Compare clinical efficacy and safety of neoadjuvant therapy and neoadjuvant chemoradiotherapy for locally advanced rectal cancer: Meta-analysis.

BACKGROUND: To compare the efficacy and safety of total neoadjuvant therapy (TNT) and neoadjuvant chemoradiotherapy (nCRT) in the treatment of middle and low locally advanced rectal cancer. Our study will systematically collect and integrate studies to evaluate the ability of these two treatments to improve tumor shrinkage rates, surgical resection rates, tumor-free survival, and severe adverse events. AIM: To provide clinicians and patients with more reliable treatment options to optimize treatment outcomes and quality of life for patients with locally advanced rectal cancer by comparing the advantages and disadvantages of the two treatment options. METHODS: A full search of all clinical studies on the effectiveness and safety of TNT and nCRT for treating locally advanced rectal cancer identified in Chinese (CNKI, Wanfang, China Biomedical Literature Database) and English (PubMed, Embase) databases was performed. Two system assessors independently screened the studies according to the inclusion and exclusion criteria. Quality evaluation and data extraction were performed for the included literature. We used RevMan 5.3 software to perform a meta-analysis of the pathologic complete response (pCR) rate, T stage degradation rate, resection 0 (R0) rate, anal grade 3/4 acute toxicity rate, perioperative complications, overall survival (OS), and disease-free survival (DFS) in the TNT and nCRT groups. RESULTS: Finally, 14 studies were included, six of which were randomized controlled studies. A total of 3797 patients were included, including 1865 in the TNT group and 1932 in the nCRT group. The two sets of baseline data were comparable. The results of the meta-analysis showed that the pCR rate [odds ratio (OR) = 1.57, 95% confidence interval (CI): 1.30-1.90, P < 0.00001], T stage degradation rate (OR = 2.16, 95%CI: 1.63-2.57, P < 0.00001), and R0 resection rate (OR = 1.42, 95%CI: 1.09-1.85, P = 0.009) were significantly greater in the nCRT group than in the nCRT group. There was no significant difference in the incidence of grade 3/4 acute toxicity or perioperative complications between the two groups. The 5-year OS [hazard ratio (HR) = 0.84, 95%CI: 0.69-1.02, P = 0.08] and DFS (HR = 0.94, 95%CI: 0.03-1.39, P = 0.74) of the TNT group were similar to those of the nCRT group. CONCLUSION: TNT has greater clinical efficacy and safety than nCRT in the treatment of locally advanced rectal cancer.

Identification of radiologic and clinicopathologic variables associated with tumor regression pattern and distribution of cancer cells after short-course radiotherapy and consolidation chemotherapy in patients with rectal cancer.

Background: Knowledge of the pattern of regression and distribution of residual tumor cells may assist in the selection of candidates for rectum-sparing strategies. Objective: To investigate and identify factors associated with tumor regression pattern and distribution of residual tumor cells. Methods: We conducted a prospective study of patients with T3/T4 N0/N+ adenocarcinoma of the middle and lower third of the rectum (≤10 cm) treated with radiotherapy (5×5 Gy) followed by 6 cycles of CAPOX chemotherapy. The pattern of tumor regression was classified as fragmented or solid. Microscopic intramural spread was measured. We used a model of distribution of residual tumor cells not yet applied to rectal cancer, defined as follows: type I (luminal), type II (invasive front), type III (concentric), and type IV (random). Results: Forty patients were included with a median age of 66 years; 23 (57.5%) were men. A fragmented pattern was identified in 18 patients (45.0%), and a solid pattern in 22 (55.0%). Microscopic intramural spread was identified in 25 patients (62.5%), extending from 1 to 18 mm (median, 4 mm). There were 14 cases (35.0%) of microscopic intramural spread ≥10 mm. All cases of fragmented regression pattern, except one, showed microscopic intramural spread. Within the fragmented pattern, microscopic intramural spread was 4-8 mm in 4 cases and ≥10 mm in the remaining cases. All cases of microscopic intramural spread ≥ 10 mm were within the fragmented pattern. Regarding the distribution pattern of residual tumor cells, 11 cases (31.5%) were classified as type I, 14 (40.0%) as type II, 10 (28.5%) as type III, and none as type IV. Carcinoembryonic antigen levels >5 ng/mL, downsizing <50%, residual mucosal abnormality >20 mm, and anatomopathologic lymph node involvement were significantly associated with the occurrence of fragmentation (P<0.05). Having received all 6 cycles of CAPOX chemotherapy and absence of microscopic intramural spread were significantly associated with the type I distribution pattern (P<0.05). Conclusion: The occurrence of a fragmented regression pattern is common, as is the presence of microscopic intramural spread. We could identify radiologic and clinicopathologic factors associated with the pattern of tumor regression and a type I distribution pattern.

Nomogram for predicting pathologic complete response following preoperative chemoradiotherapy in patients with esophageal squamous cell carcinoma.

