局限期小细胞肺癌放化疗后疗效与脑转移的关系探讨*

目的:探讨局限期小细胞肺癌（LD-SCLC ）放化疗后疗效与脑转移的关系。方法:回顾性分析天津医科大学肿瘤医院放疗科2009年4 月至2012年4 月间行放化疗的149 例LD-SCLC患者临床资料,放化疗后疗效评价根据RECIST标准分为完全缓解（CR）、部分缓解（PR）、病情稳定（SD）及疾病进展（PD）,客观缓解包括CR和PR。生存分析采用Kaplan-Meier 法并用Log-rank进行检验,χ2检验进行组间比较。结果:全组患者的中位生存时间（OS）为20.0 个月,3 年OS为33.0% 。多因素分析发现,放化疗后疗效（P < 0.001）及是否出现脑转移（P < 0.001）是影响患者OS的重要因素。全组共43例（28.8%）出现脑转移,CR、PR、SD/PD 患者分别有12例（29.3%）、9 例（11.8%）、22例（68.8%）出现脑转移（P = 0.027）。 放化疗后疗效与无脑转移生存率（BMFS）之间差异具有统计学意义（P = 0.005）,CR、PR、SD及PD患者的2 年BMFS分别为79.5% 、71.9% 、45.8% 和49.6% 。进一步分析发现,放化疗后达CR者,行脑预防性放疗（PCI）与未行PCI 患者的生存率亦存在统计学差异（P = 0.007）。 结论:LD-SCLC患者放化疗后达CR者有较好的BMFS和较低的脑转移率,且行脑预防照射者OS亦优于未行脑预防者,建议放化疗后达CR患者,应尽快考虑脑预防放疗。      

早期结外鼻型NK/T细胞淋巴瘤疗后远处淋巴结转移的临床特征

目的 分析 Ⅰ_E~Ⅱ_E期原发上呼吸消化道NK/T细胞淋巴瘤(UADT-NKTCL)经治疗后远处淋巴结转移率及危险因素。方法 1979—2012年共收治 468例Ⅰ_E~Ⅱ_E期UADT-NKTCL患者,其中 170例接受单纯放疗、19例单纯化疗、278例综合治疗、1例抗炎治疗。采用Kaplan-Meier法计算远处淋巴结转移率。结果 中位随访35个月,32例出现远处淋巴结转移,绝对转移率为6.8%(32/468),占总失败病例数的19.8%(32/162),2年远处淋巴结累积转移率为6.4%。71.9%(23/32)合并远处器官转移。最常见转移部位是腹腔淋巴结。单因素分析显示肿瘤原发于鼻腔外上呼吸消化道、Ⅱ_E期、首程治疗疗效未达CR者是远处淋巴结转移的高危因素。多因素分析显示 Ⅱ_E期和首程治疗疗效未达CR是远期复发的独立危险因素,危险度分别为2.82(1.37~5.82,P=0.005)和3.01(1.16~7.78,P=0.023)。Ⅱ_E期综合治疗组的远处淋巴结转移率显著低于单纯放疗组、单纯化疗组,2年远处淋巴结累积转移率分别为12.5%、35.1%、50.0%(P=0.011)。结论 早期UADT-NKTCL治疗后远处淋巴结转移率较低,但对于 Ⅱ_E期和首程疗效未达CR者转移率仍较高。Ⅱ_E期患者建议采用综合治疗以降低远处淋巴结转移率。     

腋窝淋巴结1～3个转移的乳腺癌根治术后辅助放疗指征探讨

目的 回顾分析412例腋窝淋巴结1～3个转移的乳腺癌根治术后患者的预后因素,探讨术后辅助放疗的指征.方法 用Kaplan-Meier法计算生存率,用Logrank法和Cox模型分别进行单因素和多因素预后分析,分析影响局部复发和远处转移的预后因素.结果 随访率为98.7%.随访满5、10年者分别为215、41例.5、10年总生存率分别为90.0%、81.3%.无、有局部复发的5年总生存率分别为92.9%、69.9%(x2=20.79,P=0.000).5、10年局部复发±远处转移率分别为10.7%、18.6%.多因素分析显示T2期,≥2个腋窝淋巴结转移,雌、孕激素受体均阴性为影响局部复发的预后因素.含0～1、2～3个预后因素的10年局部复发率分别为3.9%、36.9%(x2=20.64,P=0.000).多因素分析显示局部复发、阳性淋巴结转移率＞25%为影响远处转移的预后因素,无、有局部复发的5年远处转移率分别为9.7%、36.6%(x2=16.34,P=0.000).结论 对腋窝淋巴结1～3个转移的乳腺癌根治术后患者且含2～3个影响局部复发的预后因素者建议行术后辅助放疗.     

