Treatment of lymph node metastatic melanoma with carbon ion radiotherapy

ARTICLE

Auteur(s) : Hiroyuki Fujita¹, Hidefumi Wada¹, Katsuji Koiwa¹, Kazunori Yasumura², Tadashi Kamada³, Zenro Ikezawa¹

¹Department of Environmental Immuno-Dermatology, Yokohama City University Graduate School of Medicine, Fukuura 3-9, Kanazawa, Yokohama, 236-0004, Japan
²Department of Plastic Reconstructive Surgery, Yokohama City University Graduate School of Medicine, Yokohama, Japan
³Research Center for Charged Particle Therapy, National Institute of Radiological Sciences, Chiba, Japan

A 31-year-old Japanese man noticed a hemorrhagic black nodule on his right thigh and underwent surgical excision in January 2005. Histopathology showed a melanoma with negative margin (tumor thickness 9 mm) and he was referred to our clinic for additional treatment.

Although most laboratory tests were within normal ranges, serum LDH level was slightly high. Computed tomography scanning revealed a right inguinal lymph node swelling, 3 cm in diameter. Extended excision and right inguinal node dissection were performed in February 2005. On the basis of the above findings, this case was allocated to pT4bN3M0 (Stage IIIC) by the AJCC/UICC classification system (2002).

After the operation, although he was given multi-agent chemotherapy (dacarbazine, nimustine and vincristine) and immune therapy (interferon-beta) in six courses, following the Japanese guidelines for treatment of melanoma, he had a retroperitoneal node metastasis in September. Lymph node dissection was performed again and he received outpatient immune therapy afterwards. In January 2006, he had an external iliac node metastasis. At that time, neither distant metastasis by imaging test nor abnormal serum findings including LDH and 5-S-cysteinyldopa were recognized. Therefore, carbon ion radiotherapy was chosen because he did not have complete remission either after past operations or after chemotherapy.

A total of 64 Gray equivalent dose of carbon ion radiotherapy was given to an external iliac node metastasis in April 2006. The metastasis, 62 × 30 mm in size, was reduced with internal necrosis after six months (figures 1A, B). After one year, the tumor was reduced by more than 50%, to 36×26 mm (figure 1C). Since then he had a left cervical node metastasis in July and a mediastinal node metastasis in October 2006. Although additional carbon ion radiotherapy succeeded in local control each time, systemic metastasis developed. In spite of further multi-agent chemotherapy, he died in September 2007.

Carbon ion radiotherapy is superior to conventional photon therapy such as X-rays and γ-rays in several aspects [1-3]. As a physical advantage, carbon ion radiotherapy has a high linear energy transfer and has outstanding dose localization properties. It shows an increase in energy deposition with penetration depth up to a sharp maximum at the end of its range. Dose escalation can be performed without toxicity in surrounding normal tissues because the particle range is determined by the energy of the incoming particles and almost no dose is deposited in the normal tissue beyond the range. As biological advantages, carbon ion radiotherapy has a low rate of cancer cell recovery from radiation damage, and small variations in sensitivity according to both the stage of the cell cycle and changes in oxygen concentration. Therefore some clinical trials of carbon ion radiotherapy have shown a good outcome, not only in carcinomas but also in sarcomas such as melanoma [1, 3-5].

As far as the technique is concerned, to provide the best conditions for every patient, carbon ion radiation systems are as follows. First, the beam is spread by electromagnets and panelized by scattering. To adjust the Bragg peak to the tumor size, it is subsequently extended by ridge filters and tuned finely by a range shifter. Finally, the beam is shaped to fit the tumor by a collimator and passes through the bolus which is fitted to the distal end of tumor.

In this case, we chose carbon ion radiotherapy for lymph node metastatic melanoma subsequent to operation and chemotherapy. Although carbon ion radiotherapy succeeded at local control, distant metastasis occurred during the therapy. Therefore, we hope that carbon ion radiotherapy will come to be widely recognized by dermatologists as one treatment option and that combination therapy including carbon ion radiotherapy will someday overcome melanoma.

Acknowledgements

References

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