Hippocampal avoidance whole-brain radiotherapy with simultaneous integrated boost in lung cancer brain metastases and utility of the Hopkins verbal learning test for testing cognitive impairment in Chinese patients: a prospective phase II study.

BACKGROUND: This study aimed to evaluate the efficiency of hippocampal avoidance whole-brain radiotherapy with a simultaneous integrated boost (HA-WBRT-SIB) treating brain metastases (BM) and utility of the Hopkins Verbal Learning Test-Revised (HVLT-R) (Chinese version) in Chinese lung cancer patients. METHODS: Lung cancer patients with BM undergone HA-WBRT-SIB at our center were enrolled. Brain magnetic resonance imaging, The HVLT total learning score, and side effects were evaluated before radiotherapy and 1, 3, 6, and 12 months after radiotherapy. This study analyzed the overall survival rate, progression-free survival rate, and changes in HVLT-R immediate recall scores. RESULTS: Forty patients were enrolled between Jan 2016 and Jan 2020. The median follow-up time was 14.2 months. The median survival, progression-free survival, and intracranial progression-free survival of all patients were 14.8 months, 6.7 months and 14.8 months, respectively. Multivariate analysis indicated that male sex and newly diagnosed stage IV disease were associated with poor overall survival and progression-free survival, respectively. HVLT-R scores at baseline and 1, 3, and 6 months after radiotherapy were 21.94 ± 2.99, 20.88 ± 3.12, 20.03 ± 3.14, and 19.78 ± 2.98, respectively. The HVLT-R scores at 6 months after radiotherapy decreased by approximately 9.8% compared with those at baseline. No grade 3 toxicities occurred in the entire cohort. CONCLUSIONS: HA-WBRT-SIB is of efficiency and cognitive-conserving in treating Chinese lung cancer BM. TRIAL REGISTRATION: This study was retrospectively registered on ClinicalTrials.gov in 24th Feb, 2024. The ClinicalTrials.gov ID is NCT06289023.

Higher immune cell radiation dose is correlated with poor tumor control and survival in patients with non-small cell lung cancer receiving postoperative radiotherapy.

INTRODUCTION: The estimated dose of radiation to immune cells (EDRIC) has been shown to correlate with the overall survival (OS) of patients who receive definitive thoracic radiotherapy. However, the planning target volume (PTV) may be a confounding factor. We assessed the prognostic value of EDRIC for non-small cell lung cancer (NSCLC) in patients who underwent postoperative radiotherapy (PORT) with homogeneous PTV. METHODS: Patients with NSCLC who underwent PORT between 2004 and 2019 were included. EDRIC was computed as a function of the number of radiation fractions and mean doses to the lungs, heart, and remaining body. The correlations between EDRIC and OS, disease-free survival (DFS), locoregional-free survival (LRFS), and distant metastasis-free survival (DMFS) were analyzed using univariate and multivariate Cox models. Kaplan-Meier analysis was performed to assess the survival difference between low- and high-EDRIC groups. RESULTS: In total, 345 patients were analyzed. The mean EDRIC was 6.26 Gy. Multivariate analysis showed that higher EDRIC was associated with worse outcomes in terms of OS (hazard ratio [HR] 1.207, P = .007), DFS (HR 1.129, P = .015), LRFS (HR 1.211, P = .002), and DMFS (HR 1.131, P = .057). In the low- and high-EDRIC groups, the 3-year OS was 81.2% and 74.0%, DFS 39.8% and 35.0%, LRFS 70.4% and 60.5%, and DMFS 73.9% and 63.1%, respectively. CONCLUSIONS: EDRIC is an independent prognostic factor for survival in patients with NSCLC undergoing PORT. Higher doses of radiation to the immune system are associated with tumor progression and poor survival. Organs at risk for the immune system should be considered during radiotherapy planning.

Adenoid Cystic Carcinoma of Lobar Bronchial Origin: 20-Year Experience at a Single Institution.

