同期化疗配合后程三维适形放疗治疗食管癌的临床观察

目的：观察同期化疗配合后程三维适形放疗治疗食管癌的缓解率、局控率、生存率和毒副反应。方法：79例食管癌患者随机分为两组，放化疗组（39例）大野前后对穿常规分割照射36Gy-40Gy后，缩野三维适形照射追量26Gy，在放疗开始和放疗末期用氟脲嘧啶500mg／m^2＋顺铂20mg／m^2第1—5天全身化疗。单放组（40例）大野前后对穿常规分割照射36Gy-40Gy后，缩野照射追量26Gy。两组放疗总量62Gy-66Gy。结果：放化疗组与单放组完全缓解率分别为33％、12．5％（P〈0．05）。1、2年生存率放化疗组为79％、59％，单放组为68％、42％（P=0．13）。毒性反应放化疗组相对增加，但绝大多数患者可以耐受。结论：同期化疗配合后程三维适形放疗治疗食管癌近期疗效较好，可提高生存率。毒副反应增加，但可以耐受。     

后程加速超分割三维适形放疗食管癌的远期疗效和预后分析

目的 对比研究后程加速超分割三维适形放疗食管癌的远期疗效、副反应及失败原因。方法 将150例食管鳞癌患者用信封法随机均分至后程加速超分割三维适形放疗组（后超组）和后程常规分割三维适形放疗组（对照组）。放疗方法均为前2／3疗程普通模拟机定位常规放疗40Gy，后1／3疗程后超组改为CT模拟定位加速超分割三维适形放疗（1．5Gy／次，2次／d，18～27Gy），总剂量为58～67Gy，32～38次，全疗程36～39d；对照组常规分割三维适形放疗至上述相当剂量。结果 后超组和对照组5年生存率分别为33％和15％，后超组生存率高于对照组（P=0。029）。后超组中位复发时间也高于对照组（11．0、7．0个月，P〈0．01）。3、4、5年无瘤生存率分别为35％、33％、32％和20％、17％、17％，后超组无瘤生存率均高于对照组（P值均〈0．05）。后超组和对照组1、2、3、4、5年局部控制率分别为79％、73％、63％、61％、61％和60％、39％、31％、29％、27％，后超组局部控制率均高于对照组（P值均〈0．05）。Cox回归分析显示颈段、胸上段食管癌的疗效明显优于胸中段、胸下段食管癌，蕈伞型优于其他类型（P值均〈0．01）。结论 常规放疗后进行后程加速超分割三维适形放疗可作为颈段、胸上段和蕈伞型食管癌的首选方法之一，它提高了局部控制率和远期生存率。     

同期化放疗治疗中晚期食管癌的临床分析

目的探讨中晚期食管癌治疗的有效方案。方法中晚期食管癌70例随机分为2组：单纯放疗（单放组）35例，采用常规分割放疗，总剂量为60—70Gy／6—7W；同期化放疗（化放组）35例，应用CF／DF、单药紫杉醇化疗联合放疗。结果化放组总有效率（RR）为82．9％，单放组RR为60．0％（P〈0．05）；2组1、2、3年生存率分别为65．7％、40．0％、28．6％和54．3％、17．1％、8．6％，2,3年生存率2组有显著性差异（P〈0．05）。化放组的胃肠反应及骨髓抑制高于单放组（P〈0．05）。结论同期化放疗是治疗中晚期食管癌较为有效且安全的方案，毒副反应略增加，患者均可耐受。     

后程加速超分割放射加顺铂治疗食管癌的临床研究

目的观察后程加速超分割放疗同期单药顺铂化疗对食管癌的放射增效作用。方法将符合入选条件的104例食管鳞状细胞癌患者随机分为后程加速超分割放疗组（简称单放组，53例）和后程加速超分割放射加顺铂组（简称放化组，51例）。放疗方法2个组相同．前3周为常规放疗（2Gy／次，1次／d，5d／周），后2周改为加速超分割放疗（1．5Gy／次，2次／d，间隔6h或以上，5d／周）。顺铂于放疗第1、5周分别给予20mg／d，连续5d。结果单放组和放化组的中位生存期分别为12，2、17，0个月。单放组1、3年生存率分别为52.8％、20．8％，放化组的分别为58．0％、24.0％（P〉0．05）。放化组的胃肠道及血液方面的急性反应较明显，而急性食管炎及晚期副反应无明显增加。结论后程加速超分割放射加顺铂治疗食管癌较单纯后程加速超分割放疗有提高总生存率的趋势。     

