The membrane targeted apoptosis modulators erucylphosphocholine and erucylphosphohomocholine increase the radiation response of human glioblastoma cell lines in vitro

Cervical cancer continues to be a significant health burden worldwide. Globally, the majority of cancers are locally advanced at diagnosis; hence, radiation remains the most frequently used therapeutical modality. Currently, the value of adding cisplatin or cisplatin-based chemotherapy to radiation for treatment of locally advanced cervical cancer is strongly supported by randomized studies and meta-analyses. Nevertheless, despite these significant achievements, therapeutic results are far from optimal; thus, novel therapies need to be assayed. A strategy currently being investigated is the use of newer radiosensitizers alone or in combination with platinum compounds. In the present work, we present preclinical information on known and newer cytotoxic agents as radiosensitizers on cervical cancer models, as well as the clinical information emanating from early phase trials that incorporate them to the cervical cancer management. In addition, we present the perspectives on the combined approach of radiation therapy and molecular target-based drugs with proven radiosensitizing capacity.     

Counterpoint: test the value of hyperthermia in patients with carcinoma of the cervix being treated with concurrent chemotherapy and radiation.

Major advances in the treatment of locally advanced cervical carcinoma were reported in 1999-2000 in five studies from the Gynecologic Oncology Group, Radiation Therapy Oncology Group and Southwestern Oncology Group. Collectively these trials reported a decrease in the risk of recurrence or death from cervical cancer ranging from 30-50% with the use of concurrent chemoradiation, as compared with radiation alone. On the basis of these trials the National Cancer Institute in 1999 issued a clinical alert concluding 'Strong consideration should be given to the incorporation of concurrent cisplatin-based chemotherapy with radiation therapy in women who require radiation therapy for treatment of cervical cancer.' Concurrently with these publications there appeared the publication in the Lancet in 2000 of the Dutch Deep Hyperthermia Group trial of radiotherapy alone versus combined radiation and hyperthermia for locally advanced pelvic tumors including carcinoma of the cervix. This multi-center phase III trial demonstrated an approximate doubling of the three year survival from 27 to 51% for the addition of hyperthermia to radiotherapy in patients with locally advanced cervical carcinoma. Additional trials to test the value of hyperthermia in patients with cervical carcinoma treated with concurrent chemotherapy and radiation are imperative and take precedence over a trial to investigate the value of chemotherapy in patients treated with hyperthermia and radiation.     

Management of locally advanced cervical cancer

PURPOSE OF REVIEW: Cervical cancer is a significant global public health problem. In underdeveloped countries where screening programs are not widely available and in underserved populations in developed countries, women commonly present with locally advanced disease that is not curable by any extent of radical hysterectomy. This review will critically evaluate the evidence supporting the available treatment modalities for locally advanced cancer of the uterine cervix. RECENT FINDINGS: Concurrent cisplatin-based chemotherapy and radiation have demonstrated significant survival improvement for patients with locally advanced cervical cancer. Advances in imaging and radiotherapy technologies, the inclusion of newer agents to the chemoradiation regimens, the use of new hypoxic cell radiosensitizers and monoclonal antibodies that inhibit cell growth, with consequent increase in malignant cell kill fractions, are some of the new therapeutic options that may be used to improve the survival of these patients. SUMMARY: Continued improvement in understanding the natural history of cervical cancer, the limitations of the current staging system, and these newer therapeutic options will increase the efficacy of chemoradiation and improved the survival of these patients.     

COUNTERPOINT: Test the value of hyperthermia in patients with carcinoma of the cervix being treated with concurrent chemotherapy and radiation

