Multi-omics machine learning to study host-microbiome interactions in early-onset colorectal cancer.

The incidence of early-onset colorectal cancer (eoCRC) is rising, and its pathogenesis is not completely understood. We hypothesized that machine learning utilizing paired tissue microbiome and plasma metabolome features could uncover distinct host-microbiome associations between eoCRC and average-onset CRC (aoCRC). Individuals with stages I-IV CRC (n = 64) were categorized as eoCRC (age ≤ 50, n = 20) or aoCRC (age ≥ 60, n = 44). Untargeted plasma metabolomics and 16S rRNA amplicon sequencing (microbiome analysis) of tumor tissue were performed. We fit DIABLO (Data Integration Analysis for Biomarker Discovery using Latent variable approaches for Omics studies) to construct a supervised machine-learning classifier using paired multi-omics (microbiome and metabolomics) data and identify associations unique to eoCRC. A differential association network analysis was also performed. Distinct clustering patterns emerged in multi-omic dimension reduction analysis. The metabolomics classifier achieved an AUC of 0.98, compared to AUC 0.61 for microbiome-based classifier. Circular correlation technique highlighted several key associations. Metabolites glycerol and pseudouridine (higher abundance in individuals with aoCRC) had negative correlations with Parasutterella, and Ruminococcaceae (higher abundance in individuals with eoCRC). Cholesterol and xylitol correlated negatively with Erysipelatoclostridium and Eubacterium, and showed a positive correlation with Acidovorax with higher abundance in individuals with eoCRC. Network analysis revealed different clustering patterns and associations for several metabolites e.g.: urea cycle metabolites and microbes such as Akkermansia. We show that multi-omics analysis can be utilized to study host-microbiome correlations in eoCRC and demonstrates promising biomarker potential of a metabolomics classifier. The distinct host-microbiome correlations for urea cycle in eoCRC may offer opportunities for therapeutic interventions.

Treatment Selection and Survival in Patients with Gray Zone Lymphoma: A Comprehensive Population-Based Analysis.

BACKGROUND AND OBJECTIVES: There are no treatment guidelines for gray-zone lymphoma (GZL), given the disease's rarity and being a relatively new entity. Our objective was to assess factors affecting treatment selection in GZL and its effect on survival, focusing on combined modality treatment (CMT) versus chemotherapy alone. PATIENTS AND METHODS: We identified 1047 patients with GZL treated with CMT or chemotherapy alone between 2004 and 2016 from the National Cancer Database (NCDB). We excluded patients without histologic confirmation of the diagnosis, those who did not receive chemotherapy, and those who started chemotherapy >120 days or radiation >365 days from diagnosis to account for immortal time bias. Factors affecting treatment selection were investigated using a logistic regression model. A propensity score-matched methodology was used to compare survival outcomes. RESULTS: Only 164 patients (15.7%) received CMT, while 883 (84.3%) received chemotherapy alone. Treatment selection was affected by clinical factors (age, odds ratio [OR] 0.99, 95% confidence interval [CI] 0.98-0.997, p-value 0.01 and advanced stage, OR for stage 4: 0.21, 95% CI 0.13-0.34, p-value < 0.001) but not socioeconomic factors. Higher median income was associated with better survival, while increased age, higher comorbidity score, and B symptoms were associated with worse survival. The use of CMT had a survival advantage over chemotherapy alone (hazard ratio [HR] 0.54, 95% CI 0.351-0.833, p-value 0.005). CONCLUSION: CMT is associated with survival advantage in our analysis. Careful selection of patients is essential to achieve the best outcomes with minimal toxicity. Socioeconomic factors affect treatment selection in patients with GZL that can alter outcomes. Future work should focus on strategies that access disparities without compromising survival.

Predictors and Long-Term Outcomes for Diffuse Large B-Cell Lymphoma (DLBCL) Patients Undergoing Surgery Prior to Systemic Therapy: A Nationwide Analysis.

