Clinical impact of radiotherapy for locally advanced pancreatic cancer

Background

Although a randomized controlled trial for locally advanced pancreatic cancer (PC) has demonstrated a survival advantage for treatment with gemcitabine alone, chemoradiotherapy remains the treatment of choice for locally advanced disease in Japan. The aim of this study was to compare the survival benefits associated with gemcitabine and concurrent chemoradiotherapy in locally advanced unresectable PC.

Patients

Seventy-seven patients with locally advanced unresectable PC were retrospectively enrolled from April 2001 to December 2006. All cases were histologically proven, and patients received gemcitabine chemotherapy (n = 30) or concurrent chemoradiotherapy (based on 5-fluorouracil, n = 28, or gemcitabine, n = 19, as a radiosensitizer) at Aichi Cancer Center Hospital.

Results

Patients who received chemoradiotherapy had significantly better performance status than those who had chemotherapy. Tumor response was 0% for chemotherapy and 13% chemoradiotherapy, but survival benefit was similar among patients in the chemotherapy group (overall response (OS) 12 months; progression-free survival (PFS), 3 months) and those in the chemoradiotherapy group (OS, 13 months; PFS, 5 months). Two-year survival was 21% for chemotherapy patients and 19% for chemoradiotherapy patients. Severe toxicities (Grade 3–4 National Cancer Institute-Common Toxicity Criteria, version 3.0) were significantly more frequent for chemoradiotherapy than for chemotherapy.

Conclusions

Gemcitabine chemotherapy showed similar survival benefit compared to 5-fluorouracil- and gemcitabine-based chemoradiotherapy.     

Experience with combination of cetuximab plus intensity-modulated radiotherapy with or without chemotherapy for locoregionally advanced nasopharyngeal carcinoma

Purpose

To evaluate the safety and efficacy of cetuximab plus intensity-modulated radiotherapy (IMRT) with or without chemotherapy for locoregionally advanced nasopharyngeal carcinoma (NPC).

Methods

From June 2007 to December 2010, 33 patients with stage II (12 %), III (33 %), IVA (33 %), and IVB (21 %) NPC were treated at our hospital. Cetuximab was administered at an initial dose of 400 mg/m² followed by weekly doses of 250 mg/m². All patients completed IMRT, and a total dose of 66–70.4, 66, 60, and 54 Gy were given to the gross tumor volume, positive neck nodes, high-risk clinical target volume, and low-risk clinical target volume, respectively. Most patients (90.9 %) received platinum-based neoadjuvant, concurrent, or adjuvant chemotherapy. The efficacy and safety were evaluated retrospectively.

Results

With a median follow-up of 40.0 months, the 3-year progression-free survival (PFS), distant metastasis-free survival, and overall survival were 70.5 % (95 % CI 54.0–87.0 %), 83.6 % (95 % CI 70.3–96.9 %), and 90.9 % (95 % CI 81.1–100.0 %), respectively. Majority (75.8 %) of patients received ≥7 cycles of cetuximab (median 7 cycles, range 2–14 cycles). Patients who received ≥7 cycles of cetuximab showed a better 3-year PFS than those receiving <7 cycles (79.1 vs. 31.2 %, p = 0.050). During cetuximab + IMRT, stomatitis was the most common acute treatment toxicity, 23 (69.7 %) and 5 (15.2 %) patients with grade 3 and grade 4 stomatitis, respectively. Temporal lobe necrosis was observed in 7 patients.

Conclusions

Cetuximab plus IMRT with or without chemotherapy for locoregionally advanced NPC is effective and tolerated. Further investigations are warranted.     

Adjuvant therapy in stage II thymic carcinoma

Purpose

The aim of this study is to investigate the impact of chemotherapy and/or radiotherapy on disease-free survival and overall survival for patients with stage II thymic carcinoma.

Methods

We retrospectively evaluated the outcome of 31 patients with Masaoka stage II thymic carcinoma who were treated between 1995 and 2009 in Zhejiang Cancer Hospital. Survival curves were plotted using the Kaplan–Meier method. The Cox proportional hazard model was used for multivariate analysis.

