Steven Ades

Perioperative docetaxel, cisplatin, and 5-fluorouracil (DCF) for locally advanced esophageal and gastric adenocarcinoma: a multicenter phase II trial

BACKGROUND Although perioperative chemotherapy for esophagogastric adenocarcinoma (ADC) improves survival, the overall poor prognosis suggests that further refinement of treatment is required. Docetaxel, cisplatin, and 5-fluorouracil (5-FU) (DCF) is effective for metastatic ADC of the upper gastrointestinal (GI) tract; we thus sought to investigate the efficacy of this regimen in patients with resectable disease. PATIENTS AND METHODS Patients with resectable ADC of the upper GI tract received DCF [docetaxel (Taxotere) 75 mg/m(2) I.V. day 1, cisplatin 75 mg/m(2) I.V. day 1, 5-FU 750 mg/m(2) continuous infusion for 120 h, every 3 weeks] for three cycles before and after resection. Primary end point was complete resection; secondary end points were response, toxicity, surgical morbidity, and overall survival. RESULTS Forty-three patients with ADC of the esophagus (11), gastroesophageal junction (25), or stomach (7) started treatment and 86% completed all preoperative cycles with grade 3-4 toxicity arising in 47%. Metabolic response to chemotherapy (reduction in maximal standard uptake value >35%) was achieved in 25/33 (76%) patients. Surgery was carried out in 41/43 and complete resection was achieved in all 41 patients with pathologic complete response in 4/41. Postoperative chemotherapy was started in 29 patients and completed in 24. Three-year overall survival was 60%. CONCLUSION Perioperative DCF is a tolerable and highly effective regimen for the treatment of esophagogastric ADC.

Statin therapy and levels of hemostatic factors in a healthy population: The Multi-Ethnic study of atherosclerosis

HMG‐CoA reductase inhibitors (statins) reduce the risk of venous thromboembolism (VTE) in healthy people. Statins reduce levels of inflammation biomarkers; however, the mechanism for the reduction in VTE risk is unknown.

Tumor oncogene (KRAS) status and risk of venous thrombosis in patients with metastatic colorectal cancer

Patients with metastatic colon cancer (mCRC) are at increased risk of venous thromboembolism (VTE). Limited preclinical data suggest that the oncogene (KRAS) mutational status of the tumor represents a plausible clinical link to systemic hypercoagulability in cancer patients.

Survival and recurrence patterns after neoadjuvant docetaxel, cisplatin, and 5-fluorouracil (DCF) for locally advanced esophagogastric adenocarcinoma.

AbstractIntroduction We have previously identified Docetaxel, Cisplatin, and 5FU (DCF) as a safe, tolerable, and effective regimen in the neoadjuvant setting for locally advanced adenocarcinoma (ADC) of the esophagus and esophagogastric junction (EGJ). We hypothesized that DCF combined with enhanced surgical control would result in a low rate of local or regional recurrence, and thus reviewed our outcomes with this treatment regimen. MethodsA prospectively entered database of all esophageal and EGJ ADC patients resected at a high-volume referral center over 6 years (9/07-9/13) was reviewed for cases treated with curative intent neoadjuvant DCF followed by en bloc resection with extended lymphadenectomy (D2/D3). Recurrences was defined as locoregional (biopsy on endoscopy/regional lymph nodes (LNs)) and distant. Standard statistical techniques were used.ResultsOf 279 patients with ADC, 86 (85% male, mean age 63 years (interquartile range 56-70)) underwent preoperative DCF and curative intent resection for locally advanced ADC (cT3 93%; cN+ 69%) of the EGJ (54%) or distal esophagus (46%). After median follow-up of 40 months, the overall 5-year survival was 54% and 43 (52%) had recurred at a median time of 14 months. Sites of recurrence included locoregional only in 2 of 45 (4%), distant only in 40 of 45 (89%), and locoregional and distant in 3 of 45 (7%).DiscussionThe present study demonstrates favourable oncologic outcomes with low local/regional recurrence and an excellent overall 5-year survival after neoadjuvant DCF for esophageal and EGJ ADCs. Because the majority of recurrences were distant, our data support the notion that efforts to improve outcomes in these patients should concentrate on enhancing systemic, rather than local, therapy.

Effect of rosuvastatin on risk markers for venous thromboembolism in cancer

Essentials Statins lower venous thromboembolism risk in general but have not been studied in cancer patients. We completed a randomized trial of rosuvastatin vs. placebo among cancer patients on chemotherapy. Rosuvastatin did not significantly lower prothrombotic biomarkers including D‐dimer. The role of statins in venous thrombosis prevention in cancer patients remains unknown.

Nanoparticle‐based targeted cancer strategies for non‐invasive prostate cancer intervention

Prostate cancer is screened by testing circulating levels of the prostate‐specific antigen (PSA) biomarker, monitoring changes over time, or a digital rectal exam. Abnormal results often lead to prostate biopsy. Prostate cancer positive patients are stratified into very low‐risk, low‐risk, intermediate‐risk, and high‐risk, based on clinical classification parameters, to assess therapy options. However, there remains a gap in our knowledge and a compelling need for improved risk stratification to inform clinical decisions and reduce both over‐diagnosis and over‐treatment. Further, current strategies for clinical intervention do not distinguish clinically aggressive prostate cancer from indolent disease. This mini‐review takes advantage of a large number of functionally characterized microRNAs (miRNA), epigenetic regulators of prostate cancer, that define prostate cancer cell activity, tumor stage, and circulate as biomarkers to monitor disease progression. Nanoparticles provide an effective platform for targeted delivery of miRNA inhibitors or mimics specifically to prostate tumor cells to inhibit cancer progression. Several prostate–specific transmembrane proteins expressed at elevated levels in prostate tumors are under investigation for targeting therapeutic agents to prostate cancer cells. Given that prostate cancer progresses slowly, circulating miRNAs can be monitored to identify tumor progression in indolent disease, allowing identification of miRNAs for nanoparticle intervention before the crucial point of transition to aggressive disease. Here, we describe clinically significant and non‐invasive intervention nanoparticle strategies being used in clinical trials for drug and nucleic acid delivery. The advantages of mesoporous silica‐based nanoparticles and a number of candidate miRNAs for inhibition of prostate cancer are discussed.

