Low expression of Bax predicts poor prognosis in patients with locally advanced esophageal cancer treated with definitive chemoradiotherapy.

PURPOSE: The present study evaluated the prognostic significance of apoptosis-related proteins, p53, Bcl-2, Bax, and galectin-3 in patients with locally advanced esophageal cancer treated with definitive chemoradiotherapy. EXPERIMENTAL DESIGN: A total of 63 patients with locally advanced esophageal cancer (squamous cell carcinoma: 62; adenocarcinoma: 1; stages II-IV) were treated with definitive chemoradiotherapy using 5-fluorouracil and cisplatin combined with radiotherapy. Pretreatment tumor biopsy specimens were analyzed for p53, Bcl-2, Bax, and galectin-3 expression by immunohistochemistry. RESULTS: High expression of Bax, p53, Bcl-2, and galectin-3 was observed in 67%, 47%, 24%, and 29% of patients, respectively. The median overall survival (OS) of total patients was 14 months with 16% of 3-year OS. High expression of p53, Bcl-2, and galectin-3 did not show correlation with clinicopathologic characteristics, including patient outcome. Low expression of Bax was significantly correlated with lack of clinical complete response (P=0.023). Low expression of Bax was also associated with poor OS (median, 8 months versus 16 months; P=0.0008) in univariate analysis. In multivariate analysis, low expression of Bax was the most significant independent predictor of poor OS (P=0.009), followed by low dose intensity of cisplatin and lack of clinical complete response. CONCLUSIONS: Low expression of Bax was significantly associated with the poor survival of patients with locally advanced esophageal cancer treated with chemoradiotherapy using 5-fluorouracil and cisplatin. Immunohistochemical staining for Bax with a pretreatment biopsy specimen might be useful to select the optimal treatment options for these patients.     

Prognostic factors in patients with unresectable locally advanced pancreatic adenocarcinoma treated with chemoradiation

BACKGROUND: Although patients with locally advanced pancreatic cancer (LAPC) have an extremely poor prognosis, they are a heterogeneous group. Prognostic factors are inadequately defined for disease-free survival and overall survival in patients with LAPC who are receiving chemoradiation, so more definitive prognostic factors would be very useful for designing clinical trials. METHODS: Between December 1993 and July 2005, 247 patients with nonmetastatic LAPC were treated at M. D. Anderson Cancer Center (Houston, Tex) with concurrent chemoradiation (CRT). Median radiation dose was 30 Gy (range, 15-52.2 Gy). Radiosensitizers included 5-fluorouracil (54%), gemcitabine (33%), and capecitabine (13%). Actuarial univariate and multivariate statistical methods were used to determine significant prognostic factors for disease-free survival and overall survival. RESULTS: Median follow-up was 4.3 months (range, 1-63 months). Median disease-free survival and overall survival were 4.2 months and 8.5 months, respectively. On univariate analysis, prognostic factors for improved disease-free survival were a Karnofsky performance scale (KPS) status of >80 (P < .01) and a hemoglobin (Hgb)level at presentation of >/=12 (P = .03). On multivariate analysis, KPS was the only independent prognostic factor for disease-free survival. Median disease-free survival was 4.9 months among patients with a KPS score of >80 and was 3.9 months among those with a KPS score of /=12 (P = .02), KPS>80 (P < .001), and <5% weight loss (P = .03). On multivariate analysis, Hgb and KPS were independent prognostic factors for overall survival. CONCLUSIONS: In the current study, KPS score was an independent prognostic factor for disease-free and overall survival among patients treated with chemoradiation for LAPC. The pretreatment Hgb level was an additional independent prognostic factor for overall survival.     

Preoperative Glasgow Prognostic Score as additional independent prognostic parameter for patients with esophageal cancer after curative esophagectomy

Background

Inflammation accelerates tumor growth followed by reduced survival in patients with cancer. The aim of this study was to evaluate the prognostic relevance of preoperatively increased levels of C-reactive protein (CRP) and the corresponding Glasgow Prognostic Score (GPS) on patients with esophageal carcinoma undergoing curative esophagectomy.

