Inoperable early stage non-small cell lung cancer: Comorbidity, patterns of care and survival

Purpose

To evaluate comorbidities, patterns of care and outcomes for patients with inoperable stage I and II non-small cell lung cancer (NSCLC).

Materials and methods

Patients diagnosed with stage I or II NSCLC in British Columbia between 1996 and 2005 who did not undergo primary surgery and were referred for oncology assessment were identified in a retrospective analysis. Baseline comorbidity and pulmonary function data for patients treated with curative radiotherapy (CurRT; biologically effective dose [BED] > 58 Gy₁₀) were abstracted by chart review. Kaplan-Meier and Cox regression were used to determine factors associated with overall survival (OS) and cause-specific survival (CSS) based on treatment group [no radiotherapy (NoRT), palliative radiotherapy (PallRT), or CurRT].

Results

Of 1043 patients identified, approximately 1/3 received CurRT, and these patients had better performance status and lower stage disease than the other groups. There was a high prevalence of comorbid conditions in the CurRT group; 90% of CurRT patients had an age-adjusted Charlson comorbidity index (CCI) score ≥5. CurRT patients had a median survival 1-year longer than patients treated with PallRT or NoRT (p < 0.0001). In CurRT patients, CCI was predictive of OS (HR 1.1 per point CCI increase; p = 0.044), but not CSS. Patients receiving PallRT with a BED > 50 Gy₁₀ had significantly longer OS than those receiving PallRT of ≤50 Gy₁₀ (p < 0.0001).

Conclusions

Treatment of medically inoperable early stage NSCLC patients with CurRT is associated with a significantly longer survival, and for these patients CCI is a significant predictor of OS. For patients treated with PallRT, higher doses of palliative thoracic RT is associated with improved OS.     

IA期非小细胞肺癌的肿瘤大小对其预后的影响

背景与目的 肿瘤大小对预后的影响在肺癌的不同分期组间已明确，但其在同一分期中，尤其是直径小于3cm的肿瘤中对预后的影响尚未明确。本研究的目的是探讨IA期非小细胞肺癌中肿瘤大小对预后的影响。方法 回顾性分析自1995年1月至2003年12月我院胸外科手术治疗IA期非小细胞肺癌142例，用Kaplan-Meier生存曲线统计不同肿瘤大小患者的生存率，并对发病年龄、性别、病理类型、肿瘤大小、手术方式以及是否接受放化疗等因素进行COX回归比例风险模型多因素分析。结果 全组肿瘤直径≤2．0cm者60例，2．1～3．0cm者82例。全组3年、5年生存率分别为84．41％、70．89％，其中肿瘤直径≤2．0cm组分别为94．91％和81．40％，2．1～3．0cm组分别为82．18％和64．91％（P=0．0353）。单因素及多因素分析均显示，肿瘤大小为独立的预后因素。结论 肿瘤大小是IA期非小细胞肺癌的独立预后因素。临床工作中应进一步提高影像学诊断水平，使患者获得更早期的治疗。     

肺癌神经内分泌分化与术后生存关系探讨

目的 探讨非小细胞肺癌神经内分泌(NSCLC—NE)分化与患者手术后生存关系。方法 收集1997年4月至1999年4月98例肺癌手术切除病理标本，采用免疫组化标记特异性烯醇化酶(NSE)及突触素(SY)，并按强弱区分为“ 、 、 ”。对同一手术病例标本采用电镜观察特异性NE颗粒。术后病例随访36月，最长60月。采用Cox多因素风险模型分析NSCLC-NE分化与患者术后生存的关系。结果 91例为非小细胞肺癌。非小细胞肺癌NF阳性表达率为63．7％(58/91)，其中NSE阳性表达54例(59．3％)，SY阳性表达22例(24．1％)，电镜观察NE持异性颗粒30例(33．0%)。结合免疫组化和电镜观察，NSCLC-NE分化44例(48．4％)。Cox模型多因素分析结果表明NSCLC-NE分化者术后生存时间明显缩短(P=0.048)。术后生存与肺癌细胞分化程度(P=0．006)、病理分期(P=0．001)、NE表达强弱(P=0．054)有密切关系。结论 NSCLC-NE分化与肿瘤细胞分化和患者术后生存有关。采用NE标志物标记肿瘤，并观察其强弱改变．对术后评估具有较重要的参考意义，可作为为临床判断患者预后指标之一。     

