Cystine and theanine for chemoradiotherapy-induced esophagitis in non-small cell lung cancer: a prospective observational study.

PURPOSE: Although several potential radioprotectants have been explored, radiation esophagitis is still difficult to control. Further development of supportive therapies is required. Our purpose was to investigate the efficacy and safety of cystine and theanine for esophagitis in non-small cell lung cancer (NSCLC) patients undergoing chemoradiotherapy (CRT). METHODS: This study is a prospective observational study. The participants were recruited from unresectable locally advanced NSCLC who had scheduled to receive weekly paclitaxel or nab-paclitaxel/carboplatin plus radiation therapy (60 Gy in 30 fractions) for 6 weeks. They took an oral amino acid supplement containing 700 mg cystine and 280 mg theanine once daily regardless of CRT timing from the start of CRT until completion. The primary endpoint was the incidence of any grade esophagitis. The secondary endpoints were quality of life (QoL) and adverse events (AEs). RESULTS: A total of 26 patients were evaluated. All participants completed 60 Gy of RT in 30 fractions. The overall incidence of esophagitis was 73%; however, no ≥ grade 3 was reported. There were no AEs likely to be related to cystine and theanine. The mean EuroQoL 5-Dimension 5-Level health index score before and after chemoradiotherapy was 0.952 ± 0.0591 and 0.952 ± 0.0515 (P = 0.89), and the mean Visual Analogue Scale scores before and after treatment were 67.9 ± 15.4 and 79.4 ± 13.2 (P = 0.0047), respectively. CONCLUSION: Our study showed no severe esophagitis, any AEs, nor QoL decrease in NSCLC patients receiving CRT. Cystine and theanine are potentially effective to reduce severe CRT-induced esophagitis. TRIAL REGISTRATION: UMIN000052622, 26 October 2023, retrospectively registered.

Exosome Therapy for a Nonhealing Scalp Wound Following Chemoradiation and Surgical Therapy.

This case report describes the safety and utility of a noninvasive therapy, Purified Exosome Product (PEP), for poorly healing scalp wounds in the setting of prior chemoradiation and surgery. A man in his 60s with a history of high-grade angiosarcoma of the right temporoparietal scalp reconstruction had a 1-year history of 2 nonhealing scalp wounds after neoadjuvant chemotherapy followed by concurrent chemoradiation therapy, wide local excision, and latissimus dorsi free flap and split-thickness skin graft. The patient underwent débridement followed by 4 collagen (Bellafill)-PEP and 4 fibrin (Tisseel)-PEP applications during 7 months in 2022. Photographs of the area of exposed bone of the temporoparietal wound were measured and standardized by ImageJ open-source software. The frontal wound was not routinely measured and therefore was qualitatively assessed by reviewing photographs over time. The frontal wound completely healed, and the temporoparietal wound showed a 96% decrease in overall size. The patient had no adverse effects of treatment and continues to demonstrate ongoing healing. This case exhibits the safety and utility of topical PEP therapy for noninvasive treatment of poorly healing scalp wounds and offers the potential for an alternative treatment of patients who are poor candidates for additional surgical intervention.

The efficacy and safety of neoadjuvant chemoradiotherapy combined with immunotherapy for locally advanced rectal cancer patients: a systematic review.

Background: Several studies have explored the effectiveness of PD-1/PD-L1 inhibitors combined with neoadjuvant chemoradiotherapy (nCRT) in the treatment of locally advanced rectal cancer(LARC), particularly in microsatellite stable(MSS) or mismatch repair proficient(pMMR) LARC patients. We undertook a single-arm systematic review to comprehensively evaluate the advantages and potential risks associated with the use of PD-1/PD-L1 inhibitors in conjunction with nCRT for patients diagnosed with locally advanced rectal cancer. Methods: The PubMed, Embase, Cochrane Library, ClinicalTrials.gov, ASCO and ESMO were searched for related studies. The main outcomes were pathologic complete response (pCR), major pathological response (MPR), anal preservation, and adverse effects (AEs). Results: Fourteen articles including 533 locally advanced rectal cancer (LARC) patients were analyzed. The pooled pCR, MPR, and anal preservation rates were 36%, 66% and 86%. Grade ≥3 adverse events occurred in 20%. Subgroup analysis showed that; dMMR/MSI-H had a pooled pCR (100%) and MPR (100%), pMMR/MSS had a pooled pCR (38%) and MPR (60%); the short-course radiotherapy and long-course radiotherapy had pooled pCR rates of 51% and 30%, respectively. The rates of pCR for the concurrent and sequential immuno-chemoradiotherapy subgroups at 30% and 40%, mirroring pCR rates for the PD-L1 and PD-1 inhibitor subgroups were 32% and 40%, respectively. Conclusion: In cases of locally advanced rectal cancer, PD-1/PD-L1 inhibitors combined with neoadjuvant chemoradiotherapy have shown promising response rates and acceptable toxicity profiles. PD-1/PD-L1 inhibitors combined with neoadjuvant chemoradiotherapy hence has a positive outcome even in MSS LARC patients. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/#myprospero, identifier CRD42023465380.

