Higher 5-year Recurrence Rate Research Articles

Postoperative adjuvant hepatic arterial infusion chemotherapy combined with donafenib in hepatocellular carcinoma with solitary large tumor and microvascular invasion: A multicenter, prospective, single-arm, phase II trial.

e16227 Background: Hepatocellular carcinoma (HCC) with solitary large tumor (≥ 5 cm) and microvascular invasion (MVI) was associated with high 5-year recurrence rate and poor survival prognosis. Postoperative adjuvant hepatic arterial infusion chemotherapy (HAIC) was found to improve the recurrence-free survival (RFS) with acceptable safety profiles in HCC patients with MVI. However, the prognosis of HCC who received adjuvant HAIC after hepatectomy still remain far from satisfactory. Several studies have shown that the combination of HAIC and tyrosine kinase inhibitors (TKIs) could exhibit a synergistic anticancer effect and improve the survival outcomes of advanced HCC. Thus, the present study was conducted to explore the efficacy and safety of adjuvant HAIC plus the novel multikinase inhibitor donafenib in HCC with solitary tumor ≥ 5 cm and MVI. Methods: This prospective, single-arm phase II study was conducted in three medical centers in China. HCC patients with both solitary tumor ≥ 5 cm and MVI, no evidence of recurrence at radiological follow-up at 4-8 weeks after hepatectomy, no previous treatment for HCC other than hepatectomy, Child-Pugh score A or B7 were enrolled. Eligible patients received one cycle of HAIC with oxaliplatin, fluorouracil, and leucovorin (HAIC-FOLFOX4), and followed by donafenib (200 mg orally twice daily) for up to 1 year until disease recurrence or unacceptable toxicity. The primary endpoint was 1-year recurrence-free survival rate (1-year RFS rate). Secondary endpoints included RFS, overall survival (OS) and safety. Results: A total of 18 patients were included for analysis. The median age was 59 years (range, 28–75), the median maximum tumor size was 7.0 cm (interquartile range [IQR], 6.2–7.8), 88.9% had low-risk MVI, 61.1% had Edmondson-Steiner grade III-IV and 44.4% had incomplete tumour capsule. As of November 27, 2023, 4 of 18 patients (22.2%) recurrenced and no deaths occurred with a median follow-up of 15.0 months (95% confidence interval [CI], 5.1–19.1). The 1-year RFS rate was 64.9% (95%CI, 39.2%–100%), and current immature median RFS was 14.3 months (95%CI, not available [NA], 11.2–NA). The most common treatment-related adverse events (TRAEs) were hand-foot skin reaction (72.2%), diarrhea (38.9%), decreased platelet count (22.2%), hypoalbuminemia (22.2%), and alopecia (22.2%). Grade 3 TRAEs occurred in 6 patients (33.3%), and no grade 4 or 5 TRAEs occurred. Conclusions: In this prospective study, the preliminary data indicated that HAIC combined with donafenib is an encouraging adjuvant therapy with well-tolerated safety profiles for HCC patients with solitary tumor ≥ 5 cm and MVI. Clinical trial information: NCT04962958 .

NIR-II fluorescence-guided liver cancer surgery by a small molecular HDAC6 targeting probe

