urgent issue for both clinicians and patients. Existing literature has reviewed and summarized the definition, diagnostic criteria, reported risk factors and possible mechanisms of hyperprogression. However, with the gradual deepening of the exploration of HPD, researchers have made significant breakthroughs in elucidating the mechanism and mechanism of HPD and exploring biomarkers.
Methods:The search was conducted on Google Scholar and PubMed in January and May of 2021. We searched among English papers with no limitation on the publication year. We have included retrospective studies, case reports and basic researches related to HPD in the collection, we also referred to some review articles on HPD in recent years. A qualitative-interpretive approach was used for data extraction.Conclusions: HPD is considered to be an acceleration of tumor growth after ICI treatment that is not only due to immune infiltration but also due to real disease progression, with an incidence of about 4-30% in all retrospective published studies to date. Currently, the most widely used criteria of HPD contain Response Evaluation Criteria in Solid Tumors (RECIST) and tumor growth rate (TGR) or tumor growth kinetics.The common risk factors and underlying mechanisms of HPD have not yet been fully elucidated. However, based on the poor prognosis of HPD, there have been many advances in the exploration of biomarkers in recent years, like the prediction of HPD, such as LDH levels of peripheral blood, liquid biopsy, and radiomics, etc.
Pseudomonas plecoglossicida is an aerobic Gram-negative bacterium, which is the pathogen of “Visceral white spot disease” in large yellow croaker. P. plecoglossicida is a temperature-dependent bacterial pathogen in fish, which not only reduces the yield of large yellow croaker but also causes continuous transmission of the disease, seriously endangering the healthy development of fisheries. In this study, a mutant strain of fusA was constructed using homologous recombination technology. The results showed that knockout of P. plecoglossicida fusA significantly affected the ability of growth, adhesion, and biofilm formation. Temperature, pH, H2O2, heavy metals, and the iron-chelating agent were used to treat the wild type of P. plecoglossicida; the results showed that the expression of fusA was significantly reduced at 4°C, 12°C, and 37°C. The expression of fusA was significantly increased at pH 4 and 5. Cu2+ has a significant inducing effect on the expression of fusA, but Pb2+ has no obvious effect; the expression of fusA was significantly upregulated under different concentrations of H2O2. The expression of the fusA gene was significantly upregulated in the 0.5~4-μmol/l iron-chelating agent. The expression level of the fusA gene was significantly upregulated after the logarithmic phase. It was suggested that fusA included in the TBDR family not only was involved in the transport of ferredoxin but also played important roles in the pathogenicity and environment adaptation of P. plecoglossicida.
Background
Previous studies have shown that monotherapy with apatinib, an oral tyrosine kinase inhibitor, has promising efficacy for treating recurrent or metastatic (RM) nasopharyngeal carcinoma (NPC) patients. In this study, we aimed to assess the efficacy and safety of apatinib combined with capecitabine as a second-line therapy or beyond for treating RM-NPC patients who failed the first-line platinum-based chemotherapy.
Methods
In this single-arm, phase II study, we enrolled RM-NPC patients who had at least one measurable lesion according to the Response Evaluation Criteria in Solid Tumors (RECIST v1.1). The sample size was determined using Simon’s two-stage design. All patients were administered with apatinib 500 mg once daily and capecitabine 1000 mg/m2 twice per day on days 1–14 of each 21-day cycle. The primary endpoint was the objective response rate (ORR), and the secondary endpoints comprised disease control rate (DCR), duration of response (DoR), progression-free survival (PFS), overall survival (OS), and safety.
Results
We enrolled 64 patients from September 2018 to August 2020. The ORR and DCR were 39.1% (95% CI, 27.1–52.1) and 85.9% (95% CI, 75.0–93.4), respectively. The median DoR was 14.4 months (95% CI, 7.8–21.0). As of April 20, 2021, the median follow-up duration was 12.0 months. The median PFS was 7.5 months (95% CI, 5.0–10.0) and the median OS was 15.7 months (95% CI, 11.3–20.1). The most common toxicities of any grade were anemia (75.0%), hand-foot syndrome (65.6%), and proteinuria (64.0%). Grade 3–4 toxicities were observed in 36 (56.3%) patients, with hypertension (14.1%), mucositis (12.4%), and fatigue (10.9%) most commonly observed.
Conclusions
Apatinib plus capecitabine shows promising efficacy as a second-line treatment option in pretreated platinum-refractory RM-NPC patients. Dose selection of this combination needs further investigation considering the toxicity.
Trial registration
Chi-CTR1800017229.
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