Clinical Value of Timely Targeted Therapy for Patients With Advanced Non-Small Cell Lung Cancer With Actionable Driver Oncogenes.

BACKGROUND: A recent real-world study observed that 24% of patients with advanced non-small cell lung cancer (aNSCLC) with actionable driver oncogenes (ADOs) initiated nontargeted therapies before biomarker test results became available. This study assessed the clinical impact of the timing of first-line (1L) targeted therapies (TTs) in aNSCLC. MATERIALS AND METHODS: This retrospective analysis of a nationwide electronic health record-derived deidentified database included patients aged ≥18 years diagnosed with aNSCLC with ADOs (ALK, BRAF, EGFR, RET, MET, ROS-1, and NTRK) from January 1, 2015, to October 18, 2022, by biomarker testing within 90 days after advanced diagnosis and received 1L treatment. Cohorts were defined by treatment patterns ≤42 days after test results: "Upfront TT" received 1L TT ≤42 days; "Switchers" initiated 1L non-TT before or after testing but switched to TT ≤42 days; and "Non-switchers" initiated non-TT before or after testing and did not switch at any time. Adjusted multivariate Cox regression evaluated real-world progression-free survival, real-world time to next treatment or death, and real-world overall survival. RESULTS: A total of 3540 patients met the study criteria; 78% were treated in a community setting, and 50% underwent next-generation sequencing (NGS). There was no significant difference in outcomes between Switchers and Upfront TT; inferior outcomes were observed in Non-switchers versus Upfront TT. CONCLUSION: Our findings demonstrated improved outcomes with upfront 1L TT versus non-TT in patients with aNSCLC with ADOs and observed timely switching to TT after biomarker test result had similar outcomes to Upfront TT. Opportunities remain to improve the use of NGS for early ADO identification and determination of 1L TT.

Young Woman with Unexplained Neutropenia and Neutrophils with Bilobed Nuclei: Marrow Findings.

A 27-year-old female with a history of chronic sinusitis was referred for the evaluation of asymptomatic neutropenia. The differential demonstrated a mild neutropenia, which eventually resolved on subsequent evaluation. The liver and the spleen were not palpable. Peripheral flow cytometry was normal. Peripheral blood smear (PBS) demonstrated numerous Pelger-Huet anomalous neutrophils with characteristic "pince-nez" nuclei, without significant abnormalities in the other cell lines. Due to the benign clinical nature of hereditary PHA, a bone marrow biopsy is almost never required. However, our patient's persistent and worsening neutropenia was unusual for hereditary PHA, so a bone marrow biopsy was performed to rule out MDS and leukemia. Our patient's bone marrow smears showed dysplastic changes to other cell lines including the megakaryocytes and erythroid precursors. Due to our patient's young age and concern that she may have a more serious marrow disorder, genetic testing was pursued. Germline testing in the LBR gene revealed a heterozygous pathogenic mutation, namely, the PR57837.17 variant, confirming the diagnosis of hereditary disease. The bone marrow biopsy performed on our patient illustrates that the presence of dysplasia does not rule out hereditary PHA and further genetic testing should be done in the appropriate clinical scenario. This case was an atypical presentation of hereditary PHA with confounding morphological features that would typically classify the disease as an acquired or pseudo-PHA, hence acting as a Pseudo-Pseudo-Pelger-Huet Anomaly.

Improving biomarker testing in advanced non-small-cell lung cancer and metastatic colorectal cancer: experience from a large community oncology network in the USA.

Aim: Biomarker testing detects actionable driver mutations to inform first-line treatment in advanced non-small-cell lung cancer (aNSCLC) and metastatic colorectal cancer (mCRC). This study evaluated biomarker testing in a nationwide database (NAT) versus the OneOncology (OneOnc) community network. Patients & methods: Patients with aNSCLC or mCRC with ≥1 biomarker test in a de-identified electronic health record-derived database were evaluated. OneOnc oncologists were surveyed. Results: Biomarker testing rates were high and comparable between OneOnc and NAT; next-generation sequencing (NGS) rates were higher at OneOnc. Patients with NGS versus other biomarker testing were more likely to receive targeted treatment. Operational challenges and insufficient tissue were barriers to NGS testing. Conclusion: Community cancer centers delivered personalized healthcare through biomarker testing.