Hepatocellular carcinoma (HCC) is the sixth most common malignancy globally and ranks third in terms of both mortality and incidence rates. Surgical resection holds potential as a curative approach for HCC. However, the residual disease contributes to a high 5-year recurrence rate of 70%. Due to their excellent specificity and optical properties, fluorescence-targeted probes are deemed effective auxiliary tools for addressing residual lesions, enabling precise surgical diagnosis and treatment. Research indicates histone deacetylase 6 (HDAC6) overexpression in HCC cells, making it a potential imaging biomarker. This study designed a targeted small-molecule fluorescent probe, SeCF3-IRDye800cw (SeCF3-IRD800), operating within the Second near-infrared window (NIR-II, 1000-1700nm). The study confirms the biocompatibility of SeCF3-IRD800 and proceeds to demonstrate its applications in imaging invivo, fluorescence-guided surgery (FGS) for liver cancer, liver fibrosis imaging, and clinical samples incubation, thereby preliminarily validating its utility in liver cancer. SeCF3-IRD800 was synthesized by combining the near-infrared fluorescent dye IRDye800cw-NHS with an improved HDAC6 inhibitor. Initially, a HepG2-Luc subcutaneous tumor model (n=12) was constructed to investigate the metabolic differences between SeCF3-IRD800 and ICG invivo. Subsequently, HepG2-Luc (n=12) and HCCLM3-Luc (n=6) subcutaneous xenograft mouse models were used to assess invivo targeting by SeCF3-IRD800. The HepG2-Luc orthotopic liver cancer model (n=6) was employed to showcase the application of SeCF3-IRD800 in FGS. Liver fibrosis (n=6) and HepG2-Luc orthotopic (n=6) model imaging results were used to evaluate the impact of different pathological backgrounds on SeCF3-IRD800 imaging. Three groups of fresh HCC and normal liver samples from patients with liver cancer were utilized for SeCF3-IRD800 incubation exvivo, while preclinical experiments illustrated its potential for clinical application. The HDAC6 inhibitor 6 (SeCF3) modified with trifluoromethyl was labeled with IRDy800CW-NHS to synthesize the small-molecule targeted probe SeCF3-IRD800, with NIR-II fluorescence signals. SeCF3-IRD800 was rapidly metabolized by the kidneys and exhibited excellent biocompatibility. Invivo validation demonstrated that SeCF3-IRD800 achieved optimal imaging within 8h, displaying high tumor fluorescence intensity (7658.41±933.34) and high tumor-to-background ratio (5.20±1.04). Imaging experiments with various expression levels revealed its capacity for HDAC6-specific targeting across multiple HCC tumor models, suitable for NIR-II intraoperative imaging. Fluorescence-guided surgery experiments were found feasible and capable of detecting sub-visible 2mm tumor lesions under white light, aiding surgical decision-making. Further imaging of liver fibrosis mice showed that SeCF3-IRD800's imaging efficacy remained unaffected by liver pathological conditions. Correlations were observed between HDAC6 expression levels and corresponding fluorescence intensity (R2=0.8124) among normal liver, liver fibrosis, and HCC tissues. SeCF3-IRD800 identified HDAC6-positive samples from patients with HCC, holding advantages for perspective intraoperative identification in liver cancer. Thus, the rapidly metabolized HDAC6-targeted small-molecule NIR-II fluorescence probe SeCF3-IRD800 holds significant clinical translational value. The successful application of NIR-II fluorescence-guided surgery in liver cancer indicates that SeCF3-IRD800 has great potential to improve the clinical diagnosis and treatment of liver cancer, and could be used as an auxiliary tool for surgical treatment of liver cancer without being affected by liver pathology. This paper is supported by the National Natural Science Foundation of China (NSFC) (92,059,207, 62,027,901, 81,930,053, 81,227,901, 82,272,105, U21A20386 and 81,971,773), CAS Youth Interdisciplinary Team (JCTD-2021-08), the Zhuhai High-level Health Personnel Team Project (Zhuhai HLHPTP201703), and Guangdong Basic and Applied Basic Research Foundation under Grant No. 2022A1515011244.

Variations in dynamic tumor-associated antigen-specific T cell responses correlate with HCC recurrence after thermal ablation.

Ablative therapy is a recommended treatment for hepatocellular carcinoma (HCC) not only for its effective eradication of tumors, but also for its induction of host immunity. However, the high 5-year recurrence rate after ablation underlines the poor understanding of the antitumor immunity response. Here, we investigated the effects of thermal ablation on antitumor immunity. We analyzed the dynamics of tumor-associated antigen (TAA)-specific immune responses and changes in peripheral blood mononuclear cell phenotype in patients with HCC before and after tumor ablation. We used the IFN-γ ELISPOT assay and immunophenotyping by flow cytometry to evaluate the effects of ablation on host immunity. The correlation between the T cell response and disease outcome was explored to uncover the efficacy of the immune response in inhibiting HCC recurrence. Different TAA-specific T cell responses were identified among patients before and after ablation. One week after ablation, there was an improved immune state, with a switch from the dominance of an AFP-specific T cell response to that of a SMNMS-specific T cell response, which was correlated with better survival. Furthermore, an improvement in immune status was accompanied by a lower level of PD1+ and Tim3+ T cells in CD8+ T cells. Although this functional state was not durable, there was a higher degree of AFP-specific T cell responses at 4-weeks post-ablation. Furthermore, T cells presented a more exhausted phenotype at 4-weeks post-ablation than at the 1-week timepoint. Ablation elicits a transient antitumor immune response in patients with HCC by changing the profile of the T cell response and the expression of immune checkpoint molecules, which correlated with longer recurrence-free survival of patients with HCC.

