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The effect of immediately preoperative adjuvant radiotherapy in the surgical treatment of primary cutaneous malignant melanoma
Brifish Journal of Plastic Surgery (1992), 45, 3C-33 0 1992 The Trustees of British Association of Plastic Surgeons
The effect of immediately preoperative adjuvant radiotherapy in the surgical treatment of primary cutaneous malignant melanoma A. R. Phipps, A. M. Godfrey, the late K. R. Durrant and P. R. Millard Departments of Plastic Surgery, Radcl@e Inzrmary, Oxford, Radiotherapy and Oncology, Churchill Hospital, Oxford, and Histopathology, John RadclifSe Hospital, Oxford SUMMARY. A historical series of patients with primary cutaneous malignant melanoma is reviewed. These patients had been treated with a single therapeutic dose of irradiation to the tumour and surrounding skin immediately before surgical excision. Some patients had also received a single necrotising dose of radiotherapy to the tumour itself. Recurrence and survival rates have been examined retrospectively in the light of reviewed histology, and compared with other published series. Preoperative radiotherapy was found to have no significant influence on the outcome of surgical treatment of primary malignant melanoma.
Cutaneous malignant melanoma has generally been regarded as a radioresistant tumour; attempts to treat primary melanoma with radiotherapy alone have appeared in the past to result in survival rates lower than those expected after surgical excision. For example, in a review of 31 patients with cutaneous melanoma treated by radiotherapy at the Christie Hospital,’ 10 ‘(32%) were found to have survived for 5 years (Pearson, 1976). Radiotherapy for malignant melanoma is therefore mainly confined at present to the palliation of recurrent and metastatic disease. However, in recent years a number of articles in the oncology literature have pointed out that the response to treatment in such cases is significantly greater when’the radiotherapy is delivered in high-dose fractions (Adam et al., 1982; Johanson et al., 1983; Overgaard et al., 1986), and have suggested that malignant melanoma may be less absolutely radioresistant than was previously believed. Overgaard and his co-authors compared the outcome of differing schedules of radiotherapy for recurrent and metastatic melanoma lesions with a variety of radiobiological parameters of the treatments used, and found that the tumour response only correlated significantly with the radiation dose per fraction, with an apparent threshold at a dose-per-fraction in the region of 400 cGy. In the 1950s the departments of Plastic Surgery and Radiotherapy in Oxford elaborated a combined method of treating primary cutaneous malignant melanoma with external beam radiotherapy, immediately followed by conventional surgical excision. After 1958, this was established as the preferred method of one surgeon for treating the majority of primary malignant melanomas, and continued as such until the mid-1970s. In this paper, the outcome of this treatment in 77 patients with clinical Stage I disease is reviewed.
Patients and methods The names of patients treated for malignant melanoma were retrieved from indexes in the Plastic Surgery and Radiotherapy departments; the hospital records of 136 such patients were scrutinised for details of treatment and follow-up. Eight patients were excluded from further consideration because histological examination had not confirmed the clinical diagnosis of malignant melanoma. Fifteen patients had presented with melanoma not confined to the primary site, or had been referred from elsewhere for treatment of secondary disease. Three patients were excluded because they had received intraopkrafive chemotherapy in addition to preoperative radiotherapy. Thirty-three of the remaining patients had received radiotherapy which did not conform to one of the standard schedules under consideration for this review, or no radiotherapy to the primary tumour itself. The remaining 77 patients studied consisted of 30 men and 47 women. All had been treated in a standardised fashion for clinically Stage I primary cutaneous malignant melanoma. In every patient, the surgical procedure was preceded by radiotherapy to the site of the tumour and its surrounding area. All patients received a single dose of 400 cGy of external beam radiotherapy to an 11 cm circle of skin centred on the tumour site; in 52 patients (23 male, 29 female) an additional single-fraction necrotising dose of 2000 cGy was also delivered to the lesion itself. Surgery was carried out within 24 hours after treatment. This consisted of the conventional surgical management of the day, most frequently taking the form of an excision biopsy, followed, on histological confirmation of the diagnosis of malignant melanoma, by wide excision of the biopsy site with a 5 cm margin (Peet 30
Preoperative Adjuvant Radiotherapy
and Patterson, 1963). Some patients proceeded directly to wide excision without a tissue diagnosis, and three had already had an excision biopsy in another department. Pn most cases, therefore, the whole irradiated area was excised with the tumour, or shortly afterwards. Between 1958 and 1966 16 patients also underwent prophylactic regional lymph node dissection as a part of the then routine surgical policy : three en bloc with the primary tumour, and the remainder at an interval of 6 weeks. The demographic features of the patients studied for this paper are similar to those reported in most series. There was a 3:2 predominance of female patients over males, and the mean age at presentation was 47 (SD + 15) which does not differ significantly between the sexes (p > 0.2) (Table 1). The anatomical site of the primary lesion was similar in the two sexes, with the notable exception of a higher incidence of lower limb lesions in women. These cases account for the difference in total numbers between the sexes in this series. In surviving patients, a minimum follow-up of 10 years has been obtained in all but seven instances, by reference to hospital records and by contacting family practitioners. For many patients a considerably longer follow-up is available, with a maximum of 29 years. Mortality from malignant melanoma is recognised to be highly dependent not only on clinical staging, but also on histopathoiogical microstaging (Breslow, 1970). A retrospective examination of the available histological material from these patients has been carried out, and a Breslow thickness has been assigned in IQ cases.
