Single-fraction radiation therapy in patients with metastatic Merkel cell carcinoma
Abstract:
Merkel cell carcinoma (MCC) is an aggressive, polyomavirus-associated cancer with limited therapeutic options for metastatic disease. Cytotoxic chemotherapy is associated with high response rates, but responses are seldom durable and toxicity is considerable. Here, we report our experience with palliative single-fraction radiotherapy (SFRT) in patients with metastatic MCC. We conducted retrospective analyses of safety and efficacy outcomes in patients that received SFRT (8 Gy) to MCC metastases between 2010 and 2013. Twenty-six patients were treated with SFRT to 93 MCC tumors located in diverse sites that included skin, lymph nodes, and visceral organs. Objective responses were observed in 94% of the measurable irradiated tumors (86/92). Complete responses were observed in 45% of tumors (including bulky tumors up to 16 cm). “In field” lesion control was durable with no progression in 77% (69/89) of treated tumors during median follow-up of 277 days among 16 living patients. Clinically significant toxicity was seen in only two patients who had transient side effects. An exploratory analysis suggested a higher rate of in-field progression in patients with an immunosuppressive comorbidity or prior recent chemotherapy versus those without (30% and 9%, respectively;P = 0.03). Use of SFRT in palliating MCC patients was associated with an excellent in field control rate and durable responses at treated sites, and with minimal toxicity. SFRT may represent a convenient and appealing alternative to systemic chemotherapy for palliation, for which most patients with oligometastatic MCC are eligible. SFRT may also synergize with emerging systemic immune stimulants by lowering tumor burden and enhancing presentation of viral/tumor antigens.
Keywords:
Merkel cell carcinoma; Merkel cell polyomavirus; single-fraction radiation therapy; skin cancer
Autoři:
Jayasri G. Iyer 1; †; Upendra Parvathaneni 2; †; Ted Gooley 3; Natalie J. Miller 1; Elan Markowitz 3; Astrid Blom 1; Christopher W. Lewis 1; Ryan F. Doumani 1; Kaushik Parvathaneni 1; Austin Anderson 1; Amy Bestick 1; Jay Liao 2; Gabrielle Kane 2; Shailender Bhatia 3,4,5; Kelly Paulson 1; Paul Nghiem 1,3,4,*
Působiště autorů:
Department of Medicine/Dermatology, University of Washington, Seattle, Washington
1; Department of Radiation Oncology, University of Washington, Seattle, Washington
2; Fred Hutchinson Cancer Research Center, Seattle, Washington
3; Seattle Cancer Care Alliance, Seattle, Washington
4; Department of Medicine/Oncology, University of Washington, Seattle, Washington
†These authors contributed equally to this work.
5
Vyšlo v časopise:
Cancer Medicine 2015; 4(8)
Kategorie:
Original Research
prolekare.web.journal.doi_sk:
https://doi.org/10.1002/cam4.458
© 2015 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.
This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
© 2015 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.
Souhrn
Abstract:
Merkel cell carcinoma (MCC) is an aggressive, polyomavirus-associated cancer with limited therapeutic options for metastatic disease. Cytotoxic chemotherapy is associated with high response rates, but responses are seldom durable and toxicity is considerable. Here, we report our experience with palliative single-fraction radiotherapy (SFRT) in patients with metastatic MCC. We conducted retrospective analyses of safety and efficacy outcomes in patients that received SFRT (8 Gy) to MCC metastases between 2010 and 2013. Twenty-six patients were treated with SFRT to 93 MCC tumors located in diverse sites that included skin, lymph nodes, and visceral organs. Objective responses were observed in 94% of the measurable irradiated tumors (86/92). Complete responses were observed in 45% of tumors (including bulky tumors up to 16 cm). “In field” lesion control was durable with no progression in 77% (69/89) of treated tumors during median follow-up of 277 days among 16 living patients. Clinically significant toxicity was seen in only two patients who had transient side effects. An exploratory analysis suggested a higher rate of in-field progression in patients with an immunosuppressive comorbidity or prior recent chemotherapy versus those without (30% and 9%, respectively;P = 0.03). Use of SFRT in palliating MCC patients was associated with an excellent in field control rate and durable responses at treated sites, and with minimal toxicity. SFRT may represent a convenient and appealing alternative to systemic chemotherapy for palliation, for which most patients with oligometastatic MCC are eligible. SFRT may also synergize with emerging systemic immune stimulants by lowering tumor burden and enhancing presentation of viral/tumor antigens.