Predicting treatment response in multicenter non-small cell lung cancer patients based on federated learning.

BACKGROUND: Multicenter non-small cell lung cancer (NSCLC) patient data is information-rich. However, its direct integration becomes exceptionally challenging due to constraints involving different healthcare organizations and regulations. Traditional centralized machine learning methods require centralizing these sensitive medical data for training, posing risks of patient privacy leakage and data security issues. In this context, federated learning (FL) has attracted much attention as a distributed machine learning framework. It effectively addresses this contradiction by preserving data locally, conducting local model training, and aggregating model parameters. This approach enables the utilization of multicenter data with maximum benefit while ensuring privacy safeguards. Based on pre-radiotherapy planning target volume images of NSCLC patients, a multicenter treatment response prediction model is designed by FL for predicting the probability of remission of NSCLC patients. This approach ensures medical data privacy, high prediction accuracy and computing efficiency, offering valuable insights for clinical decision-making. METHODS: We retrospectively collected CT images from 245 NSCLC patients undergoing chemotherapy and radiotherapy (CRT) in four Chinese hospitals. In a simulation environment, we compared the performance of the centralized deep learning (DL) model with that of the FL model using data from two sites. Additionally, due to the unavailability of data from one hospital, we established a real-world FL model using data from three sites. Assessments were conducted using measures such as accuracy, receiver operating characteristic curve, and confusion matrices. RESULTS: The model's prediction performance obtained using FL methods outperforms that of traditional centralized learning methods. In the comparative experiment, the DL model achieves an AUC of 0.718/0.695, while the FL model demonstrates an AUC of 0.725/0.689, with real-world FL model achieving an AUC of 0.698/0.672. CONCLUSIONS: We demonstrate that the performance of a FL predictive model, developed by combining convolutional neural networks (CNNs) with data from multiple medical centers, is comparable to that of a traditional DL model obtained through centralized training. It can efficiently predict CRT treatment response in NSCLC patients while preserving privacy.

Rebamipide gargle and benzydamine gargle in prevention and management of chemo-radiotherapy and radiotherapy-induced oral mucositis in head and neck cancer patients (randomized clinical trial).

OBJECTIVES: This study aimed to evaluate the preventive and therapeutic effects of rebamipide gargle in comparison with benzydamine in head and neck cancer patients undergoing radiotherapy with or without chemotherapy. MATERIALS AND METHODS: Phase III randomized clinical trial was conducted from January 2021 till August 2022 on one hundred patients with head and neck cancer receiving high doses of radiotherapy. These patients were equally allocated into either rebamipide group or benzydamine group, The measured outcomes were the incidence of oral mucositis ≥ grade1, according to the WHO mucositis scale, in addition to the duration, and the onset of oral mucositis. RESULTS: There was no statistically significant difference between the two groups, regarding the incidence of a severe grade of oral mucositis (WHO grades 3), as well as the onset and duration of oral mucositis. Both gargles succeeded to prevent the development of WHO grade 4 oral mucositis. Side effects reported were mainly burning sensation in benzydamine group and nausea in rebamipide group. CONCLUSION: Rebamipide mouthwash was as beneficial as benzydamine mouthwash in minimizing the incidence of severe oral mucositis induced by treatment of head and neck cancer. However, rebamipide gargle proved to be superior to benzydamine in terms of reduction in the severity of the radiation-induced oral mucositis. TRIAL REGISTRATION: The trial was registered in the protocol Registration and Result system of Clinical Trials (Registration ID: NCT04685395)0.28-12-2020.

Simultaneous integrated boost intensity-modulated radiotherapy (SIB-IMRT) combined with nimotuzumab for locally advanced esophageal squamous cell carcinoma (ESCC): A phase II clinical trial.

