The Prognostic Impact of Type 2 Diabetes Mellitus on Early Cervical Cancer in Asia

Background.

Many studies have shown that type 2 diabetes mellitus (DM) increases the risk for several types of cancer but not cervical cancer (CC). Although DM and insulin-like growth factor 1 have preclinical and clinical implications for CC, less is known about the prognostic impact of DM on patients with early stage CC.

Patients and Methods.

We used the nationwide Taiwan Cancer Registry database to collect the characteristics of stage I–IIA cervical cancer patients diagnosed between 2004 and 2008. DM and other comorbidities were retrieved from the National Health Insurance database. Cervical cancer-specific survival (CSS) and overall survival (OS) times of patients according to DM status were estimated using the Kaplan-Meier method. We used a Cox proportional hazards model to calculate adjusted hazard ratios (HRs) for the effects of DM and other risk factors on mortality.

Results.

A total of 2,946 patients had primary stage I–IIA CC and received curative treatments, and 284 (9.6%) had DM. The 5-year CSS and OS rates for patients with DM were significantly lower than those without DM (CSS: 85.4% vs. 91.5%; OS: 73.9% vs. 87.9%). After adjusting for clinicopathologic variables and comorbidities, DM remained an independent unfavorable prognostic factor for CSS (adjusted HR: 1.46) and OS (adjusted HR: 1.55).

Conclusion.

In Asian patients with early cervical cancer, DM is an independent unfavorable prognostic factor influencing both OS and CSS, even after curative treatments.

Implications for Practice:

Type 2 diabetes mellitus (DM) increases the incidence of several types of cancer but not cervical cancer (CC); however, less is known about the impact of DM on patients who already have CC. This study suggests that DM may increase the risk of cancer recurrence and death for early stage CC patients, even after curative treatments. Incorporating DM control should be considered part of the continuum of care for early stage CC patients, and close surveillance during routine follow-up in this population is recommended.     

Diabetes mellitus is associated with increased mortality in patients receiving curative therapy for hepatocellular carcinoma

Background.

Diabetes mellitus (DM) is closely associated with hepatocarcinogenesis. This study explores the prognostic impact of DM in patients who received curative therapy for localized hepatocellular carcinoma (HCC).

Methods.

Patients who had been diagnosed with stage I or II HCC in 2003 and 2004 and received surgical resection or local ablation therapy were identified from the population-based Taiwan National Cancer Registry. Data pertaining to DM and other comorbidities were retrieved from the Taiwan National Health Insurance database. Liver cancer-specific survival (LCS), liver disease-related survival (LDS) and overall survival (OS) rates were compared between patients with and without DM. The presence of other comorbidities and tumor status were adjusted using multivariate analysis.

Results.

A total of 931 patients who fulfilled the study criteria were analyzed; 185 (20%) of them had DM (type 1 or type 2). The LCS, LDS, and OS rates were significantly worse for patients with DM than patients without DM (all p < .001). After adjusting for age, sex, tumor stage, treatment, and the presence of other comorbidities, DM remained an independent predictor of poorer LCS (hazard ratio [HR] = 1.57; p < .001), LDS (HR = 1.70; p < .001), and OS (HR = 1.69; p < .001). The associations between DM and mortality were consistent among subgroups, irrespective of tumor size, stage, treatment modality, and liver cirrhosis.

Conclusions.

DM is an independent factor for poorer prognosis in patients who received curative therapy for localized HCC.     

A cohort study of the prognostic and treatment predictive value of SATB2 expression in colorectal cancer

Background:

Special AT-rich sequence-binding protein 2 (SATB2) is a novel diagnostic marker of colorectal cancer (CRC), and loss of SATB2 has been linked to poor survival from the disease. In this study, we validated the prognostic ability of SATB2 expression in a large, prospective CRC cohort.

Methods:

Immunohistochemical SATB2 expression was assessed in 527 incident CRC cases from the Malmö Diet and Cancer Study. Kaplan–Meier analysis and Cox proportional hazards modelling were used to explore the impact of SATB2 expression on cancer-specific survival (CSS) and overall survival (OS).

