Skin, soft tissue and lymph node metastases

Patients with skin, soft tissue, and lymph node metastases (UICC III) have a better prognosis than those with distant metastases (UICC IV).Some studies reported good palliation and CR ranged from 8–59% . Patients with initial tumor response (CR) were more likely to remain free of relapse within the irradiated volume, and patients with persistent local tumor control reached a 3-year survival rate of 56% as compared to 0% in those without initial and long-term tumor control.

Brain metastases

Literature data on RT for brain metastases from MM suggest an overall symptomatic improvement of 17–83% patients and a median survival of 1–5 months. This is in agreement with our data (tumor response: 55%; median: 5.3 months; 1 year: 23 ± 16%).

Bone metastases

Literature data on RT for MM bone metastases report a symptomatic improvement of 50–86% patients and a median survival of 2.5–4 months, similarly to our own data (tumor response: 83%; median: 6.6 months; 1 year: 29 ± 14%).

  CONCLUSION: External beam radiotherapy can provide long-term local control and effective palliation in malignant melanoma UICC stages IIB-IV.

Radiotherapy as palliative treatment for metastatic melanoma.

Kirova YM,  Melanoma Res. 1999 Dec;9(6):611-3. Henri Mondor University Hospital, Creteil, France.

Most of the patients were treated with 30 Gy of irradiation in 10 fractions over 2 weeks or 20 Gy in five fractions over 1.5 weeks. Of those with bone metastases, 67% responded to palliative bone treatment with good pain relief and/or decompression. Of the patients with brain metastases, 57% had amelioration of neurological function deficits, 29% did not respond, and one patient showed aggravation of his disease and did not finish the course of irradiation. Two patients with unresectable disease obtained partial remission and good palliation of symptoms. In conclusion, short-course radiotherapy has a role to play in the palliation of metastatic melanoma, with good relief of symptoms.

Fraction size in external beam radiation therapy in the treatment of melanoma.

Sause WT, Int J Radiat Oncol Biol Phys 1991 Mar;20(3):429-32 LDS Hospital, Radiation Therapy Center, Salt Lake City, UT 84143.

RTOG 83-05 was a prospective randomized trial evaluating the effectiveness of high dose per fraction irradiation in the treatment of melanoma. Retrospective analysis suggested a dose response curve of melanoma to external beam irradiation as the dose per fraction is increased. RTOG 83-05 randomized patients with measureable lesions to 4 x 8.0 Gy in 21 days once weekly to 20 x 2.5 Gy in 26-28 days, 5 days a week. One hundred thirty-seven patients were randomized and 126 patients were evaluable: 62 patients in the 4 x 8.0 Gy arm and 64 patients in 200 x 2.5 Gy arm. Patient characteristics were essentially identical. Stratification was performed on lesions less than 5 cm or greater than or equal to 5 cm. The study was closed on May 31, 1988 when interim statistical analysis suggested that further accrual would not reveal a difference between arms. Response rate overall was complete remission 23.8%, partial remission 34.9%. The 4 x 8.0 Gy arm exhibited a complete remission of 24.2% and partial remission of 35.5%. The 20 x 2.5 Gy arm exhibited a complete remission of 23.4% and partial remission of 34.4%. There was no difference between arms.

Radiation therapy for malignant melanoma.

Geara. Surg Clin North Am 1996 Dec;76(6):1383-98
Sufficient biologic and clinical evidence now exists to refute the longstanding dogma that melanomas are uniformly radiation resistant and hence radiation therapy has little role in the management of this disease. Although surgery remains the treatment of choice for the vast majority of localized melanomas, available data indicate that radiation therapy is a viable alternative for a few subsets of patients in whom surgery would result in cosmetic or functional deformity, such as patients with large facial lentigo maligna melanomas or small or intermediate-sized uveal melanomas. Retrospective and Phase II prospective studies have revealed that elective/adjunctive radiation therapy improves the local-regional control rate in patients with thick primary lesions, nodal involvement, or mucosal melanomas. Radiation therapy has been established as a simple and cost-effective treatment modality for palliation of patients with symptomatic metastatic spread.

Malignant melanoma: analysis of dose fractionation in radiation therapy.

Konefal JB, Emami B, Pilepich MV.  Radiology 1987 Sep;164(3):607-10

Thirty-five patients with 67 measureable cutaneous or lymph node metastases from malignant melanoma were treated with radiation therapy in a variety of total doses and dose fractions. There was no correlation between total dose and response rate. However, there was a strong correlation between fraction size and response rate. There were four (9%) complete responses in 43 lesions treated with fractions less than or equal to 500 rad (5 Gy) compared with 12 (50%) complete responses in 24 lesions treated with fractions greater than 500 rad (5 Gy) (P = .0006). Initial response rate was found to correlate strongly with local control at 1 year. The results were then analyzed with respect to lesion size, cutaneous versus nodal lesions, and site of cutaneous lesion (trunk, head and neck, or extremity). Correlation between fraction size and response rate was independent of lesion size, although there were fewer complete responses with increasing lesion size. Correlation was not seen in nodal lesions but was particularly striking in cutaneous lesions. This correlation was statistically significant only for cutaneous lesions of the extremities.

