Potentially curative treatments for early‐stage hepatocellular carcinoma (HCC) have drawbacks and contraindications. Recently, radiotherapy has achieved good outcomes. We compared the outcomes of ...radiotherapy and radiofrequency ablation (RFA) for early‐stage HCC. Consecutive patients with ≤3 early‐stage HCC lesions and tumor diameters ≤3 cm treated with RFA or radiotherapy were reviewed. RFA was the first choice for HCC unsuitable for surgery. Otherwise, stereotactic body radiotherapy in five fractions was mainly performed. For HCC adjacent to the gastrointestinal tract, radiotherapy with mild hypofractionation was performed. Propensity score matching was performed to reduce the selection bias between the RFA and radiotherapy groups. Between 2012 and 2016, a total of 231 patients with 474 tumors and 143 patients with 221 tumors were eligible and were treated with RFA and radiotherapy, respectively. In an unmatched comparison, the 3‐year local recurrence rate was significantly lower for radiotherapy than for RFA (5.3%; 95% confidence interval CI, 2.7‐9.2; versus 12.9%, 95% CI, 9.9‐16.2) (P < 0.01). A propensity score matching analysis of 106 patients in each group successfully matched the two treatment groups with regard to Barcelona Clinic Liver Cancer staging, T stage, and tumor size but not the adjacency of the tumor to risk organs or first or salvage treatment. The 3‐year overall survival rates for RFA and radiotherapy patients were comparable (69.1%; 95% CI, 58.2‐77.7; and 70.4%; 95% CI, 58.5‐79.4, respectively; P = 0.86). Conclusion: Radiotherapy has excellent local control and comparable overall survival in patients with well‐compensated liver function, exhibiting advantageous characteristics and compensating for the deficiencies of other treatment modalities; radiotherapy appears to be an acceptable alternative treatment option for patients who are not candidates for RFA.
Background
A phase 3, multinational, randomized, non-inferiority trial (REFLECT) compared the efficacy and safety of lenvatinib (LEN) and sorafenib (SOR) in patients with unresectable hepatocellular ...carcinoma (uHCC). LEN had an effect on overall survival (OS) compared to SOR, statistically confirmed by non-inferiority OS: median = 13.6 months vs. 12.3 months; hazard ratio (HR) 0.92, 95% confidence interval (CI) 0.79–1.06, and demonstrated statistically significant improvements in progression-free survival (PFS) and the objective response rate (ORR) in the overall population. The results of a subset analysis that evaluated the efficacy and safety of LEN and SOR in the Japanese population are reported.
Methods
The intent-to-treat population enrolled in Japan was analyzed.
Results
Of 954 patients in the overall population, 168 Japanese patients were assigned to the LEN arm (
N
= 81) or the SOR arm (
N
= 87). Median OS was 17.6 months for LEN vs. 17.8 months for SOR (HR 0.90; 95% CI 0.62–1.29). LEN showed statistically significant improvements over SOR in PFS (7.2 months vs. 4.6 months) and ORR (29.6% vs. 6.9%). The relative dose intensity of LEN and SOR in the Japanese population was lower than in the overall population. Frequently observed, related adverse events included palmar-plantar erythrodysaesthesia syndrome (PPES), hypertension, decreased appetite, and proteinuria in the LEN arm, and PPES, hypertension, diarrhea, and alopecia in the SOR arm.
Conclusions
The efficacy and safety of LEN in the Japanese population were similar to those in the overall population of REFLECT. With manageable adverse events, LEN is a new treatment option for Japanese patients with uHCC.
Trial registration ID
ClinicalTrials.gov. No. NCT01761266.
Display omitted
•Objective responses and survival were comparable between intent-to-treat (ITT) overall population and Asian cohort.•Median overall survival in Asian patients was similar across HCC ...aetiologies.•Nivolumab had a manageable safety profile in both the ITT overall population and Asian cohort.
Nivolumab, an immune checkpoint inhibitor, is approved in several countries to treat sorafenib-experienced patients with HCC, based on results from the CheckMate 040 study (NCT01658878). Marked differences exist in HCC clinical presentation, aetiology, treatment patterns and outcomes across regions. This analysis assessed the safety and efficacy of nivolumab in the Asian cohort of CheckMate 040.
CheckMate 040 is an international, multicentre, open-label, phase I/II study of nivolumab in adults with advanced HCC, regardless of aetiology, not amenable to curative resection or local treatment and with/without previous sorafenib treatment. This analysis included all sorafenib-experienced patients in the intent-to-treat (ITT) overall population and Asian cohort. The analysis cut-off date was March 2018.
