Adult nephroblastoma--five cases treated by surgery, radiotherapy and chemotherapy

Nephroblastoma in adults is rare; consequently very little experience of treatment for adult cases has been reported. We report five cases of adult nephroblastoma managed by nephrectomy, radiotherapy and combination chemotherapy. The treatment schedules were derived from childhood nephroblastoma regimens. However, four of the five patients were dead within 12 months of nephrectomy and all five had progression of disease whilst on combination chemotherapy. A good prognosis should not be anticipated for adult nephroblastoma. The chemotherapy schedules which are so successful in childhood nephroblastoma may require modification to improve prognosis in adults.     

Cyclotron production of carrier-free 66Ga as a positron emitting label of albumin colloids for clinical use

A method for producing carrier free ⁶⁶Ga (T_1/2:9.4h; ⁺) by ⁴He bombardment of natural copper targets is presented. ⁶⁶Ga is formed by means of the ⁶³Cu (⁴He, n) ⁶⁶Ga reaction. Production yields are given in the 17.5 to 8 MeV ⁴He energy range. Chemical purification of ⁶⁶Ga from the copper target is described. The only radionuclidic impurity found in the final product was ⁶⁷Ga. Albumin colloids from commercially available kits designed for use with ^99mTc could easily be labeled with ⁶⁶Ga and employed for studies of the lymphatic system by positron emission tomography.     

Postoperative radiotherapy and radiotherapy combined with CCNU chemotherapy for treatment of brain gliomas

A prospective, randomized trial evaluates the effects of two postoperative treatment regimens on survival in 198 adult patients with supratentorial gliomas. All patients were irradiated with 6 000 rads after possibly radical removal of tumors. CCNU administration in the dosis of 100 mg/sq m of body surface every 6–8 weeks following surgery proved to have no significant effect on the survival of patients. The median survival time in patients receiving radiation therapy alone was 61±7 weeks, while in those receiving additional chemotherapy was 56±4 weeks. Tumor histological malignancy and patients age were found to be the only important prognostic factors, irrespective of the treatment modality. Address for offprints: T Trojanowski, Department of Neurosurgery, Medical School, Jaczewskiego 8, 20-950 Lublin, Poland     

儿童生殖细胞瘤全脑放射治疗中自适应消除摆位累积误差新技术探讨

目的 以影像引导放射治疗(image guided-radiotherapy, IGRT)为基础探讨儿童生殖细胞瘤全脑自适应放射治疗(以下简称放疗）(adaptive radio therapy,ART）可行性,为临床全脑ART提供依据。方法 回顾性研究首都医科大学附属北京天坛医院放射治疗科20例中枢神经系统生殖细胞肿瘤(germ cell tumors, GCTs)行全脑预防性照射的放疗患者。每例患者治疗前三次及后每周行一次锥形束电子计算机断层扫描(cone beam computed tomography,CBCT),共7次。记录整个治疗过程中左右(lateral, LAT)、进出(longitudinal, LNG)、升降(vertical, VRT)方向上的摆位误差值。原计划命名为Plan_A,将因摆位误差值产生新的治疗中心点(treatment center point,ISO)回归治疗计划系统,不改变射野权重、射野分布情况下进行体积剂量计算,用Plan Sum功能相加摆位累积误差产生新计划得到Plan_B。将摆位累积误差产生的新计划用Acuros XB算法重新快速优化后用Plan Sum功能相加得到Plan_C。对比Plan_A、Plan_B、Plan_C的靶区及危及器官(organ at risk, OAR)剂量变化并用Wilcoxon配对符号秩检验证统计学差异。结果与Plan_A相比,Plan_B 均匀性指均匀性指数（homogeneity index, HI）95计划靶区（planning target volume, PTV）、 HI98 PTV为1.058 4~1.084 7。适形度指数(conformity index, CI）PTV为0.934 4。 临床靶区（clinical target volume, CTV）D_min相对偏差为－7.22%,P值为0.000 7。OAR相对偏差为－0.1%~9.8%。与Plan_ A相比,Plan_ C的HI95 PTV、 HI98 PTV为1.056 9~1.078 8。CI PTV为0.936 5。CTV D_min相对偏差为－1.69%,P值为0.545 9。OAR相对偏差为－0.15%~3.40%。结论儿童生殖细胞瘤全脑放疗摆位累计误差对靶区及危及器官剂量差异有统计学意义,摆位累计误差导致靶区均匀性及适形度变差,CTV的D_min 变化超过5%,OAR受量增高。ART再计划可以让靶区均匀性和适形度及危及器官受量接近原计划。同时Plan_B虽然存在相对偏差,但是危及器官的绝对剂量在合理范围内。     

