Disease Recurrence In Patients Research Articles

The role of thyroglobulin doubling time in differentiated thyroid cancer: a meta-analysis.

ObjectiveIn patients with differentiated thyroid cancer (DTC), recurrences may occur in up to 20% and may have a fatal outcome in 10% of cases. Thyroglobulin doubling time (Tg-DT) values may contribute to predict response to treatment and disease recurrence in DTC patients. This study aimed to address the following questions: (1) Are Tg-DT values indicative of response to treatments in patients with DTC (i.e. ’treatment monitoring’)?; (2) Is Tg-DT predictive of 2-[18F]fluoro-2-deoxy-d-glucose (2-[18F]FDG) PET/CT in patients with DTC?; (3) Are Tg-DT values predictive of DTC prognosis (i.e. ‘prediction’)?DesignSystematic review and meta-analysis.MethodsMethodology was registered in the PROSPERO database (CRD42021257947). A systematic search was carried out in PubMed, Web Of Science, and Scopus from June to August 2021 without time and language restrictions.ResultsEleven studies were included for a total of 1421 patients. Positive association between Tg-DT < 1 year and recurrence or disease progression was observed. Tg-DT was found to be related with (2-[18F]FDG) PET/CT results in patients with DTC. The area under the curve was 0.86 (95% CI: 0.83–0.89), sensitivity was 0.84 (0.64;0.94), specificity was 0.71 (0.35; 0.92), DOR was 13.1 (3.1; 55.0), LR+ was 2.9 (1.0; 8.1), LR− was 0.22 (0.1; 0.5). For patients with Tg-DT < 1 year (n = 247), the survival risk ratio was 2.09 (95% CI: 1.49; 2.94).ConclusionsTg-DT values are valuable in predicting response to treatment and disease recurrence in patients with DTC, as well as their overall survival. In addition, Tg-DT significantly increases the detection rate of 2-[18F]-FDG PET/CT.

Lessons learned from hepatocellular carcinoma may cause a paradigm shift in intraductal papillary mucinous neoplasms: a narrative review and discussion of conceptual similarities in tumor progression and recurrence

Abstract Although the natural history of recurrence/progression in patients with intraductal papillary mucinous neoplasms (IPMN) of the pancreas has not been studied thoroughly, the three principal mechanisms have been identified: (a) presence of residual disease at the transection margin, (b) presence of intraductal/intraparenchymal metastases and (c) development of new primary lesions. Mechanisms (a) and (b) result in metastatic lesions that are genetically related to the primary, while new primary lesions (mechanism c) are genetically distinct. Interestingly, recurrence/progression in IPMN displays conceptual parallels with the well-established paradigm of disease recurrence in patients with hepatocellular carcinoma (HCC). Specifically, patients with HCC may also develop recurrent tumors due to microscopic residual disease/intrahepatic metastasis which are genetically similar to the primary while the development of genetically unrelated, de novo HCC after curative-intent resection is also common. The latter has been attributed to the presence of a widespread genetic abnormality (“field defect”) in the liver (ie, cirrhosis). Given the conceptual similarities between IPMN and HCC, a pancreatic “field defect”may also be hypothesized to exist. This review does not suggest that HCC and IPMN have identical pathogeneses, but rather that they have conceptual similarities in tumor recurrence/progression; thus, lessons learned from HCC could be applied to IPMN research and subsequent management. Conceptual similarities in tumor progression and recurrence may also be observed between IPMN and other malignancies. However, HCC was selected because it is well studied and can serve as a paradigm.

Study on the Effect of Cause Nursing on Health Behavior and Disease Recurrence of Patients with Peptic Ulcer

Study on the Effect of Cause Nursing on Health Behavior and Disease Recurrence of Patients with Peptic Ulcer

Impact of Primary Tumor Size, SUVmax of Primary Tumor and the Most Avid Neck Node on Baseline 18 FDG PET/CT upon Disease Recurrence in Head and Neck Oropharyngeal SCC Using Standardized Imaging Protocol.

