Risk Of Recurrence In Patients Research Articles

Evaluating Recurrence Risk in Patients Undergoing Breast-conserving Surgery Using E-cadherin Staining as a Biomarker.

Following the National Comprehensive Cancer Network guidelines, radiotherapy is administered after breast-conserving surgery (BCS) in patients with more than four positive lymph nodes. Four positive lymph nodes are typically considered an indicator to assess disease spread and patient prognosis. However, the subjective counting of positive axillary lymph nodes underscores the need for biomarkers to improve diagnostic precision and reduce the risk of unnecessary treatments. Loss of E-cadherin expression is associated with cancer metastasis, but its potential as a predictive marker for cancer treatment remains uncertain. This study aimed to investigate the validity of E-cadherin as a reference for adjuvant radiotherapy in breast cancer patients with positive lymph nodes post-mastectomy. Immunohistochemistry was performed on 60 clinical tissue specimens to assess these implications. Although no significant result was found in a single E-cadherin subgroup (low, medium, and high subgroups according to the X-tile algorithm), the proposed multivariate model, including the E-cadherin category, breast cancer subtype, and tumor size, yielded satisfactory recurrence risk estimation results for patients undergoing BCS. Patients with a low E-cadherin category, triple-negative breast cancers, and tumor size over 5 cm could have an increased risk of recurrence. Our study proposed a multivariate model that serves as a candidate prognostic factor for recurrence-free survival in patients undergoing BCS and radiotherapy. Utilizing this model for patient stratification in high-risk diseases and as a standard for assessing postoperative intensified therapy can potentially improve patient outcomes.

A recurrence-predictive model based on eight genes and tumor mutational burden/microsatellite instability status in Stage II/III colorectal cancer.

Although adjuvant chemotherapy (ACT) is widely used to treat patients with Stage II/III colorectal cancer (CRC), administering ACT to specific patients remains a challenge. The decision to ACT requires an accurate assessment of recurrence risk and absolute treatment benefit. However, the traditional TNM staging system does not accurately assess a patient's individual risk of recurrence. To identify recurrence risk-related genetic factors for Stage II/III CRC patients after radical surgery, we conducted an analysis of whole-exome sequencing of 47 patients with Stage II/III CRC who underwent radical surgery at five institutions. Patients were grouped into non-recurrence group (NR, n = 24, recurrence-free survival [RFS] > 5 years) and recurrence group (R, n = 23, RFS <2 years). The TCGA-COAD/READ cohort was employed as the validation dataset. A recurrence-predictive model (G8plus score) based on eight gene (CUL9, PCDHA12, HECTD3, DCX, SMARCA2, FAM193A, AATK, and SORCS2) mutations and tumor mutation burden/microsatellite instability (TMB/MSI) status was constructed, with 97.87% accuracy in our data and 100% negative predictive value in the TCGA-COAD/READ cohort. For the TCGA-COAD/READ cohort, the G8plus-high group had better RFS (HR = 0.22, p = 0.024); the G8plus-high tumors had significantly more infiltrated immune cell types, higher tertiary lymphoid structure signature scores, and higher immunological signature scores. The G8plus score was also a predict biomarker for immunotherapeutic in advanced CRC in the PUCH cohort. In conclusion, the G8plus score is a powerful biomarker for predicting the risk of recurrence in patients with stage II/III CRC. It can be used to stratify patients who benefit from ACT and immunotherapy.

Metabolic dysfunction-associated fatty liver disease in the elderly with diabetic foot ulcers: A longitudinal cohort study.

This study aimed to explore the association between metabolic-associated fatty liver disease (MAFLD) and ulcer recurrence risk in patients with diabetic foot ulcers (DFUs) through an ambispective longitudinal cohort. From December 2013 to December 2022, a total of 482 inpatients with DFUs (PEDIS grade 3 and above with a severe infection) were eligible for inclusion in this study. This was an ambispective longitudinal cohort study. All participants were followed up every 6 months for 9 years with a median of 36 months. According to whether having MAFLD or not, all subjects were placed into two groups: non-MAFLD (n = 351) and MAFLD (n = 131). The association between MAFLD and ulcer recurrence in patients with DFUs was then evaluated through multivariate Cox regression analysis, stratified analyses and Kaplan-Meier survival analysis. Throughout the follow-up period, out of 482 subjects with DFUs, 68 had ulcer recurrence (14.1%). Three Cox regression models were established for data analyses. In the model I (unadjusted), MAFLD was significantly associated with the ulcer recurrence rate in patients with DFUs (HR = 1.79; 95% CI = 1.097-2.92; p = 0.02). Model II (adjusted model I with gender and age) (HR = 1.781; 95% CI = 1.09-2.912; p = 0.021) and model III (adjusted model II with CVD, duration of diabetes and Cr.) (HR = 1.743; 95% CI = 1.065-2.855; p = 0.027) also showed that MAFLD was significantly related to the ulcer recurrence risk in patients with DFUs, respectively. Stratified analysis indicated that subjects aged ≥60 had a greater risk of ulcer recurrence in MAFLD than in non-MAFLD (HR = 2.31; 95% CI = 1.268-4.206; p = 0.006). Kaplan-Meier survival curve analysis showed that ulcer recurrence rate had a significant association with MAFLD (log-rank, p = 0.018). This study indicated a close association between ulcer recurrence risk and MAFLD in patients with DFUs, especially in the elderly (aged ≥60). Therefore, special attention should be paid to the elderly with both DFUs and MAFLD because they have a higher ulcer recurrence rate than other general populations in routine clinical practice.

