Long-Term Outcomes of Carbon-Ion Radiotherapy for Malignant Gynecological Melanoma
Abstract
:1. Introduction
2. Results
2.1. Patient Characteristics
2.2. Treatment Efficacy and Prognostic Factors
2.3. Toxicity
3. Discussion
4. Materials and Methods
4.1. Eligibility
4.2. C-ion RT
4.3. Patient Preparation for Daily Treatment
4.4. Evaluation
4.5. Statistical Analyses
5. Conclusions
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
- McLaughlin, C.C.; Wu, X.C.; Jemal, A.; Martin, H.J.; Roche, L.M.; Chen, V.W. Incidence of noncutaneous melanomas in the U.S. Cancer 2005, 103, 1000–1007. [Google Scholar] [CrossRef] [PubMed]
- Chang, A.E.; Karnell, L.H.; Menck, H.R. The National Cancer Data Base report on cutaneous and noncutaneous melanoma: A summary of 84,836 cases from the past decade. The American College of Surgeons Commission on Cancer and the American Cancer Society. Cancer 1998, 83, 1664–1678. [Google Scholar] [CrossRef]
- Irvin, W.P., Jr.; Legallo, R.L.; Stoler, M.H.; Rice, L.W.; Taylor, P.T., Jr.; Andersen, W.A. Vulvar melanoma: A retrospective analysis and literature review. Gynecol. Oncol. 2001, 83, 457–465. [Google Scholar] [CrossRef] [PubMed]
- Pusceddu, S.; Bajetta, E.; Carcangiu, M.L.; Formisano, B.; Ducceschi, M.; Buzzoni, R. A literature overview of primary cervical malignant melanoma: An exceedingly rare cancer. Crit. Rev. Oncol. Hematol. 2012, 81, 185–195. [Google Scholar] [CrossRef] [PubMed]
- Ragnarsson-Olding, B.; Johansson, H.; Rutqvist, L.; Ringborg, U. Malignant melanoma of the vulva and vagina. Cancer 1993, 71, 1893–1897. [Google Scholar] [CrossRef]
- Sanchez, A.; Rodriguez, D.; Allard, C.B.; Bechis, S.K.; Sullivan, R.J.; Boeke, C.E.; Kuppermann, D.; Cheng, J.S.; Barrisford, G.W.; Preston, M.A.; et al. Primary genitourinary melanoma: Epidemiology and disease-specific survival in a large population-based cohort. Urol. Oncol. 2016, 34. [Google Scholar] [CrossRef] [PubMed]
- Piura, B. Management of primary melanoma of the female urogenital tract. Lancet Oncol. 2008, 9, 973–981. [Google Scholar] [CrossRef]
- Bradgate, M.G.; Rollason, T.P.; McConkey, C.C.; Powell, J. Malignant melanoma of the vulva: A clinicopathological study of 50 women. Br. J. Obstet. Gynaecol. 1990, 97, 124–133. [Google Scholar] [CrossRef] [PubMed]
- Look, K.Y.; Roth, L.M.; Sutton, G.P. Vulvar melanoma reconsidered. Cancer 1993, 72, 143–146. [Google Scholar] [CrossRef]
- Clark, K.C.; Butz, W.R.; Hapke, M.R. Primary malignant melanoma of the uterine cervix: Case report with world literature review. Int. J. Gynecol. Pathol. 1999, 18, 265–273. [Google Scholar] [CrossRef] [PubMed]
- Verschraegen, C.F.; Benjapibal, M.; Supakarapongkul, W.; Levy, L.B.; Ross, M.; Atkinson, E.N.; Bodurka-Bevers, D.; Kavanagh, J.J.; Kudelka, A.P.; Legha, S.S. Vulvar melanoma at the M. D. Anderson Cancer Center: 25 years later. Int. J. Gynecol. Cancer 2001, 11, 359–364. [Google Scholar] [CrossRef]
- Frumovitz, M.; Etchepareborda, M.; Sun, C.C.; Soliman, P.T.; Eifel, P.J.; Levenback, C.F.; Ramirez, P.T. Primary malignant melanoma of the vagina. Obstet. Gynecol. 2010, 116, 1358–1365. [Google Scholar] [CrossRef]
