Why is colon cancer survival improving by time? A nationwide survival analysis spanning 35 years

There is limited information present to explain temporal improvements in colon cancer survival. This nationwide study investigates the temporal changes in survival over a 35‐year period (1970–2004) in Iceland and uses incidence, mortality, surgery rate, stage distribution, lymph node yield, tumor location and histological type to find explanations for these changes. Patients diagnosed with colon cancer in Iceland 1970–2004 were identified (n = 1962). All histopathology was reassessed. Proportions, age‐standardized incidence and mortality, relative, cancer‐specific and overall survival and conditional survival were calculated. When comparing first and last diagnostic periods (1970–1978 and 1997–2004), 5‐year relative survival improved by 12% for men and 9% for women. At the same time surgery rate increased by 12% and the proportion of stage I increased by 9%. Stage‐stratified, improved 5‐year relative survival was mainly observed in stages II and III and coincided with higher lymph node yields, proportional reduction of stage II cancers and proportional increase of stage III cancers, indicating stage migration between these stages. Improvement in 1‐year survival was mainly observed in stages III and IV. Five‐year survival improvement for patients living beyond 1 year was minimum to none. There were no changes in histology that coincided with neither increased incidence nor possibly influencing improved survival. Concluding, as a novel finding, 1‐year mortality, which previously has been identified as an important variable in explaining international survival differences, is in this study identified as also being important in explaining temporal improvements in colon cancer survival in Iceland.     

Survival benefits with the addition of adjuvant hysterectomy to radiochemotherapy for treatment of stage I‐II adenocarcinoma of the uterine cervix

Background and Objectives: To determine the survival benefits of additional adjuvant hysterectomy in the International Federation of Gynecology and Obstetrics (FIGO) stage I‐II cervical adenocarcinoma patients treated with radiochemotherapy. Methods: Patients with FIGO stage I‐II cervical adenocarcinoma were selected from the Surveillance, Epidemiology, and End Results 18 Regs research database. Propensity score matching (PSM) was used to balance patient baseline characteristics. Patient characteristics and outcomes were compared between the two groups. Results: A total of 530 patients were included, 389 (73.4%) underwent definitive radiochemotherapy and 141 (26.6%) underwent an additional adjuvant hysterectomy. The multivariate Cox analysis surgery was shown to be an independent predictor of survival. Before PSM, the hazard ratios for cause‐specific survival and overall survival in the surgery group were 0.632 (P = 0.036) and 0.674 (P = 0.041), respectively. After PSM, the respective hazard ratios were 0.392 (P < 0.001) and 0.465 (P = 0.001). The surgery group had significantly better 5‐year cause‐specific survival (80.5% vs 59.1%; P = 0.001) and overall survival than the nonsurgery group (76.3% vs 56.0%; P = 0.002). Conclusions: Additional adjuvant hysterectomy after radiochemotherapy may improve survival outcomes in patients with FIGO stage I‐II cervical adenocarcinoma.     

Higher rate of BRAF mutation in papillary thyroid cancer over time: a single-institution study

BACKGROUND:

The incidence of thyroid cancer has doubled over the past decade. The reason for this dramatic increase in incidence is controversial. Some investigators have suggested that the increased incidence is because of increased detection of small primary tumors as a result of diagnostic scrutiny. Conversely, some investigators have demonstrated an increased incidence across all tumor sizes, suggesting that other factors may play a role. This study was undertaken to investigate the clinical, pathologic, and molecular changes present in papillary thyroid cancer over a 15‐year period during which the incidence of papillary thyroid cancer doubled.

METHODS:

A total of 628 patients with conventional papillary thyroid cancer and 228 tumor samples from a single institution were analyzed from 1991 to 2005. Time‐trend analyses of demographic, clinical, pathologic, and tumor genotype were performed over three 5‐year time periods: group I (1991‐1995), group II (1996‐2000), and group III (2001‐2005).

RESULTS:

The authors found no differences in age, sex, ethnicity, primary tumor size, rate of extrathyroidal invasion, or overall TNM cancer stage among the 3 time groups. The rate of BRAF V600E mutation was significantly higher in group III (88% BRAF V600E positive) as compared with groups I and II (51% and 43%, respectively) (P < .001). The rate of all the common somatic mutations was also significantly higher in group III (92% positive) as compared with groups I and II (68% and 64%, respectively) (P < .002).

