The role of circulating tumor DNA (ctDNA) is expanding in oncology practices, and it is increasingly being used for targeted therapies and disease monitoring. It is minimally invasive and provides ...data from both primary and secondary sites of disease. Herein, we report a unique case of a patient with microsatellite instability-high (MSI-H) pancreatic adenocarcinoma (PDAC) treated with neoadjuvant chemotherapy and pembrolizumab who achieved a pathologically confirmed complete resolution of the tumor. A 75-year-old female was diagnosed with pancreatic adenocarcinoma (PDAC) in the uncinate process with aortocaval and retrocrural adenopathy. Next-generation sequencing was obtained via ctDNA testing, and the patient was initiated on cytotoxic chemotherapy while awaiting results. ctDNA revealed MSI-H status, and pembrolizumab was added to the cytotoxic chemotherapy regimen. At follow-up after five cycles of treatment, excellent treatment response was noted on magnetic resonance imaging (MRI) of the abdomen, demonstrating the resolution of the pancreatic mass and adenopathy. Six months of neoadjuvant treatment was given in total, after which the patient underwent resection with curative intent and achieved a complete pathological response with no evidence of disease. The role of ctDNA testing in directing treatment and influencing follow-up has already demonstrated great value. In our case, ctDNA adequately replaced conventional tissue biopsy, alleviating the burden of invasive testing on the patient. This is of great value, especially for patients with non-resectable tumors as well as in several other clinical scenarios. Our case also contributes to the growing body of literature demonstrating the role of immune-directed therapy for MSI-H PDAC.
No systemic therapies have been approved for the treatment of advanced cutaneous squamous-cell carcinoma. This cancer may be responsive to immune therapy, because the mutation burden of the tumor is ...high and the disease risk is strongly associated with immunosuppression. In the dose-escalation portion of the phase 1 study of cemiplimab, a deep and durable response was observed in a patient with metastatic cutaneous squamous-cell carcinoma.
We report the results of the phase 1 study of cemiplimab for expansion cohorts of patients with locally advanced or metastatic cutaneous squamous-cell carcinoma, as well as the results of the pivotal phase 2 study for a cohort of patients with metastatic disease (metastatic-disease cohort). In both studies, the patients received an intravenous dose of cemiplimab (3 mg per kilogram of body weight) every 2 weeks and were assessed for a response every 8 weeks. In the phase 2 study, the primary end point was the response rate, as assessed by independent central review.
In the expansion cohorts of the phase 1 study, a response to cemiplimab was observed in 13 of 26 patients (50%; 95% confidence interval CI, 30 to 70). In the metastatic-disease cohort of the phase 2 study, a response was observed in 28 of 59 patients (47%; 95% CI, 34 to 61). The median follow-up was 7.9 months in the metastatic-disease cohort of the phase 2 study. Among the 28 patients who had a response, the duration of response exceeded 6 months in 57%, and 82% continued to have a response and to receive cemiplimab at the time of data cutoff. Adverse events that occurred in at least 15% of the patients in the metastatic-disease cohort of the phase 2 study were diarrhea, fatigue, nausea, constipation, and rash; 7% of the patients discontinued treatment because of an adverse event.
Among patients with advanced cutaneous squamous-cell carcinoma, cemiplimab induced a response in approximately half the patients and was associated with adverse events that usually occur with immune checkpoint inhibitors. (Funded by Regeneron Pharmaceuticals and Sanofi; ClinicalTrials.gov numbers, NCT02383212 and NCT02760498 .).
Pancreatic cancer is an aggressive malignancy with poor survival and high mortality rate with 250 000 deaths per year worldwide. The unique pancreatic cancer microenvironment serves as a major ...obstacle in the effective treatment of this malignancy. The microenvironment consists not only of pancreatic ductal adenocarcinoma cells but also comprises cells of pancreatic cancer stellate, vascular, and immune origin combined with a dense extracellular matrix containing collagen. The aforementioned pathology leads to an increased intratumor pressure combined with an erratic vascular proliferation within the tumor causing hypoxia and decreased drug delivery. This has led both scientists and clinicians to develop and study drugs with unique mechanisms of action to target the pancreatic cancer microenvironment. Herein, we discuss the pancreatic cancer hypoxic microenvironment, development of hypoxia-activated prodrugs, and results of trials utilizing those drugs to target pancreatic cancer.
