Neoadjuvant Chemoembolization Research Articles

Transarterial Chemoembolization and Unresectable Hepatocellular Carcinoma: A Narrative Review.

Hepatocellular carcinoma (HCC) is an aggressive tumor, and even with the breakthrough in preventive strategies, and new diagnostic and treatment modalities, incidence and fatality rates continue to climb. Patients with HCC are most commonly diagnosed in the later stage, where the disease has already advanced, making it impossible to undertake potentially curative surgery. Transarterial chemoembolization (TACE) is a locoregional therapy regarded as a first-line treatment in patients with intermediate-stage HCC (Barcelona clinical liver cancer {BCLC}-B). TACE is a minimally invasive and non-surgical procedure that combines local chemotherapeutic drug administration with embolization to treat HCC. It helps limit tumor growth, preserve liver function, and increase overall and progression-free survival in patients with intermediate-stage HCC. This article has reviewed the efficacy, survival, limitations, and overall benefit of TACE in patients with unresectable HCC. This article has also discussed the effectiveness of TACE for neoadjuvant chemoembolization and the use of TACE with combination therapies.

Safety and efficacy of perioperative chemoradiotherapy of resectable pancreatic cancer

Background: A novel treatment method involving neoadjuvant chemoembolization of tumor vessels prior to intraoperative radiotherapy followed by adjuvant chemotherapy was established for patients with resectable pancreatic cancer. The aim of the present study was to assess the safety and efficacy of this novel treatment scheme. Methods: Records of 114 patients with PDAC treated in Botkin Hospital between 2013-2016 were reviewed. In 28 cases a combination of neoadjuvant chemoembolization (NACE) and pancratic resection was used. 33 patients underwent complex treatment (IORT and pancreatic resection). In 23 cases perioperative chemoradiotherapy (PeriCRT), a novel method, was used. 30 patients were treated by a standard scheme (pancreatic resection and adjuvant chemotherapy). Afterward a histological examination and electron microscopy of irradiated resection margin were performed. Results: All 114 patients underwent gross total resection. By the end of the study only patients in the control group had local reccurence (3/30). The estimated median survival was 336, 356, 359 and 333 days. Long-term survival was 78,6% (NACE), 87,9% (IORT), 95,7% (PeriCRT), 73,3% (control) for one-year survival, respectively (P=0,0257, 95% Cl). All treatment methods were well tolerated by all patients, with few adverse effects and no serious complications. Conclusion: Excellent local control and one-year OS for resected PDAC was achieved by using novel PeriCRT treatment method.

Safety and efficacy of perioperative chemoradiotherapy of resectable pancreatic cancer.

Background: A novel treatment method involving neoadjuvant chemoembolization of tumor vessels prior to intraoperative radiotherapy followed by adjuvant chemotherapy was established for patients with resectable pancreatic cancer. The aim of the present study was to assess the safety and efficacy of this novel treatment scheme. Methods: Records of 114 patients with PDAC treated in Botkin Hospital between 2013-2016 were reviewed. In 28 cases a combination of neoadjuvant chemoembolization (NACE) and pancratic resection was used. 33 patients underwent complex treatment (IORT and pancreatic resection). In 23 cases perioperative chemoradiotherapy (PeriCRT), a novel method, was used. 30 patients were treated by a standard scheme (pancreatic resection and adjuvant chemotherapy). Afterward a histological examination and electron microscopy of irradiated resection margin were performed. Results: All 114 patients underwent gross total resection. By the end of the study only patients in the control group had local reccurence (3/30). The estimated median survival was 336, 356, 359 and 333 days. Long-term survival was 78,6% (NACE), 87,9% (IORT), 95,7% (PeriCRT), 73,3% (control) for one-year survival, respectively (P=0,0257, 95% Cl). All treatment methods were well tolerated by all patients, with few adverse effects and no serious complications. Conclusion: Excellent local control and one-year OS for resected PDAC was achieved by using novel PeriCRT treatment method.

