Stereotactic body radiation therapy for non-small cell lung cancer:A review

Stereotactic body radiation therapy(SBRT) is the treatment of choice for medically inoperable patients with early stage non-small cell lung cancer(NSCLC). A literature search primarily based on PubMed electronic databases was completed in July 2018. Inclusion and exclusion criteria were determined prior to the search, and only prospective clinical trials were included. Nineteen trials from 2005 to 2018 met the inclusion criteria, reporting the outcomes of 1434 patients with central and peripheral early stage NSCLC. Patient eligibility,prescription dose and delivery, and follow up duration varied widely. Threeyears overall survival ranged from 43% to 95% with loco-regional control of up to 98% at 3 years. Up to 33% of patients failed distantly after SBRT at 3 years. SBRT was generally well tolerated with 10%-30% grade 3-4 toxicities and a few treatment-related deaths. No differences in outcomes were observed between conventionally fractionated radiation therapy and SBRT, central and peripheral lung tumors, or inoperable and operable patients. SBRT remains a reasonable treatment option for medically inoperable and select operable patients with early stage NSCLC. SBRT has shown excellent local and regional control with toxicity rates equivalent to surgery. Decreasing fractionation schedules have been consistently shown to be both safe and effective. Distant failure is common, and chemotherapy may be considered for select patients. However, the survival benefit of additional interventions, such as chemotherapy, for early stage NSCLC treated with SBRT remains unclear.

Effect of Stereotactic Body Radiation Therapy on Diverse Organ Lesions in Advanced Non-Small Cell Lung Cancer Patients Receiving Immune Checkpoint Inhibitors

Objective The combination of stereotactic body radiation therapy(SBRT)and immune checkpoint inhibitors(ICIs)is actively being explored in advanced non-small-cell lung cancer(NSCLC)patients.However,little is known about the optimal fractionation and radiotherapy target lesions in this scenario.This study investigated the effect of SBRT on diverse organ lesions and radiotherapy dose fractionation regimens on the prognosis of advanced NSCLC patients receiving ICIs.Methods The medical records of advanced NSCLC patients consecutively treated with ICIs and SBRT were retrospectively reviewed at our institution from Dec.2015 to Sep.2021.Patients were grouped according to radiation sites.Progression-free survival(PFS)and overall survival(OS)were recorded using the Kaplan-Meier method and compared between different treatment groups using the log-rank(Mantel-Cox)test.Results A total of 124 advanced NSCLC patients receiving ICIs combined with SBRT were identified in this study.Radiation sites included lung lesions(lung group,n=43),bone metastases(bone group,n=24),and brain metastases(brain group,n=57).Compared with the brain group,the mean PFS(mPFS)in the lung group was significantly prolonged by 13.3 months(8.5 months vs.21.8 months,HR=0.51,95%CI:0.28–0.92,P=0.0195),and that in the bone group prolonged by 9.5 months with a 43%reduction in the risk of disease progression(8.5 months vs.18.0 months,HR=0.57,95%CI:0.29–1.13,P=0.1095).The mPFS in the lung group was prolonged by 3.8 months as compared with that in the bone group.The mean OS(mOS)in the lung and bone groups was longer than that of the brain group,and the risk of death decreased by up to 60%in the lung and bone groups as compared with that of the brain group.When SBRT was concurrently given with ICIs,the mPFS in the lung and brain groups were significantly longer than that of the bone group(29.6 months vs.16.5 months vs.12.1 months).When SBRT with 8–12 Gy per fraction was combined with ICIs,the mPFS in the lung group was significantly prolonged as compared with that of the bone and brain groups(25.4 months vs.15.2 months vs.12.0 months).Among patients receiving SBRT on lung lesions and brain metastases,the mPFS in the concurrent group was longer than that of the SBRT→ICIs group(29.6 months vs.11.4 months,P=0.0003 and 12.1 months vs.8.9 months,P=0.2559).Among patients receiving SBRT with<8 Gy and 8–12 Gy per fraction,the mPFS in the concurrent group was also longer than that of the SBRT→ICIs group(20.1 months vs.5.3 months,P=0.0033 and 24.0 months vs.13.4 months,P=0.1311).The disease control rates of the lung,bone,and brain groups were 90.7%,83.3%,and 70.1%,respectively.Conclusion The study demonstrated that the addition of SBRT on lung lesions versus bone and brain metastases to ICIs improved the prognosis in advanced NSCLC patients.This improvement was related to the sequence of radiotherapy combined with ICIs and the radiotherapy fractionation regimens.Dose fractionation regimens of 8–12 Gy per fraction and lung lesions as radiotherapy targets might be the appropriate choice for advanced NSCLC patients receiving ICIs combined with SBRT.

