Timing of chest radiotherapy in patients with limited stage small cell lung cancer: a systematic review and meta-analysis of randomised controlled trials

BACKGROUND: We undertook a systematic review and literature-based meta-analysis to determine whether the timing of chest radiotherapy may influence the survival of patients with limited stage small cell lung cancer (LS-SCLC). OBJECTIVES: To establish the most effective way of combining chest radiotherapy with chemotherapy for patients with limited-stage small cell lung cancer in order to improve long-term survival. MATERIALS: Eligible studies were identified according to the Cochrane Collaboration Guidelines and were randomised controlled clinical trials comparing different timing of chest radiotherapy in patients with LS-SCLC. Early chest irradiation was defined as beginning within 30 days after the start of chemotherapy. RESULTS: Seven randomised trials were eligible. The overall survival at 2 years or at 5 years was not significantly different between early or late chest radiotherapy. When only trials were considered that used platinum chemotherapy concurrent with chest radiotherapy, significantly higher 2 and 5-year survival rates were observed when chest radiotherapy (RT) was started within 30 days after the start of chemotherapy (2-year survival: HR: 0.73, 95% CI 0.57-0.94, p=0.01; 5-year survival: HR: 0.65, 95% CI 0.45-0.93, p=0.02). This was even more pronounced when the overall treatment time of chest radiotherapy was less than 30 days. In studies that did not show a survival advantage by early chest radiation, a lower dose-intensity of chemotherapy in the early vs. late arm was observed. CONCLUSIONS: When platinum-based chemotherapy concurrently with chest RT is used, the 2- and 5-year survival rates of patients with LS-SCLC may be in favour of early chest radiotherapy, with a significant difference if the overall treatment time of chest radiation is less than 30 days.     

局限期小细胞肺癌不同剂量分割模式放疗的疗效分析

目的 比较不同剂最分割模式放疗对局限期小细胞肺癌生存的影响.方法 回顾分析本院2001-2007年收治的177例局限期小细胞肺癌患者资料.入组条件为病理学证实、局限期且接受了根治性放化疗的患者.根据剂量分割模式将患者分为常规分割组(1.8～2.0 Gy/次,1次/d,63例)、超分割组(1.4 Gy/次,2次/d,79例)和大分割组(2.5 Gy/次,1次/d,35例).对3个组的总生存率、无进展生存率和治疗失败模式进行统计分析.结果 随访率为96.6%,随访满2、5年者分别为153、92例.全组2、5年总生存率分别为43.4%、23.5%,中位生存期为22.4个月.常规分割组、超分割组、大分割组的2年总生存率和无进展生存率分别为31%、46%、59%(x2=7.94,P=0.019)和20%、31%、40%(x2=4.86,P=0.088),两两比较发现2年总生存率大分割组优于常规分割组(x2=7.81,P=0.005),超分割组介于两组之间但差别均无统计学意义(x2=2.31,P=0.128;x2=2.95,P=0.086).毒副反应以大分割组最轻,局部进展与远处转移分布3个组相似.结论 大分割放疗局限期小细胞肺癌显示了一定生存优势,有必要前瞻性临床研究验证其临床价值.     

Effect of Thoracic Radiotherapy Timing and Fractionation on Survival in Nonmetastatic Small Cell Lung Carcinoma

BackgroundThe optimal timing of thoracic radiation therapy (RT) in relation to chemotherapy is unknown in the treatment of nonmetastatic small cell lung cancer (SCLC). We analyzed the National Cancer Data Base (NCDB) to assess the effect on overall survival (OS) of RT timing with chemotherapy for patients with SCLC.Materials and MethodsThe NCDB was queried for patients diagnosed with nonmetastatic SCLC from 1998 to 2011 who had undergone definitive chemoradiation. The patients were stratified into quartiles according to the interval between the start of chemotherapy and the start of RT. The first and second quartiles (RT started 0-20 days after chemotherapy) were classified as “early” RT and the third and fourth quartiles (RT started 21-126 days after chemotherapy) as “late” RT. Patients were included if they had received hyperfractionated 45 Gy in 30 fractions or standard fractionation of ≥ 60 Gy in 1.8- to 2-Gy fractions. Kaplan-Meier analyses of OS were performed, and multivariable Cox regression analysis was conducted to assess the effect of the covariates on OS.ResultsA total of 8391 patients were included (50.5% had received early RT). Early RT was associated with significant improvement in survival (5-year OS, 21.9% vs. 19.1%; P = .01). On subgroup analysis, the survival advantage for early RT was significant for patients receiving hyperfractionated RT (5-year OS, 28.2% vs. 21.2%; P = .004) but not for those receiving standard fractionation (19.8% vs. 18.4%; P = .29). On multivariable Cox regression analysis, hyperfractionated RT was associated with reduced mortality (hazard ratio [HR], 0.90; 95% confidence interval [CI], 0.85-0.96; P = .001), but early RT was not (HR, 0.98; 95% CI, 0.94-1.04; P = .53).ConclusionThese data support the early initiation of hyperfractionated thoracic RT for nonmetastatic SCLC.     

