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Background KRAS mutations reported in non-small cell lung cancer (NSCLC) represent a significant percentage of patients diagnosed with NSCLC. However, there still remains no therapeutic option designed to target KRAS. In an era with immunotherapy as a dominant treatment option in metastatic NSCLC, the role of immunotherapy in. Kras mutated patients is not clear. Methods Eligible patients diagnosed with NSCLC and found to have a KRAS mutation were identified in an institutional lung cancer database. Demographic, clinical, and molecular data was collected and analyzed. Results A total of 60 patients were identified for this retrospective analysis. Majority of patients were Caucasian (73%), diagnosed with stage IV (70%) adenocarcinoma (87%), and had a KRAS codon 12 mutation (78%). Twenty percent of patients were treated with immunotherapy. Median overall survival was 28 months in the cohort and patients who received immunotherapy were found to have better survival versus those who did not (33 vs. 22 months, P=0.31). Furthermore, there was an association between high survival and patients who received immunotherapy (P=0.007). Conclusions Patients with KRAS mutations have a unique co-mutation phenotype that requires further investigation. Immunotherapy seems to be an effective choice of treatment for KRAS positive patients in any treatment-line setting and yields better outcomes than conventional chemotherapy. The relationship between immunotherapy and KRAS mutations requires further studies to confirm survival advantage.

Background Management of acute lymphoblastic leukemia (ALL) in a socioeconomically vulnerable population without ready access to a hematopoietic stem cell transplant (HCT) center and clinical trials is challenging. Data regarding the outcomes of such patients are sparse. Patients and Methods This retrospective analysis included 90 consecutive patients with ALL who presented to Harbor-UCLA between 2003 and 2018. The primary objective was overall survival (OS), whereas secondary objectives included leukemia-free survival, toxicities of therapy, and referral for HCT and incidence of successful HCT. Results Most patients were male (56.7%) and Hispanic (72.2%). The median age of diagnosis was 36 years (range, 18-63 years). The median OS was 26.8 months (95% confidence interval [CI], 17.4-59.0 months). In patients who achieved complete remission with therapy, the median leukemia-free survival was 16.4 months. Fifty percent of patients experienced at least 1 episode of bacteremia, and nearly 25% of patients developed an invasive fungal infection. Thirty-six percent (n = 32) of patients were referred for HCT. The referral rate increased over time, which led to improved OS in patients who underwent evaluation at a tertiary cancer center (hazard ratio, 0.44; 95% CI, 0.21-0.89; P = .02). Patients who underwent HCT had significantly better OS compared with those who did not (OS not reached vs. 21.9 months; hazard ratio, 0.16; 95% CI, 0.04-0.68; P = .01). Conclusion Risk stratification and evidence-based treatment approaches are important for patients with ALL treated in a resource-limited setting. Most patients can be induced successfully and achieve complete remission with therapy. Partnership with a cancer center with early referral for HCT can facilitate curative HCT to be performed.

Supplemental Digital Content is available in the text., Introduction: Anaplastic lymphoma kinase (ALK) gene rearrangements are observed in about 4% to 8% non–small cell lung cancer (NSCLC). ALK+ tumors have been associated with increased pleural and pericardial disease. Our primary objective was to determine the uncommon sites of metastasis of ALK+ NSCLC. Secondary objectives included study of coexisting mutations and factors impacting survival of ALK+ NSCLC. Methods: All patients with metastatic ALK+ NSCLC at the City of Hope Cancer Center in Duarte, California from 2010 to 2017 were selected for retrospective chart review. The demographic variables were collected. The molecular statuses of patients were evaluated through commercially available platforms for next-generation sequencing. Three-dimensional volumetric images were generated for the primary lesion and different sites of metastasis. Results: Sixty two patients with ALK+ NSCLC were identified from 2010 to 2017. The median age was 59 with 36 (58%) female individuals and only 20 (32%) smokers. Twenty four patients had uncommon sites of metastasis which were thyroid, soft tissue, chest and abdominal wall, spleen, peritoneum, omentum, kidney, and ovary. Common characteristics of the primary lesions were right upper lobe location (N=23 [37%]), oval shape (N=22 [35%]), irregular margins (N=26 [42%]), solid lesions (N=27 [44%]), presence of pleural contact or effusion (N=22 [35%]). Twenty four patients had next-generation sequencing testing which showed coexisting mutations such as TP53 (N=8), EGFR (N=5), KRAS (N=3). Patients with uncommon sites of metastasis had a decreased median survival compared with common sites (39 vs. 82 m, P=0.046). Conclusion: In NSCLC, ALK rearrangements may not be mutually exclusive mutations and can present with unique radiographic patterns. Patients with uncommon sites of metastasis may have worse outcomes.