CONCLUSIONS:

The rate of BRAF V600E mutation increased significantly over a 15‐year period at the authors' institution. The findings suggest that a higher rate of BRAF mutation in papillary thyroid cancer may contribute to the increasing incidence of thyroid cancer. Cancer 2011;. © 2011 American Cancer Society.     

Disparities in the application of adjuvant radiotherapy after breast-conserving surgery for early stage breast cancer: impact on overall survival

BACKGROUND:

Definitive local therapy of early stage breast cancer includes adjuvant radiotherapy after breast‐conserving surgery (BCS). The authors analyzed factors that influence the receipt of radiotherapy therapy and their resultant impact on outcome.

METHODS:

Using data from the Kentucky Cancer Registry, the authors analyzed the rate of adjuvant radiotherapy for 11,914 women who underwent BCS as a primary surgical treatment for stage 0, I, or II breast cancer between 1998 and 2007. The authors assessed the probability of receiving radiotherapy by using multivariate logistic regression and measured impact on outcome by using Cox survival analysis.

RESULTS:

Overall, 66.2% of women received adjuvant radiotherapy for BCS over a 10‐year period (annual rate range, 60.9%‐70.1%). On multivariate analysis, the rate of receiving radiotherapy was drastically lower for women aged older than 70 years (vs younger) and rural Appalachian (vs non‐Appalachian) populations. The rate was modestly lower for African American (vs white) women, those with in situ (vs invasive) disease, and uninsured (vs insured) patients. Lack of radiotherapy was associated with an increased hazard ratio for death of 1.67 (95% CI, 1.508‐1.851) on Cox survival analysis when age, stage, tumor size, grade, hormone receptors, smoking, and insurance were factored into the analysis. The 10‐year overall survival for patients who received adjuvant radiotherapy versus BCS alone was 79.7% versus 67.6% (P < .0001).

CONCLUSIONS:

Despite widespread knowledge of the benefit of RT after BCS, the rate of undertreatment remains high, with significant disparities for elderly, rural, minority, and uninsured women. Multidisciplinary management strategies, including accelerated and hypofractionated radiation regimens, are needed to eliminate disparities and improve outcomes. Cancer 2011. © 2010 American Cancer Society.     

Hospital volume of percutaneous radiofrequency ablation is closely associated with treatment outcomes for patients with hepatocellular carcinoma

BACKGROUND:

Hospital volume for several major operations is associated with treatment outcomes. In this study, the authors explored the influence of hospital radiofrequency ablation (RFA) volume on the prognosis of patients who received RFA for hepatocellular carcinoma (HCC).

METHODS:

The authors searched for all patients who were diagnosed with stage I or stage II HCC from 2004 to 2006 and who received RFA as first‐line therapy in a population‐based cohort. Overall survival (OS) and liver cancer‐specific survival (CSS) were compared according to hospital volume. A Cox proportional hazards model was used for multivariate analysis.

RESULTS:

In total, 661 patients received first‐line RFA for stage I and II HCC in 28 hospitals. Among these, there were 480 patients (72.6%) in the high‐volume group (those who received RFA at hospitals that treated >10 first‐line patients per year), and there were 181 patients (27.4%) in the low‐volume group (those who received RFA at hospitals that treated ≤10 first‐line patients per year). The sex, age, stage, tumor size, and year of diagnosis for patients in the 2 groups did not differ significantly. Patients in the high‐volume group demonstrated significantly longer OS and CSS than those in the low‐volume group (5‐year OS rate, 58.7% vs 47.2%; P = .001; 5‐year CSS rate, 67.1% vs 57.1%; P = .009). After adjusting for covariates, high‐volume hospitals remained an independent predictor of longer OS (hazard ratio, 0.57; P < .001) and CSS (hazard ratio, 0.57; P = .003).

CONCLUSIONS:

Patients who received first‐line RFA for HCC in high‐volume hospitals demonstrated better survival outcomes. Cancer 2013. © 2012 American Cancer Society.     

