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.

Immunological Checkpoint Blockade in Anal Squamous Cell Carcinoma: Dramatic Responses Tempered By Frequent Resistance.

PURPOSE OF REVIEW: Squamous cell carcinoma of the anus (SCCA) is an HPV-associated malignancy that has limited treatment options. Immunotherapy has expanded these options and here we review current and emerging immunotherapeutic approaches. RECENT FINDINGS: Multiple studies of single-agent anti-PD1/PD-L1 immunotherapy have demonstrated a modest response rate of approximately 10% to 15%. While a minority of patients (~5%) with SCCA experience durable complete responses, most advanced SCCAs are resistant to anti-PD1/PD-L1 monotherapy. Given the need for more broadly effective immunotherapies, novel strategies, such as adaptive cell therapies and therapeutic vaccination, are being explored. To reduce the recurrence risk of localized high-risk SCCA, strategies combining immunotherapy with chemoradiation are also being investigated. While a small subset of patients with SCCA have prolonged responses to PD1-directed immunotherapy, the majority do not derive clinical benefit, and new immunotherapeutic strategies are needed. Better understanding of the immune microenvironment and predictive biomarkers could accelerate therapeutic advances.

Gut Microbiome-Colorectal Cancer Relationship.

Traditionally, the role of gut dysbiosis was thought to be limited to pathologies like Clostridioides difficile infection, but studies have shown its role in other intestinal and extraintestinal pathologies. Similarly, recent studies have surfaced showing the strong potential role of the gut microbiome in colorectal cancer, which was traditionally attributed mainly to sporadic or germline mutations. Given that it is the third most common cancer and the second most common cause of cancer-related mortality, 78 grants totaling more than USD 28 million have been granted to improve colon cancer management since 2019. Concerted efforts by several of these studies have identified specific bacterial consortia inducing a proinflammatory environment and promoting genotoxin production, causing the induction or progression of colorectal cancer. In addition, changes in the gut microbiome have also been shown to alter the response to cancer chemotherapy and immunotherapy, thus changing cancer prognosis. Certain bacteria have been identified as biomarkers to predict the efficacy of antineoplastic medications. Given these discoveries, efforts have been made to alter the gut microbiome to promote a favorable diversity to improve cancer progression and the response to therapy. In this review, we expand on the gut microbiome, its association with colorectal cancer, and antineoplastic medications. We also discuss the evolving paradigm of fecal microbiota transplantation in the context of colorectal cancer management.

Plasma metabolomic differences in early-onset compared to average-onset colorectal cancer.

Deleterious effects of environmental exposures may contribute to the rising incidence of early-onset colorectal cancer (eoCRC). We assessed the metabolomic differences between patients with eoCRC, average-onset CRC (aoCRC), and non-CRC controls, to understand pathogenic mechanisms. Patients with stage I-IV CRC and non-CRC controls were categorized based on age ≤ 50 years (eoCRC or young non-CRC controls) or  ≥ 60 years (aoCRC or older non-CRC controls). Differential metabolite abundance and metabolic pathway analyses were performed on plasma samples. Multivariate Cox proportional hazards modeling was used for survival analyses. All P values were adjusted for multiple testing (false discovery rate, FDR P < 0.15 considered significant). The study population comprised 170 patients with CRC (66 eoCRC and 104 aoCRC) and 49 non-CRC controls (34 young and 15 older). Citrate was differentially abundant in aoCRC vs. eoCRC in adjusted analysis (Odds Ratio = 21.8, FDR P = 0.04). Metabolic pathways altered in patients with aoCRC versus eoCRC included arginine biosynthesis, FDR P = 0.02; glyoxylate and dicarboxylate metabolism, FDR P = 0.005; citrate cycle, FDR P = 0.04; alanine, aspartate, and glutamate metabolism, FDR P = 0.01; glycine, serine, and threonine metabolism, FDR P = 0.14; and amino-acid t-RNA biosynthesis, FDR P = 0.01. 4-hydroxyhippuric acid was significantly associated with overall survival in all patients with CRC (Hazards ratio, HR = 0.4, 95% CI 0.3-0.7, FDR P = 0.05). We identified several unique metabolic alterations, particularly the significant differential abundance of citrate in aoCRC versus eoCRC. Arginine biosynthesis was the most enriched by the differentially altered metabolites. The findings hold promise in developing strategies for early detection and novel therapies.

