Economic evaluation of serplulimab plus chemotherapy as the first-line treatment of oesophageal squamous cell carcinoma in China

Objective
The ASTRUM-007 study confirmed the significant efficacy and safety of serplulimab plus chemotherapy for patients with locally advanced/metastatic, programmed cell death-ligand 1 positive oesophageal squamous cell carcinoma (OSCC). The economics of this regimen, however, is unclear. Therefore, this study aimed to evaluate the cost-effectiveness of adding serplulimab to chemotherapy for the treatment of advanced OSCC from the perspective of the Chinese healthcare system.

Design
A partitioned survival model was established to simulate the costs and outcomes of chemotherapy versus serplulimab plus chemotherapy. The survival data came from the ASTRUM-007 study. Only direct medical costs were considered, and utility values were referred to the literature. Sensitivity analysis was performed to assess the effect of parameter uncertainty on the model.

Outcome measures
Total costs, incremental costs, life years, quality-adjusted life years (QALYs), incremental QALYs and incremental cost-effectiveness ratio (ICER).

Results
The base case analysis showed that the cost of serplulimab plus chemotherapy (US$69 356) was US$41 607 higher than that of chemotherapy (US$27 749), but it also gained 0.38 QALYs more (1.38 vs 1 QALYs), with an ICER of US$110 744.36/QALY, which was higher than the willingness to pay. The factors that most influenced the ICER were the price of serplulimab, weight and utility value of the progression-free survival stage. The subgroup analysis and scenario analysis also demonstrated that serplulimab plus chemotherapy was not economical.

Conclusions
Compared with chemotherapy, serplulimab coupled with chemotherapy was not cost-effective for the treatment of advanced OSCC in China.

Leggi
Dicembre 2023

Toripalimab Plus Chemotherapy for Recurrent or Metastatic Nasopharyngeal Carcinoma

This multicenter, double-blind, randomized trial conducted in nasopharyngeal cancer (NPC)–endemic regions assesses whether toripalimab in combination with gemcitabine-cisplatin as first-line treatment for recurrent or metastatic NPC, compared with gemcitabine-cisplatin alone, will significantly improve progression-free survival and overall survival among chemotherapy-naive patients with recurrent or metastatic NPC.

Leggi
Novembre 2023

Immunotherapy for Nasopharyngeal Carcinoma

Due to a unique immune substrate consisting of abundant lymphocytic infiltration, high programmed death–ligand 1 (PD-L1) expression, and the presence of several immune targets (CD40, CD70, CD80, and CD86), there is a strong biological rationale for incorporating immunotherapy in the treatment of nasopharyngeal carcinoma (NPC). Nonkeratinizing histological subtypes encompass more than 95% of NPC cases in endemic areas, and NPC is largely linked to Epstein-Barr virus (EBV) infection, providing an additional immune-prone factor through the expression of EBV antigens and CD4+/CD8+ T-cell target proteins. In this issue of JAMA, Mai and colleagues report the prespecified definitive overall survival analysis of the phase 3 JUPITER-02 trial. The addition of the anti–PD-1 antibody toripalimab to platinum-gemcitabine as a first-line treatment for recurrent or metastatic NPC (RM-NPC) proved to reduce by 37% the risk of death at 3 years of follow-up.

Leggi
Novembre 2023

Protocol for a mixed-method study to assess chronic cough in patients with renal cell carcinoma: the prevalence, impact on quality of life, trigger and potential clinical application of chronic cough as an early screening tool in patients with kidney cancer

Introduction
Cough as a symptom of renal cell carcinoma (RCC) was first described by Creevy in 1935, and despite one (unpublished) study suggesting it may affect 31% of these patients, as well as cough being discussed in forums for patients with kidney cancer, few clinicians are aware of this association. The cough has been described as unusual in nature, resolving rapidly after treatment with nephrectomy/embolisation but returning if the tumour recurs.

Methods and analysis
A prospective study using a questionnaire will identify the prevalence of cough in patients with suspected or confirmed RCC attending the Specialist Centre for Kidney Cancer (London, UK). A longitudinal study in a representative sample of these patients, using EQ-5D-5L and Leicester Cough Questionnaires, together with the use of semi-structured interviews with patients, will identify the impact of cough in addition to having a diagnosis of suspected or confirmed RCC on quality of life. To investigate cough mechanisms, a pilot study using cough hypersensitivity testing will be performed on patients with RCC, with and without a cough. Clinical samples (urine, blood, phlegm and breath condensate) from patients with RCC, with and without a cough, will be collected and analysed for the presence of substances known to trigger or enhance cough and compared with the results obtained from healthy volunteers.

