Impact of Preoperative and Postoperative FOLFOX Chemotherapies in Patients with Resectable Colorectal Liver Metastasis

Purpose

Whether the survival benefit of perioperative FOLFOX in patients with liver metastases of colorectal cancer (LMCRC) is provided by preoperative chemotherapy (CT), postoperative CT, or both remains unclear. This study aimed to evaluate, in patients with resectable LMCRC, the survival impact of preoperative and postoperative separately.

Methods

Between 2000 and 2010, the 179 patients (126 men, age 61?±?11 years) with initially resectable LMCRC, who underwent liver resection (LR) and were offered pre- and/or postoperative FOLFOX were included. Twenty-four (13 %) patients did not receive CT, 27(15 %) patients received only preoperative CT, 71 (40 %) patients received only postoperative CT, and 57 (32 %) patients received both pre- and postoperative CT.

Results

Operative morbidity and mortality rates were 19 and 0.6 %, respectively. At 1, 3, and 5 years, OS and DFS rates were 97, 66, 46 and 60, 32, and 24 %, respectively. Postoperative FOLFOX was an independent predictor of increased OS (HR?=?0.55 [95 % CI, 0.35–0.87] p?=?0.01) and DFS (HR?=?0.54 [0.36–0.82] p?=?0.0017), whereas the synchronous onset of the metastasis and the presence of radiographically occult liver metastases were independent predictors of poorer OS. Alternatively, preoperative FOLFOX had no significant influence on OS (HR?=?0.96 [0.57–1.60] p?=?0.83) or DFS (HR?=?1.05 [0.66–1.66] p?=?0.87).

Conclusions

The survival benefit of FOLFOX in patients with resectable LMCRC may be provided by postoperative rather than preoperative administration.     

CYP2D6 polymorphisms influence tamoxifen treatment outcomes in breast cancer patients: a meta-analysis

Purpose

To evaluate whether breast cancer (BC) patients with CYP2D6 gene variation have different clinical tamoxifen (TAM) treatment outcomes to those with normal function of CYP2D6.

Methods

Systematic searches of the PubMed up to February 21, 2013, were retrieved. The study end points were disease-free survival (DFS) and overall survival (OS). Fixed or random-effects meta-analytical models were used to calculate summary hazard ratio (HR) and corresponding 95 % confidence intervals (CIs). Meta-regression, Galbraith plots, subgroup analysis, and sensitivity analysis were also performed.

Results

A total of 11,701 BC patients from 20 trials were included. Compared with reduced CYP2D6 function, normal function was associated with a trend toward improved DFS (HR = 1.37, 95 % CI 1.12–1.69, P = 0.002) and OS (HR = 1.25, 95 % CI 1.03–1.50, P = 0.021). We found significant heterogeneity between studies. When the analysis was stratified into subgroups, significantly worse DFS was found in the groups of intermediate metabolizer versus extensive metabolizer (HR = 1.65, 95 % CI 1.04–2.64, P = 0.035), Asian population (HR = 3.29, 95 % CI 1.64–6.63, P = 0.001), 5 years TAM treatment duration (HR = 1.59; 95 % CI 1.14–2.22, P = 0.006), concomitant chemotherapy (HR = 1.35, 95 % CI 1.04–1.76, P = 0.025), and TAM alone (HR = 1.44, 95 % CI 1.44–2.06, P = 0.045). With respect to OS, no significant association was demonstrated in stratified analyses.

Conclusions

We concluded that CYP2D6 polymorphisms may influence tamoxifen treatment outcomes of DFS in BC patients.     

Retrospective Comparison of CAPOX and FOLFOX Dose Intensity,Toxicity, and Clinical Outcomes in the Treatment of Metastatic Colon Cancer

Purpose

The treatment of metastatic colon cancer (mCC) utilizes either combination therapies or sequential monotherapy followed by combination therapy in subsequent lines of treatment. Patients often receive therapy consisting of oxaliplatin with intravenous 5-fluoruacil (5-FU) (FOLFOX) or oral capecitabine (CAPOX). A retrospective analysis was performed comparing median dose intensity (MDI), overall survival (OS), progression-free survival (PFS), and toxicity profiles of these two regimens in mCC.

