Advanced Squamous Carcinoma Research Articles

Outcomes of Neoadjuvant Chemotherapy in Locally Advanced Oral Cancers: A Retrospective Analytical Study.

Introduction Head and neck cancers account for 30% of malignancies in India and oral squamous cell carcinoma is most common. 80% of the patients present with locally advanced disease and many of them are inoperable. In this study we documented the outcomes of neoadjuvant chemotherapy (NACT) in locally advanced oral cancer staged T4 with regards to downstaging the disease and to make the tumor more amenable for surgery with better access. The objectives of the study are to document the outcomes of NACT in patients with locally advanced oral cancers and to correlate the response to NACT and adequacy of resection by histopathology examination of the specimen. Methodology Clinical data of 96 patients with locally advanced squamous cell carcinoma of the oral cavity staged T4a and T4bwho received two cycles of NACT between December 2018 and November 2022 were reviewed respectively and the outcomes and response following NACT were documented. Results Among 96 patients in this study, 68 (70.9%) patients were staged T4a and 28 (29.1%) were staged T4b. 31 (30.2%) patients showed partial response, 36 (37.5%) had stable disease and 29 (30.2%) had progressive disease following 2 cycles of NACT. All patients underwent definitive surgery following NACT and were followed up for 14 months. Among those staged T4a, 12 patients (33.3%)had close margins, eight patients (34.8%) had positive margins and 10 patients (16.2%) had a recurrence. Among those staged T4b, 24 patients (66.7%) had close margins (less than 5mm distance after formalin fixation), 15 patients (65.2%) had positive margins while 17 patients (60.7%) had a recurrence in the 14 month follow-up period. Conclusion NACT makes tumors more amenable for surgery in locally advanced oral squamous carcinoma. However, 30% of patients do not respond to it.

A tumor cornification and immune-infiltration-based scheme for anti-PD-1 plus chemotherapy response in advanced squamous cell lung carcinoma

Anti-PD-1 immunotherapy plus chemotherapy (combo) exhibits significantly prolonged survival for squamous cell lung cancer (LUSC). An exploration of predictive biomarkers is still needed. High-throughput RNA sequencing (RNA-seq) of 349 LUSC samples from the randomized, multi-center, phase 3 trial ORIENT-12 (ClinicalTrials.gov: NCT03629925) was conducted for biomarker discovery, followed by flow cytometry and multiplex immunohistochemistry (mIHC) in additional clinical cohorts, and invitro experiments were performed for verification. A high abundance of activated CD8+ T and CD56bright natural killer (NK) cells benefited patients' outcomes (progression-free survival [PFS]; overall survival [OS]) with combo treatment. Tumor cornification level remarkably affected the infiltration of the two crucial immune cells. Thus, a novel scheme of LUSC immune infiltration and cornification characterization-based classification (LICC) was established for combo efficacy prediction. Patients who received combo treatment achieved significant PFS improvements in LICC1 (hazard ratio [HR]= 0.43, 95% confidence interval [CI]: 0.25-0.75, p= 0.0029) and LICC2 (HR= 0.32, 95% CI: 0.17-0.58, p= 0.0002) subtypes but not in the LICC3 subtype (HR= 0.86, 95% CI: 0.60-1.23, p= 0.4053). Via single-cell RNA-seq analysis, the tumor cornification signal was mainly mapped to SPRR3+ tumor cells, whose relationships with activated CD8+ T or CD56bright NK cells were verified using flow cytometry and mIHC. Our data suggest that SPRR3+ tumor cells might evade immune surveillance via the CD24-SIGLEC10 (M2 macrophage) axis to maintain a suppressive tumor microenvironment. Tumor cornification greatly impacts immune infiltration, and the LICC scheme may guide clinical medication of anti-PD-1+chemo treatment in patients with LUSC. The study was funded by the National Key R&D Program of China, the National Natural Science Foundation of China, Shanghia Multidisplinary Cooperation Building Project for Diagnosis and Treatment of Major Disease, and Innovent Biologics, Inc.

