Skip to main content

Main menu

  • Home
  • Current Issue
  • Archive
  • Info for
    • Authors
    • Editorial Policies
    • Subscribers
    • Advertisers
    • Editorial Board
    • Special Issues 2025
  • Journal Metrics
  • Other Publications
    • In Vivo
    • Cancer Genomics & Proteomics
    • Cancer Diagnosis & Prognosis
  • More
    • IIAR
    • Conferences
    • 2008 Nobel Laureates
  • About Us
    • General Policy
    • Contact
  • Other Publications
    • Anticancer Research
    • In Vivo
    • Cancer Genomics & Proteomics

User menu

  • Register
  • Subscribe
  • My alerts
  • Log in
  • My Cart

Search

  • Advanced search
Anticancer Research
  • Other Publications
    • Anticancer Research
    • In Vivo
    • Cancer Genomics & Proteomics
  • Register
  • Subscribe
  • My alerts
  • Log in
  • My Cart
Anticancer Research

Advanced Search

  • Home
  • Current Issue
  • Archive
  • Info for
    • Authors
    • Editorial Policies
    • Subscribers
    • Advertisers
    • Editorial Board
    • Special Issues 2025
  • Journal Metrics
  • Other Publications
    • In Vivo
    • Cancer Genomics & Proteomics
    • Cancer Diagnosis & Prognosis
  • More
    • IIAR
    • Conferences
    • 2008 Nobel Laureates
  • About Us
    • General Policy
    • Contact
  • Visit us on Facebook
  • Follow us on Linkedin
Research ArticleClinical Studies

Elective Nodal Irradiation for Non-small Cell Lung Cancer Complicated With Chronic Obstructive Pulmonary Disease Affects Immunotherapy Αfter Definitive Chemoradiotherapy

MASAHIRO MORIMOTO, KAZUMI NISHINO, KENTARO WADA, FUMIO IMAMURA, KOJI KONISHI, HANAKO KUHARA, MOTOHIRO TAMIYA, TAKAKO INOUE, KEI KUNIMASA, MADOKA KIMURA, TAKERO HIRATA, NAOYUKI KANAYAMA, MASAYASU TORATANI, HAYATO KAWACHI, KIKA OHIRA, ERINA NAKANISHI, SHINGO OHIRA, TOMOHIRO SAGAWA, MASAYOSHI MIYAZAKI, TAKASHI MATSUNAGA, TORU KUMAGAI and TERUKI TESHIMA
Anticancer Research December 2020, 40 (12) 6957-6970; DOI: https://doi.org/10.21873/anticanres.14720
MASAHIRO MORIMOTO
1Department of Radiation Oncology, Osaka International Cancer Institute, Osaka, Japan
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • For correspondence: morimoto-knk@umin.ac.jp
KAZUMI NISHINO
2Department of Thoracic Oncology, Osaka International Cancer Institute, Osaka, Japan
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
KENTARO WADA
1Department of Radiation Oncology, Osaka International Cancer Institute, Osaka, Japan
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
FUMIO IMAMURA
2Department of Thoracic Oncology, Osaka International Cancer Institute, Osaka, Japan
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
KOJI KONISHI
1Department of Radiation Oncology, Osaka International Cancer Institute, Osaka, Japan
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
HANAKO KUHARA
2Department of Thoracic Oncology, Osaka International Cancer Institute, Osaka, Japan
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
MOTOHIRO TAMIYA
2Department of Thoracic Oncology, Osaka International Cancer Institute, Osaka, Japan
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
TAKAKO INOUE
2Department of Thoracic Oncology, Osaka International Cancer Institute, Osaka, Japan
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
KEI KUNIMASA
2Department of Thoracic Oncology, Osaka International Cancer Institute, Osaka, Japan
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
MADOKA KIMURA
2Department of Thoracic Oncology, Osaka International Cancer Institute, Osaka, Japan
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
TAKERO HIRATA
1Department of Radiation Oncology, Osaka International Cancer Institute, Osaka, Japan
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
NAOYUKI KANAYAMA
1Department of Radiation Oncology, Osaka International Cancer Institute, Osaka, Japan
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
MASAYASU TORATANI
1Department of Radiation Oncology, Osaka International Cancer Institute, Osaka, Japan
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
HAYATO KAWACHI
2Department of Thoracic Oncology, Osaka International Cancer Institute, Osaka, Japan
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
KIKA OHIRA
2Department of Thoracic Oncology, Osaka International Cancer Institute, Osaka, Japan
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
ERINA NAKANISHI
1Department of Radiation Oncology, Osaka International Cancer Institute, Osaka, Japan
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
SHINGO OHIRA
1Department of Radiation Oncology, Osaka International Cancer Institute, Osaka, Japan
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
TOMOHIRO SAGAWA
1Department of Radiation Oncology, Osaka International Cancer Institute, Osaka, Japan
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
MASAYOSHI MIYAZAKI
1Department of Radiation Oncology, Osaka International Cancer Institute, Osaka, Japan
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
TAKASHI MATSUNAGA
4Department of Medical Informatics, Osaka International Cancer Institute, Osaka, Japan
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
TORU KUMAGAI
2Department of Thoracic Oncology, Osaka International Cancer Institute, Osaka, Japan
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
TERUKI TESHIMA
1Department of Radiation Oncology, Osaka International Cancer Institute, Osaka, Japan
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • Article
  • Figures & Data
  • Info & Metrics
  • PDF
Loading

