Chemotherapy in urologic oncology

Chemotherapy is an effective treatment in urologic cancers either for localized tumor or metastatic disease. In urologic cancers, chemotherapy always takes part in a multidisciplinary strategy including surgery, oncology and radiotherapy. Except for metastatic testicular germ cell cancers, chemotherapy is a palliative treatment in other metastatic urologic cancers such as bladder and castration-resistant prostate carcinomas. In metastatic clear cell renal carcinomas, it has not any indication and anti-angiogenic drugs are the only therapeutic options. Neoadjuvant chemotherapy in non-metastatic muscle-invasive bladder cancers must be considered as a standard treatment in fit patients.     

食管癌新辅助放化疗对手术及生存率的影响

新辅助化疗常应用于实体肿瘤的手术前或围手术期,常联合应用放疗以提高生存率和治愈率,并对器官加以保护.手术仍是最有效的食管癌单一治疗手段.术前的(新辅助)化疗加放疗虽已经作为治疗食管癌的3种方法中的综合治疗模式存在近20余年,但他是否可作为食管癌的标准治疗模式仍存在争议.本文阐述了新辅助放化疗对食管癌手术及生存率的影响,提出了新辅助放化疗在食管癌治疗中的不足和发展方向.     

The role of neoadjuvant chemoradiation in pancreatic cancer

Although complete surgical resection, when possible, leads to prolonged survival in pancreatic cancer, if used alone, its results remain sub-optimal. Neoadjuvant strategies are recent in pancreatic cancer: in primary resectable tumors, they ensure that all patients obtain additional treatment to complete surgery; in locally advanced tumors, they allow a better selection of candidates for curative resection. By delaying surgery, neoadjuvant strategies modify the initial diagnostic process and the symptomatic treatment of pancreatic cancer. Several recent phase I-II studies have confirmed the feasibility and efficacy of the association of chemotherapy and radiotherapy, which is well-tolerated and is associated with better local control and survival. Due to the aggressiveness of pancreatic cancers, most recent cytotoxic agents should be associated with modern radiation techniques. Neoadjuvant chemoradiation is under evaluation in pancreatic cancers, and no randomized phase III trials comparing neoadjuvant and adjuvant therapeutic sequences has been reported. Moreover, radiological and pathological evaluations, not only at diagnosis, but also after preoperative chemoradiation, must be standardized to improve the selection of patients who will benefit from this multi-modal treatment.     

Neoadjuvant and adjuvant radio- and radio-chemotherapy of rectal carcinomas

The objectives in treating rectal cancer are to achieve locoregional tumor control and to prolong overall survival. With surgery alone the reported local failure rates in recent decades have been unacceptably high, and this is associated with substantial morbidity and mortality. Perioperative radiotherapy with or without concomitant chemotherapy has been used extensively to reduce the high frequency of local recurrence. Adjuvant radiotherapy reduces the local recurrence rate dramatically if the dose is high enough and is administered preoperatively. Although a higher dose has been used in most postoperative radiotherapy trials, the reduction has not proven particularly pronounced. If the reduction were as great as that with preoperative radiotherapy, it would also have a positive effect on survival, which as yet has not been achieved with postoperative radiotherapy. However, postoperative irradiation combined with chemotherapy yields a survival benefit of the same magnitude as preoperative irradiation. Modern radiation techniques allow preoperative radiotherapy to be delivered without interfering substantially in the postoperative healing process; it does not increase mortality or morbidity and entails a low rate of late toxicity if the radiation technique is optimal. A major question today is whether radiotherapy is necessary if surgery is optimal. Control trials report an average local recurrence rate of 29% with standard surgery. With optimal surgery the figure reported from institutional series is about 10%. Other questions to be answered include whether to use superfractionation or standard fractionation in radiotherapy, and how chemotherapy should be given, concomitantly to radiotherapy or in the classical method of postoperative intravenous treatment. Accepted: 26 November 1999     

