Helical tomotherapy (HT), an image-guided, intensity-modulated, radiation therapy technique, allows for precise targeting while sparing normal tissues. We retrospectively assessed the feasibility and tolerance of the hepatobiliary HT in 9 patients. A total dose of 54 to 60 Gy was prescribed (1.8 or 2 Gy per fraction) with concurrent capecitabine for 7 patients. There were 1 hepatocarcinoma, 3 cholangiocarcinoma, 4 liver metastatic patients, and 1 pancreatic adenocarcinoma. All but one patient received previous therapies (chemotherapy, liver radiofrequency, and/or surgery). The median doses delivered to the normal liver and to the right kidney were 15.7 Gy and 4.4 Gy, respectively, below the recommended limits for all patients. Most of the treatment-related adverse events were transient and mild in severity. With a median followup of 12 months, no significant late toxicity was noted. Our results suggested that HT could be safely incorporated into the multidisciplinary treatment of hepatobiliary or pancreatic malignant disease.
Majority of patients who develop either liver malignancy (metastasis or hepatobiliary primaries) have unresectable disease [
Literature concerned with modelling liver tolerance indicate that high doses of radiation therapy can be delivered without significant toxicity, as long as a certain amount of normal liver is spared [
Between May 2008 and July 2010, 9 patients who underwent a course of HT (Hi-Art system, TomoTherapy, Madison, wis, USA) in the Radiation Department of the Institut Curie for malignant hepatic lesions entered in our study. The baseline characteristics of the nine enrolled patients as well as the treatment details are listed in Table
Patient and disease characteristics.
Patient | Sex | Age | Performance Status (ECOG) | Primary tumour site | Previous therapies | Location/number/size of liver lesions |
---|---|---|---|---|---|---|
1 | M | 51 | 0 | Rectum Ad. | Partial liver resection | Hepatic dome 3 lesions (34; 10; 9 mm) |
2 | M | 42 | 0 | Cholangio | Biliary stent | Diffuse periductal infiltration Not measurable |
3 | F | 73 | 2 | Colon Ad. | CT | Posterior to the right portal branch 1 lesion (20 mm) |
4 | F | 60 | 0 | Pancreatic Ad. | CT | Pancreatic mass 1 lesion (40 mm) |
5 | F | 72 | 0 | Cholangio. | Extensive hepatobiliary surgery | Hilar region (no macroscopic disease) |
6 | M | 64 | 1 | Colon Ad. | Colon surgery | Perihilar metastasis 1 lesion (70 mm) |
7 | M | 63 | 0 | HepatoC. | Left hepatectomy | Adjacent to the hepatic vein trunk (1 lesion-36 mm) |
8 | F | 80 | 0 | Colon Ad. | CT | Hepatic dome 1 lesion (10 mm) |
9 | F | 48 | 1 | Cholangio | No | Hilar infiltration (20 mm) |
Abbreviations: HT: helical tomotherapy; M: male; F: female; Ad: adenocarcinoma; Cholangio: cholangiocarcinoma; HepatoC: hepatocarcinoma; CT: chemotherapy; RT: radiation therapy; RF: radiofrequency ablation
Patients were immobilized for initial simulation and for treatment with the two arms above the head in a body frame. Simulation was performed in a large bore computed tomography (CT) (Aquilion LB, Toshiba medical, Puteau, France SA) of 90 cm aperture. Images were acquired with 3-mm slice thickness from the mid-neck to the pelvis. Intravenous contrast was used to facilitate the appreciation of the tumour volume. Planning images are obtained by a four-dimensional CT (4D-CT) to assess respiratory motion. Regular breathing can lead to organ motions up to several centimeters which are taken into account by adding a specific margin around the target volume. The CT data was transferred to a linac-based planning system (Eclipse 3D version 8.1; Varian Medical Systems Inc., Palo Alto, USA) for delineating target volume and organs at risk (OAR). The gross tumour volume (GTV) was contoured manually corresponding to the tumour volume seen in the CT scan and in the co registered MRI images [
Dosimetric constraints for each organ at risk: recommended dose-volume limits from Quantec [
Normal liver | Median dose <28 Gy (in 2-Gy fractions) |
V30 < 50% | |
Right kidney | Maximum dose of 20 Gy to the total kidney |
Mean dose < 18 Gy | |
Right lung | V20 < 20% |
Spinal cord | Maximum dose of 45 Gy |
The dosimetric results are listed in Table
Treatment characteristics and dosimetric results.
