UNASSIGNED: The aim was to investigate whether the stem cell marker LGR6 has prognostic value in colon cancer, alone or in combination with the prognostic biomarkers CEA and CXCL16.
UNASSIGNED: LGR6 mRNA levels were determined in 370 half lymph nodes of 121 colon cancer patients. Ability to predict relapse after curative surgery was estimated by Kaplan-Meier survival model and Cox regression analyses.
UNASSIGNED: Patients with high LGR6 levels [LGR6(+)] had a decreased mean survival time of 11 months at 5-year follow-up and 47 months at 12-year follow-up, respectively, with hazard ratios of 3.2 and 2.8. LGR6 mRNA analysis added prognostic value to CEA and CXCL16 mRNA analysis. In the poor prognosis groups CEA(+) and CXCL16(+), further division was achieved by LGR6 analysis. LGR6(+) patients had a very poor prognosis. LGR6 also identified a small number of CEA(-), TNM stage I patients who relapsed suggesting stem cell origin of these tumors. LGR6 and LGR5 levels correlated strongly in lymph nodes of stage I and IV patients but not in stage II patients, suggesting that these stem cell markers are differentially regulated.
UNASSIGNED: This study highlights LGR6 as a useful prognostic biomarker independently and in combination with CEA, CXCL16 or LGR5 identifying different risk groups.

BACKGROUND: To compare the clinical characteristics and prognoses of patients with isolated regional lymph node recurrent nasopharyngeal carcinoma (irrNPC) who underwent surgery or re-irradiation treatment.
METHODS: We retrospectively reviewed 124 irrNPC patients who underwent initial radiotherapy between January 2010 and December 2020. The staging of regional lymph node recurrence was as follows: 75.8% for rN1, 14.5% for rN2, and 9.7% for rN3. Fifty-five patients underwent regional lymph node surgery (Surgery group), and sixty-nine patients received salvage radiotherapy with or without chemotherapy (Re-irradiation group). The survival rate was compared using Kaplan‒Meier analysis and evaluated by the log-rank test. Cox proportional hazard models were used to analyze prognostic factors.
RESULTS: The median follow-up time was 70 months, the 5-year overall survival (OS) was 74%, and the median survival time was 60.8 months. There were no significant differences in 5-year OS (75.6% vs. 72.4%, P = 0.973), regional recurrence-free survival (RRFS, 62.7% vs. 71.1%, P = 0.330) or distant metastasis-free survival (DMFS, 4.2% vs.78.7%, P = 0.677) between the Surgery group and Re-irradiation group. Multivariate analysis revealed age at recurrence, radiologic extra-nodal extension (rENE) status, and recurrent lymph node (rN) classification as independent prognostic factors for OS. The rENE status was an independent prognostic factor for DMFS. Subgroup analysis of the Surgery group revealed that the rN3 classification was an adverse prognostic factor for OS. Age at recurrence ≥ 50 years, GTV-N dose, and induction chemotherapy were found to be independent prognostic factors for OS, RRFS, and DMFS, respectively, in the Re-irradiation group.
CONCLUSIONS: For NPC patients with isolated regional lymph node recurrence after initial radiotherapy, those who underwent surgery had survival prognosis similar to those who underwent re-radiotherapy with or without chemotherapy. A prospective study is needed to validate these findings.

Neck dissection for cervical lymph node metastasis is an established procedure for head and neck cancer (HNC). However, with the advent of immunotherapy, head and neck surgical oncologists need to rethink removing all lymph nodes, including those with immune function. We investigated the anti-cancer immune response of the cervical lymph nodes in four patients with human papillomavirus type 16 (HPV16)-positive head and neck squamous cell carcinoma. Using lymphocytes extracted from local, metastatic, and non-metastatic lymph nodes and peripheral blood from these patients, we performed an intracellular flow cytometric cytokine assay using anti-IFNγ and anti-TNF-α monoclonal antibodies to detect HPV16 E6- and E7-specific T cells. HPV status and p16 immunostaining were determined by in situ detection using the HPV RNAscope method and immunohistochemistry. In one case, E6-specific and E7-specific CD8+ T cells were detected in proximal metastatic nodes and distal non-metastatic nodes. This finding suggests that non-metastatic nodes should be preserved for their immune function during neck dissection and that the immune function of non-metastatic lymph nodes is important when administering immunotherapy. In this context, head and neck surgical oncologists treating HNC should consider the place of immunotherapy and neck dissection in the treatment of HNC.

