Primary amelanotic melanoma of the breast: combating a rare cancer

Background

Malignant melanoma is the foremost cause of metastasis to the breast from extramammary solid neoplasm. However primary melanoma of the breast is a distinct rarity. Primary melanoma involves the skin and less commonly the glandular parenchyma of the breast.

Method

We herein describe a case of primary amelanotic melanoma of the breast parenchyma in a 32-year-old female managed with a combination of surgery, adjuvant radiotherapy and immunotherapy.

Conclusion

This case report aims to increase awareness of unusual neoplasms of the breast which might require a different surgical and adjuvant therapeutic approach.     

Imunoexpression of Ki-67 and p53 in Rectal Cancer Tissue After Treatment with Neoadjuvant Chemoradiation

Introduction

Adjuvant or neoadjuvant chemoradiotherapy (CRT) increases the survival rates significantly, but it also increases morbidity. Molecular markers may help on prognosis evaluation and treatment choice.

Aim

The purpose of this study is to evaluate the imunoexpression of p53 and Ki-67 in rectal cancer tissue after CRT treatment.

Patients and Methods

Stage II or III rectal cancer patients were evaluated and treated with RT and 5-FU preoperatively (neoadjuvant treatment, NG) or after surgical resection of the cancer (adjuvant treatment, AG).

Results

Thirty-one patients were enrolled in the NG and 30 in the AG; 63.95% were between 50 and 70 years, 50.8% were male, and 53% were in stage III. Of the tumors, 64.5% of the NG and 63.34% of the AG had not overexpressed p53 (p?=?0.865) and 9.67% of NG and 33.33% of the AG tumors had a high proliferative index (HPI) of Ki67, p?=?0.052. We have not found any difference among metastasis development in the groups (p?=?0.708). After 5 years, patients with low proliferative index (LPI) of Ki67 tumors had the best survival rate (p?=?0.041). Patients with positive or negative p53 tumors had similar survival (p?=?0.35). Patients with HPI of Ki67 had an increased marginal risk for death (p?=?0.069).

Conclusion

The rate of tumors that overexpressed p53 was similar in both groups. Patients with p53 positive tumors survived as long as those with p53 negative. Patients treated with chemoradiotherapy before surgical resection, expressed Ki67 in a small percentage. Rectal cancer patients with LPI of Ki67 had the best prognosis.     

High recurrence risk and use of adjuvant trastuzumab in patients with small, HER2-positive, node-negative breast cancers

Background

Five randomized trials of adjuvant trastuzumab have reported significant improvements in recurrence-free survival (RFS) and overall survival. However, patients with node-negative tumors 1?cm or smaller were excluded from these trials. We assessed the recurrence risk and benefit of adjuvant therapy in such patients with small tumors.

Methods

We identified patients with node-negative breast tumors 1?cm or smaller between April 2003 and December 2007. Patients were categorized according to HER2 status and pathological tumor size (pT <5?mm vs. 5?C10?mm), hormone receptor (HR) status and adjuvant chemotherapy. The primary endpoint was RFS.

Results

Of 267 patients included in the analysis, 42 had HER2-positive tumors. The median follow-up was 4.3?years. RFS was worse in patients with HER2-positive tumors than HER2-negative tumors (90.5 vs. 97.7% at 5?years; P?=?0.031). In the group with HER2-positive tumors, there were no recurrences in patients with pT<5?mm, but 4 recurrences in those with pT 5?C10?mm. RFS was worse in patients with pT 5?C10?mm than pT <5?mm (79.0 vs. 100%, P?=?0.025). Furthermore 3 recurrences occurred in patients without adjuvant trastuzumab, and 1 recurrence occurred as soon as adjuvant trastuzumab was finished. Our results appear to establish the efficacy of adjuvant trastuzumab therapy. HR status and use of adjuvant chemotherapy were not significantly associated with RFS.

Conclusions

Patients with HER2-positive, node-negative breast tumors 1?cm or smaller (especially 0.5?C1.0?cm) have a significant recurrence risk and the decision to employ adjuvant trastuzumab therapy should be discussed with patients based on our results and those of other studies.     

