Osimertinib after definitive chemoradiotherapy in unresectable stage III epidermal growth factor receptor-mutated non-small-cell lung cancer: analyses of central nervous system efficacy and distant progression from the phase III LAURA study.

BACKGROUND: Distant metastases in non-small-cell lung cancer (NSCLC) are a poor prognostic factor that negatively impact quality of life. The central nervous system (CNS) is a common site of distant progression in epidermal growth factor receptor-mutated (EGFRm) NSCLC. Osimertinib is a third-generation EGFR-tyrosine kinase inhibitor recommended for advanced EGFRm NSCLC and as adjuvant treatment for resected EGFRm NSCLC. In LAURA (NCT03521154), osimertinib demonstrated statistically significant improvement in progression-free survival (PFS) versus placebo in unresectable stage III EGFRm NSCLC without progression during/following chemoradiotherapy (CRT). CNS efficacy and time to death or distant metastases (TTDM) analyses are reported here. PATIENTS AND METHODS: Patients without progression during/following definitive platinum-based CRT were randomised 2 : 1 to receive osimertinib (80 mg daily) or placebo until progression [by blinded independent central review (BICR)] or discontinuation. The primary endpoint was PFS by BICR. CNS PFS by neuroradiologist BICR and TTDM by BICR were secondary endpoints. RESULTS: Overall, 216 patients were randomised (143 osimertinib, 73 placebo). Median CNS PFS by neuroradiologist BICR was not reached [95% confidence interval (CI) not calculable (NC)-NC] with osimertinib versus 14.9 months (95% CI 7.4 months-NC) with placebo; hazard ratio (HR) for CNS PFS: 0.17 (95% CI 0.09-0.32). CNS PFS analysis by investigator assessment was consistent with BICR assessment. The cumulative incidence of CNS progression at 12 months was 9% (95% CI 5% to 14%) with osimertinib and 36% (95% CI 24% to 47%) with placebo. There was clinically meaningful improvement in TTDM with osimertinib versus placebo; HR for TTDM: 0.21 (95% CI 0.11-0.38). The cumulative incidence of distant metastases at 12 months was 11% (95% CI 6% to 17%) with osimertinib and 37% (95% CI 26% to 48%) with placebo. CONCLUSIONS: Osimertinib demonstrated clinically meaningful improvements in CNS PFS and TTDM versus placebo, supporting osimertinib post-CRT as the standard of care in unresectable stage III EGFRm NSCLC.

The efficacy of screening with FDG-PET/CT for distant metastases in breast cancer patients scheduled for neoadjuvant systemic therapy.

PURPOSE: This study aims to identify which breast cancer patients benefit from the routine use of FDG-PET/CT in a large cohort of patients scheduled for neoadjuvant systemic therapy (NST). METHODS: A total of 1337 breast cancer patients eligible for NST were identified from a retrospective database between 2011 and 2020 at a single tertiary care hospital. All patients underwent staging with FDG-PET/CT prior to NST. The incidence and extent of asymptomatic distant metastases in different patient subgroups were determined, as well as the impact on treatment. Logistic regression analysis was used to identify prognostic patient and tumor characteristics. RESULTS: FDG-PET/CT detected distant metastases in 109 patients (8%). Initial clinical stage was a prognostic factor for the presence of distant metastases, with a significantly higher risk for stage 2b and 3 as opposed to lower stages (p < 0.001). The incidence of distant metastases was 3% (4/125) for stage 1, 2% (8/534) for stage 2a, 7% (24/354) for stage 2b and 23% (73/324) for stage 3. Other characteristics such as age, tumor subtype, histological type and grade were not correlated with the risk of distant metastases. Among the subset of patients with distant metastases, 46% received palliative treatment, while the remaining 54% were diagnosed with oligometastatic breast cancer and were treated with curative intent. CONCLUSION: The results of the current study support the routine use of FDG-PET/CT for the detection of distant metastases in breast cancer patients with initial clinical stage 2b and 3, regardless of tumor subtype.

Prognostic value of 17-Gene genomic prostate score in patients with clinically localized prostate cancer: a meta-analysis.