Objective The purpose fo this prospective study was to find the impact of primary tumor size (Ts), standardized uptake values (SUVmax) of primary tumor, and the most avid neck node on disease recurrence in patients with head and neck oropharyngeal squamous cell carcinoma (HNOP-SCC). Material and methods We included patients with HNOP-SCC (without distant metastasis—M0 disease) who had pre- and post-treatment F-18 fluorodeoxyglucose positron emission tomography/computed tomography ( 18 FDG PET/CT) using strict standardized imaging protocol from 2017 to 2019. Based on follow-up ( 18 FDG PET/CT) findings, patients were categorized as disease free (no or minimal 18 FDG uptake ≤ background over surgical bed and no distant metastasis) and disease recurrence ( 18 FDG uptake > background over surgical bed with or without nodal and/or distant metastasis). Ts and SUVmax of primary tumor and the most avid neck node were compared and impact of these was studied upon disease recurrence. Results Total 112 patients were included. No significant difference was seen in mean age (overall: 60 ± 14 years), gender distribution (overall M:F: 69:31%), body mass index (overall: 25.20 ± 5.82), and history of diabetes (overall: 19%) between disease-free and disease recurrence groups. Similarly, no significant difference was observed for fasting blood sugar (overall: 110 ± 28 mg%), 18 FDG dose (overall: 169 ± 37 MBq), and uptake period (overall: 70 ± 12 minutes) between two groups ensuring strict adherence to standardized imaging protocol. Significant difference ( p < 0.05) was observed between disease-free and disease recurrence for Ts (25 ± 10 vs. 33 ± 14 mm), SUVmax of primary tumor (6.2 ± 6.8 vs. 9.3 ± 7.2) and the most avid neck node (2.1 ± 3.3 vs. 4.7 ± 5.9) and median follow-up (13 ± 12 vs. 08 ± 13 months), respectively. Using receiver operating characteristic analysis, Ts greater than 29 mm, baseline tumor SUVmax greater than 4.6, and nodal SUVmax greater than 6.2 were found independent predictors for disease recurrence. Nodal SUVmax greater than 6.2 was found an independent predictor of shortest disease-free survival (DFS) than Ts and tumor SUVmax. Conclusion We conclude that in HNOP-SCC, primary Ts (> 29 mm), SUVmax of primary tumor (> 4.6), and the most avid neck node (> 6.2) in baseline 18 FDG PET/CT using standardized imaging protocol are the independent predictors of disease recurrence. Furthermore, SUVmax greater than 6.2 of the most avid node predicts the shortest DFS than primary Ts and SUVmax of primary tumor.

Effectiveness of Video-Assisted Thoracoscopic Surgery with Bullectomy and Partial Pleurectomy in the Treatment of Primary Spontaneous Pneumothorax-A Retrospective Long-Term Single-Center Analysis.

Background: Video-assisted thoracoscopic surgery (VATS) with bullectomy and partial pleurectomy (VBPP) is an increasingly used and well-established surgical treatment for primary spontaneous pneumothorax (PSP). However, reports on its effectiveness and long-term outcomes are limited. The aim of this study was to assess and compare long-term recurrence rates following VBPP and chest tube (CT) treatment and to identify potential risk factors for disease recurrence in patients with PSP. Methods: A total of 116 patients treated either by VBPP or CT were included in this study. Long-term recurrence rates and associations between clinical parameters and recurrence of pneumothorax were analyzed. Results: Sixty-two patients (53.4%) underwent VBPP, whereas 54 (46.6%) patients underwent CT treatment only. During a median follow-up period of 76.5 months, VBPP patients experienced a significantly lower recurrence rate compared to CT patients (6/62 vs. 35/54; p < 0.0001). CT treatment (VBPP vs. CT; p < 0.001) and a large initial pneumothorax size (Collins < 4 vs. Collins ≥ 4; p = 0.018) were independent risk factors for pneumothorax recurrence. Conclusion: VBPP is an effective and safe surgical treatment for PSP. Therefore, patients with a large pneumothorax size might benefit from VBPP, as they are at high risk for disease recurrence.

Impact of genetic status on the survival outcomes of patients with clinical stage I non-small cell lung cancer with a radiological pure-solid appearance

PurposeTo investigate whether genetic status is associated with the prognosis of patients with clinical stage (c-stage) I non-small cell lung cancer (NSCLC) with radiological pure-solid manifestations. Materials and MethodsWe included 340 patients with pure-solid c-stage I NSCLC and evaluated their clinicopathological and genetic information. Disease recurrence and death were also observed at the end of the 5-year follow-up period. A Cox proportional hazards model was performed to identify the effect of clinicopathological variables, including genetic status, on oncological outcomes. Recurrence-free survival (RFS) and overall survival (OS) were calculated by Kaplan-Meier curves and were compared using log-rank tests. ResultsThe gene-mutation rate of c-stage I NSCLC with a radiological pure-solid appearance was 55.9% (190/340), and the frequencies of EGFR, KRAS, ALK, ROS1 and fused genes were 69.5% (132/190), 16.8% (32/190), 8.9% (17/190), 1.6% (3/190) and 3.2% (6/190), respectively. The 5-year RFS and OS rates of eligible patients were 57.1% and 76.5%, respectively. A multivariable analysis revealed that genetic status was an independent significant prognostic factor associated with RFS (hazard ratio [HR] = 1.416, 95% confidence interval [CI]: 1.020–1.964, p = 0.038) but not with OS. RFS was lower in the genetic mutation group compared with the wild-type group (p = 0.027), with 5-year RFS rate (65.7 vs. 51.6%), but the difference in OS (mutated group vs. wild-type group: 78.0% vs. 75.3%) was not statistically significant (p = 0.602). Additionally, we found that pathological nodal involvement (HR = 2.455, 95% CI: 1.745–3.454, p < 0.001 for RFS; HR = 2.204, 95% CI: 1.409–3.447, p = 0.001 for OS) was also a valuable prognostic factor in patients with pure-solid c-stage I NSCLC. ConclusionOur study provides a comprehensive description of the mutational landscape of c-stage I NSCLC, and indicates that genetic status has an impact on disease recurrence in patients with c-stage I NSCLC with pure-solid appearance.

