Treatment of hepatocellular carcinoma with portal venous tumor thrombosis: A comprehensive review

The natural history of hepatocellular carcinoma (HCC) with portal vein tumor thrombosis (PVTT) is dismal (approximately 2-4 mo), and PVTT is reportedly found in 10%-40% of HCC patients at diagnosis. According to the Barcelona Clinic Liver Cancer (BCLC) Staging System (which is the most widely adopted HCC management guideline), sorafenib is the standard of care for advanced HCC (i.e., BCLC stage C) and the presence of PVTT is included in this category. However, sorafenib treatment only marginally prolongs patient survival and, notably, its therapeutic efficacy is reduced in patients with PVTT. In this context, there have been diverse efforts to develop alternatives to current standard systemic chemotherapies or combination treatment options. To date, many studies on transarterial chemoembolization, 3-dimensional conformal radiotherapy, hepatic arterial chemotherapy, and transarterial radioembolization report better overall survival than sorafenib therapy alone, but their outcomes need to be verified in future prospective, randomized controlled studies in order to be incorporated into current treatment guidelines. Additionally, combination strategies have been applied to treat HCC patients with PVTT, with the hope that the possible synergistic actions among different treatment modalities would provide promising results. This narrative review describes the current status of the management options for HCC with PVTT, with a focus on overall survival.     

Effective treatment strategies other than sorafenib for the patients with advanced hepatocellular carcinoma invading portal vein

Patients with hepatocellular carcinoma(HCC) accompanying portal vein tumor thrombosis(PVTT) have relatively few therapeutic options and an extremely poor prognosis. These patients are classified into barcelonaclinic liver cancer stage C and sorafenib is suggested as the standard therapy of care. However, overall survival(OS) gain from sorafenib is unsatisfactory and better treatment modalities are urgently required. Therefore, we critically appraised recent data for the various treatment strategies for patients with HCC accompanying PVTT. In suitable patients, even surgical resection can be considered a potentially curative strategy. Transarterial chemoembolization(TACE) can be performed effectively and safely in a carefully chosen population of patients with reserved liver function and sufficient collateral blood flow nearby the blocked portal vein. A recent metaanalysis demonstrated that TACE achieved a substantial improvement of OS in HCC patients accompanying PVTT compared with best supportive care. In addition, transarterial radioembolization(TARE) using yttrium-90 microspheres achieves quality-of-life advantages and is as effective as TACE. A large proportion of HCC patients accompanying PVTT are considered to be proper for TARE. Moreover, TACE or TARE achieved comparable outcomes to sorafenib in recent studies and it was also reported that the combination of radiotherapy with TACE achieved a survival gain compared to sorafenib in HCC patients accompanying PVTT. Surgical resectionbased multimodal treatments, transarterial approaches including TACE and TARE, and TACE-based appropriate combination strategies may improve OS of HCC patients accompanying PVTT.     

Complete response with sorafenib and transcatheter arterial chemoembolization in unresectable hepatocellular carcinoma

Patients with advanced hepatocellular carcinoma(HCC) showing portal vein tumor thrombosis(PVTT) have an extremely poor prognosis. According to treatment guidelines, the only option for HCC patients with PVTT is sorafenib chemotherapy. However, in Asia, various treatments have been attempted and possible prolongation of overall survival has been repeatedly reported. We herein report the first case of a patient with an initially unresectable advanced HCC with PVTT who underwent curative hepatectomy after sorafenib and transcatheter arterial chemoembolization(TACE) showing complete histological response. Two months after induction with sorafenib, a significant decrease in serum alpha-fetoprotein level was observed and computed tomography imaging showed a significant decrease in tumor size. Because of remaining PVTT, TACE and curative resection were performed. The combination of sorafenib and TACE may be an effective treatment for HCC patients with PVTT.     

Management of hepatocellular carcinoma patients with portal vein tumor thrombosis: A narrative review

Background: Hepatocellular carcinoma(HCC) is one of the main reasons for malignancy-related death. Portal vein tumor thrombosis(PVTT) is the most common form of macrovascular invasion related to HCC occurring in 10%-60% of patients. HCC with PVTT is usually characterized by worsening liver function, vulnerability to blood metastasis, higher incidence of complications associated with portal hypertension, and intolerance to treatment when compared with that without PVTT. If only treated with suppo...     