Vinorelbine tartrate is a semi‐synthetic vinca alkaloid and an inhibitor of microtubule polymerization with demonstrated antitumor properties across a spectrum of cancers. The pharmacokinetics of vinorelbine may be altered in individuals with liver dysfunction, considering that hepatic metabolism serves as the predominant route of drug elimination. This article reports the pharmacokinetics and safety of vinorelbine in patients with varying degrees of hepatic impairment, including dosing recommendations in this population., Background. Vinorelbine has demonstrated anticancer activity and is primarily metabolized in the liver. This single‐institution, phase I pilot study describes the safety and pharmacokinetics of vinorelbine in patients with varying degrees of hepatic impairment. Materials and Methods. Patients with treatment‐refractory solid tumors were enrolled into treatment arms based on vinorelbine dose (weekly infusions of 7.5–30 mg/m2) and liver function (normal liver function, mild, moderate, or severe liver dysfunction). Vinorelbine pharmacokinetics were evaluated to describe its relationship with liver function. Indocyanine green (ICG) clearance was assessed for correlation with pharmacokinetics. Results. Forty‐seven patients were enrolled, and a total of 108 grade 3–4 treatment‐related adverse events (AEs) occurred. Of these, grade 3–4 myelosuppression was the most common (34.3%). Thirty‐three (30.6%), 22 (20.4%), and 9 (8.3%) grade 3–4 AEs were observed in the vinorelbine 20 mg/m2/severe, 15 mg/m2/moderate, and 7.5 mg/m2/severe liver dysfunction groups, respectively, with the majority being nonhematologic toxicities. ICG clearance decreased as liver function worsened. Vinorelbine pharmacokinetics were not correlated with ICG elimination or the degree of liver dysfunction. Conclusion. For patients with severe liver dysfunction (bilirubin >3.0 mg/dL), vinorelbine doses ≥7.5 mg/m2 are poorly tolerated. The high incidence of grade 3–4 AEs with 15 mg/m2 vinorelbine in moderate liver dysfunction (bilirubin 1.5–3.0 mg/dL) raises concerns for its safety in this population. Vinorelbine pharmacokinetics are not affected by liver dysfunction; however, levels of the active metabolite 4‐O‐deacetylvinorelbine were not measured and may be higher in patients with liver dysfunction if its elimination is impacted by liver impairment to a greater degree than the parent drug. Implications for Practice. Vinorelbine remains widely prescribed in advanced malignancies and is under development in immunotherapy combinations. Given vinorelbine is primarily hepatically metabolized, understanding its safety and pharmacokinetics in liver dysfunction remains paramount. In this phase I pilot study, weekly vinorelbine at doses ≥7.5 mg/m2 is poorly tolerated in those with severe liver dysfunction. Furthermore, a high incidence of grade 3–4 toxicities was observed with vinorelbine at 15 mg/m2 in those with moderate liver dysfunction. Vinorelbine pharmacokinetics do not appear affected by degree of liver dysfunction. Further evaluation of levels of the free drug and active metabolites in relationship to liver function are warranted.

Lung cancer remains the leading cause of cancer deaths in the world with 1.69 million deaths in 2015. A total of 85% of lung cancer cases are non-small-cell lung cancers (NSCLCs). Driver mutations associated with anaplastic lymphoma kinase (ALK) have been identified in a variety of malignancies, including NSCLC. An ALK inhibitor (crizotinib, ceritinib and alectinib) is the preferred therapeutic approach to those advanced ALK fusion variant-positive NSCLC patients. Brigatinib, a next-generation ALK inhibitor, shows promising activity in ALK-rearranged NSCLC that have previously received crizotinib with response rates in ALTA ranging from 42–50%, intracranial response 42–67% and median progression-free survival 9.2–12.9 months. Randomized Phase III trial, ALTA-1 L is investigating brigatinib in ALK inhibitor-naive patients.

Pancreatic cancer remains a deadly disease with a 5-year survival rate of only 8%. Even after surgical resection, most patients have recurrence of their cancer. Over the last 10 years, improvements in chemotherapy regimens led to a doubling in median overall survival. Here we review the management of advanced pancreatic cancer and highlight vaccine therapy as a novel modality of treatment.

Background Direct comparisons between Guardant360 (G360) circulating tumor DNA (ctDNA) and FoundationOne (F1) tumor biopsy genomic profiling in metastatic colorectal cancer (mCRC) are limited. We aim to assess the concordance across overlapping genes tested in both F1 and G360 in patients with mCRC. Materials and methods We retrospectively analyzed 75 patients with mCRC who underwent G360 and F1 testing. We evaluated the concordance among gene mutations tested by both G360 and F1 among three categories of patients: untreated, treated without, and treated with EGFR inhibitors, while considering the clonal and/or subclonal nature of each genomic alteration. Results There was a high rate of concordance in APC, TP53, KRAS, NRAS, and BRAF mutations in the treatment-naive and non-anti-EGFR-treated cohorts. There was increased discordance in the anti-EGFR treated patients in three drivers of anti-EGFR resistance: KRAS, NRAS, and EGFR somatic mutations. Based on percentage of ctDNA, discordant somatic mutations were mostly subclonal instead of clonal and may have limited clinical significance. Most discordant amplifications noted on G360 showed the magnitude below the top decile, occurred in all three cohorts of patients, and were of unknown clinical significance. Serial ctDNA in anti-EGFR treated patients showed the emergence of multiple new alterations that affected the EGFR pathway: EGFR and RAS mutations and MET, RAS, and BRAF amplifications. Conclusion G360 Next-Generation Sequencing platform may be used as an alternative to F1 to detect targetable somatic alterations in non-anti-EGFR treated mCRC, but larger prospective studies are needed to further validate our findings. Implications for practice Genomic analysis of tissue biopsy is currently the optimal method for identifying DNA genomic alterations to help physicians target specific genes but has many disadvantages that may be mitigated by a circulating free tumor DNA (ctDNA) assay. This study showed a high concordance rate in certain gene mutations in patients who were treatment naive and treated with non-anti-EGFR therapy prior to ctDNA testing. This suggests that ctDNA genomic analysis may potentially be used as an alternative to tumor biopsy to identify appropriate patients for treatment selection in mCRC, but larger prospective studies are needed to further validate concordance among tissue and ctDNA tumor profiling.