Treatment outcomes for patients with synchronous multiple primary non-small cell lung cancer

Introduction

The development of synchronous multiple primary non-small cell lung cancer (NSCLC) is not rare. Nevertheless, the diagnosis, treatment and outcome are controversial. The purposes of this study were to assess the treatment outcomes for patients with synchronous multiple primary NSCLC and to analyze the factors related to this outcome.

Methods

We retrospectively analyzed clinical characteristics and treatment outcomes of 32 patients with synchronous multiple primary NSCLC who underwent surgical resection between 1995 and 2008.

Results

A total of 68 separate tumors were identified in 32 patients. Fifteen (46.9%) patients underwent lobectomy or pneumonectomy with mediastinal lymph node dissection, and 17 (53.1%) patients underwent at least one limited resection or photodynamic therapy. The rate of immediate postoperative mortality was 9.4% (N = 3). The five-year progression-free survival (PFS) and overall survival (OS) rates were 46.0% and 60.9%, respectively. Small tumor size, similar histology, pN0, and pT1 were associated with better PFS in univariable analyses. Female gender, young age, non-smoker, FEV1/FVC ≥70%, small tumor size, similar histology, and highest pT1 were associated with better OS in univariable analyses.

Conclusions

An aggressive surgical approach offers the greatest chance for long-term survival in patient with synchronous multiple primary NSCLC and several clinical factors were associated with survivals. However, the decision of aggressive surgical treatments for synchronous MPLC should be made carefully in the patients with old age and underlying comorbidities due to poor OS and increased surgical mortality.     

527例不能手术的Ⅲ/Ⅳ期非小细胞肺癌化放综合治疗的疗效分析

背景与目的 化疗在晚期非小细胞肺癌(NSCLC)的治疗中占有极为重要的地位,以铂类药物为基础的第三代化疗方案已成为晚期NSCLC的标准方案.本研究的目的是比较四种含铂方案治疗Ⅲ/Ⅳ期NSCLC的疗效和毒副反应.方法 527例Ⅲ/Ⅳ期NSCLC患者分别非随机接受TP(紫杉醇 顺铂)、NP(长春瑞滨 顺铂)、GP(吉西他滨 顺铂)、DP(多西紫杉醇 顺铂)方案化疗,其中NP方案243例,TP方案163例,GP方案65例,DP方案56例,评价四种化疗方案的远期疗效、毒副反应、中位疾病进展时间(TTP)、中位生存时间(MST)及生存率.结果 NP、TP、GP、DP组有效率分别为46.9%、44.8%、47.7%、42.9%(P＞0.05).化疗 放疗综合治疗与单纯化疗患者的有效率分别为69.9%、40.8%(P＜0.05).NP、TP、GP、DP组中位TTP分别为5.7、5.3、5.9、5.5个月,MST分别为10.4、10.6、11.5、10.4个月,1年生存率分别为41.9%、41.1%、43.1%、42.9%,2年生存率分别为21.3%、19.4%、23.1%、23.2%,四组间差异均无统计学意义(P＞0.05).结论 含铂类的第三代化疗方案是晚期NSCLC的标准治疗方案,化疗加放疗的综合治疗可能提高疗效,延长患者的生存期.     

