Prognostic Model to Predict Overall Survival for Metastatic Non-Small Cell Lung Cancer Patients Treated With Chemotherapy Combined With Concurrent Radiation Therapy to the Primary Tumor: Analysis From Two Prospective Studies.

PURPOSE: The role of radiotherapy, in addition to chemotherapy, has not been thoroughly determined in metastatic non-small cell lung cancer (NSCLC). The purpose of the study was to investigate the prognostic factors and to establish a model for the prediction of overall survival (OS) in metastatic NSCLC patients who received chemotherapy combined with the radiation therapy to the primary tumor. METHODS: The study retrospectively reviewed 243 patients with metastatic NSCLC in two prospective studies. A prognostic model was established based on the results of the Cox regression analysis. RESULTS: Multivariate analysis showed that being male, Karnofsky Performance Status score < 80, the number of chemotherapy cycles <4, hemoglobin level ≤120 g/L, the count of neutrophils greater than 5.8 ×109/L, and the count of platelets greater than 220 ×109/L independently predicted worse OS. According to the number of risk factors, patients were further divided into one of three risk groups: those having ≤ 2 risk factors were scored as the low-risk group, those having 3 risk factors were scored as the moderate-risk group, and those having ≥ 4 risk factors were scored as the high-risk group. In the low-risk group, 1-year OS is 67.7%, 2-year OS is 32.1%, and 3-year OS is 19.3%; in the moderate-risk group, 1-year OS is 59.6%, 2-year OS is 18.0%, and 3-year OS is 7.9%; the corresponding OS rates for the high-risk group were 26.2%, 7.9%, and 0% (P<0.001) respectively. CONCLUSION: Metastatic NSCLC patients treated with chemotherapy in combination with thoracic radiation may be classified as low-risk, moderate-risk, or high-risk group using six independent prognostic factors. This prognostic model may help design the study and develop the plans of individualized treatment.

Simultaneous integrated boost of intensity-modulated radiation therapy to Stage II-III non-small cell lung cancer with metastatic lymph nodes.

Local tumor failure remains a major problem after radiation-based nonsurgical treatment for unresectable locally advanced nonsmall cell lung cancer (NSCLC）and inoperable stage II NSCLC. The aim of this study was to evaluate the feasibility of simultaneous integrated boost of intensity-modulated radiation therapy (SIB-IMRT) to stage II-III NSCLC with metastatic lymph nodes (ChiCTR 2000029304). Patients were diagnosed by pathology or PET-CT. PTV was divided into two parts as follows, the PTV of primary tumor (PTVp) and the PTV of metastatic lymph nodes (PTVn). The radiotherapy doses were simultaneously prescripted 78 Gy (BED = 101.48 Gy) for PTVp and 60-65 Gy (BED = 73.6-81.25 Gy) for PTVn, 26f/5.2 weeks. Response was scored according to WHO criteria. Radiotherapy toxicity was scored according to RTOG criteria. Hematology and gastrointestinal toxicity were scored according to CTCAE1.0 criteria. A total of 20 patients were enrolled. Seventeen patients were diagnosed by pathology and three patients were diagnosed by PET-CT. All patients were treated with SIB-IMRT. The objective response rate (ORR) was 90%, with CR 25%, PR 65%, NC 10%, and PD 0%. Although radiotherapy toxicity was common, there were no grade ≥3, with radiation pneumonitis (10 cases), esophagitis (17 cases), and dermatitis (12 cases). The local control rates at 1, 3, and 5 years were 85%, 75%, and 70%, respectively. The overall survival（OS）and local progression-free survival (LPFS) rates at 1, 3, and 5 years were 90%, 42.6%, and 35.5% and 84.4%, 35.5%, and 28.4%, respectively. SIB-IMRT can significantly improve ORR and survival for stage II-III NSCLC with metastatic lymph nodes, with high safety, and satisfactory efficacy. However, due to the limitation of small sample, these findings are needed to confirm by future trials with a larger sample size.

