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PURPOSE: To analyze the impact of sarcopenia and obesity on overall survival (OS) in patients with head and neck cancer (HNC) receiving radiotherapy (RT). METHODS: This prospective longitudinal study recruited 494 patients using convenient sampling. Weight and body composition were assessed before RT (T1), and at the end of RT (T2) using bioelectrical impedance analysis (BIA). The appendicular skeletal mass index was used to define sarcopenia, while the body mass index and fat mass index were used to define obesity. Patient OS was followed and described using Kplan-Meier analysis. Cox proportional hazard regression was used to analyze influencing factors of OS. RESULTS: The median follow-up time was 26.2 months (IQR: 18.4-34.4 months). Multivariable models indicated that sarcopenia/obesity type assessed at T1 was not significantly associated with OS. Multivariable models involving body composition at T2 showed that age (P < 0.001), tumor site (P = 0.003), tumor stage (P = 0.024), and sarcopenia/obesity type (P = 0.040) were significantly associated with OS, while sarcopenic patients without obesity at T2 had worse OS. CONCLUSIONS: Patients with sarcopenia and no obesity at the end of RT might have worse OS. Healthcare professionals should enhance HNC patients' management during RT, helping them maintain a certain amount of muscle mass and fat mass to improve their survival.
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BACKGROUND: This study aimed to investigate the efficacy and safety of pegylated recombinant human granulocyte colony-stimulating factor (PEG-rhG-CSF) for primary prophylaxis of neutropenia in patients with cervical cancer receiving concurrent chemoradiotherapy. METHODS: In this prospective, single-center, single-arm study, we enrolled patients (18-70 years) with 2018 International Federation of Gynecology and Obstetrics (FIGO) stage IIIC1r-IVA and IVB (distant metastasis only with inguinal lymph node metastasis) cervical cancer. Eligible patients should have normal function of the bone marrow (absolute neutrophil count (ANC) ≥ 2.0 × 109/L) and adequate hepatic and renal functions. Key exclusion criteria included: previous chemotherapy and/or radiotherapy; a history of bone marrow dysplasia or other hematopoietic abnormalities. All patients underwent radical radiotherapy (pelvic radiotherapy or extended-field irradiation) plus brachytherapy. The chemotherapy regimen included four cycles of 3-weekly paclitaxel and cisplatin. PEG-rhG-CSF was administered 48-72 h after each treatment cycle. Salvage granulocyte colony-stimulating factor (G-CSF) was only permitted in certain circumstances. The primary endpoint was the incidence of grade 3-4 neutropenia. The secondary endpoints included frequency of febrile neutropenia (FN), chemotherapy completion rate in cycles 2-4, time to complete radiotherapy, and safety. RESULTS: Overall, 52 patients were enrolled in this study from July 2019 to October 2020. The incidence of grade 3-4 neutropenia was 28.8%, with an average duration of grade 3-4 neutropenia persistence of 3.85 days (1-7 days). The incidence rate of FN was 3.8%. The chemotherapy completion rate was 94.2%, 82.7%, and 75.0% for cycles 2-4, respectively. The incidences of grade 3-4 neutropenia for cycles 1-4 were 9.6% (5/52), 8.2% (4/49), 14.0% (6/43), and 2.6% (1/39), respectively. All patients completed radiotherapy within 8 weeks (median, 48 days; range: 41-56 days), except one patient who withdrew consent and did not receive radiotherapy. Severe non-hematologic toxicity was not observed in any patient. CONCLUSION: PEG-rhG-CSF is an effective and safe prophylactic treatment for neutropenia in patients with cervical cancer undergoing concurrent chemoradiotherapy. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR1900024494. Date of Registration:13/July/2019.