Association between polymorphisms in interleukin‐17A and interleukin‐17F genes and risks of gastric cancer

Chronic inflammation is the hallmark of the pathogenesis of Helicobacter pylori‐induced gastric cancer. Interleukin (IL)‐17A and IL‐17F are inflammatory cytokines expressed by a novel subset of CD4+ Th cells and play critical function in inflammation and probably in cancer. We conducted a case–control study including 1,010 gastric cancer patients and 800 healthy controls to assess the association between IL‐17A G197A and IL‐17F A7488G polymorphisms and risk of gastric cancer. Genotypes were determined by polymerase chain reaction‐restriction fragment length polymorphism (PCR‐RFLP) and DNA sequencing. Logistic regression and Cox‐proportional hazards analyses were used to evaluate the associations between polymorphisms and gastric cancer susceptibility, clinicopathological features and survival. After adjusted for age and gender, IL‐17F 7488GA and GG genotypes were associated with an increased risk of gastric cancer compared with AA genotype [OR 1.51, 95% confidence interval (CI): 1.22–1.87 for GA; OR 1.61, 95% CI: 1.03–2.51 for GG]. Further stratification analyses indicated that the effect of IL‐17F 7488GA genotype was noteworthy in gastric cancer patients of noncardia, intestinal type, poorly and moderately differentiated, age older than 40, large tumor size and lymph node metastasis. IL‐17A 197AG genotype was associated with increased risk of poorly differentiated, TNM I/II, age of 40–65‐year subtypes of gastric cancer, but not with total gastric cancer risk (p = 0.098). No significant relationship was observed between polymorphisms and survival of gastric cancer patients. These findings suggest that polymorphism of IL‐17F 7488 involved in susceptibility to gastric cancer, which also influenced certain subtypes according to clinicopathological features, whereas IL‐17A 197 may be less relevant.     

The prognostic determinants of gastric cancer treatment outcome in Omani Arab patients

BACKGROUND: Gastric cancer is the most common cancer in Oman and a leading cause of cancer death. The variation in survival rates between countries and ethnic groups has been attributed to early detection policies, differences in clinicopathological features, treatment approaches, and biological characteristics. There were no previous reports on gastric cancer from Oman and very few studies on Asian Arabs. AIM: To evaluate the impact of clinicopathological and treatment variables on the survival prospects of Omani Arab patients diagnosed with gastric cancer. METHODS: The medical records of 339 Omani Arab patients diagnosed with invasive gastric adenocarcinoma during the period 1993-2004 were retrospectively reviewed. The relative importance of clinicopathological features and surgical and medical treatments were assessed using univariate and multivariate analyses. RESULTS: Most patients had distal ulcerating-type gastric cancer and presented at advanced stages. The median survival time for the entire cohort was 12 months (95% CI 9.7-14.4) with a 5-year overall survival rate of 16.7%. On univariate analysis of 237 patients who underwent surgical resection, the following positive prognostic factors emerged as significant: early overall TNM stage, early T stage, negative lymph nodes, tumor size <5 cm, ulcerating macroscopic appearance, and curative surgical attempt. The independent prognostic factors on multivariate analysis were T stage and lymph node involvement. CONCLUSION: The overall T and N stages are the most important determining factor for survival in Omani Arab patients. More efforts need to be made for the early detection of gastric cancer in developing countries such as Oman, while continuing to employ the standard surgical and medical treatments.     

The correlation between gastric cancer screening method and the clinicopathologic features of gastric cancer

Background: A gastric cancer (GC) screening program using gastrofiberscopy (GFS) or double contrast upper gastrointestinal series (UGIS), as a public policy, has been used in Korea since 1996. The aim of this study was to assess whether there have been major changes in clinicopathologic features of GC by introducing GC screening. Method: We reviewed the medical records of 1478 consecutive patients with GC who underwent gastrectomy between 1989 and 1999. Patients were divided into two groups: group I (before GC screening), 1989–1995 (n=840), and group II (after GC screening), 1996–1999 (n=638). Results: After employment of GC screening, the incidence of early cancer was significantly increased (21% vs 13%, p<0.0001). During these years, the proportion of patients using GFS as the first diagnostic procedure and the relative frequency of intestinal-type GC increased significantly (63% vs 84%, 0.6 vs 1.2, respectively, p<0.0001). Conclusions: These results suggest that GC screening is effective for early detection of GC. Furthermore, the preferred screening method of GC can attribute the clinicopathologic features of GC.     