Results:

High SATB2 expression was associated with a prolonged CSS in the full cohort (hazard ratio (HR)=0.61; 95% CI 0.41–0.92) and in colon cancer (HR=0.39; 95% CI 0.20–0.75), remaining significant in multivariable analysis of colon cancer (HR=0.49; 95% CI 0.25–0.96), with similar findings for OS. In curatively resected stage III-IV patients, a significant benefit from adjuvant and/or neoadjuvant therapy was observed for SATB2 high tumours (P_interaction=0.037 for OS) and high SATB2 expression in rectal cancer correlated with an enhanced effect of neoadjuvant therapy (P_interaction=0.033 for OS).

Conclusion:

High SATB2 expression is an independent marker of good prognosis in colon cancer and may modulate sensitivity to chemotherapy and radiation.     

Metformin Is Associated With Survival Benefit in Cancer Patients With Concurrent Type 2 Diabetes: A Systematic Review and Meta‐Analysis

Purpose.

Patients with type 2 diabetes have increased cancer risk and cancer-related mortality, which can be reduced by metformin treatment. However, it is unclear whether metformin can also modulate clinical outcomes in patients with cancer and concurrent type 2 diabetes.

Patients and Methods.

A meta-analysis of 20 publications that included 13,008 subjects was performed to investigate the association between metformin and overall survival (OS) as well as cancer-specific survival (CSS) in patients with cancer and concurrent type 2 diabetes.

Results.

We found that there was a relative survival benefit associated with metformin treatment compared with treatment with other glucose-lowering medications in both OS and CSS (hazard ratio [HR] = 0.66; 95% confidence interval [CI]: 0.55–0.79 and HR = 0.62; 95% CI: 0.46–0.84, respectively). These associations were also observed in subgroups by cancer type and country.

Conclusion.

These results suggest that metformin is the drug of choice in the treatment of patients with cancer and concurrent type 2 diabetes.     

Definitive treatment of primary vaginal cancer with radiotherapy: multi-institutional retrospective study of the Korean Radiation Oncology Group (KROG 12-09)

Objective

To assess the outcome of the treatment of primary vaginal cancer using definitive radiotherapy (RT) and to evaluate the prognostic factors of survival.

Methods

The medical records of nine institutions were retrospectively reviewed to find the patients with vaginal cancer treated with definitive RT with or without chemotherapy. A total of 138 patients met the inclusion criteria. None had undergone curative excision.

Results

The median follow-up time of the survivors was 77.6 months and the median survival time was 46.9 months. The 5-year overall survival, cancer-specific survival (CSS), and progression-free survival (PFS) rates were 68%, 80%, and 68.7%, respectively. In the survival analysis, the multivariate analysis showed that a lower the International Federation of Gynecology and Obstetrics (FIGO) stage and prior hysterectomy were favorable prognostic factors of CSS, and a lower FIGO stage and diagnosed prior to year 2000 were favorable prognostic factors of PFS. In the subgroup analysis of the patients with available human papillomavirus (HPV) results (n=27), no statistically significant relationship between the HPV status and recurrence or survival was found. Grade 3 or 4 acute and late toxicity were present in 16 and 9 patients, respectively. The FIGO stage and the tumor size were predictors of severe late toxicity.

Conclusion

The data clearly showed that a higher FIGO stage was correlated with a worse survival outcome and higher severe late toxicity. Therefore, precise RT and careful observation are crucial in advanced vaginal cancer. In this study, the HPV status was not related to the survival outcome, but its further investigation is needed.     

Effect of internal iliac artery chemotherapy after transurethral resection of bladder tumor for muscle invasive bladder cancer

Objective： To evaluate the clinical effect of transurethral resection of bladder tumor（TUR-BT） combined with internal iliac artery chemotherapy and intravesical instillation therapy for muscle invasive bladder cancer（MIBC）.
Methods： From February 2007 to April 2014, 62 patients with MIBC were treated with TUR-BT combined with intravesical instillation therapy, with or without internal iliac artery chemotherapy, and the chemotherapy regimen is gemcitabine and cisplatin（GC）. The bladder preservation and survival rate as well as cancer-specific survival（CSS） rate and overall survival（OS） rate of the two groups were compared.
Results： Sixty-two patients were followed-up for 26-102 months with an average of 58.4±3.1 months. Recurrence-free survival（RFS） at 2-year for TUR ＋ GC group and TUR group were 77.8% and 53.8%, respectively. Bladder preserved rate（BPR） at 3-year for TUR ＋ GC group and TUR group were 94.4% and 80.8%. CSS rate at 2-year for TUR ＋ GC group and TUR group were 94.4% and 84.6%. The diseasefree survival（DFS） at 1-year for TUR ＋ GC group and TUR group were 83.3% and 61.5%, and 77.8% and 53.8% for the 2nd year. OS at 2-year for TUR ＋ GC group and TUR group were 88.9% and 92.3%.
Conclusions： TUR-BT and intravesical instillation therapy combined with internal iliac artery chemotherapy for MIBC had a better outcome at RFS, BPR and DFS than the treatment without internal iliac artery chemotherapy, and no difference in OS and CSS.     

