In Response to "Acute Oral Mucositis During Hypo-Fractionated Radiation in Squamous Cell Carcinoma of Oral Cavity".

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Long-term survival after anti-PD-1 discontinuation in advanced cutaneous squamous cell carcinoma (cSCC): a proof of concept of benefit of concomitant cemiplimab and radiotherapy.

BACKGROUND: In a princeps study we conducted in patients with advanced cutaneous squamous cell carcinoma treated with concomitant anti-Programmed cell death protein 1 (PD-1) and radiotherapy, we demonstrated a clinico radiological response to cemiplimab that appeared to persist over time, 1 year after treatment discontinuation. METHOD: We conducted a single-center descriptive study at Caen Hospital from September 1, 2021 to September 2023, in 14 patients with advanced carcinoma treated with cemiplimab until September 1, 2021. The aim of this update is to examine clinical and radiological follow-up 2 years after discontinuation of cemiplimab. RESULTS: Of the 12 patients with a partial or complete response, we report 8 (66.7%) persistent responses 2 years after stopping cemiplimab, with only 2 patients progressing to distant disease, one lost to follow-up, and one death a priori unrelated to the disease. CONCLUSION: Our study confirms a long-term and persistent effect despite discontinuation of cemiplimab at least up to 2 years later.

[Concurrent simultaneous integrated boost radiotherapy and cetuximab in head and neck squamous cell cancer patients: is it feasible in daily clinical practice?] / Radioterapia a intensità modulata con boost simultaneo più cetuximab in pazienti con carcinoma a cellule squamose in stadio localmente avanzato del distretto testa collo: è fattibile nella pratica clinica quotidiana?

INTRODUCTION AND AIM: Locally advanced head and neck squamous cell carcinoma (LA-Hnscc) is a true therapeutical challenge in the modern era and the scientific community is trying to face this challenge with new therapeutical strategies, including combinations of monoclonal antibodies and radiation therapy. The aim of this study is to evaluate clinical outcomes in LA-Hnscc patients unfit to receive platinum-based chemotherapy, treated with concurrent simultaneous integrated boost-intensity modulated radiotherapy (Sib-Imrt) + cetuximab (Ctx) in daily clinical practice. METHODS: LA-Hnscc patients not included in other prospective studies treated in 4 Italian radiotherapy units (2 Messina, 1 Rome, and 1 Lecce) using Sib-Imrt and Ctx were included in this study. Acute and late toxicities and overall survival (OS) have been evaluated. RESULTS: Data regarding 27 patients with squamous tumour were collected and reviewed. The primary tumour sites were oropharynx in 14 patients (51.9%), oral cavity in 7 (25.9%), larynx in 3 (11%) and other sites in 3(11%). There were 20 (74%) patients had stage IV (16 IVa and 4 IVb). Complete remission was observed in 18 patients (66.7%), a partial remission in 4 (14.8%) whilst 4 had a progression disease (14.8%). After 3 year of follow-up 7/27 patients were deaths. The OS was 95.5%, 62.5% and 52.9% respectively at 1,2 and 3 years. Acute toxicities were observed in all treated patients (mucositis, dermatitis and dysphagia) while 66.7% of patients developed late toxicities. All observed toxicities were grade 1 to 3 and just 1 patient developed a G4 toxicity. CONCLUSION: The concurrent bio-radiotherapy of Sib-Imrt and cetuximab is feasible in real-life daily clinical practice for LA-Hnscc patients unfit for platinum-based chemoradiotherapy.

Interstitial round needles should not be used for cervical cancer patient treated with intracavitary/ interstitial brachytherapy using a Venezia applicator : a case report.

