Ikechukwu Immanuel Akunyili

Oral and Extraoral Plasmablastic Lymphoma: Similarities and Differences in Clinicopathologic Characteristics

Plasmablastic lymphoma (PBL), initially characterized as an aggressive lymphoma arising in the jaw and oral mucosa in HIV-infected patients, was recently reported to occur with extraoral manifestations, heterogeneous histologic findings, and variable association with immunodeficiency states. We reviewed clinical, morphologic, and immunophenotypic features of 13 cases of PBL to determine whether these different subtypes represent distinct morphologic and clinical entities. Two distinct subtypes of PBL were identified and classified as oral and extraoral PBL. The oral PBLs were strongly associated with HIV infection and commonly demonstrated plasmablastic morphologic features without plasmacytic differentiation. Extraoral PBLs tended to occur in patients with underlying non-HIV-related immunosuppression and universally demonstrated plasmacytic differentiation. The patients with oral PBL demonstrated better overall survival compared with patients with extraoral PBL (P = .02). Our findings suggest that PBL with oral and extraoral manifestation represent 2 distinct clinicopathologic entities.

Oral and Extraoral Plasmablastic LymphomaSimilarities and Differences in Clinicopathologic Characteristics

Plasmablastic lymphoma (PBL), initially characterized as an aggressive lymphoma arising in the jaw and oral mucosa in HIV-infected patients, was recently reported to occur with extraoral manifestations, heterogeneous histologic findings, and variable association with immunodeficiency states. We reviewed clinical, morphologic, and immunophenotypic features of 13 cases of PBL to determine whether these different subtypes represent distinct morphologic and clinical entities. Two distinct subtypes of PBL were identified and classified as oral and extraoral PBL. The oral PBLs were strongly associated with HIV infection and commonly demonstrated plasmablastic morphologic features without plasmacytic differentiation. Extraoral PBLs tended to occur in patients with underlying non-HIV-related immunosuppression and universally demonstrated plasmacytic differentiation. The patients with oral PBL demonstrated better overall survival compared with patients with extraoral PBL (P = .02). Our findings suggest that PBL with oral and extraoral manifestation represent 2 distinct clinicopathologic entities.

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.

Sustained response to FOLFOX and Bevacizumab in metastatic bronchial carcinoid – A case report and review of the literature

A 65 year old male with bronchial carcinoid developed diffuse liver metastases seventeen months after curative resection of a solitary liver metastasis. Treatment with modified (m) FOLFOX 6 (5-FU, 400mg/m 2 bolus infusion, followed by Leucovorin 400 mg/m 2 and Oxaliplatin 85 mg/m 2 given in “Y” over 2 hours followed by 5 FU 2,400 mg/m 2 continuous infusion over 46 hours) plus Bevacizumab and Octreotide were given after progression on Octreotide alone. It resulted in sustained partial response. To our knowledge, this is the first reported case demonstrating activity of FOLFOX and Bevacizumab in metastatic bronchial carcinoid. The response and clinical benefit of FOLFOX with Bevacizumab in this case of metastatic bronchial carcinoid suggest that this treatment is active and should be further studied in patients with metastatic and unresectable bronchial carcinoid tumors.

The nab -paclitaxel/gemcitabine regimen for patients with refractory advanced pancreatic adenocarcinoma

