Treatment outcomes and late toxicities of 869 patients with nasopharyngeal carcinoma treated with definitive intensity modulated radiation therapy: new insight into the value of total dose of cisplatin and radiation boost

This study was to report the long-term outcomes and toxicities of nasopharyngeal carcinoma (NPC) treated with intensity-modulated radiation therapy (IMRT). From 2009 to 2010, 869 non-metastatic NPC patients treated with IMRT were retrospectively enrolled. With a median follow-up of 54.3 months, the 5-year estimated local recurrence-free survival (LRFS), regional recurrence-free survival (RRFS), distant metastasis-free survival (DMFS), disease-free survival (DFS) and overall survival (OS) were 89.7%, 94.5%, 85.6%, 76.3%, 84.0%, respectively. In locally advanced NPC, gender, T, N, total dose of cisplatin more than 300 mg/m² and radiation boost were independent prognostic factors for DMFS and DFS. Age, T, N and total dose of cisplatin were independent prognostic factors for OS. Radiation boost was an adverse factor for LRFS, RRFS, DMFS and DFS. Concurrent chemotherapy was not an independent prognostic factor for survival, despite marginally significant for DMFS in univariate analysis. Concurrent chemotherapy increased xerostomia and trismus, while higher total dose of cisplatin increased xerostomia and otologic toxicities. In conclusion, IMRT provided satisfactory long-term outcome for NPC, with acceptable late toxicities. Total dose of cisplatin was a prognostic factor for distant metastasis and overall survival. The role of concurrent chemotherapy and radiation boost in the setting of IMRT warrants further investigation.     

Concurrent chemoradiotherapy in locoregionally advanced nasopharyngeal carcinoma: Treatment outcomes of a prospective,multicentric clinical study

Background and purpose

To evaluate long-term outcome in locoregionally advanced nasopharyngeal carcinoma (NPC) treated with intensity-modulated radiation therapy (IMRT) and concurrent chemotherapy.

Material and methods

Between January 2006 and August 2008, 249 patients with stage III–IVb NPC were treated by IMRT plus concurrent chemotherapy in this multicenter prospective study.

Results

With a mean follow-up of 54.1 months, the 5-year actuarial rates of overall survival (OS), local recurrence-free survival (LRFS), regional recurrence-free survival (RRFS), and distant metastasis-free survival (DMFS) were 78.4%, 86.8%, 88.4%, 78.0%, respectively. There were 29 local recurrences, 25 regional recurrences and 52 distant metastases, respectively. Distant metastasis is the main cause of treatment failure. N-stage was an independent prognostic factor for LRFS, RRFS, DMFS and OS. Acute toxicity ?grade III mainly consisted of mucositis (34.9%), neutropenia (11.2%), xerostomia (5.6%), and dermatitis (5.2%). The main documented late toxicity was xerostomia, and the severity of xerostomia decreased over time. At 24 months after treatment, 13.2% of patients had grade 2 xerostomia, and none had grade 3 or 4 xerostomia.

Conclusions

IMRT with concurrent cisplatin chemotherapy resulted in encouraging rates of local and distant control and overall survival with acceptable rates of acute and limited rates of late toxicity in patients with locoregionally advanced NPC. Distant metastasis remained the main cause of failure. More effective systemic therapy should be explored for patients with advanced N-stage.     

Direct surgery with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for patients with colorectal peritoneal metastases

IntroductionNeoadjuvant chemotherapy is widely used in treatment of peritoneal metastases from colorectal cancer, but there is little scientific evidence for this approach. This study aimed to study survival in patients treated with direct surgery with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS-HIPEC), i.e. without neoadjuvant chemotherapy.Material and methodsPatients with histopathologically confirmed peritoneal metastases from colorectal cancer that underwent first-time CRS-HIPEC with complete cytoreduction (CC0 or 1) at Karolinska University Hospital 2012–2019 were included. Patients with synchronous extraperitoneal metastases were excluded if not treated before end of follow-up. Factors associated with overall survival (OS) and disease-free survival (DFS) were evaluated using the Kaplan-Meier method and Cox regression models. The multivariable models were adjusted for sex, age, synchronous/metachronous peritoneal metastases, peritoneal carcinomatosis index (PCI), extraperitoneal metastases and the pathological tumor (T) and lymph node (N) stage of the primary tumor.ResultsIn all, 131 patients underwent complete CRS-HIPEC for peritoneal metastases without neoadjuvant chemotherapy. The median OS and DFS were 40.3 months and 12.5 months, respectively, in patients treated with direct surgery. In the multivariable model, PCI≥16 was the only variable associated with decreased OS, whereas elevated PCI, metachronous development of peritoneal metastases and synchronous extraperitoneal metastases were associated with decreased DFS. Age was not associated with an impaired prognosis.ConclusionPatients who underwent direct surgery with CRS-HIPEC had a good prognosis, with a median OS of more than 3 years. The results from this study question the need of neoadjuvant chemotherapy in all patients eligible for CRS-HIPEC.     