Keywords:
Merkel cell carcinoma; Merkel cell polyomavirus; single-fraction radiation therapy; skin cancer
Zdroje
1. Lemos, B. D., B. E. Storer, J. G. Iyer, J. L. Phillips, C. K. Bichakjian, L. C. Fang, et al. 2010. Pathologic nodal evaluation improves prognostic accuracy in Merkel cell carcinoma: analysis of 5823 cases as the basis of the first consensus staging system. J. Am. Acad. Dermatol. 63:751–761.
2.Miller, N. J., S. Bhatia, U. Parvathaneni, J. G. Iyer, and P. Nghiem. 2013. Emerging and mechanism-based therapies for recurrent or metastatic Merkel cell carcinoma. Curr. Treat. Options Oncol. 14:249–263.
3. Tai, P. T., E. Yu, E. Winquist, A. Hammond, L. Stitt, J. Tonita, et al. 2000. Chemotherapy in neuroendocrine/Merkel cell carcinoma of the skin: case series and review of 204 cases. J. Clin. Oncol. 18:2493–2499.
4. Heath, M., N. Jaimes, B. Lemos, A. Mostaghimi, L. C. Wang, P. F. Penas, et al. 2008. Clinical characteristics of Merkel cell carcinoma at diagnosis in 195 patients: the AEIOU features. J. Am. Acad. Dermatol. 58:375–381.
5. Paulson, K. G., J. G. Iyer, A. Blom, E. M. Warton, M. Sokil, L. Yelistratova, et al. 2013. Systemic immune suppression predicts diminished Merkel cell carcinoma-specific survival independent of stage. J. Invest. Dermatol. 133:642–646.
6. Paulson, K. G., J. G. Iyer, A. R. Tegeder, R. Thibodeau, J. Schelter, S. Koba, et al. 2011. Transcriptome-wide studies of merkel cell carcinoma and validation of intratumoral CD8+ lymphocyte invasion as an independent predictor of survival. J. Clin. Oncol.29:1539–1546.
7. Sihto, H., T. Bohling, H. Kavola, V. Koljonen, M. Salmi, S. Jalkanen, et al. 2012. Tumor infiltrating immune cells and outcome of Merkel cell carcinoma: a population-based study. Clin. Cancer Res. 18:2872–2881.
8. Lee, Y., S. L. Auh, Y. Wang, B. Burnette, Y. Wang, Y. Meng, et al. 2009. Therapeutic effects of ablative radiation on local tumor require CD8+ T cells: changing strategies for cancer treatment. Blood 114:589–595.
9. Chow, E., K. Harris, G. Fan, M. Tsao, and W. M. Sze. 2007. Palliative radiotherapy trials for bone metastases: a systematic review.J. Clin. Oncol. 25:1423–1436.
10. Foro Arnalot, P., A. V. Fontanals, J. C. Galceran, F. Lynd, X. S. Latiesas, N. R. de Dios, et al. 2008. Randomized clinical trial with two palliative radiotherapy regimens in painful bone metastases: 30 Gy in 10 fractions compared with 8 Gy in single fraction.Radiother. Oncol. 89:150–155.
11. Hoskin, P. J., P. Price, D. Easton, J. Regan, D. Austin, S. Palmer, et al. 1992. A prospective randomised trial of 4 Gy or 8 Gy single doses in the treatment of metastatic bone pain. Radiother. Oncol. 23:74–78.
12. Eisenhauer, E. A., P. Therasse, J. Bogaerts, L. H. Schwartz, D. Sargent, R. Ford, et al. 2009. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur. J. Cancer 45:228–247.
13. Howell, D. D., J. L. James, W. F. Hartsell, M. Suntharalingam, M. Machtay, J. H. Suh, et al. 2013. Single-fraction radiotherapy versus multifraction radiotherapy for palliation of painful vertebral bone metastases-equivalent efficacy, less toxicity, more convenient: a subset analysis of Radiation Therapy Oncology Group trial 97-14. Cancer 119:888–896.