Subject(s)
Chemoradiotherapy , Granulocyte Colony-Stimulating Factor , Neutropenia , Polyethylene Glycols , Recombinant Proteins , Uterine Cervical Neoplasms , Humans , Uterine Cervical Neoplasms/therapy , Female , Middle Aged , Adult , Prospective Studies , Chemoradiotherapy/adverse effects , Chemoradiotherapy/methods , Granulocyte Colony-Stimulating Factor/therapeutic use , Granulocyte Colony-Stimulating Factor/administration & dosage , Polyethylene Glycols/administration & dosage , Polyethylene Glycols/therapeutic use , Polyethylene Glycols/adverse effects , Recombinant Proteins/administration & dosage , Recombinant Proteins/therapeutic use , Aged , Neutropenia/prevention & control , Neutropenia/etiology , Cisplatin/adverse effects , Cisplatin/therapeutic use , Cisplatin/administration & dosage , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Young Adult , Adolescent , Paclitaxel/adverse effects , Paclitaxel/administration & dosage , Paclitaxel/therapeutic useABSTRACT
To compare the dosimetric differences in volumetric modulated arc therapy (VMAT) and intensity modulated proton therapy (IMPT) in stereotactic body radiation therapy (SBRT) of multiple lung lesions and determine a normal tissue complication probability (NTCP) model-based decision strategy that determines which treatment modality the patient will use. A total of 41 patients were retrospectively selected for this study. The number of patients with 1-6 lesions was 5, 16, 7, 6, 3, and 4, respectively. A prescription dose of 70 GyRBE in 10 fractions was given to each lesion. SBRT plans were generated using VMAT and IMPT. All the IMPT plans used robustness optimization with ± 3.5% range uncertainties and 5 mm setup uncertainties. Dosimetric metrics and the predicted NTCP value of radiation pneumonitis (RP), esophagitis, and pericarditis were analyzed to evaluate the potential clinical benefits between different planning groups. In addition, a threshold for the ratio of PTV to lungs (%) to determine whether a patient would benefit highly from IMPT was determined using receiver operating characteristic curves. All plans reached target coverage (V70GyRBE ≥ 95%). Compared with VMAT, IMPT resulted in a significantly lower dose of most thoracic normal tissues. For the 1-2, 3-4 and 5-6 lesion groups, the lung V5 was 29.90 ± 9.44%, 58.33 ± 13.35%, and 81.02 ± 5.91% for VMAT and 11.34 ± 3.11% (p < 0.001), 21.45 ± 3.80% (p < 0.001), and 32.48 ± 4.90% (p < 0.001) for IMPT, respectively. The lung V20 was 12.07 ± 4.94%, 25.57 ± 6.54%, and 43.99 ± 11.83% for VMAT and 6.76 ± 1.80% (p < 0.001), 13.14 ± 2.27% (p < 0.01), and 19.62 ± 3.48% (p < 0.01) for IMPT. The Dmean of the total lung was 7.65 ± 2.47 GyRBE, 14.78 ± 2.75 GyRBE, and 21.64 ± 4.07 GyRBE for VMAT and 3.69 ± 1.04 GyRBE (p < 0.001), 7.13 ± 1.41 GyRBE (p < 0.001), and 10.69 ± 1.81 GyRBE (p < 0.001) for IMPT. Additionally, in the VMAT group, the maximum NTCP value of radiation pneumonitis was 73.91%, whereas it was significantly lower in the IMPT group at 10.73%. The accuracy of our NTCP model-based decision model, which combines the number of lesions and PTV/Lungs (%), was 97.6%. The study demonstrated that the IMPT SBRT for multiple lung lesions had satisfactory dosimetry results, even when the number of lesions reached 6. The NTCP model-based decision strategy presented in our study could serve as an effective tool in clinical practice, aiding in the selection of the optimal treatment modality between VMAT and IMPT.
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BACKGROUND: Definitive chemoradiotherapy is one of the primary treatment modalities for older patients with esophageal cancer (EC). However, the evolution of prognosis over time and the factors affected non-EC deaths remain inadequately studied. We examined the conditional survival and annual hazard of death in older patients with EC after chemoradiotherapy. METHODS: We collected data from patients aged 65 or older with EC registered in the Surveillance, Epidemiology, and End Results database during 2000-2019. Conditional survival was defined as the probability of survival given a specific time survived. Annual hazard of death was defined the yearly event rate. Restricted cubic spline (RCS) analysis identified the association of age at diagnosis with mortality. RESULTS: Among 3739 patients, the 3-year conditional overall survival increased annually by 7-10%. Non-EC causes accounted for 18.8% of deaths, predominantly due to cardio-cerebrovascular diseases. The hazard of death decreased from 40 to 10% in the first 6 years and then gradually increased to 20% in the tenth year. Non-EC causes surpassed EC causes in hazard starting 5 years post-treatment. RCS indicated a consistent increase in death hazard with advancing age, following a linear relationship. The overall cohort was divided into two groups: 65-74 and ≥ 75 years old, with the ≥ 75-year-old group showing poorer survival and earlier onset of non-EC deaths (HR = 1.36, 95% CI: 1.15-1.62, P < 0.001). Patients with early-stage disease (I-II) had higher risks of death from non-EC causes (HR = 0.82, 95% CI: 0.68-0.98, P = 0.035). Tumor histology had no significant impact on non-EC death risk (HR = 1.17, 95% CI: 0.98-1.39, P = 0.081). CONCLUSIONS: Survival probability increases with time for older patients with EC treated with chemoradiotherapy. Clinicians and patients should prioritize managing and preventing age-related comorbidities, especially in older cohorts and those with early-stage disease.
Subject(s)
Esophageal Neoplasms , Humans , Aged , Esophageal Neoplasms/epidemiology , Esophageal Neoplasms/pathology , Chemoradiotherapy/methods , Prognosis , ComorbidityABSTRACT
PURPOSE: Residual lymph node metastases (RLNM) remained a great concern in the implementation of organ-preserving strategies and led to poor prognosis in locally advanced rectal cancer (LARC). In this study, we aimed to identify the clinicopathological factors correlated with RLNM in LARC patients with ypT0-2 after neoadjuvant chemoradiotherapy (NCRT). METHODS: We retrospectively analyzed 417 patients histologically diagnosed middle-low LARC after NCRT and total mesorectal excision (TME), whose pathological staging was ypT0-2. All patients received pelvic magnetic resonance imaging (MRI) before NCRT. The radiation doses were 50-50.6 Gy for the planning gross tumor volume and 41.8-45 Gy for the planning target volume, respectively. A nomogram for predicting RLNM was constructed using a binary logistic regression. Nomogram performance was assessed by receiver operating characteristic (ROC) curve, calibration curve, decision curve analysis (DCA) and clinical impact curve (CIC). RESULTS: After surgery, 191 patients (45.8%) were ypT0, 43 patients (10.3%) were ypT1 and 183 patients (43.9%) were ypT2, and a total of 49 patients (11.8%) were found the presence of RLNM. Multivariable analyses identified MRI-defined mesorectal fascia (MRF)-positive, high-grade histopathology at biopsy, advanced ypT-category, and the presence of perineural invasion (PNI) as the predictive factors. The nomogram, incorporating all these predictors, showed good discrimination and calibration efficacy, with the areas under the ROC curve of 0.690 (95% CI: 0.610-0.771). Both DCA and CIC demonstrated that this nomogram has good clinical usefulness. CONCLUSION: The nomogram model can predict RLNM in patients with ypT0-2 tumors. It can help select suitable patients for performing organ-preserving strategies after NCRT.
