Overall Survival In Female Patients Research Articles

The pregnancy-associated protein glycodelin as a potential sex-specific target for resistance to immunotherapy in non-small cell lung cancer

Lung cancer has been shown to be targetable by novel immunotherapies which reactivate the immune system and enable tumor cell killing. However, treatment failure and resistance to these therapies is common. Consideration of sex as a factor influencing therapy resistance is still rare. We hypothesize that the success of the treatment is impaired by the presence of the immunosuppressive pregnancy-associated glycoprotein glycodelin that is expressed in patients with non-small-cell lung cancer (NSCLC). We demonstrate that the glycan pattern of NSCLC-derived glycodelin detected by a lectin-based enrichment assay highly resembles amniotic fluid-derived glycodelin A, which is known to have immunosuppressive properties. NSCLC-derived glycodelin interacts with immune cells in vitro and regulates the expression of genes associated with inflammatory and tumor microenvironment pathways. In tumor microarray samples of patients, high glycodelin staining in tumor areas results in an impaired overall survival of female patients. Moreover, glycodelin colocalizes to tumor infiltrating CD8+ T cells and pro-tumorigenic M2 macrophages. High serum concentrations of glycodelin prior to immunotherapy are associated with a poor progression-free survival (p < 0.001) of female patients receiving PD-(L)1 inhibitors. In summary, our findings suggest that glycodelin not only is a promising immunological biomarker for early identification of female patients that do not benefit from the costly immunotherapy, but also represents a promising immunotherapeutic target in NSCLC to improve therapeutic options in lung cancer.

THSD7A Positivity Predicts Poor Survival and Is Linked to High FAK Expression and FGFR1-Wildtype in Female Patients with Squamous Cell Carcinoma of the Lung.

Lung cancer is the leading cause of cancer-related deaths in the western world, with squamous cell carcinoma being one of the most common histological subtypes. Prognostic and predictive markers are still largely missing for squamous cell carcinoma of the lung (LSCC). Several studies indicate that THSD7A might at least play a role in the prognosis of different tumors. FAK seems to play an important role in lung cancer and is discussed as a potential therapeutic target. In addition, there is evidence that FAK-dependent signaling pathways might be affected by THSD7A. For that reason, we investigated the role of THSD7A as a potential tumor marker in LSCC and whether THSD7A expression has an impact on the expression level of FAK. A total of 101 LSCCs were analyzed by immunohistochemistry using tissue microarrays. THSD7A positivity was associated with poor overall survival in female patients and showed a relation to high FAK expression in this subgroup. To our knowledge, we are the first to report these correlations in lung cancer. The results might be proof of the assumed activation of FAK-dependent signaling pathways by THSD7A and that as a membrane-associated protein, THSD7A might serve as a putative therapeutic target in LSCC.

Effect of postoperative adjuvant chemotherapy on prognosis of patients with intrahepatic cholangiocarcinoma:a multicenter retrospective study

Objectives: To examine the influence of adjuvant chemotherapy after radical resection on the survival of patients with intrahepatic cholangiocarcinoma(ICC) and to identify patients who may benefit from it. Methods: The clinical and pathological data of 654 patients with ICC diagnosed by postoperative pathology from December 2011 to December 2017 at 13 hospitals in China were collected retrospectively. According to the inclusion and exclusion criteria,455 patients were included in this study,including 69 patients (15.2%) who received adjuvant chemotherapy and 386 patients (84.8%) who did not receive adjuvant chemotherapy. There were 278 males and 177 females,with age of 59 (16) years (M(IQR))(range:23 to 88 years). Propensity score matching (PSM) method was used to balance the difference between adjuvant chemotherapy group and non-adjuvant chemotherapy group. Kaplan-Meier method was used to plot the survival curve,the Log-rank test was used to compare the difference of overall survival(OS) and recurrence free survival(RFS)between the two groups. Univariate analysis was used to determine prognostic factors for OS. Multivariate Cox proportional hazards models were then performed for prognostic factors with P<0.10 to identify potential independent risk factors. The study population were stratified by included study variables and the AJCC staging system,and a subgroup analysis was performed using the Kaplan-Meier method to explore the potential benefit subgroup population of adjuvant chemotherapy. Results: After 1∶1 PSM matching,69 patients were obtained in each group. There was no significant difference in baseline data between the two groups (all P>0.05). After PSM,Cox multivariate analysis showed that lymph node metastasis (HR=3.06,95%CI:1.52 to 6.16,P=0.039),width of resection margin (HR=0.56,95%CI:0.32 to 0.99,P=0.044) and adjuvant chemotherapy (HR=0.51,95%CI:0.29 to 0.91,P=0.022) were independent prognostic factors for OS. Kaplan-Meier analysis showed that the median OS time of adjuvant chemotherapy group was significantly longer than that of non-adjuvant chemotherapy group (P<0.05). There was no significant difference in RFS time between the adjuvant chemotherapy group and the non-adjuvant chemotherapy group (P>0.05). Subgroup analysis showed that,the OS of female patients,without HBV infection,carcinoembryonic antigen<9.6 μg/L,CA19-9≥200 U/ml,intraoperative bleeding<400 ml,tumor diameter>5 cm,microvascular invasion negative,without lymph node metastasis,and AJCC stage Ⅲ patients could benefit from adjuvant chemotherapy (all P<0.05). Conclusion: Adjuvant chemotherapy can prolong the OS of patients with ICC after radical resection,and patients with tumor diameter>5 cm,without lymph node metastasis,AJCC stage Ⅲ,and microvascular invasion negative are more likely to benefit from adjuvant chemotherapy.

