Gemcitabine and Taxane Adjuvant Therapy with Chemoradiation in Resected Pancreatic Cancer: A Novel Strategy for Improved Survival?

BACKGROUND: Gemcitabine-taxane combination chemotherapy has demonstrated a survival benefit clinically in metastatic pancreatic cancer (PC). The authors present their experience with gemcitabine and docetaxel (gem/tax)-based adjuvant treatment (Rx) after surgery with curative intent. METHODS: Patients with de novo resectable PC from January 2010 to December 2015 were identified from the authors' institutional database and registry. The study included only patients who received gem/tax as their initial Rx administered exclusively at the authors' institution with or without chemoradiation (CRTx). Survival analysis was performed using Kaplan-Meier methods, and prognostic factors were investigated by Cox proportional hazard modeling. RESULTS: Of 102 patients identified, 58 met the study criteria. The median age at diagnosis was 65 years, with 55% of the patients undergoing an R1 resection (margin ≤ 1 mm). Tumor characteristics included a median tumor size of 28 mm, a poor differentiation rate of 54%, and a lymph node positivity of 67%. Most of the patients (90%, 52/58) completed 80% or more of the 24 week Rx. Of these patients, 71% received post-gem/tax CRTx Rx. Grade 3 or 4 toxicity was observed in 52% of the patients. The median follow-up period was 51.2 months, and the observed median overall survival (OS) was 52 months [95% confidence interval (CI) 27.4-not reached]. The actuarial 5-year OS was 49% (95% CI 33.7-63.4%). In the multivariate analysis, an R1 resection and American Joint Committee on Cancer (AJCC) stage 2 versus stage 1 disease were negatively associated with OS, whereas administration of CRTx was positively associated with OS. CONCLUSIONS: Adjuvant gem/tax with or without CRTx is feasible, with a favorable OS. Future prospective studies of gem/taxane-based adjuvant Rx for PC are warranted.

Five-Year Actual Overall Survival in Resected Pancreatic Cancer: A Contemporary Single-Institution Experience from a Multidisciplinary Perspective.

BACKGROUND: Successful surgical resection combined with effective perioperative therapy is essential for maximizing long-term survival for pancreatic adenocarcinoma. PATIENTS AND METHODS: All patients with pancreatic adenocarcinoma who underwent curative resection at our institution from January 2003 to May 2010 were reviewed. Demographic and clinical details were retrospectively collected from medical records and cancer registry data. RESULTS: Overall, 176 patients were included in the analysis (148 with de novo resectable disease and 28 with borderline resectable disease at presentation). Among 106 patients who received all perioperative therapy at our institution, 94% received neoadjuvant and/or adjuvant treatment in addition to resection. Actual all-cause 5-year overall survival (OS) for all 176 patients was 30.7%, with a median OS of 33.9 months [95% confidence interval (CI) 28.1-39.6 months]. For patients who received all perioperative therapy at our institution, actual all-cause 5-year disease-free survival (DFS) was 32.1%, with a median DFS of 28.8 months (95% CI 20.1-43.6 months). Of these patients, 67/106 (63%) recurred: 8 (8%) locoregional only; 52 (49%) systemic only; and 7 (7%) combined recurrence. No difference in survival rates or recurrence patterns was seen between resectable and borderline resectable patients. In multivariate analysis, tumor differentiation (poor vs. non-poor) and lymph node ratio >20% produced a useful clinical model. CONCLUSION: The actual OS rates for resected pancreatic cancer shown in this study are reflective of those currently achievable at a tertiary medical center dedicated to this patient population. In considering these results, both frequency and type of adjuvant/neoadjuvant therapy administered in the context of the clinical experience/management techniques of providers administering these treatments will be discussed.

Polymorphisms in genes related to one-carbon metabolism are not related to pancreatic cancer in PanScan and PanC4.

