Chemoradiotherapy Research Articles

The significance of consolidation chemotherapy after concurrent chemoradiotherapy in esophageal squamous cell carcinoma: a randomized controlled phase III clinical trial.

This study explored the significance of consolidation maintenance chemotherapy after concurrent chemoradiotherapy with different regimens in patients with esophageal squamous cell carcinoma. A prospective randomized controlled phase III clinical trial was designed and registered in the China Clinical Trials Registry (Registration number: ChiCTR-TRC-12002719). Survival data were analyzed in terms of intention-to-treat (ITT) and per-protocol (PP) sets for patients undergoing cisplatin and 5-fluorouracil (PF) (group A), or cisplatin and paclitaxel (TP) (group B). The incidence risk of grade III-IV leukopenia in group B was higher than in group A (49.2% vs. 25.5%, p = 0.012). The survival rates at 1, 2, 3, and 5 years were 83.8%, 62.6%, 53.1%, and 41.3%, respectively. Consolidation chemotherapy after concurrent chemoradiation therapy had no benefit on median progression-free survival (PFS) (p = 0.95) and overall survival (OS) (p = 0.809). According to the ITT analysis, the median PFS in group A and group B was 28.6 months and 30.3 months (X2 = 0.242, p = 0.623), while the median OS was 31.0 months and 50.3 months (X2 = 1.25，p = 0.263). For the PP analysis, the median PFS in group A and group B were 28.6 months and 30.3 months (p = 0.584), while the median OS was 31.0 months and 50.3 months (p = 0.259), respectively. Patients receiving consolidation chemotherapy did not show significant OS benefits (46.9 months vs. 38.3 months; X2 = 0.059, p = 0.866). Similar PFS and OS were found between PF and TP regimens with concurrent chemoradiotherapy. Consolidation chemotherapy did not show any significant OS benefits.

Predictive markers for head and neck cancer treatment response: T1rho imaging in nasopharyngeal carcinoma.

To investigate the potential of T1rho, a new quantitative imaging sequence for cancer, for pre and early intra-treatment prediction of treatment response in nasopharyngeal carcinoma (NPC) and compare the results with those of diffusion-weighted imaging (DWI). T1rho and DWI imaging of primary NPCs were performed pre- and early intra-treatment in 41 prospectively recruited patients. The mean preT1rho, preADC, intraT1rho, intraADC, and % changes in T1rho (ΔT1rho%) and ADC (ΔADC%) were compared between residual and non-residual groups based on biopsy in all patients after chemoradiotherapy (CRT) with (n = 29) or without (n = 12) induction chemotherapy (IC), and between responders and non-responders to IC in the subgroup who received IC, using Mann-Whitney U-test. A p-value of < 0.05 indicated statistical significance. Significant early intra-treatment changes in mean T1rho (p = 0.049) and mean ADC (p < 0.01) were detected(using paired t-test), most showing a decrease in T1rho (63.4%) and an increase in ADC (95.1%). Responders to IC (n = 17), compared to non-responders (n = 12), showed higher preT1rho (64.0 ms vs 66.5 ms) and a greater decrease in ΔT1rho% (- 7.5% vs 1.3%) (p < 0.05). The non-residual group after CRT (n = 35), compared to the residual group (n = 6), showed higher intraADC (0.96 vs 1.09 × 10-3 mm2/s) and greater increase in ΔADC% (11.7% vs 27.0%) (p = 0.02). Early intra-treatment changes are detectable on T1rho and show potential to predict tumour shrinkage after IC. T1rho may be complementary to DWI, which, unlike T1rho, did not predict response to IC but did predict non-residual disease after CRT. T1rho has the potential to complement DWI in the prediction of treatment response. Unlike DWI, it predicted shrinkage of the primary NPC after IC but not residual disease after CRT. Changes in T1rho were detected early during cancer treatment for NPC. Pre-treatment and early intra-treatment change in T1rho predicted response to IC, but not residual disease after CRT. T1rho can be used to complement DWI with DWI predicting residual disease after CRT.

DNA Methylation in Recurrent Glioblastomas: Increased TEM8 Expression Activates the Src/PI3K/AKT/GSK-3β/B-Catenin Pathway.

