1 / 64

Practical Oncology Mast Cell Tumor

Practical Oncology Mast Cell Tumor. Wendy Blount, DVM. Mast Cell Tumor. Mast cell granules contain histamine and heparin, among other things Degranulation is largely responsible for symptoms Release of histamine Increased gastrin secretion (anorexia, ulcers, hematemesis)

moses
Download Presentation

Practical Oncology Mast Cell Tumor

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. Practical OncologyMast Cell Tumor Wendy Blount, DVM

  2. Mast Cell Tumor • Mast cell granules contain histamine and heparin, among other things • Degranulation is largely responsible for symptoms • Release of histamine • Increased gastrin secretion (anorexia, ulcers, hematemesis) • Anaphylactoid reaction • Release of heparin – less clinically significant

  3. Mast Cell Tumor • Most often found on the skin • Most common skin tumor in the dog • Brachycephalics & retrievers predisposed • 2nd most common cancer in dogs • Also visceral & elsewhere • Gastrointestinal, Spleen, bone marrow • Less common sites • Oropharyngeal • Mediastinum • CNS • Nail bed, ocular & periocular

  4. Mast Cell Tumor • Can have many different appearances • Can be infiltrated with fat • Symptoms can be waxing and waning • Tumor gets bigger and smaller over time • 5-15% have multiple masses at presentation • 20-50% will have more MCT in the future, even if the first are cured

  5. Etiology • Allergic skin disease? • C-KIT mutation (aka SCFR, CD117) • In “high risk MCT” (high grade II & all grade III) • These have decreased survival time • can be treated with tyrosine kinase inhibitors (Palladia & Kinavet-CA1 ) • SCFR – stem cell factor receptor • C-KIT normally regulates proliferation, migration and differentiation • When C-KIT is mutated, it is constantly turned on, dysregulating cell growth an promoting malignancy

  6. Clinical Signs • GI Signs • Anorexia, vomiting, melena • Pruritus and skin flushing • Facial swelling • Weakness, lethargy • Delayed wound healing • Darier’s Sign • swollen, itchy, red skin after scratching or stroking the skin

  7. Clinical Signs • GI Signs • Anorexia, vomiting, melena • Pruritus and skin flushing • Facial swelling • Weakness, lethargy • Delayed wound healing • Darier’s Sign • swollen, itchy, red skin after scratching or stroking the skin

  8. Staging for Metastasis Eva Gerome Bonham TX Chris Longo – Diamondhead, MS Melanie Enger, - Lufkin TX

  9. Diagnosis • FNA Cytology often diagnostic • Round cells with or without granules • Granules intracellular or in background • Granules form a halo around the relatively pale nucleus • eosinophils • Give diphenhydramine before or right after aspiration • FNA can cause degranulation • Dexamethasone as well if mass is visibly inflamed

  10. Diagnosis • FNA Cytology often diagnostic • Round cells with or without granules • Granules intracellular or in background • eosinophils • Give diphenhydramine before or right after aspiration • FNA can cause degranulation • Dexamethasone as well if mass is visibly inflamed

  11. Diagnosis • FNA Cytology often diagnostic • Round cells with or without granules • Granules intracellular or in background • eosinophils • Give diphenhydramine before or right after aspiration • FNA can cause degranulation • Dexamethasone as well if mass is visibly inflamed

  12. Diagnosis • FNA Cytology often diagnostic • Round cells with or without granules • Granules intracellular or in background • eosinophils • Give diphenhydramine before or right after aspiration • FNA can cause degranulation • Dexamethasone as well if mass is visibly inflamed

  13. Diagnosis • FNA Cytology often diagnostic • Round cells with or without granules • Granules intracellular or in background • eosinophils • Give diphenhydramine before or right after aspiration • FNA can cause degranulation • Dexamethasone as well if mass is visibly inflamed

  14. Staging for Metastasis • Histopathology for grading • Excisional if resectable • Incisional if not • FNA draining lymph node • Clusters of mast cells likely metastasis • Single mast cells likely not • Abdominal US with FNA liver and spleen • CBC, panel, buffy coat