Retracted: Evaluation of the Risk of Recurrence in Patients with Local Advanced Rectal Tumours by Different Radiomic Analysis Approaches

Retracted: Evaluation of the Risk of Recurrence in Patients with Local Advanced Rectal Tumours by Different Radiomic Analysis Approaches

A prediction model for identifying high-risk lymph node metastasis in clinical low-risk papillary thyroid microcarcinoma

BackgroundThe presence of high-volume lymph node metastasis (LNM) and extranodal extension (ENE) greatly increases the risk of recurrence in patients with low-risk papillary thyroid microcarcinoma (PTMC). The goal of this research was to analyze the factors that contribute to high-risk lymph node metastasis in patients with low-risk PTMC.MethodsWe analyzed the records of 7344 patients who were diagnosed with low-risk PTMC and treated at our center from January 2013 to June 2018.LNM with a high volume or ENE was classified as high-risk lymph node metastasis (hr-LNM). A logistic regression analysis was conducted to identify the risk factors associated with hr-LNM. A nomogram was created and verified using risk factors obtained from LASSO regression analysis, to predict the likelihood of hr-LNM.ResultsThe rate of hr-LNM was 6.5%. LASSO regression revealed six variables that independently contribute to hr-LNM: sex, age, tumor size, tumor location, Hashimoto’s thyroiditis (HT), and microscopic capsular invasion. A predictive nomogram was developed by integrating these risk factors, demonstrating its excellent performance. Upon analyzing the receiver operating characteristic (ROC) curve for predicting hr-LNM, it was observed that the area under the curve (AUC) had a value of 0.745 and 0.730 in the training and testing groups showed strong agreement, affirming great reliability.ConclusionSex, age, tumor size, tumor location, HT, and microscopic capsular invasion were determined to be key factors associated with hr-LNM in low-risk PTMC. Utilizing these factors, a nomogram was developed to evaluate the risk of hr-LNM in patients with low-risk PTMC.

Skin-Sparing Marginal Excision: Case Report of a Novel Approach to Dystrophic Calcification

Dystrophic calcification (DC) is a rare manifestation of calcium salt accumulation in non-skeletal tissues, often associated with local tissue damage. This case report presents a 45-year-old female patient who manifested soft-tissue calcification in an extra-articular burn scar, developing after a substantial latency period of 40 years. The conventional treatment, wide excision with skin grafting, was declined by the patient due to cosmetic and socioeconomic reasons. Instead, a skin-sparing marginal excision was performed. A thorough removal of the calcified lesions were achieved while conserving the overlying skin to reduce tension, a trigger factor of DC. Histopathological examination revealed fibrous tissue intertwined with DC. With a stringent follow-up regimen and routine X-ray examinations, no recurrence was observed over a period of 3 years. The patient expressed satisfaction with her expedited recovery and minimal postoperative scarring. This case underscores the potential of skin-sparing marginal excision as a viable alternative to wide excision and skin grafting, providing satisfactory outcomes and minimizing the risk of recurrence in patients who adhere to regular follow-up and examination schedules. However, more comprehensive research with a larger sample size is required before establishing this method as a standard treatment protocol for DC.

Nomogram based on preoperative clinical and MRI features to estimate the microvascular invasion status and the prognosis of solitary intrahepatic mass-forming cholangiocarcinoma.