Serum olfactomedin 4 (GW112, hGC‐1) in combination with Reg IV is a highly sensitive biomarker for gastric cancer patients

Gastric cancer (GC) is 1 of the most common human cancers. Early detection remains the most promising approach to improving long‐term survival of patients with GC. We previously performed Serial Analysis of Gene Expression (SAGE) on 4 primary GCs and identified several GC‐specific genes including Reg IV. Of these genes, olfactomedin 4 (OLFM4, also known as GW112 or hGC‐1) is a candidate gene for cancer‐specific expression. In this study, we examined the expression of olfactomedin 4 in human GC by immunohistochemistry. We also assessed serum olfactomedin 4 levels in GC patients by enzyme‐linked immunosorbent assay. 94 (56%) of 167 GC cases were positive for olfactomedin 4 by immunostaining. Olfactomedin 4 staining was observed more frequently in stage I/II cases than in stage III/IV cases. The serum olfactomedin 4 concentration in presurgical GC patients (n = 123, mean ± SE, 36.3 ± 3.5 ng/mL) was significantly higher than that in healthy individuals (n = 76, 16.6 ± 1.6 ng/mL). In patients with stage I GC, the sensitivity of serum olfactomedin 4 (25%) and Reg IV (35%) was superior to that of CA19‐9 (5%) or CEA (3%). Furthermore, in patients with stage I GC, the combination of olfactomedin 4 and Reg IV elevated the diagnostic sensitivity to 52%. These results suggest that serum olfactomedin 4 is a useful marker for GC and its measurement alone or in combination with Reg IV has utility in the early detection of GC. © 2009 UICC     

Survival of patients with hereditary colorectal cancer: Comparison of HNPCC and colorectal cancer in FAP patients with sporadic colorectal cancer

Conflicting data exist on the prognosis of hereditary colorectal cancer. HNPCC patients, in particular, are often reported to have a better survival. We examined 2,340 colorectal‐cancer patients treated in our Institution: 144 HNPCC patients (Amsterdam Criteria), 161 FAP patients and 2,035 patients with sporadic cancer. Data on hereditary‐cancer patients treated between 1980 and 1995 was collected in a registry. The 2,035 sporadic colorectal‐cancer patients (controls) included all new cases treated in the Department of Gastrointestinal‐Tract Surgery during the same period. Observed survival was estimated using the Kaplan‐Meier method. Cumulative survival probability was estimated at 5 years within each group and stratified by various clinical and pathological variables. The age distribution at diagnosis of sporadic patients was significantly higher than that of FAP and HNPCC patients (median 60 years vs. 43 and 49 years; p < 0.0001). In the HNPCC group, 40% had a right cancer location, vs. 14% in the FAP group and 13% in the sporadic‐cancer group. In the sporadic group, 51% were early‐stage cancers (Dukes A or B) vs. 48.4% and 52.1% in the FAP and HNPCC groups respectively. In the HNPCC, FAP and sporadic‐cancer groups, the 5‐year cumulative survival rate was 56.9%, 54.4% and 50.6% respectively. Survival analysis by the Cox proportional‐hazards method revealed no substantial survival advantage for HNPCC and FAP patients compared with the sporadic group, after adjustment for age, gender, stage and tumor location. The hazard ratio for HNPCC was 1.01 (95% CI 0.72–1.39) and 1.27 (95% CI 0.95–1.7) for FAP patients compared with the sporadic‐colorectal‐cancer group. Int. J. Cancer 80:183–187, 1999. © 1999 Wiley‐Liss, Inc.     