Abstract

Background/Aim: The aim of this retrospective study was to detect the frequency, reasons, and significant factors for not receiving immunotherapy after chemoradiotherapy in non-small cell lung cancer (NSCLC) patients. Patients and Methods: Thirty-four patients with NSCLC received definitive chemoradiotherapy. The endpoint of this study was receiving durvalumab within 45 days after chemoradiotherapy for NSCLC. Results: Twenty-five of 34 (73%) patients received immunotherapy within 45 days after chemoradiotherapy. The reasons for not receiving immunotherapy were radiation pneumonitis (50%), radiation esophagitis (10%), and four other reasons (40%). Univariate analysis showed that significant factors for not receiving immunotherapy were elective nodal irradiation (ENI)+ and chronic obstructive pulmonary disease (COPD)+. The rate of immunotherapy was 100% (17/17 cases) in the COPD− and ENI− group, and 16% (1/6 cases) in the COPD+ and ENI+ group. Conclusion: ENI for NSCLC complicated with COPD decreased the rate of immunotherapy after definitive chemoradiotherapy.

Key Words:
  • Volumetric modulated arc therapy (VMAT)
  • intensity modulated radiation therapy (IMRT)
  • involved field radiotherapy irradiation (IFR-IFI)
  • twice-daily thoracic radiotherapy (BID-TRT)
  • accelerated hyperfractionated thoracic radiotherapy (AHTRT)
  • anti-programmed cell death ligand-1 immune checkpoint inhibitor (ICIs)

The anti-programmed cell death ligand-1 immune checkpoint inhibitor, durvalumab, is a standard treatment for locally advanced non-small cell lung cancer (NSCLC) after chemoradiotherapy (1, 2). However, not all NSCLC patients can receive immunotherapy after chemoradiotherapy for various reasons. In clinical practice, reasons include adverse events from chemoradiotherapy, progressive disease, or other factors.

The characteristics of patients who cannot receive immunotherapy and the significant factors that are correlated with not receiving immunotherapy are not clear. The aim of this retrospective study was to detect the frequency, reasons, and significant factors for not receiving immunotherapy after chemoradiotherapy in NSCLC patients.

Patients and Methods

A total of 34 patients with NSCLC received definitive chemoradiotherapy between May 2018 and January 2019. Institutional review board approval was obtained for this study (number 19020). The patient characteristics and treatment factors are listed in Table I. The diagnosis of NSCLC was confirmed by histologic findings. The patients underwent the following pre-therapeutic procedures: a physical examination and chest radiography; fiberoptic bronchoscopy and endobronchial ultrasonography as needed; complete blood cell count and biochemical tests including tumor markers; electrocardiography; computed tomography (CT) imaging of the chest and abdomen; positron emission tomography/CT. A hematologic status, which included a white blood cell count >3,500/mm3, platelet count >100,000/mm3, and hemoglobin level >10 g/dl, was generally required. When febrile neutropenia or grade 3 non-hematologic adverse events excluding nausea, vomiting, appetite loss, and elevated creatinine or liver enzymes developed, radiotherapy was generally interrupted. Adverse events were evaluated using Common Terminology Criteria for Adverse Events, Version 4.0. Tumor staging was based on TMN classification 7th and 8th edition. The follow-up time was from the day radiotherapy or chemotherapy was started. Any death was counted as an event in the overall survival rate. Any deaths or progression, including distant metastases, were counted as an event in the progression-free survival rate. Any progression in the radiotherapy field was counted as an event in the local control rate. Isolated elective nodal failures (i.e., recurrences) were investigated in all thirty-four patients.

View this table:
  • View inline
  • View popup
  • Download powerpoint
Table I.

Patient characteristics and treatment factors.

Radiotherapy. Volumetric modulated arc therapy (VMAT) with mainly Dmean prescription was generally performed. All patients received four-dimensional or three-dimensional CT simulation. Clinical target volume (CTV) 1 was typically a 0.5-cm expansion of the gross tumor volume including the primary tumor and metastatic lymph nodes; planning target volume (PTV) 1 was then a 0.5-cm expansion of CTV1. Then, the radiation oncologist determined whether CTV2 should include elective hilar, mediastinal, or supraclavicular lymph nodes plus CTV1 based on the information of the patient, tumor, and treatment. This protocol is called elective nodal irradiation (ENI) and is intended to treat potential metastatic lymph nodes. The target of the elective nodal area was delineated based on the Japan Lung Cancer Society-Japanese Society for Radiation Oncology consensus-based computed tomographic atlas for defining regional lymph node stations in radiotherapy for lung cancer (3, 4). The total radiation dose of 60 Gy/30 fractions/6 weeks once daily was mainly administered to the patients. Alternatively, a more aggressive dose of 64 Gy/40 fractions/4 weeks twice daily (accelerated hyperfractionated thoracic radiotherapy) was given (5-7); in the morning, 2 Gy with or without ENI, and in the evening, 1.2 Gy with tumor boost radiotherapy were administered to other patients. ENI was performed for a median of 40 Gy/20 fractions/4 weeks. ENI was preferably adopted in good performance patients or patients in whom the tumor was located in the upper lobe, which requires a smaller lung dose compared to those with a primary location in the lower lobe.