局限期SCLC超分割比常规分割放化疗疗效及安全性Meta分析

目的 系统评价放化疗治疗局限期SCLC时超分割与常规分割不同放疗模式有效性及安全性差异。方法 计算机检索Pubmed、Embase、Cochrane Library、Web of Science、中国生物医学文献数据库、万方、中国知网和维普等数据库,查找超分割对比常规分割放化疗治疗局限期SCLC的临床对照研究文献。使用Revman 5.3统计软件对近期疗效、生存资料及不良反应进行Meta分析。结果 纳入8篇临床对照研究文献,共计1 361例患者。Meta分析结果显示,超分割组与常规分割组有着相似的客观缓解率(OR=1.31,95%CI为 0.64~2.69,P=0.46);两组间2、5年OS率相近(RR=1.10,95%CI为 0.98~1.24,P=0.12;RR=1.13,95%CI为 0.75~1.69,P=0.56);超分割组的≥2级放射性食管炎发生率较常规分割组高(RR=1.74,95%CI为 1.39~2.17,P<0.05),但两组间≥2级的放射性肺炎(RR=0.73,95%CI:0.24~2.24,P=0.58)、>3级血液学毒性(RR=1.18,95%CI为 0.99~1.39,P=0.06)发生率相近。结论 在局限期SCLC放化疗中两种放疗分割模式的近期疗效与生存获益相当,但超分割放疗的放射性食管炎发生率较高。超分割放疗并未带来较常规分割放疗更多的优越性。     

Combination carboplatin and radiotherapy in the management of stage II testicular seminoma: comparison with radiotherapy treatment alone.

PURPOSE: To assess the results of treatment in 33 patients with stage IIA/B seminoma who were treated with carboplatin and radiotherapy (RT) between January 1989 and December 1996. PATIENTS AND METHODS: Thirty patients received single course single agent carboplatin (400 mg/m2 or area under curve (AUC 7), two patients received two courses carboplatin, and one patient received single course carboplatin and etoposide, all 4-6 weeks prior to infra-diaphragmatic RT. Results were retrospectively compared with those obtained for 80 patients treated from 1970 to 1998 with radiotherapy alone. RESULTS: There was minimal toxicity associated with the use of carboplatin prior to RT. With a median follow-up of 4 years (range 2-70 months) 2/33 patients treated with chemotherapy and RT have relapsed, 5-year relapse free survival (RFS) = 96.9% (95% confidence interval (CI) 72.9-99.4%), and one patient has died of progressive disease, 5-year overall survival (OS) = 96.7%. With a median follow-up of 11.2 years (range 6 months to 25.8 years) 15/80 patients treated with RT alone have relapsed, 5-year RFS = 80.7% (95% CI 70.1-87.9%), including 13/61 patients treated with infra-diaphragmatic RT, 5-year RFS = 77.9%, and 2/19 treated with additional supra-diaphragmatic RT, 5-year RFS = 89.5% (P = 0.277). Eleven out of 80 patients have died, 5-year OS = 94.7%. For stage IIA, 1/14 patients treated with chemotherapy and RT have relapsed, 5-year RFS = 92.3%, compared with 5/34 treated with infra-diaphragmatic RT alone 5-year, RFS = 84.9% (P = 0.527). For stage IIB, 1/19 patients relapsed (at 69 months) following chemotherapy and RT (5-year RFS = 100%), whereas 8/27 relapsed following infra-diaphragmatic RT alone, 5-year RFS = 69.4% (P = 0.0595). CONCLUSION: Infradiaphragmatic RT alone cures the majority of patients with stage II seminoma, but the relapse rate remains high particularly for patients with stage IIB disease. As compared with historical controls, carboplatin with RT appears to reduce the relapse rate in stage II seminoma with minimal additional toxicity and the results approach statistical significance for stage IIB patients. Confirmation would require a phase III randomized comparison.     