Prognostic Clinicopathological Factors After Curative Resection of Small Bowel Adenocarcinoma

Purpose

Small bowel adenocarcinoma is a relatively uncommon neoplasm that accounts for approximately 0.3% to 2.4% of digestive cancers. In comparison with carcinomas of the other areas of the gastrointestinal tract, the prognosis for small bowel adenocarcinoma is generally worse. The prognostic factors of small bowel adenocarcinoma were analyzed retrospectively, and the significance of operative procedure, lymphadenectomy, and adjuvant chemotherapy was evaluated.

Methods

From 1990 to 2009, 30 patients with small bowel adenocarcinoma who underwent surgery at Osaka Medical College Hospital were analyzed with respect to tumor extent, operation method, and prognosis.

Results

Overall 5-year survival was 52.5%, and the median survival time was 27.0?months. On univariate and multivariate analyses, the location (duodenum vs. jejunum and ileum), size (greater or less than 70?mm), and tumor, nodes, and metastasis (TNM) stage (stage 0?+?I?+?II vs. III?+?IV) of the tumor were the significant prognostic factors. No differences in survival and recurrence rates were observed between patients undergoing pancreaticoduodenectomy and those undergoing partial resection, between those undergoing mural lymphadenectomy and those undergoing extended lymphadenectomy, or between those with and without adjuvant chemotherapy. The combination of surgery and adjuvant chemotherapy did not control recurrence or improve the prognosis.

Conclusions

In small bowel adenocarcinoma, location, size, and TNM stage of the tumors were the independent prognostic factors after curative resections. Partial resection with mural lymphadenectomy may be recommended as optimal surgery for small bowel adenocarcinoma.     

Final results of randomized trials by the National Surgical Adjuvant Study of Colorectal Cancer (NSAS-CC)

Objective

In the latter 1990s, adjuvant chemotherapy for completely resected Stage III colorectal cancer remained controversial in Japan. We conducted two independent randomized controlled trials in patients with Stage III colon and rectal cancer.

Methods

Patients were randomly assigned to receive surgery alone or surgery followed by treatment with UFT (400?mg/m²/day), given for five consecutive days per week for 1?year. The primary endpoint was relapse-free survival (RFS), and the secondary endpoint was overall survival (OS).

Results

A total of 334 patients with colon cancer and 276 with rectal cancer were enrolled. The patients?? characteristics were similar between the UFT group and the Surgery-alone group. There was no significant difference in RFS or OS in colon cancer. In rectal cancer, however, RFS and OS were significantly better in the UFT group than in the Surgery-alone group. The only grade 4 toxicity in the UFT group was diarrhea, occurring in one patient with colon cancer and one patient with rectal cancer.

Conclusions

Postoperative adjuvant chemotherapy with UFT is successfully tolerated and improves RFS and OS in patients with Stage III rectal cancer. In colon cancer, the expected benefits were not obtained (hazard ratio?=?0.89).     

Patterns of recurrence and outcome in patients with surgically resected small cell lung cancer

Background

Although prophylactic cranial irradiation (PCI) in limited-stage (LS) small cell lung cancer (SCLC) patients who are surgically resected and treated with adjuvant chemotherapy is considered to be a reasonable treatment option, the efficacy of PCI for those patients remains unclear.

Methods

The records of 28 patients with SCLC undergoing curative surgery at the Aichi Cancer Center Hospital between 1995 and March 2008 were retrospectively reviewed to assess patterns of relapse and overall survival.

Results

The patients were 27 men and 1 woman. Eight patients underwent induction chemotherapy. Fourteen patients (50%) had pathologic stage (p-stage) I disease, 7 patients (25%) had p-stage II, and 7 patients (25%) had p-stage III. Nineteen patients underwent adjuvant chemotherapy and one patient received adjuvant chemoradiotherapy. There were a total of 13 deaths and 8 were disease-related. Most patients developed hematogenous distant metastases before their death. The 5-year overall probability of survival was 47%. Ten (36%) of the 28 patients had a relapse. Two had a local relapse alone, one patient had combined local and distant relapses, and seven patients had distant metastases alone as their first site of failure. Four patients with p-stage II/III disease developed brain metastases with a cumulative incidence at 1 and 2?years of 25 and 36%, respectively.

Conclusions

Our retrospective study suggested that PCI might have a role in surgically resected patients with p-stage II/III SCLC because of their relatively high frequency of brain metastasis.     

