Type 2 Diabetes Mellitus Is Associated With Increased Mortality in Chinese Patients Receiving Curative Surgery for Colon Cancer

Background.

We investigated the association between diabetes mellitus (DM) and the prognosis of patients with early colon cancer who had undergone curative surgery.

Methods.

From three national databases of patients in Taiwan, we selected a cohort of colon cancer patients who had been newly diagnosed with stage I or stage II colon cancer between January 1, 2004 and December 31, 2008 and had undergone curative surgery. We collected information regarding DM (type 2 DM only), the use of antidiabetic medications, other comorbidities, and survival outcomes. The colon cancer-specific survival (CSS) and the overall survival (OS) were compared between patients with and without DM.

Results.

We selected 6,937 colon cancer patients, among whom 1,371 (19.8%) had DM. The colon cancer patients with DM were older and less likely to receive adjuvant chemotherapy but had a similar tumor stage and grade, compared with colon cancer patients without DM. Compared with colon cancer patients without DM, patients with DM had significantly shorter OS (5-year OS: 71.0% vs. 81.7%) and CSS (5-year CSS: 86.7% vs. 89.2%). After adjusting for age, sex, stage, adjuvant chemotherapy, and comorbidities in our multivariate analysis, DM remained an independent prognostic factor for overall mortality (adjusted hazards ratio: 1.32, 95% confidence interval: 1.18–1.49), but not for cancer-specific mortality. Among the colon cancer patients who had received antidiabetic drug therapy, patients who had used insulin had significantly shorter CSS and OS than patients who had not.

Conclusion.

Among patients who receive curative surgery for early colon cancer, DM is a predictor of increased overall mortality.     

Post-mastectomy radiotherapy benefits subgroups of breast cancer patients with T1–2 tumor and 1–3 axillary lymph node(s) metastasis

Background

To determine the role of postmastectomy radiotherapy (PMRT) in breast cancer patients with T1–2 and N1 disease.

Patients and methods.

A total of 207 postmastectomy women were enrolled. The 5-year Kaplan-Meier estimates of locoregional recurrence rate (LRR), distant recurrence rate (DRR) and overall survival (OS) were analyzed by different tumor characteristics. Multivariate analyses were performed using Cox proportional hazards modeling.

Results

With median follow-up 59.5 months, the 5-year LRR, DRR and OS were 9.1%, 20.3% and 84.4%, respectively. On univariate analysis, age < 40 years old (p = 0.003) and Her-2/neu over-expression (p = 0.016) were associated with higher LRR, whereas presence of LVI significantly predicted higher DRR (p = 0.026). Negative estrogen status (p = 0.033), Her-2/neu overexpression (p = 0.001) and LVI (p = 0.01) were significantly correlated with worse OS. PMRT didn’t prove to reduce 5-year LRR (p = 0.107), as well as 5-year OS (p = 0.918). In subgroup analysis, PMRT showed significant benefits of improvement LRR and OS in patients with positive LVI.

Conclusions

For patients with T1–2 and N1 stage breast cancer, PMRT can decrease locoregional recurrence and increase overall survival only in patients with lymphovascular invasion.     

[18F]‐Fluorodeoxyglucose Positron Emission Tomography Standardized Uptake Value as a Predictor of Adjuvant Chemotherapy Benefits in Patients With Nasopharyngeal Carcinoma

Background.

The role of adjuvant chemotherapy for the treatment of nasopharyngeal carcinoma (NPC) is controversial, and the identification of adequate predictive factors is warranted. Therefore, we aimed to investigate whether the mean standardized uptake value (SUV) measured on [¹⁸F]-fluorodeoxyglucose (FDG) positron emission tomography (PET) could predict the survival benefits for NPC patients that receive adjuvant chemotherapy.

Materials and Methods.

The data for 174 NPC patients who underwent PET/computed tomography before chemoradiation between January 2004 and January 2012 were reviewed. The SUV_75% was recorded for primary tumors. All patients received intensity-modulated radiotherapy and cisplatin-based chemotherapy. Adjuvant chemotherapy consisted of 3 cycles of 75 mg/m² cisplatin and 1,000 mg/m² fluorouracil for 4 days.

Results.

