Ⅳ期非小细胞肺癌287例放疗后的生存分析

背景与目的:很多Ⅳ期非小细胞肺癌(non-smallcelllungcancer,NSCLC)的患者需要放疗,特别是对脑、骨转移者放疗有很好的治疗作用。本研究旨在分析放疗对Ⅳ期NSCLC患者生存的影响。方法:对287例资料完整的Ⅳ期NSCLC放疗患者进行回顾性分析。脑放疗为平行对穿两野全脑照射,骨放疗为单野局部照射,对原发灶、区域淋巴结和其它转移部位用2维常规分割或3维适形放疗(3dimensionalconformalradiotherapy,3D-CRT)。脑和骨放疗通常采用4周20次共40Gy或2周10次共30Gy的治疗方案,原发灶和区域淋巴结的中位照射剂量是50Gy(20～70Gy),其它转移部位的中位照射剂量是46Gy(40～60Gy)。结果:全部患者中位生存期9个月(8～10个月),1年和2年生存率分别是30.2%和8.9%。有化疗和无化疗者中位生存期分别为10个月和8个月(P=0.049)。有脑转移、骨转移、其它转移者中位生存期分别为8个月、9个月、10个月,1年生存率分别24.8%、28.7%和37.5%,2年生存率分别为6.7%、7.0%和15.3%。单因素分析发现对生存有显著影响的因素为病理类型和年龄。腺癌患者的生存期高于鳞癌和其它病理类型,中位生存期分别为10个月、7个月、9个月(P=0.046);≤60岁的患者生存期显著高于>60岁的患者,中位生存期分别为11月、8个月(P=0.012);单纯骨转移患者的中位生存期要大于合并有其它转移者(10个月与6个月,P=0.033),而单纯脑转移和同时合并有其它转移的两组患者中位生存期却无明显差异(9个月与8个月,P=0.3742);肿瘤原发灶和区域淋巴结是否放疗对患者生存时间影响不大(10个月与8个月,P=0.066);是否伴有其它慢性疾病对患者的生存期无明显影响(9个月与10个月,P=0.306)。对脑和骨转移的患者采用4周20次40Gy或2周10次30Gy放疗对生存期无明显影响。结论:病理类型、年龄对Ⅳ期NSCLC患者的放疗疗效有显著影响,全脑和骨转移采用4周20次40Gy或2周10次30Gy放疗对生存期无明显影响。     

COAPC方案联合脑部放射治疗非小细胞肺癌脑转移

背景与目的：放射治疗具有治疗脑转移癌的主要手段。而到目前为止化疗与放疗联合治疗脑转移癌的研究较少,本研究旨在观察COAPC方案化疗与脑部放射同时治疗非小细胞肺癌（non-small cell lung cancer,NSCLC)脑转移患者疗效,不良反应及生存率。方法：45例NSCLC脑转移患者接受COAPC方案化疗,环磷酰胺0．3g/m^2第1天静推,长春新碱1．4mg/m^2第1天静推,阿霉素50mg/m^2第1天静推,顺铂20mg/m^2第1－5天静滴,司莫司汀80mg/m2第1天口服,每3－4周为1疗程,脑部放射治疗于化疗第1疗程的第6天开始,每次2Gy,每天1次,每周5天,脑转移灶1－3个者,全脑放疗40Gy后,缩野放疗至总量60Gy,脑转移灶＞3个者,全脑放疗至总量40Gy.结果：治疗后80％患者神经系统症状改善,对脑转移灶的客观有效率为64．4％,对肺原发灶的有效率为40％,治疗的主要不良反应为骨髓抑制(Ⅲ-Ⅳ度占35％）,中位生存期10个月,1年生存率44．1％,5年生存率6．7％,单纯脑转移患者的中位生存期14个月,高于多发远处转移患者的9个月（P＝0．012）。结论：化疗联合脑部放射治疗NSCLC脑转移患者有效率与生存率较高,且患者耐受性较好。     

Brain metastases and non-small cell lung cancer. Prognostic factors and correlation with survival after irradiation