Tumor Androgen Receptor Protein Level Is Positively Associated with a Better Overall Survival in Melanoma Patients.

Androgen receptor (AR) is expressed in numerous tissues and serves important biologic functions in skin, prostate, immune, cardiovascular, and neural systems, alongside sexual development. Several studies have associated AR expression and patient survival in various cancers, yet there are limited studies examining the relationship between AR expression and cutaneous melanoma. This study used genomics and proteomics data from The Cancer Proteome Atlas (TCPA) and The Cancer Genome Atlas (TCGA), with 470 cutaneous melanoma patient data points. Cox regression analyses evaluated the association between AR protein level with overall survival and revealed that a higher level of AR protein was positively associated with a better overall survival (OS) (p = 0.003). When stratified by sex, the AR association with OS was only significant for both sexes. The multivariate Cox models with justifications of sex, age of diagnosis, stage of disease, and Breslow depth of the tumor confirmed the AR-OS association in all patients. However, the significance of AR was lost when ulceration was included in the model. When stratified by sex, the multivariate Cox models indicated significant role of AR in OS of female patients but not in males. AR-associated genes were identified and enrichment analysis revealed shared and distinct gene network in male and female patients. Furthermore, AR was found significantly associated with OS in RAS mutant subtypes of melanoma but not in BRAF, NF1, or triple-wild type subtypes of melanoma. Our study may provide insight into the well-known female survival advantage in melanoma patients.

A propensity score-matched analysis of oncological outcome after systemic therapy for stage IV colorectal cancer: Impact of synchronous ovarian metastases.

The reported incidence of synchronous and metachronous ovarian metastases (OM) from colorectal cancer (CRC) is ~3.4%. OM from CRC are often considered sanctuary sites due to their lower sensitivity to systemic treatment. It has thus been hypothesized that the presence of OM decreases overall survival. Therefore, the purpose of our study was to evaluate the impact of synchronous OM on overall survival in female patients with stage IV CRC treated with systemic therapy alone with palliative intent. The present study used data from the Netherlands Cancer Registry and included female CRC patients with synchronous systemic metastases who were treated with systemic therapy between 2008 and 2018. A subsample was created using propensity score matching to create comparable groups. Propensity scores were determined using a logistic regression model in which the dependent variable was the presence of OM and the independent variables were the variables that differed significantly between both groups. Our study included 5253 patients with stage IV CRC that received systemic therapy. Among these patients, 161 (3%) had OM while 5092 (97%) had extra-ovarian metastases only. Three-year overall survival rates did not show a significant difference between patients with OM compared to patients without ovarian metastases. Moreover, the propensity score-matched analysis showed that the presence of OM in patients treated with systemic therapy for stage IV CRC disease was not associated with decreased 3-year overall survival. However, the results of the present study should be interpreted with caution, due to its observational character and used selection criteria.

Factors Associated With Long-term Survival in Women Who Get Pregnant After Surgery for WHO Grade II Glioma.