- Slingluff, C.L.; Flaherty, K.; Rosenberg, S.A.; Read, P.W. Cutaneous Melanoma. In Cancer: Principles and Practice of Oncology, 9th ed.; DeVita, V.T., Lawrence, T.S., Rosenberg, S.A., Eds.; Lippincott Williams & Wilkins: Philadelphia, PA, USA, 2011; pp. 1643–1691. [Google Scholar]
- Lee, S.M.; Betticher, D.C.; Thatcher, N. Melanoma: Chemotherapy. Br. Med. Bull. 1995, 51, 609–630. [Google Scholar] [CrossRef] [PubMed]
- Agarwala, S.S. Current systemic therapy for metastatic melanoma. Expert Rev. Anticancer Ther. 2009, 9, 587–595. [Google Scholar] [CrossRef] [PubMed]
- Topalian, S.L.; Sznol, M.; McDermott, D.F.; Kluger, H.M.; Carvajal, R.D.; Sharfman, W.H.; Brahmer, J.R.; Lawrence, D.P.; Atkins, M.B.; Powderly, J.D.; et al. Survival, durable tumor remission, and long-term safety in patients with advanced melanoma receiving nivolumab. J. Clin. Oncol. 2014, 32, 1020–1030. [Google Scholar] [CrossRef]
- Robert, C.; Thomas, L.; Bondarenko, I.; O’Day, S.; Weber, J.; Garbe, C.; Lebbe, C.; Baurain, J.F.; Testori, A.; Grob, J.J.; et al. Ipilimumab plus dacarbazine for previously untreated metastatic melanoma. N. Engl. J. Med. 2011, 364, 2517–2526. [Google Scholar] [CrossRef] [PubMed]
- Kanai, T.; Furusawa, Y.; Fukutsu, K.; Itsukaichi, H.; Eguchi-Kasai, K.; Ohara, H. Irradiation of mixed beam and design of spread-out Bragg peak for heavy-ion radiotherapy. Radiat. Res. 1997, 147, 78–85. [Google Scholar] [CrossRef]
- Kanai, T.; Endo, M.; Minohara, S.; Miyahara, N.; Koyama-ito, H.; Tomura, H.; Matsufuji, N.; Futami, Y.; Fukumura, A.; Hiraoka, T.; et al. Biophysical characteristics of HIMAC clinical irradiation system for heavy-ion radiation therapy. Int. J. Radiat. Oncol. Biol. Phys. 1999, 44, 201–210. [Google Scholar] [CrossRef]
- Koto, M.; Demizu, Y.; Saitoh, J.I.; Suefuji, H.; Tsuji, H.; Okimoto, T.; Ohno, T.; Shioyama, Y.; Takagi, R.; Nemoto, K.; et al. Multicenter study of carbon-ion radiation therapy for mucosal melanoma of the head and neck: Subanalysis of the Japan Carbon-Ion Radiation Oncology Study Group (J-CROS) study (1402 HN). Int. J. Radiat. Oncol. Biol. Phys. 2017, 97, 1054–1060. [Google Scholar] [CrossRef]
- Toyama, S.; Tsuji, H.; Mizoguchi, N.; Nomiya, T.; Kamada, T.; Tokumaru, S.; Mizota, A.; Ohnishi, Y.; Tsujii, H. Working Group for Ophthalmologic Tumors. Long-term results of carbon ion radiation therapy for locally advanced or unfavorably located choroidal melanoma: Usefulness of CT-based 2-port orthogonal therapy for reducing the incidence of neovascular glaucoma. Int. J. Radiat. Oncol. Biol. Phys. 2013, 86, 270–276. [Google Scholar] [CrossRef] [PubMed]
- Karasawa, K.; Wakatsuki, M.; Kato, S.; Kiyohara, H.; Kamada, T. Working Group for Gynecological Tumors. Clinical trial of carbon ion radiotherapy for gynecological melanoma. J. Radiat. Res. 2014, 55, 343–350. [Google Scholar] [CrossRef]
- Reid, G.C.; Schmidt, R.W.; Roberts, J.A.; Hopkins, M.P.; Barrett, R.J.; Morley, G.W. Primary melanoma of the vagina: A clinicopathologic analysis. Obstet. Gynecol. 1989, 74, 190–199. [Google Scholar]
- DiMarco, D.S.; DiMarco, C.S.; Zincke, H.; Webb, M.J.; Keeney, G.L.; Bass, S.; Lightner, D.J. Outcome of surgical treatment for primary malignant melanoma of the female urethra. J. Urol. 2004, 171, 765–767. [Google Scholar] [CrossRef] [PubMed]
