1 / 23

Patient

Patient . 64 yo caucasian woman noted to have elevated LFTs on annual P.E. Felt well. US Liver: 9 cm mass in right lobe of liver Biopsy: Melanoma, high mitotic rate PMH: Melanoma in situ removed from scalp 14 years earlier. Patient. PMH: Htn, osteoporosis

parley
Download Presentation

Patient

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. Patient • 64 yo caucasian woman noted to have elevated LFTs on annual P.E. Felt well. • US Liver: 9 cm mass in right lobe of liver • Biopsy: Melanoma, high mitotic rate • PMH: Melanoma in situ removed from scalp 14 years earlier

  2. Patient • PMH: Htn, osteoporosis • FamHx: Fa had prostate cancer; died of other causes at age 89; mother died of natural causes at age 84. Two healthy children. No other malignancies in family • SH: Married. Choir director, pianist. Rare EtOH. Remote, brief tobacco use.

  3. Patient • ROS: Mild fatigue, mild dyspnea with exertion, dry cough, 3# wt loss • PE: Normal vital signs. Normal funduscopic exam. No adenopathy. Normal lung exam. Normal abdominal exam. Normal skin exam. • Labs: Alk Phos 160; AST 64; ALT 46

  4. Patient • CT chest: 3 nodules, largest 7 cm in right lung base • CT abdomen: 4 liver mets, largest 9 cm; bilateral adrenal mets, 7 cm • MRI brain: Normal

  5. Melanoma • 54,000 new cases in 2003; 7600 deaths • Incidence rising • Lifetime risk 1 in 82 for women; 1 in 58 for men • Ninth most common cancer; second in terms of loss of years of potential life • At presentation, 84% localized; 12% regional; 4% distant metastatic disease

  6. Risk Factors for Melanoma • Fair complexion with red/blonde hair • Living in Australia (3X US incidence) • >5 nevi >5mm or >50 nevi over 2mm • Dysplastic nevus syndrome • Intense, intermittent sun exposure (ages 10-19) • Family history of melanoma- 1/3 have mutation in p16 (INK4a =CDKN2A cyclin dependent kinase) on chromosome 9p21

  7. UV Light & Melanoma • Intense intermittent exposure does not give time for melanocytes to synthesize melanin to protect them from UV-B irradiation & subsequent DNA mutations • Melanocytes contain antiapoptotic proteins that inhibit cell death after intense UV exposure

  8. Genetic Basis of Hereditary Melanoma • CDKN2A gene on 9p21: p16 protein that prevents phosphorylation of RB protein which regulates transcription factors and cell division • Mutations in this tumor suppressor gene can lead to unregulated cell growth • Associated with increased risk of pancreatic ca • Association of this mutation with atypical moles is unclear • Genetic testing is commercially available

  9. Other proto-oncogene links • Mutation in B-raf protooncogene in 65% of melanomas • This gene product is similar to the tyrosine kinase targeted by Gleevec which has been very successful in treating CML and GIST • Inhibitors of this gene are undergoing testing (BAY 43-9006)

  10. Melanoma Staging • Stage 0: melanoma in situ (95% cure rate) • Stage IA: <1 mm, level II-III, no ulceration (88% • IB: <1mm, level IV-V or 1-2 mm, no ulcer(79%) • IIA: 1-2mm with ulcer; 2-4mm, no ulcer (64%) • IIC: >4mm, with ulcer (45%) • IIIA: Microscopic node met (55%) • IIIB: Micro2 or 3 regional nodes (37%) • IIIC: Macroscopic dz in 2 or 3 nodes (20%) • IV: Distant metastases (<5%)

  11. Melanoma • Breslow: thickness of the melanoma, most useful prognostic factor • Clark’s: level of penetration- (I)confined to epidermis, (II) into papillary dermis, (IV) into reticular dermis, (IV) into subcutaneous fat

  12. Melanoma • Prognostic factors for localized disease: Breslow’s thickness, ulceration, Clark’s level (only for <1mm), primary tumor site, gender • Ulceration: absence of an intact epidermis overlying the melanoma (microscopic) • Likelihood of regional nodal involvement rises with increasing tumor thickness

  13. Treatment of Melanoma • In situ: Excision • < 1mm deep, 1 cm excision margin • 1-2 mm deep, 1 to 2 cm margin • >2 mm deep, 2 cm margin • Consider sentinel node evaluation if >1mm deep with Clark level IV or ulcerated; node dissection only if positive

  14. Adjuvant Therapy in Melanoma • Most pts with in situ or early stage disease are cured by excision alone • For node negative patients with <4mm without ulceration or <1mm with ulceration, no proven benefit • Clinical trial or high dose interferon adjuvant therapy appropriate for >4mm without ulceration & >1mm with ulceration • Improved relapse free survival but no improvement in overall survival in these node negative patients

  15. Adjuvant Therapy in Melanoma • For node positive patients whose disease has been resected: Adjuvant high dose interferon prolongs survival (37% 5yr RFS vs 26% with no Rx) • 20 million U/m2 IV 5 d/wk x 4 wks then 10 million U/m2 SQ 3 d/wk x 48 wks

  16. Follow up after excision • Stage 0: skin exams for life • IA: exam q3 to 12 mos • IB-III: history, physical exam (attn to regional node area), skin exam q3-6 mos x 3 yrs, q4-12 mos x 2 years, then annually. CXR, LDH, CBC “amy be considered”. CTs and PET scans not recommended. • Lifetime risk for developing second melanoma: 5%

  17. Treatment of Metastatic Disease • Solitary site: resect (often wait 8 to 12 wks to be sure there are not many subclinical sites) • Multiple sites: clinical trial vs systemic therapy (Dacarbazine or Temazolamide or IL-2 or combination chemoimmunotherapy [Dacarbazine + Vinblastine+ cisPlatin + IL2 + Interferon)

  18. Treatment of Metastatic Disease • Biochemotherapy • Cisplatinum 20mg/m2 daily x 4d • Vinblastine 1.6 mg/m2 daily x 4d • DTIC 800 mg/m2 day 1 only • Interleukin-2 9 million U/m2/d x 4d CIV • Interferon alpha: 5 million U/m2 SQ qd x 5 • Repeat q3 wks

  19. Treatment of Metastatic Disease • Biochemotherapy • 21% Complete response • 43% partial response • Half of the patients with CR remained in remission >5 years. • This complete response rate is ~3X greater than with single agent chemo

  20. Other drugs • Thalidomide: active in myeloma, gliomas, renal cell cancer • Antiangiogenesis and anti-inflammatory properties; inhibits TNF • When given with temozolomide, 25% respond

  21. Vaccine therapy in melanoma • Rare spontaneous regression of metastatic melanoma suggests host immunity plays important role in control • CancerVax: whole cell vaccine from 3 melanoma cell lines helpful in initial trial • Melacine: immunizes with 3 peptides present in/on melanoma cells; studies ongoing • No vaccine has thus far improved survival in adjuvant or metastatic setting

  22. Patient Follow Up • 3 cycles of chemoimmunotherapy • Lung nodule decreased from 7 to 5 cm • No change in liver masses but LFTs normalized • Adrenal metastases decreased from 7 to 5 cm • Mesenteric adenopathy improved • Thalidomide + Temozolamide planned for 8 weeks

  23. Lessons • Even in situ lesions can spread • Don’t allow kids to get sunburns • Look at your patients skin (everywhere) during annual exam • Understanding the molecular biology may lead to better treatments

More Related