Skip Navigation

This Article
Right arrow Abstract Freely available
Right arrow FREE Full Text (PDF) Freely available
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrow Search for citing articles in:
ISI Web of Science (9)
Right arrow Request Permissions
Google Scholar
Right arrow Articles by Tokuuye, K
Right arrow Articles by Ishii, H
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Tokuuye, K
Right arrow Articles by Ishii, H
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

Japanese Journal of Clinical Oncology Pages 170-173

Technical Considerations for Fractionated Stereotactic Radiotherapy of Hepatocellular Carcinoma
Introduction
Materials And Methods
Results
Discussion
Acknowledgement
References

Technical Considerations for Fractionated Stereotactic Radiotherapy of Hepatocellular Carcinoma

Technical Considerations for Fractionated Stereotactic Radiotherapy of Hepatocellular Carcinoma Koichi Tokuuye1, Minako Sumi1, Hiroshi Ikeda1, Yoshikazu Kagami1, Shigeyuki Murayama1, Hidetsugu Nakayama1, Mitsuhiko Kawashima1 and Hiroshi Ishii2

Departments of 1Radiation Therapy and 2Internal Medicine, National Cancer Center Hospital, Tokyo, Japan

Technical aspects of fractionated stereotactic radiotherapy for solitary hepatocellular carcinoma have been investigated. Precise positioning of the patient and substantial reduction of the liver movement due to respiration were achieved by placing the patient ventrally on the treatment couch without a body cast. Repeated CT examinations were required for verification of tumor targeting. Though there were geometrical limitations on gantry rotation when the linac couch was rotated from its standard position, dose distributions obtained were found to be excellent. A patient with a small solitary lesion in the posterior segment of the liver received 52 Gy in 13 fractions over 29 days. He tolerated the treatment well without experiencing any morbidities or deterioration of liver functions. Three months later his [alpha]-fetoprotein value returned to normal and CT examinations revealed tumor shrinkage as well as a reduction in the viability of the tumor cells. The results suggest that it is possible to overcome technical difficulties associated with fractionated stereotactic radiotherapy of intraabdominal tumors.

Key words: stereotactic radiotherapy - extracranial tumor - liver tumor

INTRODUCTION

For the last decade linac-based stereotactic radiotherapy and/or radiosurgery have proved an effective therapy for benign intracranial lesions and more recently for malignant lesions (1 ). Although this non-coplanar irradiation approach, when applied to the treatment of extracranial tumors, does not have the same advantage as it has when used for the treatment of intracranial tumors, it appears a very effective modality in some cases. Lax et al. used eight different non-coplanar ports and obtained good dose distributions for single dose stereotactic radiotherapy of abdominal tumors (2 ). Hamilton et al. applied stereotactic radiosurgery to the treatment of previously irradiated paraspinal neoplasms (3 ).

As fractionated doses are more effective than single doses in the treatment of malignant tumors (4 ), we have used fractionated stereotactic radiotherapy for patients with small intracranial tumors and have obtained very encouraging results (5 ). Recently we applied the same technique to a patient with hepatocellular carcinoma who could not have been treated otherwise. This communication describes the technical aspects of stereotactic radiotherapy of small solitary liver tumors (2 ,6 ).

MATERIALS AND METHODS

A 70 year-old man presented with a solitary hepatocellular carcinoma lesion in the posterior segment which measured 4 * 3 * 3 cm. Currently, segmentectomy, transarterial embolization, percutaneous ethanol injection and their combinations are the standard approaches in the treatment of small liver tumors. However, segmentectomy was not possible for this patient because of his poor liver function. Transarterial embolization was considered inappropriate because of inadequate arterial blood supply to the involved segment. Percutaneous ethanol injection was judged ineffective because of the large tumor size. Therefore, as a last resort, radiotherapy was chosen for this patient. Considering the fact that good local control and increased survival rates have been reported in patients with solitary liver lesions when treated with high dose proton beams (7 ), it was decided to treat this patient with stereotactic radiotherapy.

