Involved-field, low-dose chemoradiotherapy for early-stage anal carcinoma

PURPOSE: To report the results of patients with early-stage anal cancer treated using a low-dose, reduced-volume, involved-field chemoradiotherapy protocol. METHODS AND MATERIALS: Between June 2000 and June 2006, 21 patients were treated with external beam radiotherapy (30 Gy in 15 fractions within 3 weeks) and concurrent chemotherapy (bolus mitomycin-C 12 mg/m(2) on Day 1 to a maximum of 20 mg followed by infusion 5-fluorouracil 1,000 mg/m(2)/24 h on Days 1-4). Of the 21 patients, 18 underwent small-volume, involved-field radiotherapy and 3 were treated with anteroposterior-posteroanterior parallel-opposed pelvic fields. Of the 21 patients, 17 had had lesions that were excised with close (<1 mm) or involved margins, 1 had had microinvasive disease on biopsy, and 3 had had macroscopic tumor <2 cm in diameter (T1). All were considered to have Stage N0 disease radiologically. RESULTS: After a median follow-up of 42 months, only 1 patient (4.7%) had experienced local recurrence and has remained disease free after local excision. No distant recurrences or deaths occurred. Only 1 patient could not complete treatment (because of Grade 3 gastrointestinal toxicity). Grade 3-4 hematologic toxicity occurred in only 2 patients (9.5%). No significant late toxicity was identified. CONCLUSION: The results of our study have shown that for patients with anal carcinoma who have residual microscopic or very-small-volume disease, a policy of low-dose, reduced-volume, involved-field chemoradiotherapy produces excellent local control and disease-free survival, with low rates of acute and late toxicity.     

子宫颈癌根治术后同步放化疗与放疗序贯化疗及单纯放疗临床对比研究

目的:探讨子宫颈癌根治术后高危患者同步放化疗与放疗+化疗序贯治疗、单纯放疗的疗效及毒副反应.方法:117例宫颈癌术后高危患者分为同步放化疗组、放疗+化疗序贯治疗组和单纯放疗组3组,各39例.3组放疗方案相同.第1组在放疗第1周内同时给予FP方案化疗;第2组在放疗结束后1周给予FP方案化疗.结果:3组3年盆腔复发率分别为2.6%、17.9%和23.1%.第1组与第2、3组比较差异有统计学意义,x2=6.532,P=0.011,3组3年远处转移率分别为2.6%、12.8%和25.6%,第1、2组与第3组比较差异有统计学意叉,x2=6.936,P=0.008;3组3年生存率分别为94.7%、74.4%和61.5%,第1组与第2、3组比较差异有统计学意义,x2=10.268,P=0.001.第1组骨髓抑制和消化道反应发生率均高于第2、3组,x2值分别为14.204和13.882,P值均为0.000,但大部分患者能够耐受.结论:子宫颈癌术后高危患者同步放化疗组与放疗+化疗序贯治疗、单放组比较,降低了3年盆腔复发率,减少了3年远处转移率,提高了3年生存率,且早期毒副反应能耐受.     

Paradigms in chemoradiotherapy

The efficacy of radiation in locally advanced non- small cell lung cancer (NSCLC) is limited. In a search for improving the outcome, particular attention has focused on the possibility of combining radi- ation with chemotherapy. The two most frequently used combined modality strategies include induction chemotherapy (chemotherapy preceding radiation) and concurrent chemoradiation. The former allows for drug delivery in full doses and in principle aims at a reduction of micrometastatic disease, whereas the latter is believed to improve locoregional control by making tumour cells more vulnerable to radiotherapy. The results of phase III trials of induction chemo- therapy were equivocal; nevertheless, three large trials using platinum-based regimens demonstrated significant survival benefit. The role of single agent platinum compounds (believed to be radiosensitising agents) applied concurrently with radiotherapy is controversial. Improved survival with this strategy was demonstrated in two studies, but several other studies were negative. Concurrent application of multidrug platinum-based chemotherapy in conventional sched- ules has been found relatively toxic yet feasible in selected patients. The direct comparison of sequential versus concurrent use of chemotherapy and radiation demonstrated the superiority of the latter, but at the expense of higher acute in-field toxicity. More recently, several new agents, including taxanes, vinorelbine and gemcitabine, have appeared promising in NSCLC. Their role in combined modality regimens warrants further clinical research. Chemotherapy as an adjunct to radiation has become a standard in fit patients with locally advanced NSCLC. The gain from the combined modality approach, however, is modest on average and should be weighted against increased early and late toxicity. Further studies built upon recent positive results should focus on identifying the means of optimal interactions between the two modalities. This research should define the most effective types and doses of anti-cancer agents as well as the optimal features of radiotherapy. Additionally, the knowledge of the biological characteristics of individual tumours, in particular their expected response to therapy, may contribute to further progress.     