To develop a nomogram based on preoperative clinical and magnetic resonance imaging (MRI) features for the microvascular invasion (MVI) status in solitary intrahepatic mass-forming cholangiocarcinoma (sIMCC) and to evaluate whether it could predict recurrence-free survival (RFS). We included 115 cases who experienced MRI examinations for sIMCC with R0 resection. The preoperative clinical and MRI features were extracted. Independent predictors related to MVI+ were evaluated by stepwise multivariate logistic regression, and a nomogram was constructed. A receiver operating characteristic (ROC) curve was used to assess the predictive ability. All patients were classified into high- and low-risk groups of MVI. Then, the correlations of the nomogram with RFS in patents with sIMCC were analyzed by Kaplan-Meier method. The occurrence rate of MVI+ was 38.3% (44/115). The preoperative independent predictors of MVI+ were carbohydrate antigen 19-9 >37U/ml, tumor size >5cm, and an ill-defined tumor boundary. Integrating these predictors, the nomogram exerted a favorable diagnostic performance with areas under the ROC curve of 0.767 (95% confidence interval [CI] 0.654-0.881) in the development cohort, and 0.760 (95% CI 0.591-0.929) in the validation cohort. In the RFS analysis, significant differences were observed between the high- and low-risk MVI groups (6-month RFS rates: 64.5% vs. 78.8% and 46.7% vs. 82.4% in the development and validation cohorts, respectively) (P<0.05). A nomogram based on clinical and MRI features is a potential biomarker of MVI and may be a potent method to classify the risk of recurrence in patients with sIMCC.

Peak Risk of Recurrence Occurs during the First Two Years after a Pancreatectomy in Patients Receiving Neoadjuvant FOLFIRINOX

No codified/systematic surveillance program exists for borderline/locally advanced pancreatic ductal carcinoma treated with neoadjuvant FOLFIRINOX and a secondary resection. This study aimed to determine the trend of recurrence in patients who were managed using such a treatment strategy. From 2010, 101 patients received FOLFIRINOX and underwent a pancreatectomy, in a minimum follow-up of 5 years. Seventy-one patients (70%, R group) were diagnosed with recurrence after a median follow-up of 11 months postsurgery. In the multivariable analysis, patients in the R-group had a higher rate of weight loss (p = 0.018), higher carbohydrate antigen (CA 19-9) serum levels at diagnosis (p = 0.012), T3/T4 stage (p = 0.017), and positive lymph nodes (p &lt; 0.01) compared to patients who did not experience recurrence. The risk of recurrence in patients with T1/T2 N0 R0 was the lowest (19%), and all recurrences occurred during the first two postoperative years. The peak risk of recurrence for the entire population was observed during the first two postoperative years. The probability of survival decreased until the second year and rebounded to 100% permanently, after the ninth postoperative year. Close monitoring is needed at reduced intervals during the first 2 years following a pancreatectomy and should be extended to later than 5 years for those with unfavorable pathological results.

Application of multicolor flow cytometry in liquid biopsy of breast cancer

As a result of the clinical study NCT04817501 “Phenotypic characterization of circulating tumor cells (CTCs) in tumors of the female reproductive system”, we developed a method for preoperative prediction of a recurrence risk in patients with stage T1 endometrial cancer (Patent No. 2762493 of 21.12.2021).The article presents a clinical case of the use of multicolor flow cytometry in liquid biopsy of breast cancer (BC). CTCs were detected in the blood of a patient with T2N0M0 BC, stage IIA before the initiation of treatment. Using multicolor flow cytometry, various CTC phenotypes were studied and the Her2/neu and ki-67 markers were determined. These markers were also studied in the biopsy and surgical material of the BC tissue using immunohistochemistry. As a result of the study, it was shown that the molecular profile of CTCs in the blood taken before fine needle aspiration biopsy coincided with that of cancer cells in the BC tissue. In addition, the calculated risk of tumor progression before biopsy predicted recurrence of cancer in this patient 20 months before its occurrence. The obtained results show the practical utility of multicolor flow cytometry in liquid biopsy of cancers. The ability to evaluate CTCs by various molecular parameters can be useful for diagnosing, predicting, monitoring, and determining treatment strategies for cancer patients.

Selenium and Vitamin E for Prevention of Non–Muscle-Invasive Bladder Cancer Recurrence and Progression

