■■■■■【2008.1.20】【JCO文摘翻译认领专帖】试行贴－－瘤版站友总动员！！！■■■■■

与liuhs等版主探讨之后，以版主置顶的招募贴为主。欢迎大家前往报名！
以下为链接：
http://www.dxy.cn/bbs/post/view?bid=87&id=11014899&sty=1&tpg=1&age=0

下面的不成熟意见仅供参考：

结合山东小汉，liuhs版主及其他热心站友的意见，考虑在每期JCO出来后，根据需要开两类专帖，第一专帖由热心站友或小组组长贴出该期所有文章英文摘要，即【JCO 文摘翻译认领专帖】，供英文较好的站友挑选文摘进行翻译，完成翻译的摘要由开贴站友尽快贴出全文下载链接供感兴趣站友下载。部分翻译工作完成后，由临床经验或专题擅长的站友挑选某篇文章进行全文阅读后开第二专帖，即【JCO 专题文章体会讨论专帖 00×】，就该篇文章得出自己心得体会，指出其临床设计的精巧与价值，或是不足之处，然后引导其他站友进行阅读，激发其他站友就此专题文章进行深入探讨，产生GROUP的效应。【JCO 专题文章体会讨论专帖】不限数量，但每贴要精，引起站友反响要足够。
万事开头难，凡事都有个发展过程，大家一定要有信心坚持下去！好的开始是成功的一半！参与站友的数量和热情绝对是JCO讨论小组成功的基石！
术业有专攻，只求大家发挥各自所长，帮人也为帮己。



感谢版主的重视和置顶！希望我们版主能大力支持那些为JCO讨论小组的开创和翻译工作付出自己劳动的站友，予以酌情加分鼓励！尤其对阅读完全文并开设【JCO 专题文章体会讨论专帖】的站友予以大力支持！以调动站友的积极性，促进瘤版这面金字招牌的早日树立！十分感谢！

目前站友已认领翻译的文摘有：
3. cT3N0 Rectal Cancer: Potential Overtreatment With Preoperative Chemoradiotherapy Is Warranted
4. KRAS mutations as an independent prognostic factor in patients with advanced colorectal cancer treated with cetuximab
6. Relationship of Breast Magnetic Resonance Imaging to Outcome After Breast-Conservation Treatment With Radiation for Women With Early-Stage Invasive Breast Carcinoma or Ductal Carcinoma in Situ
7. Effect of Breast Cancer Radiotherapy and Cigarette Smoking on Risk of Second Primary Lung Cancer
8. Phase I Trial and Pharmacokinetic Study of Bevacizumab in Pediatric Patients With Refractory Solid Tumors: A Children's Oncology Group Study
11. Randomized Trial Comparing Bleomycin/Etoposide/Cisplatin With Alternating Cisplatin/Cyclophosphamide/Doxorubicin and Vinblastine/Bleomycin Regimens of Chemotherapy for Patients With Intermediate- and Poor-Risk Metastatic Nonseminomatous Germ Cell Tumors: Genito-Urinary Group of the French Federation of Cancer Centers Trial T93MP
14. High Numbers of Tumor-Associated Macrophages Have an Adverse Prognostic Value That Can Be Circumvented by Rituximab in Patients With Follicular Lymphoma Enrolled Onto the GELA-GOELAMS FL-2000 Trial
17. Disease Control Rate at 8 Weeks Predicts Clinical Benefit in Advanced Non–Small-Cell Lung Cancer: Results From Southwest Oncology Group Randomized Trials
18. Randomized, Phase III Study of Weekly Paclitaxel in Combination With Carboplatin Versus Standard Every-3-Weeks Administration of Carboplatin and Paclitaxel for Patients With Previously Untreated Advanced Non–Small-Cell Lung Cancer
21. Anti-Apoptosis Mechanisms in Malignant Gliomas
以上全文下载链接详见本贴二楼。

还有大家对想讨论的专题，比如对什么癌种比较感兴趣或帮助大，可以在这个帖子里提出来，也好让翻译和阅读全文开讨论贴的站友可以选择更加吸引大家感兴趣参与的话题和癌种，以提高人气。

:)ORIGINAL REPORTS

Head and Neck Cancer

1. Podoplanin: A Novel Marker for Oral Cancer Risk in Patients With Oral Premalignancy

Purpose: Oral leukoplakia (OPL) is a heterogeneous oral lesion with an increased oral cancer risk. Current clinical parameters cannot predict the potential of malignant transformation in patients with OPL. We have shown that podoplanin, a lymphatic endothelial marker, is highly expressed in oral cancer and some oral premalignancies. The purpose of this study is to determine a role of podoplanin in predicting oral cancer development in patients with OPL.

Patients and Methods: Podoplanin expression was determined in 150 OPL patients with long-term follow-up using immunohistochemistry. Association between the protein expression patterns and clinicopathologic parameters including oral cancer development during the follow-up were analyzed.

Results: Fifty-six (37%) of the 150 OPL patients exhibited podoplanin expression in the basal and suprabasal layers and were classified as podoplanin positive. Podoplanin positivity was more frequent in older patients (P = .016), females (P = .020), and dysplastic lesions (P = .040). Patients with OPL that was podoplanin positive had significantly higher incidence of oral cancer than did those whose OPL was podoplanin negative (P = .0002). In the multivariate analysis using histology and podoplanin as cofactors, podoplanin was the only independent factor for oral cancer development (hazard ratio = 3.087; 95% CI, 1.530 to 6.231; P = .002). Importantly, oral cancer risk can be further stratified by considering both histology and podoplanin information.

Conclusion: Podoplanin is frequently expressed in OPL. Together with histology, podoplanin may serve as a powerful biomarker to predict the risk for oral cancer development in patients with OPL.


Phase I and Clinical Pharmacology

2. Phase I Trial of the Novel Mammalian Target of Rapamycin Inhibitor Deforolimus (AP23573; MK-8669) Administered Intravenously Daily for 5 Days Every 2 Weeks to Patients With Advanced Malignancies

Purpose: This phase I trial was conducted to determine the safety, tolerability, pharmacokinetics, and pharmacodynamics of deforolimus (previously known as AP23573; MK-8669), a nonprodrug rapamycin analog, in patients with advanced solid malignancies.

Patients and Methods: Patients were treated using an accelerated titration design with sequential escalating flat doses of deforolimus administered as a 30-minute intravenous infusion once daily for 5 consecutive days every 2 weeks (QDx5) in a 28-day cycle. Safety, pharmacokinetic, pharmacodynamic, and tumor response assessments were performed.

Results: Thirty-two patients received at least one dose of deforolimus (3 to 28 mg/d). Three dose-limiting toxicity events of grade 3 mouth sores were reported. The maximum-tolerated dose (MTD) was 18.75 mg/d. Common treatment-related adverse events included reversible mouth sores and rash. Whole-blood clearance increased with dose. Pharmacodynamic analyses demonstrated mammalian target of rapamycin inhibition at all dose levels. Four patients (one each with non–small-cell lung cancer, mixed müllerian tumor [carcinosarcoma], renal cell carcinoma, and Ewing sarcoma) experienced confirmed partial responses, and three additional patients had minor tumor regressions.

