Allogeneic Hematopoietic Cell Transplantation for Adult T Cell Acute Lymphoblastic Leukemia.

Allogeneic hematopoietic cell transplantation (HCT) is recommended for patients with T cell acute lymphoblastic leukemia (T-ALL) in second or later complete remission (CR) and high-risk patients in first CR. Given its relative rarity, data on outcomes of HCT for T-ALL are limited. We conducted a multicenter retrospective cohort study using data from 208 adult patients who underwent HCT between 2000 and 2014 to describe outcomes of allogeneic HCT for T-ALL in the contemporary era. The median age at HCT was 37 years, and the majority of patients underwent HCT in CR, using total body irradiation (TBI)-based myeloablative conditioning regimens. One-quarter of the patients underwent alternative donor HCT using a mismatched, umbilical cord blood, or haploidentical donor. With a median follow up of 38 months, overall survival at 5 years was 34%. The corresponding cumulative incidence of non-relapse mortality and relapse was 26% and 41%, respectively. In multivariable analysis, factors significantly associated with overall survival were the use of TBI (HR, 0.57; P = .021), age >35 years (HR, 1.55; P = .025), and disease status at HCT (HR, 1.98; P = .005 for relapsed/refractory disease compared with CR). Relapse was the most common cause of death (58% of patients). Allogeneic HCT remains a potentially curative option in selected patients with adult T-ALL, although relapse is a major cause of treatment failure.

External Validation of Generic and Cancer-Specific Risk Stratification Tools in Patients With Pulmonary Embolism and Active Cancer.

Background: Numerous risk stratification tools exist to predict early post-pulmonary embolism (PE) mortality; however, few were specifically designed for use in patients with cancer. This study sought to evaluate the performance of 3 cancer-specific (RIETE, POMPE-C, and Font criteria) and 3 generic (Hestia, Pulmonary Embolism Severity Index [PESI], and Geneva prognostic score [GPS]) risk stratification tools for predicting 30-day post-PE mortality in patients with active cancer. Methods: We identified consecutive, adult, objectively confirmed patients with PE and active cancer presenting to our institution from November 2010 to January 2014. We calculated the proportion of patients categorized as low or high risk by each of the 6 risk stratification tools and determined each tools' accuracy for predicting 30-day all-cause mortality. Results: A total of 124 patients with PE and active cancer were included (mean age, 66.2 years; 46.0% with concurrent deep vein thrombosis; 49.2% with metastatic disease; and 46.8%, 16.9%, and 11.3% receiving chemotherapy, radiation, or both, respectively). Mortality at 30 days occurred in 25 patients (20.2%). The cancer-specific tools (POMPE-C, RIETE, and Font criteria) categorized between 32% and 43% of patients as low risk and displayed sensitivities and specificities of 88.0% to 96.0% and 38.4% to 52.5%, respectively. The generic PESI and Hestia tools had sensitivities >96.0%, but classified <19% of patients as low risk; specificity of these tools were low (PESI, 6.1%; Hestia, 23.2%). Although the final noncancer tool, GPS, classified 43.5% of patients as low risk, it did so with a sensitivity of 52.0% and specificity of 42.4%. Conclusions: When risk-stratifying PE in patients with active cancer, cancer-specific tools appeared to exhibit better prognostic accuracy than their generic counterparts. POMPE-C, RIETE, and the Font criteria identified a substantially greater proportion of patients with PE likely to survive to 30 days with comparable sensitivity to the generic tools.

Cost-effectiveness analysis of 1st through 3rd line sequential targeted therapy in HER2-positive metastatic breast cancer in the United States.

