局部残留和复发鼻咽癌立体定向放疗的预后因素分析

目的分析局部残留和复发鼻咽癌分次立体定向放疗(FSRT)的预后因素。方法采用FSRT治疗鼻咽癌常规放疗后局部残留和复发患者共90例,除3例治疗前已发生远处转移外,余87例(34例残留,53例复发)纳入分析。其中肿瘤位于鼻咽腔内、外者分别为44、43例;中位肿瘤体积为5.7 cm3(0.8～24.7 cm3);残留和复发病灶FSRT的中位处方剂量分别为18 Gy分3次和48 Gy分6次。用Kaplan-Meier法计算无局部失败生存率(LFFS)和疾病相关生存率(DSS),用Logrank法和Cox模型分别进行单因素和多因素的预后分析。结果中位随访时间为24.9个月(3.3～86.3个月),1、2、3、4年LFFS和DSS分别为90%、83%、81%、75%和84%、77%、61%、56%。单因素分析显示肿瘤体积(≤或>5 cm3)对患者DSS有影响(P=0.015)。多因素分析显示肿瘤体积和病灶类型(残留或复发)是影响DSS的独立因素(P<0.05)。残留组和复发组晚期副反应发生率分别为9%和26%。结论FSRT治疗残留和复发鼻咽癌可得到较好局部控制率和生存率,复发病灶和较大肿瘤体积是预后不良的独立影响因素。     

局部残留或复发鼻咽癌的分次立体定向放射治疗

目的　评价分次立体定向放射治疗 (FSRT)对局部残留和复发鼻咽癌的初步疗效。方法　应用FSRT对 30例局部残留 (11例 )或复发 (19例 )鼻咽癌患者分 2个组进行治疗 ,其残留组和复发组中位处方剂量分别为 18Gy和 4 8Gy ,中位分次量分别为 6Gy和 8Gy ,每周 2次。结果　可评价例数共 2 9例 ,FSRT治疗后 3个月残留组的CR和PR各为 6 /11和 3/11,复发组各为 8/18和 8/18。全组病例随诊 3.4～ 37.9个月 (中位值 15个月 ) ,残留组 1和 2年总生存率、无瘤生存率、无局部复发生存率和无远地转移生存率分别为 77.8%和 6 6 .7%、5 6 .8%和 5 6 .8%、88.9%和 88.9%、75 .0 %和75 .0 % ,复发组相应为 6 9.8%和 5 9.8%、5 3.4 %和 4 4 .5 %、76 .6 %和 6 3.8%、70 .5 %和 5 8.7%。残留组和复发组生存患者卡氏评分≥ 90者分别占 8/8和 11/13。结论　FSRT对局部残留或复发鼻咽癌有较好的局部控制效果和较高的安全性 ,区域和远地转移是治疗失败的主要原因。     

鼻咽癌靶体积划分的前瞻性临床验证

[目的]验证鼻咽癌靶体积划分的合理性和临床疗效。[方法]150例初治鼻咽癌患者,69例单纯放疗,81例放化综合治疗。根据靶体积划分方法勾画靶体积,并分别设置相应的计划靶体积;针对靶体积逐步缩野照射。分析治疗后局部区域控制情况以及影像学显示的残留和复发部位与靶体积的关系。[结果]治疗后单纯鼻咽残留2例,单纯颈部残留3例,两部位同时残留2例,鼻咽原发灶及颈部转移灶消退率分别为97.3%和96.7%。中位随访时间35.5个月,鼻咽复发6例,颈部复发3例,3年局部和区域控制率分别为95.1%和97.2%。影像学分析显示,鼻咽残留灶和复发灶均位于鼻咽大体肿瘤体积(GTVnx)内;颈部残留病灶均位于颈部大体肿瘤体积(GTVnd)内;颈部复发灶1例位于GTVnd内,2例位于CTV2内。[结论]依据该靶体积划分进行放疗,获得较好的局部区域控制,未观察到靶体积外和边缘复发,进一步显示了该靶体积划分较为合理,针对不同靶体积逐步缩野的照射方法是可行的。     

