Lung cancer is currently one of the most common malignancies, with 219,440 new lung cancer cases and 159,390 deaths in the United States in 2009, making it the leading cancer killer (Jemal et al. 2009). Recent data from the International Agency for Research on Cancer (IARC) show that there were 1.6 million new lung cancer cases worldwide in 2008 (1.38 million men and 950,000 women) and a total of 1.38 million deaths from lung cancer in 2010 (950,000 men and 430,000 women). Therefore, lung cancer is a huge problem and a serious challenge for the World Health Organization (IARC 2010). Much time, effort, and financial resources have been spent to optimize its treatment. In the last decade, new diagnostic methods have emerged, including new molecular oncology methods such as positron emission tomography (PET) (in combination with CT scans), which is now widely used for the diagnosis and staging of lung cancer (Vanuytsel et al. 2000; Videtic et al. 2008), and for optimizing radiation treatment planning ( Nestle et al. 1999, 2006; Faria et al. 2008; Schaefer et al. 2008; MacManus et al. 2009; Grgic et al. 2009; Hanna et al. 2010; Riegel et al. 2010; Wu et al. 2010). In the field of therapeutics, innovative approaches are mainly used. In the therapeutic field, the main innovative approaches are televised thoracoscopic surgery (VATS), new precision radiotherapy methods (3D conformal radiotherapy, intensity-modulated radiotherapy, stereotactic radiotherapy) and new chemotherapeutic agents (third-generation cytotoxic drugs, targeted drugs). These approaches have made the diagnosis and treatment of lung cancer more effective, but there are still some problems, especially since only a small percentage of lung cancer patients are detected early enough to have a chance of surgical cure. The vast majority of patients with non-small cell lung cancer and almost all patients with small cell lung cancer are already lost to surgery by the time they are detected, and for these patients, radiotherapy and/or chemotherapy, monotherapy or combination therapy has become the mainstay of treatment over the past 20 years and is widely used worldwide. Even with new biological and technological advances, the diagnosis and treatment of lung cancer has not made a qualitative leap forward, and recurrence remains the main event after lung cancer treatment, regardless of histology (non-small cell lung cancer or small cell lung cancer), stage (early, locally advanced or advanced metastatic), initial treatment (surgery, radiotherapy, chemotherapy or combination therapy). Many reports show recurrence rapidly after initial treatment of lung cancer or treatment failure a few years later. All causes of recurrence fall into three broad categories, local (e.g., lung parenchyma, bronchial stump, or chest wall) recurrence, regional (e.g., mediastinal lymph nodes) recurrence, and distant metastases (brain, liver, adrenal gland, bone, or contralateral lung). Multiple recurrences may occur in the same patient, and when they do, they are fatal events with no effective treatment. In addition, relapses lead to the development of many clinical symptoms requiring further symptomatic supportive therapy, along with a dramatic decrease in quality of life and a decrease in the treatment gain ratio. Recurrences that occur solely within the lung parenchyma (ipsilateral or contralateral lung) should be treated differently from recurrences within the treated lung parenchyma and heterochronic second primary lung tumors. Heterochronic second primary lung cancer arises after treatment of the primary lung cancer and has specific diagnostic criteria to distinguish it from recurrent or metastatic lung cancer (Martini and Melamed 1975). The second primary tumor has the following characteristics: (I) histologically different or (II) histologically identical to the primary lung cancer but (a) at least 2 years before the primary tumor, (b) the second tumor originates from the primary cancer or (c) the second tumor is located in a different lobe or in the contralateral lung, but without lymphovascular thrombosis and extrapulmonary metastasis at the time of diagnosis. Although the discussion of second primary tumors is not addressed in this article, studies of early-stage (stage I-II) non-small cell lung cancer (Jeremic et al. 2001) and stage III non-small cell lung cancer (Kawaguchi et al. 2006) have found an increased risk of developing second primary lung cancer over time in lung cancer survivors. Radiotherapy also plays an important role in the