ⅠB期非小细胞肺癌术后辅助化疗的争议和共识

临床上有20％～25％的非小细胞肺癌（NSCLC）患者可手术治疗,但5年生存率也只有40％左右。辅助化疗是部分早期可切除肺癌的标准治疗方式,可使4％～15％的患者生存获益。但是,ⅠB期NSCLC是否能从辅助化疗中获益仍存在争议。近年来,多个临床研究评价了ⅠB期NSCLC辅助化疗的疗效,我们通过分析这些临床研究,寻找ⅠB期NSCLC的高危人群和辅助化疗的适应证。     

Post-operative staging and survival based on the revised tnm staging system for non-small cell lung cancer

The revision in the international system for staging lung cancer have been adopted by the Union Internationale Contre le Cancer (UICC) and the American Joint Committee on Cancer (AJCC) in 1996 and published in 1997.[1,2] In this revisions, satellite tumor nodule(s) in the primary tumor lobe of the lung are designated T4. Separate metastatic tumor nodule(s) in the ipsilateral nonprimary-tumor lobe(s) of the lung are designated M1. The revised stage grouping rules divide stage I and stag…     

Significance of stereotactic body radiotherapy in older patients with early stage non-small cell lung cancer

Objectives

Our aim was to investigate long-term treatment outcomes in older patients with early stage non-small cell lung cancer (NSCLC) and the presence or absence of therapeutic benefits, using the G8 screening tool.

凝血指标对非小细胞肺癌患者生存状况的影响研究

目的探讨凝血功能对非小细胞肺癌患者生存状况的影响及二者的相关性。方法选取2018年1月至2020年1月间上海市宝山区罗店医院收治的82例非小细胞肺癌患者,比较不同病理分期、淋巴结转移、远处转移情况下患者凝血酶原时间(PT)、凝血酶时间(TT)、活化部分凝血活酶时间(APTT)、纤维蛋白原(FIB)、D-二聚体(D-D)和血小板(PLT)等凝血指标;比较不同指标下患者1年无瘤生存率;使用COX模型研究各凝血指标与患者生存状况的相关性。结果不同病理分期和不淋巴结转移患者的PT、APTT、FIB及D-D水平比较,差异均有统计学意义(均P <0.05)。其中病理分期Ⅲ~Ⅳ期的患者及N1~N3期淋巴结转移患者的PT、APTT、FIB和D-D水平均高于病理分期Ⅰ~Ⅱ期和N0期淋巴结转移患者。不同病理分期、淋巴结血管浸润、胸膜浸润、APTT、FIB及D-D的患者1年无瘤生存率比较,差异均有统计学意义(均P <0.05),其中病理分期Ⅲ~Ⅳ期、有淋巴结血管浸润、有胸膜浸润、APTT≤31.1s、FIB≤5.01和D-D≤2.21mg/L的患者1年无瘤生存率处于更低水平。APTT和FIB是影响非小细胞肺癌患者1年无瘤生存率的相关因素,APTT和FIB水平越高,患者生存率越低。结论凝血指标与非小细胞肺癌患者生存状况有明显相关性,APTT和FIB水平越高,患者生存率越低,可进行监测,以提高患者生存质量。     

Prognostic value of xanthine oxidoreductase expression in patients with non-small cell lung cancer

Background

Xanthine oxidoreductase (XOR) is a rate-limiting enzyme in the purine metabolism pathway. Lack of XOR expression is associated with unfavorable clinical outcomes. The objective of this study was to correlate XOR expression with prognosis in surgically resected non-small cell lung cancer (NSCLC).

Methods

Immunohistochemical staining was performed on deparaffinized specimens from 82 patients with stage I-IV NSCLC using a polyclonal anti-XOR rabbit antibody. Cytoplasmic XOR staining was scored on frequency and intensity scales from 0 to 4 with low expression defined as 0-1 and high expression defined as ≥2-4. XOR immunostaining was correlated with clinical characteristics and outcomes and analyzed using Kaplan-Meier and Cox proportional hazard methods.