局限期小细胞肺癌预防性脑照射后脑转移相关危险因素分析

目的:明确局限期小细胞肺癌患者行预防性脑照射（prophylactic cranial irradiation,PCI）后发生脑转移的危险因素,并对相关因素进行分析。以筛选出不能从PCI中获益的人群,为PCI的临床应用提供参考。方法:回顾性分析2011年08月至2019年12月在我院接受过PCI的167例局限期小细胞肺癌患者的病历资料。采用SPSS 26.0统计软件对病历资料进行统计分析。用Kaplan-Meier法计算脑转移发生率及总生存率,并用Log-rank法进行检验。采用Cox回归对影响脑转移及总生存的危险因素进行单因素及多因素分析。结果:局限期小细胞肺癌患者PCI后1、2、3年脑转移率分别为3.8%、12.7%、18.9%。单因素及多因素分析结果显示原发肿瘤为T4期(P=0.004,HR=7.06,95%CI:1.86~26.82)是影响患者PCI后脑转移的危险因素,T2期（P=0.008,HR=2.48,95%CI:1.26~4.89）、T3期(P=0.003,HR=3.38,95%CI:1.49~7.47)、T4期(P=0.001,HR=3.87,95%CI:1.79~8.35)是影响患者总生存的危险因素。结论:较高的T分期是局限期小细胞肺癌患者PCI后脑转移及总生存的独立危险因素。即使T4期患者PCI后脑转移发生率高于其他期别,但仍能够从PCI中获益。     

218例食管癌根治术后复发再治疗的疗效分析

目的 分析食管癌根治术后复发挽救治疗的疗效,为综合治疗提供依据。 方法 回顾分析2004—2014年间食管癌R₀术后复发转移行挽救治疗的218患者资料。采用Kaplan-Meier法计算生存率并Logrank法检验和单因素预后分析,Cox模型多因素预后分析。 结果 全组患者复发后中位随访时间53个月。复发后1、3年OS率分别为57.2%、24.4%。163例局部区域复发患者复发后放化疗(40例),单纯放疗(106例),支持治疗(13例)的1、3年OS率分别为70%、42%,55%、24%,23%、8%(放化疗比单纯放疗 P=0.045,单纯放疗比支持治疗 P=0.004,单纯化疗无 1年生存)。单因素分析显示术后病理N分期、TNM分期、复发后治疗方式影响预后(P均=0.001),多因素分析中只有复发后治疗方式是影响生存的独立预后因素(P=0.013)。 结论 食管癌根治术后复发转移后采用放化疗或放疗挽救治疗有明显生存获益,特别是局部区域复发患者。     

广泛期SCLC化疗后IMRT的疗效分析

目的 回顾研究广泛期SCLC化疗后IMRT的疗效及预后。方法 回顾分析2007—2012年在本院放疗科接受化疗+IMRT的130例初治广泛期SCLC患者,化疗方案以EP、CE方案为主,放疗剂量32 Gy~63 Gy,35例患者进行了PCI。Kaplan-Meier法计算生存率,Logrank法单因素预后分析,Cox模型多因素预后分析。结果 随访率96.1%。全组治疗毒性轻微,≥2级血液学毒性及放射性食管炎发生率分别为22.3%、12.2%,≥2级RP发生率7.7%。放疗后达CR、PR、SD、PD者分别占4.6%、72.3%、6.2%、13.1%,疗效未能评价5例,客观有效率76.9%。中位生存期18个月(4~66个月),1、2年OS率分别为72.3% 、38.3%。30例(23.1%)患者放疗后发生局部区域失败,83例(63.8%)发生远处失败。26例放疗计划可恢复的局部区域失败患者中,22例单纯照射野内失败,2例单纯野外失败,2例野内野外同时失败。单因素分析中年龄、LDH水平、放疗剂量、PCI是影响预后因素(P=0.014、0.049、0.043、0.003),多因素分析中放疗剂量、PCI是影响预后因素(P=0.021、0.007)。初诊无脑转移患者PCI明显改善生存(HR=2.318,95%CI为1.388~3.871;P=0.003)并降低累积脑转移率(18.4%:37.2%,P=0.038)。胸部放疗EQD₂剂量达54 Gy可改善OS (HR=1.615,95%CI为1.016~2.567;P=0.043),并有改善PFS趋势(HR=1.49,95%CI为0.965~2.299,P=0.072)。结论 化疗有效的广泛期SCLC行胸部放疗可提高LC率及OS率,适当提高胸部剂量可改善患者预后。PCI可显著改善OS并降低脑转移发生率。     