Downstaging cancer in rural Africa

Cancer is usually diagnosed late in rural Africa leading to incurability and abbreviated survival. Many curable cancers present on the body surface, often recognizable early by laymen as suspicious, justifying professional referral. Cancer diagnoses in two randomly chosen Tanzanian villages were compared after conventional dispensary self‐referral vs. proactive visits in the home. Village navigators organized trips for professional consultation. In the control village 21% were self‐referred, 20% of them were sent on as suspicious, 78% had cancer (8% in men) 0.9% of the village population. In the intervention village 99% were screened, 14% were referred for professional opinion, 93% had cancer (32% in men) 1.6% (p < 0^.01 compared with control village). In the second and third years similar activity yielded 0.5% cancer annually in the control village for a 3 year total of 1.86% whereas interventional villagers had 1.4% and 0.6% cancer for a 3 year total of 3.56% (p < 0·001). Downstaging was recognized in the second and third years of intervention from 23 to 51 to 74% Stages I and II (p < 0.001) but in the control village Stages I and II changed from 11% to 22% to 37% (p = NS). The greatest downstaging occurred in breast and cervix cancers.     

Definitive radiotherapy for stage I nonsmall cell lung cancer

BACKGROUND:

The current study characterizes the overall survival (OS) and cause‐specific survival (CSS) of patients with stage I nonsmall cell lung cancer (NSCLC) who were treated with radiotherapy alone, and analyzes the variables potentially affecting survival outcomes.

METHODS:

A total of 8524 patients with stage I NSCLC (according to the sixth edition of the American Joint Committee on Cancer staging manual) who were diagnosed between 1988 and 2008 were retrospectively analyzed using the population‐based Surveillance, Epidemiology, and End Results database. Cox regression analysis was used to calculate hazard ratios (HR) from multivariate analyses.

RESULTS:

The 1‐year, 2‐year, and 5‐year OS rates were 62%, 37%, and 11%, respectively; the corresponding lung cancer CSS survival rates were 68%, 45%, and 20%, respectively. Approximately 77% of deaths were from lung cancer (5292 of 6891 total deaths). Cardiac (n = 477 deaths) and pulmonary (other than lung cancer deaths; n = 475 deaths) deaths accounted for 14% of deaths. From Cox proportional hazards analyses, male sex (HR, 1.2) and squamous cell carcinoma histology (HR, > 1.1) were found to be significantly (P < .0001) adverse prognostic factors for both OS and lung cancer CSS. A more recent calendar year of diagnosis was associated with significantly (P < .0001) improved OS (HR, 0.84 per decade) and lung cancer CSS. This trend was also significant (P < 0.0001) when restricting analyses to those patients with tumors measuring ≤ 5 cm (n = 5402 patients). T1 classification (vs T2 or T unknown) and smaller tumor size were found to be significantly (P < .0001) favorable factors.

CONCLUSIONS:

From a population‐based registry analysis of patients with stage I NSCLC, significant (albeit modest) improvements in survival in more recent years were appreciated, which likely reflect technologic advances in the diagnosis of, staging of, and radiotherapy for NSCLC. Cancer 2012. © 2012 American Cancer Society.     

残胃癌的临床病理特征及预后分析

目的探讨残胃癌的临床病理特征及预后相关因素。方法回顾性分析45例残胃癌患者的临床病理资料,并进行随访。结果45例残胃癌患者的男女比例为44：1。初次手术距残胃癌的诊断时间为5～42年,平均23年。残胃病变位于吻合口28例,位于贲门9例,其余部位8例。未分化癌1例,低分化腺癌36例,中分化腺癌7例,高分化腺癌1例。根治性切除患者的1、3、5年生存率分别为100．0％、78．8％和47．2％,非根治性切除患者的1、3、5年生存率分别为62．5％、25．0％和0,两组患者生存率差异有统计学意义（P〈0．05）。10例病变未切除患者均于2年内死亡,平均生存时间为12个月。各病理分期患者间生存率差异有统计学意义（P〈0．05）。结论残胃癌多于Billroth Ⅱ式胃大部切除术后10年以上发生,男性多于女性,病变主要位于吻合口附近。进展期残胃癌病理类型以低分化腺癌常见。残胃癌的预后与病理分期、能否行根治性切除密切相关。     

Concurrent end‐phase boost high‐dose radiation therapy for non‐small‐cell lung cancer with or without cisplatin chemotherapy*

