[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.

Definitive weekly hypofractionated radiotherapy in surgery-ineligible older adults with cutaneous squamous cell carcinoma of the head and neck region.

This study intends to address the impact of weekly hypofractionated radiation therapy with curative intent for cutaneous squamous cell carcinoma of the head and neck region in the elderly population.

Skin metastases from prostate cancer successfully treated with radiation therapy.

Skin metastases from prostate cancer (PCa) are rare, cause considerable discomfort, and usually indicate advanced disease and a poor prognosis. To date, literature accounts for no more than 88 cases of skin metastasis from PCa, and radiation therapy (RT) is not considered a standard treatment option. Here, we have described a rare case of skin localization of castration-resistant metastatic PCa, which occurred in a 75-year-old male previously treated with RT for PCa, 11 years earlier. The skin lesions, which progressively appeared in different areas of the chest wall, were successfully treated with electron beam RT (900 cGy, for 3 consecutive days). Five months after irradiating skin metastases, the patient showed general fair conditions and no longer developed other skin lesions in the areas already treated or elsewhere. This report describes a scarce case of cutaneous metastases from PCa, underlying the crucial role of RT as a definitive palliative treatment that should be used to limit systemic chemotherapy-related toxicity.

Surgery-ineligible elderly patients with cutaneous squamous cell carcinoma of the head and neck region gain clinical benefit from definitive weekly hypofractionated radiotherapy.

BACKGROUND: To evaluate the role of definitive weekly hypofractionated radiotherapy (RT) for the treatment of surgery-ineligible elderly patients with cutaneous squamous cell carcinoma of the head and neck region (cHNSCC). METHODS: Eligible elderly patients (aged ≥75 years) with cHNSCC were included. Patients received definitive weekly hypofractionated RT, using megavoltage electrons, to a total dose of 56-64 Gy (8 Gy per fraction). Primary endpoint was objective response rate (ORR), defined as the percentage of patients with a complete (CR) or partial response (PR). Secondary endpoints included duration of response (DOR), progression-free survival (PFS), overall survival (OS), pain response, tolerability, and safety. RESULTS: A total of 19 patients with 27 lesions were included and treated with definitive weekly hypofractionated RT. All patients received the prescribed total dose. ORR was 92.6%, including 70.4% of lesions with a CR and 22.2% with a PR. Median DOR was 12 months. No severe toxicity occurred. CONCLUSIONS: Our study confirmed the satisfying efficacy and acceptable toxicity of definitive weekly hypofractionated RT for cHNSCC in elderly patients. Our results establish weekly hypofractionated scheduleas a promising treatment option for elderly patients with cHNSCC.

Nasopharyngeal cancer: the impact of guidelines and teaching on radiation target volume delineation.

Target volume delineation in the radiation treatment of nasopharyngeal cancer is challenging due to several reasons such as the complex anatomy of the site, the need for the elective coverage of definite anatomical regions, the curative intent of treatment and the rarity of the disease, especially in non-endemic areas. We aimed to analyze the impact of educational interactive teaching courses on target volume delineation accuracy between Italian radiation oncology centers. Only one contour dataset per center was admitted. The educational course consisted in three parts: (1) The completely anonymized image dataset of a T4N1 nasopharyngeal cancer patient was shared between centers before the course with the request of target volume and organs at risk delineation; (2) the course was held online with dedicated multidisciplinary sessions on nasopharyngeal anatomy, nasopharyngeal cancer pattern of diffusion and on the description and explanation of international contouring guidelines. At the end of the course, the participating centers were asked to resubmit the contours with appropriate corrections; (3) the pre- and post-course contours were analyzed and quantitatively and qualitatively compared with the benchmark contours delineated by the panel of experts. The analysis of the 19 pre- and post-contours submitted by the participating centers revealed a significant improvement in the Dice similarity index in all the clinical target volumes (CTV1, CTV2 and CTV3) passing from 0.67, 0.51 and 0.48 to 0.69, 0.65 and 0.52, respectively. The organs at risk delineation was also improved. The qualitative analysis consisted in the evaluation of the inclusion of the proper anatomical regions in the target volumes; it was conducted following internationally validated guidelines of contouring for nasopharyngeal radiation treatment. All the sites were properly included in target volume delineation by >50% of the centers after correction. A significant improvement was registered for the skull base, the sphenoid sinus and the nodal levels. These results demonstrated the important role that educational courses with interactive sessions could have in such a challenging task as target volume delineation in modern radiation oncology.

