非小细胞肺癌预防性脑放射治疗

肺癌是临床的常见肿瘤之一,其中非小细胞肺癌占80%左右.随着治疗手段的提高,患者生存期明显延长,脑转移发病率也随之增加.如何预防非小细胞肺癌患者尤其是肺腺癌患者发生脑转移,延长患者生存时间、提高患者生存质量是肿瘤科医师需要思考的重要问题.     

Short course prophylactic cranial irradiation for small cell lung cancer

Ninety-one patients with small cell carcinoma of the lung were given a shortened, intensive course of prophylactic cranial irradiation consisting of 2,000 rad in five fractions. The CNS relapse rate was 21%, but in only one of 91 patients was the brain the first and only site of relapse. Acute toxicities consisting of headache (16%) and nausea and vomiting (15%) were observed. Results are compared with previous results from other studies of cranial irradiation.     

Leukoencephalopathy in small cell lung cancer patients receiving prophylactic cranial irradiation

The cases of 283 small cell lung cancer patients who received treatment with combination chemotherapy with or without prophylactic cranial irradiation (PCI) were reviewed to determine the incidence of leukoencephalopathy. The overall incidence was 10%. Of all patients receiving PCI, 17% developed neurotoxicity, and of those receiving PCI and surviving greater than or equal to 1.5 years, 37% suffered neurologic sequelae. In those receiving PCI but surviving less than 1.5 years, the incidence of neurotoxicity was 4%. The mean time interval between the end of PCI and the onset of neurotoxicity was 17 months (range 2-63 months). The PCI dose ranged from 2600-3600 cGy. None of the patients not receiving PCI developed neurotoxicity. The incidence of neurotoxicity in long-term survivors (greater than or equal to 1.5 years) with respect to PCI dose was less than or equal to 3000 cGy (25%), 3200 cGy (56%), 3600 cGy (36%). Almost all of the patients getting PCI also received lomustine, an agent associated with DNA repair inhibition and synergism with DNA damaging agents such as ionizing radiation or alkylating agents. Under the conditions of our study, PCI was associated with an unacceptable risk of neurotoxicity. Until further information is forthcoming, one should proceed with caution when using PCI in conjunction with lomustine.     

Unexpected dementia following prophylactic cranial irradiation for small cell lung cancer: case report

Object Prophylactic cranial irradiation (PCI) is commonly offered to patients with limited stage primary small cell lung cancer following a complete response. Methods We present the unique case of a 76-year-old woman treated with PCI with a dose of 30 Gy in 15 fractions, at 200 cGy per fraction who developed progressive dementia. Conclusions This is the first reported case of dementia from PCI at this low dose per fraction. Patients need to be counseled regarding the risks and benefits of treatment, including dementia with treatment and risk of sequelae from CNS metastasis without treatment. The authors review the data supporting PCI and the incidence of radiation associated dementia.     

SCLC脑预防照射——争议中的进展

SCLC是一种强侵袭性的恶性肿瘤,自然病程短,易发生脑转移,因此在放化疗基础上,应用脑预防照射对于减少脑转移的发生及提高患者生存具有重要意义。然而近年来关于脑预防照射的适应证及应用价值却争议不断。这些争议主要集中在广泛期SCLC中脑预防照射的价值,局限期SCLC中脑预防照射适应证以及是否另有替代方法等。本文旨在对现阶段脑预防照射临床应用的相关争议及进展进行相应探讨。     

Evaluation of the use of prophylactic cranial irradiation in small cell lung cancer

BACKGROUND:

Prophylactic cranial irradiation has been used in patients with small cell lung cancer to reduce the incidence of brain metastasis after primary therapy. The purpose of this study was to evaluate the effects of prophylactic cranial irradiation (PCI) on overall survival and cause‐specific survival.

METHODS:

A total of 7995 patients with limited stage small cell lung cancer diagnosed between 1988 and 1997 were retrospectively identified from centers participating in the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) Program. Of them, 670 were identified as having received PCI as a component of their first course of therapy. Overall survival and cause‐specific survival were estimated by the Kaplan‐Meier method, comparing patients treated with or without prophylactic whole‐brain radiotherapy. The Cox proportional hazards model was used in the multivariate analysis to evaluate potential prognostic factors.