Neoadjuvant therapy in early-stage breast cancer

Neoadjuvant (preoperative) chemotherapy is becoming a commonly used option for women with early-stage breast cancer, allowing a greater proportion of patients to undergo breast conservation surgery. Neoadjuvant chemotherapy also allows the early assessment of response or resistance to chemotherapy and facilitates chemotherapy delivery prior to any surgical alterations to the vasculature. Ongoing research is examining the potential benefits of neoadjuvant therapy with cytotoxic agents as well as other treatments, including endocrine therapies and biologic agents. Additionally, biomarkers are being intensively investigated as methods for identifying patients who will most likely benefit from neoadjuvant chemotherapy. As of yet, neoadjuvant chemotherapy has not demonstrated a definitive benefit over adjuvant (postoperative) chemotherapy with regard to prolonging survival. It remains to be seen whether novel cytotoxic agents used in the neoadjuvant setting will improve pathologic clinical response rates and ultimately improve long-term outcome in women with early-stage breast cancer.     

Is There a Survival Benefit in Patients With Stage IIIA (N2) Non-small Cell Lung Cancer Receiving Neoadjuvant Chemotherapy and/or Radiotherapy Prior to Surgical Resection: A Systematic Review and Meta-analysis

Optimal management of clinical stage IIIA (N2) non-small cell lung cancer (NSCLC) is controversial. This study is a systematic review and meta-analysis of published randomized control trials of multimodality management strategies for NSCLC.We conducted a comprehensive literature search of the Pubmed, Embase, Medline, and CENTRAL databases for relevant studies comparing patients with stage IIIA (N2) NSCLC undergoing surgery alone, chemotherapy and/or radiotherapy alone, or surgical resection after neoadjuvant treatment with chemotherapy and/or radiotherapy. We estimated hazard ratios, odds ratios (ORs), and 95% confidence intervals (CIs) for survival data.Seven trials involving 1049 patients were included in this study. There was no significant difference in overall survival (OS) or progression-free survival (PFS) in stage IIIA (N2) NSCLC patients who received neoadjuvant chemotherapy or chemoradiotherapy prior to surgical resection compared to those who received neoadjuvant chemotherapy or chemoradiotherapy prior to radical radiotherapy. There was a significant increase in pathological complete remission in the mediastinal lymph nodes in stage IIIA (N2) NSCLC patients who received neoadjuvant chemoradiotherapy prior to surgical resection compared to those who received neoadjuvant chemotherapy (OR 3.61; 95% CI 1.07–12.15; P = 0.04), but no difference in tumor downstaging, OS, or PFS.Neoadjuvant chemotherapy and/or radiotherapy prior to surgical resection do not appear to be clinically superior to neoadjuvant chemotherapy and/or radiotherapy prior to definitive radiotherapy in IIIA (N2) NSCLC patients. Neoadjuvant chemoradiotherapy does not improve survival compared to neoadjuvant chemotherapy alone.     

Vaginal cancer

Because of the low incidence of vaginal cancer, phase III trials have not been carried out and current guidelines have been drawn on retrospective studies. This state of affairs explains the variety of treatments to which women affected by this disease are subjected to. In this article, we report the current results achieved by different therapeutic strategies. The primary treatment options in Stage I vaginal carcinoma are surgery and/or radiotherapy. For a small tumor, a wide excision can be used. For high risk patients, a more aggressive surgery is mandatory. The most frequently adopted treatment strategy for Stage II is a combination of brachytherapy and EBRT. Selected patients may be treated by radical surgery. Neoadjuvant chemotherapy followed by radical surgery is a valid alternative to the standard treatment in terms of survival. Combination of EBRT and brachytherapy is the most commonly adopted treatment in stages III-IV A and, in selected patients, pelvic exenteration or a combination of irradiation and exenteration can be used.     

Cell kinetics as a prognostic marker in locally advanced breast cancer

The study analyzes the prognostic implication of cell kinetics on 52 locally advanced breast cancers. All patients were subjected to a multimodal treatment, including primary chemotherapy with doxorubicin and vincristine, surgery, or radiotherapy followed by additional chemotherapy with the same drug regimen. Pretreatment labeling index (LI) is not related to response to primary chemotherapy, whereas it provides information on the course of the disease. In fact, high LI significantly predicts a higher progression rate at the end of the entire combined treatment, a shorter time to disease progression, and a poorer probability of 4-year survival in comparison to low LI. From the present findings, LI appears to be a useful tool to select women with locally advanced breast cancer that would require very aggressive treatment.     

