重离子束治疗皮肤恶性肿瘤的初步临床结果

目的:评价重离子束对皮肤恶性肿瘤放射治疗的近期疗效和毒副反应.方法:29例皮肤恶性肿瘤患者分6批接受重离子束放射治疗,其中恶性黑色素瘤13例,皮肤鳞癌及Bowen's病各6例,基底细胞癌2例,其他皮肤恶性肿瘤2例.照射总剂量(50～70)GyE/(6～12)d,单次剂量5.5～11.67 GyE,1 f/d,连续治疗.采用RTOG标准和WHO近期疗效标准分别评价毒副反应和近期疗效.结果:截止2009-05,中位随访时间为13.5个月(1～25个月),随访率为100%.29例患者中完全缓解(CR)24例(82.8%),部分缓解(PR)5例(17.2%),有效率(RR)为100%,中位生存时间为22.8个月(95%CI:20.6～24.9).皮肤反应0度11例(37.9%),Ⅰ度9例(31.0%),Ⅱ度6例(20.7%),Ⅲ度2例(6.9%),Ⅳ度1例(3.4%);血液毒副反应治疗前后无明显改变.结论:重离子束(12C6+)放射治疗皮肤恶性肿瘤近期疗效好,并发症轻,远期疗效、晚期副反应等尚需进一步长期全面的观察和更多的研究提供依据.     

重离子(12C6+)束治疗肿瘤初步临床报告

目的探讨碳离子（^12C^6＋）辐射对恶性肿瘤的治疗作用，初步确定治疗安全剂量，观察其急性副反应及近期疗效。方法12例表浅肿瘤患者（受试者）分为2个组，A组5．10～8．79GyE／次，1次／d，连续9d总剂量50．94～70．41GyE；B组5．04～8．58GyE／次，1次／d，连续7d总剂量35．88～60．06GyE。采用RTOG急性放射损伤分级标准判断急性损伤并通过局部肿物缩小程度评价近期疗效。结果治疗结束随访2个月后，A、B组受试者皮肤反应发生率分别为2／4、3／8，两组无明显血液毒性和严重皮肤反应。A、B组局部肿物缩小程度≥50％分别占3／4、5／8。结论 ^12C^6＋束治疗表浅肿瘤显示出良好的安全性和近期疗效。     

重离子束(12C6+)治疗头颈部浅表肿瘤疗效观察

目的:观察采用重离子研究装置（HIRFL）引出重离子束治疗头颈部浅表肿瘤的近期疗效和急性不良反应。方法:自2007年1月至2010年10月,我院13例头颈部浅表肿瘤患者采用能量为80MeV/u～100MeV/u的碳离子(¹²⁶⁺)束进行重离子束放射治疗。总剂量46GyE～70GyE,1次/天,连续12天。应用RTOG急性放射损伤分级标准判断不良反应,应用WHO疗效标准评价近期疗效。结果:非恶黑性皮肤癌、乳头状瘤、恶性黑色素瘤有效率（CR+PR）分别为100%（9/9）、50%（1/2）和50%（1/2）,13例患者总局部控制率为85%（11/13）。皮肤不良反应发生率1、2、3度分别为30.8%（4/13）,15.4%（2/13）,15.4%（2/13）,未观察到4级皮肤不良反应。结论:重离子束放射治疗头颈部浅表肿瘤有较好的近期疗效,不良反应轻微,患者可耐受。     

三维适形放射治疗脑胶质瘤术后残存灶近期疗效分析

目的 :探讨增大分割剂量三维适形放射治疗 (3D CRT)脑胶质瘤术后残存灶的近期疗效及早期并发症的发生率。方法 :15例脑胶质瘤进入三维放射治疗组 ,其中星形细胞瘤Ⅰ～Ⅱ级 5例 ,Ⅲ级 7例 ,Ⅳ级 3例。 2～ 3Gy 次 ,1次 d ,5次 周 ,总剂量 5 1～ 6 0Gy。结果 :除 1例生存 10个月死于局部复发外 ,其余全部生存 6个月以上。其中 5例接受 3Gy分割量 ,17次照射的患者生存 11个月以上 ,无放射性脑损伤发生。结论 :大分割三维适形放射治疗脑胶质瘤残存灶患者有较好的近期疗效 ,无早期并发症 ,晚期并发症和远期疗效有待进一步观察     