Glioblastomas (GBM) are infiltrative malignant brain tumors which mostly recur within a year's time following surgical resection and chemo-radiation therapy. Studies on glioblastoma cells following radio-chemotherapy, have been demonstrated to induce trans-differentiation, cellular plasticity, activation of DNA damage response and stemness. As glioblastomas are heterogenous tumors that develop treatment resistance and plasticity, we investigated if there exist genome-wide DNA methylation changes in recurrent tumors. Utilizing genome-wide DNA methylation arrays, we compared the DNA methylation profile of 11 primary (first occurrence) tumors with 13 recurrent (relapsed) GBM, to delineate the contribution of epigenetic changes associated with therapy exposure, therapy resistance, and relapse of disease. Our data revealed 1,224 hypermethylated- and 526 hypomethylated-probes in recurrent glioblastomas compared to primary disease. We found differential methylation of solute carrier and ion channel genes, interleukin receptor/ligand genes, tumor-suppressor genes and genes associated with metastasis. We functionally characterized one such hypomethylated-up-regulated gene, namely anthrax toxin receptor 1/tumor endothelial marker 8 (ANTXR1/TEM8), whose expression was validated to be significantly up-regulated in recurrent glioblastomas compared to primary tumors and confirmed by immunohistochemistry. Using overexpression and knockdown approaches, we showed that TEM8 induces proliferation, invasion, migration, and chemo-radioresistance in glioblastoma cells. Additionally, we demonstrated a novel mechanism of β-catenin stabilization and activation of the β-catenin transcriptional program due to TEM8 overexpression via a Src/PI3K/AKT/GSK3β/β-catenin pathway. We report genome-wide DNA methylation changes in recurrent GBM and suggest involvement of the TEM8 gene in GBM recurrence and progression.

Comparison of treatment strategies based on clinical and pathological nodal status in resectable gastric adenocarcinoma.

To determine the optimal multimodal treatment strategy between perioperative chemotherapy (PEC), postoperative chemoradiation therapy (POCR), and postoperative chemotherapy (POC) in resected gastric cancer (GC) patients based on nodal status. In this retrospective analysis, the National Cancer Database was used to identify resected non-metastatic GC (2006-2016). Patients were stratified by clinical nodal status-negative (cLN-) and positive (cLN+). In patients with cLN- disease who underwent upfront resection and were upstaged to pathological LN+, overall survival (OS) was compared between POC and POCR. In patients with cLN- and cLN+ disease, OS was compared between PEC, POCR, and POC. Kaplan-Meier survival estimate, log-rank test, and multivariable Cox proportional hazards analysis were performed. We identified 7827 patients (cLN- 4828; cLN+ 2999). On multivariable analysis in patients with cLN- disease who underwent upfront resection (n = 4314) and were upstaged to pLN+ disease (70%), POCR (n = 2300, aHR 0.78, 95% CI 0.70-0.87, p < 0.001) was associated with improved OS compared to POC (n = 907). No significant difference was noted between POCR (n = 766, aHR 1.11, 95% CI 0.88-1.40, p = 0.39) and POC (n = 341) in patients with pLN- disease. On multivariable analysis in all patients with cLN- disease, POCR (n = 3066) was significantly associated with improved OS (aHR 0.84, 95% CI 0.75-0.92, p < 0.01) compared to POC (n = 1248). No significant difference was noted between POCR (aHR 1.0, 95% CI 0.70-1.01, p = 0.958) and PEC (n = 514). These results remained consistent in patients with cLN+ disease (POCR = 1602, POC = 720, PEC = 677). Postoperative chemoradiation is associated with improved survival in GC patients upstaged from clinically node-negative disease to pathologically node-positive disease. Negative clinical nodal disease status is not a reliable indicator of pathological nodal disease.

Risk factors and treatment strategies for local recurrence of locally advanced rectal cancer treated with neoadjuvant chemoradiotherapy followed by total mesorectal excision

BackgroundDespite advancements in total mesorectal excision (TME) and neoadjuvant radiotherapy, locally advanced rectal cancer remains challenging, impacting patient quality of life and mortality. This study aimed to identify the risk factors for local recurrence in locally advanced rectal cancer treated with neoadjuvant chemoradiotherapy (CRT) and assess treatment strategies for recurrence. MethodsThis retrospective analysis included 682 patients diagnosed with locally advanced rectal cancer who were treated with neoadjuvant CRT and TME at Samsung Medical Center from 2008 to 2017. The exclusion criteria ensured a homogenous cohort. Clinical staging involved colonoscopies, computed tomography, magnetic resonance imaging, and digital rectal exam. Risk factors, treatment modalities, and oncological outcomes for local recurrence were evaluated. ResultDuring a median 62-month follow-up, 47 patients (6.9 %) experienced local recurrence. The risk factors for local recurrence included a positive circumferential resection margin (CRM), venous invasion, and perineural invasion. Of the 47 patients with local recurrence, 25 (53.2 %) were considered resectable. Out of these, 23 patients underwent curative resections, and 15 (65.2 %) achieved R0 resection. Patients with R0 resections exhibited superior 5-year survival rates compared to R1-2 resection or non-surgical treatment, and there was no survival difference between R1-2 resection and non-surgical treatment. ConclusionIn locally advanced rectal cancer, positive CRM, venous invasion, and perineural invasion were associated with local recurrence. R0 resection showed favorable outcomes, emphasizing the importance of surveillance in high-risk patients. Treatment decisions should consider these factors for improved oncologic outcomes and quality of life.

