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

<p>Abstract</p> <p>Introduction</p> <p>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.</p> <p>Case presentation</p> <p>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.</p> <p>Conclusion</p> <p>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.</p

Post-Transplant Lymphoproliferative Disease In Liver Transplant Recipients: A Single Institution Experience

Abstract Abstract 1752 Background: Post-transplant lymphoproliferative disease (PTLD) represents a major complication after solid organ transplantation, associated with high morbidity and mortality. Few, mostly small retrospective case series have reported on the clinical features, treatment and outcome of PTLD after liver transplantation, and the optimal treatment approach remains controversial. At our institution, the management of PTLD was not standardized until 2006, when a dedicated lymphoma team for PTLD treatment was formed and adopted a uniform approach based on histologic phenotype. In this approach, monoclonal diffuse large B-cell lymphoma (DLBCL) occurring post transplant was treated aggressively with immunochemotherapy. Methods: We retrospectively analyzed the clinical data of all adult patients who developed PTLD following liver transplantation at our institution between 1988 and 2010. We also compared the outcomes of patients with the most common PTLD histology - DLBCL - treated before 2006 (era 1) and thereafter (era 2). Results: We identified 26 patients (m=18, f=8) with median age of 60 (range 15–80). Underlying liver diseases included hepatitis C (n=9), non-alcoholic steatohepatitis (n=3), alcoholic cirrhosis (n=3), biliary atresia (n=3), autoimmune hepatitis (n=3), cryptogenic cirrhosis (n=2), hepatitis B (n=1), fulminant hepatic failure (n=1) and congenital syndrome (n=1). Acute transplant rejection that required additional immunosuppressive therapy was observed in 16 (62%). Median latency of PTLD after liver transplantation was 39 (range 1–192) months. Eight patients (31%) presented with early PTLD, i.e. within one year after transplantation. Histologic entities included DLBCL (n=16), polymorphic lymphoplasmacytic infiltrate (n=4), marginal zone lymphoma (n=1), Burkitt lymphoma (n=1), Hodgkin lymphoma (n=1) and plasmacytoma (n=1). Tissue staining for EBER was positive in 4/21 evaluated cases (19%). The majority of patients (65%) presented with stage IV disease, and all but one (96%) manifested with extranodal disease. Median IPI score was 3. Initial treatment approaches in patients diagnosed and treated in era 1 (n=13) included reduction or discontinuation of immunosuppression alone (n=2) or in combination with antiviral agents (n=2) and Rituximab (n=7). Two patients died before initiation of therapy. Complete remission to first-line therapy was observed in 3 and partial remission in 4 patients evaluated for response. Six patients in this group died from progressive disease (n=1), infectious complications (n=3), hemorrhagic stroke (n=1) and unknown cause (n=1). Among patients diagnosed and treated in era 2 (n=13), eleven received chemotherapy with or without Rituximab without reduction of immunosppression, one patient was on “watch and wait” for asymptomatic splenic marginal zone lymphoma and another patient decided to seek treatment elsewhere and was lost to follow-up. Eleven patients in this group (1 patient with plasmacytoma of the liver and 10 with DLBCL, including 1 case of primary CNS lymphoma) were evaluable for response and all achieved a complete remission. After a median follow-up period of 28.5 months for surviving patients, the 3-year overall survival (OS) and progression-free survival (PFS) for all patients were 73% and 71%, respectively. One- and 3-year OS was 60% and 51%, respectively, for patients treated in era 1 and 100% for patients treated in era 2 (p=0.01), with 1- and 3-year PFS of 51% in era 1 and 91% in era 2, respectively (p=0.03). Patients with DLBCL histology treated in era 1 had 1- and 3-year OS of 40% and 20% (median 11 months), respectively, while those treated in era 2 had 1- and 3-year OS of 100% (p=0.001), with corresponding 1 and 3-year PFS of 20% (median 8 months) and 90%, respectively (p=0.004). Conclusion: Our study is one of the largest ever published on PTLD in adult liver transplant recipients. The majority of these patients present with aggressive histologies and high risk features. An aggressive immunochemotherapeutic approach by experienced and dedicated lymphoma and liver transplant teams may benefit post-transplant patients with DLBCL and lead to outcomes similar to those observed in the non-transplant setting. Disclosures: No relevant conflicts of interest to declare