BACKGROUND: Pulmonary adenoid cystic carcinoma (ACC) is a rare type of lung malignancy. The prevalence of ACC of lobar bronchial origin is lower than that of other lung malignancies, and studies investigating it are lacking. This study aimed to evaluate survival of patients with ACC of the lobar bronchus after surgical resection and to explore its prognostic factors. METHODS: Between January 2000 and December 2019, 35 patients at the National Cancer Center/Cancer Hospital with a diagnosis of ACC of the lobar bronchus were included in the retrospective analysis. RESULTS: During a median follow-up period of 61 months (range, 10-194 months), the analysis showed a 5-year overall survival (OS) rate of 81.4%, a 5-year locoregional recurrence-free survival rate of 84.0%, and 5-year disease-free survival rate of 60.1%. The univariate analysis exclusively identified the surgical margin as a predictor of OS, and survival was significantly longer for the patients with negative surgical margins than for those with positive surgical margins (R0 vs. R1: 94.4% vs. 66.0%; p = 0.014). Adjuvant radiotherapy was administered to most of the patients with positive surgical margins, which might have contributed to prolonged OS (R0 vs. R1+RT: 94.4% vs. 66.7%, p = 0.173; R0 vs. R1+no RT: 94.4% vs. 62.5%, p = 0.007). CONCLUSIONS: For ACC of lobar bronchial origin, complete resection is the radical treatment, and the OS rate was significantly higher for the R0 patients than for the R1 patients. Adjuvant radiotherapy for patients with R1 may prolong survival.

MiR-323a-3p acts as a tumor suppressor by suppressing FMR1 and predicts better esophageal squamous cell carcinoma outcome.

BACKGROUND: Esophageal squamous cell carcinoma (ESCC) has unfavorable outcomes with the highest incidence seen in China. Accordingly, exploring effective molecular biomarkers is of great value. MicroRNAs (miRNAs) are posttranscriptional regulators of gene expression and modulate numerous biological processes in tumors. Our study aimed to identify prognostic miRNAs and investigate their role in ESCC. METHODS: Prognosis-related plasma miRNAs were detected by miRNA microarray and qRT-PCR. Functional assays and molecular mechanism studies were used to investigate the role of miRNA in ESCC. RESULTS: Over-expression of miR-323a-3p was associated with a favorable prognosis. MiR-323a-3p negatively regulated proliferation, migration, and invasion. Through biological predictions, the fragile X mental retardation 1 (FMR1) was found to be a potential target of miR-323a-3p. Further investigation revealed that miR-323a-3p directly targeted and suppressed FMR1. MiR-323a-3p and FMR1 mRNA, as well as miR-323a-3p and the FMR1-encoded protein FMRP, showed negative correlations. Luciferase activity of FMR1-3'-UTR, but not mutant counterparts, was decreased by mimic compared with that of the control. The compromised cell proliferation, migration, and invasion induced by transfection with miR-323a-3p mimic were rescued by transfection with a FMR1 expression plasmid. Tumors induced by miR-323a-3p overexpressed ESCC cells grew significantly slower in vivo and resulted in smaller tumor masses. Metastatic lung colonization was also inhibited by miR-323a-3p overexpression. CONCLUSIONS: MiR-323a-3p was significantly associated with survival and acted as a tumor suppressor by inhibiting proliferation, migration, and invasion via the regulation of FMR1. MiR-323a-3p is a promising biomarker and may be a potential therapeutic target.

Radiotherapy combined with nimotuzumab for elderly esophageal cancer patients: A phase II clinical trial.

OBJECTIVE: To investigate the safety and efficacy of nimotuzumab combined with radiotherapy for elderly patients with non-resectable esophageal carcinoma (EC). METHODS: Eligible patients were aged 70 years or older and had treatment-naïve, histologically proven inoperable locally advanced EC. Enrolled patients received radiotherapy with a total dose of 50-60 Gy in 25-30 fractions, concurrent with weekly infusion of nimotuzumab. The primary end point was the rate of more than grade 3 toxicities. RESULTS: From June 2011 to July 2016, 46 patients with stage II-IV EC with a median age of 76.5 years were enrolled. There were 10, 28 and 8 patients with stage II, III and IV disease, respectively. The common acute toxicities included esophagitis (grade 1-2, 75.4%; grade 3, 8.7%), pneumonitis (grade 1, 4.3%; grade 2, 6.5%; grade 3, 2.2%), leukopenia (grade 1-2, 60.9%; grade 3-4, 4.4%), gastrointestinal reaction (grade 1-2, 17.3%; grade 3, 2.2%), thrombocytopenia (grade 1-2, 21.7%; grade 3, 2.2%), and radiothermitis (grade 1-2, 39.2%). The incidence of grade 3-4 adverse effects was 17.4%. No grade 5 toxicities were observed. Clinical complete response, partial response, stable disease, and progressive disease were observed in 1 (2.2%), 31 (67.4%), 12 (26.1%), and 2 (4.3%) patients, respectively. The median overall survival (OS) and progression-free survival (PFS) were 17 and 10 months, respectively. The 2-, 3-, and 5-year OS and PFS rates were 30.4%, 21.7%, 19.6%, and 26.1%, 19.6%, 19.6%, respectively. CONCLUSIONS: Nimotuzumab combined with radiotherapy is a safe and effective therapy for elderly patients who are not surgical candidates. Further studies are warranted to confirm its therapeutic effects in elderly EC patients.