Abstract P1-13-06: The influence of the oncotype DX breast recurrence score on persistence to endocrine therapy in patients with low-risk ER/PR+ invasive breast cancer

Abstract Intro: The Oncotype DX breast recurrence score provides newly diagnosed patients with low-risk ER/PR+ invasive breast cancer with an estimation of their 10-year risk of distant recurrence if compliant with five years of endocrine therapy. Despite the well-established benefits of endocrine therapy, to include a decrease in local and distant disease recurrence, many patients will discontinue endocrine therapy prior to five years, defined as non-persistence. We hypothesized that the individual perception of risk of recurrence conveyed by the Oncotype DX breast recurrence score directly influences persistence with endocrine therapy and patients with higher Oncotype DX breast recurrence scores may have higher rates of persistence when compared to a similar cohort with lower recurrence scores. Further, we hypothesized that disease recurrence in women with low-risk (defined as less than 26) ER/PR+ breast cancer is due primarily to non-persistence with endocrine therapy. Methods: Our study included 198 patients with low-risk ER/PR+ breast cancer treated at a comprehensive cancer center between April 2011 and April 2014 with sufficient-follow-up data of at least 5 years. Persistence was determined by chart review and defined as a minimum duration of 55 months on endocrine therapy. Multivariable ANOVA and Fisher Chi Square Exact test were used to compare the recurrence score, 10-year risk of distant recurrence, and rates of recurrence between persistent vs non-persistent patients. Results: The average recurrence score of our cohort was 14.74 with an average 10-year risk of distant recurrence of 9.8 percent with five years of endocrine therapy. The average recurrence score was 15.24 in the persistent group vs. 13.18 for the non-persistent group (p=0.029). The average 10-year risk of distance recurrence was 10.1% in persistent patients vs 9% in non-persistent patients (p=0.019). The recurrence rate (both local and distant) was 4% in persistent patients vs 16% in non-persistent patients at 5- year follow (P=&amp;lt;0.01). Discussion: Non-persistence to endocrine therapy represents a major unmet need in breast cancer care. The Oncotype DX breast recurrence score significantly influences persistence to endocrine therapy as our retrospective review demonstrated that patients with low-risk ER/PR+ locally invasive breast cancer with higher Oncotype DX scores are more likely to complete the recommended 5-years of endocrine therapy. Further, despite having a lower average Oncotype DX score overall, the non-persistent group had a higher rate of recurrence when compared to the persistent group. This finding further substantiates the overall effectiveness of endocrine therapy in reducing the risk of future recurrence in patients with low-risk ER/PR+ breast cancer. Mindful framing of Oncotype DX test results by providers represents a potential avenue to increase persistence through the modulation of individual risk perception and may ultimately lead to decreased rates of disease recurrence in patients with low-risk ER/PR+ invasive breast cancer. Citation Format: Jonathan Pirruccello, Elaine Kuhn, Mary Chamberlin. The influence of the oncotype DX breast recurrence score on persistence to endocrine therapy in patients with low-risk ER/PR+ invasive breast cancer [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P1-13-06.

Abstract P2-13-14: Pattern of recurrence after pathologic complete response after neoadjuvant chemotherapy in patients with early HER2-positive breast cancer: Real-world evidence

