The Butterfly Flies - Practice Changing Results of PAPILLON, First Line Chemotherapy and Amivantamab for the Treatment of NSCLC Patients with EGFR Exon 20 Insertions.

Epidermal growth factor receptor (EGFR) exon 20 insertions are a rare subtype of EGFR mutations that do not respond to EGFR tyrosine kinase inhibitors developed for sensitizing mutations. In 2021, two drugs, amivantamab and mobocertinib each received FDA accelerated approval for second line use after platinum based therapy. These drugs were then brought to first line setting clinical trials; PAPILLON and EXCLAIM2. PAPILLON, which compared amivantamab plus chemotherapy to chemotherapy was positive, whereas EXCLAIM2, which compared mobocertinib to chemotherapy was negative. The PAPILLON regimen received subsequent FDA approval. In this commentary, we review the details of PAPILLON and also discuss why the rival trial, EXCLAIM2, may have failed.

Circadian Clock Dysregulation and Prostate Cancer: A Molecular and Clinical Overview.

Circadian clock dysregulation has been implicated in various types of cancer and represents an area of growing research. However, the role of the circadian clock in prostate cancer has been relatively unexplored. This literature review will highlight the potential role of circadian clock dysregulation in prostate cancer by examining molecular, epidemiologic, and clinical data. The influence of melatonin, light, night shift work, chronotherapy, and androgen independence are discussed as they relate to the existing literature on their role in prostate cancer.

Durable Response after Repeat Cytoreductive Surgery (CRS) and Hyperthermic Intraperitoneal Chemotherapy (HIPEC) in a Patient with Extensive Mucinous Adenocarcinoma of the Appendix.

Mucinous adenocarcinoma of the appendix is a rare form of lower gastrointestinal (GI) tract cancer. These cancers have a high tendency to progress towards peritoneal metastasis and their response to systemic treatment is typically low. Together, cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) have become an established form of therapy used to prolong the survival of patients with this disease. Repeat CRS and HIPEC have been shown to be feasible in selected patients with GI peritoneal carcinomatosis (PC), among which those with appendix cancer receive the greatest benefit. The peritoneal cancer index (PCI) and completeness of cytoreduction have been shown to be important predictors of outcomes. However, repeat cytoreduction in patients with a high-volume peritoneal tumor burden (peritoneal cancer index (PCI) > 30) is not typically performed due to concerns regarding morbidity and mortality. Herein, we describe a case of repeat CRS and HIPEC for extensive appendiceal mucinous peritoneal carcinomatosis after initial incomplete cytoreduction and durable remission of 28 months without adjuvant chemotherapy. In appendiceal mucinous cancers, repeat CRS can achieve a durable response despite an initial failed CRS and high-volume disease.

Combination of Pembrolizumab and Stereotactic Body Radiation Therapy in Recurrent Metastatic Penile Squamous Cell Carcinoma: A Case Study.

The prognosis for patients with penile squamous cell carcinoma metastatic to regional lymph nodes or distant sites remains poor with limited treatment options, especially after the failure of first-line chemotherapy. Clinical trials evaluating the use of checkpoint inhibitor therapy, or the use of checkpoint inhibitor therapy with stereotactic body radiation therapy for the treatment of metastatic penile squamous cell carcinoma, are currently unavailable. In this case report, we present a patient with relapsed advanced penile squamous cell carcinoma and an unknown (human papilloma virus) HPV status and borderline programmed death-ligand 1 (PD-L)1 status who was treated with pembrolizumab and stereotactic body radiation therapy. This patient achieved a complete durable treatment response despite having genomic features of an immunologically "cold" tumor. This case highlights the importance of investigating more into the treatment of these tumors that lack genomic features that classically have been observed to be susceptible to treatment with immunotherapy or immunotherapy augmented with stereotactic body radiation therapy in solid tumors, particularly in metastatic penile squamous cell carcinoma.

Durable Responses in Patients With Advanced Cholangiocarcinoma on Sequential Dual-agent Immunotherapy After Progressing on Single-agent Immunotherapy.