Hippocampal-Sparing Radiation Therapy in Primary Sinonasal and Cutaneous Tumors of the Head and Neck

Patients with primary sinonasal and cutaneous head and neck (H&N) malignancies often receive meaningful radiation dose to their hippocampi, but this not a classic avoidance structure in radiation planning. We aimed to characterize the feasibility and tradeoffs of hippocampal-sparing radiation therapy (HSRT) for patients with primary sinonasal and cutaneous H&N malignancies. We retrospectively selected patients who were treated definitively for primary sinonasal or cutaneous malignancies of the H&N at an academic medical center. All received (chemo)radiation alone or adjuvantly and substantial radiation dose to 1 or both hippocampi. We created new HSRT plans for each patient with intensity modulated radiation therapy using the original target and organ-at-risk (OAR) volumes. Hippocampi were contoured based on Radiation Therapy Oncology Group guidelines and reviewed by a neuroradiologist. Absolute and relative differences in radiation dose to the hippocampi, planning target volumes (PTVs), and OARs were recorded and compared. There were 18 sinonasal and 12 cutaneous H&N primary tumors (30 patients in total). Median prescription dose was 6600 cGy (range, 5000-7440 cGy), and 14 of the 30 patients received 120 cGy/fraction twice daily, 13 of the 30 patients received 200 cGy/fraction once daily, whereas others received 180-275 cGy/fraction once daily. The relative decrease in ipsilateral hippocampal Dmax and D100% using HSRT was 44% (median, 2009 cGy from 3586 cGy) and 65% (median 434 cGy from 1257 cGy), respectively. There were no statistically significant or clinically meaningful differences in PTV V100%, PTV D1%, or radiation dose to other OARs between HSRT and non-HSRT plans. HSRT is feasible and results in meaningful dose reduction to the hippocampi without reducing PTV coverage or increasing dose to other OARs. We suggest target hippocampal constraints of Dmax < 1600 cGy and D100% < 500 cGy when feasible (without compromising PTV coverage or impacting other critical OARs). The clinical significance of HSRT in patients with primary H&N tumors should be investigated prospectively.

Identifying biomarkers for nasopharyngeal carcinoma diagnosis and chemoradiotherapy response using serum endogenous small molecules profiling

Changes in metabolic characteristics are important features of tumor progression and prognosis, including nasopharyngeal carcinoma (NPC). Identifying serum metabolites as potential diagnostic and chemoradiotherapy response biomarkers for NPC is therefore crucial. In this study, ultra-performance liquid chromatography coupled with linear ion trap quadrupole orbitrap high-resolution mass spectrometry (UPLC-LTQ-Orbitrap MS) was used to analyze metabolic variations among controls, NPC patients, and NPC patients undergoing chemoradiotherapy (CRT). Univariate and multivariate analyses revealed seven differential metabolites between the control and NPC groups and eleven metabolites between the CRT and NPC groups. Five common metabolites, gluconic acid, palmitic acid, LysoPC (15:0/0:0), stearic acid, and LysoPC (20:2(11Z,14Z)/0:0), were consistently altered across groups. Notably, the first four metabolites were adjusted closer to normal after chemoradiotherapy, while this change is not reflected at LysoPC (20:2(11Z,14Z)/0:0). These common metabolites were enriched in five pathways. These findings underscore the importance of serum metabolite profiling in NPC diagnosis and treatment response assessment and offer a promising foundation for further clinical research.

