- Email: [email protected]
The treatment of malignant salivary gland tumors with fast neutrons
036~30l6/81/12173742S02.~/0 CopyrtghlO 1981 Pergamon
Phgs
In:. J. Radiation Oncology Biol Vol. 7, pp. 1737-1738 PrInted I” the U.S.A. All nghts reserved.
Press Ltd
0 Editorial THE TREATMENT
OF MALIGNANT SALIVARY GLAND TUMORS WITH FAST NEUTRONS
MARY CATTERALL, M.B., Physicianin
Charge,
B.S.,
F.R.C.R.,
F.A.C.R.
Fast Neutron Clinic, Medical Research Council, Cyclotron Unit, Hammersmith
Hospital
London WI2
Seattle’ reported that they were unable to control tumors greater than 6 ems in diameter, with any modality, including neutrons. However their experience was limited to 4 such patients of whom 2 had tumors which were recurrent after previous surgery or radiotherapy. Rafla4 drew attention to the interesting anatomy of the parotid gland and he stressed the need for accurately placed, angled wedged fields to give a uniform dose throughout the tumor. He found that the best results were achieved with doses of 6500 rads of X-rays from a linear accelerator, but even so only 40% of tumors completely regressed. The necessity for meticulous attention to details of treatment have been stated by the Hammersmith Unit’ and results from there remain those covering the longest periods of follow up. Forty patients with advanced tumors (18 adenoid cystic, 7 mucoepidermoid, 6 adenocarcinoma, 5 anaplastic and 4 malignant mixed), 14 of which had recurred after surgical excisions or radiotherapy or both, were treated with neutrons at Hammersmith before January 1980. In all cases, including very large “hopeless” tumors, treatment plans used 2 or 3 fields and normal structures were shielded. Complete regression was seen in all 40 patients and the follow up ranged from 1 to IO years, 24 being over 2 years and I9 of these exceeding 5 years. Eighteen are still alive. Three of these 40 tumors recurred l-4 years after treatment when 67%-93’S of the standard dose (I 560 rads in 12 fractions over 26 days) was given. Three other tumors extended from the edge of the treated volume because this was underestimated or reduced to avoid irradiating the spinal cord beyond 800 rads. Thus complete regression without recurrence was obtained in 34 of 40 (85%). There were 5 complications which were all temporary and all healed. Where the facial nerve was damaged by tumor, there was restoration of function after neutron therapy, provided that this was given within 2 months of the onset of paralysis. Conduction through the nerve was never impaired by fast neutrons.
The results of fast neutron therapy for malignant tumors of the salivary glands are very satisfactory and on present evidence, fast neutrons are the treatment of first choice for tumors in these sites, when compared with the results from surgery and conventional radiotherapy. In this issue, confirmation of results of neutron therapy already published from Hammersmith’ are given by workers at the Fermi Laboratory.3 These tumors are of varied histology-adenoid cystic, muco-epidermoid, anaplastic and adeno and squamous carcinoma. They may arise in any of the salivary glands and also in aberrant salivary gland tis.ue of the upper respiratory tract. They often, but by no means invariably, have a long natural history, appear usually in the 5th and 6th decades but also in younger and older age groups and in both sexes. They all may metastasize to lungs, bones and liver but the local spread is usually characteristic of the histological type, for example, adenoid cystic tumors spread along nerve sheaths towards the cranial nerve nuclei, adeno and squamous cell carcinomata spread to regional lymphatic glands or infiltrate the skin and muco epidermoid tumors extend from the primary site to any of the surrounding structures. It may seem remarkable therefore that one single form of therapy is effective against such a heterogenous group. There are however two factors common to all these tumors. The site and the geometrical shape of the tumors enables them, with careful planning, to be given an adequate and uniform dose of neutrons even from the inadequate machines which are available at present. So long as the neural spread of adenoid cystic tumors is taken into consideration, these also can be dosed adequately, although the planning of treatment is more difficult. It might be said of the report from the Fermi Laboratory3 that whilst the results are good, the follow up is not long enough for these particular tumors and that the numbers treated with a consistent dose is small. Furthermore, it has to be remembered that Henry et al in
Accepted for publication 4 September 198 1. 1737
1738
Radiation Oncology 0 Biology 0 Physics
