Long-term follow-up reveals that ulceration and sentinel lymph node status are the strongest predictors for survival in patients with primary cutaneous melanoma

Purpose

To assess the long-term outcome after sentinel lymph node biopsy (SLNB) in melanoma patients.

Methods

Between 1995-2009 450 melanoma patients underwent SLNB in a single center. Survival and prognostic factors were analyzed for 429 patients.

Results

Median age was 53 (range 11-84) years. Median Breslow thickness was 2.4 (range 1-20) mm and 36% were ulcerated melanomas. Median follow-up time was 64.8 (range 2-174) months. A tumor-positive SLN was present in 140 patients (31%). Completion lymph node dissection (CLND) was performed in 119 patients and these patients were analyzed for recurrence and survival.124 Patients (29%) relapsed during follow-up; 55 in the node-positive group who underwent CLND (55/119; 46%) and 69 in the node-negative group (69/310; 22%; p < 0.001). In the node-negative group 17 patients developed recurrence in the regional node field; false-negative rate 11%.On multivariate analysis strongest prognostic factors for disease free survival (DFS) were primary melanoma ulceration and SLN positivity (Hazard Ratio (HR) of 2.2 and 2.3; p < 0.001). For disease specific survival (DSS) the same was found to be true with an HR of 2.1 for ulceration and 2.0 for SLN positivity (p = 0.001 and p = 0.002 respectively). 10-Year DFS was 71% for node-negative patients compared with 48% for node-positive patients (p < 0.001). 10-Year DSS was 77% for node-negative patients compared to 60% for node-positive patients (p < 0.001).

Conclusions

This study shows a remarkably high percentage of tumor-positive SLN. The long-term follow-up data confirm that tumor-positive SLN patients have a worse DFS and DSS than tumor-negative SLN patients. Ulceration and SLN status proved to be the strongest prognostic factors for long-term DFS and DSS.     

三阴性对小肿块乳腺癌患者预后的影响

  目的  分析小肿块（直径≤1 cm）乳腺癌患者的临床及病理学特征,了解其生存状态,探讨三阴性对其预后的影响。  方法  收集本院收治的312例直径≤1 cm乳腺癌患者的临床病理学资料,比较三阴性乳腺癌及非三阴性乳腺癌的临床病理学特征、复发转移及生存情况。  结果  312例直径≤1 cm乳腺癌患者纳入研究,三阴组及非三阴组5年DFS分别为81.4%及90.5%（P= 0.038）,5年BCSS分别为84.7%及93.7%（P=0.047）。以淋巴结状态分组比较,淋巴结阴性患者中,三阴组及非三阴组5年DFS分别为82.8%及94.1%（P=0.033）,5年BCSS分别为85.0%及96.1%（P=0.019）。Cox比例风险模型多因素分析显示,淋巴结阳性患者复发转移风险增高（HR=3.721,95%CI:1.743~7.941,P=0.001）,死亡风险亦增高（HR=3.560,95%CI:1.521~8.330,P=0.003）,三阴性患者复发转移风险增高（HR=2.208,95%CI:1.028~4.742,P=0.042）。  结论  淋巴结阳性及三阴性是影响直径≤1 cm乳腺癌患者DFS的独立危险因素,淋巴结阳性是影响BCSS的唯一独立危险因素。淋巴结阴性三阴性乳腺癌组较非三阴组预后差。      

Impact on survival of the number of lymph nodes removed in patients with node-negative gastric cancer submitted to extended lymph node dissection

Purpose

This study was designed to establish whether the number of lymph nodes removed has an effect on prognosis in patients with node-negative gastric cancer.

Patients and Methods

We retrospectively analysed data of 114 consecutive patients who underwent gastrectomy and extended lymph node dissection for node-negative adenocarcinoma of the stomach between 2000 and 2005. Standard survival methods and restricted cubic spline multivariable Cox regression models were applied.

Results

Median age was 63 years and 67 patients out of 114 (59%) were males. Median number of dissected LNs was 22 (range 2-73). Median follow-up was 76 months. Patients who had ≤15 nodes removed had significantly worse distant disease-free survival, disease-free survival and overall survival at multivariable analysis than other patients. The results did not change when pT1 and pT2-3 cancer patients were analysed separately. The risk of distant metastases decreased as the number of dissected lymph nodes increased (>15).