EP.06G.20 Advanced Squamous Cell Lung Carcinoma in Never Smokers: A Different Entity? Analysis from the Thoracic Tumor Registry in Spain (RTT)

EP.06G.20 Advanced Squamous Cell Lung Carcinoma in Never Smokers: A Different Entity? Analysis from the Thoracic Tumor Registry in Spain (RTT)

Efficacy of PD-1 inhibitors combined with nab-paclitaxel and cisplatin in the neoadjuvant treatment of locally advanced hypopharyngeal squamous cell carcinoma

Objective: To assess the efficacy of neoadjuvant treatment with PD-1 (programmed cell death protein 1) inhibitors combined with paclitaxel (albumin-conjugated) and cisplatin (TP regimen) for locally advanced hypopharyngeal squamous cell carcinoma and laryngeal organ function preservation. Methods: Data of 53 patients, including 51 males and 2 females, aged 38-70 years old, who were diagnosed with locally advanced hypopharyngeal squamous carcinoma confirmed by histology and enhanced CT at the Cancer Prevention and Control Center of Sun Yat-sen University during the initial treatment from January 1, 2019 to January 15, 2023, were retrospectively analyzed. All patients received neoadjuvant therapy with PD-1 inhibitors combined with albumin-bound paclitaxel (260 mg/m2) and cisplatin (60 mg/m2) for 3 to 4 cycles. The main outcome measures were larynx dysfunction-free survival (LDFS), overall survival (OS), and progression-free survival (PFS). Survival curves were plotted using the Kaplan-Meier method, and Cox multifactorial analysis was further performed if Cox univariate analysis was statistically significant. Results: The overall efficiency was 90.6% (48/53). The 1-year and 2-year LDFS rates were 83.8% (95%CI: 74.0% to 94.8%) and 50.3% (95%CI: 22.1% to 91.6%), the 1-year and 2-year OS rates were 95.2% (95%CI: 88.9% to 100.0%) and 58.2% (95%CI: 25.6% to 81.8%), and the 1-year and 2-year PFS rates were 83.9% (95%CI: 74.2% to 94.9%) and 53.5% (95%CI: 32.1% to 89.1%). Adverse events associated with the neoadjuvant therapy were mainly myelosuppression (45.3%), gastrointestinal reactions (37.7%) and hypothyroidism (20.8%). Conclusion: The neoadjuvant treatment of locally advanced hypopharyngeal squamous cell carcinoma using PD-1 inhibitors combined with paclitaxel and cisplatin can provide with a higher survival rate with a improved laryngeal organ function preservation rate.

Analysis of factors affecting complete pathological remission after neoadjuvant immunocombination chemotherapy treatment for locally advanced esophageal squamous carcinoma.

e16061 Background: Chemotherapy combined with immunotherapy for locally advanced esophageal squamous carcinoma has achieved a high rate of complete pathological remission, which is conducive to a better prognosis for patients; however, not all ESCC patients benefit from ICI therapy, so finding validated prognostic markers of efficacy will help us to screen for populations that are superior to neoadjuvant immunotherapy. Methods: Patients with locally advanced esophageal squamous carcinoma treated with neoadjuvant immune-combination chemotherapy followed by radical surgery from January 2019 to June 2023 at our institution were collected. The grouping was based on whether pathologic complete remission (pCR) was achieved after neoadjuvant therapy. Clinical and treatment-related data as well as hematologic, inflammatory, and nutritional indices within 1 week before neoadjuvant therapy and within 1 week after 2 cycles of neoadjuvant immune-combination chemotherapy treatment were collected from all patients, and univariate and multivariate analyses were performed to assess independent predictors of pCR. Results: Patients in both pCR and Non-pCR groups were more likely to obtain pCR if they had pre-treatment BMI > 21Kg/m2 vs BMI ≤21Kg/m2, number of neoadjuvant therapy cycles ≥3 cycles vs number of neoadjuvant therapy cycles = 2 cycles, and CYFRA21-1ng/ml < 3.28 vs ≥3.28 before neoadjuvant therapy (p < 0.05). Patients with albumin ≥40.10g/L vs albumin < 40.10g/L, NLR < 2.50 vs NLR ≥2.50, and NRI ≥98.06 vs NRI < 98.06 were more likely to achieve pCR before treatment in both groups (p < 0.05). SII ≥521.75 VS SII < 521.75 was more likely to achieve pCR after 2 cycles of treatment (p < 0.05). Univariate analysis of the comparison of dynamic changes in nutritional inflammatory indexes during treatment between the two groups of patients showed that pCR was more likely to be achieved in patients with persistently elevated eosinophil counts and NLR after 2 cycles of neoadjuvant immune-combination chemotherapy treatment (p < 0.05). The results of multifactorial analysis showed that pre-treatment BMI, SII after 2 cycles of treatment, and dynamic changes in eosinophils during neoadjuvant therapy were independent influences on complete pathological remission after neoadjuvant immune-combination chemotherapy treatment (p < 0.05). Conclusions: Complete pathological remission after neoadjuvant immune-combination chemotherapy treatment for esophageal squamous carcinoma was significantly correlated with the patient's pre-treatment BMI, Post-treatment SII, and eosinophil dynamics during treatment.

