Chemotherapy and targeted therapy in the management of cervical cancer

Management of cervical cancer has undergone refinement in the past two decades; concurrent chemo-radiation (CCRT) (with cisplatin alone or in combination) is currently the standard treatment approach for patients with locally advanced disease (FIGO stage IIB-IVA). About 30%-40% of such patients fail to achieve complete response; alternative approaches are needed to improve outcome for them. Treatment with bevacizumab (an inhibitor of vascular endothelial growth factor) along with chemotherapy is associated with improved survival in patients with recurrent or metastatic cervical cancer. Weekly paclitaxel and carboplatin for 4-6 weeks as dose dense chemotherapy prior to CCRT is currently under study in a phase III, multicentric trial. Role of adjuvant chemotherapy after CCRT in patients with positive lymph nodes, larger tumor volume and those with stage III-IVA disease needs further exploration. Novel agents targeting molecular pathways are currently being studied. Recent development of immune check point inhibitors is exciting, results of ongoing studies are awaited with interest.     

Chemoradiotherapy for uterine cancer: current status and perspectives

The conventional local treatment methods (surgery and radiation) for cervical cancer have reached a plateau in terms of survival benefit and, therefore, in this review, new treatment strategies (combined chemotherapy [CT] and local therapy) to overcome the poor prognosis were examined in high-risk groups. The effectiveness of neoadjuvant chemotherapy (NAC) administered prior to radiotherapy (RT) has not been confirmed for any disease stages. But NAC followed by surgery may improve survival in patients with stage Ib2 compared with surgery alone; and in patients with stage Ib2 to IIB compared with RT alone. Five large randomized clinical trials (RCTs) demonstrated a significant survival benefit for patients treated with concurrent chemoradiotherapy (CCRT), using a cisplatin (CDDP)-based regimen, with a 28%–50% relative reduction in the risk of death. In addition, the results of a metaanalysis of 19 RCTs of CCRT (1981–2000) involving 4580 patients showed that CCRT significantly improved overall survival (OS) hazard ratio ([HR] 0.71; P < 0.0001), as well as progression-free survival (PFS; HR 0.61; P < 0.0001). In line with these results, CCRT is currently recommended as standard therapy for advanced cancer (stage III/IVA) in the United States. However, there remains much controversy and uncertainty regarding the optimal therapeutic approaches, especially for patients with advanced cancer. Additional RCTs should be conducted to find the optimal CT regimen and RT for Japanese patients, considering acute and late complications, as well as differences in pelvic anatomy, total radiation dose, and RT procedures between Japan and other countries. Evidence obtained from such studies should establish the optimal CCRT treatment protocol and define the patient population (disease stage) that the protocol really benefits.     

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.     

Comparison of concurrent chemoradiation therapy with weekly cisplatin versus monthly fluorouracil plus cisplatin in FIGO stage IIB-IVA cervical cancer

Objective

Concurrent chemoradiation therapy (CCRT) is the standard treatment for locally advanced cervical cancer. Although the optimal chemotherapeutic regimen is not yet defined, previous randomized trials have demonstrated that 5-fluorouracil (5-FU) plus cisplatin every 3 weeks and weekly cisplatin are the most popular regimens. The purpose of this study was to compare the outcomes of weekly CCRT with cisplatin and monthly CCRT with 5-FU plus cisplatin for locally advanced cervical cancer.

Methods

We retrospectively reviewed data from 255 patients with FIGO stage IIB-IVA cervical cancer. Patients were classified into two CCRT groups according to the concurrent chemotherapy: weekly CCRT group, consisted of CCRT with weekly cisplatin for six cycles; and monthly CCRT group, consisted of CCRT with cisplatin and 5-FU every 4 weeks for two cycles followed by additional consolidation chemotherapy for two cycles with the same regimen.

Results

Of 255 patients, 152 (59.6%) patients received weekly CCRT and 103 (40.4%) received monthly CCRT. The mean follow-up period was 39 months (range, 1 to 186 months). Planned CCRT was given to 130 (85.5%) patients in weekly CCRT group and 84 (81.6%) patients in monthly CCRT group, respectively. Severe adverse effects were more common in the monthly CCRT group than in the weekly CCRT group. There were no statistically significant differences in progression-free survival and overall survival between the two groups (p=0.715 and p=0.237).