Conclusion: The MTD of this phase I trial using an accelerated titration design was determined to be 18.75 mg/d. Deforolimus was well tolerated and showed encouraging antitumor activity across a broad range of malignancies when administered intravenously on the QDx5 schedule. On the basis of these overall results, a dose of 12.5 mg/d is being evaluated in phase II trials.


Gastrointestinal Cancer

3. cT3N0 Rectal Cancer: Potential Overtreatment With Preoperative Chemoradiotherapy Is Warranted

Purpose: Although combined-modality therapy (CMT) is the preferred treatment for T3 and/or lymph node (LN)-positive rectal cancer, the German rectal cancer study published in 2004 demonstrated that 18% of patients deemed suitable for preoperative CMT by endorectal ultrasound (ERUS) may be overstaged. Because data also suggest that LN-negative rectal cancer after total mesorectal excision may not require radiotherapy, it is reasonable to consider omitting radiotherapy for the cT3N0 subset. We therefore determined the accuracy of pre-CMT ERUS or magnetic resonance imaging (MRI) staging, to explore the validity of a nonpreoperative CMT approach for cT3N0 disease.

Patients and Methods: One hundred eighty-eight ERUS-/MRI-staged T3N0 rectal cancer patients received preoperative CMT (fluorouracil based and 45-50.4 Gy) followed by radical resection. Rates of pathologic complete response (pCR) and mesorectal LN involvement were determined.

Results: Tumors were located a median of 5 cm from the anal verge. Sphincter-preserving surgery was performed in 143 patients (76%). Overall pCR was 20%, and 41 patients (22%) had pathologically positive mesorectal LNs. The incidence of positive LNs significantly increased with T stage: ypT0, 3%; ypT1, 7%; ypT2, 20%; ypT3-4, 36% (P = .001).

Conclusion: The accuracy of preoperative ERUS/MRI for staging mid to distal cT3N0 rectal cancer is limited because 22% of patients have undetected mesorectal LN involvement despite CMT. Therefore, ERUS-/MRI-staged T3N0 rectal cancer patients should continue to receive preoperative CMT. Although 18% may be overstaged and therefore overtreated, our data suggest that an even larger number would be understaged and require postoperative CMT, which is associated with significantly inferior local control, higher toxicity, and worse functional outcome.

cT3N0的直肠癌：术前放化疗潜在的过度治疗值得关注
目的：尽管对于T3或淋巴结阳性的直肠癌倾向于综合治疗，但是德国直肠癌研究组在2004年发表文章认为18%的病人经过直肠超声内镜认为适合术前辅助治疗的病人被过度分期。由于数据同样表明了淋巴结阴性的直肠癌在TME术后可能不需要接受放疗，来分析对于cT3N0的病人不做术前辅助治疗的可行性。我们因此探讨了术前的直肠腔内B超或是MRI分期的准确性，因此有理由认为对于cT3N0的病人可能不需要接受放疗。
病例选择和方法：188个经过腔内B超或是MRI分期为T3N0的直肠癌病人接受了术前的辅助治疗（以5-FU为基础的化疗和45-50.4GY的放疗）。记录病理CR和肠系膜淋巴结受累比例。
结果：肿瘤距肛门中位距离是5cm，43 (76%)个病人接受了保留肛门的手术。病理总CR率是20%，其中41个病人（22%）有阳性肠系膜淋巴结，随T分期增加阳性淋巴结比例增加，其中ypT0, 3%; ypT1, 7%; ypT2, 20%; ypT3-4, 36% (P = .001).
结论：术前的B超或是MRI分期对于分期为cT3N0的直肠癌是有限的，因为22%的病人尽管接受了术前辅助治疗仍然可以检出阳性淋巴结。因此，术前经过腔内B超或是MRI分期为T3N0的直肠癌病人还是应该继续接受术前的辅助治疗。尽管18%的病人可能会过度分期导致过度治疗，但是，我们的研究表明更多的病人是分期不够，需要接受术后的辅助治疗。从而导致了局部控制率下降，毒性增加，更差的功能。


4. KRAS Mutations As an Independent Prognostic Factor in Patients With Advanced Colorectal Cancer Treated With Cetuximab

Purpose: Cetuximab is efficient in advanced colorectal cancer (CRC). We previously showed that KRAS mutations were associated with resistance to cetuximab in 30 CRC patients. The aim of this study was to validate, in an independent larger series of 89 patients, the prognostic value of KRAS mutations on response to cetuximab and survival.

Patients and Methods: Eighty-nine metastatic CRC patients treated with cetuximab after treatment failure with irinotecan-based chemotherapy were analyzed for KRAS mutation by allelic discrimination on tumor DNA. The association between KRAS mutations and tumor response, skin toxicity, progression-free survival (PFS) and overall survival (OS) was analyzed.

Results: A KRAS mutation was present in 27% of the patients and was associated with resistance to cetuximab (0% v 40% of responders among the 24 mutated and 65 nonmutated patients, respectively; P < .001) and a poorer survival (median PFS: 10.1 v 31.4 weeks in patients without mutation; P = .0001; median OS: 10.1 v 14.3 months in patients without mutation; P = .026). When we pooled these 89 patients with patients from our previous study, the multivariate analysis showed that KRAS status was an independent prognostic factor associated with OS and PFS, whereas skin toxicity was only associated with OS. In a combined analysis, median OS times of patients with two, one, or no favorable prognostic factors (severe skin toxicity and no KRAS mutation) was of 15.6, 10.7, and 5.6 months, respectively.

Conclusion: These results confirm the high prognostic value of KRAS mutations on response to cetuximab and survival in metastatic CRC patients treated with cetuximab.

KRAS突变作为西妥昔单抗治疗晚期结直肠癌患者的一个独立的预后因素
目的：西妥昔单抗对于晚期CRC有一定疗效。我们之前研究显示：KRAS突变与30个CRC患者对西妥昔单抗耐药有关。本研究目的是为了确认：在一个独立的更多的89个患者中，KRAS突变对于西妥昔单抗的反应与生存的预测价值。
患者与方法：89个转移性CRC患者在以伊立替康为基础的化疗失败后启用了西妥昔单抗，而我们通过肿瘤DNA等位基因鉴别的方法，分析了这些患者的KRAS突变情况。同时分析了KRAS突变与肿瘤缓解，皮肤毒性，PFS及OS之间的的关系。
结果：27％的患者存在KRAS突变，且与对西妥昔单抗耐药（在24个突变患者与65个非突变患者中，为0％比40％，分别P＜0.001）及预后不良（中位PFS：10.1比31.4周；P＝0.001；中位OS：10.1比14.3周；P=0.026）相关。当我们将这89个患者与我们之前研究的患者混合，多因素分析显示：KRAS状态是一个与OS和PFS相关的独立预后因素。而皮肤毒性则仅与OS相关。结合起来分析：具有2个，1个或没有良好预后因素的患者的中位OS时间分别为15.6，10.7和5.6个月。
结论：这些结果证实了：KRAS突变对于转移性CRC患者使用西妥昔单抗治疗时对西妥昔单抗耐药情况和生存期具有很高的预测价值。


5.Individualized Prediction of Colon Cancer Recurrence Using a Nomogram

Purpose: Estimates of recurrence after curative colon cancer surgery are integral to patient care, forming the basis of cancer staging and treatment planning. The categoric staging system of the American Joint Committee on Cancer (AJCC) is commonly used to convey risk by grouping patients based on anatomic elements. Although easy to implement, there remains significant heterogeneity within each stage grouping. In the era of multimodality treatment, a more refined tool is needed to predict recurrence.