BACKGROUND: The 17-gene Genomic Prostate Score (GPS) test has been clinically employed to predict adverse prognosis in prostate cancer. In this meta-analysis, we aimed to evaluate the prognostic value of the 17-gene GPS in patients with prostate cancer. METHODS: Potentially relevant studies were obtained by searching PubMed, Web of Science, Embase databases from their inception to December 1, 2023. Studies were considered eligible if they evaluated the association of the 17-gene GPS with distant metastases, biochemical recurrence, or prostate cancer-specific mortality (PCSM) in prostate cancer patients. To estimate the prognostic value, we pooled the adjusted hazard ratio (HR) with 95% confidence intervals (CI) for the high versus low GPS group or per 20-unit increase in GPS. RESULTS: Seven cohort studies that reported on 8 articles comprising 1,962 patients satisfied the eligibility criteria. Meta-analysis showed that per 20-unit increase in GPS was significantly associated with distant metastases (HR 2.99; 95% CI 1.97-4.53), biochemical recurrence (HR 2.18; 95% CI 1.64-2.89), and PCSM (HR 3.14; 95% CI 1.86-5.30). Moreover, patients with high GPS (> 40 points) had an increased risk of distant metastases (HR 5.22; 95% CI 3.72-7.31), biochemical recurrence (HR 4.41; 95% CI 2.29-8.49), and PCSM (HR 3.81; 95% CI 1.74-8.33) than those with low GPS (≤ 40 points). CONCLUSIONS: A higher 17-gene GPS significantly predicts distant metastases, biochemical recurrence, and PCSM in men with clinically localized prostate cancer. However, large-scale multicenter prospective studies are necessary to further validate these findings.

Breast Cancer-Major changes in the American Joint Committee on Cancer eighth edition cancer staging manual.

Answer questions and earn CME/CNE The revision of the eighth edition of the primary tumor, lymph node, and metastasis (TNM) classification of the American Joint Commission of Cancer (AJCC) for breast cancer was determined by a multidisciplinary team of breast cancer experts. The panel recognized the need to incorporate biologic factors, such as tumor grade, proliferation rate, estrogen and progesterone receptor expression, human epidermal growth factor 2 (HER2) expression, and gene expression prognostic panels into the staging system. AJCC levels of evidence and guidelines for all tumor types were followed as much as possible. The panel felt that, to maintain worldwide value, the tumor staging system should remain based on TNM anatomic factors. However, the recognition of the prognostic influence of grade, hormone receptor expression, and HER2 amplification mandated their inclusion into the staging system. The value of commercially available, gene-based assays was acknowledged and prognostic input added. Tumor biomarkers and low Oncotype DX recurrence scores can alter prognosis and stage. These updates are expected to provide additional precision and flexibility to the staging system and were based on the extent of published information and analysis of large, as yet unpublished databases. The eighth edition of the AJCC TNM staging system, thus, provides a flexible platform for prognostic classification based on traditional anatomic factors, which can be modified and enhanced using patient biomarkers and multifactorial prognostic panel data. The eighth edition remains the worldwide basis for breast cancer staging and will incorporate future online updates to remain timely and relevant. CA Cancer J Clin 2017;67:290-303. © 2017 American Cancer Society.

Lymph Node Ratio as a Predictive Factor of Persistent/Recurrent Disease in Patients With Medullary Thyroid Cancer: A Single-Center Retrospective Study.

OBJECTIVE: Thyroidectomy with neck lymph node dissection is curative for most patients with medullary thyroid cancer (MTC). Lymph node ratio (LNR, ie, the ratio between the metastatic and the removed lymph nodes) is a reliable parameter with which to estimate both disease extent and quality of neck dissection. The aim of this study was to investigate the prognostic role of LNR to predict persistent/recurrent disease in patients with MTC. METHODS: A single-center, retrospective study of a consecutive cohort of 95 patients with MTC treated with total thyroidectomy and neck dissection. Receiver operating characteristics curve analysis was performed to identify the LNR cut-off. RESULTS: LNR was positively associated with tumor size, preoperative and postoperative calcitonin values, postsurgery carcinoembryonic antigen values, persistent/recurrent disease, and the occurrence of distant metastases during follow-up. At multivariate analysis, persistent/recurrent disease was independently associated with the LNR value and was accurately predicted by a cut-off value of 0.12 (area under the curve = 0.85). Indeed, patients with LNR ≥0.12 had a higher probability of developing persistent/recurrent disease (79.3% vs 10.6%, odds ratio = 32.3, 95% CI = 9.8-106.4; P < .001) and distant metastasis (34.5% vs 3.0%, odds ratio = 16.8, 95% CI = 3.4-83.6; P < .001) than patients with LNR <0.12. The median time to progression was 15 months in patients with LNR ≥0.12 whereas it was not reached in patients with LNR <0.12 (hazard ratio: 7.18, 95% CI = 3.01-17.11, P < .001). CONCLUSIONS: LNR is a reliable prognostic factor to predict the risk of recurrence, persistence, and distant metastases in patients with MTC.

