Epithelial Cancer- NMSC & Melanoma

Transcription

1 Epithelial Cancer- NMSC & Melanoma David Chin MB, BCh, BAO, LRCP, LRCS (Ireland) MCh(MD), PhD (UQ), FRCS, FRACS (Plast) Plastic & Reconstructive Surgeon Visiting Scientist Melanoma Genomic Group & Drug Discovery Group Queensland Institute of Medical Research

2 Agenda Incidence Origin/histology Morphology Risk groups Diagnosis Treatment & controversies Prognosis Future treatments

3 Incidence for Australia BCC 788/100,000 SCC 321/100,000 BCC:SCC 2.5:1 Staples & Marcks Int J Cancer 1995 Melanoma 44/100,000 (M) 36/100,000 (F) 10/100,000 (UK) Cancer Registry

4 Queensland Highest incidence of skin cancers in the world Non-melanoma 1:3 life-time risk Melanoma 1:14 life-time risk

5 Histology

6 What is skin cancer? BCC

7 What is skin cancer? SCC

8 What is skin cancer? Actinic keratosis /Solar keratosis 0.1% SCC 25% regression

9 Histology Actinic keratosis /Solar keratosis 0.1% SCC 25% regression Intraepithelial carcinoma 5% SCC

10 Histology Melanocytes

11 Melanocyte

12 Melanocyte & melanin production

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14 Melanoma Progression Metastatic Melanoma Vertical Growth Phase Melanoma Tumourigenic Radial Growth Phase Melanoma Melanocytic Dysplasia Common Nevus Melanocyte

15 Morphology BCC nodular, superficial, sclerosing SCC verrucous, ulcerative Melanoma superficial, nodular, lentigo, amelanotic, desmoplastic

16 Morphology Molecular profiling a better determinant Diagnosis Prognosis Treatment modality

17 Treatment Surgery Radiotherapy Topical

18 Prognosis BCC 95% complete 5% incomplete 9% recurs 36% 2 nd BCC 30% residual complete 20-30% recurs 47% recurs

19 High-risk mask area

20 Post op adjuvant radiotherapy.

21 Recurrence BCC-Risk

22 Clinical presentation skin cancer (SCC) with metastasis Site Size Depth Origin ear lip <2cm >2cm <2mm >2mm >6mm Marjolin s Incidence % rare

23 Clinical presentation skin cancer (SCC) with metastasis Site Size Depth Origin ear lip <2cm >2cm <2mm >2mm >6mm Marjolin s Incidence % rare

24 Recurrence SCC-Risk

25 Melanoma

26 Melanoma <5% of all skin cancer >75% of death from skin cancer

27 Melanoma 1 node +ve <50% 5 yrs survival >1node +ve <25% 5 yrs survival 40% of node metastases are subclinical (micrometastases)

28 Data from Intergroup Study

29 Melanoma-Prognostic factors Age Anatomic trunk, H&N BANS (Back, Posterior upper Arm, posterior Neck, Scalp) Sex incidence of stage I/II equal in both sexes, higher survival in female (but also thinner lesions, more on extremities and less ulceration Desmoplastic (neurotropic) not associated with worse prognosis. Higher local recurrence. Neurotropism is associated with worse prognosis. Lymphocyte infiltration reflect host response. Correlates with improved survival Regression a poor prognostic indicator DNA ploidy aneuploidy correlated with worse prognosis Mitotic rate & index independent predictor of survival especially if >6 per mm2 Vertical Growth Phase greater metastatic potential (c.f. radial growth phase)

30 Melanoma- Not a prognostic factor Tumour vascularity no clear evidence to confirm its prognostic value Pigmentation - no significance Pregnancy no difference in survival although pregnancy may promote earlier appearance of metastatic disease. Interval between excisional biopsy and definitive excision no adverse effect of delaying WLE after excisional biopsy

31 Melanoma- Summary prognostic factors Summary for Stage I & II Melanoma: Generally good prognosis Independent indicators of survival Tumour thickness Presence of ulceration Anatomical location of primary lesion Level of Invasion Patient age and sex

32 Melanoma- SLNB Rationale: The presence or absence of LN mets is the single most powerful predictor of recurrence and survival in melanoma Most primary tumour prognostic factors contribute relatively little to prognostic models once LN met is established (except for ulceration) Therefore, melanoma patients might benefit from accurate nodal staging procedure ELND as a staging procedure is associated with significant morbidity 20% of patients with node negative intermediate thickness tumors will have micro-metastasis.

33 Melanoma- SLNB Debate on accuracy of SLNB Definition of Sentinel node especially if more than one node is submitted for pathological examination Paper claiming improved survival has flawed evidence and analysis No place for SLNB except in trials

34 Melanoma- SLNB Principles/Assumptions: Different regions of skin have specific patterns of lymphatic drainage to the regional lymphatic basin SLN is the first node/s in the lymphatic basin into which the primary melanoma consistently drains (may not necessarily be the closest) SLN can be located The status of SLN will reflect the status of higher nodes Negative SLN means negative nodes in the basin Can detect melanoma cell in SLN (PCR/IHC different results)

35 MSLT(Multicenter Selective Lymphadenectomy Trial)-1 To determine whether SLNB demonstrated survival benefit Randomise patients with melanomas over pt2 or greater into WLE with observation and WLE with SLNB groups SLNB allows nodal staging adjuvant therapy can be considered for appropriate patients No overall survival advantage for early lymphadenectomy c.f. with nodal observation (87% c.f. 86% reported)

36 MSLT(Multicenter Selective Lymphadenectomy Trial)-2 MSLT II Trial (commenced 2004) To determine whether SLN +ve patients require subsequent LND 80% of SLN +ve patients with subsequent LND has no other nodes Recruitment of 2000 SN+ve patients, randomised to receive LND + Interferon within 4 months or interferon only and observation with high-resolution U/S

37 Metastasis in epithelial cancers Eventual cause of morbidity & mortality Resistant to conventional treatment If we can prevent or inhibit metastasis, we will improve survival or cure 90% of cancers. Increase benefit from reconstructive surgery or previously deemed inoperable.

38 Metastasis markers Improve diagnosis Monitor progress/prognosis Organ/function preservation surgery Ideally, a serum marker like PSA (prostatic surface antigen)

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40 What is gene expression profiling?

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44 J Clin Invest Jan;116(1):261-70

45 Thank you Download notes form website:-