  15. Staging for Metastasis • Non-resectable MCT

  16. Staging for Metastasis • Non-resectable MCT

  17. Staging for Metastasis • Non-resectable MCT

  18. Staging for Metastasis • Lymph node cytologies

  19. Staging for Metastasis • Lymph node cytologies

  20. Staging for Metastasis • Lymph node cytologies

  21. Tumor Stage (WHO) • Stage 0 – microscopic disease only • Stage I – tumor confined to the dermis • Stage II – tumor does not infiltrate subcutaneous tissues, lymph node metastasis • Stage III – large, infiltrating tumor or multiple tumors • Stage IV – distant metastasis Consideration is being given to reducing stage of multiple dermal tumors

  22. Histopathology • grade • Mitotic Index (MI) • Surgical margins – clean, narrow or dirty • Invasiveness – dermal or invasive (subcutaneous/muscle) Histopathology tells a great deal about prognosis and treatment indicated

  23. Histopathologic Grading • Grade I – well differentiated, behaves benignly • Grade II – intermediate differentiation, behavior is widely variable • Low grade II – often behaves benignly • High grade II – C-kit mutation, often behaves malignantly • Determined by MSU prognostic panel (form) • Grade III – anaplastic, aggressive behavior This is the Patnaik System Obsolete system has grade I the worst and grade III the best prognosis

  24. Surgery • Mainstay of low grade MCT treatment • Mast Cell Tumors often extend well beyond the visible mass • Diagnose by FNA before you excise • Lateral margins 2-3 cm beyond visible mass • Small tumors <1 cm, 1.5-2cm margins may be adequate • One fascia layer deep to visible mass • Avoid manipulating the tumor • Intraoperative cytologies on 4 lateral and deep margins can be helpful

  25. Surgery Prednisone for pre-surgical cytoreduction • Out of favor by oncologists at this time • I still like use it • Stabilizes lysosomal membranes – may prevent degranulation caused by surgery • Controls inflammation around the tumor so tumor borders are easier to see • Usually makes the dog feel better, so client perceives better toleration of surgery • Prednisone 40 mg/m2 PO SID x 7days, then QOD

  26. Surgery Re-excision where borders are dirty on grade I or II • Grade III tumors considered systemic • More surgery only for local palliation • 3 cm beyond original surgery • One fascia layer deeper than original surgery • Complete resection results in long survival • If clean borders, 95% cured with second excision, using these rules

  27. Surgery NeoAdjuvant Therapy • Given to a patient with non-resectable tumor in hopes of making it resectable • Chemotherapy and/or radiation • Best managed by medical and/or radiation oncologists • Need to understand effects of neoadjuvant therapy on healing and when and how to do surgery

  28. Sandra Goodwin – Forney TX Sandra Goodwin’s Compadre Betsy Hoffman Robinson – League City TX

  29. Chemotherapy • Not indicated for multiple dermal MCT that are cured by excision • To deal with MCT at the tumor borders when radiation not possible • To improve post-surgical prognosis for high risk grade II and all grade III MCT • To palliate metastatic or systemic disease • Surprisingly, there are few studies to evaluate efficacy of various protocols

  30. Chemotherapy Vinblastine and prednisone (VP) • Median survival 134 days (5 months) – gross disease after surgery • Median survival 1013 days (3 years) – microscopic disease after surgery • 45% survival at 2 years • Half of these had surgery prior to chemo • This has not been my experience with grade III • Most dead in 2-4 months • All gone within the year • Vinblastine 2-2.2 mg/m2 IV over 10 min once weekly for 4 weeks, then every other week for 4 doses • Prednisone 40 mg/m2 PO SID x 2 weeks then QOD

  31. Chemotherapy CCNU • 60-70 mg/m2 PO q3-4 weeks • 4 week interval the first time, then shorten if symptoms return during the 4th week • Baseline liver tests (ALT, SAP, albumin) • Pretreat with diphenhydramine • Check before 3rd dose and then prior to each • Stop if signs of liver disease to prevent liver failure • 6-8 doses common maximum • I have reached 12 at most • Grade III median survival 2 months

  32. Chemotherapy Alternating VP and CCNU • Alternate vinblastine and CCNU every 2 weeks for a total of 8 treatments • Doses on previous slides • Prednisone 2 mg/kg PO SID tapered gradually to maintenance dose of 0.5 mg/kg PO SID x 6 months • Macroscopic disease grades II and III • 3 remission, 4 PR • median duration of response 58 days • 2 patients did not reach 4th CCNU treatment due to ALT >1000

  33. Chemotherapy Vinblastine, prednisone, cyclophosphamide • Study on high risk MCT • Median progression free interval of more than 2 years • Median survival 6 years • Grade III and those who needed reduction of vinblastine dose did not do as well • New protocol, but this may become a popular protocol in the future

  34. Chemotherapy • Vincristine alone not effective for MCT • COP can work well for grade II MCT • Many dirty border grade II do very well with most protocols • many months, years or cured • Some grade II with dirty borders spontaneously resolve • Are malignant MCT indistinguishable from inflammatory reaction?