Methods: An institutional database of 1,320 patients with nonmetastatic colon cancer was used to develop a nomogram to estimate recurrence after curative surgery. Prognostic factors were assessed with multivariable analysis using Cox regression, whereas nonlinear continuous variables were modeled with cubic splines. The model was internally validated with bootstrapping, and performance was assessed by concordance index and a calibration curve.

Results: The colon cancer recurrence nomogram predicted relapse with a concordance index of 0.77, improving on the stratification provided by either the AJCC fifth or sixth staging scheme. Factors in the model included patient age, tumor location, preoperative carcinoembryonic antigen, T stage, numbers of positive and negative lymph nodes, lymphovascular invasion, perineural invasion, and use of postoperative chemotherapy.

Conclusion: Using common clinicopathologic factors, the recurrence nomogram is better able to account for tumor and patient heterogeneity, thereby providing a more individualized outcome prognostication than that afforded by the AJCC categoric system. By identifying both the high- and low-risk patients within any particular stage, the nomogram is expected to aid in treatment planning and future trial design.


Breast Cancer

6. Relationship of Breast Magnetic Resonance Imaging to Outcome After Breast-Conservation Treatment With Radiation for Women With Early-Stage Invasive Breast Carcinoma or Ductal Carcinoma in Situ

Purpose: To determine the relationship of breast magnetic resonance imaging (MRI) to outcome after breast-conservation treatment (BCT) with radiation for women with early-stage invasive breast carcinoma or ductal carcinoma in situ.

Patients and Methods: A total of 756 women with early stage invasive breast carcinoma or ductal carcinoma in situ underwent BCT including definitive breast irradiation during 1992 to 2001. At the time of initial diagnosis and evaluation, routine breast imaging included conventional mammography. Of the 756 women, 215 women (28%) had also undergone a breast MRI study, and 541 women (72%) had not undergone a breast MRI study. The median follow-up after treatment was 4.6 years (range, 0.1 to 13.5 years).

Results: For the women with a breast MRI study compared with the women without a breast MRI study, there were no differences in the 8-year rates of any local failure (3% v 4%, respectively; P = .51) or local-only first failure (3% v 4%, respectively; P = .32). There were also no differences between the two groups for the 8-year rates of overall survival (86% v 87%, respectively; P = .51), cause-specific survival (94% v 95%, respectively; P = .63), freedom from distant metastases (89% v 92%, respectively; P = .16), or contralateral breast cancer (6% v 6%, respectively; P = .39).

Conclusion: The use of a breast MRI study at the time of initial diagnosis and evaluation was not associated with an improvement in outcome after BCT with radiation.

早期浸润性乳腺癌或导管内癌妇女保乳术后放疗结局与乳腺MRI检查的关系
目的：明确早期浸润性乳腺癌或导管内癌妇女保乳术（BCT）加放疗结局与乳腺MRI检查的关系。
患者与方法：共有756位早期浸润性乳腺癌或导管内癌妇女在1992年～2001年间接受了BCT和明确的乳房照射。在初始诊断、评估和包括传统乳房X线的常规乳腺影像学检查时，756位妇女中有215位（28％）妇女接受了乳腺MRI检查，541位(72%)妇女没有接受乳腺MRI检查。治疗后中位随访时间为4.6年（0.1～13.5年）。
结果：对于接受乳腺MRI和未接受乳腺MRI检查的妇女，两者在8年的任意局部复发率（3％：4％，P=0.51）或局部首次复发率（3％：4％，P=0.32）方面没有差别，而且，两者在8年的总生存率（86％：87％，P=0.51）、特定原因生存率（94％：95％，P=0.63）、无远处转移率（89％：92％，P=0.16）、无对侧乳腺癌发生率（6％：6％，P=0.39）方面均无差别。
结论：在乳腺癌的初始诊断和评估时行乳腺MRI检查与BCT加放疗的结局改善不相关。


Treatment-Related Complications

7. Effect of Breast Cancer Radiotherapy and Cigarette Smoking on Risk of Second Primary Lung Cancer

Purpose: Prior studies have found that postmastectomy radiotherapy (PMRT) for breast cancer (BC) increases the risk of lung cancer (LC). We explored the joint effects of cigarette smoking and PMRT on LC risk.

Methods: We conducted a population-based nested case-control study among women registered in the Connecticut Tumor Registry diagnosed with nonmetastatic BC between January 1, 1965 and December 31, 1989. Patient cases developed a LC 10 years after BC diagnosis. Controls were matched to patient cases on age, year of BC diagnosis, and length of survival. Medical records were reviewed for pathology, BC therapy, and smoking history. We used conditional logistic regression to estimate odds ratios for the independent and joint effects of smoking and PMRT on risk of overall, ipsilateral, and contralateral LC.

Results: Among 113 second primary LC patient cases and 364 controls, compared with nonsmoking women who did not receive PMRT, nonsmoking women who received PMRT had no higher risk of LC; adjusted odds ratios were 5.9 (95% CI, 2.7 to 12.8) for ever-smokers who did not receive PMRT and 18.9 (95% CI, 7.9 to 45.4) for ever-smokers who received PMRT. Adjusted odds ratios for the joint effects of smoking and PMRT were 10.5 (95% CI, 2.9 to 37.8) for the contralateral lung and 37.6 (95% CI, 10.2 to 139.0) for the ipsilateral lung. Smoking and PMRT were associated with increased risk for all histologic types of LC.

Conclusion: PMRT after a diagnosis of BC sharply increased the risk of second primary LC, especially in the ipsilateral lung, among ever-smokers. Clinicians should consider including smoking history in their discussions with patients about the risks and benefits of PMRT.

