重离子治疗肿瘤的两大优势

目的观察两种人恶性肿瘤细胞-人肝癌细胞SMMC-7721和人黑色素瘤细胞A375对高LET12C6+离子和γ射线照射的敏感性及分次效应,观察重离子治疗肿瘤的可行性及优势。方法以两种体外培养的来源于人体不同组织的具有高辐射抗性的恶性肿瘤细胞为实验对象,分别进行12C6+和γ射线0~6Gy内不同剂量点的单次和分次照射,采用克隆存活法统计细胞的存活分数。结果无论是单次还是分次照射,12C6+照射后两种细胞的存活分数均明显低于γ射线照射的细胞,而且重离子的分次效应明显降低。结论结果显示重离子在肿瘤治疗中的两个重要优势,即具有高的肿瘤杀伤力和低的分次效应,显示重离子照射引发的低修复现象,可使肿瘤放疗具有更高的效率。     

重离子（12 C6＋）治疗恶性黑色素瘤的临床研究现状

恶性黑色素瘤（ malignant melanoma,MM）是一种恶性程度高、迁徙能力强的皮肤肿瘤。其发病率在全球范围呈现上升趋势,正日益威胁着人类的生命健康。放射治疗在不能手术切除的恶性黑色素瘤中起着重要作用,然而MM细胞对低LET射线（ x、γ）具有显著的抗拒性限制了常规射线放疗在MM中的应用。重离子由于其特有的物理学特性和生物学优势,使其在肿瘤治疗领域展现出良好的应用前景。本文就重离子在MM中的应用做一综述。     

头颈部黏膜恶性黑色素瘤诊断与治疗进展

头颈部黏膜恶性黑色素瘤常发生于眼内、口腔、下咽、鼻腔鼻旁窦、鼻咽等部位。睫状体或脉络膜黏膜恶性黑色素瘤诊断基础是临床检查，CT，MRI，细针穿刺抽吸活检利于确诊，治疗方法为观察和局部治疗方法，如放疗、光照疗法、冷冻疗法、超声高温疗法、局部切除以及眼球摘除术。鼻腔鼻旁窦黏膜恶性黑色素瘤组织学检查是首要的诊断依据，治疗可采取：手术、化疗、免疫治疗、局部复发后采用包括外科手术切除、补充放疗、化疗、免疫治疗。口腔、鼻咽及下咽黏膜恶性黑色素瘤主要依据内窥镜及病理活检诊断，CT扫描及MRI检查利于明确病变范围及分期，可采用手术、放疗和化疗综合治疗。     

头颈部恶性黑色素瘤的临床及病理研究

目的 研究头颈部恶性黑色素瘤的临床,病理及免疫组织化学特片,以提高临床和病理诊断率,方法 收集头颈部恶性黑色素瘤（除脉络膜外）68例,其中原发于鼻腔和口腔黏膜33例,头颈部皮肤35例。发病高峰年龄为41-60岁。52例为手术切除标本,16例为活检（咬取、切除）标本。复习所有患者的临床及病理资料,并对42例进行S-100、HMB45和NSE免疫组织化学观察。结果 在68例中,手术切除者52例,其中有13例行补充放疖1例进行了化疗单纯放疗0例;抿绝治疗6例,在获得随诊的56例中,存活5年以上者12例,其中头颈部皮肤恶性黑色素瘤9例,占75.0%;鼻腔及口腔黏膜者3例外中25.0%。结论 恶性黑色素瘤在组织学结构上的改变具有重要意义;免疫组织化学对恶性黑色素瘤诊断和鉴别诊断有重要价值;发生于鼻腔和口腔黏膜的恶性黑色素瘤的预后明显比发生在头颈部皮肤的差。     

眼眶原发低度恶性粘膜相关淋巴瘤的放射治疗

目的报告6例眼眶原发低度恶性粘膜相关淋巴瘤(MAL Toma)术后放射治疗的结果.复习有关文献,探讨眼眶原发低度恶性粘膜相关淋巴瘤的病理诊断及临床特点和放射治疗的作用.方法对6例患者行术后放射治疗,6MVX线或12～16MeVβ线,单一前野+侧野照射,DT45～55Gy,常规分割.结果放疗后患者无眼损伤及并发症.局部控制良好.结论眼眶低度恶性粘膜相关淋巴瘤是非何杰金氏淋巴瘤的一个亚型,有自身的临床病理特征,应及时确诊,局部放射治疗是有效的治疗方法.     

