Karen Colleen Daily

Hepatoid adenocarcinoma of the colon

Hepatoid adenocarcinoma (HAC) is a rare extrahepatic adenocarcinoma that morphologically and immunophenotypically mimics hepatocellular carcinoma (HCC). We report the case of a 42-year-old woman with an extensive cancer history who presented with right-sided abdominal pain and lower gastrointestinal (GI) bleeding, and was ultimately diagnosed with colon adenocarcinoma. She underwent sigmoidectomy and adjuvant chemotherapy. Approximately 1 month after completion of chemotherapy, positron emission tomography showed presence of a 1.8 cm×1.4 cm mesenteric lymph node. She underwent treatment with chemotherapy and radiation followed by lymph node resection. Pathological findings from the lymph node were consistent with poorly differentiated carcinoma with hepatocellular differentiation. When compared with pathology from the colonic resection, both specimens showed histomorphological features and immunohistochemical profiles consistent with hepatocellular differentiation. Given these findings, a diagnosis of HAC of the colon with metastasis to a mesenteric lymph node was made.

Preventing Breast Cancer Recurrence through a Tailored Lifestyle Intervention: The MyLIFE (My Lifestyle Intervention with Food and Exercise) Trial Rationale and Study Design

Breast cancer risk, and risk of associated co-morbidities such as cardiovascular disease, is highest among overweight or obese women with a previous history of breast cancer. The objective of this study is to test the effectiveness of a tailored nutrition, physical activity, and behavioral weight management intervention for breast cancer survivors against a widely available commercial weight management program. We hypothesize that an intervention tailored to the unique psychological, nutritional, and physical needs of breast cancer survivors will provide superior physiological and psychological benefits compared to an existing commercial program for the general population. To test our hypothesis, we initially conducted a focus group with both breast cancer survivors and oncology affiliated health care providers in order to illicit feedback to develop an intervention customized specifically to breast cancer survivors. Subsequently, in a randomized, multicenter trial, we are studying the effect of the tailored program on overweight/obese women (N=120) with a history of breast cancer (3 months to 5 years post-primary treatment) on body weight and composition, markers of systemic inflammation related to cancer and associated chronic diseases, physical activity habits, dietary intake, health-related quality of life, and program adherence and satisfaction. Assessments will be taken prior to study initiation immediately following the intervention and at 6 months post-intervention to assess long-term maintenance of weight, lifestyle behaviors, and impact on physiological markers of disease risk. This project is unique in that it addresses weight issues in a high risk, understudied population using a tailored approach.

Stereotactic body radiation therapy for oligoprogression of metastatic disease from gastrointestinal cancers: A novel approach to extend chemotherapy efficacy

Chemotherapy and targeted therapies are effective palliative options for numerous unresectable or metastatic cancers. However, treatment resistance inevitably develops leading to mortality. In a subset of patients, systemic therapy appears to control the majority of tumors leaving 5 or less to progress, a phenomenon described as oligoprogression. Reasoning that the majority of lesions remain responsive to ongoing systemic chemotherapy, we hypothesized that local treatment of the progressing lesions would confer a benefit. The present study describes the cases of 5 patients whose metastatic disease was largely controlled by chemotherapy. The oligoprogressive lesions (≤5) were treated with stereotactic body radiotherapy (SBRT), justifying continued use of an effective systemic regimen. A total of 5 patients with metastatic disease on chemotherapy, with ≤5 progressing lesions amenable to SBRT, were treated with ablative intent. Primary tumor site and histology were as follows: 2 with metastatic colon adenocarcinoma, 2 with metastatic rectal adenocarcinoma and 1 with metastatic pancreatic adenocarcinoma. Imaging was performed prior to SBRT and every 3 months after SBRT. In total, 4 out of the 5 patients achieved disease control for >7 months with SBRT, without changing chemotherapy regimen. The median time to chemotherapy change was 9 months, with a median follow-up time of 9 months. The patient who failed to respond developed progressive disease outside of the SBRT field at 3 months. In conclusion, the addition of SBRT to chemotherapy is an option for the overall systemic control of oligoprogressive disease.

