Preoperative Treatment of Locally Advanced Rectal Cancer.

BACKGROUND: Pelvic radiation plus sensitizing chemotherapy with a fluoropyrimidine (chemoradiotherapy) before surgery is standard care for locally advanced rectal cancer in North America. Whether neoadjuvant chemotherapy with fluorouracil, leucovorin, and oxaliplatin (FOLFOX) can be used in lieu of chemoradiotherapy is uncertain. METHODS: We conducted a multicenter, unblinded, noninferiority, randomized trial of neoadjuvant FOLFOX (with chemoradiotherapy given only if the primary tumor decreased in size by <20% or if FOLFOX was discontinued because of side effects) as compared with chemoradiotherapy. Adults with rectal cancer that had been clinically staged as T2 node-positive, T3 node-negative, or T3 node-positive who were candidates for sphincter-sparing surgery were eligible to participate. The primary end point was disease-free survival. Noninferiority would be claimed if the upper limit of the two-sided 90.2% confidence interval of the hazard ratio for disease recurrence or death did not exceed 1.29. Secondary end points included overall survival, local recurrence (in a time-to-event analysis), complete pathological resection, complete response, and toxic effects. RESULTS: From June 2012 through December 2018, a total of 1194 patients underwent randomization and 1128 started treatment; among those who started treatment, 585 were in the FOLFOX group and 543 in the chemoradiotherapy group. At a median follow-up of 58 months, FOLFOX was noninferior to chemoradiotherapy for disease-free survival (hazard ratio for disease recurrence or death, 0.92; 90.2% confidence interval [CI], 0.74 to 1.14; P = 0.005 for noninferiority). Five-year disease-free survival was 80.8% (95% CI, 77.9 to 83.7) in the FOLFOX group and 78.6% (95% CI, 75.4 to 81.8) in the chemoradiotherapy group. The groups were similar with respect to overall survival (hazard ratio for death, 1.04; 95% CI, 0.74 to 1.44) and local recurrence (hazard ratio, 1.18; 95% CI, 0.44 to 3.16). In the FOLFOX group, 53 patients (9.1%) received preoperative chemoradiotherapy and 8 (1.4%) received postoperative chemoradiotherapy. CONCLUSIONS: In patients with locally advanced rectal cancer who were eligible for sphincter-sparing surgery, preoperative FOLFOX was noninferior to preoperative chemoradiotherapy with respect to disease-free survival. (Funded by the National Cancer Institute; PROSPECT ClinicalTrials.gov number, NCT01515787.).

LOAd703, an oncolytic virus-based immunostimulatory gene therapy, combined with chemotherapy for unresectable or metastatic pancreatic cancer (LOKON001): results from arm 1 of a non-randomised, single-centre, phase 1/2 study.