Background: In patients with esophageal squamous cell carcinoma (ESCC), accurately predicting a pathologic complete response (pCR) to preoperative chemoradiotherapy (PCRT) has the potential to enable an active surveillance strategy without esophagectomy. We aimed to establish a reliable multiparameter nomogram model that combines tumor characteristics, imaging modalities, and hematologic markers to predict pCR in patients with ESCC who underwent PCRT and esophagectomy. Methods: We retrospectively reviewed the medical records of 457 patients with ESCC who received PCRT followed by esophagectomy between January 2005 and October 2020. The nomogram model was developed using logistic regression analysis with a training cohort and externally validated with a validation cohort. Results: In the training and validation cohorts, 44.2% (126/285) and 48.3% (83/172) of patients, respectively, achieved pCR after PCRT. The 5-year rates of overall survival, progression-free survival, and freedom from local progression in the training cohort were 51.6%, 48.5%, and 77.6%, respectively. The parameters included in the nomogram were histologic grade, clinical N stage, maximum standardized uptake value on positron emission tomography, and post-PCRT biopsy. Hematologic markers were significantly associated with survival outcomes but not with pCR. The area under the receiver operating characteristic curve of the nomogram was 0.717, 0.704, and 0.707 for the training cohort, internal validation cohort, and external validation cohort, respectively. Conclusion: Our nomogram model based on four parameters obtained from standard clinical practice demonstrated good performance in both the training and validation cohorts and could be useful to aid clinical decision-making to determine whether surgery or active surveillance strategy should be pursued.

Chemotherapy-Induced Peripheral Neuropathy in Patients With Gastroesophageal Cancer.

BACKGROUND: Chemotherapy for various stages of gastroesophageal cancer (GEC) is often neurotoxic. Chemotherapy-induced peripheral neuropathy (CIPN) impairs health-related quality of life (HRQoL). This study investigates the incidence and severity of CIPN and its association with HRQoL in patients with GEC. PATIENTS AND METHODS: Patients who received chemoradiotherapy or chemotherapy for GEC were identified from the Netherlands Cancer Registry. Patient-reported data (measured using the EORTC QLQ-CIPN20 and EORTC QLQ-C30) were collected through the Prospective Observational Cohort Study of Esophageal-Gastric Cancer Patients (POCOP) at baseline and at 3, 6, 9, 12, 18, and 24 months after treatment initiation. Linear mixed effects models were constructed to assess CIPN and the correlation between CIPN and HRQoL was analyzed using Spearman's correlation. RESULTS: A total of 2,135 patients were included (chemoradiotherapy: 1,593; chemotherapy with curative intent: 295; palliative chemotherapy: 247). In all 3 treatment groups, CIPN significantly increased during treatment (adjusted mean score of CIPN at 6 months: chemoradiotherapy, 8.3 [baseline: 5.5]; chemotherapy with curative intent, 16.0 [baseline: 5.6]; palliative therapy, 25.4 [baseline: 10.7]). For chemoradiotherapy, the adjusted mean score continued to increase after treatment (24 months: 11.2). For chemotherapy with curative intent and palliative therapy, the adjusted mean score of CIPN decreased after treatment but did not return to baseline values. CIPN was negatively correlated with HRQoL in all treatment groups, although significance and strength of the correlation differed over time. CONCLUSIONS: Because of the poor prognosis of GEC, it is essential to consider side effects of (neurotoxic) treatment. The high prevalence and association with HRQoL indicate the need for early recognition of CIPN.

Comparative effectiveness of neoadjuvant chemotherapy plus surgery versus concurrent chemoradiotherapy in stages IB2 to IIB of cervical cancer: a meta-analysis.

Objectives: To assess the comparative efficacy of neoadjuvant chemotherapy followed by surgery (NACT+S) versus concurrent chemoradiotherapy (CCRT) for patients with cervical cancer stages IB2 to IIB. Method: An exhaustive literature search was conducted up to November 2023 in databases including PubMed, Embase, Web of Science, and the Cochrane Library, focusing on disease-free survival (DFS) and overall survival (OS). Data were analyzed using STATA version 15. Results: The meta-analysis included data from two randomized controlled trials and eight retrospective cohort studies, totaling 2,879 patients with stages IB2 to IIB cervical cancer. Pooled data showed no significant difference in OS [hazard ratio (HR) 0.71, 95% confidence interval (CI): 0.51 to 1.00, p = 0.052] and DFS (HR 0.65, 95% CI: 0.38 to 1.14, p = 0.132) between NACT+S and CCRT. Subgroup analysis revealed that NACT+S provided a better OS in Asian populations, retrospective cohort studies, TP regimen chemotherapy, and multivariate analysis. Conclusion: The findings indicate that CCRT and NACT+S are comparably effective for treating cervical cancer stages IB2 to IIB. Notably, in specific subgroups such as Asian patients and those receiving the TP regimen, NACT+S appears to enhance OS.

Prognostic Impact of Inflammation-Based Factors in Patients with Esophageal Squamous Cell Carcinoma Achieving Pathological Complete Response After Neoadjuvant Chemoradiotherapy Followed by Surgery.