Prognostic factors in patients with locally advanced pancreatic carcinoma receiving chemoradiotherapy

BACKGROUND: The combination of radiation therapy and chemotherapy (chemoradiotherapy [CRT]) has been accepted as standard therapy for patients with locally advanced pancreatic carcinoma (PC). This study investigated prognostic factors in patients with locally advanced PC receiving CRT. METHODS: Fifty-five consecutive patients with locally advanced PC, who received concurrent radiotherapy (50.4 grays) and chemotherapy using 5-fluorouracil or cisplatin, were analyzed retrospectively to investigate prognostic factors. RESULTS: Median survival time and overall survival rates at 1 and 2 years were 301 days, 35.1% and 2.4%, respectively. By multivariate analysis using the Cox proportional hazards model, performance status of 0-1 (P < 0.01), absence of regional lymph node swelling (P < 0.01), and serum CA 19-9 level of less than 1000 (P = 0.02) were independent favorable prognostic factors. A prognostic index based on the coefficients of those prognostic factors was used to classify patients into three groups with good, intermediate, and poor prognoses. The median survival times for these three groups were 410, 239, and 143 days, respectively (P < 0.01). CONCLUSIONS: The results may be helpful in predicting life expectancy, determining treatment strategies, and designing future clinical trials.     

Long-term follow-up of patients with unresectable locally advanced non-small cell lung cancer treated with chemoradiotherapy: a retrospective analysis of the data from the Japan Clinical Oncology Group trials (JCOG0003A)

To clarify the long-term survival data and factors that are correlated with survival outcome of unresectable locally advanced non-small cell lung cancer (NSCLC) following chemoradiotherapy, we analyzed patients who entered the Japan Clinical Oncology Group (JCOG) clinical trials for unresectable locally advanced NSCLC. Between October 1989 and August 1997, 240 patients (male 207, female 33; PS (performance status) 0 58, PS 1 172, PS 2 9, unknown 1; stage IIB 2, IIIA 62, IIIB 175, unknown 1) entered the 6 trials. All patients received chemotherapy and radiotherapy. The associations between survival outcome and treatment-related factors were analyzed using Cox regression analysis. Median survival times and 5-year survival rates in the trials were 11.9–19.7 months and 0–17.6%, respectively. Median survival time was 16.1 months and the 5- and 7-year survival rates of all 240 patients were 14.4% and 12.0%, respectively. No deaths were observed 7 years after initiation of the treatment or later. For stage IIIA and IIIB patients, the 5-year survival rates were 16.3% and 13.4%, respectively. Node status and age were significantly associated with survival, but no factors of the treatment were associated with survival of patients with unresectable locally advanced NSCLC. The present retrospective analysis showed that approximately 12% of patients with unresectable locally advanced NSCLC could be cured by various chemoradiotherapy regimens.     

Randomized study of low‐dose versus standard‐dose chemoradiotherapy for unresectable esophageal squamous cell carcinoma (JCOG0303)

Low‐dose cisplatin and 5‐fluorouracil (LDPF) chemotherapy with daily radiotherapy (RT) is used as an alternative chemoradiotherapy regimen for locally advanced esophageal carcinoma. We evaluated whether RT plus LDPF chemotherapy had an advantage in terms of survival and/or toxicity over RT plus standard‐dose cisplatin and 5‐fluorouracil (SDPF) chemotherapy in this study. This multicenter trial included esophageal cancer patients with clinical T4 disease and/or unresectable regional lymph node metastasis. Patients were randomly assigned to receive RT (2 Gy/fraction, total dose of 60 Gy) with SDPF (arm A) or LDPF (arm B) chemotherapy. The primary endpoint was overall survival (OS). A total of 142 patients (arm A/B, 71/71) from 41 institutions were enrolled between April 2004 and September 2009. The OS hazard ratio in arm B versus arm A was 1.05 (80% confidence interval, 0.78–1.41). There were no differences in toxicities in either arm. Arm B was judged as not promising for further evaluation in the phase III setting. Thus, the Data and Safety Monitoring Committee recommended that the study be terminated. In the updated analyses, median OS and 3‐year OS were 13.1 months and 25.9%, respectively, for arm A and 14.4 months and 25.7%, respectively, for arm B. Daily RT plus LDPF chemotherapy did not qualify for further evaluation as a new treatment option for patients with locally advanced unresectable esophageal cancer. This study was registered at the UMIN Clinical Trials Registry as UMIN000000861.     

