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Concurrent vs. sequential chemoradiotherapy: a survival boost for lung cancer patients

BioMedical Engineering OnLine volume 24, Article number: 60 (2025) Cite this article

Abstract

Objective

To investigate the clinical efficacy, incidence of radiation pneumonitis, and impact on lung function of sequential chemoradiotherapy (SCRT) and concurrent chemoradiotherapy (CCRT) in the treatment of lung cancer.

Method

From January 2020 to December 2022, 158 patients with non-small cell lung cancer (NSCLC) were admitted to our hospital and chosen as the study subjects. Their clinical data were analyzed retrospectively and organized into a control group (n = 78, received SCRT) and an observation group (n = 80, received CCRT). Lesion sizes measured through CT scans were used to compare the clinical efficacy between the two groups. The study also compared the rates of adverse reactions, radiation pneumonitis, and lung function pre- and post-treatment, including forced expiratory volume in one second (FEV1), forced vital capacity (FVC), and FEV1/FVC ratio. The comparison of serum tumor marker levels was conducted between two groups, with patients being observed over a 36-month period. Kaplan–Meier survival curves were used to analyze the changes in overall survival rate (OSR), progression-free survival (PFS), and overall survival (OS) between two groups of patients.

Results

For the observation group, the remission rate was 90.00%, and for the control group, it was 74.36%. The control rates were 96.25% for the observation group and 89.74% for the control group. Significantly higher remission and control rates were observed in the observation group than in the control group (P < 0.05). The hemoglobin reduction grade 0 was 81.2% in the observation group, compared to 58.9% in the control group. In terms of leukopenia reduction (grades 0–III) and hemoglobin reduction (grades 0–II), the observation group outperformed the control group (P < 0.05). In the observation group, 25.00% of patients experienced radiation pneumonitis, a higher rate compared to the 8.97% in the control group (P < 0.05). Overall, the control group experienced more severe radiation-induced lung injury compared to the observation group, with 6.41% of cases reaching grade IV, unlike the 0.00% in the observation group. Grade II accounted for 1.28% in the control group, a figure significantly lower than the 21.25% in the observation group (P < 0.05). Post-treatment, the FEV1, FVC, and FEV1/FVC values rose in both groups, with the observation group displaying significantly greater increases than the control group (P < 0.05). Also, after treatment, there was a decrease in CA125, SCC Ag, and CYFRA21-1 levels in both groups, with the observation group having significantly lower levels than the control group (P < 0.05). According to the Kaplan–Meier survival curve analysis, the observation group achieved an OSR of 90.00%, which exceeded the 83.33% of the control group (P > 0.05). Furthermore, PFS and OS levels were elevated in the observation group relative to the control group (P < 0.05).

Conclusion

CCRT could optimize the treatment effect for NSCLC patients by improving lung function, reducing serum tumor marker levels, and prolonging survival without increasing toxicity. Nonetheless, the occurrence of radiation pneumonitis was somewhat above expectations, and the treatment plan should be tailored to the patient's specific circumstances in clinical practice.

Introduction

Non-small cell lung cancer (NSCLC) accounts for over 80 to 85% of newly diagnosed lung cancer cases worldwide each year. As the cancer with the highest mortality rate in China, it resulted in a death toll of 733,300 in 2022 [1]. In recent years, the incidence and mortality of lung cancer have shown complex changing trends, which poses new challenges to the formulation of clinical treatment strategies [2]. The study has shown that lung cancer has become one of the leading causes of cancer mortality in China, and accurate understanding of its mortality data is of great significance for the formulation of public health strategies [3].

Sequential chemoradiotherapy (SCRT) is a strategy that involves administering chemotherapy followed by radiotherapy. The advantage of SCRT is that chemotherapy drugs can reduce tumor volume, providing a better target area for radiotherapy, while also enhancing the sensitivity of tumor cells to radiotherapy [4]. However, SCRT may lead to tumor cell proliferation due to the interval between chemotherapy and radiotherapy, which can weaken the therapeutic effect [5]. Concurrent chemoradiotherapy (CCRT) is a strategy that combines chemotherapy and radiotherapy simultaneously, effectively killing tumor cells through synergistic effects. However, CCRT may also result in higher toxicity and side effects, such as acute non-hematological toxicity reactions and radiation pneumonitis [6].

