Neoadjuvant Chemotherapy for Extremity Osteosarcoma: Preliminary Results of the Rizzoli's 4th Study

A neoadjuvant chemotherapy protocol (1/93-1/95) for extremity osteosarcoma preoperatively using high-dose methotrexate (HDMTX) as single agent per cycle and three different combinations of other drugs (CDP/IFO,CDP/ADM,IFO/ADM) is reported. The four drugs were used postoperatively as single agents. Treatment was uniform, but suspended earlier if total necrosis was attained. An improvement was found in the results of the previous study using only IFO postoperatively, with 16/119 patients (97%) avoiding amputation, and 38 (32%) attaining complete necrosis. At a 3-year (2-4 years) mean follow-up, 92 patients (76%) remained continuously disease-free, 2 died of chemotherapy-related toxicity and 25 suffered relapse. Projected 3-year DFS also improved (75% vs. 60%; p=0.04). Despite limb salvage, local recurrences (6.3%) and infections were few, although postoperative chemotherapy was restarted within a week. Therefore, until new effective drugs are found, expertise in using the four known drugs may improve cure rate and help to avoid amputation in almost all patients.     

Neoadjuvant chemotherapy for radioinduced osteosarcoma of the extremity: The Rizzoli experience in 20 cases

PURPOSE: Evaluate treatment and outcome of 20 patients with radioinduced osteosarcoma (RIO). Because of previous primary tumor treatment, RIO protocols were different from others we used for non-RIO. PATIENTS AND METHODS: Between 1983 and 1998, we treated 20 RIO patients, ages 4-36 years (mean 16 years), with chemotherapy (two cycles before surgery, three postoperatively). The first preoperative cycle consisted of high-dose Methotrexate (HDMTX)/Cisplatinum (CDP)/Adriamycin (ADM) and the second of HDMTX/CDP/Ifosfamide (IFO). The three postoperative treatments were performed with cycles of MTX/CDP; IFO was used as single agent per cycle repeated three times. RESULTS: Two patients received palliative treatment because their osteosarcoma remained unresectable after preoperative chemotherapy. The remaining 18 patients had surgery (7 amputations, 11 resections); histologic response to preoperative chemotherapy was good in 8 patients, poor in 10. At a mean follow-up of 11 years (range, 7-22 years), 9 patients remained continuously disease-free, 10 died from osteosarcoma and 1 died from a third neoplasm (myeloid acute leukemia). These results are not significantly different from those achieved in 754 patients with conventional osteosarcoma treated in the same period with protocols used for conventional treatment. However, this later group had an 18% 3-year event-free survival after treatment of relapse vs. 0% in the RIO group. CONCLUSION: Treated with neoadjuvant chemotherapy RIO seem to have an outcome that is not significantly different from that of comparable patients with conventional primary high grade osteosarcoma (5-year event-free survival: 40% vs. 60%, p = NS; 5-year overall survival 40% vs. 67%, p < 0.01).     

Neoadjuvant chemotherapy for osteosarcoma of the extremity: long-term results of the Rizzoli's 4th protocol

From January 1993 to March 1995, 162 patients with osteosarcoma of extremities were treated according to the IOR/OS-4 protocol. 133 patients had localised disease, while 29 had metastases at diagnosis. These last patients were simultaneously operated upon for their primary and metastatic lesions. Chemotherapy consisted preoperatively of two cycles of high dose methotrexate (HDMTX) and one cycle each of cisplatin (CDP)-doxorubicin (ADM), CDP/ifosfamide (IFO) and IFO/ADM. After surgery, patients were treated with the aforementioned drugs used as single agents. The mean follow-up of all patients was 6.5 years (5.5-8 years). Surgery was a limb salvage in 94% of cases, and the 5-year event-free survival (EFS) and overall survival (OS) rates were 56 and 71% for patients with localised disease, and 17 and 24% for patients with metastases at diagnosis. These results did not differ from those achieved in our previous study (IOR/OS-3) in which IFO was used only postoperatively in poor responders.     