Results

Thirty-one patients were included in current study. The most common histological subtypes were squamous cell carcinoma (48.4 %), followed by undifferentiated carcinoma (19.4 %) and neuroendocrine tumor (19.4 %).The 5-year disease-free survival and overall survival rate was 74.6 and 89.5 %, respectively. Univariate and multivariate analysis revealed that radiotherapy and/or chemotherapy did not statistically associated with disease-free survival and overall survival.

Conclusion

Our result indicated that adjuvant therapy after complete resection could not impact the disease-free survival and overall survival of patients with stage II thymic carcinoma.     

Adjuvant and salvage radiotherapy after prostatectomy: outcome analysis of 307 patients with prostate cancer

Aim

In men with adverse pathology after radical prostatectomy, the most appropriate timing to administer radiotherapy (RT) remains a topic of debate. We analyzed in terms of efficacy, prognostic factors and toxicity the two therapeutic strategies: immediate postoperative radiotherapy (PORT) and salvage radiotherapy (SART).

Materials and methods

Between January 1995 and November 2010, 307 patients underwent adjuvant or salvage radiotherapy, after prostatectomy.

Results

In the PORT group, 42 patients (20.7 %) had biochemical failure, with a median time to biochemical failure of 1.8 years; two parameters (age at diagnosis and PSA pre-RT) resulted to be significant at the survival analysis for overall survival (p = 0.003 and p = 0.046, respectively). In the SART group, 33 patients (31.7 %) had biochemical relapse; sixteen patients died of prostate cancer; postoperative hormones therapy, conformal radiotherapy and level of PSA pre-RT >1.0 ng/ml resulted to be significant at the survival analysis, p = 0.009, p = 0.039 and p = 0.002, respectively.

Conclusion

Our study is limited by its retrospective and nonrandomized design. As such, decisions to treat with adjuvant or salvage radiotherapy and the time to initiate therapy were based on patient preference and physician counseling. Our recommendation is to suggest adjuvant radiotherapy for all patients with adverse prognostic factors and to reserve salvage radiotherapy for low-risk patients, when the biochemical recurrence occurs.     

Progression-free survival and post-progression survival in patients with advanced gastric cancer treated with first-line chemotherapy

Purpose

The impact of post-progression survival (PPS) on the overall survival (OS) of patients with advanced gastric cancer (AGC) has not yet been reported in detail. We analyzed prospectively collected data from AGC patients who received first-line chemotherapy including fluoropyrimidine plus platinum.

Methods

We partitioned OS into progression-free survival (PFS) and PPS in each patient and analyzed correlations between OS and either PFS or PPS using the Spearman rank correlation coefficient (ρ).

Results

A total of 291 AGC patients met the inclusion criteria with median PFS, PPS, and OS of 5.3, 8.1, and 14.8 months, respectively. PFS and OS for each patient showed a correlation of ρ = 0.75 [95 % confidence interval (CI) 0.69–0.81]. PPS and OS showed a correlation of ρ = 0.87 (95 % CI 0.84–0.91). According to multivariate analysis, performance status at progression, PFS of first-line chemotherapy, and use of second-line chemotherapy were independently associated with PPS.

Conclusions

These results indicate that both PFS and PPS are correlated with OS in first-line chemotherapy for AGC, suggesting the importance of reporting detailed patient characteristics and treatment course after disease progression in clinical trials of first-line chemotherapy for AGC.     

Combination of Radiofrequency Ablation with Transarterial Chemoembolization for Hepatocellular Carcinoma: A Meta-Analysis

Background

Recent studies suggest that the combination of radiofrequency ablation (RFA) and transarterial chemoembolization (TACE) may have a synergistic effect for hepatocellular carcinoma (HCC).

Aims

The aim of this meta-analysis was to compare the effectiveness of combination of RFA and TACE with that of RFA alone in patients with HCC.

Methods

Randomized controlled trials and retrospective cohort studies comparing RFA plus TACE with RFA alone for HCC were included into this meta-analysis. Study quality was rated with a standardized scale and the strength of evidence was also rated by using the grading of recommendations assessment, development, and evaluation system (GRADE system).

Results

Meta-analyses showed that the combination of RFA and TACE was obviously associated with higher survival rates (odds ratio [OR]_1-year = 2.14, 95 % confidence interval [95 % CI] 1.57–2.91, P < 0.001; OR_3-year = 1.98, 95 % CI 1.28–3.07, P = 0.001; OR_5-year = 2.70, 95 % CI 1.42–5.14, P = 0.003). The overall quality of evidence was judged to be low by using the GRADE system.