BACKGROUND: Image-guided adaptive brachytherapy (IGABT) demonstrates an excellent local control rate and low toxicity while treating cervical cancer. For intracavitary/interstitial (IC/IS) brachytherapy (BT), several applicators are commercially available. Venezia (Elekta, Sweden), an advanced gynecological applicator, is designed for IC/IS BT for treating locally advanced cervical cancer. There are two types of interstitial needles for the Venezia applicator: the round needle and sharp needle. Generally, a round needle is safer because it has less risk of damaging the organ at risk than a sharp needle. However, there is currently no evidence to suggest that a round needle is better than a sharp needle for the Venezia applicator in IC/IS BT. Herein, we documented our experience of using both round and sharp needles with the Venezia applicator in IC/IS BT for cervical cancer. CASE PRESENTATION: A 71-year-old woman was diagnosed with clinical stage T2bN0M0 and the International Federation of Gynecology and Obstetrics stage IIB cervical squamous cell carcinoma. Definitive therapy, including a high-dose-rate BT boost, was planned using a round needle with the Venezia applicator in IC/IS BT. After inserting four interstitial round needles during the first and second BT sessions, an unexpectedly large gap (1.5 cm) was detected between the cervix and ovoid. We therefore used a sharp needle with the Venezia applicator for IC/IS BT during the third and fourth BT sessions. Three sharp needles were firmly inserted during the third and fourth BT sessions. CONCLUSIONS: The study findings suggest that the interstitial round needle should not be used for cervical cancer patients undergoing IC/IS BT using the Venezia applicator.

A Comparative Study of Clinical Outcomes in Locally Advanced Cervical Cancer: External Beam Radiotherapy (EBRT) and Sequential High Dose Rate Intracavitary Brachytherapy (HDRICBT) with or without Concurrent Cisplatin on the Day of ICBT Insertion - A Tertiary Care Center Randomized Controlled Trial in India.

OBJECTIVE: The current study aimed to delve into the comparative clinical outcomes between external beam radiation therapy (EBRT) and sequential High Dose Rate Intracavitary Brachytherapy (HDRICBT) with or without concurrent cisplatin administration on the day of intracavitary brachytherapy (ICBT) insertion in women with locally advanced cervical cancer. METHODS: In this study, conducted between January 2017 and July 2018 at a leading institute in India, diagnosed and untreated patients of locally advanced carcinoma cervix were randomized into two groups. Arm 1 received concurrent cisplatin before each course of brachytherapy, while Arm 2 underwent brachytherapy alone. The outcomes were compared in terms of acute and late toxicities, treatment response, and follow-up. Data analysis was performed using SPSS 16, with statistical significance set at p < 0.05. RESULTS: Both study arms showed similar complete response (CR) rates of 73.3%, with no significant advantage of concurrent cisplatin before brachytherapy. However, a noteworthy trend emerged during follow-up. In the concurrent cisplatin group, the CR rate increased from 73.3% post 1 month of brachytherapy to 86.7% at 3 months and 83.3% at 6 months. Contrastingly, the control group showed CR rates of 73.3% post 1 month, 80% at 3 months, and 76.6% at 6 months. While not statistically significant, this observation suggests a possible enhancement in response rates with concurrent cisplatin and ICBT. CONCLUSIONS: Future studies focusing on the optimal drug, dosage, scheduling, and combining cisplatin with other agents are recommended to further explore the potential benefits observed in this study.

High-tailored Anal Canal Radiotherapy (HIT-ART): Outcomes of a 10-Year Single Center Clinical Experience.

BACKGROUND/AIM: The current standard for anal cancer treatment is essentially a 'one size fits all' approach where the dose of radiotherapy is similar whether the tumor is very small or very large. Trials are ongoing to evaluate dose de-escalation or escalation in localized disease depending on tumor size. The aim of the study was to assess results of a personalized approach involving dose stratification by stage and boost dose adjusted according to tumor early response. PATIENTS AND METHODS: We retrospectively reviewed squamous cell anal cancer (SCAC) patients treated between 2011 and 2021 by long-course intensity-modulated radiotherapy (IMRT) and concomitant chemotherapy (CT); a sequential boost could be administered by IMRT or interventional radiotherapy (IRT) to obtain a total equivalent dose in 2 Gy (EQD2) of 54-60 Gy. RESULTS: We analyzed 110 patients (61% T3-4 stage, 71% node-positive). A total of 68.2% of patients received a sequential boost, mainly by IRT; median total EQD2 to primary site was 59.3 Gy. Acute ≥G3 toxicity rate was 36.4%. Median follow-up (FUP) was 35.4 months. A total of 83% of patients achieved clinical complete response (cCR); locoregional recurrence (LRR) occurred in 20.9% and distant metastases in 6.4% of cases. A total of 12.7% patients underwent salvage surgery. A total of 25.5% of patients reported ≥G2 and 4.5% ≥G3 late toxicity. The estimated 3-year overall survival, disease-free survival and colostomy-free survival were 92%, 72% and 84% respectively; 3-year-LRR was 22%. Nodal stage was associated with poorer cCR probability and higher LRR (p<0.05). CONCLUSION: Our results on a large cohort of patients with locally advanced SCAC and long FUP time confirmed the efficacy of IMRT; high local control and manageable toxicity also suggest IRT as a promising method in treatment personalization.

