Place de la radiothérapie après chimiothérapie première dans le cancer du sein

Indications for adjuvant radiotherapy in breast cancer are defined from the clinical data and the pathological extent of disease in the surgical specimen. Neoadjuvant chemotherapy could modify the pathological characteristics of the tumour, inducing a pathologic complete response in 15 to 50% of cases, challenging the classical indications of adjuvant radiotherapy. The benefit of adjuvant radiotherapy after neoadjuvant chemotherapy was not prospectively evaluated. Nonetheless, from retrospective series, some recommendations with a low level of proof could be given: (i) after lumpectomy, radiotherapy of the mammary gland must be performed even in case of pathologic complete response; (ii) after mastectomy, postoperative radiotherapy is recommended in case of cT3-T4, cN1-3 (clinical or radiological) or pathologically involved nodes; (iii) irradiation of the lymph nodes areas is more questionable, but could be also proposed in case of cN1 or pN1. These recommendations are in accordance with those recently published by the National Cancer Institute and the French National Cancer Institute.     

Preoperative induction chemotherapy with cisplatin and irinotecan for pathological N(2) non-small cell lung cancer

We conducted a phase I/II study to investigate whether the surgical resection after induction chemotherapy with cisplatin and irinotecan was feasible and could improve the treatment outcome for patients with pathological N(2) non-small cell lung cancer. Fifteen patients with stage IIIA non-small cell lung cancer having mediastinal lymph node metastases proved by mediastinoscopy were eligible. Both cisplatin (60 mg m(-2)) and irinotecan (50 mg m(-2)) were given on days 1 and 8. Patients received two cycles of chemotherapy after 3-4 weeks interval. Induction was followed by surgical resection in 4-6 weeks. Patients who had documented tumour regression after preoperative chemotherapy received two additional cycles of chemotherapy and other patients received radiotherapy postoperatively. After the induction chemotherapy, the objective response rate was 73%. All the 15 patients received surgical resection and complete resection was achieved in 11 (73%) patients. There was no operation-related death and one death due to radiation pneumonitis during postoperative radiotherapy. The median time from entry to final analysis was 46.5 months, ranging from 22 to 68 months. The 5-year survival rate was 40% for all the 15 patients and it was 55% for the 11 patients who underwent complete resection. We conclude that the surgical resection after induction chemotherapy with cisplatin and irinotecan is feasible, and associated with low morbidity and high respectability.     

Raltitrexed (Tomudex) concomitant with radiotherapy as adjuvant treatment for patients with rectal cancer: preliminary results of phase I studies

Radiotherapy, either alone or in combination with chemotherapy, may reduce local recurrence of rectal cancer following surgery and improve survival of patients with operable and advanced/recurrent/inoperable disease. Chemotherapy with 5-fluorouracil in combination with radiotherapy has been used both before and after surgery; however, the optimum schedule is unclear. In addition, alternative chemotherapy with raltitrexed (Tomudex) may be more convenient and better tolerated. The preliminary results of three phase I dose-finding studies are described, combining escalating doses of raltitrexed with radiotherapy as pre- or postoperative treatment for operable rectal cancer or as treatment for advanced/inoperable/recurrent rectal cancer. The recommended dose of raltitrexed when combined with adjuvant radiotherapy is likely to be 2.6 mg/m2. This is a small dose reduction compared with the dose of raltitrexed for the treatment of advanced colorectal cancer (3.0 mg/m2); however, toxicity appears to be lower using the pre-operative approach. Neo-adjuvant therapy with raltitrexed plus radiotherapy also demonstrated clinical activity in the pre-operative study, which showed that 22% of patients achieved a complete response and 56% a partial response. Once the recommended dose has been defined in each setting, large-scale studies will be undertaken as appropriate.     

Locally advanced rectal cancer: what is the evidence for induction chemoradiation?