B[PW&S
Of the 77 patients, 24 were known to have died of their malignant melanoma, and a further 8 from unrelated disease (Table 2). The remaining 45 were alive at the time of their last contact, which averaged 834 years from their initial treatment. There was no apparent difference in age at presentation between
TableI
Patient characteristics
Age (years)
Male
Outcome at last follow-up
Alive Dead of MM Dead, other Total
Male
Female
13 12 5
32 12 3
30
47
patients why subsequently died of melanoma (mean age 47 & 13) and those who survived (mean age 44 _t 139, but patients dying from unrelated causes had presented at a greater age (mean 70 + 7). The mean interval between treatment and death from melanoma was about 4 years, but ranged widely between 6 months and 24 years. Ns significant difference was apparent between the number of patients alive at last follow-up after a single, 400 cGy, preoperative irradiation field, and the number alive after preoperative treatment with the concentric pattern of 400 cGy and 2000 cGy (chisquare=O.88; p> 0.7). The two groups have been merged for further consideration. The fate of these patients is illustrated in Figures 1 and 2, which show the percentage of male and female patients who, at each yearly interval after treatment, were alive and recurrence-free, ahve but having suffered recurrent disease, or dead of malignant melanoma. Remaining patients at each point had died of unrelated disease or had been lost to follow-up.
The overall 5-year surival of patients of both sexes who had not undergone elective lymph node dissection was 68%, after exclusion of those lost to follow-up or dead of unrelated conditions. Fewer male patients (55%) were alive at 5 years than females (77%). IO-year swvival At the lo-year
interval after treatment, equivalent survival figures for male and female patients were respectively 41% and 67x, an average of 57%. Local recurrence and lymph node metastas63
Total
2 5 9 8 13 9 0 1
2 6 18 15 20 11 2 3
Eleven patients (14% of the whole series) suffered a recurrence of melanoma near the site of the primary lesion, within or at the margins of the irradiated, excised and grafted area, or in nearby unirradiated skin. 0f those patients, three subsequently developed disseminated disease. Eighteen patients (30% of those who had not undergone prophylactic node dissection) developed lymph node metastases and required therapeutic lymph node dissection; thirteen subsequently developed disseminated disease.
Male 11 6 2 7 4
Female 31 5 1 6 4
Total 42 11 3 “13
Discwsion
30
41
II
0 1 9 I I 2 2 2
Site ofprimary tumour
Tot&
Table 2
Female
10-19 20-29 30-39 4&49 50-59 60-69 70-79 80-89
Lower limb Upper limb Ant. trunk Post. trunk Head and neck
31
in Primary Cutaneous Malignant Melanoma
8
Preoperative radiotherapy of primary malignant melanomas was carried out in an attempt to decrease the incidence of secondary disease by eliminating mi-
British Journal of Plastic Surgery
32 n=47
l-l=30 YOO
%
100
90
90
80 70 60
80 70 II
Dead of MM
50
m
Alive, recurred
40
m
Alive, no recurrence
30
%
60
a
50
EZB Alive, recurred
40
m
Dead of MM
Alive, no recurrence
30 20
20
10
10
0 ‘1
2345678910 Years since treatment
Years since treatment
Fig. 1 Figure l-The Figure 2-The
Fig. 2
fate of male patients l-10 years after combined treatment for Stage I malignant melanoma.
fate of female patients I-10 years after treatment.
