非手术方法治疗局部侵袭性胸腺肿瘤

背景与目的手术切除是早期胸腺肿瘤的主要治疗方法,而对于IV期的病变,化疗则是最常用的方案。对于局部晚期的肿瘤,尤其是不适合手术的病例,何种治疗方案效果更优则没有明确的结论。鉴于此,我们做了这项回顾性的研究,通过对三种非手术疗法的比较,希望找到一些线索。方法自2000年10月至2010年12月,共有42例患者接受了三种非手术方案的治疗。这三种模式分别是单独放疗（radiotherapy, RT）、序贯化放疗（se-quential chemoradiation, SCRT）以及同步放化疗（concurrent chemoradiation, CCRT）。并对三种方案的缓解率（objec-tive response rate, ORR）、总生存期（overall survival, OS）以及治疗的相关毒副反应进行比较。结果全组42例患者中,总的缓解率为61.9%,5年生存率为46%。RT组、SCRT组以及CCRT组的缓解率分别是43.8%、50%和87.5%（RT vs SCRT,P=0.692; RTvs CCRT,P=0.009; SCRTvs CCRT,P=0.051）。RT组、SCRT组以及CCRT组的5年生存率分别是30%、50%和61.9%（RTvs SCRT,P=0.230; RTvs CCRT,P=0.011; SCRTvs CCRT,P=0.282）。共有11例患者发生了3度-4度的中性粒细胞减少,其中7例出现在CCRT组,另4例出现在SCRT组。有9例患者主诉有3度放射性食道炎,其中RT组2例, SCRT组3例,CCRT组4例。另外,CCRT组还出现了2例3度的放射性肺炎。未发现致命的5度毒副反应。结论在治疗不适合手术的局部晚期胸腺肿瘤上,CCRT显示出了比RT和CCRT更好的局部控制以及长期生存优势,不过也有增加肺损伤风险的可能。对于局部侵袭性的胸腺肿瘤,CCRT可提供最佳的肿瘤控制效果。     

A Recurrence Predictive Model for Thymic Tumors and Its Implication for Postoperative Management: a Chinese Alliance for Research in Thymomas Database Study

ObjectiveOur aim was to investigate appropriate postoperative management based on the risk of disease recurrence in thymic epithelial tumors after complete resection.MethodsThe Chinese Alliance for Research in Thymomas retrospective database was reviewed. Patients having stage I to IIIa tumors without pretreatment and with complete resection were included. Clinicopathologic variables with statistical significance in the multivariate Cox regression were incorporated into a nomogram for building a recurrence predictive model.ResultsA total of 907 cases, including 802 thymomas, 88 thymic carcinomas, and 17 neuroendocrine tumors, were retrieved between 1994 and 2012. With a median follow-up of 52 months, the 10-year overall survival rate was 89.5%. Distant and/or locoregional recurrences were noted in 53 patients (5.8%). The nomogram model revealed histologic type and T stage as independent predictive factors for recurrence, with a bootstrap-corrected C-index of 0.86. On the basis of this model, patients with T1 thymomas or T2 or T3 type A, AB, or B1 thymomas had a significantly lower incidence of recurrence (low-risk group) than those with T2 or T3 type B2 or B3 thymomas and all thymic carcinomas and neuroendocrine tumors (high-risk group) (2.7% versus 20.1% [p < 0.001]). In the high-risk group, more than half of the recurrences (55.2% [16 of 29]) were seen within the first 3 postoperative years, whereas all recurrences but one were recorded within 6 years after surgery. Recurrence occurred quite evenly over 10 postoperative years in the low-risk group.ConclusionsA 6-year active surveillance should be considered in high-risk patients regardless of adjuvant therapy. For low-risk patients, annual follow-up may be sufficient. Studies examining postoperative adjuvant therapies would be plausible in high-risk patients.     

老年中晚期食管癌淋巴结引流区预防照射与累及野照射的比较研究

摘 要：［目的］ 比较累及野照射（IFI）与淋巴结引流区预防照射（ENI）在老年中晚期食管癌患者中的疗效与安全性。［方法］ 收集行放射治疗的老年（年龄≥70岁）中晚期食管癌患者88例,分为淋巴结引流区预防照射（ENI）组（41例）和IFI组（47例）。随访观察两组的临床疗效、毒副反应、生存率、治疗失败情况等。［结果］ ENI组和IFI组的近期疗效（92.7% vs 91.5%,P=0.836）、1年生存率（80.5% vs 72.3%,P=0.371）、2年生存率（41.5% vs 31.9%,P=0.353）、1年无进展生存率（56.1% vs 42.6%,P=0.205）、2年无进展生存率（9.6% vs 8.5%,P=0.839）、区域失败率（39.0% vs 29.8%,P=0.327）,远处转移率（22.0% vs 14.9%,P=0.392）、中位OS（19个月 vs 18个月,χ2=0.002,P=0.967）、中位PFS（13个月 vs 10个月, χ2=1.870,P=0.171）差异均无统计学意义。IFI组≥3级放射性肺炎、≥3级放射性食管炎发生率分别为4.3%、6.4%,明显低于ENI组的17.1%（P=0.048）、22.0%（P=0.034）。单因素分析显示,性别、年龄、T分期、N分期、是否同步化疗是影响预后的因素。多因素分析显示,年龄、T分期、是否同步化疗为独立预后因素（HR=1.253、1.660、2.682,P均<0.05)。［结论］ IFI对于老年中晚期食管癌疗效与ENI相似,但毒副反应降低,对老年食管癌患者是合适的选择。     