Randomized phase II study of pemetrexed-cisplatin or docetaxel-cisplatin plus thoracic intensity-modulated radiation therapy in patients with stage IV lung adenocarcinoma.

Systemic chemotherapy is the standard treatment modality for stage IV lung adenocarcinoma patients with EGFR wild-type or unknown mutation status. Recent years, there is increasing evidence showed that selected patients with stage IV disease could benefit from aggressive thoracic radiotherapy. Either pemetrexed or docetaxel, combined with cisplatin, can be used for patients with stage IV lung adenocarcinoma. However, no prospective trials have confirmed that Pem-Cis was superior to Doc-Cis in lung adenocarcinoma. In this randomized phase 2 trial, we evaluated survival outcomes, and toxicity of Pemetrexed-Cisplatin (arm A) or Docetaxel-Cisplatin (arm B) with concurrent IMRT to the primary tumor for stage IV lung adenocarcinoma patients with EGFR wild-type or unknown mutation status. Totally, 101 patients were randomly assigned (50 in arm A and 51 in arm B). Using an intention-to-treat analysis, one-year survival rates were 72.0% and 52.9%, respectively (P=0.020). Progression-free survival was also significantly improved in the arm A (median, 12.6 v 7.5 months, P=0.013). The incidence and severity of acute pneumonitis and esophagitis was similar between two arms. Although more of grade 3 or 4 anemia and thrombocytopenia in arm A, and higher rates grade 3 or 4 neutropenia, and leukopenia were observed in arm B. Pem-Cis first-line chemotherapy with concurrent radiation therapy for stage IV lung adenocarcinoma patients with EGFR wild-type or unknown mutation status represents a potential treatment option with acceptable toxicity and high overall survival rates.

Radiation dose and survival of patients with stage IV non-small cell lung cancer undergoing concurrent chemotherapy and thoracic three-dimensional radiotherapy: reanalysis of the findings of a single-center prospective study.

BACKGROUND: The objective of this study was to evaluate the radiation dose and response in terms of local-regional progression-free survival (LRPFS) and overall survival (OS) of patients with stage IV non-small cell lung cancer (NSCLC) undergoing concurrent chemotherapy and thoracic three-dimensional radiotherapy. METHODS: In all, we enrolled 201 patients with stage IV NSCLC in this study and analyzed OS in 159 patients and LRPFS in 120. RESULTS: The 1-, 2-, 3-, and 5-year OS rates were 46.2%, 19.5%, 11.7%, and 5.8%, respectively, the median survival time being 12 months. The median survival times in differential treatment response of primary tumors were 19 of complete response, 13 of partial response, 8 of stable disease, and 6 months of progressive disease, respectively (P = 0.000). The 1-, 2-, 3-, and 5-year LRPFS rates of patients undergoing four to five cycles with doses ≥63 Gy and <63 Gy were 77.4% and 32.6%, 36.2% and 21.7%, 27.2% and 0, and 15.9% and 0, respectively (P = 0.002). According to multivariate analyses, four to five cycles of chemotherapy, gross tumor volume <175.00 cm3 and post-treatment Karnofsky Performance Status score stable or increased by at least 10 units were independent prognostic factors for better OS (P = 0.035, P = 0.008, and P = 0.000, respectively). Radiation dose to the primary tumor ≥63 Gy resulted in better OS (P = 0.057) and LRPFS (P = 0.051), both findings being of borderline significance. CONCLUSIONS: Treatment of IV NSCLC with joint administration of four to five cycles of chemotherapy and three-dimensional radiotherapy may prolong survival, particularly in patients receiving ≥63 Gy radiotherapy, with gross tumor volume <175.00 cm3 and post-treatment Karnofsky Performance Status score not lower than pretreatment values.

Prognosis of non-small cell lung cancer patients with bone oligometastases treated concurrently with thoracic three-dimensional radiotherapy and chemotherapy.

