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Keywords:

  • hepatocellular carcinoma;
  • sorafenib;
  • drug evaluation;
  • computed tomography scanners;
  • angiogenesis inhibitors

Abstract

  1. Top of page
  2. Abstract
  3. MATERIALS AND METHODS
  4. RESULTS
  5. DISCUSSION
  6. FUNDING SOURCES
  7. CONFLICT OF INTEREST DISCLOSURES
  8. REFERENCES

BACKGROUND:

A significant improvement in overall survival (OS) was demonstrated in patients with advanced hepatocellular carcinoma (HCC) who received sorafenib (Sor) in the Sorafenib HCC Assessment Randomized Protocol (SHARP) study, in contrast to a response rate (RR) of 2% assessed according to Response Evaluation Criteria in Solid Tumors (RECIST). Modified RECIST (mRECIST) were developed to assess the response in patients with HCC, based on measurement of viable tumor with arterial enhancement on a computed tomography (CT) scan. In the current study, mRECIST were evaluated and were compared with RECIST in patients who received Sor for advanced HCC.

METHODS:

The authors retrospectively analyzed 53 patients who received Sor for advanced HCC. Patients must to have undergone a 4-phase CT scan before treatment and repeatedly thereafter. CT scans were analyzed using RECIST 1.1 and mRECIST.

RESULTS:

The rates of objective response (OR), stable disease (SD), and progressive disease (PD) were 2%, 79%, and 19%, respectively, according to RECIST and 23%, 57%, and 21%, respectively, according to mRECIST (P < .001). Patients who achieved an OR according to mRECIST had a longer OS than nonresponding patients with SD or PD (median OS, 18 months and 8 months, respectively; P = .013). In the 42 patients who achieved SD according to RECIST, OS differed depending on tumor response according to mRECIST, with a median OS of 17 months, 10 months, and 4 months for patients who achieved an OR (n = 11), SD (n = 29), and PD (n = 2), respectively (P = .016).

CONCLUSIONS:

The current series validated mRECIST in patients who received Sor for advanced HCC. The majority of patients who had SD according to RECIST had a different prognosis according to mRECIST. The results indicated that, for patients with HCC, mRECIST should be used for the standard assessment of treatment efficacy, particularly in patients who are receiving antiangiogenic drugs. Cancer 2012;. © 2011 American Cancer Society.

Hepatocellular carcinoma (HCC) is the third leading cause of death from cancer worldwide1; and, at the time of diagnosis, most patients have advanced stage disease. Therapeutic modalities for patients with advanced stage HCC were very limited until results from the Sorafenib HCC Assessment Randomized Protocol (SHARP) trial were published.2 That trial tested the efficacy of sorafenib, a multikinase inhibitor that inhibits certain tyrosine kinases (vascular endothelial growth factor receptor [VEGFR], platelet-derived growth factor receptor [PDGFR], c-Kit) and raf serine/threonine kinase,3, 4 compared with placebo in 602 patients with advanced stage HCC. Despite a disappointing 2% response rate (RR) as assessed by Response Evaluation Criteria in Solid Tumor (RECIST), sorafenib demonstrated a significant improvement in overall survival (OS) (median OS increased from 7.9 months to 10.7 months) and in the median time to radiologic progression (from 2.8 months to 5.5 months). In a confirmatory phase 3 study conducted in Asia (the Asia-Pacific [AP] trial) that included 271 patients, similar improvements in OS and the time to progression were observed, also contrasting with a low RR (3.3%).5 Moreover, in the SHARP trial, there was no difference in RR between sorafenib and placebo with regard to response or stable disease (SD) according to RECIST in 2% and 71% of patients, respectively, versus 1% and 67% of patients, respectively. In clinical practice, this absence of any clear sign of therapeutic efficacy can be a problem, particularly in patients who are experiencing toxic adverse effects. It also may be a major problem when second-line treatments become available. Such results also could be problematic in the context of a phase 2 trial, potentially leading to a halt in the development of active drugs. These discrepancies and other difficulties in assessing response to locoregional treatments for HCC (percutaneous tumor ablation or transarterial chemoembolization) have led to a recent revision of evaluation criteria. Since the European Association for Study of the Liver (EASL) consensus conference on HCC in 2000,6 it has been pointed out that vascularization of a lesion is the crucial key to evaluate response to HCC treatment. Subsequently, an adaptation of RECIST, termed modified RECIST (mRECIST), was designed specifically for HCC.7, 8 The major change from RECIST is the definition of the target lesion, which is no longer the whole lesion but only the contrast-enhanced portion of the hepatic lesion at the arterial phase of a dynamic imaging technique; the definitions of progression and response follow RECIST.9, 10 mRECIST offer clearly defined criteria for the assessment of this vascularization, enabling an evaluation of response with a routine 4-phase computed tomography (CT) scan (ceCT scan) or magnetic resonance image.