Study of the impact of CT/CT image fusion radiotherapy on V_(20) and radiation pneumonitis of non-small cell lung cancer

Objective:The aim of our study was to investigate the value of CT/CT image fusion radiation treatment planning in non-small cell lung cancer(NSCLC) and the impact on V20 and radiation pneumonitis(RP).Methods:Patients who were pathologically or cytologically diagnosed of stage IIIA and IIIB NSCLC were treated with three-dimensional conformal radiation therapy(4000 cGy).Forty patients got at least 25% tumor reduction were randomly divided into two groups:group A of regular shrink field radiotherapy(20 cases) and group B of CT/CT image fused shrink field radiotherapy(20 cases).Dosage reached 6600 cGy.Clinical data,V20 and RP were observed within 3 months after radiotherapy.Statistical analysis was conducted for the NSCLC patients.Results:22.5%(9/40) patients got RP during follow-up.Group A accounted for 6 cases(30%),and group B had 3 cases(15%).There was no marked difference between the two groups(P = 0.256),univariate analysis revealed that the IV20 of A and B groups,and IV20 and CV20 of all patients were statistically related to the incidence of RP(P < 0.05).With Wilcoxon method assay,the ipsilateral lung V20 and contralateral lung V20 had statistical significance between the two groups(P < 0.05).Conclusion:The CT/CT image infusion treatment planning could increase the radical dosage with better tumor control probability but won't increase adverse reaction.

Stereotactic body radiation therapy:A good dance partner of oligometastatic non-small cell lung cancer to the sound of SINDAS study

The European Organization for Research on Treatment of Cancer Research published a consensus statement to establish the key criteria to define oligometastatic disease(OMD).According to those criteria,all lesions(both primary and metastatic)should be amenable to radical intent treatment with acceptable toxicity.Several retrospective studies have shown that adding local ablative therapy to the treatment of OMD improves outcomes;however,due to the diverse selection criteria and treatment strategies used in those studies,it is difficult to compare directly results to draw definitive conclusions.In recent years,prospective phase II trials,such as the SABR-COMET and"Oligomez"trials,have shown that stereotactic body radiation therapy(SBRT)improves outcomes in patients with OMD.More recently,interim results of the randomised phase 3 SINDAS trial were reported at the annual meeting of the American Society of Clinical Oncology 2020 demonstrating that upfront SBRT added to systemic treatment with tyrosine kinase inhibitors yielded a significant benefit in both progression-free survival and overall survival in patients with epidermal growth factor receptor-mutant oligometastatic non-small cell lung cancer.In the present editorial,we review the definition and historical context of advanced non-small cell lung cancer with OMD.In addition,we review the scientific evidence for local ablative therapy and SBRT and discuss the results of recently published prospective studies.We also discuss in depth the results of the SINDAS study,including the strengths and weaknesses of the study and the barriers to extrapolating these results to routine clinical practice.

Effect of intensity modulated radiation therapy combined with paclitaxel+ endostar chemotherapy on serum malignant molecule levels in patients with locally advanced non-small cell lung cancer