PURPOSE: The evidence of a relation between folate intake and one-carbon metabolism (OCM) with pancreatic cancer (PanCa) is inconsistent. In this study, the association between genes and single-nucleotide polymorphisms (SNPs) related to OCM and PanCa was assessed. METHODS: Using biochemical knowledge of the OCM pathway, we identified thirty-seven genes and 834 SNPs to examine in association with PanCa. Our study included 1,408 cases and 1,463 controls nested within twelve cohorts (PanScan). The ten SNPs and five genes with lowest p values (<0.02) were followed up in 2,323 cases and 2,340 controls from eight case-control studies (PanC4) that participated in PanScan2. The correlation of SNPs with metabolite levels was assessed for 649 controls from the European Prospective Investigation into Cancer and Nutrition. RESULTS: When both stages were combined, we observed suggestive associations with PanCa for rs10887710 (MAT1A) (OR 1.13, 95 %CI 1.04-1.23), rs1552462 (SYT9) (OR 1.27, 95 %CI 1.02-1.59), and rs7074891 (CUBN) (OR 1.91, 95 %CI 1.12-3.26). After correcting for multiple comparisons, no significant associations were observed in either the first or second stage. The three suggested SNPs showed no correlations with one-carbon biomarkers. CONCLUSIONS: This is the largest genetic study to date to examine the relation between germline variations in OCM-related genes polymorphisms and the risk of PanCa. Suggestive evidence for an association between polymorphisms and PanCa was observed among the cohort-nested studies, but this did not replicate in the case-control studies. Our results do not strongly support the hypothesis that genes related to OCM play a role in pancreatic carcinogenesis.

Alternating Gemcitabine/Nab-Paclitaxel (GA) and 5-FU/Leucovorin/Irinotecan (FOLFIRI) as First-Line Treatment for De Novo Metastatic Pancreatic Cancer (MPC): Safety and Effect.

BACKGROUND: Both gemcitabine- and 5-fluorouracil (5-FU)-based chemotherapy regimens have demonstrated efficacy in metastatic pancreatic cancer (MPC). Alternating these regimens may reduce toxicity, slow resistant cancer biology emergence, and provide a platform for the addition of other therapeutic agents. Alternating gemcitabine/nab-paclitaxel (GA) and 5-FU/leucovorin/irinotecan (FOLFIRI) in MPC has previously been reported at our own institution and elsewhere. An extension of our institutional observations is reported here. METHODS: Patient eligibility required the following: biopsy-proven de novo MPC, no prior evidence of disease on CT, ECOG performance status (PS) ≤ 2, and bi-dimensionally measurable disease. Treatment (Tx) entailed gemcitabine 1000 mg/m2 and nab-paclitaxel 125 mg/m2 1, (8), 15 alternating every 8 weeks (2 cycles) with FOLFIRI using standard dosing. Patients were radiographically re-staged every 8 weeks. Tx spanned up to 12 cycles. Tx thereafter was decided following patient/physician discussion. RESULTS: Median overall survival (mOS) was 13.2 months (95% CI 10.9-16.5 months). Median progression-free survival (mPFS) was 8.5 months (95% CI, 7.1-9.9). The 6-, 12-, 18-, and 24-month OS rates were 88%, 54%, 36%, and 20%, respectively. The disease control rate at 16 weeks was 83% (37% PR, 46% SD). Hematologic toxicity grade ≥ 3 included 9.3% anemia, 10.2% neutropenia, and 4.6% thrombocytopenia. Neutrophil growth factors were not used in this cohort. Non-hematologic toxicities grade ≥ 3 included neuropathy 0.9%, nausea/vomiting 0.9%, and diarrhea 0.9%. No patients experienced mucositis on this regimen. CONCLUSIONS: Alternating GA/FOLFIRI in MPC has a favorable toxicity profile in comparison to current standard regimens. Median OS was at least competitive with standard regimens, and longer-term (18 and 24 months) OS seemed particularly encouraging. Treatment for ≥48 weeks and ECOG PS of zero at the time of treatment initiation were prognostically significant. Further investigation using this regimen including randomized comparisons, the incorporation of molecular data, and use of additional agents is merited.

Pathway analysis of genome-wide association study data highlights pancreatic development genes as susceptibility factors for pancreatic cancer.