We applied mRECIST to a series of patients who received sorafenib. The objective of the current study was to determine whether the application of mRECIST improves prognosis classification compared with RECIST 1.1. To have a better overview for determining the RR, only patients who had sufficient follow-up were included.

MATERIALS AND METHODS

  1. Top of page
  2. Abstract
  3. MATERIALS AND METHODS
  4. RESULTS
  5. DISCUSSION
  6. FUNDING SOURCES
  7. CONFLICT OF INTEREST DISCLOSURES
  8. REFERENCES

Patients

We retrospectively analyzed data from all patients who received sorafenib as treatment for advanced HCC in our institution. Inclusion criteria were: HCC proven histologically or diagnosed by noninvasive criteria (in a patient with known cirrhosis, either an intrahepatic lesion that measured between 1 and 2 cm in greatest dimension with arterial enhancement and portal wash out on 2 imaging modalities or an intrahepatic lesion that measured >2 cm with arterial enhancement on 1 imaging modality and either portal wash out or α-fetoprotein [AFP] >200 ng/mL)11; initiation and follow-up of treatment done in our institution; a baseline ceCT scan obtained at least 1 month before treatment and sufficient follow-up with at least 2 ceCTscans obtained after the initiation of the treatment; and at least 1 target lesion according to RECIST 1.1 and mRECIST on the baseline CT scan. Exclusion criteria were: concomitant antineoplastic treatment, transarterial treatment, or radiofrequency ablation performed <3 months before the initiation of sorafenib. Our standard imaging follow-up in patients who received sorafenib is 1 CT scan in the first and second months and every 2 months thereafter.

Data Collection and Radiologic Interpretation

We collected clinical and biologic data needed to classify patients according to the Child-Pugh, Barcelona Clinic for Liver Cancer (BCLC), and Cancer of the Liver Italian Program (CLIP) classifications. Images were obtained on a multidetector CT with multiphasic, contrast-enhanced acquisitions at the arterial (40 seconds) and portal (70 seconds) phases. A 120-mL injection of iodine contrast media (300 mg/mL) with an average flow rate of 3 mL/second was performed. Every CT scan was reviewed retrospectively by 2 medical oncologists who specialized in liver cancers, and tumor response was evaluated separately according to RECIST 1.1 and mRECIST in a nonblinded fashion.7, 9, 10 The target lesions were defined by both physicians for all patients on their pretreatment CT scans; then, each physician made separate measurements and determined the RR; in case of disagreement, a consensus was reached. A target lesion was defined as the whole lesion for RECIST assessment and as the contrast-enhanced portion of the lesion at the arterial phase for mRECIST assessment. In case of discontinuous enhancement, the measure avoided zones of nonenhancement. In case of residual multinodular enhancement, the largest zone of continuous enhancement was measured (for an example of RECIST and mRECIST evaluations, see Fig. 1). Nonhepatic lesions, if present, also could be considered as target lesion but without taking into account their vascularization. In the event of ascites, a cytologic examination was performed, and progression was retained only after cytologic confirmation of its neoplastic nature. Every target lesion was chosen on the baseline CT scan, and the sum of the maximal dimensions of every target lesion was calculated on every CT scan. In case of a mixed response, the sum of greatest dimensions prevailed in the evaluation of each target lesion measured separately. A partial response (PR) was defined as a 30% decrease in the sum of maximal dimensions, progressive disease (PD) was defined as a 20% increase of the sum of maximal dimensions, and all other variations were classified as stable disease (SD), but documentation had to occur ≥6 weeks after the baseline determination. A complete response (CR) corresponded to the disappearance of all lesions for RECIST evaluation and to the disappearance of all contrast-enhancement at the arterial phase for mRECIST evaluation. Objective response (OR) was defined as the sum of CRs and PRs. Every response had to be confirmed by a subsequent CT scan. We also recorded the best variation (maximal decrease or minimal increase) in the sum of greatest lesion dimensions for each patient.