BACKGROUND: Patients achieving pathological complete response (pCR) post-neoadjuvant chemoradiotherapy (nCRT) and surgery for locally advanced esophageal squamous cell carcinoma (ESCC) have a favorable prognosis. However, recurrence occurs in approximately 20-30% of all patients, with few studies evaluating their prognostic factors. We identified these prognostic factors, including inflammation-based markers, in patients with ESCC showing pCR after nCRT and surgery. PATIENTS AND METHODS: Patients with ESCC undergoing esophagectomy post-nCRT (January 2007-August 2017) were studied. Survival analysis evaluated 5-year overall (OS) and recurrence-free survival (RFS). Risk factors, including inflammation factors, neutrophil-to-lymphocyte ratio, and platelet-to-lymphocyte ratio (PLR), were analyzed using Cox-proportional hazards model. RESULTS: Overall, 123patients participated herein. After a median follow-up duration of 67 months (44-86 months), 17 patients (12.3%) had recurrent disease. The 5-year OS and RFS rates were 71.6% and 68.0%, respectively. In the multivariable analysis, older age ( ≥ 60 years) [hazard ratio (HR) 3.228, 95% confidence interval (CI) 1.478-7.048, p = 0.003], higher pretreatment T stage (≥ T3; HR 2.563, 95% CI 1.335-4.922, p = 0.005), nonapplication of induction chemotherapy (HR 2.389, 95% CI 1.184-4.824, p = 0.015), and higher post-nCRT PLR (≥ 184.2; HR 2.896, 95% CI 1.547-5.420, p = 0.001) were poor independent prognostic factors for 5-year RFS. The patient group with three to four identified factors with poor outcomes exhibited a 5-year RFS rate of 46.2%. CONCLUSIONS: Significant prognostic factors include higher post-nCRT PLR, older age, higher clinical T stage, and nonapplication of induction chemotherapy. Identifying higher recurrence risk patients is crucial for tailored follow-up and treatment.

Vocal Cord Function Return After Larynx Preservation is Associated With Recurrence-Free Probability.

OBJECTIVES: Vocal cord fixation is one of the main upstaging features of laryngeal cancer. In our previously conducted retrospective study, vocal cord (VC) mobility restoration after chemoradiotherapy was a favorable prognostic variable. In this prospective study, we examined the significance of VC mobility restoration after definitive treatment as a prognostic variable. METHODS: In this prospective cohort study, we enrolled 30 patients with squamous cell carcinoma of the larynx with VC impairment/fixation (T2/3, T4a) who underwent definitive chemoradiotherapy with complete response. Video laryngoscopy before and at 3 months after treatment was used to evaluate VC mobility. The primary endpoint of the study was the local recurrence-free probability. Secondary endpoints included recurrence-free probability, disease-specific survival (DSS), and overall survival (OS). RESULTS: The median age of patients was 62 years (IQR 54-67). The primary subsites were the glottis (n = 13) and supraglottis (n = 14). After treatment, 18 (60%) patients had a full recovery of VC mobility, and 12 (40%) patients' VCs were fixed or impaired. Five-year local recurrence-free probability was worse in the VC-impaired group compared to a group with restored VC mobility (46% vs. 85%, p = 0.012). Recurrence-free probability, OS, and DSS differences were not statistically significant in both groups. VC mobility restoration predicted local recurrence-free probability on univariable analysis (HR 6.15, 95% CI 1.23-30.6). CONCLUSION: In this prospective study, we show that the absence of VC mobility restoration is associated with worse local recurrence-free probability after definitive laryngeal preservation treatment. Patients with persistent vocal cord immobility warrant closer follow-up to detect recurrence early. LEVEL OF EVIDENCE: III Laryngoscope, 2024.

Clinical outcomes of pelvic bone marrow sparing radiotherapy for cervical cancer: A systematic review and meta-analysis of randomised controlled trials.

Background: Concurrent chemoradiotherapy (CRT) is the standard treatment for locally advanced cervical cancer. We investigated how additional bone marrow sparing (BMS) affects the clinical outcomes. Methods: We queried MEDLINE, Embase, Web of Science Core Collection, Google Scholar, Sinomed, CNKI, and Wanfang databases for articles published in English or Chinese between 2010/01/01 and 2023/10/31. Full-text manuscripts of prospective, randomised trials on BMS in cervical cancer patients treated with definitive or postoperative CRT were included. Risk of bias (RoB) was assessed using Cochrane Collaboration's RoB tool. Random-effects models were used for the meta-analysis. Results: A total of 17 trials encompassing 1297 patients were included. The majority were single-centre trials (n = 1268) performed in China (n = 1128). Most trials used CT-based anatomical BMS (n = 1076). There was a comparable representation of trials in the definitive (n = 655) and postoperative (n = 582) settings, and the remaining trials included both.Twelve studies reported data on G ≥ 3 (n = 782) and G ≥ 2 (n = 754) haematologic adverse events. Both G ≥ 3 (OR 0.39; 95 % CI 0.28-0.55; p < 0.001) and G ≥ 2 (OR 0.29; 95 % CI 0.18-0.46; p < 0.001) toxicity were significantly lowered, favouring BMS. Seven studies (n = 635) reported data on chemotherapy interruptions, defined as receiving less than five cycles of cisplatin, which were significantly less frequent in patients treated with BMS (OR 0.44; 95 % CI 0.24-0.81; p = 0.016). There was no evidence of increased gastrointestinal or genitourinary toxicity.There were no signs of significant heterogeneity. Four studies were assessed as high RoB; sensitivity analyses excluding these provided comparable results for main outcomes. The main limitations include heterogeneity in BMS methodology between studies, low representation of populations most affected by cervical cancer, and insufficient data to assess survival outcomes. Conclusions: The addition of BMS to definitive CRT in cervical cancer patients decreases hematologic toxicity and the frequency of interruptions in concurrent chemotherapy. However, data are insufficient to verify the impact on survival and disease control.