Four loci have been associated with pancreatic cancer through genome-wide association studies (GWAS). Pathway-based analysis of GWAS data is a complementary approach to identify groups of genes or biological pathways enriched with disease-associated single-nucleotide polymorphisms (SNPs) whose individual effect sizes may be too small to be detected by standard single-locus methods. We used the adaptive rank truncated product method in a pathway-based analysis of GWAS data from 3851 pancreatic cancer cases and 3934 control participants pooled from 12 cohort studies and 8 case-control studies (PanScan). We compiled 23 biological pathways hypothesized to be relevant to pancreatic cancer and observed a nominal association between pancreatic cancer and five pathways (P < 0.05), i.e. pancreatic development, Helicobacter pylori lacto/neolacto, hedgehog, Th1/Th2 immune response and apoptosis (P = 2.0 × 10(-6), 1.6 × 10(-5), 0.0019, 0.019 and 0.023, respectively). After excluding previously identified genes from the original GWAS in three pathways (NR5A2, ABO and SHH), the pancreatic development pathway remained significant (P = 8.3 × 10(-5)), whereas the others did not. The most significant genes (P < 0.01) in the five pathways were NR5A2, HNF1A, HNF4G and PDX1 for pancreatic development; ABO for H.pylori lacto/neolacto; SHH for hedgehog; TGFBR2 and CCL18 for Th1/Th2 immune response and MAPK8 and BCL2L11 for apoptosis. Our results provide a link between inherited variation in genes important for pancreatic development and cancer and show that pathway-based approaches to analysis of GWAS data can yield important insights into the collective role of genetic risk variants in cancer.

Adverse events after screening and follow-up colonoscopy.

OBJECTIVE: We provide new information about how the risk of adverse events following colonoscopy varies by age and indication (screening vs. follow-up performed to evaluate a positive result from another screening modality). METHODS: We constructed a retrospective cohort comprised of 43,456 individuals aged 40-85 years enrolled in a large integrated healthcare organization in Washington State who underwent outpatient colonoscopy between 1994 and 2009. We calculated rates of serious adverse events (perforation, hemorrhage, and acute diverticulitis) in the 30 days following colonoscopy and compared rates using log-binomial regression models. RESULTS: We observed 4.7 serious adverse events per 1,000 screening colonoscopies and 6.8 per 1,000 follow-up colonoscopies. Polypectomy increased the rate of serious adverse events (relative rate [RR], 2.64; 95% confidence interval [CI], 1.97-3.56). Older age was associated with increased risk of serious adverse events, after adjusting for polypectomy, gender, and indication. Compared to individuals aged 50-64 years, risk was elevated for those aged 65-74 (RR, 1.93; 95% CI, 1.40-2.65) and 75-85 (RR, 3.21; 95% CI 2.14-4.86). We observed similar age effects in individuals with and without significant comorbid conditions. CONCLUSIONS: The risks of serious adverse events following colonoscopy performed as part of screening are low but increase with age and are more likely after polypectomy.

Colorectal cancer risk in relation to antidepressant medication use.

Laboratory studies suggest that antidepressants affect the risk of some cancers, including colorectal cancer. To investigate whether selective serotonin reuptake inhibitors (SSRIs) and tricyclic antidepressants (TCAs) are associated with colorectal cancer risk, we conducted a case-control study among enrollees of an integrated healthcare delivery system in Washington State. Cases were first diagnosed with invasive colorectal cancer between 2000 and 2003; controls were randomly selected from Group Health enrollees and matched to cases on age, sex and length of enrollment before diagnosis/reference date. We used logistic regression to estimate odds ratios (OR) and 95% confidence intervals (CI) for colorectal cancer in relation to use of any antidepressant, SSRIs only or TCAs only, among 649 cases and 656 controls. Use of any antidepressant was associated with a reduced risk of colorectal cancer (OR = 0.7, 95% CI = 0.5-0.9). Associations were similar for persons who used SSRIs exclusively (OR = 0.7, 95% CI = 0.4-1.1) and TCAs exclusively (OR = 0.7, 95% CI = 0.5-1.2); however, this reduction in risk appeared limited to persons without a prior cancer at another site. Our data support findings from previous epidemiologic and animal studies that suggest antidepressants may reduce the risk of colorectal cancer. Future studies with larger sample sizes should further examine individual drugs as well as dose, duration and recency of use.

