Radiation-associated angiosarcoma of the breast: An international multicenter analysis.

INTRODUCTION: Radiation-associated angiosarcoma (RAAS) is a rare and serious complication of breast irradiation. Due to the rarity of the condition, clinical experience is limited and publications on this topic include only retrospective studies or case reports. MATERIALS AND METHODS: All patients diagnosed with RAAS between January 2000 and December 2017 in twelve centers across the Czech Republic and Slovakia were evaluated. RESULTS: Data of 53 patients were analyzed. The median age at diagnosis was 72 (range 44-89) years. The median latency period between irradiation and diagnosis of RAAS was 78 (range 36-172) months. The median radiation dose was 57.6 (range 34-66) Gy. The whole breast radiation therapy with radiation boost to the tumor bed was the most common radiotherapy regimen. Total mastectomy due to RAAS was performed in 43 patients (81%), radical excision in 8 (15%); 2 patients were not surgically treated due to unresectable disease. Adjuvant chemotherapy followed surgical therapy of RAAS in 18 patients, 3 patients underwent adjuvant radiotherapy. The local recurrence rate of RAAS was 43% and the median time from surgery to the onset of recurrence was 7.5 months (range 3-66 months). The 3-year survival rate was 56%, the 5-year survival rate was only 33%. 46% of patients died during the follow-up period. CONCLUSION: The present data demonstrate that RAAS is a rare condition with high local recurrence rate (43%) and mortality (the 5-year survival rate was 33%.). Early diagnosis of RAAS based on biopsy is crucial for treatment with radical intent. Surgery with negative margins constitutes the most important part of the therapy; the role of adjuvant chemotherapy and radiotherapy is still unclear.

Increased efficacy of a dose-dense regimen of neoadjuvant chemotherapy in breast carcinoma: a retrospective analysis.

Neoadjuvant chemotherapy is being increasingly used in the treatment of breast carcinoma. We performed a single-center retrospective analysis of the results of neoadjuvant therapy in 376 breast carcinoma patients treated with three different regimens combining doxorubicin and paclitaxel (AT), dose-dense doxorubicin and cyclophosphamide with sequential weekly paclitaxel (DD AC-P), or the combination of trastuzumab with chemotherapy (DD AC-PT). The expression of estrogen receptors (ER), progesterone receptors (PR) and human epidermal growth factor receptor (HER)-2 was determined immunohistochemically. Pathological response was determined in 318 patients. Pathological complete response (pCR) was observed in 18% of patients. The pCR rate was significantly higher in patients treated with DD regimen (22 vs. 13%) and younger than 55 years (23 vs. 13%). The pCR rate was higher in patients with triple negative (TN) tumors (43%) and tumors over-expressing HER-2 (HER-2+; 28%) compared to patients with ER- or PR-positive tumors not expressing HER-2 (ER/PR+HER-2-; 6%). In patients with TN tumors pCR rate was significantly higher after treatment with DD AC-P compared to AT (61 vs. 22%, p=0.005). pCR was associated with significantly improved relapse-free survival (RFS) and overall survival (OS), but when analysis was performed based on tumor phenotype, the difference was significant only in patients with TN tumors. In multivariate analysis, pCR, stage, and ER expression were significant predictors of RFS, while pCR, stage, ER and DD regimen were significant predictors of OS. In conclusion, present data indicate superiority of a DD regimen in obtaining pCR in patients with breast carcinoma treated with neoadjuvant chemotherapy. The difference in efficacy is due mostly to markedly higher pCR rate in patients with TN tumors.

Expression of bcl-2 in breast cancer: correlation with clinicopathological characteristics and survival.

Breast cancer is the most common malignancy in women. It is an immensely heterogeneous disease, characterised by a broad variety of clinical development. The research in recent years has focused on finding new markers of prognosis. This study investigates the role of expression of the bcl-2 protein in breast cancer. We analysed bcl-2 expression in 57 women with primary breast carcinoma who were treated with neoadjuvant (primary) chemotherapy, followed by a surgical procedure. The bcl-2 expression was correlated with other clinicopathological characteristics of the tumour- histological grade, stage, expression of hormonal receptors, proliferation rate, and with the survival of the patients. No significant association of bcl-2 expression with either overall survival or disease free survival was found.

Survival of patients with colorectal cancer liver metastases treated by regional chemotherapy.

