Annual Report 2023
Department of Dermatologic Oncology
Naoya Yamazaki, Kenjiro Namikawa, Dai Ogata, Eiji Nakano, Yuichi Nakayama
Introduction
The Department of Dermatologic Oncology has consistently served as the core hospital for the establishment of treatment strategies for malignant skin tumors since the National Cancer Center opened in 1962, and thus far, over 4,000 cases of malignant melanoma have been accumulated, an impressive number for a hospital or research institution in Japan. Today, patients are referred from throughout Japan. Most of the patients are examined and treated for skin cancer including malignant melanoma. Surgery is the main treatment modality for skin cancer, and multi-disciplinary treatments, consisting of immunotherapy, targeted therapy, chemotherapy, and radiotherapy, are also routinely performed. However, currently, the importance of immunotherapy is increasing. Melanoma is at the center of the development of immune therapy. This department plays an active role in multicenter trials for new agents for skin cancer all over Japan.
The Team and What We Do
The department has four staff dermatologic oncologists, one chief resident and six residents. Our department is a high-volume center, where we have seen an average of 170 patients with malignant melanoma annually in the last 5 years (Table 1). At all times, approximately 14 patients are hospitalized to undergo surgery, chemotherapy, or radiation therapy. In 2023, 302 operations were performed including 168 operations under general anesthesia (Table 2). This is the result of building a national network for the development of treatment for malignant skin tumors, including malignant melanoma, and we have succeeded in consolidating cases.
Table 2. Type of procedure (2023/4/1 to 2024/3/31) 
We conduct ward rounds every morning and case presentations are held three times a week. A department conference is held every Monday to discuss treatment policies for outpatients and inpatients. We regularly hold clinical pathology conferences with pathologists, focusing on surgically removed skin specimens. In addition, we have treated advanced cases of mucosal melanoma in the nasal cavity, gastrointestinal tract, genital lesions, perianal lesions, and uveal melanoma although our origins are “dermatologic”.
We are currently participating in international joint research on acral and mucosal melanoma on behalf of institutions in Asia. In particular, we believe that first-line drug treatment options for BRAF-positive melanoma are different from those at Western facilities.
We are actively disseminating information about treatments for rare cancers such as angiosarcoma and extramammary Paget's disease.
Research Activities
- We clarified the epidemiological characteristics of rare skin cancers based on national cancer registry data.
- The median overall survival of melanoma brain metastases over the past 10 years was 7.8 months, with a 6-month survival rate of 60.7% and a 1-year survival rate of 34.8%, and recent advances in treatment have improved the prognosis.
- We conducted a retrospective study on the usefulness of remote after-loading system (RALS) brachytherapy for melanoma, reporting its high local control and symptom relief effects.
- We conducted a retrospective study on the efficacy and safety of ipilimumab + nivolumab combination immunotherapy for 100 cases of advanced melanoma. We reported that this therapy is highly effective when performed as first-line treatment for both cutaneous and mucosal primary tumors, and that liver dysfunction and skin rash are common immune-related side effects.
Clinical Trials
- A confirmatory trial of non-amputative digit preservation surgery in subungual melanoma. (JCOG1602; J-NAIL study)
- A single-arm confirmatory trial of pazopanib in patients with paclitaxel-pretreated primary cutaneous angiosarcoma. (JCOG1605)
- Confirmatory trial of narrower side margins for basal cell carcinoma in Japanese population. (JCOG2005)
- Table 3 presents a summary of our clinical trials.
Table 3. New Agent Studies in 2023 
Education
Currently, training in routine clinical practice under skilled guidance is ongoing for one chief resident and six resident physicians. In addition, conferences with the departments of oncology, radiotherapy and pathology are held on a regular basis. The trainees made a total of 15 presentations at domestic academic conferences and one at an international conference. They have also published one Japanese paper and seven international academic papers in English.