BACKGROUND: Pancreatic ductal adenocarcinoma is characterised by low immunogenicity and an immunosuppressive tumour microenvironment. LOAd703, an oncolytic adenovirus with transgenes encoding TMZ-CD40L and 4-1BBL, lyses cancer cells selectively, activates cytotoxic T cells, and induces tumour regression in preclinical models. The aim of this study was to evaluate the safety and feasibility of combining LOAd703 with chemotherapy for advanced pancreatic ductal adenocarcinoma. METHODS: LOKON001 was a non-randomised, phase 1/2 study conducted at the Dan L Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, TX, USA, and consisted of two arms conducted sequentially; the results of arm 1 are presented here. In arm 1, patients 18 years or older with previously treated or treatment-naive unresectable or metastatic pancreatic ductal adenocarcinoma were treated with standard 28-day cycles of intravenous nab-paclitaxel 125 mg/m2 plus gemcitabine 1000 mg/m2 (up to 12 cycles) and intratumoural injections of LOAd703 every 2 weeks. Patients were assigned using Bayesian optimal interval design to receive 500 µL of LOAd703 at 5 × 1010 (dose 1), 1 × 1011 (dose 2), or 5 × 1011 (dose 3) viral particles per injection, injected endoscopically or percutaneously into the pancreatic tumour or a metastasis for six injections. The primary endpoints were safety and treatment-emergent immune response in patients who received at least one dose of LOAd703, and antitumour activity was a secondary endpoint. This study was registered with ClinicalTrials.gov, NCT02705196, arm 2 is ongoing and open to new participants. FINDINGS: Between Dec 2, 2016, and Oct 17, 2019, 23 patients were assessed for eligibility, leading to 22 patients being enrolled. One patient withdrew consent, resulting in 21 patients (13 [62%] men and eight [38%] women) assigned to a dose group (three to dose 1, four to dose 2, and 14 to dose 3). 21 patients were evaluable for safety. Median follow-up time was 6 months (IQR 4-10), and data cutoff was Jan 5, 2023. The most common treatment-emergent adverse events overall were anaemia (96 [8%] of 1237 events), lymphopenia (86 [7%] events), hyperglycaemia (70 [6%] events), leukopenia (63 [5%] events), hypertension (62 [5%] events), and hypoalbuminaemia (61 [5%] events). The most common adverse events attributed to LOAd703 were fever (14 [67%] of 21 patients), fatigue (eight [38%]), chills (seven [33%]), and elevated liver enzymes (alanine aminotransferase in five [24%], alkaline phosphatase in four [19%], and aspartate aminotransferase in four [19%]), all of which were grade 1-2, except for a transient grade 3 aminotransferase elevation occurring at dose 3. A maximum tolerated dose was not reached, thereby establishing dose 3 as the highest-evaluated safe dose when combined with nab-paclitaxel plus gemcitabine. Proportions of CD8+ effector memory cells and adenovirus-specific T cells increased after LOAd703 injections in 15 (94%) of 16 patients for whom T-cell assays could be performed. Eight (44%, 95% CI 25-66) of 18 patients evaluable for activity had an objective response. INTERPRETATION: Combining LOAd703 with nab-paclitaxel plus gemcitabine in patients with advanced pancreatic ductal adenocarcinoma was feasible and safe. To build upon this novel chemoimmunotherapeutic approach, arm 2 of LOKON001, which combines LOAd703, nab-paclitaxel plus gemcitabine, and atezolizumab, is ongoing. FUNDING: Lokon Pharma, the Swedish Cancer Society, and the Swedish Research Council.

Detection of recurrent colorectal cancer with high specificity using a reporting threshold for circulating tumor DNA methylated in BCAT1 and IKZF1.

BACKGROUND: A blood assay measuring methylated BCAT1 and IKZF1 can detect recurrent colorectal cancer (CRC) with high sensitivity but suboptimal specificity. This study aimed to establish an upper reference limit (URL) of these biomarkers in a reference population without CRC, apply that threshold to detecting clinical recurrence in patients who had undergone definitive therapy for CRC, and compare the performance of the biomarkers with carcinoembryonic antigen (CEA). METHODS: The level of methylation was reported as the aggregate methylated BCAT1 and IKZF1 expressed as a percentage of total plasma DNA. A reference population of patients confirmed to have no colorectal neoplasia (n = 857) was used to determine the URL. Test accuracy for clinical recurrence was determined in a post-treatment surveillance population (n = 549; 77 recurrence cases). RESULTS: A methylation level of 0.07%, corresponding to the 98th percentile in the reference population, was set as the URL. In the surveillance population, 60 patients had methylation levels above 0.07%, and 81.7% of these had recurrence. In comparison with no minimum threshold being applied, assay sensitivity with a URL of 0.07% yielded similar sensitivity (63.6% [CI, 51.9%-74.3%] vs 64.9% [CI, 53.8%-74.7%]; P = .87) and higher specificity (97.7% [CI, 95.9%-98.8%] vs 91.3% [CI, 88.4%-93.5%]; P < .001). The BCAT1/IKZF1 test was 2.5-fold more sensitive than CEA for detecting recurrences considered amenable to surgery with curative intent (50.0% vs 20.8%; P = .016). CONCLUSIONS: Applying a threshold for positivity to the methylated BCAT1/IKZF1 blood assay improved the specificity for CRC recurrence without compromising sensitivity. Both the sensitivity and the specificity were superior to those of CEA.

Prognostic Value of Nodal Response After Preoperative Treatment of Gastric Adenocarcinoma.