There were 182 and 85 patients in the ITT population and Asian cohort, respectively. In both populations, most patients were older than 60 years, had BCLC (Barcelona Clinic Liver Cancer) Stage C disease, and had received previous systemic therapy. A higher percentage of Asian patients had HBV infections, extrahepatic metastases and prior therapies. Median follow-up was 31.6 and 31.3 months for the ITT and Asian patients, respectively. Objective response rates were 14% and 15% in the ITT population and Asian cohort, respectively. In the Asian cohort, patients with HBV, HCV or those who were uninfected had objective response rates of 13%, 14% and 21%, respectively. The median duration of response was longer in the ITT (19.4 months) vs. Asian patients (9.7 months). Median overall survival was similar between the ITT (15.1 months) and Asian patients (14.9 months), and unaffected by aetiology in Asian patients. The nivolumab safety profile was similar and manageable across both populations.
Nivolumab safety and efficacy are comparable between sorafenib-experienced ITT and Asian patients.
The CheckMate 040 study evaluated the safety and efficacy of nivolumab in patients with advanced hepatocellular carcinoma who were refractory to previous sorafenib treatment or chemotherapy. This subanalysis of the data showed that treatment responses and safety in patients in Asia were similar to those of the overall treatment population, providing support for nivolumab as a treatment option for these patients.
Clinical trial number: NCT01658878.
Background
To evaluate the efficacy and safety of cabozantinib in Japanese patients with advanced hepatocellular carcinoma (HCC) who had progressed following one or two lines of systemic therapy ...including sorafenib. An exploratory evaluation in sorafenib-naïve patients was performed.
Methods
In this open-label, single-arm, phase 2 trial, patients received oral cabozantinib 60 mg once daily. The primary endpoint was progression-free survival (PFS) rate at Week 24. Secondary endpoints included PFS, overall survival (OS), objective response rate (ORR, best response of complete/partial response), disease control rate (DCR, objective response or stable disease) and safety.
Results
Thirty-four patients received cabozantinib across 17 centers (prior sorafenib cohort,
n
= 20; sorafenib-naïve cohort,
n
= 14). PFS rate at 24 weeks was 59.8% 90% confidence interval (CI) 36.1–77.2% in the prior sorafenib cohort, 16.7% (90% CI 4.0–36.8%) in the sorafenib-naïve cohort and 40.1% (90% CI 24.8–55.0%) overall. Median PFS was 7.4 months for the prior sorafenib cohort, 3.6 months for the sorafenib-naïve cohort, and 5.6 months overall. OS rate at 6 months was 100.0%, 78.6% and 91.1%, respectively; DCR was 85.0%, 64.3% and 76.5%, respectively. The ORR was 0.0% for both cohorts. All patients required dose modifications due to adverse events, the most common of these were palmar–plantar erythrodysesthesia syndrome and diarrhea. Three patients (8.8%) discontinued due to adverse events other than disease progression.
Conclusions
Cabozantinib 60 mg/day has a favorable benefit/risk profile for Japanese patients with advanced HCC who have previously received one or two lines of systemic anticancer therapy including sorafenib. (Clinical trial registration: NCT03586973)
Hepatocellular carcinoma (HCC) has the third-highest incidence in cancers and has become one of the leading threats to cancer death. With the research on the etiological reasons for cirrhosis and ...HCC, early diagnosis has been placed great hope to form a favorable prognosis. Non-invasive medical imaging, including the associated contrast media (CM)-based enhancement scan, is taking charge of early diagnosis as mainstream. Meanwhile, it is notable that various CM with different advantages are playing an important role in the different imaging modalities, or even combined modalities. For both physicians and radiologists, it is necessary to know more about the proper imaging approach, along with the characteristic CM, for HCC diagnosis and treatment. Therefore, a summarized navigating map of CM commonly used in the clinic, along with ongoing work of agent research and potential seeded agents in the future, could be a needed practicable aid for HCC diagnosis and prognosis.
Background The discontinuation of antithrombotic drugs is recommended during endoscopic submucosal dissection (ESD) for gastric neoplasms; however, controversy remains as to whether antithrombotic ...drugs are risk factors for postoperative bleeding. Objective To determine the risk factors for post-ESD bleeding. Design Single-institution, retrospective review. Setting University hospital. Patients From June 2000 to December 2010, we treated 1192 gastric neoplasms in 1032 consecutive patients. Intervention The ESD procedures were performed by using the standard techniques. Antithrombotic drug therapy was principally interrupted preoperatively and was restarted when hemostasis was confirmed by second-look endoscopy. Main Outcome Measurements Risk factors for postoperative bleeding after ESD (early, delayed, and overall combined occurrence of bleeding during the first 5 postoperative days or thereafter) were analyzed by using logistic regression analysis. Results Among 1166 ESD-induced ulcer lesions, overall postoperative bleeding was evident in 62 lesions (5.3%); early and delayed bleeding occurred in 30 and 32 lesions (2.6% and 2.7%), respectively. Based on a multivariate analysis, a specimen size of >40 mm was the sole independent risk factor for overall bleeding. Moreover, oral antithrombotic drug therapy was selected as independent risk factor for delayed but not early bleeding, according to the multivariate analysis. The delayed bleeding rate in patients who had a specimen size of >40 mm and who used antithrombotic drugs was 11.6%. Limitations Retrospective design and single-site data collection. Conclusion Interruption of antithrombotic drug therapy may be adequate for preventing early post-ESD bleeding; however, reinitiating antithrombotic drug therapy is a significant independent risk factor for delayed post-ESD bleeding.