A multicenter prospective phase III clinical randomized study of simultaneous integrated boost intensity-modulated radiotherapy with or without concurrent chemotherapy in patients with esophageal cancer: 3JECROG P-02 study protocol.

BACKGROUND: Since the development of three-dimensional conformal radiotherapy and intensity-modulated radiotherapy (IMRT), no prospective study has investigated whether concurrent chemoradiotherapy (SIB-IMRT with 60 Gy) remains superior to radiotherapy (SIB-IMRT) alone for unresectable esophageal cancer (EC). Furthermore, the optimal therapeutic regimen for patients who cannot tolerate concurrent chemoradiotherapy is unclear. We recently completed a phase I/II radiation dose-escalation trial using simultaneous integrated boost (SIB), elective nodal irradiation, and concurrent chemotherapy for unresectable EC. We now intend to conduct a prospective, phase III, randomized study of SIB-IMRT with or without concurrent chemotherapy. We aim to find a safe, practical, and effective therapeutic regimen to replace the conventional segmentation (1.8-2.0 Gy) treatment mode (radiotherapy ± chemotherapy) for unresectable EC. METHODS: This two-arm, open, randomized, multicenter, phase III trial will recruit esophageal squamous cell carcinoma patients (stage IIA-IVB [UICC 2002]; IVB only with metastasis to the supraclavicular or celiac lymph nodes). In all, 164 patients will be randomized using a 1:1 allocation ratio, and stratified by study site and disease stage, especially the extent of lymph node metastasis. Patients in the SIB arm will receive definitive SIB radiotherapy (95% planning target volume/planning gross tumor volume, 50.4 Gy/59.92 Gy/28 f, equivalent dose in 2-Gy fractions = 60.62 Gy). Patients in the SIB + concurrent chemotherapy arm will receive definitive SIB radiotherapy with weekly paclitaxel and a platinum-based drug (5-6 weeks). Four cycles of consolidated chemoradiotherapy will also be recommended. The primary objective is to compare the 1-year, 2-year, and 3-year overall survival of the SIB + chemotherapy group and SIB groups. Secondary objectives include progression-free survival, local recurrence-free rate, completion rate, and adverse events. Detailed radiotherapy protocol and quality-assurance procedures have been incorporated into this trial. DISCUSSION: In unresectable, locally advanced EC, a safe and effective total radiotherapy dose and reasonable segmentation doses are required for the clinical application of SIB-IMRT + two-drug chemotherapy. Whether this protocol will replace the standard treatment regimen will be prospectively investigated. The effects of SIB-IMRT in patients with poor physical condition who cannot tolerate definitive chemoradiotherapy will also be investigated. TRIAL REGISTRATION: clinicaltrials.gov ( NCT03308552 , November 1, 2017).

Debulking Surgery Plus Radiation: Treatment Choice for Unresectable Stage III Thymic Carcinoma.

BACKGROUND: Total resection may not be achieved in patients with thymic carcinoma, particularly those with Masaoka stage III disease. Debulking surgery plus postoperative radiotherapy and radiation alone are treatment options for such patients. We aimed to compare the overall survival (OS) between patients with thymic carcinoma who underwent debulking surgery plus postoperative radiotherapy and those who underwent radiation alone. METHODS: This was a single-center retrospective study of patients histologically diagnosed as having Masaoka stage III thymic carcinoma between January 1980 and January 2010. Patients were classified into the following groups according to treatments received: debulking surgery plus radiotherapy (group A) and radiotherapy alone (group B). Data on demographics, histology, invasion, radiotherapy, chemotherapy, and survival were collected. Survival time was calculated and compared between the groups using the Kaplan-Meier method. Toxicities were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 3.0. RESULTS: Of the 47 enrolled patients, 26 and 21 patients were categorized into groups A and B, respectively. There are no significant differences in the Eastern Cooperative Oncology Group performance status score, histological type, great vessel invasion, and chemotherapy proportion between the groups. The median radiation dose was 60 Gy in both groups. The 5-year OS rates were 54.4 and 0% in groups A and B, respectively (p = 0.019). No operation-induced mortality was recorded. CONCLUSION: For patients with unresectable Masaoka stage III disease, debulking surgery with radiotherapy is preferred, as this was proven to be more efficient than the radiation-alone procedure.

Preoperative CT-based radiomic prognostic index to predict the benefit of postoperative radiotherapy in patients with non-small cell lung cancer: a multicenter study.