- Mihajlovic, M.; Vlajkovic, S.; Jovanovic, P.; Stefanovic, V. Primary mucosal melanomas: A comprehensive review. Int. J. Clin. Exp. Pathol. 2012, 5, 739–753. [Google Scholar]
- Hou, J.Y.; Baptiste, C.; Hombalegowda, R.B.; Tergas, A.I.; Feldman, R.; Jones, N.L.; Chatterjee-Paer, S.; Bus-Kwolfski, A.; Wright, J.D.; Burke, W.M. Vulvar and vaginal melanoma: A unique subclass of mucosal melanoma based on a comprehensive molecular analysis of 51 cases compared with 2253 cases of nongynecologic melanoma. Cancer 2017, 123, 1333–1344. [Google Scholar] [CrossRef]
- Callea, M.; Pedica, F.; Doglioni, C. Programmed death 1 (PD-1) and its ligand (PD-L1) as a new frontier in cancer immunotherapy and challenges for the pathologist: State of the art. Pathologica 2016, 108, 48–58. [Google Scholar] [PubMed]
- Inaniwa, T.; Kanematsu, N.; Matsufuji, N.; Kanai, T.; Shirai, T.; Noda, K.; Tsuji, H.; Kamada, T.; Tsujii, H. Reformulation of a clinical-dose system for carbon-ion radiotherapy treatment planning at the National Institute of Radiological Sciences, Japan. Phys. Med. Biol. 2015, 60, 3271–3286. [Google Scholar] [CrossRef] [PubMed]
- Eisenhauer, E.A.; Therasse, P.; Bogaerts, J.; Schwartz, L.H.; Sargent, D.; Ford, R.; Dancey, J.; Arbuck, S.; Gwyther, S.; Mooney, M.; et al. New response evaluation criteria in solid tumours: Revised RECIST guideline (version 1.1). Eur. J. Cancer 2009, 45, 228–247. [Google Scholar] [CrossRef] [PubMed]
- NCI Common Terminology Criteria for Adverse Events (CTCAE) V4.0 Data Files. Available online: http://evs.nci.nih.gov/ftp1/CTCAE/About.html (accessed on 15 January 2019).
- Cox, J.D.; Stetz, J.; Pajak, T.F. Toxicity criteria of the Radiation Therapy Oncology Group (RTOG) and the European Organization for Research and Treatment of Cancer (EORTC). Int. J. Radiat. Oncol. Biol. Phys. 1995, 31, 1341–1346. [Google Scholar] [CrossRef]
Characteristics | Number of Patients | % |
---|---|---|
Age (median), years | 51–88 (71) | |
Tumor site | ||
Vagina | 22 | 60 |
Vulva | 12 | 32 |
Cervix uterus | 3 | 8 |
Prior treatment | ||
Surgery | 9 | 24 |
Chemotherapy | 3 | 8 |
None | 25 | 68 |
T stage (including recurrent T stage) | ||
T1 | 8 | 22 |
T2 | 21 | 56 |
T3 | 8 | 22 |
Tumor size in maximal diameter | ||
≤30 mm | 29 | 78 |
>30 mm | 8 | 22 |
Lymph node metastasis | ||
Positive | 5 | 14 |
Negative | 32 | 86 |
The reason for inoperableness | ||
Medically inoprerable | 27 | 73 |
Patient’s refusal | 10 | 27 |
Total dose of C-ion RT | ||
57.6 Gy (RBE) in 16 fractions | 35 | 95 |
64.0 Gy (RBE) in 16 fractions | 2 | 5 |
Adjuvant therapy | ||
DAV/DAV Feron | 9 | 24 |
Nivolumab | 1 | 3 |
None | 27 | 73 |
Factor | No. of Patients | LC | PFS | OS | DM | ||||
---|---|---|---|---|---|---|---|---|---|
2-Year (%) | p-Value | 2-Year (%) | p-Value | 2-Year (%) | p-Value | 2-Year (%) | p-Value | ||
Age (years) | 0.213 | 0.617 | 0.983 | 0.041 | |||||
<71 | 17 | 49.7 | 17.6 | 57.0 | 52.9 | ||||
≥71 | 20 | 89.2 | 39.4 | 43.3 | 40.1 | ||||
Prior treatment | 0.468 | 0.547 | 0.564 | 0.242 | |||||
No | 12 | 69.4 | 30.5 | 53.5 | 37.6 | ||||
Yes | 25 | 72.2 | 25.0 | 50.0 | 58.3 | ||||