OBJECTIVE: To evaluate the feasibility, safety and efficacy of concurrent simultaneous integrated boost intensity-modulated radiotherapy (SIB-IMRT) combined with nimotuzumab in the treatment of locally advanced esophageal squamous cell cancer (ESCC). METHODS: Eligible patients were histologically proven to have locally advanced ESCC, and were unable to tolerate or refuse concurrent chemoradiotherapy (CCRT). Enrolled patients underwent concurrent SIB-IMRT in combination with nimotuzumab. SIB-IMRT: For the planning target volume of clinical target volume (PTV-C), the prescription dose was 50.4 Gy/28fractions, 1.8 Gy/fraction, 5fractions/week, concurrently, the planning target volume of gross tumor (PTV-G) undergone an integrated boost therapy, with a prescription dose of 63 Gy/28fractions, 2.25 Gy/fraction, 5 fractions/week. Nimotuzumab was administered concurrently with radiotherapy, 200 mg/time, on D1, 8, 15, 22, 29, and 36, with a total accumulation of 1200 mg through intravenous infusion. The primary endpoint of the study was the safety and efficacy of the combined treatment regimen, and the secondary endpoints were 1-year, 2-year, and 3-year local control and survival outcomes. RESULTS: (1) From December 2018 to August 2021, 35 patients with stage II-IVA ESCC were enrolled and 34 patients completed the full course of radiotherapy and the intravenous infusion of full-dose nimotuzumab. The overall completion rate of the protocol was 97.1%. (2) No grade 4-5 adverse events occurred in the entire group. The most common treatment-related toxicity was acute radiation esophagitis, with a total incidence of 68.6% (24/35). The incidence of grade 2 and 3 acute esophagitis was 25.7% (9/35) and 17.1% (6/35), respectively. The incidence of acute radiation pneumonitis was 8.6% (3/35), including one case each of Grades 1, 2, and 3 pneumonitis. Adverse events in other systems included decreased blood cells, hypoalbuminemia, electrolyte disturbances, and skin rash. Among these patients, five experienced grade 3 electrolyte disturbances during the treatment period (three with grade 3 hyponatremia and two with grade 3 hypokalemia). (3) Efficacy: The overall CR rate was 22.8%, PR rate was 71.4%, ORR rate was 94.2%, and DCR rate was 97.1%.(4) Local control and survival: The 1-, 2-, and 3-year local control (LC) rate, progression-free survival(PFS) rate, and overall survival(OS) rate for the entire group were 85.5%, 75.4%, and 64.9%; 65.7%, 54.1%, and 49.6%; and 77.1%, 62.9%, and 54.5%, respectively. CONCLUSIONS: The combination of SIB-IMRT and nimotuzumab for locally advanced esophageal cancer demonstrated good feasibility, safety and efficacy. It offered potential benefits in local control and survival. Acute radiation esophagitis was the primary treatment-related toxicity, which is clinically manageable. This comprehensive treatment approach is worthy of further clinical exploration (ChiCTR1900027936).

Enhanced MRI Radiomics Based Model for Predicting Recurrence or Metastasis of Nasopharyngeal Cancer (NC) Undergoing Concurrent Chemoradiotherapy: A Retrospective Study.

Nasopharyngeal Carcinoma (NC) refers to the malignant tumor that occurs at the top and side walls of the nasopharyngeal cavity. The NC incidence rate always dominates the first among the malignant tumors of the ear, nose and throat, and mainly occurs in Asia. NC cases are mainly concentrated in southern provinces in China, with about 4 million existing NC. With the pollution of environment and pickled diet, and the increase of life pressure, the domestic NC incidence rate has reached 4.5-6.5/100000 and is increasing year by year. It was reported that the known main causes of NC include hereditary factor, genetic mutations, and EB virus infection, common clinical symptoms of NC include nasal congestion, bloody mucus, etc. About 90% of NC is highly sensitive to radiotherapy which is regard as the preferred treatment method; However, for NC with lower differentiation, larger volume, and recurrence after treatment, surgical resection and local protons and heavy ions therapy are also indispensable means. According to reports, the subtle heterogeneity and diversity exists in some NC, with about 80% of NC undergone radiotherapy and about 25% experienced recurrence and death within five years after radiotherapy in China. Therefore, screening the NC population with suspected recurrence after concurrent chemoradiotherapy may improve survival rates in current clinical decision-making.

NC is one of the prevalent malignancies of the head and neck region with poor prognosis. The aim of this study is to establish a predictive model for assessing NC prognosis using clinical and MR radiomics data.

Clinical Outcomes and Prognostic Factors in Stage III C Cervical Cancer Patients Treated with Radical Radiotherapy or Radiochemotherapy.

