Favorable response after radiation therapy for intraductal papillary mucinous neoplasms manifesting as acute recurrent pancreatitis:A case report

BACKGROUND There has been an increasing number of elderly patients with intraductal papillary mucinous neoplasm(IPMN),who are surgically intolerant and require less invasive treatment options,which are limited.In the present study,we report a case of IPMN presenting with acute recurrent pancreatitis(ARP),in which radiation therapy effectively prevented further attacks of ARP and reduced tumor volume.CASE SUMMARY An 83-year-old man was referred to our hospital with an asymptomatic incidental pancreatic cyst.Endoscopic ultrasound imaging and magnetic resonance cholangiopancreatography revealed a multiloculated tumor in the head of the pancreas,with dilated pancreatic ducts and mural nodules.The patient was diagnosed with mixed-type IPMN,and five years later,he developed ARP.Several endoscopic pancreatic ductal balloon dilatations failed to prevent further ARP attacks.Surgery was considered clinically inappropriate because of his old age and comorbidities.He was referred to our department for radiation therapy targeted at those lesions causing intraductal hypertension and radiation was administered at a dose of 50 Gy.An magnetic resonance imaging scan taken ten weeks after treatment revealed a decrease in tumor size and improvement of pancreatic duct dilatation.Fourteen months later,he remains symptom-free from ARP.CONCLUSION This case highlights the important role of radiation therapy in mitigating the signs and symptoms of ARP in patients with inoperable IPMN.

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.

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.

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.

Dosimetric Comparison of Different Prescription Modes in Lung Stereotactic Body Radiation Therapy

The purpose of this study was to compare the dose-volume statistics of stereotactic body radiotherapy (SBRT) for lung cancer between planning target volume (PTV): D95 and gross tumor volume (GTV): D99 dose prescriptions using Monte Carlo (MC) calculation. Plans for 183 patients treated between October 2010 and April 2013 were generated based on four-dimensional (4D) computed tomography (CT) under free breathing. A uniform margin of 8 mm was added to the internal target volume (ITV) to generate PTV. A leaf margin of 2 mm was added to the PTV. The plans were calculated with two different dose prescription methods: 40 Gy to cover 95% of the PTV (PTV prescription) and 44 Gy to cover 99% of the GTV (GTV prescription). A 6-MV photon beam was used. A dose-volume histogram (DVH) analysis was performed for dose to the GTV using PTV and GTV dose prescriptions. For each treatment plan, we evaluated the minimum dose to 99% of the GTV (D99). The D99 of GTV was 44.5 ± 1.9 Gy and 44.0 ± 0.0 Gy for PTV and GTV prescriptions, respectively. The dose to the GTV had wide variations with PTV prescription. We recommend that GTV based dose prescription should be used to standardize dose to the tumor and to achieve highly conformal dose distributions in SBRT for lung cancer.

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.

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.

The Physical and Clinical Aspects of Radiation Therapy in Skin Cancer and Subcutaneous Tissue Neoplasm

Cancers, malignant melanoma and sarcomas of the skin represent the most common group of malignancies in humans. The main treatment method of almost all skin cancers and subcutaneous tissue tumours is surgery, which consists of complete removal of a neoplastic lesion, with an adequate margin of healthy tissue. Radiotherapy plays an adjuvant role in this process, meaning complementing of the surgical procedure. This study compared four methods of irradiation treatment of cancer located in the skin or in subcutaneous tissues: contact brachytherapy, conventional orthovoltage therapy, electron beam conformal teleradiotherapy and IMRT dynamically shaped photonic beams conformal teleradiotherapy. In order to compare the methods and techniques of surface radiotherapy, following specific objectives were formulated. At the beginning in order to compare the scopes of the absorbed doses at different tissue depths, an analysis of parameters describing particular beams or radiation source has been performed—the curves for the absorbed-dose depth drop-offs. Doses distribution in tissue-like phantoms stimulating homogeneous cuboidal tissue block has been determined. A quality comparison of dose distribution in 2D and 3D treatment planning system for contact brachytherapy application has been made. The dose distribution for electron beam in the system has been determined. Conformal plannings for electron beam treatment, contact brachytherapy applicator treatment and 4 photon beams treatment optimized in IMRT technology have been performed. Dose distribution has been performed for the irradiated female patient within the well chest—the target included the recurrence area in the post-operative scar. The radiation therapy with X-rays has actually been completely eliminated from skin cancer and subcutaneous tissue radiotherapy by the electrons generated in linear accelerators, contact brachytherapy HDR and by high-energy photons used in conformal techniques, ex. IMRT. It is because the residual dose beyond the target is the highest for single X-ray beam. Although in brachytherapy HDR a rapid dose drop-off is observed, 5 cm from its normalization level for the target the residual radiation remains at the level of several percent. So, both X-rays beam radiation and brachytherapy in skin cancer treatment is connected with the administration of the dose with a high gradient in the health tissues. The dose distribution for photon conformal techniques IMRT or for electron radiation looks different. There with the dose normalization at the level of 90% or 85% we deal with the dose layer, the division does not exceed 15% of heterogeneity.