Conclusions

More extended lymph node resection offered survival benefit even in the subgroup of patients with early stage disease. Lymphadenectomy involving more than 15 lymph nodes should be performed for the treatment of node-negative gastric cancer.

Synopsis

The impact on survival of the number of lymph nodes removed in patients with node-negative gastric cancer has not been established. This study suggests that more extended lymph node resection offers protection, as patients who had ≤15 nodes removed had significantly worse disease-free survival and overall survival at multivariate analysis than patients in whom >15 nodes were removed.     

Peritumoural vascular invasion: a major determinant of triple-negative breast cancer outcome

Purpose

Triple-negative breast cancers (TNBC) have the worst outcome of all breast cancer subtypes. Nevertheless TNBC are heterogeneous in terms of pathological, biological and prognostic behaviours. We explored clinical and pathological factors correlated with outcome in this phenotype.

Methods

We retrospectively studied clinical and pathological factors correlated with prognosis in a series of 344 early TNBC. Staining for blood (CD31) and lymphatic (Podoplanin) vascular endothelium markers was performed to best characterise peritumoural vascular invasion (PVI) in 108 cases available for pathological reviewing.

Results

Univariate and multivariate analyses performed on our whole cohort underlined PVI as an independent predictive factor of distant metastasis (p = 0.00012, HR = 2.72 [1.63-4.52]). Standardised pathological reviewing of 101 histologically confirmed TNBC showed that PVI, observed in 41% (28% by haematoxylin and eosin staining plus 13% by immunohistochemistry), was confirmed as the first prognostic factor in TNBC, particularly in node-negative tumours. Five-year metastasis-free survival in this subset was 87.5% and 50.8% without and with PVI, respectively (p = 0.003).

Conclusions

Vascular invasion diagnosis is improved by the combination of HES and IHC. Moreover it is a major prognostic feature and must take a greater part in therapeutic management of early TNBC with the possibility to adapt the adjuvant treatment according to the predicted relapse risk.     

Liver resection for metastatic soft tissue sarcoma: An analysis of prognostic factors

Aim

The aim of this retrospective study was to analyse the outcome following hepatic resection for metastatic STS and to identify factors predicting survival.

Methods

All patients who underwent hepatic resection for metastatic STS between August 1997 and April 2009 were included. The data was obtained from a prospectively maintained database. Patients’ demographics, clinico-pathological parameters, overall survival and the factors predicting survival were analysed.

Results

Thirty-six patients underwent hepatic resection for metastasis, with a median age of 58 years. The predominant site of primary tumour was the gastro-intestinal tract (50%). Leiomyosarcoma was the most common histological type (54%). The median interval between the primary and metastatic resections was 17 months. Thirteen patients had synchronous tumours. 24 patients had major liver resections and 10 patients had bi-lobar disease. The median number of liver lesions resected was 1(1-6) and the median maximum diameter was 11 cm (1-26 cm). R0 resection was performed in 31 patients. The 1-, 3- and 5-year overall survival from the time of metastasectomy was 90.3%, 48.0% and 31.8% respectively, with a median survival of 24 months. Factors associated with poor survival on univariate analysis were the presence of high grade tumours (p = 0.04), primary leiomyosarcoma (p = 0.01) and positive resection margin of liver metastasis (p = 0.04), whilst multivariate analysis predicted primary leiomyosarcoma as a risk factor for poor survival (p = 0.01).

Conclusion

Hepatic resection for metastatic STS appears to be valuable in carefully selected patients with acceptable long-term survival. The aim of surgery must be an R0 resection to offer a chance of cure.     

The value of pre operative S-100B and SUV in clinically stage III melanoma patients undergoing therapeutic lymph node dissection

Introduction

High preoperative serum S-100B values and Standardized Uptake Values (SUV) of Fluorodeoxyglucose (FDG) in PET for clinically stage III melanoma patients could be indicators of recurrence after surgical treatment. Aim was to assess the correlation and the prognostic value of these markers.

Methods

All melanoma patients with palpable nodal metastases, without distant metastases, were included from February 2004 to December 2007. Preoperative SUV and S-100B was determined. The correlation between SUV and S-100B and their relations with DFS and DSS were calculated by Cox Proportional Hazard Analysis.