A total of 250 patients with brain metastases from non-small cell lung cancer (NSCLC) were treated with irradiation of their brain metastases. The median overall survival was 3.1 (95% CI: 2.7-3.5) months. 32/250 patients presenting with solitary brain metastasis underwent surgical resection. Their 1-year survival rate of 58% was significantly better than 89/250 patients with a solitary lesion but without surgery (14%, P=0.001). Patients with an absent or controlled primary tumor (101/250, 40.5%) had a 1-year survival rate of 26% as opposed to 11% for patients presenting with an active primary tumor (P=0.051). Patients presenting with metastases to the brain only showed a significant survival advantage over patients with extracranial metastases (1-year survival of 21% vs 6%, P=0.001). Karnofsky performance score, neurofunction status and response to steroids were also identified as prognostic factors. The total dose whole brain irradiation (WBI) was prognostic of significance with a 1-year survival of 35% for 30 Gy and boost, 23.5% for 30 Gy and 4% for the patients irradiated to a dose of 20 Gy WBI (P=0.001). When patients were grouped into the RTOG RPA (Recursive partitioning analysis) classes, patients within class I (73/250) had a 1-year survival of 28.5%, patients in class II (145/250) a survival of 14% at 1 year and patients into class III only a 6% 1-year survival rate. In a multivariate analysis, surgical resection, neurofunction class, metastatic extent and WBI dose remained significant prognostic factors. Although survival remains poor, there needs to be a continued interest in these patients, probably by participating in clinical trials.     

Two radiation regimens and prognostic factors for brain metastases in nonsmall cell lung cancer patients

BACKGROUND: Nonsmall cell lung cancer (NSCLC) patients with brain metastases usually receive whole-brain radiotherapy (WBRT). Most of these patients survive for only a few months. A short course of WBRT would be preferable to longer regimens if it could provide similar survival. This retrospective study of NSCLC patients compared longer treatment programs with short-course WBRT with 5 x 4 Gy given during 5 days. METHODS: Data from 404 NSCLC patients treated with WBRT for brain metastases were retrospectively analyzed. The 140 patients who received 5 x 4 Gy given in 5 days were compared for survival with 264 patients who received either 10 x 3 Gy given in 2 weeks or 20 x 2 Gy given in 4 weeks. Seven further potential prognostic factors were investigated for survival including age, sex, Karnofsky performance score (KPS), number of brain metastases, extracranial metastases, interval from tumor diagnosis to WBRT, and RPA (recursive partitioning analysis) class. RESULTS: The WBRT regimen was not associated with survival (P = .55). On multivariate analysis, age < 60 years (vs > or =60 years, P = .020), KPS > or =70 (vs KPS < 70, P < .001), interval from tumor diagnosis to WBRT > 12 months (vs < or =12 months, P = .007), no extracranial metastases (P < .001), and RPA class 1 (vs RPA class 2 vs RPA class 3, P = .007) were significantly associated with improved survival. CONCLUSIONS: Short-course WBRT with 5 x 4 Gy appeared preferable for most NSCLC patients, as it was associated with survival similar to longer WBRT programs, and the short course was less time consuming.     

非小细胞肺癌脑转移患者全脑放疗不同剂量预后分析

目的:分析非小细胞肺癌(NSCLC)脑转移患者不同全脑放疗(WBRT)剂量的预后及影响因素。方法:回顾性分析2013—2015年间于河北医科大学第四医院行WBRT的244例NSCLC脑转移患者。按照不同WBRT剂量(EQD 2Gy)分为30~39 Gy组104例、≥40 Gy组140例。比较两组患者颅内无进...     