Methods

One hundred twenty-two mCC patients (pts) received either FOLFOX6 (n?=?46) or CAPOX (n?=?76). Age, gender, and Eastern Cooperative Oncology Group (ECOG) performance status at diagnosis were balanced between groups. MDI was compared by calculating a percent of target dose achieved in the average cycle for each patient and taking the median of this value.

Results

Oxaliplatin MDI trended towards being lower in those treated with CAPOX compared to FOLFOX (87.5 vs 93 %, p?=?0.0874), and capecitabine (CA) MDI was significantly lower than 5-FU (82.0 vs 100 %, p?<?0.0001). There was a trend to more dose-limiting toxicities (DLTs) in pts treated with CAPOX (68.42 vs 54.35 %, p?=?0.1268), and grade?≥?2 toxicities were more frequent in CAPOX-treated pts (38.16 vs 15.22 % of patients, p?=?0.0079). Survival analysis demonstrated trends towards improved median OS (9.86 vs 7.46 months, p?=?0.1183) and median PFS (4.34 vs 3.33 months, p?=?0.1674) with CAPOX. In multivariate analysis, CAPOX was associated with improved OS (p?=?0.0156, hazard ratio (HR) 0.559) and disease-free survival (DFS) (p?=?0.0094, HR 0.549).

Conclusions

Patients treated with CAPOX received lower doses of oxaliplatin and fluoropyrimidine compared to FOLFOX and had toxicities of higher grade but did not have worsened clinical outcomes.     

Is extracapsular tumour spread a prognostic factor in patients with early breast cancer?

Background

This study searched for extra capsular tumour spread (ECS) as a prognostic factor for recurrence in terms of Disease Free Survival (DFS) and Overall Survival (OS).

Patients and methods

For this study, from a retrospective database of the Doubs cancer registry, 823 eligible women with node positive breast cancer treated from February 1984 to November 2000 were identified. The following factors were evaluated: ECS, numbers of involved nodes, histological tumour grade, tumour size, status of estrogen and progesterone receptors, and age of patient. A Cox proportional hazards method was used to search for significant factors related to OS and DFS length.

Results

In the multivariate analysis, factors related to DFS length were found to be: tumour grade (aHR 0.76, 95 % CI 0.61–0.96, p = 0.02), ECS status (aHR 0.7, 95 % CI 0.49–0.96, p = 0.03), progesterone (PgR) status (aHR 0.63, 95 % CI 0.44–0.85 p = 0.008), number of nodes involved (aHR 0.75, 95 % CI 0.56–1, p = 0.05). The multivariate analysis for OS found as significant factors: tumour grade (aHR 0.76, 95 % CI 0.61–0.95; p = 0.02) and PgR status (aHR 0.8, 95 % CI 0.56–0.99, p = 0.02).

Conclusions

This study might suggest taking into account ECS status in the adjuvant decision-making process.     

Concurrent radiotherapy plus epidermal growth factor receptor inhibitors in patients with human papillomavirus-related head and neck cancer

Purpose

Concurrent radio-chemotherapy (RT-CT) is the standard treatment for locally advanced head and neck squamous cell carcinoma (LA-HNSCC), but RT plus epidermal growth factor receptor (EGFR) inhibitors is an effective option when CT is not appropriate. Human papillomavirus (HPV) is associated with an improved prognosis in LA-HNSCC; however, it has not been fully studied as a prognostic factor after RT + EGFR inhibitors.

Experimental design

Immunohistochemical expression of p16INK4A and PCR of HPV16 DNA were retrospectively analyzed in tumor blocks from 52 stage III/IV LA-HNSCC patients treated with RT + EGFR inhibitors. Disease-free survival (DFS) and overall survival (OS) were analyzed by the Kaplan–Meier method.

Results

DNA of HPV16 was found in six of 52 tumors (12 %) and p16 positivity in eight tumors (15 %). After a median follow-up time of 45 months (6–110), p16-positive patients treated with RT + EGFR inhibitors showed an improved DFS (2-year DFS 75 vs. 44 %, HR 0.25, 95 % CI 0.06–0.99, p = 0.047) compared with p16-negative patients. These differences were outperformed when compared by HPV16 status (2-year OS rates of 83 vs. 58 %, HR 0.17, 95 % CI 0.02–0.99, p = 0.049 and 2-year DFS rates of 83 vs. 45 %, HR 0.17, 95 % CI 0.02–0.99, p = 0.049). In the Cox regression analysis with OS as the end point, ECOG 0–1 was the only prognostic factor independently associated with a good prognosis in the multivariable analysis.

