Inr. _I. Rdidon Oncology Bid. Phys. Vol. 21. pp. 857-858 Pnnted m the U S.A All rights reserved.

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0360-3016/91 $3.00 + 00 0 1991 Per@mon Press plc

0 Editorial

OPTIMAL

TREATMENT

FOR SALIVARY

THOMAS W.

GRIFFIN,

GLAND TUMORS

M.D.

University of Washington Medical Center/School of Medicine, Seattle, WA 98195 gland malignancies. Clinical trials have confirmed these predictions. In excess of 300 patients have been treated for locally advanced, unresectable salivary gland tumors with fast neutrons (6). Patients have been treated with both neutrons alone and mixed beam irradiation over both short (4 weeks) and long (8 weeks) overall treatment times. Patients have been treated with physics-laboratory-based and hospitalbased neutron generators of both high and low energy. The results have been remarkably consistent (3, 4, 6). These studies have demonstrated long-term local/regional tumor control rates of approximately 67% compared to average long-term local/regional tumor control rates of approximately 25% for standard fractionated, low LET radiations (6). The normal tissue complication rates have been marginally higher with low energy, fixed beam neutron generators but have been equivalent to megavoltage photons when high energy and/or isocentric hospital-based neutron generators were employed (3, 4, 5). Subsequently, a prospective, cooperative, randomized clinical trial sponsored jointly by the MRC and RTOG directly compared fast neutrons with megavoltage photons for patients with locally advanced, unresectable salivary gland tumors (5). This study demonstrated a long-term local/regional tumor control rate of 67% for neutrons versus 17% for photons @ < 0.005) in this group of patients with advanced tumors (up to 16 cm in maximum dimension). The normal tissue toxicities were not statistically significantly different between the two groups. Drs. Wang and Goodman present the results of a retrospective review of accelerated, hyperfractionated, low LET radiation for malignant salivary gland tumors in this journal. The rationale for accelerated fractionation with photons is less compelling than is the rationale for high LET radiations in this tumor system. Accelerated fractionation schemes are usually advocated for fast growing tumors with rapidly cycling cells to minimize the potential for repopulation. They are not generally advocated for slowly growing tumors such as salivary gland malignancies, and, in fact, may be disadvantageous in this setting. Nonethe-

Salivary gland tumors are relatively rare when compared to other malignancies of the head and neck region. They are a histologically diverse group of tumors, generally slow growing with long doubling times, and they demonstrate a propensity for late local/regional and distant recurrences. Because of their slow growing nature, patients afflicted with these tumors often have prolonged survivals, even in the presence of distant metastatic disease (usually lung). Treatment has traditionally been either surgery alone, or surgery plus postoperative radiation therapy in the setting of potentially residual postoperative microscopic disease. Low LET radiation therapy, given with standard fractionation, has met with only limited success in the setting of gross postoperative residual, or unresectable disease (7). These suboptimal results led to the conclusion that salivary gland tumors are relatively radioresistant, and led to clinical trials with high LET radiations such as fast neutrons and high LET charged particles. The case for high LET radiation therapy is strong in this tumor system. Tumors with low growth fractions and long doubling times are predicted to be more sensitive to high LET than to low LET radiations. Reduced variation in radiosensitivity throughout the cell cycle predicts that slowly growing tumors with slowly cycling cells, such as salivary gland cancers, would be advantageously treated with high LET radiations. Batterman er al. published pioneering work clinically defining the RBE of fast neutrons for various human malignancies (1). One of the highest RBE’s of neutrons was found in adenoid cystic carcinomas (8.0 with fractionated neutron therapy), which indicates an inherent radiosensitivity of this tumor to high LET radiation. More importantly, the RBE for adenoid cystic carcinomas is substantially higher than that for normal mesenchymal tissues. Treating an adenoid cystic carcinoma with 2000 neutron cGy would be approximately equivalent to 16,000 photon cGy in its tumor effect, but equivalent to only 60004600 photon cGy in its effect on normal tissues. This differential effect gives rise to a therapeutic gain factor of approximately 250%, and is thought to be the underlying reason for the success of high LET radiations in salivary

Accepted for publication 3 June 199 1.