Adherence to US Preventative Services Task Force (USPSTF) cancer screening guidelines remains considerably lower than the recommendation of the Healthy People 2020 initiative. Patient populations ...recommended for screening are not screened at an appropriate rate, and populations not recommended for screening are inappropriately screened. Closer adherence to guidelines should improve outcomes and reduce costs, estimated to reach $158 billion/year by 2020. We evaluated whether a use of low-cost educational health maintenance (HM) card by medical residents at a university hospital could impact education and adherence to updated cancer screening guidelines. We also analyzed savings to the healthcare system. Adherence to cervical, breast, and colorectal cancer screening guidelines, defined as percentage that was screened (or not screened) in accordance with the USPSTF guidelines, in clinic visits from December 2012 (
n
= 336) was compared to those from December 2013 (
n
= 306) after a quality improvement intervention. Post-intervention, adherence to screening guidelines increased by 40.8% (
p
< 0.01) for cervical, 33.2% (
p
< 0.01) for breast, and 20.5% (
p
< 0.01) for colorectal cancer in average-risk patients. Inappropriate screening was reduced by 26.8% (
p
< 0.01) for cervical and 32.8% (
p
< 0.01) for breast cancer. A non-significant 1.1% decrease (
p
= 0.829) was observed for colorectal cancer. The annual potential savings from avoiding inappropriate screenings were $998,316 (95% CI; $644,484–$1,352,148). We showed a significant absolute increase in USPSTF knowledge of 28.3% irrespective of the house staff level that remained high at 2 years from the educational intervention. The low-cost HM card increased appropriate knowledgeable cancer screening adherence while reducing unnecessary testing and producing substantial savings to the healthcare system.
•Cancer-associated venous thromboembolism is a common cause of death.•Therapeutic anticoagulation for cancer thrombosis is indicated.•Major bleeding is a concern, especially in patients with ...gastrointestinal or genitourinary malignancies.•Apixaban appears to have lower bleeding risk than rivaroxaban.•Clinical shared decision-making with the patient is necessary to tailor treatment according to specific risk factors.
The low prevalence rate and limited literature on eccrine carcinoma (EC) pose a challenge to properly diagnosing and treating this rare malignancy. EC lesions tend to present similarly to other ...cutaneous neoplasms and dermatitis-like conditions. Efficacious treatment guidelines have not been established for patients diagnosed with EC, and few treatment regimens have demonstrated clinical benefit. Due to the high metastatic potential of EC, recognizing the clinical presentation, properly diagnosing, and utilizing beneficial treatment options are important for managing this disease. We report a case of a 66-year-old female who presented with lesions that her primary care provider misdiagnosed as basal cell carcinoma. The disease responded poorly to taxane- and platinum-based chemotherapies as well as an isolated limb perfusion of an alkylating agent. However, continuous dosing of oral capecitabine achieved an 18-month period of progression free survival (PFS) and ameliorated quality of life. We wish to highlight this rare disease and discuss presentation, diagnosis, and management as it is most often misdiagnosed leading to advanced metastatic disease when patients present to the oncologist. In addition, it is crucial to study and report potentially efficacious regimens considering the lack of clinical trials in this disease.