Background: Pathologically positive lymph nodes (ypN+) after preoperative chemotherapy are associated with poor survival in patients with gastric cancer. Little is known about the association between response to preoperative therapy and the benefit of postoperative therapy. Methods: This retrospective cohort study of the National Cancer Database included patients with clinically node-positive (cN+) gastric cancer treated with preoperative therapy followed by surgery (2006-2014). Preoperative treatment modality was categorized as the inclusion of radiation therapy (RT) or chemotherapy alone. Pretreatment clinical and pathologic stages were used to determine pathologic treatment response rates. The association between overall risk of death and preoperative treatment, disease response, and adjuvant therapy use was evaluated using multivariable Cox regression. Results: Preoperative RT was used in 53.6% of 1,976 patients with cN+ gastric cancer, (74.3% cardia and 10.1% noncardia). The nodal response rate was 38.9% and was higher with RT than with chemotherapy alone (cardia, 46.0% vs 29.1%; P<.001; noncardia, 43.8% vs 31.9%; P=.06). Preoperative RT was associated with an approximate 2-fold increase in the odds of pathologic response compared with chemotherapy. Overall, use of adjuvant therapy was not associated with a decreased risk of death. A primary tumor response with residual nodal disease was not associated with survival (hazard ratio [HR], 1.03; 95% CI, 0.66-1.60). However, a nodal response with residual primary disease was significantly associated with survival (HR, 0.54; 95% CI, 0.44-0.65). Conclusions: More than one-third of node-positive gastric cancers showed pathologic nodal response with preoperative treatment. RT is associated with a higher response than chemotherapy. Patients with ypN+ disease have worse survival, regardless of whether they receive postoperative therapy. Future gastric cancer trials should evaluate the role of preoperative RT and individualize postoperative therapy use.

National Trends in Multimodality Therapy for Locally Advanced Gastric Cancer.

BACKGROUND: Multimodality therapy (MMT) is recommended for patients with resectable gastric cancer, but no single approach has been established as standard. Little is presently known about current national practice patterns and sequencing of MMT. METHODS: Retrospective cohort study of patients with gastric cancer aged 18 to 80 y in the National Cancer Database (2006-2014) with ≥T2 and/or node-positive disease (i.e., stage Ib to III) treated with MMT. Clinical nodal staging accuracy was ascertained among those treated with upfront surgery by comparing clinical and pathologic nodal staging. Multivariable Cox regression was used to evaluate the association between overall risk of death and MMT approach (i.e., radiation used versus not and treatment sequence). RESULTS: Among 5817 patients, 16.1% received perioperative MMT, 50.6% preoperative only, and 33.3% postoperative only. The sensitivity, specificity, positive predictive value, and negative predictive values of clinical nodal staging were 68.4%, 88.8%, 91.1%, and 62.7%, respectively. Current clinical nodal staging modalities understage 37.3% of clinically node-negative patients. Over time, radiation utilization decreased (74.3% in 2006 versus 53.9% in 2014; trend test, P < 0.001), perioperative MMT increased (8.9% versus 22.2%%; trend test, P < 0.001), and postoperative MMT decreased (43.1% versus 21.0%; trend test, P < 0.001). Neither type of MMT nor treatment sequence is associated with risk of death. CONCLUSIONS: One-third of patients with gastric cancer who are candidates to receive MMT are treated with upfront surgery. Given the high false negative rate of clinical nodal staging and high noncompletion rate of postoperative treatment, efforts should be directed at improving and optimizing preoperative therapy utilization.

Physician Integrity, Templates, and the 'F' Word.

The medical profession is increasingly dependent upon electronic health records. Along with documented benefits, a number of potential ethical abuses have been outlined. Herein, we describe an ethical abuse that has received almost no attention, namely falsified medical records. We present three cases in which the medical record cited facts from history that were not elicited and findings from physical examination that was not performed. This is fraud. Prepopulated templates were almost certainly responsible. If a template is used, it must begin free of results-a skeleton onto which flesh is placed. If coders and third-party payers insist on having information than health care providers think relevant, then we, as a profession should "push back," but a template that has been prepopulated puts fraudulent data into electronic health record, seriously damaging physician integrity.

Prognostic value of neoadjuvant treatment response in locally advanced rectal cancer.