Women with a World Health Organization grade II glioma (GIIG) often question clinicians about the effects of pregnancy on their disease. Previous reports have indicated a higher risk of glioma progression during and after pregnancy. Here, the aim was to investigate postpregnancy outcomes and predictive factors affecting overall survival in female patients who underwent GIIG surgery. Inclusion criteria were adult women who have been pregnant after a GIIG resection and with a stable oncologic status at the time of pregnancy (no ongoing oncologic treatment, no contrast enhancement, no debilitating clinical condition). Relevant cases were identified from a databank (1998-2021) of patients who underwent surgical resection for a histologically confirmed GIIG in our department. Among 345 women with GIIG in their reproductive years (age <45 years), 16 patients (4.6%, mean age at delivery 30.9 ± 5.1 years) were pregnant (twice in 5 cases). The mean interval between the last oncologic treatment (surgery alone in 11 patients, surgery followed by chemotherapy and/or radiotherapy in 5 patients) and pregnancy was 3.5 years (range 0.75-10 years). Two patients experienced seizures during pregnancy. The delivery was vaginal and uneventful in all cases but 1 (1 caesarean). All children had normal mental and physical development. The glioma behavior changed in 7 patients (43.7%), with an acceleration of the velocity of diameter expansion and/or the occurrence of a contrast enhancement during or within 3 months after pregnancy, resulting in medical treatment and/or reoperation in the early postpartum period in 7 cases. The median clinical follow-up from delivery was 5.3 years (range 1.25-11.6 years). Four other patients received delayed adjuvant therapy for glioma progression. Seven patients (43.7%) died at a median time from delivery of 3.9 years (range 1.25-5.9 years). Overall, the median survival from delivery was 5.75 years. A crucial finding is that patients who underwent a complete surgical resection and patients with stable lesions before pregnancy lived longer (log rank, p = 0.046 and p = 0.0026, respectively). Tumor residual volume and tumor speed growth are strong predictive factors conditioning postpregnancy long-term survival in patients with GIIG. Identifying patients at risk is critical to provide relevant counsel to women with GIIG with a desire for motherhood.

Exploration of genes and tumor infiltrating lymphocytes in female lung adenocarcinoma microenvironment that predicted prognosis.

The tumor microenvironment has an important impact on tumor growth, invasion, metastasis, anti-tumor immune tolerance, and prognosis. The present study aimed to explore female lung adenocarcinoma microenvironment-associated tumor infiltrating lymphocytes (TILs) and genes that predict prognosis in The Cancer Genome Atlas (TCGA) database. Gene expression profiles of female patients with lung adenocarcinoma were downloaded from TCGA. Base on the CIBERSORT algorithm, we determined the fractions of TILs. By applying the ESTIMATE algorithm, immune scores and stromal scores were derived. According to the immune and stromal scores, we categorized the female patients with lung adenocarcinoma into high and low score groups. We also identified the fractions of TILs and differentially expressed genes (DEGs) that were significantly related with prognosis. The proportion of M1 macrophages was significantly negatively related to overall survival in female patients with lung adenocarcinoma. There were 269 upregulated genes and 35 downregulated genes both in immune scores and stromal scores. PTPRC (protein tyrosine phosphatase receptor type C) and GIMAP6 (GTPase, IMAP family member 6) were not only hub genes, but also were significantly related to overall survival in the Kaplan–Meier Plotter online and TCGA databases. In summary, our study provided new insight into the tumor microenvironment-related cellular and molecular mechanisms of women with lung adenocarcinoma. The results will be useful for future clinical studies.