The optimal cutoff value was 8.35 for SUV_75%, with 112 (64.4%) patients having lower SUV_75% and 62 (35.6%) having higher SUV_75%. Patients with lower SUV_75% had significantly better 5-year overall survival (OS) and distant metastasis-free survival. Multivariate analysis revealed that tumor stage, SUV_75%, and adjuvant chemotherapy were significant prognostic factors for OS. Patients with higher SUV_75% had significantly higher 5-year OS rates with adjuvant chemotherapy than without adjuvant chemotherapy (84.3% vs. 32.4%, respectively; p < .001). However, in the lower SUV_75% group, no differences in 5-year OS were observed between patients who received and those who did not receive adjuvant chemotherapy (92.4% vs. 93.3%, respectively; p = .682).

Conclusion.

The SUV_75% on FDG PET for primary tumors could successfully identify NPC patients who may benefit from adjuvant chemotherapy.     

A nomogram that predicts pathologic complete response to neoadjuvant chemoradiation also predicts survival outcomes after definitive chemoradiation for esophageal cancer

Background

Pathologic complete response (pCR) to neoadjuvant chemoradiation for esophageal cancer is associated with improved outcomes. We evaluated whether a nomogram designed to predict who would have a pCR after trimodality therapy could also predict outcome after definitive chemoradiation.

Methods

Patients in this retrospective, single-institution analysis had received chemoradiation without surgery for esophageal cancer from 1998 through 2010; 333 such patients had complete information on all variables required for the pCR nomogram: sex; T status (by endoscopic sonography); tumor grade; tumor avidity on positron emission tomography (PET); and esophagogastroduodenoscopy (EGD)-directed biopsy results after chemoradiation. We used multivariate Cox regression to test potential associations between clinical outcomes [overall survival (OS), locoregional recurrence, and distant metastasis] and patient or treatment factors and the pCR nomogram score; the component variables of the nomogram were not reintroduced into the multivariate analysis.

Results

The median follow-up time for all patients (median age 66 years) was 18.2 months (30.7 months for those alive at the time of analysis). Patients with nomogram scores ≤125 (median for all patients) had significantly worse outcomes than patients with scores >125: median OS time 19.7 vs. 48.2 months; disease-free survival (DFS) time 6.1 vs. 31.1 months; locoregional failure-free survival time 17.7 months vs. not reached; and distant metastasis-free survival time 11.7 months vs. not reached (all P<0.001). Multivariate Cox regression analysis indicated that nomogram score independently predicted each survival outcome, along with other patient and disease factors.

Conclusions

The pCR nomogram score predicted survival outcomes in patients receiving definitive chemoradiation for esophageal cancer. Although this nomogram requires further validation, it may prove useful for stratifying patients for clinical trials designed to intensify treatments for patients at the highest risk of relapse.     

The Prognostic Impact of Type 2 Diabetes Mellitus on Early Cervical Cancer in Asia

Background.

Many studies have shown that type 2 diabetes mellitus (DM) increases the risk for several types of cancer but not cervical cancer (CC). Although DM and insulin-like growth factor 1 have preclinical and clinical implications for CC, less is known about the prognostic impact of DM on patients with early stage CC.

Patients and Methods.

We used the nationwide Taiwan Cancer Registry database to collect the characteristics of stage I–IIA cervical cancer patients diagnosed between 2004 and 2008. DM and other comorbidities were retrieved from the National Health Insurance database. Cervical cancer-specific survival (CSS) and overall survival (OS) times of patients according to DM status were estimated using the Kaplan-Meier method. We used a Cox proportional hazards model to calculate adjusted hazard ratios (HRs) for the effects of DM and other risk factors on mortality.

Results.

A total of 2,946 patients had primary stage I–IIA CC and received curative treatments, and 284 (9.6%) had DM. The 5-year CSS and OS rates for patients with DM were significantly lower than those without DM (CSS: 85.4% vs. 91.5%; OS: 73.9% vs. 87.9%). After adjusting for clinicopathologic variables and comorbidities, DM remained an independent unfavorable prognostic factor for CSS (adjusted HR: 1.46) and OS (adjusted HR: 1.55).

Conclusion.

In Asian patients with early cervical cancer, DM is an independent unfavorable prognostic factor influencing both OS and CSS, even after curative treatments.