Prior to undergoing radiotherapy, the extent of liver movement due to respiration was estimated by measuring the extent of movements of the diaphragm radiographically and was found to be ~2 cm. However, the hepatic movement was reduced to <1 cm when the patient wore an abdominal pressure belt or just simply lay in a ventral position. Since the former interfered with reference skin markers and the tumor was located in the posterior segment of the liver, it was decided to treat the patient in the ventral position without a belt or a body cast. After the patient was placed on the treatment couch, the jaw and arms were strapped in place, and three reference points were marked on the skin according to horizontal and vertical CT laser beams. CT scans (CT 9800, General Electrics, Fairfield, CT, USA) were then taken at 5 mm intervals around the tumor region, and at longer intervals in the adjacent region. These 5 mm slices were used for delineating the target volume and the liver contour. Coordinates for the isocentric position of the tumor with reference points were established using a CT simulator (RT marker, Yokogawa Medical Co Ltd, Tokyo Japan).

We used a 6 MV linac unit (NELAC 1012A, NEC, Tokyo) with a 360o rotatable gantry at a source axis distance of 100 cm, and a 180o rotatable treatment couch. Since the gantry rotation was restricted by the couch position, the ranges of gantry rotation angles with respect to the couch position were determined by actual simulation. The angles were found to be 100o, 70o and 90o with corresponding couch positions of 45o, 90o and -45o respectively (Fig. 1 ) from the standard conventional radiotherapy couch position.


Figure 1. (a), Standard couch position (viewed end-on to the patient), showing the gantry above the patient and also the possible 360o rotation of the gantry. (b), Couch at 90o to its position in (a): gantry rotation is restricted by this couch position.

All the CT data were fed to a dose calculation system (FOCUS, CMS-Kanematsu Medical, Tokyo Japan). The field size used was 5 * 5 cm through built-in four-leaf collimators. Since the rotating radiation beams overlapped both in the areas 60o anterior and posterior of the isocenter of the treatment volume during treatment, these regions were not irradiated when the couch was at its normal position. Arms were strapped to the couch to avoid free movement. After adjusting the tumor's isocenter to that of the linac, the patient was irradiated according to the simulation. After each irradiation, positioning errors were found to be <5 mm when measured with linac's horizontal and vertical laser beams. To ensure the correct positioning for fractionated therapy, the 5 mm CT slices were taken at the tumor region before the first treatment and after every third treatment. A dose of 52 Gy in 13 treatments in 29 days was delivered to the tumor.

RESULTS

Evaluation of dose-volume histograms (DVH) calculated for stereotactic radiotherapy (SRT), conformal radiotherapy and conventional radiotherapy lead to the employment of SRT for the patient since it provided the best dose distributions. The patient tolerated the treatment well without experiencing any morbidities or deterioration of liver functions. Repeated CT examinations to adjust isocenters revealed the targeting error to be <5 mm. Three months after the treatment, his elevated AFP value had returned to a normal level and the CT examination suggested tumor shrinkage as well as reduction in the viability of the tumor cells (Fig. 2 ). The patient remained in good general condition 10 months after the treatment.


Figure 2.CT images taken (a) before and (b) three months after treatment. The latter shows reduced tumor viability.

DISCUSSION

There are several obstacles to overcome in the stereotactic radiotherapy of liver tumors when a relatively small tumor volume is irradiated through a small radiation field. The first is to ensure the location of the tumor where external skin marks are not reliable. Furthermore, when fractionated therapy is employed, reproducibility of accurate positioning and set up is of considerable concern, yet frequent CT scans taken before and during the course of stereotactic radiotherapy revealed that positioning errors were within 5 mm without stereotactic body frames. Lax et al. however, found that when body frames were used the deviations in the transverse plane and in the longitudinal direction were within 7 mm and 10 mm respectively in all 28 patients (2 ).