BACKGROUND: For locally advanced rectal cancer, response to neoadjuvant radiation has been associated with improved outcomes but has not been well characterized in general practice. The goals of this study were to describe disease response rates after neoadjuvant treatment and to evaluate the association between disease response and survival. MATERIALS AND METHODS: Retrospective cohort study of patients aged 18-80 y with clinical stage II and III rectal adenocarcinoma in the National Cancer Database (2006-2012). All patients underwent radical resection after neoadjuvant treatment. Treatment responses were defined as follows: no tumor response; intermediate-T and/or N downstaging with residual disease; and complete-ypT0N0. Multivariable, multinomial regression was used to evaluate the association between neoadjuvant radiation use and disease response. Multivariable Cox regression was used to evaluate the association between disease response and overall risk of death. RESULTS: Among 12,024 patients, 12% had a complete and 30% an intermediate response. Neoadjuvant chemotherapy alone was less likely to achieve an intermediate (relative risk ratio: 0.70 [0.56-0.88]) or a complete response (relative risk ratio: 0.59 [0.41-0.84]) relative to neoadjuvant radiation. Tumor response was associated with improved 5-y overall survival (complete = 90.2%, intermediate = 82.0%, no response = 70.5%; log-rank, P < 0.001). Complete and intermediate pathologic responses were associated with decreases in risk of death (hazard ratio: 0.40 [0.34-0.48] and 0.63 [0.57-0.69], respectively) compared to no response. Primary tumor and nodal response were independently associated with decreased risk of death. CONCLUSIONS: Neoadjuvant radiation is associated with treatment response, and pathologic response is associated with improved survival. Pathologic response may be an early benchmark for the oncologic effectiveness of neoadjuvant treatment.

Primary Neuroendocrine Tumor of the Orbit Presenting With Acute Proptosis.

Primary neuroendocrine tumors of the orbit are exceedingly rare and typically present with gradual, progressive exophthalmos. In this report, an otherwise healthy 64-year-old woman undergoes resection of a well-differentiated neuroendocrine tumor after presenting with acute proptosis. An extensive clinical and radiographic evaluation reveals no other evidence of disease, establishing the diagnosis of a primary neuroendocrine tumor. The case presentation is followed by a brief review of the classification, presentation, and evaluation of orbital neuroendocrine tumors.

Rising Incidence of Colorectal Cancer Among Young Hispanics in Texas.

GOALS: To investigate trends in colorectal cancer (CRC) incidence and survival among Hispanics in Texas. BACKGROUND: The incidence of CRC is rising among young adults in the United States. Given Texas' large Hispanic population, investigating CRC trends in Texas may provide valuable insight into the future of CRC epidemiology in an ever-diversifying US population. STUDY: Data from the Texas Cancer Registry (1995 to 2010) were used to calculate age-adjusted CRC rates based on the 2000 US standard population. Annual percentage change (APC) and 5-year cancer-specific survival (CSS) rates were reported by age, race/ethnicity, stage, and anatomic location. RESULTS: Of 123,083 CRC cases, 11% occurred in individuals below 50 years old, 26% of whom were Hispanic. Incidence was highest among African Americans (AAs; 76.3/100,000), followed by non-Hispanic whites (NHWs; 60.2/100,000) and Hispanics (50.8/100,000). Although overall CRC incidence declined between 1995 and 2010 (APC, -1.8%; P<0.01), trends differed by age and race/ethnicity. Among individuals 50 years and above, the rate of decline was statistically significant among NHWs (APC, -2.4%; P<0.01) and AAs (APC, -1.3%; P<0.01) but not among Hispanics (APC, -0.6%; P=0.13). In persons aged 20 to 39 years, CRC incidence rose significantly among Hispanics (APC, 2.6%; P<0.01) and NHWs (APC, 2.4%; P<0.01), but not AAs (APC, 0.3%; P=0.75). CSS rates among Hispanics and NHWs were comparable across most age groups and cancer stages, whereas CSS rates among AAs were generally inferior to those observed among NHWs and Hispanics. CONCLUSIONS: Although CRC incidence has declined in Texas, it is rising among young Hispanics and NHWs while declining more slowly among older Hispanics than among older NHWs and AAs.

