Tumor Response Evaluation after Treatment and Post-treatment Surveillance of Hepatocellular Carcinoma

Hepatocellular carcinoma is one of the most prevalent malignancies and frequent causes of death worldwide. Treatment options of hepatocellular carcinoma consist of locoregional therapy, surgical resection, liver transplantation, and systemic therapy. Assessment of tumor response is required in patients receiving locoregional and systemic therapy. The Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 is widely used tumor response evaluation criteria. However, the RECIST does not reflect the extent of tumor necrosis after some locoregional therapies and molecular targeted agents. The Modified RECIST (mRECIST), which has the concept of viable tumor, was introduced in order to overcome this problem. The mRECIST were developed on the basis of RECIST version 1.1 and only tumoral tissue showing contrast uptake in arterial phase of dynamic radiologic imaging techniques was measured to assess tumor response. Recently, immune checkpoint inhibitors have emerged as a promising therapeutic modality for the treatment of hepatocellular carcinoma. To identify tumor response after immunotherapy, immune RECIST (iRECIST) has been proposed as consensusbased criteria. After achieving complete response after curative treatment, optimal surveillance was needed to detect recurrence. Individualized surveillance schedule should be considered, taking into consideration the risk factors of the patient and the risk associated with the treatment modalities.

Maximum diameter versus volumetric assessment for the response evaluation of vestibular schwannomas receiving stereotactic radiotherapy

PURPOSE: To explore the feasibility of maximum diameter as a response assessment method for vestibular schwannomas (VS) after stereotactic radiosurgery or fractionated stereotactic radiotherapy (RT), we analyzed the concordance of RT responses between maximum diameters and volumetric measurements. MATERIALS AND METHODS: Forty-two patients receiving curative stereotactic radiosurgery or fractionated stereotactic RT for VS were analyzed retrospectively. Twelve patients were excluded: 4 did not receive follow-up magnetic resonance imaging (MRI) scans and 8 had initial MRI scans with a slice thickness >3 mm. The maximum diameter, tumor volume (TV), and enhanced tumor volume (ETV) were measured in each MRI study. The percent change after RT was evaluated according to the measurement methods and their concordances were calculated with the Pearson correlation. The response classifications were determined by the assessment modalities, and their agreement was analyzed with Cohen kappa statistics. RESULTS: Median follow-up was 31.0 months (range, 3.5 to 86.5 months), and 90 follow-up MRI studies were analyzed. The percent change of maximum diameter correlated strongly with TV and ETV (r(p) = 0.85, 0.63, p = 0.000, respectively). Concordance of responses between the Response Evaluation Criteria in Solid Tumors (RECIST) using the maximum diameters and either TV or ETV were moderate (kappa = 0.58; 95% confidence interval, 0.32-0.85) or fair (kappa = 0.32; 95% confidence interval, 0.05-0.59), respectively. CONCLUSION: The percent changes in maximum diameter and the responses in RECIST were significantly concordant with those in the volumetric measurements. Therefore, the maximum diameters can be used for the response evaluation of VS following stereotactic RT.

Optimal Phase of Dynamic Computed Tomography for Reliable Size Measurement of Metastatic Neuroendocrine Tumors of the Liver: Comparison between Pre- and Post-Contrast Phases

OBJECTIVE: The reliability of size measurements of liver metastases from neuroendocrine tumors (NETs) on contrast-enhanced computed tomography (CT) phases made by different readers may be hampered due to transient, variable rim enhancement in arterial phase (AP) or portal venous phase (PVP) images. We aimed to assess the reliability of tumor size measurements in pre- and post-contrast scans. MATERIALS AND METHODS: The study coordinator selected target lesions according to Response Evaluation Criteria in Solid Tumors 1.1 guidelines in 44 consecutive patients with pathologically confirmed NET liver metastases. Two blinded readers measured the longest diameters of target lesions on pre-contrast, AP, and PVP images twice with a 4-week interval. Inter- and intra-observer agreements were evaluated using Bland-Altman plots and 95% limit of agreement (LOA) calculations. RESULTS: Of the 79 target lesions (approximate mean size of 3 cm), 45 showed rim enhancement. Inter-observer agreement assessed based on LOA was highest in pre-contrast CT images (−6.1–5.7 mm), followed by PVP (−7.9–7.1 mm) and AP (−8.5–7.4 mm) images. Intra-observer agreement showed the same trend: −2.8–2.9 mm and −2.9–2.9 mm for readers 1 and 2, respectively, on pre-contrast CT, −2.8–2.9 mm and −3.0–3.2 mm, respectively, on PVP, and −3.2–4.2 mm and −3.4–3.2 mm, respectively, on AP images. Mean tumor diameters differed significantly among the phases in the following increasing order: pre-contrast CT, PVP, and AP images. CONCLUSION: There was better inter- and intra-observer agreement in size measurements of NET liver metastases on precontrast scans than on AP and PVP scans. Pre-contrast CT may be the optimal for measuring NET liver metastases if its accuracy is proven.