Abstract Background The real-world risk of disease recurrence in patients with HER2-positive early breast cancer who achieved pathologic complete response (pCR) after neoadjuvant chemotherapy (NAC) and/or HER2-targeted therapy is unclear. This study aims to identify the patterns and risk factors of disease recurrence after NAC in patients with HER2-positive early breast cancer who achieved a pCR or not. Methods 930 HER2 positive early breast cancer patients who received NAC were identified in the Severance Breast Cancer Registry at the Yonsei Cancer Center and Gangnam Severance Hospital in Seoul, Republic of Korea, between 2006 and 2020. NAC included 3 regimens: only chemotherapy. (CTx), chemotherapy plus trastuzumab (CTx+H), and chemotherapy plus dual anti-HER2 therapy (TCHP). The pCR was defined as the absence of residual invasive cancer in the resected breast specimen and the axillary lymph nodes (ypT0/TisN0) after neoadjuvant systemic therapy. Recurrence of disease was defined as recurrence of ipsilateral locoregional invasive breast cancer, distant disease recurrence, or death. Results The median follow-up duration was 42.0 months (range 4-171), and median age was 51 years old (range 22-80). The rate of pCR was 52.2% (485/930). Depending on the achieved a pCR, the loco-regional recurrence rate was 4.0% (18/445) vs 1.0% (5/485), and the distant recurrence rate was 11.0% (49/445) vs 3.9% (19/445). Of the 79 patients who relapsed, 30.4% (n=24) had achieved a pCR and 69.6% (n=55) had residual disease. The 4-year recurrence risk was 6.9% for patients who achieved pCR versus 12.8% for those who did not (p&amp;lt;0.001). Of the 24 patients who achieved pCR who relapse, 22 (91.7%) occurred within 4 years of diagnosis. Of the 55 patients who did not achieve a pCR who relapse, 48 (87.3%) occurred within 4 years of diagnosis. Among the 19 patients who developed distant recurrence who attained a PCR, the most common first recurrent sites were lung (42.1%), brain (36.8%), and distant lymph nodes (36.1%). Lung and brain metastases occurred in 87.5% and 85.7% within 3years of diagnosis. If pCR was reached, the NAC regimen or HR status did not affect the recurrence-free survival. However, clinical stages II and III at diagnosis (HR (hazard ratio) =35.3 and HR=114.5, p=0.037) were independent predictor of inferior recurrence-free survival in the pCR group. Conclusion Overall, patients who attained a pCR have a better outcome compared to those with residual disease, regardless of hormone status or type of NAC regimen. However, despite achieving pCR after NAC, patients with HER2-positive, clinical stage II/III remain at risk for disease recurrence within 4 years of diagnosis. Citation Format: Jee Hung Kim, Jii Bum Lee, Soong Joon Bae, Sung Gwe Ahn, Joon Jeong, Min Hwan Kim, Seul-Gi Kim, Gun Min Kim, Jee Ye Kim, Hyung Seok Park, Seho Park, Byeong Woo Park, Seung Il Kim, Joohyuk Sohn. Pattern of recurrence after pathologic complete response after neoadjuvant chemotherapy in patients with early HER2-positive breast cancer: Real-world evidence [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P2-13-14.

Pan-immune-inflammation value independently predicts disease recurrence in patients with Merkel cell carcinoma

PurposeWe aimed to determine whether the pan-immune-inflammation value (PIV) of patients with Merkel cell carcinoma (MCC) at primary diagnosis differs from controls and whether it is associated with disease stage and outcome.MethodsIn this retrospective study, we recruited MCC patients with stage I–III. PIV was calculated from absolute complete blood cell counts obtained within one week at MCC diagnosis as follows: [neutrophils (103/mm3) × platelets (103/mm3) × monocytes (103/mm3)]/lymphocytes (103/mm3). As controls, we studied age–gender-matched cutaneous melanoma (CM, stage I–III) patients and healthy controls (HC). Univariate and multivariate statistics were used.ResultsThe median PIV in MCC patients was significantly increased compared to both CM patients as well as healthy controls. PIV of MCC patients in stage II and III was significantly higher compared to stage I patients. ROC analysis revealed that MCC recurrence was significantly associated with a PIV greater than 372 [p < 0.0001, Youden index 0.58; hazard ratio: 4 (95% confidence interval: 1.7 to 9.2)]. In multivariate analysis, only a PIV greater than 372 and higher MCC stage were determined as independent predictors for disease recurrence.ConclusionWe determined, for the first time, the prognostic ability of the promising blood-based biomarker PIV in MCC patients and observed that PIV is increased in MCC patients in dependence on disease stage and independently predicts MCC recurrence.

INFLAMMATION INDEXES AS PREDICTORS OF RECURRENCE IN PATIENTS WITH SURGICALLY RESECTED NON-SMALL CELL LUNG CANCER

Introduction. Prediction of lung cancer recurrence is one of the most urgent problems of modern oncology. Scientists are trying to find independent predictors that will help intensify, personalize the patient's treatment, and prevent the disease relapse on time. The study aimed to find indicators of inflammation that could be independent predictors of disease recurrence in patients with surgically resected non-small cell lung cancer. Materials and methods. The study was conducted retrospectively. The study group included 104 patients with non-small cell lung cancer who received surgical treatment and adjuvant chemotherapy or chemoradiotherapy from 2014 to 2018 at the Sumy Regional Clinical Oncology Dispensary. Based on the results of the blood count tests, the inflammation indices were calculated before chemotherapy or chemoradiotherapy and one month after their completion. Systemic inflammatory response index (SIRI), systemic inflammatory index (SII), neutrophil/lymphocyte ratio (NLR), platelets/lymphocytes ratio (PLR), lymphocyte/monocyte ratio (LMR), monocyte/lymphocyte ratio (MLR) were calculated. Using ROC analysis, cut-off points were found. Cox regression was used to find independent predictors of lung cancer recurrence. Results. During the observation period, relapse of the disease was recorded in 42 (40.4%) patients. The average recurrence-free survival was 56.3 months, range of 4–84.0 months (95% CI = 46.866–65.683). Before chemo- or chemoradiation therapy, the cut-off points for NLR1, PLR1, MLR1, LMR1, SII1, and SIRI1 were 1.80, 126.35, 0.22, 4.80, 521.22 and 0.96, respectively. Cut-off points for NLR2, PLR2, MLR2, LMR2, SII2, and SIRI2 at stage one month after completing courses of chemotherapy or chemoradiotherapy were 1.33, 153.80, 0.26, 3.98, 450.10 and 0.82 respectively. According to ROC analysis, only PLR1, SII1, LMR1, and LMR2 indices are reliable and can be used in further Cox regression analysis. Univariant Cox regression showed that LMR1 and SII1 were significantly associated with disease recurrence. Multivariate Cox regression identified SII1 as the only independent predictor of disease recurrence. Conclusions. Among numerous inflammation indices as an independent predictor for disease recurrence in non-small cell lung cancer patients who received surgical treatment and chemotherapy or chemoradiotherapy, only systemic inflammation index (SII1) at the stage before chemotherapy or chemoradiotherapy can be used. Indicators above 521.22 could be a predictor of high-risk recurrence of lung cancer.

