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Background Total thyroidectomy is well accepted as initial surgery for papillary thyroid cancer (PTC), but the extent of the thyroidectomy remains a matter of controversy. This study was designed to investigate the long-term clinical outcome of PTC patients who had undergone thyroid lobectomy and to elucidate the indications of lobectomy as initial surgery. Methods The cases of 1,088 PTC patients who underwent thyroid lobectomy with curative intent at Ito Hospital between 1986 and 1995 were analyzed retrospectively in this study. None of the patients had received postoperative radioactive iodine (RAI) ablation therapy. The median follow-up period was 17.6 years. All clinical outcomes, including recurrence and death as a result of PTC or other reasons, were evaluated. To establish the indications for lobectomy as initial surgery for PTC, the potential risk factors, such as age, sex, primary tumor size, extrathyroidal invasion, and clinical lymph node metastasis at the time of the initial surgery, were assessed statistically for associations with recurrence and disease-related death. Results The remnant-thyroid recurrence-free survival (RT-RFS) rate, the regional- lymph-node recurrence-free survival (L-RFS) rate, and the distant-recurrence-free survival (D-RFS) rate as of 25 years after surgery were 93.5, 90.6, and 93.6%, respectively. The cause-specific survival (CSS) rate at 25 years was 95.2%. Univariate and multivariate analyses showed that none of the factors assessed were significantly associated with the RT-RFS rate. Tumor size, clinical lymph node metastasis, and extrathyroidal invasion were significantly associated with the L-RFS rate. The D-RFS and CSS rates were both significantly lower in the group of patients who were aged 45 years old or older, the group whose tumors were larger than 40 mm, and the group with extrathyroidal invasion. Based on the above findings, we classified the patients into four groups according to age <45 or ≥45 years, tumor size ≤40 or >40 mm, whether clinical lymph node metastasis was present, and whether extrathyroidal invasion was present. None of the patients without any of these four risk factors died of PTC. On the other hand, 22 patients who died of PTC were positive for one or more of these four factors. Conclusions The long-term clinical outcome of the PTC patients who had been treated by lobectomy without RAI ablation was excellent. Based on the above results, we concluded that lobectomy is a valid alternative to total thyroidectomy for the treatment of PTC patients who are younger than aged 45 years, whose tumor diameter is 40 mm or less, and who do not have clinical lymph node metastasis or extrathyroidal invasion.

Background Few studies have focused on risk factors which may predict an intrahepatic local recurrence (LR) on the surgical edge rather than a distant recurrence (DR) in other liver segments after surgery for hepatocarcinoma (HCC). The purpose of this study was to assess the risk factors for both patterns of recurrence. Methods An international, multicentre, retrospective study was conducted by collecting data on all consecutive patients with a first diagnosis of HCC who were treated between 2010 and 2017. The presence of macrovascular invasion was an exclusion criteria. Results About 376 patients were enrolled, and, among them, 62 presented LR, while 90 had DR. Baseline characteristics were comparable between the two groups, but the DR group had a much higher rate of HCV infection (48.9% vs 29%, p 0.014) and a higher median nodule size (3.40 cm IQR 2.2–5.5 versus 3.0 cm IQR 2.0–5.0 in the LR group, p 0.025). A positive surgical margin (R1, HR 4.721; 95% CI 1.83–12.17; p 0.001) was the only independent risk factor for LR, while MVI (HR 1.837; 95% CI 1.03–3.77; p 0.039) and satellitosis (HR 2.440, 95% CI 1.43–3.77, p 0.001) were the only predictive factors for DR. Conclusion MVI and satellitosis are predictive factors of intrahepatic distant recurrence, configuring a probable hallmark of advanced systemic disease, regardless of the treatment. LR has to be considered the expression of surgical failure.