treatment of second primary lung cancer (Jeremic et al. 2001). The primary question is simple: to treat or not to treat? This question seems a bit outdated nowadays, especially in Western countries, where prolonging the life of the patient is the first priority. Recently Hung et al. (2009) reaffirmed the superiority of aggressive treatment over supportive therapy alone. The next question is the use of radical or palliative treatment? More often radical approaches will be chosen, especially surgery and radiotherapy. Many studies have been unable to obtain prognostic indicators that contribute to treatment decisions due to small sample sizes, yet post-recurrence disease stage and physical status influence the choice of treatment modality. Lung cancer recurrence can occur after any treatment modality (surgery, radiation and chemotherapy) or combination, and likewise, any of the above treatments can treat lung cancer recurrence. Whether to consider surgery (reoperation) for recurrent lung cancer is a major factor, along with the presence of other recurrent foci and no concomitant disease. In addition, the site and stage of tumor recurrence play an important role in treatment decisions. A series of large surgical studies have been performed (Gabler and Liebig 1980; Dartevelle and Khalif 1985; Watanabe et al. 1992; Voltolini et al. 2000) in more than 6000 patients with local recurrence, with 1%-1.7% of patients undergoing radical surgery. The majority of reoperated patients were intrapulmonary recurrences. The majority of reoperated patients have a poor prognosis, with a 2-year survival rate of only 23% (Pairolero et al. 1984) and a median survival time of 7-26 months (Becker et al. 1990; Lesser et al. 1997; Voltolini et al. 2000; Westeel et al. 2000). The most recent small sample study (n = 12) reported a 5-year survival rate of 15.5% (Voltolini et al. 2000). Recurrent lung cancer with earlier staging has higher local control and overall survival rates after total lung resection, although cases including second primary lung cancer have 5-year survival rates of approximately 50% for stage I and 40% for stage II (Regnard et al. 1999). and 17.6 %, respectively. Studies have shown that survival rates for patients with local recurrence who undergo radical surgery are better than those who undergo radiotherapy and/or chemotherapy and even better than those who do not undergo any treatment. However, survival time after treatment for patients with local recurrence alone was not significantly different from patients with both local recurrence and distant metastases. Although studies have used newer treatment strategies including better follow-up procedures and optional treatment modalities, the results obtained are still unsatisfactory. In recent years, new treatment concepts have emerged, such as surgical modalities for patients who have relapsed after prior radiotherapy or stereotactic radiation therapy, and Bauman et al. (2008) reported that 24 patients who had relapsed after radiotherapy (22 of which were treated with concurrent radiotherapy) were treated surgically with a median survival time of 30 months and a 3-year survival rate of 47%. Two recent case reports from Japan (Suzuki et al. 2007; Neri et al. 2009) showed that patients with stage I non-small cell lung cancer who underwent lobectomy for recurrence after three-dimensional conformal radiotherapy or stereotactic radiation therapy had a tumor-free survival time of more than 12 months. Radiotherapy can be used to treat local or regional recurrent lung cancer at various sites within the thoracic cavity after surgery. Local or regional recurrences within the thoracic cavity are classified as chest wall/pleura, lung parenchyma, bronchial stump and mediastinal lymph node recurrences, singly or in combination. Many reports have shown its effectiveness (Green and Kern 1978; Kopelson and Choi 1980; Law et al. 1982; Shaw et al. 1992; Curran et al. 1992; Yano et al. 1994; Leung et al. 1995; Emami et al. 1997; Kagami et al. 1998; Kono et al. 1998; Jeremic et al. 1999a, b). These studies show that, as with the site of recurrence, dose intensity, especially high dose, has an important effect on treatment outcome. Jeremic and Bamberg (2002) analyzed the literature on recurrences of bronchial stumps only without recurrences elsewhere in the chest and found a median survival time of nearly 28.5 months and a 5-year survival rate of 31.5%. This study clarifies that external irradiation may be a treatment option for this group of recurrent patients. In