Ethics and dissemination
Ethical approval has been granted (UK HR REC 22/PR/0791 dated 25/08/2022). Study outputs will be presented and published nationally and internationally at relevant conferences. This study will establish the prevalence of cough in patients with suspected or confirmed kidney cancer and support the education of clinicians to consider this diagnosis in patients with chronic cough (eg, recommending protocols to include both kidneys when investigating respiratory symptoms with chest CT scans). If substances known to trigger or enhance cough are identified and elevated in clinical samples, this research could offer potential targets for treatment for this distressing symptom.

Trial registration number
NIHR CRN portfolio CPMS ID:53 372.

Leggi
Novembre 2023

Abstract 16055: Marantic Endocarditis – A Rare Paraneoplastic Presentation of Ovarian Carcinoma

Circulation, Volume 148, Issue Suppl_1, Page A16055-A16055, November 6, 2023. Introduction:Nonbacterial thrombotic endocarditis (NBTE) or Marantic endocarditis, involves formation of sterile platelet & fibrin thrombi on undamaged cardiac valves & adjacent endocardium. The vegetation is associated with embolization.Case presentation:A middle-aged female without cardiac history presented to the ED with blurred vision & fatigue for 3 days. The patient was afebrile with a BP of 183/97mmHg. Physical examination showed decreased visual acuity in the left eye. The EKG was normal. The patient underwent a CT scan brain that showed suspicion of bilateral occipital strokes. MRI brain revealed multiple small acute infarcts in the bilateral cerebral hemispheres & cerebellum. Blood cultures were negative. Telemetry did not show atrial fibrillation. Given a suspicion of cardioembolic stroke, the patient underwent a transesophageal echocardiogram (TEE) which demonstrated a trileaflet aortic valve (AV) with abnormal irregular thickening of leaflets, concerning for vegetation & moderate-severe aortic regurgitation (AR). figure 1. Our patient was diagnosed with marantic endocarditis based on TEE & serial negative cultures. Apixaban was started. Further workup of the patient revealed bilateral pulmonary emboli. Abdominal imaging revealed a pelvic mass, ultimately diagnosed as clear-cell ovarian cancer. Interval TEE at 3 months demonstrated complete resolution of vegetations with preserved cusp motion & mild AR. A shared decision was made to continue lifelong anticoagulation.Discussion:NBTE commonly involves mitral & AV. Risk factors include trauma, circulating immune complexes, hypercoagulability, malignancy & acute inflammation. Symptoms result from embolization, valve dysfunction, or impaired cardiac function. It is based on imaging after ruling out infectious etiologies. Management is anticoagulation & valve replacement with the treatment of the underlying etiology. Valve replacement prevents future embolic complications.

Leggi
Novembre 2023

Abstract 12450: Mystifying Masquerade: Renal Cell Carcinoma Associated Arteriovenous Fistula Presenting as High-Output Heart Failure

Circulation, Volume 148, Issue Suppl_1, Page A12450-A12450, November 6, 2023. Case Presentation:59 year-old woman with CKD stage 3b and hypertension presented with 3 months of progressive dyspnea, abdominal distension, bilateral lower extremity edema, and a 60-pound weight gain. Physical exam noted diffuse anasarca, with stable hemodynamics on room air. EKG revealed low voltage leads and chest X-ray demonstrated an enlarged cardiac silhouette. CT abdomen was remarkable for significant ascites, body wall edema, and a suspicious large right renal mass. Diagnostic paracentesis indicated cardiac ascites. Echocardiogram showed preserved ejection fraction, moderate pericardial effusion and an enlarged right side of the heart. Right heart catheterization confirmed high-output heart failure (HOHF). A suspected renal mass-related arteriovenous fistula (AVF) was confirmed through inferior vena caval and renal venogram blood gas sampling, indicating arteriovenous shunting within the renal mass. Hepatic venogram excluded portal hypertension. MRI abdomen confirmed a large necrotic right renal mass consistent with renal cell carcinoma (RCC). Symptoms significantly improved after nephrectomy, with aggressive diuresis, and therapeutic paracenteses leading to an 80-pound weight loss. Postoperative echocardiography illustrated decrease in pericardial effusion and right ventricular size. Cardiac MRI and stress test were unremarkable prior to planned immunotherapy for stage III RCC.Discussion:AVF and HOHF associated with malignancy are unusual presentations. RCC is the most prevalent underlying malignancy linked with AVF and is hypothesized to be a result of hypervascularity caused by a VHL gene mutation. The most often utilized imaging modalities for detecting a tumor-related AVF are contrast enhanced CT or MRI. When imaging is inconclusive, a venogram with blood gas sample, as observed in our case, may be considered to establish an RCC-associated AVF.