Patients | Radiation dose | Concurrent capecitabine (mg·m²·day) | Median dose to the PTV | PTV | Normal liver volume | Normal liver V30 | Median normal liver dose (Gy) | Median right kidney dose (Gy) |
---|---|---|---|---|---|---|---|---|
1 | 54 Gy | no | 56.6 | 417.7 | 1244 | 8 | 25.5 | 1.7 |
2 | 54 Gy | 1500 | 57.2 | 381 | 1726.2 | 37 | 25.9 | 5.3 |
3 | 60 Gy | 1500 | 61 | 268 | 1424,3 | 12 | 12.1 | 1.5 |
4 | 54 Gy | 1500 | 55.5 | 671.9 | 1653.9 | 7,5 | 13.2 | 9.7 |
5 | 54 Gy | 1600 | 54.1 | 174.6 | 892.9 | 17.5 | 15.7 | 4.4 |
6 | 54 Gy | no | 54 | 262.6 | 857 | 30 | 22.1 | 2.1 |
7 | 60 Gy | no | 61.1 | 121 | 1160.1 | 10 | 14.3 | 1.6 |
8 | 54 Gy | 1500 | 54 | 93.9 | 1272.3 | 6 | 9.7 | 4.5 |
9 | 54 Gy | 1500 | 54 | 275.9 | 1484.1 | 37.2 | 25.6 | 4.5 |
Distribution of isodoses with HT treatment planning in the patient 8 (hepatic dome metastasis) in axial and frontal representation. The different doses as well as the target volumes/organs at risk are represented with different colors. Red color represents the target volume dose (>54 Gy). Green color represents lower radiation doses of 30 Gy.
Distribution of isodoses with HT treatment planning in the patient 9 (cholangiocarcinoma) and the corresponding dose-volume histogram. The different doses as well as the target volumes/organs at risk are represented with different colors. Red color represents the target volume dose (>54 Gy). Green color represents lower radiation doses of 30 Gy.
Toxicities were assessed using the Radiation Therapy Oncology Group/National Cancer Institute Common Toxicity Criteria, version 3 morbidity scale [
Acute clinical and biological adverse events: maximum toxicity grade per patient (Radiation Therapy Oncology Group/National Cancer Institute Common Toxicity Criteria, version 3) [
Patient | Nausea | Pain | Diarrhea | Fatigue | Thrombopenia | Cytolysis | Cholestasis |
---|---|---|---|---|---|---|---|
Patient 1 | 0 | 0 | 0 | 0 | 1 | 1 | 1 |
Patient 2 | 0 | 0 | 0 | 1 | 2 | 0 | 1 |
Patient 3 | 0 | 0 | 0 | 1 | 0 | 0 | 1 |
Patient 4 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
Patient 5 | 1 | 0 | 0 | 1 | 0 | 0 | 0 |
Patient 6 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
Patient 7 | 0 | 0 | 0 | 0 | 1 | 0 | 0 |
Patient 8 | 0 | 0 | 0 | 1 | 1 | 0 | 0 |
Patient 9 | 1 | 1 | 0 | 1 | 0 | 1 | 4 |
One patient experienced cytolysis grade 2, ten weeks after the HT course. A persistent thrombopenia grade 2 and cholestasis grade 1 (more than 4 months) occurred in one patient with progressive disease confirmed 4 months after the end of the radiation treatment. No radiation-induced liver disease was reported during the months following the HT.
After completing chemoradiotherapy, follow up was performed at 1–3 month intervals thereafter. The tumor response was assessed with follow-up CT scans. At study analysis, all but one patient, who died from progressive disease, were still alive. The median duration of followup after the HT course was 12 months (4–32). The cholangiocarcinoma patient treated in a neoadjuvant setting underwent successful cadaveric liver transplant 3 months after chemoradiotherapy with a complete histological response and remains disease-free 2 years later as the cholangiocarcinoma patient treated in an adjuvant setting. The pancreatic adenocarcinoma patient remains disease-free during 10 months then bone metastasis and local progression occurred. The hepatocellular carcinoma patient attained complete clinical remission after the helical Tomotherapy. Two years later, however, this patient experienced lung metastasis and local hepatic progression. Only one in-field progression (progression of disease inside the targeted tumor volume) occurred in the melanoma metastatic patient (patient 1), who died from his progressive disease, while the 2 colorectal metastatic patients developed exclusively out-of-field (patient 8) and distant progression without local relapse (patient 9).
Radiation oncology has seen the development of new technology which offers significant improvements in local control and reductions in toxicity. Increased doses >50 Gy with non-3D techniques improved tumor control marginally but were associated with a relatively high incidence of liver and gastrointestinal toxicity [
Until recently, modern radiation therapies were studied for
The use of HT for
The use of high-precision external beam radiotherapy can be complementary or an alternative to other treatments. For example, radiation may be offered to patients with large tumors that exceed the size that can be treated by radiofrequency ablation or surgical resection. The shrinkage of these lesions could enable other local treatment. Moreover, a lesion that is treated by chemoembolization may be found to have an alternate vascular supply that cannot be occluded. Radiation can play a complementary role in these cases and be added to this modality. One study demonstrated that in HCC patients who had failed transarterial chemoembolization, local radiation induced an additional tumor response [
We reported, here, our preliminary experience of the use of HT in various hepatobiliary malignant diseases as a way of understanding the perspectives offered by such a modern radiotherapeutic technique. Further investigations like comparative planning studies and longer followups are needed to confirm the dosimetric and clinical benefits offered by the HT over standard techniques or other new technique such dynamic arc therapy.
No potential conflict of interests relevant to this paper was reported.