Deoxycitidine kinase is associated with prolonged survival after adjuvant gemcitabine for resected pancreatic adenocarcinoma

BACKGROUND:

Gemcitabine (2′,2′‐difluorodeoxycytidine) administration after resection of pancreatic cancer improves both disease‐free survival (DFS) and overall survival (OS). Deoxycytidine kinase (dCK) mediates the rate‐limiting catabolic step in the activation of gemcitabine. The authors of this report studied patient outcomes according to the expression of dCK after a postoperative gemcitabine‐based chemoradiation regimen.

METHODS:

Forty‐five patients with resected pancreatic adenocarcinoma received adjuvant gemcitabine based‐therapy in the context of multicenter phase 2 studies. Their tumors were evaluated retrospectively for dCK protein expression by immunohistochemistry. A composite score based on the percentage of dCK‐positive cancer cells and the intensity of staining was generated, and the results were dichotomized at the median values.

RESULTS:

The median follow‐up was 19.95 months (95% confident interval [CI], 3.3‐107.4 months). The lymph node (LN) ratio and dCK protein expression were significant predictors of DFS and OS in univariate analysis. On multivariate analysis, dCK protein expression was the only independent prognostic variable (DFS: hazard ratio [HR], 3.48; 95% CI, 1.66‐7.31; P = .001; OS: HR, 3.2; 95% CI,1.44‐7.13; P = .004).

CONCLUSIONS:

dCK protein expression was identified as an independent and strong prognostic factor in patients with resected pancreatic adenocarcinoma who received adjuvant gemcitabine therapy. The authors concluded that it deserves prospective evaluation as a predictive biomarker for patient selection. Cancer 2010. © 2010 American Cancer Society.     

Role of adjuvant chemotherapy on recurrence and survival in patients with resected ampulla of Vater carcinoma

BACKGROUND Owing to rarity of disease and lack of prospective studies, data supporting the role of adjuvant chemotherapy in ampulla of Vater(AoV) carcinoma is limited.AIM To evaluate whether adjuvant chemotherapy cases for AoV carcinoma had better disease-free survival(DFS) rates than cases of observation following curative surgery.METHODS We retrospectively analyzed the association between adjuvant chemotherapy and DFS and overall survival(OS) in patients with stage IB-Ⅲ AoV carcinoma who under...     

Improved survival in patients with breast rhabdoid tumors with multi-agent adjuvant chemotherapy combined with irradiation

Purpose  Malignant rhabdoid tumors (MRT) have poor prognoses. Breast MRT is extremely rare; only three cases have been documented, with a mean prognosis of 7 months. Multi-agent chemotherapy with mastectomy and irradiation, as used in this case, may extend survival in breast MRT. Patient and methods  A 68-year-old woman who underwent a standard mastectomy was diagnosed with breast MRT. Postoperatively she received six cycles of cyclophosphamide/methotrexate/5-fluorouracil followed by oral administration of doxifluridine and anastrozole, after which no metastasis was detected. About 8 months postoperative, magnetic resonance imaging revealed cervical bone metastasis, and local irradiation and nine doses of “basic chemotherapy” consisting of biweekly paclitaxel and anastrozole were administered. About 4 months later, multiple lung metastases were revealed, and four doses of “basic chemotherapy” with added pirarubicin hydrochloride were administered. Four months after that, multiple large liver metastases were discovered, and five doses of “basic chemotherapy” with added carboplatin were administered. Results  The 19-month survival period of our case was almost three times that of reported breast MRT patients. Conclusion  Multi-agent chemotherapy combined with irradiation may be associated with the relatively long survival of the present case.     

Outcome of adjuvant mifurol chemotherapy in patients with resected colonic carcinoma

The effectiveness of Mifurol as an adjuvant chemotherapy in colonic cancer patients has been assessed on the basis of long-term survival at various institutions. In the curative resection cases, the outcome of administrations of MMC (0.2 mg/kg x 2) + Mifurol (6-12 mg/kg/day) (group A and MMC (0.2 mg/kg x 2)+ Tegafur (12 mg/kg/day) (group B) was compared. There was no difference in the background factors or in the total amount of the alpha rugs administrated in these two groups. The five-year survival by Kaplan-Meirer's method were 56.1% and 36.1% for group A and B, respectively, the difference being particularly remarkable in Dukes C cases.     

Effect of primary treatment on survival in anaplastic thyroid carcinoma.

