ABSTRACT
Background: Curative thoracic radiotherapy (CTRT) with concurrent chemotherapy has been considered as standard treatment approach for stage-III non-small cell lung cancer (NSCLC). The hematological and esophageal toxicities that have been encountered during CTRT would affect the immunonutritional status of the patients. The aim of this study is to evaluate the prognostic value of the change in pre- and post-treatment prognostic nutritional index (PNI) in stage-III NSCLC patients. Methods: Eighty seven consecutive stage III NSCLC patients� data were collected. Pre-radiotherapy (RT) and post-RT PNI values were calculated and the impact of prognostic value of PNI change on overall survival (OS) was evaluated by univariate and multivariate Cox regression analyses. A cutoff value of PNI change was obtained by receiver operator characteristic (ROC) curve analysis. Results: The cutoff value was found to be a 22% decrease in PNI by ROC curve analysis in terms of effect on OS. The median OS of low and high PNI decrease groups were 22.5 and 16.5 months respectively (P = 0,001). In univariate and multivariate analyses PNI decrease of ? 22% was found to be an independent poor prognostic factor for OS (P = 0.012) and hazard ratio (95% confidence interval)= 2.05 (1.16�62). Conclusion: The PNI change would be a convenient parameter to assess the immunonutrition
ABSTRACT
The combination of thoracic radiotherapy and immunotherapy is increasingly widely used in clinical practice, which not only brings survival benefits but also increases the incidence of pneumonitis. The occurrence of pneumonitis affects the subsequent immunotherapy and can be life-threatening in severe cases. The occurrence and severity of pneumonitis after combination therapy depends on a variety of factors, including patient's age, physical strength, pulmonary function, race, combination therapy mode, radiotherapy dose parameters, type of immune checkpoint inhibitor, history of checkpoint inhibitor-related pneumonitis or radiation pneumonitis, serum indexes and so on. At present, further research is needed to find out the influencing factors of the occurrence and severity of pneumonitis attributed to combined therapy, so as to better avoid, predict, identify and treat related pneumonitis in clinical practice.
ABSTRACT
Background: In extensive-disease-small cell lung cancer (ED-SCLC), the median survival is 8–10 months and 2-year survival is <5%. Primary tumor progression occurs in 90% of patients approximately within 1 year. The role of consolidative thoracic radiotherapy (C-TRT) for the postchemotherapy residue with the aim of improving local control (LC) and survival is currently of great interest. The objective of this study is to determine the effectiveness of C-TRT on LC, progression-free survival (PFS), and overall survival (OS) in ED-SCLC. Materials and Methods: Medical records of patients diagnosed as SCLC between January 2010 and December 2015 were evaluated retrospectively. Patients who received C-TRT were identified. Pre- and post-chemotherapy radiological evaluations, radiotherapy schedules, relapse patterns, toxicity incidence, LC, PFS, and OS were analyzed. Results: Among 552 SCLC patients, 26 ED-SCLC patients who underwent C-TRT were analyzed. Median follow-up was 7.5 months (range, 6.5–8.5 months). Nearly 50% of the patients had >4 metastatic lesions. Restaging was performed mostly by positron emission tomography/computed tomography and cranial magnetic resonance imaging. All patients had complete or near-complete response distantly. C-TRT was 10 × 300 cGy (n = 1), 23 × 200 cGy (n = 2), 25 × 200 cGy (n = 7), 30 × 200 cGy (n = 12), and 33 × 200 cGy (n = 4). There was no toxicity ≥ Grade 3. LC rate was 77%; there was no isolated local relapse. PFS was 3 months. Median survival was 13 months. The 1- and 2-year OS rates were 62% and 8%, respectively. Conclusion: In ED-SCLC patients, C-TRT may prevent isolated local recurrence and may improve 1-year survival. This survival improvement might be the reflection of high intrathoracic control achieved in 77% of patients
ABSTRACT
