Evaluation of the target dose coverage of stereotactic body radiotherapy for lung cancer using helical tomotherapy: A dynamic phantom study

AimTo evaluate the target dose coverage for lung stereotactic body radiotherapy (SBRT) using helical tomotherapy (HT) with the internal tumor volume (ITV) margin settings adjusted according to the degree of tumor motion.BackgroundLung SBRT with HT may cause a dosimetric error when the target motion is large.Materials and methodsTwo lung SBRT plans were created using a tomotherapy planning station. Using these original plans, five plans with different ITV margins (4.0–20.0 mm for superior-inferior [SI] dimension) were generated. To evaluate the effects of respiratory motion on HT, an original dynamic motion phantom was developed. The respiratory wave of a healthy volunteer was used for dynamic motion as the typical tumor respiratory motion. Five patterns of motion amplitude that corresponded to five ITV margin sizes and three breathing cycles of 7, 14, and 28 breaths per minute were used. We evaluated the target dose change between a static delivery and a dynamic delivery with each motion pattern.ResultsThe target dose difference increased as the tumor size decreased and as the tumor motion increased. Although a target dose difference of <5 % was observed at ≤10 mm of tumor motion for each condition, a maximum difference of -9.94 % ± 7.10 % was observed in cases of small tumors with 20 mm of tumor motion under slow respiration.ConclusionsMinimizing respiratory movement is recommended as much as possible for lung SBRT with HT, especially for cases involving small tumors.     

The impact of respiratory gating on lung dosimetry in stereotactic body radiotherapy for lung cancer

The purpose of this study was to evaluate the impacts of respiratory gating and different gating windows (GWs) on lung dosimetry in stereotactic body radiotherapy (SBRT) for lung cancer.Gated SBRT plans were developed using the four-dimensional computed tomography data from 17 lung cancer patients treated with SBRT. Using amplitude-based end-exhalation gating, we established 2 fixed GWs with approximate duty cycles of 50% (50% GW) and 25% (25% GW), respectively, for this study.For highly mobile tumors (3D mobility > 10 mm), additional benefits in lung-dose reductions were achieved with the 25% GW, as a result of inadequate mobility and planning target volume reductions obtained with the 50% GW. In these tumors, the absolute differences compared to the non-gated and 50% gated plans, were 0.5 Gy and 0.33 Gy for the mean lung dose and 1.11% and 0.71% for the V20, respectively. Dosimetric benefits were achieved with the 50% GW, compared with the non-gated plan, for tumors with both low mobility and small volume (gross tumor volume ≤ 10 cc). Among the identified predictive factors of dosimetric benefits, the lateral distance from midspinal canal and the motion range in anterior–posterior direction might be stronger factors because of their correlations with many of the lung-dose parameters and greater predictive capacity.The results of the present study might facilitate the selection of appropriate patients and the optimal GW according to the tumor characteristics for gated lung SBRT.     

Dosimetric comparison of MRI-based HDR brachytherapy and stereotactic radiotherapy in patients with advanced cervical cancer: A virtual brachytherapy study

AimTo evaluate the treatment plans of 3D image-guided brachytherapy (BT) and stereotactic robotic radiotherapy with online image guidance – CyberKnife (CK) in patients with locally advanced cervix cancer.Methods and materialsTen pairs of plans for patients with locally advanced inoperable cervical cancer were created using MR based 3D brachytherapy and stereotaxis CK. The dose that covers 98% of the target volume (HR CTV D98) was taken as a reference and other parameters were compared.ResultsOf the ten studied cases, the dose from D100 GTV was comparable for both devices, on average, the BT GTV D90 was 10–20% higher than for CK. The HR CTV D90 was higher for CK with an average difference of 10–20%, but only fifteen percent of HR CTV (the peripheral part) received a higher dose from CK, while 85% of the target volume received higher doses from BT. We found a significant organ-sparing effect of CK compared to brachytherapy (20–30% lower doses in 0.1 cm³, 1 cm³, and 2 cm³).ConclusionBT remains to be the best method for dose escalation. Due to the significant organ-sparing effect of CK, patients that are not candidates for BT could benefit from stereotaxis more than from classical external beam radiotherapy.     

