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.

Progress of Immunotherapy Combined with Anti-Angiogenesis Therapy in Lung Cancer

Lung cancer is the most prevalent and fatal cancer in China and even around the world, and many patients are found in the late stage of lung cancer. For the treatment of advanced lung cancer, in addition to traditional chemotherapy modalities, many emerging treatments are increasingly significant, such as immunotherapy, anti-angiogenic therapy, and targeted therapy. An increasing number of studies have now shown that anti-angiogenic therapy improves the immune microenvironment by enhancing tumor immunity through normalization of tumor vessels. Immunization combined with anti-angiogenic therapy can exert synergistic effects and improve the prognosis of patients. This article summarizes the extent of benefit, current clinical study data, and future prospects of immunotherapy combined with anti-angiogenic agents in the treatment of advanced NSCLC.

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.

Bilateral diffuse grade 5 radiation pneumonitis after intensity modulated radiation therapy for localized lung cancer

We are reporting a case of fatal radiation pneumonitis that developed six months following chemoradiation for limited stage small cell lung cancer.The patient was a 67-year-old man with a past medical history of Hashimoto's thyroiditis and remote suspicion for CREST,neither of which were active in the years leading up to treatment.He received 6600 cG y delivered in 200 cG y daily fractions via intensity modulated radiation therapy with concurrent cisplatin/etoposide followed by additional chemotherapy with dosereduced cisplatin/etoposide and carboplatin/etoposide and then received prophylactic cranial irradiation.The subsequent months were notable for progressively worsening episodes of respiratory compromise despite administration of prolonged steroids and he ultimately expired.Imaging demonstrated bilateral interstitial and airspace opacities.Autopsy findings were consistent with pneumonitis secondary to chemoradiation as well as lymphangitic spread of small cell carcinoma.The process was diffuse bilaterally although his radiation was delivered focally to the right lung and mediastinum.

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.

An Integrated Simulation System Based on Digital Human Phantom for 4D Radiation Therapy of Lung Cancer

Purpose: To develop and test an integrated simulation system based on the digital Extended Cardio Torso (XCAT) phantom for 4-dimensional (4D) radiation therapy of lung cancer. Methods: A computer program was developed to facilitate the characterization and implementation of the XCAT phantom for 4D radiation therapy applications. To verify that patient-specific motion trajectories are reproducible with the XCAT phantom, motion trajectories of the diaphragm and chest were extracted from previously acquired MRI scans of five subjects and were imported into the XCAT phantom. The input versus the measured trajectories was compared. Simulation methods of 4D-CT and 4D-cone-beam CT (CBCT) based on the XCAT phantom were developed and tested for regular and irregular respiratory patterns. Simulation of 4D dose delivery was illustrated in a simulated lung stereotactic-body radiation therapy (SBRT) case based on the XCAT phantom. Dosimetric comparison was performed between the planned dose and simulated delivered dose. Result: The overall mean (±standard deviation) difference in motion amplitude between the input and measured trajectories was 1.19 (±0.79) mm for the XCAT phantoms with voxel size of 2 mm. 4D-CT and 4D-CBCT images simulated based on the XCAT phantom were validated using regular respiratory patterns and tested for irregular respiratory patterns. Comparison between simulated 4D dose delivery and planned dose for the lung SBRT case showed comparable results in all dosimetric matrices: the relative differences were 0.3%, 4.0%, 0%, and 2.8%, respectively, for max cord dose, max esophagus dose, mean heart dose, and V20Gy of the lungs. 97.5% of planning target volume (PTV) received prescription dose in the simulated 4D delivery, as compared to 95% of PTV received prescription dose in the plan. Conclusion: We developed an integrated simulation system based on the XCAT digital phantom and illustrated its utility in 4D radiation therapy of lung cancer. This simulation system is potentially a useful tool for quality control and development of imaging and treatment techniques for 4D radiation therapy of lung cancer.