Quality of life changes over time and predictors in a large head and neck patients' cohort: secondary analysis from an Italian multi-center longitudinal, prospective, observational study-a study of the Italian Association of Radiotherapy and Clinical Oncology (AIRO) head and neck working group.

PURPOSE: The present study examined the longitudinal trajectories, through hierarchical modeling, of quality of life among patients with head and neck cancer, specifically symptoms burden, during radiotherapy, and in the follow-up period (1, 3, 6, and 12 months after completion of radiotherapy), through the M.D. Anderson Symptom Inventory Head and Neck questionnaire, formed by three factors. Furthermore, analyses were conducted controlling for socio-demographic as well as clinical characteristics. METHODS: Multi-level mixed-effects linear regression was used to estimate the association between quality of life and time, age, gender, household, educational level, employment status, ECOG performance status, human papilloma virus (HPV) status, surgery, chemotherapy, alcohol intake, and smoking. RESULTS: Among the 166 participants, time resulted to be a predictor of all the three questionnaire factors, namely, general and specific related symptoms and interference with daily life. Moreover, regarding symptom interference with daily activities factor, HPV-positive status played a significant role. Considering only HPV-negative patients, only time predicted patients' quality of life. Differently, among HPV-positive patients, other variables, such as gender, educational level, alcohol use, surgery, age at diagnosis, employment status, and ECOG status, resulted significant. CONCLUSION: It was evident that quality of life of patients with head and neck cancer declined during RT, whereas it slowly improved after ending treatment. Our results clarified the role of some socio-demographic and clinical variables, for instance, HPV, which would allow to develop treatments tailored to each patient.

Upper-neck irradiation versus standard whole-neck irradiation in nasopharyngeal carcinoma: A systematic review and meta-analysis.

PURPOSE: To evaluate the role of upper-neck irradiation versus standard whole-neck irradiation in patients with N0-1 nasopharyngeal carcinoma. METHODS: We conducted a PRISMA guideline based systematic review and meta-analysis. Randomized clinical trials assessing upper-neck irradiation versus whole-neck irradiation with or without chemotherapy in non-metastatic N0-1 nasopharyngeal carcinoma patients were identified. The studies were searched on the PubMed, Embase and Cochrane library up to March 2022. Survival outcomes, including overall survival, distant metastasis-free survival and relapse-free survival, and toxicities rate were evaluated. RESULTS: There were two randomized clinical trials with 747 samples finally included. Upper-neck irradiation had similar overall survival (hazard ratio = 0.69, 95% confidence interval = 0.37-1.30), distant metastasis-free survival (hazard ratio = 0.92, 95% confidence interval = 0.53-1.60) and relapse-free survival (risk ratio = 1.03, 95% confidence interval = 0.69-1.55) compared to whole-neck irradiation. No differences in both acute and late toxicities were recorded between upper-neck irradiation and whole-neck irradiation. CONCLUSION: This meta-analysis supports the potential role of upper-neck irradiation in this population of patients. Further research is needed to confirm results.

A Highly Versatile X-ray and Electron Beam Diamond Dosimeter for Radiation Therapy and Protection.