对恶性黑色素瘤是否还提倡做大分割放射治疗

对贵刊的“八例鼻腔恶性黑色素瘤的诊断与放射治疗”(2 0 0 0 ,9(1) :6 6 6 7)一文提出一些不成熟的看法。从该文的治疗方法及末尾的讨论中可以看出作者仍推崇恶性黑色素瘤 (以下简称恶黑 )做大分割少分次放射治疗。对恶黑做大分割放射治疗确实曾一度非常风行 ,这主要是国外 70～ 80年代一些回顾性临床研究结果为大分割放射治疗提供了证据。这些临床结果的根本缺陷是肿瘤大小不均质 ,可比病例数少 ,均为转移性恶黑的姑息治疗 ,而且随访期又很短。后对较早提出大分割放射治疗的Ｏｖｅｒｇａｒｄ的资料严密检查后发现 ,做低分割者 ,总剂量太…     

头颈部黏膜恶性黑色素瘤的治疗

头颈部黏膜恶性黑色素瘤是一种高度恶性肿瘤,标准治疗措施为根治性手术,结合辅助放疗、免疫治疗、化疗被证实存在一定疗效。分子靶向研究是恶性黑色素瘤治疗的新趋势。     

直肠恶性黑色素瘤术后复发乳腺转移1例报道

恶性黑色素瘤是临床上较为常见的皮肤黏膜和色素膜恶性肿瘤,也是发病率增长最快的恶性肿瘤之一,年增长率为3％ ～5％.多发生于皮肤和眼睛,原发肛管直肠少见,是一种少见且预后极差的恶性肿瘤,约占肛管直肠恶性肿瘤的1％[1].恶性黑色素瘤转移部位多为肺、骨、肝、脑及局部复发,乳腺转移性恶性黑色素瘤极少见[2].本院于2012年10月收治了1例直肠恶性黑色素瘤术后复发乳腺转移患者,现报告如下.     

大剂量分割放射治疗恶性黑色素瘤10例

一般认为恶性黑色素瘤常规放射治疗难以控制,近年来,国外有不少作者报告采用大剂量分割放射治疗恶性黑色素瘤,自1987年以来,我们采用此法共治疗恶性黑色素瘤10例,临床初步效果尚较满意,报告如下。 临床资料:本组10例均经病理证实,男性7例,女性3例。年龄27～68岁;平均年龄:46岁。病变位于头颈部6例,其中术后复发2例均属病变广泛,估计手术切除有困难者;肢体恶性黑色素瘤术后区域淋巴结转移瘤4例。肿瘤最小0.5cm×1cm,最大10cm×13cm。     

原发鼻腔黑色素瘤24例临床分析

目的 评价鼻腔黑色素瘤的治疗方法及疗效。方法 对24例鼻腔黑色素瘤进行回顾性分析。临床分期中Ⅰ期6例，Ⅱ期6例，Ⅲ期8例，Ⅳ期4例。病理分型中巨细胞型12例，小细胞型7例，上皮样细胞型3例，梭形细胞型2例。治疗方法中单纯手术治疗12例，单纯放射治疗2例，手术加放射治疗7例，手术加化疗2例，化疗加生物治疗1例。生存分析采用Kaplam-Meier法，组间比较采用Logrank检验，率的比较采用χ^2检验。结果 6例首诊误诊，后经免疫组织化学确诊。治疗后总的3、5年生存率分别为40．9％、22．7％。单纯手术组5年生存率为33．3％，手术加放射治疗组5年生存率为16．7％，两者相比差异无显著性意义(P=0．708)，两组局部复发率差异也无显著性意义(P=0．350)。5年局部复发率为40％，5年远地转移率为16％。结论 免疫组织化学对黑色素瘤诊断和鉴别诊断有重要价值，手术不彻底是疗效不满意的主要原因，辅助放射治疗可能有助于提高局部控制率。     