Clinical prediction of bacteremia and early antibiotics therapy in patients with solid tumors.

OBJECTIVE: To investigate the relationship between the systemic inflammatory response syndrome (SIRS), early antibiotic use, and bacteremia in solid-tumor patients. DESIGN, SETTING, AND PARTICIPANTS: We conducted a retrospective observational study of adults with solid tumors admitted to a tertiary-care hospital through the emergency department over a 2-year period. Patients with neutropenic fever, organ transplant, trauma, or cardiopulmonary arrest were excluded. METHODS: Rates of SIRS, bacteremia, and early antibiotics (initiation within 8 hours of presentation) were compared using the χ2 and Student t tests. Binomial regression and receiver operator curves were analyzed to assess predictors of bacteremia and early antibiotics. RESULTS: Early antibiotics were administered in 507 (37%) of 1,344 SIRS-positive cases and 492 (22%) of 2,236 SIRS-negative cases (P < .0001). Of SIRS-positive cases, 70% had blood cultures drawn within 48 hours and 19% were positive; among SIRS negative cases, 35% had cultures and 13% were positive (19% vs 13%; P = .003). Bacteremic cases were more often SIRS positive than nonbacteremic cases (60% vs 50%; P =.003), but they received early antibiotics at similar rates (50% vs 49%, P = .72). Three SIRS components predicted early antibiotics: temperature (OR, 1.7; 95% CI, 1.31-2.29; P = .0001), tachycardia (OR, 1.4; 95% CI, 1.10-1.69; P < .0001), and white blood-cell count (OR, 1.8; 95% CI, 1.56-2.14; P < .0001). Only temperature (OR, 1.6; 95% CI, 1.09-2.41; P = .01) and tachycardia (OR, 1.5; 95% CI, 1.09-2.06; P = .01) predicted bacteremia. SIRS criteria as a composite were poorly predictive of bacteremia (AUC, 0.57). CONCLUSIONS: SIRS criteria are frequently used to determine the need for early antibiotics, but they are poor predictors of bacteremia in solid-tumor patients. More reliable models are needed to guide judicious use of antibiotics in this population.

Outcomes Among Minority Patients With Metastatic Colorectal Cancer in a Safety-net Health Care System.

BACKGROUND: Metastatic colorectal cancer (CRC) outcomes continue to improve, but they vary significantly by race and ethnicity. We hypothesize that these disparities arise from unequal access to care. MATERIALS AND METHODS: The Harris Health System (HHS) is an integrated health delivery network that provides medical care to the underserved, predominantly minority population of Harris County, Texas. As the largest HHS facility and an affiliate of Baylor College of Medicine's Dan L. Duncan Comprehensive Cancer Center, Ben Taub Hospital (BTH) delivers cancer care through multidisciplinary subspecialty that prioritize access to care, adherence to evidence-based clinical pathways, integration of supportive services, and mitigation of financial toxicity. We performed a retrospective analysis of minority patients diagnosed with and treated for metastatic CRC at BTH between January 2010 and December 2012. Kaplan-Meier survival curves were compared with survival curves from randomized control trials reported during that time period. RESULTS: We identified 103 patients; 40% were black, 49% were Hispanic, and 12% were Asian or Middle Eastern. Thirty-five percent reported a language other than English as their preferred language. Seventy-four percent of patients with documented coverage status were uninsured. Eighty-four percent of patients received standard chemotherapy with a clinician-reported response rate of 63%. Overall survival for BTH patients undergoing chemotherapy was superior to that of subjects enrolled in the CRYSTAL (Cetuximab Combined with Irinotecan in First-Line Therapy for Metastatic Colorectal Cancer) trial (median, 24.0 vs. 19.9 months; P = .014). CONCLUSION: HHS provides a health delivery infrastructure through which minority patients with socioeconomic challenges experience clinical outcomes comparable with highly selected patients enrolled in randomized control trials. Efforts to resolve CRC disparities should focus on improving access of at-risk populations to high-quality comprehensive cancer care.

Evaluation of Circulating Tumor DNA for Methylated BCAT1 and IKZF1 to Detect Recurrence of Stage II/Stage III Colorectal Cancer (CRC).