Risk factors of recurrence and distant metastasis in primary cutaneous melanoma in Taiwan

Risk factors of recurrence and distant metastasis of acral lentiginous melanoma (ALM) are of great interest for the high percentage of ALM in cutaneous melanoma in Asian populations. This single-center retrospective cohort including 177 patients with localized melanoma diagnosed from 2004 to 2020 aims to identify adverse predictors in cutaneous melanoma in Taiwan, with a focus on ALM. The relationship between clinicopathological features and outcomes, including incidences of recurrence and distant metastasis in 5 years from diagnosis, was analyzed. This study included 124 patients (70.1%) with ALM and 53 (29.9%) with non-ALM melanoma. Regarding clinicopathological characteristics, ALM patients were diagnosed at an older age and received sentinel lymph node biopsies (SLNBs) more often, while adjacent melanocytic nevi were more prevalent in non-ALM patients. With respect to prognostic implications of clinicopathological features, in ALM, implementation of SLNB was associated with a lower 5-year distant metastasis rate. Thickness of melanoma lesions over 4 mm, ulceration, and neurotropism, were related to both higher 5-year recurrence and distant metastasis rates. With regard to non-ALM patients, diagnoses made at or over 65 years old was linked to a higher 5-year recurrence rate, whereas ulceration was associated with both higher 5-year recurrence and distant metastasis rates. In conclusion, several clinicopathological characteristics have been identified to be associated with poor prognosis of cutaneous melanoma, especially ALM.

A systematic review and meta-analysis of the influence of STAS on the long-term prognosis of stage I lung adenocarcinoma.

BackgroundThe appearance of airway dissemination often indicates poor prognosis of lung cancer. However, the relationship between airway dissemination and early lung adenocarcinoma is not clear. Therefore, this study uses meta-analysis to study the long-term prognosis of patients with early lung adenocarcinoma.MethodsA computer search of the PubMed, EMbase, Web of Science, and other databases was conducted, and the search time limit was from the establishment of the database to December 30, 2020. Data strictly in accordance with the inclusion and exclusion criteria was extracted and the quality of the included literature was evaluated. Two reviewers then independently screened the literature and evaluated the risk of bias.ResultsA total of 11 studies were included, comprised of 5,097 patients with early lung adenocarcinoma. The results of the meta-analysis showed that among patients with stage I lung adenocarcinoma, the 5-year recurrence-free survival (RFS) and overall survival (OS) of STAS-positive patients was lower than those of the STAS-negative group, and the difference was statistically significant. In the control study, the 5-year RFS was HR =1.95, 95% CI (1.58–2.31) P<0.01, and the 5-year OS was OR =2.04, 95% CI (1.60–2.48) P<0.01, and in STAS-positive patients, sublobectomy had a worse long-term prognosis than lobectomy. While the 5-year RFS HR of the lobectomy group was 1.82, 95% CI (1.43–2.22), and the 5-year RFS HR of the sublobectomy group was 6.92, 95% CI (1.64–12.18) P<0.01, the prognosis of the STAS-positive high-expression group and the low-expression group was worse. The 5-year RFS HR of the low-expression STAS group was 2.93, 95% CI (0.21–6.07), and in the high expression group this was 8.20, 95% CI (0.55–15.85) P<0.05.DiscussionSTAS is an independent risk factor for the poor prognosis of stage I lung adenocarcinoma and a high expression of STAS results in a higher 5-year recurrence rate. When STAS is positive, the sublobectomy method should be carefully selected. However, our research has certain limitations, such as literature selection and publication bias. At the same time, the depth of literature analysis needs to be further improved.