Implications for Practice:

Type 2 diabetes mellitus (DM) increases the incidence of several types of cancer but not cervical cancer (CC); however, less is known about the impact of DM on patients who already have CC. This study suggests that DM may increase the risk of cancer recurrence and death for early stage CC patients, even after curative treatments. Incorporating DM control should be considered part of the continuum of care for early stage CC patients, and close surveillance during routine follow-up in this population is recommended.     

Treatment Outcome of Breast Cancer with Pathologically Proven Synchronous Ipsilateral Supraclavicular Lymph Node Metastases

Purpose

The aim of this study was to investigate the prognosis, patterns of failure, and prognostic factors for breast cancer patients with pathologically proven synchronous ipsilateral supraclavicular lymph node (ISCLN) metastases.

Methods

We reviewed the records of breast cancer patients with pathologically proven ISCLN metastases. Local aggressive treatment was defined as treatment including surgery, axillary lymph node dissection (ALND), ISCLN excision, radiotherapy (RT), and chemotherapy.

Results

A total of 111 patients were included. The 5-year overall survival (OS) and disease-free survival (DFS) rates were 64.2% and 56.2%, respectively. On univariate analysis, RT, ALND, trastuzumab treatment, hormone receptor (HR) status, and local aggressive treatment were identified as significant factors for OS. The 5-year OS for 73 patients who received local aggressive treatment was superior to that of 38 patients who received nonaggressive treatment (70.9% vs. 49.3%, p=0.036). Multivariate analysis showed that RT, HR status, and trastuzumab were significant variables for the 5-year OS and DFS.

Conclusion

Multimodality treatment with surgery, taxane-based chemotherapy, hormone therapy, and RT is strongly recommended for breast cancer patients with synchronous ISCLN metastases.     

Operable Breast Cancer of the Inner Hemisphere Is Associated with Poor Survival

Purpose

This study investigated the clinicopathological features of operable breast cancer lesions located in different hemispheres of the breast and determined related survival outcomes.

Methods

Data from 5,330 patients with invasive ductal carcinoma were retrospectively analyzed based on tumor location.

Results

The median follow-up time was 68 months (range, 18-176 months). Patients with breast cancer located in the outer hemisphere of the breast had lesions with more advanced nodal stages and more frequently received adjuvant chemotherapy than patients with breast cancer in the inner hemisphere. The 5-year disease-free survival (DFS) rates of patients with tumors located in outer versus inner hemispheres were 81.5% and 77.0%, respectively (p=0.004); the overall survival (OS) rates were 90.7% and 88.8%, respectively (p<0.001). The association between tumor location and the 5-year DFS rate was most apparent in node-positive patients (73.1% vs. 65.8% for outer vs. inner hemisphere lesions, p<0.001) and in patients with primary tumors greater than 2 cm in diameter (78.2% vs. 72.3%, p=0.002). Multivariate analysis showed that tumor location was an independent predictor of DFS (hazard ratio [HR], 1.23; p=0.002) and OS (HR, 1.28; p=0.006). There were no significant differences in 5-year DFS or OS rates between patients with outer versus inner hemisphere tumors when internal mammary node irradiation was performed.

Conclusion

This study demonstrated that tumor location was an independent prognostic factor for operable breast cancer. Internal mammary node irradiation is recommended for patients with breast cancer of the inner hemisphere and positive axillary lymph nodes or large primary tumors.     

Treatment outcomes and prognostic factors in uterine cervical cancer patients treated with postoperative extended field radiation therapy

Objective

To evaluate treatment outcomes and prognostic factors in uterine cervical cancer patients treated with postoperative extended field radiation therapy (POEFRT) with or without chemotherapy.

Methods

Between 1983 and 2006, 35 patients with a pathologically confirmed positive para-aortic node (PAN) or common iliac node (CIN) who underwent a radical hysterectomy with bilateral pelvic lymph node dissection and PAN dissection received POEFRT with (N=23) or without (N=12) chemotherapy. Prognostic factors such as age, stage, size, parametrium invasion, lymphovascular space invasion, nodal station, depth of stromal invasion and use of chemotherapy were analyzed.

