Neoadjuvant platinum-based chemotherapy and lymphadenectomy for penile cancer: an international, multi-institutional, real-world study.

INTRODUCTION: This study investigated the efficacy and safety of neoadjuvant chemotherapy for locally advance penile squamous cell carcinoma for which current evidence is lacking. METHODS: Included patients had locally advanced penile squamous cell carcinoma with clinical lymph node metastasis treated with at least 1 dose of neoadjuvant chemotherapy prior to planned consolidative lymphadenectomy. Objective response rates were assessed using Response Evaluation Criteria in Solid Tumors v1.1. The primary and secondary outcomes were overall survival and progression-free survival, estimated by the Kaplan-Meier method. Treatment-related adverse events were graded per the Common Terminology Criteria for Adverse Events v5.0. RESULTS: A total of 209 patients received neoadjuvant chemotherapy for locally advanced and clinically node-positive penile squamous cell carcinoma. The study population consisted of 7% of patients with stage II disease, 48% with stage III, and 45% with stage IV. Grade 2 treatment-related adverse events occurred in 35 (17%) patients, and no treatment-related mortality was observed. Of the patients, 201 (97%) completed planned consolidative lymphadenectomy. During follow-up, 106 (52.7%) patients expired, with a median overall survival of 37.0 months (95% confidence interval [CI] = 23.8 to 50.1 months) and median progression-free survival of 26.0 months (95% CI = 11.7 to 40.2 months). Objective response rate was 57.2%, with 87 (43.2%) having partial response and 28 (13.9%) having a complete response. Patients with objective response to neoadjuvant chemotherapy had a longer median overall survival (73.0 vs 17.0 months, P < .01) compared with those who did not. The lymph node pathologic complete response rate was 24.8% in the cohort. CONCLUSION: Neoadjuvant chemotherapy with lymphadenectomy for locally advanced penile squamous cell carcinoma is well tolerated and active to reduce the disease burden and improve long-term survival outcomes.

Multiplex Immunofluorescence Captures Progressive Immune Exhaustion with Advancing Penile Squamous Cell Cancer Stage.

Penile squamous cell carcinoma (PSCC) is a rare and deadly malignancy. Therapeutic advances have been stifled by a poor understanding of disease biology. Specifically, the immune microenvironment is an underexplored component in PSCC and the activity of immune checkpoint inhibitors observed in a subset of patients suggests immune escape may play an important role in tumorigenesis. Herein, we explored for the first time the immune microenvironment of 57 men with PSCC and how it varies with the presence of human papillomavirus (HPV) infection and across tumor stages using multiplex immunofluorescence of key immune cell markers. We observed an increase in the density of immune effector cells in node-negative tumors and a progressive rise in inhibitory immune players such as type 2 macrophages and upregulation of the PD-L1 checkpoint in men with N1 and N2-3 disease. There were no differences in immune cell densities with HPV status.

15 years of patient-reported outcomes in clinical trials leading to GU cancer drug approvals: a systematic review on the quality of data reporting and analysis.