The concept of spatial cooperation in neoadjuvant chemoradiation (CRT) for locally advanced rectal cancer is attractive. Chemotherapy may, as a component of CRT, not only act as a radiosensitizing agent but also potentially eradicate distant micrometastases. Recent trials have demonstrated that the addition of concurrent 5-fluorouracil (5-FU)-based chemotherapy to radiation increases the pathological complete response rate, and reduces local recurrence, but as yet, a survival advantage has not been observed. AIMS: This review aims to examine the evidence for induction CRT in locally advanced rectal cancer. The endpoints of pathological complete response, a negative circumferential margin, sphincter-sparing surgery, local control, disease-free survival (DFS), and overall survival (OS) are examined, as are acute and late morbidity, surgical complications, and late functional results. METHODS: The information to produce this review was compiled by searching PubMed and MEDLINE for English language articles published until April 2007. The search term included "induction, neoadjuvant, chemotherapy, radiotherapy, chemoradiation, combined modality" in association with rectal cancer. CONCLUSIONS: CRT in the European randomized trials of rectal cancer improves tumor downstaging, pathological complete response, and local control over radiotherapy alone, but does not translate into a benefit in terms of longer DFS or OS, or a higher chance of sphincter preservation. Metastatic disease remains a significant problem, which provides a strong rationale for the integration of a second cytotoxic drug, or biologically targeted agents.     

Neoadjuvant chemotherapy of head and neck cancer]

Chemotherapy for head and neck cancer has made great progress after CDDP was introduced at the clinical level. Chemotherapy prior to regional treatment (neoadjuvant chemotherapy) has become a popular approach for incorporating chemotherapy into multimodality treatment. Numerous studies support the general observation that response rates, especially the rates for complete response, are higher in patients who have not had prior regional treatment. The goals of this treatment are 1) to increase the effectiveness of local treatment (surgery and radiation therapy) while obtaining superior disease-free survival, and 2) to prevent metastases by eradicating micrometastatic lesions. Despite the excellent response rates after reported for regimens with CDDP, randomized studies have failed to prove statistically significant superior disease-free survival. The reason for these negative results is considered to be the patient's compliance and difficult of obtaining sufficient numbers of patients in each kind of primary sites, because this type of cancer is relatively infrequent. More study of neoadjuvant chemotherapy with high quality control is needed. Some trials with neoadjuvant chemotherapy to preserve the function of larynx or hypopharynx are promising new strategies. Concurrent chemo-radiotherapy using CDDP was proved to potentiate radiotherapy and showed a good response rate. Adjuvant chemotherapy after surgery or radiotherapy is also expected to prolong disease-free survival when it is incorporated into multimodality treatment.     

化疗和放射治疗应用时机和顺序与肺癌疗效(附94例局限期小细胞肺癌临床观察)

目的　评价局限期小细胞肺癌应用化疗和放射治疗时机和顺序的重要性。方法　94例局限期小细胞肺癌按化疗和放射治疗使用的时间和顺序随机分为先化疗后放射治疗组( 简称序贯组,46 例) 和化疗、放射治疗交替组(简称交替组,48 例) 。化疗方案用顺铂(Cisplatin,PDD) 依托泊甙(Etoposide,VP16)(EP方案) ,顺铂20 mg/m2 ,1～5 天,依托泊甙100 mg/m2 ,1 ～3 天,每3 ～4 周1疗程,共6 疗程。60Co 放射治疗:每次2 Gy,5 周,50 Gy;交替组在第1 个疗程化疗后第3 天开始,序贯组则在6 个疗程化疗结束后。结果　交替组完全缓解率高于序贯组(66 .7 % 对58.7% ),但差异无显著意义(P> 0.05) 。交替组2 年生存率高于序贯组(43.7 % 对23 .9 %) ,差异有显著意义( P<0 .05) 。结论　交替组疗效优于序贯组,提示尽早放射治疗可提高小细胞肺癌生存率;EP方案可作为与放射治疗交替使用的首选化疗方案     