Objective To compare the efficacy and safety of icotinib therapy alone versus icotinib combined with thoracic radiotherapy for the treatment of advanced non-small cell lung cancer (NSCLC) patients with an activating epidermal growth factor receptor (EGFR) gene mutation.Methods A total of 83 patients with advanced NSCLC harboring an activating EGFR gene mutation was enrolled in this study.All the patients were randomly divided into 2 groups.Patients in group A (n =41) received thoracic radiotherapy (prescribed at 60-66 Gy) combined with icotinib (three times per day,125 mg once).Patients in group B (n =42) were given icotinib therapy alone (three times per day,125 mg once).Treatment was continued until disease progression or unacceptable toxicity or death.The primary end points were median progression-free survival (mPFS) and 12 month-PFS rate.The secondary end points included objective response rate (ORR),disease control rate (DCR) and adverse events.Results With a median follow-up of 18.2 months,mPFS was 15.2 months (95％ CI:12.2-17.4) in group A and 13.2 months (95％ CI:10.8-14.9) in group B (x2 =4.29,P=0.036).PFS rates of 12 months for group A and group B were 70.3％ and 61.2％,respectively.The ORR were 78.0％ vs.57.1％ (x2 =5.16,P =0.028),and the DCR were 95.1％ vs.92.9％ (P＞0.05) in groups A and group B,respectively.No grade 3-4 adverse events was observed in both groups except the rashes (4 cases in each group).Besides,10 patients had grade 1-2 radiation-related pneumonitis and 15 patients suffered grade 1-2 radiation-related oesophagitis in group A.Conclusions In advanced NSCLC patients with an activating EGFR gene mutation,the combination of thoracic radiotherapy and icotinib had achieved an improvement on ORR and PFS with good tolerance.Clinical trial registration Chinese clinical trial registry,ChiCTRINR-16010262.
ABSTRACT
Patients with locally advanced lung cancer and very limited pulmonary function (forced expiratory volume in 1 second [FEV1] ≤ 1 L) have dismal prognosis and undergo palliative treatment or best supportive care. We describe two cases of locally advanced node-positive non-small cell lung cancer (NSCLC) patients with very limited lung function treated with induction chemotherapy and moderate hypofractionated image-guided radiotherapy (Hypo-IGRT). Hypo-IGRT was delivered to a total dose of 45 Gy to the primary tumor and involved lymph nodes. Planning was based on positron emission tomography-computed tomography (PET/ CT) and four-dimensional computed tomography (4D-CT). Internal target volume (ITV) was defined as the overlap of gross tumor volume delineated on 10 phases of 4D-CT. ITV to planning target volume margin was 5 mm in all directions. Both patients showed good clinical and radiological response. No relevant toxicity was documented. Hypo-IGRT is feasible treatment option in locally advanced node-positive NSCLC patients with very limited lung function (FEV1 ≤ 1 L).
Subject(s)
Humans , Carcinoma, Non-Small-Cell Lung , Electrons , Four-Dimensional Computed Tomography , Induction Chemotherapy , Lung Neoplasms , Lung , Lymph Nodes , Palliative Care , Prognosis , Radiotherapy , Radiotherapy, Image-Guided , Tumor BurdenABSTRACT
Thoracic radiotherapy is an important means of local treatment for non -small cell lung cancer (NSCLC).Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs)have the effect of systemic therapy.Studies have shown that NSCLC patients with EGFR exons 19,21 mutation have a synergistic effect in the combination therapy .Radiotherapy activates EGFR signaling pathway ,inducing cell proliferation and DNA damage repair,leading to radiation resistance .Therefore,EGFR-TKIs have the effect in increasing radiosensitivity .Lung injury is one of the most common side effects when the two therapies combined .Studies suggest that radiotherapy combined with EGFR-TKIs may have conflicting functions in the development of pulmonary fibrosis ,the discrep-ancy between these studies may depend on the differences in the experimental systems ,the differences in pulmo-nary fibrosis models,as well as the differences between different species and individuals .Therefore,a more com-plete understanding of the etiology for pulmonary fibrosis is necessary to the development of improved treatments .