The aim of this study was to audit the results of a high‐dose, combined‐modality prospective protocol for non‐small‐cell lung cancer in terms of survival, disease‐specific survival and toxicity. One hundred and twenty‐one patients with non‐small‐cell lung cancer were treated with a concurrent, end‐phase, boost, high‐dose radiotherapy protocol with 65 Gy in 35 fractions for more than 5 weeks. Sixty‐six patients received radiotherapy alone (group 1), 29 received concurrent chemoradiation (group 2) and 26 received neoadjuvant and concurrent chemotherapy (group 3). Thirty‐four patients had stage I disease, six had stage II and 81 had stage III. Overall median survival was 23 months: 75% at 1 year and 23% at 5 years. Median survivals for patients with stage I and stages II and III disease were 43 and 19 months, respectively. For stages II and III patients by groups 1–3, median survivals were 18, 25 and 18 months, respectively, and 2‐year survivals were 36, 52 and 38%, respectively. Toxicity was acceptable. Overall, 9% had symptomatic pneumonitis and 7% had grades 3 and 4 oesophagitis. For those who had the mediastinum included in the volume, grade ≥3 oesophagitis occurred in 0, 11 and 22% (n = 110, P = 0.001), respectively, for treatment groups 1–3. Overall treatment‐related mortality was 3%, consisting of two septic deaths, one pneumonitis and possibly one late cardiac event, all occurring in patients who had chemotherapy (7% of 55 patients). Treatment‐related mortality declined over the study period. Accelerated radiotherapy was well tolerated, with only moderate increased acute toxicity when combined with concurrent platinum chemotherapy. Toxicity was enhanced by induction chemotherapy. Overall survival outcomes were excellent for this condition. Continued use of this radiotherapy schedule is recommended as the platform for assessment of other chemotherapy schedules.     

Number of metastases, serum lactate dehydrogenase level, and type of treatment are prognostic factors in patients with brain metastases of malignant melanoma

BACKGROUND:

This multicenter study aimed to identify prognostic factors in patients with brain metastases from malignant melanoma (BM‐MM).

METHODS:

In a retrospective survey in 9 cancer centers of the German Cancer Society, 692 patients were identified with BM‐MM during the period 1986 through 2007. Overall survival was analyzed using a Kaplan‐Meier estimator and compared with log‐rank analysis. Cox proportional hazards models were used to identify prognostic factors significant for survival.

RESULTS:

The median overall survival of the entire cohort was 5.0 months (95% confidence interval [95% CI], 4 months‐5 months). Significant prognostic factors in the univariate Kaplan‐Meier analysis were Karnofsky performance status (≥70% vs <70%; P < .001), number of BM‐MM (single vs multiple; P < .001), pretreatment levels of lactate dehydrogenase (LDH) (normal vs elevated; P < .001) and S‐100 (normal vs elevated; P < .001), prognostic groups according to Radiation Therapy Oncology Group (class I vs class II vs class III; P = .0485), and treatment choice (for the cohort with single BM‐MM only) (stereotactic radiotherapy or neurosurgical metastasectomy vs others; P = .036). Cox proportional hazards models revealed pretreatment elevated level of serum LDH (hazard ratio [HR], 1.6; 95% CI, 1.3‐2.0 [P = .00013]) and number of BM‐MM (HR, 1.6; 95% CI, 1.3‐2.0 [P = .00011]) to be independent prognostic variables in the entire cohort, whereas in patients with a single BM‐MM, treatment choice (HR, 1.5; 95% CI, 1.1‐1.9 [P = .0061]) was identified as a unique prognostic factor.

CONCLUSIONS:

The overall survival of patients with BM‐MM primarily depends on the number of metastases and pretreatment level of LDH. In the case of a single brain metastasis, stereotactic radiotherapy or neurosurgical metastasectomy is by far the most important factor for improving survival. Cancer 2011. © 2010 American Cancer Society.     

Metformin intake is associated with better survival in ovarian cancer

BACKGROUND:

The objective of this case‐control study was to identify any association of metformin intake with the survival of patients with ovarian cancer.

METHODS:

In this retrospective case‐control study, women with ovarian cancer who received metformin (cases) were compared with women with ovarian cancer who did not receive metformin (controls). A 2‐layered analysis was conducted. In preliminary analysis, all cases (the OC cohort) were compared with controls at a 1:2 ratio. Subsequently, in definitive analysis, only patients who had epithelial ovarian cancer (the EOC cohort) were compared with controls at a 1:3 ratio. In the EOC cohort, cases were matched with controls for age (±5 years), International Federation of Gynecology and Obstetrics stage, and residual disease. Prognostic variables and disease specific survival were compared using chi‐square tests, the Kaplan‐Meier (log‐rank) method, and Cox proportional hazards analysis.