Frailty评分对枸橼酸伊沙佐米治疗多发性骨髓瘤不良反应的预测价值

目的 探讨Frailty评分对枸橼酸伊沙佐米治疗多发性骨髓瘤(multiple myeloma, MM)不良反应的预测价值。方法 选取MM患者72例,均予以枸橼酸伊沙佐米联合沙利度胺、地塞米松方案治疗,观察治疗效果及不良反应。并根据患者不良反应程度分为Ⅰ～Ⅱ级组和Ⅲ～Ⅳ级组。比较2组Frailty评分;采用Cox回归模型分析化疗相关Ⅲ～Ⅳ级不良反应的影响因素;采用ROC曲线模型分析Frailty评分对化疗相关Ⅲ～Ⅳ级不良反应的预测价值。结果 72例MM患者均实施枸橼酸伊沙佐米治疗,总有效率为80.55%;出现不良反应70例、以乏力占比最高,发生率为72.22%,其次为淋巴细胞降低25.00%、贫血18.06%,未出现任何不良反应2例。Ⅲ～Ⅳ级组Frailty评分高于Ⅰ～Ⅱ级组(P<0.05)。70例出现不良反应患者均随访12个月,其平均生存时间(22.30±2.28)个月。Cox回归分析结果显示,Frailty评分≥2分是MM患者发生Ⅲ～Ⅳ级不良反应的影响因素。ROC曲线分析显示,Frailty评分预测化疗相关Ⅲ～Ⅳ级不良反应AUC值为0.925(95%CI:0.816～1.00...     

The instability of membrane markers expressed by human monocytes and macrophages in culture

Surface markers were tested on freshly isolated human monocytes and following their in vitro maturation to macrophages. The markers tested were HLA-DR antigens, receptors for the Fc of IgG and complement as well as membrane markers defined by monoclonal antibodies. The results revealed a dynamic expression of some of the markers on monocytes which was influenced by several variables. The expression of the markers was modulated by the presence of different sera, by treatment with lymphokines and interferon and following the in vitro maturation of monocytes to macrophages. The most unstable marker was found to be the HLA-DR, which was modulated by all these variables. The 63D3 was affected by different sera and culture supernatant, as well as following the maturation of monocytes to macrophages, but not by lymphokines and interferon. One of the markers, the Mac 120, was found to be relatively stable and did not change significantly following the maturation of monocytes to macrophages. The Fc and complement receptors were also stable in their expression under these conditions, but were probably partially blocked in the presence of human serum. These results indicated that at least some of the heterogeneity related to the monocyte population was probably not due to the occurrence of stable subsets of cells, but rather to reversible changes in marker expression.     

Multiple phenotypic divergence of mammary adenocarcinoma cell clones.