Background Oral metronomic chemotherapy, which has low toxicity, has demonstrated promising anti-tumor and anti-angiogenic properties that may lead to prolonged progression-free survival and improved response rates in patients with recurrent epithelial ovarian cancer (EOC). These effects may be enhanced by the co-administration of anti-angiogenic agents. Methods We conducted a randomized phase II clinical trial to evaluate the therapeutic benefit of oral metronomic cyclophosphamide (CTX) alone and with the anti-angiogenic drug celecoxib in patients with gynecological malignancies. 52 patients were randomly assigned to two treatments arms: 50 mg oral CTX daily alone (Arm A) or with 400 mg celecoxib twice daily (Arm B). The primary endpoint was response rate. Secondary endpoints included toxicity, time to treatment failure, and overall survival. Results In Arm A (n = 26), 3 patients (12%) had stable disease >6 months and 1 (4%) had a partial response. In Arm B, 5 (19%) had stable disease >6 months and 1 patient (4%) had a partial response. There were no significant between-group differences in overall survival (9.69 months [95% CI 3.84–13.18] vs. 12.55 months [6.67–17.61]) or in median time to treatment failure (1.84 months [1.68–2.76] vs. 1.92 months [1.64–5.22]). The most common adverse events were nausea, vomiting, and abdominal pain. Conclusions Oral metronomic CTX has activity with no major toxicities in heavily pretreated recurrent gynecological cancers and may be considered in patients with indolent disease. We did not observe any additional benefit of celecoxib treatment, though this may be due to small sample sizes.

The treatment landscape for non-small-cell lung cancer (NSCLC) has dramatically shifted over the past two decades. Targeted or precision medicine has primarily been responsible for this shift. Older paradigms of treating metastatic NSCLC with cytotoxic chemotherapy, while still important, have given way to evaluating tumor tissues for specific driver mutations that can be treated with targeted agents. Patients treated with targeted agents frequently have improved progression-free survival and overall survival compared to patients without a targetable driver mutation, highlighting the clinical benefit of precision medicine. In this chapter, we explore the historic landmark trials, the current state of the field, and potential future targets under investigation, in this exciting, rapidly evolving discipline of precision medicine in lung cancer.

Acute disseminated intravascular coagulation (DIC) is a pathological process involving dysfunction of the coagulation cascade. In this case report, we discuss a 33-year-old woman with BRAF V600E-mutated metastatic melanoma who presented in fulminant DIC with concurrent hemorrhagic and thrombotic manifestations and discuss the patient’s brief response to combination therapy. In our discussion, we highlight the current understanding of DIC and also identify opportunities for future research to elucidate the genetic aberrations in melanoma that may result in treatment resistance to combination therapy.

e20556 Background: Despite improvements in the survival of multiple myeloma (MM) patients, disparities in outcomes persist in underserved populations, in part due to variable access to treatments including autologous stem cell transplant (ASCT), a standard treatment for fit patients. Harbor-UCLA Medical Center (HUMC) is a safety net hospital in Los Angeles with a population of socially and medically vulnerable patients, many of whom possess limited English proficiency. Historically, access to ASCT at tertiary centers has been challenging for patients at HUMC. We present the outcomes for 160 newly diagnosed MM patients between 1998 and 2019 during which our referral process for ASCT markedly improved. Methods: We retrospectively analyzed 160 MM patients evaluated at HUMC between 1998 and 2019. The cohort was divided into 2 groups based on year of diagnosis: 1998-2013 and 2014-2019. Referral for and utilization of ASCT, and 5-year survival rates were recorded. Survival rates were calculated through a Kaplan-Meier analysis. Results: 160 MM patients were included in the analysis. 93 patients were diagnosed in 1998-2013 and 64 in 2014-2019. Three patients had an unknown diagnosis date. Patient characteristics are described in Table. ASCT referrals increased from 23% to 59% (P