BACKGROUND: To evaluate the efficacy of three-dimensional radiotherapy for non-small cell lung cancer (NSCLC) patients with bone metastases. METHODS: Clinical data for 95 NSCLC patients with bone metastases were collected and prognostic factors were analyzed. All patients received radiation to their thoracic primary tumor and ≥2 cycles of chemotherapy. RESULTS: Of these 95 patients, 47 patients had only bone metastases and 48 had both bone metastases and other organ metastases. Univariate analysis showed that factors that statistically significantly contributed to patients having longer overall survival (OS) included receiving a radiation dose to the primary tumor ≥63 Gy, responding to treatment and receiving ≥4 cycles of chemotherapy (p = 0.001, p = 0.037 and p = 0.009, respectively). A radiation dose to the primary tumor ≥63 Gy remained significant for patients with bone metastases only as well as those with bone and other organ metastases when they were analyzed separately (p = 0.045 and p = 0.012, respectively). For patients with bone metastases only, those with T1-2 tumors had longer OS than those with T3-4 (p = 0.048); and patients who received ≥4 cycles chemotherapy compared with those who received <4 cycles had similar OS (p = 0.385). On multivariate analysis, only a radiation dose ≥63 Gy (p = 0.028) and having only bone metastases (p = 0.006) were independent prognostic factors for better OS. CONCLUSIONS: A radiation dose to the primary tumor ≥63 Gy and having only bone metastases were associated with better OS in NSCLC patients with bone metastases. For patients with bone metastases only, besides radiation dose, T status was also correlated with OS, whereas the number of chemotherapy cycles was not. Therefore, aggressive thoracic radiation may play an important role in improving OS.

Overall survival and toxicities regarding thoracic three-dimensional radiotherapy with concurrent chemotherapy for stage IV non-small cell lung cancer: results of a prospective single-center study.

BACKGROUND: The role of chemotherapy given concurrently with thoracic three-dimensional radiotherapy for stage IV non-small cell lung cancer (NSCLC) is not well defined. We performed this study to investigate overall survival and toxicity in patients with stage IV NSCLC treated with this modality. METHODS: From 2003 to 2010, 201 patients were enrolled in this study. All patients received chemotherapy with concurrent thoracic three-dimensional radiotherapy. The study endpoints were the assessment of overall survival (OS) and acute toxicity. RESULTS: For all patients, the median survival time (MST) was 10.0 months, and the 1-, 2- and 3-year OS rates were 40.2%, 16.4%, and 9.6%, respectively. The MST was 14.0 months for patients who received a total radiation dose ≥63 Gy to the primary tumor, whereas it was 8.0 months for patients who received a total dose <63 Gy (P = 0.000). On multivariate analysis, a total dose ≥63 Gy, a single site of metastatic disease, and undergoing ≥4 cycles of chemotherapy were independent prognostic factors for better OS (P = 0.007, P = 0.014, and P = 0.038, respectively); radiotherapy involving metastatic sites was a marginally significant prognostic factor (P = 0.063). When the whole group was subdivided into patients with metastasis at a single site and multiple sites, a higher radiation dose to the primary tumor remained a significant prognostic factor for improved OS. For patients who received ≥4 cycles of chemotherapy, high radiation dose remained of benefit for OS (P = 0.001). Moreover, for the subgroup that received <4 chemotherapy cycles, the radiation dose was of marginal statistical significance regarding OS (P = 0.063). Treatment-related toxicity was found to be acceptable. CONCLUSIONS: Radiation dose to primary tumor, the number of metastatic sites, and the number of chemotherapy cycles were independent prognostic factors for OS in stage IV NSCLC patients treated with concurrent chemoradiotherapy. In addition to systemic chemotherapy, aggressive thoracic radiotherapy was shown to play an important role in improving OS. TRIAL REGISTRATION: Registered on (ChiCTR-TNC-10001026).