Impact of primary tumor size, standardized uptake values of primary tumor, and the most avid neck node on baseline 18-fluoro-2-deoxyglucose positron emission tomography/computed tomography upon disease recurrence in head-and-neck oropharyngeal squamous cell carcinoma using standardized imaging protocol

The purpose of this prospective study was to find the impact of primary tumor size (Ts), standardized uptake values (SUVmax) of primary tumor, and the most avid neck node on disease recurrence in patients with head-and-neck (HN) oropharyngeal squamous cell carcinoma (HNOP-SCC). We included patients with HNOP-SCC (without distant metastasis – M0 disease) who had pre- and post-treatment 18-fluoro-2-deoxyglucose (18FDG) positron emission tomography/computed tomography (PET/CT) using strict standardized imaging protocol from 2017 to 2019. Based on follow-up 18FDG PET/CT findings patients were categorized as disease free (no or minimal 18FDG uptake ≤ background over surgical bed and no distant metastasis) and disease recurrence (18FDG uptake > background over surgical bed with or without nodal and/or distant metastasis). Ts and SUVmax of primary tumor and the most avid neck node were compared and impact of these was studied upon disease recurrence. A total of 112 patients were included. No significant difference was seen in mean age (overall: 60 ± 14 year), gender distribution (overall M: F: 69:31%), body mass index (overall: 25.20 ± 5.82), and history of diabetes (overall: 19%) between disease free and disease recurrence groups. Similarly, no significant difference was observed for fasting blood sugar (overall: 110 ± 28 mg%), 18FDG dose (overall: 169 ± 37 MBq) and uptake period (overall: 70 ± 12 min) between two groups ensuring strict adherence to standardized imaging protocol. Significant difference (P < 0.05) was observed between disease free and disease recurrence for Ts (25 ± 10 mm vs. 33 ± 14 mm), SUVmax of primary tumor (6.2 ± 6.8 vs. 9.3 ± 7.2) and the most avid neck node (2.1 ± 3.3 vs. 4.7 ± 5.9) and median follow-up (13 ± 12 vs. 08 ± 13 months), respectively. Using receiver operating characteristic analysis, Ts >29 mm, baseline tumor SUVmax >4.6 and nodal SUVmax >6.2 were found independent predictors for disease recurrence. Nodal SUVmax >6.2 was found an independent predictor of shortest DFS than Ts and tumor SUVmax. We conclude that, in HNOP-SCC, primary Ts (>29 mm), SUVmax of primary tumor (>4.6), and the most avid neck node (>6.2) in baseline 18FDG PET/CT using standardized imaging protocol are the independent predictors of disease recurrence. Furthermore, SUVmax >6.2 of the most avid node predicts the shortest DFS than primary Ts and SUVmax of primary tumor.

Predictors of Disease Recurrence Following Clearance of Bilobar Colorectal Liver Metastases: An International Multicentre Study

Introduction: Presence of bilobar colorectal liver metastases (BiCRLM) is a relatively poor prognostic indicator. With careful pre-operative planning, tumour clearance is offered for increased number of patients with BiCRLM. Some of the options are associated with higher postoperative morbidity, mortality rates and it is important to identify patients who benefit from such interventions. The study aims to assess the clinical and pathological determinants of recurrent disease in patients with BiCRLM. Study period and data collection: An international multicentre study was set up with endorsement from the EAHPBA. Predefined electronic case report forms were made available from BiCRLM.org website. Patients with at least two lesions each on the right and left hemiliver (minimum four) and considered for clearance of liver disease (single+/-two-stage hepatectomy+/-ablation) between 2012 and 2018 were recruited. Recurrence patterns and factors influencing recurrence were evaluated using stepwise regression analysis. Results: A total of 1243 patients were included. Recurrence was encountered in 77.3% (liver: site of previous resection/ablation:24%; liver: new location:50%; lungs:31%; peritoneum:11%. Median time to recurrence from liver surgery was 10.1months. 40% died with cancer at a median follow-up duration of 20 months. T-stage(p=0.24) and N-stage(0.18) of primary, chemotherapy at primary resection(0.02), number of liver lesions(p=0.001) and their radiological response(p=0.04), margin status of liver resection (0.004) had significant influence on the above outcomes. Conclusion: TN staging of primary, liver tumor load, chemosensitivity, margin positivity influence the oncological outcomes following clearance of BiCRLM. These factors should be taken into consideration in selection and surgical planning of patients with BiCRLM.