Radiation therapy versus chemotherapy as initial treatment for localized nasal natural killer (NK)/T-cell lymphoma: a single institute survey in Taiwan.

BACKGROUND: To clarify the role of intention to treat for patients with localized nasal natural killer (NK)/T-cell lymphoma, and to determine the prognostic factors for these patients. PATIENTS AND METHODS: We conducted a retrospective review of 46 patients with localized nasal NK/T-cell lymphomas treated at a single institute between January 1988 and July 2002. RESULTS: The type of intended treatment was a significant factor for overall survival (OS) (5-year OS: RT versus CT = 83.3% versus 28.6%, P = 0.0269) or failure-free survival (FFS) (5-year FFS: RT versus CT = 83.3% versus 27.1%, P = 0.0247). In the intended chemotherapy group, salvage with radiotherapy was superior to chemotherapy alone for OS (5-year OS: 42.2% versus 20.0%, P = 0.0252) or FFS (5-year FFS: 41.0% versus 20.0%, P = 0.0352). On multivariate analysis, both N stage and serum lactate dehydrogenase level were independent factors for OS and FFS. No radiotherapy was an independent adverse factor for OS; advanced T stage and more than one extranodal involvement were independent adverse factors for FFS. CONCLUSIONS: Patients with localized nasal NK/T-cell lymphomas were better managed with radiotherapy as front-line therapy. The advantage of radiotherapy persisted even as palliative therapy after chemotherapy.     

局限期小细胞肺癌放疗期间同步化疗周期数对预后的影响

目的 研究同步放化疗在局限期小细胞肺癌治疗中的地位及放疗中同步化疗的周期数对治疗疗效的影响。方法 本研究包括自2008-2016年间在天津医科大学肿瘤医院接受根治性放疗的局限期小细胞肺癌患者,采用总生存期作为研究终点,分析比较同步化疗周期数及其他临床因素对疗效的影响,总生存期的计算从开始治疗至患者死亡时间或最后随访时间。生存分析采用Kaplan-Meier法,Cox模型进行多因素预后分析。结果 共有 317例患者符合条件进入研究,其中序贯放化疗 129例,同步放化疗 188例。同步放化疗患者中同步化疗1周期 86例,同步化疗2周期 102例。中位随访时间22.47个月,多因素生存分析显示临床分期、放疗早晚和脑预防照射是影响总生存的独立预后因素。放疗期间同步化疗1、2个周期患者中位生存期分别为33.8、30.4个月(P=0.400)。无论老年人还是在非老年人、早放疗组还是晚放疗以及是否接受脑预防照射、同步化疗周期数均对患者总生存无影响。≥3级不良反应发生率在1个周期同步化疗组为20%,在2个周期同步化疗组为13.7%。结论 同步放化疗是局限期小细胞肺癌的标准治疗方案,2个周期同步化疗生存率不一定优于1个周期者,最佳同步化疗周期数还有待于进一步前瞻性研究确定。     

Primary non-Hodgkin's lymphoma of the nasopharynx: prognostic factors and outcome of 113 Indian patients

This single institutional study evaluated the prognostic factors and treatment outcome of 113 Indian patients with primary nasopharyngeal non-Hodgkin's lymphoma. At presentation, 28% had stage I and 62% had stage II disease. Treatment comprised of a combination of chemotherapy (CTh) and radiotherapy (RT) in the majority of the patients (76%). After a median follow-up of 56 months, the 5-year disease-free survival (DFS) and overall survival (OS) for the whole group were 55.8% and 57.9%, respectively. Multivariate analysis showed that; age > 30 years [hazard ratio (HR) = 6.59, 95% confidence interval (CI) = 2.59 - 16.7, P < 0.0001], WHO performance score > or = 2 (HR = 2.34, 95% CI = 1.01 - 5.46, P = 0.050), T-cell lymphomas (HR = 2.81, 95% CI = 1.14 - 6.96, P < 0.001) and the presence of B symptoms (HR = 3.65, 95% CI = 1.77 - 7.53, P = 0.025), had a negative influence on survival. Patients treated with a combination of CTh and RT had a significantly better outcome than those treated with CTh alone (OS: 69%vs. 31%, P < 0.00001). HR for death in the CTh alone group was 3.73 (95% CI = 1.95 - 7.13). The CR (P = 0.01), DFS (P = 0.01) and OS (P = 0.03) rates were significantly better for patients receiving a RT dose of > or =4500 cGy. HR in the subgroup that received a RT dose of <4500 cGy was 2.51 (95% CI = 1.04 - 6.06). These results suggest that combined modality treatment, comprising of CTh and RT (with an RT dose of > or =4500 cGy), results in satisfactory outcome in patients with this rare neoplasm.     