Neoadjuvant chemotherapy in malignant fibrous histiocytoma of bone and in osteosarcoma located in the extremities: Analogies and differences between the two tumors

Background: Malignant fibrous histiocytoma (MFH) is a rare bone tumor usually treated like osteosarcoma. Studies on analogies and differences between the two tumors have seldom been reported.Patients and methods: Between March 1982 and December 1994, 51 patients with high-grade MFH of bone and 390 with high-grade osteosarcoma were treated with the same regimen of neoadjuvant chemotherapy. All of the tumors in both groups were located in the limbs. Preoperative chemotherapy was performed according to three different, successively activated, regimens consisting of MTX/CDP intraarterially, MTX/CDP/ADM, and MTX/CDP/ADM//IFO.Results: The rate of limb salvage was the same in both the MFH (92%) and osteosarcoma (85%) patients. MFH showed a statistically significantly lower rate of good histologic response, 90% or more tumor necrosis (27% vs. 67%, P = 0.00001) for all three regimens. Despite this low chemosensitivity, the disease-free survivals of the two neoplasms were similar (67% vs. 65%).Conclusions: In terms of histologic response to primary chemotherapy, MFH has a lower chemosensitivity than osteosarcoma. Nevertheless, the two tumors have similar prognoses when treated with chemotherapy regimens based on MTX, CDP, ADM and IFO.     

Carboplatin and Doxorubicin in Treatment of PediatricOsteosarcoma: A 9-year Single Institute Experience in theNorthern Region of Thailand

Background: Osteosarcoma is the most common primary bone tumor in childhood and adolescence.Carboplatin, a platinum-derived agent, is used as neoadjuvant chemotherapy for pediatric osteosarcoma becauseof its anti-tumor activity and had low toxicity as compared to cisplatin. Objective: To determine demographic data,prognostic factors and outcome of childhood osteosarcoma treated with a carboplatin-based chemotherapeuticprotocol at Chiang Mai University. Method: A retrospective analysis was conducted on 34 osteosarcoma patientsaged less than 18 years and treated between 2003 and 2011. Results: Overall limb-salvage and amputation rateswere 23.5% and 70.6%, respectively. With the mean follow-up time of 29.5 months (1.5-108.9), the Kaplan-Meieranalysis for 3-year disease-free survival (DFS) and 3-year overall survival (OS) were 20.2±7.7% and 47.1±9.5%respectively. Patients who had initial pulmonary metastasis were at significantly greater risk for developingrecurrence (p=0.02, OR=7; 1.2-40.1) and had a tendency to have lower 3-year OS compared to those withoutinitial pulmonary metastasis (28.1±13%, 63.1±12.3%, respectively, p=0.202). On univariate analysis, age at diagnosis >14 years and patients who were declined surgery were significantly associated with lower 3-year OS (p=0.008 and <0.05, respectively). However, age at diagnosis, sex, tumor size and histological subtypes were not found to significantly affect recurrence or survival. Conclusions: In our study, the survival rate was far lower than those reported from developed countries. These might indicate the ineffectiveness of carboplatin in combination with doxorubicin as frontline treatment of pediatric osteosarcoma, especially in those with initial pulmonary metastasis.Refinement in risk and treatment stratification and dose intensification for pediatric osteosarcoma constitutes a future challenge to improve outcomes, especially in metastatic patients who may need a more intensive regimen.     

Long-term follow-up and post-relapse survival in patients with non-metastatic osteosarcoma of the extremity treated with neoadjuvant chemotherapy