14. Jeremic, B., Y. Shibamoto, L. Acimovic, B. Milicic, S. Milisavljevic, N. Nikolic, et al. 1998. A randomized trial of three single-dose radiation therapy regimens in the treatment of metastatic bone pain. Int. J. Radiat. Oncol. Biol. Phys. 42:161–167.
15. Badzio, A., E. Senkus-Konefka, B. A. Jereczek-Fossa, K. Adamska, S. Fajndt, I. Tesmer-Laskowska, et al. 2003. 20 Gy in five fractions versus 8 Gy in one fraction in palliative radiotherapy of bone metastases. A multicenter randomized study. J. Oncol.53:261–264.
16. Wu, J. S., R. Wong, M. Johnston, A. Bezjak, and T. Whelan. 2003. Meta-analysis of dose-fractionation radiotherapy trials for the palliation of pa inful bone metastases. Int. J. Radiat. Oncol. Biol. Phys. 55:594–605.
17. Sihto, H., T. Bohling, H. Kavola, V. Koljonen, M. Salmi, and S. Jalkanen, et al. 2012. Tumor infiltrating immune cells and outcome of merkel cell carcinoma: a population-based study. Clini. Cancer Res. 18:2872–2881.
18. Kwilas, A. R., R. N. Donahue, M. B. Bernstein, and J. W. Hodge. 2012. In the field: exploiting the untapped potential of immunogenic modulation by radiation in combination with immunotherapy for the treatment of cancer. Front Oncol. 2:104.
19. Litterman, A. J., D. M. Zellmer, K. L. Grinnen, M. A. Hunt, A. Z. Dudek, A. M. Salazar, et al. 2013. Profound impairment of adaptive immune responses by alkylating chemotherapy. J. Immunol. 190:6259–6268.
20. Sewell, H. F., C. F. Halbert, R. A. Robins, A. Galvin, S. Chan, and R. W. Blamey. 1993. Chemotherapy-induced differential changes in lymphocyte subsets and natural-killer-cell function in patients with advanced breast cancer. Int. J. Cancer 55:735–738.
21. Steele, T. A. 2002. Chemotherapy-induced immunosuppression and reconstitution of immune function. Leuk. Res. 26:411–414.
22. Kang, D. H., M. T. Weaver, N. J. Park, B. Smith, T. McArdle, and J. Carpenter. 2009. Significant impairment in immune recovery after cancer treatment. Nurs. Res. 58:105–114.
23. Hamid, O., C. Robert, A. Daud, F. S. Hodi, W. J. Hwu, R. Kefford, et al. 2013. Safety and tumor responses with lambrolizumab (anti-PD-1) in melanoma. N Engl. J. Med. 369:134–144.
24. Dewan, M. Z., A. E. Galloway, N. Kawashima, J. K. Dewyngaert, J. S. Babb, S. C. Formenti, et al. 2009. Fractionated but not single-dose radiotherapy induces an immune-mediated abscopal effect when combined with anti-CTLA-4 antibody. Clin. Cancer Res.15:5379–5388.
Štítky
OnkológiaČlánok vyšiel v časopise
Cancer Medicine
![Číslo 8](https://www.prelekara.sk/media/cache/resolve/journal_issue/media/image_pdf/31945c492165cfbc753ecde065675aa7.jpeg)
2015 Číslo 8
- Nejasný stín na plicích – kazuistika
- Preskripce léčebného konopí: Kterým pacientům pomůžete nejvíc?
- Liečba bolesti po jednodňovej chirurgii
- Lednové kolokvium PragueONCO 2017 a nejnovější poznatky v léčbě neuroendokrinních nádorů
- PragueONCO slaví jubileum
Najčítanejšie v tomto čísle
- Electrocardiographic effects of class 1 selective histone deacetylase inhibitor romidepsin
- The long-term outcomes of alternating chemoradiotherapy for locoregionally advanced nasopharyngeal carcinoma: a multiinstitutional phase II study
- Serial type-specific human papillomavirus (HPV) load measurement allows differentiation between regressing cervical lesions and serial virion productive transient infections
- Evaluation of sorafenib treatment and hepatic arterial infusion chemotherapy for advanced hepatocellular carcinoma: a comparative study using the propensity score matching method