Portal venous tumor growth-type of hepatocellular carcinoma without liver parenchyma tumor nodules: a case report

The patient was a 43-year-old man with chronic hepatitis B without history of hepatocellular carcinoma (HCC), who was first diagnosed with thrombosis in right portal vein trunk and portal vein branches and ruptured esophageal varices in October 2011. He underwent endoscopic variceal ligation, but ruptured repeatedly. Despite anti-coagulant therapy, the thrombosis expanded from right portal vein trunk to upper mesenteric vein in March 2012. Computed tomography (CT) scan showed that portal vein thrombosis had low density from early to late phase. No focal liver lesions were identified by CT scan or ultrasound, and alpha-fetoprotein (AFP) was within normal range. He died by intractable esophageal variceal bleeding in April 2012. Pathological examination of autopsy specimen showed that portal vein thrombosis was consistent with poorly-differentiated HCC. The portal vein tumor thrombosis (PVTT) had only a few tumor vessels, which were compressed by fibromatous change originating from HCC formation, so were represented as low-density lesions from arterial to portal phase of CT. In addition, PVTT was negative for AFP, so representing serum value of AFP within normal range. PVTT had positive staining for c-kit, which is a liver stem cell marker. Liver tumors in the whole liver parenchyma were not found pathologically. PVTT might have the characteristics of presumed liver cancer stem cells. We experienced the first case of HCC only in portal vein without liver parenchyma tumor nodules, with difficult differential diagnosis from a non-malignant portal vein thrombosis. We also reported new tumor profiles of the portal venous tumor growth- type of HCC.     

Radiotherapy as valid modality for hepatocellular carcinoma with portal vein tumor thrombosis

Although the current standard treatment for hepatocellular carcinoma(HCC) with portal vein tumor thrombosis(PVTT) is sorafenib, many previous studies have established the need for a reliable local modality for PVTT control, which is a major cause of liver function deterioration and metastasis. Additionally, there is growing evidence for the prognostic significance of PVTT classification according to the location of tumor thrombosis. Favorable outcomes can be obtained by applying local modalities, including surgery or transarterial chemoembolization, especially in second-order or distal branch PVTT. Rapid control of PVTT could maintain or improve liver function and reduce intrahepatic as well as distant metastasis. Radiotherapy(RT) is one of the main locoregional treatment modalities in oncologic fields, but has rarely been used in HCC because of concerns regarding hepatic toxicity. However, with the development of advanced techniques, RT has been increasingly applied in HCC management. Randomized studies have yet to definitively prove the benefit of RT, but several comparative studies have justified the application of RT in HCC. The value of RT is especially noticeable in HCC with PVTT; several prospective and retrospective studies have reported favorable outcomes, including a 40% to 60% objective response rate and median overall survival of 15 mo to 20 mo in responders. In this review, we evaluate the role of RT as an alternative local modality in HCC with PVTT.     

Transjugular intrahepatic portosystemic shunt for palliative treatment of portal hypertension secondary to portal vein tumor thrombosis

AIM: To evaluate the palliative therapeutic effects of transjugular intrahepatic portosystemic shunt (TIPS) in portal vein tumor thrombosis (PVTT) complicated by portal hypertension. METHODS: We performed TIPS for 14 patients with PVTT due to hepatocellular carcinoma (HCC). Of the 14 patients, 8 patients had complete occlusion of the main portal vein, 6 patients had incomplete thrombosis, and 5 patients had portal vein cavernous transformation. Clinical characteristics and average survival time of 14 patients were analysed. Portal vein pressure, ascites, diarrhoea, and variceal bleeding and circumference of abdomen were assessed before and after TIPS. RESULTS: TIPS was successful in 10 cases, and the successful rate was about 71%. The mean portal vein pressure was reduced from 37.2 mmHg to 18.2 mmHg. After TIPS, the ascites decreased, hemorrhage stopped and the clinical symptoms disappeared in the 10 cases. The average survival time was 132.3 d. The procedure failed in 4 cases because of cavernous transformation in portal vein and severe cirrhosis. CONCLUSION: TIPS is an effective palliative treatment to control hemorrhage and ascites due to HCC complicated by PVTT.     