Conclusion

In this study, p16/HPV16-positive patients with LA-HNSCC treated with RT + EGFR inhibitors showed a better survival, not confirmed in multivariate analysis.     

Time to Adjuvant Therapy and Other Variables in Localized Gastric and Gastroesophageal Junction (GEJ) Cancer (IJGC-D-13-00162)

Background

Adjuvant chemotherapy with or without radiation in patients with completely resected gastric and gastroesophageal (GE) junction cancer has been associated with better outcomes. In practice, however, there are often delays in commencing adjuvant therapy. The study aims to determine the prognostic importance of timing of adjuvant therapy in such patients.

Methods

A cohort of patients with early stage (IB–IVM0) gastric and GE junction cancer diagnosed between 2002 and 2007 in the province of Saskatchewan was assessed. Cox proportional hazard analysis was used to identify various clinic-pathological factors that correlate with disease-free survival (DFS).

Results

One hundred seventy-four eligible patients with a median age of 71 years (range 36–93) and M/F ratio of 113:61 were identified. Of 174 patients, 60 (35 %) received adjuvant therapy. Median follow-up was 18 months (interquartile range 9–37). Twenty-eight percent received adjuvant therapy within 56 days. Median DFS of patients who received adjuvant therapy within 56 days was 37 months (95 % CI 6.6–67.3) versus 33 months (95 % CI 18.3–47.7) if adjuvant therapy was administered beyond 56 days (p?=?0.67). On multivariate analysis, state III–IVM0 disease, hazard ratio (HR) 2.4 (95%CI 1.6–3.5), and age ≥65 years, HR 2.2 (95 % CI 1.4–3.5), were significantly correlated with inferior disease-free survival.

Conclusions

Only about one third of patients who received adjuvant therapy were treated within 56 days of surgery. Although stages III and IVM0 and older age were associated with inferior outcome, delay in adjuvant therapy was not associated with inferior survival.     

Identification of Distinct Phenotypes of Locally Advanced Pancreatic Adenocarcinoma

Background

A significant number of pancreatic ductal adenocarcinoma present as locally advanced disease. Optimal treatment remains controversial. We sought to analyze the clinical course of locally advanced pancreatic adenocarcinoma (LAPC) in order to identify potential distinct clinical phenotypes.

Methods

Patients (pts) diagnosed with LAPC who survived >2 months were identified from institutional databases. Clinical details were collected. Sequential re-staging scans were reviewed. Progression-free survival (PFS), time from progression to death (TTD), and overall survival (OS) were estimated with Kaplan–Meier method and compared with log-rank test.

Results

Between 2005 and 2011, 40 pts were identified. Median age was 66 yrs (range, 43–74) and 60 % (n?=?24) were male. All pts received chemotherapy. Median OS was 11.3 months. Twenty patients (50 %) had local progression only (LP) and 16 (40 %) had metastatic progression (MP) at first documentation of progression, while four patients (10 %) had stable disease. PFS was 4.0 vs 5.6 months (hazard ratio (HR) 0.97; 95 % CI 0.49–1.93, p?=?0.94) for LP and MP, respectively. Three of the patients with LP (15 %) eventually developed metastatic disease after a median of 4.2 months (3.7–9.6). For MP patients, five had concurrent local progression. Sites of disease were lung (eight), peritoneum (five), liver (three), and bone (one). TTD for LP and MP was 5.6 vs 1.4 months (HR 0.62; 95 % CI 0.28–1.39, p?=?0.24) and OS was 13.2 vs 8.0 months (HR 0.59; 95 % CI 0.28–1.25, p?=?0.017), respectively.

Conclusions

We identified two subgroups of LAPC with distinctive behavior, one local dominant progression with low predilection for metastases and another with rapid metastatic development and worse survival. Early recognition of these phenotypes might allow a more tailored treatment approach to improve outcome.     

Prognosis of gastric carcinoma patients aged 85 years or older who underwent surgery or who received best supportive care only

Background

There is controversy regarding strategies for treating very elderly patients with gastric carcinoma. We aimed to assess survival after surgery in very elderly patients according to their clinical characteristics.

Methods

Gastric cancer patients aged ≥85 years were retrospectively reviewed. There were no significant differences in clinical characteristics between 58 patients with curative resection (OP group) and 32 patients with best supportive care alone (BSC group) in cancer stage IA–IIIC and with a performance status of 0–3.

