Efficacy and Safety of Primary Radiotherapy in Combination with EGFR-TKIs for Non-Small Cell Lung Cancer Harboring EGFR Mutation

Objective: To evaluate the efficacy and safety of EGFR-TKI with the radiotherapy in EGFR mutant metastatic NSCLC. Methods: Retrospective analysis of 72 patients with stage IV lung cancer with EGFR-sensitive mutation. Patients in the A group were treated with the first-generation EGFR-TKI (Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor) combined with radiotherapy for primary tumors (34 cases). The B group was treated with the first-generation EGFR-TKI alone until the disease progressed (38 cases). PFS, OS, pulmonary infection and hematological toxicity during treatment were commented in both groups. Results: The objective remission rate was 47.1% (16/34) in the A group and 21.1% (8/38) in the B group. There was a significant difference between the two groups. There was no significant difference in hematological toxicity between the A group and the B group. There were 10 patients (29.4%) with degree II pulmonary infection in the A group and 3 patients (7.9%) in the B group. The difference between the two groups was statistically significant, suggesting that the incidence of pneumonia in the A group was higher than that in the B group. The median PFS (Progression-Free Survival)) and OS (Overall Survival) of the A group were significantly longer than those of the B group (16.5 months vs 9 months) and the median OS (36 months vs 19 months). The PFS and OS in the A group were significantly longer than those in the B group. Conclusion: EGFR-TKI combined with primary radiotherapy can significantly prolong the drug resistance time of EGFR mutant metastatic NSCLC.

Chemotherapy-free radiotherapy combined with immune checkpoint inhibitors:a new regimen for locally advanced non-small cell lung cancer?

Maintenance immunotherapy after concurrent chemoradiotherapy remains the standard therapeutic approach in patients with unresectable locally advanced non-small cell lung cancer(LA-NSCLC).The efficacy of pembrolizumab without chemotherapy in stage IV NSCLC has incited interest in similar approaches for LA-NSCLC.Several recent investigations involving the synergistic potential of immunotherapy combined with radiotherapy(i RT)have generated encouraging results.This review discusses the existing studies and prospective directions of chemotherapy-free i RT strategies in unresectable LA-NSCLC.Although the initial findings of chemotherapy-free i RT strategies have shown promising efficacy,we must consider the methodologic limitations of current studies and the myriad of challenges that accompany the implementation of chemotherapy-free i RT.These challenges include determining the optimal dose and fractionation,precise target volume delineation,and identification of additional suitable patient cohorts.Furthermore,the feasibility of chemotherapy-free i RT as a novel treatment modality for select patients with LA-NSCLC is contingent upon validation through randomized phase III trials.

Progress in image-guided radiotherapy for the treatment of non-small cell lung cancer

Lung cancer is one of the most common malignant tumors. It has the highest incidence and mortality rate of all cancers worldwide. Late diagnosis of nonsmall cell lung cancer(NSCLC) is very common in clinical practice, and most patients miss the chance for radical surgery. Thus, radiotherapy plays an indispensable role in the treatment of NSCLC. Radiotherapy technology has evolved from the classic two-dimensional approach to three-dimensional conformal and intensity-modulated radiotherapy. However, how to ensure delivery of an accurate dose to the tumor while minimizing the irradiation of normal tissues remains a huge challenge for radiation oncologists, especially due to the positioning error between fractions and the autonomous movement of organs. In recent years, image-guided radiotherapy(IGRT) has greatly increased the accuracy of tumor irradiation while reducing the irradiation dose delivered to healthy tissues and organs. This paper presents a brief review of the definition of IGRT and the various technologies and applications of IGRT. IGRT can help ensure accurate dosing of the target area and reduce radiation damage to the surrounding normal tissue. IGRT may increase the local control rate of tumors and reduce the incidence of radio-therapeutic complications.

Postoperative radiotherapy in resected non-small cell lung cancer:The never-ending story

This manuscript collects in a joint and orderly manner the existing evidence at the present time about postoperative treatment with radiotherapy in non-small cell lung cancer.It also systematically reviews the current evidence,the international recommendations in the most relevant guidelines,the most controversial aspects in clinical and pathological staging,the specific technical aspects of radiotherapy treatment,and also collects all the potential risk factors that have been postulated as significant in the prognosis of these patients,evaluating the possibility of segmenting a particularly sensitive subpopulation with a high risk of relapse on which an adjuvant treatment with radiotherapy could have an impact on their clinical evolution.Finally,currently active trials that aspire to provide more evidence on this topic are reviewed.