Results

62 Patients, median age 56.9 years, were included in the study. An elevated S-100B was found in 31 patients (50%) and elevated SUV in 24 patients (38.7%). No relation was found between S-100B and SUV. DFS was reduced (31.1%) for patients with an elevated S-100B (HR = 3.1; p = 0.02) in comparison to a normal S-100B (44.6%). The DFS was 42.0% for patients with a SUV below the cut-off point and 29.0% for patients with an elevated SUV (HR = 1.1; p = 0.8). DSS was 60.7% in a normal S-100B and 44.7% for patients with an elevated S-100B (HR = 2.2; p = 0.07). DSS was 59.1% for patients with a normal SUV and 43.5% for patients with elevated SUV (HR = 1.1; p = 0.8).

Conclusion

S-100B and SUV in stage III melanoma are not correlated and each have different associations with various histopathological factors. S-100B, in contrast with SUV, is associated with nodal tumor load, and when elevated, predicts a shorter DFS.

Synopsis

Preoperative serum S-100B and Fluorodeoxyglucose (FDG) Standardized Uptake Value (SUV) in clinically stage III melanoma are not correlated. S-100B is a strong predictor for Disease Free Survival (DFS) in stage III melanoma.     

Prognostic factors and recurrence pattern in node-negative advanced gastric cancer

Aims

Despite better overall survival in node-negative advanced gastric cancer (AGC), a significant proportion of patients develop recurrence and they may benefit from adjuvant therapy. The aim of this study was to evaluate the prognostic factors and recurrence pattern of node-negative AGC.

Methods

A total of 424 patients who underwent curative gastrectomy with extended lymphadenectomy for node-negative AGC between 2003 and 2005 were retrospectively reviewed. Patients with tumor involvement of adjacent organs (T4b), gastric cancer recurrence, tumor in the remnant stomach, less than 15 harvested lymph nodes, and those who received neoadjuvant chemotherapy were excluded.

Results

Invasion to deeper layers, undifferentiated histology, signet ring cell type compared with tubular adenocarcinoma, and tumor size larger than 6.3 cm correlated with poorer prognosis in univariate analysis. In multivariate one, however, only differentiation and depth of invasion, especially the presence of serosa involvement were significant. The 5-year survival rates of the four groups classified by differentiation and depth of invasion [T2/3 (differentiated type), T2/3 (undifferentiated type), T4a (differentiated type), and T4a (undifferentiated type)] were 98%, 92%, 80%, and 72%, respectively (P < 0.01). In terms of recurrence pattern, Lauren's type and depth of invasion were significant. Recurrence with peritoneal seeding was associated with the diffuse type and invasion into the subserosa or serosa, while hematogenous metastasis was related to the intestinal type and invasion to the proper muscle or subserosa layer.

Conclusions

Differentiation and serosa involvement should be considered to stratify patients with node-negative AGC for adjuvant treatment.     

Ovarian cancer in the elderly: Impact of surgery on morbidity and survival

Background

Elderly ovarian cancer patients often undergo non-optimal surgery due to their age despite of the high risk of recurrence. The aim of this study was to determine if more postoperative complications occurred in patients over 70 years and to compare extent of surgery with younger patients.

Materials and methods

Between 2001 and 2009, 172 patients with ovarian cancer were included. We compared patient characteristics, surgical course, postoperative complications and outcome for patients under and over 70 years.

Results

143 patients were under 70 years and 29 over. There were no difference between the two groups for tumors characteristics, time of surgery, FIGO stage, standard surgical procedures and rate of optimal resection. Patients over 70 years had less peritoneal surgery (p < 0.001) especially diaphragmatic surgery (p = 0.006), pelvic (p = 0.02) and para-aortic (p = 0.003) lymphadenectomy. There was no difference in the occurrence of per- or post-operative complications and patients over 70 years had shorter duration of hospitalization (p = 0.04). There was no difference between the two groups for disease-free survival (DFS) (p = 0.08) but overall survival (OS) was better in patients under 70 years (p = 0.002).

Conclusion

Elderly ovarian cancer patients undergo less extensive surgery and have lower OS despite similar postoperative morbidity, optimal resection and DFS. OS decrease could be explained by difference in the management of recurrences.     

Accelerated partial-breast irradiation using high-dose-rate interstitial brachytherapy: 12-year update of a prospective clinical study

Background and purpose

To report the 12-year updated results of accelerated partial-breast irradiation (APBI) using multicatheter interstitial high-dose-rate (HDR) brachytherapy (BT).