Chemotherapy and immunotherapy. The chemotherapy regimen mainly consisted of cisplatin and vinorelbine or carboplatin and paclitaxel. Cisplatin (80 mg/m2) on day 1 combined with vinorelbine (20 mg/m2) on days 1 and 8 in 3- to 4-week intervals were delivered concurrently with radiotherapy. In patients aged >75 years or those with a low performance status, low renal function (creatinine clearance <60 ml/min), or other severe complications, the second choice for concurrent chemotherapy consisted of weekly carboplatin (area under the curve=2) plus paclitaxel (40 mg/m2), which were administered concurrently with radiotherapy. Another regimen, carboplatin (area under the curve=6) on day 1 combined with nab-paclitaxel (100 mg/m2) on days 1, 8, and 15 delivered concurrently with radiotherapy or pre-radiotherapy, was used. After chemoradiotherapy, durvalumab (10 mg/kg) every 2 weeks for up to 12 months was given if possible.

Statistical analysis. The endpoint of this study was that durvalumab was given to patients within 45 days after chemoradiotherapy. Although 42 days (6 weeks) was the longest interval between the end of chemoradiotherapy and start of durvalumab in a previous phase III study (1, 2), the one and a half-month (45 days) interval was adopted in this daily clinical practice study. Univariate logistic regression analyses were performed for 71 clinical and therapeutic factors. Then, selected factors were entered into the multivariate logistic regression analyses. However, the results of multivariate analyses are shown in Table II for reference only, because the sample size was 34 cases, and thus, results might be unstable. Statistical analyses were performed using SPSS, version 24.0 (IBM, Armonk, NY, USA). The 1-year overall survival, 1-year local control, and 1-year progression-free survival rates were estimated, and percentages were calculated with the Kaplan-Meier method.

View this table:
  • View inline
  • View popup
  • Download powerpoint
Table I.

Patient characteristics and treatment factors.

View this table:
  • View inline
  • View popup
  • Download powerpoint
Table II.

Univariate and multivariate logistic regression analyses for no use of durvalumab after definitive chemoradiotherapy in non-small cell lung cancer patients.

Results

The median follow-up time was 13 months (range=0-17 months). The 1-year overall survival rate was 89% (range=79-100%). The 1-year progression-free survival rate was 72% (range=56-87%). The 1-year local control rate was 76% (range=60-92%). No isolated elective nodal failures were found in all thirty-four patients.

Twenty-five of 34 (73%) patients received immunotherapy after a median of 8 days (range=1-45 days) from the end of chemoradiotherapy. The reasons for not receiving immunotherapy are shown in Table III. The most frequent reason for not receiving immunotherapy was radiation pneumonitis, which accounted for 50% (5/10 reasons). Adverse events including hematologic toxicities due to chemoradiotherapy are shown in Table IV. Radiation pneumonitis ≥Grade 2 and radiation esophagitis ≥Grade 2 were found in 32% (11/34 cases) and 11% (4/34 cases), respectively. The eight significant factors in univariate analysis that affected administration of immunotherapy are listed in Table V and are as follows: chronic obstructive pulmonary disease (COPD)+, ENI+, using inhaled medicine for COPD, forced expiratory volume in 1 second (FEV1), FEV1%, %FEV1, radiation pneumonitis ≥Grade 2, and radiation esophagitis ≥Grade 2. COPD was defined as FEV1% <70% in this study. Lung dose parameters including lung VS5Gy (cc) (absolute volume of the lung spared from 5 Gy) (8) were not significant factors. To avoid multicollinearity, COPD+, ENI+, and age, were included in the multivariate logistic regression analyses. Although age was not a significant factor in univariate analysis, age was important in clinical practice. After multivariate logistic regression analysis, two significant factors affecting immunotherapy were identified as COPD+ and ENI+ (for reference only; Table II). The actual rates of immunotherapy based on COPD (+ or −) or ENI (+ or −) are shown in Table VI. The rate of immunotherapy was 100% (17/17 cases) in the COPD− and ENI− group, and 16% (1/6 cases) in the COPD+ and ENI+ group. The choice of ENI area and the background of the patients are shown in Table VII. The comparison of lung dose parameters between the group that received durvalumab and the group that did not is shown in Table VIII. No significant differences were found in any of the average lung doses between the two groups.

View this table:
  • View inline
  • View popup
  • Download powerpoint
Table II.

Univariate and multivariate logistic regression analyses for no use of durvalumab after definitive chemoradiotherapy in non-small cell lung cancer patients.

View this table:
  • View inline
  • View popup
  • Download powerpoint
Table III.

Frequency and reasons for not receiving durvalumab within 45 days after chemoradiotherapy.

View this table:
  • View inline
  • View popup
  • Download powerpoint
Table IV.

Adverse events due to chemoradiotherapy.

View this table:
  • View inline
  • View popup
  • Download powerpoint
Table V.

Univariate logistic regression analyses for not receiving durvalumab after definitive chemoradiotherapy in thirty-four non-small cell lung cancer patients.

View this table:
  • View inline
  • View popup
  • Download powerpoint
Table V.

Univariate logistic regression analyses for not receiving durvalumab after definitive chemoradiotherapy in thirty-four non-small cell lung cancer patients.

View this table:
  • View inline
  • View popup
  • Download powerpoint
Table VI.

The rate of use of durvalumab with or without chronic obstructive pulmonary diseases (COPD), and with or without elective nodal irradiation (ENI) after definitive chemoradiotherapy in thirty-four non-small cell lung cancer patients.

View this table:
  • View inline
  • View popup
  • Download powerpoint
Table VII.

Choice of elective nodal irradiation area and background of twelve patients.

View this table:
  • View inline
  • View popup
  • Download powerpoint
Table VIII.

Comparison of dosimetric parameters of lung dose between group that used durvalumab and group that did not.