Conclusions

The combination of TACE with RFA can improve the overall survival rate and provides better prognosis for patients with HCC, but more randomized controlled trials using large sample size are needed to provide sufficient evidence.     

Combination of Radiofrequency Ablation with Transarterial Chemoembolization for Hepatocellular Carcinoma: A Meta-Analysis

Background

Recent studies suggest that the combination of radiofrequency ablation (RFA) and transarterial chemoembolization (TACE) may have a synergistic effect for hepatocellular carcinoma (HCC).

Aims

The aim of this meta-analysis was to compare the effectiveness of combination of RFA and TACE with that of RFA alone in patients with HCC.

Methods

Randomized controlled trials and retrospective cohort studies comparing RFA plus TACE with RFA alone for HCC were included into this meta-analysis. Study quality was rated with a standardized scale and the strength of evidence was also rated by using the Grading of Recommendations Assessment, Development, and Evaluation system (GRADE system).

Results

Meta-analyses showed that the combination of RFA and TACE was obviously associated with higher survival rates (OR_1-year = 2.06, 95 % CI 1.46–2.91, P < 0.001; OR_3-year = 1.93, 95 % CI 1.18–3.15, P = 0.009; OR_5-year = 1.87, 95 % CI 1.23–2.83, P = 0.003). The overall quality of the evidence was judged to be low by using the GRADE system.

Conclusions

The combination of TACE with RFA can improve the overall survival rate and provides better prognosis for patients with HCC, but more randomized controlled trials using large sample sizes are needed to provide sufficient evidence.     

Is there a role for adjuvant chemotherapy in pathological complete response rectal cancer tumors following neoadjuvant chemoradiotherapy?

Purpose

To investigate the contribution of neoadjuvant chemotherapy in rectal cancer patients with pathological complete response (pCR).

Methods

Data were collected on all consecutive locally advanced rectal cancer patients treated with neoadjuvant chemotherapy and later resected in our institution between 2001 and 2013. Surgery was performed by a single proctology team, and tumor specimens were evaluated by the hospital pathologists.

Results

The medical records of 260 patients were analyzed, and 54 patients of those patients were found to have achieved pCR (20.8 %). Two of those patients were lost to follow-up. Thirty-five of the 54 pCR patients received adjuvant chemotherapy (Group A) and 17 did not (Group B). With the sole exception of the Group A patients being younger than the Group B patients (60.9 ± 11.9 vs. 68.7 ± 10.8 years, respectively, p = 0.0272), all other evaluated parameters were identical between the two groups. There was no advantage for the administration of adjuvant chemotherapy for disease-free survival (DFS) and overall survival (OS).

Conclusions

Adjuvant chemotherapy played no part in disease-free survival and OS of patients with rectal cancer who had been treated with neoadjuvant chemotherapy and achieved pCR. Our findings indicate a tendency for adjuvant chemotherapy to be administered to younger rectal cancer patients. A randomized trial should be conducted to resolve the question of whether they derive any benefit from it.     

Prognostic value of ERCC1 in head and neck carcinoma treated with definitive or adjuvant radiotherapy

Purpose

To evaluate the prognostic significance of excision repair cross-complementation group 1 (ERCC1) expression in head and neck carcinoma patients treated with definitive radiotherapy (DR) or adjuvant radiotherapy (AR).

Methods

ERCC1 expression was assessed by immunohistochemical staining. A total of 48 patients were assessed.

Results

High ERCC1 expression was found in 23 patients (48 %). More ERCC1-positive tumours were detected in patients treated with DR than in patients treated with AR (73 vs. 36 %, respectively, p = 0.03). ERCC1 expression had no impact on overall survival neither in the whole cohort of patients (p = 0.16) nor in each particular treatment group (AR p = 0.98; DR p = 0.21).

Conclusions

ERCC1 expression had no predictive value in head and neck carcinoma patients treated with DR or AR. There might be difference in ERCC1 positivity that comes out of whether the assessment is done on biopsy or surgical specimens.     

Prognostic significance of several biomarkers in epithelial ovarian cancer: a meta-analysis of published studies

Objective

Abnormal expression of several biomarkers might predict disease prognosis and response to chemotherapy in patients with epithelial ovarian cancer (EOC). However, the published data are inconsistent.