Phase II trial of chemoradiotherapy with S‐1 plus cisplatin for unresectable locally advanced head and neck cancer (JCOG0706)

We conducted a phase II study to evaluate the efficacy and safety of chemoradiotherapy concurrent with S‐1 plus cisplatin in patients with unresectable locally advanced squamous cell carcinoma of the head and neck. Chemotherapy consisted of S‐1 twice daily on days 1–14 at 60 mg/m²/day and cisplatin at 20 mg/m²/day on days 8–11, repeated twice at a 5‐week interval. Single daily radiation of 70 Gy in 35 fractions was given concurrently starting on day 1. For patients achieving an objective response after chemoradiotherapy, two additional cycles of chemotherapy were administered. Of the 45 enrolled patients, the percentage of clinical complete remission, the primary endpoint, was 64.4% (8 complete response, 21 good partial response) on central review. After a median follow‐up of 3.52 years, 3‐year local progression‐free survival was 62.2%, with 3‐year progression‐free survival of 60.0%, 3‐year overall survival of 64.4%, and 3‐year time to treatment failure of 48.9%. Grade 3 or 4 toxicity included pharyngeal mucositis (46.7%), oral mucositis (44.4%), dysphagia (46.7%), anorexia (42.2%), radiation dermatitis (26.7%), neutropenia (26.7%), and febrile neutropenia (4.4%). No treatment‐related deaths were observed. This combination showed promising efficacy with acceptable toxicities.     

Radiotherapy quality assurance review for a multi-center randomized trial of locally advanced esophageal cancer: the Japan Clinical Oncology Group (JCOG) trial 0303

Background and purpose  

The purpose of this study was to evaluate the radiotherapy (RT) quality assurance (QA) for JCOG 0303.     

局部晚期直肠癌同步放化疗前后MRI参数与预后相关性研究

目的 探索局部晚期直肠癌术前同步放化疗前后MRI指标与预后关系。方法 回顾分析2015-2017年间在中国医学科学院肿瘤医院初治局部晚期直肠癌患者,具有放疗前、后MRI且接受手术且随访资料完整患者96例,均接受术前长程同步放化疗,放疗后6~13周接受根治性手术。对放化疗前4周内及之后4~8周的直肠MRI进行评价,并与3年无瘤生存(DFS)率进行相关分析。结果 全组患者T3、T4期者分别为80例(83%)、16例(17%),N0、N1-2期者分别为14例(15%)、82例(85%),直肠系膜筋膜受侵[MRF (+)]者69例(72%),肠壁外血管侵犯[EMVI (+)]者58例(60%)。全组患者接受术前放疗中位剂量为50Gy,均接受同步化疗增敏。同步放化疗后T分期降期率及N分期转阴率分别为24%和50%,MRF (+)率、EMVI (+)率分别降至37%(P<0.001)和27%(P<0.001)。单因素及多因素分析均显示放化疗后MRI显示N分期、EMVI状态转变与患者3年DFS相关(P<0.05)。结论 同步放化疗后MRI显示EMVI持续阳性、N1-N2期是DFS预后不良因素,提示改进治疗的必要性。     