BACKGROUND: A minority of patients diagnosed with diffuse large B-cell lymphoma (DLBCL) undergo surgery before the initiation of systemic therapy. The aim of this study is to explore the characteristics of patients undergoing surgery prior to systemic therapy (surgfirst), the predictors for surgfirst, and the survival outcomes. METHODS: The National Cancer Database was queried for patients with DLBCL diagnosed between 2006 and 2015, and we performed a subgroup analysis of patients that received surgfirst. Time-to-initial therapy (TTI) was defined as the time in days (d) from diagnosis to systemic therapy. Overall survival was measured from the day of diagnosis in terms of months (m). RESULTS: Factors associated with lower likelihood of surgfirst were non-Hispanic Black race (p-value<0.005), rural location (p-value<0.005), treatment at academic center (p-value<0.005), Medicaid insurance (p-value=0.01), comorbidity score >=3 (p-value 0.007), year of diagnosis, advanced stages of disease, and presence of B-symptoms. The TTI of systemic therapy was delayed in the surgfirst group - 34 (IQR 22-52) days vs. 23 (IQR 13-38) days, p-value<0.005. The five-year overall survival was 62.7% (95% CI 62.1-63.2%) vs. 58.3% (95% CI 57.7-60.0%) - HR 0.87 (95% CI 0.85-0.89), p-value<0.005. The factors associated with higher mortality were advanced comorbidities, lower educational status, disease primarily located in the bone, brain, and spinal cord, advanced clinical stage, presence of B-symptoms, and advanced age. CONCLUSION: Despite the delay in systemic therapy, we could not identify a detrimental impact of surgfirst on survival. This needs to be confirmed in large-scale multicenter studies. We identified clinical and socioeconomic factors that affect treatment selection and survival.

AL type cardiac amyloidosis: a devastating fatal disease.

INTRODUCTION: Cardiac amyloidosis is a rare entity with a grave prognosis. Due to the low index of suspicion secondary to non-specific symptoms, it is often diagnosed at an advanced stage with multi-organ involvement. METHODS: We report a case of systemic AL amyloidosis with predominant cardiac and renal involvement associated with multiple myeloma. CASE SUMMARY: A 60-year-old male presented with progressive anasarca, orthopnea and weight gain over 8 months. On clinical examination, 3+ pitting edema was found in bilateral extremities and scrotum. Serum N-type proBNP and troponin T were elevated, and EKG showed diffuse low voltage QRS, right axis deviation, and 1st degree AV block. Echocardiography revealed granular myocardium, biventricular hypertrophy, bi-atrial dilation and apical sparing pattern on global longitudinal strain which was suggestive of cardiac amyloidosis. Light chain assessment showed elevated kappa and lambda chains with kappa to lambda ratio of 16.2. Endomyocardial biopsy revealed AL type cardiac amyloidosis, and bone marrow biopsy confirmed the diagnosis of multiple myeloma. He received six cycles of bortezomib, cyclophosphamide, and dexamethasone but continued to deteriorate. He experienced an episode of cardiac arrest following which he had a return of spontaneous circulation but due to poor prognosis, the family opted for pursuing comfort measures only. CONCLUSIONS: Cardiac involvement in AL type amyloidosis imparts significant morbidity and mortality. The management of cardiac amyloidosis entails a multidisciplinary approach with an emphasis on cardiology and oncology. Despite the novel diagnostic modalities and treatment regimens, the outcome for AL-type cardiac amyloidosis remains poor.

The use of adjuvant radiation therapy in male breast cancer and its impact on outcomes.

BACKGROUND: Male breast cancer (MBC) accounts for 1% of all breast cancers and there is a paucity of data on factors impacting the treatment strategies and outcomes. We sought to use a large national database to examine trends and predictors of the use of adjuvant radiation (Adj-RT), as well as any association with outcome. METHODS: We queried the National Cancer Database (NCDB) for patients with stages I-III MBC treated with surgery (breast conservation surgery-BCS or mastectomy-MS) within 180 days of diagnosis (years 2004-2015). Multivariable logistic regression identified predictors of adj-RT receipt. Multivariable Cox regression evaluated predictors of survival. Propensity matching for adj-RT was used to account for indication biases. RESULTS: We identified 6,217 patients meeting the eligibility criteria (1457 BCS vs. 4760 MS). The majority of patients were Caucasian (85%) and in an age range of 50-80 years (74%). Although adj-RT was omitted for 30% of BCS patients, the utilization was higher compared to MS (OR=26, p-value=0.001). The predictors of adj-RT use included African-American race, more advanced stage, higher grade, presence of lymphovascular invasion, and ER/Her-2 positivity for the entire cohort and increased age, urban location and higher income for BCS. Adj-RT was associated with lower mortality in the propensity matched model (overall HR for BCS=0.28, p-value<0.001; overall HR for MS=0.62, p-value=0.001). CONCLUSION: This study demonstrates that while adj-RT after BCS is associated with decreased mortality in MBC patients, adj-RT is omitted in up to a third of cases of MBC after BCS despite being standard of care.