Jeremic et al.’s (1999a, b) a small subgroup study of early (e.g., stage I: T2N0) bronchial stump recurrence (n = 7), the use of high-dose external irradiation (≥60 Gy) in a sample of only 7 cases of early (T2N0) bronchial stump recurrence resulted in a 5-year survival rate of 57%, almost approaching the outcome of surgery alone after the first diagnosis of non-small cell lung cancer ( Mountain 1986; Naruke et al. 1988). An interesting and unexplained phenomenon is that this survival rate is almost better than that of the first treatment with high-dose conventional or hyper-segmented irradiation for NSCLC of the same time (Ono et al. 1991; Morita et al. 1997; Jeremic et al. 1997; Sibley et al. 1998; Hayakawa et al. 1999; Jeremic et al. 1999a, b).The results of Law et al. (1982), who studied extensive recurrence of trachea and bronchi, also further support the effectiveness of external irradiation in the treatment of recurrence of bronchial stumps. Patients had a median survival time of 19 months, with 1-year and 3-year survival rates of 75% and 12.5%, respectively. The results suggest that despite extensive lesions, the disease can still benefit from radiation therapy as long as it remains localized (no lymph node metastases). Once the stump is combined with other sites of recurrence, such as regional lymph nodes, there is an immediate decrease in survival (Curran et al. 1992; Jeremic et al. 1999a, b; Kagami et al. 1998; Kono et al. 1998). External irradiation has also been used to treat recurrent intrathoracic local or regional lung cancer, especially non-small cell lung cancer, that has received prior radiotherapy. To date, only nine English-language publications have reported treatment outcomes in 249 patients. Although it has been reported in the literature that radiotherapy can be used for re-treatment of thoracic disease, it remains unclear exactly what proportion of patients who previously received radiotherapy to the chest can be re-treated during the natural course of the disease.Estall et al. (2007) studied patients with lung cancer who received multiple radiotherapy treatments and although the expected rate of radiotherapy use at first treatment was 76% (Delaney et al. 2003), the The actual rate was 52%. The first course of radiotherapy was used in the majority of cases with limited intrathoracic disease (79%), with 22% and 21% of patients treated with the second and third courses of radiotherapy, respectively. The increase in the number of treatment courses, the shortening of the time interval between courses, and the same decrease in the total dose as well as in the number of fractions, reflect the deterioration in the physical status and prognosis of patients with end-stage disease. Although these data help to refine the chest tumor treatment paradigm, the study covered only two years (1993, 1996) and did not extend the study period further. In addition, different regions/countries/institutes have different rates of first and recourse radiotherapy for lung cancer, but there are no similar studies in other regions/institutes to provide more detailed data. Some argue that the application of recourse radiotherapy is challenging. First, there are very few data to confirm the efficacy of recourse radiotherapy, and it is difficult to determine the dose and duration of treatment to achieve radical or palliative treatment, while not ignoring the toxic effects caused by recourse radiotherapy, especially with previous high doses of radical radiotherapy. However, early studies reported the feasibility and effectiveness of recurrent lung cancer recourse radiotherapy (Green and Melbye 1982; Jackson and Ball 1987; Montebello et al. 1993). These retrospective studies were biased toward cases of recurrence after surgery and metastatic or second primary lung cancer after postoperative adjuvant radiotherapy. Few patients received a third course of radiotherapy (second course of re-radiotherapy). The first course of radiotherapy provides more or less prophylactic irradiation to uninvolved lymph nodes, while the treatment target is clearly limited to the visible recurrence area with a safety boundary of 1-2 cm (Green and Melbye 1982; Jackson and Ball 1987; Montebello et al. 1993; Gressen et al. 2000; Okamoto et al. 2002). To prevent excessive toxic reactions, especially in the lung and spinal cord, the total dose and extent of re-course radiation therapy should be controlled. In 2000, Gressen et al. (2000) reviewed such reports, and the rates of control of hemoptysis, cough, dyspnea, and