Discordant HER2 expression and response to neoadjuvant chemoradiotherapy in esophagogastric adenocarcinoma

BACKGROUND Targeting human epidermal growth factor receptor 2 (HER2) with trastuzumab in metastatic esophagogastric adenocarcinoma (EGA) improves survival. The impact of HER2 inhibition in combination with chemoradiotherapy (CRT) in early stage EGA is under investigation. This study analyzed the pattern of HER2 overexpression in matched-pair tumor samples of patients who underwent neoadjuvant CRT followed by surgery. METHODS All patients with EGA who underwent standard neoadjuvant CRT followed by esophagectomy at the University of Florida were included. Demographics, risk factors, tumor features, and outcome data were analyzed. Descriptive statistics, Chi-square exact test, uni- and multivariate analyses, and Kaplan Meier method were used. HER2 expression determined by immunohistochemical (IHC) was scored as negative (0, 1+), indeterminate (2+) or positive (3+). RESULTS Among 49 sequential patients (41 M/8 F) with matched-pair tumor samples, 9/49 patients (18%) had pathologic complete response (pCR), 10/49 had near pCR or not enough tumor (NET) to examine in the post- treatment samples. Patients with initial HER2 negativity demonstrated conversion to HER2 positivity after neoadjuvant CRT (7/30 cases; 23%). Baseline HER2 overexpression was more common in lower stage/node negative patients (67% in stages I, IIA vs. 33% in stages IIB, III) and did not correlate with treatment response or survival. CONCLUSIONS Although limited by a relatively small sample size, our study failed to demonstrate that baseline HER2 protein over-expression in EGA predicts response to standard CRT. However, our data suggested that HER2 was up regulated by CRT resulting in unreliable concordance between pre-treatment (pre-tx) and post-treatment (post-tx) samples. Pre-therapy HER2 expression may not reliably reflect the HER2 status of persistent or recurrent disease.

Common variable immunodeficiency syndrome in an adult

In September, 2012, a 25-year-old woman came to our emergency department with a 3 week history of diarrhoea, generalised cramping abdominal pain, and low-grade fevers associated with an unintentional 9 kg weight loss. She had a history of immune thrombocytopenic purpura not needing treatment. On examina tion, the patient had a fever of 38·2°C and palpable axillary lymphadenopathy. CT of the chest, abdomen, and pelvis showed pulmonary nodules with patchy infi ltrates bilaterally, axillary and retroperitoneal lymphadenopathy (appendix), and splenomegaly (15·3 cm). Laboratory studies showed raised white blood cell count of 1·3 × 109/L (neutrophils 0·104 × 109/L), and platelets 104 × 109/L. Lymphoma was suspected, and the patient was admitted. Cefepime was started empirically for febrile neutropenia. Blood, urine, sputum, and stool cultures were all negative. HIV antibody and PCR tests were non-reactive. Monospot test and tests for Epstein-Barr virus and cytomegalovirus were negative for acute infection. Bronchoscopy was done because of CT fi ndings. Bronchoalveolar lavage was positive for herpes simplex type one, for which the patient was treated with valacyclovir. Diarrhoea resolved within 1 week of admission, abdominal pain at 2 weeks, and fever by 3 weeks, at which point the patient was discharged. Excisional biopsy of an axillary lymph node showed atypical follicular lymphoid hyperplasia without evidence of lymphoma. In-situ hybridisation study for Epstein-Barr virus showed rare positive cells. Focally increased numbers of Langerhans cells were seen without granulomata. The CD4/CD8 T-cell ratio was decreased (0·65 [normal range 1–4]); however, no T-cell immunophenotypic aberrancy was detected. Serum immunoglobulin concentrations showed low IgG (3·49 g/L), low IgA (<0·05 g/L), and normal IgM (0·62 g/L) (normal ranges 7·16–15·5 g/L, 0·45–2·59 g/L, and 0·71–3·77 g/L respectively). The combination of hypogammaglobulinaemia, viral infection, lymphadenopathy, splenomegaly, and gastrointestinal symptoms were suggestive of common variable immunodefi ciency syndrome (CVID). Functional antibodies to tetanus, Haemophilus infl uenzae B, and pneumo coccus were negative. The patient was vaccinated against all the above and repeat serological testing 2 months later showed no response, confi rming the diagnosis of CVID. She was last seen in December, 2013, and is well on monthly intravenous immunoglobulin infusions. Intermittent abdominal pain and diarrhoea is being followed up by gastroenterology. CVID is the most common primary immunodefi ciency, occurring in about 1:25 000 white people. The diagnostic criteria include low IgG (<4 g/L) and either low IgA or IgM, age greater than 2 years, poor response to vaccines, and the absence of other causes of hypogammaglobulinaemia. Most patients are diagnosed in adulthood (20–49 years), although there is usually a 6-year delay in diagnosis because of variation in symptoms. Infections are typically sinopulmonary with an overrepresentation for encapsulated or atypical organisms. 25% of patients have autoimmune conditions, with immune thrombocytopenia and autoimmune haemolytic anaemia being the most common. The main defect is a failure of B-cell diff erentiation into memory B cells and plasma cells. 50% of patients have reduced B-cell counts. Diminished antibody production results in increased susceptibility to recurrent bacterial infections. Intravenous immunoglobulin replacement reduces the frequency of recurrent bacterial infections, but does not prevent the development of chronic lung disease, granulomatous diseases, or malignancy. Half of CVID patients also have T-cell lymphocyte abnormalities leading to disseminated fungal and viral infections, in particular with the herpes viridae. Patients have reduced CD4 counts and regulatory T cells. By contrast, there is an expansion in the CD8 numbers leading to an inverted CD4/CD8 ratio. IVIg also provides suffi cient herpes simplex virus-specifi c IgG to neutralise or opsonise the virus. No established role of antimicrobial prophylaxis exists, but the annual infl uenza vaccine (inactivated) is recommended. CVID patients are at increased risk of developing cancer; however there are no current screening guidelines. This case is a reminder that CVID is not exclusively a paediatric disorder and should be included in the diff erential diagnosis of adults presenting with hypogammaglobulinaemia and recurrent or atypical infections, with or without diff use lymphadenopathy.