鼻咽癌复发与残存病变的分次立体定向放疗

背景与目的:鼻咽癌复发、残留患者采用常规技术推量,适应症局限,而应用分次立体定向放疗(FS-RT)能得到合理的剂量分布,保护高危器官,提高疗效.本研究旨在评价鼻咽癌患者放射治疗后局部残存、区域复发进行立体定向放射治疗的临床价值和毒副作用.方法:41例鼻咽癌放射治疗后局部残存、区域复发的患者,应用立体定向放射治疗系统,6 MV X线,60%～90%为参考剂量曲线,肿瘤边缘分次剂量为4 Gy,间隔1～2d,总剂量为12～28 Gy(中位数16 Gy)/3～7次(中位数4次)放疗.靶体积为3.56～35.75 cm3,中位靶体积11.02 cm3.患者分为2组:残存组35例为首程适形调强根治性放射治疗后;复发组6例为首程根治性放射治疗后6个月以上区域复发,二程IMRT后;全部病例1个月内经鼻咽镜、CT或MRI检查发现仍有较大肿块残存.结果:FSRT治疗后3个月,CR63.47%(26/41),PR22.0%(9/41),SD14.6%(6/41),全组病例中位随访时间为28个月(3～41个月),残留组1、2、3年总生存率分别为100%、97.1%和91.4%,局控率分别为97.1%、88.6%和88.6%,无瘤生存率分别为94.3%、85.7%和85.7%.复发组1、2年总生存率分别为83.3%和66.7%,局控率分别为66.7%和50.0%.无瘤生存率分别为66.7%和50.0%.结论:FSRT对局部残留或复发鼻咽癌有较好的局部控制效果和较高的安全性,区域复发仍是治疗失败的主要原因.     

局部复发鼻咽癌三维适形放疗初步观察

目的:探索三维适形放疗(3demensionalconformalradiationtherapy3DCRT)技术在局部复发鼻咽癌再程放疗中的应用。方法:1998年4月～1999年10月,采用3DCRT技术治疗局部复发鼻咽癌26例。其中低分化鳞癌25例,低分化腺癌1例。按92’福州分期标准再分期:T1N0M04例,T2N0M08例,T3N0M09例,T4N0M05例。密集肿瘤区(grosstumorvolumeGTV)最大径1.0～5.0cm(平均3.1cm)。全组病例均采用每次5～7个固定适形野照射,计划靶区(planningtargetvolumePTV)平均最大剂量、最小剂量、平均剂量分别为104.1±1.3%、92.1±2.8%、99.2.±1.7%。时间-剂量-分次处方:65～70Gy/26～28次,共5～5.5周。随访8～26个月,中位随访时间17个月。结果:再程放疗后随访期内靶区边缘复发2例,颈淋巴结复发3例,远处转移2例,死亡4例。随访期内肿瘤局部控制率88.5%(23/26),84.6%(22/26)患者生存,76.9%(20/26)无瘤生存。再程放疗所致急性放射反应少而轻。累计后遗症发生率19.2%(5/26),放射性功能损害发生率15.4%4/26。结论:三维适形放疗技术用于局部复发鼻咽癌具有明显的剂量分布优势。初步临床观察结果表明,这一放疗新技术用于局部复发鼻咽癌肿瘤局部控制率高、放射反应和后遗症较少,远期疗效和后遗症尚有待观察。     

立体放射治疗复发鼻咽癌的初步探讨

探讨立体放射治疗(立体定向和适形放射治疗)对复发鼻咽癌的疗效和并发症。12例根治性放疗后复发患者,初次放疗至复发的中位间隔时间为10个月(6~48个月)。7例有头痛和(或)颅神经损伤症状;3例经活检病理确诊,9例经CT和(或)MRI诊断。在CT/MRI上肿瘤最大径≥4 cm者8例,≤4 cm者4例。三维适形放射治疗(3D CRT)5例,照射剂量42 Gy(20~60 Gy);分次放射外科治疗7例,其中3例采用多靶点照射技术,4~5 Gy/次,隔日或1次/d,总剂量40~48 Gy。12例患者中6例死于局部复发和(或)远处转移,3例患者已带瘤生存22、28和34个月,另3例在放疗后肿瘤完全消退,已健康生存12、33和48个月。全组中位生存时间为10个月。有1例患者死于鼻咽大出血。初步研究结果提示,采用三维放疗技术较小靶体积照射,对局限的复发鼻咽癌能达到良好的治疗效果,值得进一步探讨。对于病变广泛的晚期患者则能达到一定姑息减症的效果。     