Background: Most of the studies of the treatment of non-metastaticosteosarcoma of the extremity have reported results in terms of probabilityof survival up to five years with a minimum follow-up of less than two tothree years. Definition of reliable indicators of prognosis and predictivefactors for survival require mature data derived from a long-term survivalanalysis.Patients and methods: A review of 127 patients with non-metastaticosteosarcoma of the extremity, treated between March 1983 and June 1986, wasperformed. The treatment protocol consisted of primary chemotherapy with MTX(randomization to high vs. moderate dosages) and CDP followed by surgery.Postoperatively, patients with <60% tumor necrosis received ADMand BCD; those with tumor necrosis 60% < 90% (FairResponders FR) were given MTX, CDP and ADM. Up to January 1984, patientswith tumor necrosis >90% received MTX and CDP only, and after thenthey were given the same treatment as for FR. A multivariate analysis totest predictive factors for survival was performed.Results: With a median follow-up of 134 months (range 114–153), the12-year DFS was 46%. A good histologic response, an LDH baselinevalue within the normal range, and the use of high-dose MTX were positivepredictive factors for DFS. With a median time of observation for survivorsof 130 months, the 12-year overall survival was 53%. None of thepatients who relapsed with local or distant recurrences other than lungmetastasis are now alive. Patients with a relapse-free interval longer than24 months had a significantly better post-relapse survival than those with ashorter relapse-free interval (40% vs. 7%; P = 0.0159). All ofthe patients who were not surgically treated had disease progression anddied within 40 months after the first recurrence. The surgically-treatedpatients had a 30% post-relapse survival probability.Conclusions: In non-metastatic osteosarcoma of the extremity,chemotherapy-induced tumor necrosis, the baseline LDH serum value and the useof HDMTX are significant predictive factors for DFS. The relapse-free intervaland the possibility of metastasectomy are significant factors conditioning thepost-relapse survival.     

局部进展期直肠癌术前3DCRT与VMAT同期化疗远期疗效比较

目的:比较术前三维适形放疗(3DCRT)与容积调强弧形治疗(VMAT)同期化疗用于局部进展期直肠癌(LARC)的5年总生存(OS)及无进展生存(DFS)结果,并分析该新辅助模式下的诱导/巩固化疗的价值。方法:回顾收集2007—2013年间在中山大学肿瘤防治中心接受术前3DCRT或VMAT同期联合化疗(主要为Xelox方...     

足叶乙甙联合氨甲喋呤治疗骨肉瘤的实验研究

目的探讨足叶乙甙联合氨甲喋呤治疗骨肉瘤的理论和实验依据,为临床设计新的化疗方案奠定基础。方法应用MTT比色法测定足叶乙甙及氨甲喋呤对OS-732和R-OS-732细胞活性的影响,比较两种化疗药物对骨肉瘤细胞的敏感性。应用免疫组化检测TOPO-Ⅱ在骨肉瘤中的表达。临床在采用日本国立癌中心化疗方案的基础上联合应用足叶乙甙治疗骨肉瘤5例,随访2～5年。结果氨甲喋呤的IC50值,OS-732为596.85mg/ml±0.85;R-OS-732为5170.965mg/ml±1.45(OS-732与R-OS-732相比差异显著P<0.05)。而足叶乙甙的IC50值,OS-732O1.25ug/ml±0.04;R-OS-732为1.45ug/ml±0.03(OS-732与R-OS-732相比差异不显著P>0.05)。TOPO-Ⅱ在骨肉瘤术前化疗组明显高于术前无化疗组,分别为60%(3/5)和40%(2/5)。经足叶乙甙联合氨甲喋呤治疗的5例骨肉瘤均存活,最长存活5年,其他仍在随访中。结论足叶乙甙联合氨甲喋呤治疗骨肉瘤是有效的,尤其是对于复发病例效果会更好。     

