Impact of P16 Positivity on Clinical Outcomes in Nasopharyngeal Carcinoma: A Single Institution Study.

Introduction Nasopharyngeal carcinoma (NPC) is a rare malignancy with unique geographical distribution. It is prevalent in East and Southeast Asia and rare in non-endemic countries like the USA. P16 is a tumor suppressor gene and there are limited studies with inconsistent results describing the association of its positivity in immunohistochemistry and clinical outcomes. In this retrospective study, we compared progression-free survival (PFS) and overall survival (OS) based on p16 positivity in 60 patients with NPC. Materials and methods Patients aged above 18 years and followed between July 2015 and December 2020 were included in the study. P16 positivity was based on the immunohistochemistry of the biopsy sample. We compared PFS and OS among all p16-positive and negative patients, and then among patients with advanced disease (stage III or IV), and between p16-positive, negative, and unknown status patients. Results There were 15 p16-positive, and 28 p16-negative, with a median age of 54.3 years and 55.7 years respectively. Most patients in both groups were male, Caucasian, and had advanced disease (stage III or stage IV). Both median PFS (p=0.838) and OS (p=0.776) were 84 months in the p16-negative group but were not reached during the study period in the p16-positive group. Among advanced-stage patients, the PFS (p=0.873), and OS (p=0.773) of both groups were not statistically significant. P16 status was unknown for 17 patients, and PFS (p=0.785) and OS (p=0.901), when compared among patients with p16-positive, negative, and unknown status, were also statistically non-significant. Discussion and conclusion Our analysis suggests that p16 status does not predict clinical outcomes in NPC patients. Our sample size was limited but is larger than most studies describing this association. With different studies in the literature reporting disparate findings, we recommend larger prospective studies to better illustrate the impact of p16 positivity on clinical outcomes in NPC.

Development of Merkel Cell Carcinoma in a Patient Receiving Rituximab.

Merkel cell carcinoma (MCC) is a rare, rapidly growing, and aggressive dermatological neoplasm. It is commonly reported in Caucasian ethnicities, and almost 50% of the patients have a concomitant malignancy and are on immunosuppressive chemotherapy. Here, we present a 79-year-old woman with a history of relapsed Stage II, grade III follicular lymphoma, receiving maintenance rituximab infusions. She presented with a raised erythematous papule on her left cheek. An excisional biopsy of the lesion confirmed a diagnosis of Merkel cell carcinoma. After which, she underwent a wider excision with 1-2 cm margins. PET scan did not reveal any FDG-avid uptake lesions that would be concerning for metastatic disease. However, she underwent a sentinel lymph node biopsy which was also negative. Thus, the diagnosis was finalized as Stage I (T1 N0 M0) MCC. There are only two reported cases in literature about the significant progression of Merkel cell carcinoma in patients who coincidentally were receiving rituximab as a part of treatment for another disease. This raises questions for future investigation and research on whether there is a direct association between rituximab use specifically and the rapid growth of MCC.

Therapeutic landscape of advanced HER2-positive breast cancer in 2022.

HER2-positive breast cancer is an aggressive subtype of breast cancer with five-year survival rates of 30% for the advanced stage. The development of anti-HER2 treatments has led to a paradigm shift in the management and clinical outcomes of advanced HER2-positive breast cancer patients. The standard first-line treatment consists of taxane-based chemotherapy plus dual anti-HER2 therapies with trastuzumab and pertuzumab. The antibody-drug conjugate (ADC) ado-trastuzumab emtansine (T-DM1) has been a second-line therapeutic standard, but the second-line treatment approach is rapidly evolving. Given a substantial advantage of another ADC, Fam-trastuzumab deruxtecan (T-DXd), compared to T-DM1 in a recent randomized trial in the second-line setting, T-DXd is currently the preferred second-line option. Optimal third-line treatment strategies are still not established, and multiple approaches have been used including combinations based on capecitabine, trastuzumab, or both with oral anti-HER2 tyrosine kinase inhibitors. Tucatinib plus capecitabine and trastuzumab, lapatinib plus trastuzumab, neratinib or lapatinib plus capecitabine are some of the FDA approved combinations. Another newer agent approved for third- or later-line therapy in the metastatic setting is margetuximab, an Fc-engineered anti-HER2 monoclonal antibody, in combination with chemotherapy. Other novel agents currently under clinical trials are the drugs that indirectly target HER2, including immune cell cycle inhibitors, PI3K/mTOR inhibitors, and immunotherapy agents.

Use of circulating tumour DNA in nasopharyngeal carcinoma to detect minimal residual disease.

Circulating tumour DNA (ctDNA) is defined as short DNA sequences shed by tumour cells into the systemic circulation. A promising use of ctDNA includes the detection of minimal residual disease (MRD) and is currently being studied in multiple types of solid tumours. Literature for the use of individualised ctDNA in nasopharyngeal carcinoma (NPC) is not available, although circulating Epstein-Barr virus DNA level is validated as a prognostic factor. We present a man in his 40s diagnosed with stage IV NPC who was started on chemotherapy with cis-platinum and gemcitabine. Serial monitoring of ctDNA completed to aid in detecting MRD after treatment demonstrated initial up-trending values correlating with subsequent imaging findings showing progression. Reinitiation of a different chemotherapy regimen significantly improved the ctDNA level, with corresponding imaging exhibiting a similar response. This case provides insight into the potential use of ctDNA in NPC and the benefit of serial ctDNA monitoring during treatment.

