Risultati per: Carcinoma della prostata

This narrative review considers the current evidence and ongoing trials of neoadjuvant or prenephrectomy immune checkpoint inhibitor therapy in patients with locally advanced and metastatic renal cell carcinoma.

This cohort study examines raw and age-adjusted differences in the incidence of keratinocyte carcinoma among Medicare beneficiaries by race and ethnicity.

To the Editor In their randomized clinical trial published recently in JAMA Oncology, Harrington and colleagues evaluated the efficacy of nivolumab/ipilimumab vs nivolumab alone for treating recurrent or metastatic squamous cell carcinoma of the head and neck. The primary end points were the patient’s objective response and duration of response (DOR). The objective response rates were 13.2% and 18.3% with nivolumab/ipilimumab and nivolumab, respectively. The median DOR was not reached for nivolumab/ipilimumab vs 11.1 months for nivolumab. Although these results are not encouraging for the combination therapy, there are several lessons we may learn from this well-intended study, which would be helpful for conducting future oncology trials in a similar setting.

In Reply We thank Parast et al for commenting on our article reporting the phase 2 CheckMate 714 study outcomes. The study did not meet its primary end point of objective response rate (ORR) benefit with first-line nivolumab and ipilimumab vs nivolumab alone in patients with platinum-refractory recurrent or metastatic squamous cell carcinoma of the head and neck (R/M SCCHN). Median duration of response (mDOR) was not reached for nivolumab plus ipilimumab vs 11.1 months for nivolumab. Although survival benefits are considered gold-standard end points for cancer clinical trials, ORR and mDOR among responders are clinically relevant and widely accepted by clinicians and regulatory agencies. While addressing comments from Parast et al, we bring your attention to similar correspondence on this issue concerning the CheckMate 143 study.

To the Editor In a recent issue of JAMA Oncology, Harrington et al reported on the outcome of the CheckMate 714 randomized clinical trial, which compared combination immunotherapy using the anti–programmed death 1 (PD-1) antibody nivolumab and the anti–cytotoxic T-lymphocyte antigen 4 (CTLA-4) antibody ipilimumab vs nivolumab monotherapy in patients with advanced head and neck cancer. The trial failed to show superiority of the combination, and as the authors briefly acknowledge, the chosen ipilimumab dosing may have contributed to the negative outcome of the study.

Objective
This study aimed to investigate the cost-effectiveness of adding Chinese-developed anti-PD-1 antibody camrelizumab to first-line platinum-doublet chemotherapy in patients with recurrent or metastatic nasopharyngeal carcinoma (L/M NPC) from the perspective of Chinese healthcare system.

Design
A Markov model consisting of four health states, progression-free survival, first progression survival, second progression survival and death, was built to simulate 3-week patient transitions over a 20-year horizon. A direct comparison between first-line camrelizumab in combination with gemcitabine plus cisplatin and gemcitabine plus cisplatin was performed by calculating transition probabilities from the CAPTAIN-1st trial. Costs and utilities were collected from the local public database and literature. One-way and probabilistic sensitivity analyses were employed to evaluate the robustness of the model.

Setting
The Chinese healthcare system perspective.

Participants
A hypothetical cohort of Chinese patients with pathologically diagnosed L/M NPC who had an Eastern Cooperative Oncology Group performance status of 0 or 1.

Interventions
First-line camrelizumab in combination with camrelizumab and gemcitabine plus cisplatin (CGP) versus gemcitabine plus cisplatin (GP).

Primary outcome measure
Cost, quality-adjusted life-years (QALYs), incremental cost-effectiveness ratio (ICER).

Results
The baseline analysis demonstrated that, compared with first-line GP, first-line CGP yields an effectiveness increase of 0.26 QALY, accompanied by an increment of US$6137.59 in healthcare cost. This results in an ICER of US$23 482.32/QALY. With the willingness-to-pay (WTP) threshold for a QALY set at US$37 654.50, first-line CGP proves to be cost-effective in 97.20% of the iterations. Deterministic sensitivity analyses indicated that the uncertainty in model parameters had no substantial effect on our results. Probability sensitivity analysis indicated that CGP was cost-effective at the assumed WTP threshold.

Conclusion
For Chinese patients with L/M NPC, adding Chinese-developed anti-PD-1 antibody camrelizumab to the first-line GP chemotherapy may be cost-effective.

Objective
The purpose of this study was to describe the clinicopathological characteristics and prognosis of primary small cell carcinoma of the breast (PSCCB) and compare PSCCB with breast invasive ductal carcinoma (IDC).

Design
A retrospective cohort study.

Setting
Data of patients with PSCCB and breast IDC were identified from the Surveillance, Epidemiology, and End Results (SEER) database between 2004 and 2016.

Participants
Eighty-three patients with PSCCB and 410 699 patients with breast IDC were enrolled in the present cohort study.

Materials and methods
Patients with PSCCB and breast IDC were identified from the SEER database between 2004 and 2016. The clinicopathological characteristics and survival of patients with PSCCB and IDC were compared. Propensity score matching (PSM) analysis was performed to adjust for differences in baseline characteristics when comparing overall survival (OS) and cancer-specific survival (CSS). Moreover, OS-/CSS-specific nomograms were established to predict the prognosis of PSCCB.

Results
Compared with IDC, PSCCB was significantly correlated with older age, male, higher pathological grade, higher TNM (tumour, node, metastases) stage, a higher proportion of triple-negative breast cancer, a lower proportion of ER/PR positivity and significantly worse clinical outcome. The median OS and CSS of patients with PSCCB were 23.0 m (95%CI 13.0 to 56.0) and 28.0 m (95%CI 18.0 to 66.0), respectively. The 5-year OS and CSS rates in the PSCCB group were 36.1% and 42.4%, respectively. In the matched cohort after PSM analysis, patients with PSCCB had significantly worse OS and CSS than IDC patients. Multivariate Cox regression analysis demonstrated that T stage and administration of chemotherapy were independent prognostic factors for both OS and CSS in patients with PSCCB. The C-index for OS-/CSS-specific nomogram was 0.75 (95%CI 0.66 to 0.85)/0.79 (95%CI 0.69 to 0.89), respectively. The calibration curve in the ROC analysis indicated that the predicted value was consistent with the actual observation value. Decision curve analysis suggested that the nomogram model has a significant positive net benefit from the risk of death and are better than the traditional TNM staging system.

Conclusion
PSCCB has distinct clinicopathological characteristics, and patients with PSCCB have significantly worse clinical outcomes than those with IDC.

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.

This cohort study compares prognostic assessments of perineural invasion in cutaneous squamous cell carcinoma and their associations with poor outcomes and implications for staging system revision.

This narrative review investigates the use of circulating tumor human papillomavirus (HPV) DNA for surveillance of HPV-positive oropharyngeal squamous cell 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.

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.

Al via il progetto Flute per promuovere diagnosi più precise

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.