Role of radiotherapy in the treatment of small cell lung carcinoma

For several years, chemotherapy has been the only treatment of small-cell carcinoma of the lung, but radiotherapy is increasingly used for its local effect in various ways. Irradiation of the chest alternating or concomitant with chemotherapy has become a basic principle in localized forms of the disease and may perhaps be useful in its diffuse forms. The so-called "prophylactic" brain irradiation is routinely performed, even though its beneficial effect on survival has not yet been demonstrated. As for extensive irradiation, it is still under study. Radiotherapy therefore plays an important role which, added to that of chemotherapy, should result in an improvement of long-term survival in patients with small-cell carcinoma of the lung.     

Trepanobiopsy as a tool for the study of the influence of presurgical treatment on the steroid receptor status of advanced breast cancer

Estrogen, progesterone and glucocorticoid receptors were determined in samples obtained by trepanobiopsy before treatment and in surgical material following chemo- or radiotherapy in 131 Stage III a, b, c breast cancer patients. The levels and distribution of the receptors in bioptates coincided with the data obtained earlier for the surgical material from patients, who didn't receive presurgical therapy. It is concluded that breast tumor trepanobioptates may be used for the determination of tumor receptor status. Radiotherapy affected the level and frequency of occurrence of steroid hormone receptors. The degree of variations depended on the dosage of irradiation and after exposure period. After presurgical chemotherapy the percent of receptor-positive tumors increased.     

立体定向适形放疗肝转移瘤临床疗效多因素分析

目的探讨立体定向适形放疗治疗肝转移瘤的预后因素。方法39例肝转移瘤患者接受立体定向适形放疗,共3—6周,肝转移瘤放疗剂量52—68Gy,平均58．8Gy,25例放疗前曾接受化疗。用Log—rank法比较各组患者的中位生存期,用单因素分析和COX回归模型多因素分析。结果39例中位生存期为14个月。单因素分析结果显示,患者的预后与肝转移瘤体积大小、数目、位置、放疗剂量、治疗时间、化疗、KPS评分有关。多因素分析显示放疗剂量、化疗是影响预后的重要因素。结论立体定向适形放疗是治疗肝转移瘤的有效方法,放疗剂量和化疗是重要的独立的预后因素。     

原发性中枢神经系统淋巴瘤23例临床分析

目的 探讨原发性中枢神经系统淋巴瘤(PCNSL)的诊断、合理治疗方案和预后的相关因素.方法 收集天津医科大学肿瘤医院2005年1月至2007年12月经病理证实且随访资料完整的23例免疫功能正常的PCNSL患者,其中男10例,女13例,中位年龄50岁.行腰穿检查者18例,检查出瘤细胞者4例.8例行开颅手术切除,15例行立体定向活检术.4例行全颅放疗,6例行以大剂量甲氨蝶呤为基础的联合化疗,13例行放疗联合化疗.分析其治疗、临床特点与预后之间的联系.结果 Kaplan-Meier分析显示本系列患者中位生存期45.0个月,3年生存率56.5％.Log-Rank检验发现放疗联合化疗组(43.8和30.0个月)与化疗组(39.7和29.7个月)的总生存期及肿瘤无进展生存期明显长于单纯放疗组(25.7和19.8个月,P值均＜0.05);放疗联合化疗组的总生存期长于单纯化疗组(P＜0.05),2组间肿瘤无进展生存期无明显差异(P＞0.05).结论 病理诊断仍是确诊的金标准,脑脊液检查发现瘤细胞者也可确诊.以全颅放疗联合化疗为主的综合治疗优于单纯放疗或化疗.     