食管癌术后放疗的临床分析

目的评价食管癌术后放疗的价值。方法1990-1992年，行根治性切除胸段食管瘤106例，其中单纯手术58例，术后放疗48例，同时合并化疗10例。结果单纯手术与术后放疗和／或化疗的2年局部控制率分别为59％和91％，5年生存率为21％和30％。2年局部控制率术后放疗组显著高于单纯手术组（P＜0．01）。5年生存率术后放疗组虽优于单纯手术组，但无显著性差异（P＜0．05）。结论术后放疗是提高食管癌局部控制率的重要手段。     

DF方案加卡莫氟联合放疗治疗食管癌的临床分析

探讨DF方案加卡莫氟联合放疗治疗食管癌的疗效和毒副反应。将76例食管癌患者随机分为两组行前瞻性临床研究。综合组38例行DF方案化疗后常规放疗，放疗同时口服卡莫氟；单放组38例行单纯放疗。放疗采用8MVX线常规照射，DT60～70Gy。两个组均随访满3年。综合组1、2和3年生存率（81．1％、68．3％和57．2％）明显高于单放组（74．2％、50．1％和27．4％），P=0．0225；且无严重毒副反应。两组的局部控制率差异有统计学意义，P=0．0143。初步研究结果提示，DF方案加卡莫氟化疗联合放射治疗食管癌疗效较好。     

后程加速超分割放疗食管癌的临床研究

目的研究后程加速超分割（LCAF）和常规分割（CF）放射治疗食管癌的远期疗效及毒副反应。方法64例食管癌患者随机分为LCAF治疗组和CF治疗组,其中LCAF组32例,先用常规分割照射40Gy,2Gy／次,1次／天,5次／周,4周完成,再用LCAF避脊髓照射28Gy,1．4Gy／次,2次／天,间隔4～6h,5次／周。总剂量68Gy分40次6周完成。CF组始终用常规分割照射,总剂量70Gy分35次7周完成。结果食管癌肿瘤完全缓解率LCAF组和CF组分别为63％、53％;1、3、5年肿瘤局部控制率LCAF组分别为72％、55％、17％,CF组分别为52％、18％、8％,两组有显著性差异（P〈0．05）。1、3、5年生存率LCAF组分别为68％、50％、18％,CF组分别为50％、30％、10％,两组有显著性差异（P〈0．05）。近期反应放射性食管炎LCAF纽与CF组存在差异（P〈0．05）,而放射性气管炎无显著性差异（P〉0．05）。两纽并发症也无显著性差异（P〉0．05）。结论食管癌LCAF的局部控制率、长期生存率均高于CF,患者能耐受LCAF治疗,不增加远期毒副反应。     

90例食管癌全程加速超分割放疗的临床研究

目的比较常规分割、后程加速超分割及全程加速超分割放疗胸中下段食管中分化鳞癌的疗效与副反应。方法将90例患者随机分成3个组：（1）常规分割（CF）组，2．0Gy／次，1次／d，5d／周，总量70Gy；（2）后程加速超分割（LCAF）组，先常规分割放疗40Gy，后1．5Gy／次，2次／d，间隔〉6h，5d／周，加量至70Gy；（3）全程加速超分割（WCAHF）组，1．5Gy／次，2次／d，间隔〉6h，5d／周，总量至72Gy。结果cF和LCAF及WCAHF组1、2、3年局部控制率分别为47％、17％、0％和60％、20％、20％及60％、40％、33％，WCAHF组局部控制率明显高于CF、LCAF组（P〈0．01）。CF和LCAF及WCAHF组1、2、3年生存率分别为47％、20％、10％和63％、43％、17％及63％、50％、33％。WCAHF、LCAF组的2、3年生存率明显高于CF组（P〈0．01）。急性副反应WCAHF、LCAF组较CF组严重，WCAHF和LCAF组急性放射性食管炎2～3级明显高于cF组，但晚期放射性食管炎3个组无差异。WCAHF组1～2级急性放射性肺炎高于LCAF、CF组，且WCAHF组1例因放射性肺炎而导致死亡。结论WCAHF组能提高食管癌的局部控制率和2、3年生存率，但副反应稍有增加。     

卡铂加放射治疗食管癌的前瞻性研究

目的：探讨卡铂提高食管癌放射治疗疗效的方法。方法：180例食管癌患者根据入选标准随机分组，90例进入卡铂＋放射治疗（卡放组），90例进入单纯放射治疗（单放组），卡放组放疗第1、4周同时用卡铂100mg／d，静脉滴入，每周连用5d，2个周期总量为1000mg，单放组放疗方法同卡放组。单放组^90Co-γ射线常规三野照射6用，共60Gy／30次。结果：近期疗效显示，卡放组完全缓解率达52．2％，单放组为36．7%，两者差异有统计学意义，P〈0．05；卡放组和单放组5年生存率分别为22．2％和10％，两者差异有统计学意义，P〈0．05；10年生存率分别为14．4％和6．7％，两者差异无统计学意义，P〉0．05。卡放组毒副反应明显高于单放组，但患者能耐受，两组的主要死亡原因是局部复发。结论：卡铂加放射治疗食管癌可以提高疗效。毒副反应虽然有所增加，但所有患者均可耐受。     