Major advances in the treatment of locally advanced cervical carcinoma were reported in 1999-2000 in five studies from the Gynecologic Oncology Group, Radiation Therapy Oncology Group and Southwestern Oncology Group. Collectively these trials reported a decrease in the risk of recurrence or death from cervical cancer ranging from 30-50% with the use of concurrent chemoradiation, as compared with radiation alone. On the basis of these trials the National Cancer Institute in 1999 issued a clinical alert concluding 'Strong consideration should be given to the incorporation of concurrent cisplatin-based chemotherapy with radiation therapy in women who require radiation therapy for treatment of cervical cancer.' Concurrently with these publications there appeared the publication in the Lancet in 2000 of the Dutch Deep Hyperthermia Group trial of radiotherapy alone versus combined radiation and hyperthermia for locally advanced pelvic tumors including carcinoma of the cervix. This multi-center phase III trial demonstrated an approximate doubling of the three year survival from 27 to 51% for the addition of hyperthermia to radiotherapy in patients with locally advanced cervical carcinoma. Additional trials to test the value of hyperthermia in patients with cervical carcinoma treated with concurrent chemotherapy and radiation are imperative and take precedence over a trial to investigate the value of chemotherapy in patients treated with hyperthermia and radiation.     

Treatment of stage IB2 (bulky) cervical carcinoma

Tumour size is an important prognostic factor in patients with stage IB cervical cancer. The patient with stage IB2 (bulky) cervical cancer represents a therapeutic challenge. Neither radical hysterectomy nor primary radiation therapy are sufficiently effective and are associated with significant treatment-related complications including ovarian failure and psychosexual deficits. A number of phase III studies have explored alternative management approaches in this patient population. It appears that extrafascial hysterectomy following radiation therapy does not improve overall survival relative to radiation therapy alone. Consistent with results seen in locally advanced cervical carcinoma, chemoradiation therapy is superior to radiation therapy alone as primary treatment for stage IB2 cervical cancer and as adjuvant therapy for surgically treated patients with high-risk factors for recurrence. Neoadjuvant chemotherapy has resulted in high clinical response rates and operability rates. There are two phase III trials suggesting an improvement in survival with neoadjuvant chemotherapy followed by radical hysterectomy versus either surgery (and selected postoperative radiation) or radiation therapy alone. These emerging treatments should be scrutinized in prospective controlled trials.     

Biological predictors of cervical cancer response to radiation therapy

The addition of cisplatin-based chemotherapy to standard radiation therapy reduces the risk of recurrence and disease-related death rates from locally advanced cervical cancers by as much as 50%. However, the absolute gains are relatively small for patients with early tumors, many of whom would have been cured with radiation alone, and recurrence rates are still high for patients who have very large or advanced-stage tumors. As a result, there is a pressing need for more accurate predictors of radiocurability. A variety of types of biomarkers have been shown to correlate with cervical cancer response to radiation therapy. These include traditional clinical and morphologic predictors, non-molecular biomarkers, including hypoxia and fluorodeoxyglucose-positron emission tomography (FDG-PET) avidity, as well as molecular biomarkers, which include single-gene markers or array-based multigene predictors. Multi-gene predictors of response remain immature in cervical cancer, but studies thus far have paved the way for future studies to validate these findings. Methods will need to be standardized and markers will need to be validated on homogeneous patient populations and treatment approaches before they can become useful tools for clinical decision making. In addition, new biomarkers will be of major value only if they add to the predictive value of traditional clinical and morphologic predictors. Ultimately, the most useful biomarkers will identify patients who will benefit from specific molecularly targeted agents in addition to radiation therapy or perhaps identify patient who are at low risk for recurrence, for whom the dose of radiation or chemotherapy can be reduced.     

Combined radiation therapy and chemotherapy for carcinoma of the cervix

Cervical cancer is the third most common cancer affecting women worldwide. Surgery, radiation therapy, and chemotherapy have been used in various settings in an effort to improve survival rates of patients with cervical cancer. Recent cooperative clinical trials have demonstrated a benefit from the concurrent use of chemotherapy and radiation therapy to treat cervical cancer. These studies have provided the most significant improvement in the treatment of locally advanced disease in more than 30 years. This review summarizes studies of sequential and concurrent combinations of chemotherapy and radiation therapy for the treatment of cervical cancer, as well as the recent controversies related to this treatment.     

Treatment of locally advanced prostate cancer: is chemotherapy the next step?