Chemotherapy use in early stage anal canal squamous cell carcinoma and its impact on long-term overall survival,,.

BACKGROUND: The standard of care for non-metastatic squamous cell carcinoma of the anal canal (SCCA) is concurrent chemoradiotherapy. It is postulated that chemotherapy could be omitted for the earliest stages without worsening outcomes. METHODS: We queried the NCDB from 2004-2016 for patients with cT1N0M0 SCCA treated non-operatively with radiation, with and without chemotherapy, and at least two months of follow-up. Of the 2,959 patients meeting eligibility, 92% received chemotherapy (n = 2722) and 8% (n = 237) did not. Most patients were white (n = 2676), female (n = 2019), had private insurance (n = 1507) and were treated in a comprehensive cancer center (n = 1389). Average age was 58.5 years. RESULTS: Predictors of chemotherapy omission were age > 58 years (OR 0.66, 95% CI [0.49-0.90], P = 0.0087), higher comorbidity score (OR 0.62, 95% CI [0.38-0.99], P = 0.0442), African American race (OR 0.57, 95% CI [0.36-0.90], P = 0.0156) and treatment at the start of the study period (OR 1 for years 2004-2006). HR for single-agent chemotherapy was 0.70 (95% CI [0.50-0.96], P = 0.0288) and 0.48 for multi-agent (95% CI [0.38-0.62], P <0.0001). Overall survival was 86% in those that received chemotherapy vs 65% in those who did not (P <0.0001). CONCLUSIONS: In conclusion, patients with early-stage squamous cell cancer of the anus who are treated with combination chemoradiation continue to demonstrate better overall survival than those who undergo radiotherapy alone.

Disparities in the enrollment to systemic therapy and survival for patients with multiple myeloma.

BACKGROUND: Disparities driven by socioeconomic factors have been shown to impact outcomes for cancer patients. We sought to explore this relationship among patients with multiple myeloma (MM) who were not considered for hematopoietic stem cell transplant in the first-line setting and how it varied over time. METHODS: We queried the National Cancer Database for patients diagnosed with MM between 2004 and 2016 and included only those who received systemic therapy as the first-line treatment. Enrollment rates for therapy were calculated as receipt of systemic therapy as the incident event of interest (numerator) over time to initiation of therapy (denominator) and used to calculate incident rate ratios that were further analyzed using Poisson regression analysis. A multivariate Cox proportional hazards model was constructed for survival analysis, and differences were reported as hazard ratios (HRs). RESULTS: We identified 56,102 patients for enrollment analysis and 50,543 patients for survival analysis. Therapy enrollment in a multivariate model was significantly impacted by race and sex (p < .005). Advanced age, earlier year of diagnosis, lack of insurance or Medicaid, and higher comorbidity were associated with poor survival (HR > 1), whereas female sex, non-Hispanic black race, higher income, and treatment at an academic center were associated with improved survival (HR < 1). CONCLUSION: Disparities in treatment of MM exist and are caused by a complex interplay of multiple factors, with socioeconomic factor playing a significant role. Studies exploring such determinants may help in equitable distribution of resources to overcome such differences.

Impact of affordable care act on the treatment and outcomes for stage-IV colorectal cancer.