Selenium and vitamin E have been identified as promising agents for the chemoprevention of recurrence and progression of non-muscle-invasive bladder cancer. To determine whether selenium and/or vitamin E may prevent disease recurrence in patients with newly diagnosed NMIBC. This multicenter, prospective, double-blinded, placebo-controlled, 2 × 2 factorial randomized clinical trial included patients with newly diagnosed NMIBC recruited from 10 secondary or tertiary care hospitals in the UK. A total of 755 patients were screened for inclusion; 484 did not meet the inclusion criteria, and 1 declined to participate. A total of 270 patients were randomly assigned to 4 groups (selenium plus placebo, vitamin E plus placebo, selenium plus vitamin E, and placebo plus placebo) in a double-blind fashion between July 17, 2007, and October 10, 2011. Eligibility included initial diagnosis of NMIBC (stages Ta, T1, or Tis); randomization within 12 months of first transurethral resection was required. Oral selenium (200 μg/d of high-selenium yeast) and matched vitamin E placebo, vitamin E (200 IU/d of d-alfa-tocopherol) and matched selenium placebo, selenium and vitamin E, or placebo and placebo. Recurrence-free interval (RFI) on an intention-to-treat basis (analyses completed on November 28, 2022). The study randomized 270 patients (mean [SD] age, 68.9 [10.4] years; median [IQR] age, 69 [63-77] years; 202 male [75%]), with 65 receiving selenium and vitamin E placebo, 71 receiving vitamin E and selenium placebo, 69 receiving selenium and vitamin E, and 65 receiving both placebos. Median overall follow-up was 5.5 years (IQR, 5.1-6.1 years); 228 patients (84%) were followed up for more than 5 years. Median treatment duration was 1.5 years (IQR, 0.9-2.5 years). The study was halted because of slow accrual. For selenium (n = 134) vs no selenium (n = 136), there was no difference in RFI (hazard ratio, 0.92; 95% CI, 0.65-1.31; P = .65). For vitamin E (n = 140) vs no vitamin E (n = 130), there was a statistically significant detriment to RFI (hazard ratio, 1.46; 95% CI, 1.02-2.09; P = .04). No significant differences were observed for progression-free interval or overall survival time with either supplement. Results were unchanged after Cox proportional hazards regression modeling to adjust for known prognostic factors. In total, 1957 adverse events were reported; 85 were serious adverse events, and all were considered unrelated to trial treatment. In this randomized clinical trial of selenium and vitamin E, selenium supplementation did not reduce the risk of recurrence in patients with NMIBC, but vitamin E supplementation was associated with an increased risk of recurrence. Neither selenium nor vitamin E influenced progression or overall survival. Vitamin E supplementation may be harmful to patients with NMIBC, and elucidation of the underlying biology is required. isrctn.org Identifier: ISRCTN13889738.

Obesity and Risk of Recurrence in Patients With Breast Cancer Treated With Aromatase Inhibitors

Clinical studies confirm that obesity is a risk factor for recurrence in postmenopausal women with hormone receptor-positive (HR+) breast cancer. Evidence suggests that women with obesity do not obtain similar protection from aromatase inhibitors as women with healthy weight. To examine the associations of body mass index (BMI) with recurrence. The cohort study was conducted using data from the Danish Breast Cancer Group and enrolled postmenopausal women diagnosed with stage I to III HR+ breast cancer from 1998 through 2016. Data analysis was conducted from November 2022 to April 2023. BMI was classified as (1) healthy weight (18.5-24.9), (2) overweight (25.0-29.9), (3) obesity (30.0-34.9), and (4) severe obesity (≥35.0) using the World Health Organization guidelines. Healthy weight was considered the reference group in statistical analyses. Follow-up began 6 months after breast cancer surgery and continued until the first event of recurrence, contralateral breast cancer, new primary malignant neoplasm, death, emigration, end of clinical follow-up at 10 years, or September 25, 2018. Cox regression was used to estimate crude and adjusted hazard ratios with 95% CIs, adjusting for patient, tumor, and treatment characteristics. A total of 13 230 patients (median [IQR] age at diagnosis, 64.4 [58.6-70.2] years) with information on BMI were enrolled. There were 1587 recurrences with a median (IQR) potential estimated follow-up of 6.2 (3.6-8.5) years. Multivariable analyses revealed increased recurrence hazards associated with obesity (adjusted hazard ratio, 1.18 [95% CI, 1.01-1.37]) and severe obesity (adjusted hazard ratio, 1.32 [95% CI, 1.08-1.62]) vs patients with healthy weight. Patients with overweight had a greater risk, but the results were not statistically significant (adjusted hazard ratio, 1.10 [95% CI, 0.97-1.24]). In this study, obesity was associated with an increased risk of breast cancer recurrence among postmenopausal patients with HR+ early-stage breast cancer treated with aromatase inhibitors. Physicians should be aware of the significance of obesity on breast cancer outcomes to secure optimal treatment benefit in all patients.

A radiomics nomogram for predicting postoperative recurrence in esophageal squamous cell carcinoma.