Weekly Versus Bolus Cisplatin Concurrent With Definitive Radiation Therapy for Squamous Carcinoma of the Head and Neck: A Systematic Review and Network Meta-Analysis

The schedule of cisplatin concurrent with definitive radiation for squamous carcinoma of the head and neck remains controversial. Most institutions deliver either a high-dose "bolus" schedule once every 3 weeks or a low-dose weekly schedule. We compared these 2 schedules via a simplified network meta-analysis with a common comparator. We performed a PRISMA-concordant systematic review to identify randomized controlled trials comparing cisplatin with cetuximab for nonmetastatic, locoregionally advanced squamous carcinoma of the head and neck treated with definitive radiation. Trials incorporating primary surgery or induction therapy were excluded. Patient survival times were extracted on a per-event basis from the published curves using a digitizer and validated against published point estimates and hazard ratios (HRs). Survival was compared using random effects Cox regression under a frequentist framework. Toxicity and secondary endpoints were analyzed qualitatively. The Cochrane method assessed the risk of bias. The analysis plan was preregistered with the Open Science Foundation. Five randomized trials were identified, including 1678 patients. There was no statistical difference in overall survival between weekly and bolus regimens (HR, 0.90; 95% CI, 0.53-1.52, P = .345). This Cox model suggested that for the average patient in the cohort, the absolute difference in 5-year overall survival between weekly and bolus regimens was +1.2% (95% CI, -6.1%-+5.9%, P = .345). Secondary endpoints and toxicity were not obviously different by regimen, qualitatively. The cetuximab trials provide indirect data suggesting that the differences between cisplatin schedules are subtle.

Prediction of combination therapy efficacy in patients with locally advanced squamous cell oropharyngeal carcinoma

Background. Oropharyngeal squamous cell carcinoma (OPSCC) is characterized by late-stage diagnosis and high rate of mortality. Combined modality treatment including preoperative chemoradiotherapy (CRT) is the standard of care for OPSCC. The search for criteria for predicting the efficacy of preoperative chemoradiotherapy with a view to prescribe it to those patients for whom it is really indicated and will be effective remains challenging. The aim of the study was to identify serum actin-binding proteins that can predict preoperative therapy efficacy in patients with OPSCC. Material and methods. Blood serum from 45 patients with stage II–IV OPSCC was studied. all patients received preoperative chemotherapy with paclitaxel and carboplatin. Radiation therapy in a standard mode was given 2 weeks after chemothetapy. serum levels of actin-binding proteins (CAP1, fascin, ezrin, gelsolin, and profiling) were determined before treatment using ELISA. Results. complete or partial response to preoperative CRT was achieved in 27 patients. Disease progression or stabilization was observed in 18 patients. A comparison of the serum levels of actin-binding proteins before treatment with those obtained after preoperative CRT showed that the serum level of ezrin was lower in patients who did not respond to preoperative CRT than in patients with partial or complete response to therapy. ROC-analysis showed that the serum level of ezrin of less than 2.50 ng/ml can predict the tumor response to CRT as unfavorable (less than 75 % according to the RECIST scale). The sensitivity was 72 % and the specificity was 71 %. Conclusion. Determination of the serum level of ezrin in patients with OPSCC has a predictive value in relation to preoperative chemoradiotherapy.

Camrelizumab in combination with chemotherapy versus concurrent chemoradiotherapy for the conversion of locally advanced unresectable oesophageal squamous carcinoma: protocol for a two-arm, open-label phase II trial

IntroductionOesophageal cancer (OC) has higher morbidity and mortality rate than most other malignancies. The standard treatment for unresectable locally advanced oesophageal squamous cell carcinoma (OSCC) is concurrent chemoradiotherapy, with tumour...

A phase 2 study of fruquintinib in combination with S-1 for second-line treatment of esophageal squamous cell carcinoma after first-line immunotherapy failure.