Clinical Research on Three-Dimensional Conformal Radiotherapy of Non-Small Cell Lung Cancer

OBJECTIVE To investigate the clinical efficacy and toxic effect of the 3-dimensional conformal radiation therapy （3DCRT） for non- small cell lung cancer （NSCLC）. METHODS Fifty-two patients with the Stage-I and IV NSCLC were treated with 3DCRT. Cross analysis of the clinical data was conducted in the comparison between the 52 cases with 3DCRT and the other 50 cases with the conventional radiation therapy （CRT）. In the 3DCRT group, only the primary tumor and positive lymph-node draining area were included in the clinical target area, setting 4 to 6 coplanar or non-coplanar irradiation fields, with 2 Gy or 3 Gy/fraction, 1 fraction a day and 5 fractions per week. The total dose ranged from a test dose （DT） of 66 Gy to 72 Gy. In the CRT group, the field area contained the primary tumor plus the homolateral hilum of the lung, the mediastinum superior or hol-mediastinum, and opposed anteroposterior irradiation. When the dosage reached DT 36-40 Gy, an oblique portal administered radiation was conducted in order to avoid injuring the spinal cord. The DT was 1.8-2.0 Gy/fraction, 1 fraction a day, 5 fractions per week, with a total dose of 60 Gy to 70 Gy. RESULTS The therapeutic effect （CR ＋ PR） was 90.4% in the 3DCRT group, and was 72% in the CRT group. There was statistically significant difference between the two groups, P 〈 0.01. There was a clinical symptom improvement attained by 96.5% and 86.4% respectively in the two groups, and there was a statistically significant difference between the groups, P 〈 0.01. The 6-month, 1 and 2-year overall survival rates were 92.3%, 75.0% and 42.3% in the 3DCRT group, and 76%, 60% and 30% in the CRT group, respectively. There was a significant difference in the 6-month overall survival rate between the groups, P 〈 0.05. There was no obvious significant difference in the 1 and 2-year overall survival rates between the two groups, P 〉 0.05. The toxic reaction was 12.5% and 23.7% respectively in the 3DCRT and CRT groups. Acute radioactive esophagitis and leucopenia were markedly lower in the 3DCRT group than in the CRT group. There was a statistically significant difference between the groups, P 〈 0.05. No toxic reaction of Stage-III and over was found in the 3DCRT group during radiation therapy. CONCLUSION The 3DCRT method has a satisfactory shortterm efficacy and improvement of clinical symptoms in treating NSCLC, with a mild toxic reaction and good tolerance in patients. It can be used for enhancing the tumor-control rate and bettering the quality of life.

Palliative chemotherapy followed by consolidation radiotherapy in patients with advanced and metastatic non-small cell lung cancer not suitable for radical treatment

Objective:This is a retrospective study to assess the effectiveness of consolidation radiotherapy (CRT) following palliative chemotherapy in patients with metastatic or locally advanced non-small cell lung cancer (NSCLC) who are not suitable for radical treatment.Methods:This study involved retrospective analysis of a prospective database of Northampton Oncology Centre from January 2005 to December 2010,63 patients with advanced/metastatic NSCLC treated at the oncology centre were enrolled.Patients were either treated with high dose (39/36 Gy /13-12 fractions,group 1) or low dose (20 Gy /5 fractions,group 2) CRT or those were not offered any CRT (group 3).Results:There was no significant difference between the three groups as regard age,sex,performance status,comorbidities or chemotherapy given.However there was a statistically significant difference as regard the stage P=0.009 with more stage IV patients at group II and III compared to group I.The mean survival for the three groups was 27 months,14 months &15 months,respectively.There was a statistically significant improvement of survival in patients treated with high dose palliative CRT compared to the other two groups (P=0.006).In multivariate analysis only the radiotherapy dose remains as the only statistical significant factor affecting the survival with hazard ratio 0.372 and confidence interval (0.147-0.726).Conclusion:Despite the limitation of our retrospective study,it is worth considering CRT approach for patients with advanced and metastatic NSCLC-not suitable for radical treatment-who have not progressed on chemotherapy.

