Melanoma is the most lethal form of skin cancer. While it only accounts for about 3% of skin cancer cases, it causes around 75% of skin cancer deaths. The rate of melanoma is increasing in older age groups. Risk factors include poor tanning ability, red or blond hair, family history, and sun exposure. Melanoma can spread locally, to lymph nodes, or distantly to organs. Staging involves tumor thickness and presence of metastases. Treatment involves surgery to remove the primary tumor and lymph nodes, with the addition of radiation therapy or immunotherapy for higher-risk cases. Advanced or metastatic melanoma may be treated with targeted therapies, immunotherapy, chemotherapy, or palliative radiation.

1. Melanoma
Susheel Yeshala

2. Epidemiology
• Among the common skin cancers, melanoma is the most lethal.
• only 3% of all skin cancers diagnosed each year
• 75% of all skin cancer-related deaths. [1]
• Incidence and mortality are decreasing in the younger population,
• Increasing in the older age groups. [2]
1.Chang DT, Amdur RJ, Morris CG, Mendenhall WM. Adjuvant radi therapy for cutaneous melanoma: comparing hypofractionation to onventional fractionation. Int J Radiat Oncol Biol Phys 2006;66:1 5
1-5. [PUBMED] [FULLTEXT]
2.French J, McGahan C, Duncan G, Lengoc S, Soo J, Cannon J. How gender, age, and geography influence the utilization of radiation therapy in the management of malignant melanoma. Int J Radiat
Oncol Biol Phys 2006;66:1056-63.
[PUBMED] [FULLTEXT]
3.Mowbray M, Stockton DL, Doherty VR. Changes in the site distribution of malignant melanoma in south-east Scotland (1979-2002). Br J Cancer 2007;96:832-5. [PUBMED] [FULLTEXT]

3. Epidemiology
The rate of increasing incidence varies
geographically
• “High incidence regions" like Australia,
• “Moderate incidence regions" like
Canada and USA, and
• “Low incidence regions" like Scotland
and India. [3]
HIGH
LOW
LOWMODERATE

4. Risk factors
Patient related
Host: poor tanning ability, white race, red hair, blond hair, blue eyes, freckles
Premalignant conditions: dysplastic nevi, congenital nevi, Spitz nevi ,or juvenile mela
noma
Past medical history: history of previous melanoma, family history of melanoma,
immunosuppression, sun exposure, sunburns
Genetic predisposition: FAMMM, xeroderma pigmentosa.
Susceptibility genes in familial melanoma include CDKN2A, p14ARF, CDK4, and MC1R
.
Patients with CDKN2A (9p21) are also at risk for developing pancreatic carcinoma at
early age

5. Risk factors
Environmental
Petroleum and its by-products,
Polyvinyl chloride,
Polycyclic aromatic hydrocarbons,
Benzene,
Pesticides

6. Pathology
Melanoma arises from melanocytes
Present in the epidermis as well as in other parts of the body including the
eye and respiratory, gastrointestinal, and genitourinary tracts.
Pathologic subtypes:
1. Superficial spreading (70%, sun exposure, slow radial, rapid vertical)
2. Nodular (30%, most malignant)
3. Lentigo malignant (4-15%, elderly, best prognosis)
4. Acral lentiginous (2-8%, 6th decade, palms and soles, metastasize),
5. Desmoplastic (1-3%, 6 -7th decade, PNI, recurs locally).

7. Patterns of spread
Local Extension
Depth of invasion correlates with survival
Strong relationship between tumor thickness and risk of nodal metastasis.
Clark’s classification and Breslow thickness defines melanoma by depth of
invasion and prognostic significance

8. Patterns of spread
Lymph Node Metastasis
• Depends on the location and extent of invasion of the primary tumor
• In thin lesions (<1 mm) lymph node metastasis is rare.
• On occasion melanoma cells present at distant sites as metastasis.

9. Patterns of spread
Distant Metastasis
Hematogenous spread to lungs, liver, bone, brain, and
More with invasive or thicker lesions.

