Application of liquid biopsy based on circulating tumor DNA in the monitoring of pseudoprogression in tumor immunotherapy / 肿瘤研究与临床

As widely-used immunotherapy has brought therapeutic benefits to cancer patients, some problems begin to come, such as pseudoprogression which has posed a major challenge for clinicians to manage patients receiving novel drugs. If pseudoprogression is mistaken for the progression of the disease, the immunotherapy is stopped, which may lead patients to lose the treatment opportunity. Liquid biopsies based on circulating tumor DNA (ctDNA) play a key role in the evaluation of therapeutic efficacy and drug-resistance mechanism of tumor immunotherapy. This article reviews the potential application of ctDNA in the identification of pseudoprogressio for patients after tumor immunotherapy.

Clinical efficacy of immunotherapy plus target therapy in the treatment of postoperative recurrence of ruptured hepatocellular carcinoma / 中华消化外科杂志

Systemic treatment is the first choice for patients with advanced hepatocellular carcinoma. Atezolizumab combined with bevacizumab can bring better survival for patients with advanced hepatocellular carcinoma. The authors introduce the efficacy and safety management of a hepatocellular carcinoma case with postoperative recurrence who received treatment of atezoli-zumab combined with bevacizumab. The patient had a probability of pseudoprogression during treatment, and had a good result of a continuous partial response over 2 years.

Comparison of DWI based on monoexponential, biexponential and stretched-exponential models in differentiating tumor recurrence and pseudoprogression of glioblastoma / 中国医学影像技术

Objective: To investigate the value of parameters derived from monoexponential, biexponential and stretched exponential intravoxel incoherent motion (IVIM) DWI models in differentiating tumor recurrence and pseudoprogression in patients with glioblastoma. Methods: Totally 38 patients with pathologically confirmed glioblastoma after surgery, chemotherapy and radiation therapy were enrolled and divided into tumor recurrence group (n=20) and pseudoprogression group (n=18) according to follow-up or reoperation results. IVIM DWI was performed, and the parameters of monoexponential model (ADC), biexponential model (true molecular diffusion coefficient [D], pseudo-diffusion coefficient [D*], perfusion fraction [f]) and stretched exponential model (distributed diffusion coefficient [DDC], stretched index [α]) were measured and compared between the 2 groups. ROC curve was used to analyze the efficacy of these parameters in differentiating tumor progression and pseudoprogression. Results: ADC, D, DDC and α values were significantly lower in tumor recurrence group than those in pseudoprogression group, while D* and f were significantly higher than those in pseudoprogression group (all P<0.05). ROC curve analysis showed AUC of ADC, D, D*, f, DDC and α value for differentiating tumor recurrence and pseudoprogression was 0.908, 0.925, 0.804, 0.743, 0.901 and 0.961, respectively. Conclusion: Parameters derived from monoexponential, biexponential and stretched exponential IVIM models have great value in differentiating tumor recurrence from pseudoprogression in patients with glioblastoma, and α from stretched exponential model has higher efficacy.

A Case of Pseudoprogression During Atezolizumab Therapy in Lung Adenocarcinoma / 中国肺癌杂志

Lung cancer is the most common cause of cancer-related death worldwide. There are two classes of lung cancer: non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC). NSCLC represents approximately 85% of all lung cancer cases. Immune checkpoint inhibitors (ICIPs) are a class of inhibitors of programmed death-1 and programmed death-ligand 1. Preclinical studies have shown that ICIPs have shown good clinical efficacy and durable response in diverse cancers. Among them, atezolizumab (MPDL3280), an anti-PD-L1 monoclonal antibody, is being investigated as a potential therapy against solid tumors and hematologic malignancies in humans. Pseudoprogression is reported as one of the unique phenomena with immune therapeutic agents. Here we report case of a person with advanced NSCLC who developed pseudoprogression after receiving immunotherapy. We hope this case could help clinicians to make appropriate decision when assessing therapeutic effects of immunotherapy.
.