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Figure 1. These images illustrate evaluation according to Response Evaluation Criteria in Solid Tumors (RECIST) and modified RECIST (mRECIST) in a voluminous lesion that had central necrosis before treatment and discontinuous peripheral enhancement after treatment. (A,B) These images illustrate RECIST measurement (arrows) of the lesion (A) before treatment and (B) after treatment. (C,D) mRECIST measurement of the same lesion is shown (C) before treatment and (D) after treatment. Note that mRECIST measurements (arrows) were not taken at the same level as RECIST measurements to ensure that the greatest dimension of continuous enhancement was measured.

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Each survival analysis started at the time sorafenib therapy was initiated. Overall survival analysis ended at the time of death or was censored at the time of the last follow-up visit.

Statistical Analysis

Each analysis was performed with the use of a 2-sided α level of .05 by using the SPSS software package (version 17.0; SPSS, Inc., Chicago, Ill). The chi-square test was used for frequency comparisons, and Pearson tests were used for correlation analyses. Survival data were analyzed by using the Kaplan-Meier method with the log-rank test.

RESULTS

  1. Top of page
  2. Abstract
  3. MATERIALS AND METHODS
  4. RESULTS
  5. DISCUSSION
  6. FUNDING SOURCES
  7. CONFLICT OF INTEREST DISCLOSURES
  8. REFERENCES

Patient selection in this series is reported in Figure 2. Of the 56 patients who had technically good imaging studies available, 54 patients (96.4%) could be evaluated by RECIST, and 53 patients (94.6%) could be evaluated by mRECIST. One nonevaluable patient according to both criteria had only bone lesions, and the other had multiple infracentimetric hepatic lesions. The only patient who was evaluable by RECIST and nonevaluable by mRECIST had 2 intrahepatic lesions, received pretreatment with transarterial chemoembolization 6 months before the initiation of sorafenib, and had documented RECIST progression of the lesions but without clear arterial enhancement.

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Figure 2. This Consolidated Standards of Reporting Trials (CONSORT) diagram illustrates the criteria used for inclusion in the current study. Sor indicates sorafenib; pts, patients; CT, computed tomography; RECIST, Response Evaluation Criteria in Solid Tumors; mRECIST, modified Response Evaluation Criteria in Solid Tumors.

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Patient characteristics are summarized Table 1. Treatments received before sorafenib were surgery or radiofrequency ablation in 13 patients, transarterial procedures in 11 patients, pravastatin12 in 6 patients, and systemic chemotherapy13 in 1 patient. All radiofrequency and transarterial procedures were received >3 months before the initiation of sorafenib, and patients experienced documented progression by RECIST 1.1 after pravastatin or chemotherapy.

Table 1. Characteristics of the Cohort
CharacteristicNo. of Patients (%)
  1. Abbreviations: BCLC, Barcelona Clinic for Liver Cancer; CLIP, Cancer of the Liver Italian Program; ECOG PS, Eastern Cooperative Oncology Group performance status.