An aggressive approach leads to improved survival in hepatocellular carcinoma patients with portal vein tumor thrombus

Purpose  

Many physicians express a relatively nihilistic approach to the treatment of hepatocellular carcinoma (HCC) with portal vein tumor thrombus (PVTT). Consensus among surgeons regarding the indications for an aggressive approach has not been reached. Current study was aimed to determine whether an aggressive approach, with an extended resection with thrombectomy and adjuvant therapy, would lead to an improved survival for HCC patients with PVTT.     

Efficacy of different treatment strategies for hepatocellular carcinoma with portal vein tumor thrombosis

AIM: To evaluate the efficacy of different treatment strategies for hepatocellular carcinoma (HCC) with portal vein tumor thrombosis (PVTT) and investigate factors influencing prognosis. METHODS: One hundred and seventy-nine HCC patients with macroscopic PVTT were enrolled in this study. They were divided into four groups and underwent different treatments: conservative treatment group (n = 18), chemotherapy group (n = 53), surgical resection group (n = 24) and surgical resection with postoperative chemotherapy group (n = 84). Survival rates of the patients were analyzed by the Kaplan-Meier method. A log-rank analysis was performed to identify group differences. Cox's proportional hazards model was used to analyze variables associated with survival. RESULTS: The mean survival periods of the patients in four groups were 3.6, 7.3,10.1, and 15.1 mo respectively. There were significant differences in the survival rates among the groups. The survival rates at 0.5-, 1-, 2-, and 3-year in surgical resection with postoperative chemotherapy group were 55.8%, 39.3%, 30.4%, and 15.6% respectively, which were significantly higher than those of other groups (p<0.001). Multivariate analysis revealed that the strategy of treatment (P<0.001) and the number of chemotherapy cycles (P = 0.012) were independent survival predictors for patients with HCC and PVTT. CONCLUSION: Surgical resection of HCC and PVTT combined with postoperative chemotherapy or chemoembolization is the most effective therapeutic strategy for the patients who can tolerate operation. Multiple chemotherapeutic courses should be given postoperatively to the patients with good hepatic function reserve.     

Complete regression of locally advanced hepatocellular carcinoma induced by sorafenib allowing curative resection

We report two cases of locally advanced hepatocellular carcinoma (HCC) with portal vein tumour thrombosis (PVTT) who complete regression by sorafenib treatment allowed curative resection. Two male adult (59 and 57 years) cirrhotic patients with HCC associated with PVTT including one with lymph node involvement had elevated α‐fetoprotein level (AFP) (867 and 17 000) and were treated with standard sorafenib treatment during 10 and 12 months respectively. Size decrease of the main tumour, disappearance of PVTT and normalization of AFP allowed curative surgical resection. No viable tumour cells were found in the specimen and the two patients are currently alive without recurrence 12 and 16 months after surgery. These first two cases of complete tumour necrosis after sorafenib treatment allow us to reconsider surgical treatment in patients with unresectable HCC responding to this medical treatment.     

Hepatocellular Carcinoma with Portal Vein Tumor Thrombosis: Clinical Characteristics, Prognosis, and Patient Survival Analysis

Hepatocellular carcinoma (HCC) with portal vein tumor thrombosis (PVTT) is associated with a poor prognosis. New therapeutic modalities, such as continuous hepatic arterial infusion chemotherapy (CHAIC), have recently been reported to be promising strategies. The aim of this study was to evaluate the clinical characteristics, prognosis, and survival of patients with PVTT according to treatment regimen. One hundred ninety-three patients with HCC complicated with PVTT at the time of diagnosis were included in this study. All patients were newly diagnosed to have HCC and were observed from January 1992 to December 2003. CHAIC was performed using an implanted drug delivery system with low-dose cisplatin and 5-fluorouracil. Clinical characteristics, prognosis, and patient survival were analyzed by the Kaplan-Meier method and Cox's proportional hazards model. The mean age of the patients complicated with PVTT was 64.3+/-10.3 years (range, 20-88 years). The survival of the 193 patients with PVTT was 37.5%, 24.0%, 18.9%, and 8.3% at 1, 2, 3, and 5 years, respectively. According to treatment, the survival of patients who underwent surgical treatment was the best, followed by CHAIC, transcatheter arterial infusion/embolization, and supportive care. The 3-year survivals for each treatment regimen were 53.0%, 19.3%, 15.0%, and 4.0%, respectively. Although the survival of patients who received surgical treatment was best, such patients were restricted. There was no difference in survival between treated and untreated patients demonstrating Child-Pugh grade C. In Child B patients, treatment for HCC significantly increased survival (P<0.01). Cox's proportional hazards model revealed the Child-Pugh classification to be an independent prognostic factor for patients with HCC and PVTT (P<0.01). We conclude that the prognosis of HCC with PVTT was quite poor. The treatment did not improve the survival of Child C patients. As a result, the prevention, early diagnosis, and development of new treatment strategies are required.     