Development and validation of survival nomograms for patients with differentiated thyroid cancer with distant metastases: a SEER Program-based study.

BACKGROUND: We aimed to develop a nomogram model of overall survival (OS) and cancer-specific survival (CSS) in patients with differentiated thyroid cancer with distant metastases, and to evaluate and validate the nomogram. Also, its prognostic value was compared with that of the 8th edition of the American Joint Committee on Cancer tumor-node-metastasis staging system (AJCC8SS). METHODS: Patients with distant metastatic differentiated thyroid cancer (DMDTC) from 2004 to 2015 were selected from the Surveillance, Epidemiology, and End Results (SEER) Program to extract the clinical variables used for analysis. A total of 906 patients were divided into a training set (n = 634) and validation set (n = 272). OS and CSS were selected as the primary end point and secondary end point. LASSO regression analysis and multivariate Cox regression analysis were applied to screen variables for constructing OS and CSS nomograms for survival probability at 3, 5, and 10 years. Nomograms were evaluated and validated using the consistency index (C-index), time-dependent receiver operator characteristic (ROC) curves, area under the ROC curve, calibration curves, and decision curve analysis (DCA). The predictive survival of the nomogram was compared with that of AJCC8SS. Kaplan-Meier curves and log-rank tests were used to evaluate the risk-stratification ability OS and CSS nomograms. RESULTS: CS and CSS nomograms included six independent predictors: age, marital status, type of surgical procedure, lymphadenectomy, radiotherapy, and T stage. The C-index for the OS nomogram was 0.7474 (95% CI = 0.7199-0.775), and that for the CSS nomogram was 0.7572 (0.7281-0.7862). The nomogram showed good agreement with the "ideal" calibration curve in the training set and validation sets. DCA confirmed that the survival probability predicted by the nomogram had high clinical predictive value. The nomogram could stratify patients more accurately, and showed more robust accuracy and predictive power, than AJCC8SS. CONCLUSIONS: We established and validated prognostic nomograms for patients with DMDTC, which had significant clinical value compared with AJCC8SS.

Clinico-pathological factors associated with radioiodine refractory differentiated thyroid carcinoma status.

PURPOSE: Risk factors for developing radioiodine refractory thyroid cancer (RAIR-TC) have rarely been analyzed. The purpose of the present study was to find clinical and pathological features associated with the occurrence of RAIR-disease in differentiated thyroid cancers (DTC) and to establish an effective predictive risk score. METHODS: All cases of RAIR-DTC treated in our center from 1990 to 2020 were retrospectively reviewed. Each case was matched randomly with at least four RAI-avid DTC control patients based on histological and clinical criteria. Conditional logistic regression was used to examine the association between RAIR-disease and variables with univariate and multivariate analyses. A risk score was then developed from the multivariate conditional logistic regression model to predict the risk of refractory disease occurrence. The optimal cut-off value for predicting the occurrence of RAIR-TC was assessed by receiver operating characteristic (ROC) curves and Youden's statistic. RESULTS: We analyzed 159 RAIR-TC cases for a total of 759 controls and found 7 independent risk factors for predicting RAIR-TC occurrence: age at diagnosis ≥ 55, vascular invasion, synchronous cervical, pulmonary and bone metastases at initial work-up, cervical and pulmonary recurrence during follow-up. The predictive score of RAIR-disease showed a high discrimination power with a cut-off value of 8.9 out of 10 providing 86% sensitivity and 92% specificity with an area under the curve (AUC) of 0.95. CONCLUSION: Predicting the occurrence of RAIR-disease in DTC patients may allow clinicians to focus on systemic redifferentiating strategies and/or local treatments for metastatic lesions rather than pursuing with ineffective RAI-therapies.

Overall survival after definitive chemoradiotherapy for patients with esophageal cancer: a retrospective cohort study.