局限期SCLC超分割或大分割放疗同步化疗预后比较

目的 比较超分割或大分割放疗同步化疗对局限期SCLC的生存影响。方法 超分割和大分割组分别入组患者92、96例。超分割组采用45 Gy分30次,2 次/d。大分割组采用55 Gy分22次,1 次/d。采用Kaplan-Meier法计算生存率,Cox模型多因素预后分析。结果 超分割和大分割组患者1、2、5年PFS率分别为82%、61%、59%和85%、69%、69%(P=0.27),OS率分别为85%、41%、27%和77%、34%、27%(P=0.37)。多因素分析显示化疗开始到放疗开始时间≤43 d是PFS的有利因素(P=0.005),化疗开始到放疗结束时间≤63 d、PCI是OS有利因素(P=0.044、0.000)。超分割组和大分割组2、3级急性放射性食管炎发生率分别为28%、9%和16%、2%(P=0.009)。结论 采用加速超分割或大分割方案联合同步化疗的PFS及OS均显著提高。控制化疗开始至放疗开始、结束时间≤43 d、≤63 d有利于提高PFS和OS。但2、3级急性放射性食管炎的发生率超分割组显著高于大分割组。     

Randomized trial of radiotherapy versus concurrent chemoradiotherapy followed by adjuvant chemotherapy in patients with American Joint Committee on Cancer/International Union against cancer stage III and IV nasopharyngeal cancer of the endemic variety.

PURPOSE: The Intergroup 00-99 Trial for nasopharyngeal cancer (NPC) showed a benefit of adding chemotherapy to radiotherapy. However, there were controversies regarding the applicability of the results to patients in endemic regions. This study aims to confirm the findings of the 00-99 Trial and its applicability to patients with endemic NPC. PATIENTS AND METHODS: Between September 1997 and May 2003, 221 patients were randomly assigned to receive radiotherapy (RT) alone (n = 110) or chemoradiotherapy (CRT; n = 111). Patients in both arms received 70 Gy in 7 weeks using standard RT portals and techniques. Patients on CRT received concurrent cisplatin (25 mg/m2 on days 1 to 4) on weeks 1, 4, and 7 of RT and adjuvant cisplatin (20 mg/m2 on days 1 to 4) and fluorouracil (1,000 mg/m2 on days 1 to 4) every 4 weeks (weeks 11, 15, and 19) for three cycles after completion of RT. All patients were analyzed by intent-to-treat analysis. The median follow-up time was 3.2 years. RESULTS: Distant metastasis occurred in 38 patients on RT alone and 18 patients on CRT. The difference in 2-year cumulative incidence was 17% (95% CI, 14% to 20%; P = .0029). The hazard ratio (HR) for disease-free survival was 0.57 (95% CI, 0.38 to 0.87; P = .0093). The 2- and 3-year overall survival (OS) rates were 78% and 85% and 65% and 80% for RT alone and CRT, respectively. The HR for OS was 0.51 (95% CI, 0.31 to 0.81; P = .0061). CONCLUSION: This report confirms the findings of the Intergroup 00-99 Trial and demonstrates its applicability to endemic NPC. This study also confirms that chemotherapy improves the distant metastasis control rate in NPC.     

Limited-Stage Small Cell Lung Cancer: Is Prophylactic Cranial Irradiation Necessary?