Results

Positive XOR expression was observed in 53/82 cases (65%). Patients with high XOR frequency had a longer median survival of 3053 days (95% CI: 2190-3916) vs. 592 days (95% CI: 492-692 days) for patients with low XOR frequency, p = 0.0089, HR 0.47. Neither XOR intensity nor the overall score of XOR frequency multiplied by XOR intensity demonstrated any significant association with survival. Surgical resection was performed on 61 patients of which 34 (56%) received adjuvant chemotherapy. Patients who received adjuvant chemotherapy with low XOR expression, 15/34 (44%) had a shortened median survival compared with patients who received adjuvant chemotherapy with high XOR expression (543 days vs. 2023 days, respectively, p = 0.007 and HR = 0.33).

Conclusion

Low XOR expression was associated with shortened survival and also conferred a worse prognosis for patients with NSCLC who received adjuvant chemotherapy. Further studies of the XOR pathway are warranted to validate and mechanistically explain these outcomes.     

手术切除的ⅢA期-N2非小细胞肺癌预后因素分析

目的：研究影响ⅢA期-N2非小细胞肺癌根治术后患者预后的目素，方法：目1995年3月-1998年2月在上海市胸科医院118例非小细胞肺癌术后病理分期为ⅢA期-N2的患者．对可能影响其生存率的各种临床、病理、治疗方法等因素进行分析．用Kaplan-Meier曲线及Log rank检验生存率差异，Cox单、多因素骨析评价各因素对生存率的影响。结果：118例ⅢA期-N2非小细胞肺癌患者的三年及五年生存率分别为40.5％和18．4％．肿瘤切除情况、N2淋巴结转移的个数和组数及术后化疗周期敖均与生存率有关。在多因素分析中．N2淋巴结转移的个数及术后化疗周期数均为影响生存率的重要因素。结论：N2淋巴结转移的个数及术后化疗周期数是影响ⅢA期-N2非小细胞肺癌预后的重要因素。     

老年人与中青年晚期非小细胞肺癌化疗后的生存分析比较

目的比较老年人和中青年人晚期非小细胞肺癌的化疗及生存情况。方法回顾性分析2001年~2003年我院肿瘤中心收治的Ⅲ~Ⅳ期非小细胞肺癌患者162例,其中年龄大于65岁的老年组有97例,年龄小于或等于65岁的中青年组有65例,比较两组的疗效及生存率。结果老年组和中青年组接受化疗周期的中位数分别为3次和4次。没有患者达到完全缓解,治疗有效率两组分别为28.9%和32.3%(P>0.05),Ⅲ度和Ⅳ度骨髓抑制的发生率两组分别为12.4%和7.7%(P>0.05)。中位生存时间(MST)两组分别为13个月和11个月(P>0.05)。Cox回归分析发现肿瘤分期和行为状态评分为影响预后的因素。结论老年非小细胞肺癌患者接受化疗的安全性和疗效与年轻人相比无明显差异。     

晚期非小细胞肺癌以手术为主综合治疗的临床观察

背景与目的确诊的非小细胞肺癌(NSCLC)患者中,65%～70%为晚期(Ⅲ、Ⅳ期)。对于这类患者,采用综合治疗有望取得较好的治疗效果。本研究的目的是探讨晚期NSCLC(ⅢB、Ⅳ期)以手术为主综合治疗的疗效。方法总结分析北京协和医院胸外科1995～2003年部分接受以手术为主综合治疗的ⅢB～Ⅳ期NSCLC患者的临床资料,通过评估患者的生存率,评价以手术为主综合治疗的疗效。结果全组51例患者,ⅢB期20例,Ⅳ期31例,总体中位生存期为37.0月±7.6月,术后1年生存率为86.35%±5.21%,3年生存率为52.96%±8.83%。结论以手术为主的综合治疗有望提高可手术晚期NSCLC患者的生存期。     

Stereotactic Ablative Radiotherapy for stage I histologically proven non-small cell lung cancer: An Italian multicenter observational study

Objectives

Aim of this retrospective multicenter observational study was to provide data on outcomes and prognostic factors in patients affected with stage I histologically confirmed NSCLC treated with Stereotactic Ablative Radiotherapy (SABR, or Stereotactic Body Radiotherapy, SBRT) outside clinical trials.