Subject(s)
Neoplasms, Second Primary , Rectal Neoplasms , Humans , Neoadjuvant Therapy , Lymphatic Metastasis , Retrospective Studies , Neoplasm Staging , Rectal Neoplasms/therapy , Rectal Neoplasms/pathology , Chemoradiotherapy , Chemoradiotherapy, Adjuvant , Neoplasms, Second Primary/pathologyABSTRACT
BACKGROUND: Adult head and neck rhabdomyosarcoma (HNRMS) is an exceptionally rare malignancy, and there is a paucity of data and research dedicated to understanding its characteristics and management in adult populations. This study aimed to assess the outcomes and identify survival predictors in adult HNRMS. METHODS: We retrospectively evaluated 42 adult patients (> 16 years) with HNRMS who received radiotherapy (RT)-based treatment at our institute between 2008 and 2022. We analysed the clinical characteristics and prognosis of these patients, including the locoregional recurrence-free survival (LRFS), progression-free survival (PFS), and overall survival (OS), using the Kaplan-Meier method. The chi-square and Fisher's exact tests were used to analyse differences between groups for dichotomous and categorical variables, respectively. Survival rates were calculated using the Kaplan-Meier method. Prognostic variables were assessed through univariate Cox analyses. RESULTS: The median patient age was 28 years (range, 16-82 years). Alveolar RMS was the most common histological type, observed in 21 patients (50.0%), followed by embryonal in 16 patients (38.1%). The anatomic sites of origin were orbital in one (2.4%), parameningeal in 26 (61.9%), and non-orbital/non-parameningeal in 15 (35.7%) patients. Nineteen patients (45.2%) had regional lymph node metastasis, and five patients (11.9%) presented with distant metastatic disease. Distant metastasis (n = 17) was the primary cause of treatment failure. At a median follow-up of 47.0 months, the 5-year LRFS, PFS, and OS rates were 69.0%, 39.7%, and 41.0%, respectively. Univariate analysis revealed that tumour size, lymph node involvement, and the local treatment pattern (surgery and RT vs. RT alone) were significant predictors of survival. CONCLUSIONS: The main failure pattern in patients with HNRMS receiving RT-based treatment was distant metastasis. Tumour size > 5 cm and lymph node involvement were predictors of worse LRFS. Multimodality local treatment, combining surgery and RT, is effective and provides survival benefits.
Subject(s)
Head , Rhabdomyosarcoma , Adult , Humans , Adolescent , Young Adult , Middle Aged , Aged , Aged, 80 and over , Retrospective Studies , Neck , Rhabdomyosarcoma/radiotherapy , Combined Modality TherapyABSTRACT
Background: Various studies support the use of programmed cell death protein 1 (PD-1) blockades, also known as immune checkpoint inhibitors (ICIs), to treat head and neck cancer (HNC). Tislelizumab is a humanised immunoglobulin G4 (IgG4) monoclonal antibody with a high affinity and specificity for PD-1. However, the "real-world" clinical evidence of tislelizumab for HNC is limited. Methods: In this study, the medical records of 39 patients with head and neck squamous cell carcinoma (HNSCC) or nasopharyngeal carcinoma (NPC) who received tislelizumab between January 2021 and March 2022 were reviewed retrospectively. Tislelizumab was administered to 15 patients during neoadjuvant therapy (Group 1), five patients during adjuvant therapy (Group 2), 14 patients during consolidation therapy (Group 3), and five patients during salvage therapy (Group 4). The Kaplan-Meier method was used to calculate progression-free survival (PFS) and overall survival (OS). Results: The median age of enrolled patients was 55 (range, 28-83) years. The median follow-up time was 27.1, 26.1, 28.6, and 20.9 months for Groups 1, 2, 3, and 4, respectively. The mean PFS and OS of Groups 1, 2, 3, and 4 were 21.5 and 22.8; 24.1 and 24.2; 26.9 and 28.1; and 13.9 and 17.1 months, respectively. In Groups 1 and 4, the objective response rate (ORR) was 86.7% and 60%, respectively. Meanwhile, except for one (2.6%) patient with grade 4 enteritis, the other observed non-haematological adverse events (AEs) were ≤ grade 2. Conclusions: Tislelizumab demonstrated promising efficacy and tolerability in patients with HNSCC or NPC in a real-world setting, consistent with previous reports.