BACKGROUND: Patients with advanced cancers are among the most vulnerable group of patients. We sought to analyze the impact of Affordable Care Act (ACA) on the interaction of socioeconomic factors with treatment and survival in patients with metastatic colorectal cancers. METHODS: National Cancer Database (NCDB) was queried for patients with Stage-IV colon(CCa) and rectal cancers(R-Ca) diagnosed 2004-2015 and excluded those who did not receive any therapies within 6 months of diagnosis. Enrollment-rates were calculated as receipt of primary therapy as the incident-event (numerator) over time-to-initiation of therapy (denominator) and used to calculate incident-rate ratios that was analyzed using Poisson regression analysis- reported as enrollment-rate ratios (ER, <1 indicating lower enrollment rate). Multivariate Cox-proportional hazard model was performed for survival analysis and reported as calculate Hazard Ratios (HR). RESULTS: For CCa, enrollment to primary therapies was significantly associated (p-value < 0.05) with gender, race, insurance status, educational status and treatment facility. The HR for non-Hispanic Blacks (NHB) vs. Whites (NHW) improved from 1.1(1.03-1.11),p-value<0.005 to no-significant difference post-ACA. For R-Ca, the enrollment rates were favorable for NHB vs. NHW and ER improved from 1.15(1.0-1.32),p-value = 0.054) to 1.29(1.06-1.58),p-value = 0.013 post-ACA. Despite this, the HR for mortality were unfavorable - 1.19(1.06-1.33),p-value = 0.003 that persisted through the post-ACA period. The HR was favorable for the insured group in both cancer groups (0.84 for R-Ca,0.86 for CCa) and for high-income vs. low-income group-0.90(0.87-0.94),p-value < 0.005 in CCa. CONCLUSION: The ACA appears to have had a positive impact overall but further research and ongoing interventions are warranted to mitigate disparities in this population.

Patterns of Care and Outcomes in Verrucous Carcinoma of the Larynx Treated in the Modern Era.

Background: Verrucous carcinoma of the larynx (VCL) is a rare form of laryngeal squamous cell carcinoma. We analyzed the National Cancer Database (NCDB) to examine national treatment pattern, identify factors associated with primary radiation therapy (RT), and compare outcomes in patients with Tis-T2 N0 VCL treated primary surgery and primary RT. Methods: We accessed the NCDB from 2004 to 2015 for patients with Tis-T2 N0 VCL and recorded the treatment modality employed. Multivariable logistic regression was used to identify predictors for radiation therapy. Cox regression was used to calculate hazard ratios for survival. A propensity score matched Kaplan-Meier analysis compared primary surgical treatment to definitive radiation. Results: We identified 732 patients with laryngeal verrucous carcinoma from the NCDB. The majority were cTis-T2 (87%) N0 (96%). We identified 286 vs. 110 Tis-T2N0 patients treated primary surgery and with definitive radiation, respectively, for the purpose of this study. Predictors of radiation were treatment at a community center, no insurance, and higher T stage. Cox regression identified increased age, higher comorbidity score, and government insurance as predictive of worse survival. Propensity matching revealed a trend toward worse survival with definitive radiation, with a median survival of 98 months compared to 143 months (p = 0.02). When including only T1-2 lesions, that is, invasive disease, the trend toward increased survival with surgery [98 months vs. 135 months (p = 0.08)] persisted. Conclusion: The results of the present study support the use of surgery in the management of Tis-T2 N0 VCL when organ preservation is possible.

Glanzmann's Thrombasthenia: How Listening to the Patient Is Sometimes the Simple Key to Good Medicine!

Introduction. Glanzmann's thrombasthenia is a rare clotting disorder caused by impaired platelet function. Lack of awareness of the appropriate management of rare medical conditions may lead to patient dissatisfaction and potentially poor treatment outcome. Case Report. A 78-year-old male with a history of Glanzmann's thrombasthenia was admitted to the trauma service following a fall in which he sustained a facial laceration as well as maxillary sinus and nasal fractures. He received DDAVP 20 mcg and tranexamic acid upon presentation to the emergency department (ED). In the ED, the patient requested administration of platelet transfusion but was refused due to a normal platelet count. During the course of his hospital stay, he complained of epistaxis and was noted to have a downtrending hemoglobin from 11.0 g/dl to 9.0 g/dl. The patient and his family were not comfortable when the discharge plan was finalized and demanded platelet transfusion (due to history of needing platelets in association with injuries or procedures in the past) was refused by the primary team as they continued to state that his platelet count is normal. On hospital day 3, hematology was consulted as the patient and his family were extremely angry and hematology recommended platelet transfusion. Further clinical information was not available as the patient was transferred to another facility per family request as they wanted to be at a center which had the patient's primary hematologist. Discussion. A delay in specialist consultation resulted in patient dissatisfaction and extended the length of stay. Patients with rare medical conditions and potential for major complications should be managed aggressively with appropriate specialist consultation to promote patient satisfaction and improve the overall quality of care. This case shows that as physicians it our duty to listen to our patient's concerns and involve them in the medical decision-making to provide optimal patient-centered care.