Reprint requests to: Thomas W. Griffin, M.D. 857

858

I. J. Radiation Oncology 0 Biology 0 Physics

less, the results reported in this issue are interesting. If the 7 patients (29% of their patient population) with Tl NO and T2 NO tumors are eliminated from their series, and if the 2 patients who failed in the neck are counted as failures of local tumor control along with the 4 reported primary tumor failures, their crude, short-term local/regional tumor control rates are still 7 1% (12/17). Unfortunately, eliminating the patients with early stage disease reduces their median follow-up time from 43 months to only 20 months. If these results hold up with a larger patient population over longer follow-up times, accelerated hyperfractionated radiation may prove to be a viable alternative to high LET treatments. With the excellent long-term local/regional tumor control rates now being reported, one must ask what is the current role of surgery for salivary gland malignancies. Buchholz et al. reported a 92% 5-year local/regional tumor control rate for fast neutron irradiation of locally advanced,

August 1991, Volume 21, Number 3

previously untreated, salivary gland tumors (compared to a 51% 5-year local control rate for unresectable tumors recurrent after one or more surgical procedures (p = 0.01) (2). None of the patients treated with neutrons alone suffered facial nerve damage. Similarly, patients treated for advanced tumors with neutrons alone had an equal or greater 5-year local control rate compared to patients treated with debulking surgery and postoperative neutrons for residual gross disease. These results have been confirmed by other series (3). In view of the results of treatment with high LET radiations, and perhaps accelerated hyperfractionated radiation, surgery for salivary gland malignancies should be limited to cases where there is a high likelihood of achieving a negative surgical margin, and where the risk of facial nerve damage is small. In all remaining cases, consideration should be given for treatment with high LET radiations alone as the definitive treatment modality.

REFERENCES 1. Battennan, J. J.; Breur, K.; Hart, G. A. M.; van Peperzeel,

H. A. Observations on pulmonary metastases in patients after single doses and multiple fractions of fast neutrons and cobalt-60 gamma rays. Eur. J. Cancer 17:539-548; 1981. 2. Buchholz, T. A.; Laramore, G. E.; Griffin, B. R.; Koh, W. J.; Griffin, T. W. The role of fast neutron radiotherapy in the management of advanced salivary gland malignancies. Young Oncologist Award-Winning Paper, presented at the 75th Annual American Radium Society Meeting, May 199 1. 3. Catterall, M.; Errington, R. D. The implications of improved treatment of malignant salivary gland tumors by fast neutron radiotherapy. Int. J. Radiat. Oncol. Biol. Phys. 13:13131318; 1987. 4. Duncan, W.; Orr, J. A.; Amott, S. J.; Jack, W. J. L. Neutron therapy for malignant tumours of salivary glands. A re-

port of the Edinburgh experience. Radiother. Oncol. 8:97104; 1987. 5. Griffin, T. W.; Pajak, T. F.; Laramore, G. E.; Duncan, W.; Richter, M. P.; Hendrickson, F. R.; Maor, M. H. Neutron vs photon irradiation of inoperable salivary gland tumors: results of an RTOG MRC cooperative randomized study. Int. J. Radiat. Oncol. Biol. Phys. 15:1085-1090; 1988. 6. Koh, W.; Laramore, G. E.; Griffin, T. W.; Russell, K.; Griffin, B. R.; Parker, R. G.; Davis, L.; Pajak, T. F. Fast neutron radiation for inoperable and recurrent salivary gland cancers. Am. J. Clin. Oncol. (CCT) 12:316-319; 1989. 7. Laramore, G. E. Fast neutron radiotherapy for inoperable salivary gland tumors: is it the treatment of choice? Int. J. Radiat. Oncol. Biol. Phys. 13:1421-1423; 1987.

Optimal treatment for salivary gland tumors.

Inr. _I. Rdidon Oncology Bid. Phys. Vol. 21. pp. 857-858 Pnnted m the U S.A All rights reserved. Copynghr 0360-3016/91 $3.00 + 00 0 1991 Per@mon Pre...
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