Evaluation of the Alpha-Fetoprotein Model for Predicting Recurrence and Survival in Patients With Hepatitis B Virus (HBV)-Related Cirrhosis Who Received Liver Transplantation for Hepatocellular Carcinoma.

Introduction: The alpha-fetoprotein (AFP) model is superior to the Milan criteria in predicting the recurrence of hepatocellular carcinoma (HCC) after liver transplantation in European and Latin American populations. The purpose of this study was to determine the predictive value of the AFP model in Chinese hepatitis B virus (HBV)–related cirrhosis HCC patients.Methods: A total of 189 patients with HBV-related cirrhotic HCC were included. The recurrence rate and survival rate were estimated, and predictability was assessed by the Net Reclassification Improvement (NRI) method.Results: Of the 189 patients, patients with an AFP score >2 had a higher recurrence rate at 5 years (48.94 vs. 13.53%, p < 0.05) and lower survival rate (43.96 vs. 68.97%, p < 0.05). Considering patients within the Milan criteria, a higher 5-year recurrence rate and lower survival rate were observed in patients with an AFP model score >2 points compared to patients with a score of ≤ 2 points (recurrence rate: 58.75 vs. 12.98%, p < 0.05; survival rate: 28.57 vs. 67.41%, p = 0.047). NRI analysis showed that the AFP model exhibited superior predictability as compared to the Milan criteria.Conclusions: The AFP model may be used as a selection tool for Chinese HBV patients who require liver transplantation due to HCC.

A nomogram predicting the recurrence of hepatocellular carcinoma in patients after laparoscopic hepatectomy

BackgroundPatients with hepatocellular carcinoma (HCC) undergoing surgical resection still have a high 5-year recurrence rate (~ 60%). With the development of laparoscopic hepatectomy (LH), few studies have compared the efficacy between LH and traditional surgical approach on HCC. The objective of this study was to establish a nomogram to evaluate the risk of recurrence in HCC patients who underwent LH.MethodsThe clinical data of 432 patients, pathologically diagnosed with HCC, underwent LH as initial treatment and had surgical margin > 1 cm were collected. The significance of their clinicopathological features to recurrence-free survival (RFS) was assessed, based on which a nomogram was constructed using a training cohort (n = 324) and was internally validated using a temporal validation cohort (n = 108).ResultsHepatitis B surface antigen (hazard ratio [HR], 1.838; P = 0.044), tumor number (HR, 1.774; P = 0.003), tumor thrombus (HR, 2.356; P = 0.003), cancer cell differentiation (HR, 0.745; P = 0.080), and microvascular tumor invasion (HR, 1.673; P =0.007) were found to be independent risk factors for RFS in the training cohort, and were used for constructing the nomogram. The C-index for RFS prediction in the training cohort using the nomogram was 0.786, which was higher than that of the 8th edition of the American Joint Committee on Cancer TNM classification (C-index, 0.698) and the Barcelona Clinic Liver Cancer staging system (C-index, 0.632). A high consistency between the nomogram prediction and actual observation was also demonstrated by a calibration curve. An improved predictive benefit in RFS and higher threshold probability of the nomogram were determined by receiver operating characteristic curve analysis, which was also confirmed in the validation cohort compared to other systems.ConclusionsWe constructed and validated a nomogram able to quantify the risk of recurrence after initial LH for HCC patients, which can be clinically implemented in assisting the planification of individual postoperative surveillance protocols.