乳腺癌脑转移68例临床特点及预后因素分析

[目的]分析乳腺癌脑转移患者的临床特点,探讨影响乳腺癌脑转移患者预后的因素。[方法]收集68例乳腺癌脑转移患者临床资料,采用单因素和多因素生存分析影响乳腺癌脑转移患者预后因素。[结果]乳腺癌脑转移患者多为未绝经、浸润性导管癌,首发症状多为颅内高压症状,多为多发颅内转移,多合并颅外转移。乳腺癌脑转移患者中位生存期8.82个月,1、2、3年生存率分别为39%、8%、8%。单因素分析显示KPS评分、合并肝转移、全身化疗、脑部放疗显著性影响乳腺癌脑转移患者的生存期;Cox多因素分析显示脑部放疗、KPS评分是影响乳腺癌脑转移生存的独立预后因素。[结论]脑部放疗、KPS评分是影响乳腺癌脑转移患者生存的独立预后因素。乳腺癌脑转移后的全身化疗价值需进一步探讨。     

乳腺癌脑转移放疗的临床疗效和预后分析

目的 观察乳腺癌脑转移的放疗效果,探讨预后相关因素。方法 对接受全脑放疗的56例乳腺癌脑转移病例进行回顾性分析,所有患者均接受全颅放疗,放疗剂量为30 Gy/10Fx。采用Kaplan-Meier法计算总生存和中位生存时间,利用COX比例风险回归模型进行多因素分析患者预后的独立危险因素。结果 确诊乳腺癌脑转移平均年龄为57.9岁(32～82岁),平均随访时间为28.4个月(95%CI:11.6,49.2)。乳腺癌脑转移放疗患者中位生存时间为12.1个月(95%CI:8.7,15.5),1、2年生存率分别为52.6%、26.1%。单因素分析显示：有统计学意义的因素包括GPA评分、无颅外转移、脑转移时KPS评分、是否幕下转移、Her-2表达状态、分子分型、是否肺转移、脑转移放疗后化疗。多因素分析显示：脑转移时KPS(P=0.027)、GPA评分(P=0.036)、分子分型(P=0.042)、无颅外转移(P=0.028)、无肺转移(P=0.002)、脑转移放疗后接受化疗(P=0.034)是乳腺癌脑转移放疗患者预后的独立预后因素。结论 分子分型可作为乳腺癌脑转移的预后指标。脑转移放疗后化疗、无...     

同期化疗对Ⅲ期鼻咽癌放疗患者预后影响的回顾性分析

目的:分析并评价同期化疗对提高Ⅲ期鼻咽癌患者放疗后远期生存率的影响和价值。方法:收集首程治疗Ⅲ期鼻咽癌患者507例,其中178例放疗同期联合含顺铂方案的化疗。Kap-lan-meier法计算生存率,Log-rank检验并行预后的单因素分析,Cox比例风险模型进行多因素预后分析。结果:中位随访时间53个月。Ⅲ期鼻咽癌患者的5年总生存率、局部区域无复发生存率、无远处转移生存率和无瘤生存率分别为65.8%、81.4%、75.0%和62.5%。放化组总生存率为71.6%,单放组为62.7%,χ2=4.830,P=0.028;局部区域无复发生存率放化组为90.5%,单放组为76.3%,χ2=11.464,P=0.001;无远处转移生存率放化组为77.4%,单放组为73.6%,χ2=1.092,P=0.296;无瘤生存率放化组为70.6%,单放组为58.1%,χ2=8.078,P=0.004。单因素分析结果表明,同期化疗是影响鼻咽癌治疗总生存率、局部区域无复发生存率和无瘤生存率的预后有利因素。多因素分析结果显示,同期化疗是影响局部区域无复发生存率和无瘤生存率的独立预后因素。结论:同期化疗有助于提高Ⅲ期鼻咽癌放疗后的局部区域无复发生存率和无瘤生存率。     