Outcomes of Treatment for HIV-Infected Lymphoma Patients: A National Cancer Database (NCDB) Analysis.

BACKGROUND: Human immunodeficiency virus (HIV) infection may be a predictor of undertreatment of patients with lymphoma. We hypothesized treatment with systemic therapy (SysT) or hematopoietic stem cell transplantation (HCT) in the first-line setting leads to improved outcomes and sought to compare the predictors for treatment and outcomes with non-HIV (HIV-) patients. METHODS: Patients with lymphoma diagnosed between 2004 and 2015 were extracted from the National Cancer Database (NCDB). Patients were categorized as HIV+ and HIV-. First-line treatment was categorized as no systemic therapy reported (noSyst), SysT, or HCT. Multivariate analysis to predict treatment and survival was performed. RESULTS: We identified 552,513 lymphoma patients, of whom 11,160 HIV+ versus 349,607 HIV- patients were eligible for analysis. Among HIV+, the positive predictors for SysT were insurance and higher income, whereas female sex and minority racial status predicted lower likelihood for SysT. Forty HIV+ patients underwent HCT. Treatment of HIV+ lymphoma patients resulted in improved outcomes: 3-year overall survival 43.6% in noSyst versus 58.1% SysT (hazard ratio [HR] 0.56; 95% confidence interval [CI], 0.52-0.61; P < .005) versus 62.2% HCT (HR 0.42; 95% CI, 0.14-1.3; P = .08). The outcomes were lower compared to non-HIV patients (3-yr overall survival 67.3% with SysT and 62.2% HCT). CONCLUSION: Patients with lymphoma with HIV benefit from SysT when feasible but outcomes are worse than non-HIV patients. HCT should be offered to HIV+ patients with lymphoma in the appropriate clinic setting. Individual characteristics of the patients and complications could not be evaluated in the present study but should be a focus for future research.

Predictors of chemotherapy and its effects in early stage squamous cell carcinoma of the larynx.

BACKGROUND: Squamous cell carcinoma (SCC) of larynx is a common head and neck cancer. For cases that are node negative, the role of definitive concurrent chemoradiation is unclear and not supported by guidelines but used at provider discretion. To address this knowledge gap, we examined the oncological outcomes with additional chemotherapy and factors correlated with the chemotherapy administration. METHODS: We queried the National Cancer Database for patients with early stage (T2N0M0) laryngeal SCC treated nonsurgically. Multivariable logistic regression identified predictors of chemotherapy. Multivariable Cox regression evaluated predictors of survival. Propensity matching accounted for indication biases. RESULTS: We identified 7181 patients meeting the eligibility criteria, of which 1568 (22%) patients received chemotherapy in addition to radiation. Predictors of chemotherapy use included younger age, Caucasian race, more remote year of treatment, higher grade, sites other than glottis, treatment at a community cancer center, and use of intensity-modulated radiation therapy. Median overall survival was not significantly different in the two arms analyzed-65 months (95% confidence interval [CI] 60, 72months) with chemotherapy compared to 70 months without chemotherapy (95% CI 66, 75 months, P<.37). Predictors for survival on propensity-matched multivariable analysis were increased age, male sex, less education, lower income, higher comorbidity score, receipt of treatment at a community center, and nonglottic sites. CONCLUSIONS: This study shows no clear survival benefit with chemotherapy in early stage disease. Although this implies that chemotherapy should not be routinely delivered, individualized judgment and prospective studies are recommended as the biology behind this interesting finding is undefined. LEVEL OF EVIDENCE: 2C (Outcomes Research).

Morbidity of curative cancer surgery and suicide risk.