Nonoperative therapies for combined modality treatment of hepatocellular cancer: expert consensus statement

Although surgical resection and liver transplantation are the only treatment modalities that enable prolonged survival in patients with hepatocellular carcinoma (HCC), the majority of HCC patients presents with advanced disease and do not undergo resective or ablative therapy. Transarterial chemoembolization (TACE) is indicated in intermediate/advanced stage unresectable HCC even in the setting of portal vein involvement (excluding main portal vein). Sorafenib has been shown to improve survival of patients with advanced HCC in two controlled randomized trials. Yttrium 90 is a safe microembolization treatment that can be used as an alternative to TACE in patients with advanced liver only disease or in case of portal vein thrombosis. External beam radiation can be helpful to provide local control in selected unresectable HCC. These different treatment modalities may be combined in the treatment strategy of HCC and also used as a bridge to resection or liver transplantation. Patients should undergo formal multidisciplinary evaluation prior to initiating any such treatment in order to individualize the best available options.     

Improved survival for hepatocellular carcinoma with portal vein tumor thrombosis treated by intra-arterial chemotherapy combining etoposide, carboplatin, epirubicin and pharmacokinetic modulating chemotherapy by 5-FU and enteric-coated tegafur/uracil: A p

AIM: To investigate the poor prognosis of HCC with PVTT, we evaluated the efficacy by a new combination chemotherapy for advanced hepatocellular carcinoma (HCC) with portal vein tumor thrombus (PVTT).METHODS: From 2002 to 2007, a total of 10 consecutive patients with Stage IVA HCC accompanied by PVTT were studied prospectively to examine the efficacy of treatment by intra-arterial infusion of a chemotherapeutic agents consisting of etoposide, carboplatin, epirubicin and pharmacokinetic modulating chemotherapy by 5-FU and enteric-coated tegafur/uracil.RESULTS: The mean course of chemotherapy was 14.4 (range, 9-21) mo. One patient showed complete response (CR) with disappearance of HCC and PVTT after treatment, and the two patients showed partialresponse (PR), response rate (CR + PR/All cases 30%).The median survival time after the therapy was 457.2 d. The one-year survival rate was 70%. Adverse reactions were tolerable.CONCLUSION: Although the prognosis of most patients with Stage IVA HCC by PVTT is poor, our combination chemotherapy may induces long-term survival and is an effective treatment and produced anti-tumor activity with tolerable adverse effects in patients for advanced Stage IVA HCC accompanied by PVTT.     

Angioechographic evaluation of tumor thrombi and the effect of transcatheter arterial embolization in patients with hepatocellular carcinoma

Background: Background: Transcatheter arterial embolization (TAE) is considered to be relatively ineffective in the treatment of portal and/or hepatic vein tumor thrombi associated with hepatocellular carcinoma (HCC). However, we have seen patients with a positively enhanced tumor thrombus on angioechography where necrosis has occurred after TAE. In this study, we compared the angioechographic enhancement of tumor thrombi with the effect of TAE to assess the use of this method in predicting the efficacy of TAE, and in predicting survival. Methods: Angioechography, using a small amount of CO₂ gas injected into the hepatic artery, was performed before TAE in 41 HCC patients with tumor thrombi of the portal vein (PVTT; n= 35) or hepatic vein (HVTT; n= 6). The relationship between the enhancement of the thrombi and the efficacy of TAE was investigated by follow-up ultrasonography. Results: All 13 PVTT that decreased in size had shown positive enhancement (PE) before treatment (P < 0.001), while 6 of the 7 cases (86%) in which the lesions increased in size had shown negative enhancement (NE). The survival of patients with PE was significantly longer than that of patients with NE (P < 0.005). Multivariate analysis identified two clinical variables associated with survival, angioechographic findings of PVTT, and age. There were no correlations between enhancement and HVTT. Conclusions: Determination of enhancement of PVTT on angioechography was useful in predicting the efficacy of TAE treatment of HCC and the survival time. Angioechography may be valuable in treatment decisions for HCC patients with PVTT, especially as a guide to the effectiveness of TAE. Received: March 1, 2001 / Accepted: November 2, 2001     