Influence of perioperative intraarterial selective chemotherapy on terms of recurrent ductal adenocarcinoma of the pancreatic head after pancreaticoduodenectomy

Aim.To analyze influence of perioperative intra-arterial selective chemotherapy on terms of recurrent ductal adenocarcinoma of pancreatic head after pancreaticoduodenectomy.Material and methods. 111 patients underwent combined treatment. Surgical stage included conventional pylorussparing pancreaticoduodenectomy in all groups. The main group consisted of 52 patients who received combined treatment: neoadjuvant chemoembolization with gemcitabine (400 mg/m2) and oxaliplatin (50 mg/m2), surgical treatment and 6 courses of regional chemotherapy – infusion of gemcitabine (800 mg/m2) and oxaliplatin (45 mg/m2) into celiac trunk in adjuvant mode. The control group was presented by 59 patients who underwent perioperative regional chemotherapy (neoadjuvant chemoembolization and adjuvant infusion of gemcitabine (800 mg/m2). Progression-free survival (PFS) and terms of recurrence were analyzed in all groups. In case of progression and recurrence we applied regional chemotherapy alone. Systemic chemotherapy was not used in the study.Results.Annual PFS in the main and the control groups was 80%. Three-year PFS in the main group was 37%, in the control group – 14% (p < 0.01). Five-year PFS was 11% in the main group and absent in the control group. Median survival was 26 months in the main group and 22.6 months in the control group. Overall annual, 2-year and 5-year survival in main group was 80%, 57% and 15%, respectively.Conclusion.Regional intra-arterial chemotherapy decreases incidence of recurrences and improves PFS after surgical treatment of pancreatic head adenocarcinoma.Further multi-center studies are necessary to assess the effectiveness of regional chemotherapy.

Combination of perioperative chemotherapy and intraoperative radiotherapy for the treatment of resectable pancreatic head cancer

Introduction: A new treatment method involving neoadjuvant chemoembolization of tumor vessels 5 days prior to surgery combined with intraoperative radiotherapy (IORT) followed by adjuvant chemotherapy was established for patients with resectable pancreatic cancer. The aim of the present study was to assess the safety and efficacy of this treatment scheme. Method: Records of 161 patients with resectable PDAC treated in Botkin Hospital between 2013–2017 were reviewed. In 49 cases was used perioperative chemoradiotherapy (PeriCRT). IORT was performed using Carl Zeiss Intrabeam PRS 500 system. After resection stage, a single dose of 20 Gy IORT boost was delivered using 50-kV x-rays to a depth of 1 mm from the applicator surface. Afterward a histological examination and electron microscopy of irradiated resection margin were performed. Results: All 161 patients with PDAC underwent gross total resection (R0) with lymphadenectomy D2. The estimated median survival was 338, 358, 372 and 337 days. Long-term survival was 70,2% (NACE), 75,1% (IORT), 80,7% (PeriCRT), 61,3% (control) for 3-year survival, respectively (p < 0,05, 95% Cl). All treatment methods were well tolerated by all patients, with few adverse effects and no serious complications. There was no association between outcomes, variations in tumor characteristics, marker concentrations and therapeutic response. Conclusions: Good 3-year OS for resected PDAC was achieved by using novel PeriCRT treatment method.

LONG-TERM RESULTS OF COMBINED TREATMENT FOR DUCTAL PANCREATIC HEAD ADENOCARCINOMA BY MEANS OF INTRAARTERIAL PERIOPERATIVE CHEMOTHERAPY WITH OXALIPLATIN AND GEMCITABINE

Aim. Evaluation of long-term results of perioperative regional chemotherapy with gemcitabine and oxaliplatin in combined treatment of ductal adenocarcinoma of the pancreatic head. Material and methods. The first group consisted of 52 patients who received combined treatment: neoadjuvant chemoembolization (CE) with gemcitabine (400 mg / m2) and oxaliplatin (50 mg / m2) (GemOx), operative treatment, as well as up to 6 courses of chemoinfusion (CI) in the celiac trunk of gemcitabine (1000 mg / m2) and oxaliplatin (75 mg / m2) in the adjuvant regime. In the second group of 51 patients, perioperative regional chemotherapy (neoadjuvant CE and adjuvant CI) with gemcitabine (1000 mg / m 2) (Gem) was performed. 54 patients of the third group performed only operative intervention. Results. No complications associated with medical-diagnostic angiography and catheterization were observed. The median of life expectancy in the group of patients who received only operative treatment was 8.4 ±1.2 months, in the group of perioperative chemotherapy Gem-22.3 ± 1.5, in the group of patients who underwent perioperative regional chemotherapy GemOx-26 ± 1.1 months. Five-year survival rates in the groups were 0%, 10% and 13% and respectively Conclusions. A use of regional chemotherapy with gemcitabine and oxaliplatin can be regarded as a useful and effective step in combined treatment of pancreatic head adenocarcinoma.