PurposeProphylactic cranial irradiation (PCI) reduces the incidence of brain metastases in patients with limited stage small cell lung cancer (LS-SCLC). However, PCI is associated with neurotoxicity. Previous studies have not consistently used pretreatment magnetic resonance imaging. Modern imaging improvements continue to enhance early metastasis detection, potentially decreasing the utility of PCI. We sought to determine whether PCI was associated with improved outcomes in LS-SCLC patients with modern imaging.Methods and MaterialsWe identified LS-SCLC patients with no intracranial disease who were treated between 2007 and 2018. Kaplan-Meier estimates of overall survival (OS) and progression-free survival (PFS) were calculated and multivariate Cox proportional hazards models were generated. The cumulative incidence of brain metastases was estimated using competing risks methodology.ResultsNinety-two patients were identified without intracranial disease at initial staging, 39 of whom received PCI. Median follow-up was 56.7 months. The median OS for the cohort was 35.5 months (95% CI, 25.8-49.3), and median PFS was 19.1 months (95% CI, 12.3-30.5). Median OS with PCI versus observation was 37.9 months (95% CI, 31.8-not reached) versus 30.5 months (95% CI, 14.6-56.1; P = .07), whereas median PFS was 26.3 months (95% CI 19.1-not reached) versus 12.3 months (95% CI, 8.5-30.5; P = .02), respectively. Overall, at 2 years, the cumulative incidence of brain metastases was 10% with PCI and 29% without; this increased to 32% and 29% by 4 years (P = .66). In those patients who had negative magnetic resonance imaging of the brain after completing initial treatment, the 1-year cumulative incidence of brain metastasis was not significantly different at 8% versus 11% (P = .46) respectively. Both PCI and treatment response were independent predictors for PFS on multivariate analysis. Stratified by disease response, patients with a complete response did not benefit from PCI (P = .50), whereas those with partial response or stable disease experienced improved PFS (P = .01).ConclusionsOverall, PCI was associated with improved PFS and reduced early incidence of brain metastases. Patients achieving a complete response to initial therapy did not experience a PFS benefit with PCI. This may indicate that subsets of LS-SCLC patients can potentially be spared from PCI in the era of modern imaging.     

Impact of concurrent versus sequential tamoxifen with radiation therapy in early-stage breast cancer patients undergoing breast conservation treatment.

PURPOSE: To assess the impact of sequencing of tamoxifen and radiation therapy (RT) on outcomes in early-stage breast cancer. PATIENTS AND METHODS: This retrospective study evaluates the effect of the sequence of tamoxifen with RT on outcomes in stage I to II breast cancer patients who underwent breast-conservation treatment (BCT) and received adjuvant tamoxifen, with or without adjuvant chemotherapy. Patients were grouped as concurrent (tamoxifen given during RT followed by continued tamoxifen; 174 patients) and sequential (RT followed by tamoxifen; 104 patients). RESULTS: Median follow-up after RT was 8.6 years for both groups. The pathologic T and N stage, race, estrogen and progesterone status, number of positive nodes, and RT were comparable between the two groups (all P >/= .08). More women age 49 years or younger and women who received chemotherapy were in the sequential group than the concurrent group (6% and 25%, respectively; P < .0001). The sequence of tamoxifen therapy did not influence 10-year local recurrence rates (sequential, 7%; concurrent, 3%; P = .52), overall survival (sequential, 86%; concurrent, 81%; P = .64), or relapse-free survival (sequential, 76%; concurrent, 85%; P = .35). When adjusting age and chemotherapy use in the multivariable Cox model, hazard ratios comparing sequential versus concurrent tamoxifen therapy were 1.56 (95% CI, 0.87 to 2.79), 1.23 (95% CI, 0.63 to 2.41), and 1.22 (95% CI, 0.33 to 4.49) for the overall survival, relapse-free survival, and local recurrence, respectively. CONCLUSION: The therapeutic regimens of tamoxifen given concurrently or sequentially with RT both appear to be reasonable options for patients treated with BCT.     

Systematic review and meta-analysis of randomised, controlled trials of the timing of chest radiotherapy in patients with limited-stage, small-cell lung cancer.

BACKGROUND: We undertook a systematic review and literature-based meta-analysis to determine whether the timing of chest radiotherapy may influence the survival of patients with limited-stage small-cell lung cancer (LS-SCLC). MATERIALS: Eligible randomised controlled clinical trials were identified according to the Cochrane Collaboration Guidelines, comparing different timing of chest radiotherapy in patients with LS-SCLC. Early chest irradiation was defined as beginning within 30 days after the start of chemotherapy. RESULTS: Considering all seven eligible trials, the overall survival at 2 or 5 years was not significantly different between early or late chest radiotherapy. When only trials were considered that used platinum chemotherapy concurrent with chest radiotherapy, a significantly higher 5-year survival was observed when chest radiotherapy was started within 30 days after the start of chemotherapy (2-year survival: OR: 0.73, 95% CI 0.51-1.03, P = 0.07; 5-year survival: OR: 0.64, 95% CI 0.44-0.92, P = 0.02). This was even more pronounced when the overall treatment time of chest radiotherapy was less than 30 days. CONCLUSIONS: There are indications that the 5-year survival rates of patients with LS-SCLC are in favour of early chest radiotherapy, with a significant difference if the overall treatment time of chest radiation is less than 30 days.     