Sex 
 Men48 (90.6)
 Women5 (9.4)
ECOG PS 
 029 (54.7)
 124 (45.3)
Cirrhosis41 (77.4)
Child-Pugh score 
 A41 (77.3)
 B12 (22.6)
Alcoholic origin of cirrhosis26 (49)
Other treatment before sorafenib31 (58.5)
Greater than 50% of liver involved16 (30.2)
Portal vein thrombosis9 (17)
Extrahepatic metastasis13 (24.5)
BCLC score 
 B22 (41.5)
 C31 (58.5)
CLIP score, n = 49 evaluable patients 
 01 (2)
 116 (32.7)
 224 (49)
 37 (14.3)
 41 (2)

Best responses as assessed by RECIST and mRECIST are reported in Table 2. Differences in response measurements between the 2 investigators were rare and were observed predominantly in voluminous lesions with central necrosis. However, there was no discrepancy in assessing response as CR, PR, SD, or PD. The OR rates according to RECIST and mRECIST were 1.9% (1 of 53 patients) and 22.6% (12 of 53), respectively. Differences in distribution of responses according to RECIST and mRECIST (Table 2) were statistically significant (P < .001). It is noteworthy that, among 42 patients who were classified with SD by RECIST, 11 patients (26.2%) were reclassified as overall responders by mRECIST, and 2 patients (3.8%) were reclassified with PD. Overall, a discordance between the response evaluations with the 2 methods was observed for 15 patients (28.3%). Examples of discordance are presented in Figure 3. We did not observe any particular imaging features on baseline CT scans (involvement of >50% of the liver, portal vein thrombosis, outside liver metastasis, massive necrotic lesions, or small plain lesions) that could predict either response or progression according to RECIST or mRECIST. There was no association between response and Child-Pugh, BCLC, or CLIP classifications. However, a performance status (PS) of 0 was associated with a 34.5% OR rate by mRECIST, as opposed to a 8.3% OR rate in patients with a PS of 1, although the difference was not strictly statistically significant (P = .063).

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Figure 3. These are 2 examples of discordance between Response Evaluation Criteria in Solid Tumors (RECIST) and modified RECIST (mRECIST). Thick arrows indicate mRECIST evaluation; thin arrows, RECIST evaluation. (A,B) A target lesion of the left liver is shown (A) at baseline and (B) 1 month after the initiation of sorafenib treatment. The enhancement disappeared completely after treatment without any change to the global greatest lesion dimension, which is defined as stable disease according to RECIST and as a complete response according to mRECIST. (C) Progression of the greatest lesion dimension without progression of the enhanced part of the lesion is defined as progressive disease according to RECIST and as stable disease according to mRECIST. (D) However, a later computed tomography scan revealed that the lesion progressed according to mRECIST. mRECIST evaluation should draw the maximal dimension of continuous arterial enhancement in such lesions with central necrosis, avoiding central necrosis. Note that the maximal dimension according to RECIST and mRECIST evaluation can be on different levels.

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Table 2. Response Evaluation According to Response Evaluation Criteria in Solid Tumors (RECIST) and Modified RECIST
 No. of Patients (%)
 mRECIST 
RECISTCRPRSDPDTotal RECIST Evaluation
  1. Abbreviations: CR, complete response; mRECIST, modified Response Evaluation Criteria in Solid Tumors; PD, progressive disease; PR, partial response; SD, stable disease.

CR0 (0)0 (0)0 (0)0 (0)0 (0)
PR1 (1.9)0 (0)0 (0)0 (0)1 (1.9)
SD1 (1.9)10 (18.9)29 (54.7)2 (3.8)42 (79.2)
PD0 (0)0 (0)1 (1.9)9 (17)10 (18.9)
Total mRECIST evaluation2 (3.8)10 (18.9)30 (56.6)11 (20.8)53 (100)

The observed maximal variations in the sum of the greatest target lesion dimensions are presented in Figure 4 for both criteria methods. There was good correlation (P < .001) between the 2 assessments (Pearson correlation coefficient r = 0.818). Differences between maximal variations in the greatest dimensions measured by RECIST or mRECIST were particularly pronounced for patients who had a decrease in greatest tumor dimension according to RECIST.

