melanoma and radiation video slides

Radiation for Malignant MelanomaRobert Miller MD

www.aboutcancer.com

Treatment of Melanoma

Treatment is generally surgery. Is there a role for radiation in this disease?

Does Melanoma Respond to Radiation?

RTOG Trial 83-05 compared to dose regimens for measurable melanoma, Response Rate as Noted:

Complete Partial

8Gy X 4 24% 36%2.5Gy X 20 23% 34%

Overall 59% response to radiation and no difference by dose

Int J Radiat Oncol Biol Phys. 1991 Mar;20(3):429-32

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

Compared 3Gy X 9 or 5Gy X 8 and no difference

Response Rate

complete and persistent69%partial response29%

total response rate 97%Int J Radiat Oncol Biol Phys.1985 Oct;11(10):1837-9.

NCCN.com

NCCN.org

Treatment Guidelines

• Early stages: wide local excision

• More advanced: wide local excision plus sentinel node biopsy, then based on the pathology consider research trial, observation or interferon

• Metastatic: clinical trial, possible radiation and systemic therapy

Treatment Guidelines

• Early stages: wide local excision

• More advanced: wide local excision plus sentinel node biopsy, then based on the pathology consider research trial, observation or interferon

• Metastatic: clinical trial, possible radiation and systemic therapy

Role for Radiation in Melanoma

Primary Disease

Consider adjuvant treatment (PostOp) in selected patients with desmoplastic melanoma with narrow margins, locally recurrent disease or extensive neurotropism (invading into the nerves or around them)

Radiation Alone for Melanoma

Old data for lentigo maligna showed control with radiation in 92%, the control for nodular or mucosal melanoma is lower

Adjuvant RT may be considered in the following settings ●Following resection of melanomas with desmoplastic or neurotropic features●Thick melanomas (>4 mm) particularly if ulcerated or associated with satellitosis●Melanomas arising from the head and neck particularly those involving mucosal sites●Inability to achieve negative resection margins

Treatment Guidelines

• Early stages: wide local excision

• More advanced: wide local excision plus sentinel node biopsy, then based on the pathology consider research trial, observation or interferon

• Metastatic: clinical trial, possible radiation and systemic therapy

Role for Radiation in Melanoma

Regional Disease

Consider adjuvant treatment (PostOp) if:

Lymph node basin radiation will reduce the risk of local recurrence but has no impact on relapse-free survival

Value of PostOp Radiation for high risk Lymph Node Patients

Category Radiation No Radiation

Relapse/5y 10.2%40.6%

Side Effects / lymphedema20% 13%

Cancer. 2009 Dec 15;115(24):5836-44

Value of PostOp Radiation for high risk Lymph Node Patients

Lancet Oncol. 2012 Jun;13(6):589-97

Randomized trail of postOp radiation in high risk patients after lymphadenectomy

Radiation No RadiationLocal Relapse 18% 32%

PostOp Lymph Node Field

PostOp Lymph Node Field

PostOp Lymph Node Field

Treatment Guidelines

• Early stages: wide local excision

• More advanced: wide local excision plus sentinel node biopsy, then based on the pathology consider research trial, observation or interferon

• Metastatic: clinical trial, possible radiation and systemic therapy

Role for Radiation in Melanoma

Brain Metastases: radiosurgery and/or whole brain radiation either as adjuvant (postOp) or primary treatment

Treat other symptomatic or potentially symptomatic soft tissue and/or bone metastases

The role of radiation therapy following resection of single brain metastasis from melanoma

Relapse in the Brain after Treatment

Surgery Only: 85%

Surgery and PostOp Radiation: 24%

Neurology January 1990 vol. 40 no. 1 158

Benefits of Palliative Radiation for Metastatic Melanoma

Significant Symptom Relief: CNS (39%) non-CNS (68-84%)

Objective Response: 49 – 97% and complete response 17-69%

Study: Response Rate: CNS (54%) and Nodes (77%, with 44% complete response)

Radiosurgery for Brain

MetastasisLocal control Rates of 73 to 94%Risk of radiation necrosis of 5 to

10%

Better than whole brain if single lesion and good performance patient in the RTOG 95-08 Trial

Radiosurgery

Right temporal lobe melanoma met before and 15 months after

radiosurgery

Radiosurgery Brain

Survival after whole brain radiation is generally 3.6 to 4.1 months

In series using radiosurgery the median survival was 11.1 months and 48%/1y and 18%/ 2yMultimodality treatment of melanoma brain metastases incorporating stereotactic radiosurgery (SRS). Cancer. 2007 May 1;109(9):1855-62.

RS Melanoma Brain Mets at UCSF

Median survival was 35 weeks (8 months) , solitary (35w) and multiple (33w)

Local control at 6 months (89%) and at 12 months (77%)

Cancer J Sci Am. 1998 Mar-Apr;4(2):103-9.

Multiple Brain Mets… Whole Brain or Radiosurgery?

RTOG Class for People with Brain Metastases

I (KPS =70, age < 65y, mets to brain only)

II KPS = 70III KPS < 70

Karnofsky Score (KPS) 70 = Cares for self; unable to carry on normal activity or do active work KPS 60 = Requires occasional assistance, but is able to care for most personal needs

Survival by Treatment (WB whole brain, S surgery, RS radiosurgery) and Performance

Score (RTOG)

RTOG WB S RS

I 7.1 mos 14.8 mos 16.1 mos

II 4.2 mos 9.9 mos 10.3 mos

III 2.3 mos 6.0 mos 8.9 mos

Radiosurgery Brain

Radiosurgery for melanoma brain metastases in the ipilimumab era and the possibility of longer survival.

RS RS + Ipilim.

mean survival 4.9 mos 21.3 months

survival/2 years 19.7% 47.2%

J Neurosurg. 2012 Aug;117(2):227-33

Role for Radiation in Melanoma

Brain Metastases: radiosurgery and/or whole brain radiation either as adjuvant (postOp) or primary treatment

Treat other symptomatic or potentially symptomatic soft tissue and/or bone metastases

Benefits of Palliative Radiation for Metastatic Melanoma

Significant Symptom Relief: CNS (39%) non-CNS (68-84%)

Objective Response: 49 – 97% and complete response 17-69%

Study: Response Rate: CNS (54%) Nodes (77%, with 44% complete response)

Response Rates

Mayo Clinic Study, 114 non-CNS lesions

Complete response: 9%Partial response: 75%No Change: 11%Worsening: 5%Cancer. 2007 Oct 15;110(8):1791-5

Radiation for Malignant MelanomaRobert Miller MD

www.aboutcancer.com