AIMS: Anaplastic thyroid carcinoma (ATC) is a fatal disease despite combined treatment consisting of chemotherapy, radiotherapy and surgery. The optimal sequence of treatment modalities is not known. The purpose of our retrospective non-randomized study was to find out whether timing of the treatment modality had any influence on survival, and to find out if primary surgery prolongs survival in comparison to primary chemotherapy and/or radiotherapy. METHODS: From our database of 162 patients with ATC treated at the Institute of Oncology Ljubljana from 1972-98, 79 patients (26 men, 53 women; age: 40-86 years, mean age 65 years) were included in this retrospective study. The 83 patients with distant metastases on admission, with the survival shorter than one month or patients without any treatment were excluded. The 79 patients were classified into (1) primary surgery group (n=26) and (2) primary chemotherapy and/or radiotherapy group (n=53), including the 12 patients in whom surgery was performed after chemotherapy and/or radiotherapy. The survival of both groups was compared by log-rank test and group characteristics by ANOVA and(2 test using SPSS program. RESULTS: In comparison to the primary surgery group, the patients from the primary chemotherapy and/or radiotherapy group were older and had faster growing, and larger tumours, which were not confined to the thyroid, and more frequently had regional metastases. There was no difference in the survival of the two groups (P=0.17). Survival for longer than one year was observed in 25% of patients with primary surgery and in 21% of patients with primary chemotherapy and/or radiotherapy. The best results (50% survival at one year) were obtained in patients in whom the tumour was surgically removed after primary chemotherapy and radiotherapy. CONCLUSION: This study suggests that the timing of the treatment modalities has an impact on survival and that treatment should start with chemotherapy and/or radiotherapy, with surgery to follow if possible.) Copyright Harcourt Publishers Limited.     

Increased VEGFR-2 gene copy is associated with chemoresistance and shorter survival in patients with non-small-cell lung carcinoma who receive adjuvant chemotherapy

VEGF receptor-2 (VEGFR-2 or kinase insert domain receptor; KDR) is a known endothelial target also expressed in NSCLC tumor cells. We investigated the association between alterations in the KDR gene and clinical outcome in patients with resected non-small-cell lung carcinoma (NSCLC; n = 248). KDR copy number gains (CNG), measured by quantitative PCR and fluorescence in situ hybridization, were detected in 32% of tumors and associated with significantly higher KDR protein and higher microvessel density than tumors without CNGs. KDR CNGs were also associated with significantly increased risk of death (HR = 5.16; P = 0.003) in patients receiving adjuvant platinum-based chemotherapy, but no differences were observed in patients not receiving adjuvant therapy. To investigate potential mechanisms for these associations, we assessed NSCLC cell lines and found that KDR CNGs were significantly associated with in vitro resistance to platinum chemotherapy as well as increased levels of nuclear hypoxia inducible factor-1α (HIF-1α) in both NSCLC tumor specimens and cell lines. Furthermore, KDR knockdown experiments using small interfering RNA reduced platinum resistance, cell migration, and HIF-1α levels in cells bearing KDR CNGs, providing evidence for direct involvement of KDR. No KDR mutations were detected in exons 7, 11, and 21 by PCR-based sequencing; however, two variant single nucleotide polymorphism genotypes were associated with favorable overall survival in adenocarcinoma patients. Our findings suggest that tumor cell KDR CNGs may promote a more malignant phenotype including increased chemoresistance, angiogenesis, and HIF-1α levels, and that KDR CNGs may be a useful biomarker for identifying patients at high risk for recurrence after adjuvant therapy, a group that may benefit from VEGFR-2 blockade.     

Sarcopenia is associated with survival in patients with urothelial carcinoma treated with systemic chemotherapy

International Journal of Clinical Oncology - Sarcopenia impacts perioperative outcomes and prognosis in various carcinomas. We aimed to investigate whether sarcopenia at the time of chemotherapy...     

西妥昔单抗联合化疗延长晚期非小细胞肺癌患者生存期

2008年6月,在美国临床肿瘤学会(ASCO)年会上公布的FLEX研究最新结果显示,西妥昔单抗联合以铂类为基础的化疗方案,可以显著提高晚期非小细胞肺癌(NSCLC)患者的总生存期,并适用于所有组织学亚型的NSCLC.西妥昔单抗成为首个被证实能够显著延长所有组织学类型NSCLC患者生存期的靶向治疗药物.     