Gastrointestinal treatment-related adverse events of combined immune checkpoint inhibitors: a meta-analysis.

Introduction: Combined immune checkpoint inhibitors can cause gastrointestinal adverse events. Methods: We performed a meta-analysis of pooled colonic, hepatic and pancreatic treatment-related adverse events of combined ICI. Results: 53 trials reporting treatment-related adverse events in 6581 patients. All grade diarrhea was the most common adverse event seen in 25.4% patients, followed by all grade hepatitis in nearly 13% patients and pancreatitis in nearly 7.5% patients. Conclusion: Our study provides pooled data of treatment-related adverse events from different combination immune checkpoint inhibitors use in solid tumors and demonstrates a high incidence of all grades and ≥3 grade gastrointestinal adverse events. Further studies are required to characterize these adverse events and assess their overall impact on treatment course and outcomes.

The article talks about a type of medicine called immune checkpoint inhibitors that are used to treat cancer. These medicines can sometimes cause problems in the stomach and liver when used in combination with other cancer treatments, which can lead to hospitalization or, rarely, death. We performed a study on 6581 people who took these medicines in combination with another treatment and determined exactly how often these side effects happened. We also looked at which combinations of medicines were safer. This information can help doctors identify the side effects early and treat them. It can also help scientists design more studies to learn more about these side effects and how to prevent them.

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.

Comparison of characteristics and outcomes of young-onset versus average onset pancreatico-biliary adenocarcinoma.

BACKGROUND: Young-onset gastrointestinal malignancies appear to be increasing in incidence. There are limited data on young-onset pancreaticobiliary adenocarcinoma (YO-PBA). METHODS: The study comprised patients with PBA (pancreatic adenocarcinoma, intra-, and extra-hepatic cholangiocarcinoma) and included in the National Cancer Database (NCDB) between 2004 and 2017. YO-PBA was defined as a diagnosis at age less than 50 years. Logistic regression to assess factors associated with YO-PBA status, and cox proportional hazards modeling to associate relevant factors with overall survival was performed. RESULTS: The study cohort comprised 360,764 patients, with 20,822 (5.8%) YO-PBA. YO-PBA was associated with (p-values<0.0001 for all): male sex (6.3% YO-male out of all male patients vs. 5.2% YO-female, OR 1.29, 95% CI 1.25-1.33), Black race (7.9% YO-Black vs. 5.0% YO-White, OR 1.72, 95% CI 1.64-1.80), lower income (6.4% YO-lowest household income based group vs. 5.5% highest, OR 1.08, 95% CI 1.03-1.13). YO-PBA were more likely to present with stage-IV disease (6.4% YO-Stage IV of all stage IV vs. 5.4% YO-Stage I-III, OR 1.25, 95% CI 1.21-1.29 p-value < 0.0001). Factors associated with overall survival (OS) in non-operable patients included-sex - male vs. female, HR 1.12 (95% CI 1.08-1.15); race - Black vs. White, HR 1.23 (95% CI 1.06-1.42); income group - lowest vs. highest, HR 1.33 (95% CI 1.27-1.39), and treatment center type - academic vs. nonacademic center, HR 0.87 (95% CI 0.85-0.90). CONCLUSIONS: Socioeconomic factors significantly impact incidence and outcomes for young-onset pancreaticobiliary adenocarcinoma (YO-PBA). More work is needed to help understand the mechanisms involved while addressing the disparities.

Macroglossia as the initial presentation of AL amyloidosis: review and updates in treatment.

We encountered a man in his 60s presenting with worsening macroglossia. The patient underwent extensive otolaryngology evaluation and was diagnosed with primary (AL) amyloidosis on tongue biopsy with Congo red stain. The patient then underwent a bone marrow biopsy and was also found to have concurrent multiple myeloma. He started induction therapy with daratumumab and CyBorD (cyclophosphamide, bortezomib, dexamethasone). Cardiac MRI revealed extensive cardiac amyloidosis and the patient was deemed high risk for autologous stem cell transplant (auto-HCT). Unfortunately, the patient underwent hospitalisation for heart failure exacerbation requiring extensive medical management and passed away as a result of this pathology. AL amyloidosis is a rare disease to begin with and macroglossia as the only presenting sign is notable. This case emphasises the importance of considering AL amyloidosis in patients presenting with similar complaints as macroglossia can be attributed to other less serious aetiologies.

