Risultati per: Carcinoma basocellulare

Introduction
Liver resection is the mainstay of curative-intent treatment for hepatocellular carcinoma (HCC), but the postoperative 5-year recurrence rate reaches 70%, and there are no adjuvant or neoadjuvant therapies recommended by major HCC guidelines that can reduce the risk of recurrence. In the recent decade, significant progress has been achieved in the systemic treatment of HCC, mainly from immune checkpoint inhibitors (ICIs) and targeted therapy. In other malignancies, ICIs in the neoadjuvant setting have shown better outcomes than in the adjuvant setting. On the other hand, the addition of radiation to ICIs incrementally improves the systemic response to ICIs. Neoadjuvant therapy of ICIs plus stereotactic body radiotherapy (SBRT) has shown promising results in several types of solid tumours but not HCC.

Methods and analysis
Here, we describe a phase Ib clinical trial of neoadjuvant SBRT plus PD-1 (tislelizumab) prior to hepatic resection in HCC patients. Prior to resection, eligible HCC patients will receive 8 Gyx3 fractions of SBRT together with two cycles of tislelizumab with an interval of 3 weeks. HCC resection is scheduled 4 weeks after the second dose of tislelizumab, followed by adjuvant tislelizumab for 1 year. We plan to enrol 20 participants in this trial. The primary study endpoints include the delay of surgery, tumour response and safety and tolerability of the sequential SBRT/tislelizumab. Other endpoints are the disease-free survival and overall survival rates every 3 or 6 months after the surgery.

Ethics and dissemination
This trial was approved by the Ethics Committee of Shandong Cancer Hospital and Institute (SDZLEC2022-021-01). The final results of this trial will be published in a peer-reviewed journal after completion.

Trial registration number
NCT05185531.

Objectives
The purpose of this study was to determine the risk factors for suicide in patients with squamous cell carcinoma (SCC) in the USA.

Setting
Patients with SCC diagnosed between 1975 and 2017 from the Surveillance, Epidemiology and End Results (SEER) database were selected for this study.

Participants
This study included patients with SCC older than 20 years who were diagnosed between 1975 and 2017.

Primary and secondary outcome measures
The general population included in data from the US Centers for Disease Control and Prevention were used to calculate the suicide rate and standardised mortality rate (SMR) of SCC patients. Univariate and multivariate Cox regression analyses were used to identify risk factors for suicide in patients with SCC.

Results
There were 415 268 SCC patients registered in the SEER database, among which 1157 cases of suicide were found, comprising a total of 2 289 772 person-years. The suicide rate for patients with SCC was 50.53 per 100 000 person-years, and the SMR was 4.13 (95% CI 3.90 to 4.38). The Cox regression analyses showed that the factors related to a high risk of suicide among patients with SCC included being male (vs female: HR 5.36, 95% CI 4.51 to 6.38, p

Objectives
The non-randomised, open-label, phase IIIb/IV multicohort CheckMate 920 trial explored the safety and efficacy with a less frequent, but continual nivolumab plus ipilimumab (NIVO+IPI) dosing regimen (cohort 1) to determine whether this modification could potentially retain efficacy benefits while improving on the manageable safety profile previously observed with this combination in patients with advanced renal cell carcinoma (aRCC).

Setting
Patients were enrolled from 48 largely community-based sites in the USA.

Participants
106 patients with previously untreated, predominantly clear cell aRCC received treatment.

Interventions
Patients received NIVO 6 mg/kg plus IPI 1 mg/kg on day 1 of the first week of each 8-week cycle; the combination alternated with NIVO 480 mg monotherapy on day 1 of the fifth week of each 8-week cycle. Treatment continued until disease progression, unacceptable toxicity, withdrawal of consent or study end. The maximum treatment duration was 2 years. The primary endpoint was the incidence of high-grade (grade 3/4 and grade 5) immune-mediated adverse events (IMAEs) within 100 days of the last dose. Select secondary endpoints included time to onset and resolution of high-grade IMAEs, progression-free survival (PFS) and objective response rate (ORR). The incidence of treatment-related adverse events and the overall survival (OS) were the exploratory endpoints.

Results
The most common grade 3/4 IMAEs were diarrhoea/colitis (7.5%) and rash (6.6%) and no grade 5 IMAEs occurred, with a minimum follow-up of 28.5 months. The median PFS was 4.8 (95% CI 3.0 to 8.3) months, the ORR in evaluable patients (n=96) was 34.4% (95% CI 25.0 to 44.8), and the median OS was not reached (95% CI 24.8 months to not estimable).

Conclusions
While no new safety signals were reported with less frequent, but continual NIVO+IPI dosing in CheckMate 920, the modified regimen was not associated with clinical benefits relative to the approved NIVO+IPI dose. These results support the continued use of the currently approved NIVO+IPI combination dosing schedule for patients with aRCC.