Objective: Since the update of the 2018 International Federation of Gynecology and Obstetrics (FIGO) staging criteria, there have been few reports on the prognosis of stage III C cervical cancer. Moreover, some studies have drawn controversial conclusions, necessitating further verification. This study aims to evaluate the clinical outcomes and determine the prognostic factors for stage III C cervical cancer patients treated with radical radiotherapy or radiochemotherapy. Methods: The data of 117 stage III C cervical cancer patients (98 III C1 and 19 III C2) who underwent radical radiotherapy or radiochemotherapy were retrospectively analyzed. We evaluated 3-year overall survival (OS) and disease-free survival (DFS) using the Kaplan-Meier method. Prognostic factors were analyzed using the Log-rank test and Cox proportional hazard regression model. The risk of para-aortic lymph node metastasis (LNM) in all patients was assessed through Chi-squared test and logistic regression analysis. Results: For stage III C1 and III C2 patients, the 3-year OS rates were 77.6% and 63.2% (P = .042), and the 3-year DFS rates were 70.4% and 47.4% (P = .003), respectively. The pretreatment location of pelvic LNM, histological type, and FIGO stage was associated with OS (P = .033, .003, .042, respectively); the number of pelvic LNM and FIGO stage were associated with DFS (P = .015, .003, respectively). The histological type was an independent prognostic indicator for OS, and the numbers of pelvic LNM and FIGO stage were independent prognostic indicators for DFS. Furthermore, a pelvic LNM largest short-axis diameter ≥ 1.5 cm and the presence of common iliac LNM were identified as high-risk factors influencing para-aortic LNM in stage III C patients (P = .046, .006, respectively). Conclusions: The results of this study validated the 2018 FIGO staging criteria for stage III C cervical cancer patients undergoing concurrent chemoradiotherapy. These findings may enhance our understanding of the updated staging criteria and contribute to better management of patients in stage III C.

Chemoradiotherapy versus surgery after neoadjuvant chemoimmunotherapy in patients with stage III NSCLC: a real-world multicenter retrospective study.

PURPOSE: The optimal treatment after neoadjuvant chemoimmunotherapy for patients with stage III non-small cell lung cancer (NSCLC) is unclear. This study aimed at comparing the efficacy and safety of chemoradiotherapy and surgery after neoadjuvant chemoimmunotherapy in stage III NSCLC. MATERIALS AND METHODS: We conducted a real-world multicenter retrospective study on patients with stage III NSCLC who received surgery or chemoradiotherapy after neoadjuvant chemoimmunotherapy between October 2018 and December 2022. Progression-free survival (PFS) and overall survival (OS) were assessed from the initiation of neoadjuvant treatment and estimated by the Kaplan‒Meier method. Univariate and multivariate Cox regression models were used to examine potential prognostic factors. One-to-one propensity score matching (PSM) was used to further minimize confounding. RESULTS: A total of 239 eligible patients were enrolled, with 104 (43.5%) receiving surgery and 135 (56.5%) receiving CRT. After 1:1 PSM, 1- and 2-year PFS rates in patients receiving radical surgery (rSurgery group) vs. patients receiving definitive cCRT (dCCRT group) were 80.0% vs. 79.2% and 67.2% vs. 53.1%, respectively (P = 0.774). One- and 2-year OS rates were 97.5% vs. 97.4% and 87.3% vs. 89.9%, respectively (P = 0.558). Patients in the dCCRT group had a numerically lower incidence of distant metastases compared to those in the rSurgery group (42.9% vs. 70.6%, P = 0.119). The incidence of treatment-related adverse events was similar in both groups, except that the incidence of grade 3/4 hematological toxicity was significantly higher in the dCCRT group (30.0% vs. 10.0%, P = 0.025). CONCLUSION: Following neoadjuvant chemoimmunotherapy, definitive concurrent chemoradiotherapy may achieve noninferior outcomes to radical surgery in stage III NSCLC.

Evaluating complete response prediction rates in locally advanced rectal cancer with different radiomics segmentation approaches.

Purpose: Studies examining prediction of complete response (CR) in locally advanced rectum cancer (LARC) from pre/post chemoradiotherapy (CRT) magnetic resonance imaging (MRI) are performed mostly with segmentations of the tumor, whereas only in two studies segmentation included tumor and mesorectum. Additionally, pelvic extramesorectal region, which is included in the clinical target volume (CTV) of radiotherapy, may contain information. Therefore, we aimed to compare predictive rates of radiomics analysis with features extracted from segmentations of tumor, tumor+mesorectum, and CTV. Methods and materials: Ninety-three LARC patients who underwent CRT in our institution between 2012 and 2019 were retrospectively scanned. Patients were divided into CR and non-CR groups. Tumor, tumor+mesorectum and CTV were segmented on T2 preCRT MRI images. Extracted features were compared for best area under the curve (AUC) of CR prediction with 15 machine-learning models. Results: CR was observed in 25 patients (26.8%), of whom 13 had pathological, and 12 had clinical complete response. For tumor, tumor+mesorectum and CTV segmentations, the best AUC were 0.84, 0.81, 0.77 in the training set and 0.85, 0.83 and 0.72 in the test set, respectively; sensitivity and specificity for the test set were 76%, 90%, 76% and 71%, 67% and 62%, respectively. Conclusion: Although the highest AUC result is obtained from the tumor segmentation, the highest accuracy and sensitivity are detected with tumor+mesorectum segmentation and these findings align with previous studies, suggesting that the mesorectum contains valuable insights for CR. The lowest result is obtained with CTV segmentation. More studies with mesorectum and pelvic nodal regions included in segmentation are needed.