Background: Regional lymph nodes (RLNs) removed combined with surgery is a standard option for patients at stage I to IIIA NSCLC. The objective of the study is to clarify the effect of removing different number of RLNs on survival outcomes for patients at stage IIIA N0 NSCLC. Methods: Patients at stage IIIA N0 NSCLC from 2004 to 2015 were identified from Surveillance, Epidemiology, and End Results (SEER) database. Prior propensity score method (PSM), survival time was compared among different number (0, 1-3 and ≥4) of RLNs removed groups. After PSM, lung cancer-specific survival (LCSS) and overall survival (OS) were compared. Kaplan-Meier analysis and Cox regression analyses were used to clarify the impact of the factors on the prognosis with hazard ratio (HR) and 95% confidence interval (CI). Results: A total of 11,583 patients at stage IIIA N0 NSCLC were included. Prior PSM, survival indicators including 1-year mortality rate, 5-year mortality rate, median survival time (MDST) and mean survival time (MST) from good to bad were all: ≥4, 1-3 and none RLNs removed group. After PSM, Kaplan-Meier survival analyses and univariate Cox regression analyses on OS and LCSS revealed a statistically significance on survival curve (P<0.001) between each two of the three groups (none, 1-3 and ≥4 RLNs removed group). Multivariable Cox regression analyses on OS and LCSS showed an independent association of RLNs removed with higher OS (HR, 0.275; 95% CI, 0.259-0.291; P<0.001) and LCSS (HR, 0.239; 95% CI, 0.224-0.256; P<0.001) compared with none RLN removed and no statistical difference with OS (HR, 1.118; 95% CI, 0.983-1.271; P=0.088) and LCSS (HR, 1.107; 95% CI, 0.954-1.284; P=0.179) between 1-3 RLNs removed and ≥4 RLNs removed. Conclusions: Removing RLNs was beneficial to survival outcomes of patients at stage IIIA N0 NSCLC. Compared with 1-3 RLNs removed, ≥4 RLNs removed could bring a better survival time but not an independent prognostic factor (P>0.05).

UNASSIGNED: Surgery combined with chemotherapy (CT) is the best treatment for tumor patients at stage I to IIIA. But there are only few studies specifically evaluated the survival benefits of removing different number of regional lymph nodes (RLNs) for patients with stage IIA non-small cell lung cancer (NSCLC). The objective of this study is to discuss the effect of removing different number of RLNs on survival outcomes in operable patients at stage IIA NSCLC.
UNASSIGNED: Through the use of the Surveillance, Epidemiology, and End Results (SEER) registry, satisfactory patients at stage IIA NSCLC, who had complete clinical information from 2004 to 2015, were identified. Lung cancer-specific survival (LCSS) and overall survival (OS) were compared by the Kaplan-Meier analysis and Cox regression analyses to determine the impact of the confounding factors on the survival outcomes. LCSS and OS as the primary endpoints were compared among patients with different number of RLNs removed.
UNASSIGNED: A total of 3,362 patients at stage IIA NSCLC met our criteria, including 173 (5.1%), 486 (14.5%), 2,703 (80.4%) patients without RLNs removed, with 1 to 3 RLNs removed and with greater than or equal to 4 RLNs removed, respectively. Kaplan-Meier survival analyses and Univariate Cox regression analyses revealed that there was a statistically significant difference on survival curve (log rank P<0.001) among the stage IIA NSCLC patients with different number of RLNs removed. Furthermore, multivariable Cox regression analyses on LCSS showed that the hazard ratio (HR) and 95% confidence interval (95% CI) of the 1 to 3 RLNs removed group and greater than or equal to 4 RLNs removed group were 0.622 (0.484-0.800, P<0.001) and 0.545 (0.437-0.680, P<0.001), respectively, compared to without any RLNs removed group.
UNASSIGNED: This study illustrated that removing different number of RLNs can affect survival outcomes of operable patients at stage IIA NSCLC. Whether more radical lymphadenectomy is beneficial to patients at stage IIA NSCLC still needs to be researched.