Background The clinical profiles of recurrent retroperitoneal liposarcoma (RLS) need to be explored. The recurrence patterns of RLS are controversial and ambiguous. Methods A total of 138 patients with recurrent RLS were finally recruited in the study. The analysis of overall survival (OS) and recurrence-free survival (RFS) was performed by Kaplan‒Meier analysis. To identify independent prognostic factors, all significant variables on univariate Cox regression analysis ( P  ≤ 0.05) were subjected to multivariate Cox regression analysis. The corresponding nomogram model was further built to predict the survival status of patients. Results Among patients, the 1-, 3-, and 5-year OS rates were 70.7%, 35.9% and 30.9%, respectively. The 1-, 3- and 5-year RFS rates of the 55 patients who underwent R0 resection were 76.1%, 50.8% and 34.4%, respectively. The multivariate analysis revealed that resection method, tumor size, status of pathological differentiation, pathological subtypes and recurrence pattern were independent risk factors for OS or RFS. Patients with distant recurrence (DR) pattern usually had multifocal tumors (90.5% vs. 74.7%, P  < 0.05); they were prone to experience changes of pathological differentiation (69.9% vs. 33.3%, P  < 0.05) and had a better prognosis than those with local recurrence (LR) pattern. R0 resection and combined organ resection favored the survival of patients with DR pattern in some cases. Conclusions Patients with DR pattern had better prognosis, and they may benefit more from aggressive combined resection than those with LR pattern. Classifying the recurrence patterns of RLS provides guidance for individualized clinical management of recurrent RLS.

Background Hormone receptor (HR)-positive, HER2/neu-negative breast cancers have a sustained risk of recurrence up to 20 years from diagnosis. TEAM (Tamoxifen, Exemestane Adjuvant Multinational) is a large, multi-country, phase III trial that randomized 9776 women for the use of hormonal therapy. Of these 2754 were Dutch patients. The current study aims for the first time to correlate the ten-year clinical outcomes with predictions by CanAssist Breast (CAB)—a prognostic test developed in South East Asia, on a Dutch sub-cohort that participated in the TEAM. The total Dutch TEAM cohort and the current Dutch sub-cohort were almost similar with respect to patient age and tumor anatomical features. Methods Of the 2754 patients from the Netherlands, which are part of the original TEAM trial, 592 patients’ samples were available with Leiden University Medical Center (LUMC). The risk stratification of CAB was correlated with outcomes of patients using logistic regression approaches entailing Kaplan–Meier survival curves, univariate and multivariate cox-regression hazards model. We used hazard ratios (HRs), the cumulative incidence of distant metastasis/death due to breast cancer (DM), and distant recurrence-free interval (DRFi) for assessment. Results Out of 433 patients finally included, the majority, 68.4% had lymph node-positive disease, while only a minority received chemotherapy (20.8%) in addition to endocrine therapy. CAB stratified 67.5% of the total cohort as low-risk [DM = 11.5% (95% CI, 7.6–15.2)] and 32.5% as high-risk [DM = 30.2% (95% CI, 21.9–37.6)] with an HR of 2.90 (95% CI, 1.75–4.80; P  < 0.001) at ten years. CAB risk score was an independent prognostic factor in the consideration of clinical parameters in multivariate analysis. At ten years, CAB high-risk had the worst DRFi of 69.8%, CAB low-risk in the exemestane monotherapy arm had the best DRFi of 92.7% [ vs CAB high-risk, HR, 0.21 (95% CI, 0.11–0.43), P  < 0.001], and CAB low-risk in the sequential arm had a DRFi of 84.2% [ vs CAB high-risk, HR, 0.48 (95% CI, 0.28–0.82), P  = 0.009]. Conclusions Cost-effective CAB is a statistically robust prognostic and predictive tool for ten-year DM for postmenopausal women with HR+/HER2−, early breast cancer. CAB low-risk patients who received exemestane monotherapy had an excellent ten-year DRFi.

Background Most patients with breast cancer treated with neoadjuvant chemotherapy (NAC) experience clinical benefit, however, a small proportion progress. We aimed to characterize factors predicting in-breast tumor progression and impact on distant recurrence. Patients and Methods We reviewed all patients with clinical stage I–III breast cancer treated with NAC in 2006–2021 at our institution. We compared in-breast progressive disease (PD), defined as ≥ 20% increase in tumor size, with stable disease (SD) or response. Distant recurrence-free survival (DRFS) was analyzed using the Kaplan–Meier method and Cox proportional hazards regression. Results Of 1403 patients, 70 (5%) experienced in-breast PD, 243 (17%) SD, 560 (40%) partial response (PR), and 530 (38%) breast pathologic complete response (breast pCR, ypT0/Tis). The rate of PD varied by tumor subtype (8% in HR+/HER2−, 5% TNBC, 2% HER2+, p  < 0.001). With median 48 months follow-up, the rates of DRFS were significantly different according to clinical breast response as follows: PD 56%, SD 68%, PR 82%, or breast pCR 93%, p  < 0.001. In patients with PD on multivariable analysis, post-NAC grade (adjusted HR 2.9, p  = 0.002) and ypT3–4 category (adjusted HR 2.4, p  = 0.03) were the strongest predictors of DRFS. Combining these factors, 23% had neither, 44% had one, and 33% had both, which stratified outcome in PD with 3-year DRFS of 100%, 77%, and 30%, respectively ( p  < 0.001). Conclusions While in-breast PD during NAC is uncommon (5%), it predicts poor survival. Among patients with in-breast PD, post-NAC tumor grade and T category predict outcomes and may be useful to guide treatment escalation.