Impact of the number of lymph node dissections and a novel risk stratification on the prognosis in elderly locally advanced esophageal adenocarcinoma.

Background: Elderly patients with locally advanced esophageal adenocarcinoma (EAC) have a poor prognosis. The purpose of this study was to identify prognostic factors and construct a risk stratification for assessing the prognosis of elderly (≥ 70 years old) EAC patients who receiving neoadjuvant chemoradiotherapy (NCRT) and esophagectomy. Methods: A total of 688 patients with non-metastatic locally advanced EAC who underwent NCRT and esophagectomy were selected from the Surveillance Epidemiology and End Results (SEER) database. Multivariable Cox analysis was used to identify prognostic factors of overall survival (OS). Restricted Cubic Splines (RCS) was used to examine the linear relationship between the number of lymph node dissection (LND) and OS. Result: RCS showed a linear relationship between LND and OS (P = 0.690). As the number of LND increased, the risk of death decreased. Multivariable analysis demonstrated that LND > 23, grade III/IV, and regional node positive were independent prognostic factors. Subgroup analysis indicated that enlarged lymph node dissection (LND > 23) did not improve OS in patients with grade I/II or T1-2 stage, whereas enlarged lymph node dissection significantly improved OS in patients with grade III/IV or T3-4 stage. Furthermore, we constructed a novel risk score based on LND, grade, and regional node status, which stratified patients into low-, medium-, and high-risk groups. Patients in the high-risk group (risk score = 3) had a worse prognosis. Conclusions: Enlarged lymph node dissection (LND > 23) improved OS in patients with grade III/IV or T3-4 stage. Moreover, a novel risk score was constructed, which facilitated risk stratification and postoperative surveillance in elderly EAC patients.

HPV status and immunohistochemical analysis of p16, p53 and PD­L1 expression as prognostic biomarkers in patients with squamous cell anal cancer receiving definitive radiotherapy/chemoradiotherapy.

Anal squamous cell carcinoma (SCC) treated with definitive radiotherapy (RT)/chemoradiotherapy (CRT) has shown high success rates, yet challenges such as treatment resistance and recurrence persist. The present study aimed to investigate the associations between immunohistochemical (IHC) evaluation, treatment response and prognosis in anal SCC. A retrospective cohort analysis included 42 patients with anal SCC treated at a single institution between 2006 and 2022. Human papillomavirus (HPV) status was determined, and the IHC analysis of p16, p53 and PD-L1 expression was conducted using formalin-fixed, paraffin-embedded biopsies. A complete response to RT/CRT was observed in 71.4% of patients. Recurrence occurred in 38.1% of cases, of which 7.1% had local-regional recurrence (LRR), 14.3% had distant recurrence (DR), and 16.7% had both LRR and DR. HPV positivity (71.4%) was significantly associated with p16 positivity. Lack of complete response was associated with HPV-negative status, p16-negative status, increased recurrence and DR. In addition, recurrence was significantly associated with p53-positive status, and p53 positivity was significantly associated with increased LRR. PD-L1 positivity, defined as a combined positive score (CPS) ≥1% was found in 73.8% of the patients, and exhibited significant associations with HPV positivity and p16 positivity. PD-L1 CPS ≥ 1% was also associated with an increased LRR. Univariate analysis revealed that age <65 years, a complete response and HPV positivity were associated with increased 5-year overall survival (OS), while a complete response, HPV positivity and p53-negative status were associated with increased 5-year disease-free survival (DFS). Multivariate analysis identified that age <65 years and HPV positivity are independent prognostic factors for 5-year OS, and a complete response and p53-negative status are independent prognostic factors for 5-year DFS. In conclusion, these findings suggust that the identification of HPV status and poor prognostic biomarkers at diagnosis may be used to guide personalized treatment strategies, with the combination of immunotherapy with standard CRT potentially providing improved outcomes.

Definitive chemoradiotherapy for a patient with anal cancer after renal transplantation.