Snail1 correlates with patient outcomes in E-cadherin-preserved gastroesophageal junction adenocarcinoma

Purpose

The poor prognosis of gastroesophageal junction (GEJ) adenocarcinoma is largely associated with metastasis. We here report the first study to investigate the expression of epithelial-mesenchymal transition (EMT) markers Snail1 and E-cadherin in GEJ adenocarcinoma.

Methods

Snail1 and E-cadherin were detected by immunohistochemistry in a cohort of 128 patients with surgically resected GEJ adenocarcinoma. We assessed the pathologic and prognostic relevance in all patients and within clinically different preserved E-cadherin and reduced E-cadherin-expressing sub-groups.

Results

Immunoreactivity for Snail1 and E-cadherin was positive in 68 and 43 % of tumors, respectively. Snail1-positive tumors had more frequent lymph node metastasis and advanced tumor stage. E-cadherin expression was highly associated with histological differentiation, tumor size, advanced stage, presence of lymph node metastasis and distant metastasis. Patients with positive E-cadherin expression or negative Snail1 expression had significantly favorable overall survival rate. In E-cadherin-preserved tumors, the expression of Snail1 was related to lymph node metastasis, advanced stage and poor patient outcome. However, Snail1 expression had no statistically significant relationship with clinicopathologic parameters or prognosis in the reduced E-cadherin-expressing sub-group. Multivariate survival analysis identified that tumor stage [hazard ratio (HR) 2.440; 95 % confidence interval (CI) 1.216–4.896; P = 0.012], lymph node metastasis (HR 2.404; 95 % CI 1.188–4.867; P = 0.015) and gender (HR 3.244; 95 % CI 1.568–6.714; P = 0.002) were independent prognostic markers for overall survival.

Conclusions

Snail1 may act more critically in E-cadherin-positive tumors. Evaluation of Snail1 and E-cadherin in GEJ adenocarcinoma may help in assessing malignant properties and stratifying patients.     

Adjuvante Strategien bei Hochrisikomelanomen

Background

For high-risk melanoma in stages II and III (thick primary tumors >?2 mm tumor thickness and presence of locoregional metastases) there is a need for adjuvant therapy to reduce the recurrence and mortality risk.

Material and methods

A literature search was performed in PubMed. Current adjuvant trials involving high-risk melanoma patients in Europe were identified in the database ClinicalTrials.gov.

Results

Several randomized phase III studies have been conducted to find a successful adjuvant therapy. Studies with systemic chemotherapy and with nonspecific immunostimulants, such as Bacillus Calmette-Guérin (BCG) vaccination or mistletoe therapy were ineffective. An improvement of recurrence-free and overall survival was demonstrated in the 1990s only for interferon alpha therapy and a high-dose regimen was approved in the USA and Europe as well as a low-dose regimen in Europe. In Germany the low-dose regimen is mainly offered to stage II and III melanoma patients; however, the clinical benefit of this treatment is moderate and new trials are currently looking for more effective adjuvant therapies for melanoma. A European Organisation for Research and Treatment of Cancer (EORTC) study with the monoclonal cytotoxicT-lymphocyte antigen 4 (CTLA-4) antibody ipilimumab has already been completed in the recruitment stage, as well as a cancer vaccination study with the recombinant melanoma-associated antigen 3 (MAGE-A3) and a study with the anti-angiogenic antibody bevacizumab. Furthermore, two studies were launched with kinase inhibitors, a study with the BRAF inhibitor vemurafenib and a study with the combination of the BRAF inhibitor dabrafenib and the mitogen-activated protein kinase (MEK) inhibitor trametinib.

Conclusion

It remains to be seen whether one or more of these treatments will show better efficacy than interferon alpha, and whether changes in the adjuvant therapy of melanoma will prevail in the coming years.     

Neuroendocrine tumors of the stomach: chemotherapy with cisplatin plus irinotecan is effective for gastric poorly-differentiated neuroendocrine carcinoma

Background

Neuroendocrine tumors (NETs) occur in various primary sites, but rarely in the stomach. NETs are classified into three types, carcinoids, malignant carcinoids and poorly differentiated neuroendocrine carcinomas (PNECs), whose clinical behavior is different. Currently, clinical outcomes and standard chemotherapy for NETs of the stomach remain unclear.