PET/CT标准摄取值与Ⅲ期非小细胞肺癌西妥昔单抗联合同期放化疗预后相关性的研究

背景与目的：PET/CT在非小细胞肺癌(non-small cell lung cancer,NSCLC)的预后判断中有重要价值,但单独针对Ⅲ期且接受靶向治疗患者的研究较少。本研究旨在探讨在这些患者中¹⁸F氟代脱氧葡萄糖(¹⁸F-fluorodeoxyghcose,¹⁸F-FDG)PET/CT基线标准摄取值(standard uptake value,SUV)与预后的相关性。方法：前瞻性分析复旦大学附属肿瘤医院放疗科2009年9月-2012年7月入组的17例接受西妥昔单抗(cetuximab,C225)联合顺铂+长春瑞宾(NP方案)诱导化疗及同期放化疗的患者,入组前两周内完成PET/CT检查。采用Cox回归风险比例模型对SUV-T、SUV-N、SUV-TOTAL、性别、年龄、组织学类型、TNM分期、功能状态评分(performance status,PS)、吸烟状态与患者生存时间进行单因素生存分析,差异有统计学意义者进行多因素生存分析。Log-rank检验及Kaplan-Meier法分别评估以SUV-T、SUV-N、SUV-TOTAL界值分组患者间生存期的差异并绘制生存曲线。结果：单因素预后分析提示,上述SUV_max、PS评分、吸烟状态与预后相关,其中SUV-T及SUV-N的界值是11、SUV-TOTAL为20。多因素分析结果显示,SUV-TOTAL(P=0.012)、SUV-T(P=0.025)、SUVN(P=0.033)是影响本组患者生存的独立预后因素,其中SUV-TOTAL>20组患者的相对危险度(hazard ratio,HR)为14.7。结论：对于C225联合同步放化疗的患者,PET/CT局部区域、原发灶及纵隔淋巴结SUV值与预后有一定相关性,值得进一步大样本研究。将3者结合起来,可指导该治疗的合理应用。     

Serum C-reactive protein predicts poor prognosis in patients with locoregionally advanced nasopharyngeal carcinoma treated with chemoradiotherapy

Background

We aimed to evaluate the association of serum C-reactive protein (crp) with prognosis in patients with locoregionally advanced nasopharyngeal carcinoma treated with chemoradiotherapy.

Methods

We retrospectively reviewed 79 patients with locoregionally advanced nasopharyngeal carcinoma (cT3–4N0–3M0) treated with chemoradiotherapy. Chemoradiotherapy consisted of external-beam radiotherapy to the nasopharynx (70–80 Gy), the lymph node–positive area (60–70 Gy), and the lymph node–negative area (50–60 Gy) combined with 3 cycles of various platinum-based regimens delivered at 3-week intervals. Elevated crp was defined as more than 8 mg/L. The survival rate was calculated using the Kaplan–Meier method, and univariate and multivariate analyses (Cox proportional hazards model) were used to identify factors significantly associated with prognosis.

Results

During the median follow-up of 3.9 years (range: 1–5.5 years), 23 patients died from nasopharyngeal cancer. The 5-year cancer-specific survival (css) rate was 62.90%. Before chemoradiotherapy, 18 patients had high serum crp; the css rate in that subgroup was significantly worse than the rate in the remaining patients (p = 0.0002). Multivariate analysis showed that crp was an independent prognostic indicator of css, with a hazard ratio of 3.04 (95% confidence interval: 1.22 to 7.55; p = 0.017). Among the 18 patients with elevated serum crp, 9 achieved normal serum crp after chemoradiotherapy, of whom 5 remained living with no evidence of recurrence or metastasis during follow-up. By contrast, the remaining 9 patients in whom serum crp did not normalize after chemoradiotherapy died within 4.2 years.

Conclusions

Elevated serum crp before treatment predicts poor prognosis in patients with locoregionally advanced nasopharyngeal carcinoma treated with chemoradiotherapy.     

Overweight and obesity as poor prognostic factors in locally advanced breast cancer patients

Obesity and overweight are established risk factors for the development of breast cancer. They are also associated with poor prognosis for higher risk of disease recurrence and lower overall survival (OS). The aim of this study was to evaluate the influence of overweight and obesity in OS in patients with locally advanced breast cancer (LABC) treated with neoadjuvant chemotherapy. This is a retrospective analysis that included 819 patients diagnosed with LABC between January 2004 and December 2008. The patients were treated with neoadjuvant chemotherapy (NAT) based on anthracyclines, taxanes, or both, followed by surgery. For comparison, patients were divided into the normal weight (NW) group or the overweight/obesity (OW/OB) group. The prevalence of overweight/obesity was 74 %. General characteristics of the patients, including age, tumor size, clinical stage, nuclear grade, hormone receptors, and HER2 expression, were similar between both groups. At a median follow-up of 28 months, we found a statistically significant difference in OS between the two groups, achieving a 91.5 % in NW patients versus 85.9 % in the OW/OB group (P = 0.050). Cox multivariate analysis demonstrated that obesity was an independent factor for poor prognosis, with a hazard ratio of 1.79 (95 % CI (Confidence Interval) 1.09–2.96; P = 0.022). This is the first Mexican study that confirms the role of OW/OB as a risk factor for poor outcome among patients with LABC. Obesity in our country is a public health problem and requires strong preventive intervention strategies for its control, especially among patients diagnosed with breast cancer.     

