NSCLC Isotoxic Hypofractionated Radiotherapy (IHR)

Radiotherapy plays an important role in non-small cell lung cancer (NSCLC), and concurrent chemoradiation is considered to be the standard treatment for locally advanced NSCLC. However, due to the patient's physical condition, comorbidities and other reasons, only about 1/3 of patients can receive concurrent chemoradiation. Radiotherapy alone or sequential chemoradiation has become the treatment protocol for most patients. Hypofractionated radiotherapy can be used in NSCLC because it can shorten the over treatment time and may potentially reduce the effect of accelerated repopulation and obtain higher biological effective dose（BED）.So far, the vast majority of radiotherapy prescriptions have given a uniform dose of 60 Gy. This unified prescription dosage approach is completely inconsistent with the concept of precision treatment. The Netherlands MAASTRO put forward the concept of in silico radiotherapy prescription, that is: the normal tissue limits are uniform, such as: V20% ≤ 30%, spinal cord 0> 45Gy, etc., This radiation prescription could reach the limits of the normal tissue of every patient; if no one tissue limits were reached, the highest dose was set up to 79.2 Gy (1.8 Gy, BID). MAASTRO applied this "iso-toxic" radiotherapy prescription and used accelerated hyperfractionation technology so that each patient received the maximum individualized radiation dose as possible. We will integrate this concept with hypofractionated radiotherapy in order to further improve patient survival.

Radiotherapy plays an important role in non-small cell lung cancer (NSCLC), and concurrent chemoradiation is considered to be the standard treatment for locally advanced NSCLC. However, due to the patient's physical condition, comorbidities and other reasons, only about 1/3 of patients can receive concurrent chemoradiation. Radiotherapy alone or sequential chemoradiation has become the treatment protocol for most patients. Hypofractionated radiotherapy can be used in NSCLC because it can shorten the over treatment time and may potentially reduce the effect of accelerated repopulation and obtain higher biological effective dose（BED） So far, the vast majority of radiotherapy prescriptions have given a uniform dose of radiotherapy to all patients, regardless of individual factors such as tumor size, location, and adjacent vital organs, which may cause two consequences: First, small-volume tumors may, not receive enough radiation dose, resulting in a decrease in local control rates. Second, for large volumes of tumors or tumors adjacent to vital organs, even the "so-called standard dose" (60 Gy) may cause serious damage to normal tissues. This unified prescription dosage approach is completely inconsistent with the concept of precision treatment. The Netherlands MAASTRO put forward the concept of in silico radiotherapy prescription, that is: the normal tissue limits are uniform, such as: V20% ≤ 30%, spinal cord 0> 45Gy, etc., and each patient receives a different dose of radiation therapy. This radiation prescription could reach the limits of the normal tissue of every patient; if no one tissue limits were reached, the highest dose was set up to 79.2 Gy (1.8 Gy, BID). MAASTRO applied this "iso-toxic" radiotherapy prescription and used accelerated hyperfractionation technology so that each patient received the maximum individualized radiation dose as .From the model study to the long-term survival results, a series of encouraging results were achieved. The use of an individualized radiotherapy prescription based on iso-toxicity for the treatment of NSCLC in large-segment radiotherapy is expected to achieve: 1. For patients with small tumor volumes and no adjacent to vital organs, a higher radiation dose is given under safe conditions. 2. For patients with larger volumes of tumors or adjacent to vital organs, give safer doses.

1. Hypofractionated radiation: 3Gy/f. 2,Individualized prescriptions for different patients: (1) Spinal cord: 0%>45 Gy, and ≤2 Gy each time Lung: V20≤30%, V5≤65%, MLD≤16Gy Esophagus: highest dose ≤ 72Gy 3. Maximum limit: If the limit of any "A" is not reached, the maximum radiation dose is 72 Gy. The lowest radiation dose: 45Gy.

the normal tissue limits are uniform, such as: V20% ≤ 30%, spinal cord 0> 45Gy, etc., and used hypofractionated radiotherapy technology so that each patient received the maximum individualized radiation dose as possible

Number of participants with treatment-related severe adverse events：Grade IV radiation esophagitis, Grade III radiation esophagitis which results in interruption of radiotherapy for 7 days or more and Grade III or above radiation pneumonitis

Inclusion Criteria: Pathological or cytological diagnosis of non-small cell lung cancer patients, the clinical stage using the eighth edition of American Joint Committee on Cancer（AJCC）, including stage III without resectable or who when SBRT/SABR are not suitable; Age ≥ 18 years; The expected survival period is ≥ 3 months; KPS score ≥ 60; Normal blood count,liver and kidney function ≤ 2.5 times the upper limit of normal; Exclusion Criteria: Serious medical problems require hospitalization, included (but not limited to ): history of pulmonary fibrosis, previous myocardial infarction within 6 months, heart failure grade II and above, uncontrolled heart failure, uncontrolled COPD, uncontrolled diabetes Wait; Esophageal invasion (cT4); Others are not suitable for receiving radiotherapy.