碳离子射线治疗10例气管腺样囊性癌的初步临床观察

目的 观察碳离子放射治疗气管腺样囊性癌的近期疗效和不良反应。方法 2016年3月至2017年10月共收治10例气管腺样囊性癌患者,其中3例为复发患者(2例术后、1例放疗后复发),1例为Ⅰ期疾病接受气管镜下冷冻术后无明显肿瘤残留者,其余均为局部晚期患者。10例患者均采用笔形束扫描技术的碳离子放疗,1例放疗后复发患者接受了60 GyE分20次照射;1例冷冻术后患者及1例术后复发患者接受了66 GyE分22次照射,其余患者均接受了69 GyE分23次照射。结果 中位随访时间5.5个月(1.5~16.4个月)。根据RECIST 1.1标准,有可见病灶的9例患者中,3例完全缓解,2例部分缓解,4例疾病稳定。冷冻术后的1例患者无复发转移迹象。除1例患者放疗后4.5个月出现4级气管狭窄外,其余患者未见≥3级放疗反应。2级急性反应包括声音嘶哑和中性粒细胞下降各1例,均在治疗后缓解;2级晚期反应为1例甲状腺功能下降。结论 短期随访提示,碳离子射线治疗气管腺样囊性癌安全、有效。     

三维适形放射治疗脑胶质瘤术后残存灶近期疗效分析

目的：探讨增大分割剂量三维适形放射治疗(3D-CRT)脑胶质瘤术后残存灶的近期疗效及早期并发症的发生率。方法：15例脑胶质瘤进入三维放射治疗组，其中星形细胞瘤Ⅰ～Ⅱ级5例，Ⅲ级7例，Ⅳ级3例。2～3Gy／次，1次／d，5次／周，总剂量51～60Gy。结果：除1例生存10个月死于局部复发外，其余全部生存6个月以上。其中5例接受3Gy分割量，17次照射的患者生存11个月以上，无放射性脑损伤发生。结论：大分割三维适形放射治疗脑胶质瘤残存灶患者有较好的近期疗效，无早期并发症，晚期并发症和远期疗效有待进一步观察。     

重离子束（12C^6＋）治疗头颈部浅表肿瘤疗效观察

目的：观察采用重离子研究装置（HIRFL）引出重离子束治疗头颈部浅表肿瘤的近期疗效和急性不良反应。方法：自2007年1月至2010年10月,我院13例头颈部浅表肿瘤患者采用能量为80MeV／u～100MeV／u的碳离子（他C6＋）束进行重离子束放射治疗。总剂量46GyE-70GyE,1次／天,连续12天。应用RTOG急性放射损伤分级标准判断不良反应,应用WHO疗效标准评价近期疗效。结果：非恶黑性皮肤癌、乳头状瘤、恶性黑色素瘤有效率（CR＋PR）分别为100％（9／9）、50％（1／2）和50％（1／2）,13例患者总局部控制率为85％（11／13）。皮肤不良反应发生率1、2、3度分别为30．8％（4／13）,15．4％（2／13）,15．4％（2／13）,未观察到4级皮肤不良反应。结论：重离子束放射治疗头颈部浅表肿瘤有较好的近期疗效,不良反应轻微,患者可耐受。     