Surveillance for asymptomatic recurrence in resected stage III colon cancer: does it result in a more favorable outcome?

Background

Evidence from dated and moderate quality trials supports a modest survival benefit for intensive surveillance in resected colon cancer (CC). This study evaluates surveillance in a modern population-based cohort of stage III CC patients (pts).

Methods

Records of pts who initiated oxaliplatin-based adjuvant chemotherapy (AC) for stage III CC between 2006-2011 at the British Columbia Cancer Agency (BCCA) were reviewed. Kaplan-Meier and log rank test were generated to investigate whether diagnosis of recurrence based on symptoms was associated with worse overall survival (OS). OS1 and OS2 were measured from date of recurrence or date of initial surgery, respectively.

Results

Of 635 pts who received AC for stage III CC, 175 pts (27.5%) recurred and 118 (18.6%) died at a median follow-up of 67.7 months. Recurrences were detected by surveillance in 149 pts (41% by CEA elevation and 44% by abnormal imaging), and symptoms in 26 pts (15%). Patients with surveillance-detected recurrences had a shorter median relapse-free survival (RFS) (18.5 vs. 25.3 months, HR 1.82, P<0.001), and longer median OS1 (28.5 vs. 6.5 months, HR 0.37, P<0.001). However, median OS2 was not significantly different (50.9 vs. 39.1 months, HR 0.66, P=0.091). Pts with surveillance-detected recurrence received more potentially curative metastasectomy (39% vs. 7%, P=0.002) and chemotherapy (70% vs. 50%, P=0.03).

Conclusions

In this modern population-based cohort study, the OS impact of detecting asymptomatic recurrences in stage III CC is unclear. However, pts with asymptomatic recurrences were more likely to receive potentially curative metastasectomy and chemotherapy.     

Postoperative radiotherapy for resected pathological stage IIIA-N2 non-small cell lung cancer: a retrospective study of 221 cases from a single institution

Background.

For patients with resected pathological stage IIIA–N2 non-small cell lung cancer (NSCLC), the role of postoperative radiotherapy (PORT) is not well defined. In this single-institutional study, we re-evaluated the effect of PORT on overall survival (OS) as well as tumor control in this subgroup of patients.

Methods.

In 2003–2005, 221 consecutive patients with resected pathological stage IIIA–N2 NSCLC at our institution were retrospectively analyzed in an institutional review board–approved study. The effect of PORT on OS, cancer-specific survival (CSS), and disease-free survival (DFS) was evaluated using the Kaplan–Meier method and log-rank tests. The impact of PORT on locoregional control and distant metastasis was also analyzed.

Results.

Compared with the control, patients treated with PORT had a significantly longer OS time (χ², 3.966; p = .046) and DFS interval (χ², 6.891; p = .009), as well as a trend toward a longer CSS duration (χ², 3.486; p = .062). Patients treated with PORT also had a significantly higher locoregional recurrence-free survival rate (χ², 5.048; p = .025) as well as distant metastasis-free survival rate (χ², 11.248; p = .001). Multivariate analyses showed that PORT was significantly associated with a longer OS duration (p = .000).

Conclusions.

PORT can significantly improve the survival of patients with resected pathological stage IIIA–N2 NSCLC. A prospective randomized multicenter clinical trial is ongoing.     

Overexpression of podocalyxin-like protein is an independent factor of poor prognosis in colorectal cancer

Background:

Podocalyxin-like 1 (PODXL) is a cell-adhesion glycoprotein and stem cell marker that has been associated with an aggressive tumour phenotype and poor prognosis in several forms of cancer. In this study, we investigated the prognostic impact of PODXL expression in colorectal cancer (CRC).