Upfront association of carboplatin plus pemetrexed in patients with brain metastases of lung adenocarcinoma

Approximately 10% of patients with non-small cell lung cancer (NSCLC) have brain metastases at the time of diagnosis. When surgical resection is not possible, whole brain radiotherapy is the standard of care, with a cerebral response rate of approximately 30%. We report our experience with an upfront association of carboplatin and pemetrexed (areas under the curve, 5 and 500 mg/m(2), respectively), every 3 weeks, in 30 patients presenting with newly diagnosed brain metastases and NSCLC. Cerebral MRIs were performed every 6-9 weeks. The radiologic response rates were assessed according to Response Evaluation Criteria in Solid Tumors. Overall survival was also determined. Twenty-six patients were evaluable for response, and the objective cerebral response rate (complete and partial response) in the intent-to-treat population was 40% (12 of 30 patients). Event-free survival was 31 weeks, and median overall survival was 39 weeks. The upfront association of carboplatin plus pemetrexed allows simultaneous treatment of cerebral and systemic disease in patients with NSCLC with newly diagnosed brain metastases and appears to be particularly interesting in terms of radiologic response and overall survival. Further clinical studies are warranted.     

Treatment of brain metastases in patients with non-small cell lung cancer (NSCLC) by stereotactic linac-based radiosurgery: prognostic factors

A restrospective study of patients with brain metastases from non-small cell lung cancer (NSCLC) is performed to identify patients who benefit from radiosurgery and to determine prognostic factors for survival. Eighty-six consecutive patients with a total of 110 brain metastases from NSCLC were treated with linac-based radiosurgery. Six patients with eight brain metastases who received radiosurgery as a focal boost to whole brain radiotherapy where excluded. Median age at treatment was 60 years. Median dose was 20 Gy/80%-isodose. A chi(2)-test was used to identify potential prognostic factors for local control of brain metastases and survival of the patients. Median follow-up was 6 months (range 1 1/2-77 months) with 17/80 patients still alive. Median actuarial survival was significantly longer (P<0.004) in patients with metachronous onset of brain metastases in comparison to synchronous onset (8.3 vs. 3.3 months). Survival was significantly increased after radiosurgery in the absence of extracranial tumor progression (P<0.03). Eleven patients (14%) developed new brain metastases after radiosurgery after a latency of median 5 months. Actuarial local control rate was 96% after 3 months. Local control was significantly increased with a prescribed dose > or=18 Gy/80%-isodose (P<0.01). We conclude that especially patients with poor prognostic factors and a limited number of brain metastases may be palliatively treated with radiosurgery alone. This approach allows to effectively control CNS manifestation of the disease and can be integrated into chemotherapeutic protocols.     

Treatment strategies for advanced and metastatic cancer in Europe

ESTRO members were surveyed by questionnaires regarding the management of three cases of advanced cancer and the organisation of cancer care in their centre. There were 278 replies from within Europe from a total of 21 countries and 231 centres. The cases were a 64-year-old man with brain metastases from a small cell carcinoma of the lung, a 64-year-old woman with bone metastases from carcinoma of the breast on tamoxifen and a 59-year-old man with a squamous cell carcinoma (NSCLC) of the bronchus and positive mediastinal lymph nodes. Over 90% of respondents replied that they would give radiotherapy in each of these cases. The median total doses were 30 Gy for the brain metastases, 30 Gy for the bony metastases and 56 Gy for the case of NSCLC. There was variation as to the perceived prognosis and appropriate aims of therapy, particularly for the case of NSCLC. The total dose and number of fractions of radiotherapy could be related to the perceived aims and expectations of treatment, e.g. those aiming to extend life gave significantly higher total doses of radiotherapy (p = 0.0001) and those aiming to relieve symptoms gave significantly lower total doses (p = 0.0001). Treatment for this case was described as "radical" by 53% of respondents and as "palliative" by 47% and the prognosis was estimated to be less than 12 months by 41% and 1-2 years by 44%. Those describing treatment as radical and estimating longer survival gave higher doses and more fractions than those treating palliatively.(ABSTRACT TRUNCATED AT 250 WORDS)     

A randomised phase III study of palliative radiation with concomitant carboplatin for brain metastases from non-small cell carcinoma of the lung