局部晚期食管癌患者累及野照射联合化疗的疗效分析

目的分析局部晚期食管癌患者累及野照射联合化疗的失败模式及预后。方法回顾性分析2003-01-01-2009-01-01山东省肿瘤医院放疗科接受累及野放疗联合化疗的80例局部晚期食管癌患者,依据首次复发部位与治疗靶区,将失败模式分为照射野内复发、野外区域淋巴结复发和远处转移,并分析不同复发模式组的生存情况。结果治疗结束后80例患者治疗有效68例（85.00%）,达临床完全缓解（CR）19例（23.75%）,部分缓解（PR）49例（61.25%）。中位随访时间52.6个月（95%CI：46.1-56.7个月）,全组患者的中位生存时间（median survival time,MST）为14.4个月。共76例患者出现复发,其中野内复发43例（53.75%）,远处转移33例（41.25%）,野外区域淋巴结复发24例（30.00%）。有野内复发或远处转移的患者MST分别为14.2和13.2个月,均显著低于未出现者的17.4个月（P=0.01）和15.9个月（P〈0.001）,而出现野外区域淋巴结转移与未出现者MST均为14.5个月,差异无统计学意义,P=0.665。结论累及野放疗联合化疗治疗局部晚期食管癌,野内复发及远处转移为主要复发模式且影响生存,而野外区域淋巴结并未明显影响患者总生存期,其可行性有待多中心大样本前瞻性随机对照试验进一步证实。     

Prognostic role of EGFR gene copy number and KRAS mutation in patients with locally advanced rectal cancer treated with preoperative chemoradiotherapy

Background:

Epidermal growth factor receptor (EGFR), evaluated by immunohistochemistry, has been shown to have prognostic significance in patients with colorectal cancer. Gene copy number (GCN) of EGFR and KRAS status predict response and outcome in patients treated with anti-EGFR therapy, but their prognostic significance in colorectal cancer patients is still unclear.

Methods:

We have retrospectively reviewed the baseline EGFR GCN, KRAS status and clinical outcome of 146 locally advanced rectal cancer (LARC) patients treated with preoperative chemoradiotherapy. Pathological response evaluated by Dworak''s tumour regression grade (TRG), disease-free survival (DFS) and overall survival (OS) were analysed.

Results:

Tumour regression grade 4 and TRG3–4 were achieved in 14.4 and 30.8% of the patients respectively. Twenty-nine (19.9%) and 33 patients (19.2%) had an EGFR/nuclei ratio >2.9 and CEP7 polisomy >50% respectively; 28 patients (19.2%) had a KRAS mutation. Neither EGFR GCN nor KRAS status was statistically correlated to TRG. 5-year DFS and OS were 63.3 and 71.5%, respectively, and no significant relation with EGFR GCN or KRAS status was found.

Conclusion:

Our data show that EGFR GCN and KRAS status are not prognostic factors in LARC treated with preoperative chemoradiation.     

局部晚期不可手术食管癌同步放化疗联合尼妥珠单抗的初步临床分析

目的:探讨局部晚期食管癌同步放化疗联合尼妥珠单抗治疗的不良反应及疗效。方法:回顾性分析北京大学肿瘤医院2015—2020年间使用同步放化疗联合尼妥珠单抗治疗的30例患者资料,采用 Kaplan- Meier法生存分析。 结果:中位随访时间22.5个月,总客观有效率为93%。1、2、3年...