323 Background: Patients with advanced esophageal squamous carcinoma (ESCC) who experience progression after first-line immunotherapy face a challenging treatment landscape. The potential of anti-vascular therapy combined with chemotherapy in the treatment of esophageal cancer is well-established. Mechanistically, anti-angiogenic agents can promote the normalization of tumor vasculature and facilitate the access of chemotherapeutic agents to tumor targets. Considering the compromised physical condition of advanced ESCC patients, there is a preference for more convenient oral medications. Therefore, we conducted this phase II study to assess the clinical efficacy and safety of combining fruquintinib with S-1 in treating advanced ESCC patients following first-line immunotherapy failure. Methods: This open-label, single-arm, phase II study consists of dose-finding and dose-expansion phases, enrolling advanced or metastatic ESCC patients after first-line immunotherapy failure. The dose-finding phase followed a 3+3 design. Patients received fruquintinib (3mg, 4mg, 5mg, d1-d14, q3w, respectively), in combination with S-1 (40mg, 50mg, 60mg, bid, d1-d14, q3w, based on body surface area (BSA)), until unacceptable toxicities, progressive disease, or death. The initial fruquintinib dose was 4 mg d1-d14, q3w, in combination with an appropriate S-1 dose. Additional patients were enrolled in the dose-expansion phase and received the maximum tolerated dose determined in the dose-finding phase. Results: As of August 1, 2023, seven patients were enrolled in the dose-finding phase. One patient withdrew consent during the DLT assessment period. Among the patients administered a 4mg dose of fruquintinib, one out of three achieved a confirmed partial response (PR) after 7 cycles of treatment. Additionally, two out of three patients at the 5mg dose level achieved PR after 2 cycles of treatment, resulting in an overall response rate (ORR) of 50% (3/6). The disease control rate (DCR) was 100% (6/6). The median progression-free survival (PFS) was observed to be 4.93 months (95% CI: 1.93 – 10.73), with overall survival (OS) at 10.73 months (95% CI: 2.1 – 10.73). In terms of safety, no dose-limiting toxicities (DLTs) were reported at 4mg dose level. While DLTs were observed in two out of the three patients at the 5mg dose level. The most common treatment-related adverse events (TRAE) across all grades were fatigue (5/7) and extremity pain (4/7). Grade 3 TRAE were identified in 5 patients, with hypertension (2/7), mucositis (2/7), and fatigue (2/7) being reported. No grade 4 or higher TRAEs were observed. Conclusions: Potential benefits were demonstrated when using fruquintinib in combination with S-1 for the treatment of ESCC patients after immunotherapy failure. The efficacy and safety of fruquintinib and S-1 will be further investigated in this trial later. Clinical trial information: NCT05636150 .

Prognostic prediction and comparison of three staging programs for patients with advanced (T2-T4) esophageal squamous carcinoma after radical resection.

Lymph node-based staging protocols are frequently employed to evaluate the prognosis of esophageal cancer, yet their accuracy remains contentious. The present study was conducted to assess the prognostic significance of three lymph node staging systems, namely N stage, lymph node rate (LNR), and log odds of positive lymph nodes (LODDS), in patients diagnosed with advanced (T2-T4) esophageal squamous cell carcinoma (ESCC). This cohort comprised 319 eligible patients, with an additional 409 individuals retrieved from the Surveillance, Epidemiology, and End Results (SEER) database, forming the validation cohort. Differences in overall survival (OS) of patients between groups were assessed using the log-rank test. Prognostic independent risk variables were identified, and lymph nodes (LN) prognostic models were built using multivariate Cox regression analysis. Besides, the predictive accuracy of each model was evaluated utilizing the (-2) log-likelihood ratio (-2LLR), the likelihood ratio χ2 score (LRχ2), the Akaike information criterion (AIC), and Harrell's concordance index (C-index). To further evaluate the potential superiority of the model, a nomogram was constructed for comparison with the conventional Tumor Node Metastasis (TNM) staging approach. Independent prognostic factors for advanced ESCC include the N stage, LNR, and LODDS. Herein, LODDS presented higher values for C-index and LRχ2, and lower values for AIC and -2LLR in OS compared to the others. Consequently, a nomogram was constructed based on LODDS. Calibration curves exhibited strong agreement, and assessment through C-index, receiver operating characteristic (ROC) curves, and clinical decision curve analysis (DCA) demonstrated promising clinical applicability. LODDS emerges as a promising future prognostic indicator. After surgery, the proposed model holds the potential to provide valuable treatment recommendations for patients with advanced ESCC.

Camrelizumab in combination with neoadjuvant chemotherapy in resectable locally advanced esophageal squamous carcinoma cancer: Results from a retrospective study.