To establish and validate a radiomics nomogram for predicting recurrence of esophageal squamous cell carcinoma (ESCC) after esophagectomy with curative intent. The medical records of 155 patients who underwent surgical treatment for pathologically confirmed ESCC were collected. Patients were randomly divided into a training group (n=109) and a validation group (n=46) in a 7:3 ratio. ​Tumor regions are accurately segmented in computed tomography images of enrolled patients. Radiomic features were then extracted from the segmented tumors. We selected the features by Max-relevance and min-redundancy (mRMR) and least absolute shrinkage and selection operator (LASSO) methods. A radiomics signature was then built by logistic regression analysis. To improve predictive performance, a radiomics nomogram that incorporated the radiomics signature and independent clinical predictors was built. Model performance was evaluated by receiver operating characteristic (ROC) curve, calibration curve, and decision curve analyses (DCA). We selected the five most relevant radiomics features to construct the radiomics signature. The radiomics model had general discrimination ability with an area under the ROC curve (AUC) of 0.79 in the training set that was verified by an AUC of 0.76 in the validation set. The radiomics nomogram consisted of the radiomics signature, and N stage showed excellent predictive performance in the training and validation sets with AUCs of 0.85 and 0.83, respectively. Furthermore, calibration curves and the DCA analysis demonstrated good fit and clinical utility of the radiomics nomogram. We successfully established and validated a prediction model that combined radiomics features and N stage, which can be used to predict four-year recurrence risk in patients with ESCC who undergo surgery.

Effect of Radioactive Iodine Therapy on Cancer-Specific Survival of Papillary Thyroid Cancer Tall Cell Variant.

Radioactive iodine (RAI) therapy is often used as an adjuvant treatment to reduce the risk of recurrence in patients with papillary thyroid cancer (PTC). However, the effect of RAI therapy on cancer-specific survival (CSS) in patients with tall cell variant (TCV) remains controversial. This study aimed to investigate the impact of RAI therapy on CSS in patients with TCV-PTC by analyzing data from the Surveillance, Epidemiology, and End Results database. We identified 1281 patients with TCV-PTC in the SEER database who underwent total thyroidectomy between 2004 and 2019. Of these, 866 (67.6%) patients received RAI therapy and 415 (32.4%) did not. Propensity score matching was conducted to balance the baseline characteristics between the 2 groups. Cox proportional hazards regression models were used to estimate the hazard ratio (HR) and 95% CI for the effect of RAI therapy on CSS. After propensity score matching, 373 pairs of patients were included in the analysis. The results showed no significant difference in CSS between the RAI therapy group and the non-RAI therapy group (HR 0.54, 95% CI 0.25-1.17, P = .120). Subgroup analyses indicated similar results. RAI therapy may not improve CSS in patients with TCV-PTC after total thyroidectomy. Future studies with larger sample sizes, longer follow-up periods, and better study designs are needed to confirm or refine our research findings.

Emotion dysregulation and affective temperaments in opioid use disorder: a 1-year follow-up study

Background Opioid use disorder (OUD) remains a significant public health challenge with high recurrence rates and varied long-term outcomes. Affective temperament and emotion regulation have been identified as influencing addictive behaviors and treatment outcomes in OUD. However, limited research has explored their association with reversion over an extended period. Objectives The EDATOUD (Emotion Dysregulation and Affective Temperaments in Opioid Use Disorder) study aimed to evaluate the effects of affective temperament and emotion regulation characteristics on recurrence over a 1-year follow-up period. The study aimed to compare the baseline characteristics of patients who achieved remission versus those who did not and identify potential predictors of recurrence risk. Methods The study included 63 patients with OUD who were assessed monthly for return-to-use through self-report, psychiatric examination, and urine analysis. Sociodemographic data, affective temperament, difficulties in emotion regulation, anxiety, and depression were measured at baseline. Statistical analyses were performed to compare the recurrent and remission groups and determine the predictive value of these clinical features on recurrence. Results Within the one-year, 77.8% of patients returned to use. Affective temperament characteristics did not differ between the groups. However, the recurrent group patients exhibited significantly more difficulties in emotion regulation. Conclusions Difficulties in emotion regulation are associated with an increased risk of recurrence in patients with OUD. Understanding these factors can inform the development of tailored treatment strategies to improve long-term outcomes. Further research is needed to explore additional factors contributing to reversion and enhance intervention and support systems for sustained recovery in OUD.