Chemoradiotherapy plus induction or consolidation chemotherapy as total neoadjuvant therapy for locally advanced rectal cancer: Pooled analysis of the CAO/ARO/AIO-12 and the OPRA randomized phase 2 trials

Total neoadjuvant therapy (TNT) has been used for patients with locally advanced rectal cancer. The optimal sequence of chemoradiotherapy (CRT) and chemotherapy (CT) is a matter of debate. We performed a pooled analysis of the CAO/ARO/AIO-12 and OPRA multicenter, randomized phase 2 trials to identify patient subsets that could benefit from one TNT sequence over the other regarding disease-free survival (DFS). Patients with stage II/III rectal cancer were randomized to CRT (50.4-54Gy) with either induction (INCT-CRT) or consolidation CT (CRT-CNCT) with fluorouracil, leucovorin, oxaliplatin (CAO/ARO/AIO-12 and OPRA) or capecitabine and oxaliplatin (OPRA) followed by mandatory total mesorectal excision (TME) (CAO/ARO/AIO-12) or selective watch-and-wait surveillance (OPRA). 311 and 324 patients were recruited from June 15, 2015 to January 31, 2018; and from April 12, 2014 to March 30, 2020 in the two trials, respectively. Pretreatment clinical and tumor characteristics included were age, sex, ECOG, cT-category, cN-category, clinical UICC stage, location from anal verge, and tumor grade. In total, 628 eligible patients were included in the pooled analysis (CAO/ARO/AIO-12, n=304; OPRA, n=324). Of those, 313 were randomly assigned to the INCT-CRT group, and 315 to the CRT-CNCT group. Median follow-up was 43 months (IQR, 35-49) months in the CAO/ARO/AIO-12 trial and 61,2 months (IQR, 42-68,4) in the OPRA trial. Pooled analysis of baseline clinical and tumor characteristics did not identify any subgroups of patients that would benefit by the one TNT sequence over the other with regard to DFS. To our knowledge, this is the first pooled analysis of two randomized trials after direct head-to-head comparison of both TNT sequences. Both trials reported higher rates of complete response with CRT-CNCT, and this should be considered the preferred TNT sequence if organ preservation is a priority.

Pre-treatment magnetic resonance imaging in anal cancer: large-scale evaluation of mrT, mrN and novel staging parameters

BackgroundIn patients with squamous cell carcinoma of the anus (SCCA), magnetic resonance (MR) imaging is recommended for pre-treatment staging prior to chemo-radiotherapy (CRT), but large-scale evaluation of its staging performance is lacking.MethodsWe re-characterised pre-treatment MRs from 228 patients with non-metastatic SCCA treated consecutively by CRT (2006–2015) at one UK cancer centre. We derived TN staging from tumour size (mrTr) and nodal involvement (mrN), and additionally characterised novel beyond TN features such as extramural vascular invasion (mrEMVI) and tumour signal heterogeneity (mrTSH). Primary outcomes were 5-year overall survival (OS) and 3-year loco-regional failure (LRF). Time-to-event analyses used Kaplan-Meier estimates; Hazard Ratios (HRs) with confidence intervals (CIs) were derived from Cox models.ResultsWith a median follow up of 60.9 months, 5-year OS was 74%. Poor OS was associated with increasing mrT (HR: 1.12 per cm [95% CI: 1.07–1.33]), nodal positivity (HR 2.08 [95% CI 1.23–3.52]) and mrEMVI (HR 3.66 [95% CI: 1.88–7.41]). 3-year LRF rate was 16.5%. Increased LRF was associated with increasing mrT (HR: 1.43 per cm [95% CI: 1.26–1.63]), nodal positivity (HR 2.70 [95% CI 1.39–5.24]) and mrTSH (HR 2.66 [95% CI 1.29–5.48]).ConclusionsIn SCCA, the study demonstrates that mrT and mrN stages are prognostic, while mrEMVI and mrTSH may be novel prognostic factors.

Treatment of Stages I-III Squamous Cell Anal Cancer: A Comparative Effectiveness Systematic Review.

To assess the effectiveness and harms of initial treatment strategies for stages I-III anal squamous cell cancer (SCC). We searched Medline®, Embase®, and CENTRAL®, between January 1, 2000- March 2024, for randomized controlled trials and nonrandomized studies of interventions comparing initial treatment strategies. Individual study risk of bias (RoB) and overall strength of evidence (SOE) were evaluated for a prespecified outcome list using standardized methods. We identified 33 eligible studies and extracted data. Six were deemed low/moderate RoB. Compared with radiotherapy (RT) alone, chemoradiotherapy (CRT) with 5-fluorouracil (FU) and mitomycin C (MMC) probably shows a benefit in locoregional failure (LRF), disease-specific (DSS), and colostomy-free survival (CFS) (moderate SOE) yet may result in greater overall and acute hematologic toxicity, with no difference in late harms (low SOE). CRT with 5FU+MMC may show a benefit in LRF, DSS, and CFS rates compared with 5FU alone (low SOE). CRT with 5FU+cisplatin vs 5FU+MMC probably results in no differences in several effectiveness outcomes or overall acute or late harms, and probably increases hematologic toxicity with MMC (moderate SOE). Compared with CRT using capecitabine+MMC, CRT with capecitabine+MMC+paclitaxel may improve OS, DSS, and CFS, yet cause more acute harms (low SOE). Evidence was insufficient for remaining comparisons. CRT with 5FU+MMC or 5FU+cisplatin is likely more effective yet incurs greater acute hematologic toxicity than RT alone or single-agent CRT. Adding paclitaxel to capecitabine+MMC may increase treatment efficacy and toxicity. Evidence is insufficient comparing post-treatment surveillance strategies and patient-reported outcomes, highlighting research opportunities.