IMPORTANCE: Curative cancer operations lead to debility and loss of autonomy in a population vulnerable to suicide death. The extent to which operative intervention impacts suicide risk is not well studied. OBJECTIVE: To examine the effects of morbidity of curative cancer surgeries and prognosis of disease on the risk of suicide in patients with solid tumors. DESIGN: Retrospective cohort study using Surveillance, Epidemiology, and End Results data from 2004 to 2011; multilevel systematic review. SETTING: General US population. PARTICIPANTS: Participants were 482 781 patients diagnosed with malignant neoplasm between 2004 and 2011 who underwent curative cancer surgeries. MAIN OUTCOMES AND MEASURES: Death by suicide or self-inflicted injury. RESULTS: Among 482 781 patients that underwent curative cancer surgery, 231 committed suicide (16.58/100 000 person-years [95% confidence interval, CI, 14.54-18.82]). Factors significantly associated with suicide risk included male sex (incidence rate [IR], 27.62; 95% CI, 23.82-31.86) and age >65 years (IR, 22.54; 95% CI, 18.84-26.76). When stratified by 30-day overall postoperative morbidity, a significantly higher incidence of suicide was found for high-morbidity surgeries (IR, 33.30; 95% CI, 26.50-41.33) vs moderate morbidity (IR, 24.27; 95% CI, 18.92-30.69) and low morbidity (IR, 9.81; 95% CI, 7.90-12.04). Unit increase in morbidity was significantly associated with death by suicide (odds ratio, 1.01; 95% CI, 1.00-1.03; P = .02) and decreased suicide-specific survival (hazards ratio, 1.02; 95% CI, 1.00-1.03, P = .01) in prognosis-adjusted models. CONCLUSIONS: In this sample of cancer patients in the Surveillance, Epidemiology, and End Results database, patients that undergo high-morbidity surgeries appear most vulnerable to death by suicide. The identification of this high-risk cohort should motivate health care providers and particularly surgeons to adopt screening measures during the postoperative follow-up period for these patients.

Aortic Endograft Infection by Pasteurella multocida: A Rare Case.

Infection of an aortic endograft is a rare complication following endovascular aneurysm repair. These patients have been treated with explantation of the graft to obtain source control followed by an extra-anatomic bypass to restore circulation. The present case study describes an interesting case of Pasteurella infection involving an aortic endograft managed nonoperatively by percutaneous drainage and graft preservation.

Cost Differential of Chemotherapy for Solid Tumors.

PURPOSE: A significant portion of national cancer expenditure is attributed to chemotherapy.Although the National Comprehensive Cancer Network has generated recommendations for the treatment of various solid tumors, the outlined chemotherapeutic strategies lack information about the cost differential for increasing effectiveness. METHODS: Chemotherapy regimens (curative [adjuvant/neoadjuvant] and metastatic therapy) and dosages outlined in the 2013 National Comprehensive Cancer Network guidelines were acquired for four common cancers: bladder, breast, colon, and lung. Baseline drug and treatment costs (in US dollars)were calculated for the average US adult male on the basis of the payment allowance in the 2013 Medicare Part B average sales price (ASP) drug pricing files. Costs were extrapolated for a treatment period of 6 months. RESULTS: Of the 62 regimens included, the 6-month mean cost of chemotherapy was $26,989 ± $29,971, and the median cost was $9,611 (interquartile range, $6,305-$39,383). The mean cost of metastatic cancer therapy regimens (n = 32) was $35,315 ± 32,962 compared with $18,107 ± 23,873 for curative therapy (P = .02). Of the 13 regimens with biologics used, the mean costs were $77,278 versus $13,646 for 49 regimens that did not use biologics (P<.001). The cost differential between extremes of costs for regimens with presumed similar efficacy was $90,843 ($79,165 for curative therapy and $90,210 for metastatic cancer therapy). The highest cost differential was noted in breast cancer regimens at $71,041 for metastatic cancer therapy and $63,926 for curative therapy. CONCLUSION: A significant cost differential exists between chemotherapeutic regimens for the most common solid tumors. Incorporation of costs and incremental effectiveness in current guidelines may encourage socially responsible practice patterns.

Age-based disparities in treatment and outcomes of retroperitoneal rhabdomyosarcoma.