ABSTRACT
Objective To investigate the protective effect of CBLB 502 on radiation pneumonitis and pulmonary fibrosis for confirming the feasibility of CBLB502 as a clinical anti-radiation drug release.Methods With a single 20 Gy irradia-tion, C57BL/6J mice was sacrificed on 24 h, 1 month, 3 months and 5 months and lung tissue was assayed by TUNEL method for apoptosis of alveolar epithelial cells and endothelial cells , HE staining showing fibrosis changes , immunohisto-chemistry detecting the expression of specific indicators , as well as pathological changes of the fur and skin radiated site . Results CBLB502 inhibits apoptosis in mice alveolar epithelial cells and vascular endothelial cells after irradiation , slowing the process of pulmonary fibrosis , while reducing the expression of laminin and maintaining the expression of surfac-tant protein B, and the skin inflammation also significantly reduced .Conclusion CBLB502 could alleviate the occurrence of radiation pneumonitis and pulmonary fibrosis as well as radiation-induced skin injury .
ABSTRACT
BACKGROUND: Irinotecan hydrochloride, a topoisomerase I inhibitor, is effective against small-cell lung cancer. Irinotecan also can act as a potential radiation sensitizer along with cisplatin. To evaluate efficacy and toxicity of irinotecan plus cisplatin (IP) with concurrent thoracic radiotherapy, we conducted a phase II study of IP followed by concurrent IP plus hyperfractionated thoracic radiotherapy in patients with previously untreated limited-stage small-cell lung cancer. METHODS: Twenty-four patients with previously untreated small-cell lung cancer were enrolled onto the study since November 2004. Irinotecan 60 mg/m2 was administered intravenously on days 1 and 8 in combination with cisplatin 60 mg/m2 on day1 every 21 days. From the first day of third cycle, twice-daily thoracic irradiation (total 45 Gy) was given. Prophylactic cranial irradiation was given to the patients who showed complete remission after concurrent chemoradiotherapy. Restaging was done after second and sixth cycle with chest CT and/or bronchosocpy. RESULTS: Up to November 2004, 19 patients were assessable. The median follow-up time was 12.5 months. A total of 99 cycles (median 5.2 cycles per patient) were administered. The actual dose intensity values were cisplatin 19.6 mg/m2/week and irinotecan 38.2 mg/m2/week. Among the 19 patients, the objective response rate was 95% (19 patients), with 9 patients (47%) having a complete response (CR). The major grade 3/4 hematological toxicities were neutropenia (35% of cycles), anemia (7% of cycles), thrombocytopenia (7% of cycles). Febrile neutropenia was 4% of cycles. The predominant grade 3/4 non-hematological toxicities was diarrhea (5% of cycles). Toxicities was not significantly different with concurrent administration of irinotecan and cisplatin with radiotherapy, except grade 3/4 radiation esophagitis (10% of patients). No treatment-related deaths were observed. The 1-year and 2-year survival rate of eligible patients was 89% (16/18) and 47% (9/18), respectively. CONCLUSION: Three-week schedule of irinotecan plus cisplatin followed by concurrent IP plus hyperfractionated thoracic radiotherapy is an effective treatment for limited disease small-cell lung cancer, with acceptable toxicity.
Subject(s)
Humans , Anemia , Appointments and Schedules , Chemoradiotherapy , Cisplatin , Cranial Irradiation , Diarrhea , DNA Topoisomerases, Type I , Drug Therapy , Esophagitis , Febrile Neutropenia , Follow-Up Studies , Lung Neoplasms , Neutropenia , Radiotherapy , Small Cell Lung Carcinoma , Survival Rate , Thrombocytopenia , Tomography, X-Ray ComputedABSTRACT
BACKGROUND: Irinotecan hydrochloride, a topoisomerase I inhibitor, is effective against small-cell lung cancer. Irinotecan also can act as a potential radiation sensitizer along with cisplatin. To evaluate efficacy and toxicity of irinotecan plus cisplatin (IP) with concurrent thoracic radiotherapy, we conducted a phase II study of IP followed by concurrent IP plus hyperfractionated thoracic radiotherapy in patients with previously untreated limited-stage small-cell lung cancer. METHODS: Twenty-four patients with previously untreated small-cell lung cancer were enrolled onto the study since November 2004. Irinotecan 60 mg/m2 was administered intravenously on days 1 and 8 in combination with cisplatin 60 mg/m2 on day1 every 21 