Total neoadjuvant therapy in rectal cancer: a network meta-analysis of randomized trials.

PURPOSE: To assess the efficacy of total neoadjuvant therapy (TNT) for rectal carcinoma in comparison with conventional chemoradiotherapy (CRT). METHODS: A systematic review was performed according to the PRISMA guidelines. A Bayesian network meta-analysis was done using NetMetaXL and WinBUGS. This study was registered in PROSPERO on March 3, 2022 (No. CRD-42022307867). RESULTS: Outcomes of 2,719 patients from 10 randomized trials between 2010 and 2022 were selected. Of these 1,191 (44%) had conventional long-course CRT (50-54 Gy) and capecitabine, 506 (18%) had induction chemotherapy followed by CRT (50-54 Gy) and capecitabine (iTNT), 230 (9%) had long-course CRT (50-54 Gy) followed by consolidation chemotherapy (cTNT), and 792 (29%) undergone modified short-course radiotherapy (25 Gy) with subsequent chemotherapy (mTNT). Total pathologic complete response (pCR) was 20% in the iTNT group, 21% in the mTNT group, 22% in the cTNT group, and 12% in the CRT group. Statistically significant difference in pCR rates was detected when comparing iTNT with CRT (odds ratio [OR], 1.76; 95% credible interval [CrI], 1.06-2.8), mTNT with CRT (OR, 1.90; 95% CrI, 1.25-2.74), and cTNT with CRT groups (OR, 2.54; 95% CrI, 1.26-5.08). No differences were found in R0 resection rates. No significant difference was found in long-term outcomes. CONCLUSION: The early administration of systemic chemotherapy in the TNT regimen has improved short-term outcomes, though long-term results are underreported. Randomized trials with survival as the endpoint are necessary to evaluate the possible advantages of TNT modes.

Blood Plasma Metabolome Profiling at Different Stages of Renal Cell Carcinoma.

Early diagnostics significantly improves the survival of patients with renal cell carcinoma (RCC), which is the prevailing type of adult kidney cancer. However, the absence of clinically obvious symptoms and effective screening strategies at the early stages result to disease progression and survival rate reducing. The study was focused on revealing of potential low molecular biomarkers for early-stage RCC. The untargeted direct injection mass spectrometry-based metabolite profiling of blood plasma samples from 51 non-cancer volunteers (control) and 78 patients with different RCC subtypes and stages (early stages of clear cell RCC (ccRCC), papillary RCC (pRCC), chromophobe RCC (chrRCC) and advanced stages of ccRCC) was performed. Comparative analysis of the blood plasma metabolites between the control and cancer groups provided the detection of metabolites associated with different tumor stages. The designed model based on the revealed metabolites demonstrated high diagnostic power and accuracy. Overall, using the metabolomics approach the study revealed the metabolites demonstrating a high value for design of plasma-based test to improve early ccRCC diagnosis.

Neoadjuvant chemoradiotherapy for locally advanced rectal cancer with peritumoral abscesses and fistulas.

PURPOSE: Rectal cancer patients who present with peritumoral abscesses and fistulas at the time of diagnosis may be denied chemoradiotherapy (CRT) as the safety is unknown. The aim of this study was to investigate the safety of preoperative CRT in this patient group. METHODS: We performed a retrospective nested case-control study to compare outcomes between patients with locally advanced rectal cancer with peritumoral abscesses and fistulas (study group) and patients with T4 locally advanced rectal cancer with no evidence of abscesses and fistulas (control group). These groups were matched by treatment center and radiotherapy delivery method. All patients received 50-54 Gy of conventionally fractionated RT with concurrent chemotherapy. Primary endpoint was grade 3-5 toxicity (by National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI CTCAE). Secondary endpoints included postoperative morbidity, pathologic complete response (pCR), disease-free survival (DFS), and overall survival (OS) at 2 years. RESULTS: A total of 33 patients were included in each group. Grade 3 toxicity was observed in 2 (6.1%) patients in the study group and 4 (12.1%) patients in the control group (p = 0.672). No patients developed grade 4-5 toxicity. Grade 3-4 Clavien-Dindo complications were observed in 5 (15.2%) patients in the study group and in 6 (18.2%) patients in the control group (p = 1.0). Pathologic CR was achieved in 3 (9.1%) and 5 (15.2%) patients, respectively (p = 0.708). Two-year OS was 78.3% vs. 81.8% (p = 0.944), 2­year DFS was 62.8% vs. 69.7% (p = 0.693), respectively. CONCLUSION: The presence of peritumoral abscesses and fistulas in patients with locally advanced rectal cancer is not associated with increased toxicity or inferior clinical outcomes after preoperative CRT.