Radiotherapy is now recognized as a pillar in the fight against cancer. Two different types are currently used in clinical practice: (1) external beam radiotherapy, using high-energy X-rays or electron beams, both in the MeV-range, and (2) intraoperative radiotherapy, using low-energy X-rays (up to 50 keV) and MeV-range electron beams. Versatile detectors able to measure the radiation dose independently from the radiation nature and energy are therefore extremely appealing to medical physicists. In this work, a dosimeter based on a high-quality single-crystal synthetic diamond sample was designed, fabricated and characterized under low-energy X-rays, as well as under high-energy pulsed X-rays and electron beams, demonstrating excellent linearity with radiation dose and dose-rate. Detector sensitivity was measured to be 0.299 ± 0.002 µC/Gy under 6 MeV X-ray photons, and 0.298 ± 0.004 µC/Gy under 6 MeV electrons, highlighting that the response of the diamond dosimeter is independent of the radiation nature. Moreover, in the case of low-energy X-rays, an extremely low limit of detection (23 nGy/s) was evaluated, pointing out the suitability of the device to radiation protection dosimetry.

High-resolution anoscopy predictive modeling of anal canal cancer response after definitive chemoradiotherapy in COVID19 era.

PURPOSE: To develop a predictive index model, integrating both clinical and high-resolution anoscopy (HRA) features to further personalize the decision making process in anal canal carcinoma in COVID19 era. METHODS AND MATERIALS: We assess HRA parameters after definitive chemoradiotherapy in patients with anal canal malignant lesions. RESULTS: HRA features could be important to assess the effect of CRT and a risk stratification system should be introduced in clinical practice to better allocate therapeutic interventions. CONCLUSION: To our knowledge this is the first proposal for HRA findings in anal canal cancer after definitive CRT. We believe that a risk score can be useful to estimate the risk of treatment failure (in term of persistence disease and/or recurrence) and its clinical relevance should not to be underestimated.

Patient-Reported Outcomes After Swallowing (SWOARs)-Sparing IMRT in Head and Neck Cancers: Primary Results from a Prospective Study Endorsed by the Head and Neck Study Group (HNSG) of the Italian Association of Radiotherapy and Clinical Oncology (AIRO).

OBJECTIVES: To prospectively investigate changes in M.D. Anderson Dysphagia Inventory (MDADI) scores in patients affected by naso- and oropharynx cancer after definitive radiochemotherapy (ChemoRT) using swallowing organs at risk (SWOARs)-sparing IMRT. METHODS: MDADI questionnaires were collected at baseline and at 6 and 12 months after treatment. MDADI scores were categorized as follows: ≥ 80 "optimal," 80-60 "adequate," < 60 "poor" deglutition-related quality of life (QoL) group, and dichotomized as "optimal" vs "adequate/poor" for the analysis. A mean MDADI composite (MDADI-C) change of 10 points was considered as minimal clinically important difference (MCID). RESULTS: Sixty-three patients were enrolled of which 47 were considered for the analysis. At baseline, 26 (55%) were "optimal" and 21 (45%) were "adequate/poor." The mean baseline MDADI-C score was 93.6 dropping to 81 at 6 months (p = 0.013) and slightly rising to 85.5 at 12 months (p = 0.321) for the "optimal" group. Indeed, the mean baseline MDADI-C score was 64.3 rising to 77.5 at 6 months (p = 0.006) and stabilizing at 76 at 12 months (p = 0.999) for the "adequate/poor" group. A statistically significant but not clinically relevant worsening of the MDADI-C score was reported for the "optimal" group, whereas both a statistically significant and clinically meaningful improvement of the MDADI-C score were reported for the "adequate/poor" group from before to post-treatment. CONCLUSION: Our results suggest a doubly clinical benefit of dose optimization to SWOARs to minimize the RT sequalae in patients with a baseline "optimal" deglutition-related QoL and to recover from cancer dysphagia in those with a baseline "adequate/poor" deglutition-related QoL.

Simultaneously Integrated Boost Affects Survival in Locally Advanced p16-Negative Oropharyngeal Squamous Cell Carcinoma.