UNASSIGNED: In (ultra-)hypofractionation, the contribution of intrafraction motion to treatment accuracy becomes increasingly important. Our purpose was to evaluate intrafraction motion and resulting geometric uncertainties for breast tumor (bed) and individual axillary lymph nodes, and to compare prone and supine position for the breast tumor (bed).
UNASSIGNED: During 1-3 min of free breathing, we acquired transverse/sagittal interleaved 1.5 T cine magnetic resonance imaging (MRI) of the breast tumor (bed) in prone and supine position and coronal/sagittal cine MRI of individual axillary lymph nodes in supine position. A total of 31 prone and 23 supine breast cine MRI (in 23 women) and 52 lymph node cine MRI (in 24 women) were included. Maximum displacement, breathing amplitude, and drift were analyzed using deformable image registration. Geometric uncertainties were calculated for all displacements and for breathing motion only.
UNASSIGNED: Median maximum displacements (range over the three orthogonal orientations) were 1.1-1.5 mm for the breast tumor (bed) in prone and 1.8-3.0 mm in supine position, and 2.2-2.4 mm for lymph nodes. Maximum displacements were significantly smaller in prone than in supine position, mainly due to smaller breathing amplitude: 0.6-0.9 mm in prone vs. 0.9-1.4 mm in supine. Systematic and random uncertainties were 0.1-0.4 mm in prone position and 0.2-0.8 mm in supine position for the tumor (bed), and 0.4-0.6 mm for the lymph nodes.
UNASSIGNED: Intrafraction motion of breast tumor (bed) and individual lymph nodes was small. Motion of the tumor (bed) was smaller in prone than in supine position.

UNASSIGNED: The purpose of this study was to evaluate the utility of ICD-O-3-classified local tumor behavior as a prognosticator of head and neck paraganglioma (HNP) outcomes.
UNASSIGNED: Retrospective cohort study.
UNASSIGNED: National Cancer Database between 2004 and 2016.
UNASSIGNED: This study included patients aged ≥18 years who were diagnosed with HNP. Clinical outcomes and clinicopathologic features were compared with regard to local tumor behavior.
UNASSIGNED: Our study included 525 patients, of which the majority had HNP classified as locally invasive (45.9%) or borderline (37.9%). The most common anatomic sites involved were the carotid body (33.7%), intracranial regions (29.0%), or cranial nerves (25.5%). Carotid body tumors were exclusively locally invasive, whereas intracranial and cranial nerve HNP were overwhelmingly benign or borderline (94% and 91%, respectively). One-fourth of patients underwent pathologic analysis of regional lymph nodes, of which the majority were positive for metastasis (80.6%). Metastasis to distant organs was twice as common in patients with locally invasive tumors vs benign (15% vs 7.1). For benign disease, surgery with radiotherapy (adjusted hazard ratio [aHR], 40.45; P = .006) and active surveillance (aHR, 24.23; P = .008) were associated with worse survival when compared with surgery alone. For locally invasive tumors, greater age (aHR, 1.07; P < .0001) and positive surgical margins (aHR, 4.13; P = .010) were predictors of worse survival, while combined surgery and radiotherapy were predictors of improved survival vs surgery alone (aHR, 0.31; P = .027).
UNASSIGNED: While criteria for tumor behavior could not be defined, our results suggest that such a classification system could be used to enhance HNP risk stratification and guide clinical management decisions.

