Nth of Scotland Cancer Netwk Clinical Management Guideline f Malignant Melanoma Based on WOSCAN CMG with further consultation within NOSCAN UNCONTROLLED WHEN PRINTED Prepared by Approved by Issue date Document Control [v1.0: Dr. R. Casasola, Dr. M. Nicolson, M. Parsons] + changes since advised to N.McLachlan NOSCAN NOTE: Under review Review date 1 September 2016 Version V 2.1 (20160609) Page 1 of 9
Background: Introduction NOSCAN Skin Cancer MCN has approved the infmation contained within this document as a guide to the management of adult patients with Malignant Melanoma only: any patients who have been entered in a clinical trial should be managed accding to the appropriate trial protocols. General principles: Note: This document is In advance of patient being discussed at the locally agreed appropriate specialist Malignant Melanoma/Skin Cancer MDT, it is imptant to take steps to establish a definitive cancer diagnosis earliest as well as an indication of clinical staging (see page 8) Confirm Diagnosis Full Histy & Physical examination Blood profile (ie FBC, U&E, LFTs) Excision confirming Melanoma + Consider SNB BRAF+LDH status Staging CT chest, abdomen and pelvis FDG-PET (as per national guidance) Histology Site Type Grade Infiltration pattern Depth of Invasion Cytology Other considerations Due to the nature of their presenting disease and likely treatment, all patients should be referred earliest to the appropriate relevant Clinical Nurse Specialist f assessment and ongoing specialist advice, education, suppt and co-dination of care f patient and their relatives throughout the treatment pathway At all stages throughout the treatment pathway: Patients should be re-presented f MDT review at appropriate decision points Any treatment plans should be discussed with patient and relatives during their preparation Patients and their relatives should be provided with written infmation Primary Care should be notified of patients pathway progress If available, clinical trials should always be considered the preferred option f eligible patients V 2.1 (20160609) Page 2 of 9
Initial Evaluation and Treatment Initial Evaluation Clinical Stage Treatment Histy & Examination Excision confirming Melanoma Arrange wide local excision Consider SNB Discuss at appropriate specialist MDT Ensure BRAF Testing Reassess f local LN & other suspicious lesions Assess tumour stage F definitions see page 9 Follow-up/Shared Care (see page 7) No evidence of nodal disease Follow-up/Shared Care* (see page 7) Clinically suspicious LN SNB +ve In-transit lesion Pathology Resect Consider adjuvant Radiotherapy if Extracapsular spread Follow-up/Shared Care 1 Resectable Not Resectable Consider palliative ILP/laser treatment Refer to vascular surgeons laser specialist Consider SACT -ve Pathology (FNAC/Biopsy) Complete CT/PET CT -ve +ve Palliative care CT No other metastatic disease LN Dissection (Discuss Pathology at Regional MDT ) Where available, clinical trials should always be considered the preferred option f eligible patients +ve Localised disease confined to 1 limb Incomplete Stage IV Disease Consider radiotherapy Regional MDT Assess tumour stage & co-mbidity 3 Stage IV (not localised confined to 1 limb) (see page 5) Widespread disease/ Significant co- mbidity Patient declines therapy V 2.1 (20160609) Page 3 of 9
Management of Resectable Disease Resect Follow-up/Shared Care (see page 7) yes Disease resectable? Consider Radiotherapy SACT f symptomatic localised unresectable metastases no Dabrafenib Verumafenib Metastatic Non-resectable (see page 5) Imatinib Temozolomide (if +ve f brain mets ) Paclitaxel/Carboplatin (weekly) Dacarbazine Consider: Temazolomide Paclitaxel/Carboplatin (weekly) Interferon ά Palliative Care Where available, clinical trials should always be considered the preferred option f eligible patients V 2.1 (20160609) Page 4 of 9