Antiestrogen use in breast cancer patients reduces the risk of subsequent lung cancer: A population-based study

BackgroundThere is accumulating epidemiological and preclinical evidence that estrogen might be a driver of lung cancer. Breast cancer survivors can offer a unique patient cohort to examine the effect of antiestrogen therapy on lung cancer carcinogenesis because many of these women would have received long-term selective estrogen receptor modulators (SERMs) and/or aromatase inhibitors (AIs) as adjuvant treatment. Our hypothesis is that estrogens play a role in lung cancer development, and that antiestrogen therapy would affect the incidence of subsequent lung cancer among breast cancer survivors.MethodsUsing the Taiwan National Health Insurance (NHI) database, the study included 40,900 survivors of non-metastatic breast cancer after primary surgery, and most antiestrogen users complied well with the medication regimen. We evaluate the effect of antiestrogen therapy on the incidence of subsequent lung cancers.ResultsThis population-based study revealed that antiestrogen use in breast cancer patients was associated with a reduced risk of subsequent lung cancer in older patients (≥50 years) (HR 0.73, 95%CI 0.54–0.99) when compared with breast cancer survivors who did not use antiestrogens.ConclusionThe study supports the hypothesis that antiestrogen therapy modifies lung cancer carcinogenesis in older women. Further well-designed clinical trials to explore the potential of antiestrogens in lung cancer prevention and treatment would be worthwhile.     

WT1 CpG islands methylation in human lung cancer: A pilot study

Background

CpG island hypermethylation of gene promoters and regulatory regions is a well-known mechanism of epigenetic silencing of tumor suppressors and is directly linked to carcinogenesis. Wilm’s tumor gene (WT1) is a tumor suppressor protein involved in the regulation of human cell growth and differentiation and a modulator of oncogenic K Ras signaling in lung cancer. Changes in the pattern of methylation of the WT1 gene have not yet been studied in detail in human lung cancer. In this study we compared the methylation profile of WT1 gene in samples of neoplastic and non-neoplastic lung tissue taken from the same patients.

Methods

DNA was extracted from neoplastic and normal lung tissue obtained from 16 patients with non small cell lung cancer (NSCLC). The methylation status of 29 CpG islands in the 5′ region of WT1 was determined by pyrosequencing. Statistical analysis was carried out by T test and Mann Whitney test.

Results

The mean percentage of methylation, considering all CpG islands of WT1 in the neoplastic tissues of the 16 NSCLC patients, was 16.2 ± 3.4, whereas in the normal lung tissue from the same patients it was 5.6 ± 1.7 (p < 0.001). Adenocarcinomas presented higher methylation levels than squamous cell carcinomas (p < 0,001).

Conclusions

Methylation of WT1 gene is significantly increased in NSCLC. Both histotype and exposure to cigarette smoke heavily influence the pattern of CpG islands which undergo hypermethylation.     

Dosimetric impact of uncorrected systematic yaw rotation in VMAT for peripheral lung SABR

AimThis study aimed to evaluate the dosimetric impact of uncorrected yaw rotational error on both target coverage and OAR dose metrics in this patient population.BackgroundRotational set up errors can be difficult to correct in lung VMAT SABR treatments, and may lead to a change in planned dose distributions.Materials and methodsWe retrospectively applied systematic yaw rotational errors in 1° degree increments up to −5° and +5° degrees in 16 VMAT SABR plans. The impact on PTV and OARs (oesophagus, spinal canal, heart, airway, chest wall, brachial plexus, lung) was evaluated using a variety of dose metrics. Changes were assessed in relation to percentage deviation from approved planned dose at 0 degrees.ResultsTarget coverage was largely unaffected with the largest mean and maximum percentage difference being 1.4% and 6% respectively to PTV D98% at +5 degrees yaw.Impact on OARs was varied. Minimal impact was observed in oesophagus, spinal canal, chest wall or lung dose metrics. Larger variations were observed in the heart, airway and brachial plexus. The largest mean and maximum percentage differences being 20.77% and 311% respectively at −5 degrees yaw to airway D0.1cc, however, the clinical impact was negligible as these variations were observed in metrics with minimal initial doses.ConclusionsNo clinically unacceptable changes to dose metrics were observed in this patient cohort but large percentage deviations from approved dose metrics in OARs were noted. OARs with associated PRV structures appear more robust to uncorrected rotational error.     