Background: Standardized, high-quality PRO data reporting is crucial for patient centered care in the field of oncology, especially in clinical trials that establish standard of care. This study evaluated PRO endpoint design, conduct and reporting methods in FDA approved drugs for GU malignancies. Methods: A systematic review of the FDA archives identified GU cancer drug approvals from Feb 2007 to July 2022. ClinicalTrials.gov and PubMed were used to retrieve relevant data. PRO data was screened, and analytic tools, interpretation methods in the published papers and study protocols were reviewed. Compliance with PRO reporting standards were assessed using PRO Endpoint Analysis Score (PROEAS), a 24-point scoring scale from Setting International Standards in Analyzing Patient-Reported Outcomes and Quality of Life Endpoints Data Consortium (SISAQOL). Findings: We assessed 40 trial protocols with 27,011 participants, resulting in 14 renal cell cancer (RCC), 16 prostate cancer (PC), and 10 urothelial cancer (UC) approvals. PRO data was published for 27 trials, with 23 PRO publications (85%) focusing solely on PRO data, while 4 (15%) included PRO data in the original paper. Median time between primary clinical and secondary paper with PRO data was 10.5 months (range: 9-25 months). PROs were not planned as primary endpoints for any study but 14 (52%) reported them as secondary, 10 (37%) as exploratory outcomes, and 3 (11%) lacked any clarity on PRO data as endpoint. Mean PROEAS score of all GU cancers was 11.10 (range: 6-15), RCC (11.86, range: 6-15), UC (11.50, range: 9-14), and PC (10.56, range: 6-15). None met all the SISAQOL recommendations. Interpretation: Low overall PROEAS score and delays in PRO data publication in GU cancer drug trials conducted in the past decade emphasize the need for improvement in quality of design and conduct of PRO endpoint in future trials and accelerated publication of PRO endpoints, using standardized analysis, and prespecified hypothesis driven endpoint. These improvements are essential for facilitating interpretation and application of PRO study findings to define patient care. Funding: None.

The Prognostic Role of Human Papillomavirus and p16 Status in Penile Squamous Cell Carcinoma-A Systematic Review.

PSCC is a rare cancer, with approximately half of all cases related to HPV. While HPV and p16 IHC testing have proven their prognostic value for oropharyngeal cancer, this is not yet established for PSCC. The current level of evidence exploring the relation between PSCC and HPV is moderate, so we conducted a systematic review following PRISMA guidelines to evaluate the prognostic role of HPV and p16 IHC in PSCC clinical outcomes. We searched the PubMed, Embase, and Cochrane databases and identified 34 relevant studies that met our inclusion criteria. Of these, 33 were retrospective cohort studies, and one was a cross-sectional study. Nine studies reported that HPV-positive and p16-positive PSCC had better overall survival (OS) and disease-free survival (DFS). This study highlights the need for a meta-analysis to determine the role of routine HPV status or p16 staining testing as part of the initial diagnosis and staging of PSCC patients worldwide.

Granulomatous and Sarcoid-like Immune-Related Adverse Events following CTLA4 and PD1 Blockade Adjuvant Therapy of Melanoma: A Combined Analysis of ECOG-ACRIN E1609 and SWOG S1404 Phase III Trials and a Literature Review.

BACKGROUND: Treatment with immune checkpoint inhibitors (ICIs) has been linked to granulomatous and sarcoid-like lesions (GSLs) affecting different organs. This study sought to evaluate GSL incidence in patients with high-risk melanoma treated with cytotoxic T-lymphocyte antigen 4 (CTLA4) or programmed cell death 1 (PD1) blockade adjuvant therapy in two clinical trials: ECOG-ACRIN E1609 and SWOG S1404. Descriptions and GSL severity ratings were recorded. METHODS: Data were collected from ECOG-ACRIN E1609 and SWOG S1404. Descriptive statistics along with GSL severity grades were reported. Additionally, a literature review for such cases was summarized. RESULTS: A total of 11 GSL cases were reported among 2878 patients treated with either ICI or with High-Dose Interferon Alfa-2b (HDI) in ECOG-ACRIN E1609 and SWOG S1404 trials. Cases were numerically more commonly reported with ipi10, followed by pembrolizumab, ipi3, and HDI, respectively. Most of the cases were grade III. Further, organs involved included lung, mediastinal lymph nodes, skin and subcutaneous tissue, and eye. Furthermore, a summary of 62 reports in the literature was described. CONCLUSIONS: GSLs following anti-CTLA4 and anti-PD1 antibody therapy in patients with melanoma were reported unusually. Reported cases ranged in grade from I to III and appeared manageable. Careful attention to these events and their reporting will be essential to better guide practice and management guidelines.

Review of Hematology-Oncology Emergencies for Internal Medicine Residents.