Rationale for chemoradiotherapy

The rationale for combining chemotherapy (CT) and radiotherapy (RT) is based mainly on two ideas, one being spatial cooperation and the other the enhancement of radiation effects. Spatial cooperation is effective if CT is sufficiently active to eradicate subclinical metastases and if the primary local tumor is effectively treated by RT. In this regard, no interaction between RT and CT is required, but differing toxicities are needed so that both modalities can be used at effective dosages. To enhance RT by CT, five major mechanisms of CT-RT interactions are required. CT can enhance RT effects by: (1) direct enhancement of the initial radiation damage by incorporating drugs into DNA, (2) inhibiting cellular repair, (3) accumulating cells in a radiosensitive phase or eliminating radioresistant phase cells, (4) eliminating hypoxic cells, or (5) inhibiting the accelerated repopulation of tumor cells. However, virtually all chemotherapeutic agents enhance radiation damage to normal tissues as well. Consequently, therapeutic benefits are only achieved if the enhanced tumor response is greater than that for normal tissues. Due to the complex interaction between CT and RT, the sequence of CT and RT is important. Clinical results of induction CT followed by RT are disappointing, and improvements in local control rates of RT by induction CT have not been observed. On the other hand, clinical trials, including metaanalyses, have clearly shown that CT given concurrently with RT results in improved local control and survival. Although acute toxicities are inevitably increased in concurrent chemoradiotherapy (CRT), no significant increases in late toxicities were reported in most clinical trials. Thus, a therapeutic benefit was observed with the use of concurrent CRT.     

Neoadjuvant chemoradiotherapy with docetaxel, cisplatin, and 5-fluorouracil for esophageal cancer

Purpose

We aimed to evaluate the safety, tolerability, and efficacy of combination preoperative chemoradiotherapy as first-line treatment in patients with advanced esophageal cancer.

Methods

We performed a phase I dose-escalation trial of docetaxel at 25–40?mg/m² in four planned dose levels in 3–6 patient cohorts on days 1, 15, 29, and 43 administered in combination with cisplatin (70?mg/m² on days 1 and 29) and 5-fluorouracil (70?mg/m²/day on days 1–4 and 29–32) and concurrent radiation therapy (40?Gy). The tumors were resected during weeks 10–13.

Results

This study included 7 patients with esophageal cancer. The dose-limiting toxicity was observed at a biweekly docetaxel dose of 30?mg/m² when patients developed grade 3 febrile neutropenia, grade 4 thrombocytopenia, and grade 4 pain/esophagus, resulting in a maximum tolerated dose of 25?mg/m². Grade 3/4 hematological toxicity was observed in 71% of the patients and grade 3/4 non-hematological toxicity in 57%. The overall tumor response rate was 86% (complete, 57% and partial, 29%). All patients underwent surgery, and there were no deaths as a result of postoperative complications.

Conclusions

This preoperative chemoradiotherapy regimen using triplets is feasible but results in moderate toxicity. It is noteworthy that this regimen was associated with a high rate of pathological complete remission.     

Alternating chemoradiotherapy for oropharyngeal cancer

To evaluate the usefulness of chemoradiotherapy for oropharyngeal cancer, we retrospectively analyzed disease-free survival (DFS) and acute toxicities of the patients treated with this therapy. Between 1990 and 1998, 15 patients were treated with alternating chemoradiotherapy (CRT). Chemotherapy (CT) mainly consisted of 5-fluorouracil 700 mg/m2 (i.v.) on days 1-5 and nedaplatin 100-140 mg/m2 (i.v.) on day 6. Chemotherapy was administered before the beginning of radiotherapy. One cycle of this treatment consisted of CT and a subsequent 27 to 36 Gy of radiotherapy, as a general rule, two cycles were performed. Radiotherapy was delivered in single daily fractions of 1.8 to 2 Gy, to a total dose of 54 to 75 Gy for local lesions and 45 to 86.3 Gy for nodal metastases in the neck. As a historical control, 52 patients treated with curative radiotherapy between 1971 and 1990 were analyzed and compared with the CRT group in terms of DFS. The complete response rate with CRT was 100%. The three-year DFS were 87% and 38% with CRT and RT, respectively. There was a significant difference between the two groups (p = 0.0081). The most frequent and severe acute toxicity was mucositis, with grade 3-4 occurring in 47%. Acute hematologic toxicities were mild. Therefore, this CRT is considered to be an effective and tolerable treatment, and is expected to improve survival for oropharyngeal cancer patients.     