We have shown that, with in vitro passage, subclones derived from clonal cell populations of 13762NF mammary adenocarcinoma undergo phenotypic drift and diversification in their cellular properties. Here we examine whether phenotypic divergence of 13762NF cell clones extends to therapeutic treatments used in eliminating mammary tumors and whether the apparent rates of phenotypic divergence vary for different treatments. Six subclones isolated from low passage clone MTF7 (T11 l; tissue culture passage 11) cells were compared to a similar number of subclones isolated from high passage clone MTF7 (T35; tissue culture passage 35) cells. Subclones derived from clone MTF7 (TI l) were relatively homogeneous (not significantly different) in their inherent sensitivities to ionizing radiation, extrapolation coefficients and quasithreshold dose values (D_o = 1·61–1·99 Gy; n=0·89–3·42; D_q = 0–2·34). When the MTF7 (Tll) subclones were examined for their sensitivities to 45°C hyperthermic treatment, the inherent sensitivities and dose-response curve parameters (D_o = 5·24–10·05 min; n = 1·08–10·47; D_q = 0·78–12·31) were heterogeneous (significantly different). In addition, the MTF7 (T1 l) subclones were heterogeneous (significantly different) in their sensitivities and dose-response curve parameters to 5-fluoro-2-deoxyuridine (FUdR) treatment (slope= –0·70 to –1·59; y-intercept = 1·31 × 10² to 47·80 × 10²). The LD₅₀ values for FUdR ranged from 14–150 nm for the MTF7 (T11) subclones. At high passage MTF7 (T35) subclones were heterogeneous in their dose-response parameters to ionizing radiation (D_o = 1·17–2·05 Gy; n = 0·80–41·18; D_q = 1·79-\24·94), hyperthermia (D_o = 3·57–6·32 min; n = 2·08–13·54; D_q = 3·68–9·30) and FUdR (slope= –0·77 to –0·93; y-intercept = 4·64 × 10² to 8·83 × 10²; LD₅₀ = 50–160nm). The results indicate that clonal cells diverge for distinct phenotypic properties at differing rates to form heterogeneous cell populations with unique sensitivities to various therapeutic treatments.     

Determining optimal two-beam axial orientations for heart sparing in left-sided breast cancer patients

BACKGROUND AND PURPOSE: The optimal intensity fluence profile of a beam depends on the profiles of other beams but most optimizations assume fixed beam orientations, a priori. Breast cancer radiotherapy attempts to cover the target and to spare critical structures such as the heart and lungs. The study aims are (1) to determine and document the optimal two-beam orientation that best spares the heart for left-sided breast cancer patients and (2) to investigate the influence of the treatment technique (i.e., conformal versus intensity modulation) on the optimal objective cost function. MATERIAL AND METHODS: Ten left-sided breast cancer patients were planned using a conformal (3DCRT) and a simplified intensity modulated (sIMRT) technique using predefined segments and different two-beam orientations. Optimal segment weights were determined exhaustively for all axial two-beam combinations, in 5 degree increments, by minimizing a quadratic objective cost function. The resulting objective cost function was analyzed with respect to target geometry and treatment technique. RESULTS: The sIMRT plans are generally less sensitive to beam orientation compared to 3DCRT plans. Optimal two-beam orientations for 3DCRT and sIMRT plans exist and they correspond to a hinge angle of approximately 188 degrees and 160 degrees or 210 degrees (the latter is bimodal), respectively. CONCLUSIONS: The optimization software is a useful tool that can test many different beam combinations and estimate their associated objective cost values. Afterwards, the most promising beam orientations could be re-optimized under the TPS to fine-tune and verify the dose distributions. Optimal uniform two-beam orientations for the breast consist of opposing tangential medial and lateral beams. Optimal nonuniform two-beam orientations for left-sided breast cancers are bimodal, containing hinge angles around 160 degrees and 210 degrees. Nonuniform beam techniques are less sensitive to beam orientation compared to uniform beam techniques and result in significantly improved heart sparing but at a cost of slightly compromised planning target volume coverage.     

Prophylaxis and treatment of experimental lung metastases in mice after treatment with liposome-encapsulated 6-O-stearoyl-N-acetylmuramyl-L-α-aminobutyryl-D-isoglutamine

A new lipophilic muramyl dipeptide analog, 6-O-stearoyl-N-acetylmuramyl-L--aminobutyryl-D-isoglutamine, when incorporated in liposomes, was effective in both the prevention and eradication of experimental pulmonary metastases in mice. Multilamellar vesicles composed of synthetic phospholipids (phosphatidylglycerol and phosphatidylcholine) containing saturated myristoyl or unsaturated dioleoyl acyl chains were found to potentiate the antimetastatic activity of this glycopeptide. Prophylactic and therapeutic efficacy was observed against the three murine tumors tested: FSa, an immunogenic fibrosarcoma; NFSa, a nonimmunogenic fibrosarcoma; and B16 melanoma. Neither the administration of empty liposomes or free glycopeptide, nor their coadministration, had a significant antimetastatic effect. This approach is promising for the therapy of cancer metastases in humans, particularly in the prevention of metastatic seeding and in the treatment of micrometastases.This is contribution No. 180 from the Institute of Bio-Organic Chemistry, Syntex Research.