BACKGROUND: Elderly patients (EPs) suffering from retroperitoneal rhabdomyosarcoma (RRMS) carry a considerably poorer prognosis compared to younger patients (YPs). We hypothesized that EPs received less aggressive and comprehensive treatment than YPs, resulting in poorer survival outcomes. MATERIALS AND METHODS: All patients diagnosed with RRMS since 1998 in the National Cancer Data Base (NCDB) were reviewed for patient demographics, tumor characteristics, treatment modalities and survival outcomes. RESULTS: Of the 100 patients identified, 35 % were ≥65 years of age. EPs (aged ≥65 years), when compared to YPs (aged <65), were less likely to receive systemic chemotherapy (20 % EPs vs 71 % YPs, p < 0.001) and treatment at an academic center (34 % EPs vs 60 % YPs, p = 0.05), although the frequency of radiation (23 % EPs vs 31 % YPs, p = 0.40) and radical surgery (26 % EPs vs 22 % YPs, p = 0.55) were similar. EPs received treatment more frequently at comprehensive community cancer programs (57 %) and had a shorter median distance of travel for care (6.4 vs 13 miles, p = 0.009). After adjusting for gender and tumor size, EPs had a hazard ratio of 3.6 (95 % CI 1.8-7.2, p < 0.001), with a median survival of 2 months (interquartile range [IQR] 1-8 months) versus 17 months for YPs (IQR 8-43 months). CONCLUSION: Altered practice patterns exist for EPs and include reduced use of systemic chemotherapy which may contribute to poorer outcomes for RRMS patients. Although regionalization of care poses challenges, this may offer benefit to the EP group.

Comparative Effectiveness of Hepatic Artery Based Therapies for Unresectable Colorectal Liver Metastases: A Meta-Analysis.

BACKGROUND: Patients with unresectable Colorectal Liver Metastases (CRLM) are increasingly being managed using Hepatic Artery Based Therapies (HAT), including Hepatic Arterial Infusion (HAI), Radioembolization (RE), and Transcatheter Arterial Chemoembolization (TACE). Limited data is available on the comparative effectiveness of these options. We hypothesized that outcomes in terms of survival and toxicity were equivalent across the three strategies. METHODS: A meta-analysis was performed using a prospectively registered search strategy at PROSPERO (CRD42013003861) that utilized studies from PubMed (2003-2013). Primary outcome was median overall survival (OS). Secondary outcomes were treatment toxicity, tumor response, and conversion of the tumor to resectable. Additional covariates included prior or concurrent systemic therapy. RESULTS: Of 491 studies screened, 90 were selected for analyses-52 (n = 3,000 patients) HAI, 24 (n = 1,268) RE, 14 (n = 1,038) TACE. The median OS (95% CI) for patients receiving HAT in the first-line were RE 29.4 vs. HAI 21.4 vs. TACE 15.2 months (p = 0.97, 0.69 respectively). For patients failing at least one line of prior systemic therapy, the survival outcomes were TACE 21.3 (20.6-22.4) months vs. HAI 13.2 (12.2-14.2) months vs. RE 10.7 (9.5-12.0). Grade 3-4 toxicity for HAT alone was 40% in the HAI group, 19% in the RE group, and 18% in the TACE groups, which was increased with the addition of systemic chemotherapy. Level 1 evidence was available in 5 studies for HAI, 2 studies for RE and 1 for TACE. CONCLUSION: HAI, RE, and TACE are equally effective in patients with unresectable CRLM with marginal differences in survival.

Retroperitoneal solitary fibrous tumor: surgery as first line therapy.