PURPOSE: Based on available phase III trial data, we performed a cost-effectiveness analysis of different treatment strategies that can be used in patients with newly diagnosed HER2-positive metastatic breast cancer (mBC). PATIENTS AND METHODS: We constructed a Markov model to assess the cost-effectiveness of four different HER2 targeted treatment sequences in patients with HER2-positive mBC treated in the U.S. The model followed patients weekly over their remaining life expectancies. Health states considered were progression-free survival (PFS) 1st to 3rd lines, and death. Transitional probabilities were based on published phase III trials. Cost data (2015 US dollars) were captured from the U.S. Centers for Medicare and Medicaid Services (CMS) drug payment table and physician fee schedule. Health utility data were extracted from published studies. The outcomes considered were PFS, OS, costs, QALYs, the incremental cost per QALY gained ratio, and the net monetary benefit. Deterministic and probabilistic sensitivity analyses assessed the uncertainty around key model parameters and their joint impact on the base-case results. RESULTS: The combination of trastuzumab, pertuzumab, and docetaxel (THP) as first-line therapy, trastuzumab emtansine (T-DM1) as second-line therapy, and lapatinib/capecitabine third-line resulted in 1.81 QALYs, at a cost of $335,231.35. The combination of trastuzumab/docetaxel as first line without subsequent T-DM1 or pertuzumab yielded 1.41 QALYs, at a cost of $175,240.69. The least clinically effective sequence (1.27 QALYs), but most cost-effective at a total cost of $149,250.19, was trastuzumab/docetaxel as first-line therapy, T-DM1 as second-line therapy, and trastuzumab/lapatinib as third-line therapy. CONCLUSION: Our results suggest that THP as first-line therapy, followed by T-DM1 as second-line therapy, would require at least a 50 % reduction in the total drug acquisition cost for it to be considered a cost-effective strategy.

Prevention and Screening in Hereditary Breast and Ovarian Cancer.

In recent years, we have learned a great deal about pathogenic mutations that increase the risk of breast and ovarian cancer, particularly mutations in the BRCA1 and BRCA2 genes. Here we review current guidelines on breast and ovarian cancer screening, prophylactic surgery, and other risk-reduction strategies in patients with these mutations, and we detail the data that drive these recommendations. We also discuss guidelines on screening and management for other cancers associated with BRCA1 and BRCA2, such as male breast cancer, pancreatic cancer, and prostate cancer. Discussions about genetic testing have become more complex with the advent of panel testing, which often allows for testing of a more comprehensive panel of genes than traditional BRCA1 and BRCA2 testing, but which is also associated with a higher likelihood of obtaining results with less clear data to inform management. It is difficult to come to a consensus on how best to address the varied and potentially challenging situations that may arise from genetic testing. The complexity inherent in managing these cases makes a multidisciplinary team-including medical oncologists, surgical oncologists, genetic counselors, reproductive endocrinologists, and medical ethicists-critical to optimization of care.

Survival of patients with de-novo metastatic breast cancer: analysis of data from a large breast cancer-specific private practice, a university-based cancer center and review of the literature.

Approximately 6 % of patients with breast cancer are diagnosed with de-novo distant metastases. We set out to look at two cohorts of patients seen at breast cancer-specific practices, compare the results to other reports and larger databases, and see how advances in treatment have impacted overall survival (OS). The records from a large breast cancer oncology private practice and a second data set from the University of Miami/Sylvester Comprehensive Cancer Center (UM/SCCC) tumor database were, retrospectively, reviewed to identify patients with de-novo metastases. We included those patients identified to have metastatic disease within 3 months of diagnosis of a breast primary cancer. Patients diagnosed between 1996 and 2006 were chosen for our study population. The OS for the private practice was 41.0 months (46.0 for ER positive and 26.0 for ER negative) and 36.0 months for UM/SCCC (52 months for ER positive and 36 months for ER negative). ER negativity and CNS- or visceral-dominant disease were associated with a significantly worse prognosis within the private practice. Dominant site was associated with a significantly worse prognosis within the UM/SCCC database but with a trend also for ER negativity. Age and ethnicity did not contribute significantly to the survival of patients within either cohort. The median survival in both cohorts and most other reported series was larger than that seen in the surveillance, epidemiology, and end results program and the National Cancer Database. The median OS among patients with de-novo metastatic breast cancer treated within two breast-specific oncology practices was over 3 years, which appears better than larger, more inclusive databases and publications from earlier decades.

Secondary Adult Acute Myeloid Leukemia: a Review of Our Evolving Understanding of a Complex Disease Process.

OPINION STATEMENT: Secondary AML (s-AML) encompasses AML evolving from myelodysplasia (AML-MDS) and treatment-related AML (t-AML) after exposure to chemotherapy, radiation, or environmental toxins. S-AML has traditionally been considered a devastating disease, affecting a vulnerable population of heavily pretreated, older adults. A limited understanding of disease pathogenesis/heterogeneity and lack of effective treatments have hampered overall improvements in patient outcomes. With the recent understanding that the secondary nature of sAML does not by itself incur a poor prognosis and incorporation of cytogenetics and molecular genetics into patient care and the advancement of treatment, including improved supportive care, novel chemotherapeutics agents, and nonmyeloablative conditioning regimens as part of allogeneic hematopoietic cell transplantation (HCT), modest gains in survival and quality of life are beginning to be seen among patients with s-AML.