Effect of prior radiotherapy on tolerance and response to chemotherapy in non-hodgkin's lymphoma

Twenty-five patients who had received radiotherapy as their primary treatment for non-Hodgkin's lymphoma subsequently relapsed; they were then treated with combination chemotherapy and their tolerance and response evaluated. Radiotherapy delivered as total body irradiation and other forms of radiotherapy delivered to > 15% of the bone marrow caused significantly lower platelet nadirs during subsequent chemotherapy when compared to patients receiving radiotherapy to ≤ 15% of their bone marrow. In spite of this thrombocytopenic effect, the eventual total doses of chemotherapy delivered were not significantly compromised. A response to chemotherapy was more likely in patients with a prolonged (> 6 months) response to radiotherapy. However, a chemotherapy response was equally likely in patients receiving involved field (IF), extended field (EF), or total nodal irradiation (TNI) as compared to those receiving total body irradiation (TBI). Chemotherapy responses (complete and partial) occurred in 75% of both radiotherapy groups with complete responses more likely in the IF, EF, or TNI group. The median durations of response were slightly longer in the IF, EF, or TNI radiotherapy group (6 months vs 5 months; p = 0.07) but were shorter than those in previously reported patients not receiving prior radiotherapy. Similarly the duration of a chemotherapy response was not affected by the histology of the tumor. However, although the survival of patients following chemotherapy was not significantly affected by the histology of the tumor there was a tendency towards a longer survival for lymphocytic histology as compared to histiocytic.     

Effect of primary treatment modality on the metastatic pattern of mammary carcinoma.

In animal tumor systems, all three major treatment modalities, surgery, radiotherapy, and chemotherapy, may increase the incidence of metastases in the presence of circulating viable tumor cells. In breast cancer patients, selected studies can be found which report an increased incidence of metastases after surgery, radiotherapy, or chemotherapy, but these effects appear to exert little influence on overall survival. Caution is advised in using systemic therapy prior to effective primary tumor cytoreductive treatment. Clinical trials in advanced local disease should be done to test this concern. Minimal surgery, loco-regional radiotherapy, and effective adjuvant systemic therapy may result in the improved survival of patients with breast cancer with minimal functional or cosmetic impairment.     

No damaging effect of chemotherapy in addition to radiotherapy on the thyroid axis in young adult survivors of childhood cancer

Late effects of treatment for childhood cancer on the thyroid axis are ascribed predominantly to radiotherapy. Whether chemotherapy has an additional detrimental effect is still unclear. Our aim was to evaluate this effect in young adult survivors of a broad spectrum of childhood cancers. The thyroid axis in 205 childhood cancer survivors was evaluated in relation to former use of chemotherapy and radiotherapy (cranial, cranio-spinal, cervical, mediastinal, or thoracic). The mean follow-up time was 17.5 yr. Damage to the thyroid axis was found in 55 patients (26.8%). Thirty-seven patients (18%) had thyroidal disease. Diagnoses varied from TSH elevation to papillary carcinoma. After multivariate analysis, high risk radiation field, irradiation dose, and the diagnosis of non-Hodgkin lymphoma/Hodgkin's disease were found to be significant risk factors for developing thyroid disease. Treatment with chemotherapy did not have an additional negative effect on the thyroid axis. For the development of central (pituitary or hypothalamic) thyroid dysfunction, patients with a brain tumor were at increased risk. Chemotherapy for childhood cancer does not contribute to the damage on the thyroid axis inflicted by radiotherapy during young adulthood.     

High-dose intravenous methotrexate in the management of breast cancer with leptomeningeal disease: Case series and review of the literature

Leptomeningeal metastasis (LM) in breast cancer is associated with significant morbidity and mortality. While there is currently no standard therapy, treatment options include craniospinal radiotherapy, intrathecal chemotherapy and systemic chemotherapy. Craniospinal radiotherapy has not demonstrated improved survival and intrathecal chemotherapy is often poorly tolerated due to associated neurotoxicity. The use of systemic chemotherapy can be limited by inadequate central nervous system penetration. High-dose systemic methotrexate administered intravenously (HD-MTX), has been reported to improve quality of life and provide durable remissions for LM in breast cancer. We present three cases of metastatic breast cancer and LM with prolonged survival after administration of HD-MTX. Based on our observations and review of the literature, HD-MTX seems to be a viable treatment option for patients with LM in breast cancer, and in select cases, the use of HD-MTX, as part of a multimodality treatment plan, may be associated with prolonged survival.     

