Meeting NewsPerspective

Stereotactic body radiation shows sustained local control in hepatocellular carcinoma

Stereotactic body radiation therapy showed promising rates of local control and survival in patients diagnosed with early-stage hepatocellular carcinoma, according to a North American pooled analysis presented at Gastrointestinal Cancers Symposium.

“Stereotactic body radiation therapy is a noninvasive, ablative treatment for patients with hepatocellular carcinoma,” Ashwathy Susan Mathew, DNB, MBBS, MD, clinical fellow in the department of radiation oncology at Princess Margaret Cancer Centre, and colleagues wrote. “Outcomes similar to radiofrequency ablation have been observed post-stereotactic body radiation therapy for early-stage hepatocellular carcinoma, primarily from Asia. There are few North American series with long-term follow-up.”

Mathew and colleagues hypothesized that patients with HCC without vascular invasion who were ineligible for or experienced recurrence after standard local treatments would have improved OS after SBRT than historical controls treated with trans-arterial chemoembolization (TACE).

The collaborative analysis included 310 patients (median age, 69.6 years) with stage I to stage IIIa HCC treated with radical-intent SBRT at a minimum of 4.5 Gy/fraction between June 2003 and December 2016.

Overall, 23% of patients were Child-Pugh class B (21%) or C (2%), and 40% previously had unsuccessful liver-aimed therapies. Median tumor size was 2.4 cm (range, 0.5-18.1).

OS served as the study’s primary endpoint. Secondary endpoints included local progression, intrahepatic progression, distant progression and toxicity.

Median follow-up was 19.9 months.

The median prescribed dose of SBRT was 39 Gy in five fractions (range, 14-60 Gy in 2-6 fractions). The median biologically equivalent dose was 78.75 Gy (range, 23.8-180).

Researchers reported local control rates of 91.5% at 1 year, and 82.6% at 3 years and 5 years.

Only 4.2% of patients showed progression of the irradiated lesion as the initial site of recurrence.

Multivariable analysis found that the use of a breath-hold motion approach was significantly correlated with local control (P = .0098), but T stage, size and dose were not.

Overall, 37.9% of patients achieved 3-year OS and 23.5% achieved 5-year OS.

Researchers observed improved rates of 3-year OS among patients with Child Pugh A disease vs. Child Pugh B/C disease (43% vs. 22.6%) and among patients with alpha-fetoprotein levels less than 10 mg/L compared with 10 mg/L or greater (44.5% vs. 29.6%).

A total of 8.4% of patients received liver transplant after SBRT. These patients showed superior rates of 3-year OS (92% vs. 32.8%).

On multivariable analysis, improved OS appeared associated with baseline Child-Pugh A score (median OS, 30.3 months vs. 17.6 months; HR = 0.47; 95% CI, 0.33-0.66) and transplant after SBRT (median OS, not reached vs. 24 months; HR = .06; 95% CI, 0.01-0.23), whereas poorer OS was associated with higher pretreatment alpha-fetoprotein levels (21.1 months vs. 32.9 months; HR = 1.59; 95% CI, 1.17-2.16).

Grade 3 or higher luminal gastrointestinal organ toxicity occurred in 2.5% of patients, whereas a decrease in Child-Pugh score of two points or more occurred in 16.7% of patients 3 months following SBRT.

Grade 3 and higher liver enzyme elevations occurred in 12.6% of patients at baseline and in 8.1% at 3 months following SBRT. – by Jennifer Byrne

Reference:

Mathew AS, et al. Abstract 350. Presented at: Gastrointestinal Cancers Symposium; Jan. 17-19, 2019; San Francisco.

Disclosures: Mathew reports an immediate family member is employed with Sanofi. Please see the abstract for all other authors’ relevant financial disclosures.

Stereotactic body radiation therapy showed promising rates of local control and survival in patients diagnosed with early-stage hepatocellular carcinoma, according to a North American pooled analysis presented at Gastrointestinal Cancers Symposium.

“Stereotactic body radiation therapy is a noninvasive, ablative treatment for patients with hepatocellular carcinoma,” Ashwathy Susan Mathew, DNB, MBBS, MD, clinical fellow in the department of radiation oncology at Princess Margaret Cancer Centre, and colleagues wrote. “Outcomes similar to radiofrequency ablation have been observed post-stereotactic body radiation therapy for early-stage hepatocellular carcinoma, primarily from Asia. There are few North American series with long-term follow-up.”

Mathew and colleagues hypothesized that patients with HCC without vascular invasion who were ineligible for or experienced recurrence after standard local treatments would have improved OS after SBRT than historical controls treated with trans-arterial chemoembolization (TACE).