Results of Liver Transplantation for Hepatocellular Carcinoma in a Multicenter Latin American Cohort Study

Background and aims. Heterogeneous data has been reported regarding liver transplantation (LT) for hepatocellular carcinoma (HCC) in Latin America. We aimed to describe treatment during waiting list, survival and recurrence of HCC after LT in a multicenter study from Latin America.Material and methods. Patients with HCC diagnosed prior to transplant (cHCC) and incidentally found in the explanted liver (iHCC) were included. Imaging-explanted features were compared in cHCC (non-discordant if pre and post-LT were within Milan, discordant if pre-LT was within and post-LT exceeding Milan).Results. Overall, 435 patients with cHCC and 92 with iHCC were included. At listing, 81% and 91% of cHCC patients were within Milan and San Francisco criteria (UCSF), respectively. Five-year survival and recurrence rates for cHCC within Milan, exceeding Milan/within UCSF and beyond UCSF were 71% and 16%; 66% and 26%; 46% and 55%, respectively. Locoregional treatment prior to LT was performed in 39% of cHCC within Milan, in 53% beyond Milan/within UCSF and in 83% exceeding UCSF (p < 0.0001). This treatment difference was not observed according to AFP values (<100, 44%; 101-1,000, 39%, and > 1,000 ng/mL 64%; p = 0.12). Discordant imaging-explanted data was observed in 29% of cHCC, showing lower survival HR 2.02 (CI 1.29; 3.15) and higher recurrence rates HR 2.34 when compared to AFP <100 ng/mL. Serum AFP > 1,000 ng/mL at listing was independently associated with a higher 5-year recurrence rate and a HR of 3.24 when compared to AFP <100 ng/mL.Conclusion. Although overall results are comparable to other regions worldwide, preLT treatment not only considering imaging data but also AFP values should be contemplated during the next years.

Impact of cervical cancer care volume on clinical outcomes of laparoscopic radical hysterectomy: A systematic review and meta-analysis.

e17013 Background: This study investigated the impact of hospital and physicain cervical cancer case volume on clinical outcomes of laparoscopic radical hysterectomy (LRH) to clarify the hypothesis that clinical outcome of cervical cancer may depend on experience of hospital and physician performing radical hysterectomy (RH). Methods: In January 2017 the PubMed search identified 556 articles. A combination of the following key words was used in the search: (cervical cancer and laparoscopy and RH) and (cervical cancer and LRH). When filtered for studies presenting operative outcomes and/or perioperative complications of LRH 59 studies including 4,367 patients met the selection criteria: high volume hospitals (HVH) (≥15 cases/year; 13 studies, 2227 patients) and low volume hospitals (LVH) (&lt;15 cases/year; 46 studies, 2140 patients); high volume physicians (HVP) (≥10 cases/year; 7 studies, 1167 patients) and low volume physicians (LVP) (&lt;10 cases/year; 35 studies, 1258 patients). Linear regression analysis which is weighted by the number of patients per year in each study was performed to evaluate differences between the groups using Stata/SE 14. Results: Analyses according to hospital volume showed following outcomes in HVH compared with LVH: tendency of lower operative time and blood loss; the higher number of lymph nodes (LN) retrieved; older age; and lower frequency of stage IA. Moreover, hospital stay, intra- and post-operative complications, adjuvant therapy, 5-year overall survival, disease free survival and recurrence rate, stage IB1, IB2, and IIA, LN metastasis, and lymphovascular space, parametrial and surgical margin invasion were not different between the groups. Analyses according to physician volume showed following outcomes in HVP compared with LVP: the higher number of LN retrieved; longer hospital stay; higher 5-year recurrence rate; and lower frequency of stage IA and surgical margin invasion. Moreover, other factors were not different between the groups. Conclusions: Higher hospital and physician volumes are associated with better operative outcomes. However, those might not be favorable prognostic factors for cervical cancer.

Axl Expression Stratifies Patients with Poor Prognosis after Hepatectomy for Hepatocellular Carcinoma