乳腺癌术后放疗和吸烟对其第二原发肺癌的影响
目的：以往研究发现对乳腺癌全乳切除术后行术后放疗(PMRT)增加肺癌发病危险。我们这个研究探索PMRT和抽烟对增加第二原发癌——肺癌发病危险的影响。
方法：我们对在1965.1.1——1989.12.31在康涅狄格州肿瘤登记处登记的非转移性乳腺癌的女性中进行巢式病例对照研究。病例组为在诊断乳腺癌10年后发生肺癌的患者，对照组为在年龄、诊断乳腺癌的年限以及生存期长度与病例组相匹配的患者。这项研究回顾了病历中病人的病理、乳腺癌疗法以及吸烟史。我们使用logistic回归分析法评估吸烟和PMRT作为独立因素及其联合作用对全部肺癌、同侧肺癌及对侧肺癌发生的优势比。
结果：在113例发生第二原发肺癌的患者和364例对照病例中，与既不吸烟又没有接受PMRT的女性相比，接受PMRT而不吸烟的女性有更高的肺癌发病危险。而没有接受PMRT的吸烟女性调整后的优势比是5.9 (95% CI, 2.7 to 12.8)；吸烟同时接受PMRT女性发生肺癌的优势比是18.9(95% CI, 7.9 to 45.4)。调整后对于同侧肺发生癌变吸烟和PMRT的联合效应优势比是37.6 (95% CI, 10.2 to 139.0)，而对侧是10.5 (95% CI, 2.9 to 37.8)，吸烟和PMRT增加所有病理类型的肺癌。
结论：对于持续吸烟者来说，诊断乳腺癌后行PMRT急剧增加第二原发肺癌的风险，尤其是在行放疗的同侧肺，临床医生在与病人讨论PMRT的风险和益处时应该将其吸烟史考虑在内。


Pediatric Oncology

8. Phase I Trial and Pharmacokinetic Study of Bevacizumab in Pediatric Patients With Refractory Solid Tumors: A Children's Oncology Group Study

Purpose: We conducted a pediatric phase I trial of the vascular endothelial growth factor (VEGF)–neutralizing antibody bevacizumab (BV). Primary aims included estimating the maximum-tolerated dose (MTD) and determining the dose-limiting toxicities (DLTs), pharmacokinetics, and biologic effects of BV in children with cancer.

Patients and Methods: BV (5, 10, 15 mg/kg) was administered intravenously every 2 weeks in 28-day courses to children with refractory solid tumors.

Results: Twenty-one patients enrolled, 20 (median age, 13 years) were eligible, and 18 completed one course and were fully assessable for toxicity. A total of 67 courses were administered (median, three courses per patient; range, one to 16 courses). Treatment was well tolerated with no DLTs observed. Non-DLTs included infusional reaction, rash, mucositis, proteinuria, and lymphopenia. Increases in systolic and diastolic blood pressure not meeting Common Terminology Criteria for Adverse Events (CTCAEv3) pediatric-specific criteria for hypertension were observed. There was no hemorrhage or thrombosis. Growth perturbation was not detected in a limited sample over the first course. The serum exposure to BV as measured by area under the concentration-time curve (AUC) seemed to increase in proportion to dose. The median clearance of BV was 4.1 mL/d/kg (range, 3.1 to 15.5 mL/d/kg), and the median half-life was 11.8 days (range, 4.4 to 14.6 days). No objective responses were observed. Exploratory analyses on circulating endothelial mobilization and viability are consistent with the available adult data.

Conclusion: BV is well tolerated in children. Phase II pediatric studies of BV in combination with chemotherapy in dosing schedules similar to adults are planned.

贝伐单抗用于儿童难治性实体瘤的I期临床试验及药物代谢动力学研究：来自一儿童肿瘤研究组的研究
目的:我们使用一种能够中和血管内皮生长因子(VEGF)的抗体---贝伐单抗（BV）在儿童肿瘤患者中进行了I 期临床试验。本试验的研究目的包括评估该药物在儿童肿瘤患者中的最大耐受剂量(MTD)，确定剂量限制性毒性（DLTs），了解药物代谢动力学以及生物效应。
入组病例和研究方法：入组的患者为患有难治性实体瘤的儿童。BV 分别按照5, 10, 15 mg/kg四个等级进行静脉注射，每两周使用一次该药物，28天为一个周期。
结果：一共入组21个病例，20例可供分析（中位年龄为13岁），18例患者完成了至少一个周期的治疗，并可供分析治疗毒性。全组患者共完成了67个周期的治疗（中位为每个病例接受3个周期的治疗，所有病例接受的治疗疗程数为1-16个周期不等）。患者能够很好地耐受治疗，未观察到剂量限制性毒性。非剂量限制性毒性包括静脉注射反应，皮疹，粘膜炎，蛋白尿以及淋巴细胞减少。另外尚观察到患者收缩压和舒张压的升高，但未达到CTCAE 3.0版本中针对儿童高血压的标准。未观察到出血或者血栓形成。在第一疗程中未观察到该药物对生长发育的干扰现象。采用AUC（曲线下面积）的方法计算BV的浓度，血清中BV的浓度似乎随着用药剂量的增加而增加。BV的中位清除率为4.1 mL/d/kg (分布在3.1 mL/d/kg ~15.5 mL/d/kg之间)，中位半衰期为11.8 天(分布在4.4~14.6天之间)。治疗未观察到客观疗效。对循环中内皮细胞的活动度行探索性分析，结果与目前成人试验数据相一致。
结论：儿童能够很好的耐受BV。我们计划在儿童肿瘤患者中采用与成人相似的方案开展BV联合化疗的II期临床研究。


9. Initial Patient Characteristics Can Predict Pattern and Risk of Relapse in Localized Rhabdomyosarcoma

Purpose: Evaluation of primary tumor-, treatment-, and patient-related factors predicting relapse pattern, risk, and survival after relapse with the aim to design a risk-adapted, tumor-directed surveillance program for patients with localized rhabdomyosarcoma (RMS).

Patients and Methods: One thousand one hundred sixty-four patients with nonmetastatic RMS achieved complete remission at the end of multimodal therapy in the consecutive trials of the Cooperative Weichteilsarkom Studiengruppe (CWS)-81, CWS-86, CWS-91, and CWS-96 between 1980 and 2002 (median follow-up, 5 years). Three hundred thirty-seven of these individuals developed either locoregional, metastatic, or combined relapses. Predictive factors for relapse, its pattern, and postrelapse survival were analyzed.

Results: Age, histology, tumor size, tumor site, postsurgical stage, and omission of radiotherapy were identified as factors associated with an increased relapse risk in multivariate analyses. Relapse rates did not differ among the CWS trials. Median time to relapse was 1.43 years from first diagnosis (range, 0.13 to 13.5 years). There were 217 locoregional, 72 metastatic, and 48 combined recurrences. Only two patients developed metastases more than 4 years after diagnosis, and both had combined recurrences. Five-year postrelapse survival was 24%. Patient subsets with consistent relapse pattern, risk, and postrelapse survival rates were identified on the basis of histologic subtype and tumor size.

Conclusion: Initial patient and tumor characteristics predict pattern and risk of relapse and also correlate with postrelapse survival probabilities. In localized RMS, tumor-directed follow-up should focus on the primary site. Screening for metastatic relapse may not be necessary more than 4 years after diagnosis. The identification of subgroups with distinctive pattern and risk of relapse may be used to develop risk-adapted, tumor-directed guidance for detection of recurrent disease in localized RMS.


10. Cardiomyopathy in Children With Down Syndrome Treated for Acute Myeloid Leukemia: A Report From the Children's Oncology Group Study POG 9421

Purpose: To determine the outcomes, with particular attention to toxicity, of children with Down syndrome (DS) and acute myeloid leukemia (AML) treated on Pediatric Oncology Group (POG) protocol 9421.

Patients and Methods: Children with DS and newly diagnosed AML (n = 57) were prospectively enrolled onto the standard-therapy arm of POG 9421 and were administered five cycles of chemotherapy, which included daunorubicin 135 mg/m2 and mitoxantrone 80 mg/m2. Outcomes and toxicity were evaluated prospectively and were compared with the non-DS–AML cohort (n = 565). A retrospective chart review was performed to identify adverse cardiac events.