Cost-effectiveness analysis of everolimus plus exemestane versus exemestane alone for treatment of hormone receptor positive metastatic breast cancer.

Everolimus in combination with exemestane significantly improved progression-free survival compared to exemestane alone in patients previously treated with non-steroidal aromatase inhibitors in the BOLERO-2 trial. As a result, this combination has been approved by the food and drug administration to treat postmenopausal women with hormone receptor positive and HER2 negative metastatic breast cancer. A cost-effectiveness analysis was conducted to determine whether everolimus represents good value for money, utilizing data from BOLERO-2. A decision-analytic model was used to estimate the incremental cost-effectiveness ratio between treatment arms of the BOLERO-2 trial. Costs were obtained from the Center for Medicare Services drug payment table and physician fee schedule. Benefits were expressed as quality-adjusted progression-free survival weeks (QAPFW) and quality-adjusted progression-free years (QAPFY), with utilities/disutilities derived from the literature. Deterministic and probabilistic sensitivity analyses were performed. A willingness to pay threshold of 1-3 times the per capita gross domestic product was adopted, as per the definition of the World Health Organization. The U.S. per capita gross domestic product in 2013 was $49,965; thus, a threshold varying between $49,965 and $149,895 was considered. Everolimus/exemestane had an incremental benefit of 11.88 QAPFW (0.22 QAPFY) compared to exemestane and an incremental cost of $60,574. This translated into an ICER of $265,498.5/QAPFY. Univariate sensitivity analyses showed important variations of the ICER, ranging between $189,836.4 and $530,947/QAPFY. A tornado analysis suggested that the key drivers of our model, by order of importance, included health utility value for stable disease, everolimus acquisition costs, and transition probabilities from the stable to the progression states. The Monte-Carlo simulation showed results that were similar to the base-case analysis. This cost-effectiveness analysis showed that everolimus plus exemestane is not cost-effective compared to exemestane alone. Further research is needed to investigate the cost-effectiveness of the drug combination within sub-groups of the population studied in BOLERO-2.

A retrospective study evaluating a fixed low dose capecitabine monotherapy in women with HER-2 negative metastatic breast cancer.

To determine if a low fixed dosing strategy of capecitabine would produce comparable clinical activity with less adverse toxicities compared to published data with higher doses in the setting of metastatic breast cancer (mBC). We retrospectively analyzed patients treated with a low fixed dose of capecitabine (CAPE-L) at 1,000 mg twice daily for 14 days every 21 days. Outcomes included clinical benefit rate (CBR), overall response rates (ORR), time to progression (TTP), and overall survival (OS). A historical comparison group of mBC patients treated on 12 prior trials at the package-insert dose of capecitabine (n = 1,949) was utilized. Eighty-six patients were analyzed in our cohort. Positive hormone receptor status (79.1 vs. 50.6 %), and capecitabine as first-line chemotherapy (44.2 vs. 16.5 %) were more frequent in our cohort relative to the historical comparison. The median starting dose in our cohort was 633.5 mg/m(2). The CBR was similar between the CAPE-L and the standard dose cohorts (55.8 vs. 49.5 %), as was ORR (24.3 vs. 24 %), and median TTP (7 mo, 95 % CI 5.5-8.5 vs. 5.1 mo, 95 % CI 4.5-5.7). Median OS was longer in our cohort (24 mo, 95 % CI 16.8-31.2) than the historic standard dose cohort (12.1 mo, 95 % CI 9.6-14.4), a difference that was likely explained by the higher proportion of patients in the CAPE-L cohort who received capecitabine as first-line chemotherapy and who had hormone receptor positive disease. As expected, adverse events were less frequent with CAPE-L. We found that CAPE-L, which translates into a dose of 600-650 mg/m(2), appeared to have good clinical efficacy and acceptable toxicity.

Cost-effectiveness of precision medicine in gastrointestinal stromal tumor and gastric adenocarcinoma.