What is this article about? Cancer therapies often work better in certain subgroups of patients. Tumors may have characteristics that can predict which therapies may be more likely to work. These cancer biomarkers may be identified by special testing, such as next-generation sequencing (NGS). If a biomarker is detected, the patient can potentially be treated with medicine that targets that biomarker. This study looked at biomarker testing of lung and colon cancers in two community cancer practices (OneOncology [OneOnc] and nationwide database [NAT]). What were the results? The biomarker testing rates were high (≥81%) and similar between OneOnc and NAT. NGS testing rates were higher at OneOnc than at NAT (58 vs 49% for non-small-cell lung cancer, 55 vs 42% for metastatic colorectal cancer [mCRC]), suggesting the success of OneOnc's networkwide educational, pathway and operational programs. NGS testing was lower in community practices due to operational challenges and insufficient tissue collection. Patients who had NGS versus other biomarker testing were more likely to receive treatment specifically for that biomarker. However, some patients started treatment before their biomarker results were reported, usually because of their disease and a long wait time for biomarker test results. What do the results of the study mean? Community cancer centers can treat patients with targeted medicine based on biomarker testing results. There are opportunities to increase the number of patients getting NGS testing, shorten turnaround times and reduce the number of patients who start treatment before getting their biomarker test results.

A randomized phase II study of SM-88 plus methoxsalen, phenytoin, and sirolimus in patients with metastatic pancreatic cancer treated in the second line and beyond.

BACKGROUND: This trial explores SM-88 used with methoxsalen, phenytoin, and sirolimus (MPS) in pretreated metastatic pancreatic ductal adenocarcinoma (mPDAC) METHODS: Forty-nine patients were randomized to daily 460 or 920 mg oral SM-88 with MPS (SM-88 Regimen). The primary endpoint was objective response rate (RECIST 1.1). RESULTS: Thirty-seven patients completed ≥ one cycle of SM-88 Regimen (response evaluable population). Disease control rate (DCR), overall survival (OS), and progression-free survival (PFS) did not differ significantly between dose levels. Stable disease was achieved in 9/37 patients (DCR, 24.3%); there were no complete or partial responses. Quality-of-life (QOL) was maintained and trended in favor of 920 mg. SM-88 Regimen was well tolerated; a single patient (1/49) had related grade 3 and 4 adverse events, which later resolved. In the intention-to-treat population of 49 patients, the median overall survival (mOS) was 3.4 months (95% CI: 2.7-4.9 months). Those treated in the second line had an mOS of 8.1 months and a median PFS of 3.8 months. Survival was higher for patients with stable versus progressive disease (any line; mOS: 10.6 months vs. 3.9 months; p = 0.01). CONCLUSIONS: SM-88 Regimen has a favorable safety profile with encouraging QOL effects, disease control, and survival trends. This regimen should be explored in the second-line treatment of patients with mPDAC. CLINICALTRIALS: gov Identifier: NCT03512756.

Pulmonary embolism diagnosed on computed tomography contrast angiography despite negative venous Doppler ultrasound after spinal surgery.

STUDY DESIGN: The focus of this study was on the frequency of negative initial/subsequent ultrasound (US) of the lower extremities but positive spinal computed tomography contrast angiography (CTA) diagnostic of pulmonary embolism (PE) among 75 patients undergoing cervical laminectomy/fusion and 165 patients having lumbar laminectomy/noninstrumented fusion. OBJECTIVE: To determine the percentage/incidence of patients undergoing spinal surgery with negative US but with positive CTA. SUMMARY OF BACKGROUND DATA: The frequency of patients with negative US but with positive CTA after spinal surgery is not well documented. METHODS: For 240 spinal surgery patients, postoperative prophylaxis against deep venous thrombosis consisted of alternating pneumatic compression stockings alone. The patients were routinely screened on postoperative days 1 to 2 for deep venous thrombosis using US. The incidence of initial/subsequent negative US and positive CTA diagnostic for PE in patients with mild/major symptoms was evaluated, in conjunction with the frequency of hypercoagulation syndromes. RESULTS: Five (6.7%) patients undergoing cervical surgery and 6 patients (3.6%) undergoing lumbar surgery exhibited negative US but positive CTA on postoperative days 1 to 21. All the patients immediately received inferior vena cava filters (2 permanent and 9 retrievable). Five patients (45%) tested positive for hypercoagulation syndromes. Two patients were fully anticoagulated on postoperative days 3 and 21 with major symptoms attributed to saddle emboli; 1 had hypercoagulation syndrome. Anticoagulation was delayed for 6 to 12 weeks in 7 patients with milder symptoms, as magnetic resonance imaging scans showed residual seromas; 4 had hypercoagulation syndromes. Two elderly patients, at high risk for falls, without hypercoagulation syndromes were not anticoagulated. CONCLUSIONS: The frequency of negative US of the lower extremities but with positive CTA for PE after 240 cervical/lumbar spinal procedures in patients with mild/major symptoms ranged from 3.6% to 6.7%; 5 of the 11 patients exhibited hypercoagulation syndromes. To avoid failure to diagnose PE after spinal surgery, one should have a "low threshold" (eg, based even on minor symptoms) for requesting the CTA.

Prognostic factors and jaw and renal complications among multiple myeloma patients treated with zoledronic acid.