Five patients could not receive immunotherapy because of radiation pneumonitis. Four of these five patients with radiation pneumonitis received ENI. Therefore, for these four patients, the virtual radiation therapy planning was done without ENI (i.e., without PTV2) in order to prove the reduction of the lung dose parameters using their past radiation therapy planning CT with fusion of diagnostic CT images of emergence of their radiation pneumonitis. The radiation pneumonitis area on diagnostic CT with fusion on the radiation therapy planning CT was delineated, and a virtual radiation therapy plan without ENI was made. For all four patients, reduction of the dose in the radiation pneumonitis area, lung dose parameters, and esophagus dose parameters could be achieved by maintaining the effective dose to PTV1 (i.e., the primary tumor and metastatic lymph nodes) (Table IX).

View this table:
  • View inline
  • View popup
  • Download powerpoint
Table IX.

Comparison of dosimetric factors between virtual radiation therapy plans without elective nodal irradiation (ENI) and actual radiation therapy plans with ENI in the four radiation pneumonitis patients who could not receive durvalumab (N=4).

View this table:
  • View inline
  • View popup
  • Download powerpoint
Table IX.

Comparison of dosimetric factors between virtual radiation therapy plans without elective nodal irradiation (ENI) and actual radiation therapy plans with ENI in the four radiation pneumonitis patients who could not receive durvalumab (N=4).

Discussion

Although our study size was small, this study calculated the actual rate of immunotherapy, analyzed clinical and dosimetric factors, and demonstrated that ENI and COPD affected whether NSCLC patients did or did not receive immunotherapy after definitive chemoradiotherapy. Radiation pneumonitis was the most common reason for not receiving immunotherapy. Virtual radiation therapy plan without ENI in patients treated with ENI who could not receive immunotherapy because of their radiation pneumonitis, achieved a reduction in the dose parameters of the lung. The results showed the possibility of palliation for their radiation pneumonitis without ENI. Although the follow-up time was short, no isolated elective nodal failures were found in all patients in the current study.

ENI has not been recommended for NSCLC in the guidelines of the European Organization for Research and Treatment of Cancer (9). In the International Atomic Energy Agency report (10), the clinical value of ENI was uncertain. The clinical trial Radiation Therapy Oncology Group 0617 did not permit ENI (11). On the other hand, ENI was regarded as an alternative standard therapy for locally advanced lung cancer in the Japanese radiation therapy planning guideline in 2016 (12) when immunotherapy was not available after definitive chemoradiotherapy. Although ENI has been used traditionally (13), its effectiveness has not been established. Yuan et al. reported that high-dose involved field irradiation (IFI) achieves a better overall response rate (90% vs. 79%, p=0.032), better 5-year local control rate (51% vs. 36%, p=0.032), and better 2-year overall survival rate (39.4% vs. 25.6%, p=0.048) than low-dose ENI in a randomized trial of 200 patients (14). The radiation pneumonitis rate in the IFI group was also lower than that in the ENI group (17% vs. 29%, p=0.044). Topkan et al. reported that isolated elective nodal failures were present in 2.5% of the ENI group (21/844 cases) vs. 2.1% (3/143 cases) of the IFI group (15). They also reported that the overall survival rate (22.3 vs. 23.7 months, p=0.47), locoregional progression-free survival rate (12.6 vs. 13.2 months, p=0.58), and progression-free survival rate (10.7 vs. 10.4 months, p=0.82) were not significantly different between the two groups. In a meta-analysis, Li et al. reported no significant difference in the incidence of elective nodal failure between the IFI and ENI groups in three randomized controlled trials and three cohort studies (16). Schild et al. reported that ENI is associated with worse survival than IFI (median survival 16 vs. 24 months, p=0.002) in a pooled analysis of 16 cooperative group trials involving 3,600 patients (17).

Staging accuracy was achieved with positron emission tomography/CT and endobronchial ultrasonography. The progressed supportive care recommendation for NSCLC patients receiving chemoradiotherapy has been described (18). Radiotherapy technology was developed by four-dimensional CT, intensity modulated radiation therapy (IMRT), VMAT, and daily cone-beam CT. Although ENI compensates for the developing staging accuracy or radiation technology, omission of ENI for decreasing radiation-induced adverse events including pneumonitis is a reasonable idea for introducing immunotherapy after chemoradiotherapy in this era. Although the radiation oncologist should decrease the normal tissue dose including the dose to the lung and concentrate the effective dose on the gross tumor, they should remember which lymph nodes lung cancers tend to spread. This way of thinking may encourage another future study such as a study that includes post-operative radiotherapy.

Around 39-62% of lung cancer patients also have COPD (19, 20). In the current study, one-third of NSCLC patients had COPD, and most of them received an acting anti-muscarinic antagonist, acting beta agonist, or inhaled corticosteroid. COPD and radiation pneumonitis are inflammatory diseases caused mainly by smoking and radiation therapy, respectively. Using univariate analysis, Shi et al. reported that COPD was a significant factor (p<0.05) in 11 patients with severe acute radiation pneumonitis among 94 NSCLC patients treated with IMRT (21). Using multivariate analysis, Inoue et al. reported that COPD was a significant factor (p=0.002) in 44 patients with prolonged minimal radiation-induced pneumonitis after stereotactic body radiation therapy among 136 stage I lung cancer patients (22). Therefore, COPD might be a risk factor in relation to radiation pneumonitis. COPD should be treated along with lung cancer to minimize the influence of loss of normal lung function by chemoradiotherapy. Continuing medications such as an acting anti-muscarinic antagonist, acting beta agonist, or inhaled corticosteroid for COPD is important before and after chemoradiotherapy for NSCLC. Prohibiting smoking and vaccination against influenza and Streptococcus pneumoniae are also important (23).