of viable tumour cells during the surgery (Peet and Patterson, 1963). This is distinct from the reported use of radiotherapy postoperatively to treat residual tumour (Johanson et al., 1983) or to justify smaller excision margins (Dickson, 1958). Comparison of survival data and locoregional recurrence patterns with those for contemporary published series suggests that irradiation prior to surgical excision of the primary tumour conferred no advantage. Tables 3 and 4 show the number of patients surviving to 5 and 10 years, with percentage survival figures calculated after exclusion of those patients lost to follow-up or dead of unrelated disease, together with comparable figures from contemporary series in croembolisation
Table 3 Five-year survival. lymph node dissection)
(Patients
without
Male
Female
Total
Alive Dead of MM Dead, other Lost to review
12 10 2 1
27 8 1 0
39 18 3 I
5-year survival (see text)
55%
77%
68%
Glasgow Scottish Melanoma Group
57%
72%
66% 68%
Table 4 Ten-year survival. lymph node dissection)
(Patients
without
elective
elective
which surgery alone was employed (Cochran, 1969; Griffiths and Briggs, 1984; MacKie et al., 1985). Since elective lymph node dissection was not practised in any of these three other series, the sixteen patients so treated in Oxford (5 male and 11 female patients) have not been included in these tables. The overall 5-year survival of 68% of such patients in the present series does not differ significantly from the 66% 5-year survival found among 102 patients with clinical Stage I disease treated in Glasgow in the 1950s and early 1960s (Cochran, 1969) (chi-square= 1.12; p >0.7), and is the same as the 68% overall survival calculated on the same basis from figures reported by the Scottish Melanoma Group for their 1979 cohort of patients (MacKie et al., 1985) (chi square = 0.016; p = 0.9). In the series reported by Griffiths and Briggs (1984), considering 258 patients with Stage I malignant melanoma treated in Bristol between 1967 and 1972, overall lo-year survival was 60%, which is similar to the 57% found in the present study (chi-square = 0.11; p>O.7). In 70 patients the Breslow thickness of the tumour has been measured. One patient was lost to follow-up and three died of unrelated causes within the first 5 years after treatment. In Table 5, the 52 of the remaining patients who had not undergone prophylactic lymph node dissection have been stratified according to tumour thickness into three groups, divided at Breslow thicknesses of 1.5 mm and 3.5 mm, and
Table 5
Survival related to tumour thickness Male
Female
Total
Male
Female
Total
Alive Dead of MM Dead, other Lost
7 10 5 3
20
21
10 3 3
20 8 6
<1.50mm 1.5-3.49 mm 3.50 mm
4 3 75% 10 5 50% 6 3 50%
10 9 90% 17 14 82% 5 240%
14 12 86% 27 19 70% 11 545%
lo-year survival (see text)
41%
67%
57%
All
20 11 55%
32 25 78%
52 36 69%
54%
74%
60%
Hypothetical (see text)
Bristol
n
5YS
n
5YS
n
”
5YS
66%
Preoperative Adjuvant Radiotherapy in Primary Cutaneous Malignant Melanoma subdivided by sex. This follows the division used by the Scottish Melanoma Croup in considering their 1979 cohort (MacKie et al., 1985). Ahhough the absolute numbers of patients in the study are too small to permit statistical treatment of individual figures within this table, we have for the purposes of comparison calculated the expected 5year survival of a hypothetical set of patients from the Scottish se&s, numerically equal to the present total, and similarly weighted according to sex and Breslow thickness. Chi-square testing indicates no significant difference in 5-year survival between the patients in the present study and the hypothetical Scottish group who did not receive preoperative radiotherapy (for males chi-square=O.Ol, p>O.9; for females chioverall chi-square = 0.11, square =0.12, p>o.7; p>o.73. The small group of 116 patients who received prophylactic regional lymph node dissection are not typica of the series as a whole, apparently having sign&cantly greater IO-year survival (p = 0.05); however, the number of patients is clearly too small to permit wider conclusions in this contentious area, which is well argued elsewhere (e.g. Balch et al., 1985). Repeating the foregoing comparisons with these patients included does not yield significant differences between this series and any of the others cited (all remain p > 0. I). Fourteen percent of the Oxford patients developed a &al recurrence of tumour, and 30% regional lymph node metastases. Comparable figures are reported for the Glasgow series (Cochran, 1969), with a local recurrence rate of twenty percent and lymph node metastases in 25x, and from Bristol (6riffiths and Briggs, 1984), yhere 10% of patients presented with local recurrence as the first manifestation of recurrent disease, and a further 29% presented with lymph node m&stases as their first recurrence. The lack of additional impact of the combined treatment either on survival rates or on the incidence of focoregional recurrence is evident from these comparisons. This apparent failure of preoperative radiotherapy ~0 influence the outcome of traditional surgery for malignant melanoma presumably either indicates radioresistance of the tumour at these doses, QP reflects the presence of micrometastases aheady existing outside the irradiated field at the time of treatment. The disadvantages of radiotherapy must clearly include economic and logistic factors, as well as an unquantifiable additional burden of stress placed upon the patient b:y the extra treatment. Adverse effects of the radiotherapy itself were found infrequently in the present series; but one patient in whom the irradiated area ‘had not been completely excised presented in 19g8 with a basal cell carcinoma near’ the site of her melanoma excision in 1959, and the notes of another patient record grossly delayed primary healing of the split-skin-grafted excision site. In the hght of these findings we do not advocate a resumption of the use of radiotherapy in this fashion.