Circulating 25-hydroxyvitamin-D and risk of colorectal adenomas and hyperplastic polyps.

Colorectal adenomas are clear precursors of cancer; hyperplastic polyps may also have malignant potential. An inverse association between circulating vitamin D metabolites and adenoma risk has been reported, but less is known about vitamin D and hyperplastic polyps. We conducted a case-control study of adenomas and hyperplastic polyps among 459 members of an integrated health plan evaluated via colonoscopy. Questionnaires provided information on colorectal polyp risk factors, and plasma samples were assayed for 25-hydroxyvitamin-D [25(OH)D]. Polytomous regression was used to estimate odds ratios for adenomas (n = 149) and hyperplastic polyps (n = 85) compared to polyp-free controls (n = 225) by tertile of 25(OH)D. An inverse association between 25(OH)D and adenomas was suggested after adjustment for potential confounding factors [comparing upper to lower tertiles, OR (95%CI): 0.71 (0.38-1.30)]. After restriction of the analyses to study participants with no history of polyps, this OR estimate was reduced further [adjusted OR (95%CI): 0.52 (0.23-1.20)]. In comparison, no inverse association between hyperplastic polyps and 25(OH)D was observed among the full study participants [adjusted OR (95%CI): 1.17 (0.55-2.51)] or among those without prior polyps [adjusted OR (95%CI): 1.42 (0.55-3.65)]. Our study suggests that the established inverse association between circulating 25(OH)D and adenoma may not apply to hyperplastic polyps.

Colorectal polyp type and the association with charred meat consumption, smoking, and microsomal epoxide hydrolase polymorphisms.

We determined the association between charred meat consumption, cigarette smoking, microsomal epoxide hydrolase (mEH) polymorphisms (rs1051740 and rs2234922), and colorectal adenomas and hyperplastic polyps (HPs) and explored gene-environment interactions. Men and women with colorectal adenomas (n = 519), HPs (n = 691), or concurrently with both types of polyps (n = 227) and polyp-free controls (n = 772) receiving a colonoscopy from December 2004 to September 2007 were recruited. Participants completed telephone interviews and provided buccal cell samples; genotyping of mEH was completed using Taqman assays. We conducted polytomous regression and calculated odd ratios (OR) and 95% confidence intervals. Interactions were evaluated using Wald chi-square tests. Consumption of >3 servings of charred meat per week was associated with distal HPs (OR = 2.0, 1.2-3.4) but not adenomas nor either type of proximal polyp. Heavy cigarette smoking (≥ 22 pack-years) was associated with an increased risk for colorectal adenomas (OR = 1.7, 95% CI: 1.2-2.4), HPs (OR = 2.4, 95% CI: 1.7-3.3), and both types (OR = 2.8, 95% CI: 1.8-4.3) with the strongest association for distal polyps. There was no association between mEH genotype and colorectal polyps, nor were any statistically significant gene-environment interactions identified. Future investigation of BaP exposure and colorectal neoplasia should analyze whether associations are dependent upon anatomic location.

Ulcerative colitis is a disease of accelerated colon aging: evidence from telomere attrition and DNA damage.

BACKGROUND & AIMS: Telomere shortening is implicated in cancer and aging and might link these 2 biologic events. We explored this hypothesis in ulcerative colitis (UC), a chronic inflammatory disease that predisposes to colorectal cancer and in which shorter telomeres have been associated with chromosomal instability and tumor progression. METHODS: Telomere length was measured by quantitative polymerase chain reaction in colonocytes and leukocytes of 2 different sets of UC patients and compared with normal controls across a wide range of ages. For a subset of patients, telomere length was measured in epithelium and stroma of right and left colon biopsy specimens. A third set of biopsy specimens was analyzed for phosphorylation of histone H2AX (gammaH2AX), a DNA damage signal, by immunofluorescence and for telomere length by quantitative fluorescence in situ hybridization. Relationships between telomere length, gammaH2AX intensity, age, disease duration, and age of disease onset were explored. RESULTS: Colonocyte telomeres shorten with age almost twice as rapidly in UC patients as in normal controls. This extensive shortening occurs within approximately 8 years of disease duration. Leukocyte telomeres are slightly shorter in UC patients than in controls, but telomeres of colon stromal cells are unaffected. gammaH2AX intensity is higher in colonocytes of UC patients than in controls and is not dependent on age or telomere length. CONCLUSIONS: Colonocytes of UC patients show premature shortening of telomeres, which might explain the increased and earlier risk of cancer in this disease. Shorter leukocyte telomeres and increased gammaH2AX in colonocytes might reflect oxidative damage secondary to inflammation.