Conclusion

ENI for NSCLC complicated with COPD decreased the rate of immunotherapy after definitive chemoradiotherapy. To increase the possibility of introducing immunotherapy, ENI should not be used for NSCLC complicated with COPD. Supportive care for NSCLC patients complicated with COPD should be done to minimize the loss of normal tissue function by chemoradiotherapy.

Acknowledgements

This study was supported by JSPS KAKENHI Grant Number 18K15616. The Authors deeply appreciate the investigator Toshiki Ikawa M.D. (Department of Radiation Oncology, Osaka International Cancer Institute, Osaka, Japan) who contributed to this study.

Footnotes

  • Authors’ Contributions

    Conception and design: M Morimoto, and K Nishino. Acquisition of data: M Morimoto, K Nishino, K Wada, F Imamura, K Konishi, H Kuhara, M Tamiya, T Inoue, K Kunimasa, M Kimura, T Hirata, N Kanayama, M Toratani, H Kawachi, K Ohira, E Nakanishi, S Ohira, T Sagawa, M Miyazaki, T Kumagai, and T Teshima. Analysis and interpretation of data: M Morimoto, K Nishino, K Wada, F Imamura, K Konishi, H Kuhara, M Tamiya, T Inoue, K Kunimasa, M Kimura, T Hirata, N Kanayama, M Toratani, H Kawachi, K Ohira, E Nakanishi, S Ohira, T Sagawa, M Miyazaki, T Matsunaga (statistician), T Kumagai, and T Teshima. Writing, review, and/or revision of the manuscript: M Morimoto, K Nishino, K Wada, and K Kunimasa.

  • This article is freely accessible online.

  • Conflicts of Interest

    K Nishino had honoraria from Nippon Boehringer Ingelheim Co., Ltd., AstraZeneca K.K., Novartis Pharma K.K., Eli Lilly Japan K.K., Roche Diagnostics K.K., Chugai Pharma, and ONO PHARMACEUTICAL CO., LTD. K Nishino had research funding from Nippon Boehringer Ingelheim Co., Ltd. F Imamura had research funding from AstraZeneca. T Kumagai received a grant from Ono Pharmaceutical., MSD K.K., Chugai Pharmaceutical Co. Ltd., AstraZeneca K.K., Takeda Pharmaceutical Company Limited., Merck Serono Co., Ltd., Pfizer Japan Inc., Taiho Pharmaceutical Co.,Ltd., Nippon Boehringer Ingelheim Co., Ltd., Eli Lilly Japan K.K., Novartis Pharma K.K., and The Osaka Foundation for The Prevention of Cancer and Life-style related Diseases (Public Interest Incorporated Foundation). T Kumagai received personal fee from Ono Pharmaceutical., AstraZeneca K. K., Taiho Pharmaceutical Co. Ltd., MSD K.K., TEIJIN PHARMA LIMITED, Novartis Pharma K.K., Nippon Boehringer Ingelheim Co., Ltd., Eli Lilly Japan K.K., Pfizer Inc., Chugai Pharmaceutical Co. Ltd., Bristol-Myers Squibb K.K., and Takeda Pharmaceutical Company Limited.

  • Received October 3, 2020.
  • Revision received October 8, 2020.
  • Accepted October 9, 2020.
  • Copyright © 2020 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