T stage (including recurrence) | 0.974 | 0.953 | 0.877 | 0.903 | |||||
T1–2 | 29 | 65.4 | 26.6 | 53.7 | 48.0 | ||||
T3 | 8 | 87.5 | 37.5 | 37.5 | 37.5 | ||||
Tumor diameter | 0.337 | 0.418 | 0.304 | 0.320 | |||||
≤30 mm | 29 | 73.9 | 33.4 | 57.2 | 46.3 | ||||
>30 mm | 8 | 60.0 | 12.5 | 37.5 | 37.5 | ||||
LN metastasis | 0.320 | 0.248 | 0.069 | 0.206 | |||||
Positive | 5 | 60.0 | 0.0 | 40.0 | 80.0 | ||||
Negative | 32 | 73.0 | 40.4 | 54.9 | 39.1 | ||||
Adjuvant chemotherapy | 0.535 | 0.142 | 0.382 | 0.796 | |||||
No | 27 | 65.8 | 20.4 | 53.8 | 43.4 | ||||
Yes | 10 | 80.0 | 50.0 | 50.0 | 50.0 | ||||
Tumor response within 6 months after commencing C-ion RT | 0.535 | 0.923 | 0.818 | 0.826 | |||||
CR | 19 | 77.7 | 23.7 | 61.5 | 43.2 | ||||
Non-CR | 18 | 61.6 | 33.3 | 43.2 | 45.8 | ||||
Primary site | N.S. | N.S. | N.S. | N.S. | |||||
Vagina | 22 | 73.4 | 26.5 | 55.2 | 53.0 | ||||
Vulva | 12 | 76.4 | 33.3 | 58.3 | 33.3 | ||||
Cervix uterus | 3 | 33.3 | 33.3 | 33.3 | 33.3 |
Acute Toxicity | CTCAE v.4 Scoring | ||||
---|---|---|---|---|---|
Grade 0 | Grade 1 | Grade 2 | Grade 3 | Grade 4–5 | |
Dermatitis/mucositis | 2 | 18 | 14 | 3 | 0 |
Genitourinary toxicity | 28 | 9 | 0 | 0 | 0 |
Lower gastrointestinal toxicity | 17 | 14 | 6 | 0 | 0 |
Late toxicity | RTOG/EORTC Scoring | ||||
Grade 0 | Grade 1 | Grade 2 | Grade 3 | Grade 4–5 | |
Dermatitis/mucositis | 28 | 9 | 0 | 0 | 0 |
Genitourinary toxicity | 30 | 3 | 4 | 0 | 0 |
Lower gastrointestinal toxicity | 29 | 5 | 3 | 0 | 0 |
Authors (ref.) | Year | Treatment Modality | Number of Patients | Primary Site | 5-Year OS |
---|---|---|---|---|---|
Bradgate et al. [8] | 1990 | Surgery | 50 | Vulva | 35% |
Look et al. [9] | 1993 | Surgery | 16 | Vulva | 30% |
Ragnarsson-Olding et al. [5] | 1993 | Mainly surgery | 245 | Mixed | 35% (vulva); 13% (vagina) |
Chang et al. [2] | 1995 | Mainly surgery | 59 | Mixed | 11% as DFS |
Clark et al. [10] | 1999 | Mainly surgery | 37 | Uterus cervix | 14% in Stage II; 0% in Stage III–IV |
Verschraegen et al. [11] | 2001 | Surgery | 31 | Vulva | 31% in Stage II–IV |
Irvin et al. [3] | 2001 | Surgery | 16 | Vulva | 17% months in MST |
Frumovitz et al. [12] | 2010 | Surgery | 37 | Vagina | 20% |
Present study | 2018 | C-ion RT | 37 | Mixed | 28% |
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Murata, H.; Okonogi, N.; Wakatsuki, M.; Kato, S.; Kiyohara, H.; Karasawa, K.; Ohno, T.; Nakano, T.; Kamada, T.; Shozu, M.; et al. Long-Term Outcomes of Carbon-Ion Radiotherapy for Malignant Gynecological Melanoma. Cancers 2019, 11, 482. https://doi.org/10.3390/cancers11040482
Murata H, Okonogi N, Wakatsuki M, Kato S, Kiyohara H, Karasawa K, Ohno T, Nakano T, Kamada T, Shozu M, et al. Long-Term Outcomes of Carbon-Ion Radiotherapy for Malignant Gynecological Melanoma. Cancers. 2019; 11(4):482. https://doi.org/10.3390/cancers11040482
Chicago/Turabian StyleMurata, Hiroto, Noriyuki Okonogi, Masaru Wakatsuki, Shingo Kato, Hiroki Kiyohara, Kumiko Karasawa, Tatsuya Ohno, Takashi Nakano, Tadashi Kamada, Makio Shozu, and et al. 2019. "Long-Term Outcomes of Carbon-Ion Radiotherapy for Malignant Gynecological Melanoma" Cancers 11, no. 4: 482. https://doi.org/10.3390/cancers11040482