BACKGROUND: Most recurrences of early-stage colorectal cancer detected with current surveillance measures are widespread and incurable. Circulating tumor DNA (ctDNA) may facilitate earlier diagnosis of recurrent colorectal cancer and improve cancer-related outcomes. METHODS: Plasma from patients undergoing standard surveillance after definitive treatment for stage II/III colorectal cancer was assayed with COLVERA and carcinoembryonic antigen (CEA) at a single time point. Results were correlated with radiographic imaging. Assay performance, including sensitivity and specificity for recurrence, were compared. Impact of potentially confounding variables was also explored. RESULTS: 322 patients were included in the final analysis, and 27 recurrences were documented over a median follow-up period of 15 months. Sensitivity for recurrence was 63% [confidence interval (CI), 42.4-80.6] and 48% (CI, 28.7-68.1) for COLVERA and CEA (≥5 ng/mL), respectively (P = 0.046), while specificity was 91.5% (CI, 87.7-94.4) and 96.3% (CI, 93.4-98.1), respectively (P = 0.016). Smoking and age were independent predictors of CEA but not COLVERA positivity. CONCLUSIONS: COLVERA was more sensitive but less specific than CEA in detecting recurrent colorectal cancer. Short median follow-up may have been responsible for apparent false positives in COLVERA. Studies with serial sampling and longer follow-up are needed to assess whether earlier detection of colorectal cancer recurrence translates into clinical benefit. IMPACT: This prospective study showed that COLVERA (a two-gene ctDNA assay) was more sensitive for detection of recurrence in a cohort of patients undergoing surveillance after definitive therapy for stages II and III colorectal cancer.

Identification of Educational Gaps Among Oncologists Who Manage Patients with Pancreatic Cancer.

INTRODUCTION: Pancreatic ductal adenocarcinoma (PDA) is associated with poor outcomes and presents oncologists with a myriad of clinical challenges. This study was conducted to assess oncologists' practice patterns and to identify the greatest areas of need for future PDA continuing medical education (CME) programs. METHODS: Case vignettes have been validated as an effective tool to assess how physicians approach and treat a wide array of diseases. In order to assess practice patterns for resectable, locally advanced unresectable, and metastatic PDA, an online case vignette survey was distributed to practicing medical oncologists. RESULTS: Responses from 150 US-practicing oncologists were analyzed, and several key opportunities for future CME programs were identified. For case 1 (patient with resectable PDA), 44% of oncologists did not select an evidence-based adjuvant chemotherapy regimen. For case 2 (patient with locally advanced PDA who develops metastases and neuropathy after first-line nab-paclitaxel/gemcitabine followed by chemoradiation), 57% of oncologists did not select an evidence-based second-line chemotherapy regimen, and 35% selected a regimen containing oxaliplatin, a chemotherapeutic known to cause neuropathy. For case 3 (patient with a pancreatic mass and liver metastases), only 34% of oncologists recommended a biopsy, chest imaging, and liver function tests which should be standard of care assessments with this presentation. For all three cases, clinical trial referral was selected by fewer than 5% of respondents. CONCLUSIONS: This study identified appreciable discrepancies between oncologists' recommendations and standard evidence-based guidelines. Well-designed CME programs may help to bridge the educational gaps identified and improve adherence to practice guidelines.

Evaluating Treatment Patterns for Small Cell Carcinoma of the Colon Using the National Cancer Database (NCDB).

OBJECTIVE(S): The objective of this study was to characterize the clinicopathological prognostic factors and treatment patterns for small cell carcinoma (SCC) of the colon, a rare disease without standard treatment guidelines. METHODS: We analyzed clinicopathological and treatment variables for 503 cases of histologically proven SCC colon entered into the National Cancer Database (NCDB) between 2004 and 2013. Survival curves were generated using Kaplan-Meier and compared by the log-rank test. Cox proportional hazard regression was used to control for covariates and evaluate the effect of different treatment modalities on overall survival. RESULTS: Four hundred seventy-two (93.8%) patients had complete clinical staging information and were therefore included in our analysis. Of these patients, 149 (31.5%) had limited stage disease (LD) and 323 (68.4%) had extensive stage disease (ED) at presentation. Median overall survival (OS) for patients with ED was significantly lower than for those with LD (4.04 months vs. 21.82 months; p < 0.001). Multivariate Cox regression analysis showed administration of chemotherapy was associated with improved survival in patients with LD and ED (p = 0.026, p < 0.001) while surgery was not associated with improved survival in patients with LD or ED (p = 0.943, p = 0.630). Radiation therapy was associated with improved survival in patients with ED (p = 0.044). CONCLUSIONS: SCC of the colon carries a poor prognosis, especially in patients presenting with metastatic disease. Surgery and chemotherapy are administered more frequently than radiation, and chemotherapy is associated with improved survival, unlike surgery.