Colorectal cancer risk in relation to use of acid suppressive medications.

PURPOSE: Acid suppressants are commonly prescribed medications. Laboratory studies suggest a mechanism by which they could increase colorectal cancer (CRC) risk. A few epidemiologic studies have investigated acid suppressant use and CRC risk; none has documented an overall association. We sought to investigate whether acid suppressants are associated with CRC risk. METHODS: We conducted a case-control study among members of an integrated healthcare delivery system in Washington State. Cases (N = 641) were diagnosed with CRC between 2000 and 2003; controls (N = 641) were randomly selected from enrollees and matched to cases on age, sex, and length of enrollment. We used conditional logistic regression to estimate the odds ratios (ORs) and 95% confidence intervals (CI) for CRC associated with the use of any acid suppressive medication, proton pump inhibitors (PPIs) only, histamine receptor antagonists (H2 blockers) only, or both PPIs and H2 blockers in relation to the use of neither PPIs nor H2 blockers. RESULTS: Use of PPIs exclusively was modestly associated with an increased risk of CRC, however this finding was consistent with chance and based on a small number of patients exposed (OR = 1.7; 95%CI = 0.8, 4.0). H2 blocker use alone was not related to CRC risk (OR = 0.8; 95%CI = 0.6, 1.1). CONCLUSIONS: PPI use may be modestly associated with CRC risk; further research should be conducted in populations with long-term PPI use.

Cardiovascular medication use and risk for colorectal cancer.

OBJECTIVE: To evaluate the association between lipid-lowering agents, antihypertensive medications, and colorectal cancer risk. We hypothesized a reduction in colorectal cancer risk with 3-hydroxy-3-methylglutaryl coA reductase inhibitors (statins) and angiotensin-converting enzyme inhibitors. METHODS: We conducted a case-control study at Group Health Cooperative, an integrated delivery system in Washington State. Incident colorectal cancer cases diagnosed between January 1, 2000, and December 31, 2003, were identified from the western Washington Surveillance, Epidemiology, and End Results cancer registry. Controls were matched by age, sex, and duration of enrollment. Data on medication use and potential confounders were obtained from health plan records. We estimated odds ratios and 95% confidence intervals (95% CI) using multivariate conditional logistic regression. RESULTS: Risk for colorectal cancer was not associated with use of statins (odds ratio, 1.02; 95% CI, 0.65-1.59), other lipid-lowering agents (odds ratio, 1.31; 95% CI, 0.70-2.47), angiotensin-converting enzyme inhibitors (odds ratio, 0.98; 95% CI, 0.67-1.43), calcium channel blockers (odds ratio, 1.06; 95% CI, 0.72-1.55), or diuretics (odds ratio, 1.00; 95% CI, 0.70-1.44). Risk did not differ by duration of medication use, including long-term use. CONCLUSIONS: Risk for colorectal cancer was not reduced by use of statins or angiotensin-converting enzyme inhibitors. Other lipid-lowering and antihypertensive medications were also not associated with colorectal cancer risk.

Utility of Left Ventricular Ejection Fraction Measurements Before the Administration of Doxorubicin-Based Chemotherapy in Patients With Diffuse Large B-Cell Lymphoma.