BACKGROUND: The value of postoperative radiotherapy (PORT) for patients with non-small cell lung cancer (NSCLC) remains controversial. A subset of patients may benefit from PORT. We aimed to identify patients with NSCLC who could benefit from PORT. METHODS: Patients from cohorts 1 and 2 with pathological Tany N2 M0 NSCLC were included, as well as patients with non-metastatic NSCLC from cohorts 3 to 6. The radiomic prognostic index (RPI) was developed using radiomic texture features extracted from the primary lung nodule in preoperative chest CT scans in cohort 1 and validated in other cohorts. We employed a least absolute shrinkage and selection operator-Cox regularisation model for data dimension reduction, feature selection, and the construction of the RPI. We created a lymph-radiomic prognostic index (LRPI) by combining RPI and positive lymph node number (PLN). We compared the outcomes of patients who received PORT against those who did not in the subgroups determined by the LRPI. RESULTS: In total, 228, 1003, 144, 422, 19, and 21 patients were eligible in cohorts 1-6. RPI predicted overall survival (OS) in all six cohorts: cohort 1 (HR = 2.31, 95% CI: 1.18-4.52), cohort 2 (HR = 1.64, 95% CI: 1.26-2.14), cohort 3 (HR = 2.53, 95% CI: 1.45-4.3), cohort 4 (HR = 1.24, 95% CI: 1.01-1.52), cohort 5 (HR = 2.56, 95% CI: 0.73-9.02), cohort 6 (HR = 2.30, 95% CI: 0.53-10.03). LRPI predicted OS (C-index: 0.68, 95% CI: 0.60-0.75) better than the pT stage (C-index: 0.57, 95% CI: 0.50-0.63), pT + PLN (C-index: 0.58, 95% CI: 0.46-0.70), and RPI (C-index: 0.65, 95% CI: 0.54-0.75). The LRPI was used to categorize individuals into three risk groups; patients in the moderate-risk group benefited from PORT (HR = 0.60, 95% CI: 0.40-0.91; p = 0.02), while patients in the low-risk and high-risk groups did not. CONCLUSIONS: We developed preoperative CT-based radiomic and lymph-radiomic prognostic indexes capable of predicting OS and the benefits of PORT for patients with NSCLC.

Silencing of spindle apparatus coiled-coil protein 1 suppressed the progression of hepatocellular carcinoma through farnesyltransferase-beta and increased drug sensitivity.

Hepatocellular carcinoma (HCC) is the major cause of cancer-associated mortality worldwide. Despite great advances have been made on the treatment of HCC, the survival rate of patients remains poor. Spindle apparatus coiled-coil protein 1 (SPDL1) is involved in the development of various cancers in humans. However, the role of SPDL1 in HCC remains unclear. In this study, we found high expression of SPDL1 in HCC tissues as compared to normal samples. In vitro, silencing of SPDL1 induced HCC cell apoptosis, and suppressed HCC cell propagation and migration. In vivo, knockdown of SPDL1 inhibited the tumor growth of HCC cells. These findings indicated the tumor-promoting role of SPDL1 in HCC. Mechanistically, we identified farnesyltransferase-beta (FNTB) as the downstream target protein of SPDL1 based on immunoprecipitation and mass spectrometry, which were confirmed by western blotting. Rescue assay determined that FNTB played a tumor promoting role in SPDL1-trigger HCC cell growth. Overexpression of FNTB recovered HCC cell viability and migration in SPDL1 knockdown cells. We also found that silencing of SPDL1 increased the sensitivity of Huh7 cells to sorafenib and lenvatinib, suggesting that SPDL1 is a new therapeutic target in HCC. Collectivity, the present study identified a new axis SPDL1/FNTB involved in the progression of HCC. Hence, SPDL1/FNTB is a potential target for the treatment of HCC.

Radiotherapy with Targeted Therapy or Immune Checkpoint Inhibitors for Hepatocellular Carcinoma with Hepatic Vein and/or Inferior Vena Cava Tumor Thrombi.