Failure to complete adjuvant chemotherapy is associated with adverse survival in stage III colon cancer patients

Two recent North American studies have shown that completion of 5-fluorouracil (5FU)-based adjuvant chemotherapy is a major prognostic factor for the survival of elderly stage III colon cancer patients. The aim of the present study was to confirm this finding in a population-based series from Australia. The study cohort comprised 851 stage III colon cancer patients treated by surgery alone and 461 who initiated the Mayo chemotherapy regime. One-third of patients who initiated chemotherapy failed to complete more than three cycles of treatment. Independent predictors for failure to complete were treatment in district or rural hospitals, low socioeconomic index and treatment by a low-volume surgeon. Patients who failed to complete chemotherapy showed worse cancer-specific survival compared not only to those who completed treatment (HR=2.24; 95% confidence interval (CI) (1.66-3.03), P<0.001) but also to those treated by surgery alone (HR=1.37; 95% CI (1.09-1.72), P=0.008). The current and previous studies demonstrate the importance of completing adjuvant 5-FU-based chemotherapy for colon cancer. Further prospective studies are required to identify better the physiological and socioeconomic factors responsible for failure to complete chemotherapy so that appropriate improvements in health service delivery can be made.     

Calpain-1 expression is associated with relapse-free survival in breast cancer patients treated with trastuzumab following adjuvant chemotherapy

The calpain family, and their endogenous inhibitor calpastatin, has been implicated in cancer progression, and recent in vitro data have indicated a role in trastuzumab resistance. The aims of our study were to examine expression levels of calpastatin, calpain-1 and calpain-2 in breast tumours from patients treated with trastuzumab following adjuvant chemotherapy to determine their potential as biomarkers to predict therapeutic response. The expression of calpastatin, calpain-1 and calpain-2 was determined, using immunohistochemistry (IHC), in tumours from a series of 93 patients with primary breast cancer treated with surgery and adjuvant chemotherapy with or without trastuzumab followed by trastuzumab to complete 1 year of therapy. IHC was performed using tissue microarrays constructed from cores taken from intratumour and peripheral tumour areas. Expression was correlated with clinicopathologic variables and patient outcome. Calpastatin expression was correlated with Nottingham prognostic index (p = 0.003) and lymph node status (p = 0.007). Trastuzumab resistance was defined as disease relapse during therapy. Calpain-1 expression is associated with relapse-free survival (p = 0.001) and remained significant in multivariate analysis accounting for confounding pathological and treatment variables (hazard ratio 4.60, 95% confidence interval 1.05-20.25; p = 0.043). Calpain-1 may be a useful biomarker to predict relapse-free survival in breast cancer patients treated with adjuvant trastuzumab and chemotherapy. A larger verification study is warranted.     

The addition of chemoradiation to adjuvant chemotherapy is associated with improved survival in lymph node-positive gastric cancer

BackgroundIn the ARTIST trial, chemoradiation did not improve disease-free survival (DFS) in gastric cancer patients treated with curative-intent surgery and adjuvant chemotherapy. Subgroup analysis suggested chemoradiation improved DFS in patients with lymph node (LN) metastases, but the role of adjuvant chemoradiation remains uncertain. This study sought to determine the role of adjuvant chemoradiation using population-based methods.MethodsSurveillance, Epidemiology and End Results-Medicare linked data from 2004 to 2013 was used to identify patients aged 66 and older with LN-positive gastric adenocarcinoma. Multivariable logistic regression evaluated factors associated with receipt of chemoradiation. The Kaplan-Meier method and Cox proportional hazards modeling were used to evaluate overall survival (OS).ResultsA total of 2409 patients with LN-positive gastric adenocarcinoma who underwent upfront surgical resection were identified; 309 (13%) received adjuvant chemotherapy and 407 (17%) received adjuvant chemotherapy and chemoradiation. Among all patients, median OS was 15 months. Median OS was 20 months for patients who received chemotherapy alone and 27 months for patients who received chemotherapy and chemoradiation (p < 0.05). Recent diagnosis, older age, tumor stage T3 or T4, and Charleston Comorbidity Index were associated with an increased hazard ratio for death (p < 0.05). Receipt of chemoradiation was associated with a decreased hazard ratio for death (p < 0.05).ConclusionsIn patients with LN-positive gastric adenocarcinoma, the addition of chemoradiation to adjuvant chemotherapy after upfront surgical resection was associated with improved survival irrespective of the extent of lymphadenectomy. These data suggest chemoradiation should be considered in patients with LN-positive gastric adenocarcinoma.     

Topoisomerase I but not thymidylate synthase is associated with improved outcome in patients with resected colorectal cancer treated with irinotecan containing adjuvant chemotherapy

Background  

Thymidylate synthase (TS) and Topoisomerase I (Topo I) are significant biomarkers in colorectal cancer (CRC). We aimed to study the expression of TS and Topo I in patients with resected CRC who received adjuvant chemotherapy and correlated it with clinical outcome.     