Platinum-based chemotherapy in triple-negative breast cancer

BackgroundExperimental data suggest that triple-negative (TN) breast cancer may have increased sensitivity to platinum-based chemotherapy but clinical data are limited. We present our long-term results with platinum-based chemotherapy for TN breast cancer.Patients and methodsIn all, 94 (17 TN), 79 (11 TN) and 155 (34 TN) patients receiving platinum-based chemotherapy in neo-adjuvant/adjuvant and advanced setting were included. Response rates and outcome were compared for TN tumours versus others.ResultsNeo-adjuvant complete response rates were significantly higher for TN tumours (88%) than others (51%; P = 0.005). The 5-year overall survival (OS) for TN tumours following adjuvant/neo-adjuvant chemotherapy was 64% [95% confidence interval (CI) 44% to 79%] compared with 85% (95% CI 79% to 90%) for others. Five-year disease-free survival for TN tumours was 57% (95% CI 37% to 73%) compared with 72% (95% CI 64% to 78%) for others. For patients with advanced breast cancer, overall response rates were 41% for TN tumours and 31% for others (P = 0.3). Patients with TN tumours had a significantly prolonged progression-free survival of 6 months compared with 4 months for others (P = 0.05), though the OS was not significantly different between the two groups (11 versus 7 months).ConclusionPlatinum-based chemotherapy achieves increased response rates for TN tumours, with a trend towards worse survival in early breast cancer through an improved survival in advanced disease. Prospective randomised trials are warranted.     

The Impact of Locoregional Treatment on Survival in Patients With Metastatic Breast Cancer: A National Cancer Database Analysis

BackgroundAlthough systemic therapy is the standard treatment for metastatic breast cancer, the value of locoregional treatment (LRT) of the primary tumor and its impact on survival is controversial. This study evaluates survival outcomes in patients with metastatic breast cancer after receiving LRT (surgery and/or radiation therapy) of the primary tumor.Materials and MethodsThe National Cancer Database was used to identify 16,128 qualifying cases of metastatic breast cancer who received systemic therapy with or without LRT from 2004 to 2013. Treatment modality was divided into surgery (Sx), radiation therapy (RT), surgery followed by RT (Sx + RT), and no LRT. The median survival and 3-year actuarial survival rates (OS) were analyzed for each treatment group. On multivariate analyses, adjusted hazard ratios (HRs) with 95% confidence intervals (CIs) were computed using Cox regression modeling to adjust for patient and clinicopathologic characteristics.ResultsOverall, the median follow-up was 28.3 months, and the median survival for all patients was 37.2 months. With 9761 deaths reported, the estimated 3-year OS was 51.3%. The Sx + RT group (n = 2166) had the highest 3-year OS of 69.4%, followed by the Sx group (n = 4293) with 57.6%, the no LRT group (n = 8955) with 44.3%, and the RT group (n = 714) with 41.5% (P < .0001). On multivariate analysis, compared with the no LRT group, a decreased HR was noted in patients receiving Sx (adjusted HR, 0.68; 95% CI, 0.65-0.71; P < .0001) and Sx + RT (adjusted HR, 0.46; 95% CI, 0.43-0.49; P < .0001).ConclusionLRT, especially surgery followed by RT, in addition to systemic therapy, was associated with improved survival in patients with metastatic breast cancer.     

High-dose therapy improves progression-free survival and survival in relapsed follicular non-Hodgkin's lymphoma: results from the randomized European CUP trial.