Neighborhood linking social capital as a predictor of lung cancer: A Swedish national cohort study

BackgroundThe aim of this nationwide follow-up study was to examine whether neighborhood linking social capital is associated with lung cancer, including incident and mortality cases, after adjustment for individual- and familial-level factors.MethodsThis follow-up study comprised 2,123,707 men and 2,046,174 women aged 25 years or older in Sweden. The follow-up period started on January 1, 2002 and proceeded until first incident of lung cancer, mortality of lung cancer, death from any other cause, emigration or the end of the study period on December 31, 2010. Multilevel logistic regression models (individual-level factors at the first level and neighborhood-level factors at the second level) were used to calculate odds ratios (ORs) with 95% confidence intervals (95% CIs).ResultsWe identified 16,561 lung cancer cases (8422 men and 8139 women) during the follow-up period. Higher ORs of lung cancer, including incident and mortality cases, were observed in individuals who lived in neighborhoods with low social capital (men: OR = 1.37, 95% CI = 1.27–1.47; women: OR = 1.32, 95% CI = 1.23–1.42) than in those living in neighborhoods with high social capital, after adjustment for potential confounding factors.ConclusionThe results of this large national cohort study suggest that neighborhood linking social capital has important independent effects on lung cancer, including incident and mortality cases. These findings indicate that decision-makers must consider the effect of neighborhood-level factors as well as individual- and familial-level factors.     

人类蛋白组学草图的肺癌分子标记物初探

传统的肺癌分子标记物探索通常基于基因组或者转录组研究,而基于蛋白质水平的肺癌分子标记物探索通常局限在低通量水平。质谱技术已经开始产生高通量的全局正常及癌症蛋白组。我们采用开源统计软件R对人类蛋白组学草图数据及已发表的肺癌蛋白质组学数据进行二次分析,筛选出91个潜在的候选肺癌分子标记物。基因注解分析显示候选肺癌基因富集了和代谢、TP53通路以及MicroRNA调控等相关的基因。最后,利用Human Protein Atlas数据库及Pubmed对前20候选标记物进行验证,结果显示大部分候选肺癌基因大多能够得到验证。可见数据挖掘在即将到来的质谱推动的组学大数据时代将发挥重要作用。     

Alcohol consumption and lung cancer risk: A pooled analysis from the International Lung Cancer Consortium and the SYNERGY study

BackgroundThere is inadequate evidence to determine whether there is an effect of alcohol consumption on lung cancer risk. We conducted a pooled analysis of data from the International Lung Cancer Consortium and the SYNERGY study to investigate this possible association by type of beverage with adjustment for other potential confounders.MethodsTwenty one case-control studies and one cohort study with alcohol-intake data obtained from questionnaires were included in this pooled analysis (19,149 cases and 362,340 controls). Adjusted odds ratios (OR) or hazard ratios (HR) with corresponding 95% confidence intervals (CI) were estimated for each measure of alcohol consumption. Effect estimates were combined using random or fixed-effects models where appropriate. Associations were examined for overall lung cancer and by histological type.ResultsWe observed an inverse association between overall risk of lung cancer and consumption of alcoholic beverages compared to non-drinkers, but the association was not monotonic. The lowest risk was observed for persons who consumed 10–19.9 g/day ethanol (OR vs. non-drinkers = 0.78; 95% CI: 0.67, 0.91), where 1 drink is approximately 12–15 g. This J-shaped association was most prominent for squamous cell carcinoma (SCC). The association with all lung cancer varied little by type of alcoholic beverage, but there were notable differences for SCC. We observed an association with beer intake (OR for ≥20 g/day vs nondrinker = 1.42; 95% CI: 1.06, 1.90).ConclusionsWhether the non-monotonic associations we observed or the positive association between beer drinking and squamous cell carcinoma reflect real effects await future analyses and insights about possible biological mechanisms.     