Prognostic value of baseline MRI features in patients treated with thermal ablation for hepatocellular carcinoma

PurposeTo investigate prognostic value of baseline MRI features for time-to-recurrence (TTR) and local recurrence in patients with early hepatocellular carcinoma (HCC). MethodBaseline and follow-up images of 88 patients treated with thermal ablation followed by adjuvant sorafenib or matching placebo due to HCC within the phase II prospective randomized trial (SORAMIC) were included. Baseline MRI images were evaluated in terms of atypical enhancement (lack of wash-in or wash-out), lesion diameter, tumor capsule, peritumoral enhancement on arterial phase, intratumoral fat, irregular margin, satellite lesions, and peritumoral hypointensity on hepatobiliary phase. Prognostic value of these features for TTR and local recurrence were assessed with univariable and multivariable Cox proportional hazard models. ResultsRecurrence at any location was diagnosed during follow-up in 30 patients, and the median TTR was 16.4 (95% CI, 15 – NA) months. The presence of more than one lesion (p = 0.028) and peritumoral hypointensity on hepatobiliary phase images (p = 0.012) at baseline were significantly associated with shorter TTR in univariable analysis. AFP > 15 mg/dL (p = 0.084), and history of cirrhosis (p = 0.099) were marginally non-significant. Peritumoral hypointensity on hepatobiliary phase images was the only significant risk factor for recurrence in multivariable analysis (p = 0.003).Local recurrence (adjacent to thermal scar) was diagnosed in eleven (8.3%) out of 132 lesions that underwent thermal ablation. The only significant risk factor for local recurrence was a lesion diameter larger than 3 cm (22.2% vs. 4.5%, p = 0.007). ConclusionsPeritumoral hypointensity on hepatobiliary phase can serve as imaging biomarker to identify increased recurrence risk in patients undergoing thermal ablation for early-stage HCC.

Survival and Local Recurrence Risk in Patients with High-Risk Neuroblastoma Treated with Proton Therapy over a 10 Year Interval

Patients (pts) with high-risk neuroblastoma (HR-NBL) require radiation (RT) to the primary tumor site (PS); approach is standardized within North American paradigms but remains a subject of global study. Long-term experience using proton therapy (PRT) in this population is lacking. We hypothesized that PRT would be associated with low risk of local recurrence (LR) in a large population of pts with HR-NBL spanning > 10 years. Sequential pts with HR-NBL at a single institution received RT to PS and persistent metastatic sites (MS). Dose to PS after subtotal resection (STR) was reduced from 36 Gy to 21.6 Gy in 2019 based on results from the Children's Oncology Group ANBL0532 trial (Liu K, 2019). Analysis using Kaplan Meier method and log rank test was performed with IRB approval. From 9/2010 - 12/2021, 99 pts with HR-NBL received PS RT during first-line therapy; most [78, (79%)] had adrenal primary tumors and 26 (26%) received MS RT. Median age was 48m at RT (R 11m to 17.5y) and 52 (53%) were female. All pts had multi-agent induction chemotherapy (CT) [+ dinutuximab [12 (13%)] and/ or therapeutic 131MIBG [19 (19%)] and resection of primary tumor prior to RT; 34 (34%) patients had STR with residual disease (RD) on post-op imaging, 65 (66%) had gross total resection (GTR). Dose to PS was 21.6 Gy for 78 (79%) pts and 36 Gy for 21 (21%) based on RD and treatment era; PRT was pencil beam [78 (79%)] or double scattered [22 (22%)], combined with IMRT in 2 (2%). With median FU of 4.2 yrs (R 0.5y - 12y), 80 pts (81%) are alive [66 (67%) disease-free, 14 (14%) with disease], 19 (19%) have died. Progressive disease (PD) occurred in 33 (33%), with median time to PD 24m (R 8-116m); two pts (2%) had isolated LR, 25 (25%) distant PD, and 6 (6%) concurrent LR and distant PD. Risk of LR at 10 years was 8%; absolute risk of any LR was 8% (6/78) in 21.6 Gy cohort and 9% (2/21) in 36 Gy cohort (p = NS). After induction CT, 34 (34%) pts had STR with > 1cm3 RD on axial imaging; 18/ 34 (53%) also had MIBG uptake (MIBG+) at PS. Based on treatment era, 21 pts (62%) after STR received 21.6 Gy + boost to RD (36 Gy), and 13 (38%) 21.6 alone. Of those who received 36 Gy (median FU 5.7y), 2/21 (9.5%) had LR with concurrent distant PD; of those who received 21.6 Gy (median FU 3.2y) 4/13 (31%) had LR (2 with concurrent distant PD and 2 LR only) (p = 0.03). In the 21.6 Gy GTR cohort, 2/65 (3%) had LR + distant PD. Of 8 total patients who experienced LR, 5 had MIBG + RD, 1 MIBG- RD, and 2 GTR. We observed excellent outcomes in 99 pts treated with proton radiotherapy for HR-NBL from 2010 through 2021, with 81% of patients alive and 92% free of LR. Our data suggest that LR is rare after GTR and 21.6 Gy, and uncommon among pts with STR treated with 36 Gy. A small number of pts received 21.6 Gy after STR, however, this experience suggests that a subset of pts with RD may require RT dose > 21.6 Gy. Further work is required to further characterize individual management of PS in pts with HR-NBL with regard to extent of RD and biologic disease features.