Advanced research of immune-related response evaluation criteria in solid tumors / 中国肿瘤生物治疗杂志

@# In recent years, therapy of immune checkpoint inhibitors have developed rapidly and made breakthrough, becoming the first-line treatment for many types of advanced cancer. However, due to its particular mode in activating the anti-tumor immune system, a variety of unconventional response patterns have emerged, such as delayed response and pseudoprogression, which have challenged the traditional response evaluation criteria and encouraged people to continuously explore new criteria for evaluating the unconventional response patterns under immunotherapy. This article mainly reviews the process of exploration, advanced research,as well as similarities and differencesamongvarious immune-related efficacy evaluation criteria, and finally prospects the current challenges and future trends.

Pseudoprogression and Pseudoresponse in the Management of High-Grade Glioma : Optimal Decision Timing According to the Response Assessment of the Neuro-Oncology Working Group

OBJECTIVE: We evaluated pseudoprogression (PsPD) following radiation therapy combined with concurrent temozolomide (TMZ), and we assessed pseudoresponse following anti-angiogenic therapy for patients with recurrent disease using the Response Assessment of the Neuro-Oncology Working Group. METHODS: Patients who were pathologically confirmed as having high-grade glioma received radiotherapy with concurrent TMZ followed by adjuvant TMZ. Bevacizumab (Avastin) with CPT-11 were used as a salvage option for cases of radiologic progression. Magnetic resonance imaging (MRI) was routinely performed 1 month after concurrent radiochemotherapy (CRT) and every 3 months thereafter. For cases treated with the bevacizumab-containing regimen for progressive disease, MRI was performed every 2 months. RESULTS: Of 55 patients, 21 (38%) showed radiologic progression within 4 weeks after CRT. Of these patients, 16 (29%) showed progression at second post-CRT MRI (etPD) and five (9%) showed improvement (PsPD). Seven of thirty-four initially non-progressed patients showed progression at the second post-CRT MRI (ltPD). No difference in survival was observed between the etPD and ltPD groups (p=0.595). Five (50%) of ten patients showed a radiological response after salvage bevacizumab therapy. Four of those patients exhibited rapid progression immediately after discontinuation of the drug (drug holiday). CONCLUSION: Twelve weeks following treatment could be the optimal timing to determine PsPD or true progression. MRI with gadolinium enhancement alone is not sufficient to characterize tumor response or growth. Clinical correlation with adequate follow-up duration and histopathologic validation may be helpful in discriminating PsPD from true progression.

Utilidad de 11C-metionina PET/CT en neurooncología / Utility of 11C-methionine PET/CT in neuro-oncology

La tomografía por emisión de positrones con metionina carbono 11 (11C-metionina PET/TC) se utiliza en la evaluación de los tumores primarios del sistema nervioso central. Describimos nuestra experiencia sobre los primeros 4 pacientes con tumores de la serie glial estudiados con 11C-metionina PET/TC. Este es un estudio descriptivo, observacional y prospectivo. Se presentan 4 pacientes entre 38-50 años de edad con diagnóstico de gliomas (clasificación de la OMS). A todos se les realizó RM y 11C-metionina PET/TC para evaluar actividad tumoral y diferenciar progresión tumoral de pseudoprogresión. Caso 1, gliomatosis cerebri grado II posradioterapia. Caso 2, glioblastoma grado IV postratamiento RT + temozolomida. Caso 3, oligodendroglioma grado II posradioterapia en 1993. Caso 4, oligoastrocitoma anaplásico grado III postratamiento RT + temozolomida. El patrón de captación de la 11C-metionina comparativamente con la RM, demostró progresión tumoral en los casos 1, 3 y 4; en el caso 2 mostró captación aunque el diagnóstico final fue pseudoprogresión. A diferencia del PET con 18fluordeoxiglucosa, la captación de 11C-metionina en el tejido cerebral normal y en la pseudoprogresión es baja, y los gliomas se visualizan como áreas metabólicamente activas. En los casos presentados, el 11C-metionina PET/TC proveyó información valiosa sobre el comportamiento y extensión de la lesión, aunque en uno de los casos presentados no diferenció progresión tumoral de pseudoprogresión. El 11C-metionina PET/TC sería una herramienta útil en el estudio y seguimiento de los pacientes con gliomas.