Evaluation of RECIST, PERCIST, EORTC, and MDA Criteria for Assessing Treatment Response with Ga68-PSMA PET-CT in Metastatic Prostate Cancer Patient with Biochemical Progression: a Comparative Study / 대한핵의학회잡지

PURPOSE: The aim of the study was to compare response evaluation criteria in solid tumours 1.1 (RECIST 1.1), positron emission tomography response criteria in solid tumours (PERCIST), European organisation for research and treatment of cancer (EORTC), andMDAnderson (MDA) criteria for response assessment by Gallium 68-prostate-specific membrane antigen positron emission tomography-computed tomography (Ga68-PSMA PET-CT) in metastatic adenocarcinoma prostate cancer (mPCa) patients with biochemical progression.METHODS: Eighty-eight mPCa patients with pre and post treatment Ga68-PSMA PET-CTwere included. A ≥ 25% increase and ≥ 2 ng/ml above the nadir if prostate specific antigen (PSA) drop or ≥ 2 ng/ml above the baseline if PSA does not drop was considered as biochemical progression. RECIST 1.1 and MDA criteria for morphology and PERCIST and EORTC criteria for molecular response were investigated. Percentages of progressive disease (PD), partial response (PR), and stable disease (SD) were calculated. Chi-square test was used for statistical significance.RESULTS: Proportion of PD, SD, and PR by RECIST 1.1 and MDA criteria were 44 (50.57%), 39 (44.83%), 4 (4.6%), and 33 (39.76%), 48 (57.83%), 2 (2.41%) respectively. Proportion of PD, SD, and PR by PERCIST and EORTC criteria were 71 (80.68%), 11 (12.50%), 6 (6.82%), and 74 (84.09%), 8 (9.09%), 6 (6.82%) respectively. Chi-square test showed statistically significant (P < 0.05) higher proportion of progression detected by both molecular criteria as compare to both morphological criteria.CONCLUSION: We concluded that for Ga68-PSMA PET-CT response evaluation, molecular criteria performed better than morphological criteria in mPCa patient with PSA progression.

18F-FDG PET/CT imaging in the monitoring of response to sorafenib in patients with radioiodine- refractory differentiated thyroid cancer / 中国癌症杂志

Background and purpose:The evaluation of treatment response is one of the most important building blocks in determining the best strategy for the management of malignant tumors. In lymphoma and several solid cancer types, PET/CT-based response evaluation has been shown to be valuable, especially in visualizing the effect of the targeted treatment, which induces tumor activity changes not necessarily followed by tumor shrinkage. This study aimed to evaluate the role of18F-FDG PET/CT in the monitoring of response to sorafenib treatment in radioiodine-refractory differentiated thyroid cancer (RR-DTC) patients; and to compare the Response Evaluation Criteria in Solid Tumors (RECIST 1.1) with the European Organization for Research and Treatment of Cancer (EORTC) criteria.Methods:This was a single-center retrospective analysis of 14 patients with RR-DTC treated with sorafenib in the period from Dec. 2011 to Dec. 2014. A Wilcoxon signed-rank sum test was used to assess the differences in percentage changes between the sum of diameter and ∑SUVmax. These values of responses were statistically compared using the chi-square test (Fisher’s exact test). The differences in PFS between response categories according to either RECIST 1.1 or the EORTC criteria were evaluated using the Wilcoxon signed-rank sum test. The Spearman rank correlation coefficient was estimated between PFS and either morphologic (RECIST 1.1) or metabolic response (EORTC criteria) categories.Results:There was an agreement between the RECIST 1.1 and EORTC criteria in 10 of the 14 patients (χ2=2.345,P=0.424). The remaining 4 patients with SD in-cluded 2 patients with PMR and 2 patients with PMD. Differences in PFS among different response categories according to either RECIST 1.1 (χ2=8.571,P=0.003) or EORTC criteria (χ2=8.781,P=0.003) were statistically significant. Correlations were found between PFS and either morphologic (r=0.741,P=0.002) or metabolic (r=0.816,P=0.0004) response criteria. Conclusion:18F-FDG PET/CT imaging is of value in the monitoring of response to sorafenib in patients with RR-DTC. Although RECIST 1.1 and EORTC criteria agree in 71.4% patients, PET-based metabolic response criteria seems to be more accurate in predicting therapeutic outcome and may be more suitable than morphologic response criteria for the eval-uation of response to targeted therapy.

