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Papillary renal cell carcinoma (pRCC) is a rare kidney cancer with limited treatment options and poor outcomes when metastatic. We present a case of a 42-year-old male with metastatic pRCC harboring a somatic ataxia-telangiectasia mutated (ATM) mutation who was treated at our institution. After progression of disease (POD) on ipilimumab/nivolumab, followed by POD on cabozantinib, the patient was treated with radiation therapy to metastatic cervical lymphadenopathy to 60 Gy in 15 fractions as well as retroperitoneal lymphadenopathy to 36 Gy in 9 fractions, which was curtailed due to intolerance. This was followed by sequential systemic therapy with a poly (ADP-ribose) polymerase (PARP) inhibitor and pembrolizumab, which was also discontinued due to adverse effects. Despite not receiving any treatment for 10 months, his disease remains stable. We believe that the prolonged progression-free survival of this patient with ATM-mutation metastatic pRCC is likely due to the enhanced sensitivity of the tumor to radiation therapy due to ATM loss.

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 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.

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.

ObjectivesBiliary 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 methodsA case series, including 3 patients treated at the University of California, Irvine Chao Family Comprehensive Cancer Center, was completed.ResultsAlthough 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.ConclusionsThis 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.

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.

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.

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.

The authors convey their concerns about the limited incorporation of television and films in medical ethics and professionalism education. Topics mentioned include the sensationalization and over-dramatization of ethical issues by Hollywood, the use of trigger films that draw upon the strength of emotionally-engaging visual narratives, and the use of trigger films to supplement ongoing didactics.

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., Competing Interests: Dr Misako Nagasaka reports personal fees from AstraZeneca, Daiichi Sankyo, Novartis, EMD Serono, Pfizer, Lilly, Genentech, Regeneron, BMS, Caris Life Sciences, Takeda, Janssen, Blueprint Medicine, Mirati; non-financial support from AnHeart Therapeutics, outside the submitted work. The authors report no other conflicts of interest in this work., (© 2024 Kaakour and Nagasaka.)