Full dose neoadjuvant FOLFIRINOX is associated with prolonged survival in patients with locally advanced pancreatic adenocarcinoma.

BACKGROUND: The efficacy of FOLFIRINOX for metastatic pancreatic cancer has led to its use in patients with earlier stages of disease. This study retrospectively analyzed a cohort of patients with locally-advanced pancreatic cancer (LAPC) treated with FOLFIRINOX. METHODS: Between 2008 and 2013, 51 treatment-naïve patients with LAPC at a single institution received first-line FOLFIRINOX with neoadjuvant intent, at the full dose as described in the PRODIGE 4/ACCORD 11 study. Combined chemoradiation was administered for those who remained unresectable after maximum response to chemotherapy. The primary outcome measure was overall survival (OS), and secondary outcomes were progression-free survival (PFS) and margin-negative (R0) resection rate, and toxicity profile. RESULTS: A total of 429 cycles of FOLFIRINOX were given with a median of 8 cycles (range 2-29) per patient; 66% of cycles were full dose. After chemotherapy, 27 (53%) received chemoradiation. The median OS was 35.4 months (95% CI 25.8-45). Ten (4 borderline resectable and 6 unresectable) patients had successful R0 resections; those who had R0 resections had a significantly longer survival than those who did not (3-year OS rate 67% versus 21%, log rank p = 0.042). Increasing number of full-dose cycles was significantly associated with increased survival. The toxicity profile was similar to previous reports of this regimen. CONCLUSIONS: FOLFIRINOX is feasible as neoadjuvant therapy for LAPC. Although the R0 resection rate was only 20%, the median OS of almost 3 years appears promising. Dose intensity and duration were associated with increased survival in this study, arguing against dose attenuated versions of this regimen.

Decreased survival in hepatitis C patients with monomorphic post-transplant lymphoproliferative disorder after liver transplantation treated with frontline immunochemotherapy.

Post-transplant lymphoproliferative disorder (PTLD) develops in 1-3% of liver transplant recipients and no consensus exists about therapeutic management. From 2006 to 2016, 1489 liver transplants were performed at our institution with 20 patients (incidence 1.3%) developing PTLD. Hepatitis C virus (HCV) was the leading cause (n = 10) of liver transplant in PTLD patients. Diffuse large B-cell lymphoma was the most frequent histologic subtype (n = 17), and we report our experience in the management of these patients. Patients were treated with frontline immunochemotherapy without immunosuppression reduction. All evaluable patients achieved a complete remission. Statistically significant decreased survival was identified in HCV-positive patients. Six patients (60%) exhibited increases in HCV RNA levels during therapy. Four patients (40%) developed graft failure and three of them (30%) died from liver dysfunction. This is the first study providing evidence of decreased survival in HCV-positive PTLD patients after liver transplant receiving immunochemotherapy.

Efficacy of sorafenib, a multi-tyrosine kinase inhibitor, in an adenoid cystic carcinoma metastatic to the lung: case report and review of literature.

INTRODUCTION: Treatment for squamous cell carcinoma of the head and neck has significantly improved with the addition of cetuximab, a monoclonal antibody against the epidermal growth factor receptor, to conventional cytotoxic agents. The most significant aspect of this treatment approach is the proof that head and neck cancers are suitable for targeted therapies as has been shown in other malignancies. Unfortunately, there are other rare histologic types of head and neck cancer such as adenocarcinoma and adenoid cystic carcinoma. The latter has traditionally been considered to be chemotherapy resistant and surgical resection with or without adjuvant radiation therapy has been the rule as far as treatment is concerned. The course of adenoid cystic carcinoma ranges from indolent to aggressive; however, most patients succumb to the disease as a result of distant metastases. This clinical scenario poses a challenge to oncologists. Several conventional chemotherapy regimens and novel targeted agents have been tried in this rare histologic subtype without success. CASE PRESENTATION: In this case report, we present a 59-year-old Caucasian female with refractory adenoid cystic carcinoma of the maxilla metastatic to the lung that responded to sorafenib, a novel multi-tyrosine kinase inhibitor, which targets angiogenesis, Raf kinase pathway, platelet-derived growth factor Ret, and c-Kit. CONCLUSION: This case illustrates the possibility that this chemoresistant tumor may need the inhibition or blocking of several oncogenic pathways. Certainly, it is imperative that more studies are done in this special population trying to identify tumorigenesis mechanisms that may be upregulated in this malignancy and could be potential targets for therapeutic development.