Objective: To discuss the effect of intensity modulated radiation therapy combined with paclitaxel + endostar chemotherapy on serum malignant molecule levels in patients with locally advanced non-small cell lung cancer. Methods: Patients with locally advanced NSCLC who were treated in the hospital between February 2015 and January 2017 were collected and divided into control group (n=59) and research group (n=59) by random number table. Control group received the routine paclitaxel + endostar chemotherapy after the operation, and research group underwent intensity modulated radiation therapy combined with paclitaxel +endostar chemotherapy after the operation. The differences in serum levels of NSCLC-related tumor markers and angiogenesis indexes were compared between the two groups before and after treatment. Results: Before treatment, the differences in serum levels of NSCLC-related tumor markers and angiogenesis indexes were not statistically significant between the two groups. After treatment, serum TK1, CYFRA21-1, Pro-GRP, CEA, CA125 and SCC-Ag levels of research group were lower than those of control group;serum EGFR, COX-2, VEGF, HIF-1 and MMP-2 levels of research group were lower than those of control group. Conclusion:Postoperative intensity modulated radiation therapy combined with paclitaxel + endostar chemotherapy can effectively reduce the serum malignant molecule levels and optimize the illness in patients with local advanced NSCLC.

Clinical study on concurrent and sequential therapy of intensity modulated radiation therapy (IMRT) combined with NP regimen chemotherapy in the treatment of middle and advanced non-small cell lung cancer

Objective: To evaluate the clinical effects of concurrent and sequential therapy for middle and advanced stage non-small cell lung cancer (NSCLC) useing IMRT combined with NP regimen chemotherapy. Methods: Eighty patients with middle and advanced stage NSCLC were randomized into two groups. Forty patients were underwent sequential therapy and other 40 patients were underwent concurrent therapy. IMRT was used in radiotherapy and NP regimen of vinorelbine+cispatin (NP) was used in chemotherapy. Results: (1) The overall response (CR+PR) rate was 75% in concurrent group and 45% in sequential group (P<0.05); (2) The treatment courses were 84 days and 140 days for concurrent group and sequential group respectively (P<0.05); (3) One-year survival rate in concurrent group was 72.4% and 52.3% in sequential group respectively; (4) The toxic effects can be tolerable by all of patients. Conclusion: The concurrent chemo-radiotherapy has better overall re- sponse, one-year survival rate and shorter treatment course than the sequential chemo-radiotherapy, so it is a better method for the treatment of middle and advanced stage NSCLC, but the long term survival rate will be studied.

Chemotherapy combined with bevacizumab for small cell lung cancer with brain metastases:A case report

BACKGROUND Small cell lung cancer(SCLC)is a common and aggressive subtype of lung cancer.It is characterized by rapid growth and a high mortality rate.Approximately 10%of patients with SCLC present with brain metastases at the time of diagnosis,which is associated with a median survival of 5 mo.This study aimed to summarize the effect of bevacizumab on the progression-free survival(PFS)and overall survival of patients with brain metastasis of SCLC.CASE SUMMARY A 62-year-old man was referred to our hospital in February 2023 because of dizziness and numbness of the right lower extremity without headache or fever for more than four weeks.The patient was diagnosed with limited-stage SCLC.He received 8 cycles of chemotherapy combined with maintenance bevacizumab therapy and achieved a PFS of over 7 mo.CONCLUSION The combination of bevacizumab and irinotecan effectively alleviated brain metastasis in SCLC and prolonged PFS.

Optimal timing of thoracic irradiation for limited stage small cell lung cancer:Current evidence and future prospects

Lung cancer is a global health concern as the leading cause of cancer related mortality worldwide.Small cell lung cancer(SCLC)poses a formidable challenge to the treating physicians with the worst prognosis among all lung cancers.However,limited stage SCLC(LS-SCLC)has a relatively better outcome with multimodality management.Efforts have been focused on optimal integration of treatment modalities to achieve an improved therapeutic ratio for patients with LS-SCLC.While chemotherapy and thoracic radiation therapy(TRT)are primary components of initial management for LS-SCLC,there is no consensus on optimal timing of TRT.Within this context,we herein provide a concise overview of current evidence and future prospects regarding the optimal timing of thoracic irradiation for LS-SCLC in light of the literature.