days. From the first day of third cycle, twice-daily thoracic irradiation (total 45 Gy) was given. Prophylactic cranial irradiation was given to the patients who showed complete remission after concurrent chemoradiotherapy. Restaging was done after second and sixth cycle with chest CT and/or bronchosocpy. RESULTS: Up to November 2004, 19 patients were assessable. The median follow-up time was 12.5 months. A total of 99 cycles (median 5.2 cycles per patient) were administered. The actual dose intensity values were cisplatin 19.6 mg/m2/week and irinotecan 38.2 mg/m2/week. Among the 19 patients, the objective response rate was 95% (19 patients), with 9 patients (47%) having a complete response (CR). The major grade 3/4 hematological toxicities were neutropenia (35% of cycles), anemia (7% of cycles), thrombocytopenia (7% of cycles). Febrile neutropenia was 4% of cycles. The predominant grade 3/4 non-hematological toxicities was diarrhea (5% of cycles). Toxicities was not significantly different with concurrent administration of irinotecan and cisplatin with radiotherapy, except grade 3/4 radiation esophagitis (10% of patients). No treatment-related deaths were observed. The 1-year and 2-year survival rate of eligible patients was 89% (16/18) and 47% (9/18), respectively. CONCLUSION: Three-week schedule of irinotecan plus cisplatin followed by concurrent IP plus hyperfractionated thoracic radiotherapy is an effective treatment for limited disease small-cell lung cancer, with acceptable toxicity.
Subject(s)
Humans , Anemia , Appointments and Schedules , Chemoradiotherapy , Cisplatin , Cranial Irradiation , Diarrhea , DNA Topoisomerases, Type I , Drug Therapy , Esophagitis , Febrile Neutropenia , Follow-Up Studies , Lung Neoplasms , Neutropenia , Radiotherapy , Small Cell Lung Carcinoma , Survival Rate , Thrombocytopenia , Tomography, X-Ray ComputedABSTRACT
PURPOSE : We evaluated the optimal combination of thoracic radiotherapy with chemotherapy in patients with limited-stage small cell lung cancer (L-SCLC). MATERIALS AND METHODS : We retrospectively analyzed the data of 95 patients with L-SCLC who completed the planned thoracic radiotherapy combined with chemotherapy between January 1998 and March 2004. Thoracic radiotherapy was done with conventional fractionation to the median dose of 60Gy. Radiotherapy was combined with chemotherapy concurrently (n=67), alternating (n=19), or sequentially (n=9). Chemotherapy consisted of EP or EC (etoposide 100 mg/m2, cisplatin 60 mg/m2 or carboplatin 5~6xAUC ). The median cycle of chemotherapy was 6 with the range of 2 to 8. RESULTS : The median survival of all 95 patients was 20 months and 2-, 3-, and 5-year overall survival rate was 39%, 26%, and 19%, respectively. Radiation dose above 55 Gy did not show better survival result than dose below 55 Gy (p=0.59). The median survival and 5-year survival rate of 67 patients with concurrent chemoradiation was 23 months and 24% while those of 28 patients with alternating or sequential chemoradiation was 16 months and 8%, respectively (p=0.007). Concurrent thoracic radiotherapy combined after 2 cycles of chemotherapy showed the best survival results among the combination methods (p=0.29). The survival was improved in patients with chemotherapy more than 5 cycles comparing to patients with less than 5 (p=0.03). Patients with PCI showed the median survival of 43 months and 5-year survival rate of 35% vs. 18 months and 16% in patients without PCI, respectively (p=0.02). In multivariate analysis, the concurrent chemoradiation was the only significant prognostic factor affecting to the survival. CONCLUSION : Concurrent chemoradiation after 2 cycles of chemotherapy showed the best survival results in our study group. Full dose of chemotherapy to 6 cycles needed to be proceeded in tolerable patients. PCI can be recommended to the patients with complete response after chemoradiation
Subject(s)
Humans , Carboplatin , Cisplatin , Drug Therapy , Lung Neoplasms , Lung , Multivariate Analysis , Radiotherapy , Retrospective Studies , Small Cell Lung Carcinoma , Survival RateABSTRACT
