Research ArticleClinical Studies
Open Access

Comparison of the Efficacy and Toxicity of Concurrent Chemoradiotherapy and Durvalumab and Concurrent Chemoradiotherapy Alone for Locally Advanced Non-small Cell Lung Cancer With N3 Lymph Node Metastasis

TAKANORI ABE, MISAKI IINO, SATOSHI SAITO, TOMOMI AOSHIKA, YASUHIRO RYUNO, TOMOHIRO OHTA, MITSUNOBU IGARI, RYUTA HIRAI, YU KUMAZAKI, YU MIURA, KYOICHI KAIRA, HIROSHI KAGAMU, SHIN-EI NODA and SHINGO KATO
Anticancer Research February 2023, 43 (2) 675-682; DOI: https://doi.org/10.21873/anticanres.16205

Abstract

Background/Aim: Efficacy and toxicity of concurrent chemoradiotherapy (CCRT) and durvalumab for locally advanced non-small cell lung cancer (LA-NSCLC) with N3 lymph node metastasis remain unclear. We aimed to evaluate the clinical outcomes of patients who received CCRT and durvalumab (durvalumab cohort) and compare their outcomes with those of patients who received CCRT alone (CCRT-alone cohort). Patients and Methods: The data of patients who had received treatment between November 2008 and February 2022 and were followed up for at least 3 months were retrospectively analyzed. Local control, progression-free survival, and overall survival were evaluated using Kaplan–Meier analysis and compared using the log-rank test. Toxicity was evaluated using the Common Terminology Criteria for Adverse Events version 5.0. Results: The data of 29 patients were analyzed (median follow-up period: 22 months). Among them, 17 received CCRT alone and 12 received CCRT and durvalumab. There were 14 patients with stage IIIB and 15 with stage IIIC LA-NSCLC. The durvalumab cohort (89%) had a significantly higher 1-year local control rate than the CCRT-alone cohort (47%; p=0.035). No significant difference was observed in either progression-free or overall survival between the two cohorts. Grade ≥2 pneumonitis was observed in 6 (50%) and 7 (41%) patients in the durvalumab and CCRT-alone cohorts, respectively. Conclusion: CCRT with durvalumab may be effective against LA-NSCLC with N3 lymph node metastasis. The incidence of grade 2 pneumonitis was slightly higher in the durvalumab cohort than in the CCRT-alone cohort, suggesting the need for careful patient monitoring after treatment.

Key Words:

Lung cancer remains a major cause of cancer death worldwide (1). Non-small cell lung cancer (NSCLC) is a major histological type of lung cancer; concurrent chemoradiotherapy (CCRT) is one of the standard treatments for locally advanced NSCLC (LA-NSCLC) (2, 3). Despite the diagnosis of a “locally advanced” disease, the extent of disease may vary widely among patients. N3 lymph node metastasis is defined as metastasis at the supraclavicular and/or contralateral media sternum nodes.

Patients with N3 lymph node metastasis show worse prognosis than those with N0-1 metastasis because of the wide spread of the disease and higher risk of distant metastasis (4). Oh et al. evaluated the outcomes of CCRT in patients with NSCLC with N3 lymph node metastasis and reported a 2-year overall survival (OS) of 57.3% and progression-free survival (PFS) of 24.1%, with an 8% incidence of grade ≥3 pneumonitis (5). Noh et al. also reported a 2-year OS and PFS of 75.2% and 38.7%, respectively, with a 30% incidence of grade ≥2 pneumonitis after CCRT in patients with NSCLC with N3 lymph node metastasis (6). Recently, the PACIFIC trial, which included patients with N3 lymph node metastasis, revealed that durvalumab improves PFS and OS after CCRT for stage III NSCLC (7). However, the trial provided no detailed information on the efficacy and toxicity of durvalumab in these patients. Consolidative durvalumab therapy may benefit these patients by suppressing disease progression. However, a concern associated with the use of CCRT and durvalumab to treat patients with NSCLC with N3 lymph node metastasis is treatment-related toxicity because these patients tend to show poor performance status because of pre-existing symptoms caused by the higher disease extent. Furthermore, the incidence of pneumonitis following the PACIFIC regimen might be higher in Asian populations (8-15). In light of the abovementioned background, the risks and benefits of the aforementioned therapy should be carefully considered before indicating CCRT followed by durvalumab for patients with LA-NSCLC with N3 lymph node metastasis, particularly among Asians. However, to the best of our knowledge, no data are available in the literature regarding the efficacy and toxicity of the PACIFIC regimen for these patients. Therefore, the present study sought to evaluate the efficacy and toxicity of CCRT and durvalumab and compare these findings with those of CCRT alone in Asian patients with NSCLC with N3 lymph node metastasis.