33
We should like to acknowledge
the assistance of the following surgeons for help, advice and information valuable in the preparation of this paper: Mr M. 6). Poole, Mr T. J. S. Patterson, Mr P. K. B. Davis, Mr D. C. McNeil& Professor W. H. Reid. Some of the data from this paper were presented at the 1988 Winter Meeting of the British Association of Plastic Surgeons, and at the January 1989 meeting of the UK Melanoma Study Group held at Queen Mary’s University Hospital, Roehampton.
References Adam, J. S., Habeshaw, T. and Kirk, J. (1982). Response rate of malignant melanoma to large fraction irradiation. Brirish Xournal of Radiology, 656,605. Balch, C. M., Cascinelli, N., Milto~~,G. W. a& Sim, F. H. (1985). Elective lymph node dissection: pros and cons. In Balch, C. M. and Milton, G. W. (Eds). Cutaneous melanoma. Philadelphia, Eippincott. BresBow, A. (1970). Thickness, cross-sectional areas and depth of invasion in the prognosis of cutaneous melanoma. Annals of Surgery, 172,902. _~_ Co&ran, A. 9. (1969). Malignant melanoma. A review of ten years’ experience in Glasgow, Scotland. Cancer, 23, 1190. Dickson, R. J. (1958). Malignant melanoma. A combined surgical and radiotherapeutic approach. American Journal of Roentgenology, 79, 1063. Griftiths, W. W. and Briggs, 9. C. (L984). Long term follow-up in cutaneous malignant melanoma: the relationship of maximal tumour thickness to disease free survival, disease recurrence and death. British Journal of Plastic Surgery, 37,507. Johanson, C. R., Harwood, A. R., Cmnmhgs, B. J. and Qtirt, I. (1983). O-7-21 radiotherapy in nodular melanoma, Cancer, Sl, 226. Ma&e, R. M., Soutar, D. S., Watson, A. C. H., Mchess, K. M., McPMe, 9. k., Hut&eon, A. W., Smyth, J. P., Crabah, K. C., MacGiivray, 3. Is., Rankin, R, and Kemp, 1. W. (1985). Malignant melanoma in Scotland 1979-1983. Luncet, 2,859. Overgaard, J., Qvergaard, M., Hansen, P. V. and van der Marse, H. (1986). Some factors of importance in the radiation treatment of malignant melanoma. Radiotherapy and CPncoIogy,5, 183. $emsopI, D. (1974). Radiotherapy in malignant melanoma. ,Proceedings of the Royal Society of Medicine,51,96. Pee& E. W. and Patterson, T. 9. S. (1963). I’%eEssentials of Plastic Surgqy. Oxford, Blackwell Scientific Publications.
The Authors Alan R. Ptipps, FRCS, formerly locum Senior Registrar in Plastic Surgery, Department of Plastic and Reconstructive SUFgeIy,The Radcliffe Infirmary, Oxford. Alan M. Godfrey, FRCS, Consultant Plastic Surgeon, Department of Plastic and Reconstructive Surgery, The Radciiffe Inthmary, Oxford. The late K. R. Durrant, FRCP, FRCR, Consultant in Radiotherapy and Oncology, Department of Radiotherapy and Oncology, Churchill Hospital, Oxford, Peter R. Millard, MD, FRCPatb, Consultant Histopathologist, Department of Histopathology, John Radclitfe Hospital, Oxford. Requests for reprints to Mr A. R. Phipps, Department of Plastic Surgery, Queen Mary’s University Hospital, Roehampton Lane, hAdoASV\'15 5PN. Paper received 5 July 1989. Accepted 12 3uly 1991 after revision.
