Single-route CNS prophylaxis for aggressive non-Hodgkin lymphomas: real-world outcomes from 21 US academic institutions.

Prophylaxis is commonly used to prevent central nervous sy stem (CNS) relapse in diffuse large B-cell lymphoma (DLBCL), with no clear standard of care. We retrospectively evaluated 1162 adult patients across 21 US academic centers with DLBCL or similar histologies who received single-route CNS prophylaxis as part of frontline therapy between 2013 and 2019. Prophylaxis was administered intrathecally(IT) in 894 (77%) and using systemic high-dose methotrexate (HD-MTX) in 236 (20%); 32 patients (3%) switched route due to toxicity and were assessed separately. By CNS-International Prognostic Index (IPI), 18% were considered low-risk, 51% moderate, and 30% high. Double-hit lymphoma (DHL) was confirmed in 243 of 866 evaluable patients (21%). Sixty-four patients (5.7%) had CNS relapse after median 7.1 months from diagnosis, including 15 of 64 (23%) within the first 6 months. There was no significant difference in CNS relapse between IT and HD-MTX recipients (5.4% vs 6.8%, P = .4), including after propensity score matching to account for differences between respective recipient groups. Weighting by CNS-IPI, expected vs observed CNS relapse rates were nearly identical (5.8% vs 5.7%). Testicular involvement was associated with high risk of CNS relapse (11.3%) despite most having lower CNS-IPI scores. DHL did not significantly predict for CNS relapse after single-route prophylaxis, including with adjustment for treatment regimen and other factors. This large study of CNS prophylaxis recipients with DLBCL found no significant difference in CNS relapse rates between routes of administration. Relapse rates among high-risk subgroups remain elevated, and reconsideration of prophylaxis strategies in DLBCL is of critical need.

Does tumor profile in gastric and gastroesophageal (GE) junction cancer justify off-label use of targeted therapy?-a narrative review.

Despite significant therapeutic progress, gastric cancer remains among the most deadly forms of cancer encountered in clinical practice, and this remains true even in the context of declining incidence. Outcomes in advanced disease remain poor and therapy is rarely curative in this setting. As our understanding of tumor profile gains sophistication, a growing interest in targeted therapies and moreover the use of tumor profile to inform these therapies has developed in the hopes of altering nearly uniformly poor outcomes. A wide and growing array of molecular targets have been identified in the recent past. Targets of potential clinical interest include human epidermal growth factor receptor-2 (HER2), epidermal growth factor receptor (EGFR), poly(ADP-ribose) polymerase (PARP), mammalian target of rapamycin (mTOR), c-MET, and fibroblast growth factor receptor (FGFR). This advanced molecular understanding has been increasingly used to justify the off-label usage of targeted therapies, though the efficacy of this approach warrants careful consideration. While targeted agents have demonstrated efficacy across a wide range of malignancies, even with molecular profiling data, efficacy is not assured. It will also be demonstrated that even within the same malignancy, what holds true in the metastatic setting does not necessarily apply to the adjuvant or neoadjuvant setting. This review will assess the current evidence for the use of targeted therapies utilizing these biomarkers in the context of gastric and gastroesophageal (GE) junction cancers.

Non-Small Cell Lung Cancer in the Era of Personalized Medicine: Molecular Tests that Matter.

The diagnosis and treatment of lung cancer is entering a new era. With increasingly advanced diagnostic tools, we are more able than ever to pinpoint genetic changes in tumor cells that allow us to treat with highly effective, targeted therapy. In a growing number of patients, we are able to avoid cytotoxic therapies altogether. The recent advent of immunotherapy has led to a similar paradigm shift. This article will review the latest advances in tumor tissue and blood biomarkers directly as they relate to available treatments. Specifically, we will review activating and sensitizing gene mutations, gene fusions, PD-L1 tumor score, and close with an appraisal of the rapidly advancing field of peripheral blood biomarkers.

Impact of neuroimaging in the pretreatment evaluation of early stage non-small cell lung cancer.