Prognostic Value of Autophagy-related Proteins in Human Gastric Cancer

PurposeAutophagy-related proteins (ATG) play a crucial role in autophagy. Recently, the functions of autophagy in cancer have been gathering attention. However, the prognostic value of ATGs in gastric cancer (GC) has not been explored.MethodsThe Kaplan–Meier plotter (KM plotter) online database was used to examine the value of ATGs gene expression levels in overall survival (OS) prediction in GC patients with different clinical stage, differentiation, gender, HER2 status, and therapeutic strategy. In vitro experiments applied VE-822, an effective GC treatment, to assess cell migration and proliferation in gastric mucosa epithelial cells, and real-time PCR was used to measure alterations of autophagy-related gene expression.ResultsHigh ATG3, ATG4C, ATG5, and ATG10 mRNA levels were associated with good OS, while increased ATG4B, ATG7, ATG12, ATG16L1, and TECPR1 mRNA levels related to unfavorable OS in patients with GC. ATG12 overexpression had different effects on OS due to high levels of heterogeneity. High ATG12 expression was correlated with good OS in female patients with GC and with bad OS for male patients. Additionally, the increased ATG12 expression was more likely to get a satisfactory OS in patients who underwent surgery alone but was associated with poor OS for patients treated with 5-FU adjuvant. In addition, elevated TECPR1 expression was related to favorable OS for patients with poorly differentiated type, while for patients with moderate differentiation, it was relevant to poor OS. The in vitro experiments showed that berzosertib could significantly inhibit the migration and proliferation of human gastric mucosa epithelial cells, and further real-time PCR assessment of ATG expressions partially coincided with the bioinformation analysis above.ConclusionThese results indicate that individual ATGs have unique prognostic significance interpreted using Kaplan–Meier plotter analysis and in vitro experiments, and this may help guide clinical therapeutic strategy and promote OS by individualizing therapy for GC patients.

Breast-Conserving Therapy is Associated with Improved Survival Compared with Mastectomy for Early-Stage Breast Cancer: A Propensity Score Matched Comparison Using the National Cancer Database.

Current recommendations for early-stage breast cancer are largely based on the NSABP B-06 trial demonstrating equivalent survival between mastectomy and lumpectomy. We sought to compare breast-conserving therapy (BCT) with mastectomy for treatment of early-stage breast cancer in a contemporary patient population. A query of the NCDB PUF identified female breast cancer patients diagnosed from 2004 to 2015. Patients with stage I or II disease were included. BCT was defined as the receipt of lumpectomy plus radiation. Propensity scores were tabulated using race, age, Charlson/Deyo score, tumor site, laterality, histology, grade, size, number of nodes positive, lymph-vascular invasion, receptor status, receipt of chemotherapy, and endocrine therapy. Patients who received BCT versus mastectomy were matched using a 1:1 nearest neighbor technique. The primary outcome measured was overall survival. After exclusions and matching, two equal groups of 101,118 patients remained. Median follow-up was 42months. The majority had invasive ductal histology (77%), and node-negative disease (84%). Receptor status included ER-positive (83%), PR-positive (73%), and HER2/Neu-positive (15%). Chemotherapy was received in 38% and endocrine therapy in 71%. Propensity score matching yielded equivalent groups across all target variables. The 5-year overall survival was superior for BCT compared with mastectomy (92.9% vs. 89.7%, p < 0.001; Fig.1). This survival advantage persisted for both stage I (p < 0.001) and stage II (p < 0.001) disease on subgroup analysis. Fig.1 Overall survival in female patients with early stage invasive breast cancer (stage I or II) undergoing breast conservation surgery with radiation compared with mastectomy. BCS breast conservation surgery CONCLUSIONS: BCT is associated with superior overall survival compared with mastectomy for early-stage breast cancer using well-matched, contemporary data.

Gender impact on renal cell carcinoma survival: A population-based analysis.

e17099 Background: Prior evidence has suggested that females diagnosed with renal cell carcinoma (RCC) present at an earlier stage compared to males, but a survival difference between males and females has been controversial. We aimed to evaluate the impact of gender on RCC survival in the US. Methods: Data of RCC patients diagnosed between 1973 and 2015 in the US was obtained using Surveillance Epidemiology and End Results (SEER) database. We studied the overall and cancer-specific survival of patients diagnosed with RCC in the US according to gender using multivariable covariate-adjusted Cox models and Kaplan-Meier test. Results: We reviewed 155,430 RCC patients, of which 96,656 were males, and 58,774 were females. The median overall survival of female patients was 122 months and was significantly higher than male patients (98 months). Cancer-specific survival showed similar trends with females having significantly higher survival (p-value &lt; 0.001). Adjusted for age, race, stage and grade of cancer, undergoing cancer-targeted surgery, and marital status, female sex was associated with improved overall and cancer-specific survival outcomes; HR = 0.829 (p-value &lt; 0.001), and HR = 0.923 (p-value &lt; 0.001), respectively. Conclusions: Females have a significantly better overall and cancer specific survival compared to males diagnosed with renal cell carcinoma. In previous studies this disparity was attributed to the lower grade and earlier stage of RCC presentation in females, but gender-based disparity persisted in this analysis after adjusting for patient baseline and tumor characteristics. This raises the question of the hormonal effects on the progression of RCC.