Few studies have evaluated prognostic factors among patients with multiple myeloma (MM) since new therapies have become available. Monthly zoledronic acid (ZOL) has been incorporated into many treatment regimens to reduce skeletal-related events (SREs), but outcomes among patients receiving this bisphosphonate have not been well-defined. The aim of this retrospective study was to determine baseline and on-treatment prognostic factors in these patients. Data were collected from the date of diagnosis on 300 consecutive MM patients treated with ZOL. Median duration of ZOL was 18 months (range 1-121 months). The skeletal morbidity rate was 0.116 events per patient year. Five-year overall survival (OS) was 69%. Risk factors for shortened OS included SREs, increased serum creatinine, and International Staging System (ISS) Stage II or III. Thirty-four (11%) patients showed worsening renal function. In 28 of these patients, ZOL was discontinued and restarted in half of these patients following a brief delay. Only 5 of the 34 patients showed worsening of their renal function. Fourteen patients (4.7%) developed osteonecrosis of the jaw (ONJ). All patients with ONJ are in remission or with stable disease except one patient who died of a myocardial infarction while in remission. Only two patients showed some worsening of ONJ despite of ongoing monthly ZOL. Overall, these results suggest that skeletal complications are an important prognostic factor for MM. Although ONJ and renal deterioration may infrequently occur with ZOL, most patients do not experience worsening of these conditions with ongoing treatment with this bisphosphonate.

Successful treatment of secondary hemophagocytic lymphohistiocytosis in a patient with disseminated histoplasmosis.

Hemophagocytic lymphohistiocytosis (HLH) is an overwhelming inflammatory response, associated with an outpouring of cytokines and inappropriate activation of the macrophage system, causing severe morbidity and possible death. HLH has inherited and acquired forms. Secondary HLH can be related to any number of underlying conditions including infections, malignancy and autoimmune diseases. There are similarities between "cytokine storm" seen in HLH and the clinical findings of avian influenza. We report a patient with a history of sarcoidosis on chronic steroid treatment, who developed HLH secondary to an infection with Histoplasma capsulatum.

Is pylorospasm a cause of delayed gastric emptying after pylorus-preserving pancreaticoduodenectomy?

BACKGROUND: Delayed gastric emptying (DGE) occurs in 14% to 61% of patients after pylorus-preserving pancreaticoduodenectomy, but its pathogenesis is unclear. We hypothesized that DGE may be due to pylorospasm secondary to vagal injuries at operation and may be preventable by the addition of pyloromyotomy. METHODS: Patients operated on consecutively between April 2000 and August 2003 were studied. Pyloromyotomy was of the Fredet-Ramstedt type combined with antroplasty. DGE-free recovery was defined as tolerance of a diet for three successive days by postoperative day 8. The symptom of nausea was used as a basis for nasogastric tube removal and diet resumption. A gastric emptying test (GET) with solid food was obtained. Patients with difficulty swallowing were fed via a feeding tube. RESULTS: There were 47 patients. Two patients were excluded because of death (n = 1) and ileus with pancreatic fistula (n = 1). Diagnoses were pancreatic cancer (n = 23), chronic pancreatitis (n = 11), ampullary cancer (n = 5), mucinous cystic neoplasm (n = 5), and duodenal villous adenoma (n = 3). Median times to nasogastric tube removal, start of liquid diet, and start of solid diet were postoperative days 2, 3, and 5, respectively. Two patients had tube feedings. Preoperative GET was abnormal in 51%, and postoperative GET was abnormal in 37%. The average length of stay was 9.5 days (median, 7 days). DGE occurred in only one patient (2.2%). There were no late complications during a 6-month follow-up. CONCLUSIONS: The addition of pyloromyotomy to pylorus-preserving pancreaticoduodenectomy is effective in preventing DGE. Results are supportive of the hypothesis that DGE may be caused by operative injuries of the vagus innervating the pyloric region.

Metastatic adenocarcinoma of the colon and follicular lymphoma within the same lymph node: a case report and review of the literature.

Concomitant adenocarcinoma and non-Hodgkin's lymphoma, both located in the intestinal tract, are unusual. We report a unique case of moderately differentiated of the cecum and a simultaneous follicular lymphoma, Grade 1, of the terminal ileum and regional lymph nodes in a 55-yr-old man. One lymph node was involved by both adenocarcinoma and follicular lymphoma. To our knowledge, this is the fifteenth reported case of concurrent adenocarcinoma and non-Hodgkin's lymphoma of the intestine, but this is the first case with involvement of follicular lymphoma and adenocarcinoma within the same lymph node.

Diffuse pulmonary infiltrates in immunocompromised patients.

Preview The approach to immunocompromised patients with diffuse pulmonary infiltrates has become increasingly complex with the evolution of more intense immunosuppressive therapy. Controversy still exists regarding the use of invasive diagnostic procedures rather than empirical therapy for this heterogeneous group. Dr Staszewski explains the reasons for the uncertainty and recommends an individualized approach that takes into account type of immunosuppression, local resources, physician experience, and patient prognosis.