The collaborative analysis included 310 patients (median age, 69.6 years) with stage I to stage IIIa HCC treated with radical-intent SBRT at a minimum of 4.5 Gy/fraction between June 2003 and December 2016.

Overall, 23% of patients were Child-Pugh class B (21%) or C (2%), and 40% previously had unsuccessful liver-aimed therapies. Median tumor size was 2.4 cm (range, 0.5-18.1).

OS served as the study’s primary endpoint. Secondary endpoints included local progression, intrahepatic progression, distant progression and toxicity.

Median follow-up was 19.9 months.

The median prescribed dose of SBRT was 39 Gy in five fractions (range, 14-60 Gy in 2-6 fractions). The median biologically equivalent dose was 78.75 Gy (range, 23.8-180).

Researchers reported local control rates of 91.5% at 1 year, and 82.6% at 3 years and 5 years.

Only 4.2% of patients showed progression of the irradiated lesion as the initial site of recurrence.

Multivariable analysis found that the use of a breath-hold motion approach was significantly correlated with local control (P = .0098), but T stage, size and dose were not.

Overall, 37.9% of patients achieved 3-year OS and 23.5% achieved 5-year OS.

Researchers observed improved rates of 3-year OS among patients with Child Pugh A disease vs. Child Pugh B/C disease (43% vs. 22.6%) and among patients with alpha-fetoprotein levels less than 10 mg/L compared with 10 mg/L or greater (44.5% vs. 29.6%).

A total of 8.4% of patients received liver transplant after SBRT. These patients showed superior rates of 3-year OS (92% vs. 32.8%).

On multivariable analysis, improved OS appeared associated with baseline Child-Pugh A score (median OS, 30.3 months vs. 17.6 months; HR = 0.47; 95% CI, 0.33-0.66) and transplant after SBRT (median OS, not reached vs. 24 months; HR = .06; 95% CI, 0.01-0.23), whereas poorer OS was associated with higher pretreatment alpha-fetoprotein levels (21.1 months vs. 32.9 months; HR = 1.59; 95% CI, 1.17-2.16).

Grade 3 or higher luminal gastrointestinal organ toxicity occurred in 2.5% of patients, whereas a decrease in Child-Pugh score of two points or more occurred in 16.7% of patients 3 months following SBRT.

Grade 3 and higher liver enzyme elevations occurred in 12.6% of patients at baseline and in 8.1% at 3 months following SBRT. – by Jennifer Byrne

Reference:

Mathew AS, et al. Abstract 350. Presented at: Gastrointestinal Cancers Symposium; Jan. 17-19, 2019; San Francisco.

Disclosures: Mathew reports an immediate family member is employed with Sanofi. Please see the abstract for all other authors’ relevant financial disclosures.

    Perspective
    David H. Ilson

    David H. Ilson

    There is increasing interest in the role of potentially ablative doses of radiotherapy in local regional cancers not amenable to curative resection. 

    Mathew and colleagues reported results of a retrospective analysis from two North American institutions of the use of SBRT in patients with focal hepatocellular cancers not amenable to surgery or either percutaneous ablative or hepatic arterial intravascular therapy. Over a 13-year period through 2016, researchers reviewed 310 patients, nearly half of whom had failed prior regional therapy, a minority of whom had Child-Pugh class B/C liver disease (23%), and among whom the median tumor size was relatively small at 2.4 cm.

    Patients received a median of 39 Gy in five fractions, with doses ranging from 14 Gy to 60 Gy given in two to six fractions.

    Researchers observed encouraging rates of local control at 3 and 5 years of 82.6%, as well as relatively improved OS in Child-Pugh A score patients compared with B/C patients. Toxicity was acceptable. 

    Results for this relatively noninvasive therapy modality are encouraging. However, limited data are available comparing this approach with other liver-directed therapies, including transarterial embolization with or without chemotherapy, radioembolization and percutaneous radiofrequency ablation. The potential to combine SBRT with other locally ablative strategies — or the use of proton therapy to reduce hepatoxicity, particularly in patients with more compromised liver function who may be less tolerant of conventional radiotherapy — remains to be established.

    Randomized trials employing SBRT include two ongoing NRG studies, a comparison of sorafenib (Nexavar, Bayer) with or without SBRT (RTOG 1112, NCT01730937), and a head-to-head comparison of proton therapy vs. SBRT (NRG-G1003, NCT03186898). The benefit of such therapies also will be limited to patients with liver-confined disease.

    • David H. Ilson, MD, PhD
    • HemOnc Today Editorial Board Member
      Memorial Sloan Kettering Cancer Center

    Disclosures: Ilson reports no relevant financial disclosures.

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