Combined treatment of anaplastic thyroid carcinoma with surgery, chemotherapy, and hyperfractionated accelerated external radiotherapy

PURPOSE: To analyze a prospective protocol combining surgery, chemotherapy (CT), and hyperfractionated accelerated radiotherapy (RT) in anaplastic thyroid carcinoma. METHODS AND MATERIALS: Thirty anaplastic thyroid carcinoma patients (mean age, 59 years) were treated during 1990-2000. Tumor extended beyond the capsule gland in 26 patients, with tracheal extension in 8. Lymph node metastases were present in 18 patients and lung metastases in 6. Surgery was performed before RT-CT in 20 patients and afterwards in 4. Two cycles of doxorubicin (60 mg/m(2)) and cisplatin (120 mg/m(2)) were delivered before RT and four cycles after RT. RT consisted of two daily fractions of 1.25 Gy, 5 days per week to a total dose of 40 Gy to the cervical lymph node areas and the superior mediastinum. RESULTS: Acute toxicity (World Health Organization criteria) was Grade 3 or 4 pharyngoesophagitis in 10 patients; Grade 4 neutropenia in 21, with infection in 13; and Grade 3 or 4 anemia and thrombopenia in 8 and 4, respectively. At the end of the treatment, a complete local response was observed in 19 patients. With a median follow-up of 45 months (range, 12-78 months), 7 patients were alive in complete remission, of whom 6 had initially received a complete tumor resection. Overall survival rate at 3 years was 27% (95% confidence interval 10-44%) and median survival 10 months. In multivariate analysis, tracheal extension and macroscopic complete tumor resection were significant factors in overall survival. Death was related to local progression in 5% of patients, to distant metastases in 68%, and to both in 27%. CONCLUSIONS: Main toxicity was hematologic. High long-term survival was obtained when RT-CT was given after complete surgery. This protocol avoided local tumor progression, and death was mainly caused by distant metastases.     

同期放化疗联合辅助化疗治疗局部晚期鼻咽癌的前瞻性临床研究

 目的　探讨同期放化疗联合辅助化疗对鼻咽癌高发区人群的疗效及不良反应情况。方法　2006年1月至2010年6月入组141例鼻咽癌患者,随机数字表法分为同期放化疗联合辅助化疗组（70例）和同期放化疗组（71例）。两组均采用二维精确放射治疗和2个疗程顺铂、5-氟尿嘧啶（5-Fu）同步化疗;同期放化疗联合辅助化疗组在放疗结束后3周开始3个疗程顺铂、5-Fu辅助化疗。结果　所有入组患者均按计划完成同期放化疗,同期放化疗联合辅助化疗组有63例完成辅助化疗。两组同步放化疗期和同期放化疗联合辅助化疗组辅助化疗期主要不良反应有黏膜炎、白细胞减少、血小板减少和胃肠道反应,两组比较差异无统计学意义。放疗结束后3个月,同期放化疗联合辅助化疗组和同期放化疗组鼻咽部、颈部淋巴结肿瘤消退率分别为94.4 %（67／70）和87.3 %（62／71）。中位随访36个月。同期放化疗联合辅助化疗组1、2、3年总生存率分别为94.3 %、84.8 %、78.6 %,中位生存期为36个月,同期放化疗组分别为90.1 %、75.0 %、62.5 %,中位生存期为27个月,两组比较差异有统计学意义（χ2＝7.356 ,P＝0.007）。同期放化疗联合辅助化疗组Ⅲ期患者1、2、3年总生存率分别为98.2 %、92.5 %、83.7 %,同期放化疗组分别为93.0 %、83.2 %、68.2 %,中位生存时间均为36个月;两组比较差异有统计学意义（χ2＝8.081, P＝0.005）。同期放化疗联合辅助化疗组Ⅳ期患者1、2、3年总生存率分别为81.3 %、53.8 %、42.9 %,同期放化疗组分别为78.6 %、36.4 %、22.3 %,中位生存时间分别为22个月和14个月,两组比较差异有统计学意义（χ2＝3.903,P＝0.048）。同期放化疗联合辅助化疗组1、2、3年无进展生存率分别为90.0 %、76.2 %、68.8 %,同期放化疗组分别为81.7 %、60.3 %、34.3 %,中位无进展生存时间分别为30个月和22个月,两组比较差异有统计学意义（χ2＝13.616,P＝0.000）。结论　对鼻咽癌高发区Ⅲ、Ⅳ期鼻咽癌患者,该同期放化疗联合辅助化疗方案依从性较高,不良反应相对较低,可提高总生存率及无进展生存率。