Results: In the DS-AML group, 54 patients (94.7%) entered remission. One experienced induction failure and two died. Of the 54 who entered remission, three relapsed and six died as a result of other causes. The remission induction rate was similar in the non-DS–French-American-British (FAB) M7 (91.7%) and non-DS–non-M7 (89.3%) groups. The 5-year overall survival was significantly better in the DS-AML group (78.6%) than in the non-DS–M7 (36.3%) or the non-DS–non-M7 (51.8%) groups (P < .001). No age-related difference in 5-year, event-free survival was seen between patients younger than 2 years (75.8%) and those aged 2 to 4 years (78.3%). Symptomatic cardiomyopathy developed in 10 patients (17.5%) with DS-AML during or soon after completion of treatment; three died as a result of congestive heart failure.

Conclusion: The POG 9421 treatment regimen was highly effective in both remission induction and disease-free survival for patients with DS-AML. However, there was a high incidence of cardiomyopathy, which supports current strategies for dose reduction of anthracyclines in this patient population.


Genitourinary Cancer

11. Randomized Trial Comparing Bleomycin/Etoposide/Cisplatin With Alternating Cisplatin/Cyclophosphamide/Doxorubicin and Vinblastine/Bleomycin Regimens of Chemotherapy for Patients With Intermediate- and Poor-Risk Metastatic Nonseminomatous Germ Cell Tumors: Genito-Urinary Group of the French Federation of Cancer Centers Trial T93MP

Purpose: Two chemotherapy regimens for intermediate- and poor-risk metastatic nonseminomatous germ cell tumors were compared for efficacy and toxicity.

Patients and Methods: From February 1994 to February 2000, 190 patients were randomly assigned between either four cycles of BEP (bleomycin 30 mg d1, d8, d15; etoposide 100 mg/m2 d1-5; cisplatin 20 mg/m2 d1-5) or four to six alternating cycles of CISCA/VB (cyclophosphamide 400 mg/m2 d1-2, doxorubicin 35 mg/m2 d1-2, cisplatin 100 mg/m2 d3/vinblastine 2.5 mg/m2 d1-5, bleomycin 25 mg/m2 d1-5). Risk was initially defined according to the Institut Gustave Roussy (Villejuif, France) prognostic model based on serum alpha-fetoprotein and human chorionic gonadotropin levels only. Patients were retrospectively assigned into the International Germ Cell Consensus Classification.

Results: Among 185 assessable patients, favorable responses did not differ statistically between the two arms: 49 in the CISCA/VB arm (56%; 95% CI, 45% to 66%), 57 in the BEP arm (65%; 95% CI, 55% to 75%). The CISCA/VB regimen induced more significant hematologic and mucous toxicities compared with the BEP arm. The 5-year event-free survival rates were 37% (95% CI, 27% to 47%) and 47% (95% CI, 37% to 57%) in CISCA/VB and BEP arms, respectively (hazard ratio [HR] = 0.76; 95% CI, 0.52 to 1.11; P = .15). With a median follow-up of 7.8 years, the 5-year overall survival rates were 59% (95% CI, 47% to 67%) and 69% (95% CI, 58% to 77%) in CISCA/VB and BEP arms, respectively (HR = 0.73; 95% CI, 0.46 to 1.18; P = .24).

Conclusion: Because of equivalent efficacy and lesser toxicity, the standard treatment for patients with intermediate- and poor-risk metastatic nonseminomatous germ cell tumors remains four cycles of BEP.

作者比较了BEP 和 CISCA/VB 交替方案在中高危转移性NSGCT中的效果。
方法：
1. four cycles of BEP (bleomycin 30 mg d1, d8, d15; etoposide 100 mg/m2 d1-5; cisplatin 20 mg/m2 d1-5)
2. four to six alternating cycles of CISCA/VB (cyclophosphamide 400 mg/m2 d1-2, doxorubicin 35 mg/m2 d1-2, cisplatin 100 mg/m2 d3/vinblastine 2.5 mg/m2 d1-5, bleomycin 25 mg/m2 d1-5).
注意危险度分组基于AFP和betaHCG，而非NCCN的分组，顺便介绍NCCN的分组因素，除了瘤标水平外，包括原发灶部位（睾丸、后腹膜、纵隔）、有无非肺的内脏转移。仅仅根据瘤标分组可能并非真正的“高危”患者。

结果：反应率 65%（BEP） vs 56%，没有差异。CISCA/VB 血液毒性和粘膜毒性更强。5年无复发生存率47% （BEP）vs 37%。总生存69% vs 59%，没有显著差异。

结论：BEP仍然是中高危M+ NSGCT的首选治疗。


Hematologic Malignancies

12. Prevention of Coagulase-Negative Staphylococcal Central Venous Catheter–Related Infection Using Urokinase Rinses: A Randomized Double-Blind Controlled Trial in Patients With Hematologic Malignancies

Purpose: Fibrin deposition at the intraluminal surface of the indwelling part of the central venous catheter (CVC) surface increases the risk of CVC-related coagulase-negative staphylococci (CoNS) infection. Therefore, repetitive enzymatic dissolution of fibrin by urokinase might reduce the risk of CVC-related infection. We undertook this study to investigate whether three times weekly urokinase rinsing of CVC reduces the incidence or severity of CVC-related infections by CoNS in patients undergoing intensive cytotoxic treatment for hematologic malignancies.

Patients and Methods: In a double-blind setting, all consecutive patients with a CVC were randomly allocated to receive either urokinase rinses (5 mL of 5,000 U/mL) or placebo (saline), both three times weekly.

Results: The percentage of patients with at least one positive culture with CoNS was lower in patients receiving urokinase compared with patients receiving placebo (26% v 42%, respectively; relative risk [RR] = 0.61; 95% CI, 0.39 to 0.94). Major CVC-related CoNS infection occurred less frequently in patients receiving urokinase versus placebo (1.2% v 14.1%, respectively; RR = 0.09; 95% CI, 0.01 to 0.50). Secondary complications, including CVC-related thrombosis, were observed less frequently in the urokinase group compared with the placebo group (1.3% v 9.0%, respectively; RR = 0.14; 95% CI, 0.02 to 0.82). No severe bleeding complications attributable to urokinase were observed.

Conclusion: Three times weekly urokinase rinsing reduces the incidence of CVC-related CoNS infection in patients treated with intensive cytotoxic therapy for hematologic malignancies, with acceptable safety.


13. Lymphocyte-Predominant and Classical Hodgkin's Lymphoma: A Comprehensive Analysis From the German Hodgkin Study Group

Purpose: Lymphocyte-predominant Hodgkin's lymphoma (LPHL) is rare and differs in histologic and clinical presentation from classical Hodgkin's lymphoma (cHL). To shed more light on the prognosis and outcome of LPHL, we reviewed all LPHL patients registered in the German Hodgkin Study Group (GHSG) database, comparing patient characteristics and treatment outcome with cHL patients.

Patients and Methods: We analyzed retrospectively 8,298 HL patients treated within the GHSG trials HD4 to HD12, of whom 394 had LPHL and 7,904 had cHL.