The evolving role of radiation therapy in the management of malignant melanoma

The incidence of melanoma is rising in the United States, leading to an estimated 68,720 new diagnoses and 8,650 deaths annually. The natural history involves metastases to lymph nodes, lung, liver, brain, and often to other sites. Primary treatment for melanoma is surgical excision of the primary tumor and affected lymph nodes. The role of adjuvant or definitive radiation therapy in the treatment of melanoma remains controversial, because melanoma has traditionally been viewed as a prototypical radioresistant cancer. However, recent studies suggest that under certain clinical circumstances, there may be a significant role for radiation therapy in melanoma treatment. Stereotactic radiosurgery for brain metastases has shown effective local control. High dose per fraction radiation therapy has been associated with a lower rate of locoregional recurrence of sinonasal melanoma. Plaque brachytherapy has evolved into a promising alternative to enucleation at the expense of moderate reduction in visual acuity. Adjuvant radiation therapy following lymphadenectomy in node-positive melanoma prevents local and regional recurrence. The newer clinical data along with emerging radiobiological data indicate that radiotherapy is likely to play a greater role in melanoma management and should be considered as a treatment option.     

A case of recurrent malignant melanoma of esophagus responsive to combined chemotherapy, radiotherapy and cellular immunotherapy

Treatment of primary malignant melanoma of the esophagus remains challenging. We treated a 53-year-old man with pT4N2M0, Stage IVa malignant melanoma of the esophagus with esophagectomy followed by adjuvant chemotherapy. Six months later, computed tomography revealed a 12 cm disseminated tumor of the mesenterium, multiple peritoneal dissemination, and a large amount of ascites. We administered chemotherapy consisting of dacarbazine combined with cisplatin and nimustine, and radiotherapy(50 Gy)was applied to the disseminated mesenteric tumor. At another clinic, the patient was administered synchronous cellular immunotherapy consisting of dendritic cells pulsed with autologous tumor lysates and lymphokine-activated killer cells. The mesenteric tumor was extremely responsive to this trimodal treatment. Because recurrence occurred later within the left orbita muscle, we added 50 Gy of radiation to prevent blindness. The patient responded to this treatment and survived another 6 months with high quality of life. It is difficult to treat advanced malignant melanoma of the esophagus, and patient prognosis is extremely poor. In this patient, the recurrent tumors responded well to trimodal therapy consisting of chemotherapy, radiotherapy and cellular immunotherapy.     

Raising hemoglobin: an opportunity for increasing survival?

Although the association between low hemoglobin levels and poorer outcomes in radiation oncology has long been recognized, anemia is often overlooked and untreated. However, a growing body of clinical evidence now indicates that low hemoglobin levels during radiation treatment are associated with decreased response and survival following radiotherapy. For example, a large Canadian retrospective study in patients receiving radical radiotherapy for cervical cancer showed that the 5-year survival rate was 19% higher in those whose hemoglobin during radiation treatment was =12 g/dl compared to those with levels <12 g/dl. The data suggest that clinical trials need to be performed to determine whether increasing hemoglobin levels leads to improved local control and survival. The mechanism by which low hemoglobin levels could cause poorer outcomes is not well understood and needs further elucidation. It is postulated that lower hemoglobin levels resulting in decreased oxygen carrying capacity may lead to increased tumor hypoxia, radiation resistance and increased tumor angiogenesis. The interrelationship of low hemoglobin levels, hypoxia, tumor angiogenesis and survival is explored in this article.     