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Background & Aims: This study aims to analyze the prognosis of null-margin (≤1.0 mm) hepatectomy (NH) in patients with hepatocellular carcinoma (HCC) adhering to the major vessels and explore the value of postoperative radiotherapy (RT) in these patients. Methods: HCC patients who underwent null-margin or wide-margin (≥1.0 cm) hepatectomy (WH) by our team from January 2008 to March 2016 were recruited and analyzed retrospectively. The patients were divided into the NH, NH + RT, and WH groups. Propensity score matching (PSM) was performed to balance baseline characteristics. Results: A total of 357 patients were recruited. Of these, 84, 49, and 224 patients were given NH alone, NH plus RT, and WH, respectively. After PSM, the 5-year overall survival (OS) and disease-free survival (DFS) rates of the NH group were significantly worse than those of the WH group (51.5 % vs. 71.4 %, P = 0.003; 32.2 % vs. 50.9 %, P = 0.005). The OS and DFS rates of the NH + RT group were significantly higher than those of the NH group (75.6 % vs. 56.1 %, P = 0.012; 46.6 % vs. 30.2 %, P = 0.015) and similar to those of the WH group (75.6 % vs. 75.1 %, P = 0.354; 46.6 % vs. 56.6 %, P = 0.717). In addition, patients in the NH + RT group experienced significantly lower early (P = 0.023) and intrahepatic (P = 0.015) recurrences than those in the NH group. Conclusions: Patients with HCC adhering to the major vessels who underwent NH alone had a poorer prognosis, and the addition of RT to NH provide a significant survival benefit for these patients, which may yield outcomes comparable to the efficacy of WH.
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This study aimed to explore the distribution, characteristics and prognostic value of baseline peripheral blood lymphocyte subsets in patients with extranodal NK/T-cell lymphoma (NKTCL). We conducted this cross-sectional study of 205 newly-diagnosed NKTCL patients receiving first-line chemotherapy and radiation at our institute between 2010 and 2020. Baseline peripheral blood lymphocytes were detected using flow cytometry, and the clinical value was analyzed. Compared with healthy controls, patients with NKTCL presented with a distinct peripheral immunity with higher levels of cytotoxic CD8+ T cells (33.230 ± 12.090% vs. 27.060 ± 4.010%, p < 0.001) and NKT cells (7.697 ± 7.219% vs. 3.550 ± 2.088%, p < 0.001) but lower proportions of suppressive regulatory T cells (Treg, 2.999 ± 1.949% vs. 3.420 ± 1.051%, p = 0.003) and CD4+ helper T cells (Th, 33.084 ± 11.361% vs. 37.650 ± 3.153%, p < 0.001). Peripheral lymphocytes were differentially distributed according to age, stage, and primary site in patients with NKTCL. The proportion of Th cells/lymphocytes was associated with tumor burden reflected by stage (p = 0.037), serum lactate dehydrogenase (p = 0.0420), primary tumor invasion (p = 0.025), and prognostic index for NK/T-cell lymphoma (PINK) score (p = 0.041). Furthermore, elevated proportions of T cells (58.9% vs. 76.4%, p = 0.005), Th cells (56.3% vs. 68.8%, p = 0.047), or Treg cells (49.5% vs. 68.9%, p = 0.040) were associated with inferior 5-year progression-free survivals (PFS) via univariable survival analysis. Multivariate cox regression revealed elevated Th cells as an independent predictor for unfavorable PFS (HR = 2.333, 95% CI, 1.030-5.288, p = 0.042) in NKTCL. These results suggested the proportion of Th cells positively correlated with tumor burden and was a potential non-invasive biomarker for inferior survival for patients with NKTCL.
Subject(s)
Lymphoma, Extranodal NK-T-Cell , Humans , Prognosis , Flow Cytometry , Cross-Sectional Studies , Lymphoma, Extranodal NK-T-Cell/drug therapy , T-Lymphocytes, Helper-Inducer , Lymphocytes/pathologyABSTRACT
The present study aimed to investigate the clinical features, prognosis, and treatment of advanced-stage non-nasal type extranodal natural killer/T-cell lymphoma (ENKTCL). This real-world study retrospectively reviewed 56 newly diagnosed advanced-stage non-nasal type ENKTCL patients from two large-scale Chinese cancer centers in the last 10-15 years and screened 139 newly diagnosed advanced-stage nasal type ENKTCLs admitted during the same period for comparison. The non-nasal type ENKTCLs exhibited significantly higher Ki-67 expression levels compared to nasal type disease (P = 0.011). With a median follow-up duration of 75.03 months, the non-nasal group showed slightly inferior survival outcomes without statistically significant differences compared to the nasal group (median overall survival (OS): 14.57 vs. 21.53 months, 5-year OS: 28.0% vs. 38.5%, P = 0.120). Eastern Cooperative Oncology Group (ECOG) score ≥ 2 (hazard ratio (HR) = 2.18, P = 0.039) and lactic dehydrogenase (LDH) elevation (HR = 2.44, P = 0.012) were significantly correlated with worse OS in the non-nasal group. First-line gemcitabine-based chemotherapy regimens showed a trend toward slightly improved efficacy and survival outcomes compared to non-gemcitabine-based ones in the present cohort of non-nasal ENKTCLs (objective response rate: 91.7% vs. 63.6%, P = 0.144; complete response rate: 50.0% vs. 33.3%, P = 0.502; median progression-free survival: 10.43 vs. 3.40 months, P = 0.106; median OS: 25.13 vs. 9.30 months, P = 0.125), which requires further validation in larger sample size studies. Advanced-stage non-nasal type patients could achieve comparable prognosis with nasal cases after rational therapy. The modified nomogram-revised index (including age, ECOG score, and LDH) and modified international prognostic index (including age, ECOG score, LDH, and number of extranodal involvement) functioned effectively for prognostic stratification in non-nasal type ENKTCLs.