Prognostic factors affecting long-term outcomes in patients with resected stage IIIA pN2 non-small-cell lung cancer: 5-year follow-up of a phase II study

The aim was to investigate the efficacy of neoadjuvant docetaxel-cisplatin and identify prognostic factors for outcome in locally advanced stage IIIA (pN2 by mediastinoscopy) non-small-cell lung cancer (NSCLC) patients. In all, 75 patients (from 90 enrolled) underwent tumour resection after three 3-week cycles of docetaxel 85 mg m-2 (day 1) plus cisplatin 40 or 50 mg m-2 (days 1 and 2). Therapy was well tolerated (overall grade 3 toxicity occurred in 48% patients; no grade 4 nonhaematological toxicity was reported), with no observed late toxicities. Median overall survival (OS) and event-free survival (EFS) times were 35 and 15 months, respectively, in the 75 patients who underwent surgery; corresponding figures for all 90 patients enrolled were 28 and 12 months. At 3 years after initiating trial therapy, 27 out of 75 patients (36%) were alive and tumour free. At 5-year follow-up, 60 and 65% of patients had local relapse and distant metastases, respectively. The most common sites of distant metastases were the lung (24%) and brain (17%). Factors associated with OS, EFS and risk of local relapse and distant metastases were complete tumour resection and chemotherapy activity (clinical response, pathologic response, mediastinal downstaging). Neoadjuvant docetaxel-cisplatin was effective and tolerable in stage IIIA pN2 NSCLC, with chemotherapy contributing significantly to outcomes.     

三维放疗联合顺铂同期化疗局部晚期宫颈癌疗效分析

目的 分析CT图像为基础三维适形放疗联合顺铂同期化疗对晚期宫颈癌患者疗效及副反应情况.方法 回顾分析2007-2008年本科收治的181例Ⅱa～Ⅳa期宫颈癌患者资料,其中年龄32～82岁(中位数50岁).放疗采用以CT图像为基础的三维适形放疗和三维192Ir后装照射技术,同期联合顺铂单药每周化疗方案.结果 随访中位数34个月,随访率为92.2%.全组患者3年总生存率为73.4%、无瘤生存率为70.4%、盆腔控制率为91.3%.肿瘤直径≥4 cm和＜4 cm者总生存率分别为66.9%和86.4%(χ2=6.29,P=0.012).RTOG分级急性胃肠道副反应1、2级发生率分别为40.0%、45.0%,泌尿系副反应l、2级发生率分别为19.9%、4.4%.RTOG分级晚期下消化道副反应3+4级发生率为4.9%.结论 以CT图像为基础三维适形放疗和三维192Ir后装照射技术联合顺铂同期化疗对局部晚期宫颈癌患者疗效较好,并对降低晚期严重副反应的发生有益.

Abstract：

Objective To analyze the therapeutic efficacy and treatment related toxicities for patients with locally advanced cervical cancer treated with three-dimensional conformal radiotherapy (3DCRT) combined with concurrent chemotherapy. Methods From January 2007 to February 2008, 181 patients with stage ⅡA-ⅣA cervical cancer were retrospectively analyzed. All patients were treated with CT-based three-dimensional external beam and 192Ir intracavity radiotherapy combined with concurrent weekly cisplatin-based chemotherapy. The median age was 50 years (range, 32 to 82 years). The overall survival ( OS), disease-free survival (DFS) and local control (LC) rates were calcalated by Kaplan-Meier method and the difference was compared using Log-rank test. The treatment related toxicities were evaluated according to Radiotherapy Oncology Group (RTOG) criteria. Results With a median follow-up time of 34 months and following rate of 92. 2%, the 3-year OS, DFS and LC rates were 73.4%, 70. 4% and 91.3%,respectively. The 3-year OS rate was 66. 9% for patients with tumor diameter ≥4 cm and 86. 4% for those with tumor diameter ＜4 cm( χ2 =6. 29 ,P =0. 012). The incidences of grade 1 and grade 2 acute toxicities of the lower gastrointestinal tract and the genitourinary system were 40. 0% ,45.0% and 19. 9% ,4. 4%,retrospectively. There were no grade 3 or more acute toxicities. The incidence of grades 3 or 4 late toxicities of the lower gastrointestinal tract was 4. 9%. Conclusions CT-based three-dimensional external beam and 192Ir intracavity radiotherapy combined with concurrent chemotherapy can achieve good therapeutic effects for locally advanced cervical cancer. The acute and late toxicities are significantly reduced compared with historic controls as a result of incorporation of 3DCRT technique.     

