Annual Report 2021
Department of Head and Neck Medical Oncology
Makoto Tahara, Susumu Okano, Tomohiro Enokida, Takao Fujisawa, Hideki Tanaka, Akihisa Wada, Naohiro Takeshita, Nobukazu Tanaka, Masanobu Sato
Introduction
The Department of Head and Neck Medical Oncology is engaged in the clinical management of patients with head and neck cancer (HNC), and research into anticancer drugs for the treatment of HNC.
Our missions are to: 1) provide the best evidence-based treatment; 2) promote the importance of supportive care in the treatment of patients with HNC; 3) facilitate the timely approval of new drugs by active participation in global clinical trials to eliminate the drug lag; 4) develop cutting-edge treatments; and 5) train experts in head and neck medical oncology.
The Team and What We Do
Our department consists of four physicians, two senior residents and three residents. We manage the treatment of HNC patients who receive anticancer drugs. An estimated 60% of HNC patients require a multidisciplinary approach, including surgery, radiotherapy, and chemotherapy. Given the increasing complexity of the management of HNC, recommended treatment for patients who are referred to our institution is decided at a weekly tumor board attended by a multidisciplinary team.
A total of 314 patients were referred to our department from April 2021 to March 2022 (Table 1 and Table 2). The outpatient service of our department is available from Monday to Friday. We carefully follow patients during and after treatment and provide palliative chemotherapy as an outpatient service.
Table 1. Number of patients according to site
Table 2. Number of patients according to procedure
Research activities
Our research activity has focused on three areas: the development of new treatments in clinical trials for HNC, biomarker analysis in HNC and retrospective analysis of management of treatment for HNC.
Chemoradiotherapy with 3-weekly cisplatin at a dose of 100 mg/m2 is the standard treatment for patients with post-operative squamous cell carcinoma of the head and neck (SCCHN) with high risk of recurrence. However, the 3-weekly dosage has attracted concern with regard to insufficient cisplatin delivery due to high-dose-related toxicities. Chemoradiotherapy with weekly cisplatin at a dose of 40 mg/m2 is widely used as a possible alternative, albeit without sufficient evidence. We conducted a randomized phase II/III trial to prove the non-inferiority of weekly cisplatin to 3-weekly cisplatin plus radiation (RT).
The results of the present study were published in the Journal of Clinical Oncology on May 2, 2022. Between October 2012 and December 2018, a total of 261 patients were enrolled (3-weekly cisplatin: 132 pts; weekly cisplatin: 129 pts). In the planned second interim analysis for the phase III part, after a median follow-up of 2.2 years (IQR 1.19-3.56), chemoradiotherapy with weekly cisplatin was non-inferior to 3-weekly cisplatin in terms of overall survival, with a hazard ratio of 0.69 (99.1% CI, 0.374-1.273 [<1.32], one-sided p for non-inferiority = 0.0027 < 0.0043). Grade 3 or more neutropenia and infection were less frequent in the weekly arm (3-weekly vs. weekly, 49% vs. 35%, 12% vs. 7%, respectively), as were renal impairment and hearing impairment. No treatment-related deaths were reported in the 3-weekly arm and two (1.6%) were reported in the weekly arm.
In conclusion, chemoradiotherapy with weekly cisplatin is non-inferior to 3-weekly cisplatin for post-operative high-risk LA-SCCHN patients. These findings suggest that chemoradiotherapy with weekly cisplatin can be a possible treatment option for these patients. More patients who are reluctant to receive high-dose cisplatin will receive weekly cisplatin, leading to improved clinical outcomes for post-operative high-risk LA-SCCHN patients.
Clinical trials
The following investigator-initiated clinical trials are ongoing; 1) a phase II study of a combination of nivolumab plus lenvatinib for unresectable anaplastic thyroid cancer and 2) a phase II study of darolutamide for androgen receptor positive recurrent or metastatic salivary gland carcinoma.
To facilitate the timely approval of new drugs and eliminate the drug lag, we have also participated in the global phase trials including immune-checkpoint inhibitors.
Education
We teach not only medical staff in our institute but also outside our institute by conducting the following education program: Seminar of the Japan Society of Supportive Care for Patients with HNC. Furthermore, our department is accepting trainees all the time.
Future Prospects
We hope that ongoing or planned clinical trials will change the standard of care for HNC and our biomarker analysis will lead to the development of new treatment strategies. Our education program will increase the number of medical oncologists who take charge of treatment for HNC, leading to improving patients’ quality of survival.