Future Prospects
With continuous progress in drug therapy for advanced cutaneous malignant melanoma, we are now facing an era where the indications of drug therapy for rare types of malignant melanoma are being expanded to include combination and neoadjuvant therapies based on international multicenter studies.
We aim to play a central role in the development of treatments and clinical research for acral melanoma and mucosal melanoma, which are more prevalent in East Asia than in Western countries.
Meanwhile, we are developing treatments for advanced squamous cell carcinoma, Merkel cell carcinoma and angiosarcoma using immune checkpoint inhibitors.
In addition to these, the Department of Radiation Oncology is developing a linear accelerator for the hospital-based boron neutron capture therapy (BNCT) as a new radiotherapy. We are participating in a phase II trial for angiosarcoma.
List of papers published in 2023
Journal
1. Takamizawa S, Koyama T, Sunami K, Sudo K, Hirata M, Kubo T, Tao K, Cho H, Narita Y, Kato K, Yamazaki N, Ohe Y, Okusaka T, Matsui Y, Ogawa C, Yonemori K, Yamamoto N. Identification of barriers to implementation of precision oncology in patients with rare cancers. Cancer science, 115:2023-2035, 2024
2. Nojima K, Hayashi M, Tanemura A, Al-Busani H, Saito T, Suzuki T, Ishikawa M, Mori T, Wada S, Yamazaki N, Katayama I, Mori H, Yokozeki H, Okiyama N, Sasaki Y, Namiki T. Activated Akt expression is associated with the recurrence of primary melanomas and further refines the prognostic and predictive values for relapse in acral melanomas. Pigment cell & melanoma research, 37:36-44, 2024
3. Fujimura T, Yoshino K, Nakamura M, Kato H, Ito T, Maekawa T, Fujisawa Y, Matsushita S, Amagai R, Yamazaki E, Takahashi M, Tamabuchi E, Hashimoto A, Kambayashi Y, Yamazaki N, Miyata T, Asano Y. Efficacy and safety of TM5614 in combination with paclitaxel in the treatment of paclitaxel-resistant cutaneous angiosarcoma: Phase II study protocol. Experimental dermatology, 33:e14976, 2024
4. Wada S, Nakano E, Nakajima M, Kishikawa S, Yoshida A, Mori T, Osada A, Ogata D, Namikawa K, Yamazaki N. Congenital dermatofibrosarcoma protuberans on the scalp enlarging and shrinking repeatedly. The Journal of dermatology, 51:e196-e197, 2024
5. Namikawa K, Nakano E, Ogata D, Yamazaki N. Long-term survival with systemic therapy in the last decade: Can melanoma be cured? The Journal of dermatology, 51:343-352, 2024
6. Hatta N, Ogata D, Asai J, Maekawa T, Ito T, Takenouchi T, Kiniwa Y, Miyashita A, Miyagawa T, Muto I, Yamamoto Y, Nagano T, Kiyohara Y, Nakano E, Ohe S, Yamaguchi B, Fukuyama M, Matsuya T, Tsutsumida A, Namikawa K, Yamazaki N. Recent treatment and prognosis in 643 patients with extramammary Paget's disease. Experimental dermatology, 33:e15030, 2024
7. Bai X, Lawless AR, Czapla JA, Gerstberger SC, Park BC, Jung S, Johnson R, Yamazaki N, Ogata D, Umeda Y, Li C, Guo J, Flaherty KT, Nakamura Y, Namikawa K, Long GV, Menzies AM, Johnson DB, Sullivan RJ, Boland GM, Si L. Benefit, recurrence pattern, and toxicity to adjuvant anti-PD-1 monotherapy varies by ethnicity and melanoma subtype: An international multicenter cohort study. JAAD international, 15:105-114, 2024
