The role of radiotherapy in the age of immunotherapySato, Hiro; Demaria, Sandra; Ohno, Tatsuya
doi: 10.1093/jjco/hyaa268pmid: 33561212
With the development of immune checkpoint inhibitors, the efficacy of immunotherapy as a cancer treatment that is effective against multiple tumor types has been established, and this modality came to be considered as the fourth pillar of cancer therapy. The clinical success of immunotherapy greatly changed the field of oncology by highlighting the importance of the immune system in cancer control and elimination. It has now become clear that research into, and the clinical application of, the immune response are important for effective cancer treatment. Moreover, it has become apparent that conventional cancer treatments, such as radiotherapy and chemotherapy, can modulate the cross-talk between the tumor and the immune system, and their efficacy depends, in part, on the ability to elicit antitumor immune response. The ability of radiotherapy to induce an immune response has become relevant in the immunotherapy age. Radiotherapy has been redefined as a partner for cancer immunotherapy, based on evidence indicating the potential synergistic effect of the combination of these therapeutic modalities. This review outlines the major findings reported to date on the immune response induced by radiotherapy and discusses the role of radiotherapy in combination with immunotherapy. Furthermore, we introduce research aimed at the clinical application of combination therapy and discuss its potential in clinical practice and future issues.
Immunotherapy for sarcomasNakata, Eiji; Fujiwara, Tomohiro; Kunisada, Toshiyuki; Ito, Tastuo; Takihira, Shota; Ozaki, Toshifumi
doi: 10.1093/jjco/hyab005pmid: 33611603
Sarcomas are a heterogeneous group of malignancies of mesenchymal origin; their molecular and genomic mechanisms differ with regard to histology. These characteristics lead to the presentation of varied immunological profiles based on the tumor microenvironment. Various immunotherapies are considered for the treatment of sarcoma. These treatments are performed either in isolation or in combination with other methods such as cytotoxic chemotherapy or the use of molecular target agents. Among these, two recently emerging immunotherapies include T-cell receptor gene therapy and immune checkpoint inhibitor therapy, which are expected to be effective for many types of sarcoma. A sarcoma with a disease-specific translocation and a limited number of mutations, such as synovial sarcoma, expresses high levels of self-antigens, like the New York esophageal squamous cell carcinoma 1, which has been targeted in T-cell receptor gene therapy. On the other hand, sarcomas with a greater number of mutations, such as undifferentiated pleomorphic sarcomas, myxofibrosarcoma and dedifferentiated liposarcomas, can be good candidates for immune checkpoint inhibitors. Among immune checkpoint inhibitor therapies, programmed cell death-1 blockade (nivolumab and pembrolizumab) and cytotoxic T-lymphocyte–associated antigen 4 blockade (ipilimumab) have been investigated most often in sarcoma. Although the sole use of immune checkpoint inhibitors provides limited efficacy, combined immunotherapy with immune checkpoint inhibitors or molecular target agents, especially antiangiogenic agents, has shown moderate results against some types of sarcoma, such as the alveolar soft part sarcoma. Several clinical trials utilizing immunotherapy, including T-cell receptor gene therapy and immune checkpoint inhibitors, in sarcomas are under progress. By clarifying the tumor microenvironment and biomarker-predictive capacity of immunotherapy in sarcomas, better clinical trials can be designed; this could lead to improved outcomes for immunotherapy in sarcoma.
Establishment of a research policy for supportive and palliative care in JapanZenda, Sadamoto; Uchitomi, Yosuke; Morita, Tatsuya; Yamaguchi, Takuhiro; Inoue, Akira
doi: 10.1093/jjco/hyab008pmid: 33561254
BackgroundWhile several small groups in Japan have attempted to conduct prospective studies in the field of supportive and palliative care, development of exploratory research into multicentre confirmatory studies has been difficult. The main reason for this is the difference in clinical research methodology in supportive and palliative care compared with medical oncology in terms of the style of multidisciplinary approaches, study design and endpoints. Here, we establish a new research policy for cancer supportive and palliative care in Japan.MethodsThe first draft was developed by a policy working group within the Japanese Supportive, Palliative and Psychosocial Care Study Group. A provisional draft was subsequently developed after review by nine Japanese scientific societies (Japanese Association of Supportive Care in Cancer, Japanese Society of Medical Oncology, Japanese Society of Clinical Oncology, Japanese Society of Palliative Medicine, Japanese Society of Cancer Nursing, Japanese Society of Pharmaceutical Oncology (JASPO), Japan Cancer Association (JCA), Japanese Society of Therapeutic Radiation Oncology and Japanese Cancer Association) and receipt of public comments. The final research policy in the area of supportive and palliative care in Japan (Ver1.0) was completed in December 2018 and underwent its first revision (Ver1.1) in February, 2020.ResultsThe policy includes the following components of clinical research: (i) objective of the research policy in the areas of supportive and palliative care; (ii) definitions of supportive care and palliative care; (iii) characteristics of supportive and palliative care research; (iv) target population for research; (v) research design; (vi) endpoints and assessment measures; (vii) handling of the deaths of subjects and (viii) operational structure and quality management.ConclusionsWe hope that studies conducted according to this policy will play important roles in the future development of the supportive and palliative field.