OBJECTIVE: To determine the utility of routine measurements of left ventricular ejection fraction (LVEF) before the administration of doxorubicin-based chemotherapy (DOX) in patients with diffuse large B-cell lymphoma (DLBCL). PATIENTS AND METHODS: We investigated the frequency of LVEF measurements before the initiation of therapy in 291 patients with DLBCL at our institution from January 1, 2001, through December 31, 2013, and reviewed whether LVEF varied in patients with an underlying risk of cardiac disease (CD), the relationship between LVEF and subsequent DLBCL treatment, and congestive heart failure (CHF) occurrence in DOX-treated patients. RESULTS: Left ventricular ejection fraction was measured in 258 patients before the administration of chemotherapy and was not associated with underlying CHF risk (P=.94). Left ventricular ejection fraction was normal in 243 patients (94%) and low in 15 patients. Doxorubicin-based chemotherapy was administered to 206 patients with normal LVEF (85%) vs 8 patients with low LVEF (53%) (P=.006). However, when previous CD was factored out, LVEF did not influence subsequent treatment decisions (P=.51). Congestive heart failure occurred in 18 patients, and the risk was similar in patients treated with and without DOX. For all patients who had LVEF measured, CHF incidence did not differ between patients who received DOX and those who did not (P>.99). Moreover, there was no difference in CHF incidence after receiving DOX between those who had normal and low LVEF results (P=.45). CONCLUSION: The decision to administer DOX was influenced by LVEF status only when previous CD was factored out. Furthermore, CHF incidence posttreatment did not differ between patients who did and did not receive DOX. These preliminary findings challenge the practice of performing cardiac screening before DOX for patients with DLBCL.

Leptin concentrations, leptin receptor polymorphisms, and colorectal adenoma risk.

Obesity has been shown to be associated with an increased risk of both colorectal cancer and adenomatous polyps. One mechanism underlying this relationship may involve the growth-promoting effects of the circulating hormones associated with obesity, such as leptin. We conducted a gastroenterology clinic-based, case-control study to evaluate the relationship between circulating leptin concentrations and colorectal adenoma risk; in addition, we evaluated the relationship between leptin receptor polymorphisms and adenoma risk. Individuals with adenomas (n = 157) and colonoscopy-negative controls (n = 191), who had a clinically indicated colonoscopy, were recruited from a large health maintenance organization in the Seattle metropolitan area from 1999 to 2003. Odds ratios and 95% confidence intervals were obtained using logistic regression, adjusting for age at diagnosis, body mass index, family history of colorectal cancer, smoking history, nonsteroidal anti-inflammatory drug use, physical activity, and, among women, menopausal status and postmenopausal hormone use. Among men, those in the highest tertile of leptin concentrations had a 3.3-fold (95% confidence interval, 1.2-8.7) increased adenoma risk compared with those in the lowest tertile (P trend = 0.01). There were no associations between leptin concentrations and adenoma risk in women. There were no associations of leptin receptor genotypes or haplotypes and adenoma risk. The results of this study suggest that, in men, leptin may be associated with risk of colorectal adenomas.

Outcome of follow-up colon examination among a population-based cohort of colorectal cancer patients.

BACKGROUND & AIMS: The benefit of colonoscopy in the follow-up of colorectal cancer survivors is uncertain, and findings of surveillance colonoscopy are not well-characterized. We sought to estimate survival among colorectal cancer patients according to receipt of a follow-up colon examination and to describe the findings of such exams. METHODS: We studied health maintenance organization enrollees with colorectal cancer who underwent surgical resection. Mortality was estimated by using survival analysis, and findings of colon examinations were determined by review of pathology reports. RESULTS: One thousand two patients were eligible for study; 5-year survival was higher (76.8%) for patients who had at least one follow-up exam than for patients who did not undergo follow-up (52.2%, P < .0001). In multivariate analysis, colon examination remained independently associated with improved survival (hazard ratio, 0.58; 95% confidence interval, 0.44-0.75). Twenty patients (3.1%) were diagnosed with a second colorectal cancer, including 9 cancers detected within 18 months of initial cancer diagnosis. Advanced neoplasia was more common (15.5%) among patients followed up between 36-60 months after diagnosis compared with patients followed up within 18 months (6.9%, P = .02). History of adenomas was associated with advanced neoplasia on follow-up (P = .002). Patients with advanced neoplasia on initial follow-up were at high risk for advanced neoplasia on subsequent examinations (13/16, 81%). CONCLUSIONS: After colorectal cancer resection, patients have a high risk of interval cancers, some of which represent missed lesions at initial diagnosis. Therefore, surveillance colonoscopy within 1 year of initial diagnosis is warranted. After adjusting for key variables, endoscopic surveillance is associated with improved survival.