RESULTS:

The median follow‐up time was 13 months (range, 1 month to 180 months). Overall survival at 2 years, 5 years, and 10 years was 23%, 11%, and 6%, respectively, in patients who did not receive PCI. In patients who received PCI, the 2‐year, 5‐year, and 10‐year overall survival rates were 42%, 19%, and 9%, respectively (P = <.001). The cause‐specific survival rate at 2 years, 5 years, and 10 years was 28%, 15%, 11%, respectively, in patients who did not receive PCI and 45%, 24%, 17%, respectively, in patients who did receive PCI (P = <.001). On multivariate analysis of cause‐specific and overall survival, age at diagnosis, sex, grade, extent of primary disease, size of disease, extent of lymph node involvement, and PCI were found to be significant (P = <.001). The hazards ratios for disease‐specific and all cause mortality were 1.13 and 1.11, respectively, for those not receiving PCI.

CONCLUSIONS:

Significantly improved overall and cause‐specific survival was observed in patients treated with prophylactic cranial irradiation on unadjusted and adjusted analyses. This study concurs with the previously published European experience. Prophylactic cranial irradiation should be considered for patients with limited stage small cell lung cancer. Cancer 2009. © 2008 American Cancer Society.     

Efficacy and safety of prophylactic cranial irradiation in patients with small cell lung cancer

Background: Prophylactic cranial irradiation (PCI) as part ofthe treament regimen for patients with limited stagesmall cell lung cancer (SCLC) remains controversial. Thepresent study was performed to analyze the efficacyand safety of PCI in patients with limitedstage SCLC who achieved complete remission.Patients and methods: Between 1983 and 1993, thirty-ninepatients with limited stage SCLC who had showncomplete remission after chemotherapy were enrolled prospectively intothe non-randomized study. Eighteen of them received PCI(PCI+), while 21 did not (PCI–). Pretreatment CTor MRI of the brain was performed inall patients. Patients were prospectively evaluated by aneurologist at regular intervals. Results: Three PCI+ patientsand seven PCI– patients developed brain metastases. Thefrequencies of brain metastases were not significantly differentbetween the groups (Fisher's exact test, p =0.207), but brain metastases in PCI+ patients tendedto occur later (log rank, p=0.008).Overall survival was significantly longer in PCI+ patients(log rank, p < 0.001).Early toxicity consisted of headache, nausea, fatigue, concentrationproblems and alopecia. These symptoms and signs weremild and usually reversible within a few months.Late toxicity was studied in patients whose survivalexceeded two years. Seven PCI+ patients survived formore than two years, while no PCI– patientssurvived for more than two years. Memory problemswere seen in six of the seven patients.These problems were non-disabling and, once established, remainedstable for months to years.The most prominent radiologic abnormalities were cortical atrophyand leukoencephalopathy, found in four of the fivepatients who underwent radiologic follow-up examination.Conclusions: This non-randomized study suggests that PCI maybe effective by decreasing the frequency of brainmetastases and by increasing the brain metastasis-free survivaland overall survival, with a minor risk ofclinical and radiologic neurotoxicity.     

A reappraisal of the role of prophylactic cranial irradiation in limited small cell lung cancer.

The use of prophylactic cranial irradiation in limited stage small cell lung cancer remains controversial. Prospective trials have demonstrated that PCI can reduce central nervous system relapse rates, but the impact on survival remains questionable except for the possible evidence of a beneficial effect for long term survivors. With higher rates of thoracic control now obtainable with hyperfractionated radiation and concomitant chemotherapy, it becomes important to analyze the benefit of PCI in that setting. Before 1982, we included PCI in the management of all patients with limited stage small cell lung cancer; thereafter, we discontinued its use. This report compares the outcome of the two treatment approaches and addresses the role of PCI among patients who achieve durable local control. There were 36 limited stage small cell lung cancer patients treated with PCI from 1979-1982 and 26 patients treated without PCI from 1985-1989. Induction chemotherapy was followed in both groups by thoracic irradiation (45 Gy). The PCI patients received 30 Gy to the whole brain in 10 fractions. Both groups received maintenance chemotherapy. Of complete responders, brain failure was the first failure in 18% (4/22) of PCI (+) versus 45% (10/22) of PCI (-) (p = .04). Survival at 2 years was 42% for PCI (+) versus 13% for PCI (-) (p less than .05). When the analysis was limited to those patients permanently controlled in the thorax; there were 25% (4/16) brain failures PCI (+) versus 70% (7/10) PCI (-) (p = .03). For this same subset the 2-year survival was 56% PCI (+) versus 14% PCI (-) (p less than .05). There were no 5 year survivors without PCI compared to 38% (6/16) with PCI. These data suggest that PCI appears to be effective in enhancing survival of patients who achieve durable thoracic control. Prospective trials are necessary to evaluate the use of PCI combined with therapeutic regimens with a documented ability to achieve high rates of sustained control of thoracic disease.     