Purpose: This study evaluated the clinical outcomes of patients with hepatocellular carcinoma (HCC) with hepatic vein tumor thrombus (HVTT) and/or inferior vena cava tumor thrombus (IVCTT) receiving radiotherapy (RT) combined with systemic therapies. Patients and Methods: Patients with HCC with HVTT and/or IVCTT who received RT were identified at our institution. The prescription doses were 30-65 Gy for planning target volume and 40-65 Gy for the gross tumor volume. Targeted therapy and immune checkpoint inhibitors were used concurrently if patients were at a high risk of or already had distant metastasis. After RT completion, follow-up was performed at 1, 3, 6, and 12 months, and 3 to 6 months thereafter. The objective response rate (ORR), overall survival (OS), progression-free survival (PFS) and toxicity were recorded. Results: Thirty-four patients were retrospectively enrolled between January 2016 and September 2021. Most patients received concurrent targeted therapy (70.6%) and/or post-RT (79.4%). The in-field ORR and disease control rates were 79.4% and 97.1%, respectively. The OS rates were 77.6% at 1 year and 36.3% at 2 years (median OS, 15.8 months). The median PFS and median in-field PFS were 4.2 months and not reached, respectively. The PFS and in-field PFS rates were 24.6% and 79.2% at 1 year, 19.7% and 72.0% at 2 years, respectively. An alpha-fetoprotein level >1000 ng/mL was a significant prognostic factor for worse OS (HR, 5.674; 95% CI, 1.588-20.276; p=0.008); in-field complete/partial response was a significant prognostic factor for better OS (HR, 0.116; 95% CI, 0.027-0.499; p=0.004). The most common site of first failure was the lungs (13/34 patients, 38.2%), followed by the liver (7/34 patients, 20.6%). No patients developed radiation-induced liver disease or pulmonary embolism during follow-up. Conclusion: Combining RT and systemic therapy was safe and effective in treating patients with HCC with HVTT and IVCTT.

Nodal recurrence mapping and clinical target volumes after resection of intrahepatic cholangiocarcinoma or combined hepatocellular-cholangiocarcinoma.

Background: Scarce evidence exists for clinical target volume (CTV) definitions of regional lymph nodes (LNs) in intrahepatic cholangiocarcinoma (iCCA) or combined hepatocellular-cholangiocarcinoma (cHCC-CCA). We investigated the mapping pattern of nodal recurrence after surgery for iCCA and cHCC-CCA and provided evidence for the nodal CTV definition. Methods: We retrospectively reviewed the medical records of patients with iCCA or cHCC-CCA who underwent surgery between 2010 and 2020. Eligibility criteria included patients pathologically diagnosed with iCCA or cHCC-CCA after surgery and a first recurrent event in regional LNs during follow-up. All recurrent LNs were registered onto reference computed tomography images based on the vascular structures to reconstruct the node mapping. Fifty-three patients were eligible. LN regions were classified into four risk groups. Results: Hepatic hilar and portal vein-vena cava were the most common recurrent regions, with recurrence rates of 62.3 % and 39.6 % (high-risk regions), respectively. Recurrence rates in the left gastric, diaphragmatic, common hepatic, superior mesenteric vessels, celiac trunk, and paracardial regions ranged from 15.1 % to 30.2 % (intermediate-risk regions). There were fewer recurrences in the para-aortic (16a1, a2, b1) and splenic artery and hilum regions, with rates <10 % (low-risk regions). No LN recurrence was observed in the para-oesophageal or para-aortic region (16b2) (very low-risk regions). Based on node mapping, the CTV should include high- and intermediate-risk regions for pathologically negative LN patients during postoperative radiotherapy. Low-risk regions should be included for pathologically positive LN patients. Conclusion: We provide evidence for CTV delineation in patients with iCCA and cHCC-CCA based on recurrent LN mapping.

Optimizing the prognostic capacity of baseline 18F-FDG PET/CT metabolic parameters in extranodal natural killer/T-cell lymphoma by using relative and absolute thresholds.

Objectives: To investigate the prognostic capacity of baseline 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) metabolic parameters in extranodal natural killer/T-cell lymphoma (ENKTCL), and the influence of relative thresholds (RT) and absolute thresholds (AT) selection on prognostic capacity. Materials and methods: Metabolic tumor volume (MTV)-based parameters were defined using RTs (41 % or 25 % of maximum standardized uptake value [SUVmax]), ATs (SUV 2.5, 3.0, 4.0, or mean liver uptake) in 133 patients. Metabolic parameters were classified into avidity-related parameters (SUVmax, mean SUV [SUVmean], standard deviation of SUV [SUVsd]), volume-related parameters (RT-MTV), and avidity- and volume-related parameters (total lesion glycolysis [TLG] and AT-MTV). The prognostic capacity of the metabolic parameters and the effects of different threshold types (RT vs. AT) were evaluated. Results: All metabolic parameters were moderately associated with prognosis. However, the area under the receiver operating characteristic curve of MTV and TLG was slightly higher than that of avidity-related parameters for predicting 5-year progression-free survival (PFS) (0.614-0.705 vs. 0.563-0.609) and overall survival (OS) (0.670-0.748 vs. 0.562-0.593). Correlations of MTV and avidity-related parameters differed between RTs (r < 0.06, P = 0.324-0.985) and ATs (r 0.56-0.84, P ≤ 0.001). AT-MTV was the optimal predictor for PFS and OS, while RT-TLG was the optimal predictor for PFS, and the combination of RT-MTV with SUVmax was the optimal predictor for OS. Conclusion: The incorporation of volume and avidity significantly improved the prognostic capacity of PET in ENKTCL. Composite parameters that encompassed both avidity and volume were recommended.