Deep-learning-based radiomics of intratumoral and peritumoral MRI images to predict the pathological features of adjuvant radiotherapy in early-stage cervical squamous cell carcinoma.

BACKGROUND: Surgery combined with radiotherapy substantially escalates the likelihood of encountering complications in early-stage cervical squamous cell carcinoma(ESCSCC). We aimed to investigate the feasibility of Deep-learning-based radiomics of intratumoral and peritumoral MRI images to predict the pathological features of adjuvant radiotherapy in ESCSCC and minimize the occurrence of adverse events associated with the treatment. METHODS: A dataset comprising MR images was obtained from 289 patients who underwent radical hysterectomy and pelvic lymph node dissection between January 2019 and April 2022. The dataset was randomly divided into two cohorts in a 4:1 ratio.The postoperative radiotherapy options were evaluated according to the Peter/Sedlis standard. We extracted clinical features, as well as intratumoral and peritumoral radiomic features, using the least absolute shrinkage and selection operator (LASSO) regression. We constructed the Clinical Signature (Clinic_Sig), Radiomics Signature (Rad_Sig) and the Deep Transformer Learning Signature (DTL_Sig). Additionally, we fused the Rad_Sig with the DTL_Sig to create the Deep Learning Radiomic Signature (DLR_Sig). We evaluated the prediction performance of the models using the Area Under the Curve (AUC), calibration curve, and Decision Curve Analysis (DCA). RESULTS: The DLR_Sig showed a high level of accuracy and predictive capability, as demonstrated by the area under the curve (AUC) of 0.98(95% CI: 0.97-0.99) for the training cohort and 0.79(95% CI: 0.67-0.90) for the test cohort. In addition, the Hosmer-Lemeshow test, which provided p-values of 0.87 for the training cohort and 0.15 for the test cohort, respectively, indicated a good fit. DeLong test showed that the predictive effectiveness of DLR_Sig was significantly better than that of the Clinic_Sig(P < 0.05 both the training and test cohorts). The calibration plot of DLR_Sig indicated excellent consistency between the actual and predicted probabilities, while the DCA curve demonstrating greater clinical utility for predicting the pathological features for adjuvant radiotherapy. CONCLUSION: DLR_Sig based on intratumoral and peritumoral MRI images has the potential to preoperatively predict the pathological features of adjuvant radiotherapy in early-stage cervical squamous cell carcinoma (ESCSCC).

A nomogram based on clinical characteristics and nutritional indicators for relative and absolute weight loss during radiotherapy in initially inoperable patients with locally advanced esophageal squamous cell carcinoma.