Utility of Bone Marrow Biopsy and Aspirate for Staging of Diffuse Large B Cell Lymphoma in the Era of Positron Emission Tomography With 2-Deoxy-2-[Fluorine-18]fluoro-deoxyglucose Integrated With Computed Tomography.

BACKGROUND: About one-third of patients with diffuse large B cell lymphoma (DLBCL) have lymphomatous bone marrow involvement (BMI) at the time of diagnosis, and bone marrow aspirate/biopsy (BMAB) is considered the gold standard to detect such involvement. [18F] fluorodeoxyglucose positron emission tomography combined with computed tomography (PET-CT), has become standard pretreatment imaging in DLBCL and may be a noninvasive alternative to BMAB to ascertain BMI. Prior studies have suggested that PET-CT scan may obviate the need for BMAB as a component for staging patients with newly diagnosed DLBCL, but this is not yet a standard of practice. The aim of this retrospective study was to determine the accuracy of PET-CT in detecting BMI in DLBCL and to define 2-year and 5-year overall survival based on BMI by BMAB versus PET-CT. METHODS: We reviewed institutional records of all patients with newly diagnosed DLBCL between January 2004 and December 2013 who underwent pretreatment PET-CT and BMAB. PET-CT images were visually assessed for BMI, including the posterior iliac crest. Patients with primary mediastinal DLBCL, previous history or coexistence of another lymphoma subtype, and those with a nondiagnostic BMAB, and in whom the PET-CT did not show marrow signal abnormality, were excluded from the analysis. Ann Arbor stage was determined using PET-CT with and without the contribution of BMAB, and the proportion of stage IV cases by each method was measured. RESULTS: Among 99 eligible patients, the median age was 62 years (range, 24-88 years), 62 (63%) were male, 53 (53%) had elevated serum lactate dehydrogenase, and 17 (16%) had an Eastern Community Oncology Group performance status of > 2. Thirteen (12%) patients had more than 1 extra-nodal site of lymphoma involvement. Revised International Prognostic Index score was 1 in 39 (37%) patients, 2 in 42 (40%) patients, 3 in 20 (19%) patients, and 4 in 4 (4%) patients. A total of 38 (36%) patients had BMI established by either PET-CT (n = 24; 24%), BMAB (n = 14; 14%), or by both modalities (n = 12; 12%). Twelve (50%) of the 24 patients with positive PET-CT had BMI by DLBCL, whereas only 2 (3%) of the 75 patients with negative PET-CT showed BMI. BMAB upstaged 1 (2%) of the 53 stage I/II patients to stage IV. The sensitivity and specificity of PET-CT scan to detect BMI by DLBCL was 86% (95% confidence interval, 51.9%-95.7%) and 87% (95% confidence interval, 76%-92%), respectively. Eighty-five (86%) patients had concordant results between lymphomatous BMAB and PET-CT (12 patients were positive for both; 73 patients were negative for both), and 14 (14%) patients had a discordant interpretation (2 patients were positive by BMAB and negative by PET-CT, and 12 patients were negative by BMAB and positive by PET-CT). The positive predictive value of PET-CT was only 50%, whereas the negative predictive value was 98%. The accuracy of PET-CT was 86%. Although patients with positive BMAB had inferior 5-year overall survival estimates compared with those with negative BMAB (66% vs. 85%; P = .08), no such difference was demonstrated between PET-CT-positive and PET-CT-negative patients (79% vs. 83%; P = .30). CONCLUSIONS: In patients with newly diagnosed DLBCL, PET-CT is accurate in detecting BMI by DLBCL. Although PET-CT has a very high negative predictive value for BMI, it overestimates the number of cases with marrow involvement by DLBCL. In clinical practice, routine BMAB may no longer be necessary for all patients with DLBCL who are staged by PET-CT, unless the results would change both staging and therapy. The prognostic implication of BMI identified by PET-CT compared with BMAB remains unknown. Whether a PET-CT precludes the need for a BMAB in patients with DLBCL remains to be evaluated in a prospective study.

