Is radiotherapy effective in treating liver cancer?29 Oct 2015
Delivery of higher doses of radiotherapy improves local control and overall survival in inoperable intrahepatic cholangiocarcinoma (IHCC), a retrospective dose analysis study has demonstrated.
A biologic equivalent dose (BED) greater than 80.5 Gy seems to be an ablative dose of radiotherapy for large IHCCs, with long-term survival rates that compare favorably with resection, according to Christopher H. Crane, MD, at the University of Texas MD Anderson Cancer Center in Houston TX, and colleagues.
Surgery is considered the only potentially curative treatment for IHCC, but only approximately 30% of patients have operable disease. Median survival for patients with inoperable IHCC is 7-12 months.
Clinical trial details
The study examined 79 consecutive patients with inoperable IHCC identified and treated with definitive radiotherapy at the University of Texas MD Anderson Cancer Center from 2002 to 2014. The median tumor size at diagnosis was 7.9 cm (range, 2.2 to 17 cm).
Prior to radiotherapy, 70 patients (89%) received systemic chemotherapy. Radiotherapy doses were 35 to 100 Gy in 3 to 30 fractions for a biologic equivalent dose of 80.5 Gy.
Median follow-up time for patients alive at the time of analysis was 33 months. Median overall survival time after diagnosis was 30 months; the 3-year overall survival rate was 44%.
The analysis of the results showed that:
- Biologic equivalent dose as a continuous variable significantly affected local control and overall survival
- Three-year overall survival rate for patients receiving biologic equivalent dose greater than 80.5 Gy was 73% versus 38% for those receiving lower doses and
- Three-year local control rate was significantly higher (78%) after a biologic equivalent dose greater than 80.5 Gy when compared to lower doses.
- Lower doses of radiation are not as effective
Radiation dose was the single most important prognostic factor, and higher doses correlated with an improved local control rate and overall survival, reported Crane and colleagues. There were no significant treatment-related toxicities.
"Ablative radiation doses given over 3 to 5 weeks with a stereotactic technique leads to durable local tumor control and a 2- to 3-year median survival benefit for patients with intrahepatic cholangiocarcinoma" Crane said.
“A major survival benefit for patients with inoperable IHCC”
If dose constraints to the liver, bile duct, stomach, and bowel can be met and image guidance used to ensure safe delivery of the dose, then higher total radiotherapy doses and higher doses delivered per fraction to achieve biologic equivalent dose greater than 80.5 Gy should be considered for all patients undergoing definitive radiotherapy for IHCC, said the investigators.
"The findings support the use of 67.5 Gy in 15 fractions in the current phase 3, NRG-GI001 randomized trial evaluating whether the addition of radiotherapy to chemotherapy affects survival," the authors wrote.
"Controlling the primary tumor with high-dose radiation produces a major survival benefit for patients with inoperable IHCC," Crane and colleagues reported. "Treatment with ablative doses of radiotherapy using high-quality daily CT image guidance with inspiration breath-hold gating can achieve survival times comparable to those achieved with resection."
"Physicians should consider the use of ablative radiation as consolidation after chemotherapy," Crane told. However, he added, there are specific solutions to the problem of organ motion and high quality image guidance is needed to deliver this treatment. "There is a significant learning curve for radiation oncologists," he pointed out. The preferred option for patients is enrollment on the NRG GI 001 trial and prospective quality assurance for individual cases, he said.
Although ablative RT prolongs survival substantially, large numbers of patients still develop distant metastatic disease, said Crane. "The focus of future research will be on combining immunotherapy ablative radiation therapy and on the development of more effective systemic therapy," he said.Source: MedPage Today