Patients and Methods

Patients. We retrospectively analyzed the data of patients with LA-NSCLC with N3 lymph node metastasis who had received treatment at our hospital. The study was approved by Saitama Medical University Institutional Review Board (Reference number: 20-167). All analyses were performed in accordance with the Declaration of Helsinki; written informed consent was obtained from all patients included herein. All tumors were diagnosed histologically via bronchoscopy or computed tomography (CT)-guided needle biopsy. Tumors were classified based on the TNM classification of malignant tumors (eighth edition) and findings obtained using multimodality diagnostic imaging tools such as CT, brain magnetic resonance imaging, and fluorodeoxyglucose positron emission tomography (FDG-PET). Lymph node metastasis was diagnosed as nodes >1 cm (short-axis measurement) or those with abnormal standardized uptake values of ≥2.5 on FDG-PET/CT. Contralateral hilar lymph node metastasis was regarded as contraindication for definitive RT at our hospital.

Treatment.

Radiotherapy. Patients included earlier in the study period received three-dimensional conformal radiotherapy (3D-CRT), whereas the others received volumetric arc modulated radiotherapy (VMAT). 3D-CRT was performed using a linear accelerator (Clinac iX, Varian Medical Systems, Palo Alto, CA, USA), whereas VMAT was performed using another linear accelerator (Trilogy, Varian Medical Systems). CT image thickness for both 3D-CRT and VMAT was 2.5 mm. For 3D-CRT, CT images obtained at both the expiratory and inspiratory phases were acquired, with the former being used for dose calculation. CT images at the inspiratory phase were fused with those at the expiratory phase via bony structure matching; afterward, the internal gross tumor volume (IGTV) was contoured encompassing the primary tumor and metastatic lymph node at both the inspiratory and expiratory phases. The clinical target volume (CTV) consisted of the volume including a 5-mm margin across all directions from the IGTV and the prophylactic lymph node area, including the nodal station where lymph node metastasis was noted. For the planning target volume (PTV) margin, 5 mm was added to the CTV. In case of exceeding dose constraints for organs at risk, we cut PTV from the irradiated field to satisfy constraints. Treatment planning for 3D-CRT was performed using XiO (Elekta AB, Stockholm, Sweden). Treatment planning for VMAT involved acquiring CT images for dose calculation using the breath-hold technique at the mid-respiratory phase. Four-dimensional CT was also performed to evaluate tumor respiratory motion. The internal gross tumor volume (IGTV) was defined based on the maximum intensity projection method using four-dimensional CT images. A CTV margin of 0-5 mm to encompass microscopic tumor extension was added to the IGTV including primary tumor and metastatic lymph node. For the PTV margin, 5 mm was added to the CTV. With VMAT, prophylactic irradiation of the regional lymph node areas was not performed in all patients. Two arcs and a rotation angle of gantry that avoided the contralateral lung were used. The aim of planning was to cover 95% of the PTV with 60 Gy. Treatment planning for VMAT was performed using Eclipse (Varian Medical Systems). Dose constraints for at-risk organs were as follows: >5 Gy to <60% of the lung volume, >20 Gy to <35% of the lung volume, maximum dose to the spinal cord >50 Gy, >50 Gy to <25% of the heart volume, and >60 Gy to <17% of the esophageal volume. Furthermore, the following were calculated and recorded: volume of the lungs receiving >30 Gy (lung V30), >40 Gy (lung V40), >50 Gy (lung V50), and >60 Gy (lung V60); volume of the esophagus receiving >40 Gy (esophagus V40), >50 Gy (esophagus V50), and >60 Gy (esophagus V60); volume of the heart receiving >40 Gy (heart V40), >50 Gy (heart V50), and >60 Gy (heart V60); and the mean lung dose (MLD), mean esophagus dose (MSD), and mean heart dose (MHD).

Chemotherapy. All patients received platinum-based concurrent chemotherapy with one of the following regimens: carboplatin plus paclitaxel, daily carboplatin, or cisplatin plus TS-1; the regimen was selected by their respiratory medicine physicians. During CCRT, the patients were evaluated weekly via physical examination, blood tests, and chest radiography.

Durvalumab. The condition and organ function of the patients who received durvalumab were carefully assessed before initiating treatment. CT was performed before durvalumab administration to check for pneumonitis and disease progression. Toxicity was classified using the National Cancer Institute Common Toxicity Criteria for Adverse Events, version 5.0. Durvalumab was administered bi-weekly until the development of grade ≥2 toxicity or completion of 24 cycles of administration. Blood tests and chest radiography were routinely performed at every hospital visit for durvalumab administration. Any suspicion of pneumonitis or disease progression prompted chest CT and any other indicated investigations.

Treatment efficacy evaluation. After the completion or cancellation of durvalumab therapy or completion of CCRT, the patients were continuously followed up with blood test, chest CT, and FDG-PET/CT to check for disease progression, including local recurrence and distant metastasis. In this study, local recurrence was defined as any recurrence at the irradiated field and disease progression at any other site was defined as distant metastasis. PFS was defined as being free from local recurrence, distant metastasis, or death. OS was defined as the duration between treatment initiation and death or last follow-up.

Statistical analysis. Cumulative local control (LC), PFS, and OS rates were calculated using Kaplan–Meier analysis and compared between the two cohorts mentioned below using the log-rank test. The median and mean values of both cohorts were compared using Mann–Whitney U and Student’s t-tests, respectively. p<0.05 was considered to denote a significant difference. All statistical analyses were performed using IBM SPSS Statistics for Windows, version 25.0 (IBM Corp., Armonk, NY, USA).