Background Patients with cancer have a high use of health care utilization at the end of life, which can frequently involve admissions to the intensive care unit (ICU). We sought to evaluate the predictors for outcome in patients with gastrointestinal (GI) cancer admitted to the ICU for nonsurgical conditions. Patients and Methods The primary objective was to determine the predictors of hospital mortality. Secondary objectives included investigating the predictors of ICU mortality and hospital overall survival (OS). All patients with GI cancer admitted to the ICU at the University of Texas MD Anderson Cancer Center between November 2012 and February 2015 were retrospectively analyzed. Cancer characteristics, treatment characteristics, and Sequential Organ Failure Assessment (SOFA) scores were analyzed for their effects on survival. Results The characteristics of the 200 patients were as follows: 64.5% male, mean age of 60 years, median SOFA score of 6.7, and tumor types of intestinal (37.5%), hepatobiliary/pancreatic (36%), and gastroesophageal (24%). The hospital mortality was 41%, and overall 6-month mortality was 75%. In multivariate analysis, high admission SOFA score > 5, poor tumor differentiation, and duration of metastatic disease ≤7 months were associated with increased hospital mortality. For OS, high admission SOFA score > 5, poor tumor differentiation, and patients who were not on active chemotherapy because of poor performance had worse outcome. In multivariate analysis, SOFA score remained significant for OS even after excluding patients who died in the ICU. Conclusion For patients with metastatic GI cancer admitted to the ICU, SOFA score was predictive for both acute and long-term survival. A patient's chemotherapy treatment status was not predictive for hospital mortality but was for OS. The SOFA score should be utilized in all patients with GI cancer upon ICU admission for prognostication. Implications for Practice Patients with cancer have a high use of health care utilization at the end of life, which can frequently involve admissions to the intensive care unit (ICU). Although there have been substantial increases in duration of survival for patients with advanced metastatic cancer, their mortality after an ICU admission remains high. GI malignancy is considered one of the top three lethal cancers estimated in 2017. Survival of critically ill patients with advanced GI cancer should be evaluated to help guide treatment planning.

While significant advances have been made in the treatment of many different solid tumors, pancreatic cancer remains a glaring exception. Overall 5-year survival rates for pancreatic cancer remain in the single digits. While newer chemotherapy regimens such as FOLFIRINOX and nab-paclitaxel/gemcitabine have demonstrated modest improvement in survival benefit for metastatic disease and have improved the resectability rates of previously borderline or locally advanced tumors, clinically significant improvements from immunotherapy and targeted therapy remain to be demonstrated. Regardless, a wealth of basic science research in pancreatic cancer has been directed at understanding its aggressive biology and its resistance to therapy. We present a brief summary of key areas of laboratory research and its translation to clinical care.

The modern treatment of locoregionally advanced disease often requires a multimodality combination approach. A number of chemotherapeutic agents can be combined with radiation, but the platinum agent cisplatin, a potent radiation sensitizer, is best studied in head and neck cancer. Newer agents such as cetuximab can be used in combination with radiation therapy for those patients who cannot tolerate cisplatin. For chemotherapy-naive patients with metastatic head and neck cancer who demonstrate a good performance status, platinum doublet regimens are commonly used. Doublet regimens generally improve response rates compared to single-agent chemotherapies, although they have not demonstrated a survival benefit over single agents and they have added toxicity. Immunotherapies, alternative cytotoxic chemotherapies, and targeted therapies are second-line options for patients with disease that has progressed on platinum-based therapy. Immunotherapy, in particular, has gained focus by enhancing the ability of the immune system to recognize and destroy malignant cells. When multimodal approaches are used, as in combined chemotherapy and radiation therapy, toxicities are increased. It is imperative that patients are followed closely in order to maximize treatment benefit while minimizing complications.

Metastatic disease to the regional lymph node (LN) is a strong predictor of worse long-term outcome after curative-intent resection of intrahepatic cholangiocarcinoma (ICC). The objectives of this study were to assess the prognostic performance of American Joint Committee on Cancer (AJCC)/International Union Against Cancer, 7th edition, N stage, LN ratio (LNR), and log odds of metastatic LN (LODDS) staging criteria in patients with ICC. The surveillance, epidemiology, and end results cancer registry was queried to identify 749 patients who underwent surgical resection of ICC during 1988–2011. The Kaplan–Meier method and Cox proportional hazards regression models were used to analyze survival. The relative discriminative abilities of the different LN staging systems were assessed by the Harrell concordance index (c statistic). Of the 749 patients, 477 (63.7 %) had no LN metastasis, while 272 (36.3 %) had LN metastasis. Patients with LN metastasis had an increased risk of death (hazard ratio 2.42, 95 % confidence interval 1.98–2.95; P

Increasing evidence shows that tumor clonal architectures are often the consequence of a complex branching process, yet little is known about the expected dynamics and extent to which these divergent subclonal expansions occur. Here, we develop and implement more than 88,000 instances of a stochastic evolutionary model simulating genetic drift and neoplastic progression. Under different combinations of population genetic parameter values, including those estimated for colorectal cancer and glioblastoma multiforme, the distribution of sizes of subclones carrying driver mutations had a heavy right tail at the time of tumor detection, with only 1 to 4 dominant clones present at ≥10% frequency. In contrast, the vast majority of subclones were present at Significance: The model presented in this paper addresses tumor heterogeneity by framing expectations for the number of resistant subclones in a tumor, with implications for future studies of the evolution of therapeutic resistance. Cancer Res; 78(3); 830–9. ©2017 AACR.