Over the past 20 years, with the incorporation of genetic sequencing and improved understanding regarding the mechanisms of cancer growth/metastasis, novel targets and their associated treatments have emerged in oncology and are now regularly incorporated into the clinical care of patients in the US. Novel, more tumor-specific, non-chemotherapy agents, including agents that are commonly used in the treatment of patients with gastric adenocarcinoma (GA) and gastrointestinal stromal tumor (GIST), fall under a broader treatment strategy, termed "precision medicine". While diagnostic testing and associated treatments in metastatic GA (mGA) are costly and may produce marginal benefit, those associated with GIST, despite being costly, produce significant improvements in patient outcomes. Despite the significant difference in impact, the agents associated with these cancers have similar acquisition costs. In this paper, we will review the current literature regarding cost and cost-effectiveness associated with precision medicine diagnosis and treatment strategies for GA and GIST.

Cognitive Behavioral Therapy for Insomnia, Mindfulness, and Yoga in Patients With Breast Cancer with Sleep Disturbance: A Literature Review.

The number of patients with breast cancer diagnosed with sleep disturbance has grown substantially within the United States over the past 20 years. Meanwhile, there have been significant improvements in the psychological treatment of sleep disturbance in patients with breast cancer. More specifically, cognitive behavioral therapy for insomnia (CBT-I), mindfulness, and yoga have shown to be 3 promising treatments with varying degrees of benefit, supporting data, and inherent limitations. In this article, we will outline the treatment approach for sleep disturbance in patients with breast cancer and conduct a comprehensive review of CBT-I, mindfulness, and yoga as they pertain to this patient population.

Cost-Effectiveness of Immune Checkpoint Inhibition in BRAF Wild-Type Advanced Melanoma.

Purpose Patients who are diagnosed with stage IV metastatic melanoma have an estimated 5-year relative survival rate of only 17%. Randomized controlled trials of recent US Food and Drug Administration-approved immune checkpoint inhibitors-pembrolizumab (PEM), nivolumab (NIVO), and ipilumumab (IPI)-demonstrate improved patient outcomes, but the optimal treatment sequence in patients with BRAF wild-type metastatic melanoma remains unclear. To inform policy makers about the value of these treatments, we developed a Markov model to compare the cost-effectiveness of different strategies for sequencing novel agents for the treatment of advanced melanoma. Materials and Methods We developed Markov models by using a US-payer perspective and lifetime horizon to estimate costs (2016 US$) and quality-adjusted life years (QALYs) for treatment sequences with first-line NIVO, IPI, NIVO + IPI, PEM every 2 weeks, and PEM every 3 weeks. Health states were defined for initial treatment, first and second progression, and death. Rates for drug discontinuation, frequency of adverse events, disease progression, and death obtained from randomized phase III trials were used to determine the likelihood of transition between states. Deterministic and probabilistic sensitivity analyses were conducted to evaluate model uncertainty. Results PEM every 3 weeks followed by second-line IPI was both more effective and less costly than dacarbazine followed by IPI then NIVO, or IPI followed by NIVO. Compared with the first-line dacarbazine treatment strategy, NIVO followed by IPI produced an incremental cost effectiveness ratio of $90,871/QALY, and first-line NIVO + IPI followed by carboplatin plus paclitaxel chemotherapy produced an incremental cost effectiveness ratio of $198,867/QALY. Conclusion For patients with treatment-naive BRAF wild-type advanced melanoma, first-line PEM every 3 weeks followed by second-line IPI or first-line NIVO followed by second-line IPI are the most cost-effective, immune-based treatment strategies for metastatic melanoma.

Detecting cancer: Pearls for the primary care physician.

Five-year survival rates have improved over the past 40 years for nearly all types of cancer, partially thanks to early detection and prevention. Since patients typically present to their primary care physician with initial symptoms, it is vital for primary care physicians to accurately diagnose common cancers and to recognize unusual presentations of highly curable cancers such as Hodgkin lymphoma and testicular cancers, for which the 5-year overall survival rates are greater than 85%. This paper reviews these cancers and provides clinically relevant pearls from an oncologic perspective for physicians who are the first point of contact.

Economics of ramucirumab for metastatic colorectal cancer.

INTRODUCTION: Despite its FDA approval and incorporation into the National Comprehensive Cancer Network (NCCN) treatment guidelines, ramucirumab (RAM) is associated with a drug acquisition cost that is substantially higher than other approved options. Given its substantial cost, the presence of a viable alternative treatment option, and its minimal survival improvement, the usefulness of RAM in clinical practice has been called into question. Areas covered: In this paper, we outline the cost, benefits, and economic implications of RAM from a US perspective, as it is used in the treatment of mCRC. We also dissect its use in other tumor types and in other healthcare systems around the world, and briefly compare it with similar drugs targeting the vascular endothelial growth factor pathway. We used the search engine PubMed using the following as search terms: cost-effectiveness; ramucirumab; metastatic colon cancer; angiogenesis; and value-based medicine. Expert commentary: The use of ramucirumab in the treatment of mCRC serves as a microcosm of the worsening healthcare crisis within the US and the ongoing controversy regarding oncology drug costs, benefits, and value. Therefore, there must be a joint effort in moving towards value based pricing models.

