Current Standards, Multidisciplinary Approaches, and Future Directions in the Management of Extrahepatic Cholangiocarcinoma.

OPINION STATEMENT: Biliary tract cancers are molecularly and anatomically diverse cancers which include intrahepatic cholangiocarcinoma, extrahepatic (perihilar and distal) cholangiocarcinoma, and gallbladder cancer. While recognized as distinct entities, the rarer incidence of these cancers combined with diagnostic challenges in classifying anatomic origin has resulted in clinical trials and guideline recommended strategies being generalized patients with all types of biliary tract cancer. In this review, we delve into the unique aspects, subtype-specific clinical trial outcomes, and multidisciplinary management of patients with extrahepatic cholangiocarcinoma. When resectable, definitive surgery followed by adjuvant chemotherapy (sometimes with selective radiation/chemoradiation) is current standard of care. Due to high recurrence rates, there is growing interest in the use of upfront/neoadjuvant therapy to improve surgical outcomes and to downstage patients who may not initially be resectable. Select patients with perihilar cholangiocarcinoma are being successfully treated with novel approaches such as liver transplant. In the advanced disease setting, combination gemcitabine and cisplatin remains the standard base for systemic therapy and was recently improved upon with the addition of immune checkpoint blockade to the chemotherapy doublet in the recently reported TOPAZ-1 and KEYNOTE-966 trials. Second-line all-comer treatments for these patients remain limited in both options and efficacy, so clinical trial participation should be strongly considered. With increased use of molecular testing, detection of actionable mutations and opportunities to receive indicated targeted therapies are on the rise and are the most significant driver of improved survival for patients with advanced stage disease. Though these targeted therapies are currently reserved for the second or later line, future trials are looking at moving these to earlier treatment settings and use in combination with chemotherapy and immunotherapy. In addition to cross-disciplinary management with surgical, medical, and radiation oncology, patient-centered care should also include collaboration with advanced endoscopists, palliative care specialists, and nutritionists to improve global patient outcomes.

Current and emerging strategies for the management of advanced/metastatic lung neuroendocrine tumors.

Pulmonary neuroendocrine tumors represent a spectrum of disease ranging from typical carcinoid tumors to small cell lung cancers. The incidence of low-grade pulmonary NETs has been increasing, leading to improved awareness and the need for more treatment options for this rare cancer. Somatostatin analogs continue to be the backbone of therapy and may be followed or accompanied by targeted therapy, chemotherapy, and immune therapy. The recent addition of peptide receptor radionuclide therapy (PRRT) to the treatment armamentarium of NETs has led to the development of targeted alpha therapy to overcome PRRT resistance and minimize off-target adverse effects. Herein, we aim to highlight current treatment options for patients with advanced low grade pulmonary NETs along with emerging therapies, sequencing of therapies, upcoming clinical trials, and the importance of a multidisciplinary team to improve patient outcomes.

Factors and Barriers to Goals-of-Care Conversations for Patients With Cancer and Inpatient Mortality.

PURPOSE: Conversations about personal values and goals of care (GOC) at the end of life are essential in caring for patients with advanced cancer. However, GOC conversations may be influenced by patient and oncologist factors during transitions of care. METHODS: We electronically administered surveys to medical oncologists of inpatients who died from May 1, 2020, to May 31, 2021. Primary outcomes included oncologists' knowledge of inpatient death, anticipation of patient death, and recollection of GOC discussions. Secondary outcomes, including GOC documentation and advance directives (ADs), were collected retrospectively from electronic health records. Outcomes were analyzed for association with patient, oncologist, and patient-oncologist relationship factors. RESULTS: For 75 patients who died, 104/158 (66%) surveys were completed by 40 inpatient and 64 outpatient oncologists. Eighty-one oncologists (77.9%) were aware of patients' deaths, 68 (65.4%) anticipated patients' deaths within 6 months, and 67 (64.4%) recalled having GOC discussions before or during the terminal hospitalization. Outpatient oncologists were more likely to report knowledge of patient death (P < .001), as were those with longer therapeutic relationships (P < .001). Inpatient oncologists were more likely to correctly anticipate patient death (P = .014). Secondary outcomes revealed 21.3% of patients had documented GOC discussions before admission and 33.3% had ADs; patients with a longer duration of cancer diagnosis were more likely to have ADs (P = .003). Oncologist-reported barriers to GOC included unrealistic expectations from patients or family (25%) and decreased patient participation because of clinical conditions (15%). CONCLUSION: Most oncologists recalled having GOC discussions for patients with inpatient mortality, yet documentation of serious illness conversations remained suboptimal. Further studies are needed to examine barriers to GOC conversations and documentation during transitions of care and across health care settings.