Patients after renal transplantation are susceptible to secondary malignancies, including anal squamous cell carcinoma. Chemoradiotherapy is the standard treatment for anal squamous cell carcinoma; however, typical irradiation fields for anal cancer encompass a transplanted kidney located in the right iliac fossa, which causes complete renal dysfunction. Thus, typical irradiation fields are not feasible for this population. Additionally, standard concurrent chemotherapy demonstrates nephrotoxicity. Here, we report a case of modified definitive chemoradiotherapy for a 40-year-old patient with locally advanced perianal squamous cell carcinoma after renal transplantation whose abdominoperineal resection was difficult because of a history of repeated open surgeries and long-term steroids. We modified the cranial side of the elective nodal irradiation fields in this case to spare the transplanted kidney, considering the lymph chains of the perianal tumor. We then used continuous 5-fluorouracil to avoid nephrotoxicity of mitomycin C, considering his life expectancy. Modified definitive chemoradiotherapy achieved complete remission with expected toxicities. Now, approximately five years after the procedure, the patient remains disease-free, preserving anal and renal function. Definitive chemoradiotherapy using modified irradiation fields and chemotherapy may be an option for patients with anal squamous cell carcinoma after renal transplantation.

Preoperative sequential chemotherapy and hypofractionated radiotherapy combined with comprehensive surgical resection for high-risk soft tissue sarcomas: a retrospective study.

Introduction: The management of soft tissue sarcomas presents considerable therapeutic challenges. This study was designed to assess the efficacy of neoadjuvant sequential chemotherapy and hypofractionated radiotherapy in conjunction with extensive surgical resection for the treatment of high-risk soft tissue sarcomas. Materials and methods: We performed a retrospective review of 31 high-risk soft tissue sarcoma patients treated at our institution from June 2021 to June 2023. The cohort consisted of 21 males and 10 females with a mean age of 55.7 years and included both initial and recurrent disease presentations. Our treatment regimen comprised two to three cycles of neoadjuvant chemotherapy coupled with hypofractionated radiotherapy, delivered at 5 Gy per fraction to a total dose of 25-35 Gy across 5-7 days, prior to surgical resection aimed at achieving wide margins. Data collection was systematic, covering surgical outcomes, chemoradiotherapy-related complications, and prognostic factors. Results: All patients completed the prescribed course of neoadjuvant chemoradiotherapy. 29% patients experienced grade 3+ chemotherapy toxicity, necessitating a reduction or interruption in their chemotherapy regimen. Limb preservation was accomplished in 30 patients finally. Response evaluation using RECIST 1.1 criteria post-neoadjuvant therapy revealed 9.7% with PD, 58.1% with SD, 29% with a PR, and 3.2% with a CR, culminating in an ORR of 32.2%. Postoperative complications included superficial wound infections in four patients and deep incisional infections in another four. 6 patients had developed metastasis, and 3 patients were still alive. Two experienced local recurrence. One-year DFS was 79.3%, with a one-year OS rate of 89.6%. Conclusion: Neoadjuvant sequential chemotherapy and hypofractionated radiotherapy followed by extensive surgical resection represents an effective treatment paradigm for high-risk soft tissue sarcomas. This multimodal approach not only facilitates tumor reduction but also significantly reduces the risks of local recurrence and distant metastasis.

Epidermal growth factor receptor­targeted antibody nimotuzumab combined with chemoradiotherapy improves survival in patients with locally advanced head and neck squamous cell carcinoma: a propensity score matching real-world study.

Patients with locally advanced head and neck squamous cell carcinoma (LA-HNSCC) have poor survival outcomes. The real-world efficacy of nimotuzumab plus intensity modulated radiotherapy (IMRT)-based chemoradiotherapy in patients with LA-HNSCC remains unclear. A total of 25,442 HNSCC patients were screened, and 612 patients were matched by propensity score matching (PSM) (1:1). PSM was utilized to balance known confounding factors. Patients who completed at least five doses of nimotuzumab were identified as study group. The primary end point was 3-year overall survival (OS) rate. Log-rank test examined the difference between two survival curves and Cloglog transformation test was performed to compare survival at a fixed time point. The median follow-up time was 54.2 (95% confidence interval [CI]: 52.7-55.9) months. The study group was associated with improved OS (hazard ratio [HR] = 0.75, 95% CI: 0.57-0.99, p = 0.038) and progression-free survival (PFS) (HR = 0.74, 95% CI: 0.58-0.96, p = 0.021). Subgroup analysis revealed that aged 50-60 year, IV, N2, radiotherapy dose ≥ 60 Gy, without previous surgery, and neoadjuvant therapy have a trend of survival benefit with nimotuzumab. Nimotuzumab showed favorable safety, only 0.2% had nimotuzumab-related severe adverse events. Our study indicated the nimotuzumab plus chemoradiotherapy provides survival benefits and safety for LA-HNSCC patients in an IMRT era.

Clinical Outcomes in T4 and/or N2 Rectal Cancer Treated With Neoadjuvant Chemoradiotherapy: A Retrospective Study.