Predictive Performance of Serum S100B Versus LDH in Melanoma Patients: A Systematic Review and Meta-Analysis

BackgroundCurrently, no consensus on the use of blood tests for monitoring disease recurrence in patients with resected melanoma exists. The only meta-analysis conducted in 2008 found that elevated serum S100B levels were associated with significantly worse survival in melanoma patients. Serum LDH is an established prognostic factor in patients with advanced melanoma.ObjectiveTo compare the discriminative and prognostic ability of serum S100B with that of serum LDH in patients with melanoma.MethodsThis systematic review and meta-analysis were reported in accordance with the PRISMA Statement. The study protocol was registered in the International Prospective Register of Systematic Reviews (PROSPERO; CRD42019137138).ResultsA quantitative analysis of data from 6 eligible studies included 1,033 patients with cutaneous melanoma. The discriminative ability of serum S100B at identifying disease relapse [pooled Area Under the ROC (AUROC) 78.64 (95% CI 70.28; 87.01)] was significantly greater than the discriminative ability of serum LDH [AUROC 64.41 (95% CI 56.05; 7278)] (p=0.013). Ten eligible studies with 1,987 patients were included in the risk of death analysis. The prognostic performance of serum S100B [pooled estimate of adjusted hazard ratio (HR) 1.78 (95% CI 1.38; 2.29)] was independent but not superior to that of serum LDH [HR 1.60 (95% CI 1.36; 2.29)].LimitationsA relatively small number of articles were eligible and there was considerable heterogeneity across the included studies.ConclusionsSerum biomarkers may provide relevant information on melanoma patient status and should be further researched. Serum S100B is a valid marker for diagnosis of melanoma recurrence.Systematic Review RegistrationThe study protocol was registered in the International Prospective Register of Systematic Reviews (PROSPERO; CRD42019137138).

Atypical Metastases in the Abdomen and Pelvis From Biochemically Recurrent Prostate Cancer: 11C-Choline PET/CT With Multimodality Correlation.

PET with targeted radiotracers has become integral to mapping the location and burden of recurrent disease in patients with biochemical recurrence (BCR) of prostate cancer (PCa). PET with 11C-choline is part of the National Comprehensive Cancer Network and European Association of Urology guidelines for evaluation of BCR. With advances in PET technology, increasing use of targeted radiotracers, and improved survival of patients with BCR because of novel therapeutics, atypical sites of metastases are being increasingly encountered, challenging the conventional view that prostate cancer rarely metastasizes beyond bones or lymph nodes. The purpose of this article is to describe such atypical metastases in the abdomen and pelvis on 11C-choline PET (including metastases to the liver, pancreas, genital tract, urinary tract, peritoneum, abdominal wall, and perineural spread) and to present multimodality imaging features and relevant imaging pitfalls. Given atypical metastases' inconsistent relationship with the serum PSA level and the nonspecific presenting symptoms, atypical metastases are often first detected on imaging. Awareness of their imaging features is important because their detection affects clinical management, patient counseling, prognosis, and clinical trial eligibility. Such awareness is particularly critical because the role of radiologists in the imaging and management of BCR will continue to increase given the expanding regulatory approvals of other targeted and theranostic radiotracers.

Prolonged SARS-CoV-2 Infection in Patients with Lymphoid Malignancies.

Coronavirus disease 2019 (COVID-19) infection results in both acute mortality and persistent and/or recurrent disease in patients with hematologic malignancies, but the drivers of persistent infection in this population are unknown. We found that B-cell lymphomas were at particularly high risk for persistent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) positivity. Further analysis of these patients identified discrete risk factors for initial disease severity compared with disease chronicity. Active therapy and diminished T-cell counts were drivers of acute mortality in COVID-19-infected patients with lymphoma. Conversely, B cell-depleting therapy was the primary driver of rehospitalization for COVID-19. In patients with persistent SARS-CoV-2 positivity, we observed high levels of viral entropy consistent with intrahost viral evolution, particularly in patients with impaired CD8+ T-cell immunity. These results suggest that persistent COVID-19 infection is likely to remain a risk in patients with impaired adaptive immunity and that additional therapeutic strategies are needed to enable viral clearance in this high-risk population. SIGNIFICANCE: We describe the largest cohort of persistent symptomatic COVID-19 infection in patients with lymphoid malignancies and identify B-cell depletion as the key immunologic driver of persistent infection. Furthermore, we demonstrate ongoing intrahost viral evolution in patients with persistent COVID-19 infection, particularly in patients with impaired CD8+ T-cell immunity.This article is highlighted in the In This Issue feature, p. 1.