Interim follow up results from a phase II study of neoadjuvant chemoembolization of resectable colorectal liver metastases (CRLM) with transcatheter hepatic therapy with irinotecan-eluting beads.

519 Background: 65% of patients undergoing liver resection for CRLM experience disease recurrence within 3 years. Perioperative chemotherapy improves 3-year progression free survival, and good pathologic response is associated with improved overall survival. However, systemic neoadjuvant chemotherapy increases operative morbidity. DEBIRI gives sustained delivery of drug directly to tumor, maximising response and reducing systemic exposure. This study examined the feasibility, safety and long-term outcome of patients treated with neoadjuvant DEBIRI before resection. Methods: Patients with resectable CRLM received single targeted DEBIRI (up to 200mg) 1 month pre-hepatectomy. Primary end-point: tumor resectability, secondary end-points: safety, pathologic response, disease-free (DFS) and overall survival (OS). Results: DEBIRI performed in 40 patients. Post-TACE complications: 1 acute pancreatitis (3%); 4 post-embolization syndromes (10%). 38 patients underwent hepatectomy (2 peritoneal disease, resectability rate 95%). 30-day operative mortality 5% (n=2), neither death TACE related (1 intraoperative pneumomediastinum, 1 aspiration pneumonia). Both operative deaths excluded from follow up analysis. 63 lesions (median 2 per patient) targeted with DEBIRI. Histology: no residual disease 17%; 1-49% residual disease 59%; &gt;50% residual disease 22%; no response 2%. Median follow up 293 days. Fourteen patients (36%) had disease recurrence, median DFS 387 days (95% CI 276-498). Eight (57%) had hepatic recurrence, 2 (14%) had pulmonary recurrence and 4 (29%) had both pulmonary and hepatic recurrence. One patient died of hepatic and pulmonary recurrence after 565 days. Conclusions: Resection after neoadjuvant DEBIRI for CRLM demonstrated a good safety profile in this study population. Single DEBIRI treatment resulted in impressive pathologic response, with patterns of recurrence comparable to reported series of resection alone. Further trials assessing combination DEBIRI and systemic chemotherapy are necessary. Clinical trial information: NCT00844233.

Expanded Criteria for Liver Transplantation in Patients With Hepatocellular Carcinoma

Introduction Liver transplantation is the only curative treatment for patients with cirrhosis and unresectable hepatocellular carcinoma (HCC) without extrahepatic dissemination. Since criteria for transplantation in HCC are controversial, we evaluated our early results of liver transplantation for unresectable HCC. Materials and methods Three women and 14 men (age range, 1.1 to 64 years) with preoperatively diagnosed or incidentally discovered HCC underwent liver transplantation. Six grafts were obtained from cadaveric donors, and each of the remaining 11 grafts from a living related donor. Criteria for participation, independent of tumor size and number of tumor nodules, were no invasion of major vascular structure and no evidence of extrahepatic disease. In nine patients, tumors were beyond the Milan criteria. Twelve patients (86.7%) received tacrolimus and 2 (13.30%), rapamycin monotherapy with early withdrawal of corticosteroid therapy. Two patients underwent neoadjuvant chemoembolization before transplantation; none received adjuvant chemotherapy. Seven patients with hepatitis B virus infection underwent antiviral prophylaxis with antibody to hepatitis B surface antigens and lamivudine. Results During follow-up (range, 1 to 17 months), all patients exhibited excellent graft function. Imaging studies revealed no evidence of tumor recurrence and no elevation of alpha fetoprotein or carcinoembryonic antigen levels. Discussion Low-dose immunosuppressive therapy and expanded criteria for liver transplantation in patients with HCC, especially when donation from a living related donor is possible, appear to inhibit disease recurrence and improve outcomes.

Neoadjuvant therapies for hepatocellular carcinoma before liver transplantation: A critical appraisal

Hepatocellular carcinoma (HCC) is a major health problem, being the fifth most common cancer worldwide. The incidence of HCC is increasing in Europe and the United States, and it is currently the leading cause of death among patients with cirrhosis. The advent of surveillance programs has led to a change in the stage of tumors detected. In more than half of the cases, these tumors will be suitable for potentially curative treatments, such as resection, transplantation, and percutaneous ablation.