Some studies have shown that the synergistic application of radiotherapy and chemotherapy has better clinical efficacy compared to conventional radiotherapy or chemotherapy alone, indicating that treatment efficacy is influenced by the chemotherapy regimen [7]. As patients undergo chest radiotherapy, they are at increased risk of developing radiation pneumonia. As a major factor affecting non-surgical comprehensive treatment for lung cancer, radiation pneumonia not only hinders treatment progress and significantly reduces patients'quality of life, but also negatively impacts clinical efficacy [8]. Some literature suggests that concurrent chemoradiotherapy (CCRT) increases the risk of radiation pneumonitis and is associated with more severe toxic reactions [9]. Additionally, other studies indicate that short-course radiotherapy (SCRT) increases the risk of pulmonary edema and fibrosis in patients due to the effects of chemotherapy drugs, leading to lung damage and adversely affecting patient prognosis and recovery [10]. The PACIFIC-6 study (NCT03693300) showed that the median progression-free survival (mPFS) of CCRT combined with immune consolidation therapy was significantly better than that of SCRT (16.8 vs. 10.2 months, P < 0.001) in patients with unresectable stage III NSCLC, while the CCRT group had a higher rate of grade ≥ 3 radiation pneumonitis (18% vs. 6%) [4]. Another study involving 610 patients compared SCRT with CCRT in patients with locally advanced NSCLC [11]. The results showed that CCRT significantly improved median survival and 5-year overall survival (OS), but also increased toxicity, such as esophagitis and hematologic toxicities (e.g., leukopenia). A meta-analysis evaluating six randomized clinical trials confirmed an improved 5-year OS with SCRT compared with 15.1% with CCRT [hazard ratio (HR) = 0.84; 95%CI, 0.74–0.95, P = 0.004]. However, the limitation of SCRT is that the treatment interval may lead to re-proliferation of tumor cells and impair the long-term efficacy [12]. The application of SCRT and CCRT in the treatment of lung cancer have always been a research hotspot. Some other studies have shown that CCRT have better overall efficacy in treating lung cancer than SCRT [13]. However, there may be differences in the dosage of chemotherapy drugs and radiotherapy used in different studies, which may lead to poor comparability. Therefore, a unified treatment plan is needed to ensure the accuracy of research results.

Herein, the clinical efficacy, incidence of radiation pneumonitis, and impact on lung function of SCRT and CCRT in the treatment of lung cancer were explored, aiming to provide more personalized treatment strategies for lung cancer patients and improve the survival rate and quality of life.

Results

Comparison of the clinical efficacy

For the observation group, the remission rate was 90.00%, and for the control group, it was 74.36%. The control rates were 96.25% for the observation group and 89.74% for the control group. Significantly higher remission and control rates were observed in the observation group than in the control group (P < 0.05, Table 1 and Fig. 1).

Table 1 Comparison of the clinical efficacy [cases (%)]
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Fig. 1
figure 1

Comparison of clinical efficacy between two groups of patients. A Distribution of clinical efficacy in the control group; B distribution of clinical efficacy in the observation group

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Comparison of the adverse reactions

In terms of leukopenia reduction in grade 0–III, the proportion of the control group (58.9 + 19.2 + 19.2 + 2.56) was 99.86%, while the proportion of the observation group (77.50 + 20.00 + 2.50 + 0.00) was 100%. In addition, the proportion of grade 0 leukopenia reduction in the observation group was 77.50%, which was higher than the control group's 58.9%. In terms of hemoglobin reduction level 0–II, the control group accounted for 100% (58.9 + 25.6 + 15.3), while the observation group accounted for 96.2% (81.2 + 15.0 + 0.0). The hemoglobin reduction grade 0 was 81.2% in the observation group, compared to 58.9% in the control group. In terms of leukopenia reduction (grades 0–III) and hemoglobin reduction (grades 0–II), the observation group outperformed the control group (P < 0.05, Table 2).