10. Clinical presentation
White adults,
4th or 5th decades(peak incidence).
Melanoma is rare in dark-skinned races.
Presentation
Suspicious pigmented lesions,
Sun-exposed areas,
Approximately 85% of melanoma patients present with localized disease,
15% with regional disease, and
5% with distant metastatic disease.
Using the mnemonic ABCDE is helpful in identifying suspicious lesions.
Asymmetry
Borders that are irregular or diffuse
Color variation
Diameter >5 mm
Enlargement or evolution

11. Staging – AJCC 8th Edition

12. Staging – AJCC 8th Edition

13. Staging – AJCC 8th Edition

14. Staging – AJCC 8th Edition

15. Staging – AJCC 8th Edition

16. Staging – AJCC 8th Edition

17. Staging – AJCC 8th Edition
I - T1, T2a
II - T2b, T3, T4a
III – N+
IV – M+

18. Diagnosis
Established by
Excisional biopsies (1- to 3-mm margin),
Full thickness incisional biopsies, or
Punch biopsies of the thickest portion of the tumor,
Biopsies - consideration of future definitive treatment in mind.

19. Diagnosis
CT and MRI are only in carefully chosen group of patients
CT - bone invasion and nodal metastases.
High-resolution MRI - PNI.
PET is useful to detect regional and distant metastases.

20. Treatment
Modalities
Surgery
Radiotherapy
Systemic therapy
Stage wise
Ia – WLE
Ib – III – WLE+ SLNB+/- Elective nodal dissection
IV – Palliative CT/RT

21. Treatment Surgery
Mainstay of definitive treatment modality
Indications
Lesions ≥1.0 mm in thickness, sentinel lymph node biopsies are recommended
Positive sentinel lymph node biopsy indicates a dissection of the involved
nodal basin
Indicated in highly selected cases with limited distant metastatic disease such as
solitary brain, lung, and subcutaneous tissue metastasis

22. Treatment Surgery
Techniques
Surgery involves a wide excision of the primary lesion
The recommended excision margin depends on the tumor thickness
5 large RCT
Narrow margin (1–2 cm) VS wide margin (3–5 cm)
No statistically significant OS
maximal surgical margin recommended is up to 2cm
(Cochrane Database of Systematic Reviews).

23. Treatment Surgery
cN0: WLE and SLN biopsy, with completion LND if SLN+.
Spares patients from the complications associated with elective lymphadenectomy
SLNB improves staging to identify patients who may need completion node dissection
and/or adjuvant therapy
The false-negative rate of SLNB is <5%
Clinically N+: WLE and nodal dissection
Patients with positive SLNB and immediate lymphadenectomy had a superior
overall survival advantage as compared with patients with lymphadenectomy
at the time of clinically evident nodal diseases[1].
1. Morton DL, Thompson JF, Cochran AJ et al (2006) Sentinel-node biopsy or nodal observation in melanoma. N Engl J Med. 355:1307–1317.

24. Treatment Radiotherapy
Primary RT
Rarely indicated
Exception of lentigo malignant melanomas on the face that would cause severe cosme
tic/functional deficits with surgery.
These can be treated with a 1.5 cm margin with 50–100 Gy/10–20# with 100–250 kV
photons.

25. Treatment Radiotherapy
Adjuvant RT
To primary site -
To reduce LRR for deep desmoplastic melanoma with narrow margins,
extensive neurotropism,
locally recurrent disease
To Node
Large lymph nodes (>3 cm)
>/= 2 positive nodes
Extranodal extension
Recurrent disease in the previously dissected nodal basin
Chronic lymphedema – Groin nodal RT

26. Treatment Systemic therapy
For node-negative IA - IIA: observation or clinical trial
For node-negative IIB–IIC: observation vs clinical trial vs high-dose IFN
For node positive: observation, clinical trial, interferon alfa, ipilimumab, or other bioche
motherapy agents
A Meta-analysis shows a statistically significant improvement in overall and disease-
free survival in patients with high risk cutaneous melanoma treated with IFN-α [1]
1. Mocellin S, Pasquali S, Rossi C et al (2010) Interferon alpha adjuvant therapy in patients with high-risk melanoma: a sy
stematic review and meta-analysis; J. Natl Cancer Inst. 102(7): 493-501; Wheatley K, Ives N, Hancock B et al (20 3) Doe
s adjuvant interferon for high risk melanoma provide a worthwhile benefi t? A meta-analysis of ranomizede trials. Cancer t
reat rev 29: 241-252

27. Treatment Metastatic
Biopsy for genetic analysis (e.g., BRAF mutation, c-KIT).
Consider resection of limited resectable metastasis.
Disseminated metastases: systemic therapy, palliative resection, or RT:
Immunotherapy: interferon alfa-2b, interleukin-2, anti-CTLA4 (ipilimumab), anti PD-1 (p
embrolizumab, nivolumab), injectable oncolytic virus (talimogene laherparepvec).
Targeted therapy: BRAF (dabrafenib, vemurafenib), MEK (trametinib, cobimetinib).
Chemotherapy: Dacarbazine, Temozolomide (for brain metastases).