Role of induction chemotherapy in advanced-stage olfactory neuroblastoma.

To evaluate the treatment outcomes in patients with advanced-stage olfactory neuroblastoma (ONB) who received induction chemotherapy (IC). The clinical data of 38 patients with advanced-stage ONB who received initial IC were retrospectively analyzed. The response was defined using the Response Evaluation Criteria in Solid Tumors version 1.1. Patients with complete remission or partial remission were defined as responders. Seventeen (44.7%) patients responded to IC. The response rate was higher in patients with high Hyams grade tumor (III/IV) compared to those with low-grade tumors (I/II) (60% vs. 22.2%, p=0.038). Overall, the 5-year cancer-specific survival (CSS) rate was 76.0%. Among nonresponders to IC, a significant difference in 5-year CSS rates was observed between surgery with adjuvant radiotherapy (RT) (100%) versus definitive RT or chemoradiotherapy (CRT) (68.6%) (log-rank p=0.006). However, for responders, there was no significant difference in 5-year CSS rates between surgery with adjuvant therapy (75%) and definitive RT or CRT (51.1%) (log-rank p=0.536). When only high-grade tumors were considered among responders, the 5-year CSS rate was significantly higher in patients who received RT or CRT (51.4%) compared to those who underwent surgery with adjuvant therapy (0%) (log-rank p=0.008). In advanced-stage ONB, RT or CRT may be preferable for high-grade tumor responding to IC. Higher response rate and a potential role for induction IC in determining the optimal definitive treatment modality suggest a positive role for advanced-stage high-grade ONB.

Utilizing machine learning to tailor radiotherapy and chemoradiotherapy for low-grade glioma patients.

There is ongoing uncertainty about the effectiveness of various adjuvant treatments for low-grade gliomas (LGGs). Machine learning (ML) models that predict individual treatment effects (ITE) and provide treatment recommendations could help tailor treatments to each patient's needs. We sought to discern the individual suitability of radiotherapy (RT) or chemoradiotherapy (CRT) in LGG patients using ML models. Ten ML models, trained to infer ITE in 4,042 LGG patients, were assessed. We compared patients who followed treatment recommendations provided by the models with those who did not. To mitigate the risk of treatment selection bias, we employed inverse probability treatment weighting (IPTW). The Balanced Survival Lasso-Network (BSL) model showed the most significant protective effect among all the models we tested (hazard ratio (HR): 0.52, 95% CI, 0.41-0.64; IPTW-adjusted HR: 0.58, 95% CI, 0.45-0.74; the difference in restricted mean survival time (DRMST): 9.11, 95% CI, 6.19-12.03; IPTW-adjusted DRMST: 9.17, 95% CI, 6.30-11.83). CRT presented a protective effect in the 'recommend for CRT' group (IPTW-adjusted HR: 0.60, 95% CI, 0.39-0.93) yet presented an adverse effect in the 'recommend for RT' group (IPTW-adjusted HR: 1.64, 95% CI, 1.19-2.25). Moreover, the models predict that younger patients and patients with overlapping lesions or tumors crossing the midline are better suited for CRT (HR: 0.62, 95% CI, 0.42-0.91; IPTW-adjusted HR: 0.59, 95% CI, 0.36-0.97). Our findings underscore the potential of the BSL model in guiding the choice of adjuvant treatment for LGGs patients, potentially improving survival time. This study emphasizes the importance of ML in customizing patient care, understanding the nuances of treatment selection, and advancing personalized medicine.

Analysis of decision-making factors for defunctioning ileostomy after rectal cancer surgery and their impact on perioperative recovery: a retrospective study of 1082 patients.