Results

Overall survival (OS) was significantly better in the OP group than in the BSC group in females [hazard ratio (HR) 0.27, 95 % confidence interval (CI) 0.12–0.57, P < 0.001] but not in males (HR 0.71, 95 % CI 0.35–1.49, P = 0.35). OS was significantly better in the OP group in patients aged 85–89 years (HR 0.44, 95 % CI 0.25–0.78, P = 0.006) but not in patients aged ≥90 years (HR 0.47, 95 % CI 0.12–1.66, P = 0.24). OS was significantly better in the OP group in patients with stage IB–IIIC cancer (HR 0.29, 95 % CI 0.14–0.58, P < 0.001) but not in patients with stage IA cancer (HR 0.52, 95 % CI 0.21–1.27, P = 0.15).

Conclusions

Females, patients aged 85–89 years, and patients with stage IB–IIIC cancer had significantly better OS with surgery than without. For males, patients aged ≥90 years, or stage IA patients, the decision to perform surgery should be carefully made, and BSC might be an optimal strategy.     

Evaluation of the Predictive and Prognostic Values of Stromal Tumor-Infiltrating Lymphocytes in HER2-Positive Breast Cancers treated with neoadjuvant chemotherapy

Background

Stromal tumor-infiltrating lymphocytes (sTILs) have been identified as a predictive biomarker for response to neoadjuvant chemotherapy (NAC) and prognosis in human epidermal growth factor receptor 2 (HER2)-positive breast cancers. However, standardized scoring methods for use in clinical practice need to be established, and the optimal threshold of sTILs to predict pathological complete response (pCR) and prognosis in HER2+ breast cancers has not yet been defined.

Objective

The predictive and prognostic values of sTILs in patients with HER2-positive breast cancer treated with NAC were evaluated, with the aim to explore the optimal thresholds of sTILs and to investigate the feasibility of scoring methods in clinical practice.

Patients and Methods

A total of 143 core needle biopsy specimens of HER2-positive invasive breast cancers obtained from Chinese patients who had been treated with trastuzumab-based NAC followed by surgery between 2009 and 2015 were extracted from the pathology database of Fudan University Shanghai Cancer Center. sTIL levels in the pre-NAC core needle biopsy specimens were scored using methods recommended by the International TILs Working Group 2014. The associations between sTILs and pCR, disease-free survival (DFS), and overall survival (OS) were evaluated, and the optimal thresholds for predictive and prognostic values of sTILs were analyzed.

Results

First, sTILs were associated with a higher pCR rate in HER2-positive breast cancers. Univariate (per 10% sTILs: odds ratio [OR] 1.05, 95% confidence interval [CI] 1.02–1.08, p?=?0.001) and multivariate regression analyses (per 10% sTILs: OR 1.04, 95% CI 1.00–1.07, p?=?0.034) indicated that sTILs as a continuous variable were a significant predictor of pCR in HER2-positive breast cancers. Receiver operating characteristics (ROC) curve analysis showed that a 20% threshold best distinguished the pCR subgroup from the non-pCR subgroup. The dichotomized sTILs with a threshold set at 20% was a strong predictor of pCR in the univariate (OR 0.25, 95% CI 0.12–0.52, p?<?0.001) and multivariate analyses (OR 0.35, 95% CI 0.14–0.87, p?=?0.024). Second, sTILs were associated with better prognosis in HER2-positive breast cancers. Univariate (DFS: hazard ratio [HR] 0.91, 95% CI 0.88–0.95, p?<?0.001; OS: HR 0.88, 95% CI 0.83–0.94, p?<?0.001), and multivariate analyses (DFS: HR 0.93, 95% CI 0.90–0.97, p?<?0.001; OS: HR 0.92, 95% CI 0.86–0.98, p?=?0.009) suggested that sTILs as a continuous variable had a strong predictive value for improved DFS and OS. As a binary variable with a threshold of 20%, univariate (DFS: HR 6.60, 95% CI 2.91–14.95, p?<?0.001; OS: HR 10.29, 95% CI 2.37–44.66, p?=?0.002) and multivariate analyses (DFS: HR 3.87, 95% CI 1.65–9.12, p?=?0.002; OS: HR 4.74, 95% CI 1.02–22.01, p?=?0.047) indicated that patients with ≥ 20% sTILs had a significantly better prognosis than the patients with < 20% sTILs.