甲氨蝶呤、顺铂、阿霉素和异环磷酰胺治疗ⅡB期肢体骨肉瘤的临床观察

目的 观察大剂量甲氨蝶呤（MTX）、顺铂（DDP）、阿霉素（ADM）和异环磷酰胺（IFO）4种药物两种不同组合方案治疗ⅡB期肢体骨肉瘤的疗效及毒副反应。方法 回顾性分析接受4种药物化疗方案的185例ⅡB期肢体骨肉瘤患者,其中93例接受意大利IOR-OS／N-5方案（MTX 8～12g／m²静滴6h,d₁;用药后12h亚叶酸钙解救12次,每次15mg;DDP 80～100mg／m²、ADM 60mg／m²静滴,d8;IFO 2.0g／m²静滴,d₂₁～d₂₅;美司那400mg每天IFO用后第0、4、8h静滴）,92例接受优化方案（除ADM由第8天静滴改为第21天与IFO联用外,其他同IOR-OS／N-5方案）。比较两种方案的疗效及毒副反应。结果 IOR-OS／N-5方案和优化方案组的保肢率分别为52.7％（49／93）和58.7％（54／92）。两组患者的3年复发率分别为14.0％、7.6％,3年转移率分别为47.3％、30.4％,差异均有统计学意义（P＜0.05）;两组患者的3年生存率分别为57.0％、75.0％,差异有统计学意义（P＜0.05）。两组患者的中位无病生存时间（DFS）分别为22.2个月（95％CI：16.2～28.2个月）和29.0个月（95％CI：23.8～34.3个月）,差异有统计学意义（P=0.024）;两组患者的中位总生存时间（OS）分别为32.2个月（95％CI：23.2～38.2个月）和36.1个月（95％CI：33.8～44.3个月）,差异有统计学意义（P=0.032）。两组患者的主要毒副反应为肝功能损害、骨髓抑制、恶心呕吐等。其中3、4级肝功能损害的发生率分别为35.2％、16.6％,3、4级白细胞减少的发生率分别为22.6％、30.2％。结论 将大剂量MTX、DDP、ADM和IFO这4种药物进行优化组合治疗骨肉瘤患者的耐受性好,疗效提高。     

局部晚期食管鳞癌术前同期放化疗疗效及预后因素分析

目的评价局部晚期食管鳞癌术前同期放化疗治疗效果和影响预后的因素。方法回顾分析2007-2017年郑州大学附属肿瘤医院收治的148例经术前同期放化疗并手术治疗的局部晚期食管鳞癌患者资料,化疗采用氟尿嘧啶+顺铂或紫杉醇+顺铂方案,放疗剂量为36~40Gy,常规分割。Kaplan-Meier法计算生存率并Logrank检验及单因素分析,Cox模型多因素分析。结果全组1、3、5年总生存率分别为74%、51%、51%,无瘤生存率分别为60%、51%、45%;中位生存期为72.4个月,无瘤生存期为60.1个月。pCR与非pCR的1、3、5年总生存率分别为86%、70%、70%与70%、44%、43%(P=0.002),无瘤生存率分别为76%、71%、68%与53%、43%、37%(P=0.002)。pN(-)与pN(+)的1、3、5年总生存率分别为83%、56%、55%与50%、38%、38%(P=0.004),无瘤生存率分别为66%、56%、51%与43%、38%、31%(P=0.006)。多因素分析显示是否pCR和pN状态是影响总生存和无瘤生存的因素(P=0.012、0.011和P=0.025、0.033)。结论术前同期放化疗治疗局部晚期食管鳞癌疗效显著,是否pCR和pN状态是预后影响因素。     

Progress in the prognosis of adult Hodgkin's lymphoma in the past 35 years through clinical trials in Argentina: a GATLA experience

The purpose of this study was to evaluate the trends in complete remission (CR) rate, disease-free survival (DFS), and overall survival (OS) through 35 years of Grupo Argentino de Tratamiento de la Leucemia Aguda (GATLA) clinical trials. A total of 1,254 adult patients with Hodgkin's Lymphoma were evaluated according to seven consecutive protocols. This 35-year study was divided into three phases. The patients in the first phase (1968-1985) were treated with CVPP (cyclophosphamide/vinblastine/procarbazine/prednisone) plus involved-field radiotherapy (IFRT). In the CVPP regimen, cyclophosphamide and vinblastine were administered intravenously on day 1 and prednisone and procarbazine were administered orally on days 1-14 every 28 days. The second phase (1986-1996) used mainly reinforced CVPP with cyclophosphamide and vinblastine on days 1-8 plus IFRT. The third phase (1997-2003) used ABVD(doxorubicin/bleomycin/vinblastine/dacarbazine) plus IFRT. In clinical stage I/II, the CR rate was 86% in 252 patients treated in the first phase and DFS and OS were 57% and 78% at 5 years and 50% and 71% at 10 years. The second phase had 148 patients with clinical stage I/II disease, and the CR rate was 91%, 5-year DFS and OS were 78% and 90%, and 10-year DFS and OS were 70% and 83%. The third phase had 182 patients with clinical stage I/II disease, and the CR rate was 95%, 5-year DFS and OS were 87% and 96%, and 10-year DFS and OS were not reached. The statistical difference was P = 0.016 in terms of CR and P < 0.001 in terms of DFS and OS. In the first phase of 394 patients with clinical stage III/IV disease, the CR rate was 71%, DFS and OS at 5 years were 37% and 62%, and DFS and OS at 10 years were 32% and 53%. In the second phase of 164 patients with clinical stage III/IV disease, the CR rate was 84%, DFS and OS at 5 years were 66% and 80%, and DFS and OS at 10 years were 60% and 75%. In the third phase of 114 patients with clinical stage III/IV disease, the CR rate was 88% and DFS and OS at 5 years were 60% and 90%. The DFS and OS were not reached at 10 years. The differences among the 3 phases in CR, DFS and OS were highly significant (P < 0.001).     

