Neoadjuvant Chemotherapy Generates a Significant Tumor Response in Resectable Pancreatic Cancer Without Increasing Morbidity: Results of a Prospective Phase II Trial

Swiss HPB-Center, Department of Surgery and Institute of Surgical Pathology, Zurich, Switzerland.
Annals of surgery (Impact Factor: 7.19). 01/2009; 248(6):1014-22. DOI: 10.1097/SLA.0b013e318190a6da
Source: PubMed

ABSTRACT To evaluate the morbidity of pancreaticoduodenectomy after neoadjuvant chemotherapy for resectable pancreatic cancer and to assess its histologic and metabolic response.
Adjuvant chemotherapy improves the outcome of pancreatic cancer, but 25% of patients remain unfit after surgery. Neoadjuvant chemotherapy can be offered to all patients in a multimodality approach, but its efficacy and surgical morbidity are unknown.
Patients with resectable, cytologically proven adenocarcinoma of the pancreatic head received 4 bi-weekly cycles of gemcitabine (1000 mg/m(2)) and cisplatin (50 mg/m(2)) in this prospective phase II trial. Staging and restaging included chest x-ray, abdominal computed tomography (CT), positron emission tomography (PET)/CT, endoscopic ultrasound, and laparoscopy. Fluorodeoxyglucose uptake was quantified by the standard-uptake value (SUV) on baseline and restaging PET/CT. Immunohistochemistry for GLUT-1 and Ki-67 was performed. The histologic response, cytopathic effects, and surgical complications were graded by respective scores.
Twenty-four of 28 patients had resection for histologically confirmed adenocarcinoma. The surgical morbidity was low without perioperative death and one pancreatic fistula. Histologic response was documented in 54% and cytopathic effects in 83% of the patients. A significant SUV decrease occurred during chemotherapy (P = 0.031), which correlated with the baseline SUV (P = 0.001), Ki-67 expression (P = 0.016), and histologic response (P = 0.01). Neither the metabolic nor the histologic response was predictive of the median disease-free (9.2 months) or overall survival (26.5 months).
Neoadjuvant chemotherapy induced a significant metabolic and histologic response, which was best predicted by PET. Most importantly, surgery after neoadjuvant chemotherapy for pancreatic cancer was safe.

Download full-text


Available from: Thomas Hany, Jul 03, 2015
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Objectives Patients with borderline resectable pancreatic cancer (BRPC) have a higher probability of undergoing margin-negative resection after completing neoadjuvant therapy. Here, we describe a novel neoadjuvant approach using induction chemotherapy followed by stereotactic body radiation therapy (SBRT) for patients with BRPC. Methods This analysis included patients with nonmetastatic BRPC treated with neoadjuvant gemcitabine-based chemotherapy and five-fraction SBRT. Chemotherapy consisted of 3 cycles of Gemzar, Taxotere, and Xeloda. Patients were restaged to determine resectability, and nonmetastatic resectable patients underwent surgical resection. Results Thirty patients completed neoadjuvant treatment and were offered surgical exploration. Seventeen patients (56.7 %) reported no acute adverse effects during SBRT. No grade 3 or higher toxicity was observed from SBRT. Twenty-nine patients (96.7 %) underwent exploration. Twenty-one (95.6 %) of those who underwent pancreatic tumor resection achieved negative margins, with none requiring vessel resection. One (3.3 %) patient was resected with microscopic positive margins. Median follow-up was 15.6 months (range, 6.3–26.1 months). Median and 1-year overall survival was 20 months and 91 %, respectively. Median and 1-year progression-free survival was 14.9 months and 61 %, respectively. Conclusion SBRT-based neoadjuvant therapy for BRPC is well tolerated and can result in a high rate of margin-negative tumor resection.
    09/2012; 1(3). DOI:10.1007/s13566-012-0039-6
  • [Show abstract] [Hide abstract]
    ABSTRACT: Hardware- fused positron emission tomography (PET) and computed tomography (CT) to PET/CT as a single-step procedure improves the diagnostic accuracy in many oncological diseases. PET/CT using the most applied tracer F-18 fluorodeoxyglucose (FDG) helps in the differentiation malignant from benign pancreatic mass lesions. In proven exocrine pancreatic cancer, additional use iodinated, intravenous contrast in PET/CT combines the considerable advantages of both imaging modalities in detecting distant metastases as well as local staging regarding vascular invasion. Since FDG-uptake in tumor is correlated with tumor viability, FDG-PET/CT can be used for therapy response assessment in a neo-adjuvant, curative setting as well in monitoring radio-chemotherapy in a palliative setting. Further, FDG-PET/CT is able to detect local as well as distant recurrence rather reliably. For neuroendocrine pancreatic ancer, newly developed tracers like F18-DOPA and 68Ga-DOTA-NOC may revolutionize the diagnostic work-up by combining diagnostic as well as therapy related informations into a single exam.
    01/1970: pages 91-99;
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The lack of consensus on how to define and grade adverse postoperative events has greatly hampered the evaluation of surgical procedures. A new classification of complications, initiated in 1992, was updated 5 years ago. It is based on the type of therapy needed to correct the complication. The principle of the classification was to be simple, reproducible, flexible, and applicable irrespective of the cultural background. The aim of the current study was to critically evaluate this classification from the perspective of its use in the literature, by assessing interobserver variability in grading complex complication scenarios and to correlate the classification grades with patients', nurses', and doctors' perception. Reports from the literature using the classification system were systematically analyzed. Next, 11 scenarios illustrating difficult cases were prepared to develop a consensus on how to rank the various complications. Third, 7 centers from different continents, having routinely used the classification, independently assessed the 11 scenarios. An agreement analysis was performed to test the accuracy and reliability of the classification. Finally, the perception of the severity was tested in patients, nurses, and physicians by presenting 30 scenarios, each illustrating a specific grade of complication. We noted a dramatic increase in the use of the classification in many fields of surgery. About half of the studies used the contracted form, whereas the rest used the full range of grading. Two-thirds of the publications avoided subjective terms such as minor or major complications. The study of 11 difficult cases among various centers revealed a high degree of agreement in identifying and ranking complications (89% agreement), and enabled a better definition of unclear situations. Each grade of complications significantly correlated with the perception by patients, nurses, and physicians (P < 0.05, Kruskal-Wallis test). This 5-year evaluation provides strong evidence that the classification is valid and applicable worldwide in many fields of surgery. No modification in the general principle of classification is warranted in view of the use in ongoing publications and trials. Subjective, inaccurate, or confusing terms such as "minor or major" should be removed from the surgical literature.
    Annals of surgery 08/2009; 250(2):187-96. DOI:10.1097/SLA.0b013e3181b13ca2 · 7.19 Impact Factor