Epidemiological, Clinical, and Histopathological Features of Breast Cancer in Haiti

Purpose Little is known about the epidemiology of breast cancer in developing countries, and Haiti has perhaps the least data of any country in the Western Hemisphere. Methods We conducted a retrospective review of all patients enrolled in an ongoing breast cancer treatment program in Port-au-Prince, Haiti, from July 1, 2013, through June 30, 2017. Data were drawn from each patients electronic medical record, paper chart, and biopsy results. Results The records of 525 women with breast cancer were reviewed for this study. The median age at presentation was 49 years (n = 507). The risk factors observed were as follows: postmenopausal, 50.8% (n = 354); nulliparity, 15.7% (n = 338); hormonal contraception use, 35.0% (n = 309); never breastfed, 20.6% (n = 316); family history of any cancer, 22.0% (n = 295); overweight, 51.5% (n = 332); and smoking, 5.0% (n = 338). Of all those staged, 83.9% (n = 447) of the patients presented with stage III/IV disease and more than half delayed care for > 12 months after first noticing a breast mass. For the subset of tumors for which estrogen receptor (ER; n = 245) and human epidermal growth factor receptor 2 (HER2; n = 179) status was available, the prevalence of ER-positive tumors was 51.8%, of HER2-positive tumors was 19.6%, and of triple-negative tumors was 38.5%. The 12-month mortality rate (n = 425) was 18.4% overall and 27.5% for those who presented with stage IV disease. Median survival was not reached. Conclusion Breast cancer in Haiti presents at an early age and advanced stage. Triple-negative, ER-negative, and high-grade tumors are common. Delays in seeking care and incomplete treatment likely contribute to the high mortality rate; however, as in black women in the United States, the distribution of tumor types may contribute to disparate outcomes.