Conclusion

Both weekly CCRT and monthly CCRT seem to have similar efficacy for patients with locally advanced cervical cancer, but the weekly cisplatin is better tolerated.     

Outcomes of Preoperative Chemoradiotherapy and Combined Chemotherapy with Radiotherapy Without Surgery for Locally Advanced Rectal Cancer

Purpose: To evaluate the treatment outcomes of patients with locally advanced rectal cancer treated with preoperative concurrent chemoradiotherapy (CCRT) or combined chemotherapy together with radiotherapy (CMTRT) without surgery. Materials and Methods: A total of 84 patients with locally advanced rectal adenocarcinoma (stage II or III) between January 1st, 2003 and December 31st, 2013 were enrolled, 48 treated with preoperative CCRT (Gr.I) and 36 with combined chemotherapy and radiotherapy (CMTRT) without surgery (Gr.II). The chemotherapeutic agents used concurrent with radiotherapy were either 5fluorouracil short infusion plus leucovorin and/or capecitabine or 5fluorouracil infusion alone. All patients received pelvic irradiation. Results: There were 5 patients (10.4%) with a complete pathological response. The 3 yearoverall survival rates were 83.2% in Gr.I and 24.8 % in Gr.II (p<0.01). The respective 5 yearoverall survival rates were 70.3% and 0% (p<0.01). The 5 yearoverall survival rates in Gr.I for patients who received surgery within 56 days after complete CCRT as compared to more than 56 days were 69.5% and 65.1% (p0.91). Preoperative CCRT used for 12 of 30 patients in Gr.I (40%) with lower rectal cancer demonstrated that in preoperative CCRT a sphincter sparing procedure can be performed. Conclusions: The results of treatment with preoperative CCRT for locally advanced rectal cancer showed comparable rates of overall survival and sphincter sparing procedures as compared to previous studies.     

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.     

Endostar,an Antiangiogenesis Inhibitor,Combined With Chemoradiotherapy for Locally Advanced Cervical Cancer

This phase II randomized clinical trial aimed to assess the efficacy and toxicity of Endostar, an antiangiogenesis inhibitor, combined with concurrent chemoradiotherapy (CCRT) for locally advanced cervical cancer (LACC). Patients with LACC were randomly assigned to either CCRT plus Endostar (CCRT+E arm) or CCRT alone (CCRT arm). All patients received pelvic intensity-modulated radiation therapy (IMRT) and brachytherapy. Weekly cisplatin was administered concurrently with IMRT. Patients in the CCRT+E arm also received concurrent Endostar every 3 weeks for two cycles. The primary endpoint was progression-free survival (PFS) and acute toxicities. The exploratory endpoint was the impact of vascular endothelial growth factor receptor-2 (VEGFR2) expression on long-term survival. A total of 116 patients were enrolled. Patients in the CCRT+E arm and in the CCRT arm had similar acute and late toxicity profile. The 1- and 2-year PFS were 91.4% versus 82.1% and 80.8% versus 63.5% (p = 0.091), respectively. The 1- and 2-year distance metastasis-free survival (DMFS) were 92.7% versus 81.1% and 86.0% versus 65.1% (p = 0.031), respectively. Patients with positive VEGFR2 expression had significant longer PFS and overall survival (OS) compared with those with negative VEGFR2 expression. Patients in the CCRT+E arm had significantly longer PFS, OS, and DMFS than those in the CCRT arm when VEGFR2 expression was positive. In conclusion, CCRT plus Endostar significantly improved DMFS but not PFS over CCRT alone. The addition of Endostar could significantly improve survival for patients with positive VEGFR2 expression.Key words: Cervical cancer, Antiangiogenesis, Radiation therapy, Concurrent chemotherapy, Randomized controlled trial     

The efficacy of concurrent cisplatin and 5-flurouracil chemotherapy and radiation therapy for locally advanced cancer of the uterine cervix

Objective

To evaluate the efficacy of concurrent chemoradiation (CCRT) using 5-flurouracil (5-FU) and cisplatin for locally advanced cervical cancer.