乳腺癌患者新辅助化疗后病理完全缓解的相关影响因素分析及列线图预测模型的构建

目的:建立关于乳腺癌新辅助化疗后病理完全缓解的综合预测模型,预测新辅助化疗后病理缓解,指导临床上诊疗方案的选择。方法:回顾分析2015年1月至2020年3月148例乳腺癌新辅助化疗患者的临床资料、化疗前核磁共振资料及病理资料,根据术后病理分为pCR组与npCR组。采用χ2检验对两组指标先行单因素分析;将P＜0.05的指标及考虑可能有临床意义的指标纳入多因素Logistic回归分析。应用多因素分析考虑有统计学意义(P＜0.05)及临床意义的指标构建乳腺癌新辅助化疗后病理缓解综合预测模型的列线图,并运用ROC曲线评价此模型的效能。结果:单因素分析表明腺体背景强化类型、最长径、病理分型对乳腺癌是否达到病理完全缓解具有预测作用;多因素分析表明,腺体背景强化类型、最长径、病理分型均是新辅助化疗后病理完全缓解的独立预测因素(P＜0.05)。乳腺癌新辅助化疗后病理缓解的预测模型的曲线下面积为0.769,特异度为65.5%,敏感度为78.9%。结论:乳腺癌新辅助化疗后病理完全缓解的综合预测模型对病理缓解状态有较好的预测能力,此模型可为乳腺癌新辅助化疗后患者选择手术方式提供参考。     

乳腺癌新辅助治疗二次活检诊断病理学应答研究进展及临床意义

随着乳腺癌新辅助治疗的发展,病理学完全缓解率明显提高。对于已经达到病理学完全缓解的患者,使用局域放疗替代手术治疗在理论上可行,因此术前准确判断病理学完全缓解至关重要。新辅助化疗后二次活检因其对病理学完全缓解预测准确率较高而被认为是有希望替代手术诊断病理学完全缓解的方法。最近发表的几项国外的前瞻性临床试验结果表明,新辅助化疗后二次活检具有相对较高的假阴性率,对新辅助化疗反应极好的患者豁免手术仍需要进一步研究。本文首先阐述二次活检的临床应用及其意义,并将国外已发表的临床研究分为小型可行性研究和大型前瞻性研究,对其主要结果及特点进行分析。     

三维适形放疗与紫杉醇周方案同步治疗老年Ⅲ期非小细胞肺癌的近期疗效观察

目的：评估三维适形放疗与紫杉醇周方案化疗同步治疗老年Ⅲ期非小细胞肺癌（NSCLC）的近期疗效。方法：2006年6月-2008年6月收治的62例老年Ⅲ期非小细胞肺癌患者,予以三维适形放疗,放疗剂量为60-70Gy/6-7周,同时行化疗,为紫杉醇周方案：紫杉醇60mg/m^2,静脉滴注第1,8,15天,28天为1周期。结果：完全缓解率（CR）20.9%,部分缓解率（PR）62.9%,总有效率（CR＋PR）83.8%。不良反应主要为骨髓抑制、消化道反应、放射性肺炎及放射性食管炎。结论：放疗与紫杉醇周方案化疗同步治疗老年Ⅲ期非小细胞肺癌的近期疗效较为满意,不良反应可以耐受。     

Randomised EORTC Head and Neck Cooperative Group trial of preoperative intra-arterial chemotherapy in oral cavity and oropharynx carcinoma

Between February 1978 and January 1984, 222 eligible patients were randomised in a multicentre trial of preoperative intra-arterial chemotherapy in the treatment of oral cavity and oropharynx carcinoma. Patients were randomised between either surgery or preoperative chemotherapy. This latter group received vincristine and bleomycin for 12 days. Patients were stratified according to the primary site: floor of the mouth (FM) versus posterior oral cavity or oropharynx (POC) and institution. The FM group received postoperative radiotherapy depending upon quality of the margins and lymph-node pathological involvement, when it was systematically applied in the POC group. Tumour regression after chemotherapy either complete (CR) or partial (PR > 50%) was observed in 48% in the FM group and 41% in the POC group, and lymph-node regression (CR + PR) was respectively 15% and 23%. Some discrepancies appeared between clinical regression and pathological response, and the number of cases without histological response was clearly higher than the number of cases without clinical response. The overall survival showed a statistically significant difference (P = 0.048) between FM and POC groups. In the FM group, median survival in the chemotherapy arm was estimated at 7 years compared with 3 years in the surgery arm. In the POC group, median survival was estimated at 3 years in both treatment arms. Chemotherapy lowered the uncontrolled disease and local recurrence in the FM group. These differences do not exist in the POC group, which may be due to the systematically postoperative radiotherapy.     