This study aimed to evaluate the safety and efficacy of camrelizumab combined with chemotherapy during preoperative neoadjuvant therapy in patients with locally advanced resectable esophageal squamous cell carcinoma (ESCC) of clinical Stages II and III. The patients received camrelizumab plus chemotherapy regimen on Day 1 for up to three to four cycles (3 weeks per cycle). The probabilities of overall survival (OS) were 55.6% at 12 months and 35.6% at 18 months (45 patients). The disease-free survival (DFS) rates were 70.0% at 12 months and 63.3% at 18 months (30 patients). The median OS and DFS were not reached. The proportion of patients at postneoadjuvant pathological tumor stages ypT0, ypT2, and ypT3 were 10 (33.3%), 14 (46.7%), and 6 (20.0%), respectively, and those at stages ypN0 and ypN1 were 19 (63.3%) and 11 (36.7%), respectively. Additionally, the pathological complete response rate was 33.3% (95% confidence interval [CI]: 0.154-0.512), and the major pathologic response rate was 46.7% (95% CI: 0.277-0.656). Grade ≥3 adverse events (AEs) were reported in five patients (11.1%), with vomiting being the most common AE (three patients; 3.3%). Other common AEs of any grade included decreased lymphocyte count (48.9%), reactive capillary endothelial proliferation (46.7%), decreased white blood cell count (40.0%), anemia (31.1%), and vomiting (31.1%). The combination of camrelizumab and neoadjuvant chemotherapy in patients with locally advanced resectable ESCC demonstrated promising efficacy and acceptable safety.

Positive lymph node ratio is an important index to predict long-term survival for advanced esophageal squamous carcinoma patients (II∼III) with R0 resection--a SEER-based analysis

BackgroundEsophageal squamous carcinoma (ESCC) is one of the most malignant cancers in the world due to nodal metastasis. Therefore, a reasonable nodal staging system is extremely important for further treatment strategies. Recently the positive lymph node ratio (PLNR) is an important prognostic factor in various solid tumors MethodIn this study, we investigated the clinical significance of the PLNR in stage II∼III ESCC patients. We collected the pathological characteristics of 272 stage II∼III ESCC patients from the SEER database from 2004–2016. ROC curves were used to calculate the best cutoff value of the PLNR; Pearson's Chi-square (χ2) and Fisher's exact probability tests were used to compare the clinical baseline and characteristics of patients. For continuous variables, Student's t-test and ANOVA were performed to evaluate statistical significance. Clinical outcomes were estimated by using the Kaplan‒Meier method and log-rank test. Furthermore, univariate and multivariate Cox regression models were utilized to analyze independent prognostic factors of ESCC patients. ResultsConsequently, advanced ESCC patients were effectively stratified into two groups by prognosis using a PLNR cutoff value of 0.15 (P value = 0.04). The median survival time of patients with PLNR <0.15 (n = 145) was much higher than that of patients (n = 127) in the PLNR ≥0.15 group (20.0 vs. 13.0 months, P value < 0.0001). Notably, the PLNR significantly predicted the prognosis of ESCC patients with stage N1 (P value 0.01) and stage III (P value < 0.001) disease. The multivariate Cox proportional hazard model showed that T stage (HR 1.33, 95 % CI 0.97–1.82), tumor size >45 mm (HR 1.32, 95 % CI 1.02–1.70), N stage (HR 1.41, 95 % CI 0.98–2.01) and PLNR ≥0.15 (HR 1.35, 95 % CI 0.87–1.74) were independent risk factors for prognostic prediction in ESCC patients. Meanwhile, 117 II∼III ESCC patients from Shaanxi Provincial People's Hospital shown that the overall survival with a PLNR <0.15 (n = 96) was significantly longer than that with a PLNR ≥0.15 (n = 21) . ConclusionsThe PLNR is useful for accurately predicting clinical outcomes and determining postoperative strategies.

Locally advanced squamous cervical carcinoma (M0): management and emerging therapeutic options in the precision radiotherapy era.

Squamous cervical carcinoma (SCC) requires particular attention in diagnostic and clinical management. New diagnostic tools, such as (positron emission tomography-magnetic resonance imaging) PET-MRI, consent to ameliorate clinical staging accuracy. The availability of new technologies in radiation therapy permits to deliver higher dose lowering toxicities. In this clinical scenario, new surgical concepts could aid in general management. Lastly, new targeted therapies and immunotherapy will have more room in this setting. The aim of this narrative review is to focus both on clinical management and new therapies in the precision radiotherapy era.

Efficacy and safety of pembrolizumab versus sintilimab treatment in patients with advanced squamous lung cancer: A real-world study in China.

