Radiotherapy for lung cancer includes radical radiotherapy, palliative radiotherapy, adjuvant radiotherapy and prophylactic radiotherapy.

Principles of radiotherapy

(1) Radical radiotherapy: for patients with a Canovskite score ≥70, including early-stage NSCLC (stereotactic radiotherapy), unresectable locally advanced NSCLC and limited-stage SCLC that are inoperable due to medical or (and) personal factors.
(2) Palliative radiotherapy: It is indicated for the treatment of advanced lung cancer primary and metastatic lesions in a decompensated manner. For patients with surgical resection of single brain metastasis of NSCLC, observation or local radiotherapy in the operation area can be performed; for patients with single metastasis or oligometastasis of NSCLC, stereotactic radiotherapy can be considered; for patients with extensive stage SCLC, chest radiotherapy is feasible.
(3) Adjuvant radiotherapy: It is suitable for patients with positive preoperative radiotherapy and postoperative radiotherapy margins (R1 and R2).
(3) Adjuvant radiotherapy: for patients with preoperative radiotherapy, positive postoperative radiotherapy margins (R1 and R2), patients with inadequate surgical exploration, or patients with close surgical margins; for patients with positive postoperative pN2, participation in clinical studies of postoperative radiotherapy is encouraged, and postoperative radiotherapy is recommended in the NCCN guidelines (2021.v4) based on the results of non-randomized studies.
(4) Design of postoperative radiotherapy: The patient’s surgical pathology report and surgical records should be consulted.
(5) After complete remission with chemotherapy and radical radiotherapy in the limited stage of SCLC, prophylactic whole-brain radiotherapy should be administered; for patients with effective chemotherapy in the extensive stage, prophylactic whole-brain radiotherapy or close follow-up with brain MRI can be chosen.
(6) Application of synchronous radiotherapy: Patients with inoperable locally advanced NSCLC are recommended to undergo synchronous radiotherapy, or sequential radiotherapy if they cannot tolerate it. The recommended regimen for synchronous chemotherapy is EP (pegylated glycosides + cisplatin) or TC (paclitaxel + carboplatin), and pemetrexed combined with cisplatin or carboplatin can also be one of the preferred regimens for synchronous or sequential administration in non-squamous cell NSCLC.
(7) The immune checkpoint inhibitor dulvalizumab (PD-L1 monoclonal antibody) has been shown to significantly prolong overall survival and progression-free survival in locally advanced NSCLC after consolidation therapy with concurrent radiotherapy (PACIFIC study, Class 1 evidence); PD-L1 expression is not mandatory, but there may be no significant benefit in overall survival for those with negative PD-L1 expression. And the incidence of grade 3 to 4 serious adverse reactions (including grade 3 and higher pneumonia) was not statistically significant from the control group.
(8) Patients receiving radiotherapy/chemotherapy have an increased likelihood of potential adverse reactions and should be informed prior to treatment. When designing and administering radiotherapy, care should be taken to protect the lungs, heart, esophagus and spinal cord. Unplanned interruptions of radiotherapy due to improper management of adverse effects should be avoided as much as possible during treatment.
(9) Advanced radiotherapy techniques such as 3D conformal radiotherapy, intensity-modulated radiotherapy or image-guided radiotherapy should be used, and stereotactic body radiation therapy (SBRT) is recommended under the condition of excellent radiation physics.
(10) When outlining the target area for radiotherapy, enhanced CT localization or PET localization is recommended. The tumor target area can be outlined in the enhanced CT localization image with reference to the tumor bio-image of PET.
(11) Patients receiving radiotherapy or radiochemotherapy should be given adequate monitoring and supportive therapy during treatment breaks.