Prognostic Value of SARS-CoV-2 Anti-RBD IgG Antibody Quantitation on Clinical Outcomes in Hospitalized COVID-19 Patients.

Background: Antibody levels against SARS-CoV-2 can be used as an indicator of recent or past vaccination or infection. However, the prognostic value of antibodies targeting the receptor binding protein (anti-RBD) in hospitalized patients is not widely reported. Purpose: Determine prognostic impact of SARS-CoV-2 antibody quantification at the time of admission on clinical outcomes in hospitalized COVID-19 patients. Methods: We conducted a pilot observational study on patients hospitalized with SARS-CoV-2 infection to determine the prognostic impact of antibody quantitation within the first two days of admission. Anti-nucleocapsid IgG (anti-N) and Anti-RBD levels were measured. Anti-RBD level of 500 AU/mL was used as a cutoff to stratify patients. Spearman's rank Coefficient (rs) was used to demonstrate association. Results: Of the 26 patients included, those who were vaccinated more frequently tested positive for Anti-RBD (100% vs 46.2%, P = 0.005) with higher median titer level (623 vs 0, P = 0.011) compared to unvaccinated patients. Anti-N positivity was more frequently seen in unvaccinated patients (53.9% vs 7.7%, P = 0.03). Anti-RBD levels >500 were associated with lower overall hospital length of stay (LOS)(5 vs 10 days, P = 0.046). The analysis employing a Spearman Rank coefficient demonstrated a strong negative correlation between anti-S titer and LOS (rs=-.515, p = 0.007) and a moderate negative correlation with oxygen needs (rs =-.401, p = 0.042). Conclusion: Anti-RBD IgG levels were associated with lower LOS and oxygen needs during hospitalization. Further studies are needed to determine if levels on admission can be used as a prognostic indicator.

Persistent Orthostatic Hypotension in a Patient With Acromegaly: Resolution With Transsphenoidal Hypophysectomy.

Acromegaly is a rare condition characterized by excessive secretion of growth hormone from a pituitary tumor. It can affect multiple systems and can be fatal with cardiac dysfunction being the most common cause of death in these patients. Autonomic dysfunction is a less studied subject in patients with acromegaly, and the exact pathophysiology is still unclear. Here we present a case of a patient with persistent orthostatic hypotension, who was found to have acromegaly and pituitary adenoma upon further evaluation. Her orthostatic symptoms failed to improve with conservative measures and medical management, but unexpectedly resolved after transsphenoidal hypophysectomy was performed.

A Case of Syncope Due to Intracardiac Leiomyomatosis.

We present a case of a 46-year-old female presenting with syncope. Echocardiography initially showed a right atrial mass. Further evaluation revealed a mass arising from the fundus of the uterus, with a tumor thrombus in the left gonadal vein, extending into the left renal vein and through the inferior vena cava (IVC) into the right heart across the tricuspid valve. She was managed with surgical resection, and postoperative pathology was consistent with intravenous leiomyomatosis (IVL). IVL is a rare uterine smooth muscle cell neoplasm which extends into the venous system. Gynecological tumors are often overlooked in differential diagnosis for atrial masses. A benign tumor like fibroid, in rare circumstances, can extend into the right side of the heart causing dynamic obstruction to outflow tract, thus increasing mortality. The objective of this article is to present such a case and highlight the broad differentials of atrial masses, including IVL.

Thrombotic thrombocytopenic purpura following administration of the Moderna booster vaccine.

Thrombotic thrombocytopenic purpura (TTP) is a type of thrombotic microangiopathy that is characterized by microangiopathic haemolytic anaemia, consumption thrombocytopenia and organ injury. It is caused by a severe deficiency of ADAMTS13, which can be either congenital or acquired. There is a plethora of things that can cause the acquired form, including medications and infections. Vaccines have also been shown to cause TTP. In the midst of the COVID-19 pandemic, with multiple new vaccines being developed and distributed to the masses, the medical community needs to be aware of adverse events associated with these new vaccines. We present a case of TTP following administration of the Moderna booster vaccine.

Chalazion in a patient with multiple myeloma treated with bortezomib.

We present a case of a woman in her early 60s with multiple myeloma who, while undergoing treatment with cyclophosphamide, bortezomib and dexamethasone (CyBorD), noticed a whitish nodular swelling on the eyelid. This occurred after one cycle of CyBorD and on subsequent treatment, it also involved the contralateral eyelid. The lesions were initially managed with conservative measures by applying warm compresses, but the lesions progressively increased in size. CyBorD was discontinued and topical antibiotics and anti-inflammatories were initiated, resulting in a decrease in size of the lesions. On resolution of symptoms, she was rechallenged with CyBorD, and symptoms did not recur. The temporal relationship between bortezomib and the development of chalazion is based on connection and no association has been proven.