辅助化疗和单纯手术治疗胰腺癌远期疗效的Meta分析

运用Meta分析评价辅助化疗和单纯手术对可切除胰腺癌的远期疗效。方法:通过MEDLINE、EBM、CBM数据库及ASCO论文集检索1969年至2011年相关文献。Jadad质量记分法评价纳入研究的质量,治疗组为可切除胰腺癌根治术后辅助化疗,对照组仅行根治性手术,Meta分析评价两组生存率（1、3、5年）及无病生存率（1、3、5年）的差异。结果:6项研究入选,共1 019例患者,分为治疗组515例,对照组504例。治疗组与对照组比较,1年生存率提高4%（P=0.400）,差异无统计学意义;3、5年生存率分别提高8%（P=0.001）、6%（P=0.000 9）,差异有统计学意义。1、3年无瘤生存率分别提高23%（P<0.000 01）、8%（P=0.006）,差异有统计学意义;5年无瘤生存率提高3%（P=0.110）,差异无统计学意义。结论:与单纯手术相比,辅助化疗可提高胰腺癌根治术后的3、5年生存率和1、3年无瘤生存率,但不能提高1年生存率和5年无瘤生存率。      

Survivin and EPR-1 expression in acute leukemias: prognostic significance and review of the literature

The aim of this study is to detect the biologic and/or prognostic significance of survivin (S) and effector protease receptor 1: EPR-1 (E) expression in acute leukemias (34 ALL and 40 AML) by using RT-PCR. S and E expressions were found in 83.8 and 20.3% of the cases, respectively. S was detected in 90%, 76.5% and E was detected in 17.5%, 23.5% of the cases with AML and ALL, respectively. There was a significant correlation between S and E (r=0.30 p=0.01). Mortality rate was higher in E(-) cases than E(+) cases (83.1 % versus 66.7%) (p=0.04). The median DFS and OS rates were shorter in S(+) and E(-) cases. In subgroup analysis, there was not a significant difference for OS between S(-) and S(+) cases and E(-) and E(+) cases in ALL group. The median OS rate was significantly longer in S(-) cases than S(+) cases, and longer in E(+) cases than E(-) in AML groups (p=0.04, 0.001, respectively). OS and DFS rates were longest in S(-) E(+) cases and shortest in S(+) E(-) cases (p=0.04 and 0.03, respectively). In multivariate analyses EPR1 negativity was found to be an independent poor risk factor for survival (OR: 2.4, p=0.02). In conclusion S expression is a bad prognostic indicator in cases with acute leukemia especially in AML. S negativity and E positivity show good clinical outcome in acute leukemias. E expression is important due to its property of the possible natural anti-sense of the S.     