Background and Objectives Several lymph node (LN) staging/scoring systems have been proposed to stratify the prognosis of patients with gallbladder adenocarcinoma (GBA). We sought to define the prognostic performance of the most commonly utilized LN staging/scoring systems including AJCC/UICC N stage, lymph node ratio (LNR), log odds (LODDS), and N score, among patients with GBA. Method Between 2004 and 2010, 1,124 patients with GBA were identified from the Surveillance Epidemiology and End Results (SEER) database. The discriminative ability of each LN staging/scoring system was assessed using the Akaike's Information Criterion (AIC) and the Harrell's concordance index. Results When assessed using categorical values, LNR had a modest, improved ability to discriminate patients with regard to prognosis (C-index: 0.615; AIC: 2118.2) compared with AJCC/UICC N stage or N score and a prognostic discrimination comparable to LODDS. Among patients who had a total number of LN examined (TNLE) of 1 or 2, all the staging/scoring systems performed comparably. In contrast, among patients who had ≥4 TNLE, LODDS performed the best (C-index: 0.613; AIC: 303.2). Conclusion The performance of the different LN staging/scoring systems varied based on the TNLE. In particular, for patients who had ≥4 TNLE, LODDS out-performed the other staging/scoring systems. J. Surg. Oncol. 2015 111:299–305. © 2014 Wiley Periodicals, Inc.

Background Advances in treatment of sarcoma patients has prolonged survival but has led to increased disease- or treatment-related complications resulting in greater number of admissions to the intensive care unit (ICU). Survival and long-term outcome information about such critically ill patients with sarcoma is unknown. Methods The primary objective of the study was to determine the ICU and post-ICU survival rates of critically ill sarcoma patients. Secondary objectives included determining the modifiable and non-modifiable predictors of poor survival. We performed a retrospective chart review of sarcoma patients admitted to the ICU at The University of Texas MD Anderson Cancer Center between January 1, 2005, and December 31, 2012. Main outcome measures were ICU mortality, in-hospital mortality and 1, 2, and 6-month survival rates. Covariates such as histological diagnosis, disease characteristics, chemotherapy use, Charlson comorbidity index, Sequential Organ Failure Assessment (SOFA) scores, and clinical findings leading to ICU admission were analyzed for their effects on survival. Results We identified 172 admissions over the 8-year study period hat met our inclusion criteria. The study population was 45.9 % males with a median age of 52 years. The most common sarcoma subgroups were high-grade unclassified sarcoma (25 %) and bone tumors (17.4 %). The ICU mortality rate was 23.3 % (95 % confidence interval [CI], 16.9–29.6 %), and an additional 6.4 % of patients died before hospital discharge (95 % CI, 22.9–37.1 %). 6-month OS rates were 41 %. The median SOFA scores on admission were 6 (inter quartile range (IQR), 3.5–9) in ICU survivors and 10 (IQR, 6.5–14) in ICU non-survivors. Increase in SOFA scores ≥6 led to poor outcomes (ICU survival 13.3 %, OS 6.7 %). Charlson comorbidity index (HR 1.139, 95 % CI 1.023–1.268, p = 0.02) and discharge SOFA scores (HR 1.210, 95 % CI 1.141–1.283, p

e21130Background: ALK gene rearrangements are observed in about 4-8% Non-small cell lung cancer (NSCLC). Due to low incidence there is limited knowledge about patterns of metastasis in ALK+ tumors....

432 Background: Prospective data to support dosing guidelines for intravenous (IV) vinorelbine in pts with LD are limited. One study recommends standard 30 mg/m2 weekly for total bilirubin ≤2 mg/dL and a 50% dose reduction for bilirubin > 2 mg/dL. Another study recommends no dose modifications for bilirubin up to 3X the upper limit of normal (ULN). This phase I study describes the safety and PKs of vinorelbine in pts with varying degrees of hepatic impairment. Methods: Pts with treatment-refractory solid tumors received weekly IV 30 mg/m2 vinorelbine for normal liver function, 20 mg/m2 for mild LD defined as bilirubin < 1.5 mg/dL but aspartate aminotransferase (AST)/alanine aminotransferase (ALT) 1.5-2.5X ULN or alkaline phosphatase (ALK) 1.5-3X ULN, 15 mg/m2 or 30 mg/m2 for moderate LD defined as bilirubin 1.5-3.0 mg/dL and/or AST/ALT > 2.5 or ALK > 3X ULN, and 7.5 mg/m2 or 20 mg/m2 for severe LD defined as bilirubin > 3.0 mg/dL. Vinorelbine PKs were evaluated to describe its relationship with liver function. Results: 47 patients were enrolled (61.7% gastrointestinal and hepatobiliary cancers) and a total of 248 treatment-related adverse events (AEs) occurred. All-grade myelosuppression was the most common AE overall (41.1%). Out of 71 grade ≥3 AEs, 17 (23.9%) were grade 4 in severity with the majority (15/17) being myelosuppression. Rates of grade 4 hematologic AEs in the normal liver function and the 7.5 mg/m2 severe LD group were low ( < 10%). 4/17 grade 4 hematologic AEs were observed in the mild LD group while the remainder and majority occurred in the moderate-severe LD groups. Vinorelbine PKs were not correlated with the degree of LD, however free drug levels or levels of the active metabolite 4-O-deacetylvinorelbine were not measured. Conclusions: Weekly vinorelbine at 30 mg/m2 and 7.5 mg/m2 appears safe with normal liver function and severe LD, respectively. High rates of grade 4 myelosuppression with 15-30 mg/m2 vinorelbine in moderate-severe LD raise concerns for its safety in this population. Vinorelbine PKs are not affected by LD. However, it is possible that levels of the active metabolite could be higher in pts with LD if its elimination is impacted by LD to a greater extent than the parent drug. Clinical trial information: NCT00540982.