Treatment outcome, toxicity, and quality of life of patients with bronchus-associated lymphoid tissue lymphoma.

The disease failure patterns and optimal treatment of bronchus-associated lymphoid tissue (BALT) lymphoma are unknown. This retrospective study involved 71 patients with primary BALT lymphoma who had received radiotherapy (RT), surgery, immunochemotherapy (IC), or observation. The median follow-up time was 66 months. The 5-year overall survival and lymphoma-specific survival were 91.2% and 96.1%, respectively, and were not significantly different among treatments. The 5-year cumulative incidence of overall failure for RT, surgery, IC, and observation was 0%, 9.7% (p = .160), 30.8% (p = .017), and 31.3% (p = .039). There was no grade ≥3 toxicity in RT group according to the CTCAE 5.0 reporting system. Quality of life (QoL) was at similarly good levels among the treatment groups. BALT lymphoma had a favorable prognosis but persistent risk of relapse after IC or observation. Given the very low disease failure risk and good QoL, RT remains an effective initial treatment for BALT lymphoma.

BALT lymphoma has a favorable prognosis but a persistent progression and relapse risk.Radiotherapy is associated with lower failure of disease progression and relapse, low toxicity and good quality of life.

Disparities in mortality risk after diagnosis of hematological malignancies in 185 countries: A global data analysis.

This study was to report proxy measures for mortality risk in patients with hematological malignancies across 185 countries globally and explore its association with their socioeconomic status and treatment. The incidence, mortality, and 5-year prevalence data were extracted from the GLOBOCAN database. The data regarding the human development index (HDI), gross national income (GNI), vulnerability index, and concordance with cancer Essential Medicines List (EML) were obtained from open-source reports. The ratio of mortality to 5-year-prevalence (MPR) and that of mortality to incidence (MIR) were calculated and age-standardized using Segi's world standard population. Finally, the possible associations were assessed using Pearson correlation analyses. In 2020, the global incidence, mortality, and 5-year prevalence of HMs were 1,278,362, 711,840, and 3,616,685, respectively. Global age-standardized MPR and MIR were 0.15 and 0.44, respectively; they varied significantly among 6 regions, 185 countries, 4 HM types, and 4 HDI groups worldwide. Older populations always had higher ratios. The correlation of MPRs and MIRs with HDI, GNI, and concordance with cancer EML was negative, whereas it was positive with the vulnerability index (lower was better). Increasing access to cancer drugs in resource-limited regions with a focus on vulnerable children may aid in reducing HM-related mortality risk.

Prediction of 5-year overall survival of diffuse large B-cell lymphoma on the pola-R-CHP regimen based on 2-year event-free survival and progression-free survival.

This study aimed to predict the 5-year overall survival (OS) benefit of pola-R-CHP versus R-CHOP in the POLARIX trial based on the 2-year event-free survival (EFS) and progression-free survival (PFS) rates in diffuse large B-cell lymphoma (DLBCL). We identified randomized controlled trials (RCT) published before 31 May 2023. The correlation between the logarithmic (log) hazard ratio (HR) for EFS (HREFS) or PFS (HRPFS) and the HR for OS (HROS) was estimated at the trial-level. Correlation analysis was performed between 2-year PFS or EFS and 5-year OS rates at the treatment arm-level. Linear regression models were used to calculate the 5-year OS of pola-R-CHP and R-CHOP. In the included 20 RCTs, a linear correlation between HREFS (r = 0.765) or HRPFS (r = 0.534) and HROS was observed at the trial- level. Two-year EFS (r = 0.918) or 2-year PFS (r = 0.865) correlated linearly with 5-year OS. Linear regression analysis between 2-year EFS/PFS and 5-year OS gave estimated 5-year OS rates between pola-R-CHP and R-CHOP of 6.4% and 6.3%, respectively. Two-year EFS and PFS are feasible early endpoints in patients with DLBCL treated primarily with immunochemotherapy. The pola-R-CHP regimen is expected to improve 5-year OS.

Real world practice of postoperative radiotherapy for patients with completely resected pIIIA-N2 non-small cell lung cancer: a national survey of radiation oncologists in China.