术后放疗对T1-2N1M0期三阴乳腺癌患者预后的影响

目的 分析T1-2N1M0期三阴性乳腺癌（TNBC）患者行改良根治术后放疗与否对生存的影响。方法 回顾性分析2004年1月至2010年9月接受改良根治术后129例T1-2N1M0期TNBC患者的临床资料,其中61例行术后常规放疗（放疗组）,68例未行放疗（未放疗组）。分析两组5年总生存率、5年无局部复发生存率和5年无病生存率以及影响局部复发的因素。结果 中位随访时间为67个月,全组患者中27例（20.9％）出现局部区域复发。放疗组较未放疗组提高了5年无局部复发生存率（88.5％ vs. 70.6％,P=0.017）和5年无病生存率（78.7％ vs.63.2％, P=0.068）。放疗组和未放疗组的5年生存率分别为88.5％和82.4％（P=0.341）。单因素分析显示年龄、T分期、淋巴结阳性数、是否放疗是影响无局部复发生存的预后因素（P＜0.05）。多因素分析显示未放疗（HR=3.432,P=0.010）和淋巴结3枚阳性（HR=2.915,P=0.020）是影响局部区域复发的独立预后因素。结论 术后放疗可明显改善T1-2N1M0期TNBC患者的无局部复发生存。淋巴结3枚阳性者局部控制更差,增加区域淋巴结照射是可行的。     

小细胞肺癌预防性脑照射的临床研究

目的 探讨性全脑照射（ＰＣＩ）对局限期小细胞肺癌（ＳＣＬＣ）脑转移率和生存率的影响。方法 １９９０年１月～１９９５年１２月间,５１例经化疗加放疗后完全缓解的局限期ＳＣＬＣ患者被承机分为脑照射组（２６例）和对照组（２５例）。脑照射组患者接受ＰＣＩ２５．２～３０．６Ｇｙ。结果 脑照射组患者的脑转移率为３．８％,明显你芋对照组的２８．０％（Ｐ〈０．０５）。脑照射组患者和,１,２,３年生存率分别为８４．６     

术后小细胞肺癌患者预防性脑照射研究进展

小细胞肺癌(SCLC)发病数较少,约占所有支气管肺癌的13%~20%,恶性程度较高,短时间内易复发转移。确诊时局限期小细胞肺癌约占SCLC的30%,符合手术患者仅占5%。放化疗后完全缓解者仍有一半以上患者发生脑转移。术后Ⅰ、Ⅱ、Ⅲ期SCLC患者脑转移发生率为6%~14%、13%~38%、11%~36%。预防性脑照射(PCI)可提高放化疗后完全缓解者总生存率,并降低脑转移发生率,是局限期SCLC综合治疗的重要组成部分。但是,PCI的临床应用仍存一些争议,手术完全切除的SCLC患者行PCI的疗效不一。本文对此问题进行文献综述,并介绍该领域的研究进展。     

The role of prophylactic cranial irradiation in the treatment of lung cancer

Patients with lung cancer face concurrent risks of their disease by local, regional as well as distant failure. The brain is one of the major sites of distant relapse and the prevention of cerebral metastasis has therefore gained rising interest. A recent meta-analysis has confirmed the benefit of prophylactic cranial irradiation in patients with limited disease small-cell lung cancer in complete remission following induction therapy. In non-small-cell lung cancer, aggressive multimodality therapy regimens including surgery have achieved locoregional control rates of 50% and higher. In these patient groups the relatively high incidence of brain relapses as a site of first failure causes substantial morbidity and worsens the prognosis. Given the proven efficacy of prophylactic cranial irradiation (PCI) to prevent metastases to the brain, the introduction of PCI into the treatment of non-small cell lung cancer in the curative setting seems promising.     