These results are important for two reasons. Firstly, they indicate the efficacy of neutrons, both in tumor control and lack of complications when an adequate dose can be correctly delivered, even when 5 different histological types of tumor are involved. Secondly, they mark an advance over both photons and surgery in the treatment of cancer in these sites. This is especially important where one alternative treatment is surgical excision, with a high probability of severing the 7th nerve or excising part of the temporal bone or mandible or of skin grafting. When such serious cosmetic and functional sequelae may result from conventional radical treatment, the results of the new treatment must be clearly stated, particularly with regard to its effect on normal structures and their function. It is neither necessary nor desirable to remove “as much as possible” of the tumor by surgical excision. If this is done, a cavity of uncertain dimensions and residual tumor at uncertain sites within it are left requiring an adequate dose of neutrons. The vascularity of the area may also be reduced, thereby compromising a highly effective form of treatment and submitting the patient to a major operation with probable morbidity following it. Biopsy is all that is required before fast neutron therapy. The decision to do this rather than excise a lump completely is sometimes difficult with parotid swellings,
December 198 1, Volume 7, Number 12
70% of which are benign and therefore unsuitable for neutron therapy. It is however indicated where there are signs of malignancy, such as pain and sudden increase in size and in all cases of swellings in the sites of other salivary glands. The use of pre-operative radiation with photons followed by surgical removal of the residual tumor has been advocated as giving good cosmetic and functional results. However if an alternative treatment can dispense with surgery, it has obvious advantages. Neutron therapy is at present extremely difficult because of the technical inadequacies of the beams, some of which are poorly penetrating, have a wide penumbra or are fixed in the horizontal or vertical positions. In all these important points, they are grossly inferior to modern megavoltage machines, with which the results will be compared. Although the salivary glands are superfically sited, they are nevertheless close to vital normal structures such as the spinal cord, the optic chiasma and the contralateral salivary gland. An adequate dose must be delivered to the whole extent of the tumor, while at the same time the vital normal structures must be protected. The technique of planning and the protection of normal structures will therefore play a major part in the outcome, the clinical results being largely dependant on the quality of the treatment given.
REFERENCES 1. Catterall, M., Bewley, D.K.: Fast Neutrons in the Treatment ofcuncer. London, Academic Press, New York, Grune and Stratton,
1979.
2. Henry, L.W., Blasko,
J.C., Griffin, I.W., Parker, R.G.: Evaluation of fast neutron therapy for advanced carcinomas of the major salivary glands. Cancer 44: 8 14-8 18, 1979.
3. Kaul, R., Hendrickson, F., Cohen, L., Rosenberg, I., Tenttaken, R., Awscha1om.M.: Fast neutrons in the treatment of salivary gland tumors. Int. J. Radiat. Oncol. Biol. Phys. 7: 1667-1671, 1981. 4. Rafla S.: Malignant parotid tumors. Natural history and treatment. Cancer 40: 136-144, 1977.
Phgs
In:. J. Radiation Oncology Biol Vol. 7, pp. 1737-1738 PrInted I” the U.S.A. All nghts reserved.
Press Ltd
0 Editorial THE TREATMENT
OF MALIGNANT SALIVARY GLAND TUMORS WITH FAST NEUTRONS
MARY CATTERALL, M.B., Physicianin
Charge,
B.S.,
F.R.C.R.,
F.A.C.R.
Fast Neutron Clinic, Medical Research Council, Cyclotron Unit, Hammersmith
Hospital
London WI2
Seattle’ reported that they were unable to control tumors greater than 6 ems in diameter, with any modality, including neutrons. However their experience was limited to 4 such patients of whom 2 had tumors which were recurrent after previous surgery or radiotherapy. Rafla4 drew attention to the interesting anatomy of the parotid gland and he stressed the need for accurately placed, angled wedged fields to give a uniform dose throughout the tumor. He found that the best results were achieved with doses of 6500 rads of X-rays from a linear accelerator, but even so only 40% of tumors completely regressed. The necessity for meticulous attention to details of treatment have been stated by the Hammersmith Unit’ and results from there remain those covering the longest periods of follow up. Forty patients with advanced tumors (18 adenoid cystic, 7 mucoepidermoid, 6 adenocarcinoma, 5 anaplastic and 4 malignant mixed), 14 of which had recurred after surgical excisions or radiotherapy or both, were treated with neutrons at Hammersmith before January 1980. In all cases, including very large “hopeless” tumors, treatment plans used 2 or 3 fields and normal structures were shielded. Complete regression was seen in all 40 patients and the follow up ranged from 1 to IO years, 24 being over 2 years and I9 of these exceeding 5 years. Eighteen are still alive. Three of these 40 tumors recurred l-4 years after treatment when 67%-93’S of the standard dose (I 560 rads in 12 fractions over 26 days) was given. Three other tumors extended from the edge of the treated volume because this was underestimated or reduced to avoid irradiating the spinal cord beyond 800 rads. Thus complete regression without recurrence was obtained in 34 of 40 (85%). There were 5 complications which were all temporary and all healed. Where the facial nerve was damaged by tumor, there was restoration of function after neutron therapy, provided that this was given within 2 months of the onset of paralysis. Conduction through the nerve was never impaired by fast neutrons.