Subject(s)
Lymphoma, Extranodal NK-T-Cell , Lymphoma, T-Cell , Humans , Prognosis , Retrospective Studies , Proportional Hazards Models , Killer Cells, Natural/pathology , Lymphoma, T-Cell/pathology , Lymphoma, Extranodal NK-T-Cell/diagnosis , Lymphoma, Extranodal NK-T-Cell/drug therapy , Neoplasm StagingABSTRACT
PURPOSE: This study aimed to assess the impact of ypT stage and tumor regression grade (TRG) on the long-term prognosis of patients with locally advanced rectal cancer (LARC) stage ypT1-4N0 after neoadjuvant chemoradiotherapy (NCRT). METHODS: We retrospectively analyzed 585 patients with histologically diagnosed middle-low LARC (cT3-4 or cN + by pelvic MRI) from 2014 to 2019. All patients underwent NCRT, followed by total mesorectal excision. Disease-free survival (DFS) rates were compared among patients with different ypT stages and TRGs by Kaplan-Meier survival analysis. The chi-square test was used to analyze the relationship between clinicopathological or therapeutic factors and ypT stage. RESULTS: The median follow-up was 35.8 months (range 2.8-71.8 months). The 3-year DFS was 79.5%. A better 3-year DFS was achieved in patients with a pathologic complete response (94.0% vs. 74.3%, p < 0.001) and those in the ypT0-2 (86.5% vs. 66.6%, p < 0.001), ypN0 (85.0% vs. 60.2%, p < 0.001), and TRG0 + 1 (83.1% vs. 73.0%, p = 0.004) subgroups. A total of 309 patients (52.8%) achieved stage ypT1-4N0 after surgery. Among these patients, the ypT1-2N0 subgroup achieved a significantly higher 3-year DFS than the ypT3-4N0 subgroup (85.4% vs. 72.8%, p = 0.018); in contrast, the 3-year DFS did not significantly differ between the TRG1 and TRG2 + 3 subgroups (79.9% vs. 81.1%, p = 0.833). In the ypT1-2N0 or ypT3-4N0 subgroup, different TRG had no significant effect on failure patterns. CONCLUSIONS: For LARC patients with a ypT1-4N0 status after NCRT, ypT stage may be a more effective predictor of long-term prognosis than TRG.
Subject(s)
Neoadjuvant Therapy , Rectal Neoplasms , Humans , Treatment Outcome , Retrospective Studies , Neoplasm Staging , Chemoradiotherapy , Prognosis , Rectal Neoplasms/pathologyABSTRACT
This study evaluated the feasibilities and outcomes following four-dimensional magnetic resonance imaging (4D-MRI) assisted stereotactic body radiation therapy (SBRT) for unresectable colorectal liver metastases (CRLMs). From March 2018 to January 2022, we identified 76 unresectable CRLMs patients with 123 lesions who received 4D-MRI guided SBRT in our institution. 4D-MRI simulation with or without abdominal compression was conducted for all patients. The prescription dose was 50-65 Gy in 5-12 fractions. The image quality of computed tomography (CT) and MRI were compared using the Clarity Score. Clinical outcomes and toxicity profiles were evaluated. 4D-MRI improved the image quality compared with CT images (mean Clarity Score: 1.67 vs 2.88, P < 0.001). The abdominal compression reduced motions in cranial-caudal direction (P = 0.03) with two phase T2 weighted images assessing tumor motion. The median follow-up time was 12.5 months. For 98 lesions assessed for best response, the complete response, partial response and stable disease rate were 57.1 %, 30.6 % and 12.2 %, respectively. The local control (LC) rate at 1 year was 97.3 %. 46.1 % of patients experienced grade 1-2 toxicities and only 2.6 % patients experienced grade 3 hematologic toxicities. The 4D-MRI technique allowed accurate target delineation and motion tracking in unresectable CRLMs patients. Favorable LC rate and mild toxicities were achieved. This study provided evidence for using 4D-MRI assisted SBRT as an alternative treatment in unresectable CRLMs.