PURPOSE: Management of locally advanced prostate cancer remains controversial. Various single and combination modality approaches have been advocated, but an accepted standard of care remains undefined. The purpose of this review is to define the current knowledge in managing locally advanced prostate cancer and to propose new treatment approaches based on current knowledge. MATERIALS AND METHODS: A MEDLINE search to detect all relevant articles on the management of locally advanced prostate cancer was performed. A review of the staging, natural history, and prognosis of this disease was also performed. RESULTS: The lack of a clearly defined treatment approach to patients with locally advanced prostate cancer stems from multiple factors, including ambiguities in clinical staging, inadequate knowledge of the natural history of the cancer, and a dearth of comparative randomized trials evaluating efficacy of different therapies. Single modality treatment, including radical prostatectomy (RP) or external-beam radiotherapy alone, is associated with high rates of failure. The use of adjuvant hormonal ablation therapy in combination with external-beam radiotherapy has shown improvement in progression-free and overall survival, although similar improvements have not been clearly demonstrated for surgical patients treated with hormonal therapy. New advances in chemotherapy for hormone-refractory prostate cancer suggest that response rates may be as high as 50% or more, and current trials are evaluating the addition of chemotherapy to hormonal ablation in either surgery or radiation therapy in locally advanced prostate cancer. CONCLUSION: Optimal management of locally advanced prostate cancer remains undefined. Standard treatment options include RP, external-beam radiotherapy, or hormonal ablation therapy, alone or in combination. New approaches being tested include improved methods for delivering radiation or combining hormonal ablation with surgery or radiation. It is possible that other forms of systemic therapy, including chemotherapy, may become important components of multimodality treatment. Clinical trials designed to test this hypothesis are ongoing.     

Optimizing treatment for cervical cancer

There are a number of ways in which surgery, radiation therapy, and more recently chemotherapy have been employed in the treatment of locally advanced cervical cancer. The evidence in favor of chemoradiation in cervical cancer was summarized in a meta-analysis of 19 trials which showed improvement with the concomitant administration of chemotherapy and radiation (CRT), not only in survival (by >10% at 5 years) but also in both local and distant recurrence rates. These results validate the National Cancer Institute Alert (USA) in February 1999, which was based on preliminary evidence from five randomized trials, and stated that concomitant chemoradiotherapy should be considered for the majority of patients with cervical cancer. However, patients with locally advanced disease with negative para-aortic nodes accounted for the majority of those selected for these trials, and the benefits of the addition of chemotherapy to radiation were clearer in stages I and II disease. Acute and late toxicity remain areas of concern. The role of surgery is also undergoing re-evaluation, both in early disease where surgery may offer equal survival to radiation with reduced morbidity, and in more locally advanced cases where recent data have shown surgery preceded by chemotherapy achieves similar gaines in absolute survival compared with radiation alone. The trials involving CRT differed in size, design, accrual period and chemotherapeutic agent used, and there has been extensive debate about optimization of the radiation dose and whether chemotherapy in some of the trials compensates for inadequate radiation dose. However, these factors would not account for the improvement in distant relapse rates observed. Similarly, surgical expertise has been shown to be a major factor affecting outcome in radical procedures, and recent developments in more conservative surgery also improve morbidity in selected cases. The alternative strategy of neoadjuvant chemotherapy prior to surgery (NACT-S) has been evaluated extensively in South America and Italy in groups similar to those in which CRT has been shown to be effective. Although the data are promising, the evidence base for outcome compared with radiation alone is much smaller, and there have been no direct comparisons with CRT. The chemotherapy in CRT may be acting predominantly through a cytotoxic effect as distinct from having a sensitization effect, and hence the rationale for these two approaches (CRT and NACT-S) may be broadly similar, that is, early control of systemic disease as well as additional local control to that achieved by either surgery or radiation alone. The sequential use of further chemotherapy after these strategies is under development. In early disease, surgery and radiation therapy are comparable in terms of efficacy, and the preference for surgery is based on reduced morbidity and the potential to preserve fertility. The addition of platinum-based chemotherapy, either prior to surgery or with radiation improves survival and distant recurrence rates in more locally advanced cases up to stage IIb, or in those patients with adverse risk factors. The available data are insufficient to recommend routine adoption of CRT in earlier (stage Ia2) or more advanced cases (stages III or IV). However, with the enrolment of over 4000 women in randomized trials and mature follow-up, chemoradiation has become an established treatment.     