Definitive chemoradiotherapy (dCRT) is a potentially curative therapy for esophageal cancer. As indications for dCRT differ widely, it is challenging to draw conclusions on outcomes and survival. The aim of this study was to evaluate overall survival (OS) and recurrence patterns according to indications for treatment. Patients who underwent dCRT (50.4 Gy concomitant with carboplatin/paclitaxel) for esophageal cancer between 2012 and 2022 were identified. Indications for dCRT were: cervical tumor, irresectable disease, unfit for surgery, and patient and/or physician preference. The primary endpoint was OS calculated with the Kaplan-Meier method. Secondary endpoints included the proportion of patients that completed the dCRT regimen, 30- and 90-day mortality, and disease recurrence. One hundred and fifty-seven patients were included (72.6% esophageal squamous cell carcinoma) with a median follow-up of 20 months (IQR 10.0-43.9). The full dCRT regimen was completed by 116 patients (73.9%). Thirty- and 90-day mortality were 2.5% and 8.3%, respectively. Median and 5-year OS for all patients were 22.9 months (95% CI 18.0-27.9) and 31.4%, respectively. The median OS per indication was 23.7 months (95% CI 6.5-40.8) for patients with cervical tumors, 10.9 months (95% 0.0-23.2) for irresectable disease, 28.2 months (95% CI 12.3-44.0) for unfit patients, and 22.9 months (95% CI 15.4-30.5) for patients' preference for dCRT (P = 0.11). Disease recurrence was observed in 74 patients (46%), located locoregionally (46%), distant (19%), or combined (35%). Patients who underwent dCRT had a 5-year OS of 31.4%, but OS differed according to indications for treatment with patients who had irresectable disease having the worst prognosis.

Prognostic factors for development of distant metastases in surgically treated high-grade salivary gland carcinomas: results of retrospective single center study with 213 patients.

PURPOSE: Distant metastases (DM) are the primary cause of treatment failure and death of patients with salivary gland carcinomas (SGC). The purpose of present study was to evaluate factors predictive on DM development in a cohort of patients with high-grade salivary gland carcinomas. METHODS: This was a retrospective cohort study of consecutive patients surgically treated with curative intention at the authors' institution from January 1993 to December 2018. Outcomes evaluated were overall survival (OS), disease specific survival (DSS), recurrence free survival (RFS), locoregional recurrence free survival (LRFS) and distant metastasis free survival (DMFS). RESULTS: A total of 213 patients, 117 males (55%) and 96 females (45%), were included in the study. Parotid gland malignancies accounted for 56% of all cases. Adenoid cystic carcinoma (119 cases; 56%) was the most common tumor type. Cumulative OS for the 5-and 10-year follow-up period was 80% and 58% respectively. DM occurred with 75 patients (35%). The most common locations for DM were lung (55 cases; 73%) and liver (12 cases; 16%). Pathological nodal status, particularly the number of metastatic nodes, was the independent prognostic factor for OS, DSS, RFS and DMFS. CONCLUSION: Number of metastatic lymph nodes, instead of extranodal extension and largest nodal diameter, was the contributing factor related to DMFS. Since the main function of staging system is to predict outcomes, the significance of extranodal extension and nodal dimension in salivary gland cancer staging system requires further clarification. The elective neck dissection could be considered therapeutic approach for high-grade SGC since occult metastases were detected in 33% of cases.

Characteristics and risk differences of different tumor sizes on distant metastases of pancreatic neuroendocrine tumors: A retrospective study in the SEER database.

BACKGROUND: The rate of distant metastasis in patients with pancreatic neuroendocrine tumors (PNETs) is 20%-50% at the time of initial diagnosis. However, whether tumor size can predict distant metastasis for PNETs remains unknown up to date. METHODS: We used Surveillance, Epidemiology, and End Results (SEER) population-based data to collect 6089 patients with PNETs from 2010 to 2019. The optimal cut-off point of tumor size to predict distant metastasis was calculated by Youden's index. Multivariate logistic regression analysis was used to figure out the association between tumor size and distant metastasis patterns. RESULTS: The most common metastatic site was liver (27.2%), followed by bone (3.0%), lung (2.3%) and brain (0.4%). Based on an optimal cut-off value of tumor size (25.5 mm) for predicting distant metastasis determined by Youden's index, patients were categorized into groups of tumor size < 25.5 mm and ≥ 25.5 mm. Multivariate logistic regression analyses showed that, compared with < 25.5 mm, tumor size ≥ 25.5 mm was an independent risk predictor of overall distant metastasis [odds ratio (OR) = 4.491, 95% confidence interval (CI): 3.724-5.416, P < 0.001] and liver metastasis (OR = 4.686, 95% CI: 3.886-5.651, P < 0.001). CONCLUSIONS: Tumor size ≥ 25.5 mm was significantly associated with more overall distant and liver metastases. Timely identification of distant metastasis for tumor size ≥ 25.5 mm may provide survival benefit for timely and precise treatment.