Initial outcome of induction chemotherapy followed by radiotherapy and concurrent weekly paclitaxel for stage Ⅲ non-small cell lung cancer

Objective： The aim of our study was to evaluate the toxicity and efficacy of induction chemotherapy （ICT） followed by three-dimensional conformal radiotherapy （3D CRT） and concurrent weekly paclitaxel on unresectable non-small cell lung cancer （NSCLC）. Methods： Stage III NSCLC patients with favorable conditions were treated with 2 to 4 cycles of carboplatin （AUC = 5-6, dl） combined with paclitaxel （175 mg/m〈 dl）, then followed by weekly paclitaxel （40 mg/m2） and concurrent 3D CRT within 3-4 weeks. The prescription dose was given as high as possible under the condition that V20 〈 31% and spinal cord dose 〈 50 Gy. Results： Thirty-one patients were enrolled. ICT was well tolerated. During the concurrent chemoradiotherapy, the treatment of 3 patients was ended ahead of the schedule because of severe pulmonary and heart toxicities; the treatment of 2 patients was delayed for 7 and 12 days because of fatigue. Myelosuppression was mild （16/31）： all were grade 1-2 except 1 was grade 3. Lymphocytopenia was more obvious （29/31, grade 3 in 21）. Three patients developed grade 3 radiation-induced esophagitis, and 2 developed grades 3-4 radiation-induced pneumonitis. Two developed grade 3 esophageal stricture. No grades 3-4 pulmonary fibrosis was observed. The overall response rate was 74.1%. The 1-, 2-, 3-year overall survival rates were 74.2%, 41.9%, and 34.6%, respectively, with the median survival time of 18.5 months. The 1-, 2-, 3-year local progression-freely survival rates were 64.5%, 32.3%, and 20.5%, respectively, with the median local progression-freely survival time of 14.3 months. Conclusion： The program of ICT followed by weekly paclitaxel and 3D CRT is accomplished in most of the favorable stage III NSCLC patients. The toxicity is tolerable, and the response rate is inspiriting.

Survival and prognostic factors of non-small cell lung cancer patients with postoperative locoregional recurrence treated with radical radiotherapy

Background: Locoregional recurrence remains the challenge for long-term survival of non-small cell lung cancer(NSCLC) patients after radical surgery, and curative-intent radiotherapy could be a treatment choice. This study aimed to assess the survival and prognostic factors of patients with postoperative locoregionally recurrent NSCLC treated with radical radiotherapy.Methods: We reviewed medical records of 74 NSCLC patients with postoperative locoregional recurrence who received radical radiotherapy between April 2012 and February 2016 at Sun Yat-sen University Cancer Center(Guangzhou, China). The efficacy and safety of radical radiotherapy were analyzed. The probability of survival was estimated using the Kaplan-Meier method and compared using the log-rank test. The Cox proportional hazards model was used to identify prognostic factors.Results: Grade 3/4 adverse events included neutropenia(8 cases, 10.8%), esophagitis(7 cases, 9.5%), pneumonitis(1 case, 1.4%), and vomiting(1 case, 1.4%).The 2-year overall survival, progression-free survival, local recurrencefree survival(LRFS), and distant metastasis-free survival(DMFS) rates of all patients were 84.2,42.5,70.0, and 50.9%,respectively. Univariate and multivariate analyses showed that a higher biological effective dose(BED) of radiation was associated with longer LRFS [hazard ratios(HR)=0.317,95% confidence interval(CI) = 0.112-0.899, P = 0.016] and that wild-type epidermal growth factor receptor(EGFR) was associated with longer DMFS compared with EGFR mutation(HR = 0.383,95% CI=0.171-0.855, P = 0.019).Conclusions: Radical radiotherapy is effective and well-tolerated in NSCLC patients with postoperative locoregional recurrence. High BED is a predictor for long LRFS, and the presence of wild-type EGFR is a predictor for long DMFS.