PURPOSE: To determine if the addition of carboplatin chemotherapy to whole brain irradiation improves response and survival in patients with brain metastases from non-small cell lung cancer (NSCLC). PATIENTS AND METHODS: Forty-two patients with brain metastases from NSCLC and performance status ECOG 0-2 were randomised to receive either whole brain radiotherapy (WBRT) alone (20Gy in five fractions) or the same radiotherapy plus concomitant carboplatin (70 mg/m(2) intravenously for 5 days). RESULTS: The median survival was 4.4 months in the radiotherapy alone (RT) arm and 3.7 months in the combined treatment (RTC) arm (P = 0.64). The objective response rates of 10% on the RT arm and 29% on the RTC arm were not significantly different (P = 0.24). The trial was closed early because of poor accrual. CONCLUSIONS: Although no firm conclusions can be made regarding the efficacy of the combined treatment, this prospective study highlights the poor objective response rates and relatively poor symptom control despite standard treatment of brain metastases from NSCLC.     

Gamma knife stereotactic radiosurgery for synchronous versus metachronous solitary brain metastases from non-small cell lung cancer

A retrospective study was conducted analyzing the clinical outcome and various prognostic factors in patients treated with gamma knife stereotactic radiosurgery (GK-SRS) for solitary brain metastasis from non-small cell lung carcinoma (NSCLC). A total of 72 patients from June of 1992 to January of 1999 were treated. All patients received GK-SRS to a median dose of 18Gy, with 45 patients receiving additional whole-brain radiation therapy. No one had evidence of extra-cranial metastasis at the time of diagnosis of brain metastases. The median follow-up was 15.7 months for the entire population and 99.5 months for those who were alive at the last follow-up. Univariate and multivariate analyses were used to test the impact of various prognostic factors on survival. The median and 5-year actuarial survivals for the entire cohort were 15.7 months and 10.4%, respectively. The presence of a metachronous versus a synchronous brain metastasis was the only factor significant in the univariate (P=0.045) and multivariate (P=0.002) analyses. Patients with metachronous solitary brain metastases had a significant median survival advantage compared to those with synchronous metastases (33.3 months versus 8.6 months, P=0.001). However, there was no statistically significant difference in median survival from the time of metastasis when treated with GK-SRS in these groups (12.5 months versus 8.4 months, P=0.50). The addition of WBRT did not improve overall survival (12.0 months versus 7.7 months, P=0.73). The 5-year actuarial survival for the metachronous and synchronous groups were 13.2 and 8.1%, respectively. In conclusion, patients presenting with a solitary metachronous brain metastasis from NSCLC achieved longer survivals than those with a synchronous metastasis. The tail in the survival curves demonstrates that a prolonged survival may be attained in patients with solitary metastases from NSCLC. This study adds to the growing body of literature that supports the use of SRS in the management of this patient population.     

选择性动脉灌注化疗联合靶向药物治疗非小细胞肺癌多发脑转移

背景与目的 本研究旨在回顾性分析选择性动脉灌注化疗联合赖氨酸激酶抑制剂( tyrosine kinase inhibitor,TKI)药物治疗非小细胞肺癌(non-small cell lung cancer,NSCLC)多发脑转移的临床疗效及预后相关因素.方法 自2008年9月-2011年10月共入组31例诊断明确的非小细胞肺癌经CT或MRI证实多发脑转移瘤(＞3个)的患者,行选择性颅内动脉、支气管动脉及相关靶动脉化疗药物灌注化疗2个-6个周期,每周期间隔4周,同步或后续联合厄洛替尼、吉非替尼或埃克替尼治疗.介入治疗2个周期或联合靶向治疗后每4周应用CT和MRI对肿瘤进行疗效评价,直至肿瘤进展或发生不可耐受性化疗药物不良反应.结果 31例患者平均行3个周期介入治疗,随访时间4个-40.9个月,完全缓解5例(16.1％),部分缓解7例(22.6％),疾病稳定11例(35.5％),疾病进展8例(25.8％).客观缓解率( objective response rate,ORR)为38.7％,疾病控制率(disease control rate,DCR)为74.2％.中位无进展生存期(progression free survival,PFS)为13.1个月,中位总生存期(overall survival,OS)为15.1个月.6个月的生存率为79％,1年生存率为61.1％,2年生存率为31.1％.分层分析显示PFS、OS与吸烟状态、病理类型、颅外转移情况、靶向药物应用时间、PS评分具有相关性;与性别、年龄、既往治疗情况、脑转移数目无明显相关.结论 选择性动脉灌注化疗联合靶向药物是治疗非小细胞肺癌多发脑转移安全有效的方法之一,吸烟状态、PS评分、肿瘤病理类型、颅外转移状况、靶向药物应用时间均可影响患者预后.     