Role of stereotactic body radiation therapy for hepatocellular carcinoma

The integration of new technologies has raised an interest in liver tumor radiotherapy,with literature evolving to support its efficacy.These advances,particularly stereotactic body radiation therapy(SBRT),have been critical in improving local control or potential cure in liver lesions not amenable to first-line surgical resection or radiofrequency ablation.Active investigation of SBRT,particularly for hepatocellular carcinoma(HCC),has recently started,yielding promising local control rates.In addition,data suggest a possibility that SBRT can be an alternative option for HCC unfit for other local therapies.However,information on optimal treatment indications,doses,and methods remains limited.In HCC,significant differences in patient characteristics and treatment availability exist by country.In addition,the prognosis of HCC is greatly influenced by underlying liver dysfunction and treatment itself in addition to tumor stage.Since they are closely linked to treatment approach,it is important to understand these differences in interpreting outcomes from various reports.Further studies are required to validate and maximize the efficacy of SBRT by a large,multi-institutional setting.

Complete response to radiation therapy of orbital metastasis from hepatocellular carcinoma

The incidence of hepatocellular carcinoma(HCC)is increasing in the United States,and 50%-75%o patients with HCC will develop metastatic disease Orbital metastases from HCC are extremely rare.We report the case of a 52-year-old male with known metastatic HCC,who presented with severe proptosis and diplopia.An orbital mass was identified on magnetic resonance imaging(MRI)and confirmed to have hypermetabolic activity on positron emission tomography/computed tomography.He received a palliative course of external beam radiation therapy to the right orbit.Intensity modulated radiation therapy (IMRT)was used to allow sparing of critical norma tissues in close proximity to the tumor.One month after completion of IMRT to 58 Gray in 30 fractions delivered over 6 wk,the patient had a complete clinical,radiologic(MRI)and symptomatic response The patient continues to have local control in the orbi 1.7 years after therapy completion.All critical norma structures were kept below the tolerance dose using IMRT,and no toxicities were observed.

Symptomatic Radiation Pneumonitis in NSCLC Patients Receiving EGFR-TKIs and Concurrent Oncedaily Thoracic Radiotherapy:Predicting the Value of Clinical and Dose-volume Histogram Parameters

Background and objectives:The incidence of symptomatic radiation pneumonitis(RP)and its relationship with dose-volume histogram(DVH)parameters in non-small cell lung cancer(NSCLC)patients receiving epidermal growth factor receptortyrosine kinase inhibitors(EGFR-TKIs)and concurrent once-daily thoracic radiotherapy(TRT)remain unclear.We aim to analyze the values of clinical factors and dose-volume histogram(DVH)parameters to predict the risk for symptomatic RP in these patients.Methods:Between 2011 and 2019,we retrospectively analyzed and identified 85 patients who had received EGFR-TKIs and oncedaily TRT simultaneously(EGFR-TKIs group)and 129 patients who had received concurrent chemoradiotherapy(CCRT group).The symptomatic RP was recorded according to the Common Terminology Criteria for Adverse Event(CTCAE)criteria(grade 2 or above).Statistical analyses were performed using SPSS 26.0.Results:In total,the incidences of symptomatic(grade≥2)and severe RP(grade≥3)were 43.5%(37/85)and 16.5%(14/85)in EGFR-TKIs group vs 27.1%(35/129)and 10.1%(13/129)in CCRT group respectively.After 1:1 ratio between EGFR-TKIs group and CCRT group was matched by propensity score matching,chi-square test suggested that the incidence of symptomatic RP in the MATCHED EGFR-TKIs group was higher than that in the matched CCRT group(χ^(2)=4.469,P=0.035).In EGFRTKIs group,univariate and multivariate analyses indicated that the percentage of ipsilateral lung volume receiving≥30 Gy(ilV_(30))[odds ratio(OR):1.163,95%CI:1.036-1.306,P=0.011]and the percentage of total lung volume receiving≥20 Gy(tlV_(20))(OR:1.171,95%CI:1.031-1.330,P=0.015),with chronic obstructive pulmonary disease(COPD)or not(OR:0.158,95%CI:0.041-0.600,P=0.007),were independent predictors of symptomatic RP.Compared to patients with lower iIV_(30)/tlV_(20)values(ilV_(30)and tlV_(20)<cut-off point values)and without COPD,patients with higher ilV_(30)/tlV_(20)values(ilV_(30)and tlV_(20)>cut-off point values)and COPD had a significantly higher risk for developing symptomatic RP,with a hazard ratio(HR)of 1.350(95%CI:1.190-1.531,P<0.001).Conclusion:Patients receiving both EGFR-TKIs and once-daily TRT were more likely to develop symptomatic RP than patients receiving concurrent chemoradiotherapy.The ilV_(30),tlV_(20),and comorbidity of COPD may predict the risk of symptomatic RP among NSCLC patients receiving EGFR-TKIs and conventionally fractionated TRT concurrently.