chest pain were 83%, 65%, 60%, and 64%, respectively, with a lower-than-expected complication rate of 5% (Green and Melbye 1982; Jackson and Ball 1982). The complication rate from recourse radiotherapy was lower than expected, with only 5% (Green and Melbye 1982; Jackson and Ball 1987; Montebello et al. 1993; Gressen et al. 2000; Okamoto et al. 2002). The most common complication is radiation pneumonia with an incidence of 3%, and radiation myelopathy and rib fractures are rare. A higher incidence of radiation pneumonia was reported in a recent study (Okamoto et al. 2002), which conducted a recourse to radiation therapy in symptomatic and asymptomatic patients, with grade 2 (moderate) radiation pneumonia after receiving cumulative doses of 12-150 Gy. This allowed the investigators the opportunity to use higher doses of irradiation, with patients receiving a median irradiation dose of 45 Gy and a 75% symptom remission rate compared to a mean dose of 30 Gy in previous studies (Green and Melbye 1982; Jackson and Ball 1987; Montebello et al. 1993; Gressen et al . 2000), the symptom relief rate was 48%-72%. This implies that high doses may lead to high remission rates without increasing the incidence of severe (≥3) radiation pneumonia, and that the study had a median survival time of 8 months and a 2-year survival rate of 27%, approaching the effect of radical and high-dose therapy, with a median survival time of 15 months and a 2-year survival rate of 51%. This compares with a median survival time of 5 months in earlier studies (Green and Melbye 1982; Jackson and Ball 1987; Gressen et al. 2000). In addition, the study found no difference in outcome between patients under and over 70 years of age (Gressen et al. 2000), implying that external irradiation has a broader indication in recurrent lung cancer, especially when palliative treatment or the occurrence of serious long-term side effects can be ignored. , completed in one week. The median survival time was 5.6 months, with 71% of patients achieving partial or complete remission of one or more symptoms. The remission rates for dyspnea, hemoptysis, and cough were 35%, 100%, and 67%, respectively. 45% of patients had increased KPS scores after treatment and had symptom remission for up to 4 months. In contrast to the study by Kramer et al. (2004), Tada et al. (2005) used radical treatment, with 19 patients with stage III non-small cell lung cancer receiving 50 Gy/25F, 1 irradiation/day, one receiving 60 Gy/30F, 1 irradiation/day, and five patients not completing the prescribed recourse irradiation dose. The time interval between the first course of radiotherapy and the recourse was 5-60 months (median 16 months). The mean field size for the recourse was 64 cm2 (30-204 cm2). The resulting overall remission rate was 43%, with 1- and 2-year survival rates of 26% and 11%, respectively, and a median survival time of 7.1 months. An effect of physical status on survival time was found, with survival times of 12.6 months (PS 0C1), 7.1 months (PS 2) and 1.1 months (PS 3) in each group, respectively. Fourteen patients completed the prescribed dose of irradiation, with a median survival time of 10.5 months. All but one patient with chest pain had symptomatic improvement, one patient developed 3rd degree radiation pneumonia, and two patients developed 2nd degree esophagitis. 2003 Wu et al. (2003) reported for the first time the results of a prospective phase ICII clinical study of patients with locally recurrent lung cancer undergoing re-course radiotherapy after external irradiation. A total of 23 patients, aged 43-79 years, with a median age of 68 years, 9 with squamous carcinoma, 7 with adenocarcinoma, and 7 with small cell carcinoma were enrolled in the study. The original stage II was 7 cases and stage III was 16 cases. The interval between the first course of radiotherapy and recurrence ranged from 6 to 42 months (median 13 months). The median total dose of the first course of radiotherapy was 66 Gy (30-78 Gy), and the re-course of radiotherapy was performed using the three-dimensional conformal technique with conventional segmentation, and the target area was mainly the visible recurrence area with a median total dose of 51 Gy (46C60 Gy). After the recourse radiotherapy, the median survival time was 14 months, the 2-year survival rate was 21%, and the 2-year local progression-free survival rate was 42%. 