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Figure 4. This waterfall plot illustrates the best variations of target lesions according to Response Evaluation Criteria in Solid Tumors (RECIST) and modified RECIST (mRECIST) represented side by side for every patient.

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Of the 12 patients who achieved an OR by mRECIST, the median time to response was 2.1 months (95% confidence interval [CI], 0.5-3.6 months). At the time of analysis, progression was observed in 41 patients (77.4%). Progression was defined only by the appearance of new lesions, without progression of the target lesions, in 9 patients (22%). The median time to progression was similar between the 2 criteria and was 4.1 months (95% CI, 2.8-5.4 months) according to RECIST and 3.9 months (95% CI, 2.8-5.1 months) according to mRECIST. Progression dates differed between the 2 methods in 10 patients (24.4%), and progression was observed with the alternative method in the next CT scan in all but 2 patients, in whom progression according to mRECIST preceded RECIST progression by 7.8 months and 9.6 months.

Survival Analysis According to Radiologic Response

At the time of data analysis, 44 patients (83%) had died, the mean OS for the entire population was 9.7 months, and the 1-year and 2-year OS rates were 41.6% and 23.7%, respectively. The Kaplan-Meier estimates of OS after the response evaluated by RECIST and mRECIST are presented in Figure 5. Both methods provided good correlation of OS according to response (log-rank test: P = .002 for RECIST; P = .001 for mRECIST). The median OS for patients with OR, SD, and PD was 33.5 months (1 patient), 11.2 months (95% CI, 7.5-14.9 months; 42 patients), and 4.2 months (95% CI, 0.9-7.5, months; 10 patients), respectively, for RECIST, and 18.2 months (95% CI, 15.4-20.9 months; 12 patients), 9.7 months (95% CI, 7.1-12.3 months; 30 patients), and 6.0 months (95% CI, 3.3-8.7 months; 11 patients), respectively, for mRECIST.

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Figure 5. Kaplan-Meier estimates of overall survival are illustrated for patients who had an objective response (short dashed line), patients with stable disease (solid line), and patients who had progressive disease (long dashed line). Survival was calculated according to response assessed with (A) Response Evaluation Criteria in Solid Tumors (RECIST) and (B) modified RECIST.

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The survival of patients who achieved an OR as assessed by mRECIST was significantly better than the survival of nonresponding patients (SD or PD), with a median OS of 18.2 months (95% CI, 15.4-20.9 months) and 7.7 months (95% CI, 6.3-9.0 months), respectively (P = .013) (Fig. 6). Finally, in the 42 patients who were classified with SD according to RECIST, response according to mRECIST distinguished a significantly different prognosis (Fig. 7), with a median OS of 17.1 months (95% CI, 14.6-19.7 months), 9.7 months (95% CI, 5.9-13.5 months), and 3.7 months in patients who had an OR (n = 11), SD (n = 29), or PD (n = 2), respectively (P = .016).

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Figure 6. Kaplan-Meier estimates of overall survival are illustrated for responders (patients who had an objective response; dashed and dotted line) and for nonresponders (patients who had either stable disease or progressive disease; dashed line). Survival was calculated according to modified Response Evaluation Criteria in Solid Tumors.

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thumbnail image

Figure 7. Kaplan-Meier estimates of overall survival are illustrated for patients who had an objective response (short dashed line), patients with stable disease (solid line), and patients who had progressive disease (long dashed line). Survival was calculated according to response assessed with modified Response Evaluation Criteria in Solid Tumors (RECIST) in 42 patients who were classified with stable disease according to RECIST.