8. Yokota K, Takenouchi T, Fujisawa Y, Fukushima S, Uchi H, Inozume T, Kiyohara Y, Uhara H, Nakagawa K, Furukawa H, Han S, Watanabe M, Noguchi K, Yamazaki N. Long-term follow-up results from KEYNOTE-041: Phase 1b study of pembrolizumab in Japanese patients with advanced melanoma. The Journal of dermatology, 51:632-642, 2024
9. Bai X, Shaheen A, Grieco C, d'Arienzo PD, Mina F, Czapla JA, Lawless AR, Bongiovanni E, Santaniello U, Zappi H, Dulak D, Williamson A, Lee R, Gupta A, Li C, Si L, Ubaldi M, Yamazaki N, Ogata D, Johnson R, Park BC, Jung S, Madonna G, Hochherz J, Umeda Y, Nakamura Y, Gebhardt C, Festino L, Capone M, Ascierto PA, Johnson DB, Lo SN, Long GV, Menzies AM, Namikawa K, Mandala M, Guo J, Lorigan P, Najjar YG, Haydon A, Quaglino P, Boland GM, Sullivan RJ, Furness AJS, Plummer R, Flaherty KT. Dabrafenib plus trametinib versus anti-PD-1 monotherapy as adjuvant therapy in BRAF V600-mutant stage III melanoma after definitive surgery: a multicenter, retrospective cohort study. EClinicalMedicine, 71:102564, 2024
10. Omura G, Namikawa K, Sakai T, Eguchi K, Matsumoto Y, Sakai A, Kobayashi K, Nakano E, Ogata D, Matsumoto F, Mori T, Yamazaki N, Yoshimoto S. Clinical outcomes of head and neck mucosal melanoma treated with surgery: a single-center study in Japan. Japanese journal of clinical oncology, 53:1045-1050, 2023
11. Ogata D, Namikawa K, Nakano E, Fujimori M, Uchitomi Y, Higashi T, Yamazaki N, Kawai A. Epidemiology of skin cancer based on Japan's National Cancer Registry 2016-2017. Cancer science, 114:2986-2992, 2023
12. Takahashi A, Namikawa K, Ogata D, Jinnai S, Nakano E, Yamazaki N. Updated analysis of nivolumab and ipilimumab combination therapy in Japanese patients with advanced melanoma. The Journal of dermatology, 50:525-535, 2023
13. Ascierto PA, Lipson EJ, Dummer R, Larkin J, Long GV, Sanborn RE, Chiarion-Sileni V, Dréno B, Dalle S, Schadendorf D, Callahan MK, Nyakas M, Atkinson V, Gomez-Roca CA, Yamazaki N, Tawbi HA, Sarkis N, Warad D, Dolfi S, Mitra P, Suryawanshi S, Grob JJ. Nivolumab and Relatlimab in Patients With Advanced Melanoma That Had Progressed on Anti-Programmed Death-1/Programmed Death Ligand 1 Therapy: Results From the Phase I/IIa RELATIVITY-020 Trial. Journal of clinical oncology, 41:2724-2735, 2023
14. Inozume T, Namikawa K, Kato H, Yoshikawa S, Kiniwa Y, Yoshino K, Mizuhashi S, Ito T, Takenouchi T, Matsushita S, Fujisawa Y, Matsuzawa T, Sugihara S, Asai J, Kitagawa H, Maekawa T, Isei T, Yasuda M, Yamazaki N, Uhara H, Nakamura Y. Analyzing the relationship between the efficacy of first-line immune checkpoint inhibitors and cumulative sun damage in Japanese patients with advanced BRAF wild-type nonacral cutaneous melanoma: A retrospective real-world, multicenter study. Journal of dermatological science, 110:19-26, 2023
15. Nishizawa A, Shinozaki E, Wakatsuki T, Satoh T, Yamazaki N, Oyamada S, Ariyoshi K, Kihara K, Tsuboi M, Yamaguchi K. Efficacy of aluminum chloride in severe regorafenib-associated hand-foot skin reactions: a single-arm trial. BMC cancer, 23:401, 2023