Table 2 Comparison of the adverse reactions [cases (%)]
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Comparison of the incidence of radiation pneumonitis between two groups

In the observation group, 25.00% of patients experienced radiation pneumonitis, a higher rate compared to the 8.97% in the control group (P < 0.05). Overall, the control group experienced more severe radiation-induced lung injury compared to the observation group, with 6.41% of cases reaching grade IV, unlike the 0.00% in the observation group. Grade II accounted for 1.28% in the control group, a figure significantly lower than the 21.25% in the observation group (P < 0.05, Table 3). There may be confounding factors due to individual differences in radiosensitivity in this study. The data of 158 patients with radiotherapy dose and response after radiotherapy were analyzed. It was found that the incidence of radiation pneumonitis after radiotherapy was not a simple linear relationship with radiotherapy dose. Some patients had radiation pneumonitis at a low radiation dose (40–50Gy) (5 cases, 10.42%), but other patients had similar symptoms at a higher radiation dose (60–70Gy) (7 cases, 14.58%).

Table 3 Comparison of the incidence of radiation pneumonitis between two groups [cases (%)]
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Comparison of lung function levels of two groups

Post-treatment, the FEV1, FVC, and FEV1/FVC values rose in both groups, with the observation group displaying significantly greater increases than the control group (P < 0.05, Table 4).

Table 4 Comparison of lung function levels of two groups (\(\overline{x} \pm s\))
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Comparison of serum tumor markers between two groups

After treatment, there was a decrease in CA125, SCC Ag, and CYFRA21-1 levels in both groups, with the observation group having significantly lower levels than the control group (P < 0.05, Table 5).

Table 5 Comparison of serum tumor markers between two groups (\(\overline{x} \pm s\))
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Comparison of PFS and OS between two groups

The follow-up lasted for 36 months. According to the Kaplan–Meier survival curve analysis, the observation group achieved an OSR of 90.00%, which exceeded the 83.33% of the control group (P > 0.05). Furthermore, PFS and OS levels were elevated in the observation group relative to the control group (P < 0.05, Table 6 and Fig. 2).

Table 6 Comparison of PFS and OS between two groups (\(\overline{x} \pm s\))
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Fig. 2
figure 2

Kaplan–Meier survival curve analysis. A Comparison of PFS between two groups; B comparison of two OS between two groups

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Discussion

Lung cancer ranks among the most prevalent malignant neoplasms globally and constitutes the primary cause of mortality in individuals with cancer-related conditions. NSCLC represents the most frequently diagnosed histological subtype of lung cancer [14]. In patients with NSCLC, the therapeutic outcomes of standalone radiotherapy and chemotherapy are frequently suboptimal. Consequently, clinical practice often employs a multimodal approach, integrating both radiotherapy and chemotherapy, particularly in the management of advanced-stage lung cancer [15]. Empirical evidence from clinical studies indicates that this combined modality therapy yields superior therapeutic benefits compared to monotherapy with either radiotherapy or chemotherapy alone. This may be related to the increased sensitivity of tumor cells to radiotherapy after oxidation, which minimizes radiation damage [16, 17]. At present, the radiotherapy and chemotherapy measures for NSCLC patients in clinical practice are mainly divided into SCRT and CCRT. Among them, SCRT can significantly improve clinical efficacy. However, due to the complete completion of chemotherapy before radiotherapy, tumor cells are eliminated during subsequent treatment, resulting in a decrease in the volume of the lesion and sufficient oxygen supply between cell tissues, which further leads to rapid proliferation of tumor cells and prolongs the treatment time [18]. CCRT is the use of chemotherapy drugs to eliminate tumor cells and increase the sensitivity of tumor tissue cells to radiotherapy. Simultaneously, radiotherapy is administered to augment therapeutic efficacy and efficiently suppress the proliferation and dissemination of tumor cells [19]. The findings of this study indicated that the remission and control rates in the observation group surpassed those observed in the control group following treatment. When chemotherapy and radiotherapy are performed simultaneously, they can enhance each other's effectiveness. Chemotherapy changes the physiological state of tumor cells, making them more sensitive to radiation therapy. Radiotherapy, on the other hand, destroys the DNA of tumor cells to make chemotherapy drugs more effective [20]. In terms of patient survival, it means that patients receiving CCRT treatment can maintain disease stability for a longer period of time, delay tumor progression, and strive for more opportunities for subsequent treatment, thus it is possible to achieve long-term survival. From the perspective of quality of life, the higher remission rate and control rate indicate that CCRT can more effectively alleviate the patients'cancer-related symptoms, such as cough, dyspnea, chest pain, etc., reduce the physical discomfort caused by tumor progression, thereby improving the patients'activities of daily living, improving the patients'psychological state, reducing anxiety and fear, and improving the overall quality of life. For example, patients may be better able to perform daily activities, such as walking and eating, as a result of relief of symptoms, and sleep quality may also improve, which may contribute to a better quality of life for patients. In contrast, the remission rate of SCRT is usually lower, as the time interval between chemotherapy and radiotherapy may give tumor cells the opportunity to restore their proliferative capacity or develop drug resistance. Research has shown [21] that in patients with advanced esophageal cancer, the total effective rate of CCRT is higher than that of SCRT, and the overall incidence of adverse reactions is lower. Another study found [22] that CCRT also showed high treatment efficacy and safety in patients with locally advanced gastric cancer.