OBJECTIVE: Radiation for locally advanced esophageal squamous cell carcinoma often is accompanied by radiation esophagitis, which interferes with oral intake. We aimed to develop a nomogram model to identify initially inoperable patients with relative and absolute weight loss who need prophylactic nutritional supplementation. METHODS: A total of 365 initially inoperable patients with locally advanced esophageal squamous cell carcinoma receiving radiotherapy between January 2018 and December 2022 were included in the study, which was divided into discovery and validation cohorts. Receiver operating characteristic and Kaplan-Meier curve analyses were performed to compare the areas under the curve and survival benefits. RESULTS: A total of 42.2% (154 of 365) of the patients had been diagnosed with cancer cachexia. The malnourished group had a higher interruption rate of radiotherapy and number of complication diseases (P < 0.05). Meanwhile, patients with malnutrition had lower lymphocytes and prognostic nutritional index (P < 0.05). The combined index showed a higher area under the curve value (0.67; P < 0.001) than number of complication diseases (area under the curve = 0.52) and prognostic nutritional index (area under the curve = 0.49) for relative weight loss (≥ 5%). Similarly, the combined index had a higher area under the curve value (0.79; P < 0.001) than number of complication diseases (area under the curve = 0.56), treatment regimens (area under the curve = 0.56), subcutaneous fat thickness (area under the curve = 0.60), pretreatment body weight (area under the curve = 0.61), neutrophils (area under the curve = 0.56), and prognostic nutritional index (area under the curve = 0.50) for absolute weight loss (≥ 5 kg). Absolute and relative weight loss remained independent prognostic factors, with short overall survival rates compared with the normal group (P < 0.05). Patients with high nomogram scores supported by nutritional intervention had less weight loss, better nutrition scores, and increased plasma CD8+ T cells, and interferon gamma. CONCLUSIONS: We developed a nomogram model that was intended to estimate relative and absolute weight loss in initially inoperable patients with locally advanced esophageal squamous cell carcinoma during radiotherapy, which might help facilitate an objective decision on prophylactic nutritional supplementation.

Effect of radiotherapy on head and neck cancer tissues in patients receiving radiotherapy: a bioinformatics analysis-based study.

Radiotherapy is pivotal in treating head and neck cancers including nasopharyngeal, tongue, hypopharyngeal, larynx, maxillary sinus, parotid gland, and oral cancers. It holds the potential for curative effects and finds application in conjunction with chemotherapy, either as a radical method to preserve organ function or as an adjuvant postoperative treatment. We used bioinformatics analysis to investigate the effects of radiotherapy on head and neck cancer tissues in patients who had received radiotherapy. In this study, the expression and mutation profiles of The Cancer Genome Atlas-Head-Neck Squamous Cell Carcinoma were downloaded from the UCSC-Xena database, categorizing patients into two groups-those receiving radiotherapy and those not receiving radiotherapy. Subsequently, differential expression analysis and gene set enrichment analysis (GSEA) were performed. Following this, single-sample GSEA (ssGSEA) scores related to glucose and lipid metabolism were compared between the two groups. Additionally, immune cell infiltration analysis and single-cell verification were performed. Finally, the mutation profiles of the two groups were compared. The analyses revealed that patients receiving radiotherapy exhibited prolonged survival, enhanced apoptosis in head and neck cancer tissue, and diminished keratinocyte proliferation and migration. A comparison of ssGSEA scores related to glucose and lipid metabolism between the two groups indicated a reduction in glycolysis, tricarboxylic acid cycle activity, and fat synthesis in tissues treated with radiotherapy, suggesting that radiotherapy can effectively inhibit tumour cell energy metabolism. Analyses of immune cell infiltration and single-cell verification suggested decreased infiltration of immune cells post-radiotherapy in head and neck cancer tissues. A comparison of mutation profiles revealed a higher frequency of TP53, TTN, and CDKN2A mutations in patients receiving radiotherapy for head and neck cancer. In conclusion, the bioinformatics analyses delved into the effect of radiotherapy on patients with head and neck carcinoma. This study provides a theoretical framework elucidating the molecular mechanisms underlying radiotherapy's efficacy in treating head and neck cancer and presents scientific recommendations for drug therapy following radiotherapy.

Accelerated hypofractionated chemoradiation for locally advanced head and neck cancer during COVID 19 pandemic: A tertiary care experience.