CLINICAL STUDY IN ACCELERATED HYPERFRACTIONATED IRRADIATION IN THE TREATMENT OF LOCAL ADVANCED NON-SMALL CELL LUNG CANCER

Objective To evaluate the effect of accelerated hyperfractionated irradiation (AHFJ) and conventional fractionated irradiation (CFI) for local advanced non- small cell lung cancer (NSCLC). Methods The patients of AI-IFJ group were irradiated to large-field target volume by a daily fraction of 2Gy, and small-field target volume by a daily fraction of 1Gy with more than 6h interval. The total dose of large-field target volume was SOGy/25Fx/SW and of small-field target volume was 7SGy/SOFx/5W. The patients in CFI group were irradiated by a daily fraction of 2Gy to the total dose of 66Gy/33Fx/6. 6W. After 3 months of radiotherapy, the tumor response rates of complete recovery (CR), partial recovery (PR), and no change (NC) and 1- and 2- year survival rate in the two groups were observed. Results The tumor response rates of CR,PR,NC in AHFI group and CFI group were 22.9%(8/35), 60.0%(21/35), 17.1%(6/35) and 11.4% (4/35), 51.4% (18/35), 37.2% (13/35) respectively (P>0. 05). All patients were followed up 2 years or more. The 1- and 2- year survival rates in AHFI group and CFI group were 62.9% (22/35), 31 .4% (11/35) and 42.9% (15/35) , 17.1% (6/35) respectively (P< 0.05). The incidences of esophagitis and pneumonitis in AHFI group and CFI group were 34.3% (12/35), 22. 9% (8/35) and 40.0% (14/35), 17.1% (6/35)(P>0. 05). Conclusion In comparison with CFI, AHFI may increase 1- and 2- year sur-vival rate after treatment of local advanced non-small cell lung cancer, while the radio-reactions, either early or late, did not increase significantly.

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.

Sequential therapy according to distinct disease progression patterns in advanced ALK-positive non-small-cell lung cancer after crizotinib treatment

Objective: Crizotinib is recommended as the first-line therapy for advanced anaplastic lymphoma kinase(ALK)-positive non-small-cell lung cancer(NSCLC). Despite its initial efficacy, patients ultimately acquire resistance to crizotinib within 1 year. In such patients, the optimal sequential therapy after crizotinib treatment remains unknown. This study explored which sequential therapy option confers the greatest benefit.Methods: A total of 138 patients with advanced ALK-positive NSCLC resistant to crizotinib were studied. Based on patterns of disease progression of metastases, patients were divided into 3 groups: brain progression, non-liver progression, and liver progression. Sequential therapies included crizotinib continuation plus local therapy, nextgeneration ALK inhibitors(ALKi's), and chemotherapy. The primary endpoint was overall survival(OS) from the time of crizotinib resistance to death or last follow-up.Results: The 138 patients included 64 cases with progression in brain, 57 cases in non-liver sites and 17 cases in liver. A significant difference in OS was observed among the distinct progression pattern(median OS, 25.4 months in brain, 15.8 months in non-liver, and 10.8 months in liver, respectively, P=0.020). The difference in OS among sequential therapies was statistically significant in the non-liver progression group(median OS, 27.6 months with next-generation ALKi's, 13.3 months with crizotinib continuation, and 10.8 months with chemotherapy,respectively, P=0.019). However, crizotinib continuation plus local therapy seems to provide non-inferior median OS compared with next-generation ALKi's for patients with brain progression(median OS, 28.9 months vs.32.8 months, P=0.204). And no significant differences in OS were found in patients with progression in liver(P=0.061).Conclusions: Crizotinib continuation together with local therapy might be a feasible strategy for patients with progression in brain beyond crizotinib resistance, as well as next-generation ALKi's. Next-generation ALKi's tended to provide a survival benefit in patients with non-liver progression.

Surgical strategies in the therapy of non-small cell lung cancer

Lung cancer represents the leading cause of cancer mortality worldwide. Despite improvements in preoperative staging, surgical techniques, neoadjuvant/adjuvant options and postoperative care, there are still major difficulties in significantly improving survival, especially in locally advanced non-small cell lung cancer(NSCLC). To date, surgical resection is the primary mode of treatment for stage?Ⅰ?and Ⅱ NSCLC and has become an important component of the multimodality therapy of even more advanced disease with a curative intention. In fact, in NSCLC patients with solitary distant metastases, surgical interventions have been discussed in the last years. Accordingly, this review displays the recent surgical strategies implemented in the therapy of NSCLC patients.