The combination therapy of radiotherapy and chemotherapy can effectively improve tumor control rate and survival rate, while radiation pneumonitis is the biggest influencing factor on treatment efficacy. With the progression of radiotherapy and chemotherapy, the risk of radiation pneumonitis also increases accordingly [23, 24]. The development of radiation pneumonitis is constrained by various factors, such as the exposure area and drug dose received by the lungs, the patient's age, medical history, physical and lung function status, the patient's sensitive biological characteristics, changes in their own cytokines, and the impact of different treatment plans [25, 26]. The results of this study showed that the incidence of radiation pneumonitis in the observation group was higher than that in the control group. The analysis suggests that simultaneous radiotherapy and chemotherapy can cause a double blow to lung tissue. Radiotherapy destroys the DNA of tumor cells through high-energy radiation, but it can also damage normal lung tissue cells. Chemotherapy drugs inhibit the growth of tumor cells by affecting their metabolism and proliferation, but they also have toxic effects on normal cells. When these two treatment methods are applied simultaneously, their damaging effects on lung tissue will overlap, thereby increasing the risk of radiation pneumonitis [22]. However, the incidence of radiation pneumonitis in the control group of this study was generally more severe, and the FEV1, FVC, and FEV1/FVC indicators in the observation group were higher than those in the control group after treatment. Among patients treated with CCRT regimen, only low-grade radiation-induced lung injury increased, while severe radiation-induced lung injury did not increase. There was no significant negative impact on the lung function quality of the observation group patients, indicating that the overall occurrence of radiation pneumonitis after treatment was more excellent. In NSCLC patients, tumor growth, radiation and chemotherapy damage may lead to airway stenosis, lung tissue elasticity decrease, and then reduce FEV1 [27]. In our study, the FEV1 increased in both groups after treatment, indicating that chemoradiotherapy partly alleviated airway obstruction and improved lung elasticity. However, the FEV1 in the observation group increased more significantly, indicating that CCRT may have more advantages in alleviating airway stenosis and restoring lung elasticity, helping patients to breathe more smoothly, reducing symptoms such as dyspnea, and improving the ability of daily activities and quality of life of patients [28]. The increase of FVC after treatment means that the ventilation function of the lung is improved, and the patients can inhale and exhale more gas, provide more sufficient oxygen for the body, and meet the metabolic needs of the body, which has a positive effect on improving the patient's physical ability and enhancing the body's resistance. In this study, the ratio of the two groups increased after treatment, and the observation group was more significant, suggesting that radiotherapy and chemotherapy can help to reduce the degree of airway obstruction. Especially in patients treated with CCRT, the FEV1/FVC ratio increased more significantly, indicating that CCRT has a more prominent effect in improving airway function, which can effectively relieve the symptoms such as shortness of breath and wheezing, and further improve the respiratory function and quality of life of patients. In a study [29], the incidence of esophagitis caused by CCRT was significantly higher than that caused by SCRT. However, due to its significant therapeutic advantages, CCRT is still recommended for locally advanced NSCLC patients [30]. In terms of clinical management, for patients with radiation pneumonitis, once diagnosed, mild patients (grade II) were given oxygen inhalation, cough, asthma and other symptomatic and supportive treatment, and the changes of the condition were closely observed. For patients with grade III and above, in addition to the above treatment, glucocorticoids should be given according to the specific situation to reduce the pulmonary inflammatory response. During the treatment, the treatment plan will be adjusted according to the patient's symptom relief. The effects of radiation pneumonitis on the completion of treatment are mainly reflected in many aspects [31, 32]. On the one hand, for patients with mild symptoms, after active treatment, the subsequent anti-tumor treatment process is generally not affected, but it may be necessary to adjust the radiation dose or chemotherapy regimen appropriately to avoid aggravating lung damage. On the other hand, for patients with severe illness, it may lead to treatment interruption, affecting the overall treatment effect, and then affecting the prognosis of patients. In addition, radiation pneumonitis may further decrease the lung function of patients, increase the risk of complications such as pulmonary infection, and affect the quality of life and long-term survival of patients.