Purpose Examine the association between circulating lipids and breast cancer outcomes in patients enrolled in the Malmö Diet and Cancer Study (MDCS). Patients and methods Circulating lipid levels were measured in blood sampled upon enrollment in the female MDCS cohort ( N  = 17,035). We identified all MDCS participants with incident invasive breast cancer diagnosed between 1991 and 2014. Follow-up time began at breast cancer diagnosis and continued until the first event of breast cancer recurrence, death, emigration, or 5 years of follow-up. We estimated the incidence rates of recurrence at 5 years and fit Cox regression models to compute crude and adjusted hazard ratios (HRs) with 95% confidence intervals (95% CI) of breast cancer recurrence as well as all-cause mortality according to cohort-specific tertiles of apolipoprotein A-1 (Apo A-1) and apolipoprotein B (Apo B). Results We enrolled 850 eligible patients. During the 5 years of follow-up, 90 invasive breast cancer recurrences were diagnosed over 3807 person-years. In multivariable analyses, high baseline levels of Apo B were associated with an increased rate of recurrence (tertile 3 vs. 1, HR = 2.30 [95% CI 1.13–4.68]). However, high baseline levels of Apo B were not associated with all-cause mortality (tertile 3 vs. 1, HR = 1.23 [95% CI 0.68–2.25]). We observed no associations between levels of Apo A-1 and recurrence (tertile 3 vs. 1, HR = 1.34 [95% CI 0.70–2.58]) or all-cause mortality (tertile 3 vs. 1, HR = 1.12 [95% CI 0.61–2.05]). Conclusion High pre-diagnostic levels of Apo B were associated with an increased risk of recurrence among breast cancer patients. Circulating Apo A-1 was not associated with breast cancer outcomes.

PurposeIn the genomic era, more women with low-risk breast cancer will forego chemotherapy and rely on adjuvant endocrine therapy (AET) to prevent metastatic recurrence. However, some of these patients will unfortunately relapse. We sought to understand this outcome. Preliminary work suggested that early discontinuation of AET, also known as non-persistence, may play an important role. A retrospective analysis exploring factors related to our breast cancer patients’ non-persistence with AET was performed. MethodsWomen who underwent Oncotype-DX® testing between 2011 and 2014 with minimum 5 years follow-up were included. ‘Low risk’ was defined as Oncotype score < 26. Outcomes of recurrence and persistence were determined by chart review. Patient, tumor and treatment factors were collected, and persistent versus non-persistent groups compared using multivariable ANOVA and Fisher Chi square exact test.ResultsWe identified six cases of distant recurrence among low-risk patients with a median follow-up of 7.7 years. Among them, five of six patients (83%) were non-persistent with AET. The non-persistence rate in our cohort regardless of recurrence was 57/228 (25%). Non-persistent patients reported more severe side effects compared with persistent patients (p = 0.002) and were more likely to be offered a switch in endocrine therapy, rather than symptom-relief (p = 0.006). In contrast, persistent patients were 10.3 times more likely to have been offered symptom-alleviating medications compared with non-persistent patients (p < 0.001). A subset analysis revealed that patients who persisted with therapy had a higher Oncotype-DX® score than patients who discontinued early (p = 0.028).ConclusionMetastatic recurrence in low-risk breast cancer patients may be primarily due to non-persistence with endocrine therapy. Further work is needed to optimize care for patients who struggle with side effects. To our knowledge, these are the first published data suggesting that Oncotype-DX® score may influence persistence with AET.

