Perioperative or only adjuvant gemcitabine plus nab-paclitaxel for resectable pancreatic cancer (NEONAX)-a randomized phase II trial of the AIO pancreatic cancer group.

BACKGROUND: Data on perioperative chemotherapy in resectable pancreatic ductal adenocarcinoma (rPDAC) are limited. NEONAX examined perioperative or adjuvant chemotherapy with gemcitabine plus nab-paclitaxel in rPDAC (National Comprehensive Cancer Network criteria). PATIENTS AND METHODS: NEONAX is a prospective, randomized phase II trial with two independent experimental arms. One hundred twenty-seven rPDAC patients in 22 German centers were randomized 1 : 1 to perioperative (two pre-operative and four post-operative cycles, arm A) or adjuvant (six cycles, arm B) gemcitabine (1000 mg/m2) and nab-paclitaxel (125 mg/m2) on days 1, 8 and 15 of a 28-day cycle. RESULTS: The primary endpoint was disease-free survival (DFS) at 18 months in the modified intention-to-treat (ITT) population [R0/R1-resected patients who started neoadjuvant chemotherapy (CTX) (A) or adjuvant CTX (B)]. The pre-defined DFS rate of 55% at 18 months was not reached in both arms [A: 33.3% (95% confidence interval [CI] 18.5% to 48.1%), B: 41.4% (95% CI 20.7% to 62.0%)]. Ninety percent of patients in arm A completed neoadjuvant treatment, and 42% of patients in arm B started adjuvant chemotherapy. R0 resection rate was 88% (arm A) and 67% (arm B), respectively. Median overall survival (mOS) (ITT population) as a secondary endpoint was 25.5 months (95% CI 19.7-29.7 months) in arm A and 16.7 months (95% CI 11.6-22.2 months) in the upfront surgery arm. This difference corresponds to a median DFS (mDFS) (ITT) of 11.5 months (95% CI 8.8-14.5 months) in arm A and 5.9 months (95% CI 3.6-11.5 months) in arm B. Treatment was safe and well tolerable in both arms. CONCLUSIONS: The primary endpoint, DFS rate of 55% at 18 months (mITT population), was not reached in either arm of the trial and numerically favored the upfront surgery arm B. mOS (ITT population), a secondary endpoint, numerically favored the neoadjuvant arm A [25.5 months (95% CI 19.7-29.7months); arm B 16.7 months (95% CI 11.6-22.2 months)]. There was a difference in chemotherapy exposure with 90% of patients in arm A completing pre-operative chemotherapy and 58% of patients starting adjuvant chemotherapy in arm B. Neoadjuvant/perioperative treatment is a novel option for patients with resectable PDAC. However, the optimal treatment regimen has yet to be defined. The trial is registered with ClinicalTrials.gov (NCT02047513) and the European Clinical Trials Database (EudraCT 2013-005559-34).

[Diagnosis and treatment of colorectal liver metastases - workflow]. / Diagnostik und Therapie von Lebermetastasen kolorektaler Karzinome - Workflow.

In this review, standards of diagnosis and treatment of colorectal liver metastases are described on the basis of a workshop discussion. Algorithms of care for patients with synchronous / metachronous colorectal liver metastases or locoregional recurrent tumour are presented. Surgical resection is the procedure of choice in the curative treatment of liver metastases. The decision about the resection of liver metastases should consider the following parameters: 1. General operability of the patient (comorbidity); 2. Achievability of an R 0 situation: i. if necessary, in combination with ablative methods, ii. if necessary, neoadjuvant chemotherapy, iii. the ability to eradicate extrahepatic tumour manifestations; 3. Sufficient volume of the liver remaining after resection ("future liver remnant = FLR): i. if necessary, in combination with portal vein embolisation or two-stage hepatectomy; 4. The feasibility to preserve two contiguous hepatic segments with adequate vascular inflow and outflow as well as biliary drainage; 5. Tumour biological aspects ("prognostic variables"); 6. Experience of the surgeon and centre! Extrahepatic disease does not contraindicate hepatectomy for colorectal liver metastases provided a complete resection of both intra- and extrahepatic disease is feasible. Even in bilobar colorectal metastases and 5 or more tumours in the liver, a complete tumour resection has been described. The type of resection (hepatic wedge resection or anatomic resection) does not influence the recurrence rate. Preoperative volumetry is indicated when major hepatic resection is planned. The FLR should be 25 % in patients with normal liver, 40 % in patients who have received intensive chemotherapy or in cases of fatty liver, liver fibrosis or diabetes, and 50-60 % in patients with cirrhosis. In patients with initially unresectable colorectal liver metastases, preoperative chemotherapy enables complete resection in 15-30 % of the cases, whereas the value of neoadjuvant chemotherapy in patients with resectable liver metastases has not been sufficiently supported. In situ ablative procedures (radiofrequency ablation = RFA and laser-induced interstitial thermotherapy = LITT) are local therapy options in selected patients who are not candidates for resection (central recurrent liver metastases, bilobar multiple metastases and high-risk resection or restricted patient operability). Patients with tumours larger than 3 cm have a high local recurrence rate after percutaneous RFA and are not optimal candidates for this procedure. The physician's experience influences the results significantly, both after hepatectomy and after in situ ablation. Therefore, patients with colorectal liver metastases should be treated in centres with experience in liver surgery.

Neoadjuvant, hyperfractionated irradiation induces apoptosis and decreases proliferation in squamous cell cancer of the oral cavity.

Twenty-eight patients with squamous cell carcinoma of the oral cavity were treated with a total dose of 20 Gy. Tissue samples for immunohistochemistry were taken at the time of diagnostic biopsy and at surgery after radiotherapy (RX). For detection of proliferating cells, the immunoperoxidase reaction with Ki67 was performed. Apoptotic cells were detected by the TdT-mediated biotin dUTP nick end labeling (TUNEL) method. RX reduced proliferation in 27 patients, only in one case did the proliferation index (PI) increase. Delta PI (PI before RX PI following RX) amounted to 4.11% (SD=3.2%; P<0.0001). The apoptotic index (AI) increased significantly subsequent to neoadjuvant RX. Delta AI (AI after RX--AI before RX) measured 1.82% (SD=0.9; P<0.001). These data indicate that RX of patients suffering from squamous cell carcinoma of the oral cavity with a dosis of 20 Gy induces apoptosis and inhibits proliferation of tumor cells.