The results of this study showed that the PFS and OS of the observation group were better than those of the control group. The possible mechanism is that CCRT enhances sensitivity by keeping cells in the G and M phases, which are most sensitive to radiation, thereby shortening the overall treatment cycle [33]. In addition, CCRT has shown advantages in eliminating tumor cell clones, effectively killing primary lesions and potential subclinical lesions, thereby significantly enhancing treatment efficacy and ensuring long-term good prognosis [34]. CCRT enables the simultaneous application of radiotherapy and chemotherapy, effectively enhancing the killing effect on tumor cells and increasing their sensitivity to chemotherapy drugs. At the same time, CCRT generates a certain drug response to enhance the killing effect on tumor cells and inhibit their regeneration [35]. Some literature suggests that during the progression of radiotherapy and chemotherapy, there may be accelerated growth of residual tumor materials. This is because radiotherapy kills tumor cells and leaves certain growth space and conditions for residual tumor cells, while CCRT can effectively control the growth rate of tumors [20].

CA125, SCC Ag, and CYFRA21-1 are substances specifically released by tumor tissue, and their levels are significantly higher than the normal range in tumor cells. They are widely used in evaluating the therapeutic effect of cancer patients to reflect the stage of disease progression and prognosis [36, 37]. The results of this study showed that the levels of CA125, SCC Ag, and CYFRA21-1 in the observation group were lower than those in the control group, indicating that CCRT had a good inhibitory and improving effect on tumor markers, promoting patients to improve their physical abilities. This may be due to the interaction between CCRT and chemotherapy drugs, which enhances the efficacy and radiosensitivity of radiotherapy. The powerful pharmacological effect effectively eliminates local and distant metastatic lesions, thereby reducing serum markers to a certain extent and enhancing overall health. In addition, the results of this study showed that the observation group had better condition in 0–III-degree leukocyte reduction and 0–II-degree hemoglobin reduction compared to the control group, indicating that CCRT had a certain protective effect on leukocyte and hemoglobin in the body. The possible reason is that CCRT effectively avoids the damage to healthy body tissues and metabolic load of important organs caused by extensive drug radiotherapy and chemotherapy, thereby reducing inflammation levels and minimizing the occurrence of adverse reactions. Compared with the studies on JCO [38], both focused on the application of SCRT and CCRT in the treatment of lung cancer. However, the JCO study may focus on the comparison of efficacy between SCRT and CCRT under specific subgroups of patients or specific combinations of chemotherapy agents. However, this study included a wider range of NSCLC patients with different age and disease stage characteristics, which makes the results of the study more generalizable. In terms of assessment indicators, the JCO study may only focus on clinical efficacy and survival rate. This study not only evaluated the clinical efficacy and survival rate, but also analyzed the incidence of radiation pneumonitis, lung function changes, serum tumor markers and other aspects, which showed the differences between the two treatment regimens from more dimensions and provided richer data support for clinicians to fully understand the treatment effect.

In general, CCRT could optimize the treatment effect of NSCLC patients by improving lung function, reducing serum tumor marker levels and prolonging the survival without increasing toxicity. However, the incidence of radiation pneumonitis was slightly higher, and the appropriate treatment plan should be selected according to the specific situation of the patient in clinical practice, such as age, physical condition, tumor staging, etc. Meanwhile, during the treatment process, it is important to closely monitor changes in the patient's condition and adjust the treatment plan in a timely manner to improve their quality of life.

Our study has certain limitations. As a retrospective study, there is patient selection bias. The selected patients in our hospital from 2020 to 2022 cannot represent all NSCLC patients, and factors such as region and economic status may affect the universality of the results. In terms of treatment compliance, it is difficult to accurately determine whether patients are strictly following the regimen, and the self-adjustment of treatment may interfere with the evaluation of efficacy. The problem of missing data cannot be ignored, as some patients are lost to follow-up and have incomplete data, and missing key information such as tumor molecular characteristics will affect the accuracy of analysis. The individual difference in radiosensitivity is a potential confounding factor, which may still interfere with the judgment of the effect of the two treatment regimens despite efforts to control the variables. Large-scale cohort and randomized controlled studies are needed to make up for these shortcomings in the future.