Results

With a median follow-up of 44 months, the 5-year overall survival (OS), disease-free survival (DFS), distant failure-free survival (DFFS) and loco-regional failure-free survival rates were 51%, 51%, 59% and 93%, respectively. The use of chemotherapy significantly improved the 5-year OS rate (61% vs. 48%, p=0.004), the 5-year DFS rate (54% vs. 38%, p=0.004) and the 5-year DFFS rate (57% vs. 48%, p=0.009). PAN involvement resulted in a compromised 5-year DFS rate (42% vs. 73%, p=0.002) and 5-year DFFS rate (47% vs. 82%, p=0.004) as compared to CIN involvement. Grade 3 or higher hematological toxicity was observed more frequently in patients who received POEFRT combined with chemotherapy as compared to patients who received POEFRT alone (52% vs. 17%, p=0.04).

Conclusion

The use of POEFRT resulted in an excellent loco-regional control rate. The addition of chemotherapy may improve outcome in patients who have received POEFRT, but with higher manageable toxicity.     

Prognosis for intrahepatic cholangiocarcinoma patients treated with postoperative adjuvant transcatheter hepatic artery chemoembolization

Objective: We used meta-analysis to evaluate the efficacy of transcatheter hepatic arterial chemoembolization (TACE) for the treatment of intrahepatic cholangiocarcinoma (ICC). Methods: We performed the meta-analysis using the R 3.12 software and the quality evaluation of data using the Newcastle-Ottawa Scale. The main outcomes were recorded as 1-year overall survival (OS), 3-year OS, 5-year OS, and hazard ratio (HR) of TACE treatment or non-TACE treatment. The heterogeneity test was performed using the Q-test based on chi-square and I² statistics. Egger's test was used to test the publication bias. The odds ratio or HR and 95% confidence interval (CI) were used to represent the effect index. Results: Nine controlled clinical trials involving 1724 participants were included in this study; patients came mainly from China, Italy, South Korea, and Germany. In the OS meta-analysis, the 1-year and 3-year OS showed significant heterogeneity, but not the 5-year OS. TACE increased the 1-year OS (odds ratio = 2.66, 95% CI: 1.10-6.46) of the patients with ICC, but the 3- and 5-year OS rates were not significantly increased. The results had no publication bias, but the stability was weak. The HR had significant heterogeneity (I² = 0%, P= 0.54). TACE significantly decreased the HR of ICC patients (HR = 0.59, 95% CI: 0.48-0.73). The results had no publication bias, and the stability was good. Conclusions: Treatment with TACE is effective for patients with ICC. Regular updating and further research and analysis still need to be carried out.     

An analysis of current treatment practice in uterine papillary serous and clear cell carcinoma at two high volume cancer centers

Objective

Despite the rarity of uterine papillary serous carcinoma (UPSC) and uterine clear cell carcinoma (UCCC), they contribute disproportionately to endometrial cancer deaths. Sufficient clinical information regarding treatment and prognosis is lacking. The aim of this study is to evaluate treatment outcomes in a rare cancer cohort based on the experience at two tertiary care cancer centers.

Methods

Clinicopathologic data were retrospectively collected on 279 patients with UPSC and UCCC treated between 1995 to 2011. Mode of surgery, use of adjuvant treatment, and dissection of paraaoritc lymph nodes were evaluated for their association with overall survival (OS) and progression-free survival (PFS).

Results

40.9% of patients presented with stage I disease, 6.8% of patients presented with stage II disease and 52.3% of patients presented with stages III and IV. Median follow-up was 31 months (range, 1 to 194 months). OS and PFS at 5 years were 63.0% and 51.9%, respectively. OS and PFS were not affected by mode of surgery (open vs. robotic approach; OS: hazard ratio [HR], 0.68; 95% confidence interval [CI], 0.28 to 1.62; PFS: HR, 0.78; 95% CI, 0.40 to 1.56). Adjuvant treatment was associated with improved OS in stages IB-II (HR, 0.14; 95% CI, 0.02 to 0.78; p=0.026) but not in stage IA disease. There was no difference in OS or PFS based on the performance of a paraaoritc lymph node dissection.

Conclusion

Minimally invasive surgical staging appears a reasonable strategy for patients with non-bulky UPSC and UCCC and was not associated with diminished survival. Adjuvant treatment improved 5-year survival in stages IB-II disease.     

Surveillance for asymptomatic recurrence in resected stage III colon cancer: does it result in a more favorable outcome?

Background

Evidence from dated and moderate quality trials supports a modest survival benefit for intensive surveillance in resected colon cancer (CC). This study evaluates surveillance in a modern population-based cohort of stage III CC patients (pts).