非小细胞肺癌调强放化疗的近期疗效观察

目的:分析调强放疗(IMRT)联合化疗治疗局部晚期非小细胞肺癌(NSCLC)的近期疗效和毒副反应.方法:48例局部晚期不能手术或不愿手术的NSCLC患者,采用IMRT同步联合化疗综合治疗.放疗采用5～7野IMRT技术,单次剂量2.0～2,2 Gy,每周5次,中位总剂量60 Gy(54～66 Gy).所有患者均接受2个周期长春瑞滨加顺铂方案同步化疗,放疗结束后辅助2～4个周期化疗.结果:所有患者均顺利完成同步放化疗计划.放疗结束3个月后评价疗效,CR为21％(10/48),PR为60％(29/48),SD为13％(6/48),PD为6％(3/48),有效率为81％(39/48).中位随访时间为11个月(7～30个月),中位生存时间为25个月,1和2年总生存率分别为73％和39％.按RTOG标准评价放疗毒副反应,放射性食管炎Ⅰ级15例,Ⅱ级11例,Ⅲ级1例;放射性气管炎Ⅰ级14例,Ⅱ级8例,Ⅲ级3例;放射性肺炎Ⅰ级6例,Ⅱ级4例,Ⅲ级1例.结论:IMRT联合化疗对局部晚期NSCLC患者有较好的疗效,毒副反应可以被绝大多数患者耐受,对生存率的提高有待进一步研究.     

适形放射治疗胰腺癌的疗效分析

目的探讨三维适形放射治疗胰腺癌的疗效及毒性.方法对21例胰腺癌患者采用三维适形放射治疗.单次剂量为2 Gy,每日照射一次,每周照射5次,总疗程6周左右,总剂量为60 Gy.结果临床获益率28.6%(6/21),疼痛完全缓解率90.5%(19/21).瘤体CR率为9.5%,PR率为52.4%,总有效率(CR PR)为61.9%(13/21).中位生存期15个月,1年生存率67.0%.治疗后出现血像下降Ⅰ～Ⅱ级者14例,Ⅲ级者1例,Ⅰ～Ⅱ级恶心、呕吐12例.结论三维适形放射治疗能够改善胰腺癌患者的生活质量,提高生存率.     

30例原发于眼眶恶性淋巴瘤的放疗疗效

目的:分析原发于眼眶恶性淋巴瘤的放射治疗方法.方法:30例原发于眼眶恶性淋巴瘤均为非霍奇金淋巴瘤.Ann-Arbor分期:Ⅰ a期21例,Ⅱa期9例.放射治疗剂量30～58Gy,3～6周.结果:1、3、5年局部控制率分别为96.7%、93.3%和90.0%.随诊3、5、10年生存率分别为100%、93.30%和76.7%,5例疾病进展.结论:局部放射治疗是原发于眼眶恶性淋巴瘤有效的治疗方法,放射治疗剂量为34～45Gy,3.5～4.5周;低度恶性放射剂量为30～35Gy,不需行淋巴引流区预防照射.对恶性程度高及有外侵犯者应辅加化疗.     

Palliative radiotherapy for recurrent and metastatic malignant melanoma: prognostic factors for tumor response and long-term outcome: a 20-year experience.