Materials and methods

General materials

Total 158 patients with NSCLC admitted to our hospital during January 2020 to December 2022 were picked as the research subjects. The clinical data were retrospectively analyzed, and the patients were then divided into a control group (n = 78, received SCRT) and an observation group (n = 80, received CCRT). The inclusion process of study subjects was shown in Fig. 3. In the control group, the ratio of males to females was 42:3, with ages ranging from 32 to 66 years and an average age of 56.78 ± 3.04 years. The condition persisted for 2 to 9 months, with an average duration of 5.89 ± 1.12 months. Among the observation group, the male-to-female ratio was 42:3, with participants aged 30 to 68 years and an average age of 56.89 ± 3.85 years. The condition lasted between 3 and 10 months, with an average duration of 5.98 ± 1.35 months. There existed no significant difference in general information between the two groups (P > 0.05).

Fig. 3
figure 3

The inclusion process of patients

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Inclusion criteria: (1) patients diagnosed with lung cancer through clinical diagnosis [39] and pathological examination (tumor cells with consistent size, uniform chromatin, indistinct nucleoli, few mitotic images, and visible punctate or focal necrosis were observed under light microscopy); (2) the patient met the clinical indications for radiotherapy and chemotherapy [40]: inoperable NSCLC in stage IIIA, IIIB, IIIC or locally advanced NSCLC (N2, N3, T4), with an Eastern United States Cancer Collaboration Group (ECOG-PS) score of 0–2; (3) patient with Karnofsky functional status score [41] ≥ 60 points; (4) the patient was aged ≥ 18 years old. Exclusion criteria: (1) patients with dysfunction or severe abnormalities of important organs such as the heart, liver, and kidneys; (2) patients with combined immune dysfunction and other primary tumors; (3) patients who could not tolerate radiotherapy and chemotherapy treatment; (4) patients with lung tumor lesions that could not be measured or evaluated through imaging examinations; (5) patients with a history of allergies, especially those who were allergic to radiation therapy or chemotherapy drugs (such as cisplatin, paclitaxel, etc.); (6) patients with mental abnormalities prevented autonomous cooperation with researchers. This study was conducted with the approval of the Hospital Ethics Committee.

Treatment methods

The control group received SCRT treatment. Chemotherapy regimen: 1000 mg/m2 gemcitabine hydrochloride (Shanxi Pude Pharmaceutical Co., Ltd., No. H20213147, specification 0.2 ml: 1.0 g) was intravenously dripped on the 1 st and 8 th days of the chemotherapy cycle. 80–100 mg/m2 cisplatin (Nanjing Pharmaceutical Factory Co., Ltd., No. H20103216, specification 2 ml: 20 mg × 5 tubes) was intravenously dripped on the 1 st and 3rd days of the chemotherapy cycle. After 3 weeks of treatment with the above-mentioned drugs, the treatment was interrupted for one week. Then, the above 4-week (21 days) treatment cycle was repeated, with 21 days being one chemotherapy cycle and a maximum of 4 cycles of treatment. Radiotherapy plan: the patient's lymph nodes and primary lesions were accurately located as treatment targets. 6 MV-X three-dimensional conformal radiotherapy was selected for routine segmented irradiation of patients. The radiation therapy target area was determined according to the standards of the International Committee on Radiation and Measurement, including lymph nodes and primary lesions confirmed by pathology, as well as lymph node areas above 1 cm in the mediastinum. The relevant parameters were set to a dose of 660-70Gy, divided into 30 doses. The dose received by the spinal cord was less than 40 Gy, and the Dmean of both lungs was less than 14–16 Gy with V20 ≤ 28% and V30 ≤ 20%; the V30 of the heart was less than 40% and V40 < 30%. The radiation therapy conducted 5 times per week, with 5 weeks being one radiotherapy cycle, for a total of one treatment cycle.