Combination chemotherapy of cisplatin, ifosfamide, and irinotecan with rhG-CSF support in patients with brain metastases from non-small cell lung cancer

BACKGROUND: Brain metastases develop frequently in patients with non-small cell lung cancer (NSCLC), and the prognosis for these patients is very poor. We evaluated the role of chemotherapy for patients with brain metastases from NSCLC. METHODS: We analyzed 30 patients who were discovered to have brain metastases during the diagnosis of 121 patients enrolled in three consecutive clinical trials on advanced NSCLC assessing combination chemotherapy of cisplatin, ifosfamide and irinotecan with rhG-CSF support. Response in the brain lesions was evaluated by contrast-enhanced MRI scans after at least two courses. RESULTS: Fourteen patients achieved a partial response (PR) but there was no change (NC) in 13 patients and progressive disease (PD) in 1. Among patients with extracranial lesions, 18 had a PR and 11 had NC. The response rate in brain metastases was 50.0%, and that in extracranial primary and metastatic lesions was 62.1%. The median duration of response for intra- and extracranial lesions was 140 and 147 days, respectively. After completing chemotherapy, Gamma Knife radiosurgery was performed on 2 patients in remission and 8 patients at disease progression. The median survival time and 1-year survival rate were 382 days and 56.1%, respectively. CONCLUSIONS: Both the response rate and survival data in this retrospective study suggest a high degree of activity of this combination chemotherapy in patients with brain metastases from NSCLC.     

Nonsmall cell lung cancer presenting with synchronous solitary brain metastasis

BACKGROUND: Solitary brain metastases occur in about 50% of patients with brain metastases from nonsmall cell lung cancer (NSCLC). The standard of care is surgical resection of solitary brain metastases, or stereotactic radiosurgery (SRS) plus whole brain radiation therapy (WBRT). However, the optimal treatment for the primary site of newly diagnosed NSCLC with a solitary brain metastasis is not well defined. The goal was to distinguish which patients might benefit from aggressive treatment of their lung primary in patients whose solitary brain metastasis was treated with surgery or SRS. METHODS: The cases of 84 newly diagnosed NSCLC patients presenting with a solitary brain metastasis and treated from December 1993 through June 2004 were retrospectively reviewed at The University of Texas M. D. Anderson Cancer Center. All patients had undergone either craniotomy (n = 53) or SRS (n = 31) for management of the solitary brain metastasis. Forty-four patients received treatment of their primary lung cancer using thoracic radiation therapy (median dose 45 Gy; n = 8), chemotherapy (n = 23), or both (n = 13). RESULTS: The median Karnofsky performance status score was 80 (range, 60-100). Excluding the presence of the brain metastasis, 12 patients had AJCC Stage I primary cancer, 27 had Stage II disease, and 45 had Stage III disease. The median follow-up was 9.7 months (range, 1-86 months). The 1-, 2-, 3-, and 5-year overall survival rates from time of lung cancer diagnosis were 49.8%, 16.3%, 12.7%, and 7.6%, respectively. The median survival times for patients by thoracic stage (I, II, and III) were 25.6, 9.5, and 9.9 months, respectively (P = .006). CONCLUSIONS: By applying American Joint Committee on Cancer staging to only the primary site, the thoracic Stage I patients in our study with solitary brain metastases had a more favorable outcome than would be expected and was comparable to Stage I NSCLC without brain metastases. Aggressive treatment to the lung may be justified for newly diagnosed thoracic Stage I NSCLC patients with a solitary brain metastasis, but not for locally advanced NSCLC patients with a solitary brain metastasis.     