Clinical Application of SPECT-CT Imaging with 99mTc-PSMA in Patients with Recurrent Prostate Cancer

Introduction: Prostate cancer is the most common malignancy in men in Europe. One of the important clinical problems is the early detection and visualization of recurrence after radical prostatectomy, radiation therapy or other radical topical treatment, in patients with PSA values above 0.2 ng/ml. With the introduction of molecular highly sensitive imaging methods after administration of radiolabeled prostate-specific membrane antigen (PSMA), it became possible to detect early functional changes associated with the development of a metastatic process in this disease, with a negative CT or MRI result. 99mTc-PSMA is a new radiopharmaceutical and is a small ligand that binds to the active core of PSMA. The aim of our study was to evaluate the clinical role of 99mTc-PSMA in imaging local recurrence and/or loco-regional and distant metastases in patients with recurrent prostate cancer and biochemical disease progression. Material and methods: A cohort of 36 prostate cancer patients was evaluated with established laboratory data for biochemical progression of the disease - increase in the serum value of the tumor marker PSA and its doubling time within 6 months. In 3/36 of the patients, prostate adenocarcinoma was accidentally detected after transurethral resection of the prostate. Hormonal and cytoreductive radiotherapy was performed in these patients as a therapy. The remaining 33/36 patients underwent radical treatment of primary cancer after a systematic or MRI/US fusion prostate biopsy. Results: All of these patients underwent a whole body scan followed by a targeted SPECT-CT study, 1–3 hours after intravenous administration of 99mTc-PSMA. The sensitivity of the SPECT-CT test with 99mTc-PSMA for the detection of recurrent prostate cancer in 36 followed patients was 84.37% (27/32), specificity - 100% (4/4) and accuracy - 86.11% 31/36). Conclusion: For the clinical application of 99mTc-PSMA SPECT-CT we can summarize that this method finds the greatest clinical application for early diagnosis of recurrent disease in patients with prostate cancer and biochemical progression, at serum PSA levels ≥0.50 ng / ml, in order to determine a personalized treatment for each individual patient. Key words: Prostate cancer, recurrent prostate cancer, 99mTc-PSMA, SPECT-CT

SOX12 Promotes Stem Cell-Like Phenotypes and Osteosarcoma Tumor Growth by Upregulating JAGGED1.

SOX12 plays a role in promoting the growth of some tumors; however, its role in osteosarcoma remains unclear. From gene expression omnibus (GEO) and tumor alterations relevant for genomics-driven therapy (TARGET) databases, Kaplan–Meier analyses were conducted to establish relationships between SOX12 expression and osteosarcoma survival and recurrence in osteosarcoma patients. We also performed in vitro and in vivo assays to determine SOX12 function in osteosarcoma etiology. SOX12 expression was increased in osteosarcoma; high SOX12 expression levels were related to a poor prognosis and a high disease recurrence in patients. Moreover, SOX12 expression in osteosarcoma cell lines was increased, similar to osteosarcoma cancer stem cells. We also observed that SOX12 knockdown inhibited the spheroidization and expression of stemness markers in osteosarcoma cells and tumor formation in nude mice. In addition, SOX12 knockdown inhibited JAGGED1 and HES1 expression. Similarly, JAGGED1 knockdown also inhibited the formation of osteosarcoma cancer stem cells into pellets and reduced the expression of stemness markers and tumor formation capabilities in nude mice. Finally, during SOX12 knockdown, JAGGED1 overexpression rescued osteosarcoma cells from spheroidizing. SOX12 promotes stem cell-like phenotypes and osteosarcoma tumor growth by upregulating JAGGED1.

Faecal Calprotectin from Ileostomy Output Is Sensitive and Specific for the Prediction of Small Bowel Inflammation in Patients with Crohn's Disease.

Severe Crohn's disease [CD] can result in extensive bowel resections and need for creation of an ileostomy. Faecal calprotectin [FC] is well studied in CD management, though its role in patients who have an ileostomy is unclear. Our aim is to understand if FC is a useful adjunct to radiographic or endoscopic studies in identifying recurrent CD after surgery in patients with an ileostomy. Between January 1, 2017, and September 30, 2020, we searched the Mayo Clinic electronic medical record retrospectively for adult patients with ICD-10 code for CD, and a surgical history of an ileostomy. Patients were included in the analysis if they had at least one FC measured and a concomitant radiographic imaging and/or endoscopic procedure. An abnormal FC was defined as greater than 60 µg/g. Of 51 patients who met our inclusion criteria, 17 had an FC level >60 µg/g. Of these 17 patients, 14 had imaging and/or an ileoscopy confirming the presence of small bowel inflammation, with a sensitivity of 87.5%. Of the remaining 34 patients with an FC level ≤60 µg/g, 32 patients had imaging and/or ileoscopy demonstrating no small bowel inflammation, with a specificity of 91.4%. FC from an ileostomy effluent had a positive predictive value of 82.3%, a negative predictive value of 94.1% and test diagnostic accuracy of 90.1%. FC from an ileostomy effluent is a highly sensitive and specific test for the assessment and monitoring of small bowel inflammation and disease recurrence in patients with CD.