Patients and methods

Forty-five prospectively selected patients with T1N0-N1mi, nonlobular breast cancer without the presence of an extensive intraductal component and with negative surgical margins were treated with APBI after breast-conserving surgery (BCS) using interstitial HDR BT. A total dose of 30.3 Gy (n = 8) and 36.4 Gy (n = 37) in seven fractions within 4 days was delivered to the tumour bed plus a 1-2 cm margin. The median follow-up time was 133 months for surviving patients. Local and regional control, disease-free (DFS), cancer-specific (CSS), and overall survival (OS), as well as late side effects, and cosmetic results were assessed.

Results

Four (8.9%) ipsilateral breast tumour recurrences were observed, for a 5-, 10-, and 12-year actuarial rate of 4.4%, 9.3%, and 9.3%, respectively. A total of two regional nodal failures were observed for a 12-year actuarial rate of 4.4%. The 12-year DFS, CSS, and OS was 75.3%, 91.1%, and 88.9%, respectively. Grade 3 fibrosis was observed in one patient (2.2%). No patient developed grade 3 teleangiectasia. Fat necrosis requiring surgical intervention occurred in one woman (2.2%). Cosmetic results were rated excellent or good in 35 patients (77.8%).

Conclusions

Twelve-year results with APBI using HDR multicatheter interstitial implants continue to demonstrate excellent long-term local tumour control, survival, and cosmetic results with a low-rate of late side effects.     

Expression and prognostic role of pan-Ras, Raf-1, pMEK1 and pERK1/2 in patients with hepatocellular carcinoma

Aims

Ras/Raf/mitogen-activated protein kinase (MEK)/extracellular signal-regulated kinase (ERK) signaling cascades play important roles in the transmission of signals involved in apoptosis. Importantly, components of these pathways are aberrantly expressed in human cancer. However, there is limited data linking clinical outcomes with the aberrant expression of this pathway. The present study analyzed the prognostic values of pan-Ras, Raf-1, phosphorylated MEK1 (pMEK1) and phosphorylated ERK1/2 (pERK1/2) in hepatocellular carcinoma (HCC).

Methods

Expression of pan-Ras, Raf-1, pMEK1 and pERK1/2 in 81 HCC patients who underwent curative resection was examined by immunohistochemical staining. Long-term survival after resection of patients according to the expression of pan-Ras, Raf-1, pMEK1 and pERK1/2 was assessed using univariate analysis and multiple Cox proportional hazards model.

Results

In univariate analysis, patients with Raf-1 or pMEK1 overexpression had shorter disease-free survival (DFS) (P＜ 0.05) and poorer overall survival (OS) (P＜ 0.05) than groups with weak-expression of Raf-1 or pMEK1, respectively. Patients with pan-Ras overexpression had poorer overall survival (OS) (P＜ 0.05) than the group with weak-expression of pan-Ras. Importantly, Raf-1 overexpression was a promising prognostic marker for poor survival according to multivariate Cox regression analysis (DFS, Hazard Ratio 1.807, P = 0.035; OS, Hazard Ratio 1.959, P = 0.044).

Conclusions

Raf-1 overexpression could be considered as an independent prognostic biomarker in HCC and may predict early tumor recurrence and death for HCC patients. It can be used to stratify patients at higher risk for poor prognosis and help to select the appropriate therapeutic regime of HCC.     

Prognostic significance of IGF-1R expression in patients treated with breast-conserving surgery and radiation therapy

Background

Insulin-like growth factor (IGF) receptor is a key receptor in apoptotic protection, cell adhesion, longevity, and transformation into a cancerous cell and can induce malignant changes in the presence of the IGF ligand. Over-expression of IGF-1R has been associated with resistance to radiation. Inhibitors of IGF-1R have been shown to enhance tumor radiation sensitivity and amplify radiation therapy-induced apoptosis. The purpose of this study is to evaluate the prognostic significance of IGF-1R expression in patients with breast cancer treated with breast conserving therapy.

Materials and methods

Paraffin specimens from 345 women with early stage breast cancer treated with BCT were constructed into tissue microarrays and stained for IGF-1R, COX-2 and p53. The molecular profiles were correlated with clinical-pathologic factors, overall, local, and distant relapse-free survival. The association between IGF-1R, other co-variables, and outcome was assessed.

Results

IGF-1R over-expression was identified in 197 cases (57%). IGF-1R over-expression was found to be correlated with African-American race (p = 0.0233), p53 status (p = 0.0082) and COX-2 expression (p < 0.0001). While IGF-1R over-expression was associated with lower overall survival (p = 0.0224) in node-negative patients, there was no impact of IGF-1R expression on local control.