[Cervical CUP Syndrome: Diagnosis and Therapy]. / Zervikales CUP-Syndrom: Diagnostik und Therapie.

In CUP syndrome (CUP = cancer of unknown primary) there are 1 or more metastases of a primary tumor that cannot be localized despite extensive diagnostics. CUP syndrome accounts for 5% of all human malignancies, making it one of the 10 most common forms of cancer. In addition to inflammatory lymph node enlargement and benign changes such as cervical cysts, lymph node metastases are among the most common cervical masses. Cervical CUP syndrome is a histologically confirmed cervical lymph node metastasis with an unknown primary tumor. In addition to anamnesis, clinical examination and histological confirmation, diagnostics include radiological imaging using PET-CT and panendoscopy with histological primary tumor search. Treatment options include surgical therapy with neck dissection and chemoradiotherapy.

Surgical vs nonsurgical treatment for esophageal squamous cell carcinoma in patients older than 70 years: a propensity score matching analysis.

PURPOSE: With the rising life expectancy and an aging population, it has become increasingly important to investigate treatments suitable for older adult patients with esophageal cancer. This study investigated whether older adult patients who underwent esophagectomy had better clinical outcomes than those who were nonsurgically treated. METHODS: We retrospectively analyzed patients with esophageal squamous cell carcinoma (ESCC) who were 70 years or older and underwent esophagectomy, radiotherapy (RT), and/or chemoradiotherapy (CRT) between January 2018 and December 2019. Patients were divided into 2 groups: the surgery group (S group) and the nonsurgery group (NS group). We then compared the clinical outcomes of the 2 groups. RESULTS: After a median follow-up duration of 36.6 months, the S group showed better overall survival (OS). The 3-year OS was 59% in the S group and 27% in the NS group (hazard ratio [HR], 0.397; 95% CI, 0.278-0.549; P < .0001). In the S group, the median progression-free survival was 38.3 months (95% CI, 30.6-46.1) compared with 12.3 months in the NS group (HR, 0.511; 95% CI, 0.376-0.695; P < .0001). In addition, the number of adverse events in the NS group was higher than that in the S group (P < .001). CONCLUSION: Overall, patients with ESCC at the age of ≥70 years who underwent esophagectomy had significantly better clinical outcomes than those who underwent nonsurgical treatment with RT and/or CRT.

Effects of concurrent chemoradiotherapy with or without Endostar on the regression of retropharyngeal lymph node and prognosis of patients with locally advanced nasopharyngeal carcinoma: a retrospective study.

BACKGROUND AND PURPOSE: To investigate the effect of combining Endostar with concurrent chemoradiotherapy (ECCRT) compared to concurrent chemoradiotherapy (CCRT) on the regression rate of retropharyngeal lymph nodes (RLNs) and the relationship between regression rate of RLNs and prognosis of patients with locally advanced nasopharyngeal carcinoma (LANPC). METHODS: A total of 122 LANPC patients with RLNs metastasis were included. Metastatic RLNs were delineated both before and after treatment slice by slice on the magnetic resonance images cross-section. The regression rate of RLNs, adverse effects (AE) were evaluated. The median regression rate of RLNs was taken as the cut-off value, and the patients were furtherly divided into high regression rate (HRR) group and low regression rate (LRR) group, then survival times were evaluated. RESULTS: The median regression rates of RLNs in the ECCRT and CCRT groups were 81% and 50%, respectively (P < 0.001). There was no statistically significant difference in the incidence of grade 3/4 AEs between the two groups, except for oral mucositis (ECCRT 26.23% vs. CCRT 44.26%, P = 0.037). The 3-year overall survival (OS), progression-free survival (PFS), distant metastasis-free survival (DMFS) and locoregional failure-free survival (LRFFS) rates in the HRR and LRR groups were 85.48% and 86.67% (P = 0.983), 80.65% and 68.33% (P = 0.037), 83.87% and 85% (P = 0.704), 93.55% and 81.67% (P = 0.033), respectively. CONCLUSIONS: Patients in the ECCRT group had higher regression rates of RLNs and lower incidence of severe oral mucositis. Furthermore, patients in the HRR group had a better 3-year PFS and LRFFS rate than those in the LRR group.