Methods

We conducted a retrospective review of histopathologically confirmed NETs of the stomach at our hospital between January 2000 and August 2006.

Results

Thirty-seven NETs were identified. Fifteen patients had carcinoids while 22 had PNECs. Among the carcinoid patients, 7 underwent endoscopic mucosal resection and 5 had gastrectomy as first-line treatment. Three patients were observed without intervention. All patients were alive after an average follow-up period of 27?months. Among the 22 PNEC patients, 3 had no metastasis, 11 had regional lymph node metastasis, and 8 had distant metastasis. Eight of 14 patients relapsed at a median of 177 days (range 120??459 days) after curative surgery. Twelve patients with metastatic or recurrent disease received palliative cisplatin plus irinotecan chemotherapy. The response rate was 75%, the median progression-free survival time was 212?days, and median survival time was 679?days.

Conclusion

Gastric PNEC patients with distant metastasis had poor outcomes. Regimens containing cisplatin plus irinotecan produced a good response in gastric PNEC.     

Endocrine carcinoma of the stomach: clinicopathological analysis of 27 surgically treated cases in a single institute

Background

Gastric endocrine carcinoma (EC) is an uncommon tumor of the stomach and the clinical features are not well known. Additionally, the classification and staging systems of this tumor are not yet unified worldwide. In this study, we reviewed 27 patients with gastric EC to evaluate the clinicopathological characteristics of this tumor.

Methods

We retrospectively reviewed 27 patients with gastric EC among 6466 patients who had undergone gastrectomy between 1986 and 2008 at our institute. Clinicopathological features including immunohistochemistry of Ki-67 were investigated to evaluate the malignant potential of the tumor. Furthermore, survivals were compared between the 7th edition of the International Union Against Cancer (UICC)-TNM (7th TNM) classification for gastric cancer (GC) and the new TNM classification for foregut neuroendocrine tumors (NET).

Results

The median survival of the patients was 19.0?months. The 5-year survival rate was 100% in pathological stage (pStage) I, 40% in pStage II, 38% in pStage III, and 11% in pStage IV according to the 7th TNM classification for GC. Survivals by stage showed great difference between the 7th TNM classification for GC and the new TNM classification for foregut NET, but each system correlated with survival. The Ki-67 labeling index was more than 20% in most of the patients. Univariate analysis revealed that maximum tumor diameter, tumor depth, lymph node metastasis, lymphatic invasion, pStage, and curability had significant correlations with survival.

Conclusion

Early detection and curative operations are essential for improving the prognosis of gastric EC. However, some adjuvant chemotherapies are required for advanced-stage tumors. Classification and staging systems may need to be unified worldwide for further analysis.     

Gastrectomy as a secondary surgery for stage IV gastric cancer patients who underwent S-1-based chemotherapy: a multi-institute retrospective study

Background

Current advances in chemotherapy provide opportunities for stage IV gastric cancer patients with distant metastasis to undergo potentially curable resection. There are, however, few data on gastrectomy as a secondary surgery aimed at rendering such patients cancer-free.

Methods

We investigated stage IV gastric cancer patients who underwent surgery with curative intent after S-1-based chemotherapy between 2000 and 2008. Twenty-eight patients from 12 hospitals were enrolled in this study. Factors indicating that the tumors were incurable included clinical stage T4 in 9 patients, para-aortic node metastasis in 15, peritoneal metastasis in 7, and liver metastasis in 4.

Results

Of the 28 laparotomy patients, 26 underwent complete resection with no residual tumor, obtaining a complete resection rate of 92.9%. There were no in-hospital deaths or reoperations. In four patients, the primary tumor showed pathological complete response. The 1-, 3-, and 5-year overall survival rates after secondary gastrectomy were 82.1, 45.9, and 34.4%, respectively, with a median survival time of 29?months. Univariate analysis revealed histological tumor length, clinical depth of tumor invasion, number of metastatic nodes, pathological depth of tumor invasion, and pathological response to be the factors influencing patient survival after secondary surgery. On multivariate analysis, histological tumor length (5.0?cm or larger) was the only significant prognostic factor (relative risk 3.23, P?=?0.028).