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.

Novel Coronavirus Infection (COVID-19) Related Thrombotic and Bleeding Complications in Critically Ill Patients: Experience from an Academic Medical Center.

INTRODUCTION: Thrombosis and bleeding are recognized complications of the novel coronavirus infection (COVID-19), with a higher incidence described particularly in the critically ill. METHODS: A retrospective review of COVID-19 patients admitted to our intensive care units (ICU) between 1 January 2020 and 31 December 2020 was performed. Primary outcomes included clinically significant thrombotic and bleeding events (according to the ISTH definition) in the ICU. Secondary outcomes included mortality vis-a-vis the type of anticoagulation. RESULTS: The cohort included 144 consecutive COVID-19 patients with a median age of 64 years (IQR 54.5-75). The majority were male (85 (59.0%)) and Caucasian (90 (62.5%)) with a median BMI of 30.5 kg/m2 (IQR 25.7-36.1). The median APACHE score at admission to the ICU was 12.5 (IQR 9.5-22). The coagulation parameters at admission were a d-dimer level of 109.2 mg/mL, a platelet count of 217.5 k/mcl, and an INR of 1.4. The anticoagulation strategy at admission included prophylactic anticoagulation for 97 (67.4%) patients and therapeutic anticoagulation for 35 (24.3%) patients, while 12 (8.3%) patients received no anticoagulation. A total of 29 patients (20.1%) suffered from thrombotic or major bleeding complications. These included 17 thrombus events (11.8%)-8 while on prophylactic anticoagulation (7 regular dose and 1 intermediate dose) and 9 while on therapeutic anticoagulation (p-value = 0.02)-and 19 major bleeding events (13.2%) (4 on no anticoagulation, 7 on prophylactic (6 regular dose and 1 intermediate dose), and 8 on therapeutic anticoagulation (p-value = 0.02)). A higher thrombosis risk among patients who received remdesivir (18.8% vs. 5.3% (p-value = 0.01)) and convalescent serum (17.3% vs. 5.8% (p-value = 0.03%)) was noted, but no association with baseline characteristics (age, sex, race, comorbidity), coagulation parameters, or treatments (steroids, mechanical ventilation) could be identified. There were 10 pulmonary embolism cases (6.9%). A total of 99 (68.8%) patients were intubated, and 66 patients (45.8%) died. Mortality was higher, but not statistically significant, in patients with thrombotic or bleeding complications-58.6% vs. 42.6% (p-value = 0.12)-and higher in the bleeding (21.2%) vs. thrombus group (12.1%), p-value = 0.06. It did not significantly differ according to the type of anticoagulation used or the coagulation parameters. CONCLUSIONS: This study describes a high incidence of thrombotic and bleeding complications among critically ill COVID-19 patients. The findings of thrombotic events in patients on anticoagulation and major bleeding events in patients on no or prophylactic anticoagulation pose a challenging clinical dilemma in the issue of anticoagulation for COVID-19 patients. The questions raised by this study and previous literature on this subject demonstrate that the role of anticoagulation in COVID-19 patients is worthy of further investigation.

Landmark Cancer Clinical Trials and Real-World Patient Populations: Examining Race and Age Reporting.

