Background:Modifications of FOLFIRINOX are widely used despite the absence of prospective data validating efficacy in metastatic disease (metastatic pancreatic cancer (MPC)) or locally advanced pancreatic cancer (LAPC). We conducted a multicentre phase II study of modified FOLFIRINOX in advanced pancreatic cancer to assess the impact of dose attenuation in MPC and efficacy in LAPC.Methods:Patients with untreated MPC or LAPC received modified FOLFIRINOX (irinotecan and bolus 5-fluorouracil reduced by 25%). Adverse events (AEs) were compared with full-dose FOLFIRINOX. Response rate (RR), median progression-free survival (PFS) and median overall survival (OS) were determined.Results:In total, 31 and 44 patients with LAPC and MPC were enrolled, respectively. In MPC, efficacy of modified FOLFIRINOX was comparable with FOLFIRINOX with RR 35.1%, OS 10.2 months (95% CI 7.65–14.32) and PFS 6.1 months (95% CI 5.19–8.31). In LAPC, efficacy was notable with RR 17.2%, resection rate 41.9%, PFS 17.8 months (95% CI 11.0–23.9) and OS 26.6 months (95% CI 16.7, NA). Neutropenia (P<0.0001), vomiting (P<0.001) and fatigue (P=0.01) were significantly decreased. [18F]-Fluorodeoxyglucose positron emission tomography imaging response did not correlate with PFS or OS.Conclusions:In this first prospective study of modified FOLFIRINOX in MPC and LAPC, we observed decreased AEs compared with historical control patients. In MPC, the efficacy appears comparable with FOLFIRINOX. In LAPC, PFS and OS were prolonged and support the continued use of FOLFIRINOX in this setting.

CD4 + primary cutaneous small/medium-sized pleomorphic T-cell lymphoma (CD4 + PCSM-TCL) is a rare T-cell lymphoma associated with a favorable prognosis. A retrospective study of 23 patients with CD4 + PCSM-TCL as defined by World Health Organization-European Organisation for Research and Treatment of Cancer (WHO-EORTC) and WHO classifications was conducted. Median age was 63 years. The head and neck were the most commonly affected locations, followed by the trunk. Two patients had evidence of systemic involvement at relapse. All tumors were CD3 + and CD4+. CD5 and CD7 loss occurred in 52% and 84%, respectively. The median follow-up was 33.6 months. Eleven patients had excisional biopsy only, six had localized radiotherapy and two received excision and localized radiation. Cytotoxic chemotherapy and localized radiation were used in one patient with aggressive and invasive features. All patients had a complete remission but one developed systemic involvement. Our case series demonstrates that CD4 + PCSM-TCL is an indolent T-cell lymphoma that can be treated with local modalities and raises the question of its current classification as a lymphoma.

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Germline mutations in the tumor suppressor genes BRCA1 and BRCA2 have been proven to predict a drastically increased lifetime risk of breast and ovarian cancers in the individuals who carry them. A number of studies have shown that the third most common cancer associated with these mutations is pancreatic cancer. There is evidence of in vivo therapeutic response to the cross-linking agents; such as mitomycin C (MMC) in BRCA2 mutated pancreatic cell lines. We present the 'first patient' who achieved a prolonged survival on irinotecan, a topoisomerase I poison, administered alone and then in combination with cetuximab. Our patient presented at the age of 71 years with a dual diagnosis of prostate carcinoma and pancreatic carcinoma on the background of a significant family history of cancer. On genetic testing, he was found to have the common Ashkenazi Jewish BRCA2 mutation, 6174delT. To date, he has received 22 cycles of docetaxel, capecitabine, and gemcitibine followed by single agent irinotecan every 3 weeks for 27 cycles, and then weekly cetuximab was added to the regimen at cycle 28. His disease then remained stable for an additional 13 months. He did not have mutated KRAS. MMC and oxaliplatin was then introduced upon progression. His current treatment is MMC plus irinotecan as oxaliplatin was removed because of a hypersensitivity reaction. This patient is stable with an Eastern Cooperative Oncology Group performance status of 0, four and a half years (56 months) after his initial diagnosis. DNA topoisomerases are nuclear enzymes responsible for the regulation of DNA topology. They are involved in basic DNA transactions during replication, transcription, and recombination. BRCA2-deficient human cells are deficient in the repair of double-strand breaks and DNA cross-links through homologous recombination. Active poisons of topoisomerase I include derivatives of camptothecin. Our case is the first clinical piece of evidence that demonstrates an increased sensitivity to camptothecin-11 and a reduced topoisomerase I relaxation activity in BRCA2 associated pancreatic cancer. This case shows that patients with metastatic pancreatic carcinoma and BRCA2 mutations may have disease that is biologically more chemosensitive and consequently prolong survival despite prognostically unfavorable disease.

Background: The safety and efficacy of FOLFIRINOX (FX) followed by consolidative chemoradiation (CRT) in borderline resectable (BRPC) and locally advanced pancreatic cancer (LAPC) has not been extensively studied. We sought to evaluate outcomes and toxicities of this regimen. Methods: A retrospective review was performed of 33 patients with BRPC or LAPC treated with FX followed by CRT. Radiotherapy was directed at the primary tumor and any involved nodes (84.8% received 50-50.4 Gy with standard fractionation and concurrent capecitabine, while 15.2% of patients received 36 Gy in 15 fractions with weekly gemcitabine). Toxicities of FX and CRT were graded using Common Terminology Criteria for Adverse Events (CTCAE v4.0), and radiographic response was evaluated using Response Evaluation Criteria in Solid Tumors (RECIST). Overall survival (OS), distant metastasisfree survival (DMFS), and local control (LC) were calculated using Kaplan-Meier analyses, and a Cox proportional hazards model was used to assess the impact of clinicopathologic factors on OS. Results: Median follow-up was 19.9 months and patients received a median of 6.4 months of chemotherapy (range, 2.2-12.0 months). There were more T4 tumors than T3 tumors (70% vs. 30%). Grade ≥3 toxicities were low, including fatigue (9.1%), diarrhea (6.1%), neuropathy (6.1%), and dehydration (6.1%). R0 surgical resection was achieved in 5 patients (15.2%) after CRT. Median OS was 22.0 months (91% at 1 year and 45% at 2 years). Median DMFS was 17.8 months (69% at 1 year and 35% at 2 years). LC was 84% at 1 year and 55% at 2 years. Conclusions: OS is promising with the use of FX in BRPC and LAPC, and consolidative CRT was well tolerated in this cohort. Therefore, the role of radiation after multi-agent chemotherapy should be further evaluated in prospective trials.