Gefitinib is active in patients with brain metastases from non-small cell lung cancer and response is related to skin toxicity

Gefitinib is active and well tolerated in patients with advanced non-small cell lung cancer (NSCLC); however, its role in patients with brain metastases has not been clearly defined. We had conducted a prospective study to give gefitinib to NSCLC patients irrespective of their performance status (PS), number of prior treatment regimens and the presence of brain metastases. A total of 76 patients were enrolled. Fifty-seven patients had measurable lesions and the objective response rate was 33.3% (95% confidence interval [95% CI], 20.7-46.0%). For all enrolled patients, the disease control rate was 63.2% (95% CI, 52.1-74.3%) with a median progression-free survival of 5.0 months (95% CI, 3.6-6.5 months) and median overall survival 9.9 months (95% CI, 4.9-14.8 months). Twenty-one patients had simultaneously assessable intracranial lesions (ICLs) and extracranial lesions (ECLs), 17 of them (81.0%) showed comparable tumor response. There was no survival difference between the patients with and without metastatic brain disease. Most drug-related adverse events were mild. Intolerable toxicities happened in five patients, four of them were interstitial pneumonia (5.8%). Severity of skin toxicity was tightly associated with tumor response and patient survival (P = 0.007 and <0.001) and the association was consistent in the analysis using early toxicity profile (P = 0.033 and 0.001). In conclusion, gefitinib is active in patients with brain metastasis from NSCLC and tumor response is related to skin toxicity. It is feasible to conduct randomized trials to identify the role of gefitinib alone or in combination with other modality for treatment of NSCLC patients who have metastatic brain lesion(s).     

High-dose 3-dimensional conformal radiotherapy with concomitant vinorelbine plus carboplatin in patients with non-small cell lung cancer: A feasibility study

The aim of this study was to evaluate the feasibility of high-dose 3-dimensional conformal radiotherapy (3DCRT) (70 Gy) with concomitant vinorelbine (NVB) plus carboplatin (CBP) chemotherapy in patients with non-small cell lung cancer (NSCLC). Patients with advanced NSCLC were treated with 3-dimensional conformal radiotherapy in conventional fractionation: 2 Gy/fraction, 1 fraction/day, 5 fractions/week; total dose 70 Gy. The radiotherapy planning of every case had met the following conditions: the percentage of total lung volume receiving 20 Gy (V20) ≤30% and the percentage of total lung volume receiving 30 Gy (V30) ≤20%. Chemotherapy was commenced on the first day of radiotherapy: NVB 25 mg/m(2), day 1 and day 8, CBP at AUC of 5 mg/ml(-1).min(-1), day 8, repeated for 28 days, two concomitant cycles during radiotherapy, and not more than 4 cycles following radiotherapy. A total of 37 patients were recruited and each of them completed the entire radiation procedure. No Grade V toxicity was observed within the group. The hematological toxicity rates were: Grade III/IV neutropenia was observed in 18.9% (7/37) of cases, Grade III/IV thrombocytopenia in 8.1% (3/37) of cases, but no cases of Grade III/IV anemia were noted. For non-hematological toxicities the rates were: Grade III radiation pneumonitis, 8.1% (3/37) of cases; Grade III radiation esophagitis, 13.5% (5/37); but no cases of Grade IV/V non-hematological toxicities. High-dose 3DCRT also achieved a favorable efficacy: the complete response (CR) rate was 13.5% (5/37) and the partial response (PR) rate was 64.9% (24/37). The total response (CR+PR) rate was 78.4% (29/37). The median survival time was 12 months and the 1-year overall survival rate was 45.1%. Given that 35% of patients in the study had stage IV disease, the survival results were comparable with other similar studies. In conclusion, in our small-sample exploratory study, the high-dose regimen of 70 Gy using 3DCRT with concomitant NVB plus CBP was feasible for patients with NSCLC. Further evaluation of this regimen is ongoing in a prospective controlled phase II trial.     