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 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.

Efficacy Differences of First-line EGFR-TKIs Alone vs in Combination with Chemotherapy in Advanced Lung Adenocarcinoma Patients with Sensitive EGFR Mutation and Concomitant Non-EGFR Genetic Alterations

Background and objective:Epidermal growth factor receptor(EGFR)mutations are often associated with non-EGFR genetic alterations,which maybe a reason for the poor efficacy of EGFR tyrosine kinase inhibitors(TKIs).Here we conducted this study to explore whether EGFR-TKIs combined with chemotherapy would benefit advanced lung adenocarcinoma patients with both sensitive EGFR mutation and concomitant non-EGFR genetic alterations.Materials and methods:Cases of advanced lung adenocarcinoma with EGFR mutation combined with concomitant nonEGFR genetic alterations were retrospectively collected.And the patients were required to receive first-line EGFR-TKIs and chemotherapy combination or EGFR-TKIs monotherapy.Demographic,clinical and pathological data were collected,and the electronic imaging data were retrieved to evaluate the efficacy and time of disease progression.Survival data were obtained through face-to-face or telephone follow-up.The differences between the two groups in objective response rate(ORR),disease control rate(DCR),progression-free survival(PFS)and overall survival(OS)were investigated.Results:107 patients were included,including 63 cases in the combination group and 44 cases in the monotherapy group.The ORR were 78%and 50%(P=0.003),and DCR were 97%and 77%(P=0.002),respectively.At a median follow-up of 13.7 mon,a PFS event occurred in 38.1%and 81.8%of patients in the two groups,with median PFS of18.8 mon and 5.3 mon,respectively(P<0.000,1).Median OS was unreached in the combination group,and 27.8 mon in the monotherapy group(P=0.31).According to the Cox multivariate regression analysis,combination therapy was an independent prognostic factor of PFS.Conclusion:In patients with EGFR-mutant advanced lung adenocarcinoma with concomitant non-EGFR genetic alterations,combination of TKIs and chemotherapy was significantly superior to EGFR-TKIs monotherapy,which should be the preferred treatment option.

Gene Polymorphisms and Chemotherapy in Non-small Cell Lung Cancer

The phamacogenetics is being used to predict whether the selected chemotherapy will be really effective and tolerable to the patient. Irinotecan,oxidized by CYP3A4 to produce inactive compounds,is used for treatment of various cancers including advanced non small cell lung cancer (NSCLC) patients. CYP3A4*16B polymorphism was associated with decreased metabolism of irrinotecan. Irinotecan is also metabolized by carboxylesterase to its principal active metabolite,SN-38,which is subsequently glucuronidated by UGT1As to form the inactive compound SN-38G. UGT1A1*28 and UGT1A1*6 polymorphisms were useful for predicting severe toxicity with NSCLC patients treated with irinotecan-based chemotherapy. Platinum-based compounds (cisplatin,carboplatin) are being used in combination with new cytotoxic drugs such as gemcitabine,paclitaxel,docetaxel,or vinorelbine in the treatment of advanced NSCLC. Cisplatin activity is mediated through the formation of cisplatin-DNA adducts. Gene polymorphisms of DNA repair factors are therefore obvious candidates for determinants of repair capacity and chemotherapy efficacy. ERCC1,XRCC1 and XRCC3 gene polymorphisms were a useful marker for predicting better survival in advanced NSCLC patients treated with platinum-based chemotherapy. XPA and XPD polymorphisms significantly increased response to platinum-based chemotherapy. These DNA repair gene polymorphisms were useful as a predictor of clinical outcome to the platinum-based chemotherapy. EGFR kinase inhibitors induce dramatic clinical responses in NSCLC patients with advanced disease. EGFR gene polymorphism in intron 1 contains a polymorphic single sequence dinucleotide repeat (CA-SSR) showed a statistically significant correlation with the gefitinib response and was appeared to be a useful predictive marker of the development of clinical outcome containing skin rashes with gefitinib treatment. The other polymorphisms of EGFR were also associated with increased EGFR promoter activity. EGFR gene mutations and polymorphisms were also associated with EGFR kinase inhibitors response and toxicity.

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.

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.