The phase III MPACT trial for metastatic pancreatic cancer (PC) showed improved overall survival (OS), progression free survival (PFS) and response rates (RRs) for first-line nab-paclitaxel (Abraxane) and gemcitabine (the AG combination) compared to gemcitabine monotherapy. The safety and efficacy of the AG combination has not been systematically studied as second-line therapy or beyond for metastatic PC. We conducted an IRB-approved retrospective analysis of all patients diagnosed between September 2010 and August 2014 with advanced refractory PC that received combination treatment with AG at our institution. Demographic and survival data were extracted from the registry. Patients received nab-paclitaxel 125 mg/m2 and gemcitabine 1,000 mg/m2 and on days 1, 8 and 15 of a 28-day cycle with subsequent dose modifications based on tolerance. Data on 59 patients was available; the median age was 61; 55% were male; 56% received AG as second line therapy and 44% received it as third-line or beyond. Five (10%) patients had a confirmed partial response (PR), 23 (47%) had stable disease (SD) and 21 (43%) had disease progression as their best response. Among the 31 (52%) patients who received prior gemcitabine, 18 (58%) had clinical benefit; 3 had a PR and 15 had SD. The median OS was 3.9 months and the median progression-free survival was 3 months. Toxicity was similar to what was reported in the MPACT trial. This retrospective analysis suggests that AG is active in PC patients previously treated with either fluoropyrimidine-based therapy or gemcitabine-based therapy with manageable toxicities.

The value of tissue protein expression as a predictor of efficacy for first- or second-line therapy (tx) in metastatic ductal pancreas cancer (PDAC) in patients (pts) receiving either gemcitabine (G)-based tx or 5FU (F)-based tx.

460 Background: No validated biomarkers exist to direct treatment decisions in PDAC. Decisions regarding tx choices are based on age, organ function, and performance status. Defining predictors of efficacy to F (alone or in combination) or G (alone or in combination) in PDAC are urgently needed. Histologic subtype by immunohistochemistry (IHC); pancreatobiliary type (PB), intestinal type (I), gastric type (Ga) and intestinal/gastric type (I/G); may predict benefit to G or F. Methods: Charts of PDAC pts from 2 institutions from 2007 to 2013 having both pathology specimen and a qualifying tx (FOLFIRINOX, FOLFOX, FOLFIRI, Capecitabine or G or G and nab-paclitaxel) were reviewed. IHC phenotypes were defined by staining >25% CDX2 = I, >25% MUC5 = Ga, >25% CDX2 and MUC5 = I/G, >25% MUC1 = PB. Results: 51 pts were identified. 4 cases had Stage II disease without recurrence after adjuvant tx and were excluded. 5 tumors were PB, 1 I, 3 I/G, 38 Ga. 41 (87%) had Ga or I/G type. Due to lack of statistical power for t...

707PSAFETY AND EFFICACY OF NEOADJUVANT FOLFIRINOX IN PATIENTS (PTS) WITH LOCALLY ADVANCED PANCREATIC ADENOCARCINOMA (LAPC)

ABSTRACT Aim: In a retrospective study of 18 pts with unresectable (UR) or borderline resectable (BR) LAPC, neoadjuvant therapy with FOLFIRINOX with or without subsequent chemoradiation (CCRT) resulted in an R0 resection rate (RR) of 44% (Hosein et al, BMC Cancer 2012). The reported 1-year progression-free survival (PFS) was 83 % and the 1-year overall survival (OS) was 100 %. Toxicity profile was tolerable. In order to confirm these preliminary results, we analyzed a large cohort of pts treated in a similar fashion with mature follow-up. Methods: Between 2008 and 2013, 51 treatment-naive pts with LAPC were treated with first-line FOLFIRINOX with neoadjuvant intent. Pts were categorized as BR or UR using the NCCN criteria. Pts received FOLFIRINOX chemotherapy (at the full dose as described in the ACCORD-11 trial) until maximum response or tolerability, and then underwent surgery if their imaging suggested resectability. Pts then received CCRT if they were still UR or BR after FOLFIRINOX. The end points of this retrospective analysis were OS, PFS, R0 RR and toxicity profile. Results: A total of 429 cycles were given with a median of 8 (range 2-29); 27 (53%) went on to receive CCRT. After a median follow-up of 17 mo (range 2-56), the Kaplan-Meier median OS was 35 mo (95% CI 26-45), the 3-yr OS rate was 42% and the median PFS was 14 mo (95% CI 11 – 16). By imaging criteria, 13 (26%) were converted to resectability and 10 (4 BR and 6 UR) of these had successful R0 resections. Pts who had R0 resections had a significantly longer survival than pts who did not (3-yr OS rate 67% vs 21%, log rank p = 0.042). Grade 1&2/3&4 chemotherapy-related toxicities were neutropenia (39%/20%), neutropenic fever (0%/12%), thrombocytopenia (53%/16%), anemia (63%/10%), fatigue (76%/6%), nausea (57%/4%) vomiting (22%/4%), neuropathy (53%/4%) and diarrhea (37%/10%). Conclusions: FOLFIRINOX followed by chemoradiotherapy is feasible as neoadjuvant therapy in patients with unresectable LAPC. Although the resection rate was only 20%, the median OS of almost 3 years is appreciably longer than historical survival rates for this population. Prospective controlled trials testing this algorithm in LAPC are ongoing. Disclosure: All authors have declared no conflicts of interest.