Survival Outcomes of Liver Metastasectomy in Colorectal Cancer Cases: A Single-Center Analysis in Turkey

Background: The purpose of this study was to analyze our series of liver resections for metastatic colorectal carcinoma (mCRC) to determine prognostic factors affecting survival and to evaluate the potential roles of neoadjuvant or adjuvant chemotherapy. Materials and Methods: Ninety-nine patients who underwent metastasectomy for liver metastases due to colorectal cancer at the Department of Medical Oncology, 9 Eylul University Hospital between 1996 and 2010 were evaluated in this study. The patients were followed through July 2013. Demographic, perioperative, laboratory, radiological and chemotherapy as well as survival data were obtained by retrospective chart review. Results: In 47 (47.5%) patients, liver metastases were unresectable at initial evaluation; the remaining 52 (52.5%) patients exhibited resectable liver metastases. Simultaneous hepaticresection was applied to 52 (35.4%) patients with synchronous metastasis, whereas 5 (64.5%) patients underwent hepatic resection after neoadjuvant chemotherapy. Forty-two patients with metachronous metastasis underwenthepatic resection following neoadjuvant chemotherapy. R0 resection was obtained in 79 (79.8%) patients. A second hepatectomy was performed in 22 (23.2%) patients. Adjuvant chemotherapy was given to 85 (85.9%) patients after metastasectomy. The median disease-free and overall survivals after initial metastasectomy were 12 and 37 months, respectively, the 1-year, 3-year and 5-year disease-free survival (DFS) and overall survival (OS) rates being 46.5%, 24.3% and 17.9%and 92.3%, 59.0% and 39.0%, respectively. On multivariate analysis, the primary tumor site, tumor differentiation, resection margin and DFS were independent factors predicting better overall survival. Conclusions: In selected cases, hepatic metastasectomy for mCRC to the liver can result in long-term survival. Neoadjuvant chemotherapy did not exert a positive effect on DFS or OS. Adjuvant chemotherapy also did not appear to impact DFS and OS.     

Radiologic and pathologic response to neoadjuvant chemotherapy predicts survival in patients undergoing the liver-first approach for synchronous colorectal liver metastases

Purpose

To investigate the short- and long-term outcomes of liver first approach (LFA) in patients with synchronous colorectal liver metastases (CRLM), evaluating the predictive factors of survival.

初治鼻咽癌调强放疗的前瞻性多中心临床研究

目的 观察调强放疗(IMRT)初治鼻咽癌的临床疗效及不良反应,并分析影响预后的因素。方法 2006—2008年,6个治疗中心共 300例经病理活检确诊为鼻咽癌的初治患者接受全程IMRT。UICC/AJCC 2002分期Ⅰ、Ⅱ、Ⅲ、Ⅳ_a+b期分别为6、45、141、108例。放疗处方剂量鼻咽原发灶计划把体积为 70~74 Gy,颈部转移淋巴结计划把体积为 68~70 Gy,计划靶体积 -1为 60~64 Gy,计划靶体积 -2为 50~54 Gy,均分30次6周完成。Ⅲ~Ⅳ_a+b期患者接受了以铂类为基础化疗。Cox法多因素预后分析。结果 随访率为99.7%。4年局部控制率、区域控制率、无远处转移率、无瘤生存率及总生存率分别为94.0%、95.5%、87.4%、80.8%及86.1%。急性1、2、3级放射性黏膜炎分别占18.0%、48.7%、33.3%,晚期 0、1、2级口干分别占12.0%、 75.7%、12.3%。18、15、42例出现局部﹑颈部淋巴结复发、远处转移。多因素分析显示N分期影响总生存率(χ²=5.17,P=0.023)、无远处转移率(χ²=6.91,P=0.009)、无瘤生存率(χ²=8.15,P=0.004)。结论 IMRT可提高初治鼻咽癌患者临床疗效,不良反应可耐受,治疗失败最主要原因为远处转移,N分期是影响预后的主要因素。     