e21045 Background: Both pembrolizumab and sintilimab have been approved for the first-line treatment of patients with advanced squamous lung cancer in China. The differences of the two drugs in efficacy and safety are unclear. The aim of this study was to compare the efficacy and safety in advanced squamous lung cancer patients in real world. Methods: This was a retrospective review of patients with advanced squamous carcinoma who received sintilimab or pembrolizumab in combination with chemotherapy as first-line therapy between June 2018 and April 2022 in the Chinese PLA Hospital. The aim was to compare the objective response rate (ORR), disease control rate (DCR),progression-free survival (PFS), overall survival (OS) and adverse events (AEs). Results: A total of 164 patients were enrolled, including 63 patients (38.4%) in the sintilimab-combined chemotherapy group and 101 patients (61.6%) in the pembrolizumab group. The ORR was 65.10% in the sintilimab group and 61.40% in the pembrolizumab group (P = 0.634). The DCR was 92.10% and 92.10% in two groups respectively (P = 0.991). The median PFS was 22.2 months in sintilimab group compared with 16.5 months in pembrolizumab group[ HR = 0.743; 95% CI: 0.479-1.152; P = 0.599]. Patients treated with sintilimab had a median OS of 30.7 months and a median OS did not achieve with pembrolizumab. The incidence of all treatment-related adverse events (TRAEs) was 92.1% (58/63)in the sintilimab group, and 90.1% (91/101) in the pembrolizumab group. Conclusions: Sintilimab and pembrolizumab were similar as a first-line treatment for patients with advanced squamous lung cancer in efficacy and safety. [Table: see text]

Phase 2 clinical trial of the proautophagic drug ABTL0812 combined with paclitaxel and carboplatin in first-line patients with advanced squamous non-small cell lung carcinoma.

9059 Background: ABTL0812 induces the inhibition of Akt/mTOR pathway by upregulation of TRIB3 protein, an endogenous Akt inhibitor, and promotes endoplasmic reticulum (ER) stress. As a result, ABTL0812 induces cytotoxic autophagy that leads to specific death of cancer cells, without affecting non-tumor cell viability. A Phase II clinical trial was designed where ABTL0812 was evaluated in combination with paclitaxel and carboplatin in first-line patients with advanced squamous non-small cell lung cancer (NSCLC). Methods: ABTL0812 was administered 1300 mg TID orally with 175 mg/m2 paclitaxel and AUC5 carboplatin every 3 weeks, for up to 8 cycles, followed by ABTL0812 as a maintenance until disease progression or unacceptable toxicity. The study enrolled patients with non-irradiable IIIb stage or stage IV squamous NSCLC. Primary endpoint was overall response rate (ORR) by RECIST criteria v.1.1. Secondary endpoints were progression free survival (PFS), overall survival (OS), duration of response (DOR), safety and tolerability according to CTCAE v4.03, pharmacokinetics (PK) of ABTL0812 enantiomers ((-)-ABTL and (+)-ABTL) and pharmacodynamics assessed by two surrogate blood biomarkers: TRIB3 and CHOP. Results: Forty patients were included; median age was 66.1 years old; 90% men/10% women; 100% ECOG 0-1; 30% current smokers/67.5% former smokers and 37.5% had received prior chemotherapy &gt; 12 months before inclusion. 39 patients had at least 1 adverse event (AE), anemia appeared in 32.5% of the patients (5.0% grade 3), neutropenia in 27.5% (25% grades 3-4) and thrombocytopenia in 17.5% of the patients (2.5% grade 3). For non-hematological AEs, asthenia was reported in 62.5% of the patients (2.5% grade 3); diarrhea in 45% (no grade 3-4) and nausea in 37.5% (5% grades 3-4). Twenty-five patients reach the primary endpoint for efficacy evaluation. ORR was 52.0% (95% CI 34.2-65.9) and 32.0% of the patients had stable disease. Median OS was 22.5 months (10.4-NC), median progression free survival 6.2 months (4.4-8.8), and DOR 5.1 months (3.9-7.4). Area under the curve (µg·h/ml) for (-)-ABTL and (+)-ABTL were 39.0±12.3 and 17.1±6.3 respectively, maximal concentrations (µg/ml) were 6.4±2.6 and 5.1±2.2 and minimum concentrations (µg/ml) 2.2±1.5 and 0.8±1.3. TRIB3 and CHOP PD biomarkers were induced by the treatment. Conclusions: The combination of ABTL0812 with paclitaxel and carboplatin shows survival outcomes that compare favorably with historical controls in squamous-NSCLC with an acceptable safety profile. PK analysis is compatible with drug activity, and pharmacodynamic analysis shows drug engagement. Clinical trial information: NCT03366480 .

Inflammatory biomarkers as predictors of immune activation to different irradiated sites and short-term efficacy in advanced squamous cell esophageal carcinoma received radioimmunotherapy.