16. Wada S, Ogata D, Nakano E, Namikawa K, Yamazaki N. Efficacy of chemotherapies for unresectable extramammary Paget disease: a single-centre retrospective study. Clinical and experimental dermatology, 48:1019-1023, 2023
17. Nakano E, Ogata D, Namikawa K, Yamazaki N. Merkel cell carcinoma: a review of clinical management with focus on Asian patients. Japanese journal of clinical oncology, 53:673-679, 2023
18. Dummer R, Flaherty KT, Robert C, Arance A, B de Groot JW, Garbe C, Gogas HJ, Gutzmer R, Krajsová I, Liszkay G, Loquai C, Mandalà M, Schadendorf D, Yamazaki N, Pietro AD, Cantey-Kiser J, Edwards M, Ascierto PA. COLUMBUS 5-year update: a randomized, open-label, phase III trial of encorafenib plus binimetinib versus vemurafenib or encorafenib in patients with BRAF. Future oncology (London, England), 19:1091-1098, 2023
19. Yamazaki N, Kiyohara Y, Uhara H, Tsuchida T, Yoshida A, Yamada T, Komoto A. Postmarketing surveillance of nivolumab plus ipilimumab combination therapy in Japanese patients with unresectable malignant melanoma. The Journal of dermatology, 50:1108-1120, 2023
20. Okumura M, Ogata D, Namikawa K, Takahashi A, Akiyama M, Yamazaki N. Functional preservation benefits of minimal surgery for extramammary Paget's disease. Experimental dermatology, 32:1644-1650, 2023
21. Nakayama Y, Ogata D, Wada S, Tsuruta S, Matsui Y, Okumura M, Hiki K, Nakano E, Namikawa K, Yamazaki N. Treatment of high tumor mutation burden metastatic extramammary Paget disease with an anti-PD-1 antibody. The Journal of dermatology, 50:e396-e397, 2023
22. Ascierto PA, Dummer R, Gogas HJ, Arance A, Mandala M, Liszkay G, Garbe C, Schadendorf D, Krajsova I, Gutzmer R, Chiarion-Sileni V, Dutriaux C, de Groot JWB, Yamazaki N, Loquai C, Robert C, Flaherty KT. Contribution of MEK Inhibition to BRAF/MEK Inhibitor Combination Treatment of BRAF-Mutant Melanoma: Part 2 of the Randomized, Open-Label, Phase III COLUMBUS Trial. Journal of clinical oncology, 41:4621-4631, 2023
23. Namikawa K, Ito T, Yoshikawa S, Yoshino K, Kiniwa Y, Ohe S, Isei T, Takenouchi T, Kato H, Mizuhashi S, Fukushima S, Yamamoto Y, Inozume T, Fujisawa Y, Yamasaki O, Nakamura Y, Asai J, Maekawa T, Funakoshi T, Matsushita S, Nakano E, Oashi K, Kato J, Uhara H, Miyagawa T, Uchi H, Hatta N, Tsutsui K, Maeda T, Matsuya T, Yanagisawa H, Muto I, Okumura M, Ogata D, Yamazaki N. Systemic therapy for Asian patients with advanced BRAF V600-mutant melanoma in a real-world setting: A multi-center retrospective study in Japan (B-CHECK-RWD study). Cancer medicine, 12:17967-17980, 2023
24. Mizuta H, Yoshida A, Takahashi A, Namikawa K, Ogata D, Yamazaki N. Congenital dermatofibrosarcoma protuberans with PDGFB gene rearrangement detected using fluorescence in situ hybridization. Dermatology online journal, 29:2023
25. Okumura M, Ogata D, Namikawa K, Takahashi A, Nishimura Y, Mori T, Yoshida H, Akiyama M, Yamazaki N. Adenosquamous carcinoma of the Bartholin gland treated with surgery and radiotherapy. European journal of dermatology, 33:309-311, 2023