Leggi
Novembre 2023

Nomogram incorporating log odds of positive lymph nodes improves prognostic prediction for ovarian serous carcinoma: a real-world retrospective cohort study

Objectives
Ovarian serous carcinoma (OSC) is a major cause of gynaecological cancer death, yet there is a lack of reliable prognostic models. To address this, we developed and validated a nomogram based on conventional clinical characteristics and log odds of positive lymph nodes (LODDS) to predict the prognosis of OSC patients.

Setting
A Real-World Retrospective Cohort Study from the Surveillance, Epidemiology and End Results programme.

Participants
We obtained data on 4192 patients diagnosed with OSC between 2010 and 2015. Eligibility criteria included specific diagnostic codes, OSC being the primary malignant tumour and age at diagnosis over 18 years. Exclusion criteria were missing information on various factors and unknown cause of death or survival time.

Primary and secondary outcome measures
The primary outcome were overall survival (OS) and ovarian cancer-specific survival (OCSS).

Results
For OS and OCSS outcomes, we selected 7 and 5 variables, respectively, to establish the nomogram. In the training and validation cohorts, the C index for OS or OCSS was 0.716 or 0.718 and 0.731 or 0.733, respectively, with a 3-year time-dependent area under the curve (AUC) of 0.745 or 0.751 and a 5-year time-dependent AUC of 0.742 or 0.751. Calibration curves demonstrated excellent consistency between predicted and observed outcomes. The Net Reclassification Index, integrated discrimination improvement and decision curve analysis curves indicated that our nomogram performed better than the International Federation of Gynaecology and Obstetrics (FIGO) staging system in predicting OS and OCSS for OSC patients in both the training and validation cohorts.

Conclusion
Our nomogram, which includes LODDS, offers higher accuracy and reliability than the FIGO staging system and can predict overall and OCSS in OSC patients.

Leggi
Ottobre 2023

Survival analysis and nomogram for pulmonary sarcomatoid carcinoma: an SEER analysis and external validation

Objective
Uncommon and particularly deadly, pulmonary sarcomatoid carcinoma (PSC) is an aggressive type of lung cancer. This research aimed to create a risk categorisation and nomogram to forecast the overall survival (OS) of patients with PSC.

Methods
To develop the model, 899 patients with PSC were taken from the Surveillance, Epidemiology, and End Results database from the USA. We also used an exterior verification sample of 34 individuals with PSC from Fujian Provincial Hospital in China. The Cox regression hazards model and stepwise regression analysis were done to screen factors in developing a nomogram. The nomogram’s ability to discriminate was measured employing the area under a time-dependent receiver operating characteristic curve (AUC), the concordance index (C-index) and the calibration curve. Decision curve analysis (DCA) and integrated discrimination improvement (IDI) were used to evaluate the nomogram to the tumour–node–metastasis categorisation developed by the American Joint Committee on Cancer (AJCC-TNM), eighth edition, and an additional sample confirmed the nomogram’s accuracy. We further developed a risk assessment system based on nomogram scores.

Results
Six independent variables, age, sex, primary tumour site, pathological group, tumour–node–metastasis (TNM) clinical stage and therapeutic technique, were chosen to form the nomogram’s basis. The nomogram indicated good discriminative ability with the C-index (0.763 in the training cohort and 0.746 in the external validation cohort) and time-dependent AUC. Calibration plots demonstrated high congruence between the prediction model and real-world evidence in both the validation and training cohorts. Nomogram outperformed the AJCC-TNM eighth edition classification in both DCA and IDI. Patients were classified into subgroups according to their risk ratings, and significant differences in OS were observed between them (p

Leggi
Ottobre 2023