Methods

Eligible studies that investigated the association between survival or response to platinum-based chemotherapy in EOC and the expression status of Bcl-2, EGFR, GST, LRP, p16, p21, P-gp and TNF-α were identified by an electronic search of PubMed and Embase. The measures of interest were hazard ratio (HR) for survival or risk ratio for chemotherapy response. A meta-analysis was performed using the fixed-effect or random-effect models.

Results

The number of eligible studies analyzed was 27 for Bcl-2, 22 for EGFR, 29 for GST, 12 for LRP, 16 for p16, 22 for p21, 27 for P-gp and three for TNF-α. A meta-analysis showed that high EGFR and P-gp expression was associated with poor overall survival (OS) (pooled adjusted HR = 1.826 and HR = 1.822). Only high GST expression was associated with improved OS (HR = 0.780). Furthermore, high p16 and P-gp expression was associated with poor progression-free survival (PFS) (HR = 1.550 and HR = 2.136). High GST expression was associated with improved PFS (HR = 0.689). Among these factors, only LRP, P-gp and TNF-α were associated with response to platinum-based chemotherapy.

Conclusions

The markers we analyzed are unlikely to be useful as predictors of prognosis and response to platinum-based chemotherapy in EOC patients in clinical practice.     

Effect of prior chemotherapy regimens on the efficacy of endocrine therapy within a German cohort of the TEAM trial

Purpose

Prior chemotherapy may affect the efficacy of endocrine therapy.

Methods

The tamoxifen exemestane adjuvant multinational (TEAM) trial compared 5 years of adjuvant exemestane with the sequence of tamoxifen followed by exemestane in postmenopausal women with hormone-receptor-positive breast cancer. A total of 1,502 patients were enrolled in Germany (739 received tamoxifen followed by exemestan and 610 exemestan alone). A retrospective analysis of the German cohort of TEAM was conducted to determine whether prior chemotherapy affected clinical outcome of endocrine therapy.

Results

Overall survival, disease-free survival and distant recurrence were similar between patients who received sequential therapy and those who received exemestane monotherapy, irrespective of prior chemotherapy. Overall survival was not significantly different between patients who had received prior chemotherapy and those who had not (P = 0.2836). Disease-free survival and distant recurrence were significantly better in patients who had not received prior chemotherapy versus those who had (P = 0.0308 and P = 0.0001). In patients receiving sequential therapy, there were no significant differences in overall survival according to prior chemotherapy use (P = 0.1812). However, disease-free survival and distant recurrence were significantly different dependent on prior chemotherapy (P = 0.0143 and P = 0.0053).

Conclusion

In conclusion, there was no difference in overall survival between breast cancer patients who did receive prior chemotherapy before endocrine therapy and those who had not. Patients who had not received prior chemotherapy had significantly improved disease-free survival and less distant recurrence versus those who had received chemotherapy.     

Addition of docetaxel to S-1 without platinum prolongs survival of patients with advanced gastric cancer: a randomized study (START)

Purpose

Cisplatin plus 5-fluorouracil has been globally accepted as a standard regimen for the treatment for advanced gastric cancer. However, cisplatin has several disadvantages, including renal toxicity and the need for admission. S-1 plus cisplatin has become a standard treatment for advanced gastric cancer in East Asia. This phase III study was designed to evaluate the potential benefits of adding docetaxel to S-1 without a platinum compound in patients with advanced gastric cancer.

Methods

Patients were randomly assigned to receive docetaxel plus S-1 or S-1 alone. The docetaxel plus S-1 group received docetaxel on day 1 and oral S-1 on days 1–14 of a 21-day cycle. The S-1 alone group received oral S-1 on days 1–28 of a 42-day cycle. The primary end point was overall survival.

Results

Of the 639 patients enrolled, 635 were eligible for analysis. The median overall survival was 12.5 months in the docetaxel plus S-1 group and 10.8 months in the S-1 alone group (p = 0.032). The median progression-free survival was 5.3 months in the docetaxel plus S-1 group and 4.2 months in the S-1 alone group (p = 0.001). As for adverse events, neutropenia was more frequent in the docetaxel plus S-1 group, but remained manageable.