Treatment of Skin Reaction Induced by Nivolumab Combined with Radiotherapy in Non-small Cell Lung Cancer:A Case Report

Skin reaction or dermatological toxicities induced by immunotherapy is common.It usually manifests skin rash or erythema and can be cured by skin lotion or steroid.Nivolumab,a human IgG4 programmed cell death protein 1(PD-1)inhibitor,blocks T cells activation preventing signal and allows the immune system to clear cancer cells.Nivolumab was approved in the second-line therapy in squamous cell lung cancer by FDA,with less than 10%unusual skin reaction,like sensory neuropathy,peeling skin,erythema multiforme,vitiligo,and psoriasis.Radiotherapy could aggravate this skin reaction through inflammatory response and promotion of immunity.The combined treatment of anti-PD-1 and radiotherapy represented a new promising therapeutic approach in many studies,but the risk of side effects may be high.We reported a patient with advanced squamous cell lung cancer who suffered from serious skin immune-related adverse events when he was treated with nivolumab and radiotherapy.The immune overreaction of the treatment of anti-PD-1 treatment and radiotherapy might cause these serious skin adverse events.Our report warranted careful workup to reduce the risk of side effects by combinative therapy with anti-PD-1 and radiotherapy.

Effect analysis of chemoradiotherapy after operation in patients with stage ⅢA non-small cell lung cancer

Objective:To investigate the effect of chemoradiotherapy after surgery onⅢA stage nonsmall cell lung cancer(NSCLC).Methods:A total of 156 NSCLC patients undergoing total pneumonectomy or pulmonary lobectomy were included in this study.The chemotherapy group (n=75) received the protocol of cisplatin(DDP) + gemcitabine(GEM) / docetaxel(DOC) / vinorelbine (NVB);the radiotherapy + chemotherapy group(n=81) received sequential chemoradiotherapy. The response rale,local control rale in1 to 2 years,overall survival(OS),progression-free survival(PFS) and adverse reactions were evaluated.Results:The overall response rate was obviously higher in radiotherapy + chemotherapy group(79.4%) than in chemotherapy group(56.8%) (P【0.01).The 1 year local control rates for chemotherapy group and radiotherapy + chemotherapy group were(69.1±7.9)%and(77.8±8.2)%respectively and the difference reached statistical significance (P【0.001).The 2 year local control rates were(42.1±6.1%and(61.5±6.9)%respectively(P【0.001). The difference in median follow-up time between the two groups did not reach statistical meaning(P】0.05),while the median PFS of two groups were 10.8 months and 16.9 months respectively(P【0.001).1-year and 3-year survival rates were obviously higher in radiotherapy + chemotherapy group than in chemotherapy group,and the difference reached statistical significance(P【0.05 or P【0.01).The adverse reactions manifested as hematological toxicity and digestive tract reaction in the two groups.In the radiotherapy + chemotherapy group,incidences of radiation-induced esophagus injury and lung injury were 24.7%and 34.6%respectively,all occurring within 2 to 6 weeks after the start of radiation and both below grade 2.Conclusions: Chemoradiotherapy after surgery can improve local control rate and reduce or prevent distant metastasis,but there are still many controversies.In clinical work,we should carefully evaluate each patient’s age,lung function,basic physical condilion scoring and complications to choose a therapeutic schedule that is suitable for the patient.

Clinical analysis of concurrent chemoradiotherapy in 83 patients with locally advanced non-small cell lung cancer

Objective:The purpose of this study was to evaluate the efficacy and safety of concurrent chemoradiotherapy (CCRT) in patients with locally advanced non-small cell lung cancer (LANSCLC). Methods:83 cases of patients who have been diagnosed for locally advanced NSCLC by determined cytology or pathology were divided into two groups randomly, 42 patients in NP group and 41 patients in EP group. All patients accepted thoracic three-dimensional conformal radiotherapy (3D-CRT) and concurrent either NP chemotherapy in NP group or EP chemotherapy in EP group. 3D-CRT were started on day 1 in the first cycle of chemotherapy. Chemotherapy were carried out for 4 cycles, every cycle was 21 days. Thoracic radiotherapy adopted conventional fractionated irradiation with 15 MeV-X ray, a total dose of 60 Gy. Results: In 83 patients were evaluable, there were 5 cases complete regression to be observed, 29 cases had partial regression (PR), 7 cases with stable disease (SD) and 1 case with progression disease (PD) in NP group. CR 3 cases, PR 27 cases, SD 9 cases and PD 2 cases in EP group. The overall response rate (RR) both NP group and EP group were 80.9%, 73.2%, respectively (P = 0.785).1-, 2-, 3-year survival rate were 90.5%, 69.0%, 28.6% and 82.9%, 51.2%, 21.9%, respectively (P = 0.393). The incidence of leukopenia and thrombocytopenia in NP group was higher than that in the EP group (P < 0.05). Conclusion:CCRT in patients with locally advanced non-small cell lung cancer, 3D-CRT with concurrent NP or EP chemotherapy. 1-, 2-, 3-year overall survival (OS) and average survival time (AST) were not statistically differences, a higher incidence of toxicities were observed in NP group but can be tolerable.

