Introduction
Rechallenge with antibodies targeting programmed cell death protein‐1 or its ligand (PD‐1/L1) after discontinuation or disease progression in solid tumors following a prior PD‐1/L1 ...treatment is often practiced in clinic. This study aimed to investigate if adding PD‐1/L1 inhibitors to cabozantinib, the most used second‐line treatment in real‐world patients with metastatic clear cell renal cell carcinoma (mccRCC), offers additional benefits.
Methods
Using de‐identified patient‐level data from a large real‐world US‐based database, patients diagnosed with mccRCC, who received any PD‐1/L1‐based combination in first‐line (1L) setting, followed by second‐line (2L) therapy with either cabozantinib alone or in combination with PD‐1/L1 inhibitors were included. Patients given a cabozantinib‐containing regimen in 1L were excluded. The study end points were real‐world time to next therapy (rwTTNT) and real‐world overall survival (rwOS) by 2L.
Results
Of 12,285 patients with metastatic renal cell carcinoma in the data set, 348 patients met eligibility and were included in the analysis. After propensity score matching weighting, cabozantinib with PD‐1/L1 inhibitors versus cabozantinib (ref.) had similar rwTTNT and rwOS in the 2L setting. Hazard ratios and 95% confidence interval (CI) for rwTTNT and rwOS are 0.74 (95% CI, 0.49–1.12) and 1.15 (95% CI, 0.73–1.79), respectively.
Conclusion
In this study, the results align with the phase 3 CONTACT‐03 trial results, which showed no additional benefit of adding PD‐L1 inhibitor to cabozantinib compared to cabozantinib alone in 2L following PD‐1/L1–based therapies in 1L. These results from real‐world patients strengthen the evidence regarding the futility of rechallenge with PD‐1/L1 inhibitors.
This study reports, in a large real‐world data set, that there is no survival benefit of adding a PD‐1/L1 inhibitor to cabozantinib given in a second‐line setting in patients with metastatic clear cell renal cell carcinoma with prior treatment with a PD‐1/L1 inhibitor. The real‐world data concur with the results reported in the phase 3 CONTACT‐03 clinical trial further questioning the common practice of PD‐1/L1 inhibitors rechallenge in patients with metastatic renal cell carcinoma.
Accurate and efficient triage is crucial for prioritizing care and managing resources in emergency rooms. This study investigates the effectiveness of ChatGPT, an advanced artificial intelligence ...system, in assisting health providers with decision-making for patients presenting with metastatic prostate cancer, focusing on the potential to improve both patient outcomes and resource allocation.
Clinical data from patients with metastatic prostate cancer who presented to the emergency room between 1 May 2022 and 30 April 2023 were retrospectively collected. The primary outcome was the sensitivity and specificity of ChatGPT in determining whether a patient required admission or discharge. The secondary outcomes included the agreement between ChatGPT and emergency medicine physicians, the comprehensiveness of diagnoses, the accuracy of treatment plans proposed by both parties, and the length of medical decision making.
Of the 147 patients screened, 56 met the inclusion criteria. ChatGPT had a sensitivity of 95.7% in determining admission and a specificity of 18.2% in discharging patients. In 87.5% of cases, ChatGPT made the same primary diagnoses as physicians, with more accurate terminology use (42.9% vs. 21.4%,
= 0.02) and more comprehensive diagnostic lists (median number of diagnoses: 3 vs. 2,
< 0.001). Emergency Severity Index scores calculated by ChatGPT were not associated with admission (
= 0.12), hospital stay length (
= 0.91) or ICU admission (
= 0.54). Despite shorter mean word count (169 ± 66 vs. 272 ± 105,
< 0.001), ChatGPT was more likely to give additional treatment recommendations than physicians (94.3% vs. 73.5%,
< 0.001).
Our hypothesis-generating data demonstrated that ChatGPT is associated with a high sensitivity in determining the admission of patients with metastatic prostate cancer in the emergency room. It also provides accurate and comprehensive diagnoses. These findings suggest that ChatGPT has the potential to assist health providers in improving patient triage in emergency settings, and may enhance both efficiency and quality of care provided by the physicians.
Androgen deprivation therapy (ADT) intensification (ADTi) (i.e., ADT with androgen receptor pathway inhibitor or docetaxel, or both) has significantly improved survival outcomes of patients with ...metastatic hormone-sensitive prostate cancer (mHSPC). However, the impact of prior ADTi in the mHSPC setting on the disease presentation and survival outcomes in metastatic castration-resistant prostate cancer (mCRPC) is not well characterized. In this study, our objective was to compare the disease characteristics and survival outcomes of patients with new mCRPC with respect to receipt of intensified or nonintensified ADT in the mHSPC setting.