The role of chemoradiotherapy and immunotherapy in stage III NSCLC.

Locally advanced non-small lung cancer encompasses a diverse range of tumors. In the last few years, the treatment of stage III unresectable non-small lung cancer has evolved significantly. The PACIFIC trial opened a new therapeutic era in the treatment of locally advanced NSCLC, establishing durvalumab consolidation therapy as the new standard of care worldwide. A careful evaluation of this type of lung cancer and a discussion of the management of these patients within a multidisciplinary team represents a crucial step in defining the best treatment strategy for each patient. For unresectable stage III NSCLC, definitive concurrent chemoradiotherapy (CCRT) was historically recommended as a treatment with a 5-year survival rate ranging from 20% to 30%. The PACIFIC study conducted in 2017 compared the use of chemoradiotherapy and maintenance therapy with the anti-PD-L1 monoclonal antibody durvalumab to a placebo in patients with locally advanced NSCLC who had not experienced disease progression. The study was prospective, randomized, and phase III. The administration of this medication in patients with locally advanced non-small cell lung cancer (NSCLC) has demonstrated a notable improvement in overall survival. Multiple clinical trials are currently exploring various immune checkpoint inhibition regimens to enhance the treatment efficacy in patients with stage III cancer. Our goal is to offer an up-to-date summary of the planned clinical trials for treatment options, focusing on the significant obstacles and prospects in the post-PACIFIC era.

Evaluating the clinical efficacy and safety of concurrent chemoradiotherapy with cisplatin and nab-paclitaxel in postoperative early-stage cervical cancer.

OBJECTIVE: A preclinical study showed that nab-paclitaxel acted as a radiosensitizer and improved tumor radiotherapy in a supra-additive manner. In this study, we aimed to evaluate the clinical efficacy and safety of concurrent chemoradiotherapy (CCRT) with cisplatin and nab-paclitaxel in postoperative early-stage cervical cancer with an unfavorable prognosis. METHODS: Eligible patients with stage IB1-IIA2 (FIGO 2009) cervical carcinoma were recruited retrospectively between August 2018 to May 2021. Patients in both the cisplatin and nab-paclitaxel groups received postoperative radiotherapy and weekly intravenous cisplatin 40 mg/m2 or nab-paclitaxel 100 mg concurrently. An analysis of overall survival, progression-free survival, and adverse reactions was conducted. RESULTS: A total of 105 early-stage cervical cancer patients were included into our study. The median follow-up time was 38.7 months. The 3-year overall survival and progression-free survival in both group was similar. The cycles of chemotherapy in the cisplatin group were less than those in the nab-paclitaxel group (4.5 vs. 5.0; p = 0.001). Patients in the cisplatin group had a significantly higher frequency of hematological adverse events than patients in the nab-paclitaxel group (P < 0.05). Patients in the cisplatin group had a significantly higher frequency of grade 3-4 leukopenia (46.1% vs. 18.9%; P = 0.03), grade 1-2 thrombocytopenia (32.7% vs. 9.5%; P = 0.014) than patients in the nab-paclitaxel group. Gastrointestinal reactions, such as vomiting, nausea, and anorexia were significantly reduced in the nab-paclitaxel group compared with those in the cisplatin group. Regarding the effects on alopecia, the incidence rate of the nab-paclitaxel group was higher than that of the cisplatin group (P = 0.001). There were no differences between the groups in terms of other adverse reactions. CONCLUSION: The results of this study indicate that nab-paclitaxel-based concurrent radiotherapy is tolerable and effective, and can be considered an alternative to cisplatin chemotherapy.

Clinical significance of the advanced lung cancer inflammation index in patients with limited-stage small cell lung cancer treated with chemoradiotherapy.