BACKGROUND: Preoperative prognostic biomarkers to guide individualized therapy are still in demand in esophageal squamous cell cancer (ESCC). Some studies reported that radiomic analysis based on CT images has been successfully performed to predict individual survival in EC. The aim of this study was to assess whether combining radiomics features from primary tumor and regional lymph nodes predicts overall survival (OS) better than using single-region features only, and to investigate the incremental value of the dual-region radiomics signature.
METHODS: In this retrospective study, three radiomics signatures were built from preoperative enhanced CT in a training cohort (n = 200) using LASSO Cox model. Associations between each signature and survival was assessed on a validation cohort (n = 107). Prediction accuracy for the three signatures was compared. By constructing a clinical nomogram and a radiomics-clinical nomogram, incremental prognostic value of the radiomics signature over clinicopathological factors in OS prediction was assessed in terms of discrimination, calibration, reclassification and clinical usefulness.
RESULTS: The dual-region radiomic signature was an independent factor, significantly associated with OS (HR: 1.869, 95% CI: 1.347, 2.592, P = 1.82e-04), which achieved better OS (C-index: 0.611) prediction either than the single-region signature (C-index:0.594-0.604). The resulted dual-region radiomics-clinical nomogram achieved the best discriminative ability in OS prediction (C-index:0.700). Compared with the clinical nomogram, the radiomics-clinical nomogram improved the calibration and classification accuracy for OS prediction with a total net reclassification improvement (NRI) of 26.9% (P=0.008) and integrated discrimination improvement (IDI) of 6.8% (P<0.001).
CONCLUSIONS: The dual-region radiomic signature is an independent prognostic marker and outperforms single-region signature in OS for ESCC patients. Integrating the dual-region radiomics signature and clinicopathological factors improves OS prediction.

The role of neutrophils during cancer formation and elimination is diverse. Here, for the first time, we investigate neutrophil helper cells (NBH), their influence on B cell activity in the regional lymph nodes (RLN) of head-and-neck cancer patients and the effect of this neutrophil/B cell interaction on patient prognosis. Circulating and RLN neutrophils of patients with stage I-IV head-and-neck squamous cell carcinoma were investigated with flow cytometry and qPCR. In addition, neutrophil/B cell co-localization in RLNs was evaluated using immunohistochemistry. B cell proliferation was assessed and correlated with the distance to neutrophils. Patient survival was evaluated. Neutrophils with the helper cell phenotype were identified in the RLN of HNC patients. B cells in close proximity to such NBH showed significantly higher proliferation rates, together with elevated activation-induced cytidine deaminase (AID) expression. Notably, patient survival was significantly higher in individuals with high NBH frequencies in the B follicles of RLNs. Neutrophils in RLN can support T cell-independent activation of the adaptive immune system through B cell stimulation, capturing helper cell phenotype character. The presence of such helper neutrophils in the RLNs of HNC patients positively correlates with patient prognosis.

To improve the homogeneity and conformity of the irradiation dose for postoperative breast cancer including regional lymph nodes, we planned Hybrid volumetric-modulated arc therapy (VMAT), which combines conventional tangential field mainly for the chest area and VMAT mainly for the supraclavicular area and marginal zone. In this study, we compared the dosimetric impact between traditional 3D conformal radiotherapy (3DCRT) and Hybrid VMAT and observed toxicities following Hybrid VMAT. A total of 70 patients indicated between October 2016 and December 2017 were included. The prescribed dose was 50 Gy/25 fractions. For the dosimetric impact, 3DCRT and Hybrid VMAT plans were compared in each patient with respect to the dosimetric parameters. Toxicities were followed using the Common Terminology Criteria for Adverse Events version 4.0. The median follow-up duration was 319 days. For the dosimetric impact, the homogeneity index (HI) and conformity index (CI) of PTV were significantly improved in the Hybrid VMAT plan compared with that in the 3DCRT plan (HI, 0.15 ± 0.07 in Hybrid VMAT vs 0.41 ± 0.19 in 3DCRT, P < 0.001; CI, 1.61 ± 0.44 in Hybrid VMAT vs 2.10 ± 0.56 in 3DCRT, P < 0.001). The mean irradiated ipsilateral lung dose was not significantly different in both plans (12.0 ± 2.4 Gy in Hybrid VMAT vs 11.8 ± 2.8 Gy in 3DCRT, P < 0.533). Regarding toxicity, there were no patients who developed ≥grade 3 acute toxicity and ≥grade 2 pneumonitis during the follow-up. Hybrid VMAT for postoperative breast cancer including regional lymph nodes was a reasonable technique that improved the homogeneity and conformity of the irradiation dose to the planning target volume while keeping the irradiation dose to organs at risk to a minimum.