Multimodal treatment for inflammatory breast cancer

This is a retrospective study of 61 patients with clinically diagnosed breast cancer (IBC) treated with multimodality therapy between September 1977 and September 1985. All patients were scheduled to receive three courses of doxorubicin-based chemotherapy followed by mastectomy, further chemotherapy, and postoperative irradiation. Ten patients (16%) obtained a complete response, defined as either resolution of the clinical signs of inflammatory breast cancer (IBC) (4 patients) or no evidence of tumor in the mastectomy specimen (6 patients). Twenty-seven patients (45%) obtained a partial response, defined as a greater than 50% reduction in the clinical signs of inflammatory breast cancer. No response occurred in 24 patients (39%). Immediate mastectomy was done in 56 patients. Five patients whose disease was not resectable received preoperative irradiation. Nine patients at high risk for locoregional failure received postoperative irradiation immediately after mastectomy and before additional chemotherapy. Postoperative irradiation was given to the chest wall and peripheral lymphatics using standard or accelerated fractionation to a maximum dose of 60 Gy. Forty-six patients completed planned treatment including chemotherapy, surgery, and radiotherapy without failure. The minimum follow-up was 36 months. The 5-year actuarial disease-free survival was 70% for the complete response group, and 35% for the partial response group. All patients with no response failed by 34 months. The actuarial 5-year disease-free survival rate for the entire group was 27%. The 5-year actuarial locoregional control was 89% in the complete response group, 68% in the partial response group, 33% in the no response group, and 58% for all patients. Most failures were on the chest wall within the irradiated volume. Chest wall failures were more frequent in those who did not achieve brisk erythema or moist desquamation after postoperative irradiation. We conclude that multimodal treatment of patients with inflammatory breast cancer results in a low incidence of failure if complete response is obtained following initial chemotherapy. The locoregional control rate and actuarial 5-year disease-free survival for the entire group were not improved when mastectomy was done. Surgery should be done in those patients who respond adequately to chemotherapy, so that late sequelae of high-dose breast irradiation can be eliminated. Higher doses of postoperative irradiation may be required to improve local control in those patients with the poorest response to initial chemotherapy.     

Limited stage small cell lung cancer: Treatment and therapy

Opinion statement Chemotherapy remains the key treatment for small cell lung cancer; today, that chemotherapy remains cisplatin and etoposide in a variety of acceptable schedules. Attempts to use new drugs in extensive disease have not been as successful as hoped; however, a recent trial from Japan supports the use of irinotecan and cisplatin over the standard cisplatin and etoposide, but these facts need to be verified in western countries. For limited disease, the addition of thoracic radiotherapy for all patients and prophylactic cranial irradiation (PCI) in complete, or near complete, responders have resulted in improved survival. The best results occur with early, intensive thoracic radiotherapy concurrent with chemotherapy and PCI after completion of systemic and local therapy. The use of PCI and thoracic radiotherapy in extensive disease is more controversial and less evidence based. PCI and thoracic radiotherapy may be considered only in patients who have achieved a “systemic” complete response and excellent response in the chest. However, both prospects should be supported if there is complete response systemically and near complete response locally. The role of surgery is of limited value in the unusual cases of mediastinal negative disease, but it is a good treatment for patients with peripheral nodules and sufficient pulmonary function to withstand thoracotomy.     

Surgical resection after preoperative chemoradiotherapy benefits selected patients with unresectable pancreatic cancer