The Influence of Dental Rehabilitation on the Detection and Rate of Cancer Recurrence after Oral Cavity Malignant Tumor Ablation

Immediate microvascular tissue reconstruction is the reconstructive modality of choice after head and neck malignant tumor ablation. Although delayed reconstruction allows for definitive analysis of pathologic margins, studies have shown that immediate reconstruction does not yield higher rates of recurrence.1 Immediate reconstruction is associated with less financial burden, decrease in treatment time, and improved quality of life.1 The use of an implant-retained or -supported prosthetics furthers this improvement in quality of life. Although the previously discussed benefits also apply when endosseous implants are placed immediately at the time of reconstruction, there are concerns of their impact on recurrence in the treatment of malignant tumors. It has been hypothesized that immediate implant placement can result in seeding, interference with the efficacy of adjuvant radiation therapy, and delay in the diagnosis of recurrent disease secondary to radiographic artifact and lack of clinical visibility.2 The primary aim of this study was to assess the impact of dental rehabilitation in the diagnosis of disease recurrence in patients with oral cavity malignancies that underwent free flap reconstruction with endosseous implant placement. The secondary aim was to determine the rate of osteoradionecrosis in patients who underwent adjuvant radiation treatment.This is a retrospective study from a sample of subjects who underwent immediate reconstruction with a free tissue transfer and either immediate or delayed implant placement for treatment of oral cavity malignancies by the Division of Oral and Maxillofacial Surgery at the Mayo Clinic, MN. Descriptive data were collected on patient demographics, diagnosis, number of implants, history of radiation therapy, and type of prosthesis utilized. The tumors were staged according to the AJCC eighth edition tumor-node-metastasis classification. All subjects received an implant-retained or -supported prosthesis and had a minimum follow-up of 24 months. Recurrence was confirmed by incisional biopsy.A total of 29 patients with an average age of 54.6 years old, including 12 females (41.4%) and 17 males (58.6%), with an oral cavity malignancy met inclusion criteria. Squamous cell carcinoma was the most common malignancy, occurring in 20 patients (69%), followed by 5 subjects (17.2%) with osteosarcoma. Seven patients (24.1%) experienced a local recurrence and, of these, and 5 had an initial pathologic T4a squamous cell carcinoma. Six of the 24 subjects (25.0%) restored with a fixed prosthesis experienced a recurrence. Fifteen patients (51.7%) had implants placed at the time of reconstruction. Of those, 5 (33.3%) experienced recurrence with the average number of days from reconstruction to diagnosis of recurrence being 810.8 days. Two (14.3%) subjects in the delayed implant group experienced recurrence with the average number of days from reconstruction to the diagnosis of recurrence being 4550 days. Fourteen subjects received adjuvant radiation therapy, of which 4 (28.6%) experienced osteoradionecrosis. Timing of implant placement was equally distributed in patients who experienced osteoradionecrosis.In conclusion, subjects who underwent immediate implant placement had a higher rate of recurrence (33.3%) when compared to those with delayed implant placement (14.3%). None of the recurrences were directly adjacent to the endosseous implants and the clinical diagnosis of local recurrence was not affected by the presence of a prosthesis. The timing of implant placement was not associated with a higher risk of osteoradionecrosis.

Clinical, Pathological, Laboratory Characteristics, and Treatment Regimens of Kimura Disease and Their Relationships With Tumor Size and Recurrence.

Objective: As of date, Kimura disease (KD) has an unclear etiology, no accepted diagnostic standard, and no definite treatment regimen. In this study, clinical and pathological laboratory characteristics and treatment regimens of patients with KD with different tumor sizes and status of tumor recurrence were analyzed. This was performed to identify the factors, which determine tumor size and recurrence, and to identify effective treatment methods for patients with KD.Methods: A total of 33 hospitalized patients with a definite diagnosis of KD were enrolled in this study.Results: There were 15 patients (45.5%) with a maximum tumor diameter of <3 cm. There were no statistically significant differences in age, gender, clinical symptoms, lesion sites, laboratory indicators, and treatment regimens among patients with a maximum tumor diameter <3 cm or ≥3 cm (P > 0.05). Among the 25 patients who completed the follow-up, there were 18 patients (72%) who had a recurrence of KD. There were no statistically significant differences in age, gender, clinical symptoms, the maximum tumor diameter, lesion sites, laboratory indicators, and initial treatment regimens between patients with or without the recurrence of KD (P > 0.05). There was a statistically significant difference in systolic blood pressure (SBP) between patients with or without the recurrence of KD (P < 0.05). All patients who received only surgical treatment had disease recurrence, 33.3% of patients who received prednisone therapy had no disease recurrence, and 37.5% of patients who received combination therapy showed recurrence.Conclusion: The current study summarized clinical manifestations, pathological features, laboratory indicators, and treatment regimens of patients with KD. There were no significant differences in these aspects among patients with different tumor sizes, and there was no significant difference in these aspects except in the SBP between patients with or without the recurrence of KD, indicating that SBP is a significant clinical factor affecting disease recurrence in patients. Combination therapy with prednisone was found to be superior to surgical treatment.