Newer Agents in Colon Cancer: What’s Next?

Colorectal cancer (CRC) was the third leading cause of cancer deaths in the United States in 2012, and most patients eventually develop metastatic disease. The use of cytotoxic chemotherapy, the antiangiogenesis drug bevacizumab, and the anti-EGFR monoclonal antibodies cetuximab and panitumumab have led to an improvement in median OS for metastatic CRC. Despite this improvement in survival, few agents have activity against CRC. Between 2006 and 2012, the FDA approved no new agents for patients with metastatic CRC (mCRC). Recently, the FDA has approved aflibercept and regorafenib for use in the treatment of patients with mCRC, and several new agents are currently in development. This paper reviews the use of new agents and new uses for established agents in mCRC.

EUS-FNA with rescue FISH for the diagnosis of pancreatic carcinoma in patients with inconclusive on-site cytopathology.

e14641 Background: Endoscopic ultrasound guided biopsy and cytology (EUS-FNA) is commonly used in the diagnosis of pancreatic cancer (PC) with a sensitivity (Sn) of 60%-90%. This study is to determine the Sn and specificity (Sp) of FISH analysis in patients with inconclusive on-site cytopathology (OC). METHODS Retrospective analysis of patients undergoing diagnostic EUS-FNA for solid pancreatic masses in a single University Tertiary Cancer Center from January 2009 to December 2010. Non-diagnostic OC samples were sent for cytology and FISH (UroVysion probe, Abbott Molecular, Des Plaines, IL) to detect aneuploidies of chromosomes 3, 7, 17 and deletions of 9p21. Positive FISH for malignancy was defined as ≥5 cells with ≥3 signals in at least two chromosomes (polysomy), >5 cells with 9p21 deletion, extra copy of chromosome 7 in > 10 cells (trisomy). Confirmation of cancer was based on pathologic diagnosis on surgical specimen, disease progression on extended follow-up or autopsy. Sn, Sp, positive and negative predictive values of cytology and FISH were obtained based on binomial distribution. The Fisher exact test was utilized to compare sensitivity between cytology, FISH and cytology plus FISH. A p value < 0.05 was considered statistically significant. RESULTS 212 EUS-FNA were performed in 206 patients over a 24 month period. The diagnosis of carcinoma was obtained in 164 patients. OC established the diagnosis in 110 patients that were excluded in addition to patients with neuroendocrine tumor (22), insufficient follow-up (1), FISH not obtained (3) and pancreatic metastasis (1). Sixty-nine patients with inconclusive or non-available OC comprised the study cohort and had FISH analysis, of which 15 patients had benign diseases. The Sn for the diagnosis of PC by cytology, FISH and the combination were 61%, 74% and 85% respectively (p=0.009). FISH detected an additional 13 cases missed by cytology with no false positives in benign diseases. CONCLUSIONS FISH to detect polysomy of chromosomes 3, 7, 17 and deletion of 9p21 should be considered when cytology is negative for malignancy in patients with pancreatic mass. Rescue FISH can detect additional cases missed by cytology without compromising specificity.