The present study aimed to compare immune activation among different irradiated sites and identify potential short-term efficacy prognostic factors in patients with advanced squamous cell esophageal carcinoma (ESCC) who received radiotherapy (RT) and immunotherapy. We recorded the clinical characteristics, blood cell counts, and derived blood index ratios, including neutrophil-to-lymphocyte ratio (NLR), lymphocyte-to-monocyte ratio (LMR), platelet-to-lymphocyte ratio (PLR), and systemic immune-inflammation index (SII), at three time points (before, during, and after RT) in 121 patients with advanced ESCC who had received RT and immunotherapy. Chi-square test and univariate and multivariate logistic regression analyses were used to calculate the relationships among inflammatory biomarkers (IBs), irradiated sites, and short-term efficacy. Delta-IBs were calculated as (medio-IBs - pre-IBs) ÷ pre-IBs. The medians of delta-LMR, and delta-ALC were the highest, whereas the median of delta-SII was the lowest in patients with brain radiation. Treatment responses were observed within 3 months after RT or until the beginning of the next line therapy, and the disease control rate (DCR) was 75.2%. The areas under the receiver operating characteristic curve (AUCs) for delta-NLR and delta-SII were 0.723 (p = 0.001) and 0.725 (p < 0.001), respectively. Multivariate logistic regression analysis showed that the treatment lines of immunotherapy (odds ratio [OR], 4.852; 95% confidence interval [CI], 1.595-14.759; p = 0.005) and delta-SII (OR, 5.252; 95% CI, 1.048-26.320; p = 0.044) were independent indicators of short-term efficacy. In this study, we found that RT to the brain had a stronger immune activation effect than RT to extracranial organs. We also found that earlier-line immunotherapy plus RT and a decrease in SII during RT may generate better short-term efficacy in advanced ESCC.

Competing risk models versus traditional Cox models for prognostic factors' prediction and care recommendation in patients with advanced laryngeal squamous carcinoma: a population-based study.

To explore the prognostic factors and the optimal treatment modalities for patients with stage IVA laryngeal squamous cell carcinoma (LSCC), so as to improve the survival rate of patients. Patients with stage IVA LSCC between 2004 and 2019 were selected from the Surveillance, Epidemiology, and End Results (SEER) database. We used competing risk models to build nomograms for predicting cancer-specific survival (CSS). The effectiveness of the model was assessed using the calibration curves and the concordance index (C-index). The above results were compared with the nomogram established by Cox regression analysis. The patients were grouped into low-risk and high-risk groups by competing risk nomogram formula. And the Kaplan-Meier (K-M) method and log-rank test were used to make sure that these groups had a survival difference. Overall, 3612 patients were included. Older age, black race, a higher N stage, a higher pathological grade, and a larger tumor size were independent risk factors for CSS; married marital status, total/radical laryngectomy, and radiotherapy were protective factors. The C-index was 0.663, 0.633, and 0.628 in the train set and 0.674, 0.639, and 0.629 in the test set of the competing risk model, and 0.672, 0.640, and 0.634 in the traditional Cox nomogram for 1, 3, and 5years. In overall survival and CSS, the prognosis of the high-risk group was poorer than that of the low-risk group. For patients with stage IVA LSCC, a competing risk nomogram was created to help screen risk population and guide clinical decision-making.

Efficacy and safety of pembrolizumab versus sintilimab treatment in patients with advanced squamous lung cancer: A real-world study in China.

Both pembrolizumab and sintilimab have been approved by the Chinese State Drug Administration (NMPA) for the first-line treatment of patients with advanced squamous lung cancer. The differences of the two drugs in efficacy and safety are unclear. To compare the real-world efficacy and safety of first-line treatments in patients with advanced squamous lung cancer. This was a retrospective review of patients with advanced squamous carcinoma who received sintilimab or pembrolizumab in combination with chemotherapy as first-line therapy between June 2018 and April 2022 in the Chinese PLA Hospital. The primary objective was to compare the objective response rate (ORR), progression-free survival (PFS), and overall survival (OS) between the two groups. Secondary objectives were to compare the disease control rate (DCR) and to analyze adverse events (AEs) between the two groups. A total of 164 patients were enrolled, including 63 patients (38.4%) in the sintilimab-combined chemotherapy group and 101 patients (61.6%) in the pembrolizumab-combined chemotherapy group. The ORR was 65.10% in the sintilimab group and 61.40% in the pembrolizumab group (P=0.634). The DCR was 92.10% and 92.10% in the sintilimab and pembrolizumab groups, respectively (P=0.991). The median PFS was 22.2 months for patients treated with sintilimab group compared with 16.5 months for patients treated with pembrolizumab group[hazard ratio (HR) = 0.743; 95% confidence interval (CI): 0.479-1.152; P = 0.599]. Patients treated with pembrolizumab did not achieve a median OS, and patients treated with sintilimab had a median OS of 30.7 months. In the sintilimab group, the incidence of all treatment-related adverse events (TRAEs) was 92.1% (58/63), and the incidence of grade 3-4 TRAEs of 42.9% (27/63). In the pembrolizumab group, the incidence of all TRAEs was 90.1% (91/101), and the incidence of grade 3-4 TRAEs was 37.6% (38/101). In the clinical treatment of Chinese patients with advanced squamous lung cancer, first-line treatment with sintilimab in combination with chemotherapy provided similar efficacy to pembrolizumab in combination with chemotherapy, and the treatment-related adverse effect profiles were comparable between the two groups, including similar rates of grade 3-4 and all adverse events.

