Whole-liver Radiation Research Articles

Successful treatment of unresectable advanced rectal cancer with liver metastases by hemostasis re-irradiation of the rectal cancer and palliative low-dose whole-liver radiation therapy: a case report

A 72-year-old man was admitted to the hospital with fatigue. Colonoscopy revealed a 50 × 50mm rectal tumor with bleeding. Based on close inspection, he was diagnosed with unresectable advanced rectal cancer with multiple liver metastases. Chemotherapy was administered as 10 cycles of bevacizumab + mFOLFOX6 and 7 cycles of bevacizumab + FOLFIRI. Nine months later, he presented with hematochezia and progression of anemia. It was difficult to stop the bleeding via endoscopy. He underwent radiation therapy (39Gy in 13 fractions), and hemostasis was confirmed. Then, further chemotherapy was performed with 3 cycles of bevacizumab + FOLFIRI and 2 cycles of TAS102. However 14months after the initial visit, he presented with right hypochondralgia and abdominal fullness due to the progression of multiple liver metastases. Palliative low-dose whole-liver radiation therapy (WLRT) (30Gy in 10 fractions) was performed. He developed Grade 2 nausea, but his right hypochondralgia reduced, liver dysfunction improved, and he successfully completed radiotherapy. At approximately the same time his anemia progressed, and colonoscopy revealed recurrent bleeding from the tumor. Re-irradiation (15Gy in 5 fractions) of the rectal tumor was carried out and a blood transfusion was performed for the bleeding. He was discharged after confirmation the anemia had not progressed. Few reports have been published on the use of both palliative re-irradiation to stop bleeding from rectal cancer and palliative low-dose WLRT. Based on our experience with this case, we believe that palliative radiotherapy can be useful in treating patients with a poor prognosis.

Dose Response for Veno-Occlusive Disease After Whole-Liver Radiation Therapy: A Preliminary Report From the Pediatric Normal Tissue Effects in the Clinic (PENTEC) Group

Dose Response for Veno-Occlusive Disease After Whole-Liver Radiation Therapy: A Preliminary Report From the Pediatric Normal Tissue Effects in the Clinic (PENTEC) Group

Changes in Liver Volume Observed Following Sorafenib and Liver Radiation Therapy

The purpose of this study was to quantify unexpected liver volume reductions in patients treated with sorafenib prior to and during liver radiation therapy (RT). Fifteen patients were treated in a phase 1 study of sorafenib for 1week, followed by concurrent sorafenib-RT (in 6 fractions). Patients had either focal cancer (treated with stereotactic body RT [SBRT]) or diffuse disease (treated with whole-liver RT). Liver volumes were contoured and recorded at planning (day 0) from the exhale CT. After 1week of sorafenib (day 8), RT image guidance at each fraction was performed using cone beam CT (CBCT). Planning liver contours were propagated and modified on the reconstructed exhale CBCT. This was repeated in 12 patients treated with SBRT alone without sorafenib. Three subsequent patients (2sorafenib-RT and 1 non-sorafenib) were also assessed with multiphasic helical breath-hold CTs. Livervolume reductions on CBCT were observed in the 15 sorafenib-RT patients (median decrease of 68cc, P=.02) between day 0 and 8; greater in the focal (P=.025) versus diffuse (P=.52) cancer stratum. Seven patients (47%) had reductions larger than the 95% intraobserver contouring error. Liver reductions were also observed from multiphasic CTs in the 2 additional sorafenib-RT patients between days 0 and 8 (decreases of 232.5cc and 331.7cc, respectively) and not in the non-sorafenib patient (increase of 92cc). There were no significant changes in liver volume between planning and first RT in 12 patients with focal cancer treated with SBRT alone (median increase, 4.8cc, P=.86). Liver volume reductions were observed after 7days of sorafenib, prior to RT, most marked in patients with focal liver tumors, suggesting an effect of sorafenib on normal liver. Careful assessment of potential liver volume changes immediately prior to SBRT may be necessary in patients in sorafenib or other targeted therapies.