References

  1. ↵
    1. Antonia SJ,
    2. Villegas A,
    3. Daniel D,
    4. Vicente D,
    5. Murakami S,
    6. Hui R,
    7. Yokoi T,
    8. Chiappori A,
    9. Lee KH,
    10. de Wit M,
    11. Cho BC,
    12. Bourhaba M,
    13. Quantin X,
    14. Tokito T,
    15. Mekhail T,
    16. Planchard D,
    17. Kim YC,
    18. Karapetis CS,
    19. Hiret S,
    20. Ostoros G,
    21. Kubota K,
    22. Gray JE,
    23. Paz-Ares L,
    24. de Castro Carpeño J,
    25. Wadsworth C,
    26. Melillo G,
    27. Jiang H,
    28. Huang Y,
    29. Dennis PA and
    30. Özgüroğlu M
    : Durvalumab after chemoradiotherapy in stage III non-small-cell lung cancer. N Engl J Med 377: 1919-1929, 2017. PMID: 28885881. DOI: 10.1056/NEJMoa1709937
    OpenUrlCrossRefPubMed
  2. ↵
    1. Antonia SJ,
    2. Villegas A,
    3. Daniel D,
    4. Vicente D,
    5. Murakami S,
    6. Hui R,
    7. Kurata T,
    8. Chiappori A,
    9. Lee KH,
    10. de Wit M,
    11. Cho BC,
    12. Bourhaba M,
    13. Quantin X,
    14. Tokito T,
    15. Mekhail T,
    16. Planchard D,
    17. Kim YC,
    18. Karapetis CS,
    19. Hiret S,
    20. Ostoros G,
    21. Kubota K,
    22. Gray JE,
    23. Paz-Ares L,
    24. de Castro Carpeño J,
    25. Faivre-Finn C,
    26. Reck M,
    27. Vansteenkiste J,
    28. Spigel DR,
    29. Wadsworth C,
    30. Melillo G,
    31. Taboada M,
    32. Dennis PA and
    33. Özgüroğlu M
    : Overall survival with durvalumab after chemoradiotherapy in stage III NSCLC. N Engl J Med 379: 2342-2350, 2018. PMID: 30280658. DOI: 10.1056/NEJMoa1809697
    OpenUrlCrossRefPubMed
  3. ↵
    1. Itazawa T,
    2. Tamaki Y,
    3. Komiyama T,
    4. Nishimura Y,
    5. Nakayama Y,
    6. Ito H,
    7. Ohde Y,
    8. Kusumoto M,
    9. Sakai S,
    10. Suzuki K,
    11. Watanabe H and
    12. Asamura H
    : The Japan Lung Cancer Society-Japanese Society for Radiation Oncology consensus-based computed tomographic atlas for defining regional lymph node stations in radiotherapy for lung cancer. J Radiat Res 58: 86-105, 2017. PMID: 27609192. DOI: 10.1093/jrr/rrw076
    OpenUrlCrossRefPubMed
  4. ↵
    1. The JLCS – JASTRO joint committee for developing an atlas of the regional lymph node stations in radiotherapy treatment planning for lung cancer,
    2. Komiyama T,
    3. Itazawa T,
    4. Tamaki Y,
    5. Nisimura Y,
    6. Nakayama Y,
    7. Ito H,
    8. Ohde Y,
    9. Kusumoto M,
    10. Sakai S,
    11. Suzuki K,
    12. Watanabe H and
    13. Asamura H
    : A consensus-based computed tomographic atlas for defining the regional lymph node stations in radiotherapy for lung cancer (in Japanese). Haigan 55: 189-205, 2015.
    OpenUrl
  5. ↵
    1. Imamura F,
    2. Konishi K,
    3. Uchida J,
    4. Nishino K,
    5. Okuyama T,
    6. Kumagai T,
    7. Kawaguchi Y and
    8. Nishiyama K
    : Novel chemoradiotherapy with concomitant boost thoracic radiation and concurrent cisplatin and vinorelbine for stage IIIA and IIIB non-small-cell lung cancer. Clin Lung Cancer 15: 281-286, 2014. PMID: 24656641. DOI: 10.1016/j.cllc.2014.02.001
    OpenUrlCrossRef
    1. Wada K,
    2. Kishi N,
    3. Kanayama N,
    4. Hirata T,
    5. Morimoto M,
    6. Konishi K,
    7. Imamura F,
    8. Teshima T and
    9. Ogawa K
    : Radiation dose escalation in accelerated hyperfractionated radiotherapy for stage III non-small-cell lung cancer. Anticancer Res 38: 5951-5958, 2018. PMID: 30275224. DOI: 10.21873/anticanres.12941
    OpenUrlAbstract/FREE Full Text
  6. ↵
    1. Wada K,
    2. Kishi N,
    3. Kanayama N,
    4. Hirata T,
    5. Ueda Y,
    6. Kawaguchi Y,
    7. Morimoto M,
    8. Konishi K,
    9. Imamura F,
    10. Ogawa K and
    11. Teshima T
    : Predictors of acute radiation esophagitis in non-small cell lung cancer patients treated with accelerated hyperfractionated chemoradiotherapy. Anticancer Res 39: 491-497, 2019. PMID: 30591500. DOI: 10.21873/anticanres.13139
    OpenUrlAbstract/FREE Full Text
  7. ↵
    1. Tsujino K,
    2. Hashimoto T,
    3. Shimada T,
    4. Yoden E,
    5. Fujii O,
    6. Ota Y,
    7. Satouchi M,
    8. Negoro S,
    9. Adachi S and
    10. Soejima T
    : Combined analysis of V20, VS5, pulmonary fibrosis score on baseline computed tomography, and patient age improves prediction of severe radiation pneumonitis after concurrent chemoradiotherapy for locally advanced non-small-cell lung cancer. J Thorac Oncol 9: 983-990, 2014. PMID: 24922010. DOI: 10.1097/JTO.0000000000000187
    OpenUrlCrossRef
  8. ↵
    1. De Ruysscher D,
    2. Faivre-Finn C,
    3. Moeller D,
    4. Nestle U,
    5. Hurkmans CW,
    6. Le Péchoux C,
    7. Belderbos J,
    8. Guckenberger M and
    9. Senan S
    : European Organization for Research and Treatment of Cancer (EORTC) recommendations for planning and delivery of high-dose, high precision radiotherapy for lung cancer. Radiother Oncol 124: 1-10, 2017. PMID: 28666551. DOI: 10.1016/j.radonc.2017.06.003
    OpenUrlCrossRefPubMed
  9. ↵
    1. Belderbos JS,
    2. Kepka L,
    3. Spring Kong FM,
    4. Martel MK,
    5. Videtic GM and
    6. Jeremic B
    : Report from the International Atomic Energy Agency (IAEA) consultants’ meeting on elective nodal irradiation in lung cancer: non-small-cell lung cancer (NSCLC). Int J Radiat Oncol Biol Phys 72: 335-342, 2008. PMID: 18793953. DOI: 10.1016/j.ijrobp.2008.04.081