To explore the decision-making factors for defunctioning ileostomy (DI) after rectal cancer surgery and to analyze the impact of the DI on perioperative outcomes. A retrospective case-control study was conducted that included rectal cancer patients who underwent low anterior resection from January 2013 to December 2023. Among them, 33 patients did not undergo DI but with anastomotic leakage (AL) after surgery, and 1030 patients were without AL. Preoperative, operative and tumor factors between these two groups were compared to explore the decision-making factors for DI. Meanwhile, the differences of perioperative outcomes between the DI group of 381 cases and non-DI group of 701 cases were compared. For preoperative factors, the proportions of male patients and preoperative chemoradiotherapy (CRT) in the AL with non-DI group were greater than those in the non-AL group (p < 0.05); for operative factors, the proportion of patients in the AL with non-DI group with a surgical time > 180min were greater (p < 0.05); for tumor factors, the proportion of T3-4 stage was higher in the AL with non-DI group (p < 0.05). Multiple regression analysis revealed that male sex and preoperative CRT were the independent risk factors affecting DI. For perioperative outcomes, the DI did not reduce the incidence of all and symptomatic AL and non-AL postoperative complications (p > 0.05) but with 12.07% stoma-related complications, and increase hospitalization costs (p < 0.05); however, it can shorten the postoperative hospital stay, pelvic drainage tube removal time, and reduce the anal tube placement rate and readmission rate (all p < 0.05). Male patients and preoperative CRT were the independent risk factors affect the decision of DI in our study, and DI can shorten the postoperative hospitalization, pelvic drainage tube removal time, and decrease the anal tube placement rate and readmission rate during the perioperative period but with a higher economic cost.

Prospects for the use of perampanel in the treatment of epilepsy in patients with malignant gliomas of the brain

Epilepsy occurs in 35-95% of patients with malignant cerebral gliomas of low malignancy and in 29-71% of patients with gliomas of high malignancy. Seizures can be both the first manifestation of malignant cerebral glioma and appear in the postoperative period and during chemoradiotherapy. This requires the use of antiepileptic drugs, which should control the seizure syndrome, provide control and secondary prevention of seizures, without reducing the response of anti-tumour therapy and the the patient QoL. The processes of epileptogenesis and oncogenesis are closely interrelated through common developmental mechanisms in which glutamate plays a key role. Hypersecretion of glutamate is accompanied by increased expression and activation of its receptors, which increases convulsive readiness. This is accompanied by increased level of brain neurotrophic growth factor, the number of synapses between peritumoral neurons and glioma cells, and increased expression of a number of growth factors, which contributes to tumourous proliferation. In this regard, special attention when treating epilepsy in patients with malignant cerebral gliomas is given to perampanel, a glutamate receptor blocker, a 3rd generation antiepileptic drug. The findings show that perampanel not only effectively controls seizures in patients with malignant cerebral gliomas, but also suppresses tumourous proliferation. Perampanel is able to dose-dependently enhance apoptosis and disrupt cell migration in malignant glioma cell lines. The findings have revealed synergistic effect of perampanel in combination with temozolamide. In conditions of chemoradiation therapy perampanel has a protective effect on healthy peritumoral tissues. Undesirable drug reactions during the use of perampanel are infrequent and insignificant. Additional studies are needed to further research the anticonvulsant and antitumour efficacy of perampanel to treat epilepsy in patients with malignant brain tumours.

Diffusion-Weighted MRI for Recurrent/Persistent Head and Neck Squamous-Cell Carcinoma After Radiotherapy: Systematic Review and Meta-Analysis.

To evaluate the accuracy of diffusion-weighted magnetic resonance imaging (DWI-MRI) in diagnosing persistent/recurrent head and neck squamous cell carcinomas (HNSCCs) after primary chemoradiotherapy (CRT). Scopus, PubMed/MEDLINE, and Cochrane Library databases were searched for relevant publications until April 18, 2023. A systematic review and meta-analysis was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses of Diagnostic Test Accuracy statement. The search was conducted independently by 2 investigators. Methodological quality of included studies was assessed using the Quality Assessment of Diagnostic Studies-2 questionnaire. Extracted data were used to calculate the pooled DWI-MRI sensitivity, specificity, diagnostic odds ratio, and positive and negative likelihood ratio. A total of 618 patients from 10 studies were included for calculation of diagnostic accuracy parameters. At the level of the primary tumor, the pooled sensitivity and specificity were, respectively, 0.96 (95% confidence interval [CI]: 0.89-1.00) and 0.81 (95% CI: 0.54-0.98) in the case of qualitative analysis, and, respectively, 0.79 (95% CI: 0.66-0.89) and 0.88 (95% CI: 0.77-0.96) for quantitative analysis. At the level of the neck, the pooled sensitivity and specificity were, respectively, 0.87 (95% CI: 0.75-0.95) and 0.84 (95% CI: 0.74-0.93) when images were analyzed qualitatively, and 0.79 (95% CI: 0.60-0.94) and 0.90 (95% CI: 0.82-0.97) when analyzed quantitatively. DWI-MRI showed high diagnostic accuracy and should be considered if persistent/recurrent HNSCCs is suspected after primary CRT. No significant differences were found between qualitative and quantitative imaging assessment.