局部晚期宫颈癌化疗联合放疗最佳模式探讨

目的 放疗是局部中晚期宫颈癌的主要治疗方式,目前同步放化疗已经成为局部中晚期宫颈癌的标准治疗模式,诱导化疗和辅助化疗在同步放化疗时代的角色未明,其疗效与预后的优劣并未达成共识,本研究旨在通过回顾性分析探讨局部中晚期宫颈鳞癌的最佳治疗模式,为临床治疗提供理论依据.方法 回顾性分析2008-01-01-2010-01-31湖南省肿瘤医院收治的212例初治中晚期宫颈鳞癌患者,根据治疗方式分为A、B和C3组,诱导及辅助化疗为TP方案,即紫杉醇联合顺铂,同步放化疗为顺铂单药或顺铂联合紫杉醇,A组(对照组):同步放化疗82例,B组(观察组):诱导化疗联合同步放化疗98例,C组(观察组):同步放化疗联合辅助化疗32例,观察比较3组的近期疗效、远期疗效和不良反应.结果 A、B和C组近期疗效分别为93.90％、94.90％和96.88％,差异无统计学意义,P＞0.05;A、B和C组总生存率(0S)第1年分别为90.24％、90.82％和87.50％;第3年分别为85.37％、87.76％和81.25％;第5年分别为82.93％、83.67％和75.00％;3组比较差异均无统计学意义,P＞0.05.A、B和C组局控率分别为86.58％、86.73％和87.50％,差异性无统计学意义,P＞0.05;A、B和C组无进展生存率分别为67.07％、74.49％和68.75％,差异均无统计学意义,P＞0.05;A、B和C组无远处转移生存率分别为70.73％、93.08％和71.88％,差异有统计学意义,P＜0.05.不良反应主要表现为观察组3级以上白细胞及血小板减少.进一步比较观察组间骨髓抑制差异无统计学意义,P＞0.05;消化道反应及肝功能损害3组比较差异均无统计学意义,P＞0.05;晚期放射性损伤主要表现为放射性直肠炎和放射性膀胱炎,3组比较差异无统计学意义,P＞0.05.结论 诱导化疗可以提高局部晚期宫颈癌的无远处转移率,有延长OS趋势;辅助化疗对局部晚期宫颈癌未见明显生存获益;诱导化疗联合同步放化疗是一种较为有效的局部晚期宫颈癌治疗方案,值得临床进一步推广使用,并通过大样本资料研究加以证实.     

Modern management of locally advanced cervical carcinoma

Radiation was until recently the key and only modality for the routine treatment of locally advanced cervical carcinoma. However after years of studying multi-modality treatments as an alternative to radiation alone in randomized phase III trials, the standard treatment has changed to chemo-radiation based on cisplatin. Three recent meta-analyses have confirmed that cisplatin-based chemo-radiation adds an absolute 12% benefit in five-year survival over radiation therapy alone. Neoadjuvant chemotherapy followed by radiation has not been of proven benefit, but when neoadjuvant chemotherapy is followed by surgery, an absolute increase of 15% in five-year survival over radiation alone is seen. This benefit in survival is comparable to that obtained with the current chemo-radiation schedules based on cisplatin. Despite these encouraging results there remains room for improvement as the five-year survival of patients treated with chemo-radiation ranges from nearly 80% in bulky IB tumours to only 25% in stage IVA disease. Other therapeutic approaches need to be fully evaluated including the use of chemo-radiation after neoadjuvant chemotherapy; the use of new drug combinations and the multi-modality combination of neoadjuvant chemotherapy followed by radical surgery plus adjuvant chemo-radiation. Likewise, the addition of radiosensitizers to cisplatin, preoperative chemo-radiation and/or adjuvant chemotherapy may eventually improve the currents results of cisplatin-based chemo-radiation. Nevertheless, it is hard to foresee a dramatic increase in cure rate, even with the most optimal combination of cytotoxic drugs, surgery and radiation, and thus the testing of molecular targeted therapies against cervical cancer is a logical step to follow.     

