In-field and abscopal response after short-course radiation therapy in patients with metastatic Merkel cell carcinoma progressing on PD-1 checkpoint blockade: a case series

Xu, Melody J.; Wu, Susan; Daud, Adil; Yu, Siegrid S.; Yom, Sue S.

doi:10.1186/s40425-018-0352-8

Cited by 38 publications

(35 citation statements)

References 22 publications

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“…Despite the lower BED of SFRT, the similar local control may be explained by emerging data demonstrating that higher dose per fraction may potentiate a greater immune-mediated effect compared with conventionally fractionated RT. 17 , 18 , 19 This is relevant given MCC is a highly immunogenic malignancy. 20 Ongoing work will refine the ideal patient population for postoperative SFRT.…”

Section: Discussionmentioning

confidence: 99%

Postoperative, Single-Fraction Radiation Therapy in Merkel Cell Carcinoma of the Head and Neck

Cook

Schaub

Goff

et al. 2020

Advances in Radiation Oncology

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Purpose Conventionally fractionated, postoperative radiation therapy (cPORT; 50 Gy in 25 fractions) is considered for patients with Merkel cell carcinoma (MCC) to improve locoregional control. However, cPORT is associated with acute toxicity, especially in the head and neck (H&N) region, and requires daily treatments over several weeks. We previously reported high rates of durable local control with minimal toxicity using 8-Gy single-fraction radiation therapy (SFRT) in the metastatic setting. We report early results on a cohort of patients with localized H&N MCC who received postoperative SFRT if a cPORT regimen was not feasible. Methods and Materials Twelve patients with localized MCC of the H&N (clinical/pathologic stages I-II) and no prior radiation therapy to the region were identified from an institutional review board-approved prospective registry who underwent surgical resection followed by postoperative SFRT. Time to event was calculated starting from the date of resection before SFRT. The cumulative incidence of in-field locoregional recurrences and out-of-field recurrences was estimated with death as a competing risk. Results Twelve patients with H&N MCC were identified with clinical/pathologic stages I-II H&N MCC. Median age at diagnosis was 81 years (range, 58-96 years); 25% had immunosuppression. At a median follow-up of 19 months (range, 8-34), there were no in-field locoregional recurrences. A single out-of-field regional recurrence was observed, which was successfully salvaged. There were no MCC-specific deaths. No radiation-associated toxicities greater than grade 1 (Common Terminology Criteria for Adverse Events v5) were observed. Conclusions Preliminary data suggest that SFRT could offer a potential alternative to cPORT to treat the primary site for localized H&N MCC, particularly in elderly or frail patients, with promising in-field local control and minimal toxicity. Further data with validation in larger cohorts are needed to confirm the sustained safety and efficacy of postoperative SFRT.

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Section: Discussionmentioning

confidence: 99%

Postoperative, Single-Fraction Radiation Therapy in Merkel Cell Carcinoma of the Head and Neck

Cook

Schaub

Goff

et al. 2020

Advances in Radiation Oncology

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“…Before the advent of immunotherapy, RT was mainly seen as a palliative measure. The search to overcome refractory disease has brought with it a rise in reports on the abscopal effect in metastatic MCC [24,46]. RT modulates the tumour immunoediting process by various and partly unidentified mechanisms, such as altering tumour cell antigen presentation, increasing the infiltration of regulatory T-cells in the tumour microenvironment and staging of T-cell exhaustion with debulking the tumour mass [47,48].…”

Section: Discussionmentioning

confidence: 99%

“…It has also been shown that RT effects are achieved at least partially through immune system response. RT does not only affect the targeted tumour areas, but can have a beneficial abscopal effect on malignant growth elsewhere [23,24].…”

Section: Introductionmentioning

confidence: 99%

Merkel Cell Carcinoma Treatment in Finland in 1986–2016—A Real-World Data Study

Sahi

Their

Gissler

et al. 2020

Cancers

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Merkel cell carcinoma (MCC) is a rare cutaneous carcinoma that has gained enormous interest since the discovery of Merkel cell polyoma virus, which is a causative oncogenic agent in the majority of MCC tumours. Increased research has focused on effective treatment options with immuno-oncology. In this study, we reviewed the real-world data on different treatments given to MCC patients in Finland in 1986–2016. We used the Finnish Cancer Registry database to find MCC patients and the Hospital Discharge Register and the Cause-of-Death Register to obtain treatment data. We identified 376 MCC patients and 33 different treatment entities and/or combinations of treatment. An increase was noted in the incidence of MCC since 2005. Therefore, the cohort was divided into two groups: the “early“ group with time of diagnosis between years 1986 and 2004 and the “late” group with time of diagnosis between 2005 and 2016. The multitude of different treatment combinations is a relatively new phenomenon; before the year 2005, only 11 treatments or treatment combinations were used for MCC patients. Our data show that combining radiation therapy with simple excision provided a survival advantage, which was, however, lost after adjustment for stage or age. Our registry study serves as a baseline treatment efficacy comparison as we move into the age of immunotherapy in MCC. Standardizing the treatment of MCC patients in Finland requires more work on awareness and multidisciplinary co-operation.

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“…For instance, RT is often used as an adjuvant to surgery, as well as it is an alternative to lymph node dissection 30. Palliative RT is used in inoperable disease,30 and single-fraction palliative RT has shown benefit in two patients who have progressed on immune checkpoint inhibitors, leading to long-term abscopal responses in non-irradiated sites 31…”

Section: Discussionmentioning

confidence: 99%

Combined radio-immunotherapy leads to complete clinical regression of stage IV Merkel cell carcinoma

et al. 2019

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Merkel cell carcinoma (MCC) is a rare, aggressive neuroendocrine tumour of the skin. While localised disease carries an overall favourable prognosis, metastatic disease is associated with poor clincal outcomes. Most cases of metastatic MCC are managed with systemic chemotherapy or immunotherapy, though 5-year survival for these patients remains a dismal 17%. Here, we present the case of a 79-year-old man with MCC of the right ear with metastases to regional lymph nodes, ipsilateral parotid gland and thoracic spine. He was treated with a combination of first-line radiotherapy and concurrent immune checkpoint inhibition (avelumab), which led to complete clinical regression of disease with minimal adverse effects. This observation suggests that combined radio-immunotherapy warrants larger-scale investigation for use in patients with unresectable MCC.

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In-field and abscopal response after short-course radiation therapy in patients with metastatic Merkel cell carcinoma progressing on PD-1 checkpoint blockade: a case series

Cited by 38 publications

References 22 publications

Postoperative, Single-Fraction Radiation Therapy in Merkel Cell Carcinoma of the Head and Neck

Postoperative, Single-Fraction Radiation Therapy in Merkel Cell Carcinoma of the Head and Neck

Merkel Cell Carcinoma Treatment in Finland in 1986–2016—A Real-World Data Study

Combined radio-immunotherapy leads to complete clinical regression of stage IV Merkel cell carcinoma

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