List of papers published in 2021
Journal
1. Kiyota N, Tahara M, Mizusawa J, Kodaira T, Fujii H, Yamazaki T, Mitani H, Iwae S, Fujimoto Y, Onozawa Y, Hanai N, Ogawa T, Hara H, Monden N, Shimura E, Minami S, Fujii T, Tanaka K, Homma A, Yoshimoto S, Oridate N, Omori K, Ueda T, Okami K, Ota I, Shiga K, Sugasawa M, Asakage T, Saito Y, Murono S, Nishimura Y, Nakamura K, Hayashi R. Weekly Cisplatin Plus Radiation for Postoperative Head and Neck Cancer (JCOG1008): A Multicenter, Noninferiority, Phase II/III Randomized Controlled Trial. Journal of clinical oncology: official journal of the American Society of Clinical Oncology, JCO2101293, 2022
2. Imamura Y, Kiyota N, Tahara M, Hanai N, Asakage T, Matsuura K, Ota I, Saito Y, Sano D, Kodaira T, Motegi A, Yasuda K, Takahashi S, Yokota T, Okano S, Tanaka K, Onoe T, Ariizumi Y, Homma A. Systemic therapy for salivary gland malignancy: current status and future perspectives. Japanese journal of clinical oncology, 52:293-302, 2022
3. Kotani D, Nakamura Y, Fujisawa T, Bando H, Sakamoto N, Johns AL, Park K, Casolino R, Yoshino T, Biankin AV. ICGC-ARGO precision medicine: targeted therapy according to longitudinal assessment of tumour heterogeneity in colorectal cancer. The Lancet. Oncology, 23:463-464, 2022
4. Burtness B, Rischin D, Greil R, Soulières D, Tahara M, de Castro G Jr, Psyrri A, Brana I, Basté N, Neupane P, Bratland Å, Fuereder T, Hughes BGM, Mesia R, Ngamphaiboon N, Rordorf T, Wan Ishak WZ, Ge J, Swaby RF, Gumuscu B, Harrington K . Pembrolizumab Alone or With Chemotherapy for Recurrent/Metastatic Head and Neck Squamous Cell Carcinoma in KEYNOTE-048: Subgroup Analysis by Programmed Death Ligand-1 Combined Positive Score. Journal of clinical oncology: official journal of the American Society of Clinical Oncology, JCO2102198, 2022
5. Haddad RI, Seiwert TY, Chow LQM, Gupta S, Weiss J, Gluck I, Eder JP, Burtness B, Tahara M, Keam B, Kang H, Muro K, Albright A, Mogg R, Ayers M, Huang L, Lunceford J, Cristescu R, Cheng J, Mehra R. Influence of tumor mutational burden, inflammatory gene expression profile, and PD-L1 expression on response to pembrolizumab in head and neck squamous cell carcinoma. Journal for immunotherapy of cancer, 10:2022
6. Rischin D, Harrington KJ, Greil R, Soulières D, Tahara M, de Castro G Jr, Psyrri A, Braña I, Neupane P, Bratland Å, Fuereder T, Hughes BGM, Mesía R, Ngamphaiboon N, Rordorf T, Ishak WZW, Hong RL, Mendoza RG, Jia L, Chirovsky D, Norquist J, Jin F, Burtness B . Pembrolizumab alone or with chemotherapy for recurrent or metastatic head and neck squamous cell carcinoma: Health-related quality-of-life results from KEYNOTE-048. Oral oncology, 128:105815, 2022
7. Tahara M, Okano S, Enokida T, Ueda Y, Fujisawa T, Shinozaki T, Tomioka T, Okano W, Biel MA, Ishida K, Hayashi R. A phase I, single-center, open-label study of RM-1929 photoimmunotherapy in Japanese patients with recurrent head and neck squamous cell carcinoma. International journal of clinical oncology, 26:1812-1821, 2021
8. Nakamura Y, Fujisawa T, Taniguchi H, Bando H, Okamoto W, Tsuchihara K, Yoshino T, Ohtsu A. SCRUM-Japan GI-SCREEN and MONSTAR-SCREEN: Path to the realization of biomarker-guided precision oncology in advanced solid tumors. Cancer science, 112:4425-4432, 2021
9. Taylor MH, Takahashi S, Capdevila J, Tahara M, Leboulleux S, Kiyota N, Dutcus CE, Xie R, Robinson B, Sherman S, Habra MA, Elisei R, Wirth LJ. Correlation of Performance Status and Neutrophil-Lymphocyte Ratio with Efficacy in Radioiodine-Refractory Differentiated Thyroid Cancer Treated with Lenvatinib. Thyroid: official journal of the American Thyroid Association, 31:1226-1234, 2021