The results of fast neutron therapy for malignant tumors of the salivary glands are very satisfactory and on present evidence, fast neutrons are the treatment of first choice for tumors in these sites, when compared with the results from surgery and conventional radiotherapy. In this issue, confirmation of results of neutron therapy already published from Hammersmith’ are given by workers at the Fermi Laboratory.3 These tumors are of varied histology-adenoid cystic, muco-epidermoid, anaplastic and adeno and squamous carcinoma. They may arise in any of the salivary glands and also in aberrant salivary gland tis.ue of the upper respiratory tract. They often, but by no means invariably, have a long natural history, appear usually in the 5th and 6th decades but also in younger and older age groups and in both sexes. They all may metastasize to lungs, bones and liver but the local spread is usually characteristic of the histological type, for example, adenoid cystic tumors spread along nerve sheaths towards the cranial nerve nuclei, adeno and squamous cell carcinomata spread to regional lymphatic glands or infiltrate the skin and muco epidermoid tumors extend from the primary site to any of the surrounding structures. It may seem remarkable therefore that one single form of therapy is effective against such a heterogenous group. There are however two factors common to all these tumors. The site and the geometrical shape of the tumors enables them, with careful planning, to be given an adequate and uniform dose of neutrons even from the inadequate machines which are available at present. So long as the neural spread of adenoid cystic tumors is taken into consideration, these also can be dosed adequately, although the planning of treatment is more difficult. It might be said of the report from the Fermi Laboratory3 that whilst the results are good, the follow up is not long enough for these particular tumors and that the numbers treated with a consistent dose is small. Furthermore, it has to be remembered that Henry et al in
Accepted for publication 4 September 198 1. 1737
1738
Radiation Oncology 0 Biology 0 Physics
These results are important for two reasons. Firstly, they indicate the efficacy of neutrons, both in tumor control and lack of complications when an adequate dose can be correctly delivered, even when 5 different histological types of tumor are involved. Secondly, they mark an advance over both photons and surgery in the treatment of cancer in these sites. This is especially important where one alternative treatment is surgical excision, with a high probability of severing the 7th nerve or excising part of the temporal bone or mandible or of skin grafting. When such serious cosmetic and functional sequelae may result from conventional radical treatment, the results of the new treatment must be clearly stated, particularly with regard to its effect on normal structures and their function. It is neither necessary nor desirable to remove “as much as possible” of the tumor by surgical excision. If this is done, a cavity of uncertain dimensions and residual tumor at uncertain sites within it are left requiring an adequate dose of neutrons. The vascularity of the area may also be reduced, thereby compromising a highly effective form of treatment and submitting the patient to a major operation with probable morbidity following it. Biopsy is all that is required before fast neutron therapy. The decision to do this rather than excise a lump completely is sometimes difficult with parotid swellings,
December 198 1, Volume 7, Number 12
70% of which are benign and therefore unsuitable for neutron therapy. It is however indicated where there are signs of malignancy, such as pain and sudden increase in size and in all cases of swellings in the sites of other salivary glands. The use of pre-operative radiation with photons followed by surgical removal of the residual tumor has been advocated as giving good cosmetic and functional results. However if an alternative treatment can dispense with surgery, it has obvious advantages. Neutron therapy is at present extremely difficult because of the technical inadequacies of the beams, some of which are poorly penetrating, have a wide penumbra or are fixed in the horizontal or vertical positions. In all these important points, they are grossly inferior to modern megavoltage machines, with which the results will be compared. Although the salivary glands are superfically sited, they are nevertheless close to vital normal structures such as the spinal cord, the optic chiasma and the contralateral salivary gland. An adequate dose must be delivered to the whole extent of the tumor, while at the same time the vital normal structures must be protected. The technique of planning and the protection of normal structures will therefore play a major part in the outcome, the clinical results being largely dependant on the quality of the treatment given.
REFERENCES 1. Catterall, M., Bewley, D.K.: Fast Neutrons in the Treatment ofcuncer. London, Academic Press, New York, Grune and Stratton,
1979.
2. Henry, L.W., Blasko,
J.C., Griffin, I.W., Parker, R.G.: Evaluation of fast neutron therapy for advanced carcinomas of the major salivary glands. Cancer 44: 8 14-8 18, 1979.
3. Kaul, R., Hendrickson, F., Cohen, L., Rosenberg, I., Tenttaken, R., Awscha1om.M.: Fast neutrons in the treatment of salivary gland tumors. Int. J. Radiat. Oncol. Biol. Phys. 7: 1667-1671, 1981. 4. Rafla S.: Malignant parotid tumors. Natural history and treatment. Cancer 40: 136-144, 1977.