Methods:

Using tissue microarrays and immunohistochemistry, PODXL expression was evaluated in 536 incident CRC cases from a prospective, population-based cohort study. Kaplan–Meier analysis and Cox proportional hazards modelling were used to assess the impact of PODXL expression on cancer-specific survival (CSS) and overall survival (OS).

Results:

High PODXL expression was significantly associated with unfavourable clinicopathological characteristics, a shorter CSS (hazard ratio (HR)=1.98; 95% confidence interval (CI) 1.38–2.84, P<0.001) and 5-year OS (HR=1.85; 95% CI 1.29–2.64, P=0.001); the latter remaining significant in multivariate analysis (HR=1.52; 95% CI 1.03–2.25, P=0.036). In addition, in curatively resected stage III (T1–4, N1–2, M0) patients (n=122) with tumours with high PODXL expression, a significant benefit from adjuvant chemotherapy was demonstrated (p_interaction =0.004 for CSS and 0.015 for 5-year OS in multivariate analysis).

Conclusion:

Podocalyxin-like 1 expression is an independent factor of poor prognosis in CRC. Our results also suggest that PODXL may be a useful marker to stratify patients for adjuvant chemotherapy.     

Survival advantage observed with the use of metformin in patients with type II diabetes and colorectal cancer

Background:

Patients with type II diabetes mellitus (DM) have an increased risk of adenomatous colorectal (CRC) polyps and CRC cancer. The use of the anti-hyperglycemic agent metformin is associated with a reduced incidence of cancer-related deaths.

Methods:

We retrospectively evaluated the medical records of 4758 patients seen at a single institution and determined that 424 patients were identified by their physicians as having type II DM and CRC cancer. Data were subsequently acquired determining the subject''s age, body mass index (BMI), and disease date of diagnosis, stage, site of cancer, treatment, and survival.

Results:

Patients with type II DM and CRC cancer treated with metformin as one of their diabetic medications had a survival of 76.9 months (95% CI=61.4–102.4) as compared with 56.9 months in those patients not treated with metformin (95% CI=44.8–68.8), P=0.048. By using a multivariable Cox regression model adjusted for age, sex, race, BMI, and initial stage of disease, we demonstrated that type II diabetic patients treated with metformin had a 30% improvement in overall survival (OS) when compared with diabetic patients treated with other diabetic agents.

Conclusion:

Colorectal cancer patients with DM treated with metformin as part of their diabetic therapy appear to have a superior OS.     

The impact of diabetes mellitus on prognosis of early breast cancer in Asia

Background.

Diabetes mellitus (DM) has been implicated in influencing the survival duration of patients with breast cancer. However, less is known about the impact of DM and other comorbidities on the breast cancer–specific survival (BCS) and overall survival (OS) outcomes of Asian patients with early-stage breast cancer.

Patients and Methods.

The characteristics of female patients with newly diagnosed, early-stage breast cancer were collected from the Taiwan Cancer Registry database for 2003–2004. DM status and other comorbidities were retrieved from Taiwan''s National Health Insurance database. The BCS and OS times of patients according to DM status were estimated via the Kaplan–Meier method. Cox''s proportional hazard model was used to estimate adjusted hazard ratios (HRs) for the effects of DM, comorbidities, and other risk factors on mortality.

Results.

In total, 4,390 patients were identified and 341 (7.7%) presented with DM. The 5-year BCS and OS rates were significantly greater in DM patients than in non-DM patients (BCS, 85% versus 91%; OS, 79% versus 90%). Furthermore, after adjusting for clinicopathologic variables and comorbidities, DM remained an independent predictor of shorter BCS (adjusted HR, 1.53) and OS (adjusted HR, 1.71) times. Subgroup analyses also demonstrated a consistent prognostic influence of DM across different groups.

Conclusion.

In Asian patients with early-stage breast cancer, DM is an independent predictor of lower BCS and OS rates, even after adjusting for other comorbidities. The integration of DM care as part of the continuum of care for early-stage breast cancer should be emphasized.     

Outcomes and Prognostic Factors in Radioiodine Refractory Differentiated Thyroid Carcinomas

Background.

Outcomes vary among patients with radioiodine refractory (RR) differentiated thyroid cancer (DTC). The prognostic factors for survival are not well-known, resulting in difficulty in selecting patients for new targeted therapies. We assessed overall survival (OS) and cancer-specific survival (CSS) from RR-DTC to identify prognostic factors associated with survival.