Results

Patient and tumor characteristics. This study included a total of 29 patients who received treatment between November 2008 and February 2022 and were followed up for at least 3 months. VMAT has been used since 2019 at our hospital. Among the patients, 17 received CCRT alone (CCRT-alone cohort) and 12 received CCRT followed by durvalumab (durvalumab cohort). The CCRT-alone cohort comprised 15 men and 2 women (median age: 68 years). Their median follow up period was 22 months (range=3-89 months). There were nine patients with stage IIIB and eight with stage IIIC LA-NSCLC. The total dose of radiotherapy was 54 Gy in 1 patient, 60 Gy in 11 patients, and >60 Gy in 5 patients. The durvalumab cohort comprised eight men and four women (median age, 70 years). Their median follow up period was 14 months (3-37 months). There were five patients with stage IIIA and seven with stage IIIC LA-NSCLC. The total dose of radiotherapy was 60 Gy for all patients. These characteristics are summarized in Table I. The median number of durvalumab cycles was seven. Among the 12 patients who received durvalumab, five discontinued durvalumab because of radiation pneumonitis (three patients) and disease progression (two patients).

View this table:
Table I.

Patient characteristics (n=29).

Dose–volume parameters of radiotherapy. In the CCRT-alone cohort, mean lung volumes were V5, V20, V30, V40, V50, and V60 and MLDs were 34.5%, 21.2%, 16.7%, 13.6%, 10.1%, and 4.7%, respectively (11.9 Gy). The mean esophagus volumes were V40, V50, and V60 and MSDs were 33.3%, 22.8%, and 8.7%, respectively (22.9 Gy). The mean heart volumes were V40, V50, and V60 and MHDs were 3.7%, 2.0%, and 0.3%, respectively (4.9 Gy).

In the durvalumab cohort, the mean lung volumes were V5, V20, V30, V40, V50, and V60 and MLDs were 47.1%, 21.3%, 14.9%, 10.6%, 6.6%, and 1.9%, respectively (12.3 Gy). The mean esophagus volumes were V40, V50, and V60 and MSDs were 18.8%, 12.6%, and 7.8%, respectively (18.4 Gy). The mean heart volumes were V40, V50, and V60 and MHDs were 11.9%, 8.8%, and 2.8%, respectively (11.5 Gy). These data are summarized in Table II. PTV D95 was 100% and 55.0% in patients who received VMAT and 3D-CRT, respectively (p<0.001).

View this table:
Table II.

Dose–volume parameters of radiotherapy (n=29).

Treatment efficacy. The 1-year LC rate was 89% and 47% in the durvalumab and CCRT-alone cohorts, respectively (p=0.035; Figure 1). The 1-year PFS rate was 53% and 38% in the durvalumab and CCRT-alone cohorts, respectively (p=0.627; Figure 2). The 1-year OS rate was 88% and 79% in the durvalumab and CCRT-alone cohorts, respectively (p=0.934; Figure 3).

Figure 1.
Figure 1.

Cumulative local control rate. The solid line represents the durvalumab cohort, whereas the dashed line represents the concurrent chemoradiotherapy (CCRT)-alone cohort. The 1-year local control rate was 89% in the durvalumab cohort and 47% in the CCRT-alone cohort (p=0.035).

Figure 2.
Figure 2.

Cumulative progression-free survival rate. The solid line represents the durvalumab cohort, whereas the dashed line represents the concurrent chemoradiotherapy (CCRT)-alone cohort. The 1-year progression-free survival rate was 53% in the durvalumab cohort and 38% in the CCRT-alone cohort (p=0.634).

Figure 3.
Figure 3.

Cumulative overall survival rate. The solid line represents the durvalumab cohort, whereas the dashed line represents the concurrent chemoradiotherapy (CCRT)-alone cohort. The 1-year overall survival rate was 88% in the durvalumab cohort and 79% in the CCRT-alone cohort (p=0.934).

Treatment failure patterns. In the CCRT-alone cohort, seven patients developed distant metastases, nine developed local recurrence, and seven died of the disease by the last follow-up. In the durvalumab cohort, six patients developed distant metastasis, one developed local recurrence, and three died of the disease.

Toxicity. In the CCRT-alone cohort, over a median follow-up duration of 22 months (range=3-89 months), grades 1, 2, and 3 pneumonitis were diagnosed in 10 patients (59%), 6 patients (35%), and 1 patient (6%), respectively. None of the patients developed grade 4 or 5 pneumonitis. Grade ≥2 esophagitis was observed in six patients. In the durvalumab cohort, over a median follow-up of 14 months (3-37 months), grades 1 and 2 pneumonitis were diagnosed in 6 (50%) and 6 (50%) patients, respectively. None of the patients developed grade ≥3 pneumonitis. Grade ≥2 esophagitis was observed in one patient.