PURPOSE: Radiotherapy is used as a "last resort" for patients with advanced cutaneous malignant melanoma. We have analyzed our 20-year clinical experience with respect to different endpoints and prognostic factors in patients with locally advanced, recurrent, or metastatic malignant melanoma. METHODS: From 1977 to 1995, 2,917 consecutive patients were entered in the melanoma registry of our hospital. Radiotherapy was indicated in 121 patients (56 females, 65 males) for palliative reasons in advanced malignant melanoma stages UICC IIB/III/IV. The histology of the primary lesion was nodular in 51 patients, superficial spreading in 35, acral-lentiginous in 8, and lentigo maligna melanoma in 4 patients. Eleven patients had primary or recurrent lesions which were either not eligible for surgery or had residual disease (R2) after resection of a primary or recurrent lesion (UICC IIB); 57 patients had lymph node (n = 33) or in-transit metastases (n = 24) (UICC III), and 53 had distant organ metastases (7 M1a; 46 M1b) (UICC IV). Time from first diagnosis to on-study radiotherapy averaged 19 (median: 18; range: 3-186) months. In most cases, conventional RT was applied with 2-6 Gy single fractions up to a median total radiation dose of 48 (mean: 45; range: 20-66) Gy. RESULTS: At 3 months follow-up, complete response (CR) was achieved in 7 (64%) and overall response [complete (CR) and partial response (PR)] in all (100%) UICC IIB patients, in 25 (44%) and 44 (77%) of 57 UICC III patients, and in 9 (17%) and 26 (49%) of 53 UICC IV patients. Tumor progression during radiotherapy occurred in 25 (21%) patients. Patients with CR survived longer (median: 40 months) than those without CR (median 10 months) (p < 0.01). At last follow-up (Dec 31, 1996), 26 patients were still alive: 6 (55%) UICC IIB, 17 (30%) UICC III, and 3 (6%) UICC IV patients (p < 0.01). Univariate analysis revealed the following prognostic factors for complete response and long-term survival: UICC stage (p < 0.001), primary location in the head and neck region, total radiation dose above 40 Gy (all p < 0.05), while age, gender, and histology had no impact. In multivariate analysis, UICC stage was the only independent prognostic factor (p < 0.001). CONCLUSION: External beam radiotherapy can provide long-term local control and effective palliation in malignant melanoma UICC stages IIB-IV. The current UICC staging system is an excellent prognostic factor for initial and long-term tumor response in metastatic melanoma. Therefore, prospective randomized trials using external radiotherapy with or without adjuvant therapy for advanced malignant melanoma are justified.     

恶性黑色素瘤的生物治疗和生物化疗

OBJECTIVE: To evaluate the efficacy of postoperative biochemotherapy on survival of patients with malignant melanoma. METHODS: One hundred and five patients with malignant melanoma received postoperative biotherapy/biochemotherapy or radiotherapy/chemotherapy. The median time of follow-up was 3 years (from 1 to 5 years). RESULTS: The median survival time (MST) in the whole series of patients was 27 months (range: 2-72 months). The MST in patients received postoperative biotherapy/biochemotherapy (57 cases) was 32 months with a 3-year survival rate of 36.8%. That in patients received postoperative radiotherapy/chemotherapy (54 cases) was 20 months. CONCLUSION: Biotherapy/biochemotherapy following surgery may significantly improve survival in patients with malignant melanoma.     

Phase II study of weekly Kahalalide F in patients with advanced malignant melanoma

This phase II clinical trial evaluated the antitumour response of Kahalalide F (KF) 650 μg/m² given as a 1-h weekly infusion in advanced malignant melanoma patients, both untreated and those who relapsed or progressed after one line of systemic therapy. Of 24 enrolled patients (median age, 55 years; range, 28–89), 14 patients had been previously treated with chemotherapy or biological therapy. No RECIST responses occurred; five chemotherapy-naïve patients with cutaneous melanoma had disease stabilisation for ?3 months; median progression-free survival was 1.7 months (95% CI, 1.2–1.9 months); and median overall survival was 10.8 months (95% CI, 5.0-upper limit not reached). The most common laboratory toxicities were non-cumulative increase of transaminases (ALT/AST) and gamma-glutamyltransferase (GGT). No patients experienced leukopenia and thrombocytopenia during the study. KF was a well-tolerated and safe chemotherapy regimen. Despite a favourable safety profile, this trial was closed after the first stage because of the lack of objective response in patients with malignant melanoma.     

Temozolomide With or Without Radiotherapy in Melanoma With Unresectable Brain Metastases

Summary Brain metastases are a common complication in patients suffering from metastatic malignant melanoma. We analyzed efficacy and toxicity of the alkylating agent temozolomide with excellent CNS penetration and known activity in brain metastasis in 35 patients with unresectable melanoma brain metastases. Patients received 200 mg/m² temozolomide on days 1 to 5 every 28 days as first or second-line therapy. This therapy regimen was combined with radiotherapy of the brain metastases in 22/35 patients. Grade III and IV toxicity was observed in 8/35 patients (leukopenia, granulocytopenia, thrombocytopenia, anemia, nausea and obstipation). Complete remission was observed in 1/34, partial remission in 2/34 and stable disease in 9/34 patients. In 5/34 a mixed response was assessed, 17/34 had disease progression and in one patient tumor response was not evaluable. The median progression free time was 5 (0–8) months for all patients, the median survival time for all patients from start of therapy was 8 (0–28) months, 9 (2–28) months in patients with concurrent stereotactic radiotherapy and 7 (3–17) months in patients with concurrent whole brain radiotherapy. Our results demonstrate that temozolomide can be combined with radiotherapy for the treatment of brain metastases in malignant melanoma, and that this combination may prolong survival in this patient group.     