BackgroundAxl is a receptor tyrosine kinase which plays an important role in multiple human malignancies.DesignThe Axl expression was examined in several hepatocellular carcinoma(HCC) cell lines, paired tumor and nontumorous samples. Then, we examined cell growth curve, cell apoptosis and cell migration in SMMC-7721 cells over-expressed with Axl or siRNA against Axl, respectively. Finally, the prognostic value of Axl was investigated in a prospective cohort of 246 consecutive HCC patients undergoing curative hepatoectomy.ResultsWe found Axl was positive in 22% of examined tumor tissues and all four cell lines. Over-expressing Axl in SMMC-7721 cells accelerated cell growth, cell migration and inhibited cell apoptosis, while knock-down of Axl exerted opposite effect. Axl expression was closely associated with serum AFP, multiple tumors, absence of encapsulation, microvascular invasion, and advanced BCLC or TNM stage. Patients with positive Axl staining had a higher 5-year recurrence rate (92% vs. 71%, P<0.001) and a lower 5-year survival rate (9% vs. 48%, P<0.001) than those with negative staining. The multivariate analyses showed that Axl expression was an independent factor for both tumor recurrence (HR: 1.725; 95% CI: 1.219–2.441) and survival (1.847; 1.291–2.642).ConclusionAxl expression suggests more aggressive tumor invasiveness and predicts worse prognosis for HCC patients undergoing resection.

Diabetes mellitus in patients with pulmonary tuberculosis in an aging population in Shanghai, China: Prevalence, clinical characteristics and outcomes

AimsTo determine the prevalence of diabetes mellitus among pulmonary tuberculosis patients and the difference of clinical characteristics and outcomes between pulmonary tuberculosis patients with and without diabetes mellitus in an aging population in Shanghai, China. MethodsThis is a retrospective population-based study. 201 newly diagnosed pulmonary tuberculosis patients in Changning District, Shanghai during 2007–2008 were included. Clinical characteristics and outcomes were collected. Determination of diabetes mellitus was based on the medical records before pulmonary tuberculosis was diagnosed. ResultsThe prevalence of diabetes mellitus among pulmonary tuberculosis patients was 19.9% (40/201). Pulmonary tuberculosis patients with diabetes mellitus were more likely to be old (≥50, OR=5.23, 95% CI=2.07–13.25), to have pulmonary cavities (OR=3.02, 95% CI=1.31–6.98), to be sputum smear positive (OR=2.90, 95% CI=1.12–7.51), and to have extension of anti-tuberculosis treatment duration (OR=2.68, 95% CI 1.17–6.14). Besides, they had a higher 2nd month sputum smear positive proportion (OR=2.97, 95% CI 1.22–7.22) and a higher 5-year recurrence rate (OR=5.87, 95% CI 1.26–27.40). ConclusionsHigh prevalence, severe clinical characteristics and poor outcomes of pulmonary tuberculosis patients with diabetes mellitus highlight the necessity of early bi-directional screening and co-management of these two diseases in Shanghai, China.

Patterns of cancer recurrence in localized resected hepatocellular carcinoma

Tumor resection in non-metastatic hepatocellular carcinoma (HCC) patients with adequate liver reserve offers a potential cure, but has a high 5-year recurrence rate. We analyzed the patterns of cancer relapse after partial hepatectomy to guide post-operative management. A total of 144 HCC patients (1996-2011) after partial hepatectomy were reviewed. Statistical correlations were determined using univariate and partition analyses. A median follow-up of 20 months showed recurrence in 71 (49%) patients, and the median time to recurrence was 11.9 months. Vascular invasion (P<0.01) and number of lesions (P<0.01) predicted for recurrence. Histologic grade was not correlated with recurrence. Twenty-two (31%) patients developed both surgical margin (SM) and concurrent intrahepatic recurrences, and 28 (40%) had non-SM intrahepatic recurrences with no other signs of recurrence. On partition analysis, the risk of marginal recurrence in patients with SM <1 mm and SM ≥1 mm was 35% and 13.5% respectively. Approximately 57% of patients with intrahepatic recurrence had recurrence ≤2.5 cm from SM. Intrahepatic recurrence after partial hepatectomy is common and is significantly associated with vascular invasion and tumor stage. About 57% of patients with intrahepatic relapse had a recurrence close (≤2.5 cm) to the SM. Additionally, patients with SM <1 mm have a higher recurrence rate and may benefit from adjuvant local therapy.