Conclusion

As first-line treatment for advanced gastric cancer, docetaxel plus S-1 significantly improves median overall and progression-free survival as compared with S-1 alone. (ClinicalTrials.gov number: NCT00287768).     

Feasibility and short-term outcome of adjuvant FOLFOX after resection of colorectal liver metastases

Background

The role of adjuvant chemotherapy for stage IV colorectal cancer has so far been under-investigated. The aim of this study was to assess the feasibility and short-term outcome of adjuvant chemotherapy with the FOLFOX regimen following liver resection for patients with colorectal liver metastasis (CRLM).

Methods

From May 2005 to September 2010, 86 patients with CRLM underwent hepatic resection in the Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University. Of these patients, 24 received FOLFOX4 or modified FOLFOX6 as postoperative adjuvant chemotherapy.

Results

Nineteen male and 5 female patients received adjuvant chemotherapy following liver resection. Twenty-one (87.5 %) of these patients completed 6 cycles of adjuvant chemotherapy. Five patients required a dose reduction due to neutropenia, and the dose intensities of oxaliplatin and 5-FU were 93.6 and 94.1 %, respectively. There were no severe adverse events from the treatments. The median follow-up period was 48.4 months. Recurrences developed in 12 patients, and 3 patients died during the follow-up period. The 3- and 5-year disease-free survival and overall survival were 51.6 and 45.1 % and 95.5 and 76.0 %, respectively.

Conclusions

Adjuvant FOLFOX is feasible and might provide a good prognosis for CRLM patients who undergo liver resection.     

A phase II study of nedaplatin and 5-fluorouracil in metastatic squamous cell carcinoma of the esophagus: The Japan Clinical Oncology Group (JCOG) Trial (JCOG 9905-DI)

Background

This phase II study evaluated the efficacy and toxicity of combination chemotherapy with nedaplatin and 5-fluorouracil (5-FU) for metastatic esophageal squamous cell carcinoma.

Methods

Eligibility criteria included squamous cell carcinoma with organ metastasis, ECOG performance status (PS) 0–2, ≤ 75 years, measurable disease, and adequate organ function. Chemotherapy consisted of 5-FU (800 mg/m²/day) on days 1–5 and a 2-h infusion of nedaplatin (90 mg/m²) on day 1, repeated every 4 weeks. Therapy was continued until disease progression or intolerable adverse events. The primary end point was response rate. Secondary end points included overall survival, progression-free survival, and toxicities.

Results

Forty-two patients (39 men, 3 women; median age 59 years; range 44–70 years) were enrolled. Twenty-one, 21, and 0 patients had PS 0, 1, and 2, respectively. 23, 6, 3, and 18 patients had a history of surgical resection, radiotherapy, adjuvant chemotherapy, and no therapy, respectively. Among the 38 eligible patients, 1 and 14 complete and partial responses were observed, respectively; the overall response rate was 39.5 % (90 % confidence interval: 26.1–54.1 %). The median survival time was 8.8 months. The one-year survival rate was 32.9 %. Grade 4 neutropenia and thrombocytopenia were observed in 7 and 2 % of 41 patients, respectively. Grade 3 nausea, diarrhea, and stomatitis were observed in 12, 2, and 2 %, respectively.

Conclusion

Combination therapy with nedaplatin and 5-FU is highly active and well tolerated in metastatic or recurrent esophageal squamous cell cancer and is therefore a chemotherapy option for esophageal squamous cell carcinoma.     

Effect of bevacizumab in older patients with metastatic colorectal cancer: pooled analysis of four randomized studies

Background

Bevacizumab is frequently combined with 5-fluorouracil-based chemotherapy for patients with metastatic colorectal cancer (mCRC). The relative benefit of bevacizumab in older patients has not been widely studied and is of interest.

Patients and methods

This retrospective analysis used data from three first-line randomized controlled studies and one second-line randomized controlled study of bevacizumab plus chemotherapy in medically fit (Eastern Cooperative Oncology Group performance status 0 or 1) patients with mCRC. Overall survival (OS) and on-treatment progression-free survival (PFS) were assessed in patients aged <65, ≥65, and ≥70 years. Results were compared using unstratified hazard ratios (HRs). Grade 3–5 adverse events were also assessed.