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BACKGROUND: Mutated KRAS may indicate an invasive nature and predict prognosis in locally advanced rectal cancer (LARC). We aimed to establish a radiomic model using pretreatment T2W MRIs to predict KRAS status and explore the association between the KRAS status or model predictions and lung metastasis. METHODS: In this retrospective multicentre study, LARC patients from two institutions between January 2012 and January 2019 were randomly divided into training and testing cohorts. Least absolute shrinkage and selection operator (LASSO) regression and the support vector machine (SVM) classifier were utilized to select significant radiomic features and establish a prediction model, which was validated by radiomic score distribution and decision curve analysis. The association between the model stratification and lung metastasis was investigated by Cox regression and KaplanâMeier survival analysis; the results were compared by the log-rank test. RESULTS: Overall, 103 patients were enrolled (73 and 30 in the training and testing cohorts, respectively). The median follow-up was 38.1 months (interquartile range: 26.9, 49.4). The radiomic model had an area under the curve (AUC) of 0.983 in the training cohort and 0.814 in the testing cohort. Using a cut-off of 0.679 defined by the receiver operating characteristic (ROC) curve, patients with a high radiomic score (RS) had a higher risk for lung metastasis (HR 3.565, 95% CI 1.337, 9.505, p = 0.011), showing similar predictive performances for the mutant and wild-type KRAS groups (HR 3.225, 95% CI 1.249, 8.323, p = 0.016, IDI: 1.08%, p = 0.687; NRI 2.23%, p = 0.766). CONCLUSIONS: We established and validated a radiomic model for predicting KRAS status in LARC. Patients with high RS experienced more lung metastases. The model could noninvasively detect KRAS status and may help individualize clinical decision-making.
Subject(s)
Lung Neoplasms , Rectal Neoplasms , Humans , Proto-Oncogene Proteins p21(ras)/genetics , Lung Neoplasms/diagnostic imaging , Lung Neoplasms/genetics , Retrospective Studies , Magnetic Resonance Imaging/methods , Rectal Neoplasms/diagnostic imaging , Rectal Neoplasms/genetics , Rectal Neoplasms/therapyABSTRACT
BACKGROUND AND PURPOSE: Motion estimation from severely downsampled 4D-MRI is essential for real-time imaging and tumor tracking. This simulation study developed a novel deep learning model for simultaneous MR image reconstruction and motion estimation, named the Downsampling-Invariant Deformable Registration (D2R) model. MATERIALS AND METHODS: Forty-three patients undergoing radiotherapy for liver tumors were recruited for model training and internal validation. Five prospective patients from another center were recruited for external validation. Patients received 4D-MRI scans and 3D MRI scans. The 4D-MRI was retrospectively down-sampled to simulate real-time acquisition. Motion estimation was performed using the proposed D2R model. The accuracy and robustness of the proposed D2R model and baseline methods, including Demons, Elastix, the parametric total variation (pTV) algorithm, and VoxelMorph, were compared. High-quality (HQ) 4D-MR images were also constructed using the D2R model for real-time imaging feasibility verification. The image quality and motion accuracy of the constructed HQ 4D-MRI were evaluated. RESULTS: The D2R model showed significantly superior and robust registration performance than all the baseline methods at downsampling factors up to 500. HQ T1-weighted and T2-weighted 4D-MR images were also successfully constructed with significantly improved image quality, sub-voxel level motion error, and real-time efficiency. External validation demonstrated the robustness and generalizability of the technique. CONCLUSION: In this study, we developed a novel D2R model for deformation estimation of downsampled 4D-MR images. HQ 4D-MR images were successfully constructed using the D2R model. This model may expand the clinical implementation of 4D-MRI for real-time motion management during liver cancer treatment.
Subject(s)
Image Processing, Computer-Assisted , Liver Neoplasms , Humans , Prospective Studies , Retrospective Studies , Image Processing, Computer-Assisted/methods , Magnetic Resonance Imaging/methods , Motion , Liver Neoplasms/diagnostic imaging , Liver Neoplasms/radiotherapyABSTRACT
BACKGROUND: The study aimed to investigate the efficacy of induction immunochemotherapy before radiotherapy (RT) for patients with locally advanced or metastatic esophageal cancer. METHODS: Patients with unresectable locally advanced or metastatic esophageal cancer who received induction immunochemotherapy followed by RT (ICIs + RT group) and RT alone (RT group) were retrospectively identified in two cancer centers, respectively. Propensity score matching (PSM) was used to balance the potential confounders between the two groups. Overall survival (OS), progression-free survival (PFS), and recurrence patterns were evaluated. RESULTS: A total of 467 patients were reviewed, and 66 were matched in each group. After PSM, the 1- and 2-year OS rates were 84.6% and 57.9% in ICIs + RT group, and 71.1% and 43.0% in RT group (HR 0.60, 95% CI 0.36-1.00, p = 0.050). The absolute increase of restricted mean survival time (RMST) for OS in ICIs + RT group compared with RT group were 0.89 years (p = 0.023) at one year and 2.59 years at two years (p = 0.030). The median PFS time, 1- and 2-year PFS rates were 20.3 months, 69.3%, and 45.7% in ICIs + RT group, and 12.2 months, 51.4%, and 35.8% in RT group (HR 0.64, 95% CI 0.41-0.99, p = 0.045). The cumulative locoregional recurrence (LRR) rate was significantly lower in ICIs + RT group (1-year rate, 17.4% vs. 38.8%, p = 0.011), and distant metastasis (DM) rates were comparable (p = 0.755). Consolidation ICIs was associated with a trend of improved 1-year OS and PFS. CONCLUSION: Induction immunochemotherapy followed by RT might improve locoregional control and survival outcomes for patients with unresectable locally advanced or metastatic esophageal cancer.