Discussion

The present study determined the efficacy and toxicity of CCRT and durvalumab for N3 LA-NSCLC and compared them with those of CCRT alone. The 1-year LC, PFS, and OS rates were 89%, 53%, and 88%, respectively, (median follow-up period: 14 months) in the durvalumab cohort and 47%, 38%, and 79%, respectively, (median follow-up period: 22 months) in the CCRT-alone cohort. Although we did not observe grade ≥3 pneumonitis, grade 2 was observed in 50% of the patients in the durvalumab cohort. We believe that the efficacy of CCRT and durvalumab for N3 NSCLC was similar to that reported by studies assessing patients with N0-2 metastasis. However, the patients should be carefully followed up because of the higher incidence of grade 2 pneumonitis.

The durvalumab cohort had a 1-year PFS and OS rates of 53% and 88%, respectively. In the present study, no significant difference in either PFS (p=0.627) or OS (p=0.934) was observed between the CCRT-alone and durvalumab cohorts. However, previous studies have reported 1-year PFS and OS rates of 30%-48% and 62%-86%, respectively, after CCRT alone in patients with N3 NSCLC (4, 6, 16). Thus, the PFS and OS in our durvalumab cohort appear to be slightly better than the results of CCRT alone reported in the aforementioned previous studies. In the PACIFIC trial, the durvalumab cohort had 1-year PFS and OS rates of 56% and 83%, respectively (17). Offin et al. reported that patients with stage III NSCLC who received CCRT and durvalumab had 1-year PFS and OS rates of 65% and 85%, respectively (18). The results obtained from our durvalumab cohort were similar to those reported in the aforementioned studies, although our study focused on patients with N3 lymph node metastasis. These results appear to be very encouraging, warranting further studies with larger cohorts to clarify the efficacy of CCRT followed by durvalumab for patients with LA-NSCLC with N3 lymph node metastasis.

In the present study, the durvalumab and CCRT-alone cohorts had 1-year LC rates of 89% and 47%, respectively (p=0.035). One of the reasons of this result is the difference in the treatment technique in the CCRT-alone and durvalumab cohorts. Median PTV D95 was 67% in the CCRT-alone cohort whereas it was 100% in the durvalumab cohort, although there was no statistically significant difference. This tendency may result from the difference in the proportion of patients who received 3D-CRT or VMAT in each cohort. It is sometimes difficult to cover PTV with an adequate dose and sparing organs at risk by 3D-CRT for LA-NSCLC with N3 lymph node metastasis. We think that intensity modulated radiotherapy (IMRT) is advantageous regarding dose coverage of target volume and sparing of organs at risk. In addition to improved dose coverage of PTV, we think that durvalumab itself might affect local control.

We previously reported that patients with NSCLC with N0-N3 lymph node metastasis who received CCRT and durvalumab had significantly better LC than those who received CCRT alone (19). Offin et al. also reported that patients with stage III NSCLC who received CCRT and durvalumab exhibited better local regional control than those who received CCRT alone (18). The results presented herein are, therefore, consistent with those reported in previous studies despite this study focusing on patients with N3 lymph node metastasis. Local recurrence is a significantly poor prognostic factor for patients with stage III NSCLC (20). In this study, it was difficult to differentiate contribution of treatment technique and effect of durvalumab on LC due to the small number of patients. However, improving LC with IMRT and durvalumab in patients with N3 lymph node metastasis may confer survival benefits.

The incidence of grade 2 pneumonitis in our durvalumab cohort was 50%, although no grade ≥3 pneumonitis was observed. Notably, studies based on real-world data obtained from Asian countries have demonstrated that the incidence of grade ≥2 pneumonitis after the PACIFIC regimen was 29%-47% (8-15). The incidence of grade 2 pneumonitis in the present study was slightly higher than that reported in previous studies conducted in Asian countries. The reason for obtaining such a result may be complex. A recent meta-analysis on the efficacy and safety of the PACIFIC regimen for stage III NSCLC identified older age and Asian ethnicity as risk factors for pneumonitis (21). Median age of the durvalumab cohort was 70 years, which was higher than that of the PACIFIC trial cohort (17); all patients were Asians in the present study. Given the high extent of disease, patients with N3 lymph node metastasis tend to show symptoms at diagnosis. In fact, 7 of 12 patients in the durvalumab cohort exhibited symptoms such as cough, sputum, and dyspnea, including two patients with a performance status of 2 because of these symptoms. These patient characteristics might have facilitated the incidence of grade 2 pneumonitis in our study. Although the incidence of grade 2 pneumonitis in our study was slightly higher than that reported in other studies, we did not observe grade ≥3 pneumonitis. We believe that pneumonitis could be manageable, although careful follow-up is necessary.

In this study, lung V20 and MLD did not vary significantly between the CCRT-alone and durvalumab cohorts, whereas lung V5 was significantly high in the durvalumab cohort; this might be because of the higher proportion of patients who received VMAT in the durvalumab cohort. We previously reported that with IMRT for LA-NSCLC, lung V5 may be inevitably higher than that noted after 3D-CRT (9). Tsukita et al. reported that lung volume V5 was a significant predictive factor for grade ≥2 pneumonitis after IMRT and durvalumab for LA-NSCLC (8). In a previous study, a lung V5 of 58.9% was identified as a significant cutoff value for differentiating the occurrence of grade ≥2 pneumonitis. Other studies have also reported that a high value of lung V5, such as 60%-70%, may represent a risk factor for pneumonitis (22, 23). In this study, mean lung V5 in the durvalumab cohort was 46.4%, which was far below the aforementioned cutoff range. Furthermore, lung V20 and MLD did not vary significantly between the two cohorts. Thus, probably lung V5 in the durvalumab cohort did not facilitate the incidence of grade 2 pneumonitis.

