The role of the microbiome in the development and propagation of head and neck squamous cell cancer (HNSCC) is largely unknown and the surrounding knowledge lags behind what has been discovered related to the microbiome and other malignancies. In this review, the authors performed a structured analysis of the available literature from several databases. The authors discuss the merits and detriments of several studies discussing the microbiome of the structures of the aerodigestive system throughout the development of HNSCC, the role of the microbiome in the development of malignancies (generally and in HNSCC) and clinical applications of the microbiome in HNSCC. Further studies will be needed to adequately describe the relationship between HNSCC and the microbiome, and to push this relationship into a space where it is clinically relevant outside of a research environment.
Vasculitic immune checkpoint inhibitor-related adverse events (irAEs) are rare, with limited data to guide their management. Here, we present a case of a 67-year-old female with stage IV cutaneous melanoma who received first-line pembrolizumab. She had completed 21 cycles of pembrolizumab dosed at 200 mg every 21 days over 15 months when she developed fatigue, chills, decreased appetite, night sweats, nausea, diarrhea, dry cough, and chest pain. A routine, staging positron emission tomography (PET) scan revealed aortitis of the transverse aortic arch. An extensive workup was unremarkable for other causes, so her condition was labeled a grade III immune-related vasculitis. Based on this diagnosis, we started high-dose prednisone and discontinued pembrolizumab. After two months of high-dose prednisone, she developed bothersome weight gain and insomnia, leading to a switch from prednisone to tocilizumab as a steroid-sparing agent. The selection of tocilizumab was based on its routine use for giant cell arteritis which can have extracranial symptoms including thoracic aortitis. Her symptoms resolved, and subsequent PET scans showed resolution of the aortitis and no evidence of metastatic melanoma. As the indications for immunotherapy expand, rare complications are becoming more prevalent, and more data will be needed to guide their management. While there is evidence for tocilizumab use as a steroid-sparing treatment for large-vessel vasculitides due to other conditions, this is the first case of its use to treat an aortitis irAE to our knowledge. In this case, it was an effective means of treating the patient while sparing them from prolonged corticosteroids.
Immune checkpoint inhibitors (ICIs) are the current guideline recommended treatment for many malignancies considered to be terminal. Despite considerable advances, their utility remains limited, and the field requires synergistic partners to further improve outcomes. Oncolytic viruses (OV) are emerging as contenders for the role of the synergistic agent of choice due to their multi-mechanistic effect on activating the tumor ‘cold’ immune microenvironment. Herpes simplex virus 1, a naturally selective OV, is the most advanced virotherapeutic compound in clinical applications for use in combination with ICI. We here present the case of a 72 year-old patient with a heavily pre-treated, advanced maxillary sinus squamous cell cancer with distant metastases who developed complete response (CR) with only three administrations of a programmed death 1 inhibitor after treatment interference by a severe herpes zoster infection, based on the related alpha-herpesvirus varicella zoster virus (VZV). This exceptional response has been followed and confirmed with imaging studies over more than 5 years. Although the patient had several favorable predictors for response to immunotherapy, we reason that the exceptional response may in part be secondary to the serendipitous VZV infection. Documented cases of cancer patients that achieved CR after few administrations of treatment with ICI are rare, with most reporting follow up of just over 1 year or less. In this case, it is conceivable that the interference of the infection with VZV, soon after the start of immunotherapy with ICI, led to a lasting antitumor immunity and sustained CR. This hypothesis is supported by the concept of ‘oncolytic immunotherapy’ which is reviewed in this manuscript. In addition, persistence of a TP53 mutation found in a liquid biopsy, despite clinical and radiologic remission, is discussed.
6577 Background: Immune checkpoint inhibitors (ICI) can prolong survival for various cancers and are generally available as treatment options for most patients because of their favorable adverse effect profile. Although ICIs provide treatment for many patients who would otherwise be out of options, their variable and often delayed efficacy may postpone the de-escalation of care at the end of life. Palliative Care consultation (PCC) is well-established among patients receiving cytotoxic chemotherapy, but its effectiveness is less certain among patients receiving newer treatment modalities. We aimed to test the association of PCC with end-of-life (EOL) outcomes among patients treated with an ICI for any type of cancer. Methods: We created a retrospective registry of all patients who received at least one dose of ICI for any indication between 2/1/2011 and 4/7/2022 at a comprehensive cancer center and its outreach clinics. The investigators created a secure, cloud-based registry (REDCap), validated it with data quality rules, and resolved all discrepancies; clinical research specialists at Vasta Global captured most of the data. We used the chi-square test to compare categorical variables, defined statistical significance as p < 0.05, and used SAS version 9.4 for analyses. The study had institutional IRB approval. Results: The cohort consisted of 3,142 patients with lung cancer (45%) as the most common cancer type, followed by melanoma (14%) and head and neck squamous cell carcinoma (9%). ICI was most often given in the first line setting (46%) with good baseline performance status (ECOG 0-1, 50%). 915 (29%) patients had PCC, which was associated with a higher rate of code status de-escalation from “Full Code” at any point before death (92% vs. 87%, p 0.007). There was no association between PCC and either the initiation of ICI within 30 days of death (7% vs. 5%, p .0172) or any dose of ICI within 14 days of death (5% vs. 6%, p 0.33). Among patients with a confirmed location of death (1013, 32%), PCC was associated with a similar rate of death in the hospital at any level of care (30% vs. 28%, p 0.51). Conclusions: PCC was associated with code status de-escalation before death but similar risks of late ICI dosing or inpatient status at the time of death. Further studies are needed to risk-stratify patients starting ICI to identify the subgroups that would benefit the most from PCC.
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