BACKGROUNDGastrointestinal cancer (GICA) is associated with a higher incidence of venous thromboembolism (VTE) compared to other solid tumors, moreover, recurrent VTE and major bleeding (MB) ...complications during anticoagulation treatment have an associated increase rate. GICA-VTE remains a challenging clinical scenario with MB concerns for utilization of direct oral anticoagulants (DOAC), especially with active cancer therapies. AIMTo evaluate patient risk factors, effectiveness (VTE) and safety (MB) of DOACs and low molecular weight heparin (LMWH) in patients with active GICA-VTE. METHODSA retrospective chart review of patients receiving DOACs and LMWH with GICA and symptomatic or incidental VTE treated at comprehensive cancer center from November 2013 to February 2017 was performed. Inclusion criteria included active GI cancer diagnosed at any stage or treatment +/- 6 mo of VTE diagnosis, whom were prescribed 6 mo or more of DOACs or LMWH. The Chi-squared test was used for overall and the Fisher exact test for pairwise comparisons of the proportions of patients experiencing recurrent VTE and MB events. Odds ratios were used to compare the relative odds of the occurrence of the outcome given exposure to the risk factor. RESULTSA total of 144 patients were prescribed anticoagulation, in which 106 fulfilled inclusion criteria apixaban (27.3%), rivaroxaban (34.9%) and enoxaparin (37.7%), and 38 were excluded. Patients median age was 66.5 years at GICA diagnosis and 67 years at CAVTE event, with 62% males, 80% Caucasian, 70% stage IV, pancreatic cancer (40.5%), 30% Khorana Score (≥ 3 points), and 43.5% on active chemotherapy. Sixty-four percent of patients completed anticoagulation therapy (range 1 to 43 mo). Recurrent VTE at 6 mo was noted in 7.5% (n = 3), 6.8% (n = 2) and 2.7% (n = 1) of patients on enoxaparin, apixaban and rivaroxaban, respectively (all P = NS). MB at 6 mo were 5% (n = 2) for enoxaparin, 6.8% (n = 2) for apixaban and 21.6% (n = 8) for rivaroxaban (overall P = 0.048; vs LMWH P = 0.0423; all other P = NS). Significant predictors of a primary or secondary outcome for all anticoagulation therapies included: Active systemic treatment (OR = 5.1, 95%CI: 1.3-19.3), high Khorana Score ≥ 3 points (OR = 5.5, 95%CI: 1.7-17.1), active smoker (OR = 6.7, 95%CI: 2.1-21.0), pancreatic cancer (OR = 6.8, 95%CI: 1.9-23.2), and stage IV disease (OR = 9.9, 95%CI: 1.2-79.1). CONCLUSIONRivaroxaban compared to apixaban and enoxaparin had a significantly higher risk of MB on GICA-VTE patients with equivocal efficacy.
Neuroblastoma is considered a pediatric malignancy as over 95% of cases are diagnosed in patients ≤10 years old. This cancer is extremely rare in elderly patients. We conducted a Surveillance, ...Epidemiology, and End Results (SEER) database analysis in the USA between 1973-2007 that revealed only 35 elderly patients (>60 years of age) with neuroblastoma of whom only 2 patients had primary mediastinal neuroblastoma. There is a paucity of treatment and survival outcomes data for the elderly owing to the rarity of neuroblastoma in this population. Currently there are no standard guidelines or protocols for treatment of adult neuroblastoma. We report a rare and challenging case of an 86-year old patient presenting with mediastinal neuroblastoma and syndrome of inappropriate antidiuretic hormone secretion (SIADH) successfully treated with resection. Herein, we also provide a review of the literature and updated survival data on neuroblastoma based on results of our SEER database review.
Purpose: To evaluate the maximum tolerated dose, safety profile, pharmacokinetics, and pharmacodynamics of pegaspargase (PEG-ASP) in combination with gemcitabine in patients with advanced metastatic ...solid tumors and lymphoma. Methods: We conducted a multicenter, open label, nonrandomized, Phase 1 dose escalation study designed to evaluate up to 10 cohorts of patients with advanced or metastatic solid tumors and lymphoma. Seventeen patients were treated with of PEG-ASP in combination with gemcitabine. Results: The study was terminated early because the doses for PEG-ASP suggested for de-escalation were predicted not to provide desired sustained asparaginase concentrations based on the analysis of treated patients.
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