Conclusions

Our study indicates that baseline sTILs scored by methods recommended by the International TILs Working Group in pre-NAC core needle biopsy specimens are significantly correlated with pCR and prognosis in HER2-positive breast cancers. A 20% threshold for sTILs may be a feasible diagnostic marker to predict pCR to NAC and prognosis in patients with HER2-positive breast cancers.

     

Prognostic significance of p53 expression in malignant bone tumors: a meta-analysis

Osteosarcoma and Ewing’s sarcoma are the two most common primary malignant bone tumors, and findings of prognostic factors are important for clinicians to decide treatment options. High p53 expression has been implicated in tumor development and progression, but studies investigating the prognostic role of p53 overexpression in malignant bone tumors report conflicting findings. We performed a meta-analysis to assess the relationship between p53 overexpression and the survival of malignant bone tumors. A meta-analysis of 13 studies with a total of 703 patients was carried out to evaluate the association between p53 overexpression and overall survival (OS) and disease-free survival (DFS) in patients with malignant bone tumors. The pooled hazard ratio (HR) with its 95 % confidence interval (CI) was used as the effect size estimate. There was no between-study heterogeneity in both OS studies (I ²?=?0.0 %) and DFS studies (I ²?=?0.0 %). Overall, high p53 expression predicted both poor OS (HR 2.13, 95 % CI 1.81–2.52, P?<?0.001) and poor DFS (HR 2.06, 95 % CI 1.58–2.69, P?<?0.001) in patients with malignant bone tumors. Subgroup analyses by tumor types suggested that p53 expression predicted poor OS in both osteosarcoma patients (HR 2.15, 95 % CI 1.78–2.60, I ²?=?15.2 %, P?<?0.001) and Ewing’s sarcoma patients (HR 2.09, 95 % CI 1.47–2.97, I ²?=?0.0 %, P?<?0.001). Besides, p53 expression also predicted poor DFS in both osteosarcoma patients (HR 2.38, 95 % CI 1.60–3.52, I ²?=?0.0 %, P?<?0.001) and Ewing’s sarcoma patients (HR 1.83, 95 % CI 1.28–2.63, I ²?=?0.0 %, P?=?0.001). Egger’s test also did not suggest evidence for publication bias in both OS studies (P?=?0.615) and DFS studies (P?=?0.258). High p53 expression indicates a poorer prognosis for patients with osteosarcoma and Ewing’s sarcoma.     

Frequency and impact of grade three or four toxicities of novel agents on outcomes of older patients with chronic lymphocytic leukemia and non-Hodgkin lymphoma (alliance A151611)

Objective

Older patients with cancer suffer from chemotherapy-related toxicities more frequently than younger patients. As novel agents are being used more commonly in chronic lymphocytic leukemia (CLL) and non-Hodgkin lymphoma (NHL), toxicities of these agents in older patients have not been well studied. Further, impact of these toxicities on outcomes in the elderly is unknown. This study aimed to answer both questions.

Association of obesity and overweight with overall survival in colorectal cancer patients: a meta-analysis of 29 studies

Purpose

Previous studies that assessed the relationship between obesity, overweight, and survival in colorectal cancer (CRC) have provided conflicting results. Therefore, we quantitatively summarized existing evidence to estimate the association between obesity/overweight and overall survival (OS) in CRC patients and explored potentially important sources of variability.

Methods

Eligible studies were identified via PubMed and EMBASE searches. The summary hazard ratio (sHR) was estimated using a fixed-effects or random-effects model according to the heterogeneity between the studies. Meta-regression and subgroup analyses were performed to explore potential sources of heterogeneity.

Results

A total of 29 eligible studies, with 51,303 CRC patients, were finally included. The overall analysis showed worse OS among obese patients [sHR 1.10, 95 % confidence intervals (CI) 1.06–1.15], but not among overweight patients (sHR 0.92, 95 % CI 0.86–1.00), than in normal-weight patients. Considerable heterogeneity was observed across studies, which was primarily attributed to the timing of body mass index (BMI) assessment (meta-regression p < 0.05). The association between obesity and worse OS was strengthened when BMI was assessed before diagnosis (sHR 1.30, 95 % CI, 1.17–1.44). Conversely, post-diagnostic, in particular post-treatment, overweight was associated with a better OS (sHR 0.79, 95 % CI 0.70–0.91). Other factors, including gender, geographic location, and stage, may also modify the prognostic value of obesity or overweight.