Cisplatin, gemcitabine, and treosulfan in relapsed stage IV cutaneous malignant melanoma patients

To evaluate the efficacy of cisplatin, gemcitabine, and treosulfan (CGT) in 91 patients with pretreated relapsed AJCC stage IV cutaneous malignant melanoma. Patients in relapse after first-, second-, or third-line therapy received 40 mg m(-2) intravenous (i.v.) cisplatin, 1000 mg m(-2) i.v. gemcitabine, and 2500 mg m(-2) i.v. treosulfan on days 1 and 8. Cisplatin, gemcitabine, and treosulfan therapy was repeated every 5 weeks until progression of disease occurred. A maximum of 11 CGT cycles (mean, two cycles) was administered per patient. Four patients (4%) showed a partial response; 15 (17%) patients had stable disease; and 72 (79%) patients progressed upon first re-evaluation. Overall survival of all 91 patients was 6 months (2-year survival rate, 7%). Patients with partial remission or stable disease exhibited a median overall survival of 11 months (2-year survival rate, 36%), while patients with disease progression upon first re-evaluation had a median overall survival of 5 months (2-year survival rate, 0%). Treatment with CGT was efficient in one-fifth of the pretreated relapsed stage IV melanoma patients achieving disease stabilisation or partial remission with prolonged but limited survival.     

Cerebral metastases of cutaneous melanoma.

Cerebral metastases of cutaneous melanoma carry a very poor prognosis. We report our experience of 31 patients who presented with cerebral metastasis of cutaneous melanoma in a 5-year period between mid-1991 and mid-1996. Cerebral metastases were diagnosed on computerized tomography (CT) scan after patients became symptomatic. The overall median survival in our series was 4 months. Seventeen patients (55%) received treatment with radiotherapy and dexamethasone with resolution of their symptoms, although median survival remained at 4 months. Six patients (19%) had surgery followed by whole brain radiotherapy, with median survival of 5 months. The remaining eight patients received dexamethasone alone. Data from patients surviving less than 2 months and over 6 months suggest that the poor prognostic factors are the presence of more than one cerebral metastasis and additional extracranial metastases.     

357例中国皮肤黑色素瘤临床特征与预后分析

目的对357例皮肤黑色素瘤患者的临床特点进行分析,以了解其流行病学特点及预后相关因素。方法对我科近3年来收治的黑色素瘤患者的临床特点与预后进行记录与随访,用SPSS11.5软件,采用寿命表法进行生存分析及Cox回归进行分析。结果Ⅰ期患者的中位生存期超过144.0月,Ⅱ、Ⅲ、Ⅳ期患者的中位生存期分别为95.7月、132.0月和26.8月;肢端黑色素瘤218例(61.1%);多因素分析发现,分期及溃疡是影响生存期的独立预后因子。结论肢端黑色素瘤发病率最高,所有患者的预后与初诊时的分期及溃疡密切相关。     

A pilot study of low-dose thalidomide and interferon alpha-2b in patients with metastatic melanoma who failed prior treatment