Patients and Methods.

The data on all cases of metastatic RR-DTC treated in our center from 1990 to 2011 were retrospectively reviewed. Survival was estimated using the Kaplan-Meier method; associated prognostic factors were assessed using Cox’s model.

Results.

Of 153 cases of metastatic DTC, 59% (n = 91) met a criterion for RR: that is, 60% (n = 55) had at least 1 metastasis without ¹³¹I uptake; 21% (n = 19) had progressive disease (PD) despite ¹³¹I; 19% (n = 17) had persistent disease despite a cumulative activity of ¹³¹I of ≥600 mCi. After the diagnosis of RR, median OS was 8.9 years (95% confidence interval [CI]: 5.4-NR); median CSS was 9.6 years (95% CI: 6.01-NR). In multivariate analyses, PD despite ¹³¹I as a criterion for RR disease and the time from initial diagnosis of DTC to diagnosis of RR <3 years were the only independent prognostic factors for poor OS and CSS. Thyroglobulin doubling time (Tg-DT) was assessed in 31 of 91 cases. Among the 11 patients with Tg-DT for <1 year or undetectable Tg, 6 deaths occurred, whereas only 3 died of 20 patients with Tg-DT >1 year or negative Tg-DT.

Conclusion.

The identification of prognostic factors for decreased survival in RR-DTC may improve the selection of patients for targeted agents.

Implications for Practice:

This study shows a great heterogeneity in terms of prognosis in radioiodine refractory differentiated thyroid carcinoma. Poorer prognosis is observed in patients with tumor progression or with a diagnosis of radioiodine resistance within 3 years after the initial diagnosis of thyroid cancer. Those findings could lead to improvements in the selection of patients for targeted therapies.     

Prognostic significance of preoperative inflammatory response biomarkers in patients undergoing curative thoracoscopic esophagectomy for esophageal squamous cell carcinoma

Background

Recent studies have revealed significant relationships between the lymphocyte-to-monocyte ratio (LMR), neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PLR) and survival in various cancers. The purpose of this study was to confirm whether the LMR, NLR, and PLR have prognostic values, independent of clinicopathological criteria, in patients undergoing curative resection for esophageal cancer.

A clinical risk score to predict 3-, 5- and 10-year survival in patients undergoing surgery for Dukes B colorectal cancer

Background:

The prognosis of patients with Dukes stage B colorectal cancer is unpredictable and there is continuing interest in simply and reliably identifying patients at high risk of developing recurrence and dying of their disease. The aim of this study was to devise a clinical risk score to predict 3-, 5- and 10-year survival in patients undergoing surgery for Dukes stage B colorectal cancer.

Methods:

A total of 1350 patients who underwent surgery for Dukes stage B colorectal cancer between 1991 and 1994 in 11 hospitals in Scotland were included in the analysis.

Results:

On follow-up, 926 patients died of whom 479 died of their cancer. At 10 years, cancer-specific survival was 61% and overall survival was 38%. On multivariate analysis, age ⩾75 (hazard ratio (HR) 1.45, 95% confidence interval (CI) 1.15–1.82, P=0.001), emergency presentation (HR 1.59, 95% CI 1.27–1.99, P<0.001) and anastomotic leak (HR 2.17, 95% CI 1.24–3.78, P<0.01) were independently associated with cancer-specific survival in colon cancer. On multivariate analysis, only age ⩾75 (HR 1.58, 95% CI 1.14–2.18, P<0.01) was associated with cancer-specific survival in rectal cancer. Age, presentation and anastomotic leak hazards could be simply added to form a clinical risk score from 0 to 2 in colon cancer. In patients with Dukes B stage colon cancer, the cancer-specific survival at 5 years for patients with a cumulative score 0 was 81%, 1 was 67% and 2 was 63%. The cancer-specific survival rate at 10 years for patients with a clinical risk score of 0 was 72%, 1 was 58% and 2 was 53%.

Conclusion:

The results of this study, in a mature cohort, introduce a new simple clinical risk score for patients undergoing surgery for Dukes B colon cancer. This provides a solid foundation for the examination of the impact of additional factors and treatment on prediction of 3-, 5- and 10-year cancer-specific survival.     