三阴性乳腺癌患者的临床特征及新辅助化疗疗效与预后的相关性

 目的　探讨三阴性乳腺癌（TNBC）的临床病理特点及远期生存率。并分析其新辅助化疗的疗效与生存率的相关性。方法　研究对象为535例乳腺癌患者,其中TNBC患者75例,非TNBC患者460例,对其临床和病理资料以及 5年的无病生存（DFS）率及总生存（OS）率进行回顾性分析,并与同期的非TNBC患者进行对比。535例中88例患者接受术前新辅助化疗,TNBC患者26例,非TNBC患者62例,分析其化疗疗效与远期生存的相关性。结果　TNBC患者与非TNBC患者相比,中位年龄轻（35岁比44岁）,绝经前患者居多（88.0 % 比67.2 %,P＝0.009）;浸润性导管癌多见（92. 0 % 比80.4 %,P＝0.020）,组织学分级Ⅱ级者居多（56.0 %比17.2 %,P＝0.000）;淋巴结转移阳性者较少（33.3 %比53.9 %,P＝0.001）;TNBC组5年DFS（66.67 %）、OS（80.0 %）明显低于非TNBC组（74.78 %、90.0 %）。接受新辅助化疗的TNBC患者与非TNBC患者相比,化疗的总有效（OR）率（88.46 %比82.26 %）、临床完全缓解（cCR）率（65.38 %比37.10 %）、部分缓解（PR）率（23.08 %比45.16 %）差异均有统计学意义（P＜0.05）。新辅助化疗的TNBC患者与非TNBC患者相比,5年的OS率（73.08 %比80.65 %）差异具有统计学意义（P＝0.049）;5年的DFS率（65.38 %比72.58 %）差异具有统计学意义（P＝0.253）。分层分析发现：获得cCR的TNBC与非TNBC患者的5年DFS及OS差异无统计学意义（P＞0.05）。未获得cCR TNBC患者的5年DFS及OS均显著低于非TNBC患者（P＜0.05）,临床OR对两组的5年DFS及OS无影响（P＞0.05）。结论　TNBC多见于年轻的绝经前妇女,主要病理类型为浸润性导管癌,核分级高,淋巴结转移少见,但相对非TNBC患者有较低的DFS率和OS率,TNBC患者对新辅助化疗更敏感,更易获得cCR,获得cCR的TNBC患者预后好,未获得cCR的TNBC患者远期生存率明显低于非TNBC患者     

Neoadjuvant chemotherapy with infusional 5-fluorouracil, adriamycin and cyclophosphamide (iFAC) in locally advanced breast cancer: an early response predicts good prognosis.

BACKGROUND: The aim of this study was to evaluate the efficacy and safety of neoadjuvant chemotherapy with infusional 5-fluorouracil (5-FU), adriamycin and cyclophosphamide (iFAC) in locally advanced breast cancer (LABC). PATIENTS AND METHODS: Eighty-two LABC patients were treated with neoadjuvant iFAC chemotherapy including infusional 5-FU (1000 mg/m2, continuous intravenous infusion, days 1-3), adriamycin (40 mg/m2, intravenous bolus, day 1) and cyclophosphamide (600 mg/m2, intravenous bolus, day 1) every 3 weeks until maximum tumor response. Patients subsequently received surgery, adjuvant chemotherapy, radiotherapy and hormonal therapy as appropriate. RESULTS: Downstaging occurred in 71 of the 82 patients (86.6%). Seventy-two patients (67 patients with downstaging and five patients without downstaging) were resectable (resectability rate, 87.8%). The clinical response rate was 84.2%, with a complete response (CR) rate of 17.1% and a pathological CR rate of 7.8%. During 891 cycles of chemotherapy, the most common grade 3/4 hematological toxicity was leukopenia (36.0%). There were no treatment-related deaths. The median follow-up period was 51 months, with a median overall survival (OS) of 66 months, and a 5 year OS rate of 50.9% for all patients. The 5 year OS and disease-free survival (DFS) rates of the 64 patients who underwent surgery were 55.8% and 44.7%, respectively. CONCLUSIONS: Neoadjuvant chemotherapy with iFAC had a comparable response rate and DFS to the conventional bolus FAC regimen, with an acceptable toxicity in LABC using the AJCC 2002 staging system. An early response to neoadjuvant iFAC was a favorable prognostic factor.     

Comparison of CVF (Cyclophosphamide+Vinorelbine+5-Fluorouracil) and CMF (Cyclophosphamide+Methotrexate+5-Fluorouracil) Adjuvant Chemotherapy in Early Breast Cancer

Purpose

Our study aimed to evaluate the feasibility of adjuvant cyclophosphamide/vinorelbine/5-fluorourail (CVF) chemotherapy as an alternative to cyclophosphamide/methotrexate/5-fluorouracil (CMF) chemotherapy for treating early breast cancer.