Methods

Records of pts who initiated oxaliplatin-based adjuvant chemotherapy (AC) for stage III CC between 2006-2011 at the British Columbia Cancer Agency (BCCA) were reviewed. Kaplan-Meier and log rank test were generated to investigate whether diagnosis of recurrence based on symptoms was associated with worse overall survival (OS). OS1 and OS2 were measured from date of recurrence or date of initial surgery, respectively.

Results

Of 635 pts who received AC for stage III CC, 175 pts (27.5%) recurred and 118 (18.6%) died at a median follow-up of 67.7 months. Recurrences were detected by surveillance in 149 pts (41% by CEA elevation and 44% by abnormal imaging), and symptoms in 26 pts (15%). Patients with surveillance-detected recurrences had a shorter median relapse-free survival (RFS) (18.5 vs. 25.3 months, HR 1.82, P<0.001), and longer median OS1 (28.5 vs. 6.5 months, HR 0.37, P<0.001). However, median OS2 was not significantly different (50.9 vs. 39.1 months, HR 0.66, P=0.091). Pts with surveillance-detected recurrence received more potentially curative metastasectomy (39% vs. 7%, P=0.002) and chemotherapy (70% vs. 50%, P=0.03).

Conclusions

In this modern population-based cohort study, the OS impact of detecting asymptomatic recurrences in stage III CC is unclear. However, pts with asymptomatic recurrences were more likely to receive potentially curative metastasectomy and chemotherapy.     

Adjuvant therapy in high-risk early endometrial carcinoma: a retrospective analysis of 46 cases

Objective

We assessed the prognostic factors and the efficacy of adjuvant therapy and reviewed randomized studies carried out on patients receiving adjuvant therapy with early endometrial carcinoma.

Methods

One hundred and five patients that received primary surgical treatment for stage IB, IC and II endometrial cancer were enrolled in this study. The clinical outcomes were compared among the patients with variable prognostic factors and adjuvant treatments.

Results

One hundred and five patients fulfilled the eligibility criteria and 46 patients (43.8%) underwent adjuvant therapy. Disease recurrence occurred in nine patients within a median time of 24 months. Cervical involvement was an independent prognostic factor for the disease-free survival rates. Eight of 16 patients with FIGO stage II disease received adjuvant chemotherapy consisting of cisplatin and etoposide (or cyclophosphamide) or combined chemoradiation. The 5-year disease-free survival rate for these patients was 87.5%, a value significantly higher than for patients that received radiation therapy alone (30%).

Conclusion

Adjuvant chemotherapy or combination chemo-radiotherapy might be superior to radiation therapy alone in high-risk early endometrial cancer patients.     

Survival analysis of endometrial cancer patients with cervical stromal involvement

Objective

Stage II endometrial cancer is relatively uncommon. There is no consensus for appropriate adjuvant therapy in endometrial cancer patients with cervical stromal involvement (International Federation of Gynecology and Obstetrics [FIGO] stage II). This study investigates how adjuvant treatments and tumor characteristics influence overall survival (OS) and disease-free survival (DFS) in stage II patients in order to establish better treatment guidelines.

Methods

This multi-institution, Institutional Review Board approved, study is a retrospective review of 40 endometrial cancer patients with cervical stromal involvement treated from 1993 to 2009. Kaplan-Meier estimates were used to evaluate OS and DFS.

Results

OS was 85% at three years and 67% at five years. There were no significant differences in age, histology, depth of invasion, comorbid conditions, surgical staging or recurrence between patients who received radiation therapy (RT) and those who did not. However, patients with FIGO grade 1 cancers were less likely to receive RT (p=0.007). Patients treated with RT had a similar 5 year OS (n=33, 69%) to those treated with surgery only (n=7, 60%, p=0.746). There were no OS differences when evaluating by grade, histology, or depth of invasion between patients who did and did not receive RT. Four patients recurred: three were locoregional failures only, and one failed locally and distant.

Conclusion

Patients receiving RT had higher grade tumors. Despite this, OS was comparable between the RT and the no RT cohorts. Local failure was the predominant pattern of failure. Endometrial cancer patients with cervical stromal involvement likely receive better locoregional control with the addition of adjuvant RT and we continue to advocate for RT in most cases.     