Stage IIIC epithelial ovarian cancer classified solely by lymph node metastasis has a more favorable prognosis than other types of stage IIIC epithelial ovarian cancer

Objective

To verify whether it can be justified to classify patients to stage IIIC epithelial ovarian cancer based on nodal involvement only.

Methods

This study included all consecutive patients with stage IIIC epithelial ovarian cancer who underwent upfront cytoreductive surgery according to the FIGO guideline followed by platinum based chemotherapy from September 1989 to September 2006 at Asan Medical Center.

Results

During the study period, a total of 272 patients met the inclusion criteria. Optimal cytoreduction was achieved in 213 patients, and complete cytoreduction was achieved in 85 patients. Median follow-up time was 37 months (range, 6-181 months). The 5-year disease free survival (DFS) and overall survival (OS) rate of all patients were 23% and 57%, respectively. Forty-one patients were allocated to stage IIIC by positive nodes only. Patients with stage IIIC disease due to positive nodes only had significantly longer DFS and OS compared to other stage IIIC patients (p<0.001 and p<0.001). The DFS and OS of these patients was significantly better than those of other stage IIIC patients who achieved complete or optimal cytoreduction (p<0.001 and p<0.001). The outcome was even better than that of stage IIIA and IIIB patients (p<0.05 and p<0.05).

Conclusion

Patients with stage IIIC epithelial ovarian cancer due to positive nodes only had a more favorable prognosis compared to other stage IIIC patients. Therefore, reevaluation of the current FIGO staging system for stage IIIC epithelial ovarian cancer is required.     

Ubiquitin D is correlated with colon cancer progression and predicts recurrence for stage II-III disease after curative surgery

Background:

Our recent study observed that the expression of ubiquitin D (UBD), a member of ubiquitin-like modifier family, was upregulated in colon cancer parenchymal cells. The present study further investigated the clinical signicance of UBD in colon cancer.

Methods:

Using quantitative PCR, tissue microarray (TMA), western blot analysis and immunohistochemical stain, we evaluated UBD mRNA and protein levels in tumour tissues from patients with colon cancer at different stages and in paired adjacent normal epithelium.

Results:

Immunohistochemical detection of UBD on a TMA containing 203 paired specimens showed that increased cytoplasmic UBD was signicantly associated with depth of cancer invasion, lymph node metastasis, distant metastasis, tumour histologic grade, advanced clinical stage and Ki-67 proliferative index. Patients with UBD-positive tumours had a significantly higher disease recurrence rate and poorer survival than patients with UBD-negative tumours after the radical surgery. Stratification analysis according to tumour stage revealed UBD as an independent predictor for tumour recurrence in patients with stage II and III tumours.

Conclusion:

UBD may contribute to the progression of colon carcinogenesis and function as a novel prognostic indicator of forecasting recurrence of stage II and III patients after curative operations.     

Palliative oxaliplatin-based chemotherapy after exposure to oxaliplatin in the adjuvant setting for colon cancer

Background

Little is known regarding the efficacy of oxaliplatin-based chemotherapy for metastatic colon cancer patients who have already received adjuvant oxaliplatin-based chemotherapy.

Methods

We retrospectively reviewed 22 consecutive patients who developed recurrence after adjuvant oxaliplatin-based chemotherapy for stage III colon cancer and received another course of oxaliplatin-based chemotherapy for their metastatic disease. The main endpoint was progression-free survival (PFS).

Results

A total of 635 patients received oxaliplatin-based chemotherapy for stage III colon cancer at the British Columbia Cancer Agency from 2006 to 2011. A total of 176 patients recurred, 22 (12.5%) of whom were re-exposed to oxaliplatin in the metastatic scenario. Oxaliplatin in combination with fluoropyrimidine was given as first, second and third line in in 3 (13.6%), 14 (63.6%), and 5 (22.7%) patients respectively. Median time from the last cycle of adjuvant oxaliplatin-based chemotherapy to the first cycle of palliative oxaliplatin-based chemotherapy was 44.3 months. Median PFS and overall survival (OS) were 3.3 (95% CI, 1.4-5.1) and 10.0 months (95% CI, 5.3-14.6), respectively. There was no difference in PFS for patients re-exposed to oxaliplatin less than 36 months compared to longer (3.6 versus 3.1 months, P=0.793, HR =0.88).