Clinical observation of gemcitabine and concomitant three-dimensional conformal radiotherapy in the treatment of locally advanced non-small cell lung cancer

Objective： To evaluate the clinical effect of gemcitabine and concurrent three-dimensional conformal radiation therapy （3D-CRT） for locally advanced non-small cell lung cancer （NSCLC）. Methods： From April 2002 to June 2005, 38 patients with inoperable stage Ⅲ NSCLC were treated with gemcitabine and 3D-CRT simultaneously. Chemotherapy consisted of intravenously gemcitabine 350 mg/m^2 on days 1, 8, 15, 22, 29, 36.3D-CRT was delivered up to a total dose of 60-64 Gy with a 2.0 Gy dose fraction per day, 5 days per week. Results： The overall response rates of primary tumor and mediastinum metastatic node were 86.8% （33/38） and 90.6% （29/32） respectively, and 91.7% （22/24） and 78.6% （11/14） for squamous cell carcinoma and adenocarcinoma respectively. The acute side effects of patients were mostly myelosuppression, nausea, vomiting, radiation-induced esophagitis and pneumonitis （RTOG 1/11）, however, all of them were cured. Conclusion： Concurrent application of gemcitabine and 3D-CRT can improve the overall response rate for locally advanced NSCLC without aggravating the side effects.

Concurrent gemcitabine and cisplatin combined with 3D conformal radiotherapy for stage III non-small cell lung cancer

Objective： To study the toxicities and efficacy of concurrent gemcitabine plus cisplatin combined with three-dimensional conformal radiotherapy for stage Ⅲ non-small cell lung cancer （NSCLC）. Methods： Thirty-six patients with pathologically diagnosed NSCLC received radiotherapy and concurrent chemotherapy. There were 22 patients with stage Ilia and 14 patients with IIIb. Radiotherapy was given a total of 60-70 Gy in conventional fractionation. Chemotherapy included gemcitabine （600 mg/m^2） and cisplatin （20 mg/m^2）, once per week. Results： Thirty-two patients received a total dose of 60-72 Gy. Two patients received 56 Gy and another two patients received 58 Gy. Thirty-four patients received 4-6 weeks of chemotherapy, while two patients received only 2 weeks of chemotherapy. The overall response rate （CR ＋ PR）, complete response rate （CR）, partially response rate （PR） were 83.3% （30/36）, 11.1% （4/36） and 72.2% （26/36） respectively. The median follow-up duration was 18.4 months. The 1- and 2-year overall survival rates were 77.8% （28/36） and 55.6% （20/36）, respectively. Conclusion： Concurrent gemcitabine and cisplatin combined with three-dimensional conformal radiotherapy for stage III non-small cell lung cancer is effective and well tolerated. Lone-term results need further study.

Feasibility of cetuximab and chemoradiotherapy combination in Chinese patients with unresectable stage Ⅲ non-small cell lung cancer:a preliminary report