INTRODUCTION: Total neoadjuvant therapy (TNT) in the management of locally advanced rectal cancer (LARC) did not show survival benefit over the standard long course chemoradiotherapy. Trials of TNT did not address the impact of each risk feature in isolation from other high-risk features. METHODOLOGY: In this retrospective study, we describe the clinical outcomes of patients with T4 and/or N2 rectal adenocarcinoma who were treated with chemoradiotherapy followed by total mesorectal excision (TME). After obtaining the local regulatory approvals, demographic and clinical data were collected for patients in Manitoba between January 2007 and December 2019. RESULTS: The cohort included 331 patients. 61 patients had T4-only disease and 218 had N2-only disease. Mean age was 59.65 years. 74.3% received adjuvant chemotherapy (ACT), but only 56.5% completed the planned course. R0 resection was achieved in 93.4% of patients (78.7% and 97.2% in T4 and N2, respectively). Median follow up was 4.93 years. 3-year overall recurrence rate was 29%. 3-year locoregional recurrence (LRR) rate was 8% (16% and 6% in T4 and N2, respectively). 3-year overall survival (OS) rate was 84% in the whole cohort (72.6% and 87.1% in T4 and N2, respectively). Incomplete surgical resection was a poor prognostic factor for both OS and LRR. ACT was associated with a survival benefit in the whole cohort (P = .001) and in the N2 sub-cohort (P = 003) but there was no survival benefit observed in T4 sub-cohort. ACT did not have an impact on LRR. CONCLUSIONS: Achieving R0 resection in LARC with neoadjuvant therapy improves recurrence and survival rates. T4 disease carries a worse clinical outcome than N2 and consideration should be given to upstage T4 to stage III. Different high-risk features in LARC predict different clinical outcomes. In the era of TNT, personalization of treatment strategy based on these factors could potentially improve outcomes.

Results of the study of factors predicting the risk of the development of grade III radiation-induced mucositis during radiation or chemoradiation therapy in patients with oral cavity and oropharynx cancer.

BACKGROUND: Today, a number of methods and ways of prevention and treatment of radiation- -induced mucositis of the oral cavity and oropharynx have been developed, but the represented approaches are still not effective enough. Therefore, to increase the effectiveness of the prevention and treatment of radiation-induced mucositis, it is necessary to approach this problem comprehensively and individually, and to evaluate the factors affecting the development of mucositis. MATERIALS AND METHODS: In this single-center prospective controlled non-randomized clinical trial, the results of clinical observation of the development of complications of radiation and chemoradiation therapy in 105 patients with a newly diagnosed squamous cell cancer of the oral cavity and oropharynx were analyzed. Factors affecting the risk of the development of grade III radiation-induced mucositis including the age, gender of the patients, their general condition before the treatment according to World Health Organisation scales, type of the treatment and its doses, additional use of immunotherapy with alpha/beta defensins, characteristic signs of the tumor process and all indices of the immune status of the patients before the treatment have been analyzed. RESULTS: The method of construction and analysis of one-factor logistic regression models, where 24 indices were analyzed as factorial features, showed that the reduction of the risk of the development of grade III radiation-induced mucositis is predicted by several factors: immunotherapy, gender, serum concentrations of IgG and IgA. A decrease (P < 0.001) in the risk of the development of grade III radiation-induced mucositis was revealed if immunotherapy with alpha/beta defensins (with a total dose of 40 mg) was included into the treatment scheme (relative odds (RO) 0.05; 95% reference interval (RI) 0.02-0.18), in comparison with patients of the groups where it was not present or this immune agent was used in a total dose of 60 mg (P = 0.001, RO 0.06; 95% RI 0.01-0.30). The next factorial sign was gender, namely the risk of the development of grade III radiation-induced mucositis was lower for men (P = 0.003; RO 0.15; 95% RI 0.04-0.53) compared to women. An increase (P = 0.024) in the risk of the development of grade III radiation-induced mucositis with an increase in the initial level of IgG serum concentration was revealed, (RO 1.08; 95% RI 1.01-1.16) for each 1 mg/mL, as well as an increase (P = 0.044) in the possibility of the appearance of grade III radiation-induced mucositis with an increase in the serum concentration of IgA (RO 1.23; 95% RI 1.01-1.50) for every 1 mg/mL also before the beginning of the treatment. Multifactorial analysis has also confirmed that the risk of the development of grade III radiation-induced mucositis increases (P = 0.008) with a high serum IgG concentration before the treatment or with an increase in this index during therapy (RO 1.13; 95% RI 1.03-1.09) for every 1 mg/mL (when standardized by other risk factors). It was determined that when standardizing according to other factors (gender, IgG level), the risk of the development of grade III radiation-induced mucositis in the use of the immune agent alpha/beta defensins in a total dose of 40 mg per course decreases (P < 0.001; RO 0.08; 95% RI 0.02-0.27) compared to patients with oral cavity and oropharynx cancer who were not treated with immunotherapy. The risk of the development of grade III radiation-induced mucositis also decreases (P = 0.001) in the use of immunotherapy in a higher dose, i.e. 60 mg per course (RO 0.03; 95% RI 0.004-0.24 compared to patients whose treatment did not include immunotherapy (when standardized by other factors). CONCLUSION: As a result of this controlled clinical study, some factors were determined in addition to the radiation as those affecting the risk of the development of grade III radiation-induced mucositis in patients with oral cavity and oropharynx cancer during special treatment. These factors comprise the inclusion of immunotherapy with alpha/beta defensins into the specific treatment; gender, and baseline levels of serum IgG and IgA concentrations suggest a pattern in which the higher the serum IgG and IgA concentrations are before the start of the treatment, the greater is the likelihood of severe radiation-induced mucositis degree during special therapy. The results of the study of humoral state of the immune system in patients with oral cavity and oropharynx cancer before the beginning of chemoradiation therapy can be used as prognostic risk factors for the development of severe gamma-irradiation-induced mucositis of the oropharyngeal area, as well as an indication for the use of immunotherapeutic agents (in particular, alpha/beta defensins) that are able to polarize the immune response towards type 1 T-helpers through their immunomodulatory action.