1-2 degree esophagitis occurred in 9% of patients, 1-2 degree pneumonia occurred in 22% of patients, and no toxic reaction of degree 3 or higher occurred during the follow-up period (median follow-up time after the end of recourse radiotherapy was 15 months), 17 cases (74%) had 0-1 degree distant toxicity, and 6 cases (26%) Pulmonary fibrosis was detected on CT, with corresponding symptoms (3rd degree) in 2 of the patients. This study uses a new and widely used conformal technique that deserves further extension for patients with localized regional recurrence and can disregard the effect of the first course of radiotherapy, but long-term toxicity requires longer observation before conclusions can be obtained. In recent years, the use of highly precise radiotherapy techniques for the treatment of non-small cell lung cancer has been reported for the first time. poltinnikov et al. (2005) treated 17 patients with recurrence after radiotherapy for the first time by large segmentation stereotactic technique, and all patients were treated for the first time with simultaneous radiotherapy at a median dose of 52 Gy (50-66 Gy). The median time interval between the completion of the first course of radiotherapy and the start of the second course of radiotherapy was 13 months (2-39 months). The median total dose of the large fraction was 32 Gy (4-42 Gy) and the median fraction dose was 4 Gy (2.5-4.2 Gy), with 3-5 irradiations per week. 5 patients underwent concurrent chemotherapy, 5 patients (29%) had imaging-confirmed tumor remission, 5 patients (29%) had stable disease, and the median survival time after the recourse was 5.5 months (2.5-30 months). 11/13 patients ( 85%) patients had symptomatic remission and 2 patients (15%) had no symptomatic remission, and no side effects of 3rd degree or higher were observed in the study. In 2008, two other publications also reported the results of using stereotactic radiotherapy for recurrent NSCLC. Chang et al. (2008) used a 4-dimensional CT-based radiotherapy program to treat 14 patients with isolated recurrent tumors at a dose of 40-50 Gy who had received previous radical radiotherapy, or combined chemotherapy and surgery. At a median follow-up of 17 months (6-40 months), the local control rate in the treated area irradiated with 50 Gy was 100%, with three (21%) patients developing mediastinal lymph node metastases, five (36%) developing distant metastases, and four (29%) developing second-degree radiation pneumonitis.Coon et al. (2008) reported a similar technique of fractionated stereotactic radiation therapy with new irradiation technique CyberKnife, enrolling 12 recurrent cases with a total dose of 60 Gy in 3 fractions, and using PET/CT to outline the tumor area in most patients. All patients were followed up for disease by CT or PET/CT. The results showed an overall remission rate of 75%, stable disease in 17% of patients, local recurrence after 7 months in 1 (8%) patient, local or regional recurrence or distant metastases in 9 (75%) patients, and a median time to disease progression of 3 months (2-7 months). The median follow-up was 11 months, with a local control rate of 92% and an overall survival rate of 67%. Figure 1 shows the CyberKnife dose distribution. 2008 Zimmermann et al. (Zimmermann et al. 2008) reported a summary of the progress of the study, and the full text is to be expected. These data shed light on the application of large split stereotactic recourse radiation therapy. Beavis et al. (2005) reported for the first time the role of another radiotherapy technique, beam intensity modulated radiotherapy (IMRT), in the recourse treatment of non-small cell lung cancer. Although the intensity-modulated radiotherapy technique has a similar dose distribution for the organ at risk compared to conventional radiotherapy techniques, the target area dose distribution, IMRT, is superior. Due to the superiority of intensity-modulated radiotherapy (e.g., the site and shape of the tumor are equally suitable for recourse radiotherapy), its application is becoming more widespread and will play an important role in the recourse radiotherapy of lung cancer. Recently, Cetingoz et al. (2009) reported the largest case study to date of 38 non-small cell lung cancer patients treated with recourse external irradiation, the majority (81%) due to the presence of adverse prognostic factors such as advanced disease, poor physical status, significant weight loss, and previous palliative radiotherapy. The median interval between the first course of radiotherapy and the second course of radiotherapy was only 8 months (1-42 months), and the second course of radiotherapy was for palliative purposes. The median total dose of recourse radiotherapy was 25 Gy (5-30 Gy), the median number of fractions was 10 (1-10), the median fractional dose was 3 Gy (2-10 Gy), and the median overall survival time (calculated from the first course of radiotherapy) was 13.5 months (4-65 months), while the median survival time after recourse radiotherapy was 3 months (0-65 months). The survival rates were 57.8% at 1 year and 28.8% at 2 years after disease diagnosis, and 8.7% at 1 year and 5.8% at 2 years after recourse to radiotherapy. 