Leveraging diverse cell-death patterns to predict the clinical outcome of immune checkpoint therapy in lung adenocarcinoma:Based on muti-omics analysis and vitro assay

Advanced LUAD shows limited response to treatment including immune therapy.With the development of sequencing omics,it is urgent to combine high-throughput multi-omics data to identify new immune checkpoint therapeutic response markers.Using GSE72094(n=386)and GSE31210(n=226)gene expression profile data in the GEO database,we identified genes associated with lung adenocarcinoma(LUAD)death using tools such as“edgeR”and“maftools”and visualized the characteristics of these genes using the“circlize”R package.We constructed a prognostic model based on death-related genes and optimized the model using LASSO-Cox regression methods.By calculating the cell death index(CDI)of each individual,we divided LUAD patients into high and low CDI groups and examined the relationship between CDI and overall survival time by principal component analysis(PCA)and Kaplan-Meier analysis.We also used the“ConsensusClusterPlus”tool for unsupervised clustering of LUAD subtypes based on model genes.In addition,we collected data on the expression of immunomodulatory genes and model genes for each cohort and performed tumor microenvironment analyses.We also used the TIDE algorithm to predict immunotherapy responses in the CDI cohort.Finally,we studied the effect of PRKCD on the proliferation and migration of LUAD cells through cell culture experiments.The study utilized the TCGA-LUAD cohort(n=493)and identified 2,901 genes that are differentially expressed in patients with LUAD.Through KEGG and GO enrichment analysis,these genes were found to be involved in a wide range of biological pathways.The study also used univariate Cox regression models and LASSO regression analyses to identify 17 candidate genes that were best associated with mortality prognostic risk scores.By comparing the overall survival(OS)outcomes of patients with different CDI values,it was found that increased CDI levels were significantly associated with lower OS rates.In addition,the study used unsupervised cluster analysis to divide 115 LUAD patients into two distinct clusters with significant differences in OS timing.Finally,a prognostic indicator called CDI was established and its feasibility as an independent prognostic indicator was evaluated by Cox proportional risk regression analysis.The immunotherapy efficacy was more sensitive in the group with high expression of programmed cell death models.Relationship between programmed cell death(PCD)signature models and drug reactivity.After evaluating the median inhibitory concentration(IC50)of various drugs in LUAD samples,statistically significant differences in IC50 values were found in cohorts with high and low CDI status.Specifically,Gefitinib and Lapatinib had higher IC50 values in the high-CDI cohort,while Olaparib,Oxaliplatin,SB216763,and Axitinib had lower values.These results suggest that individuals with high CDI levels are sensitive to tyrosine kinase inhibitors and may be resistant to conventional chemotherapy.Therefore,this study constructed a gene model that can evaluate patient immunotherapy by using programmed cell death-related genes based on muti-omics.The CDI index composed of these programmed cell death-related genes reveals the heterogeneity of lung adenocarcinoma tumors and serves as a prognostic indicator for patients.

Inetetamab combined with pyrotinib and chemotherapy in the treatment of breast cancer brain metastasis: A case report