Methods

One hundred and forty-nine patients were randomly assigned to CMF or CVF adjuvant chemotherapy for treating their early stage breast cancer between September 2000 and December 2007. The disease-free survival (DFS), the overall survival (OS), and the toxicity profiles of both groups were compared.

Results

Sixty-seven patients underwent CMF chemotherapy whereas 82 patients underwent CVF chemotherapy. The DFS and OS were 88 months (95% confidence interval [CI], 76-101 months) and 94 months (95% CI, 83-104 months), respectively for the CMF group, and 97 months (95% CI, 93-101 months), and 101 months (95% CI, 98-104 months), respectively for the CVF group. However, those survival gains of the CVF group were not statistically significant (p-value=0.069 for the DFS and 0.99 for the OS). The CVF group showed a favorable toxicity profile in terms of the grade 3/4 hematologic toxicities as compared to that of the CMF group.

Conclusion

Clinical outcome of CVF chemotherapy was comparable to CMF with a favorable toxicity profiles. However, it is difficult to conclude the feasibility of CVF regimen because of small number of studied patients.     

Efficacy and safety of camrelizumab (a PD-1 inhibitor) combined with chemotherapy as a neoadjuvant regimen in patients with locally advanced non-small cell lung cancer

Camrelizumab is a novel programmed cell death protein 1 (PD-1) inhibitor developed in China that exhibits good efficacy in several advanced cancer types, including non-small cell lung cancer (NSCLC); however, its utility as a neoadjuvant regimen in NSCLC remains unclear. Thus, the present study aimed to explore the efficacy and safety of neoadjuvant camrelizumab plus chemotherapy in patients with locally advanced NSCLC. A total of 56 patients with stage IIIA/IIIB resectable NSCLC were analyzed in the present prospective observational study. Amongst the cohort, 31 patients underwent neoadjuvant camrelizumab (200 mg every 2 weeks) plus paclitaxel and carboplatin (PC) chemotherapy, while another 25 cases underwent neoadjuvant PC chemotherapy alone. The pathological response, disease-free survival (DFS) time, overall survival (OS) time and adverse events (AEs) were analyzed. The complete pathological response (25.8 vs. 8.3%; P=0.159) and major pathological response (MPR) (61.3 vs. 37.5%; P=0.080) rates were higher in the camrelizumab plus PC group compared with the findings in the PC group, although the results were not statistically significant. DFS time was significantly prolonged in the camrelizumab plus PC group compared with that in the PC group (P=0.030); however, there was no difference in OS time between these two groups (P=0.251). Following adjustment by multivariate analysis, the camrelizumab plus PC regimen versus the PC regimen alone was independently associated with higher MPR [odds ratio, 5.216; 95% confidence interval (CI), 1.178-23.086; P=0.030], and favorable DFS [hazard ratio (HR), 0.055; 95% CI, 0.007-0.442; P=0.006] and OS (HR, 0.025; 95% CI, 0.002-0.416; P=0.010) times. The most common AEs of the neoadjuvant camrelizumab plus PC regimen were alopecia (51.6%), nausea and vomiting (45.2%), anemia (41.9%) and fatigue (41.9%), the majority of which occurred in patients with grade 1–2 disease. The present results indicated that neoadjuvant camrelizumab plus PC chemotherapy exhibited a superior pathological response and survival profile to PC chemotherapy alone, and was well tolerated in patients with locally advanced NSCLC.     

Short course continuous, hyperfractionated, accelerated radiation therapy (CHART) as preoperative treatment for rectal cancer

Determine feasibility and toxicity of preoperative short course pelvic CHART (25 Gy in 15 fractions over 5 days) for treatment of clinically resectable primary rectal tumours. Between 1998 and 2004, 20 patients with clinically staged T3 resectable rectal carcinoma were treated in this prospective pilot study with preoperative short course CHART to their pelvis. The aim was for total mesorectal excision within 7 days. Radiation toxicity, surgical morbidity, locoregional control (LRC), overall (OS), cause specific (CSS) and disease free survival (DFS) outcomes were documented. Nineteen of the 20 patients completed planned radiotherapy. One discontinued radiotherapy due to toxicity. All patients underwent potentially curative radical surgery. One patient developed grade 3, and three patients grade 2 gastrointestinal toxicity. With a median follow-up of 31 months (range 0.9-88), there is no grade 3, 4 or 5 late toxicity. Two patients experienced grade 2, and three patients grade 1 late bowel toxicity. Two patients died from postoperative complications, and two developed grade 2 abdominal wound infections. At 3 years LRC is 95% (95% CI 83-100), OS 72% (95% CI 51-94), CSS 86% (95% CI 68-100) and DFS 80% (95% CI 60-100). Two patients died from metastatic disease, one patient from a second primary and one patient is alive after successful resection of hepatic metastases. This small study suggests preoperative short course CHART for clinically resectable rectal carcinoma is feasible with acceptable compliance and tolerable side effects.     