Dose to the heart tended to be high in the durvalumab cohort in this study. The main reason of this result was the difference in the location of the primary tumor between the CCRT-alone and durvalumab cohorts. If the large primary tumor was located near the heart, it was difficult to spare the heart although maximum effort had to be made to reduce unnecessary dose to the heart. It is reported that dose to the heart significantly associated with patient’s prognosis after CCRT for LA-NSCLC (24). Reduction of the dose to the heart with appropriate techniques becomes more important because prognosis of patients is prolonged with PACIFIC regimen.

PTV D95 was significantly better in patients who received VMAT (100% vs. 54%, p<0.001). The advantage of IMRT may be larger for patients with N3 lymph node metastasis because it is sometimes difficult to cover target volume with adequate dose of 3D-CRT because of the wide spread of the disease. Esophageal dose was significantly higher in the CCRT alone cohort, and the incidence of grade 2 esophagitis was also higher in this cohort. This resulted from the difference in the use of elective nodal irradiation and involved-field radiotherapy (IFRT) between the two cohorts. With IFRT, dose to the esophagus can be significantly reduced; thus, esophageal toxicity can be reduced significantly (25). Thus far, we have not observed out-of-irradiated-field regional recurrence in patients who received IFRT. We believe that IMRT and IFRT may be more favorable for patients with N3 lymph node metastasis than 3D-CRT in terms of dose conformity and reduced esophageal toxicity.

Some limitations of the present study should be noted. First, the number of patients was limited in this study. However, to the best of our knowledge, no previous studies have explored the efficacy and toxicity of CCRT and durvalumab in patients with N3 NSCLC. Thus, this study remains significant even with the limited number of patients. Second, the short follow-up period of this study might have resulted in the underestimation of events such as disease progression or toxicity. However, most pneumonitis cases occur within 6 months from treatment (8-11); thus, our follow-up period appears to be sufficient for assessing pneumonitis. Third, the proportion of patients who received 3D-CRT or VMAT was different between the CCRT-alone cohort and durvalumab cohort because we did not perform VMAT for lung cancer in the earlier period of this study. This might cause bias on the results of this study. Further studies with fixed treatment technique, larger number of patients, and longer follow-up period are necessary to reach concrete conclusions regarding the efficacy and toxicity of CCRT and durvalumab in N3 NSCLC.

Conclusion

We reported the efficacy of CCRT followed by durvalumab for N3 NSCLC and compared it with that of CCRT alone. Patients who received CCRT followed by durvalumab had 1-year PFS and OS rates that were similar to those reported in the PACIFIC trial; furthermore, CCRT followed by durvalumab promoted significantly better LC than CCRT alone. Grade 2 pneumonitis was more frequent than that reported for the PACIFIC regimen, suggesting the need for adequate caution during the follow-up of such patients.

Acknowledgements

The Authors thank Edanz (https://jp.edanz.com/ac) for editing a draft of this manuscript. The study was approved by Saitama Medical University Institutional Review Board (Reference number: 20-167).

Footnotes

  • Authors’ Contributions

    T.A. and M.I. contributed to the study concept. S.S., T.A., Y.R., T.O., M.I., R.H., Y.K., and Y.M. contributed to clinical data acquisition. K.K., H.K., and S.N. contributed to data analyses. S.K. contributed to data interpretation. All Authors have read and approved the final version of the manuscript.

  • Conflicts of Interest

    K Kaira has received research grants and speaker honorarium from Ono Pharmaceutical Company, Boehringer Ingelheim, Chugai Pharmaceutical, Taiho Pharmaceutical, Eli Lilly Japan, and AstraZeneca. H Kagamu received annual remuneration from ImmuniT Research Inc.; speaker honorarium from Ono Pharmaceutical Company, Boehringer Ingelheim, Chugai Pharmaceutical, and AstraZeneca; and research grants from Boehringer Ingelheim, Chugai Pharmaceutical, and AstraZeneca. The other Authors declare no conflicts of interest in relation to this study.

  • Received November 21, 2022.
  • Revision received December 5, 2022.
  • Accepted December 6, 2022.

This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY-NC-ND) 4.0 international license (https://creativecommons.org/licenses/by-nc-nd/4.0).