PB2331 IMPACT OF PRETRANSPLANT CHEMOTHERAPY, GRAFT VERSUS HOST DISEASE PROPHYLAXIS, GENDER AND RISK GROUP ON ALLOGENEIC REDUCED INTENSITY CONDITIONING TRANSPLANTS FOR ELDERLY ACUTE MYELOID LEUKEMIA PATIENTS

Background:Allogeneic reduced intensity conditioning transplant (RICT) has become an accepted treatment modality for patients (pts) age ≥50 years with acute myeloid leukemia (AML). Reports on patient and transplant related factors that may influence outcome in this population are rare.Aims:To analyze the possible impact of number of chemotherapy courses, recipient gender, choice of graft versus host disease (GVHD) prophylaxis and disease risk on the outcome of elderly pts with AML in CR1 receiving an allogeneic RICT.Methods:Patients were allografted from a matched sibling donor (MSD) as part of a multinational, prospective, controlled study (NCT00342316) which aimed to compare RICT and chemotherapy in an elderly population. Patients with a median age of 63 years (yrs) (52‐70) were transplanted between 2004 and 2015. Fifty‐eight pts (29 females, 29 males) were allografted using a RICT regimen: fludarabine (150‐180 mg/m2) and busulfan (8 mg/kg orally or 6.4 mg/kg iv.) in 93%. Peripheral blood stem cells were given in 54 pts (93%). Median follow up was 36 months (2‐149). Prespecified high risk criteria were poor risk cytogenetics, secondary or therapy related AML, or blasts ≥15% after induction 1.Results:Overall survival (OS) at study termination was 36%. Twenty‐four (41%) pts relapsed. Acute GVHD grade 2 to 4 was noted in 28%, chronic extensive GVHD in 36%.Twenty‐one pts (36%) received up to 2 chemotherapy courses prior to transplant and 36 (62%) received more than 2 courses. Data was missing in 1 patient. These groups were well balanced with respect to age (63 years in both groups), gender and risk category. Neither OS, 38% versus 36%, nor relapse rate (RR), 38% versus 42% were significantly different.Data on GVHD prophylaxis was available on 57 pts, the two main immunosuppressive treatments were cyclosporine/methotrexate given to 29 pts, whereas 20 pts received cyclosporine/MMF based regimens. Age, gender, risk group distribution, number of chemotherapy regimens and performance status prior to transplant were not different in these two groups. OS was 38% versus 40% (not significant). There was no difference in either RR or acute or chronic GVHD between these two groups.Twenty‐nine of 58 (50%) pts were female. Median age of females was 62 yrs, of males 63 yrs (p = 0.275). There were no differences regarding disease risk between female and male groups, or between numbers of chemotherapy regimens. OS of female patients was 45% versus 28% in male patients (p = 0.17).Thirty‐eight pts were considered intermediate and 20 high risk. Median age was slightly higher in the high risk group, 64 vs 61 yrs (p = 0.042), and high‐risk pts received a higher number of chemotherapy courses. There was a trend to better OS in the intermediate risk group compared with the high risk group, 45% versus 20%, respectively (p = 0.087). RR was 34 versus 55%, which did not reach statistical significance.Summary/Conclusion:In our cohort of elderly patients with AML in CR1 receiving a RICT transplant from related donors, the number of pretransplant chemotherapy regimens, choice of graft versus host disease prophylaxis, patients gender, and comparison of high versus intermediate risk groups did not appear to impact on OS. Relapse rates in all patient groups were high, possibly masking any survival difference between the groups.