The effect of immediately preoperative adjuvant radiotherapy in the surgical treatment of primary cutaneous malignant melanoma A. R. Phipps, A. M. Godfrey, the late K. R. Durrant and P. R. Millard Departments of Plastic Surgery, Radcl@e Inzrmary, Oxford, Radiotherapy and Oncology, Churchill Hospital, Oxford, and Histopathology, John RadclifSe Hospital, Oxford SUMMARY. A historical series of patients with primary cutaneous malignant melanoma is reviewed. These patients had been treated with a single therapeutic dose of irradiation to the tumour and surrounding skin immediately before surgical excision. Some patients had also received a single necrotising dose of radiotherapy to the tumour itself. Recurrence and survival rates have been examined retrospectively in the light of reviewed histology, and compared with other published series. Preoperative radiotherapy was found to have no significant influence on the outcome of surgical treatment of primary malignant melanoma.
Cutaneous malignant melanoma has generally been regarded as a radioresistant tumour; attempts to treat primary melanoma with radiotherapy alone have appeared in the past to result in survival rates lower than those expected after surgical excision. For example, in a review of 31 patients with cutaneous melanoma treated by radiotherapy at the Christie Hospital,’ 10 ‘(32%) were found to have survived for 5 years (Pearson, 1976). Radiotherapy for malignant melanoma is therefore mainly confined at present to the palliation of recurrent and metastatic disease. However, in recent years a number of articles in the oncology literature have pointed out that the response to treatment in such cases is significantly greater when’the radiotherapy is delivered in high-dose fractions (Adam et al., 1982; Johanson et al., 1983; Overgaard et al., 1986), and have suggested that malignant melanoma may be less absolutely radioresistant than was previously believed. Overgaard and his co-authors compared the outcome of differing schedules of radiotherapy for recurrent and metastatic melanoma lesions with a variety of radiobiological parameters of the treatments used, and found that the tumour response only correlated significantly with the radiation dose per fraction, with an apparent threshold at a dose-per-fraction in the region of 400 cGy. In the 1950s the departments of Plastic Surgery and Radiotherapy in Oxford elaborated a combined method of treating primary cutaneous malignant melanoma with external beam radiotherapy, immediately followed by conventional surgical excision. After 1958, this was established as the preferred method of one surgeon for treating the majority of primary malignant melanomas, and continued as such until the mid-1970s. In this paper, the outcome of this treatment in 77 patients with clinical Stage I disease is reviewed.
Patients and methods The names of patients treated for malignant melanoma were retrieved from indexes in the Plastic Surgery and Radiotherapy departments; the hospital records of 136 such patients were scrutinised for details of treatment and follow-up. Eight patients were excluded from further consideration because histological examination had not confirmed the clinical diagnosis of malignant melanoma. Fifteen patients had presented with melanoma not confined to the primary site, or had been referred from elsewhere for treatment of secondary disease. Three patients were excluded because they had received intraopkrafive chemotherapy in addition to preoperative radiotherapy. Thirty-three of the remaining patients had received radiotherapy which did not conform to one of the standard schedules under consideration for this review, or no radiotherapy to the primary tumour itself. The remaining 77 patients studied consisted of 30 men and 47 women. All had been treated in a standardised fashion for clinically Stage I primary cutaneous malignant melanoma. In every patient, the surgical procedure was preceded by radiotherapy to the site of the tumour and its surrounding area. All patients received a single dose of 400 cGy of external beam radiotherapy to an 11 cm circle of skin centred on the tumour site; in 52 patients (23 male, 29 female) an additional single-fraction necrotising dose of 2000 cGy was also delivered to the lesion itself. Surgery was carried out within 24 hours after treatment. This consisted of the conventional surgical management of the day, most frequently taking the form of an excision biopsy, followed, on histological confirmation of the diagnosis of malignant melanoma, by wide excision of the biopsy site with a 5 cm margin (Peet 30
Preoperative Adjuvant Radiotherapy
and Patterson, 1963). Some patients proceeded directly to wide excision without a tissue diagnosis, and three had already had an excision biopsy in another department. Pn most cases, therefore, the whole irradiated area was excised with the tumour, or shortly afterwards. Between 1958 and 1966 16 patients also underwent prophylactic regional lymph node dissection as a part of the then routine surgical policy : three en bloc with the primary tumour, and the remainder at an interval of 6 weeks. The demographic features of the patients studied for this paper are similar to those reported in most series. There was a 3:2 predominance of female patients over males, and the mean age at presentation was 47 (SD + 15) which does not differ significantly between the sexes (p > 0.2) (Table 1). The anatomical site of the primary lesion was similar in the two sexes, with the notable exception of a higher incidence of lower limb lesions in women. These cases account for the difference in total numbers between the sexes in this series. In surviving patients, a minimum follow-up of 10 years has been obtained in all but seven instances, by reference to hospital records and by contacting family practitioners. For many patients a considerably longer follow-up is available, with a maximum of 29 years. Mortality from malignant melanoma is recognised to be highly dependent not only on clinical staging, but also on histopathoiogical microstaging (Breslow, 1970). A retrospective examination of the available histological material from these patients has been carried out, and a Breslow thickness has been assigned in IQ cases.