BACKGROUND/AIM: Intensity modulated radiotherapy (IMRT) is the standard of care for oropharyngeal cancer management. IMRT can be applied using either the sequential boost or simultaneous integrated boost (SIB-IMRT) techniques. The purpose of the study was to assess the efficacy of sequential boost technique or SIB-IMRT) in locally advanced p16-negative oropharyngeal squamous cell carcinoma. PATIENTS AND METHODS: Baseline characteristics and treatment outcomes were compared between patients with locally advanced p16-negative oropharyngeal squamous cell carcinoma, who received sequential RT (n=40) and those who received SIB-IMRT (n=38). RESULTS: In total, 78 patients with locally advanced p16-negative oropharyngeal cancer were identified. Mean age was 63 years. Patients treated with SIB-IMRT had better 5-year overall survival (OS; 78.7% vs. 52.5%, p=0.023) and 5-year disease-free survival (DFS; 87.4% versus 63.5%, p=0.046) compared to sequential group. There was no difference of total severe acute and late toxicity (grade ≥3) incidences. Patients treated with SIB technique had higher rates of mild to moderate late xerostomia (73.7% vs. 52.5%), dysgeusia (63.2% vs. 20%), and dysphagia (44.7% vs. 17.5%). CONCLUSION: Compared to sequential technique, SIB-IMRT improved both OS and DFS, but higher mild to moderate late toxicity was observed. As long as RT dose constraints to surrounding normal organs can be maintained, SIB technique should be the technique of choice for locally advanced p16-negative oropharyngeal squamous cell carcinoma treatment.

AIRO GORTEC consensus on postoperative radiotherapy (PORT) in low-intermediate risk early stages oral squamous cell cancers (OSCC).

Evidence on the efficacy of postoperative radiotherapy (PORT) in low-intermediate risk squamous cell carcinoma of the oral cavity (OSCC) remains inconclusive. Members of a task force from two national radio-oncology Associations (AIRO and GORTEC) defined 14 clinically relevant questions to identify "gray areas" pertinent to the indication for PORT in this clinical setting. Consequently, a literature review was performed on the topic. The resulting statements were then rated by an Expert Panel (EP) using a modified Delphi method. Only radiation oncologists were part of the discussion and voting on the scenarios. There was agreement on the 14 statements at the first round of voting. The task force then decided to propose clinical cases for the two more controversial statements that had received a lower agreement to better capture the Experts' attitudes. The clinical cases highlighted a more significant decisional heterogeneity. However, the good level of consensus reached among the two Associations gives relevant support in informing clinical choices while acknowledging general indications cannot fit all clinical situations and do not replace multidisciplinary discussion.

Survival Analysis Using the Covid-death Mean-imputation (CoDMI) Algorithm: A First Clinical Application in Radiation Oncology.

BACKGROUND/AIM: To report long-term survival results after trimodal approach for locally advanced rectal cancer (LARC) in the Covid-19 era. We herein illustrate a clinical application of Covid-death mean-imputation (CoDMI) algorithm in LARC patients with Covid-19 infection. PATIENTS AND METHODS: We analyzed 94 patients treated for primary LARC. Overall survival was calculated in months from diagnosis to first event (last follow-up/death). Because Covid-19 death events potentially bias survival estimation, to eliminate skewed data due to Covid-19 death events, the observed lifetime of Covid-19 cases was replaced by its corresponding expected lifetime in absence of the Covid-19 event using the CoDMI algorithm. Patients who died of Covid-19 (DoC) are mean-imputed by the Kaplan-Meier estimator. Under this approach, the observed lifetime of each DoC patient is considered as an "incomplete data" and is extended by an additional expected lifetime computed using the classical Kaplan-Meier model. RESULTS: Sixteen patients were dead of disease (DoD), 1 patient was DoC and 77 cases were censored (Cen). The DoC patient died of Covid-19 52 months after diagnosis. The CoDMI algorithm computed the expected future lifetime provided by the Kaplan-Meier estimator applied to the no-DoC observations as well as to the DoC data itself. Given the DoC event at 52 months, the CoDMI algorithm estimated that this patient would have died after 79.5 months of follow-up. CONCLUSION: The CoDMI algorithm leads to "unbiased" probability of overall survival in LARC patients with Covid-19 infection, compared to that provided by a naïve application of Kaplan-Meier approach. This allows for a proper interpretation/use of Covid-19 events in survival analysis. A user-friendly version of CoDMI is freely available at https://github.com/alef-innovation/codmi.

