Results: First locoregional recurrence

Efficacy and toxicity of hypofractionated adjuvant radiotherapy in Merkel cell carcinoma

• MCC is a rare and aggressive neuroendocrine skin cancer• Incidence: approximately 2,500 new cases in U.S./year and

increasing1• Risk factors: Male, age > 50, Caucasian race, UV exposure,

immunodeficiency1,2• Treatment of localized (AJCC 8th edition stage I-IIIB) often involves:

excision of primary tumor bed and sentinel lymph-node biopsy followed by adjuvant conventional radiotherapy (RT) (50-60Gy in 25-30 fractions)3

• Conventional RT is associated with increased locoregional control but also significant toxicity (e.g. fibrosis, delayed wound healing, skin erythema, mucositis)4

• Hypofractionated RT of 8-24Gy in 1-3 fractions has proven to be effective in treating metastatic, gross tumors with minimal toxicity5

Patients with recurrences were effectively salvaged• 6/7 patients with recurrences had complete clinical response to

salvage treatment• 1/3 deaths during entire follow-up was MCC related

Limitations• Small sample size• Possible ascertainment bias with patient enrollment• Some patients were treated in the recurrent disease setting• Unable to compare cohort against current literature

Future directions• Continue following patients and increase cohort to compare

recurrence rates with adjuvant conventional RT and surgery alone

Merkel Cell Carcinoma (MCC) Summary

Discussion

References1. Paulson, K.G., et al., Merkel cell carcinoma: Current US incidence and projected increases based

on changing demographics. J Am Acad Dermatol, 2018. 78(3): p. 457-463 e2.2. Bichakjian, C.K., et al., Merkel cell carcinoma: critical review with guidelines for multidisciplinary

management. Cancer, 2007. 110(1): p. 1-12.3. Nccn clinical practice guidelines in oncology: Merkel cell carcinoma. V 2.2019. In: Editor,^editors.

Book Nccn clinical practice guidelines in oncology: Merkel cell carcinoma. V 2.2019, January 18, 2019.; 2019.

4. Bhatia, S., et al., Adjuvant Radiation Therapy and Chemotherapy in Merkel Cell Carcinoma: Survival Analyses of 6908 Cases From the National Cancer Data Base. J Natl Cancer Inst, 2016. 108(9).

5. Iyer, J.G., et al., Single-fraction radiation therapy in patients with metastatic Merkel cell carcinoma. Cancer Med, 2015. 4(8): p. 1161-70.

Maclean M. Cook, BS[1], Stephanie K. Schaub, MD[2], Song Y. Park, MD [1], Daniel S. Hippe, MS[4], Jay J. Liao, MD[2], Smith Apisarnthanarax, MD[2], Shailender Bhatia, MD[3], Paul T. Nghiem, MD, PhD[1], Yolanda D. Tseng, MD[2], Upendra Parvathaneni, MBBS[2]

University of Washington School of Medicine, Division of Dermatology [1], Department of Radiation Oncology [2], Division of Medical Oncology [3], Department of Radiology [4], Seattle, WA.

Acknowledgments

Demographics• Median follow-up time: 567 days (90-1303 days)• Median age: 74• 8Gy: 19 patients, 24Gy: 2 patients• n=15 patients treated in the initial disease setting and n=6

patients treated in the recurrent settingAdjuvant hypofractionated RT in-field control rate• 2/21 (9.5%) of patients had a recurrence within irradiated

field during entire follow-up periodActuarial recurrence rates (first event per patient)• In-field recurrence rate: 4.8% 1-year, 4.8% 2-year• Out-of-field recurrence rate: 21% 1-year, 36% 2-yearPatients experienced minimal radiation induced toxicity after treatment • No toxicity greater than CTCAE Grade 1• Majority of patients experienced no acute radiation-

induced symptoms: 12/21 (57%)

Figure 2: 81-year-old immunosuppressed man with a history of clinical stage I Merkel cell carcinoma of the right cheek status post wide local excision with negative margins and a failed sentinel lymph node biopsy, who elected to undergo adjuvant 8 Gy single-fraction radiation therapy (SFRT) to his primary surgical tumor bed site with electrons (A-B). 124-days after SFRT, he exhibited out-of-field regional failures in the lymph nodes in the parotid (C), level 2A (D) and level 5 (E). He was successfully salvaged with surgical resection followed by adjuvant conventional fractionated proton radiation therapy. He never failed within his initial SFRT field.

Figure 2. Recurrence-free survival. Rates for first recurrence were estimated using the cumulative incidence function with death as a competing risk. Follow-up was calculated using date of surgical excision as the start date. Patients were censored at date of last follow-up. LRR = locoregional recurrence

Hypothesis1-3 fractions of 8Gy adjuvant radiotherapy may provide

adequate control in a majority of MCC patients with significantly diminished toxicity.

Funding: MCC gift fund and P01 grant: 1P01CA-225517-01A1We would like to thank all of the MCC patients and theirfamilies who participate in our research so we may betterunderstand and treat this aggressive cancer.

SID 2019 ID: 550

Cohort Selection

Radiation Treatment Characteristics

<1 week of acute side effects

1-3 treatments (<1 week)

1-2 months of acute side effects

25-30 treatments

Hypofractionated RT: 8Gy per fraction (8-24Gy total)

Conventional RT: 2Gy per fraction (50-60Gy total)

• Especially difficult for patients with older age, social/financial/transport difficulties, and medical-comorbidities

(5-6 weeks)

0 200 400 600 800

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0.8

1.0

Days since SurgeryFr

eedo

m fr

om L

RR

0 200 400 600 800

0.0

0.2

0.4

0.6

0.8

1.0

0 200 400 600 800

0.0

0.2

0.4

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1.0

In-fieldOut-of-field

Cohort (n=21)• Seattle-based data repository• Patients treated from 2014-2018

A B

C D E

A

Results: Patient example