Correlation of clinico-pathologic and radiologic parameters of response to neoadjuvant chemotherapy in breast cancer.

CONTEXT: As of today, there is no validated standard method to assess clinical response of breast cancer to neo- adjuvant chemotherapy (NACT). Some centers use clinical dimensions while others use radiological measurements to evaluate response according to RECIST criteria. AIMS: The aim was to correlate and compare the clinical, radiological, and pathological parameters for assessing the tumor response in patients of breast cancer receiving NACT. SETTINGS AND DESIGN: Single institution, prospective nonrandomized study conducted over a 2-year period. MATERIALS AND METHODS: Patients with diagnosed breast cancer were assessed for response to NACT prior to surgery using clinical and radiological techniques. This was correlated with pathological reponse which was assessed by measuring gross dimensions and Miller-Payne grading of response to chemotherapy. STATISTICAL ANALYSIS USED: Spearman’s rho nonparametric. RESULTS: Fifty two patients completed the evaluation (out of 313 cases of ca breast treated during the same period) with a median age of 52.5 years. We noted a 26.9% clinical complete response (CR) and 19.2% had pathological CR. Clinical evaluation had a sensitivity and specificity of 73.5% and 88.5% respectively compared to 14.2% and 100% respectively for radiological assessment. CONCLUSIONS: Clinical assessment of response to NACT shows a higher sensitivity compared to radiological assessment. However the overall low sensitivity and specificity rates of clinical assessment mandate a search for a better method of evaluation.

Prediction of response by FDG PET early during concurrent chemoradiotherapy for locally advanced non-small cell lung cancer

PURPOSE: To evaluate the predictive value of the early response of 18F-flurodeoxyglucose positron emission tomography (FDG PET) during concurrent chemoradiotherapy (CCRT) for locally advanced non-small cell lung cancer (NSCLC). MATERIALS AND METHODS: FDG PET was performed before and during CCRT for 13 NSCLC patients. Maximum standardized uptake value (SUVmax), mean standardized uptake value (SUVmean), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) were measured and the changes were calculated. These early metabolic changes were compared with the standard tumor response by computed tomograms (CT) one month after CCRT. RESULTS: One month after the completion of CCRT, 9 patients had partial response (PR) of tumor and 4 patients had stable disease. The percent changes of SUVmax (%DeltaSUVmax) were larger in responder group than in non-responder group (55.7% +/- 15.6% vs. 23.1% +/- 19.0%, p = 0.01). The percent changes of SUVmean (%DeltaSUVmean) were also larger in responder group than in non-responder group (54.4% +/- 15.9% vs. 22.3% +/- 23.0%, p = 0.01). The percent changes of MTV (%DeltaMTV) or TLG (%DeltaTLG) had no correlation with the tumor response after treatment. All the 7 patients (100%) with %DeltaSUVmax > or = 50% had PR, but only 2 out of 6 patients (33%) with %DeltaSUVmax or = 50% had PR, but only 3 out of 7 patients (43%) with %DeltaSUVmean < 50% had PR after CCRT (p = 0.026). CONCLUSION: The degree of metabolic changes measured by PET-CT during CCRT was predictive for NSCLC tumor response after CCRT.