Objective： In recent years, the combination of cetuximab and chemoradiotherapy （CRT） has been used to treat stage III non-small cell lung cancer （NSCLC）; however, limited data are available for Chinese patients. Herein, we report preliminary data from a phase I/II study testing the combination of cetuximab with inductive chemotherapy, followed by concurrent CRT （CCRT） in Chinese patients with stage III NSCLC. Methods： Eligibility criteria were Zubrod performance status （PS） 0-1, forced expiratory volume in 1 second （FEV1） 〉_1.2 L and adequate organ function. Enrolled patients received weekly cetuximab （initial dose of 400 mg/m2 on day 1 of week 1 and a maintenance dose of 250 mg/m2 on week 2 to the end of CCRT） with cisplatin/vinorelbine （NP） chemotherapy （every 3 weeks for 2 cycles from week 2, followed by two cycles of concomitant NP chemotherapy and intensity-modulated thoracic radiotherapy （TRT） （60-66 Gy/2 Gy）. The primary endpoints were toxicity and feasibility. All patients received positron emission tomography- computerized tomography （PET-CT） scans within the 2 weeks prior to enrollment. Univariate analyses were used to assess the correlation between SUV-T, SUV-N, SUV-TOTAL, gender, age, histology, tumor-node- metastasis （TNM） stage, PS and smoking status and survival. Survival curves were generated for different populations using the Kaplan-Meier method and compared using a log-rank test. Results： Seventeen patients were enrolled and 16 completed the full regime. The overall response rate （ORR） was 58.8% and 82.3% after the induction and CCRT phases, respectively. With a median follow-up duration of 27.6 months, the median survival was 27.6 months [95% confidence interval （CI）： 11.3-43.9 months] with 1- and 2-year survival rates of 88.2% （95% CI, 60.6-96.9%） and 58.8% （95% CI, 60.6-77.8%）, respectively. Three patients remain progression-free to date, and the median progression-free survival （PFS） was 13.5 months （95% CI, 6.8-20.2 months）. No treatment-related death occurred; however, 76% of the patients experienced grade 3＋ adverse events （AEs）, including nansea/vomiting, intestinal obstruction, and esophagitis （〈6%）, while other AEs were mostly of hematological nature （71%）. The cut-off values for SUV-T and SUV-TOTAL were 11 and 20, respectively. Univariate analyses revealed SUV-TOTAL （P=0.027）, SUV-T （P=0.025）, and PS （P=0.006） as potential survival predictors, with a hazard ratio （HR） of 3.4, 3.7, and 9.9, respectively. Conclusions： The combination of cetuximab with induction chemotherapy followed by CCRT appears feasible and promising. Local and locoregional maximal SUVs, defined by 18F-FDG PET-CT scanning, may represent a prognostic indicator for long-term survival for these patients, which warrants further study.

Clinical study on concurrent chemoradiotherapy combined with Kanglaite injection in the treatment of regionally advanced unresectable non-small cell lung cancer

Objective： To evaluate the clinical effects and toxicity of concurrent chemoradiotherapy combined with Kanglaite injection in the treatment of regionally advanced unresectable non-small cell lung cancer. Methods： 48 patients with regionally advanced unresectable non-small cell lung cancer were randomized to two groups, 25 patients in the combination group （concurrent chemoradiotherapy ＋ Kanglaite） and 23 patients in the control group （concurrent chemoradiotherapy）. The combination group received chemotherapy of vinorelbine （NVB） plus cisplatin （DDP） regimen, radiotherapy was given with conventional fraction in 2 Gy per fraction and five fractions per week concurrently. The total tumor doses were 56-60 Gy. Combined with Kanglaite injection 200 mud for twenty-one days for two courses in the combination group, the control group was chemoradiotherapy only. Effects and toxicities were evaluated according to the criteria of WHO. Results： The CR rates in the combination group and control group were 24.0% （6/25） and 13.0% （3/23）, respectively （P 〉 0.05）. Response （CR ＋ PR） rates of combination group were 76.0 % （19/25） and 69.6% （16/23） in control group, P 〉 0.05. The incidence rates of grades 3-4 leukocytopenia, grades 3-4 digestive system （nausea and vomiting） and grades 3-4 esophagitis in the combination group and control group were 40.0% （10/25）, 8.0% （2/25）, 16.0% （4/25） and 69.6% （16/23）, 34.8% （8/23）, 43.5% （10/23）, respectively （P 〈 0.05）. KPS and body weight score significantly increased in combination group after the combined treatment, P 〈 0.05. Conclusion： Concurrent chemoradiotherapy combined with Kanglaite injection can relieve side effects of chemoradiotherapy in the treatment of regionally advanced unresectable non-small cell lung cancer, and improve quality of life. Kanglaite injection may increase effective rate of regionally advanced unresectable non-small cell lung cancer combined with concurrent chemoradiotherapy.