Survival after docetaxel for metastatic castration-resistant prostate cancer in a rural health care setting.

Introduction: The aim of this study was to evaluate overall survival of men who received systemic therapy with docetaxel for metastatic castration- resistant prostate cancer (MCRPC) in rural Nordland County, Norway. Prognostic factors related to treatment and other variables were evaluated. Material and methods: Overall, 132 pa- tients were included in this retrospective study covering the years 2009-2022. Uni- and multivariate survival analyses were performed. Results: In this elderly cohort (median age 72 years), weekly low-dose docetaxel was the preferred regimen (44%). Seventy-three percent were treated in the first line. Only 11 patients (8%) were pre-exposed to docetaxel in the hormone-sensitive phase. Median survival was 14.3 months. Prognostic factors for longer survival included higher hemoglobin, lower lactate dehydrogenase, administration of docetaxel as first-line MCRPC treatment, and use of fewer prescription drugs for comorbidity. Pre-exposure to docetaxel did not play a major role, p = 0.76. Conclusions: In this rural health care setting, survival after docetaxel was shorter than reported by other groups. Blood test results were confirmed as important prognostic factors. In the present era of evolving treatment sequences, we recommend monitoring of real-world treatment results.

Risk stratification for radioactive iodine refractoriness using molecular alterations in distant metastatic differentiated thyroid cancer.

Objective: Patients with radioactive iodine-refractory differentiated thyroid cancer (RAIR-DTC) are often diagnosed with delay and constrained to limited treatment options. The correlation between RAI refractoriness and the underlying genetic characteristics has not been extensively studied. Methods: Adult patients with distant metastatic DTC were enrolled and assigned to undergo next-generation sequencing of a customized 26-gene panel (ThyroLead). Patients were classified into RAIR-DTC or non-RAIR groups to determine the differences in clinicopathological and molecular characteristics. Molecular risk stratification (MRS) was constructed based on the association between molecular alterations identified and RAI refractoriness, and the results were classified as high, intermediate or low MRS. Results: A total of 220 patients with distant metastases were included, 63.2% of whom were identified as RAIR-DTC. Genetic alterations were identified in 90% of all the patients, with BRAF (59.7% vs. 17.3%), TERT promoter (43.9% vs. 7.4%), and TP53 mutations (11.5% vs. 3.7%) being more prevalent in the RAIR-DTC group than in the non-RAIR group, except for RET fusions (15.8% vs. 39.5%), which had the opposite pattern. BRAF and TERT promoter are independent predictors of RAIR-DTC, accounting for 67.6% of patients with RAIR-DTC. MRS was strongly associated with RAI refractoriness (P<0.001), with an odds ratio (OR) of high to low MRS of 7.52 [95% confidence interval (95% CI), 3.96-14.28; P<0.001] and an OR of intermediate to low MRS of 3.20 (95% CI, 1.01-10.14; P=0.041). Conclusions: Molecular alterations were associated with RAI refractoriness, with BRAF and TERT promoter mutations being the predominant contributors, followed by TP53 and DICER1 mutations. MRS might serve as a valuable tool for both prognosticating clinical outcomes and directing precision-based therapeutic interventions.

Impact of non-adherence to endocrine therapy on recurrence risk in older women with stage I breast cancer after breast-conserving surgery.