Early or up-front radiotherapy improved survival of localized extranodal NK/T-cell lymphoma, nasal-type in the upper aerodigestive tract

PURPOSE: To investigate the role of early or up-front radiotherapy (RT), the optimal RT dose required to achieve appropriate treatment outcome and prognostic factors for patients with localized extranodal NK/T-cell lymphoma, nasal-type, in the upper aerodigestive tract. METHODS AND MATERIALS: Eighty-two patients were reviewed. Eight patients were treated with chemotherapy (CT) alone, 9 patients received RT alone, and 65 patients were given combined modality treatment of CT and RT (CMT). Of those 74 patients receiving RT, 31 patients were given up-front RT, whereas CT was the initial therapy for 43 patients and 41 of those 43 patients received early RT. RESULTS: Five-year overall survival (OS) and disease-free survival (DFS) were 52.3% and 39.2%, respectively. RT was the only independent prognostic factor for both OS and DFS at both the univariate and multivariate level. The 5-year OS and DFS were better in patients receiving >or=54 Gy of RT as compared with that of <54 Gy (5-year OS 75.5% vs. 46.1%, p = 0.019; 5-year DFS 60.3% vs. 33.4%, p = 0.004). Up-front RT presented better survival in Stage I patients when compared with that of initial CT followed by early RT (5-year OS 90.0% vs. 48.9%, p = 0.012; 5-year DFS 78.7% vs. 39.9%, p = 0.021). CONCLUSION: Early or up-front RT had an essential role in improved OS and DFS in patients with localized extranodal NK/T-cell lymphoma, nasal-type, in the upper aerodigestive tract. The recommended tumor dose was at least 54 Gy. Up-front RT may yield more benefits on survival in patients with Stage I disease.     

蟾毒灵诱导骨肉瘤U-2OS和U-2OS/MTX300细胞系的凋亡

目的 研究蟾毒灵对人骨肉瘤细胞株的增殖抑制和诱导凋亡作用.方法 以不同浓度的蟾毒灵分别作用于骨肉瘤细胞U-2OS和甲氨蝶呤(MTX)耐药骨肉瘤细胞U-2OS/MTX300.采用四甲基偶氮唑蓝(MTT)法检测细胞增殖,Hoechst 33258荧光染色检测细胞凋亡,流式细胞仪检测细胞周期,DNA琼脂糖凝胶电泳检测DNA ladder凋亡条带,Western blot法检测凋亡相关蛋白p53、bax和bcl-2的表达.结果 蟾毒灵能明显抑制骨肉瘤细胞的增殖,其对U-2OS和U-2OS/MTX300细胞的IC50值分别为(8.49±2.1)ng/ml和(10.19±1.7)ng/ml(P＞0.05).蟾毒灵处理U2OS和U-2OS/MTX300细胞48 h后,细胞均出现明显的染色质凝集,有典型的凋亡小体产生.同时,蟾毒灵能诱导骨肉瘤细胞凋亡,其作用机制是通过阻滞细胞周期于G2/M期、上调p53、bax表达和下调bcl-2的表达来实现.结论 蟾毒灵能显著抑制人骨肉瘤细胞U-2OS和U-2OS/MTX300的生长,并诱导细胞凋亡,其抗骨肉瘤作用不受MTX耐药的影响.     

Perineural invasion is a prognostic factor in stage II colorectal cancer but not a treatment indicator for traditional chemotherapy: a retrospective cohort study

BackgroundPerineural invasion (PNI) is considered a risk factor of survival but does not yet inform treatment decisions, and has not been studied separately in stage II colorectal cancer (CRC) patients whose postoperative traditional chemotherapy is controversial. This cohort study aimed to assess the association of PNI with basic clinicopathological features and patient outcomes after curative resection and the effects of PNI on responses to adjuvant chemotherapy in stage II CRC.MethodsThe clinical data of 371 stage II CRC patients who underwent curative-intent surgery at the National Cancer Center/Cancer Hospital in 2014 were retrospectively reviewed. The adjuvant chemotherapy data were acquired from follow-up information. PNI status was examined, and the overall survival (OS) and disease-free survival (DFS) rates were analyzed.ResultsPNI was detected in 82 of the 371 patients (22.1%) and was closely correlated with preoperative serum carcinoembryonic antigen (CEA) levels (P=0.030), gross tumor type (P=0.010), tumor differentiation (P=0.010), p stage (P<0.001), and extramural vascular invasion (EMVI) (P<0.001). The median follow-up time was 71 months. The 5-year OS was 84.1% and 96.5% (P<0.001), and the 5-year DFS was 75.6% and 91.3% (P<0.001) for PNI-positive (+) and PNI-negative (−) patients, respectively. The multivariate regression analyses identified PNI as an independent negative prognostic factor for DFS [hazard ratio (HR): 2.95; 95% confidence interval (CI), 1.546–5.626; P=0.001] and OS (HR: 3.966; 95% CI, 1.642–9.575; P=0.002). Among PNI (+) patients, DFS and OS were positively correlated with CEA levels (P=0.005 and P=0.004, respectively). Postoperative chemotherapy failed to improve DFS (P=0.480 and P=0.267, respectively) and OS (P=0.940 and P=0.077, respectively) regardless of whether the patients were PNI positive or not.ConclusionsIn stage II CRC patients, PNI was a poor independent predictor for DFS and OS. Among PNI (+) patients, CEA levels were positively correlated with DFS and OS. Traditional postoperative adjuvant chemotherapy does not improve outcomes of PNI (+) patients. Therefore, as to the active role of PNI and vacancy for treatment in allusion to PNI, follow-up of PNI (+) patients with elevated CEA level should be strengthened and further research on drug conducted on PNI deserve to be carried on.     