References

  1. ↵
    1. Siegel RL,
    2. Miller KD,
    3. Fuchs HE and
    4. Jemal A
    : Cancer statistics, 2021. CA Cancer J Clin 71(1): 7-33, 2021. PMID: 33433946. DOI: 10.3322/caac.21654
    OpenUrlCrossRefPubMed
  2. ↵
    1. Herbst RS,
    2. Morgensztern D and
    3. Boshoff C
    : The biology and management of non-small cell lung cancer. Nature 553(7689): 446-454, 2018. PMID: 29364287. DOI: 10.1038/nature25183
    OpenUrlCrossRefPubMed
  3. ↵
    1. National Comprehensive Cancer Network Clinical Practice Guidelines in Oncology
    , Non-small cell lung cancer, Version 5. 2022. Available at: https://www.nccn.org/professionals/physician_gls/pdf/nscl.pdf [Last accessed on November 15, 2022]
  4. ↵
    1. Koul R,
    2. Rathod S,
    3. Dubey A,
    4. Bashir B and
    5. Chowdhury A
    : Comparison of 7th and 8th editions of the UICC/AJCC TNM staging for non-small cell lung cancer in a non-metastatic North American cohort undergoing primary radiation treatment. Lung Cancer 123: 116-120, 2018. PMID: 30089581. DOI: 10.1016/j.lungcan.2018.06.029
    OpenUrlCrossRefPubMed
  5. ↵
    1. Oh D,
    2. Ahn YC,
    3. Park HC,
    4. Lim DH,
    5. Noh JM,
    6. Cho WK and
    7. Pyo H
    : The prognostic impact of supraclavicular lymph node in N3-IIIB stage non-small cell lung cancer patients treated with definitive concurrent chemo-radiotherapy. Oncotarget 8(22): 35700-35706, 2017. PMID: 28415687. DOI: 10.18632/oncotarget.16054
    OpenUrlCrossRefPubMed
  6. ↵
    1. Noh JM,
    2. Kim JM,
    3. Ahn YC,
    4. Pyo H,
    5. Kim B,
    6. Oh D,
    7. Ju SG,
    8. Kim JS,
    9. Shin JS,
    10. Hong CS,
    11. Park H and
    12. Lee E
    : Effect of radiation therapy techniques on outcome in N3-positive IIIB non-small cell lung cancer treated with concurrent chemoradiotherapy. Cancer Res Treat 48(1): 106-114, 2016. PMID: 25687865. DOI: 10.4143/crt.2014.131
    OpenUrlCrossRefPubMed
  7. ↵
    1. Spigel DR,
    2. Faivre-Finn C,
    3. Gray JE,
    4. Vicente D,
    5. Planchard D,
    6. Paz-Ares L,
    7. Vansteenkiste JF,
    8. Garassino MC,
    9. Hui R,
    10. Quantin X,
    11. Rimner A,
    12. Wu YL,
    13. Özgüroğlu M,
    14. Lee KH,
    15. Kato T,
    16. de Wit M,
    17. Kurata T,
    18. Reck M,
    19. Cho BC,
    20. Senan S,
    21. Naidoo J,
    22. Mann H,
    23. Newton M,
    24. Thiyagarajah P and
    25. Antonia SJ
    : Five-year survival outcomes from the PACIFIC trial: Durvalumab after chemoradiotherapy in stage III non-small-cell lung cancer. J Clin Oncol 40(12): 1301-1311, 2022. PMID: 35108059. DOI: 10.1200/JCO.21.01308
    OpenUrlCrossRefPubMed
  8. ↵
    1. Tsukita Y,
    2. Yamamoto T,
    3. Mayahara H,
    4. Hata A,
    5. Takeda Y,
    6. Nakayama H,
    7. Tanaka S,
    8. Uchida J,
    9. Usui K,
    10. Toyoda T,
    11. Tamiya M,
    12. Morimoto M,
    13. Oya Y,
    14. Kodaira T,
    15. Miyauchi E,
    16. Jingu K and
    17. Sugiura H
    : Intensity-modulated radiation therapy with concurrent chemotherapy followed by durvalumab for stage III non-small cell lung cancer: A multi-center retrospective study. Radiother Oncol 160: 266-272, 2021. PMID: 34023330. DOI: 10.1016/j.radonc.2021.05.016
    OpenUrlCrossRefPubMed
  9. ↵
    1. Abe T,
    2. Iino M,
    3. Saito S,
    4. Aoshika T,
    5. Ryuno Y,
    6. Ohta T,
    7. Igari M,
    8. Hirai R,
    9. Kumazaki Y,
    10. Miura Y,
    11. Kaira K,
    12. Kagamu H,
    13. Noda SE and
    14. Kato S
    : Feasibility of intensity modulated radiotherapy with involved field radiotherapy for Japanese patients with locally advanced non-small cell lung cancer. J Radiat Res 62(5): 894-900, 2021. PMID: 34260719. DOI: 10.1093/jrr/rrab063
    OpenUrlCrossRefPubMed
    1. Saito S,
    2. Abe T,
    3. Kobayashi N,
    4. Aoshika T,
    5. Ryuno Y,
    6. Igari M,
    7. Hirai R,
    8. Kumazaki Y,
    9. Miura Y,
    10. Kaira K,
    11. Kagamu H,
    12. Noda SE and
    13. Kato S