PURPOSE: To assess the role of Accelerated Hypofractionated Chemoradiation for Locally Advanced Head & Neck squamous cell cancer (HNSCC) during COVID 19 pandemic. MATERIALS AND METHODS: Previously untreated 20 patients with locally advanced HNSCC (Oral cavity/oropharynx/larynx/hypopharynx) were treated with definitive hypofractionated radiotherapy of 60Gy in 25 fractions with concurrent cisplatin @35 mg/m2 once weekly for 5 weeks from March 2020 to November 2021. The patients were treated on 6MV LINAC with Volumetric modulated arc therapy (VMAT) by the Sequential boost technique and concurrent chemotherapy @35 mg/m2. All the patients received 48Gy in 20 fractions to low-risk volume (CTV LR) in Phase I followed by 12Gy in 5 fractions boost to High-risk volume (CTV HR) in Phase II. The organs at risk (OARs) were contoured and appropriate constraints were given considering the hypofractionated regimen. RESULTS: Out of 20 patients, most of the patients were Stage IV (15;75%) & stage III 20%, out of which (55%) 11 were of the oral cavity, (40%) 8 were of the oropharynx, and (5%) 1 of larynx. All patients were treated with 60Gy/25#/5 weeks with the majority of the patients (17;85%) completing their treatment in less than 45 days. The Median follow-up was of 214 days. The locoregional control at 6 Months was 55%. Maximum acute toxicity was grade 3 mucositis which was observed in 18 (90%) patients. Ryle's tube feeding was needed in 11 (55%) patient. Out of 20 patients, 5 patients did not receive concurrent chemotherapy, and 8 (40%) patients received all 5 cycles of chemotherapy. 7, 35% of the patients could not complete all 5 cycles of concurrent chemotherapy due to grade 3 mucositis. CONCLUSION: During a pandemic crisis with limited manpower & technical resources accelerated hypofractionated radiotherapy with concurrent chemotherapy can be considered a feasible therapeutic option for HNSCC which can significantly reduce the overall Treatment Time (OTT) with comparable local control and manageable toxicities.

Upfront surgery versus definitive radiotherapy: competing risk analyses for cancer-specific and noncancer mortality in oropharyngeal cancer.

PURPOSE: The optimal treatment strategy for oropharyngeal cancer (OPC) is undetermined. We aim to compare the survival outcomes of OPC patients treated with upfront surgery versus definitive radiotherapy (RT). METHODS: A total of 8057 cases were retrieved from the Surveillance, Epidemiology, and End Results database. Primary endpoints were cancer-specific and noncancer mortalities, which were estimated using cumulative incidence function and compared by Gray's test. Univariate and multivariate Fine-Gray subdistribution hazard models were used to estimate the effects of treatment modality on mortality. Subgroup analyses were performed in propensity-score-matched cohorts. All the analyses were conducted separately in human papillomavirus (HPV)-negative and HPV-positive cohorts. RESULTS: In the HPV-negative cohort, definitive RT was independently associated with increased risk of cancer-specific mortality (adjusted subdistribution hazard ratio [SHR], 1.31; 95% confidence interval [CI], 1.05-1.64; P = 0.017) and noncancer mortality (adjusted SHR, 1.59; 95% CI 1.13-2.25; P = 0.008). In the HPV-positive cohort, definitive RT was independently associated with increased risk of cancer-specific mortality (adjusted SHR, 1.51; 95% CI 1.23-1.85; P < 0.001) and noncancer mortality (adjusted SHR, 1.53; 95% CI 1.11-2.12; P = 0.009). CONCLUSION: Upfront surgery is a superior treatment modality compared with definitive RT in terms of lowering cancer-specific and noncancer mortality in OPC patients, regardless of HPV status. Further prospective clinical trials are needed to confirm our findings.

Are oral cancers effectively palliated with radiotherapy? Outcomes of treatment with a modified QUAD SHOT regimen.

BACKGROUND: This study assessed a palliative radiotherapy regimen using daily radiation over 4 days for three courses in inoperable head and neck cancers, emphasizing oral primary cancers. METHODS: Retrospective data of 116 patients treated with a daily dose of 3.6-3.7 Gy in four fractions over 4 days to a total of three courses, with a 2-week gap after every course, were analyzed for survival outcomes. A subgroup analysis was done for oral cancer. RESULTS: Ninety-nine (85%) completed three courses. Overall subjective response rate was 77%. Median overall survival and progression-free survival were 12 months (95% confidence interval [CI]: 8-20) and 8 months (95% CI: 6-10), with numerically higher overall survival in oral cancer. The treatment was well tolerated, with no on-treatment hospitalization or grade 3-4 toxicities. CONCLUSION: The modified QUAD SHOT regimen is practical for palliation in head and neck cancers.

Tumor volume and cancer stem cell expression as prognostic markers for high-dose loco-regional failure in head and neck squamous cell carcinoma - A DAHANCA 19 study.