Cytologically proven axillary lymph node metastases are eradicated in patients receiving preoperative chemotherapy with concurrent trastuzumab for HER2‐positive breast cancer

BACKGROUND:

The axillary pathologic complete response rate (pCR) and the effect of axillary pCR on disease‐free survival (DFS) was determined in patients with HER2‐positive breast cancer and biopsy‐proven axillary lymph node metastases who were receiving concurrent trastuzumab and neoadjuvant chemotherapy. The use of neoadjuvant chemotherapy is reported to result in pCR in the breast and axilla in up to 25% of patients. Patients achieving a pCR have improved DFS and overall survival. To the authors' knowledge, the rate of eradication of biopsy‐proven axillary lymph node metastases with trastuzumab‐containing neoadjuvant chemotherapy regimens has not been previously reported.

METHODS:

Records were reviewed of 109 consecutive patients with HER2‐positive breast cancer and axillary metastases confirmed by ultrasound‐guided fine‐needle aspiration biopsy who received trastuzumab‐containing neoadjuvant chemotherapy followed by breast surgery with complete axillary lymph node dissection. Survival was evaluated by the Kaplan‐Meier method. Clinicopathologic factors and DFS were compared between patients with and without axillary pCR.

RESULTS:

Eighty‐one patients (74%) achieved a pCR in the axilla. Axillary pCR was not associated with age, estrogen receptor status, grade, tumor size, initial N classification, or median number of lymph nodes removed. More patients with an axillary pCR also achieved a pCR in the breast (78% vs 25%; P < .001). At a median follow‐up of 29.1 months, DFS was significantly greater in the axillary pCR group (P = .02).

CONCLUSIONS:

Trastuzumab‐containing neoadjuvant chemotherapy appears to be effective in eradicating axillary lymph node metastases in the majority of patients treated. Patients who achieve an axillary pCR are reported to have improved DFS. The success of pCR with concurrent trastuzumab and chemotherapy in eradicating lymph node metastases has implications for surgical management of the axilla in these patients. Cancer 2010. © 2010 American Cancer Society.     

Serum markers and prognosis in locally advanced breast cancer

BACKGROUND: Locally advanced breast cancer (LABC) represents a heterogeneous subgroup of breast cancer with an often dismal outcome. Identifying prognostic factors has acquired great significance for the selection of optimal treatment in individual patients. METHODS: Between January 1993 and December 1997, 103 patients were treated in our institution with multimodality treatment consisting of neoadjuvant chemotherapy followed by surgery, adjuvant chemotherapy and radiotherapy; tamoxifen was added in hormone receptor-positive cases. In the search for prognostic factors well-established parameters (clinical, pathological and treatment-related) as well as new features with potential value (c-erbB-2, baseline serum levels of CA 15.3 and CEA) were included in the univariate and multivariate analysis. RESULTS: At a median follow-up of 92 months (range, 8-130), the estimated five-year cancer-specific overall survival (OS) and disease-free survival (DFS) were 71.34% and 57.7%, respectively. Among the 22 different variables studied, only 10 were significantly correlated with OS and DFS. In multivariate analysis five retained independent prognostic value for both OS and DFS: tumor grade, serum markers, features of inflammatory breast cancer (IBC), response to neoadjuvant chemotherapy and lymph node status. With cutoff values of 35 U/mL for CA 15.3 and 5 ng/mL for CEA, the probability of five-year OS (Cox hazard ratio 3.91, P = 0.0009) and DFS (Cox hazard ratio 2.40, P = 0.02) decreased from 78% to 52% and from 68% to 47%, respectively, when at least one of these markers was abnormal. CONCLUSIONS: Baseline serum levels of CEA and CA 15.3 emerged from this study as strong independent predictors of outcome in LABC, whose value adds to other established prognostic factors such as postoperative nodal status, IBC, histological grade and response to neoadjuvant chemotherapy.     