RESULTS:

In a preliminary analysis of the OC cohort (72 cases and 143 controls), cases had better survival (5‐year disease‐specific survival for cases vs controls, 73% vs 44%; P = .0002). In the definitive analysis of the EOC cohort (61 cases and 178 controls), the distribution of age, disease stage, optimal cytoreduction, serous histology, and platinum chemotherapy remained similar between cases and controls (P > .05). Despite these similarities, cases had significantly better survival (5‐year disease‐specific survival for cases vs controls, 67% vs 47%; P = .007). On multivariate analysis, metformin remained an independent predictor of survival (hazard ratio, 2.2; 95% confidence interval, 1.2‐3.8; P = .007) after controlling for disease stage, grade, histology, chemotherapy, body mass index, and surgical cytoreduction.

CONCLUSIONS:

The results of this study indicated an association of metformin intake with survival in patients with ovarian cancer. The receipt of metformin was associated with better survival, and the authors concluded that metformin is worthy of clinical trials in ovarian cancer. Cancer 2013. © 2012 American Cancer Society.     

Can the new American Joint Committee on Cancer staging system predict survival in rectal cancer patients treated with curative surgery following preoperative chemoradiotherapy?

BACKGROUND:

Although ypStage has been known as a strong prognosticator of recurrence and survival, the detailed interaction of ypT and ypN classification on a survival rate has never been evaluated.

METHODS:

Between October 2001 and December 2007, in total, 960 patients with locally advanced rectal cancer were enrolled retrospectively at 3 centers. Five‐year overall survival (OS) and disease‐free survival (DFS) rate were calculated for each ypTN classification.

RESULTS:

The ypT classification interacted with ypN classification to affect survival in most categories. Patients with ypStage 0 and I cancers showed a >90% 5‐year OS (ypStage 0, 96.5%; ypStage I, 92.9%; P = .346) and 5‐year DFS (ypStage 0, 90.2%; ypStage I, 90.7%; P = .879). Among ypStage III subgroups, large differences in 5‐year OS (ypStage IIIA, 90.1%; ypStage IIIB, 68.3%; ypStage IIIC, 40.5%; P < .001) and 5‐year DFS (ypStage IIIA, 74.8%; ypStage IIIB, 55.1%; ypStage IIIC, 12.3%; P < .001) were observed. OS and DFS in patients with ypStage IIIA disease were similar to or greater than those in patients with ypStage IIA or IIB/IIC disease. Four patient risk groups were defined: 1) low (ypT0‐isN0, ypT1N0, ypT2N0), 2) intermediate (ypT0‐2N1, ypT3N0), 3) moderately high (ypT0‐2N2, ypT3N1, ypT4N0), and 4) high risk (ypT3N2, ypT4N1‐2). Risk grouping showed a narrower range of survival rate compared with ypStage grouping.

CONCLUSIONS:

ypStage in rectal cancer, defined according to the 7th edition of the American Joint Committee on Cancer staging system, predicts survival for most ypNT classifications. However, patients with ypStage I rectal cancer have a similar prognosis to those with ypStage 0 cancer, and risk grouping reflects more precise survival outcomes than ypStage. Cancer 2012. © 2012 American Cancer Society.     

Prognostic value of BRAF and KRAS mutation status in stage II and III microsatellite instable colon cancers