Concurrent chemoradiotherapy for oropharyngeal carcinoma

The clinical results of definitive chemoradiotherapy for oropharyngeal carcinoma were retrospectively analyzed. Thirty-one patients with oropharyngeal carcinoma who received definitive radiation therapy between January 1986 and June 1998 were analyzed. The median age was 61 years. All patients had squamous cell carcinoma. According to the Union International Contre le Cancer 1997 classification system, stage I, II, III, IVA, and IVB were 1,0, 9, 14, and 7, respectively. Regarding the primary site, 23 tumors were in the lateral wall, whereas 2 were in the superior wall, and 3 each were in the anterior and posterior walls. The median total dose was 66 Gy, with a range of 60 Gy to 74.4 Gy. The overall treatment time ranged from 39 days to 113 days, with a median of 50 days. Seven patients underwent hemilateral radical neck dissection. Fourteen patients received concurrent chemotherapy using weekly cisplatin (50 mg/d) at least three times. The 5-year overall and cause-specific survival (CSS) rates were 55% and 62%, respectively. All local recurrences occurred within 2 years. The CSS rate in patients with lateral or superior wall origin was significantly superior to that of patients with anterior or posterior wall origin (p < 0.05). The 3-year CSS rate was 83% for patients treated with concurrent chemoradiotherapy using weekly cisplatin at least 3 times, whereas that was 53% for the remaining patients (p < 0.05). No serious adverse effects were observed. It is concluded that definitive concurrent chemoradiotherapy using weekly cisplatin for oropharyngeal carcinoma appear promising.     

食管癌放化疗研究进展

国外对食管癌同时放化疗已有了肯定的临床结果。为了更好地提高疗效，人们更多地在研究术前同时放化疗后加手术的治疗方法，有些研究应用加速超分割放疗联合化疗治疗食管癌也获得了初步结果。     

Postoperative chemoradiotherapy for cerebral glioblastoma

We developed a new method of accelerated chemoimmunoradiotherapy for cerebral glioblastoma and evaluated the immediate effects. A single focal dose of 3Gy was administered once a day 5 times a week until the total focal dose of 51 Gy was reached. Chemoradiotherapy was followed by a course of biotherapy with recombinant interleukine-2 (roncoleukine). On administering a total dose of 10 million units, a course of chemoimmunotherapeutic support was given after a 2-week break. Vincristine 1 mg was injected on day 1 and nitrosourea preparations (lomustine 160 mg or carmustine 100 mg) on day 2. Later on, the same regimen of roncoleukine was used. Our method was followed by longer survival as compared with standard treatment (control) and use of incomplete course chemoimmunotherapy.     

食管癌放化疗研究进展

国外对食管癌同时放化疗已有了肯定的临床结果。为了更好地提高疗效,人们更多地在研究术前同时放化疗后加手术的治疗方法,有些研究应用加速超分割放疗联合化疗治疗食管癌也获得了初步结果。     

Improving chemoradiotherapy in rectal cancer

The optimal management of rectal cancer remains a major challenge for oncologists. The treatment of stage II/III rectal cancer has historically been associated with a high risk of local recurrence and poor survival, which led to the development of adjuvant treatments in the hope of improving outcomes. The approach to adjuvant therapy for rectal cancer currently varies widely between Europe and the U.S. Postoperative adjuvant chemoradiation is the standard of care in the U.S. In contrast, in Europe, because there is a greater emphasis placed on preoperative imaging, meticulous surgical technique, and accurate pathologic reporting of the circumferential or radial margin, preoperative treatment (radiotherapy and chemoradiation) is used widely. The aims of preoperative radiotherapy and chemoradiation are to facilitate a curative resection (R0) and to increase the chance of performing sphincter-sparing procedures, and, therefore, to improve both survival and quality of life. This article reviews the clinical trials that led to these diverging standards of care. An interesting new approach in chemoradiation is the use of the oral fluoropyrimidine capecitabine as a combination partner for radiotherapy. Preclinical studies have demonstrated that the combination of capecitabine and radiotherapy has highly enhanced antitumor activity. This is most likely attributable to the upregulation of thymidine phosphorylase (the rate-limiting enzyme needed to convert capecitabine to 5-fluorouracil [5-FU]) in tumor cells following radiotherapy. A phase I study has consequently been performed to establish a feasible chemoradiotherapy combination. Capecitabine has the potential to replace bolus or continuous infusion 5-FU as the standard treatment for rectal cancer and offers a potentially enhanced therapeutic ratio. Oral chemotherapy has the additional advantage of simplifying chemoradiation and providing a treatment that is more appealing to patients.     

直肠癌新辅助化放疗

近年来的前瞻性研究已证实新辅助化放疗即术前化放疗可以明显提高直肠癌患者的局部控制率和保肛率,但直肠癌新辅助化放疗的理论基础、适应证、治疗方案、治疗时间等尚未明确.     