Analysis of dose fractionation in the palliation of metastases from malignant melanoma.

Konefal. Cancer 1988 Jan 15;61(2):243-6
Sixty-five visceral metastases from malignant melanoma were treated with radiation therapy.  Significant palliation was achieved in 40 of 65 (62%) symptomatic lesions. There was no correlation between total dose or dose fraction size and significant palliation. Brain and bone metastases were separately analyzed. Nineteen of 28 (68%) bone metastases were palliated. Appendicular bony metastases were more likely to be palliated than axial bony metastases (88% versus 60%).  Nine of 23 (39%) symptomatic brain metastases were palliated. These findings suggest that unlike treating cutaneous or nodal melanoma lesions for local control, there is no advantage in large fraction size when treating with palliative intent visceral melanoma lesions.

A randomized study comparing two high-dose per fraction radiation schedules in recurrent or metastatic malignant melanoma.

Overgaard J, von der Maase H, Overgaard M.   Int J Radiat Oncol Biol Phys 1985 Oct;11(10):1837-9

Thirty-five tumors in 14 patients with metastatic or recurrent malignant melanoma were randomized to high dose per fraction radiotherapy at either 9 Gy X 3 or 5 Gy X 8 twice weekly. Complete and persistent regression was found in 24/35 (69%) and partial response in 10/35 of the tumors. The overall response rate was 97%. No difference was observed between the two treatment regimens. Acute and late radiation damage to normal tissue was acceptable and of the same magnitude in both schedules.

The role of radiotherapy in recurrent and metastatic malignant melanoma: a clinical radiobiological study.

Overgaard J.   Int J Radiat Oncol Biol Phys 1986 Jun;12(6):867-72

Six hundred eighteen radiotherapy-treated malignant melanoma lesions were analyzed with regard to radiobiological parameters such as total dose, dose per fraction, treatment time, tumor volume, and various fractionation models. Forty-eight per cent of the treated tumors achieved complete response, which was persistent in 87% after 5 years. Neither total dose, treatment time, nor various modifications of the NSD concept showed any well-defined correlation with response. There was, however, a significant relationship between dose per fraction and response, and a high dose per fraction yielded a significantly better response (59% CR for doses greater than 4 Gy versus 33% CR for doses per fraction less than or equal to 4 Gy).  In a group of 131 patients with only local or regional disease, a 5 year survival rate of 49% was observed in 77 patients with persistent local tumor control, but only 3% survived among the 54 patients in whom local therapy failed. It is therefore, highly important to the probability of survival in recurrent melanoma that proper local treatment be performed.

Postoperative radiotherapy for cutaneous melanoma of the head and neck region.

Ang. Int J Radiat Oncol Biol Phys 1994 Nov 15;30(4):795-798

To assess the efficacy and toxicity of elective-adjunctive radiotherapy given in five 6-Gy fractions to patients with cutaneous melanoma of the head and neck at high risk for local-regional relapse.  Each group had a projected local-regional recurrence rate of approximately 50%. The radiotherapy consisted of five fractions of 6 Gy each, specified at Dmax, delivered twice a week, to a total dose of 30 Gy in 2.5 weeks. Electron beams of appropriate energies were used whenever possible. The actuarial 5-year local-regional control (LRC) and survival rates for the whole group were 88% and 47%, respectively. lesion thickness strongly affected the 5-year survival rate of group 1 patients (i.e., 100% for < or = 1.5 mm thick, but Clark's level IV, 72% for > 1.5-4 mm, and 30% for > 4 mm). In groups 2 and 3, the 5-year survival rate of patients with > three involved nodes was lower than that of patients with one to three positive nodes (23% vs. 39%). The overall 5-year actuarial LRC rate of 88% was much higher than that of our historical group and that reported in the literature (50%). The survival rate of patients with lesion of 1.5-4 mm thickness was also higher than that observed in other series.

Role of radiation therapy in the management of cutaneous malignant melanoma.

Fenig. Am J Clin Oncol 1999 Apr;22(2):184-6

Traditionally, cutaneous malignant melanoma is regarded as a radioresistant tumor. Recently, however, an increasing number of clinical studies have refuted this notion. In the palliative radiation therapy group, the response rate was 52% with a fraction size < or = 300 cGy and 35% with a larger fraction size.. Local regional control rates after adjuvant radiation therapy using conventional fractionation and larger fraction size were 87% and 82%, respectively. Radiation therapy is effective in the management of cutaneous malignant melanoma. It plays an important role in the palliation of metastatic disease and as an adjuvant treatment. No advantage in using a large fraction size over conventional dose schedules was found.

Radiation therapy of malignant melanomas: an evaluation of clinically used fractionation schemes.

Strauss. Cancer 1981 Mar 15;47(6):1262-6

To assess the importance of radiation dose fraction size in the treatment of malignant melanomas, the records of 48 patients (83 sites) treated at Tufts-New England Medical Center from 1971 to 1979 have been retrospectively reviewed. Fractions of 600-800 rad resulted in the best overall response (80%). The rapid fractionation scheme of 800-400-400 rad on successive days resulted in intermediate response (58%) and may be useful for the palliative treatment of selected patients.