OBJECTIVES: Biliary tract tumors have a poor prognosis despite advancements in targeted therapies. More recent studies have started to investigate the use of combination immunotherapy in advanced biliary cancers. However, currently, there are no clinical trials investigating the use of dual-agent immunotherapy with ipilimumab and nivolumab as a sequential treatment after patients have progressed on single-agent immunotherapy. In this case series, we discussed 3 patients with advanced cholangiocarcinoma who have an objective response to dual-agent immunotherapy with ipilimumab and nivolumab after having disease progression on pembrolizumab and multiple other failed lines of treatment. MATERIALS AND METHODS: A case series, including 3 patients treated at the University of California, Irvine Chao Family Comprehensive Cancer Center, was completed. RESULTS: Although none of the 3 patients had microsatellite instability or high tumor-mutation burden and were not necessarily predicted to have a response to dual-agent immunotherapy, all 3 patients had an objective radiographic and/or tumor-marker response to a combination of ipilimumab and nivolumab. CONCLUSIONS: This case series serves as proof of the concept that sequential immunotherapy can be beneficial after progression on single-agent immunotherapy for patients with advanced cholangiocarcinoma. This study can also serve as the foundation to build further tests on the true effectiveness and ideal duration of sequential therapy with dual immunotherapy agents.

Early Adoption of Checkpoint Inhibitors in Patients with Metastatic Gastric Adenocarcinoma-A Case Series of Non-Operative Long-Term Survivors.

Checkpoint inhibitor (CPI) therapy has only recently been introduced in the first-line treatment of advanced gastric cancer. However, later line monotherapy CPI efficacy in a subset of patients was presented about four years prior. Here, we present three cases of advanced gastric adenocarcinoma cancers treated with CPI in early lines years prior to the availability of randomized first line data. All three patients remain in remission without gastrectomy, with the median time from initial diagnosis of approximately 52 months. With long-term follow-up of more than four years, we present a proof of concept that, with early integration of CPI therapy, highly durable responses are possible even in the absence of surgery in patients with advanced gastric and gastroesophageal junction cancers.

Acute Epiploic Appendagitis in a COVID-19-Positive Patient With Antiphospholipid Syndrome.

As the coronavirus disease 2019 (COVID-19) pandemic is still underway, a range of clinical presentations and pathologies continue to present themselves in unexpected ways. One such pathology is that of epiploic appendagitis, an uncommon and underdiagnosed cause of acute abdominal pain. We present the case of a 50-something-year-old male who presented with left lower quadrant abdominal pain in the setting of acute COVID-19 infection, found to have acute epiploic appendagitis. After persistent moderate to severe abdominal pain, epiploic appendagitis was diagnosed by computed tomography (CT) imaging findings. The patient was managed for his COVID-19 pneumonia over the course of his hospitalization, as well as conservatively managed with pain control measures for his epiploic appendagitis. This is the second reported case in the literature to the best of our knowledge that shares the case of acute epiploic appendagitis in a patient presenting with acute abdominal pain, who is also found to be COVID-19-positive. Procoagulant changes in coagulation pathways are found in patients with severe COVID-19, and contribute to venous thromboembolism in this patient population. Diagnosing and conservatively managing epiploic appendagitis will lead to decreasing misdiagnosis, preventing invasive or inappropriate treatments that may increase harm to patients, and more adequately understanding the complications associated with COVID-19.

Changing the channel on medical ethics education: systematic review and qualitative analysis of didactic-icebreakers in medical ethics and professionalism teaching.

As medical ethics and professionalism education continues to equip medical students and residents with long-lasting tools, educators should continue to supplement proven teaching strategies with engaging, relatable, and generationally appropriate didactic supplements. However, popular teaching aids have recently been criticized in the literature and summative information on alternatives is absent. The purpose of this review is to evaluate and assess the functional use and application of short form audiovisual didactic supplements or "icebreakers" in medical ethics and professionalism teaching. A systematic review of both the medical and humanities literature (i.e., PubMed/MEDLINE, Cochrane Library, and JSTOR) was conducted from inception to August 1, 2019. Final articles were subjected to a qualitative appraisal and thematic analysis. Thirteen articles were included for final analysis. Sixty-nine percent (n = 9) of the studies were published after 2000. Two studies were qualitative, one study was quantitative, and the remaining articles were commentaries. Short form audiovisual media was most popular outside of the United States (n = 10). Sixty-nine percent (n = 9) of articles advocated for self-contained media in the form of trigger films or short films/videos, while the remaining articles (n = 4) discussed the use of TV/film clips. Producibility of media was exclusive to short/trigger films. Nine themes were identified in the content analysis: adaptability, conversation catalyst, effective, engaging, nuance, practice, producibility, real, and subject diversity. The three most common themes in descending order of frequency were: conversation catalyst, realness, and adaptability. Trigger films represent an effective and unique pedagogical strategy in supplementing current medical ethics and professionalism teaching at the medical school level.