Induction chemotherapy followed by weekly paclitaxel and carboplatin with concurrent radiotherapy in inoperable stage Ⅲ non-small cell lung cancers: results of a phase Ⅱ trial

Objective： several trials have suggested the superiority of concurrent chemoradiotherapy. It has been hypothesized that the addition of systemic dose sequential chemotherapy to concurrent chemoradiotherapy, as induction or as consolidation, might further improve survival rates. So we sought to evaluate the safety and efficacy of induction paclitaxel and carboplatin followed by weekly paclitaxel and carboplatin with concurrent radiotherapy in inoperable stage III non-small cell lung cancer （NSCLC）. Methods： Fifty-six patients with stage III inoperable NSCLC received induction chemotherapy with 2 cycles of paclitaxel 200 mg/m2 and carboplatin AUC-6 every 3 weeks then patients were assigned to concurrent chemoradiotherapy with paclitaxel 45 mg/m2 and carboplatin AUC-2 weekly along with concurrent radiotherapy at dose of 60 Gy （1.8 Gy/d x 5 d/week）. Results： Median age of the 56 eligible patients was 61 years, most of them were males （87.5%）. Squamous cell carcinoma was the most common pathological type （55.4%） and 85.7% had a performance status of 1. The majority of patients were presented with stage IIIB （62.5%）. Neutropenia was the most common toxicity during induction therapy （12.5% expressed grade 3） whereas esophagitis was the most common non hematologic adverse reaction during concurrent chemoradiotherapy （14.3% of grade 3）. The overall response rate was 71.6% with complete response in 19.6%. After median follow up of 20 months, the median survival time was 13 months （95% CI： 10.917-15.083） and 1 year overall survival rate was 53.6%. Conclusion： This regimen has demonstrated an acceptable toxicity profile and encouraging response to treatment. Evaluation of this regimen in larger number and a phase III trial are recommended.

New challenges in the combination of radiotherapy and immunotherapy in non-small cell lung cancer

Immunotherapy has represented one of the main medical revolutions of recent decades,and is currently a consolidated treatment for different types of tumors at different stages and scenarios,and is present in a multitude of clinical trials.One of the diseases in which it is most developed is non-small cell lung cancer.The combination of radiotherapy and immunotherapy in cancer in general and lung cancer in particular currently represents one of the main focuses of basic and clinical research in oncology,due to the synergy of this interaction,which can improve tumor response,resulting in improved survival and disease control.In this review we present the biochemical and molecular basis of the interaction between radiotherapy and immunotherapy.We also present the current clinical status of this interaction in each of the stages and cases of non-small cell lung cancer,with the main results obtained in the different studies both in terms of tumor response and survival as well as toxicity.Finally,we mention the main studies underway and the challenges of this interaction in the coming years,including how these treatments should be combined to achieve the greatest efficacy with the fewest possible side effects(dose,type of radiotherapy and drugs,sequence of treatments).

Evaluation of conventional radiotherapy vs. conformal radiotherapy in the treatment of non-small-cell lung cancer after surgical resection

Objective： To compare the survival fractions and radiation-induced complications of conventional radiotherapy （CV） vs. conformal radiotherapy （CF） for non-small-cell lung cancer （NSCLC） after surgical resection. Methods： Between 1990 and 2002, 167 patients underwent post-radiotherapy either CV （n = 90） or CF （n = 77） for pathological IliA NSCLC at the University of Texas M.D. Anderson Cancer Center. Patients and tumor charactedstics were balanced in the two treatment groups. Surgical resection mainly consisted of Iobectomy and mediastinal lymph node dissection. In the CV group, postoperative radiotherapy was delivered to 54.3 Gy （range 22-69.6 Gy） in 27 fractions （range 11-58 f） for 5-6 weeks, while the CF group with RT to 53.9 Gy （range 50-63 Gy） in 26 fractions （range 25-33 f） for 5-6 weeks. Overall survival, disease-free survival, local control and distant metastasis-free survival were calculated using the Kaplan-Meier method. The complications of radiotherapy were also compared between the two groups. The median follow-up duration was 36 months in the CV group while 24 months in the CF group. Results： No statistically significant differences were found in terms of disease-free survival, local-regional control and distant metastasis-free survival in the two treatment groups. However, the overall survival was found statistically significant different in the two groups （P = 0.014）. Postoperative radiotherapy complications such as weight loss, skin reaction, dysphagia, and cardiac related complication were similar in the two groups although the lung fibrosis, cardiac complications and hematologic complications were significantly different, and 8 cases of death in the CV group associated with cardiac complications while none was observed in the CF group. Conclusion： The treatment of stage IliA NSCLC using either CV or CF postoperative radiotherapy resulted in similar outcomes in terms of local control, disease-free survival and most of complications. However, CF could achieve better overall survival and less complications such as lung fibrosis, cardiac complications and hematologic complications. The advantage is worth further observation.