Radiotherapeutic management of brain metastases from breast cancer

We have reviewed the medical records of 28 breast cancer patients with brain metastases who were treated with radiotherapy at our clinic from 1980 through 1994 (4 patients, postoperatively; 24 patients, radiotherapy alone). Radiotherapy was delivered as whole brain irradiation using lateral opposed 10 MV X-rays. Ten patients received an additional boost to a reduced field. One patient was treated with localized stereotactic irradiation alone. The radiation dose for tumors ranged from 32 Gy to 60 Gy (mean, 49 Gy) in 2 or 3 Gy daily fractionated doses. The brain was the first site of metastatic involvement in only two patients. In the 26 evaluable patients, neurologic functional improvement was achieved in 24 patients (92%) with complete response (CR) in 1 2 patients (46%) and partial response (PR) in 1 2 patients (46%). The survival rates from the initial treatment were 39% at 5 years and 16% at 10 years (median survival time, 50 months), and those after treatment of brain metastases were 29% at one year and 18% at 2 years (median survival time, 6 months). Performance status tended to be associated with survival (p=0.10), and the presence of liver metastasis was the most important risk factor concerning survival (p=0.056). Two patients suffered severe chronic complications. One patient developed severe dementia after whole brain irradiation with a total dose of 45 Gy in 3 Gy daily fractionated dose, and another patient developed widespread brain necrosis after combined radiotherapy with intrathecal local infusion of methotrexate. Radiotherapeutic management is useful for breast cancer patients with brain metastasis, and long-term survival may also be possible even if patients have preexisting extracranial metastases, except for hepatic involvement. Radiation-related complications should therefore be avoided in these patients.     

羟基喜树碱为主的联合化疗结合同期放射治疗晚期非小细胞肺癌

目的：探讨羟基喜树碱联合顺铂和氟尿嘧啶结合同期放疗治疗晚期非小细胞肺癌的临床疗效和毒性反应。方法：羟基喜树碱6mg/m^2，静脉滴注第1～5天，顺铂30mg/m^2，静脉滴注第1～3天，氟尿嘧啶300mg/m^2，静脉滴注第1～5天，28天为一个周期，至少治疗2周期。放射治疗与化疗同期进行，原发灶总剂量DT50～70Gy／25～35次／5～9周，转移病灶30～60Gy/10～30次／2～8周。结果:全组共31例，完全缓解(CR)6例，部分缓解(PR)18例，总有效率为77．4％。中位生存期16．7个月，1、2年生存率分别为54．7％、30．2％，1、2年局部控制率分别为61％、40％。主要毒副反应是骨髓抑制和消化道反应，但均可耐受。结论:羟基喜树碱为主的联合化疗结合同期放疗是治疗晚期非小细胞肺癌的有效方法，能减轻症状，改善生存质量，延长生存期。     

The use of recursive partitioning analysis grouping in patients with brain metastases from non-small-cell lung cancer

BACKGROUND: This study evaluates the use of recursive partitioning analysis (RPA) grouping in an attempt to predict the survival probabilities in patients with brain metastases from non-small-cell lung cancer (NSCLC). METHODS: Seventy-two patients with brain metastases from NSCLC treated with radiation therapy were included in the study. Sixty-three patients were male and nine patients were female. Their median age was 57 years and their median Karnofsky performance status was 70. At the time of brain metastases, there was no evidence of the intrathoracic disease in 27 patients and the extrathoracic disease was limited to the intracranial disease in 42 patients. In accordance with RPA grouping, 12 patients were in Group 1, 24 patients were in Group 2, and 36 patients were in Group 3. Radiation therapy was delivered to the whole brain at a dose of 30 Gy in 10 fractions in most of the patients. RESULTS: The median survival time was 7 months for Group 1, 5 months for Group 2 and 3 months for Group 3. The survival probability at 1 year was 50% for Group 1, 26% for Group 2 and 14% for Group 3. CONCLUSIONS: This study presents evidence supporting the use of RPA grouping in an attempt to predict the survival probabilities in patients with brain metastases from NSCLC.     