Methods

We reviewed the medical records of 57 patients with locally advanced cervical cancer (stage IIB-IVA and bulky IB2-IIA tumor) who underwent the CCRT at Dong-A University Hospital from January 1997 to June 2007. The CCRT consisted of 5-FU, cisplatin and pelvic radiation. Every three weeks, 75 mg/m² cisplatin was administered on the first day of each cycle and 5-FU was infused at the dose of 1,000 mg/m²/d from the second day to the fifth day of each cycle. Radiation was administered to the pelvis at a daily dose of 1.8 Gy for five days per week until a medium accumulated dose reached to 50.4 Gy. If necessary, the radiation field was extended to include paraaortic lymph nodes. Consolidation chemotherapy was performed using 5-FU and cisplatin.

Results

Fifty-seven patients were enrolled and the median follow-up duration was 53 months (range 7-120 months). The overall response rate was 91.5% (74% complete response and 17.5% partial response). The 5-year overall survival and 3-year progression free survival rates were 69.4% and 74.9%, respectively. During the follow-up period (median 23 months, range 7-60 months), fourteen patients were diagnosed as recurrent disease.

Conclusion

CCRT with 5-FU and cisplatin which is the primary treatment for patients with locally advanced cervical cancer was effective and well tolerated.     

Phase II study of consolidation chemotherapy after concurrent chemoradiation in cervical cancer: preliminary results

PURPOSE: Our aim was to determine the efficacy of consolidation chemotherapy after concurrent chemoradiation (CCRT) using high-dose-rate brachytherapy in patients with locally advanced cervical carcinoma. METHODS AND MATERIALS: Patients with cervical carcinoma (FIGO stage IB2-IVA) were treated with external beam radiation therapy to the whole pelvis (50.4 Gy) and high-dose-rate brachytherapy (24 Gy to point A). Cisplatin 60 mg/m(2) (Day 1) and 5-fluorouracil 1000 mg/m(2) (Days 1-5) were given every 3 weeks starting concurrently with the radiation and followed by 3 more cycles of consolidation for a total of 6 cycles. RESULTS: Thirty patients (94%) received 3 more cycles of post-CCRT consolidation chemotherapy and were evaluable for the toxicity and efficacy of consolidation. The most common toxicities of Grade 2 or higher were nausea or vomiting (47%) and anemia (33%). Late complications of the rectum and bladder occurred in 13% and 6% of the patients, respectively. The clinical complete response rate was 87% (95% CI, 75%-99%). During a median follow-up of 27 months (range, 6-58 months), 5 patients (17%) had recurrence; the sites of failure were 3 (10%) inside the radiation field and 2 (7%) outside the radiation field. The estimated 3-year progression-free survival rate was 83% (95% CI, 67%-99%) and overall survival rate was 91% (95% CI, 79%-100%). CONCLUSIONS: Consolidation chemotherapy after CCRT is well tolerated and effective in patients with locally advanced cervical carcinoma. A prospective randomized trial to compare this treatment strategy with standard CCRT seems to be worthwhile.     

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.     

Current trends in the treatment of advanced non-small cell lung cancer (Review)

Several advances have been made in the treatment of advanced non-small cell lung cancer in the last few years. Combined modality therapies utilizing chemotherapy have improved survival of patients with locally advanced disease (stage III) when compared to either radiation or surgery alone. New chemotherapeutic agents, used alone or in combination, have also made a strong impact in patients with metastatic disease (stage IV). Ongoing randomized trials will certainly define new treatment standards and hopefully improve the outcome of patients with advanced non-small cell lung cancer.     

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.     