Chemical modifiers in radiotherapy

The halogenated pyrimidine analogue bromodeoxyuridine (BrdU), which is incorporated into nuclei during DNA synthesis, has long been known to be a radiation sensitizer. Since 1965, BAR therapy (BrdU-antimetabolite-radiation therapy), in which BrdU was administered intraarterially as a radiosensitizer, has been applied to patients with malignant gliomas and the improvement in survival rate within two years has been reported. Recently, intravenous infusion of BrdU has prove to be sufficiently effective as a radiosensitizer and BrdU is still being utilized as a chemical modifier for patients with malignant gliomas. Misonidazole was developed as a hypoxic cell sensitizer and was expected to enhance the radiation response of malignant tumors. However, the clinical trial of misonidazole in patients with brain tumors showed little clinical benefit of this agent as a radiosensitizer, and therefore it is no longer used in the treatment of malignant gliomas. Synchronized chemoradiotherapy, in which alkaloid and alkyl agents are used to accumulate cells into the radiosensitive G2 and M phases, was developed for the treatment of malignant gliomas in 1976 and significant improvement in survival has been reported. However, phase II studies demonstrated that radiotherapy with alkyl agents such as BCNU and ACNU did not prolong the survival of patients with malignant gliomas as compared with radiotherapy alone, although they did increase the response rate. Since 1985, the Brain Tumor Interferon Study Group has clinically applied one of the biological response modifiers (BRM), interferon-beta (INF-beta) as a chemical modifier in patient with malignant gliomas. They have reported that the response rates in patients treated with ACNU + radiation and INF-beta + ACNU + radiation were 19.6% and 41.2%, respectively. Their results suggested that IFN-beta with ACNU was a promising regimen as a chemical modifier in radiotherapy for patients with malignant gliomas. In order to improve the rate of local control of malignant gliomas and to prolong the survival of patients, it is necessary to continue to seek effective chemical modifiers including BRMs, as well as to develop irradiation techniques.     

The role of radiotherapy in recurrent and metastatic malignant melanoma: a clinical radiobiological study

A review of the literature and our data has been completed to analyze the clinical radiobiology of malignant melanoma. Six hundred eighteen radiotherapy-treated malignant melanoma lesions were analyzed with regard to radiobiological parameters such as total dose, dose per fraction, treatment time, tumor volume, and various fractionation models. Forty-eight per cent of the treated tumors achieved complete response, which was persistent in 87% after 5 years. Neither total dose, treatment time, nor various modifications of the NSD concept showed any well-defined correlation with response. There was, however, a significant relationship between dose per fraction and response, and a high dose per fraction yielded a significantly better response (59% CR for doses greater than 4 Gy versus 33% CR for doses per fraction less than or equal to 4 Gy). The lack of treatment time influence allowed analysis of the data according to the linear-quadratic model, resulting in an alpha/beta ratio of 2.5 Gy. Using this ratio, an iso-effect for different fractionation schedules could be estimated by the extrapolated total-dose (ETD). The ratio was further improved when corrected for the tumor volume. Thus, an iso-effect formula for malignant melanoma could be calculated as: ETDvol (Gy) = D X [d + 2.5)/2.5) X M-.33, where D and d are total dose and dose per fraction in Gy, respectively, and M is the mean tumor diameter in cm. Based on a logit analysis, a complete response level of 50% appeared at an ETDvol value of 83 Gy. The formula is currently the best way to determine an optimal radiation schedule for an effective radiation treatment of malignant melanoma. The tumor response was further improved in 134 additional cases receiving adjuvant hyperthermia. Here, a thermal enhancement ratio (TER) of 2.0 was observed. In a group of 131 patients with only local or regional disease, a 5 year survival rate of 49% was observed in 77 patients with persistent local tumor control, but only 3% survived among the 54 patients in whom local therapy failed. It is therefore, highly important to the probability of survival in recurrent melanoma that proper local treatment be performed.     