Results: Complete remission and unconfirmed complete remission after first-line treatment was achieved in 91.6% v 85.9% of patients in early favorable stages, 85.7% v 83.3% of patients in early unfavorable stages, and 76.8% v 77.8% of patients in advanced stages of LPHL compared with cHL, respectively. Tumor control (freedom from treatment failure [FFTF]) for LPHL and cHL patients at a median observation of 50 months was 88% and 82% (P = .0093) and overall survival (OS) was 96% and 92%, respectively (P = .0166). In LPHL patients, negative prognostic factors were advanced stage (P = .0092), Hb less than 10.5 g/dL (P = .0171), and lymphopenia (P = .010) for FFTF. Age 45 years (P = .0125), advanced stage (P = .0153), and Hb less than 10.5 g/dL (P = .0014) were negative prognostic factors for OS.

Conclusion: The better prognosis of LPHL as compared with cHL might allow different treatment strategies, particularly for early-stage LPHL patients.

淋巴细胞为主性霍奇金淋巴瘤与经典霍奇金淋巴瘤：来自德国霍奇金淋巴瘤研究组的综合分析。
目的：淋巴细胞为主性霍奇金淋巴瘤(LPHL) 是一种少见的，而且在组织学以及临床表现上与经典霍奇金淋巴瘤(cHL)不同的疾病。为进一步明确LPHL的预后和疗效，我们回顾了所有在德国霍奇金淋巴瘤研究组(GHSG)记录的LPHL病人数据，并将其病例特点和治疗结果与cHL病人进行对照。
病例和方法：我们回复分析了在GHSG接受处理的8298例霍奇金淋巴瘤病例。其中394例为LPHP。7904例为cHL。
结果：LPHL与cHL比较，在一线治疗后，取得完全缓解率（含不确定的完全缓解），在早期无不利因素病例为：91.6% v 85.9%。在早期含不利因素病例为： 85.7% v 83.3% 。在进展期病例为76.8% v 77.8%。
在中位观察时间为50个月的随诊下， LPHL 与cHL 的肿瘤控制率[无治疗失败生存率（FFTF）]88% v 82% (P = .0093)。总生存率（OS）96% v 92% (P = .0166。
在LPHL病例中，与FFTF相关的不良预后因子包括：进展期 (P = .0092), 血红蛋白小于10.5 g/dL (P = .0171), 淋巴球减少(P = .010)。
与OS相关的不良预后因子包括：年龄大于45岁 (P = .0125), 进展期（P = .0153), 以及血红蛋白小于10.5 g/dL (P = .0014) 。
结论：LPHL比cHL有更好的预后情况。对于LPHL，特别是早期的LPHL病例，可能可以采用与cHL不同的分期治疗手段。


14. High Numbers of Tumor-Associated Macrophages Have an Adverse Prognostic Value That Can Be Circumvented by Rituximab in Patients With Follicular Lymphoma Enrolled Onto the GELA-GOELAMS FL-2000 Trial

Purpose: High amounts of intratumoral macrophages have been shown to correlate with poor prognosis in patients with follicular lymphoma (FL) treated with chemotherapy without rituximab. We tried to establish whether intratumoral macrophage count (MC) definitely is able to predict the outcome of FL patients in the rituximab era.

Patients and Methods: We analyzed immunohistochemical CD68 expression in 194 FL patients from the FL-2000 trial, randomly assigned to receive cyclophosphamide, doxorubicin, etoposide, prednisolone, and interferon (CHVP-I) or rituximab plus CHVP-I. Immunohistochemistry was performed on paraffin sections using anti-CD68 KP1 antibody, and stained macrophages were scored on high-power field (hpf) in either intrafollicular (IF) or extrafollicular (EF) areas.

Results: For IF MC, the best cutoff point was estimated at 10 macrophages/hpf. Low IF MC was significantly associated with a better event-free survival (EFS; P = .011). However, this effect was observed only in the CHVP-I arm (P = .012) and not in the rituximab plus CHVP-I arm. Using a cutoff of 15 IF MC, we found no significant association with EFS. For EF MC, fewer than 22 macrophages/hpf were associated with better EFS in the CHVP-I arm (P = .02) but not in the rituximab plus CHVP-I arm.

Conclusion: These results show that MC can predict outcome of FL patients and that rituximab is able to circumvent the unfavorable outcome associated with high MC.

GELA-GOELAMS FL-2000实验证实：利妥昔单抗有助于改善肿瘤相关性巨噬细胞高表达的滤泡性淋巴瘤患者的不良预后
目的：有研究表明，肿瘤相关性巨噬细胞高表达的滤泡性淋巴瘤患者以不含利妥昔单抗的方案进行化疗，预后较差。我们试图证明是否瘤内巨噬细胞数可以判断预后。
病人与方法：在FL-2000试验中，我们对194名滤泡性淋巴瘤患者随机应用环磷酰胺，阿霉素，足叶乙甙，强的松和干扰素方案(CHVP-I)或利妥昔单抗联合CHVP-I方案，免疫组化法通过抗CD－68单克隆抗体对石蜡切片的巨噬细胞进行标记，高倍镜下计数滤泡内或小结间区的巨噬细胞数。
结果：瘤内巨噬细胞的最佳分界点是10个细胞每高倍镜视野。在CHVP-I组，瘤内巨噬细胞低表达与无病生存期有显著性相关(P = .011)；在利妥昔单抗联合CHVP-I组则没有相关性。当分界点定为15个细胞每高倍镜视野时，巨噬细胞表达与无病生存期没有显著性相关。在CHVP-I组可以观察到小结间区巨噬细胞数小于22个细胞每高倍镜视野时无病生存期较长(P = .02)，在利妥昔单抗联合CHVP-I组则没有差异性。
结论：巨噬细胞数目有助于判断滤泡性淋巴瘤患者预后，而利妥昔单抗能够改善巨噬细胞高表达滤泡性淋巴瘤患者的不良预后。


15. LMO2 Protein Expression Predicts Survival in Patients With Diffuse Large B-Cell Lymphoma Treated With Anthracycline-Based Chemotherapy With and Without Rituximab

Purpose: The heterogeneity of diffuse large B-cell lymphoma (DLBCL) has prompted the search for new markers that can accurately separate prognostic risk groups. We previously showed in a multivariate model that LMO2 mRNA was a strong predictor of superior outcome in DLBCL patients. Here, we tested the prognostic impact of LMO2 protein expression in DLBCL patients treated with anthracycline-based chemotherapy with or without rituximab.

Patients and Methods: DLBCL patients treated with anthracycline-based chemotherapy alone (263 patients) or with the addition of rituximab (80 patients) were studied using immunohistochemistry for LMO2 on tissue microarrays of original biopsies. Staining results were correlated with outcome.

Results: In anthracycline-treated patients, LMO2 protein expression was significantly correlated with improved overall survival (OS) and progression-free survival (PFS) in univariate analyses (OS, P = .018; PFS, P = .010) and was a significant predictor independent of the clinical International Prognostic Index (IPI) in multivariate analysis. Similarly, in patients treated with the combination of anthracycline-containing regimens and rituximab, LMO2 protein expression was also significantly correlated with improved OS and PFS (OS, P = .005; PFS, P = .009) and was a significant predictor independent of the IPI in multivariate analysis.