Lung cancer. Radiotherapy in lung cancer: Actual methods and future trends

This survey is performed to update knowledge about methods and trends in lung cancer radiotherapy. A significant development has been noticed in radiotherapeutic techniques, but also in the identification of clinical prognostic factors. The improvement in the therapeutic line includes: application of the four-dimensional computer tomography (4DCT), taking advantage of positron emission tomography (PET-CT), designing of new computational algorithms, allowing more precise irradiation planning, development of treatment precision verification systems and introducing IMRT techniques in chest radiotherapy. The treatment outcomes have improved with high dose radiotherapy, but other fractionation alternations have been investigated as well.     

Genetic polymorphisms involved in the inflammatory response and lung cancer risk: A case-control study in Japan

Evidence is accumulating that chronic inflammation may have an important mechanism for the development and progression of lung cancer. Therefore, genetic polymorphisms in genes that involved in the inflammatory response may be associated with lung cancer risk. We evaluated the role of tumor necrosis factor α (TNFA) rs1799724, interleukin 1β (IL1B) rs16944, IL6 rs1800796, myeloperoxidase (MPO) rs2333227 and C-reactive protein (CRP) rs2794520 in a case-control study comprised of 462 lung cancer cases and 379 controls in a Japanese population. Unconditional logistic regression was used to assess the adjusted odds ratios (OR) and 95% confidence intervals (95% CI). CRP rs2794520 (OR = 1.64, 95% CI = 1.19–2.26) and IL6 rs1800796 (OR = 1.41, 95% CI = 1.02–1.96) were associated with lung cancer risk. In addition, we assessed interactions between the polymorphisms and smoking. The polymorphisms did not significantly modify the association between smoking and lung cancer. As TNFA triggers a cytokine cascade, the modifying effect of the TNFA rs1799724 genotypes on the association of any of the remaining polymorphisms with lung cancer risk was also examined. There was a significant interaction between TNFA rs1799724 and MPO rs2333227 (P_interaction = 0.058). Future studies involving larger control and case populations will undoubtedly lead to a more thorough understanding of the role of the polymorphisms involved in the inflammation pathway in lung cancer.     

Dosimetric impact of volumetric modulated arc therapy for nasopharyngeal cancer treatment

BackgroundThe purpose of the study was to evaluate the toxicity and outcome of nasopharyngeal carcinoma patients treated using 3-dimensional conformal radiotherapy (3DCRT) or volumetric modulated arc therapy (VMAT) technique.Materials and methods68 patients treated between 2006 and 2018 were retrospectively analysed. Since 2009 patients received 3DCRT with 50/70 Gy to the elective/boost volumes in 35 fractions; from then, VMAT with simultaneous integrated boost (SIB) with 54.45/69.96 Gy in 33, or 54/66 Gy in 30 fractions. Induction chemotherapy was administered in 74% of the patients, concomitant cisplatinum in 87%. Acute and late toxicity data, progression-free survival PSF and overall survival OS, and toxicity correlations with dose metrics were reported.ResultsWith a median follow-up of 64 months, complete remission at the last evaluation was in 68% of the patients, while 28% and 9% had locoregional relapse and distant disease, respectively. The 5- and 10-year progression free survival (PFS) rates were 62.7 ± 6.5% and 53.2 ± 8.7%, respectively. The 5- and 10-year OS rates were 78.9 ± 5.5% and 61.4 ± 9.2%, respectively. At the multivariate Cox analysis TNM stage (p = 0.02) and concomitant chemotherapy (p = 0.01) resulted significant for PFS, concomitant chemotherapy (p = 0.04) for OS.Improvements in acute toxicity were presented for VMAT patients due to its ability to spare OARs. Odds ratio (OR) for acute salivary toxicity, between VMAT and 3DCRT, was 4.67 (p = 0.02). Dosimetrically, salivary toxicity correlated with mean parotid dose (p = 0.05), dysphagia with laryngeal (p = 0.04) and mean oral cavity (p = 0.06) doses, when dose-volume histograms (DVHs) are corrected for fractionation.ConclusionThis study is a proof of a significant benefit of the VMAT technique compared with 3DCRT in terms of side effects in nasopharynx patients, and adds dosimetric correlations.     