Improved survival for hepatocellular carcinoma with portal vein tumor thrombosis treated by intra-arterial chemotherapy combining etoposide, carboplatin, epirubicin and pharmacokinetic modulating chemotherapy by 5-FU and enteric-coated tegafur/uracil： A pilot study

AIM： To investigate the poor prognosis of HCC with PVTT, we evaluated the efficacy by a new combination chemotherapy for advanced hepatocellular carcinoma （HCC） with portal vein tumor thrombus （PVTT）.
METHODS： From 2002 to 2007, a total of 10 consecutive patients with Stage IVA HCC accompanied by PVTT were studied prospectively to examine the efficacy of treatment by intra-arterial infusion of a chemotherapeutic agents consisting of etoposide, carboplatin, epirubicin and pharmacokinetic modulating chemotherapy by 5-FU and enteric-coated tegafur/uracil.
RESULTS： The mean course of chemotherapy was 14.4 （range, 9-21） too. One patient showed complete response （CR） with disappearance of HCC and PVI-F after treatment, and the two patients showed partial response （PR）, response rate （CR ＋ PR/All cases 30%）. The median survival time after the therapy was 457.2 d. The one-year survival rate was 70%. Adverse reactions were tolerable.
CONCLUSION： Although the prognosis of most patients with Stage IVA HCC by PVTT is poor, our combination chemotherapy may induces long-term survival and is an effective treatment and produced anti-tumor activity with tolerable adverse effects in patients for advanced Stage IVA HCC accompanied by PVTT.     

Efficacy comparison of optimal treatments for hepatocellular carcinoma patients with portal vein tumor thrombus

Introduction and objectivesOptimal treatment of hepatocellular carcinoma (HCC) involving portal vein tumor thrombus (PVTT) remains controversial.Materials and methodsA total of 627 HCC patients with PVTT after initial treatment with one of the following at Affiliated Tumor Hospital of Guangxi Medical University: liver resection (LR, n = 225), transarterial chemoembolization (TACE, n = 298) or sorafenib (n = 104) were recruited and randomly divided into the training cohort (n = 314) and internal validation cohort (n = 313). Survival analysis were repeated after stratifying patients by Cheng PVTT type.ResultsResection led to significantly higher OS than the other two treatments among patients with type I or II PVTT. TACE worked significantly better than the other two treatments for patients with type III. All three treatments were associated with similar OS among patients with type IV. These findings were supported by the internal validation cohort.ConclusionsOur results suggest that the optimal treatment for HCC involving PVTT depends on the type of PVTT. LR may be more appropriate for type I or II PVTT; TACE, for type III Sorafenib may be more appropriate than invasive treatments for patients with type IV PVTT.     

Positron emission tomography/computed tomography with (18)F-fluorodeoxyglucose identifies tumor growth or thrombosis in the portal vein with hepatocellular carcinoma

Patients suffering from hepatocellular carcinoma (HCC) with tumor thrombus in the portal vein generally have a poor prognosis. Portal vein tumor thrombus must be distinguished from portal vein blood thrombus, and this identification plays a very important role in management of HCC. Conventional imaging modalities have limitations in discrimination of portal vein tumor thrombus. The application of positron emission tomography (PET) with 18F-fluorodeoxyglucose (18F-FDG) for discrimination between tumor extension and blood thrombus has been reported in few cases of HCC, while portal tumor thrombosis and portal vein clot identified by 18F-FDG PET/CT in HCC patients has not been reported so far. We present two HCC cases, one with portal vein tumor thrombus and one thrombosis who were identified with 18F-FDG PET/CT. This report illustrates the complimentary value of combining the morphological and functional imaging in achieving a correct diagnosis in such clinical situations.     