Conclusions

Secondary gastrectomy following S-1-based chemotherapy was a safe and effective treatment for stage IV gastric cancer. Primary tumor size is an indicator for the appropriate selection of patients for this treatment.     

Immunotherapy for the Treatment of Uveal Melanoma: Current Status and Emerging Therapies

Purpose of Review

Uveal melanoma is a distinct subset of melanoma with a biology and treatment approach that is unique from that of cutaneous melanoma. Here we will review the current data evaluating immunotherapies in both the adjuvant and metastatic settings in uveal melanoma.

Recent Findings

In the adjuvant setting, interferon demonstrated no survival benefit in uveal melanoma, and studies evaluating immune-based strategies such as vaccine therapy are ongoing. Anti-CTLA-4 and anti-PD-1/ PD-L1 blockade in uveal melanoma have been evaluated in several small prospective and/or retrospective studies with rare responses and no overall survival benefit demonstrated. Ongoing studies evaluating combination checkpoint inhibition and other antibody-based therapies are ongoing.

Summary

Although immunotherapy with anti-CTLA-4 and anti-PD-1 agents has dramatically changed the treatment approach to cutaneous melanoma, its success in uveal melanoma has been much more limited. Clinical trial participation should be prioritized in patients with uveal melanoma.

     

Beta-elemene inhibits melanoma growth and metastasis via suppressing vascular endothelial growth factor-mediated angiogenesis

Purpose

It was to assess antiangiogenic effect of ??-elemene in?vitro and in?vivo, and it was involved in inhibiting melanoma growth and metastasis, as well as to elucidate its intrinsic mechanism.

Methods

Inhibitive effect of ??-elemene on B16F10 cells was performed by cell proliferation assay. Angiogenesis assays in vitro including rat aortic ring and chick embryo chorioallantoic membrane were used, as well as melanoma growth and metastasis assay in C57BL/6 mice. Vascular endothelial growth factor (VEGF) expression in?vitro and in?vivo was measured respectively by western blot analysis and enzyme-linked immunosorbent assay (ELISA). Immunohistochemistry analysis of CD34 and VEGF expression in primary melanoma was also presented.

Results

??-Elemene inhibited B16BF10 cell proliferation starting from 200???M, but VEGF from 20???M. Both 20 and 50???M ??-elemene in?vitro inhibited VEGF-induced sprouting vessel of rat aortic ring and microvessel formation of chick embryo chorioallantoic membrane. In?vivo, tumor size of primary melanoma in mice intraperitoneally treated with ??-elemene was significantly smaller than that of the control; CD34 expression of primary melanoma was also suppressed; and the metastatic melanoma colonies and content of melanin in lung were detected obviously decreased in mice of ??-elemene-treated groups. Furthermore, results of VEGF expressing in primary melanoma, serum and lung of mice also disclosed that VEGF was inhibited in?vivo.

Conclusions

??-Elemene inhibited melanoma growth and metastasis through suppressing VEGF-mediated angiogenesis. It is a natural potential antiangiogenic agent.     

延迟辅助化疗对乳腺癌患者生存期的影响(英文)

Objective: The proper time to commence adjuvant chemotherapy after primary surgery for breast cancer is unknown. It is usually prescribed within 2-3 months after definitive surgery. The aim of this retrospective study was to assess the impact of adjuvant chemotherapy (CT) delay beyond 3 weeks ( 21 days) in premenopausal patients with ER-absent tumors being treated for early stages breast cancer on overall survival (OS) and disease-free survival (DFS). Methods: This retrospective study was conducted through revision of medical records of premenopausal patients diagnosed with early stage Ⅰ-ⅢA breast cancer and ER-absent tumors who received adjuvant CT after definitive surgery at the Department of Clinical Oncology, Ain-Shams University Hospitals. Results: Between 2005 and 2008, 105 patients were retrospectively analyzed and included. Patients were divided into 2 groups: Group A including 48 patients who started adjuvant CT<21 days of surgery and group B which included 57 patients who had CT delay ≥ 21 days. Both groups were matched demographically. Comparisons of overall survival, and disease-free survival between group A and group B patients all favored group A. At 5-year the OS rates were 87% and 73% for groups A and B respectively (P=0.001), while DFS rates were 85% and 64% in groups A and B respectively (P=0.001). Analysis of other prognostic factors (age, T, N, grade, HER2 status, surgery type, CT type, local radiotherapy received) were analyzed. Only nodal status predicted for worse DFS (P=0.05) and OS (P=0.006). Conclusion: Delay in initiating adjuvant chemotherapy for early stage breast cancer patients with ER-absent tumors was associated with a decrease in both OS and DFS rates.     