The efficacy of hepatic arterial infusion chemotherapy (HAIC) for advanced hepatocellular carcinoma (HCC) remains unclear. We conducted a multi-center randomized phase II study comparing a sequential ...HAIC-sorafenib regimen versus sorafenib alone as an initial therapy for HCC.
Patients were randomly assigned (ratio, 1:1) to receive sequential HAIC with cisplatin followed by sorafenib (HAIC group, n = 35) or sorafenib alone (sorafenib group, n = 33) as an initial therapy. The primary endpoint was the one-year survival rate. Secondary endpoint included overall survival (OS), the 2-year survival rate, the time-to-progression (TTP), the objective response rate (ORR), the disease control rate (DCR), and safety.
For the primary endpoint, the one-year survival rates were 46% in the HAIC group and 58% in the sorafenib group. The median OS period was 10.0 months (95% CI, 7.0-18.8) in the HAIC group and 15.2 months (95% CI, 8.2-19.7) in the sorafenib group (hazard ratio HR, 1.08; 95% CI, 0.63 to 1.86, P = 0.78). The median TTP, ORR and DCR in the HAIC group were 2.8 months (95% CI, 1.7-5.5), 14.3, and 45.7%, respectively, while those in the sorafenib group were 3.9 months (95% CI, 2.3-6.8), 9.1, and 45.5%, respectively. No unexpected adverse events related to HAIC or sorafenib were observed in either group.
Sequential HAIC with cisplatin and sorafenib does not improve the survival benefit, compared with sorafenib alone, when used as an initial therapy for advanced HCC. However, this study was underpowered in regard to its primary and secondary endpoints, so the results should be interpreted with caution.
UMIN ID 000006147 , registration data: August 11, 2011.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
AIM To evaluate whether pathologically early hepatocellular carcinoma(HCC) exhibited local tumor progression after radiofrequency ablation(RFA) less often than typical HCC.METHODS Fifty ...pathologically early HCCs tumor diameter(mm): mean, 15.8; range, 10-23; follow-up days after RFA: median, 1213; range, 216-2137 and 187 typical HCCs tumor diameter(mm): mean, 15.6; range, 6-30; follow-up days after RFA: median, 1116; range, 190-2328 were enrolled in this retrospective study. The presence of stromal invasion(namely, tumor cell invasion into the intratumoral portal tracts) was considered to be the most important pathologic finding for the diagnosis of early HCCs. Typical HCC was defined as the presence of a hyper-vascular lesion accompanied by delayed washout using contrastenhanced computed tomography or contrast-enhanced magnetic resonance imaging. Follow-up examinations were performed at 3-mo intervals to monitor for signs of local tumor progression. The local tumor progression rates of pathologically early HCCs and typical HCCs were then determined using the Kaplan-Meier method.RESULTS During the follow-up period for the 50 pathologically early HCCs, 49(98%) of the nodules did not exhibit local tumor progression. However, 1 nodule(2%) was associated with a local tumor progression found 636 d after RFA. For the 187 typical HCCs, 46(24.6%) of the nodules exhibited local recurrence after RFA. The follow-up period until the local tumor progression of typical HCC was a median of 605 d, ranging from 181 to 1741 d. Among the cases with typical HCCs, local tumor progression had occurred in 7.0%(7/187), 16.0%(30/187), 21.9%(41/187) and 24.6%(46/187) of the cases at 1, 2, 3 and 4 years, respectively. Pathologically early HCC was statistically associated with a lower rate of local tumor progression, compared with typical HCC, when evaluated using a log-rank test(P = 0.002). CONCLUSION The rate of local tumor progression for pathologically early HCCs after RFA was significantly lower than that for typical HCCs.
Enhanced imaging techniques have the overwhelming advantages of being noninvasive and sensitive enough to evaluate the microcirculation of lesions, thus making them accurate in the diagnosis of ...hepatic lesions. Unfortunately, there is very little research on and knowledge of the imaging features of a rare cancerous condition: hepatic angiosarcoma (HA).
In this study, we retrospectively collected the data of six patients who underwent both contrast-enhanced ultrasound (CEUS) and contrast-enhanced computed tomography (CECT), and subsequently obtained a definitive histopathologic diagnosis of HA. We described the imaging appearances of HA by comparing CEUS and CECT images. Furthermore, we analyzed these imaging characteristics from the perspective of histopathology and tumorigenesis. The study included the largest number (six) of histopathologically confirmed HA patients who had received CEUS examinations to date.
By offering readers comprehensive knowledge of contrast imaging, especially CEUS, in the diagnosis of HA, our study may reduce misdiagnosis and further improve treatment options.
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