Weekly albumin-bound paclitaxel/cisplatin versus gemcitabine/cisplatin as first-line therapy for patients with advanced non-small-cell lung cancer:A phase II open-label clinical study

Objective: The aim of this trial was to compare both the efficacy and the safety of a weekly nanoparticle albumin-bound paclitaxel(nab-paclitaxel) plus cisplatin vs. gemcitabine plus cisplatin in patients with advanced non-small-cell lung cancer(NSCLC).Methods: A total of 84 participants received either 100 mg/m^2 nab-paclitaxel each week on d 1, 8 and 15 of a 28 day cycle, as well as cisplatin 75 mg/m^2 on d 1 every three weeks(nab-TP arm); or gemcitabine 1,000 mg/m^2 on d 1 and 8, plus cisplatin 75 mg/m^2 on d 1 every three weeks(GP arm). The primary end point was progression-free survival(PFS). The secondary end points were overall response rate(ORR) and overall survival(OS).Results: According to our analysis, the median PFS was 4.8 months for the nab-TP arm vs. 5.2 months for the GP arm(P=0.55). Analysis showed the median OS was 14.6 months for participants who were in the nab-TP arm vs. 15.1 months for those in the GP arm(P=0.94). Besides, nab-TP showed OS advantages over GP in patients harboring epidermal growth factor receptor(EGFR) mutation(26.7 vs. 15.3 months, P=0.046) and patients with a performance status of 0(23.5 vs. 14.7 months, P=0.020). It was found that incidences of drug-related grade 3 or 4 toxicities were comparable between the two treatment arms.Conclusions: Therefore, it can be seen that weekly nab-TP treatment has a similar efficacy and tolerability to GP treatment for patients who are undergoing their first-line treatment for NSCLC. It could be that survival differences among platinum doublets in the context of both EGFR mutation and performance status have the potential to be the basis for our further clinical trials.

Advances in adjuvant systemic therapy for non-small-cell lung cancer

Non-small-cell lung cancer remains a leading cause of death around the world. For most cases, the only chance of cure comes from resection for localised disease, however relapse rates remain high following surgery. Data has emerged over recent years regarding the utility of adjuvant chemotherapy for improving disease-free and overall survival of patients following curative resection. This paper reviews the clinical trials that have been conducted in this area along with the studies integrating radiation therapy in the adjuvant setting. The role of prognostic gene signatures are reviewed as well as ongoing clinical trials including those incorporating biological or targeted therapies.

GOECP/SEOR radiotherapy guidelines for small-cell lung cancer

Small cell lung cancer(SCLC)accounts for approximately 20%of all lung cancers.The main treatment is chemotherapy(Ch).However,the addition of radiotherapy significantly improves overall survival(OS)in patients with non-metastatic SCLC and in those with metastatic SCLC who respond to Ch.Prophylactic cranial irradiation reduces the risk of brain metastases and improves OS in both metastatic and non-metastatic patients.The 5-year OS rate in patients with limited-stage disease(non-metastatic)is slightly higher than 30%,but less than 5%in patients with extensive-stage disease(metastatic).The present clinical guidelines were developed by Spanish radiation oncologists on behalf of the Oncologic Group for the Study of Lung Cancer/Spanish Society of Radiation Oncology to provide a current review of the diagnosis,planning,and treatment of SCLC.These guidelines emphasise treatment fields,radiation techniques,fractionation,concomitant treatment,and the optimal timing of Ch and radiotherapy.Finally,we discuss the main indications for reirradiation in local recurrence.

A Phase Ⅱ Trial of Gefitinib as Maintenance Therapy after First-Line Chemotherapy for Advanced Non-Small Cell Lung Cancer in China