Conclusions

Obese but not overweight patients appear to have worse OS than normal-weight patients with CRC. The associations of obesity and overweight with OS in CRC patients majorly depend upon the timing of BMI assessment.     

The influences of peritumoral lymphatic invasion and vascular invasion on the survival and recurrence according to the molecular subtypes of breast cancer

Purpose

We aimed to compare the influences of lymphatic invasion (LI) and vascular invasion (VI) on survival and recurrence according to the molecular subtypes of breast cancer.

Methods

We retrospectively analyzed data on 820 breast cancer patients and assessed overall survival (OS) and disease-free survival (DFS) according to LI and VI using the Kaplan–Meier estimator and the Cox proportional hazards model.

Results

Both positive LI and positive VI showed inferior OS and DFS compared with negative LI and negative VI (all p < 0.001). Both positive LI and positive VI showed higher local, regional, and distant recurrence rates (p = 0.002 for regional recurrence of VI, p < 0.001 for all the others). Although LI was a significant independent predictor of OS (hazard ratio [HR] 1.927; 95% confidence interval [CI] 1.046–3.553) and DFS (HR 1.815; 95% CI 1.063–3.096), VI was not in the multivariate analyses. Regarding OS, both positive LI and positive VI showed worse survival rates in the luminal A (p = 0.016 and p = 0.024, respectively) and triple negative subtypes (both p < 0.001). Regarding DFS, LI was a significant prognosticator in the luminal A and triple negative (both p < 0.001) subtypes. VI was a significant prognosticator across all molecular subtypes, although the prognostic impact was most prominent in the luminal A subtype (p < 0.001).

Conclusions

Both LI and VI were significant, unfavorable prognostic factors of OS and DFS, especially in the luminal A and triple negative breast cancer subtypes. Although LI was a significant independent predictor of OS and DFS, VI was not after the multivariate analyses.

     

Influence of the in situ component in 389 infiltrating ductal breast carcinomas

Background

Our aim was to evaluate and compare lymph node involvement, as well as disease-free survival (DFS) and overall survival (OS), between infiltrating ductal carcinoma with (group 1) and without (group 2) intraductal carcinoma component in order to determine the prognostic value of the intraductal component.

Methods

Data from 389 cases of infiltrating ductal carcinoma of the breast were included in the study by means of reviewing medical charts and pathology slides.

Results

There was no statistically significant difference between both groups regarding node status. The 5-year DFS rate was 90.7% in group 1 and 81.8% in group 2 (p = 0.014), with a median follow-up of 73.2 months (95% CI 68.3–77.4). There was no statistically significant difference in 5-year OS between groups (98% group 1 vs. 93% group 2) with a median global survival of 134 months (95% CI 131–137).

Conclusions

The presence of intraductal component in the infiltrating carcinoma seems to increase DFS and may be an independent and favorable prognostic factor for breast cancer.     

Three-year outcomes of a phase II study of adjuvant chemotherapy with S-1 plus docetaxel for stage III gastric cancer after curative D2 gastrectomy

Background

We have previously reported the superior feasibility and safety of adjuvant S-1 plus docetaxel in patients with stage III gastric cancer during a prospective phase II study. We report 3-year follow-up data on patients enrolled in this study.

Patients and methods

Fifty-three patients with histologically confirmed stage III gastric cancer who underwent gastrectomy with D2 lymphadenectomy were enrolled into this study. They received oral S-1 (80 mg/m²/day) for 2 consecutive weeks and intravenous docetaxel (40 mg/m²) on day 1, repeated every 3 weeks (one cycle). Treatment was initiated within 45 days after surgery and repeated for four cycles, followed by S-1 monotherapy (4 weeks on, 2 weeks off) until 1 year after surgery. Three-year overall survival (OS) and disease-free survival (DFS) were evaluated.

Results

The OS rate at 3 years was 78.4 % [95 % confidence interval (CI), 67.9–90.6 %] and the DFS rate at 3 years was 66.2 % (95 % CI, 54.4–80.7 %). Subgroup analyses according to disease stage showed a 3-year OS and DFS rate of 85.7 % (95 % CI, 74.9–98.1 %) and 70.8 % (95 % CI, 57.1–87.8 %) for stage IIIA, and 62.5 % (95 % CI, 42.8–91.4 %) and 56.2 % (95 % CI, 36.5–86.7 %) for stage IIIB, respectively.

