Concurrent chemoradiotherapy (CCRT) has remained the standard treatment for unresectable locally advanced esophageal squamous cell carcinoma (ESCC), yet survival remains poor. This single-arm, phase II trial aims to evaluate the efficacy and safety of two cycles of induction chemotherapy with camrelizumab followed by CCRT in previously untreated patients with unresectable locally advanced ESCC. The primary endpoint, the 1-year overall survival (OS) rate in the per-protocol population (N = 46), was 87.0% (95% confidence interval [CI]: 77.7%–97.3%), exceeding the pre-specified target. Secondary endpoints included OS in the intention-to-treat (ITT) population, progression-free survival (PFS), overall response rate (ORR), disease control rate (DCR), duration of response, safety, and health-related quality of life. In the ITT population (N = 49), the 1-year OS rate was 85.7% (95% CI: 76.5%–96.1%). The 1-year PFS rates in the per-protocol and ITT populations were 71.7% (95% CI: 59.8%–86.0%) and 71.4% (95% CI: 59.8%–85.3%), respectively. The median OS, PFS, and duration of response were not reached. Following CCRT, the ORR was 93.5%, with a DCR of 95.7%. Lymphopenia was the most frequent Grade ≥3 adverse event (100%). One patient died from treatment-related myelosuppression. Health-related quality of life generally improved after induction therapy, with significant improvements in global health status, emotional functioning, and some symptom relief, despite a slight decline in physical functioning. Here, we show that induction chemoimmunotherapy followed by CCRT exhibits promising efficacy and manageable safety in patients with unresectable locally advanced ESCC, thus warranting further randomized controlled trials. Trial number: ChiCTR2000034304.

Background: The optimal treatment for the rare subtype of non‐Hodgkin lymphoma, extranodal natural killer/T‐cell lymphoma (ENKTL), nasal‐type, has not been clearly defined. The purpose of the study was to investigate the efficacy of sequential and “Sandwich” chemotherapy and extended involved‐field intensity‐modulated radiotherapy (IMRT) in patients with stage I_E/II_E extranodal ENKTL, nasal‐type.Methods: One hundred and fifty‐five patients with stage I_E/II_E nasal‐type ENKTL were enrolled in the study, including 99 patients treated with sequential chemotherapy and extended involved‐field IMRT (SCRT) and 56 patients with “Sandwich” chemotherapy and extended involved‐field IMRT and chemotherapy (SCRCT). All patients were treated with extended involved‐field IMRT with median dose of 54.6 Gy to the primary tumor and positive lymph nodes. Ninety‐four patients had Ann Arbor stage I_E disease, and 61 patients had stage II_E disease.Results: The 5‐year rates of loco‐regional recurrence (LRR), progression‐free survival (PFS), and overall survival (OS) were 17.0%, 78.5%, and 84.7%, respectively. Univariate analysis revealed that EBV DNA copy after treatment (normal vs elevated level) was significant prognostic factor for LRR, PFS, and OS (P < 0.001); therapeutic method (SCRT vs SCRCT) was significant prognostic factor for PFS (71.0% vs 91.8%, P = 0.011), but there was no significant effect on 5‐year LRR and OS (22.2% vs 8.2%, P = 0.051 for LRR; 80.9% vs 91.8%, P = 0.199 for OS).Conclusions: Compared with SCRT, SCRCT was significantly associated with higher PFS rates and showed a trend toward improved loco‐regional control. EBV DNA copy after treatment is a good index for recurrence and prognosis for stage I_E/II_E ENKTL patients.

The aim of this study was to evaluate the effect of pelvic bone dose-volume parameters on bone marrow suppression during radiation therapy (RT) in patients with rectal cancer stage I to III disease receiving either neoadjuvant radiation therapy (neo-RT) or curative-intent radiation therapy (cur-RT). This was a retrospective study with data mined from an electronic medical record review at a single institution. Between January 2016 and September 2022, patients with rectal cancer who consecutively received neo-RT or cur-RT in our department were included. The data collected included complete baseline peripheral blood counts and hematologic toxicity (HT) data collected during RT. The radiation dose-volume parameters of 3 pelvic bone marrow subsites (iliac bone marrow [IBM], lumbosacral bone marrow, and lower pelvis bone marrow) were collected. The primary endpoint was grade ≥ 2 HT (HT2+), including leukopenia, neutropenia, anemia, thrombocytopenia, and total HTs. Logistic regression was employed to analyze the associations of HT2+ with dosimetric parameters and clinicopathologic characteristics. Receiver operating characteristic curves and the area under the curve (AUC) were generated to verify the prediction efficacy of the pelvic bone dose-volume parameters combined with clinicopathologic indices. A total of 130 patients with stage I to III rectal cancer with complete clinical data were included. During neo-RT and cur-RT, 57 (43.8%) of these patients experienced HT2+. Multivariate analysis revealed that gender, the IBM-Dmean, the IBM-V15, and the IBM-V40 were significantly associated with grade 2+ leukopenia (P < .05), and the AUC of gender combined with the IBM-Dmean, the IBM-V15, and the IBM-V40 in predicting grade 2+ leukopenia was 0.834. The optimal cutoff values were an IBM-Dmean = 2692.75 cGy, an IBM-V15 = 86.65%, and an IBM-V40 = 20.75%. Patients who received oxaliplatin-containing concurrent chemotherapy (ChT) regimens were more likely to experience grade 2+ thrombocytopenia (P = .054). The AUC of concurrent ChT regimens in predicting grade 2+ thrombocytopenia was 0.678. Female gender was significantly associated with grade 2+ anemia and total HT2+ status. Among patients with rectal cancer stage I to III disease who received neo-RT or cur-RT, female patients with higher IBM-Dmean, IBM-V15, and IBM-V40 were more likely to experience grade 2+ leukopenia, and oxaliplatin-containing concurrent ChT regimens were identified as a potential factor for increasing the incidence of grade 2+ thrombocytopenia.