甘氨双唑钠对局部复发鼻咽癌放射增敏近期疗效观察

目的：观察甘氨双唑钠（CMNa）对放疗后局部复发鼻咽癌放疗增敏的近期疗效及毒副反应。方法：鼻咽癌首程根治放疗1年后出现局部复发患者72例，随机分为实验组和对照组。实验组（37例），采用甘氨双唑钠0．75g，每周给药3次（于放疗前半小时至1小时静滴完）＋放疗；对照组（35例），采用单纯放疗。均用直线加速器局部复发病灶三维适形放疗，剂量60Gy-70Gy／6周～7周。结果：局部鼻咽复发病灶消除率：肿瘤量至50Gy时两组分别为50％、25．7％，P〈0．05。全程治疗结束后1个月两组复发病灶消除率分别为63．9％、40％，P〈0．05。两组不良反应方面无差异。结论：甘氨双唑钠对放疗后局部复发鼻咽癌患者的再程放疗有较好的临床放射增敏作用，值得推广。     

Oncogénétique et psycho-oncologie, une collaboration recommandée...

Résumé: La possibilité depuis 1994, de connaître la probabilité individuelle de développer certains cancers a permis de proposer de nouvelles modalités de prévention, de traitements et contribué au développement actuel de loncogénétique. Une meilleure connaissance des répercussions psychologiques tant pour les patients que pour les apparentés est désormais possible et limplication des psycho-oncologues dans ce cadre de la réalisation des tests prédictifs, recommandée. La mission de «messager» qui incombe au «cas-index» doit faire lobjet dune attention particulière. La complexité de linformation et la dimension paradoxale que peut avoir parfois la communication à propos des choix, rend difficile lévaluation de la qualité du consentement. La situation particulièrement délicate dune aide à la décision à légard de la chirurgie prophylactique, exige une collaboration étroite des généticiens et des psycho-oncologues.Les soins de support en oncologie     

The role of papillomaviruses in human cancers

This review comprehensively evaluates the influence of gene-gene, gene-environment and multiple interactions on the risk of colorectal cancer (CRC). Methods of studying these interactions and their limitations have been discussed herein. There is a need to develop biomarkers of exposure and of risk that are sensitive, specific, present in the pathway of the disease, and that have been clinically tested for routine use. The influence of inherited variation (polymorphism) in several genes has been discussed in this review; however, due to study limitations and confounders, it is difficult to conclude which ones are associated with the highest risk (either individually or in combination with environmental factors) to CRC. The majority of the sporadic cancer is believed to be due to modification of mutation risk by other genetic and/or environmental factors. Micronutrient deficiency may explain the association between low consumption of fruit/vegetables and CRC in human studies. Mitochondrial modulation by dietary factors influences the balance between cell renewal and death critical in colon mucosal homeostasis. Both genetic and epigenetic interactions are intricately dependent on each other, and collectively influence the process of colorectal tumorigenesis. The genetic and environmental interactions present a good prospect and a challenge for prevention strategies for CRC because they support the view that this highly prevalent cancer is preventable.     

Antifungal combination therapy in localized candidosis

A mouse model of localized candidosis in air-filled subcutaneous cysts imitating thrush has been developed. We have now tested various antifungal combinations in this animal model. Flucytosine (5-FC) + amphotericin B (Amph B) showed the highest efficacy, a clear additive or even synergistic effect was seen. The combination of 5-FC + imidazole or triazole derivative was less efficacious, an additive effect was rare. The combination of 5-FC + Amph B was also tested against Candida albicans strains showing various degrees of 5-FC-resistance. A significant reduction in 5-FC-resistant mutants was seen after the treatment with the combination.     

Les génériques en cancérologie: à molécule identique, médicaments identiques? Les biosimilaires, des super-génériques?

Résumé: Les biosimilaires vont bientôt voir leur apparition en Europe. Comment un laboratoire peut-il aborder le développement de son dossier dAMM? Quelles sont les bases légales et les recommandations officielles? Comment la similarité et/ou le caractère générique peuvent-ils être démontrés? Les règles sont-elles identiques à celles des produits chimiques conventionnels pour lesquels, notamment en cancérologie, il existe des médicaments génériques? Comment faire pour que la sécurité et lefficacité des médicaments biosimilaires soient assurées pour les patients?     