The prevalence of cancer continues to grow globally every year. With therapeutic advances over the recent decades, the prevalence of individuals living with cancer continues to increase. Internal medicine residents can see patients admitted to the hospital for cancer-related emergencies. Early identification and appropriate management of these emergencies have been shown to improve mortality and morbidity. In this article, we aim to review the recent updates in the management of commonly encountered oncologic emergencies in the practice of internal medicine residents. This review will cover spinal cord compression, superior vena cava syndrome, tumor lysis syndrome, hypercalcemia, pericardial tamponade, hypoglycemia, hyponatremia, bowel obstruction, increased intracranial pressure, leukostasis, hyperviscosity syndrome, neutropenic fever, and hypersensitivity reactions.

Incidental diagnosis of a rare pancreatic plasmacytoma with plasmablastic features.

Multiple myeloma is a plasma cell neoplasm that accounts for 10% of all hematologic malignancies, characterized by malignant proliferation of monoclonal plasma cells in the bone marrow. It predominantly affects men 60 to 70 years of age. Plasmacytoma is a discrete mass of neoplastic monoclonal plasma cells that may be osseous or extramedullary. Though extramedullary plasmacytomas are uncommon, they can involve any tissue or organ. Only a few cases of pancreatic involvement have been reported. We report a case of a 78-year-old woman with a long-standing history of multiple myeloma noted to have pancreatic tail involvement with plasmacytoma with plasmablastic features. Multiple myeloma with plasmablastic transformation has a poor prognosis; hence, a multidisciplinary team approach is crucial to identify and initiate appropriate management in these cases.

Video education about side effects of chemotherapy and immunotherapy and its impact on the anxiety, depression, and distress level of cancer patients.

BACKGROUND: Patients diagnosed with cancer are at higher risk of anxiety, depression, and overall distress. These mood disturbances are risk factors for non-adherence to cancer treatment, increased length of stay during hospital admissions, increased number of visits to the emergency department, and also impact survival. Although paper handouts about the potential side effects are widely used in the oncology practice studies have shown that digital educational material is known to work better when compared to traditional methods. However, the impact of video education on anxiety, depression, and distress have not been previously evaluated. Our study aimed to assess whether video education about potential chemotherapy and immunotherapy can reduce anxiety, depression, and distress levels. METHODS: After IRB approval, we enrolled patients who were fluent in English, younger than 80 years of age, and who were able to provide informed consent. The Hospital Anxiety and Depression Scale and Distress Thermometer were used to assess distress, as well as depression and anxiety before and after watching video educational material. Paired t-test was used to compare the differences between the scores before and after watching educational videos. The statistical software GraphPad Prism 9, San Diego, California, was used to perform the statistical analysis. RESULTS: We enrolled 29 patients, of whom 20 completed the study, six withdrew, two were lost to follow-up, and one did not complete the initial questionnaire. Of all patients that completed the study 85% of the patient found videos helpful, and they were 7/10 likely to recommend them to other patients who may experience symptoms. The mean depression score changed from 4.75 before to 4.9 after watching the videos (p 0.77), distress score from 2.3 to 2.65 (p 0.52), and anxiety scores changed from 4.85 to 6.15 (p 0.03). The feedback provided by the patients indicated that they were more willing to watch the videos related to the side effects they experienced at their free time and convenience. CONCLUSIONS: Our study suggests that patients were open to video education and found it helpful and worth watching. However, the exposure of the patients to the videos about potential side effects of cancer treatment, including those patients do not experience, may lead to increased anxiety.

A Rare Cause of Gastrointestinal Bleeding: Aorto-Enteric Fistula.

Aorto-enteric fistula is defined as an abnormal connection between the gastrointestinal system and the aorta. The patients who develop this condition usually have a grim prognosis and the cases are universally fatal unless intervened with an endovascular repair or open surgical repair. Given the rarity and the relative unfamiliarity of this condition, an understanding of the presentation, pathogenesis, and management is vital to prevent catastrophic complications.

Predictive Ability of Pressure-Corrected Arterial Stiffness Indices: Comparison of Pulse Wave Velocity, Cardio-Ankle Vascular Index (CAVI), and CAVI0.