Multimodality treatment in hepatocellular carcinoma patients with tumor thrombi in portal vein

AIM To compare the therapeutic effect andsignificances of multimodality treatment forhepatocellular carcinoma (HCC) with tumorthrombi in portal vein (PVTT).METHODS HCC patients (n=147) with tumortrombi in the main portal vein or the first branchof portal vein were divided into four groups bythe several therapeutic methods. There wereconservative treatment group in 18 out ofpatients (group A); and hepatic artery ligation(HAL) and/or hepatic artery infusion (HAI)group in 18 patients (group B), in whompostoberative chemoembolization was doneperiodically; group of removal of HCC with PVTTin 79 (group C) and group of transcatheterhepatic arterial chemoembolization (TACE) orHAI and/or portal vein infusion (PVI) afteroperation in 32 (group D).RESULTS The median survival period was 12months in our series and the 1-, 3-, and 5-yearsurvival rates were 44.3%, 24.5% and 15.2%,respectively. The median survival times were 2,5, 12 and 16 months in group A, B, C and D,respectively. The 1-, 3- and 5-year survival rateswere 5.6%, 0% and 0% in group A; 23.2%,5.6% and 0% in group B; 53.9%, 26.9% and16.6% in group C; 79.3%, 38.9% and 26.8% ingroup D, respectively. Significant differenceappeared in the survival rates among the groups (P<0.05).CONCLUSION Hepatic resection with removalof tumor thrombi and HCC should increase thecurative effects and be encouraged for theprolongation of life span and quality of life forHCC patients with PVTT, whereas the besttherapeutic method for HCC with PVTT is withregional hepatic chemotherapy orchemoemblization after hepatic resection withremoval of tumor thrombi.     

Successful preoperative treatment for hepatocellular carcinoma with tumor thrombus in the major portal branch by three-dimensional conformal radiation therapy--two case reports

The prognosis of hepatocellular carcinoma (HCC) patients with tumor thrombus in the main portal branch (PVTT) is very poor and a standard treatment regimen for HCC with PVTT has not yet been established. Therefore, a new strategy is necessary to control the patients of HCC with PVTT. Conventional radiation therapy for HCC was not effective because of low liver tolerance. On the other hand, because three-dimensional conformal radiation therapy (3D-CRT) can focus high-dose irradiation on a small area, we tried it for patients with PVTT as the preoperative adjuvant treatment. 3D-CRT which targeted the PVTT was performed for two HCC patients with PVTT before radical hepatectomy. Treatment schedules of 3D-CRT were as follows: in Case 1, the daily fraction size was 3 Gy, given five times per week, and the total dose was 39 Gy. In Case 2, the daily size was 6 Gy and the total dose was 60 Gy. Three or four weeks after 3D-CRT, the main tumor and PVTT were completely removed. On histological examination, the PVTT showed complete necrosis in Case 1, and 60% necrosis in Case 2. No serious complications occurred, and there have been no recurrences for more than one year after surgery in both cases. 3D-CRT targeting the PVTT may be promising as a preoperative adjuvant therapy for HCC with PVTT.     

Practical Effect of Sorafenib Monotherapy on Advanced Hepatocellular Carcinoma and Portal Vein Tumor Thrombosis

Background/Aims

We investigated the effects of sorafenib monotherapy on advanced hepatocellular carcinoma (HCC) and portal vein tumor thrombosis (PVTT) in a clinical setting.

Methods

In total, 143 consecutive patients with unresectable HCC were treated with sorafenib. Among these patients, 30 patients with advanced HCC and PVTT (Vp3 or 4) were treated with sorafenib monotherapy.

Results

All patients had a performance status of 1 to 2 (Eastern Cooperative Oncology Group 1/2, 20/10) and Child-Pugh class A or B (A/B, 17/13). Eleven patients had modified Union for International Cancer Control stage IVA tumors, whereas 19 had stage IVB tumors. All patients had PVTT (Vp3, 6; Vp4, 24). Following sorafenib monotherapy, three patients (10.0%) had a partial response with PVTT revascularization, and nine (30.0%) had stable disease, with a disease control rate of 33.3%. The median overall survival was 3.1 months (95% confidence interval [CI], 2.70 to 3.50), and the median progression-free survival was 2.0 months (95% CI, 1.96 to 2.05). Fatigue and hand-foot skin reactions were the most troublesome side effects.

Conclusions

A limited proportion of patients with advanced HCC and PVTT exhibited a remarkable outcome after sorafenib monotherapy, although the treatment results in this type of patient is extremely poor. Further studies to predict good responders to personalized therapy are warranted.