A Review of Systemic Treatment in Metastatic Triple-Negative Breast Cancer.

Patients with breast cancer along with metastatic estrogen and progesterone receptor (ER/PR)- and human epidermal growth factor receptor 2 (HER2)-negative tumors are referred to as having metastatic triple-negative breast cancer (mTNBC) disease. Although there have been many new treatment options approved by the Food and Drug Administration for ER/PR-positive and Her2/neu-amplified metastatic breast cancer, relatively few new agents have been approved for patients with mTNBC. There have been several head-to-head chemotherapy trials performed within the metastatic setting, and much of what is applied in clinical practice is extrapolated from chemotherapy trials in the adjuvant setting, with taxanes and anthracyclines incorporated early on in the patient's treatment course. Select synergistic combinations can produce faster and more significant response rates compared with monotherapy and are typically used in the setting of visceral threat or symptomatic disease. Preclinical studies have implicated other possible targets and mechanisms in mTNBC. Ongoing clinical trials are underway assessing new chemotherapeutic strategies and agents, including targeted therapy and immunotherapy. In this review, we evaluate the standard systemic and future treatment options in mTNBC.

Metastatic Colorectal Cancer: A Systematic Review of the Value of Current Therapies.

To evaluate, from a US payer perspective, the cost-effectiveness of treatment strategies for metastatic colorectal cancer (mCRC), we performed a systematic review of published cost-effectiveness analyses. We identified 14 papers that fulfilled our search criteria and revealed varying levels of value among current treatment strategies. Older agents such as 5-fluorouracil, irinotecan, and oxaliplatin provide high-value treatments. More modern agents targeting the EGFR or VEGF pathways, such as bevacizumab, cetuximab, and panitumumab, do not appear to be cost-effective treatments at their current costs. The analytical methods used within the papers varied widely, and this variation likely plays a significant role in the heterogeneity in incremental cost-effectiveness ratios. The cost-effectiveness of current treatment strategies for mCRC is highly variable. Drugs recently approved by the US Food and Drug Administration for mCRC are not cost-effective, and this is primarily driven by high drug costs.

Strategies for individualizing management of patients with metastatic melanoma: a managed care perspective.

The management of metastatic melanoma has been revolutionized in recent years with the development of both targeted therapy and immunotherapy. Although potentially extending the life expectancy for patients, these therapies also significantly increase the healthcare expenditure. In this paper, we review the monthly costs for drugs approved by the FDA since 2011. Additionally, factors that affect the cost, such as dosing strategies, biomarkers, combination therapies, and political/legislative issues, will be discussed.

Improved clinical outcomes associated with vitamin D supplementation during adjuvant chemotherapy in patients with HER2+ nonmetastatic breast cancer.

BACKGROUND: Vitamin D (VD) supplementation has pleiotropic effects that extend beyond their impact on bone health, including the disruption of downstream VD receptor signaling and human epidermal growth factor receptor 2 (HER2) signaling through the ErbB2/AKT/ERK pathway. In the present study, we examined our institutional experience with patients having nonmetastatic HER2-positive (HER(+)) breast cancer and hypothesized that those patients who received VD supplementation during neoadjuvant chemotherapy would have improved long-term outcomes. PATIENTS AND METHODS: We performed a retrospective review of all patients (n = 308) given trastuzumab-based chemotherapy between 2006 and 2012 at the University of Miami/Sylvester Comprehensive Cancer Center (UM/SCCC). We identified 2 groups of patients for comparison-those who received VD supplementation during neoadjuvant chemotherapy (n = 134) and those who did not (n = 112). Univariate and multivariate Cox proportional hazard regression models were fitted to overall survival (OS) and disease-free survival (DFS). RESULTS: More than half of the patients received VD during neoadjuvant chemotherapy (54.5%), with 60% receiving a dose < 10,000 units/wk and 33.3% having a VD deficiency at the start of therapy. In our final multivariate model, VD use was associated with improved DFS (hazard ratio [HR], 0.36; 95% confidence interval [CI], 0.15-0.88; P = .026], whereas larger tumor size was associated with worse DFS (HR, 3.52; 95% CI, 1.06-11.66; P = .04). There were no differences in OS based on any of the categories, including VD use, tumor size, number of metastatic lymph nodes, age at diagnosis, or lymphovascular invasion (LVI). CONCLUSION: VD supplementation in patients with nonmetastatic HER2(+) breast cancer is associated with improved DFS.