A rare presentation of choroidal metastasis from primary esophageal adenocarcinoma successfully treated with intensity-modulated radiation therapy.

PURPOSE: In this case report, we present a case of choroidal metastasis from a primary esophageal adenocarcinoma that was treated successfully with intensity-modulated radiation therapy. OBSERVATIONS: A 65-year-old male with known stage IV esophageal adenocarcinoma presented with a central scotoma in his left eye and was ultimately found to have a large choroidal metastatic lesion with overlying subretinal fluid. IMRT was administered over the course of four weeks, resulting in restoration of the patient's vision, regression of the metastatic lesion, and resolution of the subretinal fluid. As of 16 months following completion of radiation, there remains no evidence of choroidal recurrence or radiation-associated ocular complications. CONCLUSIONS: and Importance: To our knowledge, this is the first published case report of a choroidal metastasis from esophageal cancer responding durably to IMRT. IMRT should therefore be considered a viable treatment option for this rare disease.

Pancreatic cancer disparities in African Americans.

OBJECTIVES: Pancreatic cancer is the fourth leading cause of cancer-related deaths in the United States. The incidence of pancreatic cancer in African Americans is 50% to 90% higher than the incidence in other racial groups. African Americans also have the worst prognosis. This is an evidence-based review of pancreatic cancer in African Americans with particular emphasis on baseline characteristics, treatment, and survival. METHODS: We queried PubMed in search for articles describing racial disparities in pancreatic cancer. Two categories of terms were "anded" together: pancreatic cancer terms and race terms. The last search was performed on November 14, 2013. RESULTS: We summarized the data on pancreatic cancer baseline characteristics, treatment, and survival for African Americans that we obtained from the following databases: (1) Surveillance, Epidemiology, and End Results, 1988-2008; (2) California Cancer Registry 1988-1998; (3) Cancer Survivor Program of Orange County/San Diego Imperial Organization for Cancer Control, 1988-1998; and (4) Harris County, 1998-2010. CONCLUSIONS: Overall, pancreatic cancer survival of African Americans has not significantly improved over the past several decades despite advances in multimodality therapy; African Americans continue to face worse outcomes than whites. Although baseline characteristics, treatment, and biological factors offer some explanation, they do not completely explain the disparities in incidence and survival.

Administration of protein-conjugate pneumococcal vaccine to patients who have invasive disease after splenectomy despite their having received 23-valent pneumococcal polysaccharide vaccine.

Patients who undergo splenectomy are at greatly increased risk for overwhelming pneumococcal bacteremia and death. Twenty-three-valent pneumococcal polysaccharide vaccine (PPV-23), which contains capsular polysaccharides (PSs) from 23 common serotypes of Streptococcus pneumoniae, is strongly recommended for such patients. The capacity to respond to PPV-23 by producing immunoglobulin (Ig) G is genetically regulated. Some proportion of adults do not respond and, despite postsplenectomy administration of PPV-23, may remain susceptible to recurrent pneumococcal sepsis. Here, we describe 2 patients who had recurring pneumococcal bacteremia after undergoing splenectomy despite having received numerous doses of PPV-23. Heptavalent protein-conjugate pneumococcal vaccine (PCPV-7) was then administered, and it induced high levels of IgG to all 7 PSs; in one of the patients, functional activity against 5 of the 7 PSs was demonstrable, both in vitro and in vivo. Recurrent pneumococcal bacteremia in patients who have undergone splenectomy may indicate a genetically regulated failure to respond to PPV-23; PCPV-7 may stimulate production of IgG to PSs in such patients.