Phase II Trial of Preoperative Radiation With Concurrent Capecitabine,Oxaliplatin, and Bevacizumab Followed by Surgery and Postoperative 5‐Fluorouracil,Leucovorin, Oxaliplatin (FOLFOX), and Bevacizumab in Patients With Locally Advanced Rectal Cancer: 5‐Year Clinical Outcomes ECOG‐ACRIN Cancer Research Group E3204

Lessons Learned

• The 5-year oncologic outcomes from the trial regimen were excellent. However, the neoadjuvant and surgical toxicity of this regimen was significant and was the primary reason for the low compliance with adjuvant systemic therapy.
• Due to the lack of an improvement in the pathologic complete response rate, the substantial associated toxicity, and the negative phase III trials of adjuvant bevacizumab in colon cancer, this regimen will not be pursued for further study.

Background.

The addition of bevacizumab to chemotherapy improves overall survival for metastatic colorectal cancer. We initiated a phase II trial to evaluate preoperative capecitabine, oxaliplatin, and bevacizumab with radiation therapy (RT) followed by surgery and postoperative 5-fluorouracil, leucovorin, oxaliplatin (FOLFOX), and bevacizumab for locally advanced rectal cancer. The purpose of this report is to describe the 5-year oncologic outcomes of this regimen.

Methods.

In a phase II Simon two-stage design study, we evaluated preoperative treatment with capecitabine (825 mg/m² b.i.d. Monday–Friday), oxaliplatin (50 mg/m² weekly), bevacizumab (5 mg/kg on days 1, 15, and 29), and RT (50.4 Gy). Surgery was performed by 8 weeks after RT. Beginning 8–12 weeks after surgery, patients received FOLFOX plus bevacizumab (5 mg/kg) every 2 weeks for 12 cycles (oxaliplatin stopped after 9 cycles). The primary endpoint was a pathologic complete response (path-CR) rate of 30%. Fifty-seven patients with resectable T3/T4 rectal adenocarcinoma were enrolled between 2006 and 2010.

Results.

Of 57 enrolled patients, 53 were eligible and included in the analysis. Forty-eight (91%) patients completed preoperative therapy, all of whom underwent curative surgical resection. Nine patients (17%) achieved path-CR. There were 29 worst grade 3 events, 8 worst grade 4 events, and 2 patient deaths, 1 of which was attributed to study therapy. Twenty-six patients (54%) began adjuvant chemotherapy. After a median follow-up period of 41 months, the 5-year overall survival (OS) rate for all patients was 80%. Only 2 patients experienced cancer recurrence: 1 distant (liver) and 1 loco-regional (pelvic lymph nodes), respectively. Both of these patients are still alive. The 5-year relapse-free survival rate was 81%.

Conclusion.

Despite the path-CR primary endpoint of this trial not being reached, the 5-year OS and recurrence-free survival rates were excellent. However, the neoadjuvant and surgical toxicity of this regimen was significant and was the primary reason for the low compliance with adjuvant systemic therapy. Because of the lack of an improvement in the path-CR rate, the substantial associated toxicity, and the negative phase III trials of adjuvant bevacizumab in colon cancer, this regimen will not be pursued for further study.     

Clinicopathological and Immunohistochemical Characteristics in Male Breast Cancer: A Retrospective Case Series

Background.

Due to its rarity, male breast cancer (mBC) remains an inadequately characterized disease, and current evidence for treatment derives from female breast cancer (FBC).

Methods.

We retrospectively analyzed the clinicopathological characteristics, treatment patterns, and outcomes of mBCs treated from 2000 to 2013.

Results.

From a total of 97 patients with mBC, 6 (6.2%) with ductal in situ carcinoma were excluded, and 91 patients with invasive carcinoma were analyzed. Median age was 65 years (range: 25–87 years). Estrogen receptors were positive in 88 patients (96.7%), and progesterone receptors were positive in 84 patients (92.3%). HER-2 was overexpressed in 13 of 85 patients (16%). Median follow-up was 51.5 months (range: 0.5–219.3 months). Five-year progression-free survival (PFS) was 50%, whereas overall survival (OS) was 68.1%. Patients with grades 1 and 2 presented 5-year PFS of 71% versus 22.5% for patients with grade 3 disease; 5-year OS was 85.7% for patients with grades 1 and 2 versus 53.3% of patients with grade 3. Ki-67 score >20% and adjuvant chemotherapy were also statistically significant for OS on univariate analyses. Twenty-six of 87 patients (29.8%) experienced recurrent disease and 16 of 91 patients (17.6%) developed a second neoplasia.