Systemic Therapy for Pancreatic Neuroendocrine Tumors.

Patients with metastatic or advanced pancreatic neuroendocrine tumors (NETs) carry poorer prognoses relative to patients with other NETs due to bulkier and often, more proliferative baseline disease. Patients with these tumors also possess more approved treatment options relative to patients with other NETs, making therapeutic sequencing nuanced. As such, defining optimal therapeutic sequencing and developing more potent cytoreductive treatments for patients are significant areas of research need in the field. Herein this review, we discuss the current systemic therapy landscape, our approach to therapeutic sequencing in the clinic and ongoing studies seeking to define optimal sequencing of systemic therapies, and novel therapeutics in development, for patients with pancreatic NETs. We limit the scope of this latter topic to agents with preclinical or clinical rationale over the last 8 years to provide a contemporary view of the drug development landscape and focus primarily on new types of peptide receptor radionuclide therapy, anti-vascular endothelial growth factor receptor tyrosine kinase inhibitors and anti-vascular endothelial growth receptor tyrosine kinase inhibitor plus immunotherapy combinations.

Long-Term Exposure and Safety of a Novel Topical Rapamycin Cream for the Treatment of Facial Angiofibromas in Tuberous Sclerosis Complex: Results From a Single-Center, Open-Label Trial.

Facial angiofibromas, composed of fibrous tissue and blood vessels appearing on the face, are closely associated with tuberous sclerosis complex. Historically, oral rapamycin, a mammalian target of the rapamycin inhibitor of cell proliferation, has been used to treat visceral tuberous sclerosis-related tumors; however, the side effect profile of this medicine generally precludes its use in patients lacking significant internal involvement. The authors developed a novel topical formulation of rapamycin cream to treat the facial angiofibroma without exposing patients to possible systemic side effects. We followed 11 patients in a long-term, open-label, prospective study to evaluate the safety and effectiveness of rapamycin cream when used chronically. All of the patients showed an improvement in the appearance of their facial angiofibroma which was maintained in long-term follow-up without safety concerns or systemic absorption. The novel rapamycin cream was tolerated well by all patients and represents a way to address the cutaneous manifestation of tuberous sclerosis complex.

SmartWatch by SmartMonitor: Assessment of Seizure Detection Efficacy for Various Seizure Types in Children, a Large Prospective Single-Center Study.

INTRODUCTION: Patients with epilepsy and their caregivers are constantly burdened with the possibility of a seizure and its consequences, such as accidents, injuries, and sudden unexplained death in epilepsy. It is the unpredictable nature of seizures that often affects both patients with seizures and their caregivers, limits independence, and hinders quality of life. There are several types of motion detectors on the market, each with varying degrees of sensitivity. MATERIAL AND METHODS: We prospectively tested the SmartWatch, a wrist-worn monitor, on children, adolescents, and young adults with various types of seizures in an epilepsy monitoring unit. Confirmation of seizure type and if there was rhythmic upper extremity jerking associated with the seizure was determined by review of the video electroencephalograph. This was compared with the standard detection system of the watch. RESULTS: This study analyzed a total of 191 seizures in 41 patients aged 5-41 years. Fifty-one of the seizures were generalized tonic-clonic. Forty-seven of the seizures had a rhythmic arm movement component. The SmartWatch detected 30 seizures (16%) of the total, 16 (31%) of the generalized tonic-clonic seizures, and 16 (34%) seizures associated with rhythmic arm movements. DISCUSSION: Overall, only a minority of generalized tonic-clonic seizures or seizures with rhythmic movements were detected, highlighting the need for an effective seizure detection device.