Stereotactic body radiation therapy (SBRT) for liver metastases: A clinical review

For over half a century, conventionally fractionated whole-liver radiation has been used for the palliation of diffuse, symptomatic liver metastases. More recently, interest has grown in identifying subsets of patients with a limited disease burden where focal ablation of metastases may improve disease control and prolong survival. Although promising outcomes have been reached following resection of liver metastases, most patients are not resection candidates. Stereotactic body radiation therapy (SBRT) is a modern technique for the delivery of ablative, high-dose external beam radiation with subcentimeter accuracy. SBRT is supported by a large body of prospective clinical trials and has emerged as a highly effective, safe, and non-invasive therapy for hepatic metastases. The following review examines the evolution of hepatic radiation, focusing on the emergence of SBRT and its associated outcomes and clinical considerations.

A Phase I Clinical and Pharmacology Study Using Amifostine as a Radioprotector in Dose-escalated Whole Liver Radiation Therapy

Diffuse intrahepatic tumors are difficult to control. Whole-liver radiotherapy has been limited by toxicity, most notably radiation-induced liver disease. Amifostine is a prodrug free-radical scavenger that selectively protects normal tissues and, in a preclinical model of intrahepatic cancer, systemic amifostine reduced normal liver radiation damage without compromising tumor effect. We hypothesized that amifostine would permit escalation of whole-liver radiation dose to potentially control microscopic disease. We also aimed to characterize the pharmacokinetics of amifostine and its active metabolite WR-1065 to optimize timing of radiotherapy. We conducted a radiation dose-escalation trial for patients with diffuse, intrahepatic cancer treated with whole-liver radiation and intravenous amifostine. Radiation dose was assigned using the time-to-event continual reassessment method. A companion pharmacokinetic study was performed. Twenty-three patients were treated, with a maximum dose of 40 Gy. Using a logistical regression model, compared with our previously treated patients, amifostine increased liver tolerance by 3.3 ± 1.1 Gy (p = 0.007) (approximately 10%) with similar response rates. Peak concentrations of WR-1065 were 25 μM with an elimination half-life of 1.5 h; these levels are consistent with radioprotective effects of amifostine in patients. These findings demonstrate for the first time that amifostine is a normal liver radioprotector. They further suggest that it may be useful to combine amifostine with fractionated or stereotactic body radiation therapy for patients with focal intrahepatic cancer.

Radiation therapy for liver metastases

The liver is a common site of metastatic disease. Systemic therapy is most frequently the preferred therapy for patients with liver metastases, but surgical excision or tumor ablation strategies are often considered for patients with limited disease and favorable histology. Advances in radiation therapy technology made it possible to deliver potent biological doses to limited volumes of the liver with high precision in a few fractions. This method is known as stereotactic body radiation therapy (SBRT). Low-dose radiation therapy administered to the whole-liver radiation therapy (WLRT) is not regularly used for palliation of patients with massive liver metastases. The purpose of this review is to present an update of the most recent literature on SBRT and WLRT. Recently published studies confirm the role of SBRT as a highly effective treatment for ablation of liver metastases. The toxicity related to the therapy is mild or moderate. This treatment is indicated for patients with limited burden of intrahepatic and extrahepatic disease. Low-dose WLRT is a useful treatment for symptom palliation in patients with end-stage cancer and diffuse metastatic infiltration of the liver which became refractory to systemic treatment. SBRT and WLRT are highly efficient in the treatment of patients with liver metastases. However, prospective randomized trials in radiation therapy for liver metastases are warranted.

Final Results of a Phase I Whole-Liver Radiation Dose Escalation Trial using Amifostine as a Radioprotector

Final Results of a Phase I Whole-Liver Radiation Dose Escalation Trial using Amifostine as a Radioprotector

Phase I whole-liver radiation dose escalation trial using amifostine as a radioprotector

Phase I whole-liver radiation dose escalation trial using amifostine as a radioprotector

Phase I whole-liver radiation dose escalation trial using amifostine as a radioprotector

Phase I whole-liver radiation dose escalation trial using amifostine as a radioprotector

The treatment of colorectal liver metastases with conformal radiation therapy and regional chemotherapy