Conclusion.

Male breast cancer shows different biological patterns compared with FBC, with higher positive hormone-receptor status and lower HER-2 overexpression. Grade 3 and Ki-67 >20% were associated with shorter OS.

Implications for Practice:

There is little evidence that prognostic features established in female breast cancer, such as grading and Ki-67 labeling index, could be applied to male breast cancer as well. This study found that grade 3 was associated with shorter overall survival and a trend for Ki-67 >20%; this could help in choosing the best treatment option in the adjuvant setting. Many questions remain regarding the impact of HER-2 positivity on survival and treatment with adjuvant anti-HER-2 therapy. Regarding metastatic male breast cancer, the results suggest that common regimens of chemo-, endocrine and immunotherapy used in female breast cancer are safe and effective for men. Male breast cancer patients show a higher incidence of second primary tumors, especially prostate and colon cancers and should therefore be carefully monitored.     

An external validation study of nomograms designed to predict isolated loco-regional and distant endometrial cancer recurrences: how applicable are they?

Background:

To externally validate and assess the robustness of two nomograms to predict the recurrence risk of women with endometrial cancer (EC).

Methods:

Using an independent, multicentre external patient cohort we assessed the discrimination and calibration of two nomograms – the 3-year isolated loco-regional (ILRR) and distant (DR) recurrence nomograms – in women with surgically treated stage I–III EC.

Results:

Two hundred and seventy one eligible women were identified from two university hospital databases and the Senti-Endo trial. The median follow-up and initial recurrence time were 38.1 (range: 12–69) and 22.0 (range: 8.3–55) months, respectively. The overall recurrence rate was 13.8% (37 out of 271). Predictive accuracy according to the discrimination was 0.69 (95% CI, 0.58–0.79) and 0.66 (95% CI, 0.60–0.71) for the 3-year ILRR and DR nomograms, respectively. The correspondence between observed recurrence rate and the nomogram predictions suggests a moderate calibration of the nomograms in the validation cohort.

Conclusion:

The nomograms were externally validated and shown to be partly generalisable to a new and independent patient population. The tools need to be improved by including information on the lymph node status and adjuvant therapies.     

Effect of (Neo)adjuvant zoledronic acid on disease-free and overall survival in clinical stage II/III breast cancer

Background:

Despite neoadjuvant/adjuvant chemotherapy, women with resectable stage II/III breast cancer (BC) have high risk of recurrent disease. Recent data suggest that zoledronic acid (ZOL) therapy concurrent with adjuvant treatments may improve cancer-related outcomes in patients with BC.

Methods:

Disease-free survival (DFS; secondary end point) and overall survival (OS; tertiary end point) were evaluated in 119 women with stage II/III BC randomised to intravenous ZOL 4 mg every 3 weeks for 1 year or no ZOL (control) starting with the first chemotherapy cycle.

Results:

At 61.9 months'' median follow-up, there was no significant difference in recurrence or survival between study arms. However, time to recurrence or death (DFS) was significantly different between subgroups defined by oestrogen receptor (ER) status (interaction P=0.010 for DFS and 0.025 for OS). Hazard ratios (HRs) for disease recurrence and death were significantly less among patients with ER-negative (ER⁻) tumours who received ZOL vs no ZOL (DFS: HR=0.361, 95% confidence interval (CI) 0.148, 0.880; OS: HR=0.375, 95% CI 0.143, 0.985).

Conclusion:

ZOL administered with chemotherapy may improve DFS and OS in a subset of BC patients with ER⁻ tumours. This study was not powered to compare subgroups of patients; thus, these findings should be considered hypothesis generating.     

The survival outcome and patterns of failure in node positive endometrial cancer patients treated with surgery and adjuvant radiotherapy with curative intent

Objective

The purpose of this study was to evaluate the patterns of failure, overall survival (OS), disease-free survival (DFS) and factors influencing outcome in endometrial cancer patients who presented with metastatic lymph nodes and were treated with curative intent.