B[PW&S
Of the 77 patients, 24 were known to have died of their malignant melanoma, and a further 8 from unrelated disease (Table 2). The remaining 45 were alive at the time of their last contact, which averaged 834 years from their initial treatment. There was no apparent difference in age at presentation between
TableI
Patient characteristics
Age (years)
Male
Outcome at last follow-up
Alive Dead of MM Dead, other Total
Male
Female
13 12 5
32 12 3
30
47
patients why subsequently died of melanoma (mean age 47 & 13) and those who survived (mean age 44 _t 139, but patients dying from unrelated causes had presented at a greater age (mean 70 + 7). The mean interval between treatment and death from melanoma was about 4 years, but ranged widely between 6 months and 24 years. Ns significant difference was apparent between the number of patients alive at last follow-up after a single, 400 cGy, preoperative irradiation field, and the number alive after preoperative treatment with the concentric pattern of 400 cGy and 2000 cGy (chisquare=O.88; p> 0.7). The two groups have been merged for further consideration. The fate of these patients is illustrated in Figures 1 and 2, which show the percentage of male and female patients who, at each yearly interval after treatment, were alive and recurrence-free, ahve but having suffered recurrent disease, or dead of malignant melanoma. Remaining patients at each point had died of unrelated disease or had been lost to follow-up.
The overall 5-year surival of patients of both sexes who had not undergone elective lymph node dissection was 68%, after exclusion of those lost to follow-up or dead of unrelated conditions. Fewer male patients (55%) were alive at 5 years than females (77%). IO-year swvival At the lo-year
interval after treatment, equivalent survival figures for male and female patients were respectively 41% and 67x, an average of 57%. Local recurrence and lymph node metastas63
Total
2 5 9 8 13 9 0 1
2 6 18 15 20 11 2 3
Eleven patients (14% of the whole series) suffered a recurrence of melanoma near the site of the primary lesion, within or at the margins of the irradiated, excised and grafted area, or in nearby unirradiated skin. 0f those patients, three subsequently developed disseminated disease. Eighteen patients (30% of those who had not undergone prophylactic node dissection) developed lymph node metastases and required therapeutic lymph node dissection; thirteen subsequently developed disseminated disease.
Male 11 6 2 7 4
Female 31 5 1 6 4
Total 42 11 3 “13
Discwsion
30
41
II
0 1 9 I I 2 2 2
Site ofprimary tumour
Tot&
Table 2
Female
10-19 20-29 30-39 4&49 50-59 60-69 70-79 80-89
Lower limb Upper limb Ant. trunk Post. trunk Head and neck
31
in Primary Cutaneous Malignant Melanoma
8
Preoperative radiotherapy of primary malignant melanomas was carried out in an attempt to decrease the incidence of secondary disease by eliminating mi-
British Journal of Plastic Surgery
32 n=47
l-l=30 YOO
%
100
90
90
80 70 60
80 70 II
Dead of MM
50
m
Alive, recurred
40
m
Alive, no recurrence
30
%
60
a
50
EZB Alive, recurred
40
m
Dead of MM
Alive, no recurrence
30 20
20
10
10
0 ‘1
2345678910 Years since treatment
Years since treatment
Fig. 1 Figure l-The Figure 2-The
Fig. 2
fate of male patients l-10 years after combined treatment for Stage I malignant melanoma.
fate of female patients I-10 years after treatment.