Liver Transplantation and Tacrolimus Monotherapy for Hepatocellular Carcinoma With Expanded Criteria

Liver transplantation is the only curative treatment option for patients with cirrhosis and unresectable hepatocellular carcinoma (HCC) without extrahepatic dissemination. Criteria for transplantation in HCC are controversial. In this study, we evaluate the early results of liver transplantation for unresectable HCC. Between 2003 and 2004, 10 patients (three woman, seven men; aged 1.1 to 64 years) with occult or incidental HCC underwent liver transplantation. The inclusion criteria (independent of tumor size and number of tumor nodules) were: no invasion of major vascular structures and no evidence of extrahepatic disease, including that based on hilar lymph node biopsy and cytopathological examination of intraperitoneal fluid. Eight patients (80%) received tacrolimus and two patients (20%) received rapamycin monotherapy with early withdrawal of the corticosteroid. Four patients had neoadjuvant chemoembolization before transplantation. None of the patients received adjuvant chemotherapy. Two patients with hepatitis B virus cirrhosis underwent antiviral prophylaxis with anti-HBs antibody and lamivudine. During follow-up (range, 8 to 19 months), all patients did well with excellent graft function. There was no evidence of tumor recurrence on imaging studies, and there were no elevations in alpha fetoprotein or carcinoembryonic antigen levels. Low-dose immunosuppression and expanded criteria for liver transplantation for HCC appear to have beneficial effects on disease recurrence and patient outcomes, especially in regard to living donation.

Drop-out rates of patients with hepatocellular cancer listed for liver transplantation: outcome with chemoembolization.

Patients with hepatocellular carcinoma (HCC) are assigned model for end stage liver disease (MELD) scores to provide access to liver transplantation (LT). An equitable policy would equate HCC progression beyond acceptable transplantation criteria with death on the waiting list. However, limited information is available regarding this issue. Thus, our aim was to analyze drop-out rates on the waiting list for patients with HCC. Between January 1994 and August 2001, 54 patients with HCC were listed for LT. Patients underwent chemoembolization prior to LT, and were assessed every three months for disease progression until LT. Two patients were stage T1, 45 patients were stage T2, and 7 patients were stage T3 at time of first chemoembolization. Median time was 211 days (range 28-1099 days) for patients that were eventually transplanted. Eight patients were removed from the list. Cumulative probability of drop out on the waiting list, assessed by Kaplan-Meier analysis, was 15% and 25% at 6 and 12 months, respectively. There were no significant differences in age, gender, initial tumor stage, or serum AFP levels in those who eventually underwent LT vs. those who dropped out. In conclusion, neoadjuvant chemoembolization for patients with HCC has a drop-out rate of 15% over 6 months.

Liver transplantation for hepatic and biliary malignancy.

The treatment of liver cancer by transplantation has evolved into a process of selecting early stage tumors that have a high likelihood of cure. Carefully selected cirrhotic patients with early hepatocellular cancer (< or = 5 cm. diameter and single; < or = 3 cm. diameter if multiple and 3 or fewer lesions; no vascular invasion) have 5-year actuarial survival rates of approximately 75% after transplantation. Preoperative imaging should be as extensive as necessary to accurately define the characteristics of tumor size, location, and number and exclude signs of extrahepatic involvement. Adjuvant and neoadjuvant chemotherapy became part of treatment protocols in many centers at the same time that more stringent criteria for transplant candidacy were applied to patients with cancer, making it difficult to attribute improved results to the chemotherapy. Nevertheless, neoadjuvant chemoembolization for hepatocellular cancer is logical for patients who may wait long periods before receiving transplants. The fibrolamellar variant of hepatoma is a less aggressive tumor and patients can do well after transplantation, but late recurrences are common. Hepatoblastoma in children can respond very favorably to chemotherapy combined with transplantation. Cholangiocarcinoma remains a dreadful malignancy. The rare cases of insitu cholangiocarcioma in patients who receive transplants for sclerosing cholangitis can be cured, but known cholangiocarcinoma has an exceedingly high rate of recurrence after transplantation alone. Recent work combining chemotherapy and radiation with transplantation has not had dramatic success at improving cure rates. Patients with metastatic neuroendocrine tumors of the liver can receive good palliation by transplantation, but the majority of patients eventually develop recurrent cancer.