Materials and Methods

We analyzed a cohort of 196 patients with histological/cytological diagnosis of NSCLC. Median age at treatment was 75 years old; median tumor diameter was 2.48 cm, and median GTV 13.3 cc. One hundred fifty-five patients had stage IA disease (79.1%) and 41 patients stage IB disease (20.9%). Total doses ranged from 48 to 60 Gy in 3–8 fractions. Primary endpoints of the study were safety (acute and late toxicity) and efficacy (Local Control, Disease-Free Survival, Overall and Cancer-Specific Survival).

Results

Median follow-up time was 30 months. The percentage of grade ≥2 pulmonary toxicity was 3%, and the 30 and 60 days mortality rate was 0%. Local Recurrence-Free Survival was 89.7% at 3 years. Fifty-nine patients (30.1%) had at least one failure (local and/or nodal and/or distant), with a Disease-Free Survival (DFS) rate at 3 years of 65.5%. Overall Survival (OS) and Cancer-Specific Survival (CSS) rates were 68% and 82.1% at 3 years, respectively. Median time to any recurrence was 15 months, while median overall survival time was 54 months. At multivariate analysis, stage IB was the only variable associated to a decrease in DFS, OS and CSS (HR 2.77, p = 0.006; HR 2.38, p = 0.009; HR 4.06, p ≤ 0.001, respectively). A difference in survival according to stage was also evident at the log-rank test (p ≤ 0.0001 for CSS and OS).

Conclusion

The results of the present study support the routine use of SABR for stage I NSCLC in a daily practice environment. The only prognostic factor that has been confirmed by our analysis was tumor stage (IA vs. IB).     

The influence of provider characteristics on resection rates and survival in patients with localized non-small cell lung cancer

Surgery remains the mainstay of treatment for localized non-small cell lung cancer (NSCLC). However, wide variations have been reported regarding rates of operative therapy. We examined the influence of characteristics of the hospital of diagnosis on the likelihood of receiving surgical treatment and on survival. We evaluated patients with primary, first-time, localized NSCLC diagnosed from 1998 to 2003 in the region of the Amsterdam Cancer Registry. Treatment and survival data were extracted from the registry database. We investigated which provider characteristics (hospital category, mean annual lung cancer caseload, presence of a cardiothoracic surgery unit) were predictive of receiving surgical treatment and of survival. 1591 patients were diagnosed with clinically localized NSCLC, of which 1097 (69%) had surgery. Resection rates varied significantly between the various hospitals (48-90%, chi(2), P<0.001). Patients diagnosed at specialized centers or higher volume hospitals were more likely to receive surgical therapy, especially for patients over 80 years of age. In addition, there was a trend that octogenarians had higher odds of undergoing surgery when diagnosed in a center with a cardiothoracic surgery unit. Patients had a better survival after resection than without surgery (P<0.001). Survival after surgery did not differ between the various hospital categories. In conclusion, there is wide institutional variability in rates of surgical treatment in lung cancer patients. In addition to patient characteristics, attributes of the hospital of diagnosis also have significant influence on the likelihood of receiving surgical therapy. Future studies should examine the underlying mechanisms for this phenomenon.     

Effect of body mass index on colorectal cancer

Objective: To evaluate the association between obesity and the risk of colorectal cancer. Methods: 331 patients with rectal cancer and 175 with colon cancer who accepted surgical operation at Beijing Cancer Hospital during 1995 and 2002 were enrolled. Data were collected by reviewing the pathology materials and hospital records. 258 healthy people who accepted health examination at Beijing Cancer Hospital during 2000 and 2002 were also enrolled as control. Data of height, weight and gender at the time of examination were also collected. Obesity was estimated by body mass index (BMI), computed as weight in kilograms divided by height in meters squared (kg/m^2). The degree of obesity was compared between the two groups using BMI≤18.5, 24-27.9 and ≥28 (kg/m^2) as the cut-off points for underweight, overweight and obesity. Associations with obesity were estimated by odds ratios (ORs) and 95% confidence intervals (CIs). All ORs were adjusted for age and sex. Results: Obesity was significantly prevalent in female patients with rectal cancer. All the patients with colon cancer showed lower level of BMI than control subjects. The ORs for rectal cancer rose with increasing BMI in women. Meanwhile, the ORs for colon cancer dropped with increasing BMI in both men and women.Obesity was an independent risk factor for rectal cancer,but not an independent risk factor for colon cancer.Conclusion: Rectal cancer and colon cancer may have different biological behavior. Obese women have relatively high risk for rectal cancer.     