Safety and efficacy of combining afatinib and whole-brain radiation therapy in treating brain metastases from EGFR-mutated NSCLC: a case report and literature review.

Combining EGFR-tyrosine kinase inhibitors (TKIs) to whole brain radiation therapy (WBRT) has been shown to be more effective than EGFR-TKIs or WBRT alone in treating brain metastases (BMs) from EGFR-mutated Non Small-Cell Lung Cancer (NSCLC). However, despite the combination results well tolerated, EGFR-TKIs are often discontinued before WBRT, to reduce the risk of possible side effects, potentially resulting in reduced treatment efficacy and possible progression of intra- and extra-cranial disease. Afatinib, an irreversible inhibitor of EGFR-TK, has been shown to radiosensitize NSCLC in pre-clinical models and, compared to the other EGFR-TKIs, more efficiently penetrates the blood-brain barrier. However, nowadays, only two case reports describe the therapeutic efficiency and safety of combining afatinib with WBRT. Herein, we report on a 58-year-old woman patient with symptomatic BMs from NSLCL, treated with afatinib and concomitant WBRT, 30 Gy in 10 fractions. Treatment induced a remarkable and persistent radiological regression of BMs and the disappearance of neurological symptoms. However, the patient experienced severe skin toxicity of G3, corresponding to the irradiation area. Toxicity was successfully treated pharmacologically, and the patient did not experience any BMs-related symptoms for the next 10 months. She died of COVID-19-related respiratory failure. The association of afatinib with WBRT appears to be a successful strategy in the control of BMs from EGFR-mutated NSCLC. However, it should be considered that the combination could be responsible for serious dermatological toxicity.

Relationship between Salivary Amylase and Xerostomia in Intensity-Modulated Radiation Therapy for Head and Neck Cancer: A Prospective Pilot Study.

PURPOSE: A single-institution prospective pilot study was conducted to the assess correlation between salivary amylase and xerostomia in patients with head and neck squamous cell carcinoma (HNSCC) treated with intensity-modulated radiotherapy (IMRT). METHODS AND MATERIALS: Serum saliva amylase, clinician-reported xerostomia (using Common Terminology Criteria for Adverse Events), and patient-reported xerostomia (using 8-item self-reported xerostomia-specific questionnaire) were prospectively collected at baseline, during treatment and thereafter. Correlations between variables were assessed by correlation matrices. RESULTS: Twelve patients with locally advanced HNSCC formed the cohort. Eighty-three percent were male, 75% were smokers, 100% had clinical positive lymph nodes at diagnosis, and 42% received induction chemotherapy. All patients received IMRT with concurrent cisplatin-based chemotherapy. No grade ≥4 xerostomia was observed. Severe (G3) acute and late xerostomia occurred in five cases (41.7%) and two cases (16.7%), respectively. Patient-reported xerostomia scores were highly correlated with the clinician-reported scores (ρ = 0.73). A significant correlation was recorded between the concentration of amylase and the acute (ρ = -0.70) and late (ρ = -0.80) xerostomia. CONCLUSION: Preliminary results are encouraging. Prospective clinical trials are needed to define the value of salivary amylase in the management of HNSCC tumors.

Synchronous Anal Canal Cancer and Cervical Cancer: Report of a Case and Management Implication.