BACKGROUND: There are limited data and conflicting guideline recommendations regarding the role of neuroimaging in the pretreatment evaluation of non-small cell lung cancer (NSCLC). METHODS: We performed a retrospective, pragmatic cohort study of patients with NSCLC diagnosed between January 1 and December 31, 2015. Eligible patients were identified from an institutional tumor registry. We collected all records of pretreatment neuroimaging within 12 weeks of diagnosis, including CT head (CT) and MRI brain (MRI). We abstracted the indication for neuroimaging, presence of central neurologic symptoms and cancer stage (with and without neuroimaging findings) from the tumor registry and the electronic health record. RESULTS: We identified 216 evaluable patients with newly diagnosed NSCLC. 157 of 216 patients (72.7%) underwent neuroimaging as part of initial staging, and 41 (26%) were found to have brain metastases. Of 43 patients with central neurologic symptoms at the time of neuroimaging, 28 (67%) had brain metastasis. In patients without central neurologic symptoms, brain metastases were discovered in 0 of 33 patients with clinical stage I or II, 4 of 36 (11%) with clinical stage III and 9 of 45 (20%) with clinical stage IV disease. CONCLUSIONS: In patients with early stage NSCLC (i.e. clinical stage I and II) without central neurologic symptoms, brain metastases are unlikely. The continued use of neuroimaging in the pretreatment evaluation of clinical stage I patients without central neurologic symptoms is not needed.

Breast metastasis from colonic primary: a case report and review of the literature.

Colorectal cancer most commonly metastasizes to the liver and lung. The development of breast metastases is exceptionally rare and is associated with poor clinical outcomes. We report a case of colonic adenocarcinoma metastatic to the breast and review the literature.

Upfront intraperitoneal chemotherapy for patients with epithelial ovarian cancer: long-term follow-up of a previously published trial.

OBJECTIVE: To update previously published work on the long-term survivorship of patients with surgically debulked epithelial ovarian cancer who were treated with intraperitoneal cisplatin-based chemotherapy after initial debulking surgery during the pretaxane era. METHODS: The records of 15 ovarian cancer patients treated with i.p. cisplatin (CDDP) and either i.v. doxorubicin or i.v. cyclophosphamide from 1985-1993 were reviewed. Data on long-term survivorship, toxicity and ultimate cause of death were updated. RESULTS: Recurrence-free survival rates for all subjects were 67% at two years, 47% at five years and 40% at 10 years. Five of the 15 (33%) original patients are alive with no evidence of disease (NED) at 180, 183, 205, 228 and 228 months respectively with a median of 205 months since last treatment. Toxicity was present yet posed no long-term threat. CONCLUSION: As presented in the original paper, i.p. chemotherapy can be safely utilized in a community hospital setting. Long-term survival is possible even with suboptimal regimens of chemotherapy as compared with today's standard treatments.

The Epidemiology and Clinical Associations of Stroke in Patients With Acute Myeloid Leukemia: A Review of 10,972 Admissions From the 2012 National Inpatient Sample.

BACKGROUND: Acute leukemia is known to confer an elevated risk of both hemorrhagic and thrombotic complications, but the development of stroke in this population is poorly characterized. This study assesses clinical and epidemiologic factors in a population of inpatients with acute myeloid leukemia (AML) and stroke. METHODS: Using the 2012 National Inpatient Sample, demographic and clinical data including age, gender, race, length of stay, in-hospital procedures, discharge diagnosis, disposition, and mortality incidence were extracted. RESULTS: Of 7,296,968 admissions, 10,984 patients with active AML were analyzed. Of these, 65 patients had a concomitant cerebrovascular accident (CVA) (hemorrhagic or ischemic). There was a 50-fold increase in the risk of stroke in patients with active AML compared with all admissions. Patients with AML and CVAs were found to have significantly higher inpatient mortality than for all admitted patients with stroke (36.9% vs. 6.7%; odds ratio, 5.5; 95% confidence interval, 2.3-8.8; P < .0001). Multivariate logistic regression, after controlling for confounding variables, identified acute renal failure with tubular necrosis, hypernatremia, urinary tract infection, and secondary thrombocytopenia as significant predictors of stroke. CONCLUSIONS: Patients with AML have an elevated risk of CVA compared with all inpatients, and mortality in this population is high. Better characterization of risk factors of stroke in this vulnerable population is still needed.

A case of rituximab-induced hepatitis.

A case of hepatitis in a patient receiving rituximab for ITP is reported. After an extensive workup, no infectious or autoimmune etiology could be found. The authors believe that this represents a case of drug-induced hepatitis, which has not been reported for this agent in the past.