Results

Bevacizumab statistically significantly improved PFS [HR 0.58; 95% confidence interval (CI) 0.49–0.68] and OS (HR 0.85; 95% CI 0.74–0.97) in patients aged ≥65 years; patients aged ≥70 years had similar improvements. Benefits were consistent across the studies, irrespective of setting, bevacizumab dose, or chemotherapy regimen. Increases in thromboembolic events were observed in patients aged ≥65 and ≥70 years in the bevacizumab group compared with the control group, mainly as a result of increases in arterial thromboembolic events. No other substantial age-related increases in grade 3–5 adverse events were observed.

Conclusions

In medically fit older patients, bevacizumab provides similar PFS and OS benefits as in younger patients.     

Definitive chemoradiotherapy with capecitabine and cisplatin for elder patients with locally advanced squamous cell esophageal cancer

Purpose

The aim of this retrospective study is to evaluate the feasibility and efficacy of concurrent chemoradiotherapy (CCRT) or sequential chemoradiotherapy (SCRT) with capecitabine and cisplatin for elderly patients with locally advanced esophageal squamous cell carcinoma (ESCC).

Methods

A total of 75 patients elder than 65 years with histologically proven stage II–III ESCC were enrolled, in whom 40 patients were treated with CCRT consisted of two cycles of intravenous cisplatin and oral capecitabine during and after radiotherapy and 35 patients were treated with SCRT as two cycles of capecitabine plus cisplatin before and after radiotherapy. Response rate, overall survival, progression-free survival and toxicity were compared.

Results

The overall response rate (CR + PR) in the CCRT group (91.6 %) was significantly higher than that in the SCRT group (67.7 %), P = 0.023. The median PFS and median OS were significantly higher in CCRT group (19.7 and 33.6 months) than those in SCRT group (11.6 and 15.7 months), P < 0.05. The acute toxic effect was more severe in the CCRT group than in the SCRT group, but the grade 3–4 acute toxicities were similar in two groups.

Conclusions

It suggested that both CCRT and SCRT with capecitabine and cisplatin are tolerable and effective for elderly patients with locally advanced ESCC. Concurrent CRT might be superior to SCRT.     

Prognostic value of tumor volume for patients with nasopharyngeal carcinoma treated with concurrent chemotherapy and intensity-modulated radiotherapy

Purpose

We aimed to analyze prognostic factors in patients with nasopharyngeal carcinoma (NPC) treated with concurrent chemotherapy and intensity-modulated radiotherapy (IMRT); in addition, we aimed to elucidate the value of primary gross tumor volume (GTVp) in predicting prognosis of patients.

Methods

Between February 2001 and December 2008, 321 patients with NPC treated with concurrent chemotherapy and IMRT were analyzed retrospectively. GTVp was calculated from treatment planning computed tomography scans. A receiver operating characteristics (ROC) curve was used to determine the best cutoff point of GTVp.

Results

The 5-year local failure-free survival (LFFS), distant metastasis-free survival (DMFS), disease-free survival (DFS), and overall survival (OS) for NPC patients were 93.8, 80.1, 73.0, and 83.7 %, respectively. Univariate and multivariate analyses indicated that GTVp had exhibited a statistically significant correlation with LFFS, DMFS, DFS, and OS (P < 0.05, all), whereas T classification was not an independent prognostic factor. According to ROC curve analysis, 49 and 19 mL were determined as the cutoff points of GTVp for local control and distant metastasis, respectively. Based on this, 321 patients were divided into three volume subgroups. LFFS, DMFS, DFS, and OS demonstrated significant differences among patients in different volume subgroups (P < 0.001, all) and were superior to T classification for predicting prognosis of NPC patients.

Conclusions

Primary gross tumor volume is an independent prognostic factor in local control, distant metastasis, disease-free survival, and overall survival in NPC. An adjusted TNM staging system that includes GTVp as a quantitative indicator to evaluate prognosis is warranted.     

The role of adjuvant chemotherapy in stage II colorectal cancer patients

Purpose

Adjuvant chemotherapy use in stage II colorectal cancer (CRC) is debated. We evaluated the prognostic significance of clinicopathological features recommended by most guidelines for identifying high-risk stage II CRC and adjuvant chemotherapeutic response.

Methods

We enrolled 1,039 stage II CRC patients who underwent curative surgery at Taipei Veterans General Hospital from January 2005 to December 2010. Seventy-seven patients who received radiotherapy were excluded. The endpoint was disease-free survival.