Comparison of immunochemotherapy followed by surgery or chemoradiotherapy in locally advanced esophageal squamous cell cancer

BackgroundSeveral studies have shown that the survival outcomes of chemoradiotherapy (CRT) are not inferior to surgery alone in patients with esophageal squamous cell carcinoma (ESCC). This study aimed to compare survival outcomes of ESCC treated with immunochemotherapy (ICT) followed by surgery or definitive CRT and to explore subgroups of patients who could benefit from one treatment strategy. MethodsPooled data were obtained from two prospectively registered clinical trials of patients with ESCC at the Affiliated Cancer Hospital of Nanjing Medical University. One trial involved treatment with neoadjuvant ICT followed by surgery, while the other involved induction ICT followed by definitive CRT. To balance potential biases, we conducted an overlap weighting (OW) analysis to compare the rates of 2-year progression-free survival (PFS), locoregional relapse-free survival (LRRFS), distant relapse-free survival (DRFS), and overall survival (OS). Additionally, propensity score matching (PSM) was performed to analyze failure pattern. ResultsThe median follow-up time of the survivors was 39.3 months. After overlap weighting, the rates of 2-year PFS, LRRFS, DRFS, and OS for patients undergoing surgery and CRT were 61.5 % and 59.7 %, 67.2 % and 69.9 %, 81.3 % and 90.7 %, 84.6 % and 79.1 %, respectively (P>.05 for all). A trend for improved 2-year OS was observed in the surgery group in patients who did not respond to ICT (P=.07). ConclusionThe differences in the rates of 2-year PFS, LRRFS, DRFS, and OS between the surgery group and the chemoradiotherapy group did not reach statistical significance.

Importance of early detection of esophageal cancer before the tumor progresses too much for effective treatment

This editorial comments on an article by Qu et al published in the World Journal of Gastrointestinal Oncology . It focuses on the importance of early detection of esophageal cancer, including recurrence or secondary malignancy after chemoradiotherapy (CRT). Endoscopic resection is the first choice for treatment for esophageal cancer remaining within the mucous membrane, while surgery or radical CRT are treatment options for advanced stages depending on the patient’s general condition and desire. Although these treatments are potentially curative, they are more invasive than endoscopic resection. Early-stage esophageal cancer is often asymptomatic and difficult to detect. Uniform periodic endoscopy is unrealistic. Although less burdensome tests exist, including liquid biopsy and urinary biomarkers, these have not yet been widely used in clinical practice. Early detection is important after radical CRT because the local recurrence rate is higher than that after surgery. However, endoscopic resection or photodynamic therapy is indicated if detected in the early stages, and positive results have been reported. Early detection of esophageal cancer is crucial. Endoscopy is the main diagnostic method; however, new and less burdensome methods should be established to ensure early treatment for patients with esophageal cancer.

Survival Outcome Superiority of Total Pharyngolaryngectomy Compared with Chemoradiotherapy for T4aM0 Hypopharyngeal Squamous Cell Carcinoma: A Nationwide Database Study of Japan.

The purpose of this study is to elucidate whether total pharyngolaryngectomy (TPL) or chemoradiotherapy (CRT) provides a better prognostic outcome in patients with T4aM0 hypopharyngeal carcinoma (HPSCC) using a nationwide database. All data were obtained from the Head and Neck Cancer Registry of Japan, and information from patients who were newly diagnosed with T4aM0 HPSCC between 2011 and 2015 was extracted. The primary endpoint was disease-specific survival (DSS), and the secondary endpoint was overall survival (OS). The inverse probability of treatment weighting (IPTW) adjustments was used for survival analyses. Our cohort included 1143 patients. The TPL and CRT groups included 724 and 419 patients, respectively. Following IPTW adjustments, both the OS and DSS of the TPL group were significantly longer than those of the CRT group (P = .02 and P = .002, respectively). Survival superiority was demonstrated for patients with T4aM0 HPSCC treated with TPL compared with those treated with CRT.

Analysis of proliferating Treg cells as a predictor for immunotherapy response using systemic longitudinal immune profiling: Biomarker analysis of the phase 3 CONTINUUM trial.