Bevacizumab Eligibility in Patients with Metastatic and Recurrent Cervical Cancer: A Retrospective Review:

Objective: Bevacizumab is approved for use in combination with chemotherapy for metastatic/recurrent cervical cancer (CC), with increased survival/response rates. However, use of bevacizumab is not always feasible or safe. The purpose of this study was to identify the percentage of metastatic/recurrent CC patients at our institution who would have been eligible to receive bevacizumab. Methods: A retrospective study was conducted to identify metastatic/recurrent CC patients treated at UFHealth between 2006 and 2016. Chart review was performed to determine if the patient met bevacizumab eligibility criteria. Results: In total, 79 patients with metastatic/recurrent CC were identified; 85.5% would have been ineligible to receive bevacizumab, and 14.5% would have been eligible. The most common reason for exclusion was active bleeding (68.4%); 94% of which was vaginal. In all, 27.6% would be excluded due to poor renal function, and 23.7% due to poor performance status (PS). Conclusions: Despite improved survival, only 14.5% of metastatic/recurrent CC patients treated over a 10-year period would have been eligible to receive bevacizumab. Most patients would have been excluded due to active bleeding, most commonly vaginal bleeding, a common complication from their disease. Identifying novel therapies for metastatic/recurrent CC patients with improved safety profiles that would allow for their use in this challenging population is critical.

Gemcitabine-induced chronic systemic capillary leak syndrome

A 56-year-old woman presented with anasarca, hypoalbuminaemia and hypotension following cycle 3 day 1 of adjuvant gemcitabine for stage II pancreatic cancer. Due to the temporal nature of presentation, suspicion for gemcitabine-induced capillary leak syndrome was included in the differential diagnosis. Vascular endothelial growth factor levels were elevated at 707 pg/mL (reference range: 9–86 pg/mL). Corticosteroids were initiated, resulting in complete resolution of symptoms and hypotension. The patient suffered relapse of symptoms on discontinuation of steroids, further supporting chronic capillary leak syndrome.

Development of a Breast Cancer Treatment Program in Port-au-Prince, Haiti: Experiences From the Field

Purpose The nonprofit Project Medishare launched a breast cancer treatment program in Port-au-Prince in July 2013 to address the demand for breast cancer care in Haiti. We outline the development of the program, highlight specific challenges, and discuss key considerations for others working in global oncology. Methods We reflected on our experiences in the key areas of developing partnerships, building laboratory capacity, conducting medical training, using treatment algorithms, and ensuring access to safe, low-cost chemotherapy drugs. We also critically reviewed our costs and quality measures. Results The program has treated a total of 139 patients with breast cancer with strong adherence to treatment regimens in 85% of patients. In 273 chemotherapy administrations, no serious exposure or adverse safety events were reported by staff. The mortality rate for 94 patients for whom we have complete data was 24% with a median survival time of 53 months. Our outcome data were likely influenced by stage at presentation, with more than half of patients presenting more than 12 months after first noticing a tumor. Future efforts will therefore focus on continuing to improve the level of care, while working with local partners to spread awareness, increase screening, and get more women into care earlier in the course of their disease. Conclusion Our experiences may inform others working to implement protocol-based cancer treatment programs in resource-poor settings and can provide valuable lessons learned for future global oncology efforts.

Src inhibition through a phase II study of 5-fluorouracil, oxaliplatin, plus dasatinib (FOLFOX-D) in first-line metastatic pancreatic adenocarcinoma.

319 Background: Triplet drug therapy is now a standard for metastatic pancreatic cancer (mPCa) but limited in use due to toxicity. Src is constitutively active in mPCa and associated with increased chemoresistance. Src inhibition increases oxaliplatin (ox) activity. Inhibition of Src reduces tumor expression of thymidylate synthase with subsequent 5FU chemoresistance reversal. Dasatinib (D) is an oral multi-tyrosine kinase inhibitor (TKI) capable of inhibiting Src. Demonstrating activity of this triplet combination therapy in mPCa represents a scientifically rational approach to a clinical unmet need. Methods: Eligible pts have biopsy proven, RECIST measurable disease with no prior therapy for met disease and at least 6 months since completing adjuvant therapy, ECOG PS 0-2 and adequate organ function. Pts received standard doses of mFOLFOX6 chemotherapy (5-FU/LV 400mg/m2 bolus and Ox 85 mg/m2 D1; 5-FU 2,400 mg/m2CIVI x 46h D1-2) with continuous D (150 mg PO daily) repeated q14d with tumor assessments q8w....