ER(-)PR(+)乳腺癌辅助内分泌治疗的疗效

背景与目的：孕激素受体（PR）状态是雌激素受体（ER）状态预测乳腺癌辅助内分泌治疗的补充，临床上推荐ER阳性（＋）或PR（＋）患者均可接受内分泌治疗。ER阴性（-）PR（＋）肿瘤应用辅助内分泌治疗的疗效如何还存在争议。本研究将探讨辅助内分泌治疗对ER（＋）PR（＋）与ER（-）PR（＋）乳腺癌的疗效，并研究ER（-）PR（＋）患者的临床病理特性及预后。方法：回顾了1991年1月-2001年12月间的1863位ER／PR资料可用的可手术乳腺癌患者资料，ER、PR均采用免疫组化法检测。中位随访48个月，比较ER（-）PR（＋）组（205例）和ER（＋）PR（＋）组（798例）接受或不接受辅助内分泌治疗（3～5年的他莫昔芬）的无病生存（DFS）和总生存（0s）的差异。结果：ER（-）PR（＋）患者占全部乳腺癌患者的11．0％，中位年龄49岁，肿块中值大小3．0cm，其中未绝经者比例高达63．9％。ER（-）PR（＋）组较ER（＋）PR（＋）组而言，腋淋巴结转移数高、肿块大、分期晚。ER（＋）PR（＋）组和ER（-）PR（＋）组未行内分泌治疗时，组间生存差异无显著性；内分泌治疗后，两组的生存率均有所提高，但ER（＋）PR（＋）组的预后比ER（-）PR（＋）组更好（DFS：P=0．016，OS：P=0．007）。多因素分析显示对ER（-）PR（＋）患者，仅有腋淋巴结状态是独立的预后指标。结论：辅助内分泌治疗对ER（＋）PR（＋）乳腺癌的疗效优于对ER（-）PR（＋）乳腺癌的疗效，ER（-）PR（＋）患者能从内分泌治疗中得到一定收益，但较有限。     

Primary central nervous system lymphoma treated with high-dose methotrexate, high-dose busulfan/thiotepa, autologous stem-cell transplantation and response-adapted whole-brain radiotherapy: results of the multicenter Ostdeutsche Studiengruppe Hamato-Onkologie OSHO-53 phase II study.