Conclusions

In node-negative patients, patients with high levels of IGF-1R were found to have a significant reduction in overall survival, but no apparent effect on local control. Given the limited published data on IGF-1R in early stage, conservatively treated patients, further studies investigating IGF-1R expression in this cohort are necessary.     

Triple-negative breast cancer has worse overall survival and cause-specific survival than non-triple-negative breast cancer

Purpose

The current American Joint Committee on Cancer (AJCC) staging manual uses tumor size, lymph node, and metastatic status to stage breast cancer across different subtypes. We examined the prognosis of triple-negative breast cancer (TNBC) versus non-TNBC within the same stages and sub-stages to evaluate whether TNBC had worse prognosis than non-TNBC.

Methods

We reviewed the National Cancer Institute Surveillance, Epidemiology, and End Results (SEER) data and identified 158,358 patients diagnosed with breast cancer from 2010 to 2012. The overall survival (OS) time and breast cancer cause-specific survival time were compared between patients with TNBC and non-TNBC in each stage and sub-stages. The results were validated using a dataset of 2049 patients with longer follow-up from our institution.

Results

Compared with patients with non-TNBC, patients with TNBC had worse OS and breast cancer cause-specific survival time in every stage and sub-stage in univariate and multivariate analyses adjusting for age, race, tumor grade, and surgery and radiation treatments in the SEER data. The worse OS time in patients with TNBC was validated in our institutional dataset.

Conclusions

Patients with TNBC have worse survival than patients with non-TNBC. The new AJCC staging manual should consider breast cancer biomarker information.

     

Characteristics of combined hepatocelluar-cholangiocarcinoma and comparison with intrahepatic cholangiocarcinoma

Background

The 7th American Joint Committee on Cancer (AJCC) currently classifies combined hepatocellular-cholangiocarcinoma (cHCC-CC) and intrahepatic cholangiocarcinoma (ICC) into one category. Study outcomes comparing the two carcinomas have shown contrary results. This study was designed to compare the survival and prognostic factors of both carcinomas.

Methods

We retrospectively reviewed the medical records of 107 patients with cHCC-CC or ICC who underwent liver resection between January 2000 and December 2009.

Results

Thirty patients (28%) were diagnosed with cHCC-CC, and 77 patients (72%) had ICC. Disease-free survival (DFS) was poorer in the cHCC-CC patients (six months), and the overall survival (OS) durations were similar (p = 0.477) between cHCC-CC (58 months) and ICC (45 months) patients. A tumor size larger than 5 cm, vascular invasion and lymph node (LN) metastasis were prognostic factors in all patients. However, tumor size and LN metastasis in cHCC-CC patients and carbohydrate antigen 19-9, differentiation and LN metastasis in ICC patients were found to be independent prognostic factors.

Conclusions

Patients with cHCC-CC showed poorer DFS and similar OS rates compared to those with ICC. Our study revealed different prognostic factors in cHCC-CC. To understand more accurately cHCC-CC's prognosis, difference of genetic characteristics and tumor biology should be further evaluated.     

Prognostic effect of steatosis on hepatocellular carcinoma patients after liver resection

Aims

Overweight/obesity is currently a common health issue that may cause many diseases, even malignancies. The influence of steatosis on long-term results of surgical treatment for hepatocellular carcinoma (HCC) is not well known. The aim of this study is to analyze the results of hepatectomy for HCC patients with steatosis.

Methods

The study included 1048 patients who underwent hepatectomy for HCC from 1999 to 2005. The patients were divided into two groups; group A patients without steatosis (n = 693) and group B patients with steatosis (n = 355). The clinicopathological data and long-term survival were analyzed.

Results

Mean tumor size in group B patients was smaller than that in group A patients (4.61 ± 3.40 vs. 5.91 ± 4.36 cm, p < 0.01). Group B patients showed lower tumor differentiation grade, lower vascular invasion rate and better 5-year overall survival compared to group A patients (61.2% vs. 50.1%, p = 0.001). By multivariate analysis, steatosis was found to be associated with well-differentiated, small-sized, and less α-fetoprotein productive tumors. When focusing on the tumors >5 cm in diameter, group B patients had better survival rate than group A patients (p = 0.041). Vascular invasion and steatosis were independent prognostic factors for the overall survival.