Impact of relative cisplatin dose to skeletal muscle mass on adverse events in patients with head and neck cancer undergoing chemoradiotherapy.

BACKGROUND: Chemoradiotherapy (CRT) with high-dose cisplatin (CDDP) is the standard treatment for locally advanced head and neck squamous cell carcinoma (HNSCC). Although dosing is based on body surface area (BSA), some patients experience CDDP-related adverse events (AEs). We aimed to evaluate the impact of relative CDDP dose to skeletal muscle mass (SMM) on chemotherapy-associated AEs in patients with HNSCC undergoing CRT with high-dose CDDP. MATERIALS AND METHODS: We retrospectively analyzed data of patients who underwent CRT with high-dose CDDP (80-100 mg/m2, triweekly) between 2010 and 2023. SMM was measured as the cross-sectional muscle area at the third cervical vertebra (C3-SMM) using computed tomography; the skeletal muscle index (SMI) was defined as SMM normalized by squared height. The CDDP index was defined as the prescribed CDDP dose divided by SMI. CDDP-related AEs were assessed during the first cycle using Common Terminology Criteria for Adverse Events v5.0. RESULTS: Overall, 306 patients were identified. The CDDP index cutoff value best associated with grade ≥ 3 AEs was 10.312. Grade ≥ 3 hematological toxicities exhibited stronger association with high CDDP index value than with low CDDP index value (26.9% vs 16.3%, P = .033). Multivariate analysis revealed that high CDDP index value and creatinine clearance < 70 mL/minute were predictive factors for grade ≥ 3 AEs (odds ratio [OR] 2.55, P = .008; OR 3.68, P = .002, respectively). CONCLUSION: The CDDP index based on C3-SMM was an independent predictive factor for grade ≥ 3 CDDP-related AEs. C3-SMM is potentially more useful than BSA for determining the optimal CDDP dose in patients with HNSCC.

Predicting the response to neoadjuvant chemoradiation for rectal cancer using nomograms based on MRI tumour regression grade.

PURPOSE: This study aimed to develop nomograms that combine clinical factors and MRI tumour regression grade to predict the pathological response of mid-low locally advanced rectal cancer to neoadjuvant chemoradiotherapy. METHODS: The retrospective study included 204 patients who underwent neoadjuvant chemoradiotherapy and surgery between January 2013 and December 2021. Based on pathological tumour regression grade, patients were categorized into four groups: complete pathological response (pCR, n=45), non-complete pathological response (non-pCR; n=159), good pathological response (pGR, n=119), and non-good pathological response (non-pGR, n=85). The patients were divided into a training set and a validation set in a 7:3 ratio. Based on the results of univariate and multivariate analyses in the training set, two nomograms were respectively constructed to predict complete and good pathological responses. Subsequently, these predictive models underwent validation in the independent validation set. The prognostic performances of the models were evaluated using the area under the curve (AUC). RESULTS: The nomogram predicting complete pathological response incorporates tumour length, post-treatment mesorectal fascia involvement, white blood cell count, and MRI tumour regression grade. It yielded an AUC of 0.787 in the training set and 0.716 in the validation set, surpassing the performance of the model relying solely on MRI tumour regression grade (AUCs of 0.649 and 0.530, respectively). Similarly, the nomogram predicting good pathological response includes the distance of the tumour's lower border from the anal verge, post-treatment mesorectal fascia involvement, platelet/lymphocyte ratio, and MRI tumour regression grade. It achieved an AUC of 0.754 in the training set and 0.719 in the validation set, outperforming the model using MRI tumour regression grade alone (AUCs of 0.629 and 0.638, respectively). CONCLUSIONS: Nomograms combining MRI tumour regression grade with clinical factors may be useful for predicting pathological response of mid-low locally advanced rectal cancer to neoadjuvant chemoradiotherapy. The proposed models could be applied in clinical practice after validation in large samples.