10. Tahara M, Kiyota N, Hoff AO, Badiu C, Owonikoko TK, Dutcus CE, Suzuki T, Ren M, Wirth LJ. Impact of lung metastases on overall survival in the phase 3 SELECT study of lenvatinib in patients with radioiodine-refractory differentiated thyroid cancer. European journal of cancer (Oxford, England: 1990), 147:51-57, 2021
11. Okano S, Homma A, Kiyota N, Tahara M, Hanai N, Asakage T, Matsuura K, Ogawa T, Saito Y, Sano D, Kodaira T, Motegi A, Yasuda K, Takahashi S, Tanaka K, Onoe T, Yokota T, Imamura Y, Ariizumi Y, Akimoto T, Hayashi R. Induction chemotherapy in locally advanced squamous cell carcinoma of the head and neck. Japanese journal of clinical oncology, 51:173-179, 2021
12. Katada C, Sugawara M, Hara H, Fujii H, Nakajima TE, Ando T, Kojima T, Watanabe A, Sakamoto Y, Ishikawa H, Hosokawa A, Hamamoto Y, Muto M, Tahara M, Koizumi W. A management of neutropenia using granulocyte colony stimulating factor support for chemotherapy consisted of docetaxel, cisplatin and 5-fluorouracil in patients with oesophageal squamous cell carcinoma. Japanese journal of clinical oncology, 51:199-204, 2021
13. Adkins DR, Lin JC, Sacco A, Ley J, Oppelt P, Vanchenko V, Komashko N, Yen CJ, Wise-Draper T, Lopez-Picazo Gonzalez J, Radulovic S, Shen Q, Thurm H, Martini JF, Hoffman J, Huang X, Melichar B, Tahara M. Palbociclib and cetuximab compared with placebo and cetuximab in platinum-resistant, cetuximab-naïve, human papillomavirus-unrelated recurrent or metastatic head and neck squamous cell carcinoma: A double-blind, randomized, phase 2 trial. Oral oncology, 115:105192, 2021
14. Kramer R, Zaremba A, Moreira A, Ugurel S, Johnson DB, Hassel JC, Salzmann M, Gesierich A, Weppler A, Spain L, Loquai C, Dudda M, Pföhler C, Hepner A, Long GV, Menzies AM, Carlino MS, Sachse MM, Lebbé C, Baroudjian B, Enokida T, Tahara M, Schlaak M, Hayani K, Bröckelmann PJ, Meier F, Reinhardt L, Friedlander P, Eigentler T, Kähler KC, Berking C, Zimmer L, Heinzerling L . Hematological immune related adverse events after treatment with immune checkpoint inhibitors. European journal of cancer (Oxford, England: 1990), 147:170-181, 2021
15. Enokida T, Tahara M. Management of VEGFR-Targeted TKI for Thyroid Cancer. Cancers, 13:2021
16. Zaremba A, Kramer R, De Temple V, Bertram S, Salzmann M, Gesierich A, Reinhardt L, Baroudjian B, Sachse MM, Mechtersheimer G, Johnson DB, Weppler AM, Spain L, Loquai C, Dudda M, Pföhler C, Hepner A, Long GV, Menzies AM, Carlino MS, Lebbé C, Enokida T, Tahara M, Bröckelmann PJ, Eigentler T, Kähler KC, Gutzmer R, Berking C, Ugurel S, Stadtler N, Sucker A, Becker JC, Livingstone E, Meier F, Hassel JC, Schadendorf D, Hanoun M, Heinzerling L, Zimmer L . Grade 4 Neutropenia Secondary to Immune Checkpoint Inhibition - A Descriptive Observational Retrospective Multicenter Analysis. Frontiers in oncology, 11:765608, 2021
17. Enokida T, Tahara M. Electrochemotherapy in the Treatment of Head and Neck Cancer: Current Conditions and Future Directions. Cancers, 13:2021
18. Shiga K, Nibu KI, Fujimoto Y, Asakage T, Homma A, Mitani H, Ogawa T, Okami K, Murono S, Hirano S, Ueda T, Hanai N, Tsukahara K, Ota I, Yoshimoto S, Shinozaki T, Iwae S, Katagiri K, Saito D, Kiyota N, Tahara M, Takahashi F, Hayashi R. Multi-institutional Survey of Squamous Cell Carcinoma of the External Auditory Canal in Japan. The Laryngoscope, 131:E870-E874, 2021