of viable tumour cells during the surgery (Peet and Patterson, 1963). This is distinct from the reported use of radiotherapy postoperatively to treat residual tumour (Johanson et al., 1983) or to justify smaller excision margins (Dickson, 1958). Comparison of survival data and locoregional recurrence patterns with those for contemporary published series suggests that irradiation prior to surgical excision of the primary tumour conferred no advantage. Tables 3 and 4 show the number of patients surviving to 5 and 10 years, with percentage survival figures calculated after exclusion of those patients lost to follow-up or dead of unrelated disease, together with comparable figures from contemporary series in croembolisation
Table 3 Five-year survival. lymph node dissection)
(Patients
without
Male
Female
Total
Alive Dead of MM Dead, other Lost to review
12 10 2 1
27 8 1 0
39 18 3 I
5-year survival (see text)
55%
77%
68%
Glasgow Scottish Melanoma Group
57%
72%
66% 68%
Table 4 Ten-year survival. lymph node dissection)
(Patients
without
elective
elective
which surgery alone was employed (Cochran, 1969; Griffiths and Briggs, 1984; MacKie et al., 1985). Since elective lymph node dissection was not practised in any of these three other series, the sixteen patients so treated in Oxford (5 male and 11 female patients) have not been included in these tables. The overall 5-year survival of 68% of such patients in the present series does not differ significantly from the 66% 5-year survival found among 102 patients with clinical Stage I disease treated in Glasgow in the 1950s and early 1960s (Cochran, 1969) (chi-square= 1.12; p >0.7), and is the same as the 68% overall survival calculated on the same basis from figures reported by the Scottish Melanoma Group for their 1979 cohort of patients (MacKie et al., 1985) (chi square = 0.016; p = 0.9). In the series reported by Griffiths and Briggs (1984), considering 258 patients with Stage I malignant melanoma treated in Bristol between 1967 and 1972, overall lo-year survival was 60%, which is similar to the 57% found in the present study (chi-square = 0.11; p>O.7). In 70 patients the Breslow thickness of the tumour has been measured. One patient was lost to follow-up and three died of unrelated causes within the first 5 years after treatment. In Table 5, the 52 of the remaining patients who had not undergone prophylactic lymph node dissection have been stratified according to tumour thickness into three groups, divided at Breslow thicknesses of 1.5 mm and 3.5 mm, and
Table 5
Survival related to tumour thickness Male
Female
Total
Male
Female
Total
Alive Dead of MM Dead, other Lost
7 10 5 3
20
21
10 3 3
20 8 6
<1.50mm 1.5-3.49 mm 3.50 mm
4 3 75% 10 5 50% 6 3 50%
10 9 90% 17 14 82% 5 240%
14 12 86% 27 19 70% 11 545%
lo-year survival (see text)
41%
67%
57%
All
20 11 55%
32 25 78%
52 36 69%
54%
74%
60%
Hypothetical (see text)
Bristol
n
5YS
n
5YS
n
”
5YS
66%
Preoperative Adjuvant Radiotherapy in Primary Cutaneous Malignant Melanoma subdivided by sex. This follows the division used by the Scottish Melanoma Croup in considering their 1979 cohort (MacKie et al., 1985). Ahhough the absolute numbers of patients in the study are too small to permit statistical treatment of individual figures within this table, we have for the purposes of comparison calculated the expected 5year survival of a hypothetical set of patients from the Scottish se&s, numerically equal to the present total, and similarly weighted according to sex and Breslow thickness. Chi-square testing indicates no significant difference in 5-year survival between the patients in the present study and the hypothetical Scottish group who did not receive preoperative radiotherapy (for males chi-square=O.Ol, p>O.9; for females chioverall chi-square = 0.11, square =0.12, p>o.7; p>o.73. The small group of 116 patients who received prophylactic regional lymph node dissection are not typica of the series as a whole, apparently having sign&cantly greater IO-year survival (p = 0.05); however, the number of patients is clearly too small to permit wider conclusions in this contentious area, which is well argued elsewhere (e.g. Balch et al., 1985). Repeating the foregoing comparisons with these patients included does not yield significant differences between this series and any of the others cited (all remain p > 0. I). Fourteen percent of the Oxford patients developed a &al recurrence of tumour, and 30% regional lymph node metastases. Comparable figures are reported for the Glasgow series (Cochran, 1969), with a local recurrence rate of twenty percent and lymph node metastases in 25x, and from Bristol (6riffiths and Briggs, 1984), yhere 10% of patients presented with local recurrence as the first manifestation of recurrent disease, and a further 29% presented with lymph node m&stases as their first recurrence. The lack of additional impact of the combined treatment either on survival rates or on the incidence of focoregional recurrence is evident from these comparisons. This apparent failure of preoperative radiotherapy ~0 influence the outcome of traditional surgery for malignant melanoma presumably either indicates radioresistance of the tumour at these doses, QP reflects the presence of micrometastases aheady existing outside the irradiated field at the time of treatment. The disadvantages of radiotherapy must clearly include economic and logistic factors, as well as an unquantifiable additional burden of stress placed upon the patient b:y the extra treatment. Adverse effects of the radiotherapy itself were found infrequently in the present series; but one patient in whom the irradiated area ‘had not been completely excised presented in 19g8 with a basal cell carcinoma near’ the site of her melanoma excision in 1959, and the notes of another patient record grossly delayed primary healing of the split-skin-grafted excision site. In the hght of these findings we do not advocate a resumption of the use of radiotherapy in this fashion.