PURPOSE: To determine, in a randomized clinical trial, whether high-dose therapy (HDT) followed by autologous stem-cell transplantation is more effective than standard treatment with regard to progression-free survival (PFS) and overall survival (OS) in patients with relapsed follicular non-Hodgkin's lymphoma; and to assess the additional value of B-cell purging of the stem-cell graft with regards to PFS and OS. PATIENTS AND METHODS: Patients received three cycles of chemotherapy. Responding patients with limited bone marrow infiltration were eligible for random assignment to three further cycles of chemotherapy (C), unpurged HDT (U), or purged HDT (P). RESULTS: Between August 1993 and April 1997, 140 patients were registered from 36 centers internationally, and 89 were randomly assigned. Reasons for not randomizing included patient refusal, early progression, or death on induction therapy. With a 69-month median follow-up, the log-rank P value for PFS and OS were.0037 and.079, respectively. For PFS, the hazard ratios (95% CIs) for U versus C, P versus C, and P versus U were 0.33 (0.16 to 0.70), 0.38 (0.19 to 0.79), and 1.02 (0.51 to 2.05), respectively. The hazard ratio (95% CI) for C versus U + P was 0.30 (0.15 to 0.61). Hazard ratios (95% CIs) for OS were 0.43 (0.18 to 1.06), 0.43 (0.18 to 1.02), and 0.72 (0.32 to 1.63). For C versus U + P, the hazard ratio (95% CI) was 0.40 (0.18 to 0.89). Kaplan-Meier estimates (95% CIs) of 2-year PFS for C, U, and P were 26% (8% to 44%), 58% (37% to 79%), and 55% (34% to 75%), respectively. OS at 4 years for C, U, and P are 46% (25% to 67%), 71% (52% to 91%), and 77% (60% to 95%) respectively. CONCLUSION: HDT significantly improves PFS and OS. There is no clear evidence of benefit through purging.     

Combined chemoradiation vs radiation therapy alone in stage-II nasopharyngeal carcinoma: A meta-analysis of the published literature

The aim of this meta-analysis was to evaluate the efficacy and toxicity of adding chemotherapy to radiotherapy (RT) in the treatment of stage-II nasopharyngeal carcinoma (NPC). We searched Pubmed, Cochrane Library, Embase, China National Knowledge Internet, China Biology Medicine, VIP, and Wanfang database for studies of the RT with or without chemotherapy in patients with stage-II NPC that were published in any language. Analyses were carried out using RevMan 5.3 software. The relative risk was used to evaluate the data, the I² test was used to compare heterogeneity, sensitivity analysis was used to evaluate the stability and reliability of the results. There were 16 studies with 3038 patients that were included in this analysis. Risk ratios (RR) of 1.04 (95% CI: 1.01-1.06), 1.05 (95% CI: 1.00-1.10), 1.05 (95% CI: 1.02-1.07), and 1.00 (95% CI: 0.97-1.03) were observed for overall survival (OS), progression-free survival (PFS), locoregional failure-free survival (LRFS), and distant metastasis-free survival (DMFS). Subgroup analysis showed that compared with conventional RT alone, chemoradiation (CRT) could significantly improve OS (RR = 1.09, 95% CI: 1.03-1.15), PFS (RR = 1.20, 95% CI: 1.08-1.35), and LRFS (RR = 1.09, 95% CI: 1.04-1.14), but did not significantly improve the rate of DMFS (RR = 1.03, 95% CI: 0.94-1.12). However, compared with intensity modulated radiation therapy alone, CRT did not significantly improve the rate of OS (RR = 1.01, 95% CI: 0.99-1.03), PFS (RR = 0.99, 95% CI: 0.95-1.03), LRFS (RR = 1.02, 95% CI: 0.99-1.05), and DMFS (RR = 0.99, 95% CI: 0.96-1.01). Compared with conventional RT alone, CRT could significantly improve patients’ prognoses in terms of OS, PFS, and LRFS for stage-II NPC, but not DMFS, and CRT can provide greater benefits from concurrent chemotherapy than neoadjuvant chemotherapy. With intensity modulated radiation therapy, the stage-II NPC patients did not benefit from the addition of chemotherapy.     