BACKGROUND: Pulse wave velocity (PWV) is blood pressure (BP) dependent, leading to the development of the BP-corrected metrics cardio-ankle vascular index (CAVI) and CAVI0. We aimed to assess risk prediction by heart-to-ankle PWV (haPWV), CAVI, and CAVI0 in a US population. METHODS: We included 154 subjects (94.8% male; 47.7% African American) with and without heart failure (HF). Left and right haPWV, CAVI, and CAVI0 were measured with the VaSera 1500N device. We prospectively followed participants for a mean of 2.56 years for the composite endpoint death or HF-related hospital admission (DHFA). RESULTS: Left and right haPWV, CAVI, and CAVI0 values did not differ significantly. In unadjusted analyses, haPWV (left standardized hazard ratio [HR] = 1.51, P = 0.007; right HR = 1.66, P = 0.003), CAVI (left HR = 1.45, P = 0.012; right HR = 1.58, P = 0.006), and CAVI0 (left HR = 1.39, P = 0.022; right HR = 1.44, P = 0.014) significantly predicted DHFA. Predictive ability showed a decreasing trend from haPWV to CAVI to CAVI0; in line with the increasing amount of BP correction in these metrics. In Cox models, right-sided metrics showed a trend toward stronger predictive ability than left-sided metrics. After adjustment for baseline HF status, the Meta-Analysis Global Group in Chronic Heart Failure (MAGGIC) risk score, and systolic BP, right haPWV (HR = 1.58, P = 0.025) and CAVI (HR = 1.44, P = 0.044), but no other stiffness metrics, remained predictive. CONCLUSIONS: Although conceptually attractive, BP-corrected arterial stiffness metrics do not offer better prediction of DHFA than conventional arterial stiffness metrics, nor do they predict DHFA independently of systolic BP. Our findings support PWV as the primary arterial stiffness metric for outcome prediction.

Treatment of Refractory Lactic Acidosis With Thiamine Administration in a Non-alcoholic Patient.

Lactate, or lactic acid, is an end-product of anaerobic metabolism. The build-up of lactate in the body is commonly due to type A lactic acidosis, resulting from an inability to meet the body's oxygen delivery demands. When lactic acidosis persists, other causes need to be ruled out. Here, we describe the case of a 63-year-old female who initially presented with hypoglycemia and was found to have significant lactic acidosis. Her blood sugar levels improved with dextrose supplementation; however, lactic acidosis persisted despite fluid hydration and empiric antibiotics. After excluding other causes of lactic acidosis, she was started on intravenous thiamine due to suspicion of thiamine deficiency secondary to poor nutrition. Lactic acid levels improved drastically after starting thiamine supplementation. Thiamine is a water-soluble vitamin that plays an essential role as a cofactor in several biochemical reactions. Thiamine deficiency is a rare, underdiagnosed cause of type B lactic acidosis, with early diagnosis and intervention playing crucial roles in preventing severe cardiac and neurological impairment.

Dermatofibrosarcoma protuberans of the scrotum.

Dermatofibrosarcoma protuberans is a rare tumor that arises in the dermis, with a strong tendency to recur locally. It is slow growing and often presents as a skin-colored plaque on the trunk, although it may arise anywhere on the body. Dermatofibrosarcoma protuberans has a distinctive histologic appearance, and immunohistochemical studies can help make the diagnosis. This case report describes a young man who presented with complaints of an enlarging right scrotal mass and was diagnosed with dermatofibrosarcoma protuberans.

Rapid Development of Pernicious Anemia Unmasking Underlying Gastric Adenocarcinoma.

Gastric cancer is one of the most common malignancies, often detected at later stages as patients remain asymptomatic until later stages. Pernicious anemia (PA), a well-known cause of vitamin B12 deficiency, is a classic risk factor for gastric cancer. Patients with PA usually present with megaloblastic anemia and peripheral neuropathy; however, they can also present with nonspecific symptoms. We describe below the case of a 56-year-old male who presented with symptoms of nausea, vomiting, and fatigue. Initial lab work revealed severe B12 deficiency, pancytopenia, and intramedullary hemolysis warranting endoscopy that revealed a gastric fundus mass significant for adenocarcinoma on biopsy.