    OpenUrlCrossRefPubMed
  10. ↵
    1. Bradley JD,
    2. Paulus R,
    3. Komaki R,
    4. Masters G,
    5. Blumenschein G,
    6. Schild S,
    7. Bogart J,
    8. Hu C,
    9. Forster K,
    10. Magliocco A,
    11. Kavadi V,
    12. Garces YI,
    13. Narayan S,
    14. Iyengar P,
    15. Robinson C,
    16. Wynn RB,
    17. Koprowski C,
    18. Meng J,
    19. Beitler J,
    20. Gaur R,
    21. Curran W Jr.. and
    22. Choy H
    : Standard-dose versus high-dose conformal radiotherapy with concurrent and consolidation carboplatin plus paclitaxel with or without cetuximab for patients with stage IIIA or IIIB non-small-cell lung cancer (RTOG 0617): a randomised, two-by-two factorial phase 3 study. Lancet Oncol 16: 187-199, 2015. PMID: 25601342. DOI: 10.1016/S1470-2045(14)71207-0
    OpenUrlCrossRefPubMed
  11. ↵
    1. Japanese Society for Radiation Oncology
    : Radiation therapy planning guideline 2016 edition. Tokyo: Kanahara Co., Ltd., 2016.
  12. ↵
    1. Perez CA,
    2. Stanley K,
    3. Grundy G,
    4. Hanson W,
    5. Rubin P,
    6. Kramer S,
    7. Brady LW,
    8. Marks JE,
    9. Perez-Tamayo R,
    10. Brown GS,
    11. Concannon JP and
    12. Rotman M
    : Impact of irradiation technique and tumor extent in tumor control and survival of patients with unresectable non-oat cell carcinoma of the lung: report by the Radiation Therapy Oncology Group. Cancer 50: 1091-1099, 1982. PMID: 6286087. DOI: 10.1002/1097-0142(19820915)50:6<1091::aid-cncr2820500612>3.0.co;2-0
    OpenUrlCrossRefPubMed
  13. ↵
    1. Yuan S,
    2. Sun X,
    3. Li M,
    4. Yu J,
    5. Ren R,
    6. Yu Y,
    7. Li J,
    8. Liu X,
    9. Wang R,
    10. Li B,
    11. Kong L and
    12. Yin Y
    : A randomized study of involved-field irradiation versus elective nodal irradiation in combination with concurrent chemotherapy for inoperable stage III nonsmall cell lung cancer. Am J Clin Oncol 30: 239-244, 2007. PMID: 17551299. DOI: 10.1097/01.coc.0000256691.27796.24
    OpenUrlCrossRefPubMed
  14. ↵
    1. Topkan E,
    2. Guler OC and
    3. Yildirim BA
    : Omission of elective nodal irradiation has no impact on isolated elective nodal failure and survival outcomes in stage III non-small-cell lung cancer patients treated with definitive concurrent chemoradiotherapy. Ann Oncol 26: i24, 2015. DOI: https://doi.org/10.1093/annonc/mdv049.08
    OpenUrlCrossRef
  15. ↵
    1. Li R,
    2. Yu L,
    3. Lin S,
    4. Wang L,
    5. Dong X,
    6. Yu L,
    7. Li W and
    8. Li B
    : Involved field radiotherapy (IFRT) versus elective nodal irradiation (ENI) for locally advanced non-small cell lung cancer: a meta-analysis of incidence of elective nodal failure (ENF). Radiat Oncol 11: 124, 2016. PMID: 27655339. DOI: 10.1186/s13014-016-0698-3
    OpenUrlCrossRef
  16. ↵
    1. Schild SE,
    2. Pang HH,
    3. Fan W,
    4. Stinchcombe TE,
    5. Vokes EE,
    6. Ramalingam SS,
    7. Bradley JD,
    8. Kelly K and
    9. Wang X
    : Exploring radiotherapy targeting strategy and dose: A pooled analysis of cooperative group trials of combined modality therapy for stage III NSCLC. J Thorac Oncol 13: 1171-1182, 2018. PMID: 29689435. DOI: 10.1016/j.jtho.2018.04.011
    OpenUrlCrossRef
  17. ↵
    1. De Ruysscher D,
    2. Faivre-Finn C,
    3. Nackaerts K,
    4. Jordan K,
    5. Arends J,
    6. Douillard JY,
    7. Ricardi U and
    8. Peters S
    : Recommendation for supportive care in patients receiving concurrent chemotherapy and radiotherapy for lung cancer. Ann Oncol 31: 41-49, 2020. PMID: 31912794. DOI: 10.1016/j.annonc.2019.10.003
    OpenUrlCrossRef
  18. ↵
    1. Abal Arca J,
    2. Parente Lamelas I,
    3. Almazán Ortega R,
    4. Blanco Pérez J,
    5. Toubes Navarro ME and
    6. Marcos Velázquez P
    : Cáncer de pulmón y EPOC: una asociación frecuente [Lung cancer and COPD: a common combination] (in Spanish, abstract). Arch Bronconeumol 45: 502-507, 2009. PMID: 19748721. DOI: 10.1016/j.arbres.2009.07.005
    OpenUrlCrossRefPubMed
  19. ↵
    1. Loganathan RS,
    2. Stover DE,
    3. Shi W and
    4. Venkatraman E
    : Prevalence of COPD in women compared to men around the time of diagnosis of primary lung cancer. Chest 129: 1305-1312, 2006. PMID: 16685023. DOI: 10.1378/chest.129.5.1305
    OpenUrlCrossRefPubMed
  20. ↵
    1. Shi A,
    2. Zhu G,
    3. Wu H,
    4. Yu R,
    5. Li F and
    6. Xu B
    : Analysis of clinical and dosimetric factors associated with severe acute radiation pneumonitis in patients with locally advanced non-small cell lung cancer treated with concurrent chemotherapy and intensity-modulated radiotherapy. Radiat Oncol 5: 35, 2010. PMID: 20462424. DOI: 10.1186/1748-717X-5-35
    OpenUrlCrossRefPubMed
  21. ↵
    1. Inoue T,
    2. Shiomi H and
    3. Oh RJ.
    Stereotactic body radiotherapy for Stage I lung cancer with chronic obstructive pulmonary disease: special reference to survival and radiation-induced pneumonitis. J Radiat Res 56: 727-734, 2015. PMID: 25887042. DOI: 10.1093/jrr/rrv019
    OpenUrlCrossRefPubMed
  22. ↵
    1. The Japanese Respiratory Society
    : The JRS Guidelines for the Management of Chronic Obstructive Pulmonary Disease 5th edition. Tokyo: Medical Review Co., Ltd., 2018.
PreviousNext
Back to top

