Short german guidelines: malignant melanoma

Guidelines
Guideline
Short German guidelines: Malignant melanoma
Claus Garbe, Dirk Schadendorf, Wilhelm Stolz, Matthias Volkenandt, Uwe Reinhold, Rolf-Dieter Kortmann,Christoph Kettelhack, Bernhard Frerich, Ulrich Keilholz, Reinhard Dummer, Günther Sebastian, WolfgangTilgen, Gerold Schuler, Andreas Mackensen, Roland Kaufmann, Axel Hauschild Definition
• Confirmation of diagnosis with an • Histopathologic diagnosis should sent mixed forms or are not classifiable.
• Sentinel lymph node biopsy should can also arise in the eye (conjunctiva and ging in melanomas thicker than 1 mm.
Superficial spreading melanoma (SSM) often with multiple colors and pale areas • Laboratory evaluation includes sed may also develop. A characteristic histo- logic feature is pagetoid spread of clear • Chest X-ray in two planes.
epidermis. Nodular melanoma in con- • Sonography of the abdomen inclu- excessive sun exposure. In central Europe ding the pelvis and retroperitoneum.
yearly; and in Australia the highest inci- • High-resolution sonography to mea- dence, 50-60 / 100,000 yearly. In indivi- tical phase. Thus early identification in • CT, MRI or PET evaluation as alter- sible. Lentigo maligna melanoma arises exclusively on the face of elderly indivi- Prognosis and Staging
duals. Acral-lentiginous melanoma is stic nevi, congenital nevi) are at greater as primary tumors without any evidence pigmentation; later a nodular region sig- these genetic and constitutional factors, prognostic factors for primary melanoma Preoperative and Staging Evaluation
• Vertical tumor thickness (Breslow depth) measured on histological speci- • Dermatoscopy to enhance differential • Presence of a histologically recogniza- status of the patient plays a major role in • Clinical evaluation of draining lym- • Lymph node sonography for lesions Blackwell Verlag, Berlin • No claim to orignal government works • JDDG • 1860-6024/2008/Suppl 1 – S9-S14 JDDG | Supplement 1˙2008 (Volume 6)
Guidelines
of regional lymph nodes. A regional me- thick tumors, radical surgery does little to influence the risk of distant metasta- • Satellite metastases (up to 2 cm from associated with an increased risk of local • In-transit metastases (in the skin be- ven Stage I melanoma is surgical excision • Regional lymph node metastases allow a narrower margin of safety. Radia- tion therapy is a possible alternative tosurgery for facial lentigo maligna.
Sentinel lymph node biopsy should be Table 1: T classification of primary tumor for melanoma.
performed for all tumors thicker than1mm. If other unfavorable signs are pre- T classification
Tumor thickness Additional prognostic parameters
sent (Clark level IV/V, ulceration of pri- gic staging procedure and not a thera-peutic measure with a proven positive ef- *Tumor thickness or information on ulceration not available, or unknown of recurrence-free status in the regional lymph nodes and may be used to helpdecide on adjuvant systemic therapy. Formelanomas thicker than 1 mm in thehead and neck region, lymph node sta- Table 2: N classification of the regional lymph nodes for melanoma .
ging can also be accomplished with an el- Number of involved
Extent of lymph
N classification
lymph nodes (LN)
node metastases
excision, depending on the site of the tu- mor. If there is no indication of involve- ment of the sentinel lymph node, no fur-ther surgical procedures are indicated on tion is typically performed. There is not in-transit metastases plus node involvement Palliative Surgical TherapyWhen the patient has satellite and/or intransit metastases, complete excision ofmetastases is performed. When a single Table 3: M classification of distant metastases for melanoma.
limb is involved with multiple satelliteand/or in transmit metastases, hyper- M classification
Type of distant metastasis
dified or selective neck dissection) is acurative attempt. If a tumor-free status JDDG | Supplement 1˙2008 (Volume 6)
Guidelines
Table 4: Staging of melanoma.
Primary tumor (pT)
Regional lymph node metastases (N)
Distant metastases (M)
Level IV or V1.01–2.0 mm, no ulceration Any tumor thickness, no ulceration Micrometastases Any tumor thickness with ulceration Micrometastases Any tumor thickness, no ulceration Up to three macrometastases None but satellite and/ or in-transit metastases None Any tumor thickness with ulceration Up to three macrometastases Four or more macrometastases, or lymph node Noneinvolvement extending beyond capsule, orsatellite and/or intransit metastases withlymph node involvement therapy with IFN-␣ should be offered to Table 5: Recommended excision
all patients with an increased risk of me- tastasis, as long as there are no contrain- Tumor thickness
Safety margin
(Breslow)
acids and are identical in regards to re- group, so consideration is being given to ceptor binding, efficacy, and side effects.
first offering adjuvant therapy to patients cannot be obtained or if the operation is not appropriate for the patient, then ra- varying dosages of IFN-␣ have been per- Stage IV diseases if the metastases are po- of metastasis, three prospective randomi- tentially completely resectable (R0 inten- tastases. The clearest results are available low-dose IFN-␣. All studies used IFN-␣ in this setting are unclear and should be months, and in all studies there was a sig- decided on an individual basis by a mult- contrast to control patients. This therapy free time. In the largest study where pa- the toxicity of high-dose INF-␣ and the Interferon-␣ is the first substance for ad- overall survival. Thus patients in this risk fact that only a subgroup of patients ben- group should be offered IFN-␣ 3 million efit, other interferon regimens are being JDDG | Supplement 1˙2008 (Volume 6)
Guidelines
cant increase in recurrence-free survival.