Gastrointestinal follicular lymphoma (GI‐FL) is a rare extranodal variant of follicular lymphoma (FL) that has been increasingly reported in the literature. An especially indolent course is linked to the disease after a lack of observed patient death in past studies. However, overall survival (OS) and associated prognostic factors remain unclear. A large population‐based database was utilized to identify demographic and clinicopathologic characteristics of GI‐FL, along with survival differences among primary sites. The Surveillance, Epidemiology, and End Results Registry was used to identify GI‐FL cases between the years of 1973 and 2012. Kaplan–Meier curves compared OS differences and Cox proportional hazard models analyzed prognostic factors. Final analysis included 1109 cases. Small intestinal cases, which included those with single‐site and multi‐segment involvement, were most common (63.6%) followed by gastric (18.2%) and colorectal cases (18.2%). Small intestinal GI‐FL presented more frequently with grade I histology, and less often with grade III histology (P

Malignant small bowel obstruction (MSBO) that does not resolve with conservative measures frequently leaves few treatment options other than palliative care. This single‐institution retrospective study assesses the outcomes of a more aggressive approach—concurrent systemic chemotherapy and total parenteral nutrition (TPN)—in the treatment of MSBO. The MD Anderson pharmacy database was queried to identify patients who received concurrent systemic chemotherapy and TPN between 2005 and 2013. Only patients with MSBO secondary to peritoneal carcinomatosis requiring TPN for ≥8 days were included. Survival and multivariate analyses were performed using the Kaplan–Meier method and Cox proportional hazard models. The study included 82 patients. MSBO resolution was observed in 10 patients. Radiographic assessments showed a response to chemotherapy in 19 patients; 6 of these patients experienced MSBO resolution. Patients spent an average of 38% of their remaining lives hospitalized, and 28% of patients required admission to the intensive care unit. In multivariate modeling, radiographic response to chemotherapy correlated with MSBO resolution (odds ratio [OR] 6.81; 95% confidence interval [CI], 1.68–27.85, P = 0.007). Median overall survival (OS) was 3.1 months, and the 1‐year OS rate was 12.6%. Radiographic response to chemotherapy (HR 0.30; 95% CI, 0.16–0.56, P

Purpose Several indices have been developed to predict overall survival (OS) in patients with breast cancer with brain metastases, including the breast graded prognostic assessment (breast-GPA), comprising age, tumor subtype, and Karnofsky performance score. However, number of brain metastases—a highly relevant clinical variable—is less often incorporated into the final model. We sought to validate the existing breast-GPA in an independent larger cohort and refine it integrating number of brain metastases. Patients and Methods Data were retrospectively gathered from a prospectively maintained institutional database. Patients with newly diagnosed brain metastases from 1996 to 2013 were identified. After validating the breast-GPA, multivariable Cox regression and recursive partitioning analysis led to the development of the modified breast-GPA. The performances of the breast-GPA and modified breast-GPA were compared using the concordance index. Results In our cohort of 1,552 patients, the breast-GPA was validated as a prognostic tool for OS (P < .001). In multivariable analysis of the breast-GPA and number of brain metastases (> three v ≤ three), both were independent predictors of OS. We therefore developed the modified breast-GPA integrating a fourth clinical parameter. Recursive partitioning analysis reinforced the prognostic significance of these four factors. Concordance indices were 0.78 (95% CI, 0.77 to 0.80) and 0.84 (95% CI, 0.83 to 0.85) for the breast-GPA and modified breast-GPA, respectively (P < .001). Conclusion The modified breast-GPA incorporates four simple clinical parameters of high prognostic significance. This index has an immediate role in the clinic as a formative part of the clinician's discussion of prognosis and direction of care and as a potential patient selection tool for clinical trials.

Case Report We present an 81-year-old man with a history of prostate cancer and leptomeningeal metastases. He was diagnosed to have CRPC with extensive bone metastases coupled with a prostate-specific antigen (PSA) 894 ng/mL diagnosed 18 months earlier. He had received docetaxel in combination with prednisone for 6 cycles in conjunction with zoledronic acid. Upon progression, he was offered a clinical trial evaluating a novel autologous antigen-presenting cell-based vaccine. He experienced an improvement in pain during the trial and progressed approximately 6