BACKGROUND: Concern exists that the clinical trial populations differ from respective cancer populations in terms of their age distribution affecting the generalizability of the results, especially in underrepresented minorities. We hypothesized that the clinical trials that do not report race are likely to suffer from a higher degree of age disparity. METHODS: Food and Drug Administration (FDA) drug approvals from July 2007 to June 2019 were reviewed to identify oncology approvals, and trials with age details were selected. The outcomes studied were the weighted mean difference in age between the clinical trial population and real-world population for various cancers, the prevalence of race reporting and association of age and race reporting with each other. RESULTS: Of the 261 trials, race was reported in 223 (85.4%) of the trials, while 38 trials (14.6%) had no mention of race. Race reporting improved minimally over time: 29 (85.3%) in 2007-2010 vs. 49 (80.3%) in 2011-2014 vs. 145 (85.4%) during the period 2015-2019 (p-value = 0.41). Age discrepancy between the clinical trial population and the real-world population was higher for studies that did not report race (mean difference -8.8 years (95% CI -12.6 to -5.0 years)) vs. studies that did report it (mean difference -5.1 years, (95% CI -6.4 to -3.7 years), p-value = 0.04). CONCLUSION: The study demonstrates that a significant number of clinical trials leading to cancer drug approvals suffer from racial and age disparity when compared to real-world populations, and that the two factors may be interrelated. We recommend continued efforts to recruit diverse populations.

Characteristics and Outcomes of COVID-19 Patients Admitted to Intensive Care Units in a Large Health System in Western Pennsylvania.

Importance Despite growing literature, there is still limited understanding of factors that can predict outcomes in coronavirus disease 2019 (COVID-19) patients who require intensive care. Objective To evaluate the characteristics of COVID-19 patients admitted to the intensive care unit (ICU) and identify their associations with outcomes. Background There are limited data on the outcomes in COVID-19 patients in Pennsylvania. Design Retrospective study Setting Intensive care units in an academic health system in Western Pennsylvania. Participants Patients with reverse transcriptase-polymerase chain reaction (RT-PCR)-confirmed COVID-19 admitted to ICUs as direct admission or transfers from regular floors between March 1, 2020, and April 30, 2020. Main outcome(s) and measure(s) The primary outcome was inpatient mortality. Secondary outcomes included complications during ICU stay, hospital length of stay, discharge disposition, and the need for oxygen at discharge. Categorical variables are described as frequencies and continuous variables as median with interquartile range (IQR). Regression modeling was used to identify the predictors of inpatient mortality in these patients. P-value <0.05 was considered statistically significant. Analysis was performed using Stata version 15.1 (StataCorp, College Station, Texas). Results The cohort included 58 consecutive patients, with a median age of 62 years (IQR 54-73), 63.8% of which were male. On presentation, constitutional symptoms were the most common (91.4%), followed by lower respiratory tract symptoms (87.9%). Tachypnea (65.5%) and hypoxia (67.2%) were the most common abnormal vital signs at presentation. Common comorbidities were cardiovascular disease (74.1%), obesity (53.5%), and diabetes (39.7%). The median Acute Physiology and Chronic Health Evaluation (APACHE) score on admission to ICU was 11 (IQR 8.5-17.5). The major complications included acute respiratory distress syndrome (ARDS) 50.0%, shock 41.4%, and acute kidney injury 41.4%. The proportion of patients who underwent mechanical ventilation, required vasopressors, or were on renal replacement therapy were 58.6%, 41.4%, and 10.3%, respectively. Overall mortality was 32.8%. Age, Charlson-comorbidity index, tachypnea, lymphopenia at presentation, high APACHE score, shock, ARDS, mechanical ventilation, and steroid use were significantly associated with mortality. Of the patients who survived their ICU stay, 63.2% were discharged home and 44.7% had a new oxygen requirement at discharge. Conclusion and relevance Our study reports high mortality in COVID-19 patients requiring ICU care in Western Pennsylvania. Identifying factors associated with poor prognosis could help risk-stratify these patients. Prospective studies are needed to assess whether early risk stratification and triaging result in improved outcomes.

Disparities in ovarian cancer treatment and overall survival according to race: An update.