Protein profiles correlated with recurrence of early stage non-small cell lung cancer

Objective:To elucidate protein markers that differentiate stage Ⅰ non-small cell lung cancer (NSCLC) that subsequently develop metastatic disease to those that do not develop metastasis by protein expression profiles.Methods:Matrix assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) and two dimensional difference gel electrophoresis (2D-DIGE) platforms were used to separate proteins in whole tumor specimens. Quantitating mRNA expression was used for validation. Results:Twelve proteins were identified as expressed differentially between two groups from protein expression platforms. But from gene expression platform no marker could distinguish patients with recurrent vs. nonrecurrent disease. Conclusion:Analysis of multiple protein markers may be more informative to predict prognosis of early stage lung cancer.     

分析吉非替尼有效的非小细胞肺癌患者骨转移对其生存期的影响及骨转移患者的预后因素

目的：研究吉非替尼有效的非小细胞肺癌患者,骨转移是否影响其生存期,并分析骨转移患者的预后因素。方法比较骨转移和无骨转移患者总生存、无进展生存、1年、2年及3年生存率,并分析影响骨转移患者预后的因素。结果无骨转移组44例,骨转移组32例。无骨转移组与有骨转移组总生存期（19．000±3．317月 vs．26．000±2．121月,P＝0．625）和无进展生存期（14．000±1．843月 vs．16．000±1．411月,P＝0．328）无统计学差异。前组患者1年生存率63．6％低于后者96．9％,2年和3年生存率分别为（34．1％vs．56．3％,P＝0．054）和（18．2％vs．18．4％,P＝0．950）,无统计学差异。对骨转移组进行单因素分析显示年龄＞60岁及有肺内进展者预后更差,多因素分析显示影响骨转移患者生存的有效因素为有肺内进展,而性别、病理、吸烟指数、是否合并脑转移、骨相关事件及是否应用放疗、双膦酸盐与骨转移患者中位生存时间均无明显相关性。结论吉非替尼治疗有效的非小细胞肺癌患者,骨转移可能不是影响其生存期的主要因素,肺内进展有可能是非小细胞肺癌骨转移者的主要死因,不能将骨转移作为停用吉非替尼的指征。     

Adjuvant immunotherapy for non-small cell lung cancer

Non-small cell lung cancer (NSCLC) is the biggest cancer killer in the United States and worldwide. In 2011, there are estimated to be 221,130 new cases of lung cancer in the United States. Over a million people will die of lung cancer worldwide this year alone. When possible, surgery to remove the tumor is the best treatment strategy for patients with NSCLC. However, even with adjuvant (postoperative) chemotherapy and radiation, more than 40% of patients will develop recurrences locally or systemically and ultimately succumb to their disease. Thus, there is an urgent need for developing superior approaches to treat patients who undergo surgery for NSCLC to eliminate residual disease that is likely responsible for these recurrences. Our group and others have been interested in using immunotherapy to augment the efficacy of current treatment strategies. Immunotherapy is very effective against minimal disease burden and small deposits of tumor cells that are accessible by the circulating immune cells. Therefore, this strategy may be ideally suited as an adjunct to surgery to seek and destroy microscopic tumor deposits that remain after surgery. This review describes the mechanistic underpinnings of immunotherapy and how it is currently being used to target residual disease and prevent postoperative recurrences after pulmonary resection in NSCLC.