Patterns of recurrence and outcome in patients with surgically resected small cell lung cancer

Background

Although prophylactic cranial irradiation (PCI) in limited-stage (LS) small cell lung cancer (SCLC) patients who are surgically resected and treated with adjuvant chemotherapy is considered to be a reasonable treatment option, the efficacy of PCI for those patients remains unclear.

Methods

The records of 28 patients with SCLC undergoing curative surgery at the Aichi Cancer Center Hospital between 1995 and March 2008 were retrospectively reviewed to assess patterns of relapse and overall survival.

Results

The patients were 27 men and 1 woman. Eight patients underwent induction chemotherapy. Fourteen patients (50%) had pathologic stage (p-stage) I disease, 7 patients (25%) had p-stage II, and 7 patients (25%) had p-stage III. Nineteen patients underwent adjuvant chemotherapy and one patient received adjuvant chemoradiotherapy. There were a total of 13 deaths and 8 were disease-related. Most patients developed hematogenous distant metastases before their death. The 5-year overall probability of survival was 47%. Ten (36%) of the 28 patients had a relapse. Two had a local relapse alone, one patient had combined local and distant relapses, and seven patients had distant metastases alone as their first site of failure. Four patients with p-stage II/III disease developed brain metastases with a cumulative incidence at 1 and 2?years of 25 and 36%, respectively.

Conclusions

Our retrospective study suggested that PCI might have a role in surgically resected patients with p-stage II/III SCLC because of their relatively high frequency of brain metastasis.     

局限期小细胞肺癌预防性脑照射后脑转移相关危险因素分析

小细胞肺癌具有易复发和转移的生物学特点,脑是小细胞肺癌肺外转移的好发部位。局限期小细胞肺癌患者行预防性脑照射(PCI)能够有效降低脑转移的发生率,延长总生存期。但是在PCI后仍有近1/3的患者发生脑转移。本文对PCI后脑转移的危险因素进行综述,目的在于判断何种局限期小细胞肺癌亚组患者能够从PCI中获益,从而为PCI的临...     

Prophylactic cranial irradiation in lung cancer

Opinion statement Patients with locally advanced lung cancer (non-small cell lung cancer or small cell lung cancer [SCLC]) are threatened by concurrent risks of local, regional, and distant failure. By improving locoregional and systemic control within multimodality protocols, the brain emerges as one of the major relapse sites; therefore, prevention of brain relapse has become a primary focus of attention. Prophylactic cranial irradiation (PCI) has a high potential to reduce the risk of brain metastases. Clear evidence exists from meta-analysis that PCI improves overall and disease-free survival rates for patients with SCLC in complete remission. Long-term toxicities, predominantly neurocognitive impairments, represent potential risks, but within large prospective trials, including adequate control groups, late complications of clinical significance rarely have been observed. PCI is the recommended standard of care for the patients with limited disease SCLC in complete remission. As long as the optimal dose and fractionation remain to be defined in this setting, conventional fractionation with moderate total doses of approximately 30 Gy is preferred. In patients with locally advanced stage III non-small cell lung cancer treated within multimodality protocols, comparable relative risks for cumulative brain relapse have been demonstrated in long-term survivors. Although not the standard of care in this situation, the scientific community should be encouraged to further investigate PCI in these patient subgroups within carefully designed clinical trials, including untreated control arms.     

Risk of cerebral metastases and neurological death after pathological complete response to neoadjuvant therapy for locally advanced nonsmall-cell lung cancer: clinical implications for the subsequent management of the brain

BACKGROUND: The incidence and pattern of brain metastases was analyzed among patients who achieved a pathological complete response (pCR) after neoadjuvant chemotherapy or chemoradiotherapy for locally advanced nonsmall-cell lung cancer (NSCLC). METHODS: Between 1990 and 2004, 211 patients were treated with neoadjuvant therapy before surgical resection for stage III NSCLC. The clinical course of 51 patients who demonstrated a pCR were reviewed. The neoadjuvant regimen consisted of either chemotherapy (29 patients) or chemoradiotherapy (22 patients). Histology was 45% adenocarcinoma, 41% squamous cell, and 14% large cell carcinoma. No patient received prophylactic cranial irradiation (PCI). RESULTS: Overall survival at 1, 3, and 5 years was 82%, 63%, and 42%, respectively. The most common site of initial recurrence was the brain. Twenty-two (43%) patients developed brain metastasis as the site of first failure, which represented 71% of all isolated recurrences. Ultimately, 28 (55%) patients developed brain metastases at some point during their clinical course. The 5-year estimates of brain metastasis-free survival for patients with squamous and nonsquamous cancers were 57% and 34%, respectively (P = .02). Median survival from the time of brain metastasis was 10 and 5 months for those with isolated and nonisolated recurrences, respectively. CONCLUSION: Patients with a pCR after multimodality therapy for locally advanced NSCLC are at excessively high risk for the subsequent development of brain metastases. Implications for management strategies including PCI and stereotactic radiosurgery (SRS) are discussed.     