11624 Background: Disease heterogeneity with variable molecular mutations is one of the main contributory factors in non-small cell lung cancer (NSCLC). The goal of this study was to better understand the KRAS patients with co-occurring mutations. Methods: We identified 60 patients with a diagnosis of NSCLC and a KRAS mutation in the COH Cancer Registry from 2009 to 2016. Next generation sequencing was performed. Results: Of the 60 patients identified, 42 (70%) were Stage IV at diagnosis, 7 (12%) Stage I and 7 (12%) stage II and 4 (6%) Stage III. 47 (78) patients were smokers. Caucasian was the most common (n = 44, 73%) racial group, followed by Asians (n = 9, 15%), African-Americans (n = 3, 5%), other (n = 3, 5%) and Pacific Islander (n = 1, 1.7%). The average age at diagnosis was 67 (median 69.50) years; 30 patients (50%) were over 70 years, 23 (38%) patients were 51-69 years, and 7 (12%) 50 years or below. Majority of the patients had metastatic disease (n = 52, 87%) with 20% (n = 12) having brain metastasis with average metastatic sites 1.6. An average of 1.97 (range = 0-5) lines of therapy including chemotherapy, biologic agents or immunotherapy were received. 12 (20%) patients received immunotherapy, radiation in 28 (47%) and surgery in 22 (37%) with a median overall survival at 15 months. The most frequent molecular alteration was codon 12 mutation (n = 47, 78%), followed by codon 13 (n = 7, 12%) and codon 61 (n = 6, 10%) mutations. The most common co-occurring mutations in this cohort were TP53 (n = 15, 25%), ATM (n = 9, 15%), LRP1B (n = 9, 15%), ARID1A (n = 8, 13%), STK11 (n = 8, 13%), ARID1B (n = 7, 12%), TERT (n = 7, 12%), EGFR (n = 6, 10%), RBM10 (n = 6, 10%), SPTA1 (n = 6, 10%). We are currently evaluating the relevance of the Circos plot analysis for these mutations, clinical response to immunotherapy and potential biomarkers. Conclusions: KRAS mutations are among the most common molecular alterations identified in NSCLC. Effective treatments targeting KRAS mutations have represented a challenge so far. Understanding the significance of co-mutations and their therapeutic implications, especially in response to immunotherapy and other agents represents an important step to develop better treatment options for KRAS mutated lung cancers.

e18050 Background: Cancer patients have a high use of healthcare utilization at the end of life which can frequently involve admissions to the intensive care unit (ICU). We sought to evaluate the predictors for outcome in gastrointestinal (GI) cancer patients admitted to the ICU for non-surgical conditions. Methods: The objective of this study was to determine the factors associated with ICU mortality, hospital mortality and overall survival (OS). A total of 200 patients with GI cancer admitted to the ICU at The University of Texas MD Anderson Cancer Center between November 2012 and February 2015 were retrospectively analyzed. Cancer characteristics, treatment characteristics, and Sequential Organ Failure Assessment (SOFA) scores defining severity based on 6 organ systems with scores ranging from 0 to 24 were analyzed for their effects on survival endpoints using multivariate logistic regression models and a multivariate Cox proportional hazards regression model. Results: The characteristics of the 200 patients were: 64.5% male, mean age of 60 years, median admission SOFA score of 6.0, and tumor types of primary intestinal (37.5%), hepatobiliary/pancreatic (36%), and gastroesophageal (GE) (24%). The ICU mortality was 26%, hospital mortality was 41%, and 6-month OS estimate was 25%. In multivariate analysis, ICU admission SOFA score > 10 (odds ratio (OR) 17.1, p < 0.0001), poorly differentiated tumor grade (OR 3.2, p = 0.02), and shorter duration of metastatic disease (OR 2.3, p = 0.07) were associated with increased odds of ICU mortality. These same variables were associated with increased odds of hospital mortality. In multivariate OS analysis, SOFA score 6-10 (hazard ratio (HR) 2.1, p = 0.0006) and SOFA score > 10 (HR 4.4, p < 0.0001), patients with GE primary (HR 2.2, p = 0.002) and patients with a poor outpatient performance status that precluded active chemotherapy (HR 2.2, p = 0.01) were associated with increased risk of death. Conclusions: The SOFA score was the most predictive factor for ICU mortality, hospital mortality, and OS for GI cancer patients admitted to the ICU. It should be utilized in all GI cancer patients upon ICU admission to improve both acute and longer-term prognostication.

The most common type of metabolic acidosis in hospitalized patients is lactic acidosis which is caused by the accumulation of lactic acid in the body fluids resulting from either overproduction or reduced metabolism of lactate [1, 2]. Lactic acidosis is classified as type A, in the setting of reduced tissue perfusion and poor blood oxygenation, or type B, when no clinical evidence of those conditions exists. Both hematologic and non-hematologic malignancies have been associated with the latter [3–6]. However, lactic acidosis as a complication of gastrointestinal malignancies is limited to case reports, and distinguishing among the types of lactic acidosis in this setting is challenging [5, 6]. We present a patient diagnosed with type B lactic acidosis secondary to metastatic gastric adenocarcinoma.