Textbook outcome in low rectal cancer after neoadjuvant chemoradiotherapy: Post hoc analysis of the LASRE randomized clinical trial.

BACKGROUND: Textbook outcome has been incorporated into quality assessment measures in various oncological settings; however, it has not been applied to patients with low rectal cancer after neoadjuvant chemoradiotherapy (nCRT). This study aimed to examine the prevalence and predictors of achieving a textbook outcome in patients undergoing surgical resection of low rectal cancer after nCRT. PATIENTS AND METHODS: This study was a post hoc subgroup analysis of the prospective multicentric LASRE trial, which specifically enrolled patients with rectal cancer located within 5 cm from the dentate line at diagnosis, tumors with diameters less than 6 cm, and patients who underwent radical laparoscopic or open resection. A total of 597 patients who had clinically staged cT3-4aN0-2M0 tumors with diameters less than 6 cm and who underwent neoadjuvant chemoradiotherapy followed by radical resection were included. RESULTS: Textbook outcome was achieved in 60.0 % of patients. Multivariate logistic regression analysis revealed that body mass index >25 kg/m2 (OR = 0.594, P = 0.01), tumor distance from the anal verge >40 mm (OR = 5.518, P < 0.001), operative time >202 min (OR = 0.675, P = 0.04), and laparoscopic approach (OR = 1.497, P = 0.04) were independently predictive factors for the achievement of a textbook outcome in low rectal cancer patients undergoing nCRT and radical resection. A predictive nomogram for achieving a textbook outcome was constructed, yielding a C-index of 0.727. CONCLUSIONS: Laparoscopic resection exhibited promising potential in improving the probability of achieving a textbook outcome.

The effect of incidental dose to pelvic nodes in bladder-only irradiation in the era of IMRT: a dosimetric study.

PURPOSE: While three-dimensional radiotherapy (RT) causes high incidental nodal doses in bladder-only irradiation for muscle-invasive bladder cancer (MIBC), the impact on pelvic lymphatics is unclear in the era of intensity-modulated RT (IMRT). This study evaluates incidental doses to pelvic lymphatics in MIBC patients treated with IMRT. METHODS: The data of 40 MIBC patients treated with bladder-only IMRT and concurrent chemotherapy were retrospectively evaluated. The pelvic lymphatics were contoured on initial simulation images and incidental nodal doses were evaluated. The Statistical Package for the Social Sciences (SPSS) version 23.0 (IBM, Armonk, NY, USA) was used for statistics. RESULTS: Median RT dose to the bladder was 60 Gy in 30 fractions. In dosimetric analysis, median values of mean dose (Dmean) of the obturator, presacral, external iliac, internal iliac, and distal common iliac lymphatics were 33 Gy (range 4-50 Gy), 3 Gy (range 1-28 Gy), 9.5 Gy (range 3-41 Gy), 7.5 Gy (range 2-14 Gy), and 1 Gy (range 0-15 Gy), respectively. The Dmean of the obturator lymphatics was significantly higher (p < 0.001) and the Dmean of the distal common iliac lymphatics was significantly lower (p < 0.001) than all remaining lymphatic stations. The Dmean of the external iliac lymphatics was significantly higher than that of the presacral lymphatics (p < 0.001), but the difference with the internal iliac lymphatics was not statistically significant (p = 0.563). CONCLUSION: The incidental nodal doses with bladder-only IMRT are heterogeneous and remain below the generally accepted doses for microscopic disease eradication for bladder cancer.

Clinical significance of the maximum standardized uptake value on positron emission tomography to predict treatment response and outcomes in patients with rectal cancer undergoing neoadjuvant chemoradiotherapy.

PURPOSES: The association between the reduction rate of the maximum standardized uptake value (SUVmax) on positron emission tomography (PET) during neoadjuvant chemoradiotherapy (NACRT) and the prognosis in patients with locally advanced rectal cancer is unknown. METHODS: We retrospectively analyzed 62 patients with locally advanced rectal cancer who underwent curative surgery after NACRT at Kobe University between 2008 and 2021. The SUVmax reduction rate was calculated from preoperative and postoperative PET scans, and its association with the prognosis was investigated. RESULTS: The cutoff value for SUVmax reduction rate was 61.5%. Twenty patients had an SUVmax reduction rate > 61.5% (SUV responder group) and 38 patients had an SUVmax reduction rate ≤ 61.5% (SUV nonresponder group). Regarding pathological outcomes, the rate of a good histological response was significantly higher in the SUV responder group than in the SUV nonresponder group (80.0% vs. 21.1%, p < 0.001). Both the overall (OS) and relapse-free survival (RFS) rates were significantly better in the SUV responder group than in the SUV nonresponder group (OS, p = 0.035; RFS, p = 0.019). In the SUV responder group, only 1 case of recurrence was observed, with a median follow-up period of 56 months. CONCLUSION: The rate of SUVmax reduction during NACRT might predict the long-term prognosis of patients with locally advanced rectal cancer.