Conclusion: We conclude that LMO2 protein expression is a prognostic marker in DLBCL patients treated with anthracycline-based regimens alone or in combination with rituximab. After further validation, immunohistologic analysis of LMO2 protein expression may become a practical assay for newly diagnosed DLBCL patients to optimize their clinical management.


Bone Marrow Transplantation

16. Reduced-Intensity Conditioning Compared With Conventional Allogeneic Stem-Cell Transplantation in Relapsed or Refractory Hodgkin's Lymphoma: An Analysis From the Lymphoma Working Party of the European Group for Blood and Marrow Transplantation

Purpose: To compare the clinical outcome in terms of nonrelapse mortality (NRM), relapse rate (RR), overall survival (OS), and progression-free survival (PFS) in patients with relapsed Hodgkin's lymphoma (HL) treated with reduced-intensity conditioning (RIC) or myeloablative conditioning followed by allogeneic stem-cell transplantation (alloSCT).

Patients and Methods: A total of 168 patients with HL undergoing a first alloSCT (RIC, n = 89; myeloablative conditioning, n = 79) between January 1997 and December 2001 and registered in the European Group for Blood and Marrow Transplantation database were analyzed.

Results: NRM was significantly decreased in the RIC group (hazard ratio [HR], 2.85; 95% CI, 1.62 to 5.02; P < .001). OS was better in the RIC group (HR, 2.05; 95% CI, 1.27 to 3.29; P = .04) and there was a trend for better PFS in the RIC group (HR, 1.53; 95% CI, 0.97 to 2.40; P = .07). RR was higher in the RIC group in univariate but not in multivariate analysis. The development of chronic graft-versus-host disease (GVHD) significantly decreased the incidence of relapse, which translated into a trend for a better PFS.

Conclusion: The lower incidence of NRM in the RIC group is encouraging, particularly because these patients experienced adverse pretransplantation characteristics more frequently. This analysis also indicates the existence of a graft-versus-HL effect correlated to the development of GVHD. Additional efforts to reduce the high RR seen in both groups of patients will be necessary to improve the modest PFS (31% v 27%) and OS (59% v 36%) for patients prepared with RIC or myeloablative conditioning.


Thoracic Oncology

17. Disease Control Rate at 8 Weeks Predicts Clinical Benefit in Advanced Non–Small-Cell Lung Cancer: Results From Southwest Oncology Group Randomized Trials

Purpose: Tumor shrinkage categorized as complete response (CR) or partial response (PR) is a fundamental efficacy measure for new cancer treatments and often considered a surrogate for overall survival. However, for any given treatment, many more patients typically achieve stable disease (SD) or have progressive disease (PD) than achieve response. We hypothesized that PD (or its converse, disease control rate [DCR], consisting of CR, PR, SD) is a stronger predictor of survival than response alone in advanced non–small-cell lung cancer (NSCLC), and that this determination might be assessable early on during therapy.

Patients and Methods: Data from 984 NSCLC patients entered onto three randomized Southwest Oncology Group trials of platinum-based chemotherapy were pooled and subjected to Landmark survival analysis. Patients were categorized according to proportions alive at weeks 8, 14, and 20 after registration, as well as response status. Elements were fitted into a Cox proportional hazards model.

Results: Tumor response (CR, PR) was seen in 260 patients (27%). Median time to response, time to progression, and survival time were 2.0, 4.3 and 8.9 months, respectively. Median survival times among patients with CR/PR, SD, or PD were 13.5, 8.4, and 3.1 months, respectively. Of 892 patients alive at week 8, DCR was 62%. Although CR/PR at week 8 was associated with longer survival (hazard ratio [HR] = 0.61; P < .001), DCR was superior in predicting survival (HR = 0.45; P < .0001).

Conclusion: DCR at week 8 is a more powerful predictor of subsequent survival than is the traditional tumor response rate in advanced NSCLC and provides an early assessment of subsequent outcome.

8周的疾病控制率预示着晚期非小细胞肺癌的临床受益－来自西南肿瘤组随机试验结果
目的：肿瘤缩小归为完全缓解（CR）或部分缓解（PR）是肿瘤新治疗措施的主要有效衡量之一，且常被认为代表总生存。然而，对于任何既定治疗，更多的患者与其说是有反应，还不如说是疾病稳定（SD）或疾病进展（PD）。在晚期非小细胞肺癌（NSCLC），我们假设PD（或与其相反的疾病控制率[DCR]，包括CR，PR,SD）是生存的一个较肿瘤反应单项更强的预测因子，并且这种判定在治疗早期也许就可以进行评估。
患者和方法：收集参加西南肿瘤组的三个以铂类为基础化疗试验的984名NSCLC患者的数据进行Landmark 生存分析。患者按入组后8周、14周20周生存比例及反应状况进行分类，各因子填入COX比例风险模型。
结果：260个（27％）患者有反应（CR，PR），其中位反应时间、进展时间和生存时间分别是：2.0月，4.3月和8.9月。获CR/PR、 SD、或PD患者的中位生存时间分别是13.5月，8.4月和3.1月。在存活超过8周的892位患者中，DCR是62％，尽管8周的CR/PR与长期生存有关（风险比率[HR]＝0.61；P<0.001）；但DCR在生存预后方面却更显优势（HR＝0.45；P<0.0001）。
结论：在晚期NSCLC，相对传统的肿瘤反应率，8周的DCR是随后生存的一个更强的预后因子，并且能为随后的结局提供一个早期的评估。


18. Randomized, Phase III Study of Weekly Paclitaxel in Combination With Carboplatin Versus Standard Every-3-Weeks Administration of Carboplatin and Paclitaxel for Patients With Previously Untreated Advanced Non–Small-Cell Lung Cancer

Purpose: To compare the efficacy and safety of weekly paclitaxel in combination with carboplatin administered every 4 weeks to the standard regimen of paclitaxel and carboplatin administered every 3 weeks for the treatment of patients with advanced non–small-cell lung cancer (NSCLC).

Patients and Methods: Four hundred forty-four patients with previously untreated stage IIIB/IV NSCLC were randomly assigned to either arm 1 (n = 223), paclitaxel 100 mg/m2 weekly for 3 of 4 weeks with carboplatin area under the curve (AUC) = 6 mg/mL · min on day 1 of each 4 week cycle, or arm 2 (n = 221), paclitaxel 225 mg/m2 and carboplatin AUC = 6 on day 1 of each 3-week cycle. After four cycles of therapy, patients in both treatment arms were eligible to continue weekly paclitaxel (70 mg/m2, 3 of 4 weeks) as maintenance therapy until unacceptable toxicity or disease progression.

Results: The objective response rate was 27.6% for arm 1 and 19.2% for arm 2. Median time to progression (TTP) was 18.4 and median survival (MS) was 38.6 weeks for arm 1. For arm 2, the median TTP and MS were 16.7 weeks and 42.9 weeks respectively. Grade 3/4 anemia was more common with arm 1, although grade 2/3 neuropathy and arthralgia were less common. The remainder of the toxicities were similar between the two arms.