BACKGROUND/AIMS: Liver is the most common site of metastatic disease in colorectal cancer. Superior response rate was demonstrated in trials comparing hepatic arterial administration of cytotoxic agents with systemic chemotherapy. METHODOLOGY: Records of 109 consecutive patients with colorectal carcinoma metastatic to the liver treated by regional chemotherapy, who underwent implantation of a port system into hepatic artery or portal vein tributaries between 1991 and 1999, were reviewed and survival was evaluated using the log-rank test and multivariate analysis (Cox's proportional hazard regression). RESULTS: The median survival from diagnosis was 24 months. Survival was significantly longer for patients treated by radical resection, and patients treated in 1997-1999. On multivariate analysis, treatment by 6 or more chemotherapy cycles, stage 1 liver metastases, treatment with irinotecan and radical resection were associated with better survival, while the presence of extrahepatic disease had an adverse effect on the risk of death. Extrahepatic spread was subsequently detected in almost half of the patients who had originally isolated liver metastases. CONCLUSIONS: Patients treated by liver resection had the best outcome, while patients with extrahepatic diseases had poor prognosis. The prognosis of patients treated by regional chemotherapy improved significantly with the advent of irinotecan and better selection.

Regional chemotherapy in patients with breast carcinoma liver metastases.

BACKGROUND/AIMS: Although liver is a common site of metastases in breast cancer, isolated liver metastases in patients with disseminated breast cancer are rare. The role of liver-directed therapies in these patients is based on data derived from retrospective analysis of case series. METHODOLOGY: We have reviewed the records of 8 patients with liver metastases and a history of breast cancer treated at our institution over a period of 11 years with regional chemotherapy administered through surgically implanted port systems. RESULTS: Three of the patients also had a history of second primary colorectal carcinoma. One patient had evidence of extrahepatic spread. All patients were treated by regimens based on the combination of 5-fluorouracil and folinic acid. Three patients were also treated by cytoreductive procedures. The median survival times from the diagnosis and port systems implantation were 34 months and 31 months, respectively. CONCLUSIONS: Our data support the use of regional intraarterial chemotherapy in patients with metastatic breast cancer limited to the liver.

Hepatic arterial infusion chemotherapy in sarcoma liver metastases: a report of 6 cases.

AIMS AND BACKGROUND: Liver metastases in patients with sarcoma are rare and associated with a poor prognosis. The experience with liver-directed therapies, eg hepatic arterial infusion, in these patients is limited. METHODS: Six patients with sarcoma metastatic to the liver (4 patients with gastrointestinal stromal tumors and 2 patients with leiomyosarcoma) were treated by hepatic arterial infusion in our center over a 12-year period. Since the experience was limited, a pooled analysis of reports with data on survival of 22 individual patients was performed. RESULTS: None of the 5 assessable patients responded to the therapy, and liver metastases progressed in all patients. The median survival was 20 months. In the pooled analysis, partial response was observed in 10 of 21 assessable patients (48%) and median survival was 20 months. The survival was significantly longer in responding patients compared to nonresponders (35 vs 14 months; logrank test, P = 0.009). CONCLUSIONS: Hepatic arterial infusion has little efficacy in the treatment of sarcoma metastatic to the liver. More promising results have been reported for chemoembolization. The survival of responding patients seems to be better compared to non-responders.

Hepatic arterial infusion chemotherapy in gastric cancer: a report of four cases and analysis of the literature.

AIMS AND BACKGROUND: Gastric cancer is associated with high mortality. Although the liver is a common site of metastases in this tumor, the experience with liver-directed therapies is limited. METHODS: We report a single-center experience involving four patients with liver metastases from gastric cancer treated by hepatic arterial infusion (HAI). In addition, we performed a search for reports on HAI in gastric cancer metastatic to the liver and used the studies with data on survival of individual patients for a pooled analysis. RESULTS: Among three valuable patients, one had a complete response, one had stable disease and one had progressive disease. The patient with complete response is still alive 41 months after the diagnosis of liver metastases, while the other patients died 6, 22 and 31 months after the diagnosis. Objective responses were observed in 48% of the 25 patients in the pooled analysis. Objective response and limited hepatic involvement were independent predictors of survival in these patients. CONCLUSIONS: Although isolated liver involvement in metastatic gastric cancer is rare, HAI seems to be similarly effective in these patients as in patients with liver metastases from colorectal cancer. The prognosis is significantly better in gastric cancer patients who have limited hepatic involvement and attain an objective response after HAI.

Transduodenal intraluminal high dose rate brachytherapy in the treatment of carcinomas of the subhepatic region.