In this issue

Anticancer Research: 40 (12)
Anticancer Research
Vol. 40, Issue 12
December 2020
  • Table of Contents
  • Table of Contents (PDF)
  • Index by author
  • Back Matter (PDF)
  • Ed Board (PDF)
  • Front Matter (PDF)
Print
Download PDF
Article Alerts
Sign In to Email Alerts with your Email Address
Email Article

Thank you for your interest in spreading the word on Anticancer Research.

NOTE: We only request your email address so that the person you are recommending the page to knows that you wanted them to see it, and that it is not junk mail. We do not capture any email address.

Enter multiple addresses on separate lines or separate them with commas.
Elective Nodal Irradiation for Non-small Cell Lung Cancer Complicated With Chronic Obstructive Pulmonary Disease Affects Immunotherapy Αfter Definitive Chemoradiotherapy
(Your Name) has sent you a message from Anticancer Research
(Your Name) thought you would like to see the Anticancer Research web site.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
7 + 0 =
Solve this simple math problem and enter the result. E.g. for 1+3, enter 4.
Citation Tools
Elective Nodal Irradiation for Non-small Cell Lung Cancer Complicated With Chronic Obstructive Pulmonary Disease Affects Immunotherapy Αfter Definitive Chemoradiotherapy
MASAHIRO MORIMOTO, KAZUMI NISHINO, KENTARO WADA, FUMIO IMAMURA, KOJI KONISHI, HANAKO KUHARA, MOTOHIRO TAMIYA, TAKAKO INOUE, KEI KUNIMASA, MADOKA KIMURA, TAKERO HIRATA, NAOYUKI KANAYAMA, MASAYASU TORATANI, HAYATO KAWACHI, KIKA OHIRA, ERINA NAKANISHI, SHINGO OHIRA, TOMOHIRO SAGAWA, MASAYOSHI MIYAZAKI, TAKASHI MATSUNAGA, TORU KUMAGAI, TERUKI TESHIMA
Anticancer Research Dec 2020, 40 (12) 6957-6970; DOI: 10.21873/anticanres.14720

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
Reprints and Permissions
Share
Elective Nodal Irradiation for Non-small Cell Lung Cancer Complicated With Chronic Obstructive Pulmonary Disease Affects Immunotherapy Αfter Definitive Chemoradiotherapy
MASAHIRO MORIMOTO, KAZUMI NISHINO, KENTARO WADA, FUMIO IMAMURA, KOJI KONISHI, HANAKO KUHARA, MOTOHIRO TAMIYA, TAKAKO INOUE, KEI KUNIMASA, MADOKA KIMURA, TAKERO HIRATA, NAOYUKI KANAYAMA, MASAYASU TORATANI, HAYATO KAWACHI, KIKA OHIRA, ERINA NAKANISHI, SHINGO OHIRA, TOMOHIRO SAGAWA, MASAYOSHI MIYAZAKI, TAKASHI MATSUNAGA, TORU KUMAGAI, TERUKI TESHIMA
Anticancer Research Dec 2020, 40 (12) 6957-6970; DOI: 10.21873/anticanres.14720
Twitter logo Facebook logo Mendeley logo
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Jump to section

  • Article
    • Abstract
    • Patients and Methods
    • Results
    • Discussion
    • Conclusion
    • Acknowledgements
    • Footnotes
    • References
  • Figures & Data
  • Info & Metrics
  • PDF

Related Articles

  • No related articles found.
  • PubMed
  • Google Scholar

Cited By...

  • Impact of Chronic Obstructive Pulmonary Disease on the Long-term Prognosis of Patients Undergoing Lobectomy for Non-small-cell Lung Cancer: A Propensity Score-matched Analysis
  • Sleep Disturbances in Lung Cancer Patients Assigned to Definitive or Adjuvant Irradiation
  • Google Scholar

More in this TOC Section

  • Assessment of Breakthrough Cancer Pain Among Female Patients With Cancer: Knowledge, Management and Characterization in the IOPS-MS Study
  • Low-dose Apalutamide in Non-metastatic Castration-resistant Prostate Cancer: A Case Series
  • Bone Toxicity Case Report Combining Encorafenib, Cetuximab and WNT974 in a Phase I Trial
Show more Clinical Studies

Similar Articles

Keywords

  • Volumetric modulated arc therapy (VMAT)
  • intensity modulated radiation therapy (IMRT)
  • involved field radiotherapy irradiation (IFR-IFI)
  • twice-daily thoracic radiotherapy (BID-TRT)
  • accelerated hyperfractionated thoracic radiotherapy (AHTRT)
  • anti-programmed cell death ligand-1 immune checkpoint inhibitor (ICIs)
Anticancer Research

© 2025 Anticancer Research

Powered by HighWire