Radiation Oncology/Melanoma/Radiobiology

Radiobiology for Malignant Melanoma

Majority of retrospective data suggests that large fractional doses result in better outcomes than small fractional doses
Two randomized trials were performed. Dutch trial compared large fractional doses (9 Gy vs. 5 Gy) and found no difference. RTOG compared large vs smaller fractional doses (8 Gy vs 2.5 Gy) and similarly found no difference
Best conclusion that can be drawn is that at least 2.5 Gy/fx should be used

Randomized

RTOG 83-05 (1984-1988) -- RT 32/4 vs. RT 50/20
- Randomized. Trial stopped prematurely due to no difference between arms. 126 patients, with measurable lesions. Arm 1) RT 32/4 vs. Arm 2) RT 50/20
- 1991 PMID 1995527 — "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.)
  - Outcome: CR hypofractionated 24% vs. standard 23% (NS); PR 35% vs. 34% (NS)
  - Conclusion: No difference between arms

Denmark -- RT 27/3 vs. RT 40/8
- 1985 PMID 4044346 -- "A randomized study comparing two high-dose per fraction radiation schedules in recurrent or metastatic malignant melanoma." (Overgaard J, Int J Radiat Oncol Biol Phys. 1985 Oct;11(10):1837-9.)
- Randomized. 35 tumors, 14 patients, metastatic or recurrent malignant melanoma. Arm 1) RT 27/3 vs Arm 2) RT 40/8
  - Outcome: No difference
  - Toxicity: Comparable and acceptable
  - No difference between 9 Gy/fx and 5 Gy/fx

Retrospective

University of Florida; 2006 (1980-2004) PMID 16973303 -- "Adjuvant radiotherapy for cutaneous melanoma: comparing hypofractionation to conventional fractionation." (Chang DT, Int J Radiat Oncol Biol Phys. 2006 Nov 15;66(4):1051-5. Epub 2006 Sep 12.)
- Retrospective. 56 patients (H&N 87%), high risk disease (recurrent 52%, cervical LNs, lymph nodes >3cm, >3 LN+, ECE, gross residual disease, close/positive SM, satellitosis), treated with adjuvant RT. Hypofractionated RT 30/5 (73%) or conventional with median dose 60/30 (27%). Median F/U 4.4 years
- Outcome: 5-year LRC 87%, CSS 57%, OS 46%. No difference between schedules (p=0.97) for any endpoint
- Toxicity: late toxicity 4% (1 osteoradionecrosis of external auditory canal, 1 radiation plexopathy), both in hypofractionated regimens
- Conclusion: Hypofractionation and conventional fractionation equally efficacious. Bias for hypofractionation in absence of contraindications

Konefal et al, 1987 - PMID 3112864 — "Malignant melanoma: analysis of dose fractionation in radiation therapy." Konefal JB et al. Radiology. 1987 Sep;164(3):607-10.
- Retrospective. 67 pts with skin lesions or nodal mets. Various dose schedules.
- For fraction size > 5 Gy, 50% CR, vs 9% for < 5 Gy/fx. Local control @ 1 yr 25% vs 7%.

1986: Overgaard - PMID 2424880 — "The role of radiotherapy in recurrent and metastatic malignant melanoma: a clinical radiobiological study." Overgaard J et al. Int J Radiat Oncol Biol Phys. 1986 Jun;12(6):867-72.
- Analysis of total dose, dose per fraction, treatment time. 618 lesions.
- CR in 48% (sustained in 87% at 5 yrs). Correlation with high dose per fraction with response (59% CR for >4 Gy vs. 33% <= 4 Gy). Total dose, treatment time, and NSD did not correlate with response.
- Calculated isoeffect formula for dose and volume. Use of hyperthemia: thermal enhancement ratio (TER) of 2.0.

UK; 1978 PMID 709039 -- "The relationship between total dose, number of fractions and fractions size in the response of malignant melanoma in patients." (Hornsey S, Br J Radiol. 1978 Nov;51(611):905-9.)
- Retrospective. 52 patients. Isoeffect curve generated
- Conclusion: Response to 4-8 Gy/fx better than 2-3 Gy/fx

MD Anderson Regimen