Simultaneous chemoradiation is used in unresectable pancreatic cancer for palliation. It is not known if the use of adjuvant surgery will benefit this group of patients. From November 1991 to September 1998, 47 patients with unresectable pancreatic cancer were treated with simultaneous preoperative radiation therapy (45 Gy) and chemotherapy. Chemotherapy followed three different protocols: cisplatin, 5-fluorouracil +/- paclitaxel; cisplatin, 5-fluorouracil (protracted infusion); and docetaxel and gemcitabine. Whipple pancreatoduodenectomy was performed 1 month after the end of radiation in patients selected for resection. Twenty-three unresectable tumors after preoperative treatment (47%) received an additional dose (10-12 Gy) of radiotherapy using intraoperative or external radiation therapy. Twelve patients (26%) were considered to have clinically resectable tumors after the preoperative treatment. Nine patients had surgery (19% of the total number of patients), and 2 of them had complete pathologic response. After chemoradiation, two patients died of pneumonia and gastrointestinal bleeding, respectively, and another two patients died in the postoperative period. Local recurrence was observed in 22% of the patients and 57% had distant metastases. Three-year survival rates for patients with unresectable and resectable tumors was 0% (median survival 10 months) and 48% (median survival 23 months), respectively (p = 0.0004). Preoperative treatment with chemotherapy and radiotherapy in patients with unresectable pancreatic cancer is feasible. In some patients, the tumor can be resected, and in addition some cases of complete pathologic response were found. Long-term survivors were observed in the group of resected tumors. More effective chemotherapy regimens are needed because the majority of the patients died of metastatic disease.     

化疗联合γ-刀放疗在晚期复治肺癌治疗中的作用

目的探讨化疗联合γ-刀放疗在晚期复治肺癌治疗中的作用。方法83例晚期肺癌复治患者依据再次接受主要治疗方法,分为同步化放疗组（35例）、序贯化放疗组（26例）、单纯化疗组（22例）。放疗均采用γ-刀,总剂量35～50Gy。结果同步化放疗组、序贯化放疗组及单纯化疗组总有效率分别为17,1％、11．5％及31．8％,差异无统计学意义（P〉0．05）。Ⅲ期者以同步化放疗组略高（23．1％）,Ⅳ期患者以单纯化疗组较高（38．5％）。总平均生存期及中位生存期以单纯化疗组最高,分别为14．2个月及9．3个月。各组先前曾行手术治疗的患者在后续复治中,生存期均长于非手术者。结论对于晚期复治肺癌患者,化疗联合γ-刀放疗同步治疗在Ⅲ期者中肿瘤缓解率略高,Ⅳ期者以单纯化疗有效率高,但各组相近。单纯化疗更有利于延长生存期。手术后复治患者生存优势明显。     

序贯性化疗、放疗和手术切除治疗肺尖癌28例分析

目的 探讨肺尖癌的综合治疗模式。方法 回顾分析我院1989年1月～1997年1月应用化疗(2个周期)、放疗(30～40Gy)加扩大性手术切除治疗肺尖癌28例。结果 化、放疗后CR 6例,PR 18例,MR 4例,总有效率为85.0％。全组出现并发症6例,肿块中心癌细胞变形和残存22例。纵隔淋巴结癌细胞阳性3例。全部达到根治性切除。术后5年生存率为42.8％(12/28)。结论 化疗可以杀灭部分癌细胞,消灭微小转移灶,对放疗起到增敏作用,放疗可以使局部病灶缩小,使患者的TNM分期提前。因此,序惯性化疗、放疗加扩大性手术切除应作为肺尖癌治疗的首选方案。     

早期乳腺癌保乳术后放化疗的最佳顺序

目的 探讨早期乳腺癌保乳治疗后放化疗最佳顺序，使保乳治疗的局部控制、远处转移和保乳效果达到最佳。方法 2000年1月～2002年11月，对38例符合保乳治疗条件的早期乳腺癌实施了保乳治疗。手术方式为局部广泛切除术和腋窝淋巴结清扫，术后2周开始化疗，化疗2周期后再开始放疗，全乳剂量50Gy，瘤床补充照射10～18Gy。放疗结束后根据使用化疗方案选择立即化疗或休息1周后再开始化疗，化疗共6周期。治疗结束后每3个月复查1次，放疗后6个月行乳房钼靶摄影。此后1年1次乳房照片检查。结果 38例保乳治疗的患者均定期复查，中位随访24个月(5～35个月)。未发现局部复发和远处转移。放疗后1年或以上的28例患者乳房外观良好。结论 早期乳腺癌保乳治疗中“三明治”式放化疗能满足保乳治疗的目的。     

Breast cancer response to neoadjuvant chemotherapy: predictive markers and relation with outcome