Influence of organ location and sex of patient on pancreatic neuroendocrine tumor 5-year survival.

e15713 Background: Pancreatic neuroendocrine tumors (PNET) represent a rare tumor histology among patients diagnosed with pancreatic cancer (less than 2% incidence). These tumors arise from the endocrine tissues of the pancreas and can present with a variable clinical course. We sought to examine the overall survival (OS) of patients based upon sex and anatomic location via the SEER database. Methods: Accessing the SEER-Medicare database, we identified 3,242 patients with both Pancreatic Cancer and Neuroendocrine Tumor (NET) histologic validation using ICD-O-3 Codes while excluding Large Cell, Small Cell, and Mixed Endocrine-Exocrine tumors. We then sub-stratified the data to male (N = 1816) and female (N = 1426) sex as well as pancreatic location: Head (Male = 831; Female = 657), Body (Male = 283; Female = 258), or Tail (Male = 701; Female = 510). We excluded PNETs of the pancreatic duct as there were only 2 cases (Male = 1; Female = 1). All comparison tests were run with SEER*STAT 8.3.2 via a Two-Sample t-Test Assuming Equal Variances. OS was analyzed using the Kaplan–Meier method. Results: Overall, both Male and Female patients with PNET have significantly improved 5-Year survival compared with those patients with Pancreatic Adenocarcinoma ((47.47% (n = 3242) vs 6.6% (n = 117,204), p &lt; 0.05). There is no difference in 5-Year OS between Male (44.9%) and Female (50.5%) patients with PNET accounting for all locations. There is a trend towards significance in improved 5-Year OS in Female patients with Tail PNET versus Male patients with Tail PNET (55.8% (n = 510) vs 48.6% (n = 701), p &lt; 0.06). Significantly, Female patients with Tail PNET have a significantly higher 5-Year OS compared to Female patients with Head PNET (55.8% (n = 510) vs 46.9% (n = 657), p &lt; 0.05). There was a trend towards improved 5-Year OS in Female patients with Tail PNET versus those within the Body (55.8% (n = 510) vs 48.6% (n = 258), p &lt; 0.01). Conclusions: Based upon this population study, Female patients with PNET localized to the Tail have a significantly higher 5-Year OS than Female patients with PNET localized to the Head of the Pancreas. These same patients trend towards improved survival when compared with Female patients with Body PNET as well as Male patients with Tail PNET.

Gender Specific Mutation Incidence and Survival Associations in Clear Cell Renal Cell Carcinoma (CCRCC).

Renal cell carcinoma (RCC) is diagnosed in >200,000 individuals worldwide each year, accounting for ~2% of all cancers, but the spread of this disease amongst genders is distinctly uneven. In the U.S. the male:female incidence ratio is approximately 2:1. A potential hypothesis is mutation spectra may differ between tumors dependent upon the gender of the patient, such as mutations of X chromosome encoded genes being more prevalent in male-derived tumors. Combined analysis of three recent large-scale clear cell renal cell carcinoma (CCRCC) mutation sequencing projects identified a significantly increased mutation frequency of PBRM1 and the X chromosome encoded KDM5C in tumors from male patients and BAP1 in tumors from female patients. Mutation of BAP1 had previously been significantly associated with poorer overall survival; however, when stratified by gender, mutation of BAP1 only significantly affected overall survival in female patients. Mutation of chromatin remodeling genes alters gene regulation, but the overall effect of these alterations may also be modified by the presence of other gender specific factors. Thus, the combination of gender and mutation of a specific gene, such as BAP1, may have implications not only for prognosis but also for understanding the role of chromatin remodeling gene mutations in kidney cancer progression.

Skeletal Muscle Depletion Predicts the Prognosis of Patients with Advanced Pancreatic Cancer Undergoing Palliative Chemotherapy, Independent of Body Mass Index.

IntroductionBody composition has emerged as a prognostic factor in cancer patients. We investigated whether sarcopenia at diagnosis and loss of skeletal muscle during palliative chemotherapy were associated with survival in patients with pancreatic cancer.MethodsWe retrospectively reviewed the clinical outcomes of pancreatic cancer patients receiving palliative chemotherapy between 2003 and 2010. The cross-sectional area of skeletal muscle at L3 by computed tomography was analyzed with Rapidia 3D software. We defined sarcopenia as a skeletal muscle index (SMI)< 42.2 cm2/m2 (male) and < 33.9 cm2/m2 (female) using ROC curve.ResultsAmong 484 patients, 103 (21.3%) patients were sarcopenic at diagnosis. Decrease in SMI during chemotherapy was observed in 156 (60.9%) male and 65 (40.6%) female patients. Decrease in body mass index (BMI) was observed in 149 patients (37.3%), with no gender difference. By multivariate analysis, sarcopenia (P< 0.001), decreasedBMI and SMI during chemotherapy (P = 0.002, P = 0.004, respectively) were poor prognostic factors for overall survival (OS). While the OS of male patients was affected with sarcopenia (P< 0.001) and decreased SMI (P = 0.001), the OS of female patients was influenced with overweight at diagnosis (P = 0.006), decreased BMI (P = 0.032) and decreased SMI (P = 0.014). Particularly, while the change of BMI during chemotherapy did not have impact on OS within the patients with maintained SMI (P = 0.750), decrease in SMI was associated with poor OS within the patients with maintained BMI (HR 1.502; P = 0.002).ConclusionsSarcopenia at diagnosis and depletion of skeletal muscle, independent of BMI change, during chemotherapy were poor prognostic factors in advanced pancreatic cancer.

