Radiation Oncology/Merkel

Current revision (unreviewed)

[edit] Epidemiology

Cutaneous malignancy of neuroendocrine origin
Initially described in 1972 as "trabecular carcinoma"
Nomenclature changed to MCC due to structural and IHC similarities to Merkel cells
Merkel cells were initially described as non-dendritic, non-keratinocyte epidermal cells that function as tactile skin receptors

High rate of local failure and regional recurrence (50-80%)
Considered highly radiosensitive
Management is controversial; surgery tends to be mainstay, with some investigators suggesting margins of 3cm
Role of adjuvant RT is not well defined. However, a recent retrospective SEER analysis shows a significant survival benefit for all patients, and particularly for tumors >2cm
Only one prospective trial has been conducted to date (TROG 96:07), which suggests a benefit for concurrent chemo-RT in N+ patients

SEER, 2007 (1973-2002) PMID 17369567 -- "Adjuvant radiation therapy is associated with improved survival in merkel cell carcinoma of the skin." (Mojica P, J Clin Oncol. 2007 Mar 20;25(9):1043-7.)
- Retrospective. 1665 patients in SEER registry. Surgery in 89% cases, adjuvant RT 40%. Median F/U 40 months
- Median survival: 49 months (surgery only 45 months vs. adjuvant RT 63 months)
- RT benefit: for all patients, but highly significant if tumor size >2 cm (median OS 21 vs. 50 months). For tumors <1cm (48 months vs. 93 months), for tumors 1-2cm (52 months vs. 86 months)
- Conclusion: "The use of adjuvant radiation therapy is associated with improved survival in patients with MCC."
- Comment & author reply: PMID 17906216

Sydney; 2007 (Australia)(1992-2004) PMID 17356954 -- "Merkel cell carcinoma: assessing the effect of wide local excision, lymph node dissection, and radiotherapy on recurrence and survival in early-stage disease--results from a review of 82 consecutive cases diagnosed between 1992 and 2004." (Jabbour J, Ann Surg Oncol. 2007 Jun;14(6):1943-52.)
- Retrospective. 82 patients with early-stage
- Outcome: Recurrence rate 51%,
- Predictors: LN+ status negative, lymphadenectomy prolonged DFS (28 months vs. 12 months, SS) but not OS. SM- not associated with better outcome. RT in 58%, improved DFS (24 months vs. 12 months); improved OS for both primary site (54 months vs. 46 months) and N+ (103 months vs. 34 months)
- Conclusion: Adjuvant RT recommended for early-stage disease; involved regional LN should be treated

Cologne; 2002 (1990-2000) PMID 11823697 -- "Role of postoperative radiotherapy in the management of Merkel cell carcinoma." (Eich HT, Am J Clin Oncol. 2002 Feb;25(1):50-6.)
- Retrospective. 31 patients, 13 H&N, 13 limbs, 5 trunk. Stage I 26, Stage II 4, Stage III 1. Surgery alone 14/31, adjuvant RT 16/31, definitive RT 1/31
- Outcome: median OS 2.7 years; local recurrence 20%, regional LN mets 30%, DM 23%. RT decreased locoregional reccurence from 36% to 6%
- Negative predictive factors: H&N location, lack of post-op RT
- Conclusion: Post-op RT to primary tumor and regional lymphatics effective

MD Anderson; 2001 (1945-95) - PMID 11177031 — "Merkel cell carcinoma of the head and neck: effect of surgical excision and radiation on recurrence and survival." Gillenwater AM et al. Arch Otolaryngol Head Neck Surg. 2001 Feb;127(2):149-54.
- Retrospective. 66 pts. No difference in local relapse for surgical margins <1 vs 1-2cm vs >2cm. Improved local recurrence (12% vs 44%) and regional recurrence (27% vs 85%) rate for addition of RT. No difference in OS. Distant disease developed in 36% of pts regardless of treatment.

Queensland Radium Institute; 1995 (1981-91) - PMID 7836086 — "The importance of postoperative radiation therapy in the treatment of Merkel cell carcinoma." Meeuwissen JA et al. Int J Radiat Oncol Biol Phys. 1995 Jan 15;31(2):325-31.
- Retrospective. 80 pts. 38 of 38 pts treated with surgery alone relapsed, versus 10 of 34 pts with S+RT.

Queensland Radium Institute / TROG; 2006 PMID 16125873 — "Does chemotherapy improve survival in high-risk stage I and II Merkel cell carcinoma of the skin?" Poulsen MG et al. Int J Radiat Oncol Biol Phys. 2006 Jan 1;64(1):114-9.
- Retrospective. Compared 53 pts from TROG 96:07 (chemo + RT) to 144 pts treated at Queensland from 1988-96 (RT only).
- Chemotherapy does not improve survival.

TROG 96:07 (1996-2001)
- Phase II. Pts with disease limited to the primary and nodes with at least 1 risk factor: recurrence after initial therapy, involved nodes, size > 1 cm, gross residual disease, or occult primary with nodes. N+ in 62%. 50 Gy in 25 fx with concurrent carboplatin/etoposide on days 1-3 on weeks 1, 4, 7, and 10.
- 2001 PMID 11516865 — "Analysis of toxicity of Merkel cell carcinoma of the skin treated with synchronous carboplatin/etoposide and radiation: a Trans-Tasman Radiation Oncology Group study." Poulsen M et al. Int J Radiat Oncol Biol Phys. 2001 Sep 1;51(1):156-63. Median F/U 1.8 years
  - Toxicity: Grade 3-4 skin 63%; neutropenia 40%
  - Conclusion: Toxicity acceptable. No outcome measures reported
- 2003 PMID 14645427 -- "High-risk Merkel cell carcinoma of the skin treated with synchronous carboplatin/etoposide and radiation: a Trans-Tasman Radiation Oncology Group Study--TROG 96:07." (Poulsen M, J Clin Oncol. 2003 Dec 1;21(23):4371-6.). Median F/U 4 years
  - 3-year outcome: OS 76%, LR control 75%, DM control 76%
  - Conclusion: Addition of chemo to RT resulted in high control

NCCN - PMID 16884673 — "Role of radiotherapy in the management of merkel cell carcinoma of the skin." Decker RH and Wilson LD. J Natl Compr Canc Netw. 2006 Aug 4;(7):713-8.

http://www.merkelcell.org - run by Seattle Cancer Care Alliance
- Resource for physicians + patients. General info. Useful photographs and contains a few good publications in PDF format