BACKGROUND AND PURPOSE: Reliable and accessible biomarkers for patients with Head and Neck Squamous Cell Carcinoma (HNSCC) are warranted for biologically driven radiotherapy (RT). This study aimed to investigate the prognostic value of putative cancer stem cell (CSC) markers, hypoxia, and tumor volume using loco-regional high-dose failure (HDF) as endpoint. MATERIALS AND METHODS: Tumor tissue was retrieved from patients treated with primary chemo-(C-)RT and nimorazole for HNSCC in the Danish Head and Neck Cancer Study Group (DAHANCA) 19 study. Tumor volume, hypoxic classification, and expression of CSC markers CD44, SLC3A2, and MET were analyzed. For patients with eligible data on all parameters (n = 340), the risk of HDF following primary chemo-(C-)RT were analyzed by these biomarkers as a whole and stratified for p16-positive oropharynx (p16 + OPSCC) vs p16-negative (p16-) tumors (oral cavity, p16- oropharynx, hypopharynx and larynx). RESULTS: Higher risk of HDF was seen for patients with larger primary and nodal volume (>25 cm3, Hazard Ratio (HR): 3.00 [95 % CI: 1.73-5.18]), high SLC3A2 (HR: 2.99 [1.28-6.99]), CD44 (>30 % positive, HR: 2.29 [1.05-5.00]), and p16- tumors (HR: 2.53 [1.05-6.11]). p16- tumors had a higher CSC marker expression than p16 + OPSCC. The factors associated with the highest risk of HDF were larger volume (HR: 3.29 [1.79-6.04]) for p16- tumors (n = 178) and high SLC3A2 (HR: 6.19 [1.58-24.23]) for p16 + OPSCC (n = 162). CONCLUSION: Tumor volume, p16, and CSC markers are potential biomarkers for HDF for patients with HNSCC treated with (C-)RT. Lower expression of CSC in p16 + OPSCC may contribute to better tumor control.

JunD-miR494-CUL3 axis promotes radioresistance and metastasis by facilitating EMT and restraining PD-L1 degradation in esophageal squamous cell carcinoma.

Therapy resistance and metastatic progression jointly determine the fatal outcome of cancer, therefore, elucidating their crosstalk may provide new opportunities to improve therapeutic efficacy and prevent recurrence and metastasis in esophageal squamous cell carcinoma (ESCC). Here, we have established radioresistant ESCC cells with the remarkable metastatic capacity, and identified miR-494-3p (miR494) as a radioresistant activator. Mechanistically, we demonstrated that cullin 3 (CUL3) is a direct target of miR494, which is transcriptionally regulated by JunD, and highlighted that JunD-miR494-CUL3 axis promotes radioresistance and metastasis by facilitating epithelial-mesenchymal transition (EMT) and restraining programmed cell death 1 ligand 1 (PD-L1) degradation. In clinical specimens, miR494 is significantly up-regulated and positively associated with T stage and lymph node metastasis in ESCC tissues and serum. Notably, patients with higher serum miR494 expression have poor prognosis, and patients with higher CUL3 expression have more conventional dendritic cells (cDCs) and plasmacytoid DCs (pDCs), less cancer-associated fibroblasts (CAF2/4), and tumor endothelial cells (TEC2/3) infiltration than patients with lower CUL3 expression, suggesting that CUL3 may be involved in tumor microenvironment (TME). Overall, miR494 may serve as a potential prognostic predictor and therapeutic target, providing a promising strategy for ESCC treatment.

Postoperative Radiotherapy and Survival in Oral Cavity Squamous Cell Carcinoma With Mandibulectomy.