BACKGROUND: Results from Lung ART and PORT-C trials suggest that postoperative radiotherapy (PORT) cannot routinely be recommended as standard treatment in completely resected pIIIA-N2 NSCLC patients, but their effects on the real-world practice of PORT in China remain unclear. METHODS: A national cross-section survey was conducted by using an online survey service. Participants were voluntarily recruited using a river sampling strategy. A link to the survey was posted on websites of radiation oncologist associations and tweets from public WeChat accounts. The survey collected the real names of participants to ensure that they were board-certified radiation oncologists. RESULTS: A total of 484 radiation oncologists were included with a median age of 40 years (IQR, 35-47). A total of 377 (77.9%) participants were male, and 282 (58.1%) had more than 10 years of clinical experience practicing thoracic radiotherapy. Before Lung ART and PORT-C trials were published, 313 (64.7%) respondents recommended PORT, 11 (2.3%) did not recommend it, and 160 (33.1%) reported that they made decisions based on risk factors. After the presentation of two trials, only 42 (8.7%) did not recommend PORT, while 108 (22.3%) recommended it, and 334 (69.0%) made decisions based on risk factors. The five most commonly considered risk factors among these 334 respondents were as follows: nodal extracapsular extension, the highest lymph node (LN) station involved, the number of dissected mediastinal LN stations, the number of positive mediastinal LN stations, and surgical approaches. In addition, the majority of all 484 respondents recommended a total dose of 50 Gy, lung stump + ipsilateral hilus + regions containing positive LNs as the targeted region, lung V20 < 25%, and heart V30 < 40% as dose constraints for PORT. CONCLUSION: Most Chinese radiation oncologists recommended PORT for completely resected IIIA-N2 NSCLC patients based on risk factors, especially status of LN station.

Higher Lung and Heart Doses Decrease Early and Long-Term Survival, Respectively, in Patients With Non-Small Cell Lung Cancer Undergoing Postoperative Radiation.

Purpose: Cardiopulmonary toxic effects may reduce the efficacy of postoperative radiation therapy (PORT) in patients with non-small cell lung cancer (NSCLC). However, few studies have examined whether the heart and lung doses affect overall survival (OS). We investigated the correlation of heart and lung doses with OS in patients with NSCLC undergoing PORT. Methods and Materials: This retrospective analysis included 307 patients with NSCLC undergoing PORT. The total dose was 50 Gy. Landmark analyses were performed at 36 months, with hazard ratios (HRs) calculated separately for events occurring up to 36 months (early survival) and after 36 months (long-term survival). Stabilized inverse probability of treatment weighting (sIPTW) was performed to balance the characteristics of the high- and low-dose groups. We performed sensitivity analyses at 24 and 48 months. Results: The median follow-up period was 67.42 months. Heart doses were significantly correlated with long-term survival (HR, 1.14; P = .015) but not with early survival (HR, 0.97; P = .41) or whole survival (HR, 1.02; P = .58). Lung doses were marginally significantly correlated with early survival (HR, 1.03; P = .07) but not with long-term survival (HR, 1.00; P = .85) or whole survival (HR, 1.02; P = .12). Higher heart and lung doses were associated with decreased long-term and early survival, respectively, before and after sIPTW. Landmark analyses at 24 and 48 months showed consistent results. Conclusions: For patients with NSCLC undergoing PORT, a higher heart dose was associated with decreased long-term survival, whereas a higher lung dose was associated with decreased early survival.

Efficacy and safety of neoadjuvant immunotherapy combined with chemoradiotherapy or chemotherapy in esophageal cancer: A systematic review and meta-analysis.

Background: Significant progress has been made in the investigation of neoadjuvant immune-chemoradiotherapy (NICRT) and neoadjuvant immune-chemotherapy (NICT) on the outcomes of esophageal cancer patients. To summarize the current developments, a systematic review and meta-analysis were conducted to evaluate the efficacy and safety of neoadjuvant immunotherapy combined with chemoradiotherapy or chemotherapy. Methods: A search strategy of prospective studies on esophageal cancer receiving neoadjuvant immunotherapy was predefined to scan PubMed, Embase, Cochrane, and additional major conferences for prospective studies. Efficacy was assessed by pathological complete response (pCR), major pathological response (MPR), and R0 resection rates. Safety was evaluated based on the incidence of grade ≥ 3 treatment-related adverse events (TRAEs), neoadjuvant therapy completion rate, surgical resection rate, and surgical delay rate. Differences between the NICRT and NICT groups were also analyzed. Results: A total of 38 studies qualified for the analysis. The pooled pCR, MPR, and R0 resection rates were 30, 58, and 99%, respectively. The pCR and MPR in the NICRT vs. NICT group were 38% vs. 28% (p=0.078) and 67% vs. 57% (p=0.181), respectively. The pooled incidence of grade ≥ 3 TRAEs was 24% (NICRT,58%, I2 = 61% vs. NICT,18%, I2 = 79%; p<0.001). In addition, the pooled neoadjuvant therapy completion and surgical resection rates were 92% and 85%, respectively; the difference was not statistically significant between the NICRT and NICT groups. Conclusions: Neoadjuvant immunotherapy combined with chemoradiotherapy or chemotherapy is effective and safe in the short term for locally advanced esophageal cancer. However, further randomized trials are needed to confirm which combined model is more favorable. Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021284266, identifier CRD42021284266.