Prophylactic cranial irradiation in small cell lung cancer

Prophylatic cranial irradiation (PCI) in patients with small cell lung cancer (SCLC) is a treatment under evaluation for about 30 years. Since the first randomized trials, it was clear that its use significantly decreased the brain metastasis rate. However, its effect on overall survival was not demonstrated. Retrospective reviews suggested that PCI could induce late neurologic damage. In recent years, two large randomized trials did not confirm this deleterious effect and even suggested a beneficial effect on survival. A recent meta-analysis including almost 1,000 randomized patients confirmed an improvement in overall survival. We discuss here the different aspects of this preventive treatment in a potentially curable disease.     

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。     

Neurocognitive function in patients with small cell lung cancer : effect of prophylactic cranial irradiation

BACKGROUND: The use of prophylactic cranial irradiation (PCI) in patients with small cell lung cancer (SCLC) has been tempered by fears of detrimental effects on cognitive function. Neuropsychologic testing was prospectively conducted before and after PCI to evaluate its effects on cognitive function in patients with SCLC. METHODS: Ninety-six patients who completely or partially responded to initial therapy underwent formal neurocognitive testing before PCI. Three patients who had central nervous system metastasis were excluded. Of the remaining patients, 69 received PCI (mean dose, 25 grays [Gy] in 10 fractions). Repeat testing was performed on 37 patients (median follow-up, 23 months; range, 6-120 months). RESULTS: Baseline impairment was defined as > or =1.5 standard deviations below the normative mean. Before undergoing PCI, 47% of patients had evidence of impaired cognitive function. After PCI, univariate analysis revealed significant transient declines in executive function (pre-PCI mean, 15.6 +/- 11.5; post-PCI, 27.1 +/- 17.6 [P = .008]) and language (pre-PCI mean, 33.8 +/- 9.9; post-PCI, 31.0 +/- 9.0 [P = .049]) at early timepoints. Controlling for noncentral nervous system disease progression the deficit in executive function was no longer significant. Moreover, these deficits were not sustained, and significant improvements in language and motor coordination were recorded. On multivariate analysis, no significant differences before and after PCI were found. CONCLUSIONS: Neurocognitive testing demonstrated that a substantial portion of patients with SCLC had impaired brain functioning at baseline. Persistent declines in cognitive function were not observed after cranial irradiation. These data do not favor the omission of PCI on the basis of fears of neurotoxic effects.     

局限期小细胞肺癌海马保护脑预防性照射初步研究

目的 分析局限期小细胞肺癌放化疗后行海马保护的脑预防性照射(PCI)的可行性。方法 2016-2019年于浙江省肿瘤医院对进行PCI的小细胞肺癌患者随机分至常规组 22例与海马保护组 18例。根据RTOG 0933试验勾画靶区,海马保护组采用容积调强弧形治疗(VMAT)技术,放疗结束后对患者进行霍普金斯言语测试及脑MRI随访。结果 海马体积(4.01±1.57) cm³,海马回避区体积(20.13±4.14) cm³,海马保护区 域D100%为(7.19±0.38) Gy,Dmax为(14.38±1.18) Gy。霍普金斯言语测试中,放疗后1个月与放疗前(测试3、测试4、学习数、保留百分比)相比,以及放疗后1个月与放疗后(测试3、学习数)相比,海马保护组较常规组下降程度低。平均随访时间(17.00±8.47)个月,共 2例患者出现脑部转移,均为常规放疗组且转移灶位于海马保护区之外。结论 采用VMAT技术进行海马保护的PCI在剂量学上具有可行性,测试结果提示海马保护对于记忆的保护作用,值得临床上进一步推广。     