Subject(s)
Esophageal Neoplasms , Neoplasm Recurrence, Local , Humans , Retrospective Studies , Propensity Score , Esophageal Neoplasms/therapy , Progression-Free SurvivalABSTRACT
The study investigated the treatment and prognosis of advanced-stage extranodal natural killer/T-cell lymphoma (ENKTL). With a median follow-up of 75.03 months, the median overall survival (mOS) for the 195 newly diagnosed stage III/IV ENKTL patients was 19.43 months, and estimated 1-, 2-, 3- and 5-year OS were 59.5%, 46.3%, 41.8% and 35.1%, respectively. Chemotherapy (CT) + radiotherapy (RT) compared to CT alone (P = .007), and hematopoietic stem cell transplantation (HSCT) compared to non-HSCT (P < .001), both improved OS. For patients ≤60 years and ineligible for HSCT, other therapies with complete remission led to comparable OS (P = .141). Nine patients ever treated with chidamide achieved a median progression-free survival (mPFS) and mOS of 53.63 (range, 3.47-92.33) and 54.80 (range, 5.50-95.70) months, and four with chidamide maintenance therapy (MT) achieved a mPFS and mOS of 55.83 (range, 53.27-92.33) and 60.65 (range, 53.70-95.70) months, possibly providing an alternative option for non-HSCT patients. Non-anthracycline (ANT)- compared to ANT-, asparaginase (Aspa)- compared to non-Aspa- and gemcitabine (Gem)- compared to non-Gem-based regimens, prolonged PFS (P = .031; P = .005; P = .009) and OS (P = .010; P = .086; P = .003), respectively. Multivariate analysis demonstrated that Gem-based regimens improved PFS (HR = 0.691, P = .061) and OS (HR = 0.624, P = .037). Gem + Aspa combinations slightly improved PFS and OS compared to regimens containing Gem or Aspa alone (P > 0.05). First-line "intensive therapy," including CT (particularly Gem + Aspa regimens), RT, HSCT and alternative chidamide MT, was proposed and could improve long-term survival for advanced-stage ENKTLs. Ongoing prospective clinical studies may shed further light on the value of chidamide MT.
Subject(s)
Lymphoma, Extranodal NK-T-Cell , Humans , Lymphoma, Extranodal NK-T-Cell/drug therapy , Prospective Studies , Aminopyridines , Benzamides/therapeutic use , Asparaginase , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Gemcitabine , Anthracyclines/therapeutic use , Retrospective StudiesABSTRACT
INTRODUCTION: Whether supraclavicular lymph node (SCLN) metastasis in patients with oesophageal cancer belongs to regional disease is controversial, leading to heterogeneity in clinical treatment decisions. This study aimed to determine the optimal treatment for lower thoracic oesophageal cancer (LTOC) with SCLN metastasis. METHODS: Patients with LTOC registered in the Surveillance, Epidemiology, and End Results database during 2010-2015 were identified. Selected patients were grouped according to disease spread as those with locoregional disease, with SCLN metastasis or with distant metastasis, as well as according to treatment modality (neoadjuvant chemoradiotherapy followed by surgery (nCRT+S group), upfront surgery ± adjuvant therapy (upfront S group) and definitive chemoradiotherapy (dCRT group)). The Cox regression analysis and inverse probability of treatment weighting (IPTW) were used to identify the optimal treatment modality for different groups. RESULTS: Of 11,767 LTOC patients identified from the database, the 5-year overall survival (OS) rates for patients with the locoregional disease (n = 7,541), SCLN metastasis (n = 120) and distant metastasis (n = 4,106) were 28.3%, 10.0% and 3.0%, respectively (P < 0.001). Among patients with SCLN metastasis, median OS in the nCRT+S, upfront S and dCRT groups were 25, 14 and 8 months, respectively (P < 0.001). After IPTW, the nCRT+S group was still associated with better median OS compared with other groups. The multivariate analysis identified treatment modality as an independent prognostic factor for OS. CONCLUSIONS: Neoadjuvant chemoradiotherapy followed by oesophagectomy may be the optimal treatment modality for LTOC with SCLN metastasis. The findings of this study need to be validated in large prospective studies.