  35. Chemotherapy • Because of the VP study, most oncologists prefer VP to CCNU or both for grade III • My experience is that outcome is similar with all 3 protocols for grade III MCT • Palliative therapy often does just as well • A significant proportion do not respond at all

  36. Chemotherapy

  37. Chemotherapy Palladia and Kinavet-CA1/Masivet • Tyrosine kinase (TKI) inhibitors • Prednisone and TKI are the chemo drugs with direct cytotoxicity for MCT • Probably the most effective chemo for high grade MCT • Not appropriate for low grade MCT due to toxicity A game changer for high grade very large MCT

  38. Chemotherapy Palladia and Kinavet-CA1/Masivet • 25% of grade II & III MCT have C-KIT mutation • Blocking wild type or mutated KIT causes apoptosis in MCT • antiproliferative through KIT blockade • antiangiogenic through other MOA

  39. Chemotherapy Palladia and Kinavet-CA1/Masivet • Indications for use: • Dogs >11-15 lbs only (not cats) • Non-resectable MCT • Dirty borders after re-excision • Multiple diffuse or coalescing high grade MCT • Concurrent conditions precluding surgery or multiple sedations for radiation therapy • High grade MCT or C-KIT mutation • Indicated with or without metastasis • Post Chemo – VP x 4 weeks, then Palladia

  40. Chemotherapy Palladia and Kinavet-CA1/Masivet • Though both are TKIs, there can be resistance to one but not the other • If one fails, try the other • Stable disease is a victory with either • Palladia has more broad spectrum activity, and is thought to be more likely to cause clinical response than Kinavet • Kinavet response can take up to 2-3 weeks • Gleevec is a TKI used in people, but it is very expensive ($100-150 per pill) • Palladia $6-800, Kinavet $500 /month - 70lb dog

  41. Chemotherapy Kinavet Administration • 12.5 mg/kg PO SID • Dose chart on package insert (Client Info) • Cannot be used in dogs weighing less than 15 pounds • Dose reduction in response to adverse events • stop Kinavet for 1-2 weeks • Reduce dose to 9 mg/kg/day when resumed • Weekly CBC/panel for the first 6 weeks • Then every 3 weeks x 2 • Then every 6 weeks thereafter

  42. Chemotherapy Palladia Administration • 3.25 mg/kg PO QOD (or MWF) • Dose chart on package insert • With or without food • Dose reduction in response to adverse events • Stop Palladia for 1-2 weeks • 0.5 mg/kg reduction when reduced • Minimum dose 2.2 mg/kg PO QOD • Weekly CBC/panel for the first 6 weeks • Then every 3 weeks x 2 • Then every 6 weeks thereafter

  43. Chemotherapy Palladia Administration • GI side effects common • Make sure owner knows to STOP drug if anorexia, vomiting, diarrhea • Dispense Cerenia and metronidazole at the first visit to have on hand • Administer H1 and H2 blockers concurrently

  44. Chemotherapy Palladia Study – Bergman & Clifford, 2009 • Dogs with progressive disease on the blinded phase could enter open-label phase at any time

  45. Chemotherapy Palladia Study – Bergman & Clifford, 2009 • Statistically significant improvement in objective response rate

  46. Chemotherapy Palladia Study – Bergman & Clifford, 2009 • 57.2% did not respond • Among responders, median duration of response was 12 weeks • Median time to non-response or death was 18 weeks • 82% of dogs with C-KIT mutation responded • 54% of dogs without mutation responded • There was a placebo response • Likely due to spontaneously resolving degranulation • Clin Cancer Res 2009; 15:3856-3865.

  47. Chemotherapy Palladia Side effects

  48. Chemotherapy Palladia Side effects • Dec. albumin – 13% Palladia, 8% Placebo • Palladia given long term leads to glomerular disease and renal failure

  49. Chemotherapy Kenneth Kimbrough – Longview TX Stephen Garner – Nacogdoches TX

  50. Chemotherapy Kinavet-CA1

More Related