BACKGROUND: Solitary fibrous tumors (SFT) of the retroperitoneum are rare spindle cell neoplasms, with a paucity of data on treatment outcomes. We hypothesized that surgical excision offered acceptable outcomes in SFTs. METHODS: The National Cancer Database (NCDB) was used to identify patients with SFT from 2004 to 2011. Primary outcome measures were 30 day mortality and overall survival. Descriptive analyses were performed. Furthermore, a systematic review of published literature was conducted after creating a pre-specified search strategy. RESULTS: Of 51 patients in the NCDB, 58.8 % (n = 30) were males, with a median age 60 years (IQR 49-72 years). Median tumor size was 16 cm (IQR 11-21 cm). Surgical resection was performed in 92.2 % (n = 47) with 63.8 % (n = 30) having a margin negative resection. Peri-operative mortality was 2.1 % (n = 1). Of survival outcomes available for 18 patients, the median OS was 51.1 months. From the systematic review, we identified 8 studies, with 24 patients. Median age and tumor size was similar to the NCDB [47.5 years (IQR 39-66.5 years), 12 cm (IQR 7-17 cm)]. Majority [91.7 % (n = 22)] underwent surgical excision alone while one received adjuvant chemotherapy and none received radiation. After median follow up of 54 months (IQR 28-144 months), 79.2 % (n = 19) were alive without disease. Three patients (12.5 %) died of disease, one was alive with disease and one was lost to follow up. Recurrence was reported in 16.7 % (n = 4) of patients. CONCLUSION: Complete surgical excision is a viable treatment modality for retroperitoneal SFT leading to long term survival. Low recurrence rates would argue against the need for routine adjuvant radiation or chemotherapy.

Incorporation of diagnostic laparoscopy in the management algorithm for patients with peritoneal metastases: A multi-institutional analysis.

INTRODUCTION: Diagnostic laparoscopy (DL), which can predict complete cytoreduction (CC), is often considered unfeasible in patients with Peritoneal metastases (PM) due to a hostile abdomen, prior surgeries, incomplete assessment or risk of port site recurrence. We hypothesized that DL can be successfully incorporated into the management of patients with PM. METHODS: Retrospective review and data analysis of prospectively maintained databases from two high volume institutions was performed between 2007 and 2013. RESULTS: DL was successfully completed in 211/217 (92.6%) patients with PM. The technique for entry was the Hasson in 57%, optical trocar in 38% and Veress needle in 5%. Serosal injury from DL occurred in one patient (0.4%). Predominant histology included appendiceal (40%) and colorectal primaries (34%). Exclusion from cytoreduction by DL occurred in 68 (31.3%). Among those excluded, 7 (of 68, 10.3%) subsequently underwent CRS + HIPEC after receiving systemic chemotherapy. Overall survival (from laparoscopy) for those that underwent CRS + HIPEC at the original operation was 36 versus 12.7 months among those who were excluded by laparoscopy. There were no cases of port site recurrence. CONCLUSION: Diagnostic laparoscopy can be safely incorporated in the management of patients with peritoneal metastases, and can be especially beneficial in excluding patients from attempted incomplete cytoreduction.

Comparative effectiveness of hepatic artery based therapies for unresectable intrahepatic cholangiocarcinoma.

BACKGROUND: Hepatic artery based therapies (HAT) are offered for patients with unresectable intrahepatic cholangiocarcinoma (ICC). We aimed to evaluate the comparative effectiveness of HAT -hepatic arterial infusion (HAI), transcatheter arterial chemoembolization (TACE), drug-eluting bead TACE (DEB-TACE), and Yttrium(90) radioembolization (Y-90) for unresectable ICC. METHODS: A meta-analysis was performed using a prospectively registered search strategy at PROSPERO (CRD42013004830) that utilized PubMed (2003-2013). Primary outcome was median overall survival (OS), and secondary outcomes were tumor response to therapy and toxicity. RESULTS: A total of 20 articles (of 793, n=657 patients) were selected for data extraction. Highest Median OS was observed for HAI (22.8, 95% CI 9.8-35.8) months versus Y90 (13.9, 9.5-18.3) months versus TACE (12.4, 10.9-13.9) months versus DEB-TACE (12.3, 11-13.5) months. Response to therapy (complete and partial) was highest for HAI (56.9%, 95%CI 41.0-72.8) versus Y90 (27.4%, 17.4-37.5) versus TACE (17.3%, 6.8-27.8). The grade III/IV toxicity (Events per patient) was highest for HAI (0.35, 95% CI 0.22-0.48) versus TACE (0.26, 0.21-0.32) versus DEB-TACE (0.32, 0.17-0.48). CONCLUSION: For patients with unresectable ICC treated with HAT, HAI offered the best outcomes in terms of tumor response and survival but may be limited by toxicity.