(R1 resection). Single doses of 1.8-2.0 Gy Bone metastases can be effectively pallia- IFN-␣ -2a and IFN-␣ -2b have achieved conflicting results in prospective rando- inoperable recurrences, inoperable regio- stability (fracture risk), and compression in the recurrence-free survival, and a po- (Stage IV). Since the treatment is prima- rily palliative, careful attention should be 35-36 Gy with individual doses of paid to its effect on quality of life.
5-year survival statistics (Table 6).
threat to structural stability, considerably used to shorten the total treatment time. For patients with solitary brain metasta- ses, either surgery or stereotactic single with extensive disease (metastases in the with radiation therapy, but still accepta- ded. The radiation therapy is less toxic.
liver, skeleton, brain or generalized vis- The combination of local therapy ceral metastases).
(operation or stereotactic radiation) and whole brain irradiation has been effective ment in mean survival time (from Palliative monochemotherapy may given in 10 fractions over 2 weeks. High- survival, so that in individual cases local nation of cytostatic agents and cytokines from retrospective and prospective clini- diated if they are inoperable or if surgery has failed to effect complete removal procedure is more effective than radia- Table 6: Dosage schedules for adjuvant therapy of melanoma with IFN-␣.
Schedule
Frequency
Duration
Indication
High dose
Pegylated IFN-␣-2b
JDDG | Supplement 1˙2008 (Volume 6)
Guidelines
Table 7: Monotherapy of advanced cutaneous melanoma.
Medication
Response rate
250 mg/m2 i.v. daily for 5 days every 3–4 weeks or Dacarbazine
800 – 1200 mg/m2 i.v. daily on one day every 3–4 weeks Temozolomide
150 – 200 mg/m2 p.o. daily for 5 days every 4 weeks 100 mg/m2 i.v. on days 1, 8 and 15; then 5 week pause, Fotemustine
Vindesine
Interferon-␣
6 million IU/kg as 15 min. every 8 hours Interleukin-2
infusion i.v. for 5 days (total of 14 doses).
the patient’s quality of life while receiving notherapy but fail to prolong the overall DTIC require highly effective anti-emetic notherapy may in special cases offer bet- ter palliation or more effectively control tumor-associated signs and symptoms.
tance to regular re-evaluation. Follow-up Because of the potential toxicity of poly- Table 8: Polychemotherapy and chemoimmunotherapy of advanced cutaneous melanoma.
Regimen Dose
Response
BCNU 150 mg/m2 i.v. day 1 in every other cycle; DTIC 150 mg/m2 i.v. days 1–5 every 4 weeks Bleomycin 15 mg i.v. days 1+4Vincristine 1 mg/m2 i.v. days 1+5 CCNU 80 mg/m2 p.o. day 1DTIC 200 mg/m2 i.v. days 1–5 every 4–6 weeks Cisplatin 100 mg/m2 i.v. day 1 every 3–4 weeks Cisplatin 50 mg/m2 i.v. days 1+8 every 3–4 weeks Carboplatin AUC6 i.v. day 1, after four cycles reduce to AUC4 CarboTax
Paclitaxel 225 mg/m2 i.v. day 1 every 3 weeks, Treosulfan 3500 mg/m2 i.v. days 1 and 8 every 4 weeks JDDG | Supplement 1˙2008 (Volume 6)
Guidelines
Table 9: Recommendations for the follow-up of melanoma patients (intervals in months) .
Physical
Physical exami-
Lymph node
Serum S100 pro- Imaging studies
Stage and tumor
examination
sonography
tein levels
Years 1–5 ***
thickness
Years 1–5
Years 6–10
Years 1–5
Years 1–5**
*Stage III includes all forms of local and regional metastasis. The new AJCC Stage IIC (> 4 mm tumor thickness and ulce-ration) should be followed as Stage III, since the prognosis is similar.
**S100 protein is the only parameter suited for detecting recurrences.
***Abdominal sonography and chest x-ray, or CAT, MRI or PET.
****Patients receiving adjuvant therapy should receive imaging studies every 6–12 months.
Consensus-building Process and
dizinische Universitäts-Klinik III, Cam- Participants
full-length guidelines published as „In- ren“ (C. Garbe, ed.), Kapitel „Deutsche Frankfurt; Axel Hauschild, Universitäts- Next update planned: Spring 2010.
The guideline coordinator is queried yearly tes. In case these are needed, the updated version of the guidelines will be published Conflict of interest
Guideline coordinator: Prof. Dr. C.
Garbe, Universitäts-Hautklinik Tübingen.
conflict of interest: In the past 2 years he Authors: Claus Garbe, Universitäts-
has acted as a consultant for or accepted New York: Georg Thieme Verlag: 23–55.
JDDG | Supplement 1˙2008 (Volume 6)

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