Localized pancreatic cancer with positive peritoneal cytology as a sole manifestation of metastatic disease: a single-institution experience.

BACKGROUND: Pancreatic cancer patients with positive peritoneal cytology (PPC) as a sole metastatic site are poorly characterized. Whether they behave similarly to other stage IV patients is unknown. METHODS: Patients with stage IV disease at our institution between 2003 and 2013 were identified. Inclusion criteria for PPC cohort were PPC at laparoscopy and no laparoscopic and/or radiographic evidence of metastasis. Patients with gross metastasis had laparoscopic and/or radiographic evidence of metastasis. RESULTS: Among 308 patients, 43 patients had PPC and 265 had gross metastasis. PPC cohort: 3 (7%) resectable, 8 (19%) borderline resectable, and 32 (74%) unresectable tumor. Disease progression occurred in 37 (86%). Sixteen of 43 (37%) also received local therapy (1 surgery and 15 chemoradiation). PPC vs gross metastasis cohort differed as follows: baseline Ca 19-9 (440 vs 1,904 IU/mL, P < .0001); Eastern Cooperative Oncology Group (ECOG) score ≤1 (98 vs 88%, P = .04); median overall survival (13.9 vs 9.4 months, P = .0001). CONCLUSIONS: Patients with PPC failed to display long-term disease-free survival, although overall survival was superior compared with those with gross metastasis. Patients with PPC may need to be considered a specific subgroup for staging and survival analysis.

Telomere length in the colon declines with age: a relation to colorectal cancer?

Telomeres shorten with age, which may be linked to genomic instability and an increased risk of cancer. To explore this association, we analyzed telomere length in normal colorectal tissue of individuals at different ages using quantitative-fluorescence in situ hybridization (Q-FISH) and quantitative-PCR (Q-PCR). Using Q-FISH, we also examined the histologically normal epithelium adjacent to, or distant from, colon adenomas and cancers, in addition to the neoplasms. Q-FISH and Q-PCR showed that telomere length was inversely associated with age until approximately ages 60 to 70; surprisingly, beyond this age, telomere length was positively associated with age. This association was found exclusively in epithelial, and not in stromal, cells. Peripheral blood lymphocytes showed an inverse association between telomere length and age, but without any apparent increase in telomere length in the oldest individuals. Telomere length in larger adenoma lesions (>2 cm) was significantly shorter than in normal adjacent (P = 0.004) or normal distant (P = 0.05) tissue from the same individuals. However, telomere length in histologically normal epithelium adjacent to cancers or in adenomas <2 cm was not statistically different from that of the normal distant mucosa or from normal controls, evidence that a telomere-shortening field effect was not present. We suggest that the positive association between telomere length and age in the oldest patients is a consequence of selective survival of elderly patients with long colonocyte telomeres.

Rare long-term survivors of pancreatic adenocarcinoma without curative resection.

Long-term outcome data in pancreatic adenocarcinoma are predominantly based on surgical series, as resection is currently considered essential for long-term survival. In contrast, five-year survival in non-resected patients has rarely been reported. In this report, we examined the incidence and natural history of ≥ 5-year survivors with non-resected pancreatic adenocarcinoma. All patients with pancreatic adenocarcinoma who received oncologic therapy alone without surgery at our institution between 1995 and 2009 were identified. Non-resected ≥ 5-year survivors represented 2% (11/544) of all non-resected patients undergoing treatment for pancreatic adenocarcinoma, and 11% (11/98) of ≥ 5-year survivors. Nine patients had localized tumor and 2 metastatic disease at initial diagnosis. Disease progression occurred in 6 patients, and the local tumor bed was the most common site of progression. Six patients suffered from significant morbidities including recurrent cholangitis, second malignancy, malnutrition and bowel perforation. A rare subset of patients with pancreatic cancer achieve long-term survival without resection. Despite prolonged survival, morbidities unrelated to the primary cancer were frequently encountered and a close follow-up is warranted in these patients. Factors such as tumor biology and host immunity may play a key role in disease progression and survival.