JAMA Oncol: Superprogressia in nSCLC immunotherapy for advanced non-small cell lung cancer.

The study reported that rapid growth in tumor attack, known as hyperprogression (HPD), may occur during the application of PD-1/PD-L1 single-drug immunotherapy.
, however, to date, there is no definition of the HPD consensus.
a study published in JAMA Oncology,
, to assess the accuracy of each previous HPD definition to determine the incidence of HPD in patients with advanced non-small cell lung cancer (NSCLC) under different HPD definitions and the correlation with adverse outcomes of immunocheckpoint inhibitors (ICI) treatments, and to provide an optimized, consistent and consistent definition of HPD on top of all previous HPD criteria. The
Methods retrospective analysis of data from 406 patients with Stage III or Phase IV IV NSCLC treated with PD-1/PD-L1 inhibitors in eight French institutions between November 1, 2012 and April 5, 2017, most of whom have received other treatments.
the reCIST 1.1 standard is defined to measure lesions and evaluate efficacy, at least 2 CT scans before starting ICI treatment, and at least 1 CT scan during treatment to evaluate dynamic indicators.
a baseline CT scan within 6 weeks prior to the start of ICI treatment, at least 2 weeks between the two different CtTs used for evaluation, 60 days between the baseline and the baseline CT scan, and 62 days from baseline to subsequent CT scan, resulting in an analysis of data from November 1, 2012 to August 1, 2019.
define the incidence of HPD under different definitions, the relationship between each HPD and the total survival rate.
calculate all the dynamics used in previous definitions, such as tumor growth rate (TGR) or tumor growth dynamics (TGK) before and during treatment.
previous studies, there are five different standard definitions for HPD, as shown in Table 1.
Champiat et al. (defined A) definehped HPD as at least twice as much as during treatment (exp) TGR (TGR-exp: TGR-ref 2), in other words, the percentage of tumor volume increased more than twice the previous percentage during immunotherapy.
Kato et al. (definition B) defined HPD in three cases: tumor dynamics (2x progression rate), RECIST percentage (50% increase in tumor load during ICIs treatment) and duration of treatment (2 months of treatment failure).
Saada-Bouzid and others (defining C) define HPD son-in-law on TGK, but TGK does not use tumor diameter rather than volume, based on the assumption of natural exponential growth in tumors.
Singavi and others (definition D) define HPD by defining A and a 50% increase in tumor volume.
Ferrara et al. (defined E) define HPD as a 50% increase in tumor volume per month during ICI treatment than expected prior to treatment. in order to study the relationship between HPD and survival outcomes,
classified patients with disease progression (PD) as HPD and non-HPD patients.
total survival time is defined as the time from the start of ICI therapy to the time of death of a patient for any reason. the time
treatment failure is defined as the duration of termination of treatment from the beginning to termination for any reason, including toxic side effects, disease progression, patient selection, or death.
use the Kaplan-Meier method for survival analysis and compare it with log rank tests.
two-sided P 0.05 is considered statistically significant.
results were 5.4% to 18.5% of HPD sized under different definitions in 406 patients with non-small cell lung cancer (259 in men; 64 at the start of ICI treatment), between 33.3% and 69.3% in different definitions, and for each definition, HPD and lower survival survival Rate correlation (median total survival rate range, 3.4 to 6.0 months (95% CI, 3.7-9.4), differences in TGR before and during treatment (TGR) and overall survival differences were the greatest, and it had the highest ability to distinguish HPD patients from patients with progressive diseases not classified as HPD.
, the study also identified an optimal threshold, the TGR 100.
N-1, i.e. up to 1 patient is HPD, N-2, up to 2 patients are HPD, and so on.
when n-values are compared to hours, only a small number of patients may be assessed as HPD, and this part of the patient should have a significantly shorter survival time than non-HPD PD patients.
when the N-value is large, more patients are evaluated as HPD, meaning that the total survival time of the HPD patient group should be close to that of the non-HPD patient group.
a good indicator should be more spaced between the two curves when the N value is small, and the longer the gap between the two curves, the better the indicator can distinguish between HPD patients and non-HPD patients.
the TGR-exp/TGR-ref curve, and the TGK-exp/TGK-ref curve, which looks similar, showing an initial platform period before 20 patients, but then the median total survival time rose sharply, even surpassing The PD patient when N is large enough. The
TGR curve still shows the initial platform period when N reaches 40 to 50, and the growth is slow, confirming a stronger correlation with total survival.
in order to confirm the correlation between the three indicators and the prognosis of HPD/non-HPD patients, the log-rank test of different indicators and different thresholds n was further studied.
all three indicators reached the statistical difference of P 0.05 when N was smaller.
However, when N is large, only the P value of the TGR is still 0.05, while the other two indicators fluctuate around 0.05.
discussion and summary studies have shown that the incidence of HPD in immunotherapy is about 4% to 29%.
the reasons for this difference may include the diversity of cancer histology and the scale and source of cohort studies.
However, indicators used to assess HPD may also be the main cause of inconsistencies in incidence.
the study is the first to make a detailed analysis and comparison of all definitions used so far to evaluate HPD.
studies show that hpD incidence is highly inconsistent due to the definition itself, and that hpD incidence varies widely based on previous HPD definitions, and these definitions are not associated with total survival rates.
indicator, TGR, seems likely to distinguish between patients with rapid progress and poor prognosis.
the study developed a new standard that defines HPD as a 20% increase in THE percentage of RECIST, and a tGR 100, which will require additional research into a larger patient population in the future to confirm the accuracy and effectiveness of the definition.
the study has some limitations.
first, HPD was initially evaluated in people with mixed tumors or patients with head and neck squamous cell carcinoma, and the study only included Patients with NSCLC, and it was necessary to study more patients with different characteristics.
second, in general, the characteristics of HPD are still difficult to determine because of the need for two imaging tests prior to treatment.
, all definitions of HPD are based on the measurement of target lesions in accordance with the RECIST 1.1 standard and therefore do not explain the definite progression of non-target lesions or new lesions.
this bias and the artificial exclusion of patients who died before the necessary imaging tests were performed after treatment, making it impossible to associate death with HPD, may lead to an underestimation of the HPD phenomenon.
Li Mingjun, Deputy Director Physician, Ph.D., Deputy Director of Oncology Department, First Affiliated Hospital, Zhengzhou University, Ph.D., JCO Lung Cancer Special Issue Chinese Edition Editorial Committee, Member of the Oncology Immunotherapy Committee of the Chinese Medical Education Association, Member of the Precision Medical Branch of the Chinese Society of Gerontology and Gerontology, Director of the Lung Cancer Branch of Henan Respiratory and Critical Illness Society Member, Deputy Chairman of the Youth Committee of the Professional Committee on Clinical Precision Diagnosis and Treatment of Cancer Oftinals of Henan Province Anti-Cancer Association, Standing Member of the Precision Medical Branch of Henan Respiratory and Critical Illness Society, Standing Member of the Youth Committee of the Henan Cancer Association's Lung Cancer Professional Committee, Standing Committee of the Henan Anti-Cancer Association's Targeted Treatment Professional Committee, and Standing Committee of the Anti-Cancer Association of Henan Province.
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