Purpose Radiotherapy is a critical treatment for early-stage extranodal nasal-type NK/T-cell lymphoma (ENKTL) and has yielded favorable survival outcomes. However, their postradiotherapy quality of life (QOL) has not been investigated. Here, we conducted a cross-sectional study to assess the QOL of ENKTL patients with disease-free survival after definitive radiotherapy and to identify factors associated with QOL and treatment optimization. Methods This cross-sectional study included 310 patients with stage I–II ENKTL of the upper aerodigestive tract (UADT) who had received simultaneous integrated boost intensity-modulated radiotherapy (SIB-IMRT) with a consistent design and achieved disease-free survival. The median postradiotherapy time was 47.2 months (range, 3.1–115.7). The EORTC QLQ-H&N35 questionnaire was used to assess symptom-related QOL, and nine additional items were added to incorporate nasal, optical, and aural-related symptoms. The scores indicate the severity of the symptoms. Results The most common postradiotherapy symptoms among patients with ENKTL were nose problems (49.7%), dry mouth (44.8%), tooth problems (41.3%), sensory problems (32.6%), and less sexuality (25.8%). Tooth problems had the highest average score of 18.6, which is still acceptable. The severity of these symptoms decreased over time and reached a plateau in the second year after radiotherapy. Multivariable regression analysis showed that whole-neck irradiation was an independent predictive factor for xerostomia (P = 0.013, OR = 1.114), while age > 60 years was a predictive factor for lower sexuality (P < 0.001, OR = 1.32). Conclusion The QOL of patients with early-stage ENKTL after radiotherapy was favorable, and most symptoms improved over time. Radiotherapy was correlated with specific symptoms, which may suggest a direction for further improvement in SIB-IMRT.

Calcyclin-binding protein (CACYBP) is a multidomain adaptor protein implicated in the development of various cancers. However, its molecular and biological roles in lung adenocarcinoma (LUAD) remain unclear. In this study, we aimed to elucidate the biological impact of CACYBP in LUAD. Immunohistochemistry was used to assess CACYBP expression in LUAD tissues. Lentivirus-mediated CACYBP knockdown was established in LUAD cell lines, and target gene expression was analyzed via Western blotting and qRT-PCR. Cell proliferation, apoptosis, and migration were evaluated using flow cytometry, colony formation assays, cell counting kit-8 (CCK 8) assays, Celigo cell counting, wound healing assays, Transwell assays, and mouse xenograft models. Co-immunoprecipitation was performed to verify the interaction between CACYBP and cyclin-dependent kinase 1 (CDK1). Additionally, the phosphoinositide 3-kinase (PI3K) inhibitor LY294002 was used to investigate the involvement of CDK1 in the PI3K/AKT pathway. Our findings revealed that CACYBP was upregulated in LUAD tissues and correlated with advanced disease stages and poor prognosis. CACYBP knockdown inhibited LUAD progression and metastasis, promoted cell apoptosis in vitro, and reduced tumorigenicity in vivo. Mechanistically, we identified CDK1 as a direct interacting partner of CACYBP. CDK1 overexpression enhanced the malignant phenotype of LUAD cells and partially reversed the inhibitory effects of CACYBP knockdown. Furthermore, inhibition of the PI3K/AKT pathway using LY294002 significantly suppressed CDK1-mediated LUAD cell growth. In conclusion, CACYBP appears to function as a tumor promoter in LUAD, at least in part through CDK1-mediated activation of the PI3K/AKT pathway. These findings suggest that CACYBP could serve as a promising therapeutic target and a novel biomarker for LUAD prognosis.