Importance: Oral cavity squamous cell carcinoma (SCC) tumors with mandibular invasion are upstaged to pT4a regardless of their size. Even small tumors with boney invasion, which would otherwise be classified as pT1-2, are recommended for the locally advanced treatment pathway to receive administration of postoperative radiotherapy (PORT). Objective: To evaluate the association of PORT with overall survival according to tumor size among patients who received mandibulectomy for pT4aN0 oral cavity SCC. Design, Setting, and Participants: This was a retrospective analysis using data from the US National Cancer Database from January 1, 2004, through December 31, 2019. All patients who received mandibulectomy for treatment-naive pT4aN0 oral cavity SCC with negative surgical margins were included. Data analyses were performed in January 2023 and finalized in July 2023. Exposure: PORT vs no PORT. Main Outcomes and Measures: Entropy balancing was used to balance covariate moments between treatment groups. Weighted multivariable Cox proportional hazards regression was used to measure the association of PORT with overall survival associated with tumor size. Results: Among 3268 patients with pT4aN0 oral cavity SCC (mean [SD] age, 65.9 [12.1] years; 2024 [61.9%] male and 1244 [38.1%] female), 1851 (56.6%) received PORT and 1417 (43.4%) did not receive PORT. On multivariable analysis was adjusted for age, insurance status, Charlson Comorbidity Index score, tumor site, tumor grade, tumor size, and PORT. Findings indicated that PORT was associated with improved overall survival and that this relative survival advantage trended upwards with increasing tumor size. That is, the larger the tumor, the greater the survival advantage associated with the use of PORT. For the 1068 patients with tumors greater than 4 cm, the adjusted hazard ratio (aHR) in favor of PORT was 0.63 (95% CI, 0.48-0.82); for the 1774 patients with tumors greater than 2 cm but less than or equal to 4 cm, the aHR was 0.76 (95% CI, 0.62-0.93); and for 426 patients with tumors less than 2 cm, the aHR was 0.81 (95% CI, 0.57-1.15). Conclusions and Relevance: In this retrospective analysis of patients who received mandibulectomy for pT4aN0 oral cavity SCC, PORT was associated with improved overall survival, the benefit of which improved relatively with increasing tumor size. These findings suggest that tumor size should be considered in guidelines for PORT administration in this patient population.

SALL4 promotes cancer stem-like cell phenotype and radioresistance in oral squamous cell carcinomas via methyltransferase-like 3-mediated m6A modification.

Radioresistance imposes a great challenge in reducing tumor recurrence and improving the clinical prognosis of individuals having oral squamous cell carcinoma (OSCC). OSCC harbors a subpopulation of CD44(+) cells that exhibit cancer stem-like cell (CSC) characteristics are involved in malignant tumor phenotype and radioresistance. Nevertheless, the underlying molecular mechanisms in CD44( + )-OSCC remain unclear. The current investigation demonstrated that methyltransferase-like 3 (METTL3) is highly expressed in CD44(+) cells and promotes CSCs phenotype. Using RNA-sequencing analysis, we further showed that Spalt-like transcription factor 4 (SALL4) is involved in the maintenance of CSCs properties. Furthermore, the overexpression of SALL4 in CD44( + )-OSCC cells caused radioresistance in vitro and in vivo. In contrast, silencing SALL4 sensitized OSCC cells to radiation therapy (RT). Mechanistically, we illustrated that SALL4 is a direct downstream transcriptional regulation target of METTL3, the transcription activation of SALL4 promotes the nuclear transport of ß-catenin and the expression of downstream target genes after radiation therapy, there by activates the Wnt/ß-catenin pathway, effectively enhancing the CSCs phenotype and causing radioresistance. Herein, this study indicates that the METTL3/SALL4 axis promotes the CSCs phenotype and resistance to radiation in OSCC via the Wnt/ß-catenin signaling pathway, and provides a potential therapeutic target to eliminate radioresistant OSCC.

Oncological and functional outcomes in T3 and T4 laryngeal cancer patients: choice for larynx preservation or total laryngectomy based on expected laryngeal function.

OBJECTIVE: To determine oncological and functional outcomes in patients with T3 and T4 laryngeal carcinoma, in which choice of treatment was based on expected laryngeal function and not T classification. METHODS: Oncological outcomes (disease-specific survival and overall survival) as well as functional outcomes (larynx preservation and functional larynx preservation) were analysed. RESULTS: In 130 T3 and 59 T4 patients, there was no difference in disease-specific survival or overall survival rates after radiotherapy (RT) (107 patients), chemoradiotherapy (36 patients) and total laryngectomy (46 patients). The five-year disease-specific survival rates were 83 per cent after RT, 78 per cent after chemoradiotherapy and 69 per cent after total laryngectomy, whereas overall survival rates were 62, 54 and 60 per cent, respectively. Five-year larynx preservation and functional larynx preservation rates were comparable for RT (79 and 66 per cent, respectively) and chemoradiotherapy (86 and 62 per cent, respectively). CONCLUSION: There is no difference in oncological outcome after (chemo)radiotherapy or total laryngectomy in T3 and T4 laryngeal carcinoma patients whose choice of treatment was based on expected laryngeal function.