80% of patients had symptomatic improvement, with relief of hemoptysis, cough, dyspnea and chest pain at 86%, 77%, 69% and 60%, respectively. Survival time was longer for those who received a second course of radiotherapy at intervals of 35 weeks or more than those who received a second course of radiotherapy at intervals of 35 weeks or less. Only one patient developed 3rd degree esophagitis. Figure 2 shows one patient with routine palliative recourse radiotherapy. Taking into account the current relevant literature, especially the recent studies using highly precise radiotherapy planning and advanced radiotherapy techniques, the following issues should still be considered: 1. the large differences in irradiation parameters due to the use of different irradiation techniques, especially the differences in total irradiation dose, fractionated dose and prescribed dose, and the question of whether the dose inhomogeneity is corrected; 2. the current trend is that the external tumor radiation boundary It is not known whether this is set for a specific recurrent tumor or is a routine technical requirement; 3. There is a trend to apply different toxicity scoring systems to report toxic events during and after recourse radiotherapy; 4. Recent studies have described in detail the time interval between the first and recourse radiotherapy (Okamoto et al. 2002; Wu et al. 2003; Tada et al. 2005; Poltinnikov et al. 2005; Cetingoz et al. 2009), but not every study has described it (Chang et al. 2008; Coon et al. 2008). Studies of the time interval between the first course of radiotherapy and the second course of radiotherapy are important for understanding the natural course of disease, potential prognostic factors, and reducing the severity of toxic effects expected to occur between exposures. In various studies, recourse radiotherapy started as early as 1-6 months after the first course and as late as 39-87 months, with a median value of 13-16 months (Wu et al. 2003; Tada et al. 2005; Poltinnikov et al. 2005), while Cetingoz et al. (2009) reported 8.5 months and Okamoto et al. 2002) reported 23 months. The importance of studies to determine the time interval between the first course of radiotherapy and the second course of radiotherapy comes from the results of Tada et al. (2005), where, in addition to physical status, the time interval between irradiation is an important factor in the efficacy of the treatment. The median survival times for patients with time intervals of less than 12 months, 12-18 months and more than 18 months were 2.1 months, 7.1 months and 11.5 months, respectively. While the study by Gressen et al. (2000) did not find this effect, the study by Cetingoz et al. (2009) used multivariate analysis to show that time interval was the only independent prognostic factor affecting overall survival. These findings imply that those with longer time intervals may have less aggressive tumors, but radiation oncologists are more inclined to use higher doses to treat such patients. Radiation therapy is not usually used to treat locally recurrent small cell lung cancer. In patients with limited-stage disease who have received prior concurrent radiotherapy, a second course of radiotherapy will only increase toxicity and not benefit the patient. For patients with extensive disease, radiotherapy may be considered in patients with recurrence after initial chemotherapy with symptoms. Several retrospective studies (Ihde et al 1979; Ochs et al. 1983; Salazar et al. 1991) have analyzed the use of 21-60 Gy dose irradiation for the treatment of recurrent limited-stage and extensive-stage small cell lung cancer. Although the remission rate of lesions in the irradiated field was 52-77%, the median survival time was only 3-4 months, similar to the survival rate of early progression. However, the wider dose distribution has led some scholars to suggest that higher doses (≥40 Gy) of irradiation may result in higher palliative remission rates for the limited remaining life of patients.