Efficacy and Safety of Concurrent Chemoradiotherapy Combined with Nimotuzumab in Elderly Patients with Esophageal Squamous Cell Carcinoma: A Prospective Real-world Pragmatic Study.

BACKGROUND: Concurrent or definitive chemoradiotherapy is the standard treatment of locally advanced esophageal squamous cell carcinoma (ESCC). Elderly patients could not tolerate the standard concurrent chemotherapy and were treated with radiotherapy because of weak physical status and multiple comorbidities. OBJECTIVE: The efficacy and safety profile of concurrent (chemo) radiotherapy combined with nimotuzumab in elderly patients with ESCC were investigated. METHODS: Eligible elderly (≥70 years) patients with locally advanced ESCC were enrolled in this prospective, real-world pragmatic study and received concurrent chemoradiotherapy or radiotherapy combined with nimotuzumab. The primary endpoint was overall survival (OS). Secondary endpoints were objective response rate, disease control rate, progression-free survival (PFS), and adverse drug reactions. RESULTS: Fifty-three elderly patients were enrolled. Thirty-two (60.4%) were treated with radiotherapy combined with nimotuzumab (RT+N), and 21 (39.6%) with concurrent chemoradiotherapy combined with nimotuzumab (CRT+N). The median age was 75.8 years. Fourteen (56.0%) patients achieved a partial response, and 11 (44.0%) patients achieved stable disease at 3 months. The median follow-up duration was 24.4 (95%CI, 21.6-26.7) months. Median OS (mOS) was 27.0 (95%CI, 14.8-48.4) months. Median PFS (mPFS) was 22.6 (95%CI, 12.4-not reached) months. Higher mPFS (not reached vs. 12.0 months; p=0.022) and mOS (48.4 vs. 15.3 months; p=0.009) were observed in the CRT+N group compared with the RT+N group. Most adverse reactions were grade 1-2 (46, 86.8%). CONCLUSIONS: Concurrent chemoradiotherapy or radiotherapy combined with nimotuzumab was safe and well-tolerated in elderly patients with locally advanced ESCC. ESCC patients treated with CRT+N could live longer.

Enhanced prediction of postoperative radiotherapy-induced esophagitis in non-small cell lung cancer: Dosiomic model development in a real-world cohort and validation in the PORT-C randomized controlled trial.

BACKGROUND: Radiotherapy-induced esophagitis (RE) diminishes the quality of life and interrupts treatment in patients with non-small cell lung cancer (NSCLC) undergoing postoperative radiotherapy. Dosimetric models showed limited capability in predicting RE. We aimed to develop dosiomic models to predict RE. METHODS: Models were trained with a real-world cohort and validated with PORT-C randomized controlled trial cohort. Patients with NSCLC undergoing resection followed by postoperative radiotherapy between 2004 and 2015 were enrolled. The endpoint was grade ≥2 RE. Esophageal three-dimensional dose distribution features were extracted using handcrafted and convolutional neural network (CNN) methods, screened using an entropy-based method, and selected using minimum redundancy and maximum relevance. Prediction models were built using logistic regression. The areas under the receiver operating characteristic curve (AUC) and precision-recall curve were used to evaluate prediction model performance. A dosimetric model was built for comparison. RESULTS: A total of 190 and 103 patients were enrolled in the training and validation sets, respectively. Using handcrafted and CNN methods, 107 and 4096 features were derived, respectively. Three handcrafted, four CNN-extracted and three dosimetric features were selected. AUCs of training and validation sets were 0.737 and 0.655 for the dosimetric features, 0.730 and 0.724 for handcrafted features, and 0.812 and 0.785 for CNN-extracted features, respectively. Precision-recall curves revealed that CNN-extracted features outperformed dosimetric and handcrafted features. CONCLUSIONS: Prediction models may identify patients at high risk of developing RE. Dosiomic models outperformed the dosimetric-feature model in predicting RE. CNN-extracted features were more predictive but less interpretable than handcrafted features.