BACKGROUND: This is the case report of a synchronous anal canal cancer and cervical cancer in a patient who underwent definitive chemoradiotherapy (CRT) and radical surgery for anal canal and cervical carcinoma, respectively. CASE REPORT: A 55-year-old woman was diagnosed with cT4a cN1 Mx anal canal squamous cell carcinoma and stage IA2 cervical squamous cell carcinoma, based on biopsy and imaging. Definitive CRT consisted of radiotherapy (total dose of 59.4 Gy) and concomitant mitomycin (10 mg/m2) and 5-fluorouracil (750 mg/m2/5 daily continuous infusion) during the first and last week of radiation. The patient exhibited a complete clinical and radiological response. A radical hysterectomy with pelvic lymphadenectomy was then performed. At the last follow-up (30 months), the patient is still disease-free without any treatment-associated complications. CONCLUSION: There is limited information in the literature regarding treatment strategy and outcome of patients with synchronous anal canal and cervical cancer. A two-step treatment, including CRT and radical hysterectomy, is likely to be accepted as valid option.

Hearing Loss After Cisplatin-based Chemoradiotherapy for Locally Advanced Head and Neck Cancer: A Prospective Single-institution Study.

BACKGROUND/AIM: A single-institution prospective study was conducted to evaluate hearing loss rate after intensity modulated radiotherapy with concomitant cisplatin-based chemotherapy (CRT) for locally advanced head and neck cancer and identify cochlear dosimetric parameters associated with hearing loss risk. PATIENTS AND METHODS: Hearing assessment, patients' characteristics, tumor-related variables, and cochlear quantitative dosimetric factors for adults with locally advanced head and neck cancer treated with CRT were prospectively collected. Each patient repeated audiometry at baseline (pre-CRT), 1 month after CRT, and then every 3 to 6 months. For each cochlea minimum dose (Dmin), mean dose (Dmean), and maximum dose (Dmax) were extracted from treatment plans. Logistic analysis was used for multivariate modeling. The relation between cochlear dosimetric factors and significant hearing loss was also analyzed with receiver operating characteristic (ROC) curves. RESULTS: Between January 2016 and December 2018, 35 patients (70 cochleae) were included. Most patients (n=29; 82.9%) had primary cancer in a low-risk region (oral cavity, oropharynx, larynx). All patients completed the programmed CRT. During follow-up, significant hearing loss was recorded in 13 cases (37.1%). The ROC areas for significant hearing loss in relation to Dmin, Dmean, and Dmax were 0.70, 0.66, and 0.66, respectively. A dose-dependent relationship was noted between cochlear Dmin and significant hearing loss. CONCLUSION: Dmin <14.4 Gy is associated with reduced rates of significant hearing loss after concomitant cisplatin-based CRT in patients with locally advanced head and neck cancer.

Intensified Total Neoadjuvant Therapy Versus Intensified Concurrent Chemoradiotherapy in Locally Advanced Rectal Cancer: A Propensity Score Matching Analysis.

BACKGROUND/AIM: To compare clinical outcomes following intensified total neoadjuvant therapy (TNT) and intensified neoadjuvant chemoradiotherapy (CRT) in patients with locally advanced rectal cancer (LARC). PATIENTS AND METHODS: Of the 79 patients with LARC admitted to our department, 51 received intensified neoadjuvant CRT (CRT group) and 28 received intensified TNT (TNT group). Intensified TNT was defined as multi-agent chemotherapy, including FOLFOXIRI regimen plus bevacizumab (mutated Ras-BRAF) or panitumumab/cetuximab (wild-type Ras-BRAF) followed by oxaliplatin-5-fluorouracil-based CRT and surgery. Kaplan-Meier and Log rank test were used for survival analysis. Survival rates of the two groups were compared using propensity score matching. RESULTS: Data from 28 TNT patients and 28 CRT patients were analyzed after a 1:1 propensity matching with replacement. Kaplan-Meier curve showed that overall survival (OS), disease-free survival (DFS) and distant metastasis-free survival (DMFS) rates with TNT were comparable to those with CRT. The 5-year DMFS rates for TNT and CRT were 61.5% versus 63.0% (p=0.82), respectively. In the TNT group, 32.1% patients (n=9) achieved pathological complete response (pCR), whereas 21.4% patients (n=6) achieved pCR with CRT (p=0.37). CONCLUSION: Intensified TNT and CRT resulted in similar survival outcomes, while intensified TNT led to higher pCR, albeit not statistically significant.