    : Incidence and dose-volume relationship of radiation pneumonitis after concurrent chemoradiotherapy followed by durvalumab for locally advanced non-small cell lung cancer. Clin Transl Radiat Oncol 23: 85-88, 2020. PMID: 32529055. DOI: 10.1016/j.ctro.2020.05.006
    OpenUrlCrossRefPubMed
  11. ↵
    1. Mayahara H,
    2. Uehara K,
    3. Harada A,
    4. Kitatani K,
    5. Yabuuchi T,
    6. Miyazaki S,
    7. Ishihara T,
    8. Kawaguchi H,
    9. Kubota H,
    10. Okada H,
    11. Ninomaru T,
    12. Shindo C and
    13. Hata A
    : Predicting factors of symptomatic radiation pneumonitis induced by durvalumab following concurrent chemoradiotherapy in locally advanced non-small cell lung cancer. Radiat Oncol 17(1): 7, 2022. PMID: 35033139. DOI: 10.1186/s13014-021-01979-z
    OpenUrlCrossRefPubMed
    1. Shintani T,
    2. Kishi N,
    3. Matsuo Y,
    4. Ogura M,
    5. Mitsuyoshi T,
    6. Araki N,
    7. Fujii K,
    8. Okumura S,
    9. Nakamatsu K,
    10. Kishi T,
    11. Atsuta T,
    12. Sakamoto T,
    13. Narabayashi M,
    14. Ishida Y,
    15. Sakamoto M,
    16. Fujishiro S,
    17. Katagiri T,
    18. Kim YH and
    19. Mizowaki T
    : Incidence and risk factors of symptomatic radiation pneumonitis in non-small-cell lung cancer patients treated with concurrent chemoradiotherapy and consolidation durvalumab. Clin Lung Cancer 22(5): 401-410, 2021. PMID: 33678582. DOI: 10.1016/j.cllc.2021.01.017
    OpenUrlCrossRefPubMed
    1. Jung HA,
    2. Noh JM,
    3. Sun JM,
    4. Lee SH,
    5. Ahn JS,
    6. Ahn MJ,
    7. Pyo H,
    8. Ahn YC and
    9. Park K
    : Real world data of durvalumab consolidation after chemoradiotherapy in stage III non-small-cell lung cancer. Lung Cancer 146: 23-29, 2020. PMID: 32505077. DOI: 10.1016/j.lungcan.2020.05.035
    OpenUrlCrossRefPubMed
    1. Inoue H,
    2. Ono A,
    3. Kawabata T,
    4. Mamesaya N,
    5. Kawamura T,
    6. Kobayashi H,
    7. Omori S,
    8. Wakuda K,
    9. Kenmotsu H,
    10. Naito T,
    11. Murakami H,
    12. Yasui K,
    13. Ogawa H,
    14. Onoe T,
    15. Endo M,
    16. Harada H and
    17. Takahashi T
    : Clinical and radiation dose-volume factors related to pneumonitis after treatment with radiation and durvalumab in locally advanced non-small cell lung cancer. Invest New Drugs 38(5): 1612-1617, 2020. PMID: 32128667. DOI: 10.1007/s10637-020-00917-2
    OpenUrlCrossRefPubMed
  15. ↵
    1. Miura Y,
    2. Mouri A,
    3. Kaira K,
    4. Yamaguchi O,
    5. Shiono A,
    6. Hashimoto K,
    7. Nishihara F,
    8. Shinomiya S,
    9. Akagami T,
    10. Murayama Y,
    11. Abe T,
    12. Noda SE,
    13. Kato S,
    14. Kobayashi K and
    15. Kagamu H
    : Chemoradiotherapy followed by durvalumab in patients with unresectable advanced non-small cell lung cancer: Management of adverse events. Thorac Cancer 11(5): 1280-1287, 2020. PMID: 32160383. DOI: 10.1111/1759-7714.13394
    OpenUrlCrossRefPubMed
  16. ↵
    1. Qin A,
    2. Lusk E,
    3. Daignault-Newton S and
    4. Schneider BJ
    : Chemotherapy and radiation versus chemotherapy alone for elderly patients with N3 stage IIIB NSCLC. Clin Lung Cancer 20(4): e495-e503, 2019. PMID: 31088760. DOI: 10.1016/j.cllc.2019.04.003
    OpenUrlCrossRefPubMed
  17. ↵
    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,
    33. Özgüroğlu M and PACIFIC Investigators
    : Overall survival with durvalumab after chemoradiotherapy in stage III NSCLC. N Engl J Med 379(24): 2342-2350, 2018. PMID: 30280658. DOI: 10.1056/NEJMoa1809697
    OpenUrlCrossRefPubMed
  18. ↵
    1. Offin M,
    2. Shaverdian N,
    3. Rimner A,
    4. Lobaugh S,
    5. Shepherd AF,
    6. Simone CB 2nd.,
    7. Gelblum DY,
    8. Wu AJ,
    9. Lee N,
    10. Kris MG,
    11. Rudin CM,
    12. Zhang Z,
    13. Hellmann MD,
    14. Chaft JE and
    15. Gomez DR