LDCT lung cancer screening eligibility and use of CT scans for lung cancer among sexual minorities

ObjectiveTo compare eligibility for lung cancer screening and receipt of a CT scan for lung cancer among sexual minorities.MethodsSecondary data analysis of cross-sectional data from older U.S. adults in the Behavioral Risk Factor Surveillance System survey during the 2017 cycle (n = 20,685).ResultsRates of eligibility for low-dose helical computed tomography (LDCT) were roughly twice as high among sexual minorities than among heterosexuals (21.1% vs. 11.7%). The odds of gay men and lesbian women indicating eligibility for LDCT screening were four to five times higher when compared to their heterosexual peers. No statistically significant differences were found between sexual minorities and heterosexuals with respect to having a CT scan for lung cancer in the past year.ConclusionsThere are potential sexual-identity-related disparities in the utilization of lung cancer screening among eligible smokers. Interventions are needed to increase awareness and uptake of lung cancer screening in order to detect and manage this common form of cancer in the U.S.     

Cisplatin cytotoxicity is enhanced with zoledronic acid in A549 lung cancer cell line: preliminary results of an in vitro study

We tested whether zoledronic acid, a biphosphonate with proposed apoptotic activity, augmented the cytotoxicity of cisplatin and/or gemcitabine in A549 lung cancer cell line. This cell line was subjected to different concentrations of the above chemotherapeutic agents and zoledronic acid. Cytotoxicity was assessed by the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrasodium bromide) assay. Particularly, zoledronic acid in 100 micromolar (microM) concentration augmented the cytotoxicity by cisplatin 1microg/ml from 25% to 70% (Z=3.22, P=0.0072). A significant portion of cells underwent apoptosis with or without zoledronic acid, but more so with the combination treatment as assessed by an Annexin V-FITC apoptosis detection kit. However, 100microM zoledronic acid showed 50% cytotoxicity on its own, but failed to improve cytotoxicity by Gemcitabine. Thus, we show for the first time in a lung cancer cell line that zoledronic acid bears cytotoxic potential on its own and in conjunction with cisplatin. The clinical potential of this finding should be further studied.     

肺炎克雷伯菌致肺癌患者术后肺部感染的病因与耐药性分析

目的探讨肺癌术后并发肺炎克雷伯菌肺部感染的病因和耐药情况,为术后肺炎克雷伯菌感染的预防和治疗提供病原学依据。方法收集2011年1月1日至2014年6月30日本院肺癌术后合并肺部感染患者下呼吸道标本,常规分离培养肺炎克雷伯菌,K-B纸片法进行药敏试验,利用WHONET 5.6软件分析处理试验数据。结果从肺癌术后患者下呼吸道分离的肺炎克雷伯菌产ESBLs高,达68.1%;对头孢替坦、阿米卡星、亚胺培南和美罗培南都较敏感,耐药率分别为6.0%、21.4%、18.1%和20.9%,其余抗菌药物的耐药率均30.0%。结论肺癌术后并发肺炎克雷伯菌肺部感染耐药率高,对碳青霉烯类抗菌药物仍保持高度敏感性,临床应加强耐药性监测,并根据药敏试验结果合理选用抗菌药物。     