Interaction between synchronous bilateral prophylactic oophorectomy and adjuvant chemotherapy in female patients with locally advanced colorectal cancer

In this study we explored the prognostic impact of synchronous bilateral prophylactic oophorectomy in female patients with primary colorectal cancer undergoing radical surgery. From 1991 to 2000, 267 female patients with stage II or stage III colorectal cancer, who had undergone curative resection, were retrospectively reviewed. In 224 patients, the ovaries were preserved. The other 43 patients underwent synchronous bilateral prophylactic oophorectomy. Univariate and multivariate analyses (Kaplan-Meier and Cox regression, respectively) were used to evaluate the effect of prophylactic oophorectomy and other clinical factors on the prognosis of patients. Both univariate and multivariate analyses showed that tumor stage and adjuvant chemotherapy were the only two significant clinical factors that affected the 5-year overall survival of patients (P < 0.01). There was no significant difference in the 5-year overall survival between patients who had, or had not, undergone prophylactic oophorectomy (75%vs 73%, P > 0.05). In the subgroup analysis by adjuvant chemotherapy, the 5-year overall survival in patients receiving adjuvant chemotherapy was similar between nonoophorectomy and oophorectomy groups. However, in patients without adjuvant chemotherapy, the oophorectomy group was shown to have a significantly better 5-year overall survival than the nonoophorectomy group (76%vs 51%, P = 0.047). Prophylactic oophorectomy may improve the overall survival of female patients with locally advanced colorectal cancer without adjuvant chemotherapy, but its survival benefit vanished in patients receiving adjuvant chemotherapy. The role of prophylactic oophorectomy may be substituted by adjuvant chemotherapy, which makes prophylactic oophorectomy unnecessary during surgery for locally advanced colorectal cancer.

Colorectal cancer susceptibility variants and clinical outcome in adjuvant and metastatic colorectal cancer

4051 Background: Recent genome-wide association studies had identified colorectal cancer susceptibility loci on chromosomes 8q24 (rs6983267), 15q13(rs4779584), 18q21(rs4939827, rs12953717 and rs4464148), 10p14(rs10795668) and 8q23.3(rs16892766). Although the function role of these germline variants are unclear, given the importance of these variants and colorectal cancer risk, we have carried out the first pilot study to explore the association of these variants and clinical outcome. We used pooled data from two CRC-cohorts (locally advanced and metastatic CRC), and investigated the hypothesis that these germline variants may be associated with clinical outcome in adjuvant and metastatic colorectal cancer patients. Methods: Whole blood was collected from 515 patients with locally advanced (n=197) and metastatic CRC (n=318). After extraction of genomic-DNA, germline variants were genotyped as previously described (Haiman et al, Nat Genet, 2007). The genotype success rate was 98%. Blinded repeat samples (5%) were included for quality control purposes; genotype concordance was ≥ 99%. Results: Our results suggest that rs10795668 at 10p14 and rs719725 are significantly associated with time to tumor recurrence in adjuvant colorectal cancer patients, patients with rs10795668 AA genotype had significantly increased risk of time to tumor recurrence compared with those harboring G allele (TG+GG) patients(p=0.05, log-rank test). In metastatic cancer patients, we found rs4939827 at 18q21.1 were significantly associated with overall survival in female patients and rs10795668 at 10p14 were significantly associated with OS in male patients, respectively (p&lt;0.05). Conclusions: Our preliminary results suggest cancer risk alleles may also associated with clinical outcome in adjuvant and metastatic colorectal cancer. Moreover, this correlation is sex-specific in metastatic colorectal cancer. Further comprehensive trials warranted to confirm our pilot findings. [Table: see text]