Subject(s)
Esophageal Neoplasms , Neoadjuvant Therapy , Humans , Lymphatic Metastasis/pathology , Esophagectomy , Prospective Studies , Esophageal Neoplasms/therapy , Lymph Nodes , Chemoradiotherapy/methods , Probability , Retrospective Studies , Neoplasm StagingABSTRACT
OBJECTIVE: The identification of biomarkers for predicting chemoradiotherapy efficacy is essential to optimize personalized treatment. This study determined the effects of genetic variations in genes involved in apoptosis, pyroptosis, and ferroptosis on the prognosis of patients with locally advanced rectal cancer receiving postoperative chemoradiotherapy (CRT). METHODS: The Sequenom MassARRAY was used to detect 217 genetic variations in 40 genes from 300 patients with rectal cancer who received postoperative CRT. The associations between genetic variations and overall survival (OS) were evaluated using hazard ratios (HRs) and 95% confidence intervals (CIs) computed using a Cox proportional regression model. Functional experiments were performed to determine the functions of the arachidonate 5-lipoxygenase (ALOX5) gene and the ALOX5 rs702365 variant. RESULTS: We detected 16 genetic polymorphisms in CASP3, CASP7, TRAILR2, GSDME, CASP4, HO-1, ALOX5, GPX4, and NRF2 that were significantly associated with OS in the additive model (P < 0.05). There was a substantial cumulative effect of three genetic polymorphisms (CASP4 rs571407, ALOX5 rs2242332, and HO-1 rs17883419) on OS. Genetic variations in the CASP4 and ALOX5 gene haplotypes were associated with a higher OS. We demonstrated, for the first time, that rs702365 [G] > [C] represses ALOX5 transcription and corollary experiments suggested that ALOX5 may promote colon cancer cell growth by mediating an inflammatory response. CONCLUSIONS: Polymorphisms in genes regulating cell death may play essential roles in the prognosis of patients with rectal cancer who are treated with postoperative CRT and may serve as potential genetic biomarkers for individualized treatment.
Subject(s)
Polymorphism, Genetic , Rectal Neoplasms , Humans , Prognosis , Chemoradiotherapy , Cell Death , Biomarkers , Rectal Neoplasms/genetics , Rectal Neoplasms/therapyABSTRACT
Background: Induction chemotherapy combined with neoadjuvant chemoradiotherapy has been recommended for patients with high-risk, locally advanced rectal cancer. However, the benefit of more intensive total neoadjuvant treatment (TNT) is unknown. This study aimed to assess the safety and efficacy of induction chemotherapy combined with chemoradiotherapy and consolidation chemotherapy for magnetic resonance imaging-stratified high-risk rectal cancer. Methods: This was a single-center, single-arm, prospective Phase II trial in Peking University Cancer Hospital (Beijing, China). Patients received three cycles of induction oxaliplatin and capecitabine (CapeOX) followed by chemoradiotherapy and two cycles of consolidation CapeOX. The primary end point was adverse event rate and the second primary end points were 3-year disease-free survival rate, completion of TNT, and pathological downstaging rate. Results: Between August 2017 and August 2018, 68 rectal cancer patients with at least one high risk factor (cT3c/3d/T4a/T4b, cN2, mesorectal fascia involvement, or extramural venous invasion involvement) were enrolled. The overall compliance of receiving the entire treatment was 88.2% (60/68). All 68 patients received induction chemotherapy, 65 received chemoradiotherapy, and 61 received consolidation chemotherapy. The Grade 3-4 adverse event rate was 30.8% (21/68). Nine patients achieved clinical complete response and then watch and wait. Five patients (7.4%) developed distant metastasis during TNT and received palliative chemotherapy. Fifty patients underwent surgical resection. The complete response rate was 27.9%. After a median follow-up of 49.2 months, the overall 3-year disease-free survival rate was 69.7%. Conclusions: For patients with high-risk rectal cancer, this TNT regimen can achieve favorable survival and complete response rates but with high toxicity. However, it is necessary to pay attention to the possibility of distant metastasis during the long treatment period.
ABSTRACT
Background: Few studies have evaluated the significance of sarcopenia in predicting the outcomes of patients with adenocarcinoma of the esophagogastric junction (AEG), especially those who received neoadjuvant chemoradiotherapy (NCRT). We aimed to identify the sarcopenic status and its impact on the outcomes of patients with locally advanced AEG who received NCRT followed by radical surgery or systemic therapy. Materials and methods: Patients with T3-4N+M0 AEG with accessible abdominal computed tomography (CT) before and after NCRT were retrospectively analyzed. Body composition parameters, particularly the skeletal muscle index (SMI), were assessed using a CT-based method, and sarcopenia was defined using a predetermined SMI cutoff value. Survival analysis was conducted using the Kaplan-Meier method. A Cox proportional hazards regression model was used to identify independent prognostic factors. Receiver operating characteristic curve analysis was carried out, and the area under the curve (AUC) was calculated to test the prognostic accuracy of different factors. Results: A total of 63 patients were enrolled, 65.1 and 79.4% of whom developed pre- and post-NCRT sarcopenia, respectively. Patients with pre-NCRT sarcopenia had lower radical surgery rates (70.7 vs. 95.5%, p = 0.047) than those without sarcopenia; however, sarcopenic status did not affect other short-term outcomes, including treatment-related toxicity and efficacy. Pre-NCRT sarcopenia was identified as an independent predictive factor for poor overall survival (OS) [adjusted hazard ratio (HR), 6.053; p = 0.002] and progression-free survival (PFS) (adjusted HR, 2.873; p = 0.031). Compared with nutritional indices such as the Nutritional Risk Screening 2002, weight loss during NCRT, and post-NCRT sarcopenia, pre-NCRT sarcopenia was regarded as the best predictive index for the 5-year OS (AUC = 0.735) and PFS rates (AUC = 0.770). Conclusion: Pre-NCRT sarcopenia may be an independent predictive factor for OS and PFS rates in patients with locally advanced AEG receiving multimodal treatment.