Delayed human herpes virus 6 encephalitis in a patient with allogeneic stem cell transplant

Human herpes virus 6 (HHV-6) can become reactivated in immunosuppressed individuals typically within the first 50–100 days following an allogeneic stem cell transplant [1,2]. Invasion of neural tissue by HHV-6 5 months following hematopoietic stem cell transplant (HSCT) was first documented in 1994 [3]. HHV-6 encephalitis during HSCT is associated with a poor prognosis [4,5]. Routinely, patients in the post-engraftment period are put on chemoprophylaxis and undergo cytomegalovirus (CMV) monitoring, but it is not currently recommended to screen or actively provide prophylaxis for HHV-6 [6]. We present a case of HHV-6 encephalitis more than 200 days after a 7/8 unrelated allogeneic stem cell transplant. In our review of the literature, this is the first reported case of HHV-6 encephalitis more than 6 months after a stem cell transplant. The patient was a 58-year-old male with acute myelogenous leukemia (AML) who received a non-myeloablative 7/8 matched unrelated donor stem cell transplant. He received fludarabine and busulfan for conditioning and tacrolimus, methotrexate and bortezomib for prophylaxis against graft-versus-host disease (GVHD). The patient then presented five and a half months after his transplant with relapsed AML, and was admitted for chemotherapy with decitabine in the setting of neutropenic fever and pneumonia. The patient was continued on acyclovir along with weekly CMV testing. He was tapered off his immunosuppression, which resulted in grade 2 GVHD of the skin. Systemic immunosuppression was not reinstated for this, but supportive care with ointments and steroid lotions was pursued. At 223 days post-transplant, 31 days since the initiation of decitabine and 30 days after his current admission, he developed progressively worsening disorientation and hallucinations. He was afebrile. Cerebrospinal fluid (CSF) examination revealed glucose 67 mg/dL (49% of plasma glucose, normal range: 60–80%), protein 52 mg/dL (15–60 mg/dL) and 12 white blood cells/cm3 (upper limit of normal [ULN] 5 cells/cm3) with 91% lymphocytes (normal range: 40–80%). On cytological evaluation there was lymphocytic pleocytosis with a small component of atypical lymphocytes. All cerebrospinal and blood cultures for bacterial, fungal or viral organisms were negative. The CSF was also negative for enterovirus RNA, herpes simplex virus (HSV) type 1 or type 2, varizella zoster virus (VZV) DNA and JC virus by polymerase chain reaction (PCR). A cryptococcal antigen performed on the CSF was also negative. Computed tomography (CT) of the head was negative for acute intracranial pathology. He could not tolerate magnetic resonance imaging (MRI) because of his mental status, and an electroencephalogram was not done. Ganciclovir was initiated empirically without improvement after 24 h. The family decided to transition the patient to comfort care, and the patient died 6 days later. HHV-6 by reverse transcription (RT)-PCR was positive in qualitative assays on both the CSF and serum. Autopsy findings showed acute anoxic changes in the left hippocampus without demyelinating lesions of the limbic system. However, there were rare foci of perivascular lymphocytes present in the cortical ribbon in the inferior frontal cortex and in the left temporal cortex. The perivascular lymphocytic infiltration is consistent with HHV-6 encephalitis as seen in prior case reports (Figure 1) [3,7]. There were no signs of interstitial pneumonia or hepatitis, which can be seen with HHV-6 infection. The diagnosis of HHV-6 encephalitis was made on the basis of the qualitative PCR result (serum and CSF), a typical CSF profile and characteristic autopsy findings. Also, other etiologies were excluded by a thorough work-up on the serum and CSF as above. HHV-6 is documented to cause encephalitis in patients after allogeneic stem cell transplant [8]. However, most studies of HHV-6 reactivation and its role in encephalitis investigate the acute post-engraftment phase [1,2]. Our patient did not experience his encephalopathy until  200 days postengraftment. There is a known increased risk for HHV-6 reactivation in allelic mismatched donors. Cases reported have noted a peak in HHV-6 viral load in CSF and serum weeks prior to encephalopathy and death [3,9]. Although our patient was 200  days from transplant, perhaps the manipulation of Leukemia & Lymphoma, September 2015; 56(9): 2709–2710

Tu1597 Outcomes of Salvage Curative Intent Therapy for Recurrences of Esophago-Gastric Adenocarcinoma

difference was seen in total lymph nodes harvested. Conclusion: The findings of this study suggest an important association between esophageal cancer tumor length and regional lymph node metastasis as well as overall survival. Future clinical staging of esophageal cancer may benefit from adding tumor length to current methods relying on depth of invasion (T status) and an estimation of positive lymph nodes from CT or EUS (N status).