Purposes: Although the standard management of limited stage small cell lung cancer is concurrent platinum-based chemotherapy with thoracic radiotherapy (TRT), the optimal timing of the TRT remains controversial. We investigated the feasibility of concurrent chemoradiation for the patients with limited stage small cell lung cancer after 2 cycles of combination chemotherapy with Etoposide/Cisplatin (EP). MATERIALS AND METHODS: EP consisted of Etoposide 100 mg/m2 on day 1 to 3 and Cisplatin 70 mg/m2 on day 1. Six cycles were given to the responders every 4 weeks. Total 55 Gy (1.8 Gy once-daily or 1.2 Gy twice-daily, 5 days per week) of TRT were given to the patients who showed at least a partial response after 2 cycles of EP. The other patients were treated by the physician's decision. The patients with complete remission were recommended to receive prophylactic cranial irradiation. RESULTS: Fifty patients were enrolled. Thirty-five (70%) of them showed responses (2 complete remissions and 33 partial remissions) after 2 cycles of EP. Thirty-three of the responders were given TRT starting with the 3rd cycle of EP. The nonresponders were treated with salvage chemotherapy and TRT. After completion of treatment for 50 patients, the overall response rate was 86% (29 complete remissions, 14 partial remissions). One patient (2%) showed stable disease, and 6 (12%) showed a progressive disease. The median progression free survival was 326 days and the median survival time was 410 days. One-, 2-, 3-, 4- and 5-year survival rates were 62%, 24%, 14%, 9% and 6%, respectively. As hematologic toxicities during chemoradiation, 35.1% with grade III/IV neutropenia and 18.9% with grade III/IV thrombocytopenia were noted. Grade II/III radiation pneumonitis and radiation esophagitis were noted in 5/1 and 13/1 patients (15.2%/ 3.0% and 39.4%/3.0%), respectively. One patient died of septicemia during chemoradiation. CONCLUSION: The concurrent EP and TRT after 2 cycles of EP was feasible in limited stage small cell lung cancer. Further study is required for the indentification of optimum timing of TRT during combination chemotherapy.
Subject(s)
Humans , Chemoradiotherapy , Cisplatin , Cranial Irradiation , Disease-Free Survival , Drug Therapy , Drug Therapy, Combination , Esophagitis , Etoposide , Neutropenia , Radiation Pneumonitis , Radiotherapy , Sepsis , Small Cell Lung Carcinoma , Survival Rate , ThrombocytopeniaABSTRACT
Background: Combination chemotherapy is now considered to be the cornerstone of small cell lung cancer (SCLC). management but the optimal management of limited SCLC is not well defined. The role of thoracic radiotherapy (TRT) is less well established. Recent meta-analyses reports revealed that TRT combined with chemotherapy produce "good" local control and prolonged survival. But other reports that survival was not changed. The timing, dose, volume and fractionation for TRT with the combined chemotherapy of SCLC remains unsettled. In this study, we analyzed the effects according to the timing of thoracic radiotherapy in limited SCLC. Method: All fifty one patients received cytoxan, adriamycin and vincristine(CAV) alternating with etoposide and cisplatin(VPP) every 3 weeks for 6 cycles were randomized prospectively into two groups: concurrent and sequential. 27 patients received 4500cGy in 30 fractions(twice daily 150cGy fractional dose) over 3 weeks to the primary site concurrent with the first cycle of VPP(concurrent gorup). 24 patients received 4000 to 5000cGy over 5 or 6 weeks after completion of sixth cycles of chemotherapy(sequential group). Results: 1. Response rates and response duration: Response rates were not significantly different between two groups(p=0.13). But response duration was superior in the concurrent group(p=0.03). 2. Survival duration was not different between two groups(p=0.33). 3. Local control rate was superior in the concurrent group(p=0.00). 4. Side effects and toxicities: Hematologic toxicides, especially leukopenia, infection and frequency of radiation esophagitis were higher in the concurrent group(p=0.00, 0.03, 0.03). Conclusion: The concurrent use of TRT with chemotherapy failed to improve the survival of limited stage SCLC patients compared with the sequential use of TRT but response duration and local control rate were superior in the concurrent group. Frequency of radiation esophagitis, life threatening hematologic toxicities and infection were more frequent in the concurrent group than sequential group. So, the selection of an optimal schedule of chemotherapy combined with TRT that would lead to a major increase in survival with minimal toxicity is remained to be validated in large scale study in the future.