In this institutional review board-approved retrospective study, eligibility criteria were as follows: patients diagnosed with mCRPC, treated with an approved first-line mCRPC therapy, and who received either intensified or nonintensified ADT in the mHSPC setting. Progression-free survival (PFS) was defined from the start of first-line therapy for mCRPC to progression per Prostate Cancer Working Group 2 criteria or death, and overall survival (OS) was defined from the start of first-line therapy for mCRPC to death or censored at the last follow-up. A multivariable analysis using the Cox proportional hazards model was used, adjusting for potential confounders.
Patients (n = 387) treated between March 20, 2008, and August 18, 2022, were eligible and included: 283 received nonintensified ADT, whereas 104 were treated with ADTi. At mCRPC diagnosis, patients in the ADTi group were significantly younger, had more visceral metastasis, lower baseline prostate-specific antigen (all p < 0.01), and lower hemoglobin (p = 0.027). Furthermore, they had significantly shorter PFS (median 4.8 vs. 8.4 months, adjusted hazard ratio HR: 1.46, 95% confidence interval 95% CI: 1.07-2, p = 0.017) and OS (median 21.3 vs. 33.1 months, adjusted HR: 1.53, 95% CI: 1.06-2.21, p = 0.022) compared to patients in the nonintensified ADT group.
Patients treated with ADTi in the mHSPC setting and experiencing disease progression to mCRPC had more aggressive disease features of mCRPC (characterized by a higher number of poor prognostic factors at mCRPC presentation). They also had shorter PFS on first-line mCRPC treatment and shorter OS after the onset of mCRPC compared to those not receiving ADTi in the mHSPC setting. Upon external validation, these findings may impact patient counseling, prognostication, treatment selection, and design of future clinical trials in the mCRPC setting. There remains an unmet need to develop novel life-prolonging therapies with new mechanisms of action to improve mCRPC prognosis in the current era.
Immune checkpoint inhibitors have ushered in a new era in cancer management. Nivolumab is a human immunoglobulin G4 (IgG4) monoclonal antibody that selectively inhibits programmed cell death-1 (PD-1) ...activity by binding to the PD-1 receptor. This inhibits suppression of the T-cell activity, which can in turn cause increased killing of cancer cells. This alteration in the activity of the T cells can cause them to lose their ability to identify host cells and leads to immune-related adverse effects (irAE). Nivolumab-induced hepatotoxicity is rare and accounts for 3–6% of all irAE. We present a case of nivolumab-induced hepatitis. A woman who was treated for recurrent renal cell carcinoma presented with hepatitis. Workup for other causes was negative and the hepatitis was attributed to the administration of nivolumab. She was started on oral steroids followed which she initially improved. However, she later presented with massive upper gastrointestinal bleeding secondary to gastroduodenal ulcers and subsequently developed acute tubular necrosis and passed from the complications. Immune checkpoint inhibitors have proven to be a promising approach in the management of a wide array of neoplasms by immunomodulation. As these agents are becoming standard of therapy in the management of cancers, a heightened vigilance in the diagnosis of irAE is warranted. With heightened vigilance, early recognition can lead to decreased mortality and morbidity.
Idiopathic granulomatous mastitis (IGM) is a chronic inflammatory disease of the breast, the etiology of which, has still not been elucidated. There have been several mechanisms proposed to explain ...the pathogenesis. Since the first description of the disease, it has proved itself to be a great diagnostic and therapeutic challenge. It is very often misdiagnosed as cancer, resulting in myriad workup by the physician and great distress to the patient. Clear guidelines as to the management have still not been described. Here, we describe two patients who presented with IGM and have been successfully treated. The first patient was treated with a combination of steroids and antibiotics. The second patient achieved remission of the disease with antibiotics alone. We also propose an algorithm for the management of IGM.