Management of Stage IV Disease Initial Evaluation Following MDT Assessment: Potentially Resectable Disease Brain yes yes no Discuss at Neuro MDT no Other Resect BRAF Status Complete resection yes no BRAF -ve BRAF +ve Re- Discuss at Regional MDT Rapidly progressing disease Rapidly progressing disease First Line Second Line Third Line Dacarbazine Temozolomide (if brain metastases) BRAF Inhibit Ipilumab Dacarbazine Temozolomide (if brain metastases) Carboplatin and Paclitaxel Interferon ά Dacarbazine Temozolomide (brain metastases) Carboplatin and Paclitaxel Interferon ά Resect Stereotactic Radiotherapy Follow up with MRI Brain (at 3-monthly intervals) Follow-up/Shared Care (see page 7) Note: Further details of SACT regimens provided on page 6 Where available, clinical trials should always be considered the preferred option f eligible patients V 2.1 (20160609) Page 5 of 9
Systemic Anti Cancer Therapy NOSCAN Skin Cancer MCN has approved the following SACT regimens (together with their maximum starting dosages and treatment durations) f the management of Malignant Melanoma. Dose reductions and modifications may be considered due to co-mbidity and toxicity Dabrafenib 1st Line BRAF+ve ONLY Dabrafenib 150mg Administered Orally (twice daily) Continue until relapse Dacarbazine Dacarbazine 800mg/m 2 IV infusion (? Duration) on Day 1 Repeat every 3 weeks/21days Continue f a maximum of 6 cycles Imatinib Imatinib 400mg Orally daily Continue until relapse. Interferon ά Interferon 3mu Administered subcutaneously (on Monday/Wednesday/Friday ) Continue until relapse. Ipilumumab Ipilumumab 3mg/kg IV infusion (? Duration) on Day 1 Repeat every 3 weeks /21days Continue f a maximum of 4 cycles Paclitaxel +Carboplatin (Weekly) Paclitaxel 80mg/m 2 IV infusion (?duration) on Day 1 Carboplatin AUC3 IV infusion (? Duration) on Day 1 Repeat weekly /7days Continue f a maximum of 18 cycles. Advanced (unresectable metastatic) melanoma 2 mg/kg IV infusion (30 mins duration) on Day 1 Repeat every 3 weeks /21days Continue f a maximum of? Cycles/until disease progression unacceptable toxicity. Temozolomide Temozolamide 200mg/m 2 Orally (once daily ) on Days 1-5 Repeat every 4 weeks/28 days Continue f a maximum of 6 cycles. Vemurafenib BRAF+ve only Vemurafenib 960mg Administered Orally (twice daily) Continue until disease progression the development of unacceptable toxicity after dose reduction. Where available, clinical trials should always be considered the preferred option f eligible patients V 2.1 (20160609) Page 6 of 9
Follow Up and Aftercare The following is provided f guidance only and is derived from WoS Skin Cancer MCN Cutaneous Melanoma Follow-up Regional Consensus Guideline 28/01/2011 (Amended December 2012), NICE & BAD/BAPRAS Guidelines, with further amendment to reflect NoS service arrangement Frequency of Follow up Melanoma Stage Schedule of Care (FUA = Follow Up Appointment) Total duration of recommended Follow up In situ* 1 FUA then discharge n/a Stage 1A 3-6 monthly 12 months Stage 1B-2C 3-6 monthly f years 1-3 Stage 3A (positive SLNB) 2 FUA/year f years 4-5 5 years Stage 3B 3 FUA/year f years 1-3 - Resectable 2 FUA/year f years 4-5 10 years Stage 4 1 FUA/year f years 6-10 Stage 4 Un-resectable Accding to clinical need and applicable Clinical Trials Follow up model of Care Melanoma Stage Stage 1-2 Stage 3-4 Guidance Local MDT (Dermatologists & surgeons with CNS suppt) f continuity of care Applicable Local /Regional Specialist Skin Cancer MDT should lead the care Named lead clinician Melanoma Stage Suggested first point of contact Stage 1 Dermatologist Stage 2 Dermatologist Plastic Surgeon Stage 3 Plastic Surgeon Stage 4 Oncologist Note: Patients who are participating in a clinical trial should always be followed up accding to the study protocol V 2.1 (20160609) Page 7 of 9