140 Background: The discovery of predictive biomarkers for immunotherapy is hindered by the lack of control groups in most translational studies, making it impossible to discern whether the identified biomarkers are merely prognostic or truly predictive for treatment outcomes. This study reported on prospectively designed biomarker analyses of the phase 3 CONTINNUUM trial (NCT03700476), the first trial that demonstrated prolonged event-free survival (EFS) with the addition of anti-PD-1 (aPD1) to chemoradiotherapy (CRT) in locoregionally-advanced nasopharyngeal carcinoma (LA-NPC). Methods: Mass cytometry was performed to generate a dynamic single-cell atlas on longitudinal peripheral blood mononuclear cell (PBMC) samples from 12 pairs of matched patients with or without relapse in the aPD1-CRT arm. The machine-learning algorithm CellCnn was applied to identify a cell subset that was most strongly associated with disease relapse, which was further confirmed by flow cytometry (n = 120). Single-cell RNA sequencing data from matched PBMC and tumor samples were analyzed and multiplex immunohistochemistry was performed on baseline tumor samples (n = 249) to verify the predictive value of the cell subset within tumors. Results: Baseline circulating regulatory T cells (Tregs), with a Ki67+ proliferating phenotype, were found to display a higher frequency in LA-NPC patients who developed posttreatment relapse ( P &lt; 0.001), which was further validated by flow cytometry. The intratumoral Ki67+ Tregs were also identified and correlated with an immunosuppressive tumor microenvironment. In patients with a low baseline level of Ki67+ Tregs, additional aPD1 significantly improved EFS compared with CRT alone (log-rank P = 0.011, HR = 0.22, 95% CI: 0.06−0.79), while EFS was almost identical in both treatment arms in patients with high Ki67+ Treg levels (log-rank P = 0.995, HR = 1.00, 95% CI: 0.49−2.05; interaction P = 0.047). This predictive value was further validated in datasets from two independent randomized trials in renal cancer. Conclusions: The frequency of Ki67+ Tregs can serve as a reliable predictive tool in selecting patients who are more likely to benefit from immunotherapy, potentially informing individualized immunotherapy strategies.

Correlation of enriched specific subset of immune cells nearby tumor associated macrophage (TAM) with pathologic complete response (pCR) of concurrent chemoradiotherapy followed by nivolumab in locally advanced rectal cancer (LARC).

58 Background: We previously reported tumor-infiltrating lymphocyte (TIL) dynamics predictive of pCR in microsatellite-stable (MSS) LARC. In the current analysis, we investigate whether an immune cell-to-cell spatial network may predict pCR in MSS LARC. Methods: VOLTAGE study is a phase I/II study to evaluate the efficacy of chemoradiotherapy (CRT) followed by nivolumab and subsequent surgery in LARC pts. H&amp;E images and multiplex immunofluorescence (mIF) images containing a total of 35 markers for T cells, TAM, Myeloid-derived suppressor cells, and Dendritic cells were analyzed with the Lunit SCOPE platform (Lunit, Republic of Korea). The proportion of T cells among all DAPI-positive (-pos) cells in a 50-micrometer radius centered on the TAM cells was counted. Results: In the samples of MSS LARC pts gathered at baseline, pre-treatment (n=38), TIL density in tumor microenvironment (TME) analyzed by H&amp;E images was significantly correlated with the proportions of CD8-pos, CD4-pos, and FOXP3-pos cells (coefficient [coeff] 0.635, 0.482, and 0.580, respectively), but loosely correlated with PDL1-pos, PD1-pos, and CTLA4-pos cells (coeff 0.255, 0.174, and 0.180, respectively). Interestingly, intratumoral TIL density was more strongly correlated with TAM markers such as CD68 (coeff 0.269), compared to stromal TIL density (coeff 0.086). pCR rate was 28.9% in all MSS LARC, with baseline TIL density in TME predicting pCR with area under the receiver operating characteristic curve (AUROC) of 0.636 (p = 0.101). Interestingly, the ratio of baseline PDL1-pos cell proportion nearby CD68-pos cells, over that in all TME area (hereafter referred to as 'TAM-PDL1-proximity score') showed the best predictive performance for pCR, with an AUROC of 0.768 (p = 0.005). At the optimal cutoff of 1.66 times TAM-PDL1-proximity score, pCR rates for pts ≥ the cutoff and &lt; the cutoff were 44% (11/25) and 0% (0/13), respectively (p = 0.006). Conclusions: PDL1-expressing immune cells nearby tumor associated macrophages before treatment is a promising predictive biomarker for pCR of neoadjuvant CRT followed by nivolumab in MSS LARC.