OBJECTIVE: To determine whether guideline non-adherence is associated with Black race. METHODS: A retrospective review of National Cancer Database records of women diagnosed with epithelial ovarian cancer from 2012 to 2016 who identified as "White" or "Black" was performed. Exposure was adherence or non-adherence to National Comprehensive Cancer Network guidelines for treatment. Outcomes were differences in disease characteristics and overall survival in months. RESULTS: Of the 29,948 eligible patients, 93% (n = 27,744) were White and 7% (n = 2204) were Black. Having stage IV disease (OR 1.45, 95% CI 1.23-1.70; P < 0.001) and treatment in a comprehensive (OR 1.58, 95% CI 1.16-2.15; P = 0.0039) or academic (OR 2.30, 95% CI 1.70-3.12; P < 0.001) treatment facility were associated with Black race. Adherence to guidelines did not predict Black race (OR for adherence 1.0021, 95% CI 0.89-1.13; P = 0.97). Median survival for White patients with adherent care was 63.4 months and 51.4 months for Black patients (P = 0.0001). Median survival for White patients with non-adherent care was 60.5 months and 47.2 months for Black patients (P < 0.0001). Median overall survival was 61.1 months in White patients and 49.3 months in Black patients (P < 0.0001). CONCLUSIONS: Our data suggest that while Black patients and patients who receive non-NCCN guideline directed care have worse survival outcomes, guideline adherence is not independently associated with Black race. We must consider other socioeconomic, environmental and system factors that are contributing to the survival discrepancy in Black patients with ovarian cancer.

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.

Desmoplastic Small Round-cell Tumor: Retrospective Review of Institutional Data and Literature Review.

BACKGROUND: Desmoplastic small round-cell tumor (DSCRT) in adults is an extremely rare (age-adjusted incidence 0.3 per million) and aggressive sarcoma with limited data for optimal management. PATIENTS AND METHODS: Retrospective analysis of patients with DSCRT diagnosis (2010-2020) was performed following Institutional Review Board approval. The follow-up period was from pathological diagnosis to the last patient contact. Endpoints were type of response and duration of response. RESULTS: In the current analysis, first-line treatment in all cases was vincristine, anthracycline, and cyclophosphamide alternating with ifosfamide and etoposide (VAC-IE) with 100% response for a mean duration of 9.8 (range=5-12) months. Patients received 1-4 subsequent lines of therapy. All patients received temozolomide with irinotecan (50% partial response, duration 8-9 months). Two patients that underwent consolidative cytoreductive surgery with hyperthermic intraperitoneal chemotherapy had a longer survival (30.6 vs. 11.2 months). Patients suffered 100% mortality with a median survival was 17.8 (range=11.2-30.6) months. CONCLUSION: While aggressive multimodality treatment is always warranted for DSCRT, the options are limited by the multicentric presentation, short-lived initial response and lack of established subsequent therapy portending a poor prognosis. Consolidative cytoreductive surgery following first-line therapy may improve survival.

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.

Haemophagocytic lymphohistiocytosis that spontaneously resolved: a case of EBV.

A 23-year-old Caucasian woman, presented with recurrent fevers, elevated liver function tests and pancytopenia. Her labs at presentation were white blood cells 1.5 ×109/L, haemoglobin 8 g/L, platelets 59 k/mcl, lactate dehydrogenase (LDH) over 2000 U/L, aspartate aminotransferase 593 U/L, alanine aminotransferase 1321 U/L, alkaline phosphatase 223 U/L and ferritin 7665 µg/L. Epstein-Barr virus (EBV) IgM and IgG antibodies were positive in serum. A soluble interleukin 2 receptor was elevated at 2458. A bone marrow biopsy revealed scattered macrophages containing erythrocytes and other cellular elements. Immunohistochemistry for CD68 highlighted macrophages with erythrophagocytosis and in situ hybridisation was positive for EBV. She met the diagnostic criteria for haemophagocytic lymphohistiocytosis (HLH). She was initially treated with broad spectrum antibiotics which were eventually discontinued once the diagnosis was established. Over a period of 2-3 weeks her fever, transaminitis, ferritin and LDH improved spontaneously. She continued to improve clinically and was subsequently discharged. HLH is an aggressive, life-threatening hyper-inflammatory syndrome which, if not promptly recognised and treated, can be fatal. Treatment involves etoposide-based chemotherapy and possible stem-cell transplantation. This patient showed signs of improvement spontaneously and a decision was made to not treat her. This was a rare case of EBV-associated HLH which resolved spontaneously without any intervention. This young patient was not subjected to unnecessary chemotherapy. So far only few cases of spontaneous resolution of EBV-associated HLH have been reported.