Objective： To investigate the efficacy and safety of gefitinib as maintenance therapy for advanced non-small cell lung cancer （NSCLC） patients who obtained disease control （DC） after first-line chemotherapy in Chinese population. Methods： Chinese patients with advanced NSCLC treated with standard chemotherapy and obtained DC were assigned to receive gefitinib as maintenance treatment. The primary end point was overall survival time （OS）, the second end point was disease control rate （DCR） and progression-free survival time （PFS）. DCR included complete response （CR） plus partial response （PR） and plus stable disease （SD）. The impact of epidermal growth factor receptor （EGFR） mutation status on the treatment as exploratory point was also evaluated by denaturing high-performance liquid chromatography （DHPLC）. Results： Among 75 enrolled patients, the overall response rate was 37% and the DCR （CR ＋ PR ＋SD） was 66%. The median PFS and OS were 17.13 months and 26.13 months respectively, with 1- and 2-year survival rates 89.3% and 34.7%. Patients harboring somatic EGFR mutations obtained a prolonged median PFS and OS compared with EGFR wide type （25.1 vs. 13.0 months, P=0.019 and 33.37 vs. 25.57 months, P=0.014, respectively）. In COX regression model, only EGFR mutation status was the independently factor influencing both PFS and OS （P=0.029 and 0.017, respectively）, however, rash status was the predictor in terms of PFS （P=0.027）. Conclusion： Gefitinib produced encouraging survival when delivered as maintenance therapy in Chinese patients obtaining DC after first-line chemotherapy, especially for patients carrying somatic EGFR mutations. EGFR mutation is an independently predictive factor of survival.

Review of the current targeted therapies for non-small-cell lung cancer

The last decade has witnessed the development of oncogene-directed targeted therapies that have significantly changed the treatment of non-small-cell lung cancer(NSCLC). In this paper we review the data demonstrating efficacy of gefitinib, erlotinib, and afatinib, which target the epidermal growth factor receptor(EGFR), and crizotinib which targets anaplastic lymphoma kinase(ALK). We discuss the challenge of acquired resistance to these small-molecular tyrosine kinase inhibitors and review promising agents which may overcome resistance, including the EGFR T790 Mtargeted agents CO-1686 and AZD9291, and the ALKtargeted agents ceritinib(LDK378), AP26113, alectinib(CH/RO5424802), and others. Emerging therapies directed against other driver oncogenes in NSCLC including ROS1, HER2, and BRAF are covered as well. The identification of specific molecular targets in a significant fraction of NSCLC has led to the personalized deployment of many effective targeted therapies, with more to come.

Re-challenge chemotherapy with gemcitabine plus carboplatin in patients with non-small cell lung cancer

Despite recent improvements to current therapies and the emergence of novel agents to manage advanced non-small cell lung cancer(NSCLC),the patients′overall survival remains poor.Re-challenging with first-line chemotherapy upon relapse is common in the management of small cell lung cancer but is not well reported for advanced NSCLC.NSCLC relapse has been attributed to acquired drug resistance,but the repopulation of sensitive clones may also play a role,in which case re-challenge may be appropriate.Here,we report the results of re-challenge with gemcitabine plus carboplatin in 22 patients from a single institution who had previously received gemcitabine plus platinum in the first-line setting and had either partial response or a progression-free interval of longer than 6 months.In this retrospective study,the charts of patients who underwent second-line chemotherapy for NSCLC in our cancer center between January 2005 and April 2010 were reviewed.All the patients who received a combination of gemcitabine and carboplatin for re-challenge were included in the study.These patients were offered second-line treatment on confirmation of clear radiological disease progression.The overall response rate was 15%and disease control rate was 75%.The median survival time was 10.4 months,with 46%of patients alive at 1 year.These results suggest that re-challenge chemotherapy should be considered in selected patients with radiological partial response or a progression-free survival of longer than 6 months to the initial therapy.

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.

Better to be alone than in bad company:The antagonistic effect of cisplatin and crizotinib combination therapy in non-small cell lung cancer

AIM To investigate the potential benefit of combining the cMET inhibitor crizotinib and cisplatin we performed in vitro combination studies.METHODS We tested three different treatment schemes in four non-small cell lung cancer(NSCLC) cell lines with a different cMET/epidermal growth factor receptor genetic background by means of the sulforhodamine B assay and performed analysis with Calcusyn.RESULTS All treatment schemes showed an antagonistic effect in all cell lines,independent of the cMET status.Despite their different genetic backgrounds,all cell lines(EBC-1,HCC827,H1975 and LUDLU-1) showed antagonistic combination indexes ranging from 1.3-2.7.These results were independent of the treatment schedule.CONCLUSION These results discourage further efforts to combine cMET inhibition with cisplatin chemotherapy in NSCLC.