Symptomatic brain metastases from small-cell carcinoma of the urinary bladder: The Netherlands Cancer Institute experience and literature review

BackgroundThe incidence of symptomatic brain metastases in small-cell carcinoma of the urinary bladder (SCBC) is unknown. This precludes advice about prophylactic cranial irradiation (PCI).Patients and methodsThe medical records of all patients with SCBC seen at The Netherlands Cancer Institute from 1993 to 2009 (n = 51) were reviewed. Limited disease (LD) was defined as any pT, cN_0–1, and cM₀. Patients with LD were offered bladder-preserving treatment involving combined chemoradiotherapy. Patients with extensive disease (ED) were treated with palliative chemotherapy. PCI was not applied in any patient.ResultsAmong 39 patients with LD, median disease-specific survival was 35 months. Four developed symptomatic brain metastases after a median follow-up of 15 months (range 3–24) and were treated with whole-brain radiotherapy. No patient with ED developed symptomatic brain metastases during a median follow-up of 6 months. The reported incidence of brain metastases in SCBC in the literature ranges between 0% and 40%. On the basis of all reported series, the pooled estimate of the cumulative incidence of brain metastases is 10.5% (95% confidence interval 7.5% to 14.1%).ConclusionsThe incidence of symptomatic brain metastases from SCBC is significantly lower than that from small-cell lung cancer. Therefore, we do not routinely advise PCI in patients with SCBC.     

Randomized phase III trial of prophylactic cranial irradiation versus observation in patients with fully resected stage IIIA–N2 nonsmall-cell lung cancer and high risk of cerebral metastases after adjuvant chemotherapy

This prospective, randomized, phase III trial shows that prophylactic cranial irradiation prolongs disease-free survival, decreases the rate of cerebral metastases and does not affect quality-of-life for patients with fully resected postoperative pathologically confirmed stage IIIA-N2 non-small-cell lung cancer and high risk of cerebral metastases after adjuvant chemotherapy.BackgroundThis study compared prophylactic cranial irradiation (PCI) with observation in patients with resected stage IIIA–N2 non-small-cell lung cancer (NSCLC) and high risk of cerebral metastases after adjuvant chemotherapy.Patients and methodsIn this open-label, randomized, phase III trial, patients with fully resected postoperative pathologically confirmed stage IIIA–N2 NSCLC and high cerebral metastases risk without recurrence after postoperative adjuvant chemotherapy were randomly assigned to receive PCI (30 Gy in 10 fractions) or observation. The primary end point was disease-free survival (DFS). The secondary end points included the incidence of brain metastases, overall survival (OS), toxicity and quality of life.ResultsThis trial was terminated early after the random assignment of 156 patients (81 to PCI group and 75 to control group). The PCI group had significantly lengthened DFS compared with the control group, with a median DFS of 28.5 months versus 21.2 months [hazard ratio (HR), 0.67; 95% confidence interval (CI) 0.46–0.98;P = 0.037]. PCI was associated with a decrease in risk of brain metastases (the actuarial 5-year brain metastases rate, 20.3% versus 49.9%; HR, 0.28; 95% CI 0.14–0.57;P < 0.001). The median OS was 31.2 months in the PCI group and 27.4 months in the control group (HR, 0.81; 95% CI 0.56–1.16;P = 0.310). While main toxicities were headache, nausea/vomiting and fatigue in the PCI group, they were generally mild.ConclusionIn patients with fully resected postoperative pathologically confirmed stage IIIA–N2 NSCLC and high risk of cerebral metastases after adjuvant chemotherapy, PCI prolongs DFS and decreases the incidence of brain metastases.