Conclusions

On the basis of 3-year follow-up data, postoperative adjuvant therapy with S-1 plus docetaxel yielded promising OS and DFS in stage IIIA gastric cancer patients who had undergone D2 gastrectomy. We believe that this regimen is a candidate for future phase III trials studying the optimal adjuvant chemotherapy regimen for stage III gastric cancer.     

Carcinosarcoma of the ovary compared to ovarian high-grade serous carcinoma: impact of optimal cytoreduction and standard adjuvant treatment

Objective

The purpose of this retrospective study was to compare the prognoses of women with ovarian carcinosarcoma (OCS) who had optimal cytoreductive surgery followed by platinum plus taxane combination chemotherapy to those of women with ovarian high-grade serous carcinoma (HGSC) treated in the same manner.

Methods

A multicenter, retrospective department database review was performed to identify patients with OCS at eight gynecologic oncology centers in Turkey. A total of 54 women with OCS who had undergone optimal cytoreductive surgery followed by platinum plus taxane combination chemotherapy between 1999 and 2017 were included in this case–control study. Each case was matched to two women with ovarian HGSC who had undergone optimal cytoreductive surgery followed by platinum plus taxane combination chemotherapy. The Kaplan–Meier method was used to generate survival data. Factors predictive of outcome were analysed using Cox proportional hazards models.

Results

Median disease-free survival (DFS) was 29 months [95% confidence interval (CI) 0–59, standard error (SE) 15.35] versus 27 months (95% CI 22.6–31.3, SE 2.22; p = 0.765) and median overall survival (OS) was 62 versus 82 months (p = 0.53) for cases and controls, respectively. For the entire cohort, the presence of ascites [hazard ratio (HR) 2.32; 95% CI 1.02–5.25, p = 0.04] and platinum resistance [HR 5.05; 95% CI 2.32–11, p < 0.001] were found to be independent risk factors for decreased OS.

Conclusion

DFS and OS rates of patients with OCS and HGSC seem to be similar whenever optimal cytoreduction is achieved and followed by platinum plus taxane combination chemotherapy.

     

Increasing preoperative body size in breast cancer patients between 2002 and 2016: implications for prognosis

Overweight and obesity are increasing worldwide, but the extent in breast cancer patients is unknown. The two aims were to study secular trends in preoperative body mass index (BMI), waist circumference, and breast volume and their impacts on clinical outcome. BMI, waist circumference, and breast volume were measured preoperatively in 24–99-year-old primary breast cancer patients (n?=?640) in Sweden 2002–2016. The measurements were analyzed alone and combined in relation to recurrence and overall survival (OS). BMI, waist circumference, and breast volume increased 2002–2016 (p_trends?<?0.0001). Of these, a breast volume?≥?850 mL was associated with the strongest recurrence-risk (adjusted hazard ratio [_adjHR] 1.67; 95% CI 1.17–2.39), especially combined with waist circumference?≥?80 cm (_adjHR 2.07; 95% CI 1.25–3.44), while BMI?≥?25 kg/m² or large waist circumference conferred almost a twofold risk for death (both Log-Rank p?≤?0.0001). Chemotherapy seemed to counteract the negative impact of a high BMI or large waist circumference on OS. Large breast volume was the strongest predictor for recurrence in all treatment groups. In conclusion, preoperative BMI, waist circumference, and breast volume increased between 2002 and 2016. Larger body size negatively impacted breast cancer-free interval and OS. If confirmed, body measurements may help select patients requiring more individualized treatment.     