Clinicopathological features of young patients (<35 years of age) with breast cancer in a Japanese Breast Cancer Society supported study

Background

To clarify the clinicopathological features of breast cancer in young females, surveillance data of the Registration Committee of the Japanese Breast Cancer Society were analyzed.

Methods

The clinicopathological characteristics were compared between young (<35) patients and non-young (≥35) patients among 109,617 records registered between 2004 and 2009.

Results

The numbers of young and non-young patients were 2,982 (2.7 %) and 106,295 (97.0 %), respectively. The young patients had more cases of a familial history of breast cancer, more subjective symptoms, fewer bilateral tumors, lower BMIs, larger tumors, more positive lymph nodes, fewer instances of an ER-positive status, more instances of an HER2-positive status, more triple-negative tumors and more advanced TNM stages. The young patients more frequently received neoadjuvant chemotherapy and breast-conserving therapy (BCT) compared with the non-young patients. Eighty percent of all patients received adjuvant therapy. The young patients were more frequently treated with chemotherapy, molecular targeted therapy and radiation therapy than the non-young patients.

Conclusions

In this study, young patients with breast cancer were diagnosed at more advanced stages and had more endocrine-unresponsive tumors than non-young patients. Further prognostic analyses should be conducted in this cohort.     

Tratamiento adyuvante del carcinoma de recto

Objective

Our objective was to assess the value of adjuvant treatment of patients undergoing surgery for locally-advanced rectal carcinoma, treated with concomitant, or alternating, radiochemotherapy.

Material and methods

Between January 1994 and September 1997, 122 patients with B2-C rectal adenocarcinoma were treated with a post-operative scheme of radiochemotherapy which was alternating (n=77) or concomitant (n=45). The chemotherapy agents were 5-FU and leucovorin in all cases. Radiotherapy volume included pelvis and was administered in 25 fractions up to a total dose of 50 Gy.

Results

With a median follow-up of 68.9 months, the overall survival, cancer-specific survival and disease-free survival at 5 years were 58.6%, 60.5% and 51.3%, respectively. The 5-year overall recurrence rate was 48.7%, local recurrence rate was 34.6%, and metastases rate was 32.6%. The nodal stage and the Astler-Coller classification stage were the main prognostic factors (p<0.0001). The combined treatment scheme showed no statistical influence on outcome. Severe acute toxicity occurred in 20.5% of patients, with no case of toxicity grade 4 nor any toxic deaths. Two-field radiotherapy technique and the sequence of combination of radiochemotherapy were predictive factors of acute toxicity, both in incidence and severity. Delayed grade 3 toxicity occurred in 15 patients (10.6%) and, of these, 10 patients (8.2%) required surgical treatment to resolve an intestinal obstruction.

Conclusions

Our results indicate that adjuvant radiochemotherapy for rectal carcinoma is an effective treatment. The rates of survival, recurrence and toxicity are similar to other major published studies, and with the sequence of administration having no significant effect on outcomes.     

Resectable Pancreatic Metastasis of Left Thighbone Leiomyosarcoma: Case Report and Literature Review

Introduction

Metastases to the pancreas gland are uncommon, especially from leiomyosarcoma. We report a case of asymptomatic pancreatic metastasis resection of leiomyosarcoma.

Case Report

A 59-year-old patient was treated for thighbone leiomyosarcoma, with surgical resection and adjuvant radiotherapy. After 4?years of follow-up, although that patient was asymptomatic, a pancreatic metastasis was identified by CT and fine needle aspiration. Open left pancreatectomy was performed.

Discussion

We discuss diagnosis findings and interest in the surgical resection. Furthermore, we reviewed previously reported cases.     

Pilot phase III immunotherapy study in early-stage breast cancer patients using oxidized mannan-MUC1 [ISRCTN71711835]

Introduction

Mucin 1 (MUC1) is a high molecular weight glycoprotein overexpressed on adenocarcinoma cells and is a target for immunotherapy protocols. To date, clinical trials against MUC1 have included advanced cancer patients. Herein, we report a trial using early stage breast cancer patients and injection of oxidized mannan-MUC1.