Response to Dr Shikata’s letter: ‘Secondhand smoke exposure and risk of lung cancer in Japan: a systematic review and meta-analysis of epidemiologic studies’Hori, Megumi; Tanaka, Hirokazu; Saito, Eiko; Wakai, Kenji; Katanoda, Kota
doi: 10.1093/jjco/hyaa255pmid: 33454775
To the Editor This is in response to the letter by Dr Shikata and Prof. Takemura. We appreciate their comments and are glad to have deeper discussions about the effects of secondhand smoke (SHS) on lung cancer. Our meta-analysis published in 2016 showed that exposure to SHS increased the risk of lung cancer in a Japanese non-smoking population (1). We validated the robustness of the results by conducting several analyses and concluded that there was an association of SHS with lung cancer. However, the article reported the relative risk of SHS exposure and did not discuss absolute risk. As Shikata and Takemura (2) note in their comment on our meta-analysis, relative risk tells us nothing about the magnitude of absolute risk. To evaluate the health and economic effects of SHS comprehensively, relative risks need to be interpreted in combination with absolute risks. Lifetime cumulative risk is an index for absolute risk. In 2020, we reported lifetime cumulative mortality risk by smoking status in the Japanese Journal of Clinical Oncology (3). We estimated the lifetime cumulative mortality risk for lung cancer by SHS exposure status in never smokers, classified by those exposed or not exposed to SHS at home. The risk for never smokers aged 20 years not exposed to SHS at home and those exposed was 3.2 and 4.1% for men, and 1.9 and 2.4% for women, respectively. Regardless of current age, the estimated lifetime cumulative mortality risk for men and women was ~1% point and 0.5% point higher for never smokers exposed to SHS at home than for those not exposed, respectively. Although the absolute risk of lung cancer associated with SHS exposure was small, SHS exposure nevertheless made an observable difference in lifetime mortality risk in both sexes. Our new addition of an absolute risk estimate allows individual-based evaluation of the lung cancer risk of SHS. From both relative and absolute perspectives, prevention of SHS exposure is an effective and actionable strategy in improving total health. We trust that our estimation results will prove helpful and meaningful to many people, including those in clinical situations. References 1. Hori M , Tanaka H, Wakai K, Sasazuki S, Katanoda K. Secondhand smoke exposure and risk of lung cancer in Japan: a systematic review and meta-analysis of epidemiologic studies . Jpn J Clin Oncol 2016 ; 46 : 942 – 51 . Google Scholar Crossref Search ADS PubMed WorldCat 2. Shikata S , Takemura Y. Secondhand smoke exposure and risk of lung cancer in Japan: a systematic review and meta-analysis of epidemiologic studies . Jpn J Clin Oncol 2017 ; 47 :282. Google Scholar OpenURL Placeholder Text WorldCat 3. Hori M , Saito E, Katanoda K, Tsugane S. Estimation of lifetime cumulative mortality risk of lung cancer by smoking status in Japan . Jpn J Clin Oncol 2020 ; 50 : 1218 – 24 . Google Scholar Crossref Search ADS PubMed WorldCat © The Author(s) 2021. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: [email protected] This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (https://academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model)
Age-specific pancreas cancer incidence rate in the worldMachii, Ryoko; Saika, Kumiko
doi: 10.1093/jjco/hyab041pmid: 33712847
In order to make a comparison of the age-specific pancreas cancer incidence rate between Japan and other countries, we abstracted cancer incidence rate from the Cancer Incidence in Five Continents Vol. XI (CI5) (1). The International Agency for Research on Cancer provides the CI5 databases on the incidence of cancer recorded by cancer registries (regional and national) worldwide. We used cancer incidence rate in five countries in Asia (China, India, Japan, Republic of Korea and Thailand), three countries in America (USA, Canada and Brazil), two countries in Oceania (Australia and New Zealand) and four countries in Europe (UK, France, and Germany and Italy). Some countries have plural cancer registries, and we aggregated all the registries to calculate the incidence rate in the countries from the CI5-XI database. The period of years at cancer diagnosis were from 2008 to 2012. Pancreas cancer was coded as C25 based on International Classification of Diseases, 10th Revision. Figure 1 shows the age-specific incidence rates of pancreas cancer in male by countries. In most of the studied countries, incidence rates increased with age. In America, Oceania and Europe, differences in age-specific incidence rates between countries were not very large, whereas in Asia, the differences were greater over 35 years of age. Specifically, Japan had the highest incidence rate at 121 (per 100 000 population aged 75), followed by the Republic of Korea at 92 and China at 59, whereas Thailand and India had extremely low incidence rate at 25 and 14, respectively. The incidence rate over 50 years of age in Japan was the highest in the world, and those in all the countries except in Asia were higher than that in China. Figure 2 shows the age-specific incidence rates of pancreas cancer in female by countries. Over ages 40–50, the incidence rates for female were lower than those for male in most of the countries studied. The similar trend of age-specific incidence rate was observed among male and female, such as large differences between countries only in Asia. However, among male, the incidence rate in Japan was clearly high, followed by Italy, Germany and Australia, which were close to the rates in the Republic of Korea, whereas among female, the rates in Japan was the highest and the second highest rates in Italy, Germany and Australia were close to that in Japan. Figure 1. Open in new tabDownload slide Age-specific pancreas cancer incidence rate per 100 000 people in male. Figure 1. Open in new tabDownload slide Age-specific pancreas cancer incidence rate per 100 000 people in male. Figure 2. Open in new tabDownload slide Age-specific pancreas cancer incidence rate per 100 000 people in female. Figure 2. Open in new tabDownload slide Age-specific pancreas cancer incidence rate per 100 000 people in female. Note: Data were downloaded from the Global Cancer Observatory, which is an interactive web-based platform presenting global cancer statistics (https://gco.iarc.fr/). Responsibility for this presentation and interpretation lies with the authors of this article. Reference 1. Bray F , Colombet M, Mery L, et al. , editors. Cancer Incidence in Five Continents, Vol. XI (electronic version) . Lyon : International Agency for Research on Cancer . http://ci5.iarc.fr ( 9 February 2021, date last accessed ). Google Scholar Google Preview OpenURL Placeholder Text WorldCat COPAC © The Author(s) 2021. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: [email protected] This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (https://academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model)