Induction chemotherapy followed by radical local therapy for locally advanced non-small cell lung cancer

Many patients who receive a diagnosis of non-small cell lung cancer (NSCLC) have locally advanced disease at initial presentation. Historically, these patients were treated with primary thoracic radiation therapy and had poor long-term survival rates, secondary to both progression of local disease and development of distant metastases. With the goal of improving clinical outcomes, multiple concepts of combined-modality therapy for locally advanced NSCLC have been investigated. The rationale for using chemotherapy in the induction regimen is to eliminate subclinical metastatic disease while improving local control. The optimal treatment of locally advanced NSCLC continues to evolve, but combined-modality therapy has led to improved survival rates compared to treatment with radiation alone and has become the new standard of care. This report reviews the major trials that have investigated various combinations of surgery, radiation therapy, and chemotherapy in the treatment of locally advanced NSCLC.     

Chemotherapy and immune check point inhibitors in the management of cervical cancer

Management of locally advanced cervix cancer underwent major change 2 decades back when concurrent chemotherapy (CCRT) (with cisplatin alone or in combination) along with definite radiation therapy (external + brachytherapy) was found to be superior compared to radiation alone in a series of randomized trials. Since then CCRT has been the standard treatment approach; this has resulted in 5-year overall survival rate of 66% and disease-free survival (DFS) of 58%. About 30% to 40% of patients with locally advanced cervical cancer continue to have treatment failure. Also, some patients experience early and late side effects of treatment with negative impact on quality of life. To improve the outcome further – recent approaches have explored use of weekly paclitaxel and carboplatin for 4 to 6 weeks as dose dense chemotherapy prior to CCRT, adjuvant chemotherapy after CCRT in high risk patients. For patients with early stage disease (IA2-IIA), short course chemotherapy prior to surgery is associated with improved outcome in many studies.Bevacizumab- an inhibitor of vascular endothelial growth factor – is associated with improved survival. More recently, addition of treatment with immune check inhibitors (to boost the ability of T cells to destroy cancer cells) have improved responses and survival in the treatment of recurrent and metastatic cervical cancer. Whether these and other similar novel agents targeting molecular pathways could be brought in front line treatment along with cytotoxic chemotherapy along with bevacizumab are potential areas of current research.     

局部进展期胰腺癌的多学科综合治疗

胰腺癌是恶性程度高且预后极差的消化系统肿瘤。对可手术切除的局限性胰腺癌,因其术后局部复发儿率也较高,故建议采用以手术为主的多学科综合治疗。外放射治疗是无法手术胰腺癌的主要治疗手段。对无法切除的局部进展期肿瘤,主要采用局部外放射治疗联合全身化疗的多学科综合治疗。Ⅲ期随机临床研究结果已经证实,同期联合放化疗较单一放射治疗对患者的生存具显著优势。与放射治疗同步应用的化疗药物目前主要包括5-FU、卡培他滨与吉西他滨等。同期联合放化疗中应用多药联合化疗方案可明显增加治疗相关的不良反应,但临床研究结果并未显示多药方案对疗效及患者预后有所助益。放疗技术目前推荐三维适形放射治疗或调强放疗（IMRT）。靶区范围建议包括临床影像检查可见肿瘤外放安全边界,对未被侵及的淋巴引流区域不行预防性照射。IMRT不仅可减低周围正常组织的照射剂量,还可提高肿瘤靶区的照射剂量,实现剂量递增。     