Buscando una curva general de respuesta a la quimioterapia basada en la evaluación radiológica con criterio RECIST / Looking for a general response curve to chemotherapy based on radiological evaluation with RECIST criteria

Radiological evaluation of response to chemotherapy can be carried out by applying the RECIST (Response Evaluation Criteria in Solid Tumors) criteria, currently considered the most objective method for monitoring lesions. Aimed at finding a general response curve, 21 patients with lung and kidney tumors, as well as colorectal carcinoma were studied between 2006 and 2008. Statistical proceedings included variance (ANOVA), co-variance (ANCOVA) and logarithmic regression analysis. Target-lesion size reduction, duration of response and overall response of different types of tumors did not differ significantly A general response curve was obtained: log (RR)= 1,897-0,0281, where RRt is the relative RECIST count, and t is time (expressed in months). As an expected outcome -because of variety of drugs, type of tumors and variability rates in individual response- the determination coefficient in regression was 10.9 percent. However, it constitutes a first approach to solid tumors response and proves the accuracy and usefulness of RECIST methodology.

La evaluación radiológica de respuesta a la quimioterapia se puede hacer con el criterio RECIST, considerado actualmente el método más objetivo de seguimiento de lesiones. Con el objetivo de buscar una curva general de respuesta, entre los años 2006 y 2008 estudiamos 21 pacientes con tumores pulmonares, renales y cáncer colo-rectal. La estadística consistió en análisis de varianza (ANOVA), covarianza (ANCOVA) y regresión logarítmica. La reducción en tamaño y el tiempo de respuesta no difirieron significativamente, así como tampoco la respuesta global de los diferentes cánceres. Se obtuvo una curva general de respuesta: log (RR)= 1,897 -0,028 t, (RR= evaluación RECIST actual dividida por inicial y t= tiempo en meses). El coeficiente de determinación de la regresión fue 10,9 por ciento, esperable por la diversidad de fármacos, tipo de tumor y respuesta individual; sin embargo constituye una primera aproximación a la respuesta esperada mostrando la utilidad y objetividad del método.

RECIST Criteria for Tumor Response in the Patients with Breast Cancer Who Had Neoadjuvant Chemotherapy

PURPOSE: This study compared the response evaluation using the WHO (World Health Organization) criteria for patients with breast cancer with that of the RECIST (Response Evaluation Criteria In Solid Tumor) criteria in order to determine the significance of the RECIST criteria in breast cancer. METHODS: Between 2001 and 2005, 42 patients with measurable lesions radiologically receiving neoadjuvant chemotherapy for a breast carcinoma were enrolled in this study. The results were compared using a kappa test as a concordance measure between the two response criteria. RESULTS: With the WHO criteria, the overall response and progression rate were 35.7% (CR 0, PR 15) and 16.6% (PD 7) respectively. On the other hand, the overall response and progression rate using the RECIST criteria were 38.0% (CR 0, PR 16) and 7% (PD 3) respectively. The kappa value as a concordance measure between two response criteria was 0.718. CONCLUSION: The RECIST criteria are comparable to the WHO criteria in evaluating the response of breast cancer patients who have undergone neoadjuvant chemotherapy. A comparison of these results with other studies of more common tumor types supports the implementation of RECIST as the standard criteria for evaluating the treatment response but also for monitoring progression.

Comparison of WHO and RECIST Criteria for Response in Metastatic Colorectal Carcinoma / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: This study compared the WHO criteria with the response evaluation criteria in solid tumors (RECIST) in the same patients with metastatic colorectal cancer in order to determine the significance of the RECIST. In addition, this study compared the estimations of medical oncologists with those of a radiologist. MATERIALS AND METHODS: Between 2002 and 2005, a total of 48 patients (male: female ratio, 29: 19; median age, 58 years) with measurable lesions receiving chemotherapy for metastatic colorectal carcinoma were enrolled in this study. Two medical oncologists and one radiologist, who were blinded to the patients' condition, independently reviewed all the CT images. The results were compared using a kappa test. RESULTS: The kappa test for concordance between the WHO and RECIST criteria of the medical oncologists and the radiologist were 0.908 and 0.841, respectively. The level of concordance between the investigators using the WHO and RECIST were 0.722 and 0.753, respectively. CONCLUSIONS: The RECIST criteria are comparable to the WHO criteria in evaluating the response of colorectal carcinoma, but have simple and reproducible guidelines. The use of RECIST is recommended for evaluating the treatment efficacy in clinical trials and practice.