Clinical Investigation
Prospective Longitudinal Assessment of Quality of Life for Liver Cancer Patients Treated With Stereotactic Body Radiation Therapy

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Purpose

To evaluate quality of life (QoL), an important outcome owing to poor long-term survival, after stereotactic body radiation therapy (SBRT) to the liver.

Methods and Materials

Patients (n=222) with hepatocellular carcinoma (HCC), liver metastases, or intrahepatic cholangiocarcinoma and Child-Pugh A liver function received 24-60 Gy of 6-fraction image-guided SBRT. Prospective QoL assessment was completed with the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core-30 (QLQ-C30) and/or Functional Assessment of Cancer Therapy-Hepatobiliary (FACT-Hep, version 4) questionnaires at baseline and 1, 3, 6, and 12 months after treatment. Ten HCC patients with Child-Pugh B liver function were also treated.

Results

The QLQ-C30 was available for 205 patients, and 196 completed the FACT-Hep. No difference in baseline QoL (P=.17) or overall survival (P=.088) was seen between the HCC, liver metastases, and intrahepatic cholangiocarcinoma patients. Appetite loss and fatigue measured by the QLQ-C30 clinically and statistically worsened by 1 month after treatment but recovered by 3 months. At 3 and 12 months after treatment, respectively, the FACT-Hep score had improved relative to baseline in 13%/19%, worsened in 36%/27%, and remained stable in 51%/54%. Using the QLQ-C30 Global Health score, QoL improved in 16%/23%, worsened in 34%/39%, and remained stable in 50%/38% at 3 and 12 months, respectively. Median survival was 17.0 months (95% confidence interval [CI] 12.3-19.8 months). Higher baseline scores on both FACT-Hep and QLQ-C30 Global Health were associated with improved survival. Hazard ratios for death, per 10-unit decrease in QoL, were 0.90 (95% CI 0.83-0.98; P=.001) and 0.88 (95% CI 0.82-0.95; P=.001), respectively. Tumor size was inversely correlated with survival.

Conclusions

Liver SBRT temporarily worsens appetite and fatigue, but not overall QoL. Stereotactic body radiation therapy is well tolerated and warrants comparison against other liver-directed therapies.

Introduction

Liver cancer generally portends poor prognosis. Metastatic disease is the most common cause and may develop in 40-50% of adult primary cancers, most commonly arising from colorectal, lung, or breast primary. Primary liver cancer incidence, mostly hepatocellular carcinoma (HCC), is increasing in North America owing to increasing hepatitis C and cirrhosis from nonalcoholic fatty liver disease and metabolic syndrome (1).

Surgery or transplant can potentially cure organ-confined primary liver cancer, but advanced disease or medical comorbidities render most patients ineligible for such treatments. Radiofrequency ablation (RFA) (2), transarterial chemoembolization (TACE) 3, 4, or systemic therapy with targeted agents like sorafenib 5, 6 can control disease and improve survival, but outcomes remain poor.

Stereotactic body radiation therapy (SBRT) refers to delivery of few (usually 3-6) doses of highly precise, conformal radiation therapy with high dose per fraction. These techniques have improved the therapeutic ratio of liver radiation therapy, with tumor control rates of 70-90% at 1-2 years reported.

Health-related quality of life (QoL) measures patients' perspectives on physical health, psychological state, independence, and social relationships (7). Because of poor long-term survival, QoL is an important posttreatment outcome to consider for liver cancer patients. Higher baseline QoL can predict improved survival 8, 9.

Literature regarding the effect of SBRT on QoL for liver cancer patients is sparse. We report QoL outcomes from a large, prospective cohort treated with SBRT for liver cancer.

Section snippets

Patients

Patients with HCC, intrahepatic cholangiocarcinoma (IC), or liver metastases (LM) were treated between March 2003 and May 2011. Eligibility and trial methodology has been described previously (10,12,13). Although the primary cohort consisted of patients with Child-Pugh A liver function, a small number of HCC patients with Child-Pugh B liver function were also treated. Institutional research ethics board approval was obtained.

Treatment

Treatment techniques have been previously described 10, 11, 12, 13, 14

Results

Of 222 treated patients, 205 were eligible for QoL analysis. Data are available for the QLQ-C30 in 205 patients and for the FACT-Hep in 196 patients. Figure 1 illustrates a Consolidated Standards of Reporting Trials diagram. Patient characteristics are summarized in Table 1. Compliance rates are summarized in Table 2. Table 3 summarizes mean QoL scores over time.

Discussion

Despite increasing utilization, and prospective studies describing favorable outcomes 10, 12, 13, 26, 27, 28, SBRT for liver cancer is still not included in practice guidelines 29, 30, 31. As acceptance grows, QoL outcomes relative to other modalities will increasingly factor into treatment decisions.

In our cohort, as in previous studies 8, 9, 23, baseline QoL significantly predicted OS. A meta-analysis (32) concluded that baseline QLQ-C30 Global Health/QoL score predicted OS for breast (P

Conclusions

Stereotactic radiation therapy for liver cancer may temporarily worsen appetite and fatigue at approximately 1 month after treatment. These effects quickly resolve, and QoL returns to baseline levels by 1 year. Other QoL domains do not show significant change from baseline after SBRT on 2 well-accepted QoL instruments. Stereotactic body radiation therapy is well-tolerated but requires comparison against other local therapies for liver cancer.

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    Note—An online CME test for this article can be taken at http://astro.org/MOC.

    Supported by National Cancer Institute of Canada grant 18207 (L.A.D.), and a Bayer research grant paid to the institution (L.A.D.).

    Conflict of interest: none.

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