Primary Tumour (T) TX T0 Tis T1 T2 T3 T4 The primary tumour cannot be evaluated (f example, curettaged severely regressed melanoma) There is no evidence of primary tumour Melanoma in situ is present (ie early cancer that has not spread to other tissue) Melanomas 1.0 mm less in thickness Melanomas 1.01 2.0 mm Melanomas 2.01 4.0 mm Melanomas me than 4.0 mm TNM Staging 7 th Edition, AJCC NOTE: a and b subcategies of T are assigned based on ulceration and number of mitoses per mm², as shown below: TCLASSIFICATION THICKNESS(mm) ULCERATION STATUS/MITOSES T1 1.0 a: w/o ulceration and mitosis <1mm b: with ulceration mitoses >1mm T2 1.01-2.0 a: w/o ulceration b: with ulceration T3 2.01-4.0 a: w/o ulceration b: with ulceration T4 >4.0mm a: w/o ulceration b: with ulceration Regional Lymph Nodes (N) NX Patients in whom the regional lymph nodes cannot be assessed (f example, previously removed f another reason) N0 No regional metastasis detected N1-3 Regional metastases based upon the number of metastatic nodes and presence absence of intralymphatic metastases (in transit satellite metastases) Distant Metastasis (M) NOTE: N1-3 and a-c subcategies assigned as shown below : N NUMBER OF CLASSIFICATON METASTATIC NODES NODAL METASTATIC MASS N1 1 node a: micrometastasis¹ b: micrometastasis² N2 2-3 nodes a: micrometastasis¹ b: micrometastasis² c: in transit met(s)/satellite(s) without metastatic node(s) N3 4 me metastatic nodes, matted nodes, in transit met(s)/satellite(s) with metastatic node(s) NOTE: Serum LDH is incpated into the M categy as shown below : M0 M1a M1b M1c No detectable evidence of distant metastases Metastases to skin, subcutaneous distant lymph nodes Metastases to lung Metastases to all other visceral sites distant metastases to any site combined with an elevated serum LDH M CLASSIFICATON SITE SERUM LDH M1a Distant skin, subcutaneous, nodal mets Nmal M1b Lung metastases Nmal M1c All other visceral metastases Nmal Any distant metastasis Elevated Notes: ¹Micrometastases are diagnosed after sentinel lymph node biopsy and completion lymphadenectomy (if perfmed) ²Macro metastases are defined as clinically detectable nodal metastases confirmed by therapeutic lymphadenectomy when nodal metastasis exhibits gross extracapsular extension V 2.1 (20160609) Page 8 of 9
Glossary The following definitions have been used throughout the preceding document: BAD British Association of Dermatologists http://www.bad.g.uk/ BAPRAS British Association of Plastic Reconstructive Aesthetic Surgeons http://www.bapras.g.uk/ BRAF CNS CT FBC FDG FNAC ILP LDH LFT s LN MCN MDT NICE PET SACT SLN A biological (gene) marker (implicated in promoting growth, proliferation, and differentiation of some cancer cells, (such as in Melanoma) Clinical Nurse Specialist Computed Tomography Full Blood Count FluoDeoxyGlucose - a radiolabelled sugar (glucose) molecule used in radiological imaging Fine Needle Aspiration Ce Isolated Limb Perfusion Lactate DehydroGenase - a non-specific test that may be used in the evaluation of a number of diseases and conditions. Liver Function Tests Lymph Node Managed Clinical Netwk Multidisciplinary Team National Institute f Clinical Excellence Positron Emission Tomography Systemic Anti-Cancer Therapy (ie chemotherapy) Sentinel Lymph Node V 2.1 (20160609) Page 9 of 9