Fulvestrant, a selective estrogen receptor down-regulator, sensitizes estrogen receptor negative breast tumors to chemotherapy

Drug resistance frequently results in poor prognosis and high 5-year recurrence rate in estrogen receptor-negative (ER−) breast cancer patients. Herein, we examined the reversal effects of fulvestrant on multidrug resistance (MDR) in ER− breast cancer cells. Co-administration of fulvestrant significantly sensitized ER− MDR tumors to paclitaxel both in vitro and in vivo. Further analyses indicated that fulvestrant did not affect P-gp expression, but could inhibit P-gp function and subsequently reverse P-gp mediated drug resistance in ER− breast cancer cells. These results showed that combination of fulvestrant and chemotherapeutic agents might provide an effective treatment for ER− MDR breast cancers.

TUFM is a potential new prognostic indicator for colorectal carcinoma

Mitochondrial Tu translation elongation factor (TUFM) is a nuclear encoded protein that participates in mitochondrial polypeptide translation. TUFM has been reported to be over-expressed in many tumour types including colorectal carcinoma (CRC) by proteomics. The present study aims to examine the prognostic implication of TUFM in CRC. Immunohistochemical staining was performed in tissue microarrays composed of 123 cases of CRC using a polyclonal anti-TUFM antibody. Immunoreactivity was quantified using Image-Pro plus software, and analysed in association with patients' clinicopathological parameters and survival time. The immunoreactivity of TUFM was negative in 25%, weak in 50% and strong in 25% of CRC cases. TUFM immunoreactivity had no significant association with the clinicopathological parameters examined including TNM stage and grade. However, strong TUFM expression significantly correlated with a higher 5-year recurrence rate (p = 0.024). Kaplan-Meier analysis revealed that patients with strong TUFM expression had significantly shorter cancer-specific survival than patients with negative TUFM (log-rank test, p = 0.038). In multivariate analysis, strong TUFM expression remained a stage-independent unfavourable prognostic indicator (p = 0.024). Increased expression of TUFM is a promising new prognostic indicator for CRC. Selective inhibition of TUFM in tumour cells may present a new avenue for the targeted therapy of this cancer.

Association Between African American Race and Outcomes in Patients With Nonmetastatic Triple-Negative Breast Cancer: A Retrospective Analysis by Using Results From the Georgia Cancer Specialist Database

IntroductionThe objective of this study was to evaluate, in a real-world context, the impact of race on disease recurrence and survival in patients with nonmetastatic triple-negative breast cancer (TNBC) treated with adjuvant chemotherapy. Patients and MethodsThe study selected patients from the 2003-2008 Georgia Cancer Specialist Database with stage I-III confirmed TNBC who had received adjuvant chemotherapy. These patients were followed-up from initial diagnosis to death, cancer recurrence, or loss to follow-up. The primary outcome was disease-free survival (DFS). Kaplan-Meier curves compared DFS and recurrence between African American and non-African American groups. The impact of African American status was examined further through multivariate Cox models by adjusting for age, comorbidity, body mass index (BMI), smoking status, initial TNBC stage, surgery, and radiation therapy. ResultsAmong 209 patients with TNBC, 89 (42.6%) were African American. The 2 groups (African American vs. non–African American) were similar in mean age at diagnosis (53.2 vs. 54.4 years; P =.487) and with surgery and radiation rates (98.9% vs. 100%; P = .244; 68.5% vs. 62.5%; P = .365, respectively). Compared with non–African Americans, African American patients had a higher BMI (30.4 vs. 28.6 kg/m2; P = .0477) and were less likely to be diagnosed at stage I (31.5% vs. 51.7%; P = .0107). The African American patients had a lower 5-year DFS rate (45.2% vs. 79.7%; P = .0005) and a higher 5-year recurrence rate (42.5% vs. 7.0%; P = .0005) compared with the non–African American patients. ConclusionsAmong patients with TNBC treated with adjuvant chemotherapy, African American race was associated with a worse outcome irrespective of later stage at presentation or higher BMI.

Association of black race and outcomes in patients with nonmetastatic triple-negative breast cancer (TNBC): Results from a U.S. local oncology practice.