Serial D-dimers after anticoagulant cessation in unprovoked venous thromboembolism: Data from the REVERSE cohort study

IntroductionWhile several risk stratification tools have been developed to predict the risk of recurrence in patients with an unprovoked venous thromboembolism (VTE), only 1 in 4 patients are categorized as low-risk. Rather than a one-time measure, serial D-dimer assessment holds promise to enhance the prediction of VTE recurrence after oral anticoagulant (OAC) cessation. MethodsUsing the REVERSE cohort, we compared VTE recurrence among patients with normal D-dimer levels (<490 ng/mL among males under age 70, <500 ng/mL in others) at OAC cessation and 1-month follow-up, to those with an elevated D-dimer level at either timepoint. We also evaluated VTE recurrence based on absolute increase in D-dimer levels between the two timepoints (e.g., ∆D-dimer) according to quartiles. ResultsAmong 214 patients with serial D-dimer levels measured at OAC cessation and 1-month follow-up, an elevated D-dimer level at either timepoint was associated with a numerically higher risk of recurrent VTE than patients with normal D-dimer levels at both timepoints (6.9 % vs. 4.2 % per year, hazard ratio 1.6; 95 % CI 0.9–2.7). Among women with <2 HERDOO2 criteria, a normal D-dimer level at both timepoints predicted a very low risk of recurrent VTE during follow-up (0.8 % per year, 95 % CI 0.1–2.8). Irrespective of baseline value, recurrent VTE risk was only 3 % per year (95 % CI 1.4–5.6) among patients in the lowest ∆D-dimer quartile. ConclusionSerial normal D-dimer levels have the potential to identify patients at a low risk of recurrent VTE. In addition, ∆D-dimer, irrespective of its elevation above cutoff threshold, may predict recurrent VTE.

Effect of primaquine dose on the risk of recurrence in patients with uncomplicated Plasmodium vivax: a systematic review and individual patient data meta-analysis

Primaquine is used to eliminate Plasmodium vivax hypnozoites, but its optimal dosing regimen remains unclear. We undertook a systematic review and individual patient data meta-analysis to investigate the efficacy and tolerability of different primaquine dosing regimens to prevent P vivax recurrence. For this systematic review and individual patient data meta-analysis, we searched MEDLINE, Web of Science, Embase, and Cochrane Central for prospective clinical studies of uncomplicated P vivax from endemic countries published between Jan 1, 2000, and June 8, 2023. We included studies if they had active follow-up of at least 28 days, and if they included a treatment group with daily primaquine given over multiple days, where primaquine was commenced within 7 days of schizontocidal treatment and was given alone or coadministered with chloroquine or one of four artemisinin-based combination therapies (ie, artemether-lumefantrine, artesunate-mefloquine, artesunate-amodiaquine, or dihydroartemisinin-piperaquine). We excluded studies if they were on prevention, prophylaxis, or patients with severe malaria, or if data were extracted retrospectively from medical records outside of a planned trial. For the meta-analysis, we contacted the investigators of eligible trials to request individual patient data and we then pooled data that were made available by Aug 23, 2021. We assessed the effects of total dose and duration of primaquine regimens on the rate of first P vivax recurrence between day 7 and day 180 by Cox's proportional hazards regression (efficacy analysis). The effect of primaquine daily dose on gastrointestinal symptoms on days 5-7 was assessed by modified Poisson regression (tolerability analysis). The study was registered with PROSPERO, CRD42019154470. Of 226 identified studies, 23 studies with patient-level data from 6879 patients from 16 countries were included in the efficacy analysis. At day 180, the risk of recurrence was 51·0% (95% CI 48·2-53·9) in 1470 patients treated without primaquine, 19·3% (16·9-21·9) in 2569 patients treated with a low total dose of primaquine (approximately 3·5 mg/kg), and 8·1% (7·0-9·4) in 2811 patients treated with a high total dose of primaquine (approximately 7 mg/kg), regardless of primaquine treatment duration. Compared with treatment without primaquine, the rate of P vivax recurrence was lower after treatment with low-dose primaquine (adjusted hazard ratio 0·21, 95% CI 0·17-0·27; p<0·0001) and high-dose primaquine (0·10, 0·08-0·12; p<0·0001). High-dose primaquine had greater efficacy than low-dose primaquine in regions with high and low relapse periodicity (ie, the time from initial infection to vivax relapse). 16 studies with patient-level data from 5609 patients from ten countries were included in the tolerability analysis. Gastrointestinal symptoms on days 5-7 were reported by 4·0% (95% CI 0·0-8·7) of 893 patients treated without primaquine, 6·2% (0·5-12·0) of 737 patients treated with a low daily dose of primaquine (approximately 0·25 mg/kg per day), 5·9% (1·8-10·1) of 1123 patients treated with an intermediate daily dose (approximately 0·5 mg/kg per day) and 10·9% (5·7-16·1) of 1178 patients treated with a high daily dose (approximately 1 mg/kg per day). 20 of 23 studies included in the efficacy analysis and 15 of 16 in the tolerability analysis had a low or unclear risk of bias. Increasing the total dose of primaquine from 3·5 mg/kg to 7 mg/kg can reduce P vivax recurrences by more than 50% in most endemic regions, with a small associated increase in gastrointestinal symptoms. Australian National Health and Medical Research Council, Bill & Melinda Gates Foundation, and Medicines for Malaria Venture.