术后放疗在I期/II期/III期胸腺肿瘤中的作用--ChART回顾性数据库研究结果

背景与目的胸腺肿瘤术后放疗尚存在争议,此研究目的为评价术后放疗在I期-III期胸腺肿瘤中的作用。方法搜索中国胸腺瘤研究协作组（Chinese Alliance of Research for hTymomas, ChART）数据库中1994年至2012年接受手术切除未行新辅助治疗的I期-III期胸腺肿瘤患者的资料。对临床病理资料进行单因素、多因素分析,Cox比例风险模型用于决定死亡风险比。结果 ChART数据库中I期-III期胸腺肿瘤共1,546例。其中649例（41.98%）接受术后放疗。术后放疗与性别、组织学类型（World Health Organization, WHO）、胸腺切除程度、是否完全切除、Masaoka-Koga分期及辅助化疗相关。手术后辅助放疗患者5年、10年总生存和无瘤生存分别为90%和80%、81%和63%,而单纯手术者5年、10年总生存和无瘤生存分别为96%和95%、92%和90%,两组生存有统计学差异（P=0.001, P<0.001）。单因素表明年龄、组织学分类（WHO）、Masaoka-Koga分期、是否完全切除和术后放疗与总生存相关。多因素分析提示组织学分类（WHO）（P=0.001）、Masaoka-Koga分期（P=0.029）和是否完全切除（P=0.003）是总生存的独立预后因素。单因素分析表明性别、重症肌无力、组织学分类、Masaoka-Koga分期、手术方式、术后放疗和是否完全切除与无瘤生存相关。多因素分析表明组织学类型（P<0.001）、Masaoka-Koga分期（P=0.005）和是否完全切除（P=0.006）是无瘤生存的独立预后因素。亚组分析表明不完全切除患者接受术后放疗可以提高总生存和无瘤生存（P=0.010, P=0.017）。然而,完全切除者接受术后放疗则会降低总生存和无瘤生存（P<0.001, P<0.001）。结论此回顾性研究表明不完全切除I期-III期胸腺肿瘤患者术后放疗可以提高总生存和无瘤生存。但是,对于完全切除患者,术后放疗总体上并未显示出生存获益。     

Elective Nodal Irradiation for Limited-stage Small-cell Lung Cancer: Survey of US Radiation Oncologists on Practice Patterns

BackgroundTraditionally, elective nodal irradiation (ENI) has been used in clinical trials that have established thoracic radiotherapy as instrumental in improving survival for patients with limited-stage small-cell lung cancer (LS-SCLC). However, several reports have suggested that the omission of ENI might be appropriate. Current US practice patterns are unknown regarding ENI for patients with LS-SCLC.Materials and MethodsWe surveyed US radiation oncologists via an institutional review board-approved questionnaire. The questions covered demographics, treatment recommendations, and self-assessed knowledge of key clinical trials. χ² and Cochran-Armitage tests were used to evaluate for statistically significant correlations between responses.ResultsWe received 309 responses. Of the respondents, 21% recommended ENI for N0 LS-SCLC, 29% for N1, and 30% for N2; 64% did not recommend ENI for any of these clinical scenarios. The respondents who recommended ENI were more likely to have been practicing for > 10 years (P < .001), more likely to be in private practice (P = .04), and less likely to be familiar with the ongoing Cancer and Leukemia Group B 30610 trial (P = .04). Almost all respondents (93%) prescribed the same radiation dose to the primary disease and involved lymph nodes. When delivering ENI, 36% prescribed the same dose to the involved and elective nodes, and 64% prescribed a lower dose to the elective nodes.ConclusionNearly two thirds of respondents did not recommend ENI, which represents a shift in practice. A recent large clinical trial that omitted ENI reported greater overall survival than previously reported and lower-than-expected radiation toxicities, lending further evidence that omitting ENI should be considered a standard treatment strategy.     