Indications for radiotherapy for NSCLC

Radiotherapy can be used for the radical treatment of patients with early-stage NSCLC who are medically inoperable or refuse surgery, for the preoperative and postoperative adjuvant treatment of operable patients, for the local treatment of patients with unresectable locally advanced lesions, and for the palliative treatment of patients with advanced incurable disease.
SBRT is recommended for patients with stage I NSCLC who are medically unsuitable for surgery or who refuse surgery. The tolerated dose of radiotherapy to organ tissues such as spinal cord, esophagus, trachea, heart, chest wall and brachial plexus nerve should be carefully evaluated.
For patients with surgically treated NSCLC who have negative postoperative surgical margins and positive mediastinal lymph nodes (pN2 stage), postoperative radiotherapy may be added to the usual postoperative adjuvant chemotherapy, with a recommended sequence of chemotherapy followed by sequential radiotherapy. For those with significant residual (R2 excision), simultaneous postoperative radiotherapy is recommended if physically possible.
For patients with stage II-III NSCLC who cannot undergo surgery due to medical reasons, conformal radiotherapy or intensity-modulated radiotherapy combined with concurrent chemotherapy should be given if physically possible. For patients with clinical hope of cure, a more conformal radiotherapy plan and more aggressive supportive therapy should be used to minimize the interruption of treatment time or reduction of treatment dose when receiving radiotherapy or concurrent radiotherapy. For patients with stage IV NSCLC with extensive metastases, some patients may receive radiation therapy to both primary and metastatic sites for palliative reduction. When the benefit of systemic therapy is evident in patients with oligometastases, SBRT techniques may be considered for treatment of residual primary and/or oligometastases for potential curative effect.

Indications for radiotherapy in SCLC

A combination of radiotherapy and chemotherapy is the standard of care for limited-stage SCLC. Patients with limited-stage SCLC are recommended to have synchronized chemoradiotherapy with initial treatment or 2 cycles of induction chemotherapy followed by synchronized chemoradiotherapy. If the patient cannot tolerate it, sequential chemoradiotherapy is also available. Radiation therapy for limited-stage SCLC should be started as early as possible if the disease permits, and may be considered in conjunction with the first or second cycle of chemotherapy. If the lesion is large and the risk of lung injury from radiation therapy is too high, concurrent radiation therapy with the third cycle of chemotherapy may also be considered.
For patients with extensive SCLC, the addition of chest radiotherapy after control of distant metastases with chemotherapy may also improve tumor control and prolong survival; there is no evidence from prospective randomized controlled clinical trials to further improve the efficacy of chest radiotherapy in patients treated with chemotherapy combined with immunotherapy; participation in clinical studies is encouraged.

Preventive Brain Irradiation

Prophylactic brain irradiation is recommended for patients with limited-stage SCLC after complete remission of the intrathoracic lesion and for patients who achieve partial remission. Prophylactic brain irradiation may also reduce the risk of brain metastases in SCLC when chemotherapy is effective in extensive SCLC. The recommended time for prophylactic brain irradiation is approximately 3 weeks after the completion of all chemoradiotherapy and should be preceded by brain-enhanced MRI to rule out brain metastases.
The decision for whole brain prophylaxis in extensive SCLC should be fully discussed between the physician and the patient, weighing the pros and cons of each patient’s case.

Oligometastatic Stage IV Patients

Definitions are not uniform; no more than 3 metastatic organs, no more than 5 metastatic lesions, and the feasibility of radical therapy are considered important factors in defining oligometastatic status. If systemic therapy is effective (chemotherapy, targeted therapy, etc.), aggressive local therapy (SBRT, surgery, etc.) targeting the residual primary site and/or oligometastases may prolong disease control and patient survival, with potentially curative results. Due to the lack of high-level evidence, consolidation of local therapy after oligometastatic stage IV patients should be decided through MDT discussions and participation in clinical studies is recommended.

Palliative radiotherapy for patients with advanced lung cancerThe primary goal of palliative radiotherapy for patients with advanced lung cancer is to address local compression symptoms due to primary or metastatic foci, pain due to bone metastases, and neurologic symptoms due to brain metastases. The use of large fractionated irradiation techniques can be considered for these patients to make treatment more accessible and to provide more rapid symptom relief.

Effectiveness of treatment

The recent efficacy of radiation therapy was evaluated according to WHO criteria for evaluating the efficacy of solid tumors.

Protection

As far as possible, advanced radiotherapy techniques should be used to protect the lung, heart, esophagus, and spinal cord to avoid serious radiation injury. Acute radiation lung injury is based on the International Collaborative Group on Radiation Therapy for Oncology (ICRG) grading criteria for acute radiation injury.