BACKGROUND/AIMS: The prognosis of carcinomas of the subhepatic region is poor, and therapeutic efforts are limited mostly to palliation. The aim of this study was to retrospectively evaluate the effectiveness of transduodenal administration of intraluminal high dose rate brachytherapy in the palliative treatment of bile duct and pancreatic head carcinomas. METHODOLOGY: Twelve patients with inoperable bile duct and pancreatic head carcinomas were treated by transduodenal brachytherapy using high dose rate remote afterloading system. Eleven patients were treated by intraluminal brachytherapy inserted via a nasobiliary drain and one patient by intraluminal brachytherapy via a nasopancreatic drain inserted in the duct of Wirsung. RESULTS: After transduodenal intraluminal brachytherapy, a control of icterus was observed in all patients. The treatment was well tolerated with the mean survival of 284 days. CONCLUSIONS: Transduodenal intraluminal brachytherapy is technically feasible. The addition of intraluminal brachytherapy may be beneficial to patients in whom drainage can be established. Transduodenal insertion of brachytherapy is not competitive to the percutaneous approach but spreads the possibilities of the treatment of bile duct carcinoma. Intraluminal brachytherapy of pancreatic head carcinoma is feasible only via transduodenal approach.

Regional chemotherapy in biliary tract cancers--a single institution experience.

BACKGROUND/AIMS: The prognosis of biliary tract cancers is poor. The aim of the present report was to analyze retrospectively the effectiveness of regional chemotherapy in patients with biliary tract cancers treated at a single institution. METHODOLOGY: Thirty-two patients with biliary tract cancers, 17 patients with cholangiocarcinoma and 15 patients with gallbladder carcinoma, were treated by regional administration of the chemotherapy, usually the combination of 5-fluorouracil, cisplatin and folinic acid. Eighteen patients with inoperable tumors received no surgical treatment, 10 patients were treated by palliative resection (cohort B), and 4 patients received radical surgery (cohort C). RESULTS: The median survival of the patients is (mean +/- standard deviation) 14 +/- 17+ (median 7+) months for cohort A patients, 22 +/- 17+ (median 17+) months for cohort B patients, and 32 +/- 4+ (median 33+) months for cohort C patients. One-year survival was 38% (6 out of 16 patients) for cohort A, 80% (8 out of 10 patients) for cohort B, and 100% (4 out of 4 patients for cohort C). Two-year survival was 15% (2 out of 13) for cohort A, 30% (3 out of 10) for cohort B, and 100% (4 out of 4) for cohort C. One out of 12 patients (8%) in cohort A and 1 out of 10 patients (10%) in cohort B survived more than 5 years. After intraarterial chemotherapy, a significant increase was observed in the absolute numbers of CD3+, CD3+CD8+ and CD8+CD28+ lymphocytes, as well as an increase in CD3+CD4+ and natural killer lymphocytes. CONCLUSIONS: Regional chemotherapy is active in controlling the disease, and seems to result in prolongation of survival in patients with biliary tract cancer. Administration of regional chemotherapy is also associated with a rise of circulating lymphocyte numbers.

Intraluminal high dose rate brachytherapy in the treatment of bile duct and gallbladder carcinomas.

BACKGROUND/AIMS: The prognosis of biliary tract carcinomas is poor, and therapeutic efforts are limited mostly only to palliation. The aim of this study was to retrospectively evaluate the effectiveness and tolerability of intraluminal high dose rate brachytherapy in the treatment of bile duct and gallbladder carcinomas. METHODOLOGY: Thirteen patients with bile duct and gallbladder carcinomas were treated by brachytherapy administered through high dose rate remote afterloading system. Five patients after Roux-en-Y hepaticojejunoanastomosis were treated by intraluminal brachytherapy inserted via a diahepatal drain, and 8 inoperable patients were treated by intraluminal brachytherapy via a percutaneous biliary drain. RESULTS: After intraluminal brachytherapy, a control of icterus was observed in all patients. The treatment was well tolerated and mean survival was 275 days. CONCLUSIONS: The addition of intraluminal brachytherapy may be beneficial to patients with carcinomas causing biliary obstruction in whom bile drainage can be established.

Pegylated liposomal doxorubicin in combination with hyperthermia in the treatment of a case of advanced hepatocellular carcinoma.

BACKGROUND: Currently, there is no standard treatment of inoperable advanced hepatocellular carcinoma. STUDY: A patient with advanced hepatocellular carcinoma was treated with intravenous infusion of pegylated liposomal doxorubicin (PLD, Caelyx) in combination with ultrasound hyperthermia of the liver. Each cycle consisted of infusion of 60 mg of PLD followed by two fractions of hyperthermia 41 degrees C to 43 degrees C for 45 minutes 1 and 48 hours after infusion, respectively. RESULTS: A substantial regression of the tumor was observed on computed tomography scans. No toxicity of combined treatment was noted. CONCLUSIONS: This may be the first report of the combination of PLD and hyperthermia in the treatment of advanced hepatocellular carcinoma. Our observation suggests that the combination of PLD with hyperthermia is technically feasible, well tolerated, and could have synergistic potential.