Conclusion

HCC in steatotic liver was less aggressive than that in non-steatotic liver. HCC patients with steatosis have better surgical outcomes than those without steatosis. Vascular invasion and steatosis were independent prognostic factors for the overall survival if tumors were >5 cm in diameter.     

Prognostic significance of the number of examined lymph nodes in node-negative gastric adenocarcinoma

Aim

In this study, we investigated the prognostic significance of the number of examined lymph nodes in node-negative gastric adenocarcinoma (GC).

Patients and methods

A total of 1194 node-positive and 1030 node-negative GC patients undergoing potentially curative gastrectomy was enrolled in this study. Patients were stratified into 3 groups according to the number of examined lymph nodes: group 1, ≤15; group 2, 16–25; group 3, >25.

Results

Patients with node-negative GC had significantly favorable survival compared with those with node-positive. Among patients with node-negative T2–T4 disease, the percentage of locoregional relapse was higher in those with <25 examined lymph nodes than in those with ≥25 examined lymph nodes. The number of examined lymph nodes affected the overall survival rates for patients with node-negative T2–T4 GC but not for patients with T1 lesions. Tumor size, tumor location, the number of examined lymph nodes, T status, and the presence of perineural invasion were significant prognostic factors as determined by multivariate analysis in node-negative GC.

Conclusions

No survival benefit of examining ≥15 lymph nodes was noted for patients with node-negative T1 GC. Extensive lymphadenectomy in patients with node-negative T2–T4 lesions in whom the number of examined lymph nodes was >25 had favorable survival.     

Sentinel lymph node biopsy in gastric cancer: Possible applications and limits

Aims

To explore the feasibility and accuracy of sentinel lymph node (SLN) biopsy in gastric cancer.

Patients and Methods

Twenty-nine patients with clinical T1 and T2 N0 M0 gastric cancer less than 5 cm in diameter underwent SLN biopsy with the intraoperative Patent blue method. The procedure continued with radical gastrectomy and D2 lymphadenectomy. We investigated all technical aspects of the blue dye technique and determined the accuracy, sensitivity, specificity, positive predictive value, and negative predictive value of the SLN technique.

Results

SLNs were detected in 28 of 29 patients; the total number of excised SLNs was 45, with a median of two (range 1-3). Seventeen patients had metastatic SLN, with 21 lymph nodes retrieved. Twenty-two patients had SLNs located at the first level. Four patients had SLNs at the second level, one at the first and second levels, and one at the first and third levels. Five patients had false negative SLNs. The ability of SLN biopsy to predict the status of the other lymph nodes was summarised by an accuracy of 75%, a sensitivity of 75%, a specificity of 75%, a positive predictive value of 88%, and a negative predictive value of 55%.

Conclusions

Our study demonstrates that pick-up SLN biopsy in gastric cancer is technically feasible but has very low sensitivity. Regarding the utility of SLN navigation when attempting to detect the nodal basin, the high rate of false negative SLNs and lymph node level jumping warrant further studies with a large accrual before the method can be introduced into daily practice.     

High PD-L1 expression was associated with poor prognosis in 870 Chinese patients with breast cancer

Background

To investigate the role of PD-L1 expression in tumor recurrence and metastasis in Chinese patients with breast cancer.

Methods

Suitable tissue samples were available from 870 patients with breast cancer. Paraffin-embedded tumor sections were stained with PD-L1 antibody. The correlations between PD-L1 expression and clinical characteristics, ER/PR/HER2 status and survival parameters were analyzed. Kaplan-Meier and univariate Cox proportional hazards model analyses were used to compare the survival of patients with high PD-L1 expression and patients with no PD-L1 expression.

Results

The median follow-up time was 98 months(range, 17–265 months). The positive rate of PD-L1 expression in breast cancer was 21.7% (189/870). PD-L1 high expression was inversely associated with larger tumor size, higher tumor grade, more positive lymph node number, as well as negative ER and PR status. PD-L1 expression was particularly higher in TNBC compared with non-TNBC, although no statistical significance was observed. Nomogram logistic regression results based on clinical and pathological features showed that the following factors were more likely associated with high PD-L1 expression: patient age younger than 35 years, larger tumor size, lymphovascular invasion and advanced stage. Our data indicated that patients with high PD-L1 expression had poor DFS, DMFS and overall survival compared with those with no PD-L1 expression. Univariate Cox proportional hazards model analysis showed that PD-L1 was an independent prognostic factor for tumor prognosis.