28. Treatment Metastatic
Dacarbazine (DTIC) is the only single-agent approved by FDA for treating metastatic
melanoma.
20% objective response rate
Median response duration of 5 to 6 months
complete response rates of 5%.
CBDT (cisplatin, carmustine, DTIC and tamoxifen) or "Dartmouth regimen"
Response rates, up to 55%
Complete responses, up to 82 months,

29. RT Techniques Simulation
Treatment setup
• Head and neck: supine or open neck position; depending on tumor location, bolus
can be used to reduce dose to temporal lobe, larynx, ear canal.
• Axilla: supine with treatment arm akimbo, AP/PA.
• Groin: unilateral frog-leg position.
Primary volume
• Target volume for primary lesion: primary site +2–4 cm margin.

30. RT Techniques Simulation
Nodal target volume depends on primary site:
• H&N: preauricular, postauricular LN for facial and posterior scalp primaries, and
• ipsilateral cervical LN levels I through V, including ipsilateral supraclavicular fossa,
for tumors at high risk.
• Axilla: levels I through III; for bulky high axillary disease, include supraclavicular fos
sa and low cervical LN.
• Groin: include entire scar and regions with confirmed nodal disease. Can include
external iliac LNs for cases with positive inguinal lymphadenopathy, but toxicity will
increase.

31. Dose Prescription
For electrons, prescribe to 90%
Fractionation
• Hypofractionation approaches are well tolerated and more convenient.
• MDACC - 30Gy/5# twice weekly.
• RTOG 8305 – 32Gy/4#/4 weeks vs 50Gy/20#

32. Dose Prescription
COMPLICATIONS
• Site dependent:
• Most sites: erythema, tanning, dry or moist desquamation
• Late complications: thinning of subcutaneous fat; mild to moderate fibrosis
• Lymphedema, particularly in patients with high body mass index or treated with
adjuvant RT to groin
• Other late effects: osteitis, fracture, joint stiffness, and neuropathy

33. Follow up
Follow up
HPE, CBC, Dermatoscope, Imaging (if required)
1st follow up – 4-6 weeks after radiotherapy
First 1-2 yrs – 3-6 months
3-5yrs – 6-12 months

34. Thank you

35. RT Techniques Orthovoltage
Orthovoltage
Most early skin cancers are managed with ortho-voltage RT
Potential ranging from 150 to 500 Kv
Mostly operated at 200 to 300 kv
10-20 mA
HVL 1-4 mm Cu
SSD 50 cm – Limit size of treatment field
Maximum dose occurs close to skin surface
90% occuring at 2cm depth.
primarily suited for treatment of superficial tumors that do not involve adjacent bone

36. RT Techniques Orthovoltage

37. RT Techniques Orthovoltage

38. RT Techniques Orthovoltage
Advantages
• Maximum dose is at the skin surface
• Bolus is not required
• Less beam constriction both at the
surface and at depth
• Smaller fields can be used
• It is less expensive;
• Tumor control may be higher,
• possibly as a result of increased
• radiobiologic effectiveness (RBE)
• Relatively easy to repair and maintain
• Less shielding and space is required
for operation
Disadvantages
• Higher dose to deeper tissues and to
underlying bone and cartilage
• Higher dose to skin if adequate
doses needed to treat deep seated
tumours – penetrating beam
• Increased absorbed dose in bone
• Increased scattering
• Unavailability

39. RT Techniques Electron beam
• Electron therapy
• Clinically useful energy range for electron is 6 to 20 MeV
• Used for treating superficial tumors ( <5 cm deep) with a
• Characteristically sharp drop off in dose beyond the tumor
• Dose uniformity in the target volume
• Minimizing dose to deeper tissues
• The skin-sparing effect with the clinical electron beams is only modest or nonexistent

40. RT Techniques Electron beam

41. RT Techniques Electron beam

42. RT Techniques Photon beam
Photon beam therapy
Advanced skin cancers that are
deeply invasive are often
adequately cover the deep extent of the tumor.
Bolus is used to ensure an adequate surface dose.
3DCRT/IMRT