进展期胃癌新辅助化疗期间伴急性上消化道出血患者的生存分析

  目的  探讨进展期胃癌新辅助化疗期间合并急性上消化道出血(acute upper gastrointestinal bleeding, AUGB)患者的临床特征和生存预后。  方法  回顾性分析河北医科大学第四医院自2015年1月至2017年1月行术前新辅助化疗的476例胃癌患者, 筛选出新辅助治疗期间出现AUGB的患者, 分析临床特征及影响预后的因素。  结果  476例胃癌患者行新辅助化疗期间出现AUGB者35例(7.35%), 其中经补液止血保守治疗好转者6例, 内镜下成功止血者5例, 血管造影栓塞术成功止血者7例, 余17例患者均行剖腹探查手术止血。全组患者3年总生存率(overall survival, OS)为65.13%, 3年无病生存率(disease-free survival, DFS)为60.71%。其中出现AUGB者3年OS为48.57%, 3年DFS为42.86%, 而未出现AUGB者3年OS、DFS分别为66.44%、62.13%, 两组患者的3年OS、DFS差异均具有统计学意义(P=0.033、P=0.025)。Cox比例风险模型多因素分析发现, 肿瘤组织学类型为低分化-未分化型(P=0.004、P=0.008)、肿瘤cTNM分期为Ⅲ期(P=0.002、P=0.013)和出现AUGB后未继续行化疗治疗(P=0.003、P=0.005)是影响AUGB患者预后及复发的独立危险因素。  结论  进展期胃癌患者进行新辅助化疗期间出现AUGB与多种危险因素有关, 此类患者需引起临床重视; 新辅助化疗期间出现AUGB后需积极对症止血治疗, 止血成功后继续化疗才可能延长此类患者生存期。      

133例Ⅲ期鼻咽癌调强放疗的疗效及不良反应分析

背景与目的:调强放疗(intensity-modulated radiation therapy,IMRT)是最大限度提高肿瘤靶区照射剂量的同时明显减少周围正常组织的剂量的放疗技术,调强放疗联合化疗治疗局部晚期鼻咽癌取得了较好的疗效,如何在此基础上进一步提高疗效成为肿瘤学者共同关注的话题.鼻咽癌分期不同,疗效不同,同一分期各亚组间疗效有无差别,尚有待研究.通过回顾性分析临床Ⅲ期鼻咽癌各亚组间调强放疗联合化疗的疗效,探讨进一步提高疗效的方法.方法:对我院2003年1月-2006年6月期间收治的133例临床Ⅲ期鼻咽癌患者进行分析,根据AJCC 2002分期,其中T3N0 7例(5.3％),T3N1 39例(29.3％),T2N2 48例(36.1％),T3N2 39例(29.3％).所有患者均完成调强放疗,124例患者行诱导化疗,其中24例患者行同期化疗,33例患者行辅助化疗.结果:全组5年局部控制率、无远处转移生存率、无瘤生存率和总生存率分别为:90.9％、89.9％、82.5％和83.4％.T2、T3期患者5年局部控制率分别为93.1％、89.4％(x2=0.407,P=0.524),无远处转移生存率分别为91.2％、89.3％(x2=0.152,P=0.697),无瘤生存率分别为86.5％、80.0％(x2=0.899,P=0.343),总生存率分别为81.1％、84.7％(x2=0.311,P=0.577).N0-1、N2期患者5年局部控制率分别为91.1％、90.9％(x2=0.007,P=0.933),无远处转移生存率分别为97.8％、85.8％ (x2=4.69,P=0.030),无瘤生存率分别为88.9％、79.2％(x2=1.746,P=0.183 6),总生存率分别为93.5％、78.1％(x2=5.052,P=0.025).辅助化疗对IMRT Ⅲ期鼻咽癌未能获益,但3、4级毒性不良反应明显增加(48％ vs 27.6％,P＜0.005).结论:对临床Ⅲ期鼻咽癌患者,IMRT联合化疗可以取得较好的疗效,N0-1期较N2期患者有较高的总生存率和无远处转移生存率,进一步提高IMRT Ⅲ期鼻咽癌疗效还需寻找更有效的化疗药物、靶向药物及更合理的联合治疗方案.     

Cisplatin-based combined modality therapy for anal carcinoma: a wider therapeutic index