BACKGROUND: We investigated the efficacy and safety of tandem high-dose methotrexate (HD-MTX) induction followed by high-dose busulfan/thiotepa (HD-BuTT) with autologous peripheral blood stem-cell transplantation (aPBSCT) and response-adapted whole-brain radiation therapy (WBRT) in patients with newly diagnosed primary central nervous system lymphoma. PATIENTS AND METHODS: Twenty-three patients were treated with HD-MTX on days 1 and 10. In case of at least a partial remission (PR), HD-BuTT followed by aPBSCT was given. Patients without response to induction or without complete remission (CR) after HD-BuTT received WBRT. RESULTS: Sixteen patients received HD-MTX and HD-BuTT achieving a CR/PR rate of 69%/13%. CR/PR rates for all patients (n = 23) were 70%/13%. There were three deaths during therapy. With longer follow-up three neurotoxic deaths occurred in irradiated patients (n = 9), while no persistent neurotoxicity was seen after HD-BuTT without subsequent WBRT. At a median follow-up of 15 months (range 1-69) median event-free survival (EFS) and overall survival (OS) for all patients were 17 and 20 months (Kaplan-Meier), after HD-BuTT 27 months and "not reached", respectively. Estimated 2-year EFS and OS were 45% and 48% for all patients versus 56% and 61% for the HD-BuTT group, respectively. CONCLUSION: MTX induction followed by HD-BuTT is an effective and very short time-on-treatment regimen. Median survival for patients treated with high-dose chemotherapy is not reached yet. The induction regimen needs optimisation. In this study WBRT was associated with a high incidence of severe neurotoxicity.     

Combined analysis of HPV-DNA, p16 and EGFR expression to predict prognosis in oropharyngeal cancer

Molecular prognostic indicators for oropharyngeal squamous cell carcinoma (OSCC), including HPV-DNA detection, epidermal growth factor receptor (EGFR) and p16 expression, have been suggested in the literature, but none of these are currently used in clinical practice. To compare these predictors, 106 newly diagnosed OSCC for the presence of HPV-DNA and expression of p16 and EGFR were analyzed. The 5-year disease-free survival (DFS) and overall survival (OS) were calculated in relation to these markers and a multivariate Cox analysis was performed. Twenty-eight percent of the cases contained oncogenic HPV-DNA and 30% were positive for p16. The p16 expression was highly correlated with the presence of HPV-DNA (p < 0.001). Univariate analysis of the 5-year DFS revealed a significantly better outcome for patients with p16-positive tumors (84% vs. 49%, p = 0.009). EGFR-negative tumors showed a tendency toward a better prognosis in DFS (74% vs. 47%, p = 0.084) and OS (70% vs. 45%, p = 0.100). Remarkable and highly significant was the combination of p16 and EGFR expression status, leading to 5-year DFS of 93% for p16+/EGFR- tumors vs. 39% for p16-/EGFR+ tumors (p = 0.003) and to a 5-year OS of 79% vs. 38%, respectively (p = 0.010). In multivariate analysis p16 remained a highly significant prognostic marker for DFS (p = 0.030) showing a 7.5-fold increased risk for relapse in patients with p16-negative tumors. Our data indicate that p16 expression is the most reliable prognostic marker for OSCC and further might be a surrogate marker for HPV-positive OSCC. HPV+/p16+ tumors tended to have decreased EGFR expression, but using both immunohistological markers has significant prognostic implications.     

147例鼻咽癌调强放疗结果分析

目的 总结我院鼻咽癌调强放疗的经验和结果.方法 5年内采用调强放疗初程鼻咽癌患者147例.T1-2期38例鼻咽原发病变靶区(GTVnx)和阳性淋巴结(GTVnd)的处方剂量为70.0～72.6 Gy,高危区(CTV1)处方剂量为60Gy,低危区(CTV2)处方剂量为50Gy.T3-4期109例GTVnx74`78Gy,其他靶区处方剂量同T1-2期.局部控制率、生存率用Kaplan-Meier方法计算.结果 中位随访时间15个月,全组3年局部控制率、总生存率、无瘤生存率和无远转生存率分别为93.2%、93.5%、72.6%～1174.4%,T1-2、T3-4期局部控制率分别为100%和86.9%(P=0.007),总生存率为95.5%和91.3%(P=0.030).N0-1和N2-3期的总生存率、无瘤生存率、无远转生存率分别为99%和68.5%(P=0.030)、79%和64.O%(P=0.004)、81%和65.2%(P=0.000).急性腮腺功能损伤1+2级为96.6%,3级为1.4%,2级发生于放疗后3、6个月和1、2年的分别为43.0%、12.O%和4.9%、3.2%.结论 鼻咽癌凋强放疗方案取得了很好的疗效同时保护了腮腺功能.