Surgical therapy, often combined with adjuvant systemic chemotherapy, is the best therapeutic option to treat patients with colorectal liver metastasis (CRLM), However, while overall survival (OS) has improved, many patients with CRLM will recur and ultimately die of their disease.1,3 The factors used to predict outcome following surgical resection of CRLM largely focus on clinicopathological prognostic factors such as preoperative carcinoembryonic antigen (CEA) level, presentation of disease (ie, synchronous vs metachronous disease), disease-free interval between primary tumor and hepatic metastasis, and metastatic tumor number and size.4 There has been increasing interest in the use of biologic and molecular markers in the prognostic assessment of patients with metastatic colorectal cancer undergoing liver resection.4 Among patients with colorectal adeno-carcinoma, mutated Kirsten rat sarcoma viral oncogene homolog (KRAS) is the most common oncogene of the RAS family, reported in up to 30% to 40% of patients.5–9 While the frequency and prognostic impact of KRAS mutation status have been described for both primary and metastatic colorectal cancer, to our knowledge, the role of specific mutations on KRAS codons remains undefined.10–14 Most KRAS mutations are detected in codons 12 and 13, while mutations in codons 61 and 146 are less common.15–17 KRAS mutations in codons 12 and 13 include different point mutations; the most common are codon 12 Gly→Asp (G12D), codon 12 Gly→Val (G12V), and codon 13 Gly→Asp (G13D) substitutions.18 Previous evidence has suggested that different biologic characteristics of specific KRAS mutations can lead to variations in epidermal growth factor receptor resistance.19–21 In addition, some investigators have suggested that specific KRAS mutations may also be associated with a more aggressive tumor phenotype in patients with unresectable stage IV metastatic colorectal cancer.5,22 However, the prognostic implication of different point mutations on survival of patients following curative intent liver resection for CLRM has not been previously investigated. As such, the purpose of the present study was to define the incidence of different specific KRAS mutations among patients with resected CRLM. Specifically, we sought to characterize the prognostic impact of different KRAS point mutations on recurrence and the survival of patients undergoing curative intent liver resection for CRLM.

e20701 Background: The development of malignant SBO represents a poor prognosis event with limited therapeutic options. Surgical intervention for cases that fail conservative management is associat...

Background: Sarcopenia, defined as loss of muscle mass, may be a more objective means to determine peri-operative performance status. Traditionally, sarcopenia has exclusively been characterized using total psoas area (TPA). Defining sarcopenia using only a single axial cross-sectional image may, however, be inadequate. We sought to evaluate total psoas volume (TPV) as a new tool to define sarcopenia and compared TPV with traditional TPA. Method: Sarcopenia was assessed in 763 patients who underwent pancreatectomy for pancreatic adenocarcinoma between 1996-2014. Sarcopenia was defined as the TPA and TPV in the lowest sex-specific quartile. The impact of TPA and TPV sarcopenia on overall morbidity and mortality was assessed using multivariable analysis. Result: Median patient age was 67 years and 54.8% (n= 418) was male. Median TPA and TPV were both lower in women (506.3mm2/m2 and 22.4 cm3/m2, respectively) versus men (685.1mm2/m2 and 33.0 cm3/m2, respectively)(both P

Aim: To study the auditory effects of chemoradiotherapy with cisplatin and paclitaxel. Materials and Methods: Eighty patients with head and neck cancer undergoing chemoradiotherapy with cisplatin or paclitaxel were enrolled for the present study and monitored for any auditory alterations. Results: Forty-eight patients underwent chemotherapy with cisplatinum while 32 patients with paclitaxel. Hearing loss was observed along with tinnitus, vertigo, and nausea and vomiting. Conclusion: Taxanes-based chemoradiotherapy cause less auditory alterations than cisplatin-based chemoradiotherapy.

10576 Background: Survival and long-term outcomes of the critically ill patients with sarcoma who are admitted to the intensive care unit (ICU) are unknown. As a result, oncologists are often unsur...

10071 Background: Atypical vascular neoplasms are rare cutaneous lesions that develop following radiation therapy to the breast that have evidence of atypia but do not meet all criteria for a diagnosis of angiosarcoma. They typically have a benign course and are managed by surgical resection. Histopathological changes consistent with atypical vascular neoplasm are commonly found adjacent to angiosarcoma and have lead some investigators to believe that these may be precursor lesions to development of angiosarcoma. Methods: We performed a retrospective review of all patients with a diagnosis of atypical vascular neoplasm from 2002 to 2012. Patient with a prior/concurrent history of angiosarcoma were excluded from the analysis. Primary objective of the study was to determine the percentage of patients with atypical vascular neoplasms that progressed to angiosarcoma on long-term follow-up. Results: 37 patients were identified in the tumor registry at MD Anderson cancer center with a diagnosis of atypical vascular neoplasm between 2002 and 2012 with a median follow-up of 24 months. The median age of the study population was 53. Females represented 89% of the study population. Atypical vascular neoplasms occurred most frequently in the breast/chest (70%) and 68% of patients had a prior history of breast cancer. 54% of patients had prior radiation therapy. The median time to development of atypical vascular neoplasms from radiation therapy was 52 months. Among patients who underwent surgical resection with negative margins, there were no recurrences. We failed to observe any progression to angiosarcoma in the study population. Conclusions: Patients with atypical vascular neoplasms may not progress to angiosarcoma and are best managed with surgical resection.