新辅助化疗后根治性手术与同步放化疗在局部晚期宫颈癌的远期疗效评价

目的本研究的目的是比较ⅠB2-ⅡB期局部晚期宫颈癌新辅助化疗后根治性手术与同步放化疗的远期生存情况。方法回顾性分析从2000年1月—2004年12月间ⅠB2-ⅡB期局部晚期宫颈癌共222例,将其分为二组：新辅助化疗＋根治性全子宫切除术＋盆腔淋巴结切除术共155例;同步放化疗组67例。所有患者最长随访时间为114个月,最短随访时间为54个月,中位随访时间为72．6个月。且对所有可能影响无瘤生存时间和总生存时间的高危因素进行评估。结果本研究中位随访时间为72．6个月,新辅助化疗后根治性手术组和同步放化疗组5年无瘤生存率分别是88．39％和70．94％,两组比较有统计学意义（P：0．006）;而5年总生存率分别为88．52％和72．91％,两组比较有统计学意义（P=0．0004）。在Cox风险回归模型中,调整宫颈癌患者的年龄、病理分型后,结果显示：接受新辅助化疗后根治性手术组和同步放化疗组治疗的宫颈癌患者5年无瘤生存时间有明显差异（HR：2．765,95％CI：1．446—5．288,P=0．0021）;在5年总生存时间上也有显著性差异（HR=3．516,95％CI：1．822—6．784,P=0．0002）。结论本研究ⅠB2-ⅡB期局部晚期宫颈癌新辅助化疗后根治性手术组在无瘤生存时间和总生存时间方面显著优于同步放化疗组。     

An Approach to Radiosensitizing Cervical Cancer by Use of Chemical Modulators of Nucleoside Metabolism

Although radiation alone is the treatment of choice for patients with cervical cancer that is not surgically respectable, locoregional failures rates approach 50% for locally advanced stages of disease. Therefore, decades of clinical trials using chemoradiotherapy have been performed in an attempt to enhance cure rates. Unfortunately, the addition of chemotherapy has not been shown to unequivocally improve outcome compared with radiation alone. Reasons for this include inadequate radiation doses, radiation treatment delays caused by higher acute toxicities of combined modality therapy, and insufficient understanding of both the optimal sequencing and mechanisms of radiosensitizers. Some of the chemotherapy agents tested include the fluoropyrmidines (5-fluorouracil [5-FU]), the halogenated thymidine analogues (iododeoyxuridine [IdUrd] and bromodeoyxuridine [BrdUrd] and hydroxyurea (HU). This article focuses on clinical results using these compounds, the evolving understanding of these different types of drug-radiation interactions, and potential new strategies for the use of these radiosensitizers in patients with locally advanced cervical cancer.     

Endostar,an Antiangiogenesis Inhibitor,Combined With Chemoradiotherapy for Locally Advanced Cervical Cancer

This phase II randomized clinical trial aimed to assess the efficacy and toxicity of Endostar, an antiangiogenesis inhibitor, combined with concurrent chemoradiotherapy (CCRT) for locally advanced cervical cancer (LACC). Patients with LACC were randomly assigned to either CCRT plus Endostar (CCRT+E arm) or CCRT alone (CCRT arm). All patients received pelvic intensity-modulated radiation therapy (IMRT) and brachytherapy. Weekly cisplatin was administered concurrently with IMRT. Patients in the CCRT+E arm also received concurrent Endostar every 3 weeks for two cycles. The primary endpoint was progression-free survival (PFS) and acute toxicities. The exploratory endpoint was the impact of vascular endothelial growth factor receptor-2 (VEGFR2) expression on long-term survival. A total of 116 patients were enrolled. Patients in the CCRT+E arm and in the CCRT arm had similar acute and late toxicity profile. The 1- and 2-year PFS were 91.4% versus 82.1% and 80.8% versus 63.5% (p=0.091), respectively. The 1- and 2-year distance metastasis-free survival (DMFS) were 92.7% versus 81.1% and 86.0% versus 65.1% (p=0.031), respectively. Patients with positive VEGFR2 expression had significant longer PFS and overall survival (OS) compared with those with negative VEGFR2 expression. Patients in the CCRT+E arm had significantly longer PFS, OS, and DMFS than those in the CCRT arm when VEGFR2 expression was positive. In conclusion, CCRT plus Endostar significantly improved DMFS but not PFS over CCRT alone. The addition of Endostar could significantly improve survival for patients with positive VEGFR2 expression.     