Outcomes With Pembrolizumab Plus Platinum-Based Chemotherapy for Patients With NSCLC and Stable Brain Metastases: Pooled Analysis of KEYNOTE-021, -189, and -407

IntroductionThis exploratory analysis retrospectively evaluated outcomes in patients with advanced NSCLC to determine whether baseline brain metastases influenced the efficacy of first-line pembrolizumab plus chemotherapy versus chemotherapy alone.MethodsWe pooled data for patients with advanced NSCLC in KEYNOTE-021 cohort G (nonsquamous), KEYNOTE-189 (nonsquamous), and KEYNOTE-407 (squamous). Patients were assigned to platinum-doublet chemotherapy with or without the addition of 35 cycles of pembrolizumab 200 mg every 3 weeks. All studies permitted enrollment of patients with previously treated or untreated (KEYNOTE-189 and KEYNOTE-407 only) stable brain metastases. Patients with previously treated brain metastases were clinically stable for 2 or more weeks (≥4 wk in KEYNOTE-021 cohort G), had no evidence of new or enlarging brain metastases, and had no steroid use at least 3 days before dosing. Patients with known untreated asymptomatic brain metastases required regular imaging of the brain.ResultsA total of 1298 patients were included, 171 with and 1127 without baseline brain metastases. Median (range) durations of follow-up at data cutoff were 10.9 (0.1‒35.1) and 11.0 (0.1‒34.9) months, respectively. Hazard ratios (pembrolizumab + chemotherapy/chemotherapy) were similar for patients with and without brain metastases for overall survival (0.48 [95% confidence interval (CI): 0.32‒0.70] and 0.63 [95% CI: 0.53‒0.75], respectively) and progression-free survival (0.44 [95% CI: 0.31‒0.62] and 0.55 [95% CI: 0.48‒0.63], respectively). In patients with brain metastases, median overall survival was 18.8 months with pembrolizumab plus chemotherapy and 7.6 months with chemotherapy, and median progression-free survival was 6.9 months and 4.1 months, respectively. Objective response rates were higher and duration of response longer with pembrolizumab plus chemotherapy versus chemotherapy regardless of brain metastasis status. Incidences of treatment-related adverse events with pembrolizumab plus chemotherapy versus chemotherapy were 88.2% versus 82.8% among patients with brain metastases and 94.5% versus 90.6% in those without.ConclusionsWith or without brain metastasis, pembrolizumab plus platinum-based histology-specific chemotherapy improved clinical outcomes versus chemotherapy alone across all programmed death ligand 1 subgroups, including patients with programmed death ligand 1 tumor proportion score less than 1% and had a manageable safety profile in patients with advanced NSCLC. This regimen is a standard-of-care treatment option for treatment-naive patients with advanced NSCLC, including patients with stable brain metastases.     

沙利度胺联合全脑放化疗治疗20例非小细胞肺癌脑转移疗效分析

[目的]探讨沙利度胺联合全脑放化疗对晚期非小细胞肺癌脑转移治疗的疗效及毒副作用。[方法]20例晚期非小细胞肺癌脑转移患者,接受全脑放疗DT30～36Gy／20～24F,2-2．5周（加速超分割放疗）,脑单个病灶患者追加每周DT9～15Gy／6～10F,所有患者从放疗开始均口服沙利度胺200mg／d,直至疾病进展或出现不可耐受的毒副反应。全脑放疗15Gy／10F后根据患者的病理类型和一般状况选择不同的化疗方案。[结果]沙利度胺联合全脑放化疗对非小细胞癌脑转移的总有效率（CR＋PR）为70．0％,临床获益率（CR＋PR＋SD）为100％（3例CR,11例PR,6例SD）;口服沙利度胺时间〉6个月者中位生存期与〈6个月者比较差异有统计学意义（14．1个月vs．6．9个月,Х^2=4．615,P〈0．05）;主要毒副反应为轻中度便秘和疲乏,但可耐受。[结论]沙利度胺联合全脑放化疗治疗晚期非小细胞肺癌脑转移有明显的疗效．有必要进一步开展随机对照临床研究,以明确抗血管生成药物联合放化疗对脑转移的作用。