BACKGROUND Breast cancer brain metastasis(BCBM)is an advanced breast disease that is difficult to treat and is associated with a high risk of death.Patient prognosis is usually poor,with reduced quality of life.In this context,we report the case of a patient with HER-2-positive BCBM treated with a macromolecular mAb(ine-tetamab)combined with a small molecule tyrosine kinase inhibitor(TKI).CASE SUMMARY The patient was a 58-year-old woman with a 12-year history of type 2 diabetes.She was compliant with regular insulin treatment and had good blood glucose control.The patient was diagnosed with invasive carcinoma of the right breast(T3N1M0 stage IIIa,HER2-positive type)through aspiration biopsy of the ipsilateral breast due to the discovery of a breast tumor in February 2019.Immunohistochemistry showed ER(-),PR(-),HER-2(3+),and Ki-67(55-60%+).Preoperative neoadjuvant chemotherapy,i.e.,the AC-TH regimen(epirubicin,cyclophosphamide,docetaxel-paclitaxel,and trastuzumab),was administered for 8 cycles.She underwent modified radical mastectomy of the right breast in November 2019 and received tocilizumab targeted therapy for 1 year.Brain metastasis was found 9 mo after surgery.She underwent brain metastasectomy in August 2020.Immunohistochemistry showed ER(-)and PR.(-),HER-2(3+),and Ki-67(10-20%+).In November 2020,the patient experienced headache symptoms.After an examination,tumor recurrence in the original surgical region of the brain was observed,and the patient was treated with inetetamab,pyrotinib,and capecitabine.Whole-brain radiotherapy was recommended.The patient and her family refused radiotherapy for personal reasons.In September 2021,a routine examination revealed that the brain tumor was considerably larger.The original systemic treatment was continued and combined with intensity-modulated radiation therapy for brain metastases,followed by regular hospitalization and routine examinations.The patient’s condition is generally stable,and she has a relatively high quality of life.This case report demonstrates that in patients with BCBM and resistance to trastuzumab,inetetamab combined with pyrotinib and chemotherapy can prolong survival.CONCLUSION Inetetamab combined with small molecule TKI drugs,chemotherapy and radiation may be an effective regimen for maintaining stable disease in patients with BCBM.

Unraveling the efficacy network: A network meta-analysis of adjuvant external beam radiation therapy methods after hepatectomy

BACKGROUND Primary liver cancer is a malignant tumor with a high recurrence rate that significantly affects patient prognosis.Postoperative adjuvant external radiation therapy(RT)has been shown to effectively prevent recurrence after liver cancer resection.However,there are multiple RT techniques available,and the differ-ential effects of these techniques in preventing postoperative liver cancer re-currence require further investigation.AIM To assess the advantages and disadvantages of various adjuvant external RT methods after liver resection based on overall survival(OS)and disease-free survival(DFS)and to determine the optimal strategy.METHODS This study involved network meta-analyses and followed the PRISMA guidelines.The data of qualified studies published before July 10,2023,were collected from PubMed,Embase,the Web of Science,and the Cochrane Library.We included relevant studies on postoperative external beam RT after liver resection that had OS and DFS as the primary endpoints.The magnitudes of the effects were determined using risk ratios with 95%confidential intervals.The results were analyzed using R software and STATA software.RESULTS A total of 12 studies,including 1265 patients with hepatocellular carcinoma(HCC)after liver resection,were included in this study.There was no significant heterogeneity in the direct paired comparisons,and there were no significant differences in the inclusion or exclusion criteria,intervention measures,or outcome indicators,meeting the assumptions of heterogeneity and transitivity.OS analysis revealed that patients who underwent stereotactic body radiotherapy(SBRT)after resection had longer OS than those who underwent intensity modulated radiotherapy(IMRT)or 3-dimensional conformal RT(3D-CRT).DFS analysis revealed that patients who underwent 3D-CRT after resection had the longest DFS.Patients who underwent IMRT after resection had longer OS than those who underwent 3D-CRT and longer DFS than those who underwent SBRT.CONCLUSION HCC patients who undergo liver cancer resection must consider distinct advantages and disadvantages when choosing between SBRT and 3D-CRT.IMRT,a RT technique that is associated with longer OS than 3D-CRT and longer DFS than SBRT,may be a preferred option.

Impacts of radiation therapy on quality of life and pain relief in patients with bone metastases

Bone metastases(BM)are a common complication in advanced cancer patients,significantly contributing to morbidity and mortality due to their ability to cause pain,fractures,and spinal cord compression.Radiation therapy(RT)is vital in managing these complications by targeting metastatic lesions to ease pain,improve mobility,and reduce the risk of skeletal-related events such as fractures.Evidence supports the effectiveness of RT in pain relief,showing its ability to provide significant palliation and lessen the need for opioid painkillers,thereby enhancing the overall quality of life(QoL)for patients with BM.However,optimizing RT outcomes involves considerations such as the choice of radiation technique,dose fractionation schedules,and the integration of supportive care measures to mitigate treatment-related side effects like fatigue and skin reactions.These factors highlight the importance of personalized treatment planning tailored to individual patient needs and tumor characteristics.This mini-review aims to provide comprehensive insights into the multifaceted impacts of RT on pain management and QoL enhancement in BM patients,with implications for refining clinical practices and advancing patient care through the synthesis of findings from various studies.

