Chemo-immunotherapy Induction Followed by Hypo-radiotherapy in LA-NSCLC(CHIC)

Inclusion Criteria:

* Be able to provide written informed consent and understand and agree to follow the research requirements and evaluation schedule.
* Age \> 18 years at time of study entry
* Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
* Life expectancy of \> 12 weeks
* Histologically- or cytologically-documented NSCLC, in locally advanced (Stage IIB-III-v.8 IASLC), without known EGFR mutations, or ALK and ROS1 rearrangements
* Patients not eligible for surgery
* Main criteria for hypoRT:

  * Residual extranodal mass is less than 7 cm in diameter on computed tomography (CT) at the end of induction immuno-chemotherapy.
  * The longitudinal length of the PTV-esophagus overlap\* is less than 3 cm（\*The PTV-esophagus distance of less than 0.5 cm is considered overlapping）.
  * The transverse PTV-esophagus overlap is less than one-third of esophageal lumen cross-sectional area. If exceed one-third, the longitudinal length of the overlap must be less than 1 cm.
  * Lung dose constraint: Mean lung dose≤14Gy.
* Adequate normal organ and marrow function as defined below:

  * Haemoglobin ≥9.0 g/dL (5.59 mmol/L)
  * Absolute neutrophil count (ANC) 1.5 x 109/L (\> 1500/mm3)
  * Platelet count ≥100 x 109/L (100000/mm3)
  * Serum bilirubin ≤1.5 x institutional upper limit of normal (ULN). This will not apply to patients with confirmed Gilbert's syndrome (persistent or recurrent hyperbilirubinemia that is predominantly unconjugated in the absence of hemolysis or hepatic pathology), who will be allowed only in consultation with their physician.
  * AST (SGOT)/ALT (SGPT) ≤2.5 x institutional upper limit of normal.
  * Adequate renal function defined as normal serum creatinine levels or calculated creatinine clearance (according to Cockroft-Gault or by 24 hour-urine collection).

Cockcroft-Gault formula (Cockcroft and Gault 1976):

Males: Creatinine CL (mL/min) = Weight (kg) x (140 - Age) 72 x serum creatinine (mg/dL) Females: Creatinine CL (mL/min) = Weight (kg) x (140 - Age) x 0.85 72 x serum creatinine (mg/dL).

* Women of childbearing age should take the urine or serum pregnancy test, and the result of which should be negtive within ≤ 72 hours before treatment. For females, who have agreed with contraception from start of investigational drug administration to 5 months after last dose of investigational drug. For males who have agreed with contraception from start of investigational drug administration to 7 months after last dose of investigational drug.
* Patient willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations including follow up.

Exclusion Criteria:

* Previous radiotherapy to the thorax (prior to inclusion), including radiotherapy for breast cancer
* Mixed small cell and non-small cell lung cancer histology
* Patients with severe malnutrition, with body mass index lower than 18.5kg/m2, or PG-SGA score ≥9
* Any active autoimmune disease or history of autoimmune disease (as follows, but not limited to: interstitial pneumonia, uveitis, enteritis, autoimmune hepatitis, pituitritis, vasculitis, nephritis, hyperthyroidism, thyroid dysfunction); Subjects with vitiligo or who have had complete remission from childhood asthma without any intervention after adulthood may be included; Asthma requiring medical intervention with bronchodilators was not included.
* Has a previous radiotherapy, chemotherapy, hormone therapy, surgery, molecular targeted therapy or immune therapy for this malignancy or for any other past malignancy;
* Any condition requiring systemic corticosteroid therapy (prednisone with a dose higher than 10 mg / day or equivalent dose of similar drugs) or other immunosuppressants within 14 days before treatment. （Excluding the following steroid regimens：Local, ophthalmic, intra-articular, nasal and inhaled corticosteroids with minimal systemic absorption；Prophylactic short-term (≤ 7 days) use of corticosteroids (e.g., prevention of contrast media allergy) or for the treatment of non-autoimmune disorders (e.g., delayed hypersensitivity caused by exposure to allergens)
* Live vaccine injection was received in ≤ 4 weeks before treatment
* A history of immunodeficiency, including HIV infection, other acquired or congenital immunodeficiency, or a history of organ or bone marrow implantation that need immunosuppressive medications.
* There are clinical symptoms or diseases of the heart that are not well controlled, such as: 1). heart failure above grade 2 by the Criteria of NYHA; 2). unstable angina pectoris; 3). myocardial infarction occurred within 1 year; 4). Clinically meaningful supraventricular or ventricular arrhythmias require treatment or intervention;
* Has severe infections（CTCAE\>2 grade）within 4 weeks before treatment; basal thoracic imaging indicating active pneumonia, or other infectious situation that need oral or intravenous antibiotic treatment (excluding Prophylactic medication for antibiotics).
* A history of interstitial lung disease, non-infectious pneumonia or uncontrolled disease, including pulmonary fibrosis, acute lung disease, etc.
* Has active pulmonary tuberculosis found by CT imaging; or has active pulmonary tuberculosis less than 1 year before inclusion; or has active pulmonary tuberculosis but without standard treatment over 1 year before inclusion;
* Uncontrolled intercurrent illness including, but not limited to,, active peptic ulcer disease or gastritis, active bleeding diatheses, ongoing or active infection, including any patient known to have evidence of acute or chronic hepatitis B (positive HBV surface antigen (HBsAg) result), hepatitis C, human immunodeficiency virus (HIV) (positive HIV 1/2 antibodies) or tuberculosis (clinical evaluation that includes clinical history, physical examination and radiographic findings, and TB testing in line with local practice), psychiatric illness/social situations that would limit compliance with study requirements or compromise the ability of the patient to give written informed consent. \[Patients with a past or resolved HBV infection (defined as the presence of hepatitis B core antibody \[anti-HBc\] and absence of HBsAg) are eligible. Patients positive for hepatitis C (HCV) antibody are eligible only if polymerase chain reaction is negative for HCV RNA\].
* Female patients who are pregnant or breastfeeding or male or female patients of reproductive potential who are not willing to employ effective birth control from screening to 90 days after the last dose of durvalumab monotherapy.
* Known allergy or hypersensitivity to radiotherapy.
* History of another primary malignancy except for

  * Malignancy treated with curative intent and with no known active disease ≥3 years before the first dose of study drug and of low potential risk for recurrence
  * Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease
  * Adequately treated carcinoma in situ without evidence of disease, e.g. cervical cancer in situ
  * Superficial bladder cancer without evidence of disease
* Judgment by the investigator that the patient is unsuitable to participate in the study and the patient is unlikely to comply with study procedures, restrictions and requirements.