Conclusions

PD-L1 expression is an important indicator of unfavorable prognosis in breast cancer patients.     

Activity of Dutasteride Plus Ketoconazole in Castration-Refractory Prostate Cancer After Progression on Ketoconazole Alone

Background

Ketoconazole is a commonly used secondary hormonal therapy in castration-refractory prostate cancer (CRPC), but disease progression inevitably occurs. Both prostatic and metastatic lesions in patients with CRPC overexpress 5-α reductase (SRDA5) type I. We hypothesized that SRDA5 inhibition in combination with ketoconazole would mitigate progression after treatment with ketoconazole alone.

Patients and Methods

A total of 10 patients with CRPC with progression after ketoconazole treatment were treated with a combination of ketoconazole plus dutasteride 0.5 mg/day, a dual SRDA5 inhibitor.

Results

After dutasteride addition, 8 (80%) of the 10 patients had varying degrees of prostate-specific antigen (PSA) decline relative to baseline. Median progression-free survival after dutasteride addition was 4.9 months (range, 2.7+ to 9.8 months); no patient had a ≤ 50% PSA decline.

Conclusion

We conclude that dutasteride added to ketoconazole at the time progression might prolong time to PSA progression in patients with CRPC.     

Prognostic relevance of the lymph node ratio in surgical patients with extrahepatic cholangiocarcinoma

Aim

Few studies have investigated the influence of the lymph node ratio (LNR), the ratio of the number of lymph nodes harboring metastatic cancer to the total number of lymph nodes removed, on the outcome after surgery for extrahepatic cholangiocarcinoma. This study was conducted to examine the prognostic impact of LNR in patients undergoing resection for extrahepatic cholangiocarcinoma.

Patients and Methods

We retrospectively analyzed a total of 60 consecutive patients who underwent resection for extrahepatic cholangiocarcinoma. We focused on the LNR, which was classified as 0 in 34 patients, between 0 and 0.2 in 13 patients, and greater than 0.2 in 13 patients.

Results

The overall five-year survival rates for patients with LNRs of 0, 0 to 0.2, and ≥0.2 were 44%, 10%, and 0%, respectively (p = 0.023). LNR was an independent predictive factor for estimated survival by both univariate (p = 0.016) and multivariate (p = 0.022) analyses including LNR, the sites of the primary tumors, and surgical margin as the variables. There were no statistically significant differences between patients who had less than 12 lymph nodes removed and those who had 12 or more lymph nodes removed (p = 0.484).

Conclusion

LNR was a powerful, independent predictor of estimated survival in patients undergoing surgical resection for extrahepatic cholangiocarcinoma. LNR should be considered when stratifying patients for future clinical trials.     

Mesothelioma at era of helical tomotherapy: results of two institutions in combining chemotherapy, surgery and radiotherapy

Purpose

There is a scarce clinical experience about adjuvant helical tomotherapy (HT) in patients affected by malignant pleural mesothelioma (MPM) even though it appears as a useful technique to treat complex volume as the pleural cavity, and seems to have better dose distribution than the “classic” intensity modulated radiotherapy (IMRT).

Methods and materials

Twenty-four patients received adjuvant radiotherapy (RT) by HT from August 1st, 2007 to December 1st, 2009 at Curie Institute (Paris) and René Gauducheau Cancer Center (Nantes). Thirteen patients had neoadjuvant chemotherapy. Extrapleural pleuropneumonectomy (EPP) was done in 23 patients. Median dose to PTV was 50 Gy [48.7-55.9 Gy] (2 Gy/fraction). Acute and long term toxicities, disease free survival (DFS), overall survival (OS) and relapses are presented.

Results

Average follow up after RT was 7 months. The disease was staged mostly as T2-T3, N1-N2. Nineteen patients had epithelial type histology. Most patients tolerated radiotherapy with grade 1-2 side effects: redness of the skin, light cough or dyspnea, fatigue, nausea and odynophagia, mild increase of the post-operative thoracic pain. Grade 3 pneumonitis was suspected in 2 patients. Two grade 5 pneumonitis were also suspected. Eleven patients had a follow up of more than 6 months and no long term side effects related with HT were noted. At 24 months, 51.8% of patients were free of disease. Thirty percent of patients relapsed, with 2 patients presenting local relapses. Two patients died from recurrence.

Conclusion

With limited follow up, HT has comparable toxicity to those observed with traditional IMRT. Higher radiation dose and good coverage results in excellent local control.