The second obstacle concerning geometric miss is the movement of the liver due to respiration. In our case respiratory movements were reduced to within 1 cm when the patient lay in a ventral position, though the best approach may vary individually. Using a body cast Lax et al. were able to reduce the respiratory movements to within 1 cm (2 ).


Figure 3.Dose distributions for (a), stereotactic radiotherapy and (b), conformal radiotherapy.

The linac gantry has geometric rotational limitations when the treatment couch is moved from its standard position, and this is reflected in the dose distributions. According to Lawrence's biological model NTCP (normal tissue complication probability) (8 ), both conformal and stereotactic therapy are considered acceptable for the treatment of liver tumors. To select the best therapeutic approach for this patient, we compared dose distributions obtained for stereotactic and conformal radiotherapy (Fig. 3 ). Tumor DVHs showed that the target volume was uniformly covered by both approaches. However, normal liver tissue DVHs showed that stereotactic radiotherapy reduced the dose to the normal liver by 10-60% (Fig. 4 ). This was the reason that stereotactic radiotherapy was used for this patient. Lax et al. used eight different non-coplanar ports for their single dose stereotactic radiotherapy and achieved good dose distributions (2 ). Fractionated treatment was used in this study. However, it is unclear at this time if fractionated therapy is advantageous over high single dose therapy when the tumor size is small. Lax et al. gave a single dose of 20 Gy to their patients (2 ).


Figure 4.DVHs of normal liver tissue for stereotactic radiotherapy, conformal radiotherapy and conventional radiotherapy (parallel opposite ports and rectangle two ports with 45o wedges) were compared. Target volume was uniformly covered by each approach. Substantial reduction in radiation dose in the normal liver tissue was achieved by stereotactic radiotherapy. -, stereotactic radiotherapy; -----, conformal radiotherapy; ·······, conventional radiotherapy (parallel opposite ports); ·-·-·-·-·, conventional radiotherapy (rectangle two ports).

Current treatment options available for patients with hepatocellular carcinoma are surgical resection, transarterial embolization (TAE) and percutaneous ethanol injection (PEI) (9 -11 ). Although surgical resection is preferred because higher survival rates are expected (9 ), most patients suffer from advanced liver cirrhosis, and surgery is not frequently performed. Though TAE and PEI are alternatives for medically or technically unresectable liver tumors, the former is ineffective when the blood supply to the tumor is insufficient or when extracapsular invasion is present (10 ). The latter is not effective for large tumors or those invading extracapsularly (11 ). Stereotactic radiotherapy is also limited to those who present relatively small tumors. It is of interest to compare both the local control and survival in patients treated by surgery, TAE, PEI and stereotactic radiotherapy.

Further technical improvements are necessary for stereotactic radiotherapy of liver tumors. Firstly, movement due to respiration might be offset by couch movements synchronized with respiration, or by gating, synchronous with respiratory movements, the beam output during gantry rotations, as performed during proton therapy. Secondly, irradiation of the surrounding normal tissue may be reduced if the field size can be modulated according to the tumor shape during gantry rotations. Thirdly, geometrical limitations on gantry rotation when the linac couch is rotated from its standard position may be eased if the linac's source axis distance is made considerably longer than 100 cm. Since rotational angles of the linac gantry and the treatment couch depend on the tumor location, there is no standard approach for liver tumors. The best approach is only found by individual simulation studies.

Acknowledgement

The study was supported in part by a Grant-in-Aid for Cancer Research (5-45) from the Ministry of Health and Welfare of the Japanese Government.