BACKGROUND: Definitive chemoradiation therapy is the standard of care for anal carcinoma. The chemotherapy regimen comprising 5-fluorouracil (5-FU) and mitomycin-C is the most commonly used among patients with anal carcinoma but causes well documented toxicities. In the current study, the authors evaluated their experience in treating anal carcinoma with combined modality therapy using cisplatin and 5-FU. METHODS: A retrospective analysis was performed of 92 patients with nonmetastatic squamous cell carcinoma of the anus who were treated between 1989 and 1998. The primary tumor and involved lymph nodes received a total dose of 55 grays (Gy) administered in more than 30 daily fractions. Cisplatin (4 mg/m(2)/day) and 5-FU (250 mg/m(2)/day) were given as a continuous infusion, 5 days each week during the entire radiation course. Kaplan-Meier methodology was used to determine local control (LC), disease-free survival (DFS), and overall survival (OS). RESULTS: Ten patients had T1 or Tx, 43 had T2, 27 had T3, and 12 patients had T4 disease. There were 21 male and 71 female patients. Sixty-five patients (71%) were lymph node negative. With a median follow-up duration of 44 months, the actuarial 5-year OS rate was 85%, the DFS rate was 77%, and the colostomy-free survival rate was 82%. Local recurrences occurred in 16 patients (17%). Distant metastases (DM) occurred in eight patients (9%). Advanced T classification (> T2) predicted lower LC and DFS rates. Advanced N classification (> N1) predicted worse DFS, OS, and DM rates. Greater than 90% of patients completed treatment without significant treatment interruption. Only five patients developed acute toxicities of Radiation Therapy Oncology Group (RTOG) Grade 4 or higher and only three patients developed chronic toxicities of RTOG Grade 4 or higher. CONCLUSIONS: Combined modality therapy with continuous infusion of cisplatin and 5-FU is a well tolerated regimen that results in high rates of LC, OS, and sphincter preservation. These rates are comparable to the best results reported with mitomycin-C and 5-FU. Without the normally severe toxicity, cisplatin-based therapy results in a wider therapeutic index.     

Nasopharyngeal carcinoma in children: ten years' experience at the Tata Memorial Hospital, Mumbai

PURPOSE: To evaluate the disease characteristics and outcome of children with nasopharyngeal carcinoma treated at the Tata Memorial Hospital, Mumbai. METHODS AND MATERIALS: Between 1990 and 2000, 81 pediatric patients with a diagnosis of nasopharyngeal carcinoma were treated at the Tata Memorial Hospital. The median age was 14 years. The male/female ratio was 2.8:1. Of the 81 patients, 32 (39%), 21 (26%), and 28 (35%) had T1-T2, T3, and T4 (TNM International Union Against Cancer staging system, 1997), respectively. Ninety-one percent presented with nodal metastasis. Thirty patients (37%) had lymph nodes >6 cm, and 45 (56%) had bilateral nodes at presentation. Histologically, 77 patients (95%) had undifferentiated carcinoma. Eighty-five percent received neoadjuvant multiagent chemotherapy containing bleomycin, methotrexate, and cisplatin, followed by radiotherapy (RT). RESULTS: After a median follow-up of 50 months, the disease-free survival (DFS) and overall survival (OS) rate for the entire group was 45% and 54%, respectively. Kaplan-Meier curves were used for evaluation of prognostic factors and were compared using the log-rank test. Nodal status had a significant impact on DFS (p = 0.021) and OS (p = 0.006). Complete responders to chemotherapy had superior DFS (p = 0.000) and OS (p = 0.000). RT doses >60 Gy resulted in better DFS (p = 0.020) and OS (p = 0.012). Combined chemotherapy plus RT resulted in improved DFS (p = 0.457) and OS (p = 0.296), although the difference was not statistically significant. CONCLUSION: Combined modality management using chemotherapy and RT resulted in satisfactory locoregional control and OS in pediatric patients with nasopharyngeal carcinoma. Nodal involvement, response to chemotherapy, and RT dose were important prognostic factors.     

局部进展期中低位直肠癌新辅助放化疗临床疗效及预后影响因素分析

目的 探讨新辅助放化疗对局部进展期中低位直肠癌患者的临床疗效,研究相关临床因素对远期生存的影响。方法 收集我院2010-2014年收治的101例局部进展期中低位直肠癌患者的临床资料,全部患者完成术前调强放疗DT45~50.4 Gy,同步给予奥沙利铂+卡培他滨/氟尿嘧啶或单药卡培他滨化疗,于新辅助治疗后4-13周行全直肠系膜切除术(TME)。评估近期疗效及远期预后,Kaplan-Meier法计算总生存(OS)、无瘤生存(DFS)率,Cox回归模型进行预后因素分析。结果 全组患者总体保肛率53.5%,术后T、N分期及TNM总分期下降率分别为73.26%、67.32%、72.3%,病理完全缓解率16.8%;中位随访41个月,3年OS、DFS、局部复发、远处转移率分别为82.2%、80.7%、7.2%、12.1%。单因素分析显示ypT、ypN分期是影响患者3年OS、DFS、远处转移的相关因素(P均<0.05);多因素分析显示ypT分期是影响患者3年OS因素,ypT、ypN分期是影响患者3年DFS因素(P均<0.05)。结论 新辅助放化疗联合TME治疗局部进展期中低位直肠癌,使部分患者达到术前降期,提高保肛率,且远期预后表现良好,ypT、ypN分期与患者预后相关。