Prognostic role of D-dimer in patients with lung cancer: a meta-analysis

D-dimer detection in patients suffering from a variety of different types of cancer has become a hot point as an emerging and promising biomarker. In this study, therefore, we evaluated the prognostic role of D-dimer in lung cancer. Initial literature was identified using the PubMed, EMBASE, and CNKI. The primary data was hazard ratio (HR) with 95 % confidence interval (CI) of survival outcomes in candidate articles, including overall survival (OS) and disease-free survival (DFS). Finally, 11 eligible studies were included in this meta-analysis, which were published between 1996 and 2013. The estimated pooled HR and 95 % CI for OS of all studies was 2.06 (95 % CI 1.64–2.58, p?<?0.00001) and the HR and 95 % CI for DFS in one study was 3.38 (95 % CI 1.17–9.75, p?=?0.002). The HRs and 95 % CIs for OS in Asian and non-Asian patients were 2.48 (95 % CI 1.60–3.84, p?<?0.0001) and 1.89 (95 % CI 1.44–2.47, p?<?0.00001), respectively. When we further analyzed the data by various detecting methods, the pooled HR and 95 % CI for OS were 3.22 (95 % CI 1.99–5.21, p?<?0.00001) for ELISA, 1.52 (95 % CI 1.25–1.86, p?<?0.0001) for Latex assay, and 1.79 (95 % CI 1.19–2.69, p?=?0.005) for immunoturbidimetry assay. We also did subgroup analysis according to the ratio of histological type and clinical stage. All the above analysis had positive results. This meta-analysis showed that D-dimer had a fine predictive role in lung cancer patients, especially in Asian group. Also, it demonstrated that D-dimer had a stronger predictive value by using the method ELISA.     

Treatment outcomes of gemcitabine alone versus gemcitabine plus platinum for advanced biliary tract cancer: a Korean Cancer Study Group retrospective analysis

Purpose

ABC-02 trial of gemcitabine plus cisplatin combination showed prolongation of overall survival in biliary tract cancer (BTC) patients. In this multicenter retrospective study, we evaluated the treatment outcome of gemcitabine combined with platinum (GP) compared to that of gemcitabine (G) alone in Korean BTC patients.

Methods

One hundred and fifty-one patients with histologically confirmed biliary tract adenocarcinoma were enrolled at nine institutions between July 2003 and May 2011, including 100 treated with GP and 51 treated with G.

Results

With a median follow-up of 7.7 months (range 0.4–38.3 months), the median overall survival (OS) was 12.4 months [95 % confidence interval (CI) 9.4–15.6 months] of the G group, which was not significantly different for the median OS of 11.0 months (95 % CI 9.7–12.3 months) of the GP group (p = 0.599). The median progression-free survival (PFS) was 3.9 months (95 % CI 0.8–7.0 months) in the G group and 3.3 months (95 % CI 2.6–4.0 months) in the GP group (p = 0.504). Overall response rates (ORR) were 18.8 % in G group and 23.9 % in GP group (p = 0.485).

Conclusions

There was no significant difference in ORR, PFS, or OS for patients between the G group and the GP group, which was different from the ABC-02 trial. Therefore, gemcitabine monotherapy and GP combination are both effective regimens for Korean BTC patients.     

The prognosis and clinicopathology of CXCR4 in gastric cancer patients: a meta-analysis

The chemokine receptor 4 (CXCR4) has been widely investigated in diagnosis and prognosis of gastric cancer (GC). However, the impact of CXCR4 on GC patients remains controversial; Here, we conducted a meta-analysis to obtain the precise role of CXCR4 in GC prognosis and clinicopathology. Thirteen published studies with a total of 1,936 patients were included. Original data included the hazard ratio (HR) of overall survival (OS) and odds ratio (OR) in GC patients. We combined HR/OR with 95 % confidence interval (CI) to estimate the hazard. In this study, OS was significantly related to CXCR4 expression, with the HR 2.63 (95 % CI 1.69–4.09; p?<?0.0001), and a significant correlation was also revealed between CXCR4 expression and stage (I?+?II, +) (OR 0.52, 95 % CI 0.32–0.83; p?=?0.007), depth of invasion (T1/T2, +) (OR 0.44, 95 % CI 0.27–0.73; p?=?0.001), lymph node metastasis (LN, +) (OR 2.30, 95 % CI 1.57–3.36; p?<?0.0001), as well as vascular invasion (vas.inv, +) (OR 0.72, 95 % CI 0.53–0.98; p?=?0.04). Heterogeneity was observed among the included studies with OS (I ²?=?51 %), stage (I ²?=?78 %), depth of invasion (I ²?=?74 %), lymph node metastasis (I ²?=?64 %), and histology differentiation (I ²?=?79 %). No publication bias was observed. In conclusion, this meta-analysis showed CXCR4 expression indicates poor prognosis in GC patients with advanced stage or deep invasion in GC tissues, which also implied lymph node metastasis and vascular invasion. Thus, CXCR4 could help predict patient prognosis and guide clinical diagnosis and treatment.