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Patients with stage III non-small-cell lung cancer initially evaluated as unresectable are selected for the program, who are remained unresectable after 2-4 cycles of conversion chemotherapy combined with immune checkpoint inhibitors. Investigators will stratify the treatment according to different performance status scores and radiotherapy plan bi-lung receptor volume to evaluate the safety and efficacy of immunotherapy followed by combined radiotherapy.
This is a prospective, real-world cohort study, which aimed to evaluate the safety and efficacy of immunotherapy followed by combined radiotherapy. Participants will be selected and entered into three different cohorts according to different performance status(PS) scores and radiotherapy schedules based on the amount of bilateral lungs treated. Cohort A: PS=0-1 and bilateral lung V20≤20%, mean lung dose(MLD)≤11 gray(Gy), radiotherapy and immunotherapy, followed by immunotherapy for up to 1 year; Cohort B: PS=0-1 and 20%\
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Cohort A: concurrent chemoradiotherapy combined with ICIs | Experimental | For performance status (PS)=0-1 and both lungs V20≤20%, mean lung dose (MLD)≤11 gray(Gy), then the patient should be treated with concurrent chemo-radiotherapy and immunotherapy, and immunotherapy should be given after chemo-radiotherapy to maintain up to 1 year. Participants eligible for enrollment will receive radiotherapy within 8 weeks of the end of chemotherapy combined with Immune checkpoint inhibitors (ICIs) at a radical prescribed dose of 60 Gy ± 10% at 2 Gy once daily for 5 days per week. The chemotherapy regimen will be cisplatin at a dose of 25 mg/m2 once a week for 5-6 cycles. Marketed programmed cell death 1 (PD-1) or programmed cell death L1 (PD-L1) inhibitors are chosen as immunotherapy agents. Immunotherapy will be given every 3 weeks, with no more than 3 cycles of immunotherapy during radiotherapy. The dosage is recommended according to the drug insert. |
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| Cohort B: concurrent radiotherapy combined with ICIs | Experimental | For PS=0-1 and 20%\ |
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| Cohort C: radiotherapy | Experimental |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| radiotherapy | Radiation | Radiotherapy techniques: Volumetric-modulated arc therapy (VMAT) and image guided radiotherapy (IGRT). Radiotherapy dose: Radical prescription dose of 60 gray (Gy) ± 10%, 2 Gy per session, once a day, 5 days a week. |
| Measure | Description | Time Frame |
|---|---|---|
| radiation pneumonitis | Incidence of grade 2 or higher radiation pneumonitis. | Within 6 months after radiation therapy |
| Measure | Description | Time Frame |
|---|---|---|
| progression-free survival | Time from enrolment to disease progression or death from any cause or censored at the last follow-up. | 2 years |
| overall survival | Time from enrolment to death or censored at the last follow-up. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Xu Yujin, PhD | Contact | 86-13858037993 | xuyj@zjcc.org.cn |
| Name | Affiliation | Role |
|---|---|---|
| Xu Yujin, PhD | Zhejiang Cancer Hospital | Study Director |
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| ID | Term |
|---|---|
| D002289 | Carcinoma, Non-Small-Cell Lung |
| D017564 | Radiation Pneumonitis |
| ID | Term |
|---|---|
| D002283 | Carcinoma, Bronchogenic |
| D001984 | Bronchial Neoplasms |
| D008175 | Lung Neoplasms |
| D012142 | Respiratory Tract Neoplasms |
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| ID | Term |
|---|---|
| D011878 | Radiotherapy |
| D002945 | Cisplatin |
| D007167 | Immunotherapy |
| D000077594 | Nivolumab |
| C000594389 | atezolizumab |
| C000613593 | durvalumab |
| C582435 | pembrolizumab |
| C000707970 | tislelizumab |
| C000723018 | sugemalimab |
| C000632826 | sintilimab |
| C000631724 | camrelizumab |
| D000276 | Adjuvants, Immunologic |
| ID | Term |
|---|---|
| D013812 | Therapeutics |
| D017606 | Chlorine Compounds |
| D007287 | Inorganic Chemicals |
| D017672 | Nitrogen Compounds |
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For PS=2 or 25%\
|
| Platinum-Based Drug | Drug | Cisplatin 25 mg/m2 once per week for a total of 5-6 cycles. For participants who have not completed 4 cycles of conversion chemotherapy in combination with immunotherapy, the original chemotherapy regimen may also be used, with the total number of chemotherapy cycles not exceeding 6 cycles. |
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| Immunotherapy | Drug | Concurrent programmed cell death 1 (PD-1) or programmed cell death L1 (PD-L1) inhibitors every 3 weeks during radiotherapy and no more than 3 doses during the course of radiotherapy. |
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| Immunotherapeutic Agent | Drug | All participants will be evaluated within 1-42 days after receiving radiation (chemotherapy). If disease progression does not occur, adjuvant therapy with a PD-1 or PD-L1 inhibitor is continued until disease progression up to 1 year. |
|
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| 3 years |
| D013899 |
| Thoracic Neoplasms |
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
| D008171 | Lung Diseases |
| D012140 | Respiratory Tract Diseases |
| D017563 | Lung Diseases, Interstitial |
| D055370 | Lung Injury |
| D011832 | Radiation Injuries |
| D014947 | Wounds and Injuries |
| D017671 |
| Platinum Compounds |
| D056747 | Immunomodulation |
| D001691 | Biological Therapy |
| D061067 | Antibodies, Monoclonal, Humanized |
| D000911 | Antibodies, Monoclonal |
| D000906 | Antibodies |
| D007136 | Immunoglobulins |
| D007162 | Immunoproteins |
| D001798 | Blood Proteins |
| D011506 | Proteins |
| D000602 | Amino Acids, Peptides, and Proteins |
| D012712 | Serum Globulins |
| D005916 | Globulins |
| D007155 | Immunologic Factors |
| D045505 | Physiological Effects of Drugs |
| D020228 | Pharmacologic Actions |
| D020164 | Chemical Actions and Uses |