Postoperative UFT-/Tegafur-based Chemotherapy Versus Postoperative Radiotherapy for Early-stage Non-small Cell Lung Cancer:A Systematic Review and Network Meta-analysis

Background:Both of UFT-/Tegafur-based postoperative chemotherapy and postoperative radiotherapy have made large progress in treatment of early-stage non-small cell lung cancer.While it is unclear that,whether UFT-/Tegafur-based postoperative chemotherapy is superior to postoperative radiotherapy for early-stage non-small cell lung cancer with no direct evidence.Methods:Electronic databases(Pubmed,embase,cochrane library and clinicaltrials.gov)were searched to obtain relevant studies.This systematic review and meta-analysis is reported in accordance with the Preferred Items for Systematic Reviews and Meta-analysis(PRISMA)Statement and was registered at International Prospective Register of Systematic Reviews(number CRD42018095979).Sensitive analysis was conducted by excluding overweight studies.Funnel plot and egger’s test were performed to conduct publication bias.Results:Twenty-one randomized control trials were included.Our results suggested UFT-/Tegafur-based postoperative chemotherapy could improve overall survival over postoperative radiotherapy[HR=0.69(0.59-0.80),p=0.000].But subgroup analysis about stage showed there was no significant difference between them,no matter of stage I,II and III.As to chemotherapy regime,both UFT-/Tegafur+platinum+vinca alkaloid[HR=0.68(0.56-0.82),p=0.000]and UFT-/Tegafur only[HR=0.66(0.54-0.79),p=0.000]were superior to radiotherapy.Subgroup analysis about radiotherapy delivery method and dose showed,significant improvement of chemotherapy over radiotherapy for Cobalt-60 only[HR=0.54(0.39-0.75),p=0.000],Cobalt-60 and linac[HR=0.69(0.59-0.81),p=0.000]and≥45 Gy[HR=0.64(0.54-0.75),p=0.000],but not for linac only[HR=0.78(0.60-1.03),p=0.081]and≥45 Gy[HR=0.86(0.67-1.11),p=0.241].Conclusion:UFT-/Tegafur-based postoperative chemotherapy was superior to postoperative radiotherapy for improving overall survival of early-stage non-small cell lung cancer,but it is not always so under certain circumstance,such as RT delivery method and radiation dose.Of course,it is imperative to further explore differences in specific stage,such as I A and I B.

Postoperative Radiotherapy and N2 Non-small Cell Lung Cancer Prognosis: A Retrospective Study Based on Surveillance, Epidemiology, and End Results Database

The purpose of this study is to clarify the significance of postoperative radiotherapy for N2 lung cancer.This study aimed to investigate the effect of postoperative radiotherapy on the survival and prognosis of patients with N2 lung cancer.Data from 12,000 patients with N2 lung cancer were extracted from the Surveillance,Epidemiology,and End Results database(2004-2012).Age at disease onset and 5-year survival rates were calculated.Survival curves were plotted using the Kaplan-Meier method.The univariate log-rank test was performed.Multivariate Cox regression were used to examine factors affecting survival.Patients’median age was 67 years(mean 66.46±10.03).The 5-year survival rate was 12.55%.Univariate analysis revealed age,sex,pathology,and treatment regimen as factors affecting prognosis.In multivariate analysis,when compared to postoperative chemotherapy,postoperative chemoradiotherapy was better associated with survival benefits(hazard ratio[HR]=0.85,95%confidence interval[CI]:0.813-0.898,P<0.001).Propensity score matching revealed that patients who had received postoperative chemoradiotherapy had a better prognosis than did patients who had received postoperative chemotherapy(HR=0.869,95%CI:0.817-0.925,P<0.001).Female patients and patients aged<65 years had a better prognosis than did their counterparts.Patients with adenocarcinoma had a better prognosis than did patients with squamous cell carcinoma.Moreover,prognosis worsened with increasing disease T stage.Patients who had received postoperative chemoradiotherapy had a better prognosis than did patients who had received postoperative chemotherapy.Postoperative radiotherapy was an independent prognostic factor in this patient group.