Metastatic urinary tract cancer (mUTC) is challenging to treat in older adults due to comorbidities. We compared the clinical courses of younger and older (≥70 years) adults with mUTC receiving ...first-line (1L) systemic therapy in a tertiary cancer center. Baseline clinical characteristics, treatments received, tolerability, and survival outcomes were analyzed. Among 212 patients (103 older vs. 109 younger), the older patients had lower hemoglobin at baseline (84% vs. 71%, p = 0.03), the majority were cisplatin-ineligible (74% vs. 45%, p < 0.001), received more immunotherapy-based treatments in the 1L (52% vs. 36%, p = 0.01), received fewer subsequent lines of treatment (median 0 vs. 1, p = 0.003), and had lower clinical trial participation (30% vs. 18%, p = 0.05) compared to the younger patients. When treated with 1L chemotherapy, older patients required more dose adjustments (53.4% vs. 23%, p = 0.001) and received fewer cycles of chemotherapy (median 4 vs. 5, p= 0.01). Older patients had similar OS (11.2 months vs. 14 months, p = 0.06) and similar rates of treatment-related severe toxicity and healthcare visits, independent of the type of systemic treatment received, compared to younger patients. We conclude that select older adults with mUTC can be safely treated with immunotherapy and risk-adjusted regimens of chemotherapy with tangible survival benefits.
Meningiomas are primary CNS tumors that arise from the arachnoid layer of the meninges. Genomic sequencing has revealed that NF2 mutations are the most common genetic alteration seen in meningiomas. ...Meningiomas although usually low grade, can sometimes progress to high grade. A patient who had several recurrences of meningiomas since childhood presented with recurrent headaches. Imaging showed that he had another recurrence of a meningioma. He underwent surgery for resection of the meningioma and histopathology showed NF2 mutation. He was started on everolimus and bevacizumab with good effect. Studies have shown that NF-2 mutated meningiomas have a good response to everolimus and bevacizumab with increased progression-free survival time and progression-free survival time at 6 months.
Thromboembolic events (TE) are a common complication in patients with metastatic renal cell carcinoma (mRCC) and are associated with poorer clinical outcomes. However, the incidence of TE and ...clinical and genomic characteristics of patients with mRCC who develop this complication are poorly understood. Herein, we describe the incidence and clinical features of patients with mRCC with or without TE at our institution, and examine their association with the underlying genomic and transcriptomic characteristics of the tumor. This retrospective study included all consecutive cases of mRCC seen at our institution. A CLIA-certified lab performed tumor genomics and transcriptomics. Patients were classified based on the presence of a TE within the first year of diagnosis. Three hundred and seventy patients with mRCC were included in the study. TE was seen in 11% (42) of the patients. Patients with favorable International mRCC Database Consortium (IMDC) risk were less likely to develop a TE. In contrast, patients receiving combination treatment with a tyrosine kinase inhibitor (TKI) and an immune checkpoint inhibitor were more likely to develop a TE. No difference in overall survival among patients with or without TE was observed (52 vs. 55 months; HR 0.85, 95% CI 0.5574–1.293, p = 0.24). The most upregulated pathways in mRCC with TEs versus those without were the xenobiotic metabolism and mTORC1 signaling pathways. Our findings suggest potential biomarkers that, after external validation, could be used to better select patients who would benefit from prophylactic anticoagulation.
Cervical cancer is the fourth most common cancer in females. Clear cell adenocarcinoma of the cervix is an uncommon histological variant and is usually seen with intrauterine exposure to ...diethylstilbestrol. A 28-year-old female with no intrauterine exposure to diethylstilbestrol presented with postcoital bleeding. A pelvic exam revealed a cervical mass. Imaging confirmed the cervical mass and positron emission tomography scan showed an increased uptake in the cervical mass as well as the para-aortic and pelvic lymph nodes. Biopsy showed a clear cell carcinoma of the cervix. She was treated with cisplatin and paclitaxel for eight cycles and concurrent radiation therapy. She had a complete response to therapy and has been in complete remission nine months from the end of therapy. There are no clear guidelines for the treatment of clear cell carcinoma with current therapy based on the treatment of squamous and non-clear cell adenocarcinoma. Cisplatin and paclitaxel could be an option, given the successful treatment of the patient in our case.
Levamisole is a common contaminant in cocaine and has led to the emergence of an entity known as levamisole-induced vasculitis (LIV). There is no consensus on the management of this condition. We ...describe a patient who presented with acute on chronic LIV who was treated with pulse dose steroids. We aim to discuss the diagnosis and current management options for LIV. We have compared seven case reports that have measured C-reactive protein (CRP) and compared the CRP levels, site involved, dose, and mode of steroid administration. We postulate that elevated CRP may warrant steroid therapy over conservative management and could lead to a possible decreased hospital stay.
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