Clinical experience of carbon ion radiotherapy for malignant tumors

The carbon ion (C-ion) beams provide unique advantageous biological and physical properties in radiotherapy (RT) for malignant tumors. C-ion beams have a high relative biological effectiveness (RBE) resulting from the high linear energy transfer (LET). In terms of their physical characteristics, C-ion beams exhibit a spread-out Bragg peak (SOBP) and make for a better dose distribution of the target volume by specified beam modulations. Between June 1994 and August 2005, a total of 2,371 patients with malignant tumors were registered in phase I/II dose-escalation studies and clinical phase II trials using C-ion beams generated at Heavy Ion Medical Accelerator in Chiba (HIMAC). In the initial dose-escalation studies, grade 3 or more late rectal complications had developed in some patients. However, the adverse effects were resolved because of the use of appropriate dose levels and modification of the radiation technique. C-ion beams can carry out hypofractionated radiotherapy with a large fraction dose and reduce the overall treatment times compared with conventional radiotherapy. They can also achieve better local tumor control even for radio-resistant tumors such as malignant melanoma, hepatocellular carcinoma and bone and soft tissue sarcomas with minimal morbidity to the normal surrounding tissues.     

44例原发性鼻粘膜恶性黑色素瘤的临床特征及预后分析

背景与目的:原发性鼻粘膜恶性黑色素瘤是一种罕见肿瘤,其临床资料主要来源于西方人群。本文总结原发性鼻粘膜恶性黑色素瘤患者的临床资料,分析其临床特征和影响预后的因素。方法:回顾性分析1971年1月至2005年7月中山大学肿瘤防治中心收治的原发性鼻粘膜恶性黑色素瘤66例,其中有完整随访资料的44例。复习病历登记的临床表现和治疗方法,信件或电话随访记录肿瘤复发和患者生存情况。用Kaplan-Meier方法计算生存率,用Cox比例风险模型进行多因素分析。结果:44例有完整随访资料的患者中,37例原发于鼻腔粘膜,5例原发于副鼻窦粘膜,2例原发于鼻咽粘膜。初治时12例患者出现颈淋巴结转移。31例接受以手术为主的治疗,其中8例接受辅助性放疗,13例接受辅助性化疗,6例接受辅助性非特异性免疫治疗。中位随访时间29个月,局部复发率为54.5%(24例),10例(22.7%)患者发生颈淋巴结转移复发,11例(25%)发生远处转移。中位生存时间为24个月,5年生存率为25%。预后分析显示,临床分期影响患者5年生存率,而性别、年龄、原发肿瘤部位、原发肿瘤大小、是否接受辅助治疗与5年生存率无关。结论:原发性鼻粘膜恶性黑色素瘤局部复发率和远处转移率高,且易出现颈淋巴结转移。临床分期影响患者5年生存率。     

碳离子束治疗皮肤恶性黑色素瘤的近期疗效

目的 评价碳离子(~(12)C~(6+))束对皮肤恶性黑色素瘤放射治疗的近期疗效和副反应.方法 13例皮肤恶性黑色素瘤患者分6批接受~(12)C~(6+)束放射治疗,其中Ⅱ_a期2例,Ⅱ_b期3例,Ⅱ_c期5例,Ⅲ_c期3例.照射总剂量60～66 GyE分6～12 d,单次剂量2.2～4.4 GyE,1次/d,连续治疗.采用RTOG标准和WHO近期疗效标准分别评价副反应和近期疗效.结果 中位随访时间为13.5个月(1～25个月),随访率为100%.13例患者中完全缓解10例,部分缓解3例,有效率为100%,中位生存时间为21.3个月(95%可信区间为18.1～24.5个月).皮肤反应0级3例,1级6例,2级2例,3级2例.血液系统副反应治疗前后无明显改变.结论 ~(12)C~(6+)束治疗皮肤恶性黑色素瘤近期疗效好,且并发症轻.     

重离子束联合免疫疗法治疗恶性肿瘤的基础研究进展

近年来重离子束因其放射物理学及生物学特性在恶性肿瘤放疗方面受到高度关注。重离子治疗已经在临床上取得了一定成果,局部肿瘤控制率高是其一大优势,但在多数恶性肿瘤治疗中转移病灶的控制仍然至关重要。常规放疗与免疫疗法联合应用的临床研究提示两者联合不仅可以控制原发病灶,还有可能减少或完全消除远处转移性病灶。而高能量线性传递射线尤其是重离子束在联合免疫治疗方面可能具有更强的潜力,故本文重点综述了重离子束调节抗肿瘤免疫效应及与免疫疗法联合应用的基础研究进展。