Induction chemotherapy with paclitaxel and cisplatin, followed by concomitant cisplatin and radiotherapy for the treatment of locally advanced nasopharyngeal carcinoma

PURPOSE: To evaluate the efficacy and outcome of neoadjuvant paclitaxel and cisplatin chemotherapy followed by concurrent cisplatin and irradiation in patients with locally advanced nasopharyngeal (NP) squamous cell carcinoma. PATIENTS AND METHODS: The trial included 36 patients with locally advanced nasopharyngeal squamous carcinoma presented to Radiation Oncology and Otolaryngology departments-Ain Shams university hospitals, and Sohag Cancer Center between November 2002 and March 2006. Eligible patients were treated first with three cycles of induction chemotherapy (IC), paclitaxel (175 mg/m2 on day 1) and cisplatin (80 mg/m2 on day 1) followed by concomitant conventionally fractionated radiation (70 Gy in 2 Gy fractions) and cisplatin 20-mg/m2/day on days 1- 5, 22-26 and 43-47 of the radiation therapy. RESULTS: Twenty nine patients (80%) and 32 patients (89%) achieved objective response after IC and concomitant chemoradiation (CCRT) respectively. The actuarial 3 years survival was 68%, and the actuarial 3 year progression free survival (PFS) was 66%. Survival and PFS were significantly better for patients with smaller tumor volume (stage III), compared with patients with stage IV. Thirteen patients (36%) have elements of local and/or regional failure and 5 patients (14%) have an element of distant metastasis. Neutropenia (25%), mucositis (22%) and vomiting (20%) were the most severe toxicities recorded (grade 3 and 4) during IC while mucositis (36%), dermatitis (28%), anemia (14%) and vomiting (14%) were the most pronouncing toxicities (grade 3 and 4) during CCRT. CONCLUSIONS: IC followed by CCRT treatment program is feasible, tolerable and safe. This strategy improved local control and distant disease control. However combined treatment program have failed to improve survival rates over the historical result of CCRT trials.     

Combined chemo-radiotherapy in locally advanced nasopharyngeal carcinomas

AIM: To provide efficacy and safety data about the combined use of radiotherapy and chemo-radiotherapy in nasopharyngeal carcinoma (NPC).METHODS: We reviewed data of 40 patients with locally advanced NPC treated with induction chemotherapy followed by concomitant chemo-radiotherapy (CCRT) (22/40 patients) or CCRT alone (18/40) from March 2006 to March 2012. Patients underwent fiberoscopy with biopsy of the primitive tumor, and computed tomography scan of head, neck, chest and abdomen with and without contrast. Cisplatin was used both as induction and as concomitant chemotherapy, while 3D conformal radiation therapy was delivered to the nasopharynx and relevant anatomic regions (total dose, 70 Gy). The treatment was performed using 6 MV photons of the linear accelerator administered in 2 Gy daily fraction for five days weekly. This retrospective analysis was approved by the review boards of the participating institutions. Patients gave their consent to treatment and to anonymous analysis of clinical data.RESULTS: Thirty-three patients were males and 7 were females. Median follow-up time was 58 mo (range, 1-92 mo). In the sub-group of twenty patients with a follow-up time longer than 36 mo, the 3-year survival and disease free survival rates were 85% and 75%, respectively. Overall response rate both in patients treated with induction chemotherapy followed by CCRT and in those treated with CCRT alone was 100%. Grade 3 neutropenia was the most frequent acute side-effect and it occurred in 20 patients. Grade 2 mucositis was seen in 29 patients, while grade 2 xerostomia was seen in 30 patients. Overall toxicity was manageable and it did not cause any significant treatment delay. In the whole sample population, long term toxicity included grade 2 xerostomia in 22 patients, grade 1 dysgeusia in 17 patients and grade 1 subcutaneous fibrosis in 30 patients.CONCLUSION: Both CCRT and induction chemotherapy followed by CCRT showed excellent activity in locally advanced NPC. The role of adjuvant chemotherapy remains to be defined.     