The aim of the study was to investigate the prognostic significance of the advanced lung cancer inflammation index (ALI) in patients with limited-stage small-cell lung cancer (LS-SCLC) undergoing definite chemo-radiotherapy (CRT). We included 87 patients with LS-SCLC from South Korea, treated between 2005 and 2019 with definite CRT. ALI was calculated using body mass index, serum albumin, and neutrophil-lymphocyte ratio. We categorized 38 patients into the high ALI group (ALI ≥ 44.3) and 48 into the low ALI group (ALI < 44.3). Patients in the high ALI group exhibited longer overall survival (OS) than patients in the low ALI group. In multivariate analysis, prophylactic cranial irradiation (hazard ratio [HR] = 0.366, 95% confidence interval [CI] 0.20-0.66, P = 0.0008), and high ALI (HR = 0.475, 95% CI 0.27-0.84, P = 0.0103) were identified as independent prognostic factors for predicting better OS. Notably, a high ALI score was particularly indicative of longer survival in patients treated with the combination of etoposide and cisplatin. In conclusion, this study demonstrated that a high pretreatment ALI was significantly associated with better OS in patients with LS-SCLC undergoing definite CRT. This suggests that ALI could be a useful tool for predicting prognosis and guiding chemotherapy regimen selections in clinical practice for LS-SCLC.

Influence of radiotherapy interruption on esophageal cancer with intensity-modulated radiotherapy: a retrospective study.

BACKGROUND: Radiotherapy interruption (RTI) prolongs the overall total treatment time and leads to local control loss in many cancers, but it is unclear in esophageal cancer. We aimed to evaluate the influence of RTI on the overall survival (OS), progression-free survival (PFS), and local-regional recurrence-free survival (LRFS) of patients with esophageal cancer undergoing chemoradiotherapy. METHODS: A total of 299 patients with esophageal squamous cell carcinoma from 2017 to 2019 were retrospectively analyzed to investigate the effect of RTI on OS, PFS, and LRFS. The delayed time of radiotherapy interruption was calculated as the actual radiation treatment time minus the scheduled time. The univariate and multivariate analyses were performed by the COX proportional hazards regression models, and the survival analysis was performed through the Kaplan‒Meier method, and compared with the log-rank test. RESULTS: The 3-year OS, PFS, and LRFS rates were 53.0%, 42.0%, and 48.0%, respectively. The univariate and multivariate analyses showed that the delayed time > 3 days was an independent adverse prognostic factor for OS (HR = 1.68, 95% CI 1.10-2.55, p = 0.016), and LRFS (HR = 1.74, 95% CI 1.18-2.57, p = 0.006). The patient with a delayed time of > 3 days had poorer survival rates of OS, and LRFS than patients with a delayed time of ≤ 3 days (OS, p = 0.047; LRFS, p = 0.013), and the survival outcomes of patients with shorter delayed time (1-3 days) were slightly different from the patients without interruptions. The impact of delay time on PFS is not statistically significant, but the survival outcomes of the two groups were slightly different. CONCLUSION: There was a significant correlation between delayed time and local control of esophageal cancer. The delayed time for more than 3 days might decrease the survival outcome, and increase the local recurrence risk.

Immune cell patterns before and after neoadjuvant immune checkpoint blockade combined with chemoradiotherapy in locally advanced esophageal squamous cell carcinoma.

BACKGROUND: Neoadjuvant immune checkpoint blockade (ICB) combined with chemoradiotherapy offers high pathologic complete response (pCR) rate for patients with locally advanced esophageal squamous cell carcinomas (ESCC). But the dynamic tumor immune microenvironment modulated by such neoadjuvant therapy remains unclear. PATIENTS AND METHODS: A total of 41 patients with locally advanced ESCC were recruited. All patients received neoadjuvant toripalimab combined with concurrent chemoradiotherapy. Matched pre- and post-treatment tissues were obtained for fluorescent multiplex immunohistochemistry (mIHC) and IHC analyses. The densities and spatial distributions of immune cells were determined by HALO modules. The differences of immune cell patterns before and after neoadjuvant treatment were investigated. RESULTS: In the pre-treatment tissues, more stromal CD3 + FoxP3 + Tregs and CD86+/CD163 + macrophages were observed in patients with residual tumor existed in the resected lymph nodes (pN1), compared with patients with pCR. The majority of macrophages were distributed in close proximity to tumor nest in pN1 patients. In the post-treatment tissues, pCR patients had less CD86 + cell infiltration, whereas higher CD86 + cell density was significantly associated with higher tumor regression grades (TRG) in non-pCR patients. When comparing the paired pre- and post-treatment samples, heterogeneous therapy-associated immune cell patterns were found. Upon to the treatment, CD3 + T lymphocytes were slightly increased in pCR patients, but markedly decreased in non-pCR patients. In contrast, a noticeable increase and a less obvious decrease of CD86 + cell infiltration were respectively depicted in non-pCR and pCR patients. Furthermore, opposite trends of the treatment-induced alterations of CD8 + and CD15 + cell infiltrations were observed between pN0 and pN1 patients. CONCLUSIONS: Collectively, our data demonstrate a comprehensive picture of tumor immune landscape before and after neoadjuvant ICB combined with chemoradiotherapy in ESCC. The infiltration of CD86 + macrophage may serve as an unfavorable indicator for neoadjuvant toripalimab combined with chemoradiotherapy.