PURPOSE: We examined the impact of non-adherence to adjuvant endocrine therapy (ET) on the risk and site of recurrence among older women with early stage, hormone receptor positive (HR+) breast cancer (EBC). METHODS: A population-based cohort of women age ≥ 65 years with T1N0 HR + EBC who were diagnosed between 2010 and 2016 and treated with breast-conserving surgery (BCS) + ET was identified. Treatment and outcomes were ascertained through linkage with administrative databases. ET non-adherence was examined as a time-dependent covariate in multivariable cause-specific Cox regression models to evaluate its effect on the risks of ipsilateral local recurrence (LR), contralateral breast cancer, and distant metastases. RESULTS: The population cohort includes 2637 women; 73% (N = 1934) received radiation (RT) + ET and 27% (N = 703) received ET alone. At a median follow-up of 8.14 years, the first event was LR in 3.6% of women treated with ET alone and 1.4% for those treated with RT + ET (p < 0.001); the risk of distant metastases was < 1% in both groups. The proportion of time adherent to ET was 69.0% among those treated with RT + ET and 62.8% for those treated with ET alone. On multivariable analysis, increasing proportion of time non-adherent to ET was associated with increased risk of LR ((HR = 1.52 per 20% increase in time; 95%CI 1.25, 1.85; p < 0.001), contralateral BC (HR = 1.55; 95%CI 1.30, 1.84; p < 0.001), and distant metastases (HR = 1.44; 95%CI 1.08, 1.94; p = 0.01) but absolute risks were low. CONCLUSION: Non-adherence to adjuvant ET was associated with an increased risk of recurrence, but absolute recurrence rates were low.

Comparison of whole-body 18F-FDG PET/CT and PET/MRI for distant metastases in patients with malignant tumors: a meta-analysis.

BACKGROUND: As a first-line imaging modality, whole-body fluorine-18 fluorodeoxyglucose (18F-FDG) positron emission tomography (PET)/computed tomography (CT) and 18F-FDG PET/magnetic resonance imaging (MRI) had been widely applied in clinical practice. However, 18F-FDG PET/MRI may be superior to PET/CT for the diagnosis of distant metastases in patients with advanced-stage. Therefore, it is timely and important to systematically determine the diagnostic accuracy of 18F-FDG PET/MRI compared with that of 18F-FDG PET/CT for the diagnosis of distant metastases. METHODS: This study aimed to compare the diagnostic accuracy of 18F-FDG PET/CT and PET/MRI for the diagnosis of distant metastases in patients with malignant tumors. Relevant studies using both 18F-FDG PET/CT and PET/MRI for assessment of distant metastases in patients with malignant tumors were searched in PubMed, Embase, The Cochrane Library, and Scopus from January 2010 to November 2023. Two reviewers independently selected studies according to the inclusion and exclusion criteria. A reviewer extracted relevant data and assessed the quality of the eligible studies. The pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, and area under the summary receiver operating characteristic curve (AUC) for 18F-FDG PET/CT and PET/MRI were analyzed. Subgroup analysis was performed. RESULTS: Across 14 studies (1042 patients), 18F-FDG PET/MRI had a higher sensitivity (0.87 versus 0.81), AUC value (0.98 versus 0.95), and similar specificity (0.97 versus 0.97), than PET/CT for detecting distant metastases. In 3 studies of breast cancer (182 patients), 18F-FDG PET/MRI had a higher sensitivity (0.95 versus 0.87) and specificity (0.96 versus 0.94) than PET/CT. In 5 studies of lung cancer (429 patients), 18F-FDG PET/CT had a higher sensitivity (0.87 versus 0.84) and a lower specificity (0.95 versus 0.96) to PET/MRI. CONCLUSIONS: 18F-FDG PET/MRI and PET/CT both performed well as detectors of distant metastases in patients with malignant tumors, and the former has higher sensitivity. The subgroup analysis highlights that 18F-FDG PET/MRI and PET/CT hold different advantages for distant metastases staging in different tumors, PET/MRI has a higher accuracy in patients with breast cancer patients, while PET/CT has a higher accuracy in patients with lung cancer.

Metastasis pattern and prognosis in children with neuroblastoma.