Association between surgical extent and recurrence in unilateral intermediate- to high-risk papillary thyroid cancer

BackgroundGuidelines recommend total thyroidectomy (TT) to facilitate radioactive ablation and serological follow-up for intermediate- to high-risk papillary thyroid carcinoma (PTC). However, the association between surgical extent and tumor recurrence in these patients has not been well validated. We aimed to examine the association between the extent of surgery and recurrence in patients with completely resected unilateral intermediate- to high-risk PTC.MethodsPatients with completely resected unilateral PTC from 2000 to 2017 in a single institute were reviewed. Those who had extrathyroidal extension (ETE) or lymph node metastasis (LNM, cN1 or pN1 > 5 lymph nodes involved) were included for analysis. Cox proportional hazards models were applied to measure the association between surgical extent and recurrence-free survival (RFS) while adjusting for patient demographic, clinicopathological and treatment variables.ResultsA total of 4550 patients (mean[SD] age, 43.0[11.7] years; 3379 women[74.3%]) were included. Of these patients, 2262(49.7%), 656(14.4%), 1032(22.7%), and 600 (13.2%) underwent lobectomy, TT, lobectomy + neck dissection (ND) and TT + ND, respectively. With a median follow-up period of 68 months, after multivariate adjustment, lobectomy was associated with a compromised RFS compared with other surgical extents (HR[95%CI], TT 0.537[0.333–0.866], P = 0.011, lobectomy + ND 0.531[0.392–0.720] P < 0.0001, TT + ND 0.446[0.286–0.697] P < 0.0001). RFS was similar between the two extents with ND (lobectomy + ND, HR [95%CI], 1.196 [0.759–1.885], P = 0.440).ConclusionLobectomy alone is associated with an elevated recurrence risk in patients with unilateral intermediate- to high-risk PTC compared with larger surgical extents. However, lobectomy and ND may provide similar tumor control compared with the conventional approach of TT and ND.

Predictive capacity of a genetic risk score for coronary artery disease in assessing recurrences and cardiovascular mortality among patients with myocardial infarction.

This study aimed to evaluate the capacity of a genetic risk score (GRS) for coronary artery disease (CAD) independent of classical cardiovascular risk factors to assess the risk of recurrence in patients with first myocardial infarction. The secondary aim was to determine the predictive value of this GRS. We performed a meta-analysis of individual data from three studies, namely, a prospective study including 75 patients aged <55 years, a prospective study including 184 patients with a mean age of 60.5 years, and a case-control study (77 cases and 160 controls) nested in a cohort of patients with first myocardial infarction. A GRS including 12 CAD genetic variants independent of classical cardiovascular risk factors was developed. The outcome was a composite of cardiovascular mortality and recurrent acute coronary syndrome. The GRS was associated with a higher risk of recurrence [hazard ratio = 1.24; 95% confidence interval (CI): 1.04-1.47]. The inclusion of the GRS in the clinical model did not increase the model's discriminative capacity (change in C-statistic/area under the curve: 0.009; 95% CI: -0.007 to 0.025) but improved its reclassification (continuous net reclassification index: 0.29; 95% CI: 0.08-0.51). The GRS for CAD, independent of classical cardiovascular risk factors, was associated with a higher risk of recurrence in patients with first myocardial infarction. The predictive capacity of this GRS identified a subgroup of high-risk patients who could benefit from intensive preventive strategies.