鼻咽癌照射靶体积划定的临床探讨

目的通过分析针对靶体积逐步缩野放疗的临床结果，初步探讨鼻咽癌照射靶体积划定的合理性。方法共81例初治鼻咽癌患者进入研究，按1992年福州分期Ⅰ、Ⅱ、Ⅲ和Ⅳa期分别为4、23、35和19例。43例接受单纯放疗，38例接受放化综合治疗。将照射靶体积划分为鼻咽大体肿瘤体积(GTVnx)、颈部大体肿瘤体积(GTVnd)、临床靶体积1(CTV1)、临床靶体积2(CTV2)，相应计划靶体积分别为PTVnx、PTVnd、PTN1、PTN2。处方剂量PTVnx60-76Gy，PTVnd62-66Gy，PTV160Gy，PTV250—52Gy；按靶体积的剂量要求逐步缩野照射。采用三维治疗计划系统对8例不同期别患者的靶体积受照剂量进行计算，Kaplan—Meier方法计算局部区域无进展生存率、无远地转移生存率和总生存率。结果剂量计算结果显示，各靶体积均获得了所需的剂量覆盖。治疗后鼻咽及颈部肿瘤残留各2例，残留病灶分别位于PTVnx及GIVnd内；鼻咽原发灶及颈部转移灶全消率均为97．5％。中位随访时间15个月，未观察到复发病例；2年局部区域无进展生存率、无远地转移生存率和总生存率分别为100．0％、96．3％、100．0％。结论采用上述靶体积划分方法进行放疗可获得较好局部控制，未观察到靶体积内、外和边缘的复发。但该划分方法的合理性和准确性仍需进一步观察和研究。     

胰腺癌根治术联合放疗后局部复发与放疗靶区剂量的关系北大核心CSCD

目的分析胰腺癌根治术联合辅助放疗后局部复发与放疗靶区剂量的关系,为辅助放疗提供靶区范围及处方剂量参考。方法回顾性分析2012—2020年接受根治术后行辅助放疗的T_(1‐4)N_(0‐2)M_(0)期胰腺导管腺癌患者138例,分析其局部复发的影响因素,以及局部复发部位与放射治疗靶区剂量的相关性。结果中位随访时间37.2个月,全组患者中位总生存(OS)期29.9个月,5年OS率为27.4%,中位无进展生存(PFS)期13.9个月,局部复发24例(17.4%),局部复发合并远处转移10例(7.2%)。其中可评估局部复发与放疗靶区剂量关系的共19例:首次局部复发位于腹主动脉旁、腹腔干旁和肠系膜上动脉旁的各有8、5和4例。单纯在PTV野内复发8例,其放疗剂量均在45 Gy以上。PTV野内、野外均复发8例,其中在剂量线40~52 Gy者3例,20~47.5 Gy者2例,0.5~52.5 Gy者3例。PTV野外者3例,均在剂量线0~20 Gy。结论胰腺导管腺癌根治术联合放疗后局部复发率较低。少部分患者发生放射野内高剂量范围内复发以及区域内野外复发,需探索更合适的靶区剂量及范围。     

大于3 cm脑转移瘤分次立体定向放疗初探

目的 回顾分析>3 cm脑转移瘤分次立体定向放疗(FSRT)的初步疗效,评价其临床应用价值.方法 搜集2006年前10年间采用FSRT且资料完整的直径>3 cm的脑转移瘤患者47例,其中男34例,女13例,年龄31～87岁(中位值58岁).原发灶病理为腺癌19例,鳞癌7例,小细胞癌7例,腺鳞癌3例,黑色素瘤2例,低分化癌、透明细胞癌、移行细胞癌各1例,病理类型不明6例.初治组26例,复发组21例.脑转移瘤直径3.1～6.0 cm(中位值3.8 cm).计划靶体积2.5～33.8 cm3(中位值9.4 cm3).FSRT总剂量16～68 Gy(中位值31 Gy)分2～15次(中位值5次).原发灶治疗方法 :手术23例,放、化疗22例,未治2例.结果 随访截止2008年4月,随访率为100%,满5年随访的例数为28例.1、2、5年局部控制率分别为49%、44%、44%.中位生存期11.0个月(0.5～88.0个月,95%CI=8.1～13.8个月);1、2、5年总生存率分别为40%、17%、6%.在死亡的46例中,21例死于颅内病变进展,17例死于颅外病变进展,8例死于其他原因.结论 FSRT通过分次治疗、个体化给量、全脑放疗或一程FSRT后推量,能有效控制最大径>3 cm的脑转移瘤、延长生存并改善生活质量.     

鼻咽癌局部残留和复发的立体定向放射治疗

鼻咽癌是我国常见的恶性肿瘤之一，放射治疗为首选治疗方式，鼻咽癌患者在全程放疗后约10％～20％局部仍残存肿块，其中肿瘤残留占6．7％～13％，复发率为20％～35％。分次立体定向放射治疗（fractionated stereotaction radiotherapy FSRT）具有靶区剂量集中、靶区周围正常组织和器官接受的剂量大大下降的特点，目前已成为鼻咽癌放疗后局部残留和复发的重要治疗手段之一。我院自1997年引用X刀并应用FSRT技术治疗36例，使局部残留和复发鼻咽癌患者取得较好疗效，现报道如下。     

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.