26. Mori T, Namikawa K, Yamazaki N, Kiniwa Y, Yamasaki O, Yoshikawa S, Inozume T, Kato H, Nakai Y, Fukushima S, Takenouchi T, Maekawa T, Matsushita S, Otsuka A, Nomura M, Baba N, Isei T, Saito S, Fujimoto N, Tanaka R, Kaneko T, Kuwatsuka Y, Matsuya T, Nagase K, Onishi M, Onuma T, Nakamura Y. Efficacy of salvage therapies for advanced acral melanoma after anti-PD-1 monotherapy failure: a multicenter retrospective study of 108 Japanese patients. Frontiers in medicine, 10:1229937, 2023
27. Tsuruta S, Ogata D, Namikawa K, Nakano E, Hiki K, Okumura M, Matsui Y, Nakayama Y, Wada S, Yamazaki N. Prognostic factors in cutaneous apocrine carcinoma: a single-institution retrospective study of 32 patients. International journal of clinical oncology, 28:1690-1696, 2023
28. Igaki H, Nakamura S, Yamazaki N, Kaneda T, Takemori M, Kashihara T, Murakami N, Namikawa K, Nakaichi T, Okamoto H, Iijima K, Chiba T, Nakayama H, Nagao A, Sakuramachi M, Takahashi K, Inaba K, Okuma K, Nakayama Y, Shimada K, Nakagama H, Itami J. Acral cutaneous malignant melanoma treated with linear accelerator-based boron neutron capture therapy system: a case report of first patient. Frontiers in oncology, 13:1272507, 2023
29. Wada S, Watanabe T, Ishii T, Ichinose Y, Rikitake R, Ogata D, Nakano E, Namikawa K, Yamazaki N, Higashi T. A retrospective study of sentinel lymph node biopsy for skin cancer in Japan: Comparison with breast cancer and evaluation of factors related to its use. Cancer medicine, 12:21364-21372, 2023
30. Nishimura Y, Ryo E, Inoue S, Kawazu M, Ueno T, Namikawa K, Takahashi A, Ogata D, Yoshida A, Yamazaki N, Mano H, Yatabe Y, Mori T. Strategic Approach to Heterogeneity Analysis of Cutaneous Adnexal Carcinomas Using Computational Pathology and Genomics. JID innovations, 3:100229, 2023
31. Bai X, Shaheen A, Grieco C, d'Arienzo PD, Mina F, Czapla JA, Lawless AR, Bongiovanni E, Santaniello U, Zappi H, Dulak D, Williamson A, Lee R, Gupta A, Li C, Si L, Ubaldi M, Yamazaki N, Ogata D, Johnson R, Park BC, Jung S, Madonna G, Hochherz J, Umeda Y, Nakamura Y, Gebhardt C, Festino L, Capone M, Ascierto PA, Johnson DB, Lo SN, Long GV, Menzies AM, Namikawa K, Mandala M, Guo J, Lorigan P, Najjar YG, Haydon A, Quaglino P, Boland GM, Sullivan RJ, Furness AJS, Plummer R, Flaherty KT. Dabrafenib plus trametinib versus anti-PD-1 monotherapy as adjuvant therapy in BRAF V600-mutant stage III melanoma after definitive surgery: a multicenter, retrospective cohort study. EClinicalMedicine, 65:102290, 2023
32. Wada S, Ogata D, Kashihara T, Okuma K, Eto H, Nakano E, Takahashi A, Namikawa K, Igaki H, Yamazaki N. A single-center retrospective analysis of prognoses in patients with melanoma brain metastases and effectiveness of treatment in Japan. Cancer medicine, 12:21933-21943, 2023
33. Itoyama M, Ohara A, Yokoyama K, Yamamoto S, Kato K, Mori T, Igaki H, Nakano E, Yamazaki N, Sunami K, Nishigori C, Honma Y. Successful Use of Anti-PD-1 Antibody to Treat Multiple Metastatic Carcinomas in a Patient with Xeroderma Pigmentosum: Case Report and Literature Review. Clinical Images and Case Reports Journal, 5:312, 2023