The efficacy and safety of adding PD-1 blockade to induction chemotherapy and concurrent chemoradiotherapy (IC-CCRT) for locoregionally advanced nasopharyngeal carcinoma: an observational, propensity score-matched analysis.

BACKGROUND: Despite the success of PD-1 blockade in recurrent/metastatic nasopharyngeal carcinoma (NPC), its effect for locoregionally advanced NPC (LANPC) remains unclear. This study aimed to evaluate the benefit of adding PD-1 blockade to the current standard treatment (gemcitabine and cisplatin IC  plus cisplatin CCRT ) for LANPC patients. METHODS: From January 2020 to November 2022, 347 patients with non-metastatic high-risk LANPC (stage III-IVA, excluding T3-4N0) were included. Of the 347 patients, 268 patients were treated with standard treatment (IC-CCRT), and 79 received PD-1 blockade plus IC-CCRT (PD-1 group). For the PD-1 group, PD-1 blockade was given intravenously once every 3 weeks for up to 9 cycles (3 induction and 6 adjuvant). The primary endpoint was disease-free survival (DFS) (i.e. freedom from local/regional/distant failure or death). The propensity score matching (PSM) with the ratio of 1:2 was performed to control confounding factors. RESULTS: After PSM analysis, 150 patients receiving standard treatment and 75 patients receiving additional PD-1 blockade remained in the current analysis. After three cycles of IC, the PD-1 group had significantly higher rates of complete response (defined as disappearance of all target lesions; 24% vs. 9%; P = 0.006) and complete biological response (defined as undetectable cell-free Epstein-Barr virus DNA, cfEBV DNA; 79% vs. 65%; P = 0.046) than that in the standard group. And the incidence of grade 3-4 toxicity during IC was 47% in the PD-1 group and 41% in the standard group, with no significant difference (P = 0.396). During follow-up period, additional PD-1 blockade to standard treatment improved 3-year DFS from 84 to 95%, with marginal statistical significance (HR, 0.28; 95%CI, 0.06-1.19; P = 0.064). CONCLUSION: Additiaonl PD-1 blockade to gemcitabine and cisplatin IC and adjuvant treatment results in significant improvement in tumor regression, cfEBV DNA clearance, superior DFS, and comparable toxicity profiles in high-risk LANPC patients.

Efficacy and safety of different chemotherapy regimens concurrent with radiotherapy in the treatment of locally advanced cervical cancer.

BACKGROUND: Evaluate the efficacy and safety of different chemotherapy regimens concurrent with radiotherapy in treating locally advanced cervical cancer (LACC). METHODS: Retrospective data was collected from LACC patients who were treated at our institution. These patients were categorized into three groups: the single-agent cisplatin (DDP) chemoradiotherapy group, the paclitaxel plus cisplatin (TP) chemoradiotherapy group, and the nanoparticle albumin-bound (nab-) paclitaxel combined with cisplatin (nPP) chemoradiotherapy group. The primary endpoints were overall survival (OS) and progression-free survival (PFS) and the secondary endpoints were objective response rate (ORR) and incidence of adverse events (AEs). RESULTS: A total of 124 patients were enrolled (32 in the DDP group, 41 in the TP group, and 51 in the nPP group). There were differences in OS (P = 0.041, HR 0.527, 95% CI 0.314-0.884) and PFS (P = 0.003, HR 0.517, 95% CI 0.343-0.779) between the three groups. Notably, the 2-year OS rate was significantly higher in the nPP group compared to the DDP group (92.2% vs. 85.4%, P = 0.012). The 2-year PFS rates showed a marked increase in the TP group (78.0% vs. 59.4%, P = 0.048) and the nPP group (88.2% vs. 59.4%, P = 0.001) relative to the DPP group, with multiple comparisons indicating that the 2-year PFS rate was significantly superior in the nPP group versus the DDP group (88.2% vs. 59.4%, P = 0.001). Moreover, the ORR was also significantly higher in the nPP group than in the DDP group (P = 0.013); and no statistically significant differences were found in the incidence of AEs among the groups (P > 0.05). CONCLUSIONS: In LACC treatment, the two cisplatin-based doublet chemotherapy regimens are associated with better outcomes, with the nab-paclitaxel plus cisplatin regimen showing better efficacy than the paclitaxel plus cisplatin regimen. Furthermore, the AEs associated with these regimens were deemed tolerable. These findings could provide a reference for the clinical treatment of LACC. However, further prospective studies are needed to verify it.