Cardiac substructures dosimetric predicts cardiac toxicity and prognosis in esophageal squamous cell cancer treated by radiotherapy.

PURPOSE: To look into the relationship between cardiac substructures (CS) dosimetric parameters and cardiac events (CE) or overall survival (OS) in patients undergoing radiation therapy (RT) for esophageal squamous cell carcinoma (ESCC). METHODS AND MATERIALS: A retrospective study included 350 patients with ESCC receiving definitive chemoradiotherapy or radiotherapy (d-CRT/d-RT) or neoadjuvant chemoradiotherapy (NCRT) from March 2013 to May 2022. Our study examined the adverse cardiac events of any grade or G3+, as defined by the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. Competing risk analysis and Cox regression analysis were used to assess the relationship between CS doses and CEs or OS. RESULTS: 201 (57.4 %) patients received any grade CEs over a median follow-up time of 22.50 months (IQR, 12.40-45.60), and 24 (6.86 %) patients suffered G3+ CEs. On landmark analysis, patients with any grade CEs had significantly lower OS (P = 0.003). Multivariable analysis revealed that any grade CEs were predicted by the dose of CSs in all populations. In addition, for G3+ cardiac events, arrhythmic and small probability of cardiac events, LAD V20 ((HR: 1.02, 95 % CI: 1.00-1.03, P = 0.012; HR: 1.01, 95 % CI: 1.00-1.02, P = 0.005; HR; 1.01, 95 % CI: 1.00-1.02, P = 0.012) was also an independent predictive factor. LAD V50 (HR: 1.07, 95 % CI: 1.03-1.10, P <0.001) predicted pericardium effusion events. Moreover, the multivariable analysis revealed that OS was predicted by LAD V30 (HR: 1.03; 95 % CI, 1.01-1.05, P = 0.015). CONCLUSIONS: In the population of ESCC patients receiving RT, we showed that the CS factors had a substantial predictive value for the various types and grades of CEs. The elevated radiation dose of LAD was a significant contributor to a higher rate of cardiac events and a worse prognosis.

Impact of Fluorodeoxyglucose-Positron Emission Tomography/Computed Tomography on Therapeutic Decisions and Radiotherapy Planning in Head and Neck Squamous Carcinoma: A Retrospective Study of 46 Patients.

BACKGROUND Positron emission tomography/computed tomography (PET/CT) using fluorodeoxyglucose (FDG) is essential in oncology for precise tumor delineation. This study evaluated FDG PET/CT's impact on therapeutic decisions in head and neck cancer, comparing metabolic tumor volumes (MTV) measured by different methods with radiotherapy targets, crucial for treatment planning and patient outcomes. MATERIAL AND METHODS We retrospectively analyzed 46 patients with histologically confirmed head and neck cancer who underwent FDG PET/CT examination before radiotherapy. The mean age was 62 years (46-78 years). Then, we calculated MTV of the primary tumor or local recurrence using a local threshold of 41% of the standard uptake volume (SUV) corrected for lean body mass (SULmax) of the lesion and absolute threshold of SUV 2.5. Descriptive analysis of the recruited patients was assessed based on the clinical database (Medsol). RESULTS The study included 45 patients with squamous carcinoma and 1 with sarcoid cell carcinoma. PET/CT examination led to therapeutic decision changes in 11 cases. No significant difference was found in median values of Gross Tumor Volume (GTV) and MTV absolute (p=0.130). However, significant differences were observed in MTV local, MTV absolute, and GTV median values (p<0.001), with both MTVs showing significant correlation with GTV (p<0.01), especially MTV absolute (r=0.886). CONCLUSIONS FDG PET/CT examination prior to radiotherapy significantly influences therapeutic decisions in head and neck cancer patients. Based on our findings, the absolute threshold method (SUV: 2.5) appears to be an effective approach for calculating MTV for radiotherapy planning purposes.