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DISCUSSION

  1. Top of page
  2. Abstract
  3. MATERIALS AND METHODS
  4. RESULTS
  5. DISCUSSION
  6. FUNDING SOURCES
  7. CONFLICT OF INTEREST DISCLOSURES
  8. REFERENCES

Sorafenib represents a breakthrough in the treatment of advanced HCC with a clinically meaningful improvement in OS, despite a minimal RR as assessed by RECIST 1.0 of only 2%2 or 3.3%.5 This discrepancy, as well as others observed with locoregional or transarterial treatments,14 led the EASL to recommend studying tumor vascularization for the evaluation of treatment response.6 After these recommendations, numerous studies evaluated the RR with different methodologies.15-27 Those studies tended to indicate a benefit from taking tumor vascularization into account and reported an increase in the RR despite great variations in methodology.28, 29 However, reproducibility is an issue when these techniques require the definition of a region of interest, which can be more prone to bias than the measure of a single tumor dimension. In 1 study, investigators tried to correlate response as assessed by World Health Organization (WHO), RECIST 1.0, or EASL criteria with survival.23 That study concerned patients who underwent chemoembolization or radioembolization, and the 3 methods of response assessment allowed for a good correlation between response and prognosis, including excellent concordance between WHO and RECIST but quite discordant results between EASL and other criteria. However, in that study, differences in survival between patients classified as responders or nonresponders appeared to be quite similar irrespective of the evaluation technique used. To our knowledge, no study examining mRECIST assessment of response to targeted therapies has been published to date. One study has been presented that was based on a phase 2 brivanib (a multitarget tyrosine kinase inhibitor) first-line trial, and the results reflected increases in the RR and in the time to progression using mRECIST compared with modified WHO criteria.30 In other contexts, such as gastrointestinal stromal tumors or antiangiogenic treatments, alternatives to RECIST focusing on tissue viability also have been proposed, but they do not have the precision of mRECIST.31, 32 Another potential approach to response assessment is the use of AFP. One study applied AFP response in a population that underwent transarterial procedures,33 another study applied AFP response to patients who received treatment with different antiangiogenic drugs,34 and a third study applied AFP response to patients who received chemotherapy.35 Those 3 studies reflected better survival for responders; however, only the third study tried to investigate the benefit of AFP response in patients who were classified as stable according to WHO criteria. Those authors observed a nonsignificant trend toward better survival for AFP responders versus nonresponders (median survival, 10.3 months vs 8.2 months; P = .056).35

In our current retrospective study of patients who received sorafenib, we compared RECIST 1.1 and mRECIST to determine whether mRECIST could be useful as a tool for clinical research and clinical practice. Our population was composed of 70 patients in a 2.5-year period; this population was somewhat biased (frequency of patients with Child-Pugh B, of pretreated patients, and of patients with BCLC B disease) because of concomitant phase 2 and 3 trials of novel agents in this setting. Nevertheless, our population was quite similar to patients who are treated in routine clinical practice. Fourteen patients were excluded because they had received another treatment (mostly radioembolization) while they were receiving sorafenib, or because their initial CT scan was of poor quality (no arterial phase), or because they died too early to allow an evaluation of response. Thus, among the 56 patients who had technically good imaging studies and sufficient follow-up, mRECIST evaluation appeared to be widely applicable for 53 assessable patients (94.6%) compared with 54 assessable patients (96.4%) by RECIST. Only 1 patient assessed by RECIST could not be assessed by mRECIST because of the absence of clear tumor hypervascularization. In this retrospective study, we used CT scans, because this modality is the most commonly used in our institution. However, mRECIST also can be applied to contrast-enhanced magnetic resonance imaging, probably with the same feasibility and results as attained with CT scanning.

mRECIST assessment of response to sorafenib identified a population that included 22.6% responders, which is more in line with the efficacy of treatment in terms of OS than the 2% to 3.3% RR as assessed by RECIST (reported in the SHARP study,2 in the AP trial,5 and also in the current series). Maximal variations in the analysis of target lesion greatest dimensions emphasizes this point: Even with RECIST evaluation, decreases in greatest tumor dimensions were noted, but they were not sufficient to reach the threshold for an OR. mRECIST evaluation increases the amplitude of the observed shrinkage and provides a more striking appraisal of the therapeutic effect. Such differences are of particular importance for the evaluation of new drugs in phase 2 trials.36-38 It is noteworthy that the development of sorafenib in metastatic renal cell carcinoma used an alternative phase 2 design: the randomized discontinuation trial.39 Otherwise, responses were observed quite early during treatment (median time to response, 2.1 months). However, despite small variations, there was no meaningful difference in terms of progression between RECIST and mRECIST.