The observation group received CCRT treatment. The radiotherapy method was the same as that of the control group. Conventional 6 MV-X-ray three-dimensional conformal radiotherapy was performed with a dose of 60-70Gy. Chemotherapy regimens were as follows: chemotherapy was started on the first day of radiotherapy, and 1000 mg/m2 of gemcitabine hydrochloride (Shanxi Pude Pharmaceutical Co., LTD., national license number H20213147, size 0.2 ml:1.0 g) was intravenously infused on the first and eighth day of the chemotherapy cycle. 80–100 mg/m2 of cisplatin (Nanjing Pharmaceutical Factory Co., LTD., National code H20103216, size 2 ml:20 mg × 5) was intravenously infused on the 1 st to 3rd day of the chemotherapy cycle. After 3 weeks of treatment, the above drugs were interrupted for one week, and the above treatment cycle was repeated for 4 weeks (21 days). 21 days was a cycle of chemotherapy, and the maximum treatment cycle was 4 cycles. Chemotherapy was started on the same day as radiotherapy and was synchronized throughout the treatment cycle.

Outcome measures

  1. (1)

    Clinical efficacy: After the completion of the treatment course, the clinical efficacy of the two groups was analyzed through clinical and imaging examinations. Complete relief: patients whose disease symptoms and lesions had completely disappeared and had not recurred within a certain period of time (such as 4 or 6 weeks); partial relief: symptoms had improved, and the longest diameter of the tumor lesion had decreased by ≥ 30% compared to before treatment. No new lesions had appeared for 4 weeks or more; disease stability: the combined longest diameters of the lesions either increased by less than 20% or decreased by less than 30% relative to before treatment. Disease progression: an increase of more than 20% in the total longest diameter of the lesion was observed, along with the development of new lesions. The disease remission rate and disease control rate of two groups of patients were calculated, where the remission rate was the sum of the proportion of patients in complete remission and partial remission; the control rate was the sum of the proportion of remission rate and stable disease patients.

  2. (2)

    A comparison was made between the two groups regarding adverse reactions, focusing on the incidence of leukopenia and hemoglobin reduction. According to the CTCAE grading standard [42], white blood cell abnormalities were classified into five levels: level 0: white blood cell count ≥ 4 × 109/L; Grade I: white blood cell count 3.9–3.0 × 109/L; Grade II: white blood cell count 2.9–2.0 × 109/L; Grade III: white blood cell count 1.9–1.0 × 109/L; Grade IV: white blood cell count < 1.0 × 109/L. According to the CTCAE grading criteria, hemoglobin reduction was divided into five levels: Level 0: hemoglobin ≥ 110 g/L; Grade I: hemoglobin 109–95 g/L; Grade II: hemoglobin 94–80 g/L; Grade III: hemoglobin 79–65 g/L; Grade IV: hemoglobin < 65 g/L.

  3. (3)

    A comparison was made regarding the incidence of radiation pneumonitis: according to the US version guidelines of the Radiation Therapy Oncology Group (RTOG) [43], radiation lung injury was graded and evaluated. Grades 0–IV represented gradually worsening injury severity, while grades ≥ II could be diagnosed as radiation pneumonitis.

  4. (4)

    An analysis was conducted on the lung function levels of two groups: the lung function levels of patients were compared before and after treatment, including the forced expiratory volume in one second (FEV1), forced vital capacity (FVC), and FEV1/FVC indicators before and after treatment. Steps: the lung function tester (purchased from Shanghai Ouqi Electronic Technology Co., Ltd., item number: Spirolab III) was calibrated, and its sensors, flow measurement devices, etc., were checked to ensure normal operation. The measurement process and precautions were explained to the patient. The patients were asked to fast for 2 h, and refrain from smoking, vigorous exercise, and caffeinated beverages for 30 min before the test. The patient should take a sitting position, keeping the body straight and the head tilted back, and securing the chest and waist with a strap. An oral and nasal mask were worn for the patient, ensure sealing. Then, the breathing tube was connected, and an abdominal breathing sensing device was placed. The patients were guided to breathe calmly, then took a deep breath until the total lung volume was reached, and quickly and fully inhale. Then the patient exhaled with maximum force and speed for at least 6 s, observing the changes in the instrument curve to ensure smoothness without interruption. The operation was repeated 3 times, with an interval of 1–2 min each time, and the best results were recorded, including FEV1 FVC、FEV1/FVC.