Cancer immunotherapy

Unprecedented progress has seen made in the last decade in the field of cancer immunotherapy. The recent approval of nivolumab （Opdivo）, the first anti-programmed cell death-1 （PD-1） antibody, for metastatic melanoma in Japan, marked a milestone in the rapidly advancing field of cancer immunotherapy. Nivolumab together with ipilimumab （Yervoy）, the anti-cytotoxic T-lymphocyte-associated antigen-4 （CTLA-4） antibody, are the first 2 drugs in the class of ＂immune checkpoint inhibitors＂ that have delivered impressive responses in patients with metastatic melanoma and renal cell cancer （RCC） as well as a variety of solid tumors.     

Effect of tumor therapeutic irradiation on the mechanical properties of teeth tissue

Tumor irradiation of the head-neck area is accompanied by the development of a so-called radiation caries in the treated patients. In spite of conservative therapeutic measures, the process results in tooth destruction. The present study investigated the effects of irradiation on the demineralization and remineralization of the dental tissue. For this purpose, retained third molars were prepared and assigned either to a test group, which was exposed to fractional irradiation up to 60 Gy, or to a non-irradiated control group. Irradiated and non-irradiated teeth were then demineralized using acidic hydroxyl-cellulose gel; afterwards the teeth were remineralized using either Bifluorid12 or elmex gelee. The nanoindentation technique was used to measure the mechanical properties, hardness and elasticity, of the teeth in each of the conditions. The values were compared to the non-irradiated control group. Irradiation decreased dramatically the mechanical parameters of enamel and dentine. In nonirradiated teeth, demineralization had nearly the same effects of irradiation on the mechanical properties. In irradiated teeth, the effects of demineralization were negligible in comparison to non-irradiated teeth. Remineralization with Bifluorid12 or elmex gelee led to a partial improvement of the mechanical properties of the teeth. The enamel was more positively affected by remineralization than the dentine.     

Consultation multidisciplinaire pour les patients atteints d’une pathologie tumorale (carcinome infiltrant ou lésion précancéreuse) liée à HPV : la consultation multidisciplinaire papillomavirus

Given the recent increase in the number of human papillomavirus (HPV)-induced cancers in other locations than gynaecological, the number of patients with two cancers at distinct sites, and because of the lack of exhaustive data, we decided to create a multidisciplinary network around an HPV consultation at the Georges-Pompidou European Hospital (HEGP). This network aims to set up the best tools for detecting HPV-associated “multisite” precancerous lesions in order to determine the possible impact of dedicated care for this at-risk population. This monthly consultation was created at the HEGP in June 2014. It is currently organized around five consultations: gynaecological, ENT, urological, digestive and immunological. Every patient who has been diagnosed with HPV-related cancer and whose care is provided at the HEGP is offered this particular follow-up: systematically, once the initial lesion has been treated, the patient is convened annually for a day during which it benefits from the consultations mentioned above. A consultation with a psychologist is systematically proposed. Local samples are taken at each site: a cytological examination, the analysis of known predictive and prognostic virological markers are carried out. This study fits more broadly in a theme of clinical and fundamental research around cancers related to HPV.     

Differentiation state and invasiveness of human breast cancer cell lines

Summary Eighteen breast cancer cell lines were examined for expression of markers of epithelial and fibroblastic differentiation: E-cadherin, desmoplakins, ZO-1, vimentin, keratin and ₁ and ₄ integrins. The cell lines were distributed along a spectrum of differentiation from epithelial to fibroblastic phenotypes. The most well-differentiated, epithelioid cell lines contained proteins characteristic of desmosomal, adherens and tight junctions, were adherent to one another on plastic and in the basement membrane matrix Matrigel and were keratin-positive and vimentin-negative. These cell lines were all weakly invasive in anin vitro chemoinvasion assay. The most poorly-differentiated, fibroblastic cell lines were E-cadherin-, desmoplakin- and ZO-1-negative and formed branching structures in Matrigel. They were vimentin-positive, contained only low levels of keratins and were highly invasive in thein vitro chemoinvasion assay. Of all of the markers analyzed, vimentin expression correlated best within vitro invasive ability and fibroblastic differentiation. In a cell line with unstable expression of vimentin, T47D_CO, the cells that were invasive were of the fibroblastic type. The differentiation markers described here may be useful for analysis of clinical specimens and could potentially provide a more precise measure of differentiation grade yielding more power for predicting prognosis.