同步放化疗与序贯放化疗治疗食管癌的Meta分析

目的采用循证医学的方法评价同步放化疗与序贯放化疗在食管癌治疗中的有效性和安全性。方法电子检索Cochrane Library、Pubmed、Embase、CNKI、VIP、CBM、万方,手工检索相关杂志、会议论文、学位论文,收集同步放化疗对比序贯放化疗治疗食管癌的临床随机对照试验(RCT),检索时间为各数据库建库至2012年8月,对文献进行质量评价,按照Cochrane handbook并采用RevMan 5.1软件对数据进行Meta分析。结果纳入9项RCT,共收入754例患者。结果显示,同步放化疗与序贯放化疗治疗食管癌比较,总有效率和1、2、3年生存率以及局控率同步组均高于序贯组,差异有统计学意义(P<0.05);远处转移两组间差异无统计学意义(P=0.85);放射性食管炎、胃肠道反应的发生同步组较序贯组高(P<0.05)。血液学毒性中白细胞减少有统计学意义(P<0.05),而血小板减少无统计学意义(P=0.53)。结论 Meta分析表明,同步放化疗治疗食管癌近期疗效及1、2、3年生存率和局控率优于序贯放化疗,但放射性食管炎、血液学毒性中的白细胞减少及胃肠道反应高于序贯组。     

Cervix carcinoma, concurrent chemoradiotherapy, and salvage of isolated paraaortic lymph node recurrence

PURPOSE: To determine the effect of concurrent chemoradiotherapy on the outcome of invasive cervical carcinoma patients with disease recurrence isolated to the paraaortic lymph nodes. METHODS AND MATERIALS: Between 1987 and 2003, 816 cervical carcinoma patients received radiotherapy at Mallinckrodt Institute of Radiology. Of these 816 patients, 14 had clinically or radiographically detected isolated paraaortic lymph node metastases. Before 1998, imaging was done if warranted by the presence of one or more classic findings, including lower extremity edema, sciatic pain, and hydronephrosis. After 1998, radiographic imaging was a routine part of follow-up for all patients. The median age at recurrence was 42.5 years (range, 32-54 years). Follow-up for all living patients was current at last follow-up. Full-dose radiotherapy equaled at least 45 Gy. RESULTS: All 7 patients with a classic finding of recurrence, none of whom had been treated to at least 45 Gy and concurrent chemotherapy, were dead of disease within 1.5 years. The 7 patients without a classic finding of recurrence, all of whom had been treated with salvage full-dose concurrent chemoradiotherapy, had a 5-year overall survival rate of 100% (p <0.01). CONCLUSION: Salvage concurrent full-dose chemoradiotherapy afforded excellent survival of patients who did not have classic findings but had disease recurrence exclusively in the paraaortic lymph nodes. The effectiveness of salvage concurrent full-dose chemoradiotherapy in patients with symptomatic disease recurrence remains unclear. However, chemotherapy or radiotherapy alone produced dismal survival in patients with classic findings of recurrence.     

肿瘤同时放化疗治疗的研究进展

综合治疗是治疗肿瘤的基本原则，同时放化疗已成为肿瘤临床治疗中最常见的综合治疗形式。本文将对肿瘤放疗化疗综合治疗的形成和发展，放疗、化疗相互作用的可能生物学机制，同时放化疗临床应用的形式以及生物靶向治疗联合放疗发展前景进行讨论。     

诱导化疗联合同期放化疗与同期放化疗治疗局部晚期鼻咽癌的对比研究

  目的  比较诱导化疗联合同期放化疗与同期放化疗治疗局部晚期鼻咽癌(LA-NPC)的临床结果及探讨预后因素。  方法  分析2005年1月至2006年12月本院收治的433例无转移LA-NPC患者的临床资料, 按是否行诱导化疗分为诱导化疗联合同期放化疗组(A组)209例与同期放化疗组(B组)224例。采用Kaplan-Meier法进行生存分析, 差异比较采用Log-Rank法双侧检验, 预后因素分析采用Cox模型。  结果  A组、B组的3年总生存率(OS)、无局部区域复发生存率(LR-FFS)、无远处转移生存率(D-FFS)、无瘤生存率(FFS)分别为87% vs. 88%、95% vs. 95%、85% vs. 85%、81% vs. 81%;A组、B组的5年OS、LR-FFS、D-FFS、FFS分别为80% vs. 82%(P=0.503), 95% vs. 93%(P=0.673), 82% vs. 82%(P=0.992), 78% vs. 77%(P=0.851)。两组生存差异无统计学意义, 对于Ⅲ期鼻咽癌, A组FFS优于B组(P=0.075)。多因素分析显示老年、临床分期晚、颅神经侵犯、贫血、N分期晚为OS、D-FFS的独立不良预后因素。  结论  与同期放化疗相比, 诱导化疗联合同期放化疗未提高LA-NPC的OS、LR-FFS、D-FFS及FFS, 但具有改善Ⅲ期鼻咽癌FFS的趋势。诱导化疗联合同期放化疗不是鼻咽癌的必选治疗模式。