References

1. Larson DA, Bova F, Eisert D, Kline R, Loeffler J, Lutz W et al. Current radiosurgery practice: results of an ASTRO survey. Int J Radiat Oncol Biol Phys 1994;28:523-6. MEDLINE Abstract

2. Lax I, Blomgren H, Näslund I, Svanström. Stereotactic radiotherapy of malignancies in the abdomen. Acta Oncol 1994;33:677-83. MEDLINE Abstract

3. Hamilton AJ, Lulu BA, Fosmire H, Sttea B, Cassady JR. Preliminary clinical experience with linear accelerator-based spinal stereotactic radiosurgery. Neurosurgery 1995;36:311-8. MEDLINE Abstract

4. Brenner DJ, Martel MK, Hall EJ. Fractionated regimens for stereotactic radiotherapy of recurrent tumors in the brain. Int J Radiat Oncol Biol Phys 1991;21:819-24. MEDLINE Abstract

5. Tokuuye K, Akine Y, Tokita N, Satoh M, Churei H, Tsukiyama I et al. Linac-based small-field radiotherapy for brain tumors. Radiother Oncol 1993;27:55-8. MEDLINE Abstract

6. Haken RKT, Lawrence TS, McShan DL, Tesser RJ, Fraass BA, Lichter AS. Technical consideration in the use of 3-D beam arrangements in the abdomen. Radiother Oncol 1991;22:19-28.

7. Matsuzaki Y, Osuga T, Saito Y, Chuganji Y, Tanaka N, Shoda J et al. A new, effective, and safe therapeutic option using proton irradiation for hepatocellular carcinoma. Gastroenterology 1994;106:1032-41. MEDLINE Abstract

8. Lawrence TS, Haken RKT, Kessler ML, Robertson JM, Lyman JT, Lavigne ML et al. The Use of 3-D Dose Volume Analysis to Predict Radiation Hepatitis. Int J Radiat Oncol Biol Phys 1992;23:781-8. MEDLINE Abstract

9. Kanematsu T, Matsumata T, Shirabe K, Sugimachi K, Sakamoto S, Nawata H et al. A comparative study of hepatic resection and transcatheter arterial embolization for the treatment of primary hepatocellular carcinoma. Cancer 1993;71:2181-6. MEDLINE Abstract

10. Taniguchi K, Nakata K, Kato Y, Sato Y, Hamasaki K, Tsuruta S. Treatment of hepatocellular carcinoma with transcatheter arterial embolization. Cancer 1993;73:1341-5.

11. Ishii H, Okada S, Nose H, Okusaka T, Yoshimiri M, Takayama T et al. Local recurrence of hepatocellular carcinoma after percutaneous ethanol injection. Cancer 1996;77:1792-6. MEDLINE Abstract

Received September 18, 1996; accepted December 17, 1997
For reprints and all correspondence: Koichi Tokuuye, Department of Radiation Therapy, National Cancer Center Hospital, 1-1, Tsukiji 5-chome, Chuo-ku, Tokyo, 104, Japan
Abbreviations: DVH, dose-volume histogram; SRT, stereotactic radiotherapy; TAE, transarterial embolization; PEI, percutaneous ethanol injection.

This page is run by Oxford University Press, Great Clarendon Street, Oxford OX2 6DP, as part of the OUP Journals
Comments and feedback: www-admin{at}oup.co.uk
Last modification: 19 May 1998
Copyright© Japanese Journal of Clinical Oncology, 1997.
Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?


This article has been cited by other articles:


Home page
 JCOHome page
K. K. Herfarth, J. Debus, F. Lohr, M. L. Bahner, B. Rhein, P. Fritz, A. Hoss, W. Schlegel, and M. F. Wannenmacher
Stereotactic Single-Dose Radiation Therapy of Liver Tumors: Results of a Phase I/II Trial
J. Clin. Oncol., January 1, 2001; 19(1): 164 - 170.
[Abstract] [Full Text] [PDF]

This Article
Right arrow Abstract Freely available
Right arrow FREE Full Text (PDF) Freely available
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrow Search for citing articles in:
ISI Web of Science (9)
Right arrow Request Permissions
Google Scholar
Right arrow Articles by Tokuuye, K
Right arrow Articles by Ishii, H
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Tokuuye, K
Right arrow Articles by Ishii, H
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?