The aim of this study was to provide a better insight into breast cancer response to chemotherapy. Chemotherapy improves outcome in breast cancer patients. The effect of cytotoxic treatment cannot be predicted for individual patients. Therefore, the identification of tumour characteristics associated with tumour response and outcome is of great clinical interest. We studied 97 patients, who received anthracycline-based neoadjuvant chemotherapy. Tumour samples were taken prior to and after chemotherapy. We quantified the response to chemotherapy clinically and pathologically and determined histological and molecular tumour characteristics. We assessed changes in the expression of Bcl-2, ER, P53 HER2 and Ki-67. Association with response and outcome was tested for all parameters. The experimental results showed 15 clinical (17%) and three (3%) pathological complete remissions. There were 18 (20%) clinical vs 29 (33%) pathological nonresponders. The expression of most markers was similar before and after chemotherapy. Only Ki-67 was significantly decreased after chemotherapy. Factors correlated with response were: large tumour size, ER negativity, high Ki-67 count and positive P53 status. Tumour response and marker expression did not predict disease-free or overall survival. In conclusion, clinical and pathological response assessments are poorly associated. Proliferation decreases significantly after chemotherapy. ER negativity and a high proliferation index are associated with better response. HER2 status does not predict response, and outcome is not related to tumour response.     

Complete response in a case of advanced esophageal and gastric double cancer treated by chemotherapy of TS-1 and low-dose cisplatin

A 78-year-old man was admitted to our hospital complaining of dysphagea on April 8, 2005. Upper gastrointestinal endoscopic examination showed type 2 esophageal cancer in the lower thoracic area and type 3 gastric cancer in the upper body. Computed tomography showed No. 3 lymph node swelling, but no distant metastasis. Surgery was contraindicated because of many complications, so the patient was given combined chemotherapy with TS-1 and low-dose cisplatin. Chemotherapy was started on April 18. After 2 courses of chemotherapy the esophageal lesion showed a complete response, and after 5 courses the gastric lesion evidenced a complete response.     

Chemoradiotherapy and adjuvant chemotherapy for rectal cancer

Local recurrence is an important factor in determining the outcome of patients after surgery for rectal cancer, and various attempts have been made to reduce the local recurrence rate. Randomized controlled trials have shown that radiotherapy combined with total mesorectal excision can reduce the local recurrence rate in rectal cancer patients who undergo curative surgery. Chemoradiotherapy is more effective in achieving local control than radiotherapy alone, and preoperative chemoradiotherapy is superior to postoperative chemoradiotherapy in terms of adverse events. Recent advances have led to the identification of potential therapeutic targets such as epidermal growth factor receptor, vascular endothelial growth factor, and endothelial receptors. These new agents have been used in combination with conventional chemoradiotherapy, and higher pathological complete response rates have been reported for such combinations in comparison with conventional regimens. With regard to lateral node dissection, a recent study showed that postoperative chemoradiotherapy was more effective in reducing the local recurrence rate than lateral node dissection. As for adjuvant chemotherapy, one randomized controlled trial showed that patients who received uracil and tegafur as adjuvant therapy had significantly prolonged relapse-free survival times and overall survival times. As well, one metaanalysis has shown the efficacy of oral uracil-tegafur as adjuvant chemotherapy for rectal cancer.     

Adjuvant postoperative radiotherapy, chemotherapy, and immunotherapy in stage III breast cancer. II. 5-year results and influence of levamisole

One hundred twenty pathologically confirmed operable Stage III breast cancer patients were randomized to receive either postoperative radiotherapy or chemotherapy, or a combination of these, with or without levamisole immunotherapy. Radiotherapy was given to regional lymph nodes and chest wall. Chemotherapy consisted of six cycles of vincristine, doxorubicin, and cyclophosphamide. Radiotherapy provided local and chemotherapy systemic control over the tumor, but the best patient-saving results were achieved with a combination of radiotherapy and chemotherapy. This clinical trial was commenced in 1976, and the first 60 of 120 patients also received oral levamisole, 150 mg/day, on 2 consecutive days weekly as immunotherapy. All patients were followed for at least 5 years. At this stage levamisole seems to increase disease-free and overall survival in all three treatment arms (radiotherapy, chemotherapy, combined treatment). Significance is reached in disease-free survival (P = 0.035) and overall survival, adjusted for all other treatment modalities (P = 0.019).