Positron emission tomography (PET) with 11C-methionine (11C-methionine PET/CT) is a new technique used to evaluate primary central nervous system (CNS) tumors. We describe our experience regarding the first 4 patients with glial tumors and 11C-methionine PET/CT. This is a descriptive, observational and prospective study of 4 patients between 38-50 years of age, with different gliomas (WHO classification). MRI and 11C-methionine PET/CT were performed in all cases. Case 1, gliomatosis cerebri grade II post-radiotherapy. Case 2, oligodendroglioma grade II diagnosed and treated with radiotherapy in 1993. Case 3, glioblastoma grade IV post-radiotherapy + temozolomide. Case 4, anaplastic oligoastrocytoma grade III post-radiotherapy + temozolomide. The pattern of 11C-methionine uptake compared with MRI showed tumor progression in cases 1, 3 and 4, and in case 2 showed uptake although the final diagnosis was pseudoprogression. Unlike 18fluordeoxiglucose PET/TC, 11C-methionine uptake in normal brain tissue and pseudoprogression is low, and gliomas are displayed as metabolically active areas. The 11C-methionine PET/CT provided valuable information on the tumoral behavior and extension, although in one case presented did not differentiate tumor progression from pseudoprogression. 11C-methionine PET/CT could be a useful tool in the study and follow-up to patients with gliomas.

True Progression versus Pseudoprogression in the Treatment of Glioblastomas: A Comparison Study of Normalized Cerebral Blood Volume and Apparent Diffusion Coefficient by Histogram Analysis

OBJECTIVE: The purpose of this study was to differentiate true progression from pseudoprogression of glioblastomas treated with concurrent chemoradiotherapy (CCRT) with temozolomide (TMZ) by using histogram analysis of apparent diffusion coefficient (ADC) and normalized cerebral blood volume (nCBV) maps. MATERIALS AND METHODS: Twenty patients with histopathologically proven glioblastoma who had received CCRT with TMZ underwent perfusion-weighted imaging and diffusion-weighted imaging (b = 0, 1000 sec/mm2). The corresponding nCBV and ADC maps for the newly visible, entirely enhancing lesions were calculated after the completion of CCRT with TMZ. Two observers independently measured the histogram parameters of the nCBV and ADC maps. The histogram parameters between the true progression group (n = 10) and the pseudoprogression group (n = 10) were compared by use of an unpaired Student's t test and subsequent multivariable stepwise logistic regression analysis to determine the best predictors for the differential diagnosis between the two groups. Receiver operating characteristic analysis was employed to determine the best cutoff values for the histogram parameters that proved to be significant predictors for differentiating true progression from pseudoprogression. Intraclass correlation coefficient was used to determine the level of inter-observer reliability for the histogram parameters. RESULTS: The 5th percentile value (C5) of the cumulative ADC histograms was a significant predictor for the differential diagnosis between true progression and pseudoprogression (p = 0.044 for observer 1; p = 0.011 for observer 2). Optimal cutoff values of 892 x 10-6 mm2/sec for observer 1 and 907 x 10-6 mm2/sec for observer 2 could help differentiate between the two groups with a sensitivity of 90% and 80%, respectively, a specificity of 90% and 80%, respectively, and an area under the curve of 0.880 and 0.840, respectively. There was no other significant differentiating parameter on the nCBV histograms. Inter-observer reliability was excellent or good for all histogram parameters (intraclass correlation coefficient range: 0.70-0.99). CONCLUSION: The C5 of the cumulative ADC histogram can be a promising parameter for the differentiation of true progression from pseudoprogression of newly visible, entirely enhancing lesions after CCRT with TMZ for glioblastomas.