Clinical analysis of liver dysfunction induced by SHR-1210 alone or combined with apatinib and chemotherapy in patients with advanced esophageal squamous cell carcinoma

Objective: To investigate the clinical characteristics of abnormal liver function in patients with advanced esophageal squamous carcinoma treated with programmed death-1 (PD-1) antibody SHR-1210 alone or in combination with apatinib and chemotherapy. Methods: Clinical data of 73 patients with esophageal squamous carcinoma from 2 prospective clinical studies conducted at the Cancer Hospital Chinese Academy of Medical Sciences from May 11, 2016, to November 19, 2019, were analyzed, and logistic regression analysis was used for the analysis of influencing factors. Results: Of the 73 patients, 35 had abnormal liver function. 13 of the 43 patients treated with PD-1 antibody monotherapy (PD-1 monotherapy group) had abnormal liver function, and the median time to first abnormal liver function was 55 days. Of the 30 patients treated with PD-1 antibody in combination with apatinib and chemotherapy (PD-1 combination group), 22 had abnormal liver function, and the median time to first abnormal liver function was 41 days. Of the 35 patients with abnormal liver function, 2 had clinical symptoms, including malaise and loss of appetite, and 1 had jaundice. 28 of the 35 patients with abnormal liver function returned to normal and 7 improved to grade 1, and none of the patients had serious life-threatening or fatal liver function abnormalities. Combination therapy was a risk factor for patients to develop abnormal liver function (P=0.007). Conclusions: Most of the liver function abnormalities that occur during treatment with PD-1 antibody SHR-1210 alone or in combination with apatinib and chemotherapy are mild, and liver function can return to normal or improve with symptomatic treatment. For patients who receive PD-1 antibody in combination with targeted therapy and chemotherapy and have a history of long-term previous smoking, alcohol consumption and hepatitis B virus infection, liver function should be monitored and actively managed in a timely manner.

Moderately hypo-fractionated radiotherapy combined with S-1 in inoperable locally advanced esophageal squamous cell carcinoma: A prospective, single-arm phase II study (GASTO-1045).

We launched this prospective phase II single-arm trial on the combination of moderately hypo-fractionated radiotherapy and S-1, to explore the safety and efficacy of the new potent regimen in inoperable locally advanced esophageal squamous carcinoma (LA-ESCC) patients. Patients with unresectable stage II-IVB LA-ESCC (UICC 2002, IVB only with metastatic celiac or supraclavicular lymph nodes) were included. Moderately hypofractionated radiotherapy (60Gy in 24 fractions) concurrent with S-1 was delivered. Meanwhile, gastrostomy tube placement by percutaneous endoscopic gastrostomy (PEG) was performed to provide nutritional support. Nutritional supplements were prescribed to meet requirements. The study outcomes included objective response rate (ORR), progression-free survival (PFS), overall survival (OS), locoregional progression-free survival (LRPFS), distant metastasis-free survival (DMFS), failure pattern, toxicities, nutritional status and treatment compliance. Endoscopy was routinely performed during post-treatment follow-up. Fifty-eight patients were included with a median follow-up of 24.4 months. The median age was 63 years (range 49-83 years) and 42 patients (72.4%) had stage III or IV diseases. The ORR was 91.3% and the CR rate was 60.3%. The estimated 2-year PFS rate and 2-year OS rate was 44.2% (95% confidence interval (CI), 31.3-57.1%) and 71.4% (95% CI, 59.4-83.4%), respectively. Radiation-induced esophagitis was the most common non-hematologic toxicity and 5 patients (8.6%) developed grade≥3 esophagitis. While, with PEG nutrition support, the nutrition-related indicators presented a clear trend toward a gradual improvement. Treatment-related death was not observed. The moderately hypo-fractionated radiotherapy combined with S-1 showed promising loco-regional disease control and survival benefit in inoperable LA-ESCC patients. Meanwhile, favorable nutritional status and low incidence of severe radiation-induced esophagitis were observed with PEG nutritional support. Moreover, endoscopy examination contributed to the early detection of recurrent esophageal lesions and timely salvage treatment. The efficacy and toxicity of the combined regimen deserved further evaluation. Clinicaltrials.gov, identifier NCT03660449.