Microsatellite instability (MSI) has been associated with favourable survival in early stage colorectal cancer (CRC) compared to microsatellite stable (MSS) CRC. The BRAF V600E mutation has been associated with worse survival in MSS CRC. This mutation occurs in 40% of MSI CRC and it is unclear whether it confers worse survival in this setting. The prognostic value of KRAS mutations in both MSS and MSI CRC remains unclear. We examined the effect of BRAF and KRAS mutations on survival in stage II and III MSI colon cancer patients. BRAF exon 15 and KRAS exon 2–3 mutation status was assessed in 143 stage II (n = 85) and III (n = 58) MSI colon cancers by high resolution melting analysis and sequencing. The relation between mutation status and cancer‐specific (CSS) and overall survival (OS) was analyzed using Kaplan–Meier and Cox regression analysis. BRAF V600E mutations were observed in 51% (n = 73) and KRAS mutations in 16% of cases (n = 23). Patients with double wild‐type cancers (dWT; i.e., BRAF and KRAS wild‐type) had a highly favourable survival with 5‐year CSS of 93% (95% CI 84–100%), while patients with cancers harbouring mutations in either BRAF or KRAS, had 5‐year CSS of 76% (95% CI 67–85%). In the subgroup of stage II patients with dWT cancers no cancer‐specific deaths were observed. On multivariate analysis, mutation in either BRAF or KRAS vs. dWT remained significantly prognostic. Mutations in BRAF as well as KRAS should be analyzed when considering these genes as prognostic markers in MSI colon cancers.     

Excellent outcomes with angiographic subsegmentectomy in the treatment of typical hepatocellular carcinoma

BACKGROUND:

The authors successfully adopted an interesting and effective treatment for hepatocellular carcinoma (HCC) referred to as angiographic subsegmentectomy (AS). This treatment involved simultaneous embolization of the peripheral feeding artery and the portal vein. The result was that almost all of the HCC and peripheral liver parenchyma developed complete anatomic necrosis.

METHODS:

To determine the effectiveness of this method, the authors retrospectively studied the local recurrence rates of 49 solitary HCCs and the long‐term survival rates of 120 patients with HCC between 2000 and 2008.

RESULTS:

The results indicated that, in 31 small, solitary HCCs (<2.0 cm), the local recurrence rate was only 9.6%; and, in 10 slightly larger HCCs (<3.0 cm), the local recurrence rate was only 10%. The 5‐year, 8‐year, and 10‐year survival rates for patients with stage I and stage I/Child‐Pugh grade A HCC were 74.27% and 77.65%, 53.05% and 51.76%, and 53% and 51.76%, respectively; and the 5‐year, 8‐year, and 10‐year survival rates for patients with stage II and stage II/Child‐Pugh grade A HCC were 66.21% and 71.41%, 39.9% and 39.60%, and 29.92% and 25%), respectively. There were no severe complications.

CONCLUSIONS:

AS should be investigated further as potential first‐line therapy for the treatment of patients with stage I and II HCC. Cancer 2010. © 2010 American Cancer Society.     

Lysyl oxidase: a lung adenocarcinoma biomarker of invasion and survival

BACKGROUND:

Lung adenocarcinoma invasion and metastasis arises from autocrine and paracrine signaling events between tumor epithelial cells and the stromal microenvironment that is mediated in part by transforming growth factor‐β (TGF‐β) signaling. The copper‐dependent amine oxidase lysyl oxidase (LOX) plays a role in extracellular matrix structure and is up‐regulated in invasive type II TGF‐β receptor‐deficient cells. The authors hypothesized that LOX expression is associated with extent of invasion and survival in patients with lung adenocarcinoma.

METHODS:

LOX immunohistochemical staining was examined in 166 surgically resected lung adenocarcinomas and results were correlated with clinicopathological features and survival.

RESULTS:

High‐intensity LOX staining was found to be associated with the linear extent of invasion (Spearman correlation coefficient = 0.2; P = .01). There was an association between high LOX staining and decreased 5‐year survival observed within the entire cohort (log‐rank P < .001) and among the patients with stage I disease (n = 119; P < .001). Cox proportional hazards regression analysis confirmed that LOX was a significant prognostic indicator of increased risk of 5‐year mortality for all patients (hazard ratio [HR], 2.55; 95% confidence interval [95% CI], 1.51‐4.30 [P < .001]) and for patients with Stage I disease (HR, 3.51; 95% CI, 1.77‐6.99 [P < .001]). LOX expression was found to be independently associated with risk of death after adjustment for relevant covariates (HR, 2.29; 95% CI, 1.33‐3.94 [P = .003]).

CONCLUSIONS:

Higher expression of LOX is associated with invasion and is an independent predictor of poor prognosis in patients with early stage lung adenocarcinoma. Cancer 2011. © 2010 American Cancer Society.