Trial registration number
NCT02982954.

Introduction
In early-stage oral tongue squamous cell carcinoma (OTSCC), elective neck dissection (END) is recommended when occult lymph node metastasis is suspected; however, there is no unanimous consensus on the risks and benefits of END in such cases. The management of clinically node-negative (cN0) OTSCC remains controversial. This study, therefore, aimed to evaluate the efficacy of END and its impact on the quality of life (QoL) of patients with cN0 OTSCC.

Methods and analysis
This is a prospective, multicentre, nonrandomised observational study. The choice of whether to perform END at the same time as resection of the primary tumour is based on institutional policy and patient preference. The primary endpoint of this study is 3-year overall survival. The secondary endpoints are 3-year disease-specific survival, 3-year relapse-free survival and the impact on patient QoL. Propensity score-matching analysis will be performed to reduce selection bias.

Ethics and dissemination
This study was approved by the Clinical Research Review Board of the Nagasaki University. The protocol of this study was registered at the University Hospital Medical Information Network Clinical Trials Registry. The datasets generated during the current study will be available from the corresponding author on reasonable request. The results will be disseminated internationally, through scientific and professional conferences and in peer-reviewed medical journals.

Trial registration number
UMIN000027875.

New England Journal of Medicine, Volume 387, Issue 17, Page 1557-1568, October 2022.

Single-agent anti-PD1 checkpoint inhibitors convey outstanding clinical benefits in a small fraction (∼20%) of patients with advanced hepatocellular carcinoma (aHCC) but the molecular mechanisms determining response are unknown. To fill this gap, we herein analyze the molecular and immune traits of aHCC in patients treated with anti-PD1.

Hepatocellular carcinoma (HCC) represents 75%–85% of primary liver cancers1 and is a major global disease, with a high incidence particularly in parts of South-East Asia and sub-Saharan Africa. While the overall incidence is low in countries such as the USA and Australia, risk factors like chronic HBV and HCV infections, autoimmune hepatitis, chronic alcohol abuse and obesity have led to an increased number of cases in recent years.2 Unfortunately, HCC remains a disease with high mortality, despite new therapeutic advances such as liver transplantation or ablation, which can have good outcomes if high-grade dysplastic nodules or small HCCs (

Objective
We aimed to construct and validate nomograms to predict overall survival (OS) and cancer-specific survival (CSS) for patients with chromophobe renal cell carcinoma (chRCC) after nephrectomy.

Design
This study is a retrospective cohort study.

Setting and participants
There were 2810 patients with chRCC from Surveillance, Epidemiology and End Results database diagnosed between 2010 and 2015 included in the study who were randomly divided into a training cohort (n=1970) and a validation cohort (n=840). Another single-centre external validation cohort containing 124 patients from our hospital was also involved in our study.

Primary and secondary outcome measures
OS and CSS.

Results
Nomograms for OS and CSS include four and five variables, respectively, from the result of least absolute shrinkage and selection operator regression analyses. Nomograms reveal the accurate discrimination by the area under the curve of receiver operating characteristic (ROC) curves and C-indexes, with a C-index value of 0.777 (95% CI 0.728 to 0.826), 0.810 (95% CI 0.747 to 0.873) and 0.863 (95% CI 0.773 to 0.953) for the training cohort, the internal validation cohort and the external validation cohort in the nomogram for OS; and a C-index value of 0.884 (95% CI 0.829 to 0.939), 0.868 (95% CI 0.772 to 0.964) and 0.862 (95% CI 0.760 to 0.964) for the training cohort, the internal validation cohort and the external validation cohort in the nomogram for CSS. It was also proven that there was a high degree of conformance between the predicted and observation results by calibration plots. In addition, the comparison of ROC curves and C-indexes between nomograms and seventh tumour, node and metastasis stage demonstrated that nomograms were better in accuracy and efficacy ability.

Conclusions
We successfully constructed two accurate and effective nomograms to predict OS and CSS for patients with chRCC after nephrectomy, which can help clinical doctors choose individual treatment strategies for chRCC patients.

Epidermal growth factor receptor (EGFR) is a therapeutic target in nasopharyngeal carcinoma (NPC). The optimal combined modality of optimal combined modality of anti-­EGFR monoclonal antibodies, induction chemotherapy (ICT), concurrent chemotherapy and radiotherapy for NPC remains poorly defined. None of previous studies have developed subsequent treatment strategies on the basis of stratification according to the efficacy following ICT plus anti-EGFR mAbs. This study aims to increase treatment intensity for patients with poor efficacy of ICT and reduce treatment toxicity for patients with favourable efficacy of ICT by assessing whether the efficacy of this treatment regimen is non-inferior to ICT plus concurrent chemoradiotherapy (historic controls).
Introduction

Methods and analysis
Pathology-confirmed WHO type II/III NPC patients at clinical stage III–IVA (eighth American Joint Committee on Cancer/Union for International Cancer Control staging system) will be included in the study. They will receive ICT plus nimotuzumab (NTZ), followed by radiotherapy plus NTZ or concurrent chemoradiotherapy plus NTZ (stratified based on the efficacy of ICT plus NTZ). The primary endpoint is 3-year failure-free survival rate; while the secondary endpoints are 3-year overall survival rate, distant metastasis-free survival rate and locoregional recurrence-free survival rate, and short-term remission rate of tumour and treatment toxicity.