Characterization of a Novel Entity of G3 (High-grade Well-differentiated) Colorectal Neuroendocrine Tumors (NET) in the SEER Database.

OBJECTIVES: Small studies suggest that a new entity of high-grade (HG) (G3, by Ki-67 or mitotic index) well-differentiated (histologically) gastrointestinal neuroendocrine tumors (NETs) exists, but prognosis and characteristics are unknown. We further characterized demographics and prognosis of patients with colorectal G3 NETs. MATERIALS AND METHODS: We used the Surveillance Epidemiology and End Results (SEER) database to study colorectal NETs diagnosed from 2000 to 2015. We evaluated demographic, clinical, and tumor characteristics. We compared overall survival (OS) for G1-2 NET, G3 NET, and NEC (neuroendocrine carcinoma). We used logistic regression to detect grade associations and Cox proportional hazards models to examine predictors of survival. RESULTS: We identified 5894 cases with colorectal NET (5780 [98.1%] G1-2 and 114 [1.9%] G3); the cohort was 66% white, 47% male, and had a median age of 54. Patients with G3 NET were likely to be older (odds ratio [OR]: 2.23; 95% confidence interval [CI]: 1.19-4.19 for 60 to 69 vs. <50), unmarried (OR: 1.56; 95% CI: 1.02-2.38), and less likely to be diagnosed after 2010 (OR: 0.09; 95% CI: 0.06-0.15). OS for G3 NET (median, 36 mo; 95% CI: 13-92) fell between OS for NEC (median, 7 mo; 95% CI: 6-8), and G1-2 NET (median not reached, >120 mo). Among G1-3 NETs, black patients (hazard ratio [HR]: 1.30; 95% CI: 1.03-1.62), older patients (HR: 3.63; 95% CI: 2.63-5.01 for age 60 to 69 vs. <50), unmarried patients (HR: 1.40; 95% CI: 1.17-1.68), and those with HG features (HR: 3.97; 95% CI: 3.15-4.99) had worse survival. CONCLUSIONS: We defined a subset of G3 NETs that are HG and well differentiated, more common in older, unmarried patients, with a prognosis between that of NEC and G1-2 NETs. Our analysis adds the first national registry study in support of a new classification of nonpancreatic HG and well-differentiated NETs.

Diabetes mellitus and colorectal carcinoma outcomes: a meta-analysis.

OBJECTIVES: The impact of diabetes mellitus (DM) on colorectal cancer (CRC) outcomes remains unknown. We studied this by conducting a meta-analysis to evaluate (1) CRC outcomes with and without DM and (2) treatment patterns. METHODS: We searched PubMed, EMBASE, Google Scholar, and CINAHL for full-text English studies from 1970 to 12/31/2017. We searched keywords, subject headings, and MESH terms to locate studies of CRC outcomes/treatment and DM. Studies were evaluated by two oncologists. Of 14,332, 48 met inclusion criteria. In accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses method, we extracted study location, design, DM definition, covariates, comparison groups, outcomes, and relative risks and/or hazard ratios. We utilized a random-effects model to pool adjusted risk estimates. Primary outcomes were all-cause mortality (ACM), disease-free survival (DFS), relapse-free survival (RFS), and cancer-specific survival (CSS). The secondary outcome was treatment patterns. RESULTS: Forty-eight studies were included, 42 in the meta-analysis, and 6 in the descriptive analysis, totaling > 240,000 patients. ACM was 21% worse (OR 1.21, 95% CI 1.15-1.28) and DFS was 75% worse (OR 1.75, 95% CI: 1.33-2.31) in patients with DM. No differences were detected in CSS (OR 1.10, 95% CI 0.98-1.23) or RFS (OR 1.12, 95% CI 0.91-1.38). Descriptive analysis of treatment patterns in CRC and DM suggested potentially less adjuvant therapy use in cases with DM and CRC. CONCLUSIONS: Our meta-analysis suggests that patients with CRC and DM have worse ACM and DFS than patients without DM, suggesting that non-cancer causes of death in may account for worse outcomes.