    : Clinical outcomes, local-regional control and the role for metastasis-directed therapies in stage III non-small cell lung cancers treated with chemoradiation and durvalumab. Radiother Oncol 149: 205-211, 2020. PMID: 32361014. DOI: 10.1016/j.radonc.2020.04.047
    OpenUrlCrossRefPubMed
  19. ↵
    1. Abe T,
    2. Saito S,
    3. Iino M,
    4. Aoshika T,
    5. Ryuno Y,
    6. Ohta T,
    7. Igari M,
    8. Hirai R,
    9. Kumazaki Y,
    10. Miura Y,
    11. Kaira K,
    12. Kagamu H,
    13. Noda SE and
    14. Kato S
    : Effect of durvalumab on local control after concurrent chemoradiotherapy for locally advanced non-small cell lung cancer in comparison with chemoradiotherapy alone. Thorac Cancer 12(2): 245-250, 2021. PMID: 33289347. DOI: 10.1111/1759-7714.13764
    OpenUrlCrossRefPubMed
  20. ↵
    1. Machtay M,
    2. Paulus R,
    3. Moughan J,
    4. Komaki R,
    5. Bradley JE,
    6. Choy H,
    7. Albain K,
    8. Movsas B,
    9. Sause WT and
    10. Curran WJ
    : Defining local-regional control and its importance in locally advanced non-small cell lung carcinoma. J Thorac Oncol 7(4): 716-722, 2012. PMID: 22425920. DOI: 10.1097/JTO.0b013e3182429682
    OpenUrlCrossRefPubMed
  21. ↵
    1. Wang Y,
    2. Zhang T,
    3. Huang Y,
    4. Li W,
    5. Zhao J,
    6. Yang Y,
    7. Li C,
    8. Wang L and
    9. Bi N
    : Real-world safety and efficacy of consolidation durvalumab after chemoradiation therapy for stage III non-small cell lung cancer: a systematic review and meta-analysis. Int J Radiat Oncol Biol Phys 112(5): 1154-1164, 2022. PMID: 34963558. DOI: 10.1016/j.ijrobp.2021.12.150
    OpenUrlCrossRefPubMed
  22. ↵
    1. Yom SS,
    2. Liao Z,
    3. Liu HH,
    4. Tucker SL,
    5. Hu CS,
    6. Wei X,
    7. Wang X,
    8. Wang S,
    9. Mohan R,
    10. Cox JD and
    11. Komaki R
    : Initial evaluation of treatment-related pneumonitis in advanced-stage non-small-cell lung cancer patients treated with concurrent chemotherapy and intensity-modulated radiotherapy. Int J Radiat Oncol Biol Phys 68(1): 94-102, 2007. PMID: 17321067. DOI: 10.1016/j.ijrobp.2006.12.031
    OpenUrlCrossRefPubMed
  23. ↵
    1. Khalil AA,
    2. Hoffmann L,
    3. Moeller DS,
    4. Farr KP and
    5. Knap MM
    : New dose constraint reduces radiation-induced fatal pneumonitis in locally advanced non-small cell lung cancer patients treated with intensity-modulated radiotherapy. Acta Oncol 54(9): 1343-1349, 2015. PMID: 26198657. DOI: 10.3109/0284186X.2015.1061216
    OpenUrlCrossRefPubMed
  24. ↵
    1. Atkins KM,
    2. Rawal B,
    3. Chaunzwa TL,
    4. Lamba N,
    5. Bitterman DS,
    6. Williams CL,
    7. Kozono DE,
    8. Baldini EH,
    9. Chen AB,
    10. Nguyen PL,
    11. D’Amico AV,
    12. Nohria A,
    13. Hoffmann U,
    14. Aerts HJWL and
    15. Mak RH
    : Cardiac radiation dose, cardiac disease, and mortality in patients with lung cancer. J Am Coll Cardiol 73(23): 2976-2987, 2019. PMID: 31196455. DOI: 10.1016/j.jacc.2019.03.500
    OpenUrlCrossRefPubMed
  25. ↵
    1. Fleckenstein J,
    2. Kremp K,
    3. Kremp S,
    4. Palm J and
    5. Rübe C
    : IMRT and 3D conformal radiotherapy with or without elective nodal irradiation in locally advanced NSCLC: A direct comparison of PET-based treatment planning. Strahlenther Onkol 192(2): 75-82, 2016. PMID: 26438071. DOI: 10.1007/s00066-015-0900-9
    OpenUrlCrossRefPubMed
Back to top

In this issue

Print
Download PDF
Article Alerts
Email Article
Citation Tools
Reprints and Permissions
Comparison of the Efficacy and Toxicity of Concurrent Chemoradiotherapy and Durvalumab and Concurrent Chemoradiotherapy Alone for Locally Advanced Non-small Cell Lung Cancer With N3 Lymph Node Metastasis
TAKANORI ABE, MISAKI IINO, SATOSHI SAITO, TOMOMI AOSHIKA, YASUHIRO RYUNO, TOMOHIRO OHTA, MITSUNOBU IGARI, RYUTA HIRAI, YU KUMAZAKI, YU MIURA, KYOICHI KAIRA, HIROSHI KAGAMU, SHIN-EI NODA, SHINGO KATO
Anticancer Research Feb 2023, 43 (2) 675-682; DOI: 10.21873/anticanres.16205
Twitter logo Facebook logo Mendeley logo

Jump to section

Keywords