影像组学在局限期小细胞肺癌脑预防照射优化中的价值

目的探讨治疗前胸部增强CT影像组学模型对局限期小细胞肺癌(LS-SCLC)脑转移的预测能力以及指导个体化预防性脑照射(PCI)的价值。方法回顾性分析2012年1月至2018年12月在山西省肿瘤医院经病理确诊为小细胞肺癌及影像学检查确定为局限期患者资料97例。基于最小绝对值收缩和选择算子(LASSO)Cox与相关性检验筛选与LS-SCLC脑转移显著相关的影像组学特征构建模型, 使用校正曲线、受试者操作特征曲线下面积(AUC)、内部5折交叉验证、决策曲线分析(DCA)与整合布莱尔评分(IBS)评估影像组学模型的预测效能与临床获益, 使用Kaplan-Merier曲线和log-rank检验绘制生存曲线和评估组间差异。结果提取出影像组学特征1272个, 使用LASSO Cox回归和相关性检验筛选特征, 最后通过8个与LS-SCLC患者脑转移发生相关的影像组学特征构建影像组学模型。影像组学模型预测LS-SCLC患者1年与2年脑转移的AUC分别为0.845(95%CI为0.746～0.943)和0.878(95%CI为0.774～0.983)。5折内部交叉验证、校正曲线、DCA以及IBS显示模型有...     

Research progress on prophylactic cranial irradiation in non-small cell lung cancer

Brain metastasis has become a major failure pattern with the prolonged survival of patients with non-small cell lung cancer (NSCLC). Prophylactic cranial irradiation (PCI) has been proven to play a significant role in small cell lung cancer, whereas its value in NSCLC is still controversial. Therefore, this article reviewed the role of PCI in NSCLC, high-risk factors of brain metastasis, timing, dose fraction and toxicity of PCI, etc.     

Advance of prophylactic cranial irradiation in lung cancer

Brain metastases in patients with lung cancer are a devastating problem with profound impact on survival. Prophylactic cranial irradiation has been discussed as an option to reduce the risk of brain metastases. This report provides an extensive review of the current evidence from non-randomized and randomized trials regarding the use of prophylactic cranial irradiation in lung cancer.     

术后局限期小细胞肺癌预防性脑照射疗效分析

目的 探讨局限期小细胞肺癌(SCLC)术后行预防性脑照射(PCI)的疗效。方法 回顾分析2003-2015年浙江省肿瘤医院收治的接受根治性手术治疗的52例局限期SCLC患者资料。根据术后是否行PCI治疗分为PCI组(19例,Ⅰ、Ⅱ、Ⅲ期分别为5、5、9例)和非PCI组(33例,Ⅰ、Ⅱ、Ⅲ期分别为12、5、16例)。采用Kaplan-Meier法生存分析,Cox模型多因素预后分析。结果 PCI组和非PCI组中位总生存时间分别为32.9、20.4个月,2年总生存率高于非PCI组(72%∶38%,P=0.023);中位颅内无进展生存时间分别为32.5、17.1个月,PCI组2年颅内无进展生存率优于非PCI组(89%∶53%,P=0.026)。亚组分析结果显示PCI治疗可使Ⅲ期患者总生存获益(P=0.031),而Ⅰ、Ⅱ期患者生存获益不显著(P=0.924、0.094)。多因素Cox回归分析结果显示PCI是总生存的影响因素(HR=0.330,P=0.041)。结论 SCLC术后行PCI治疗可降低术后脑转移的发生率,并使SCLC患者总OS获益。     

Results of therapeutic cranial irradiation in small cell lung cancer

A large proportion of patients with small cell lung cancer develop intracranial metastases which are often severely disabling. The optimal radiotherapeutic program for treating these metastases is unknown. We therefore evaluated objective response rates, response duration, and survival after therapeutic cranial irradiation in 59 patients with proven brain metastases from small cell lung cancer. Objective responses to a variety of doses and schedules were observed in 37 (63%) patients. However, progression of intracranial disease after radiotherapy was common, with 24 responding patients having relapsed in the brain prior to death. The actuarial likelihood of remaining free of progressive brain tumor at 1 year was only 37% in complete and 0% in partial responders. Patients who received radiation doses of more than 40 Gy had longer response durations than those given lower doses, although patient selection could well explain this observation. Brain metastases presenting after initiation of systemic chemotherapy or occurring in conjunction with other sites of extrathoracic disease were associated with a poor prognosis. In patients who present with brain metastases as the sole site of metastatic disease, higher doses of cranial irradiation should be considered, in view of the high intracranial relapse rate associated with currently accepted dose and fractionation schedules.