Results

Of 962 patients, 37 had stage T4 tumors; 50, lymphovascular invasion; 39, poor differentiation; 249, preoperative carcinoembryonic antigen (CEA) levels >5 ng/mL; and 53 underwent emergent operations. One hundred ninety-four patients received 5-fluorouracil-based adjuvant chemotherapy. During a median follow-up period of 60.2 months, recurrence developed in 110 patients (11.4 %). The 5-year disease-free survival (DFS) was 87.6 %. In multivariate analysis, preoperative CEA >5 ng/ml (p?=?0.001), emergent operation for obstruction/perforation (p?=?0.008), lymphovascular invasion (p?=?0.014), and T4 disease (p?=?0.030) were significantly associated with poor DFS. High-risk stage II patients (n?=?484) benefited from adjuvant chemotherapy (5-year DFS with and without adjuvant chemotherapy, 87.3 vs. 78.9 %; p?=?0.028).

Conclusions

Adjuvant chemotherapy improved DFS in high-risk stage II CRC patients, but not in low-risk patients.     

Prognostic factors associated with primary cancer in curatively resected stage IV colorectal cancer

Purpose

The aim of this study is to evaluate the prognostic factors associated with primary cancer in patients with curatively resected stage IV colorectal cancer, based on lymph node status.

Methods

A total of 468 consecutive patients with curatively resected stage IV colorectal cancer from October 1994 to December 2010 were prospectively enrolled. Survival curves were constructed using the Kaplan–Meier method, and multivariate analysis assessed independent prognostic factors.

Results

During the median follow-up period of this study, which was 37 months (range 1–177), the 3- and 5-year overall survival rates were 66.5 and 52.1 %, respectively, and the 3- and 5-year disease-free survival rates were 43.0 and 38.2 %, respectively. According to multivariate analysis, adjuvant chemotherapy and the preoperative serum carcinoembryonic antigen (CEA) level were independent prognostic factors for overall survival, and primary tumor location and preoperative serum CEA level were independent variables for disease-free survival. For the patients with N0 and N1 tumors, the overall survival curves in the preoperative CEA groups differed significantly (P = 0.046 and P < 0.013, respectively). However, for patients with pN2 tumors, the overall survival did not differ significantly according to the preoperative CEA (P = 0.948).

Conclusion

The preoperative serum CEA level is a reliable predictor of recurrence and survival after curative surgery in patients with metastatic colorectal cancer. A multidisciplinary approach that combines both complete resection and adjuvant chemotherapy may achieve improved overall survival in these patients.     

Predictive value of excision repair cross-complementation group 1 expression for platinum-based chemotherapy and survival in gastric cancer: a meta-analysis

Purpose

The predictive value of excision repair cross-complementation group 1 (ERCC1) gene for survival and response to platinum-based chemotherapy in gastric cancer (GC) remains controversial. We performed a meta-analysis to clarify the precise estimation of the prognostic and predictive effect of ERCC1.

Methods

A systematic literature search was conducted using PubMed, ScienceDirect, Wiley and American Society of Clinical Oncology (ASCO) before March 2014. Studies analyzing survival data and/or chemotherapy response in GC by ERCC1 status were identified. The principal outcome measures were hazard ratios (HRs) for survival and relative risks (RRs) for chemotherapy response. Pooled HRs and RRs were calculated using fixed- or random-effects models according to the heterogeneity.

Results

Twenty-one studies involving 1,628 patients met our inclusion criteria. High ERCC1 expression was significantly associated with shorter overall survival (OS) and lower response to chemotherapy in advanced GC patients receiving palliative chemotherapy (HR 1.83; 95 % CI 1.45–2.31; P < 0.001; RR 0.49; 95 % CI 0.38–0.62; P < 0.001). There was no significant difference in survival between high and low ERCC1 expression in adjuvant setting (OS: HR 1.38; 95 % CI 0.77–2.45; P = 0.276; EFS 0.72; 95 % CI 0.38–1.33; P = 0.291). Some evidence of heterogeneity and possible publication bias were discovered in few meta-analyses.

Conclusions

High ERCC1 expression might be an adverse prognostic and a drug-resistance predictive factor for advanced GC patients. However, further studies with consistent ERCC1 assessment methodology are needed.