老年局限期SCLC放疗时机选择探讨

目的 探讨老年局限期SCLC放化疗中放疗时机选择对预后影响。方法 回顾分析2008—2014年行根治性胸部序贯放化疗的80例老年局限期SCLC患者的临床资料,分析从治疗开始至放疗结束时间(SER)、诱导化疗周期数与OS及PFS的关系,进而比较早放疗组(诱导化疗周期数≤3个37例)与晚放疗组(诱导化疗周期数>3个43例)疗效的差别。采用Kaplan-Meier法进行生存分析。结果 全组中位OS、PFS分别为23.5、13.3个月;SER与OS、PFS差异有统计学意义(P=0.001、0.001);2、3、4、5、6周期诱导化疗后接受放疗病例的中位OS分别为33.2、26.7、20.6、16.9、17.9(P=0.000);中位OS及1、2、5年OS早放疗组分别为27.8个月及87%、62%、34%,晚放疗组分别为17.9个月、74%、37%、15%(P=0.017);中位PFS及1、2、5年PFS早放疗组分别为17.1个月及65%、43%、28%,晚放疗组分别为11.9个月及49%、21%、14%(P=0.022)。结论 老年局限期SCLC序贯放化疗患者SER越短疗效越好,早放疗可使生存获益。     

费城染色体阳性成年急性淋巴细胞白血病患者治疗效果及预后因素分析

目的 分析费城染色体阳性(Ph+)的成年急性淋巴细胞白血病(ALL)患者治疗效果及预后影响因素.方法 回顾性分析49例Ph+ALL患者的临床资料,探讨治疗效果及不同因素对预后的影响.结果49例患者中,男性24例,女性25例;中位年龄38岁(15~77岁),酪氨酸激酶抑制剂(TKI)治疗组血液学完全缓解(CR)率、主要分子生物学反应(MMR)率及完全分子生物学缓解(CMR)率均高于单纯化疗组(96.8 %比72.2 %,64.5 %比16.7 %,25.8 %比11.1 %),差异均有统计学意义(χ2=4.308,P=0.038;χ2=10.468,P=0.001;χ2=4.250,P=0.039).生存分析提示中位总生存(OS)时间为24个月(3~70个月),3年OS率及无复发生存(RFS)率分别为32.7 %、21.4 %;TKI治疗组3年OS率及1年RFS率高于单纯化疗组(40.3 %比11.1 %,67.8 %比11.1 %),差异有统计学意义(χ2=12.725, P<0.001;χ2=17.401,P<0.001);异基因造血干细胞移植(allo-HSCT)组3年OS率及RFS率高于非移植组(62.5 %比25.7 %、41.7 %比15.0 %),差异有统计学意义(χ2=6.196,P=0.013;χ2=8.032,P=0.005);经2个疗程治疗后达MMR组3年OS率及RFS率分别为45.1 %和28.9 %,高于未达MMR组(17.6 %和11.7 %),差异有统计学意义(χ2=5.446,P=0.020;χ2=6.484,P=0.011);Cox多因素分析结果显示,联合TKI治疗(HR=0.227,95 % CI 0.094~0.550,P=0.001)是OS的独立预后因素;联合TKI治疗(HR=0.225,95 % CI 0.082~0.618,P=0.004)及移植(HR=0.275,95 % CI 0.077~0.983,P=0.047)是RFS的独立预后因素.结论 联合TKI治疗能提高患者CR、MMR及CMR率,提高长期生存,为患者接受移植提供更多机会;在TKI时代,移植仍是治疗Ph+ALL的重要方法,尤其那些经化疗联合TKI治疗但早期未达MMR者预后差,应尽早行造血干细胞移植.     

IMRT下局限期SCLC放化疗疗效及预后分析

目的 探讨IMRT技术下局限期SCLC放化疗疗效及预后分析。方法 回顾分析2006—2014年于本中心行放化疗的 484例局限期SCLC患者临床资料。IMRT有效者行PCI。采用Kaplan-Meier法计算生存率,Logrank检验进行单因素分析,Cox模型进行多因素分析。结果 全组随访率为93%,中位OS期23.8个月,2、3、5年OS率分别为48.7%、39.8%、28.6%,中位PFS期14.1个月,2、3、5年PFS率分别为34.4%、30.5%、28.3%。SCLC患者IMRT后≥3级骨髓抑制发生率26.9%,≥2级放射性食管炎发生率24.8%,≥2级放射性肺炎发生率18.4%。治疗客观有效率84.5%。单因素分析显示年龄、吸烟史、TNM分期、PCI、放疗前化疗周期数是预后影响因素(P=0.006、0.001、0.047、0.000、0.046),多因素分析显示吸烟史、PCI是影响预后的因素(P=0.001、0.000)。结论 IMRT技术下局限期SCLC放化疗取得了较好疗效,吸烟史、PCI是局限期SCLC的预后影响因素。