水飞蓟宾抑制人肺癌细胞浸润的作用机制研究

目的通过观察水飞蓟宾对有高转移能力的人肺癌细胞A549相关酶的作用来研究水飞蓟宾对浸润和运动性的影响。方法应用细胞活性测定、细胞浸润和运动性分析、细胞-基质黏附实验、逆转录聚合酶链反应等技术完成实验。结果A549细胞用高达100μM的不同浓度的水飞蓟宾处理一定时间后,行明胶酶谱、酪蛋白酶谱以及蛋白印迹分析来确定水飞蓟宾对金属蛋白酶-2（MMP-2）的影响。结论水飞蓟宾治疗可以浓度以及时间依存性方式减少MMP-2表达。半定量RT—PCR分析进一步表明,水飞蓟宾可在转录水平调节MMP-2表达。     

痰液肺癌细胞Ras基因和P63基因的表达与分子生物学意义

目的研究骨髓间充质干细胞分化为心肌细胞过程中Notch表达的研究。方法别用免疫细胞化学方法和Western-blot方法检测167例患者痰液中Ras基因和P63基因的表达情况,分析其对早期肺癌诊断的意义。结果肺癌患者痰液中的Ras基因在痰脱落细胞中有明显高表达,阳性率为75%。P63基因在肺癌痰细胞中阳性表达率为34.78%。结论利用Ras基因标记物可以标记出痰液中的肺非典型增生细胞和肺癌细胞,有利于肺癌的早期发现和诊断,并且可以作为肺癌的普查指标或手段。     

Trends in incidence and mortality of lung cancer in Switzerland: Possible explanations and open questions

BackgroundUsing US population-level data, it has been suggested that novel treatment advances, particularly targeted therapies, have contributed to a sharp fall in NSCLC mortality.Switzerland is a high-income country, with a universal, highly performant health care system, easy access to novel drugs but with different dynamics concerning the smoking epidemic than the US.MethodsWe use population-based data from Swiss cancer registries to analyze the trends in incidence, mortality and survival and relate them to recent drug approvals.ResultsThe incidence of NSCLC and SCLC was stable from 1980 to 2018. We noted an important difference between sexes, with an important decrease in men and increase in women, especially for NSCLC. 1-y and 5-y survival have improved for NSCLC between 2004 and 2008 and 2014–2018.ConclusionThese findings should be regarded as the results of a multifactorial improvement in care and it is difficult for us to pinpoint a unique cause explaining the reduction in mortality     

Impact of comorbidity on survival by tumour location: Breast,colorectal and lung cancer (2000–2014)

BackgroundTo assess the impact of comorbidity, measured by the Charlson Comorbidity Index (CCI), on survival in breast, colorectal and lung cancer.MethodsWe identified 3455 breast cancer, 3336 colorectal cancer and 2654 lung cancer patients through the Hospital del Mar cancer registry. The prevalence of comorbidities according to the CCI was calculated. Kaplan-Meier curves and the log-rank test were used to compare survival curves for each cancer location. Cox regression was used to calculate survival hazard ratios and 1-, 3- and 5-year mortality rate ratios adjusted by age, sex, CCI, place of first consultation, stage, treatment and period of diagnosis.ResultsThe overall unadjusted 5-year follow-up survival proportion was 82.6% for breast cancer, 55.7% for colorectal cancer, and 16.3% for lung cancer. Overall survival was associated with CCI ≥ 3 in breast cancer (HR: 2.33 95%CI: 1.76–3.08), colorectal cancer (HR: 1.39; 95%CI: 1.13–1.70) and lung cancer (HR: 1.22; 95%CI: 1.06–1.40). In breast cancer, the higher the CCI, the higher the adjusted mortality rate ratio and differences were greater in 5-year than in 1-year follow-up survival.ConclusionsComorbidity is a significant predictor of overall survival in cancer patients; however, it has a stronger impact on survival in breast cancer than in colorectal and lung cancer.