Clinical Experience Of Lenalidomide Plus Low Dose Dexamethasone As First-Line Therapy For Multiple Myeloma At a Large County Hospital Caring For An Indigent Population

Abstract Background There is ample data for the response rates and clinical outcomes for patients with newly diagnosed multiple myeloma (MM) treated with first-line lenalidomide and dexamethasone (LEN/DEX). Phase II and III studies have reported objective response rates (ORR) in the range of 70-90%.  However, extrapolating from clinical trials to ‘real world' clinical practice is sometimes difficult. This is particularly so when it comes to large city hospital systems such as Jackson Memorial Hospital (JMH) in Miami, Florida. JMH is the third-largest public hospital and third-largest teaching hospital in the United States. Patients are primarily uninsured or insured through Medicaid. Additionally, one might surmise, that for a medication like LEN- with a relatively narrow therapeutic index, high cost, and cumbersome prescribing/dispensing requirements- outcomes in the ‘real world' might be inferior to those cited in clinical study. We endeavored to explore such outcomes in JMH to determine whether the benefits of this high cost drug in this setting are concordant with published data. Methods We conducted a retrospective analysis of all patients enrolled into the Celgene patient assistance program and prescribed LEN from January 1, 2010 through July 30, 2013 at JMH. We identified 96 patients enrolled into this program, 35 patients received LEN/DEX as first-line therapy for MM and are evaluable for this analysis. The primary end-point for analysis was response at 4 months. Results Medical records of 35 patients were reviewed. The mean age was 59 (46-75), majority of patients were female (60%), and 29% were black. Consistent with our patient population, 71.4% of patients were Hispanic, 44% were uninsured, and 64% had Medicaid. IgG (60%) was the most common heavy chain involved while 3 patients had light chain disease only. The majority of patients (88.6%) had stage III disease by the Durie-Salmon criteria, and 37.1% had ISS stage III disease. Cytogenetic studies were evaluable in 30 patients: 66.7% were standard-risk, 30% intermediate-risk and 3.3 % high-risk according to mSMART risk classification. At 4-month follow-up, 26 (74.3%) patients had an OR: 6 (17.1%) patients had CR, 7 (20%) had VGPR, and 13 (37.1%) had PR. 6 (17.1%) patients had progressive disease, change in therapy, or were lost to follow-up. There were no documented deep venous thromboses, a known risk of LEN therapy. Only 8 patients (23%) underwent autologous stem cell transplant following primary therapy. Conclusion Responses with upfront LEN/DEX in MM at JMH, were relatively similar to published data in large clinical studies. This provides support for the extrapolation of data from well supported clinical trials at fully-resourced medical institutions, for an oral chemotherapy drug with significant potential toxicities and logistical barriers, to a primarily Medicaid patient population in a county hospital. Disclosures: No relevant conflicts of interest to declare

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

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

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. 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. 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. 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

Considerations and consequences of allowing DNA sequence data as types of fungal taxa

Nomenclatural type definitions are one of the most important concepts in biological nomenclature. Being physical objects that can be re-studied by other researchers, types permanently link taxonomy (an artificial agreement to classify biological diversity) with nomenclature (an artificial agreement to name biological diversity). Two proposals to amend the International Code of Nomenclature for algae, fungi, and plants (ICN), allowing DNA sequences alone (of any region and extent) to serve as types of taxon names for voucherless fungi (mainly putative taxa from environmental DNA sequences), have been submitted to be voted on at the 11th International Mycological Congress (Puerto Rico, July 2018). We consider various genetic processes affecting the distribution of alleles among taxa and find that alleles may not consistently and uniquely represent the species within which they are contained. Should the proposals be accepted, the meaning of nomenclatural types would change in a fundamental way from physical objects as sources of data to the data themselves. Such changes are conducive to irreproducible science, the potential typification on artefactual data, and massive creation of names with low information content, ultimately causing nomenclatural instability and unnecessary work for future researchers that would stall future explorations of fungal diversity. We conclude that the acceptance of DNA sequences alone as types of names of taxa, under the terms used in the current proposals, is unnecessary and would not solve the problem of naming putative taxa known only from DNA sequences in a scientifically defensible way. As an alternative, we highlight the use of formulas for naming putative taxa (candidate taxa) that do not require any modification of the ICN.Peer reviewe