According to mRECIST evaluation, responders have a better prognosis than nonresponders. This applies to a much larger population of responders than the 2% of patients classified as responders according to RECIST. The difference is in the same range as the difference observed with AFP responders reported by Shao et al34 (median OS, 18.2 months vs 7.7 months for mRECIST responders and nonresponders, respectively, in our study and 15.3 months vs 4.1 months for AFP responders and nonresponders, respectively, in the study by Shao et al). In any event, AFP response can be applied only to patients who have elevated AFP levels before therapy, which defines a narrower population than patients who are evaluable by mRECIST, and AFP can be increased in liver disease without HCC, particularly in patients who have an underlying viral disease.

More important, in the 79.2% of patients classified as stable by RECIST, the use of mRECIST enabled the prediction of different prognostic subgroups with a significantly better median OS of 17.1 months for responding patients compared with 9.7 months for stable patients. Hence, the differences observed in vascularization reflect a real biologic change in the tumor with clinically meaningful implications for the patient. Efforts should be made in a different setting (eg, preoperative transarterial procedure) to address the correlation between radiologic mRECIST response and pathologic or biologic changes. In some ongoing randomized controlled trials of targeted therapies in HCC, an analysis of both RECIST and mRECIST is done, and we will have more robust prospective data in the future.

However, in the current study, there was no significant difference in assessing the time to progression between the 2 methods. Disease progression seems to involve an increase in vascularization that immediately translates into an increase in the greatest lesion dimension. The time to progression in different subgroups according to the 2 methods did not clearly differ; however, the 2-month interval between the CT scan and the poor number of included patients may have hidden a difference.

Targeted therapies are expensive and are associated with certain adverse effects that impair quality of life. It is important in clinical practice to have a relevant tool to guide treatment planning. ceCT scan is the usual method for tumor assessment in HCC. In this retrospective study, we observed that mRECIST provided a useful evaluation of response to sorafenib. Determination was easy and applicable in almost all patients. The prognostic information obtained was better than that obtained with RECIST. mRECIST allowed us to characterize a population of responders, corresponding to >20% of patients, who had significantly better outcomes than nonresponders. Moreover, among patients who were classified as stable according to RECIST, the use of mRECIST differentiated a subset of patients that undoubtedly benefited from sorafenib despite having the same prognosis assessment provided by RECIST. Therefore, mRECIST evaluation may help to guide the continuation of sorafenib, especially in patients who have difficulty tolerating treatment. In such patients, stability is the most frequent response according to RECIST (almost 80% of patients). The value of AFP level changes in these stable patients needs to be evaluated prospectively. If the patient is categorized as a responder by mRECIST, then efforts should be made in supportive care to keep the patient on sorafenib; conversely, if the patient is categorized with PD by mRECIST, then sorafenib probably should be stopped, because there is a low probability that it will be useful for the patient. It also would be interesting to study this alternative to RECIST in other situations, such as gastrointestinal stromal tumors or the evaluation of antiangiogenic therapies.31, 32 In any event, mRECIST should become the new standard for evaluating new treatments in HCC.

CONFLICT OF INTEREST DISCLOSURES

  1. Top of page
  2. Abstract
  3. MATERIALS AND METHODS
  4. RESULTS
  5. DISCUSSION
  6. FUNDING SOURCES
  7. CONFLICT OF INTEREST DISCLOSURES
  8. REFERENCES

Jean-Luc Raoul is a member of the Bayer and BMS advisory boards and has received lecture fees from Bayer and BMS.

REFERENCES

  1. Top of page
  2. Abstract
  3. MATERIALS AND METHODS
  4. RESULTS
  5. DISCUSSION
  6. FUNDING SOURCES
  7. CONFLICT OF INTEREST DISCLOSURES
  8. REFERENCES
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