Whole-liver radiation, with or without chemotherapy, has been of modest benefit in the treatment of unresectable hepatic metastases from colorectal cancer. A Phase I/II study combining escalating doses of conformally planned radiation therapy (RT) with intraarterial hepatic (IAH) fluorodeoxyuridine (FdUrd) was performed. Twenty-two patients with unresectable hepatic metastases from colorectal cancer, 14 of whom had progressed after previous chemotherapy (2 with prior IAH FdUrd), were treated with concurrent IAH FdUrd (0.2 mg/kg/day) and conformal hepatic radiation therapy (1.5-1.65 Gy/fraction twice a day). The total dose of radiation given to the tumor (48-72.6 Gy) depended on the fraction of normal liver excluded from the high-dose volume. All patients were assessed for response, toxicity, hepatobiliary relapse, and survival. Median potential follow-up was 42 months. Eleven of 22 patients demonstrated an objective response, with the remainder showing stable disease. Actuarial freedom from hepatic progression was 25% at 1 years. The most common acute toxicity was mild to moderate nausea and transient liver function test abnormalities. There were three patients with gastrointestinal bleeding (none requiring surgical intervention) after the completion of treatment. Overall median survival was 20 months. The presence of extrahepatic disease was associated with decreased survival (p < 0.01). Combined conformal radiation therapy and IAH FdUrd can produce an objective response in 50% of patients with hepatic metastases from colorectal cancer. However, response was not durable, and hepatic progression was frequent. Improvements in hepatic tumor control for patients with metastatic colorectal cancer may require higher doses of conformal radiation and/or improved radiosensitization. In an effort to increase radiosensitization, we have recently initiated a clinical trial combining IAH bromode-oxyuridine, a thymidine analog radiosensitizer, with conformal high dose radiation therapy.

Treatment of primary hepatobiliary cancers with conformal radiation therapy and regional chemotherapy.

To develop more effective regional therapy for patients with unresectable primary hepatobiliary cancer using concurrent conformal radiation therapy and intraarterial hepatic (IAH) fluorodeoxyuridine (FdUrd). Twenty-six patients with unresectable, nonmetastatic primary hepatobiliary cancer were treated with concurrent IAH FdUrd (0.2 mg/kg/d) and conformal hepatic radiation therapy (1.5 to 1.65 Gy per fraction twice per day). The total dose of radiation administered to the tumor depended on the fraction of normal liver excluded from the high-dose volume. All patients were assessed for toxicity, hepatobiliary relapse, and survival; 17 patients were assessable for response (eight had cholangiocarcinoma not assessable by computed tomographic [CT] scan and one progressed distantly during treatment). The median potential follow-up duration was 27 months. Whole-liver radiation was administered to six patients with diffuse hepatocellular carcinoma (HCC). Eleven patients with localized HCC and nine with cholangiocarcinoma received focal radiation to a dose of 48 to 72.6 Gy. An objective response for assessable patients was observed in 11 of 11 patients treated with focal radiation, but only one of six patients treated with whole-liver radiation. Whole-liver radiation accounted for five of seven patients with > or = grade 3 toxicity and four of six local treatment failures. Two patients had nonfatal radiation hepatitis. The median survival duration for patients with localized hepatobiliary cancer was 19 months, while patients with diffuse HCC had a median survival duration of 4 months. The rate of actuarial freedom from hepatobiliary progression in patients with localized disease was 72% at 24 months. These findings suggest that three-dimensional planned focal liver radiation and IAH FdUrd can produce a high, durable response rate and an encouraging median survival duration in patients with nondiffuse, unresectable primary hepatobiliary cancer.

Therapy of liver tumors metastatic from colorectal cancer with whole-liver radiation combined with 5-FU, adriamycin, and methotrexate.

Twenty-seven patients with liver metastasis from colorectal cancer were treated with intrahepatic arterial chemotherapy and external radiotherapy consisting of 5-fluorouracil (5-FU) (10 mg/kg/day for 8 days), adriamycin (5 mg/m2/day for 7 days) and methotrexate (MTX) (240 mg/m2/X1), combined with 2,100 rads of whole liver irradiation. Twenty of these patients (74%) had previously received systemic chemotherapy. Of the 21 patients who could be fully evaluated, seven (33%) had an objective partial response and another 10 (48%) had stable disease following treatment. The median duration of survival for all patients after initiation of treatment was 6.5 months. Those patients responding to therapy survived longer (12.7 months) than those who had stable disease (5.5 months) or disease progression (2.5 months). The response rate was not affected by previous chemotherapy. Additionally, of the 14 patients with symptoms related to the disease, nine (64%) experienced substantial relief of these symptoms. Toxicity with the therapy used in this study was generally moderate. The median nadiR WBC was 3,500 cells/mm3; the median nadir platelet count, 121,000 cells/mm3. There was, however, one treatment-associated fatality from sepsis in a patient whose WBC was 900 cells/mm3.