Defining the survival benchmark for breast cancer patients with systemic relapse.

BACKGROUND: Our original paper, published in 1992, reported a median overall survival after first relapse in breast cancer of 26 months. The current retrospective review concentrates more specifically on patients with first systemic relapse, recognizing that subsets of patients with local recurrence are potentially curable. METHODS: Records of 5,168 patients from a largely breast-cancer-specific oncology practice were reviewed to identify breast cancer patients with their first relapse between 1996 and 2006 after primary treatment. There were 189 patients diagnosed with metastatic disease within 2 months of being seen by our therapeutic team and 101 patients diagnosed with metastatic disease greater than 2 months. The patients were divided in order to account for lead-time bias than could potentially confound the analysis of the latter 101 patients. RESULTS: Median survival for our primary study population of 189 patients was 33 months. As expected, the median survival from first systemic relapse (MSFSR) for the 101 patients excluded because of the potential for lead-time bias was better at 46 months. Factors influencing prognosis included estrogen receptor (ER) status, disease-free interval (DFI), and dominant site of metastasis. Compared with our original series, even with elimination of local-regional recurrences in our present series, the median survival from first relapse has improved by 7 months over the past two decades. CONCLUSION: The new benchmark for MSFSR approaches 3 years.

Gastric small-cell carcinoma found on esophagogastroduodenoscopy: a case report and literature review.

Introduction. Characterized as an undifferentiated, neuroendocrine tumor arising from totipotent stem cells, small-cell carcinoma (SCC) most commonly arises from the lung. Extrapulmonary small-cell carcinomas (ESCC) are rare and account for only four percent of SCC. Gastric ESCC, more commonly seen in Japanese male patients in their seventh decade of life, accounts for approximately 0.1 percent of ESCC. Case Presentation. A 75-year-old Hispanic male presented with a several week history of worsening epigastric pain with nausea and vomiting. Computer tomography (CT) of the abdomen and pelvis showed a large heterogeneous mass involving the posterior gastric wall with diffuse extension into the gastric cardia. Esophagogastroduodenoscopy (EGD) revealed a large fungating mass in the lesser curvature of the stomach. Biopsy of the mass revealed small-cell carcinoma of the stomach. The patient was diagnosed with extensive/stage 4 disease and started on chemoradiation. Discussion. Our case, of a very rare condition highlights, the importance of recognizing atypical pathologic diagnoses. More research will need to be conducted with GSCC patients in order to better characterize disease pathogenesis, genetic mutations, and optimal disease management. The hope is to identify biomarkers that will identify patients earlier in their disease course when cure is possible.

A De Novo Germline APC Mutation (3927del5) in a Patient with Familial Adenomatous Polyposis: Case Report and Literature Review.

INTRODUCTION: Characterized by the development of hundreds to thousands of colonic adenomas, classic familial adenomatous polyposis (FAP) is one of the most common hereditary syndromes associated with an increased risk of colorectal cancer. Several studies have attempted to correlate specific APC mutations with clinical phenotype.6 However, there is considerable variability in the expression of specific phenotypes within families and among individuals with identical mutations.7 CASE PRESENTATION: A 30 year-old Hispanic female presented to the emergency department with a 2-week history of persistent, worsening, left lower quadrant abdominal pain. She had no family history of malignancy. Sigmoidoscopy revealed innumerable polyps in the rectum and sigmoid colon and a large mass in the sigmoid colon. Biopsy of the mass revealed a moderately differentiated adenocarcinoma invading the subserosa. Endoscopy revealed innumerable polyps. Genetic testing of the patient via southern blot revealed a germline APC mutation 3927del5, resulting in a premature truncation of the APC protein at amino acid position 1312. CONCLUSION: Genetic information has only recently started being incorporated into clinical care. More research and randomized clinical trials need to be conducted to definitively characterize random mutations. Once these mutations are further understood, FAP patients may be able to be risk stratified and this may ultimately improve the screening, diagnosis, and treatment of this rare condition.