Ethics and dissemination
The study protocol has been approved by the Ethics Committee of the Second Affiliated Hospital of Nanchang University. Our findings will be disseminated in a peer-reviewed journal. Implementation strategies are in place to ensure privacy and confidentiality of participants.

Trial registration number
ChiCTR2000041139.

We demonstrate that quantitative analysis of digitized images of colorectal carcinoma can improve prediction of tumor recurrence and place tumors into clinically relevant prognostic risk groups.

Introduction
Up to one-fifth of patients with colorectal cancer will develop peritoneal metastases, frequently without other districts’ involvement. Despite the recent unsuccesses of hyperthermic intraperitoneal chemotherapy (HIPEC) for colorectal cancer peritoneal metastases treatment, the rationale in the prophylactic setting remains strong. Several clinical and pharmacokinetic data suggest that the efficacy of intraperitoneal chemotherapy is highest when the disease is microscopic. However, robust evidence demonstrating whether the addition of HIPEC for high-risk colorectal cancers offers better control of local recurrence is lacking.

Methods and analysis
This is a multicentre randomised phase 3 trial comparing prophylactic surgery plus HIPEC CO2 with mitomycin, over standard surgical excision in patients with colorectal cancer at high risk of peritoneal carcinomatosis; 388 patients will be included in this study. The primary objective is to compare the efficacy of prophylactic surgery (radical colorectal resection, omentectomy, appendectomy, round ligament of the liver resection and bilateral adnexectomy) plus HIPEC CO2 with mitomycin and standard surgery in terms of local recurrence-free survival. The main secondary endpoints are disease-free survival (DFS), overall survival (OS) and safety. The primary endpoint will be described with a cumulative incidence function and will be analysed with Grey test to take account of the competing risks. DFS and OS will be described with the Kaplan-Meier method.

Ethics and dissemination
This trial has been evaluated by the Italian Medicines Agency, local ethics committees and will be submitted to the Ministry of Health to notify the start of the trial according to the regulation of trials on devices with CE mark/certification.
The results will be submitted for presentation at academic meetings and for publication in a peer-reviewed journal, whatever the findings.

Trial registration number
NCT03914820.

This secondary analysis of the Keynote 048 trial examines treatment with pembrolizumab in patients with recurrent and metastatic head and neck squamous cell carcinoma.

To the Editor With great interest, we read the phase 3 randomized clinical trial by Liu et al that reported a profound improvement in progression-free survival (PFS) with capecitabine maintenance therapy plus best supportive care (BSC) compared with BSC only in patients with newly diagnosed metastatic nasopharyngeal carcinoma who had response to initial induction chemotherapy (35.9 months vs 8.2 months). But there are certain concerns over the results that need to be addressed.

In Reply We appreciate the comments made by Ganguly and Gogia on our phase 3 randomized clinical trial. When we designed this trial, either combination chemotherapy (eg, cisplatin/gemcitabine, cisplatin/fluorouracil, cisplatin/paclitaxel) or monotherapy (eg, cisplatin, paclitaxel, capecitabine) was equivalently recommended in the National Comprehensive Cancer Network guidelines (version 1.2015). Additionally, the retrospective comparative study showed no significant differences between the gemcitabine plus cisplatin (GP) and taxane, cisplatin, and fluorouracil (TPF) regimens. Capecitabine is designed to generate fluorouracil in tumors preferentially and is more tolerable and convenient for patients with nasopharyngeal carcinoma (NPC). Though not directly compared, our results showed that the paclitaxel, cisplatin, and capecitabine (TPC) regimen did not significantly increase the toxicity compared with the GP regimen. Nevertheless, we have initiated a prospective trial to directly compare the efficacy and safety of TPC and the standard GP regimen in metastatic NPC (ChiCTR1900027112).

To the Editor In their recent phase 3 randomized clinical trial published in JAMA Oncology, Liu et al reported improvement in progression-free survival in patients with metastatic nasopharyngeal carcinoma (NPC). With current evidence of capecitabine as an adjuvant treatment after definitive chemoradiation in locoregionally advanced disease, this finding is indeed an exciting shift in the treatment paradigm of NPC.

The SMAD4 tumor suppressor gene regulates communication between colon cells and surrounding immune cells. In the setting of colitis, SMAD4 loss leads to increased immune cells and promotes tumor development.