Conclusion: All efficacy parameters were similar between the two treatment arms. The favorable nonhematologic toxicity profile of arm 1 makes this an alternative treatment option for patients with advanced NSCLC.

未经治疗的晚期非小细胞肺癌卡铂加紫杉醇三周方案和每周方案比较的随机、III期临床试验
目的：比较未经治疗的晚期非小细胞肺癌卡铂加紫杉醇三周标准方案和每周方案的安全性和有效性。
病人和方法：444个未经治疗的IIIB/IV期NSCLC被随机分为两组：一组（n = 223）方案为每周方案，具体为：紫杉醇 100 mg/m2 d1、d8、d15，卡铂 AUC=6 d1，四周为一周期；另一组（n = 221）为三周方案，具体为：紫杉醇 225 mg/m2 d1、卡铂 AUC=6 d1，三周为一周期。两组病人在四周期化疗后继续行每周紫杉醇方案单药化疗（70 mg/m2, 3 of 4 weeks）作为维持治疗，直到其出现不可耐受的毒性反应或疾病进展。
结果：组一和组二的客观反应率分别为27.6%和19.2%，组一的中位进展时间（TTP）和中位生存期（MS）为18.4周和38.6周，组二的中位进展时间（TTP）和中位生存期（MS）为16.7周和42.9周，尽管第一组患者2-3级神经病变和关节痛少见，但3-4级贫血在更为常见，其他毒性两组相似。
结论：两组患者所有的有效性的参数都相似，但第一组患者非血液学毒性较小可以为部分晚期非小细胞肺癌患者提供一个选择。


Aids-Related Cancer

19.Human Immunodeficiency Virus–Associated Squamous Cell Cancer of the Anus: Epidemiology and Outcomes in the Highly Active Antiretroviral Therapy Era
Purpose: To evaluate and determine predictors of squamous cell carcinoma of the anus (SCCA) outcomes in the highly active antiretroviral therapy (HAART) era for HIV-positive and -negative individuals using large national Veterans Affairs (VA) Administration databases.

Patients and Methods: We used the VA administrative databases to perform a retrospective cohort study in 1,184 veterans diagnosed with SCCA between 1998 and 2004. We calculated HIV infection rates and used logistic regression to identify epidemiologic factors that were associated with HIV infection. Kaplan-Meier curves and Cox proportional hazards models were calculated to compare survival between HIV-positive and HIV-negative veterans.

Results: In our cohort, 175 patients (15%) were HIV positive. The median age of the HIV-negative and -positive patients was 63 and 49 years, respectively (P < .001). Individuals with HIV were eight times more likely to be male (P = .01) and three times more likely to be African American (P < .001). There were no differences between HIV-positive and HIV-negative individuals in the receipt of treatment. The 2-year observed survival rates were 77% and 75% among HIV-positive and HIV-negative individuals, respectively. In multivariate Cox analysis, significant predictors of survival were age, sex, metastasis at diagnosis, and comorbidity score. HIV infection did not affect survival.

Conclusion: A noteworthy proportion of individuals with SCCA in the VA system are HIV positive. HIV-associated SCCA seems mainly to be a disease among younger men. Survival of SCCA is equivalent between HIV-positive and HIV-negative individuals in the HAART era. Treatment should not be withheld or deintensified based on HIV status.


:)REVIEW ARTICLES

20.Stem-Cell Transplantation for Multiple Myeloma in the Era of Novel Drugs

The treatment of multiple myeloma (MM) is changing rapidly. During the last 10 years, higher rates of complete response (CR) and prolonged progression-free and overall survival have been seen with high-dose chemotherapy plus autologous stem-cell transplantation (HDT-ASCT). Achievement of CR and good partial response have been shown to be key prognostic factors for prolonged survival, with eradication of minimal residual disease seeming crucial to long-term disease-free survival. Until recently, high rates of CR and other major responses were primarily seen with HDT-ASCT, but insights into the biology of MM have led to the development and approval of new drugs with significant activity, and new induction regimens based on these novel agents are offering improved responses. Thalidomide, bortezomib, and lenalidomide have been combined with corticosteroids, alkylators, and anthracyclines in front-line MM treatment. Phase II studies have indicated that high rates of response and CR may be achieved. The substantial activity seen with these new drug combinations has prompted a re-examination of the role of SCT in MM treatment. Will achievement of major responses with these new regimens translate into improved survival after consolidation with transplantation? Will these improved induction regimens reduce the need for tandem transplantation, or does achievement of CR obviate the need for front-line transplantation altogether? To help address these questions, randomized trials are needed, as well as tests with improved sensitivity to better define depth of remission.

多发性骨髓瘤新药时期的干细胞移植
多发性骨髓瘤（MM）的治疗日新月异，在过去的10年里，大剂量化疗加自体干细胞移植（HDT-ASCT）已经显示出了更高的完全缓解(CR)率、无进展生存率和总生存率。获得CR和良好的部分缓解已被证明是延长生存的关键预后因子，对于长期无病生存来说，疾病极微残留的根除似乎是关键。直到最近，高CR率和其他较多反应率主要见于HDT-ASCT。然而，对MM生物学认识的深入使有明显活性的新药得到发展和认可，而且，以上述新药为基础的新诱导方案正显示了进一步的反应。沙力度胺、硼替咪唑及雷力度胺已经与类固醇类、烷化剂和蒽环类联合用于MM的一线治疗，II期临床研究显示这可能将获得高有效率和CR率。新药联合显示的充分活性促使了干细胞移植（SCT）在MM治疗中作用的再评估。较多有效的获得在这些新方案联合移植治疗中将能否转化为生存的改善？这些改良的诱导方案将能否减少再次移植的需要，或达到CR可完全不需要一线移植？要回答上述问题，需要进行随机临床试验，同时也需要改进敏感性的检测，以更好确定疾病的缓解程度。


21. Anti-Apoptosis Mechanisms in Malignant Gliomas

Malignant gliomas are characterized by an intrinsic resistance to apoptosis. Increasing evidence suggests that this is a fundamental mechanism by which gliomas evade elimination when treated with both conventional and targeted therapies. In this review, we describe the multiple anti-apoptotic signals that have been demonstrated to be active in malignant gliomas. We describe the preclinical evidence that suggests that targeting those signaling anomalies can increase tumor responsiveness and enhance the elimination of gliomas in preclinical models. We discuss recent advances in translating pro-apoptotic compounds to clinical trial, and the potential for implementing agents that target the apoptotic pathway as a strategy for improving the outcomes for patients with high-grade gliomas.

恶**质瘤的抗凋亡机制
恶**质瘤本身具有抗凋亡特性，越来越多的证据表明这一机制是交质瘤细胞逃避传统和靶向治疗的重要原因。我们对在恶**质瘤中多种具有活性的抗凋亡信号进行综述，临床前研究显示以这些异常信号为治疗靶点能增强抗肿瘤反应和肿瘤细胞清除率，讨论近期临床实验通过转换凋亡前复合物和以凋亡路径靶向治疗来提高高级别交质瘤患者治疗效果的可行性。