Method

In a randomized, double-blind study, 31 patients with stage II breast cancer and with no evidence of disease received subcutaneous injections of either placebo or oxidized mannan-MUC1, to immunize against MUC1 and prevent cancer reoccurrence/metastases. Twenty-eight patients received the full course of injections of either oxidized mannan-MUC1 or placebo. Survival and immunological assays were assessed.

Results

After more than 5.5 years had elapsed since the last patient began treatment (8.5 years from the start of treatment of the first patient), the recurrence rate in patients receiving the placebo was 27% (4/15; the expected rate of recurrence in stage II breast cancer); those receiving immunotherapy had no recurrences (0/16), and this finding was statistically significant (P = 0.0292). Of the patients receiving oxidized mannan-MUC1, nine out of 13 had measurable antibodies to MUC1 and four out of 10 had MUC1-specific T cell responses; none of the placebo-treated patients exhibited an immune response to MUC1.

Conclusion

The results suggest that, in early breast cancer, MUC1 immunotherapy is beneficial, and that a larger phase III study should be undertaken.     

A Population-Based Comparison of Overall and Disease-Specific Survival Following Local Excision or Abdominoperineal Resection for Stage I Rectal Adenocarcinoma

Purpose

The use of local excision (LE) for early stage rectal adenocarcinoma is increasing due to the associated morbidity of radical resection. To determine if survival in stage I rectal cancer differs following LE or abdominoperineal resection (APR), we analyzed the Surveillance, Epidemiology, and End Results Database.

Material and Methods

We selected patients diagnosed between 1988 and 2002 with T1-2N0M0 rectal adenocarcinoma measuring ≤4 cm who underwent either local excision with (LE + RT) or without adjuvant radiation (LE alone) or APR alone. Overall survival (OS) and disease-specific survival (DSS) curves were calculated using the Kaplan–Meier method. Univariate and multivariate Cox regression was also performed to determine the effect of covariates on OS and DSS.

Results

A total of 2,391 patients were identified including 981 (41 %) treated with APR, 1,018 (43 %) treated with LE alone, and 392 (16 %) treated with LE + RT. With a median follow-up of 69 months, there was no difference in OS or DSS seen between the three groups (p?>?0.05 for all comparisons). When stratifying by T-stage, there was a significant difference in overall survival between LE alone and APR for T2 disease. However, there was no difference in DSS between these two subgroups. There were no other significant survival differences between all comparable subgroups.

Conclusions

In this large population-based study, there was no difference in long-term DSS between patients who underwent an APR compared to selected patients who underwent LE with or without adjuvant radiation. Although these data further reinforce the promising data regarding the selected use of LE, further prospective studies are needed to further elucidate the role of LE in this setting.     

Adjuvante Therapiekonzepte beim Ovarialkarzinom

Background

The overall survival of patients with advanced ovarian cancer after optimal cytoreductive surgery and adjuvant chemotherapy could be improved over the last four decades but is still limited with 35–45?%. Thus ovarian cancer is still the deadliest of all genital cancers. There is a great need for optimization in efficacy of the current adjuvant treatment standard of carboplatin and paclitaxel and a reduction of acute and long-term side effects.

Objective

This article presents an evidence-based review of the current state of the art therapy as well as new developments

Material and methods

A systematic literature search was carried out and relevant publications, congress reports as well as current clinical trials are summarized.

Results

Management of early stage ovarian cancer requires an adequate intraoperative staging. For all patients other than FIGO stage Ia, G1 chemotherapy should be recommended following the individual risk situation. Inhibition of angiogenesis is a new and highly effective treatment strategy for treatment of advanced ovarian cancer. Bevacizumab has been approved since 2011 for the adjuvant therapy of advanced stage disease FIGO stages IIIb-IV in combination with carboplatin and paclitaxel.

Conclusion

The long-term focus of management of ovarian cancer aims at the implementation of targeted strategies to reduce toxicity and optimize the therapeutic index. Currently running clinical trials are focusing on additional inhibitors of angiogenesis. The great challenge for clinicians is to identify subgroups of patients who may benefit of different targeted treatment strategies.