BACKGROUND: We aimed to investigate the different metastases and prognoses of neuroblastoma (NB) and determine the risk factors of metastasis. METHOD: Data of 1224 patients with NB were obtained from the Surveillance, Epidemiology and End Results database (2010-2018). Pearson's chi-square test, Kaplan-Meier analysis, multivariable logistic regression and Cox regression analysis were used to determine the factors associated with prognosis. RESULTS: The overall incidence of NB was an age-adjusted rate of 8.2 patients per 1,000,000 children. In total, 1224 patients were included in our study, with 599 patients (48.9%) exhibiting distant metastases. Compared to patients with non-metastatic NB, a greater proportion of patients with metastatic NB were under 1 year, male, had an adrenal primary site, unilateral tumour, a tumour size > 10 cm, neuroblastoma-not otherwise specified (NB-NOS), second malignant neoplasms and were more likely to choose radiotherapy and chemotherapy. Multivariate Cox regression showed that metastasis was an independent risk factor for overall survival (OS) and cancer-specific survival (CSS). The survival rate of non-metastatic patients with NB was better than those with metastasis (OS: hazard ratio (HR): 0.248, P < 0.001; CSS: HR: 0.267, P < 0.001). The bone and liver were the two most common isolated metastatic sites in NB. However, no statistical difference was observed in OS and CSS between the only bone metastasis group, only liver metastasis group and bone metastasis combined with liver metastasis group (all P > 0.05). Additionally, age at diagnosis > 1 year (odds ratio (OR): 3.295, P < 0 .001), grades III-IV (OR: 26.228, P < 0 .001) and 5-10 cm tumours (OR: 1.781, P < 0 .001) increased the risk of bone metastasis of NB. Moreover, no surgical treatment (OR: 2.441, P < 0 .001) increased the risk of liver metastasis of NB. CONCLUSION: Metastatic NB has unique clinicopathological features, with the bone and liver as the most common single metastatic sites of NB. Therefore, more aggressive treatment is recommended for high-risk children with NB displaying distant metastases.

Local tumor regrowth after clinical complete response following neoadjuvant therapy for rectal cancer: what happens when organ preservation falls short.

Organ preservation strategies, especially watch and wait, after neoadjuvant treatment in locally advanced rectal cancer, have become topics that generate significant interest, for both patients and clinicians. The obvious advantage of these strategies is the avoidance of surgery with its associated risks and functional consequences. Over time, it has become evident that these strategies offer acceptable safety in oncological terms and, in most patients, allows preservation of the rectum without harming patients in terms of distant metastasis or survival. However, there is a small group of patients in whom the tumor returns after an initially diagnosed clinical complete response; patients with local tumor regrowth. The main threat in these patients is not simply local disease, which can be successfully managed in most cases, but the possible effects it may have on distant metastases. The pathophysiology of the phenomenon of local tumor regrowth is not well known and, therefore, strategies to minimize possible impact on survival are not well defined. Our aim is to review key issues in this subgroup that pose a substantial threat to the safety and viability of organ-preserving and watch-and-wait strategies. We also explore possible pathophysiologic explanations and future directions and perspectives that may improve both local and systemic disease control.

Construction of Prognostic Nomogram in Patients with N3-Stage Nasopharyngeal Carcinoma.

INTRODUCTION: The aim of the study was to retrospectively identify the metastatic influence factors and predict the prognosis and develop an individualized prognostic prediction model for patients with N3-stage nasopharyngeal carcinoma (NPC). METHODS: The study collected 446 NPC patients with N3 stage from the Surveillance, Epidemiology, and End Results database between 2010 and 2015. The patients were classified into subgroups based on the histological types and metastatic status. Multivariable logistic, Cox regression, and Kaplan-Meier method with the log-rank test were performed. The nomogram model was created using the prognostic factors identified from Cox regression analysis. The predictive accuracy was determined based on the concordance index (c-index) and calibration curves. RESULTS: The 5-year overall survival (OS) of the NPC patients with N3 stage was 43.9%, and the prognosis of patients without any distant metastases was largely longer than that with metastases. No difference was observed between different pathological types in the entire cohort. However, patients with non-keratinized squamous cell carcinoma had a better OS than that of the patients with keratinized squamous cell carcinoma in a nonmetastatic subgroup. Using the Cox regression analysis results, the nomogram successfully classified these patients into low- and high-risk subgroups and presented the survival difference. The c-index of the nomogram for predicting the prognosis was satisfactory. CONCLUSION: This study identified metastatic risk factors and developed a convenient clinical tool for the prognosis of NPC patients. This tool can be used for individualized risk classification and decision-making regarding treatment of NPC patients with N3 stage.

EVALUATION OF PRE-ABLATION NLR AND LMR AS PREDICTORS OF DISTANT METASTASES IN PATIENTS WITH DIFFERENTIATED THYROID CANCER.