33
We should like to acknowledge
the assistance of the following surgeons for help, advice and information valuable in the preparation of this paper: Mr M. 6). Poole, Mr T. J. S. Patterson, Mr P. K. B. Davis, Mr D. C. McNeil& Professor W. H. Reid. Some of the data from this paper were presented at the 1988 Winter Meeting of the British Association of Plastic Surgeons, and at the January 1989 meeting of the UK Melanoma Study Group held at Queen Mary’s University Hospital, Roehampton.
References Adam, J. S., Habeshaw, T. and Kirk, J. (1982). Response rate of malignant melanoma to large fraction irradiation. Brirish Xournal of Radiology, 656,605. Balch, C. M., Cascinelli, N., Milto~~,G. W. a& Sim, F. H. (1985). Elective lymph node dissection: pros and cons. In Balch, C. M. and Milton, G. W. (Eds). Cutaneous melanoma. Philadelphia, Eippincott. BresBow, A. (1970). Thickness, cross-sectional areas and depth of invasion in the prognosis of cutaneous melanoma. Annals of Surgery, 172,902. _~_ Co&ran, A. 9. (1969). Malignant melanoma. A review of ten years’ experience in Glasgow, Scotland. Cancer, 23, 1190. Dickson, R. J. (1958). Malignant melanoma. A combined surgical and radiotherapeutic approach. American Journal of Roentgenology, 79, 1063. Griftiths, W. W. and Briggs, 9. C. (L984). Long term follow-up in cutaneous malignant melanoma: the relationship of maximal tumour thickness to disease free survival, disease recurrence and death. British Journal of Plastic Surgery, 37,507. Johanson, C. R., Harwood, A. R., Cmnmhgs, B. J. and Qtirt, I. (1983). O-7-21 radiotherapy in nodular melanoma, Cancer, Sl, 226. Ma&e, R. M., Soutar, D. S., Watson, A. C. H., Mchess, K. M., McPMe, 9. k., Hut&eon, A. W., Smyth, J. P., Crabah, K. C., MacGiivray, 3. Is., Rankin, R, and Kemp, 1. W. (1985). Malignant melanoma in Scotland 1979-1983. Luncet, 2,859. Overgaard, J., Qvergaard, M., Hansen, P. V. and van der Marse, H. (1986). Some factors of importance in the radiation treatment of malignant melanoma. Radiotherapy and CPncoIogy,5, 183. $emsopI, D. (1974). Radiotherapy in malignant melanoma. ,Proceedings of the Royal Society of Medicine,51,96. Pee& E. W. and Patterson, T. 9. S. (1963). I’%eEssentials of Plastic Surgqy. Oxford, Blackwell Scientific Publications.
The Authors Alan R. Ptipps, FRCS, formerly locum Senior Registrar in Plastic Surgery, Department of Plastic and Reconstructive SUFgeIy,The Radcliffe Infirmary, Oxford. Alan M. Godfrey, FRCS, Consultant Plastic Surgeon, Department of Plastic and Reconstructive Surgery, The Radciiffe Inthmary, Oxford. The late K. R. Durrant, FRCP, FRCR, Consultant in Radiotherapy and Oncology, Department of Radiotherapy and Oncology, Churchill Hospital, Oxford, Peter R. Millard, MD, FRCPatb, Consultant Histopathologist, Department of Histopathology, John Radclitfe Hospital, Oxford. Requests for reprints to Mr A. R. Phipps, Department of Plastic Surgery, Queen Mary’s University Hospital, Roehampton Lane, hAdoASV\'15 5PN. Paper received 5 July 1989. Accepted 12 3uly 1991 after revision.