Clinical Application and Prospect of New Radiotherapy Technology in Cancer Treatment

Objective: Carbon ion therapy, a new radiotherapy technology, has shown its remarkable efficacy and potential in cancer treatment, especially in the treatment of refractory tumors. Methods: This paper clarifies the physical basis, technological change, and clinical practice effect of carbon ion therapy, comprehensively discusses the future prospects, and evaluates the clinical application effect. Results: The technology has significantly improved the treatment effectiveness and received a positive response from patients. Conclusion: Carbon ion therapy technology has become a major innovation in the field of cancer treatment. It not only has a profound impact on many current cancer therapy methods but also indicates the application blueprint for a wider range of cancer types in the future, showing a new chapter of medical technology advancement.

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.

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.

Intensity-modulated radiation therapy with concurrent chemotherapy for locally advanced cervical and upper thoracic esophageal cancer

AIM： To evaluate the dosimetry, efficacy and toxicity of intensity-modulated radiation therapy （IMRT） and concurrent chemotherapy for patients with locally advanced cervical and upper thoracic esophageal cancer. METHODS： A retrospective study was performed on 7 patients who were definitively treated with IMRT and concurrent chemotherapy. Patients who did not receive IMRT radiation and concurrent chemotherapy were not included in this analysis. IMRT plans were evaluated to assess the tumor coverage and normal tissue avoidance. Treatment response was evaluated and toxicities were assessed. RESULTS： Five- to nine-beam IMRT were used to deliver a total dose of 59.4-66 Gy （median： 64.8 Gy） to the primary tumor with 6-MV photons. The minimum dose received by the planning tumor volume （PTV） of the gross tumor volume boost was 91.2%-98.2% of the prescription dose （standard deviation [SD]： 3.7%-5.7%）. The minimum dose received by the PTV Of the clinical tumor volume was 93.8%-104.8% （SD： 4.3%-11.1%） of the prescribed dose. With a median follow-up of 15 rno （range： 3-21 too）, all 6 evaluable patients achieved complete response. Of them, 2 developed local recurrences and 2 had distant metastases, 3 survived with no evidence of disease. After treatment, 2 patients developed esophageal stricture requiring frequent dilation and 1 patient developed tracheal-esophageal fistula. CONCLUSION： Concurrent IMRT and chemotherapy resulted in an excellent early response in patients with locally advanced cervical and upper thoracic esophageal cancer. However, local and distant recurrence and toxicity remain to be a problem. Innovative approaches are needed to improve the outcome.

Role of radiation therapy in neoadjuvant era in patients with locally advanced rectal cancer

Surgery remains the primary determinant of cure in patients with localized rectal cancer, and total mesorectal excision is now widely accepted as standard of care. The widespread implementation of neoadjuvant shortcourse radiotherapy (RT) or long-course chemoradiotherapy (CRT) has reduced local recurrence rates from 25% to 40% to less than 10%; Preoperative RT in resectable rectal cancer has a number of potential advantages, most importantly reducing local recurrence, and down-staging effect. In this article making a comprehensive literature review searching the reliable medical data bases of PubMed and Cochrane we present all available information on the role of radiation therapy alone or in combination with chemotherapy in preoperative setting of rectal cancer. Data reported show that in locally advanced rectal cancer the addition of radiation therapy or CRT pre surgically has significantly improved sphincter prevention surgery. Moreover, the addition of chemotherapy to radiation therapy in preoperative setting has significantly improved pathologic complete response rate and loco-regional control rate without improvement in sphincter preserving surgery. Finally, the results of recently published randomized trials have shown a significant improvement of prevs postoperative CRT on local control; however, there was no effect on overall survival.

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.