The use of large fractions in radiotherapy for malignant melanoma.

Pyrhonen. Radiother Oncol 1992 Jul;24(3):195-7

Eighty-nine cutaneous, subcutaneous or lymph node metastases of malignant melanoma in 15 patients were treated with radiotherapy using electron beams at appropriate energies (6-15 MeV). A total dose of 40 Gy was given in 8 fractions (fraction size 5 Gy) over 23 days. The therapy was given as two weekly fractions on two consecutive days with a 24-h interval. The next two fractions were given after a pause of 6 days. Eighty-six of 89 lesions (97%) responded to treatment, response rate being clearly dependent on tumour size. All the 67 lesions less than 2 cm in diameter responded, 51 of them (78%) completely disappearing, while in tumours over 4 cm among 10 lesions only 2 CR lesions were achieved. In cases where prolonged follow-up (greater than one year) was possible no major late side-effects were observed. The treatment scheme with large fractions appears to be well-tolerated and effective for metastatic malignant melanoma.

Radiation therapy for nodal disease in malignant melanoma.

Burmeister . World J Surg 1995 May-Jun;19(3):369-71

Radiation therapy has been widely used for palliative management of inoperable metastatic malignant melanoma. For patients with nodal disease, response rates of approximately 70% have been reported. There are limited data concerning the role of adjuvant irradiation following therapeutic lymph node dissection. In this review, 57 patients with isolated resectable and nonresectable nodal disease have been treated with radiation. The overall response rate is 84% for bulky disease. Large fractions are beneficial.

Adjuvant radiation therapy after axillary lymphadenectomy for metastatic melanoma: toxicity and local control.

Strom. Ann Surg Oncol 1995 Sep;2(5):445-9

Certain patients with locally advanced melanoma have a high risk of regional recurrence after surgical excision and lymphadenectomy alone. Growing evidence suggests that radiation therapy may improve local control with acceptable morbidity for patients with melanoma in some sites. We conducted a retrospective evaluation of patients who received postoperative radiation therapy to the axillary lymphatics for malignant melanoma at the M. D. Anderson Cancer Center between 1980 and 1992. Twenty-two patients were irradiated using a hypofractionated treatment regimen (4-7 Gy/fraction), generally to 30 Gy in five fractions. Postoperative irradiation of the axilla for malignant melanoma has acceptable toxicity, even in those with extensive axillary dissection. In this group, patients treated for subclinical disease had a low rate of recurrence (5%).

High-dose fraction radiation therapy for intracranial metastases of malignant melanoma: a comparison with low-dose fraction therapy.

Vlock.   Cancer 1982 Jun 1;49(11):2289-94

Malignant melanoma is considered unresponsive to conventional radiation therapy when it is delivered at a daily dose rate of 130--300 rad/fraction. High-dose fraction therapy is effective for local control of cutaneous, lymph node, and soft-tissue metastases. Results in 46 patients treated with high- or low-dose fractions for intracranial metastases over the last decade in the Melanoma Unit and Department of Radiotherapy at Yale have been examined. Twenty-six patients received high-dose fraction therapy, generally 600 rad/fraction/week to 2400--3600 rad; 20 patients received low-dose fraction radiotherapy with 125--400 rad/fraction daily. Comparison of high- and low-dose fraction patients revealed: improvement in 38 and 35%, respectively, stability in 23 and 25%, and deterioration in 38 and 40%. Median survival was three months in the high-dose fraction group and 2 1/2 months in the low-dose fraction group.

Brain metastases from malignant melanoma: conventional vs. high-dose-per-fraction radiotherapy.

Ziegler.   Int J Radiat Oncol Biol Phys 1986 Oct;12(10):1839-42

Treatment consisted of whole-brain irradiation, either with dose fractions of 300 cGy (conventional fractionation, CF) or 500-600 cGy (high-dose-per-fraction, HDF) to a total of 3000 cGy. Two-thirds of the patients responded to radiotherapy as measured by improvement of at least one functional level. No difference in response could be attributed to dose schedules, either overall or in the subgroups of patients who had solitary or multiple brain metastases. Median survival was not significantly affected by fractionation schedule; however, patients who had solitary metastases survived longer, probably because of the nature of their disease. Treatment related toxicity was more frequent in the HDF group.


Radiation therapy of malignant melanoma: experience with high individual treatment doses.

Habermalz HJ, Fischer JJ  Cancer 1976 Dec;38(6):2258-62

Reports of the existence of a large shoulder on the radiation survival curve of cultured mouse and human malignant melanoma cells prompted a clinical trial of radiation therapy using high individual-dose-fractionation schedules. Typically, individual doses of larger than or equal to 600 rads were delivered once or twice weekly. The most clear-cut effect was against skin metastases. Twenty-nine of 33 lesions showed partial or complete regression when treated in this manner. None of 11 lesions responded that were treated with individual treatment doses of 200 to 500 rads, although in some cases the total doses were greater than 5000 rads. Some of the possible roles for an effective radiation regimen in the overall management of this complex disease are discussed.