Objective: This research aim was to evaluates the role of the pre-ablation neutrophil-to-lymphocyte ratio (NLR) and lymphocyte-to-monocyte ratio (LMR) as predictors of distant metastases in patients with differentiated thyroid cancer (DTC). Methods: A retrospective analysis was given to 140 patients with DTC who received 131I remnant ablation after surgery. The patients were divided into two groups based on the existence of distant metastasis. Results: The two groups showed no significant difference in age, gender, WBCs, neutrophils, monocytes, eosinophils, basophils and whether the tumor was multifocal. In the univariate analysis, significant differences were found in tumor size (p=0.021), lymphocyte (p=0.012), NLR (p=0.027), and LMR (p=0.007). According to the ROC curves, NLR had an AUC of 0.612 ± 0.097 with a cut-off value of 1.845, sensitivity of 60.0%, and specificity of 66.2% (p=0.027). LMR had an AUC of 0.638 ± 0.095 with a cut-off value of 4.630, sensitivity of 84.6%, and specificity of 35.4% (p=0.007). In the multivariate analysis, larger tumor size (OR=5.246, 95% CI 1.269-10.907, p=0.009) and higher NLR (OR=2.087, 95% CI 0.977-4.459, p=0.034) were statistically significant for distant metastases. Conclusion: This research reveals that pre-ablation NLR and tumor size are significantly statistically correlated with distant metastases in patients with DTC.

Treatment patterns and survival in advanced unresectable esophageal squamous cell cancer: A population-based study.

Data on treatment and survival of patients with advanced unresectable esophageal squamous cell carcinoma (ESCC) from Western populations are limited. Here we describe treatment and survival in patients with advanced unresectable ESCC: patients with cT4b disease without metastases (cT4b), metastases limited to the supraclavicular lymph nodes (SCLNM) or distant metastatic ESCC at the population level. All patients with unresectable (cT4b) or synchronous metastatic ESCC at primary diagnosis (2015-2018) or patients with metachronous metastases after primary non-metastatic diagnosis in 2015-2016 were selected from the Netherlands Cancer Registry. Fifteen percent of patients had cT4b disease (n = 146), 12% SCLNM (n = 118) and 72% distant metastases (n = 681). Median overall survival (OS) time was 6.3, 11.2, and 4.4 months in patients with cT4b, SCLNM, and distant metastases, respectively (P < .001). Multivariable Cox regression showed that patients with cT4b (hazard ratio 1.44, 95% CI 1.04-1.99) and patients with distant metastases (hazard ratio 1.42, 95% CI 1.12-1.80) had a worse survival time compared with patients with SCLNM. Among patients who received chemoradiotherapy and/or underwent resection (primary tumor and/or metastases), median OS was 11.9, 16.1, and 14.0 months in patients with cT4b, SCLNM, and distant metastases, respectively (P = .76). Patients with SCLNM had a better survival time compared with patients with cT4b and patients with distant metastases. Survival of patients with advanced unresectable ESCC in clinical practice was poor, even in patients treated with curative intent.

Clinical outcomes of a cohort of 271 patients with lung metastases from differentiated thyroid carcinoma.

CONTEXT: Lung is the most common site of distant metastases from differentiated thyroid carcinoma (DTC). OBJECTIVE: To investigate the outcomes of a cohort of patients with DTC and lung metastases (LM). METHODS: A retrospective analysis of a cohort of 271 patients with LM was performed. RESULTS: The female-to-male ratio was 1:1 and the median follow-up time was 5.9 (1.1-38.4) years. Papillary thyroid carcinoma (PTC) was the most frequent type (83.4%), mainly the classic variant, followed by follicular thyroid carcinoma (FTC, 10.3%) and Hürthle cell carcinoma (HTC, 6.3%). The prevalence of PTC, FTC and HCC was different between the micronodular and macronodular LM groups [87.4%, 6.3% and 6.3% vs. 74.6%, 19.0% and 6.3%, respectively (p = .013)]. Only 5.0% of the patients had LM diagnosed after a period of remission. LM were submitted to radioactive iodine treatment (RAIT) in 84.5% (52.8% showed 131 iodine avid metastases). Complete remission was only achieved in 12.2%. Micronodular disease and age <55 years at LM diagnosis were associated with a better prognosis (p < .05). We found no difference in survival between patients with LM treated or not with RAIT. However, in patients submitted to RAIT, there was a tendency for longer survival in the group of patients with 131 I avid lesions. CONCLUSION: The classic variant of PTC was the most frequent histology found in LM of DTC. LM are rarely diagnosed in the follow-up when complete remission is achieved after surgery and 131 I. Younger age at LM diagnosis and a micronodular pattern are associated with a better prognosis.