6107 Background: TNBC carries a poor prognosis. African American (AA) race has been shown as an adverse prognostic factor in many cancers. The objective of this study was to evaluate, in a real-world context, the impact of AA on disease recurrence and survival among nonmetastatic TNBC patients treated with adjuvant chemotherapy (CT). Methods: The Georgia Cancer Specialist Database (2003- 2008) was used. Patients with stage (I-III) BC, confirmed TN status, treated with adjuvant CT were followed from initial BC diagnosis to the earliest of death, BC recurrence, or loss to follow-up. The primary outcome was disease-free survival (DFS). The secondary outcome was recurrence. DFS and recurrence were compared between AA and non-AA groups with Kaplan-Meier curves. The impact of AA status was further examined using multivariate Cox models adjusting for age, comorbidity, BMI, smoking status, initial BC stage, surgery, and radiation therapy. Results: Among 209 TNBC patients, 89 (42.6%) were AA. The two groups (AA vs. non-AA) were similar in mean age at BC diagnosis (53.2 vs. 54.4, p = 0.487), surgery and radiation rates (98.9% vs. 100%, p = 0.244; 68.5% vs. 62.5%, p = 0.365, respectively). Compared to non-AA, AA patients were more obese (BMI: 30.4 vs. 28.6, p=0.048), and more likely to be diagnosed at stage II (stage I: 31.5% vs. 51.7%; stage II: 64.0% vs. 43.3%; stage III: 4.5% vs. 5.0%; p = 0.0107). Compared to non-AA, AA patients had lower 5-year DFS rate (45.2% vs. 79.7%, p = 0.0005), and higher 5-year recurrence rate (42.5% vs. 7.0%, p = 0.0005). The median DFS was significantly shorter for AA than non-AA patients (615 vs. 775 days, p = 0.0005). The multivariate Cox models showed that AA was associated with lower likelihood for DFS (HR = 0.15, p = 0.0005), and higher risk for recurrence (HR = 8.16, p = 0.0006), compared to non-AA patients. Conclusions: This study suggested that AA race was associated with worse outcomes irrespective of later stage at presentation among TNBC patients who were treated with currently available adjuvant CT. Future studies need to explore genotypic as well as behavioral reasons for inferior outcomes associated with AA race. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration sanofi-aventis sanofi-aventis sanofi-aventis

Pronostic et fertilité après traitement conservateur d’une tumeur ovarienne à la limite de la malignité : revue d’une série continue de 68 cas

The aim of this retrospective study was to evaluate the rate of recurrence and the reproductive outcome after surgical conservative treatment of low malignant ovarian tumors (LMOT). Material and methods – Sixty-eight patients with 50 Stage I LMOT and 18 LMOT with peritoneal implants treated conservatively at institut Gustave-Roussy, between January 1969 and December 2000. Fifty-nine patients had an unilateral adnexectomy (associated twelve times with a contralateral cystectomy), Seven had a bilateral cystectomy and two an unilateral cystectomy. Five patients recieved adjuvant therapy. Results – With a median follow-up of 71,5 months, 16 patients recurred and one had evolutive peritoneal disease. The histologic pattern of ovarian recurrences was always of borderline type. The histologic patterns of peritoneal recurrence was similar to those initially diagnosed except in one case. Peritoneal implants, exophytic tumor and serous type tumor were significatively associated with a higher 5-year recurrence rate. Recurrence was more frequent after cystectomy than unilateral adnexectomy ( p = 0.13). None of patients treated conservatively recurred under the form of ovarian carciboma. None patient died of tumor. Nineteen patients experienced 26 pregnancies : 24 were spontaneous in a median delay of 19 months. Seven infertile patients underwent ovarian stimulation. None recurred after infertility treatments. The 2-year and 5-year cumulative pregnancy rate were respectively 41,9 % and 59,8 %. Four patients experienced a pregnancy after a conservative treatment of their recurrence. Conclusion – Despite a high recurrence rate, especially in stage II and III serous LMOT, conservative treatment of LMOT does not affect survival and should be considered in young patients. Such treatment is not advised in case of invasive peritoneal implants. Spontaneous pregnancy rate is good but the frequent infertility associated with these tumors can afterwards require ovarian stimulation. Limited number of stimulation cycles is acceptable in such patients.