Melanoma is a hypervascular tumor and angiogenesis plays a critical role in the development/progression of metastases. As various pathways are involved in tumor angiogenesis, a combination of agents with different antiangiogenesis activities is a reasonable approach. To determine the efficacy and toxicity of combination treatment with low-dose thalidomide and low-dose interferon (IFN) in patients with stage IV melanoma who failed prior treatment(s), fifteen patients with metastatic melanoma (nine cutaneous, six uveal) received oral thalidomide (200 mg daily) with subcutaneous interferon (IFN)-alpha2b (3 MIU, 3x/week). Stabilization or regression of metastases (as evidenced by computed tomographic measurement) was the primary endpoint of the study. Patients were evaluated monthly for toxicity and every 2 months for clinical response. At a median follow-up of 22.8 months (range, 12-32 months), one patient with metastatic cutaneous melanoma achieved partial response, three patients achieved stable disease (one uveal, two cutaneous), nine patients progressed, and two were not evaluable. The time to progression was 6 months for the patient with partial response, and 2, 5.5+ and 11 months for three patients with stable disease. The estimated median overall survival was 4.7 months (confidence interval, 2.2-9.9 months; range, 0.9-31.5 months), and median progression-free survival was 1.8 months (confidence interval, 1.5-3.0 months; range, 0.5-14 months). Grade 3 toxicities related to treatment included neutropenia (n=5), elevation of transaminases (n=2), and neuropathy (n=1). No treatment-related deaths were experienced. Thalidomide+IFN is a safe and tolerable palliative treatment for previously treated stage IV melanoma.     

碳离子治疗IMRT后局部区域复发鼻咽癌初步研究——上海市质子重离子医院临床经验

目的 分析再程调强碳离子放疗(IMCT)对IMRT后局部区域复发鼻咽癌的疗效及不良反应。方法 纳入112例于2015-2018年接受挽救性再程IMCT的局部区域复发鼻咽癌患者,Ⅰ、Ⅱ、Ⅲ、Ⅳ期患者分别为10例(9%)、26例(23%)、41例(37%)、35例(31%),中位年龄48岁(17~70岁),中位照射剂量为60GyE(50~69GyE)。结果 中位随访20个月(5~45个月),共20例患者死亡,42例患者局部复发,2年总生存(OS)率与无局部进展生存(LPFS)率分别为85%与52%。单因素与多因素分析中Ⅳ期患者OS均显著差于其他患者,未发现与LPFS显著相关的预后因素。治疗期间未见≥3级急性不良反应。≥3级晚期不良反应包括1例口干、2例听力下降、1例大脑颞叶损伤与19例鼻咽黏膜坏死。结论 再程IMCT治疗局部区域复发鼻咽癌取得了较好疗效且严重不良反应发生率较低,远期疗效及不良反应有待进一步随访。     

Phase II study of recombinant leukocyte A interferon (rIFN-alpha A) in disseminated malignant melanoma

Thirty-one patients with disseminated malignant melanoma received intramuscular recombinant leukocyte A interferon (rIFN-alpha A), 50 X 10(6) units/m2 three times weekly for a planned treatment duration of 3 months. Seven objective regressions (23%), which ranged in duration from 3 to 11.2+ months, were observed. Forty-two percent of 12 patients who were fully active (Eastern Cooperative Oncology Group [ECOG] performance score, 0) responded compared to 11% of 19 patients with impairment of performance status (ECOG, 1-3). Prior chemotherapy did not influence response rate. For all patients the median time to progression and of survival was 2 months and 6 months, respectively. Four patients had partial regressions in soft tissue (3, 4.6 months), pulmonary (7 months), and prostatic lesions (3 months). The latter was biopsy-proven and assessed by serial computerized tomography (CT) scans. Three had complete regressions of soft tissue disease (2 patients, 6.4 and 10+ months each), and liver involvement (11.2+ months). The major toxicities were moderate to severe fatigue (87%), anorexia (58%), and confusion (23%). Performance score deteriorated in 84% of patients during the time they were receiving rIFN-alpha A. Among the 13 patients whose tumors did not progress for at least 12 weeks, 7 required dose reductions or termination of treatment due to toxicities. Hematologic and hepatic toxicity was transient and of little clinical significance. The study indicates that rIFN-alpha A has some antitumor activity accompanied by difficult side effects in patients with disseminated malignant melanoma.