Conclusions

In this population-based study, only a small proportion of pts who recurred after oxaliplatin-based adjuvant therapy received oxaliplatin in the metastatic setting. Re-exposure of oxaliplatin in combination with fluoropyrimidine is associated with only modest PFS benefit. Larger studies evaluating the role of oxaliplatin re-exposure are needed.     

Expression of cyclin D1a and D1b as predictive factors for treatment response in colorectal cancer

Background:

The aim of this study was to investigate the value of the cyclin D1 isoforms D1a and D1b as prognostic factors and their relevance as predictors of response to adjuvant chemotherapy with 5-fluorouracil and levamisole (5-FU/LEV) in colorectal cancer (CRC).

Methods:

Protein expression of nuclear cyclin D1a and D1b was assessed by immunohistochemistry in 335 CRC patients treated with surgery alone or with adjuvant therapy using 5-FU/LEV. The prognostic and predictive value of these two molecular markers and clinicopathological factors were evaluated statistically in univariate and multivariate survival analyses.

Results:

Neither cyclin D1a nor D1b showed any prognostic value in CRC or colon cancer patients. However, high cyclin D1a predicted benefit from adjuvant therapy measured in 5-year relapse-free survival (RFS) and CRC-specific survival (CSS) compared to surgery alone in colon cancer (P=0.012 and P=0.038, respectively) and especially in colon cancer stage III patients (P=0.005 and P=0.019, respectively) in univariate analyses. An interaction between treatment group and cyclin D1a could be shown for RFS (P=0.004) and CSS (P=0.025) in multivariate analysis.

Conclusion:

Our study identifies high cyclin D1a protein expression as a positive predictive factor for the benefit of adjuvant 5-FU/LEV treatment in colon cancer, particularly in stage III colon cancer.     

KRAS mutation detection and prognostic potential in sporadic colorectal cancer using high-resolution melting analysis

Background:

The development of targeted therapies has created a pressing clinical need for molecular characterisation of cancers. In this retrospective study, high-resolution melting analysis (HRMA) was validated and implemented for screening of 164 colorectal cancer (CRC) patients to detect KRAS hot-spot mutations and to evaluate its prognostic value. Direct sequencing was used to confirm and characterise HRMA results.

Methods:

After establishing its sensitivity, HRMA was validated on seven cell lines and inter- and intra-variation were analysed. The prognostic value of KRAS mutations in CRC was evaluated using survival analysis.

Results:

HRMA revealed abnormal melting patterns in 34.1% CRC samples. Kaplan–Meier survival curves revealed a significantly shorter overall (OS) and disease-free survival (DFS) for CRC patients harbouring a KRAS mutation. In the Cox regression analysis, only when colon and rectal cancer were analysed separately, KRAS mutation was a negative predictor for OS in patients with rectal cancer and DFS in those with stage II colon cancer.

Conclusions:

HRMA was found to be a valid screening method for KRAS mutation detection. The KRAS mutation came forward as a negative predictive factor for OS in patients with rectal cancer and for DFS in stage II colon cancer patients.     

Redefining high-risk patients with stage II colon cancer by risk index and microRNA-21: results from a population-based cohort

Background:

The aim of the present study was to analyse the prognostic value of microRNA-21 (miRNA-21) in patients with stage II colon cancer aiming at a risk index for this group of patients.

Methods:

A population-based cohort of 554 patients was included. MicroRNA-21 was analysed by qPCR based on tumour tissue. An index was created using the coefficients obtained from a collective multiple Cox regression. The entire procedure was cross-validated (10-fold). The performance of the index was quantified by time-dependent receiver operating characteristics curves.

Results:

High miRNA-21 expression was associated with an unfavourable recurrence-free cancer-specific survival (RF-CSS), hazard ratio 1.35 (95% confidence interval, 1.03–1.76) (P=0.028). The generated RF-CSS index divided the traditional high-risk patients into subgroups with 5-year RF-CSS rates of 87% and 73%, respectively (P<0.001). The overall survival (OS) index identified three different subgroups (P<0.001). Cross-validated 5-year OS rates were 88%, 68%, and 50%, respectively.

Conclusions:

This population-based study supports miRNA-21 as an additional prognostic biomarker in patients with stage II colon cancer. Furthermore, the introduction of a risk index may guide the use of postoperative adjuvant treatment in a more appropriate way compared with current practice.