  5. (5)

    The serum tumor markers were compared between groups: fasting venous blood from patients was collected before and after treatment, and upper layer serum was separated by centrifuge (3000 r/min, 10 min), and kept for following testing. Enzyme linked immunosorbent assay (ELISA) and reagents (Shanghai Kehua Bioengineering Co., Ltd., Approval No. S20010057) were used to strictly detect the levels of carbohydrate antigen 125 (CA125), squamous cell carcinoma antigen (SCC Ag), and cytokeratin 19 fragment antigen 21-1 (CYFRA21-1) in the blood. Steps: the 96-well plate was coated with specific antibodies against the target antigen to ensure that the test antigen could firmly adhere to the surface of the well. The test sample was added to the pre-coated microplate and incubated for a period of time to promote antigen antibody binding. The microplate was rinsed with washing buffer to remove unbound antibodies or other impurities. Horseradish peroxidase (H-radiation pneumonitis) labeled detection antibodies was added to each well and incubated to form antigen antibody complexes. The microplate was rinsed again with washing buffer to remove unbound enzyme labeled antibodies. Substrate solution was added to each well and the enzyme was incubated to catalyze the color change of the substrate. After the color reaction was stopped by termination solution, the absorbance value (OD value) of each well was measured at the specified wavelength using an ELISA reader, and the concentration of the target antigen was calculated.

  6. (6)

    Prognosis: The follow-up was conducted for 2 years until November 31, 2024. The progression-free survival (PFS) and overall survival (OS) time between the two groups were compared. Imaging examinations were regularly conducted to detect changes in tumors. PFS referred to the period from the beginning of treatment to the progression of the disease (such as continuous tumor development, expansion, or the appearance of new lesions) or death due to any factor. OS referred to the time from when a patient was assigned to the treatment group until death occurred for any reason. If the patient was lost to follow-up, the last follow-up time should be recorded. The OSR was the proportion of surviving patients to the total number of cases as of the follow-up deadline.

Statistical analysis

Statistical analysis was conducted using SPSS 24.0. The measurement data that conformed to a normal distribution were represented by (\(\overline{x} \pm s\)), and independent sample t-test was used for inter group comparison. The enumeration data were presented as [cases (%)], and the comparison between groups was analyzed using the χ2 test. Kaplan–Meier survival curve was used to assess the patient's survival status. P < 0.05 was considered as statistically significant.

Availability of data and materials

The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.

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Acknowledgements

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Funding

This work was supported by the following funding: 1. Nanchang Science and Technology Bureau Medical Health Science and Technology support General project (No: 2022-KJZC-029). 2. Science and Technology Project of Jiangxi Provincial Health Commission (No: 202211645).

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  1. Jinbiao Xu and Qiao Ji have contributed equally to this project.

Authors and Affiliations

  1. Departerment of Oncology, Gaoxin Branch of the First Affiliated Hospital of Nanchang University, No. 7889 Changdong Avenue, High-tech Zone, Nanchang, 330000, Jiangxi, China

    Jinbiao Xu, Jianxiong Deng & Feng Yu

  2. Department of Radiation Oncology, Nanchang People’s Hospital, Nanchang, 330000, Jiangxi, China

    Qiao Ji

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Contributions

Jinbiao Xu and Qiao Ji confirmed the authenticity of all the raw data and edited the manuscript, Jinbiao Xu and Jian xiong Deng collected data and processed the data. Qiao Ji and Feng Yu conducted the statistics. Jinbiao Xu and Feng Yu reviewed and revised the article. All authors read and approved the final manuscript.

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Correspondence to Feng Yu.

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This study was approved by The Ethics Committee of Gaoxin Branch of The First Affiliated Hospital of Nanchang University. Written informed consent was obtained from all individual participants included in the study. All procedures performed in studies involving human participants were in accordance with the standards upheld with those of the 1964 Helsinki Declaration and its later amendments for ethical research involving human subjects. The patients participating in the study all agree to publish the research results.

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Xu, J., Ji, Q., Deng, J. et al. Concurrent vs. sequential chemoradiotherapy: a survival boost for lung cancer patients. BioMed Eng OnLine 24, 60 (2025). https://doiorg.publicaciones.saludcastillayleon.es/10.1186/s12938-025-01390-9

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BioMedical Engineering OnLine

ISSN: 1475-925X

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