Anaplastic thyroid carcinoma

Anaplastic thyroid carcinoma may represent the ultimate dedifferentiation step of thyroid tumorigenesis and is one of the poorest cancers in human. It accounts for less than 2% of thyroid cancers and affects older patients in their sixth to eighth decade. Usual clinical presentation is a rapidly growing thyroid mass invading surrounding structures with compressive symptoms. Cervical lymph nodes enlargement and distant metastases occur frequently. Though cytological results obtained by fine needle aspiration may be suggestive of diagnosis, tissue biopsy for immunohistochemical study can be necessary to exclude lymphoma and to validate aggressive therapies. Patients developing anaplastic thyroid cancer must be referred urgently in cancer centers to plan multimodality therapeutic approach depending on their performance status. The treatment regimen combines surgery when feasible, hyperfractionated and accelerated external beam radiotherapy and doxorubicin based chemotherapy. Such treatment can provide control of locoregional disease but does not impact on overall survival in patients with distant metastases. The prognosis is dismal with a mean survival of four to nine months after diagnosis. Long survivors are patients with emerging disease presenting a resectable tumor and receiving adjuvant radiotherapy and/or chemotherapy. Therapeutic researches investigate redifferenciation strategies and targeted therapies to inhibit EGF receptors and neoplastic angiogenesis. Primary prevention of this lethal disease may consist of adequate treatment of differentiated thyroid cancers and goiters in elderly.     

Perioperative radiotherapy in the management of rectal cancer.

Surgery for rectal cancer has resulted in unacceptably high local failure rates, and substantial morbidity and mortality. In an attempt to reduce the high frequency of local recurrence, perioperative radiotherapy has been used extensively, alone or in combination with chemotherapy. The local recurrence rate has been reduced dramatically with the use of radiotherapy, and provided that the dose is high enough and given preoperatively, the reduction rate has been about 50%. Despite that a higher dose is used in postoperative radiotherapy, the reduced recurrence rate is not that prominent. The reduced recurrence rate demonstrated after preoperative radiotherapy has a positive influence on survival, which has not been seen when radiotherapy is given postoperatively. However, when postoperative irradiation has been combined with chemotherapy, a survival benefit has been demonstrated. With modern radiation techniques, preoperative radiotherapy can be delivered without any substantial increase in postoperative mortality or morbidity, and a low rate of late toxicity, provided that the radiation technique is optimal. The main question is whether radiotherapy is necessary, provided that surgery is optimized. With standard surgery, the average local recurrence rate is 29% in all reported controlled trials. With optimal surgery, from institutional series, this figure is about 10%. Other questions to be answered are whether superfractionated or standard fractionation should be used in radiotherapy and exactly to whom it should be given.     

同步放化疗在中晚期宫颈癌中的应用进展

同步放化疗治疗中晚期宫颈癌较单纯放疗能提高总生存率和无进展生存率,降低复发率,改善预后。同步放化疗不是简单的放疗与化疗相加,化疗不仅能杀死癌细胞,杀灭肿瘤亚临床病灶,同时对放疗有增敏作用。同步放化疗机制可能是化疗抑制肿瘤细胞放疗后损伤的修复,减少对放疗不敏感的乏氧细胞的比例和促使肿瘤细胞同步化进入对放疗敏感的细胞周期。目前大多数研究者认为使用以顺铂为基础的同步放化疗方案效果更佳。同步放化疗较单纯放疗的毒副作用相对较大,具体使用仍处于摸索阶段。     

Combination chemotherapy in Hodgkin's disease: relation to radiotherapy.

The results of modern radiotherapy for Hodgkin's disease are correlated to the stage of the disease. Five-year disease-free survival for pathologically staged patients can be estimated as follows: PS I & II A...90%, PS III A & IIIsA...60%, PS I & II B ...75%, PS III B & IIIsB ...40%. Combination chemotherapy of the MOPP (nitrogen mustard, vincristine, procarbazine, and prednisone) type can be successfully employed for patients who develop recurrent disease after total lymphoid irradiation. There have been several randomized clinical trials attempting to improve the curative potential of radiotherapy by combining modern chemotherapy with the irradiation as an adjuvant. The tolerance of patients to total lymphoid irradiation and chemotherapy will be presented. The Stanford trial, initiated 5 years ago (1968), has demonstrated prolonged disease free survival when both forms of treatment are used initially in certain stages of the disease. However, actual survival has not yet improved, probably because the chemotherapy is successful in inducing durable remissions for patients who recur after irradiation.