The Impact of Postoperative Radiotherapy for Thymoma and Thymic Carcinoma

IntroductionThe optimal role for postoperative radiotherapy (PORT) for thymoma and thymic carcinoma remains controversial. We used the National Cancer Data Base to investigate the impact of PORT on overall survival (OS).MethodsPatients who underwent an operation for thymoma or thymic carcinoma were categorized into Masaoka-Koga stage groups I to IIA, IIB, III, and IV. Patients who did not undergo an operation or those who received preoperative radiation were excluded. Kaplan-Meier estimates of OS and univariate and multivariate Cox proportional hazards regression analyses were performed. Propensity score–matched analyses were performed to further control for baseline confounders.ResultsFrom 2004 to 2012, 4056 patients were eligible for inclusion, 2001 of whom (49%) received PORT. On multivariate analysis of OS in the thymoma cohort adjusted for age, WHO histologic subtype, Masaoka-Koga stage group, surgical margins, and chemotherapy administration, PORT was associated with superior OS (hazard ratio [HR] = 0.72, p = 0.001). Propensity score–matched analyses confirmed the survival advantage associated with PORT. Subset analysis indicated longer OS in association with PORT for patients with stage IIB thymoma (HR = 0.61, p = 0.035), stage III (HR = 0.69, p = 0.020), and positive margins (HR = 0.53, p < 0.001). The impact of PORT for stage I to IIA disease did not reach significance (HR = 0.76, p = 0.156).ConclusionsIn this large database analysis of PORT for thymic tumors, PORT was associated with longer OS, with the greatest relative benefits observed for stage IIB to III disease and positive margins. In the absence of randomized studies assessing the value of PORT, these data may inform clinical practice.     

Minimally Invasive Thymectomy Could Be Attempted for Locally Advanced Thymic Malignancies: A Real-World Study With Propensity Score-Matched Analysis

IntroductionIncreasing evidence supports minimally invasive thymectomy (MIT) for early stage thymic malignancies than open median sternotomy thymectomy (MST). Nevertheless, whether MIT could be attempted for locally advanced disease remains unclear.MethodsThe clinical data of consecutive patients with stage T2-3NxM0 (eighth edition TNM staging) thymic malignancies who underwent MIT or MST were identified from a prospectively maintained database. The co-resected structures were rated with a resection index to evaluate surgical difficulty. The impact of surgical approach on treatment outcomes was investigated through propensity score-matched analysis and multivariable analysis.ResultsFrom January 2008 to December 2019, a total of 128 patients were included; MIT was initially attempted in 58 (45.3%) cases, and eight (13.8%) were converted to MST during surgery. The conversion group had similar perioperative outcomes to the MST group, except for a longer operation time. After propensity score matching, the resection index scores were similar between the MIT and MST groups (3.5 versus 3.7, p = 0.773). The MIT group had considerably less blood loss (p < 0.001), fewer postoperative complications (p = 0.048), a shorter duration of chest drainage (p < 0.001), and a shorter hospitalization duration (p < 0.001) than the MST group. The 5-year freedom from recurrence rate was not different between the two groups (78.2% versus 78.5%, p = 0.942). In multivariable analysis, surgical approach was not associated with freedom from recurrence (p = 0.727).ConclusionsMIT could be safely attempted in carefully selected patients with locally advanced thymic tumors. Conversion did not compromise the surgical outcomes. Patients may benefit from the less traumatic procedure and thus better recovery, with comparable long-term oncologic outcomes.     

Impact of Regional Nodal Irradiation on the Outcomes of N1 Breast Cancer Patients Referred for Adjuvant Treatment: A Patient-Level Pooled Analysis of 2 Clinical Trials

Purpose

To evaluate the impact of regional nodal irradiation (RNI) among N1 operable breast cancer patients who underwent adequate axillary dissection and received adjuvant chemotherapy.

Intensive Chemotherapy with Cisplatin, Doxorubicin, Cyclophosphamide, Etoposide and Granulocyte Colony-stimulating Factor for Advanced Thymona or Thymic Cancer: Preliminary Results

A study was conducted to evaluate the impact of cisplatin, doxorubicin,cyclophosphamide and etoposide (PACE) with granulocyte colony-stimulatingfactor (G-CSF) on advanced thymoma or thymic cancer. BetweenAugust 1989 and December 1994, 14 patients with invasive, metastaticor recurrent thymoma or thymic cancer were treated with cisplatin(80 mg/m², on day 1), doxorubicin (45 mg/m², on day 1), cyclophosphamide(800 mg/m², on day 1) and etoposide (80 mg/m², on day 1–3)with G-CSF (90 mg/m², on day 5–18) at the National CancerCenter Hospital, Tokyo. Courses were repeated every 3 or 4 weeksfor a maximum of 4 cycles. Twelve patients were treated with2 or more courses of PACE. Two patients were treated with onlyone course, one refused and another required emergency thoracicradiotherapy after one course of PACE. Six patients had partialresponses (3 thymomas and 3 thymic cancers) but there were nocomplete remissions (response rates, 42.9%; 95% confidence interval,17.7% to 71.1%). Moderate hematological toxicities were observed:grade 3 or 4 leukopenia, neutropenia, anemia and thrombocytopeniain 10, 13, 8 and 6 patients, respectively. Six patients developedinfections that required antibiotics. Surgical resection orthoracic radiotherapy after PACE treatment was performed in2 and 7 patients, respectively. The overall median survivaltime was 14.7 months (range, 5.9 to 59.7 months). For 9 patientswho had received no prior treatment before chemotherapy, themedian survival time was 8.9 months, and one patient survivedfor 4 years and is still alive. In conclusion, PACE with G-CSFfrequently produces objective remissions in patients with advancedthymoma or thymic cancer. A large-scale intergroup study isnecessary to determine the impact of this regimen on advancedthymoma and thymic cancer.