非手术方法治疗局部侵袭性胸腺肿瘤

背景与目的手术切除是早期胸腺肿瘤的主要治疗方法,而对于IV期的病变,化疗则是最常用的方案。对于局部晚期的肿瘤,尤其是不适合手术的病例,何种治疗方案效果更优则没有明确的结论。鉴于此,我们做了这项回顾性的研究,通过对三种非手术疗法的比较,希望找到一些线索。方法自2000年10月至2010年12月,共有42例患者接受了三种非手术方案的治疗。这三种模式分别是单独放疗（radiotherapy, RT）、序贯化放疗（se-quential chemoradiation, SCRT）以及同步放化疗（concurrent chemoradiation, CCRT）。并对三种方案的缓解率（objec-tive response rate, ORR）、总生存期（overall survival, OS）以及治疗的相关毒副反应进行比较。结果全组42例患者中,总的缓解率为61.9%,5年生存率为46%。RT组、SCRT组以及CCRT组的缓解率分别是43.8%、50%和87.5%（RT vs SCRT,P=0.692; RTvs CCRT,P=0.009; SCRTvs CCRT,P=0.051）。RT组、SCRT组以及CCRT组的5年生存率分别是30%、50%和61.9%（RTvs SCRT,P=0.230; RTvs CCRT,P=0.011; SCRTvs CCRT,P=0.282）。共有11例患者发生了3度-4度的中性粒细胞减少,其中7例出现在CCRT组,另4例出现在SCRT组。有9例患者主诉有3度放射性食道炎,其中RT组2例, SCRT组3例,CCRT组4例。另外,CCRT组还出现了2例3度的放射性肺炎。未发现致命的5度毒副反应。结论在治疗不适合手术的局部晚期胸腺肿瘤上,CCRT显示出了比RT和CCRT更好的局部控制以及长期生存优势,不过也有增加肺损伤风险的可能。对于局部侵袭性的胸腺肿瘤,CCRT可提供最佳的肿瘤控制效果。     

Prognostic factors for patients with cervical cancer treated with concurrent chemoradiotherapy: a retrospective analysis in a Japanese cohort

Objective

Concurrent chemoradiotherapy (CCRT) is the primary treatment for locally advanced cervical cancer. We studied prognostic factors for patients treated with CCRT.

Methods

We retrospectively reviewed records of 85 consecutive patients with cervical cancer who were treated with CCRT between 2002 and 2011, with external beam radiation therapy, intracavitary brachytherapy, and platinum-based chemotherapy. Survival data were analyzed with Kaplan-Meier methods and Cox proportional hazard models.

Results

Of the 85 patients, 69 patients (81%) had International Federation of Gynecology and Obstetrics (FIGO) stage III/IV disease; 25 patients (29%) had pelvic lymph node enlargement (based on magnetic resonance imaging), and 64 patients (75%) achieved clinical remission following treatment. Median maximum tumor diameter was 5.5 cm. The 3- and 5-year overall survival rates were 60.3% and 55.5%, respectively. Cox regression analysis showed tumor diameter >6 cm (hazard ratio [HR], 2.3; 95% confidence interval [CI], 1.2 to 4.6), pelvic lymph node enlargement (HR, 2.2; 95% CI, 1.1 to 4.5), and distant metastasis (HR, 10.0; 95% CI, 3.7 to 27.0) were significantly and independently related to poor outcomes.

Conclusion

New treatment strategies should be considered for locally advanced cervical cancers with tumors >6 cm and radiologically enlarged pelvic lymph nodes.     

Feasibility and effectiveness of postoperative adjuvant concurrent chemoradiation therapy in Japanese patients with high-risk early-stage cancer of the uterine cervix

BACKGROUND: This study was undertaken to evaluate the feasibility and effectiveness of postoperative concurrent chemoradiation (CCRT) in patients with high-risk early-stage cervical cancer who were treated by radical hysterectomy and pelvic lymphadenectomy. METHODS: From July 2001 to September 2005, CCRT was performed in 37 patients who had undergone radical hysterectomy with pelvic lymph node dissection at Nagoya University Hospital. Adjuvant chemotherapy consisted of cisplatin (70 mg/m(2) on day 1) and 5-fluorouracil (5-FU; 700 mg/m(2) per day on days 1-4) every 4 weeks for a total of three cycles. Pelvic radiotherapy was started concurrently with the first cycle of chemotherapy. The radiation dose was 45 Gy in 25 fractions. A nonrandomized control group of 52 patients who had undergone radiation therapy alone after radical hysterectomy between 1991 and 2000 served for historical comparison. RESULTS: In the CCRT group, the incidences of grade 3/4 toxicities were 24.3% for neutropenia, 8.1% for nausea and vomiting, and 18.9% for diarrhea. The 5-year progression-free survival (PFS) rates in the CCRT group and control group were 89.2% and 69.2%, respectively (P = 0.0392). CONCLUSION: This study showed that adjuvant CCRT with cisplatin and 5-FU could be safely performed and improved the prognosis in Japanese patients with high-risk early-stage cervical cancer after radical hysterectomy.