以顺铂为基础不同化疗方案同期放化疗治疗局部中晚期子宫颈癌临床研究

目的 探讨单药顺铂与TP(紫杉醇+顺铂)方案同步放化疗治疗中晚期子宫颈癌的临床疗效及不良反应比较.方法 随机入组44例局部中晚期子宫颈癌患者随机给予单药顺铂方案或TP方案化疗,两组同期放疗均采用盆腔外照射+高剂量率腔内后装.结果 所有患者均完成治疗,治疗结束3月评价其有效率,TP组为66.7 ％,顺铂组为55.0％.1年生存率分别为88.3％、70.0％,差异无统计学意义(P值＞0.05).毒副反应主要是粒细胞减少、胃肠道反应.同期放化疗期间TP组、单药顺铂组发生Ⅲ～Ⅳ度粒细胞减少和Ⅲ～Ⅳ度胃肠道反应分别为16.7％vs5.0％(P＞O.05),12.5％ vs 5.0％(P＞0.05).结论 TP方案与单药顺铂同期放化疗治疗局部中晚期子宫颈癌患者的疗效比较,前者的近期疗效及1年生存率均较后者有所提高,差异无统计学意义(P＞0.05),但从百分率来看,TP组在近期疗效及1年生存率方面均有升高的趋势.尽管联合化疗方案中出现Ⅲ、Ⅳ度放化疗反应的病例数较单药组有所增加,但可以耐受,不影响治疗的完成.     

A retrospective review of 15 years of radical radiotherapy with or without concurrent cisplatin and/or 5-fluorouracil for the treatment of locally advanced cervical cancer

Radiation therapy is the standard of care treatment for locally advanced cervical cancer in the United States. In 1999 the addition of concomitant chemotherapy to radical radiotherapy became standard. The addition of cisplatin (CDDP) with or without 5-fluorouracil (5-FU) chemotherapy to radiation therapy was based on the near simultaneous reporting of five randomized, controlled clinical trials which all showed an improvement in survival with a magnitude of approximately 35%. The purpose of our study was to test the hypothesis that the addition of chemotherapy improved survival in our patients. We identified 291 patients treated with primary 'intent-to-cure' radiation therapy for locally advanced carcinoma of the cervix between 1985 and 2000. We analyzed patients using a stepwise Cox regression, including as possible predictors: clinical stage, age at diagnosis, use of concurrent chemotherapy with radiation and method of teletherapy delivery. We also examined survival as a function of CRT with a CDDP and/or 5-FU containing regimen using the Kaplan-Meier estimates of overall survival. The use of concurrent CDDP and/or 5-FU chemotherapy with radiation (CRT) was not associated with an increase in disease free survival (p=0.734) or overall survival (p=0.989). In this retrospective study there was no disease free or overall survival benefit from the addition of CDDP and/or 5-FU chemotherapy to radical radiotherapy for the treatment of locally advanced cervical carcinoma, although there was a trend favoring CRT.     

Treatment of locally advanced pancreatic cancer: the role of radiation therapy

Pancreatic cancer remains associated with an extremely poor prognosis. Surgical resection can be curative, but the majority of patients present with locally advanced or metastatic disease. Treatment for patients with locally advanced disease is controversial. Therapeutic options include systemic therapy alone, concurrent chemoradiation, or induction chemotherapy followed by chemoradiation. We review the evidence to date regarding the treatment of locally advanced pancreatic cancer (LAPC), as well as evolving strategies including the emerging role of targeted therapies. We propose that if radiation is used for patients with LAPC, it should be delivered with concurrent chemotherapy and following a period of induction chemotherapy.     

Neoadjuvant chemotherapy prior to preoperative chemoradiation or radiation in rectal cancer: should we be more cautious?