Methods

One hundred and twenty-six patients treated between January 1996 to December 2008 with surgery and adjuvant radiotherapy were identified from our service''s prospective database. Radiotherapy consisted of 45 Gy in 1.8 Gy fractions to the whole pelvis. The involved nodal sites were boosted to a total dose of 50.4 to 54 Gy.

Results

The 5-year OS rate was 61% and the 5-year DFS rate was 59%. Grade 3 endometrioid, serous, and clear cell histologies and involvement of upper para-aortic nodes had lower OS and DFS. The number of positive nodes did not influence survival. Among the histological groups, serous histology had the worst survival. Among the 54 patients relapsed, only three (6%) failed exclusively in the pelvis and the rest of the 94% failed in extrapelvic nodal or distant sites. Patients with grade 3 endometrioid, serous and clear cell histologies did not influence pelvic failure but had significant extrapelvic failures (p<0.001).

Conclusion

Majority of node positive endometrial cancer patients fail at extrapelvic sites. The most important factors influencing survival and extrapelvic failure are grade 3 endometrioid, clear cell and serous histologies and involvement of upper para-aortic nodes.     

Isolated tumor cells and micrometastases in regional lymph nodes in stage I to II endometrial cancer

Objective

The aim of this study was to clarify the clinical significance of isolated tumor cells (ITCs) or micrometastasis (MM) in regional lymph nodes in patients with International Federation of Gynecology and Obstetrics (FIGO) stage I to II endometrial cancer.

Methods

In this study, a series of 63 patients with FIGO stage I to II were included, who had at least one of the following risk factors for recurrence: G3 endometrioid/serous/clear cell adenocarcinomas, deep myometrial invasion, cervical involvement, lympho-vascular space invasion, and positive peritoneal cytology. These cases were classified as intermediate-risk endometrial cancer. Ultrastaging by multiple slicing, staining with hematoxylin and eosin and cytokeratin, and microscopic examination was performed on regional lymph nodes that had been diagnosed as negative for metastases.

Results

Among 61 patients in whom paraffin-embedded block was available, ITC/MM was identified in nine patients (14.8%). Deep myometrial invasion was significantly associated with ITC/MM (p=0.028). ITC/MM was an independent risk factor for extrapelvic recurrence (hazard ratio, 17.9; 95% confidence interval [CI], 1.4 to 232.2). The 8-year overall survival (OS) and recurrence-free survival (RFS) rates were more than 20% lower in the ITC/MM group than in the node-negative group (OS, 71.4% vs. 91.9%; RFS, 55.6% vs. 84.0%), which were statistically not significant (OS, p=0.074; RFS, p=0.066). Time to recurrence tended to be longer in the ITC/MM group than in the node-negative group (median, 49 months vs. 16.5 months; p=0.080).

Conclusions

It remains unclear whether ITC/MM have an adverse influence on prognosis of intermediate-risk endometrial cancer. A multicenter cooperative study is needed to clarify the clinical significance of ITC/MM.     

Postoperative adjuvant transcatheter arterial chemoembolisation improves survival of intrahepatic cholangiocarcinoma patients with poor prognostic factors: Results of a large monocentric series

Background

The prognosis of patients with intrahepatic cholangiocarcinoma (ICC) is currently unsatisfactory. The aims of this study were to identify prognostic factors after curative ICC resection, and to evaluate the effects of postoperative transcatheter arterial chemoembolisation (TACE).

Methods

A retrospective analysis was conducted of 114 ICC patients who underwent curative resection from January 2005 to December 2006. Relationships between survival and clinicopathological factors were evaluated using univariate and multivariate analyses. The benefits of adjuvant TACE were investigated separately.

Results

The cumulative 1-, 3-, and 5-year survival rates were 63%, 26%, and 15%, respectively. Multivariate analysis revealed that tumour size ≥5 cm (hazard ratio [HR] 1.875, 95% CI 1.139–3.088, P = 0.013) and advanced TNM stage (stage III or IV) (HR 1.681, 95% CI 1.035–2.732, P = 0.036) were independently associated with poor prognosis. Fifty-seven patients underwent adjuvant TACE. In patients with poor prognostic factors, TACE improved the survival rate (P < 0.001). However, in patients without poor prognostic factors, TACE did not significantly change the survival rate (P = 0.724).

Conclusions

Postoperative adjuvant TACE can prolong survival in ICC patients with tumour size ≥5 cm or advanced TNM stage.