Impact of Chronic Obstructive Pulmonary Disease in Heart Failure With Preserved Ejection Fraction.

COPD often coexists with HFpEF, but its impact on cardiovascular structure and function in HFpEF is incompletely understood. We aimed to compare cardiovascular phenotypes in patients with Chronic Obstructive Pulmonary Disease (COPD), Heart Failure with Preserved Ejection Fraction (HFpEF), or both. We studied 159 subjects with COPD alone (n = 48), HFpEF alone (n = 79) and HFpEF + COPD (n = 32). We used MRI and arterial tonometry to assess cardiac structure and function, thoracic aortic stiffness, and measures of body composition. Relative to participants with COPD only, those with HFpEF with or without COPD exhibited a greater prevalence of female sex and obesity, whereas those with HFpEF + COPD were more often African-American. Compared to the other groups, participants with HFpEF and COPD demonstrated a more concentric LV geometry (LV wall-cavity ratio 1.2, 95%CI: 1.1-1.3; p = 0.003), a greater LV mass (67.4, 95%CI: 60.7-74.2; p = 0.03, and LV extracellular volume (49.4, 95%CI: 40.9-57.9; p = 0.002). Patients with comorbid HFpEF + COPD also exhibited greater thoracic aortic stiffness assessed by pulse-wave velocity (11.3, 95% CI: 8.7-14.0 m/s; p = 0.004) and pulsatile load imposed by the ascending aorta as measured by aortic characteristic impedance (139 dsc; 95%CI=111-166; p = 0.005). Participants with HFpEF, with or without COPD, exhibited greater abdominal and pericardial fat, without difference in thoracic skeletal muscle size. In conclusion, individuals with co-morbid HFpEF and COPD have a greater degree of systemic large artery stiffening, LV remodeling, and LV fibrosis than those with either condition alone.

A Case Report on Bortezomib-Induced Bilateral Chalazion.

A chalazion is a swollen bump on the eyelid that occurs when the eyelid's oil gland clogs up. Bortezomib is an FDA-approved novel agent for the treatment of patients with multiple myeloma (MM). Recently, there have been a few case reports on the possible association between eyelid chalazion and bortezomib therapy. We describe the case of an 87-year-old female diagnosed with MM who developed bilateral eye chalazion after being initiated on bortezomib. She was evaluated by an ophthalmologist, started on eye lubricants and antibiotic eye drops, and the bortezomib was discontinued until the resolution of the lesions was achieved. Physicians should be aware of these ocular complications of bortezomib, as early intervention can prevent worsening eyelid complications.

Primary Vaginal Malignant Melanoma: A Case Report and Review of Literature.

Primary vaginal malignant melanoma is an extremely rare and aggressive tumor with very few reported cases worldwide. It often occurs in post-menopausal women, with a mean age of 57 years. The most common presenting symptom is vaginal bleeding. Other less common presenting symptoms are vaginal discharge, vaginal mass, and pain. Vaginal melanomas are often diagnosed at an advanced stage, and despite the aggressive treatment approach, the prognosis is poor. We present to you a case of a 56-year-old post-menopausal woman who presented with intermittent vaginal bleeding and passage of dark clots. She was found to have symptomatic anemia requiring blood transfusions. Further workup revealed a mass in the upper vagina on imaging studies, and the patient eventually underwent a biopsy, which confirmed the diagnosis of malignant melanoma of the vagina on pathological examination.

Thyrotoxic Periodic Paralysis- A Diagnostically Challenging Rare Clinical Entity.

Thyrotoxic periodic paralysis (TPP) is characterized by a classic triad of muscle paralysis, hypokalemia, and hyperthyroidism. The underlying thyroid disorder is often very subtle making it challenging to recognize TPP. It is a completely reversible condition if diagnosed early; however, it is associated with fatal outcomes if delayed.