Neoadjuvant chemotherapy (NACT) is a term originally used to describe the administration of chemotherapy preoperatively before surgery. The original rationale for administering NACT or so-called induction chemotherapy to shrink or downstage a locally advanced tumour, and thereby facilitate more effective local treatment with surgery or radiotherapy, has been extended with the introduction of more effective combinations of chemotherapy to include reducing the risks of metastatic disease. It seems logical that survival could be lengthened, or organ preservation rates increased in resectable tumours by NACT. In rectal cancer NACT is being increasingly used in locally advanced and nonmetastatic unresectable tumours. Randomised studies in advanced colorectal cancer show high response rates to combination cytotoxic therapy. This evidence of efficacy coupled with the introduction of novel molecular targeted therapies (such as Bevacizumab and Cetuximab), and long waiting times for radiotherapy have rekindled an interest in delivering NACT in locally advanced rectal cancer. In contrast, this enthusiasm is currently waning in other sites such as head and neck and nasopharynx cancer where traditionally NACT has been used. So, is NACT in rectal cancer a real advance or just history repeating itself? In this review, we aimed to explore the advantages and disadvantages of the separate approaches of neoadjuvant, concurrent and consolidation chemotherapy in locally advanced rectal cancer, drawing on theoretical principles, preclinical studies and clinical experience both in rectal cancer and other disease sites. Neoadjuvant chemotherapy may improve outcome in terms of disease-free or overall survival in selected groups in some disease sites, but this strategy has not been shown to be associated with better outcomes than postoperative adjuvant chemotherapy. In particular, there is insufficient data in rectal cancer. The evidence for benefit is strongest when NACT is administered before surgical resection. In contrast, the data in favour of NACT before radiation or chemoradiation (CRT) is inconclusive, despite the suggestion that response to induction chemotherapy can predict response to subsequent radiotherapy. The observation that spectacular responses to chemotherapy before radical radiotherapy did not result in improved survival, was noted 25 years ago. However, multiple trials in head and neck cancer, nasopharyngeal cancer, non-small-cell lung cancer, small-cell lung cancer and cervical cancer do not support the routine use of NACT either as an alternative, or as additional benefit to CRT. The addition of NACT does not appear to enhance local control over concurrent CRT or radiotherapy alone. Neoadjuvant chemotherapy before CRT or radiation should be used with caution, and only in the context of clinical trials. The evidence base suggests that concurrent CRT with early positioning of radiotherapy appears the best option for patients with locally advanced rectal cancer and in all disease sites where radiation is the primary local therapy.     

Dose fractionation and biological optimization in lung cancer

The treatment of choice of patients with locally advanced non-small cell lung cancer is radiotherapy combined or not with chemotherapy. Only 30% of lung cancer patients are operable for cure at diagnosis. Consequently the knowledge of the radiobiological basis and of clinical outcomes achieved with radiation therapy is of the utmost importance. Total dose, fractionation, concomitant chemotherapy are the main factors to be examined. In order to improve local control several attempts are reported in the literature. They concern: changes in fractionation and total dose; the use of radiosensitizers and radioprotectors; combined chemoradiation and molecular therapies.     

序贯化放疗治疗局部晚期胃癌的临床疗效

目的:观察化疗-放疗-化疗(化-放-化)序贯治疗局部晚期胃癌的临床疗效和毒副反应.方法:2009年1月-2014年10月我科收治的局部晚期胃癌84例,采用同期对照研究,分为化-放-化序贯治疗组(观察组)44例和单纯化疗组(对照组)40例.观察组及对照组均采用DCF(多西他赛、顺铂、5-氟尿嘧啶)或FOLFOX4(5-氟尿嘧啶、奥沙利铂、亚叶酸钙)方案化疗3~4周期,观察组化疗2周期后开始肿瘤累及区域三维适形放疗/调强适形放射治疗(3DCRT/IMRT),放疗剂量DT(45~50.4)Gy/[(25~28)f?(5~6)w],放疗结束再予相同方案化疗1~2周期.对照组不予放疗.结果:84例患者均可评价疗效,观察组与对照组总有效率(CR+PR)分别为65.9%、37.5%,疾病控制率(CR+PR+SD)分别为88.6%、60.0%,临床症状缓解率分别为88.6%、65.0%,中位生存期分别为12.0个月、10.0个月,1、2年生存率分别为56.8% vs 32.5%、18.2% vs 7.5%.两组比较,在治疗有效率、疾病控制率、临床症状缓解率、中位生存期、1年生存率方面观察组高于对照组,差异具有统计学意义;2年生存率观察组较对照组有增高,但无统计学差异.两组Ⅲ-Ⅳ度骨髓抑制、胃肠道反应、肝肾功能受损发生率相近.结论:序贯化放疗较单纯化疗提高了局部晚期胃癌的治疗有效率,明显缓解患者的临床症状,且使部分患者改善了生存质量,延长生存期,并未增加治疗毒副反应,是不能手术局部晚期胃癌的较好治疗方案.