PurposeThis study aimed to examine the clinical characteristics and outcomes of patients with estrogen receptor-negative (ER−)/progesterone receptor-positive (PR+) early breast cancer. We also aimed to investigate the benefits of adjuvant endocrine therapy (ET) in this patient population.MethodsPatients with early breast cancer diagnosed at West China Hospital were divided into the ER−/PR+, ER+, and ER−/PR− groups. The chi-square test was used to analyze differences in clinical and pathological features among the groups. Multivariable Cox and Fine–Gray regression models were used to compare mortality and locoregional recurrence (LRR)/distant recurrence (DR), respectively. We performed a subgroup analysis to determine which ER−/PR+ patients can benefit more from ET.ResultsFrom 2008 to 2020, we enrolled 443, 7104, and 2892 patients into the ER−/PR+, ER+, and ER−/PR− groups, respectively. The ER−/PR+ group showed more unfavorable clinical features and aggressive pathological characteristics than the ER+ group. The mortality, LRR, and DR rates were higher in the ER−/PR+ than in the ER+ group. Most clinical features and pathological characteristics were similar between the ER−/PR+ and ER−/PR− group and their outcomes were comparable. In the ER−/PR+ group, patients who received ET showed significantly lower LRR and mortality rates than those who did not; however, no difference was observed in DR. Subgroup analysis suggested that ER−/PR+ patients age ≥ 55 years, and postmenopausal status can benefit from ET.ConclusionER−/PR+ tumors have more aggressive pathological characteristics and more unfavorable clinical features than ER+ tumors. ET can reduce the LRR and mortality rates in ER−/PR+ patients. Postmenopausal and age ≥ 55 years ER−/PR+ patients can benefit from ET.

High-risk cutaneous squamous cell carcinoma (hr-cSCC) tumors exhibit aggressive behavior, leading to local recurrence, metastasis, and mortality. The management of hr-cSCC tumors is not well-defined. To clarify the impact of clinical risk factors and management strategies on disease-related outcomes (DROs) in patients with hr-cSCCs. This dual-center retrospective cohort study reviewed patient records from 2007 to 2023, focusing on hr-cSCC tumors classified as high-risk according to two staging systems. 160 adult patients with hr-cSCC were included. Tumors > 2 cm were associated with a higher risk of recurrence, metastasis, and mortality, with greater risk for tumors > 4 cm. Nonsurgical therapies were linked to higher recurrence and mortality rates compared to surgical monotherapy. Patients whose initial treatment was delayed > 60 days following biopsy had increased incidence of DROs. Other variables associated with at least one DRO included female sex, higher tumor grade, lymphovascular invasion, and advanced AJCC-8 stages. Limitations of this study include its retrospective design, narrow demographics, and variable follow-up times. This study identifies increased tumor diameter, non-surgical treatments, delayed treatment > 60 days after biopsy, female sex, tumor grade, lymphovascular invasion, and advanced tumor stage as significant risk factors for DROs in hr-cSCC. Importantly, our study provides new clarifying evidence that delayed surgical treatment of hr-cSCCs > 60 days after biopsy is associated with elevated incidence of DROs.

BackgroundIntrahepatic hepatocellular carcinoma (HCC) has a high recurrence rate after radiofrequency ablation (RFA). However, to date, no standalone predictive factors for intrahepatic distant recurrence after curative ablation have been reported.AimsThe aim of this study was to investigate predictive factors for intrahepatic distant recurrence after curative treatment with RFA for HCCs.MethodsThis multicenter study consisted of 17 institutions that registered 821 patients. The risk factors for intrahepatic distant recurrence after complete ablation by RFA for primary HCC ≤ 2 cm in diameter were identified in a retrospectively collected training set (n = 636) and then validated in a prospectively collected validation set (n = 185).ResultsThe cumulative intrahepatic distant and local recurrence rates (i.e., entire recurrence rate) in the training set were 23.6% and 53.7% at 1 and 3 years, respectively. The cumulative intrahepatic distant recurrence rates in the training set were 17.0% and 43.8% at 1 and 3 years, respectively. Multivariate analysis of the training set showed that tumor number and serum levels of α-fetoprotein (AFP) and des-γ-carboxy prothrombin (DCP) were independent risk factors for both entire recurrence and intrahepatic distant recurrence. Intrahepatic distant recurrence risk in both the training and validation cohorts was stratified using a scoring system with three factors: tumor number (single or multiple), AFP (< 10 ng/ml or ≥ 10 ng/ml), and DCP (< 50 mAU/ml or ≥ 50 mAU/ml).ConclusionThe scoring system composed of tumor number, AFP, and DCP is useful for classifying the risk of intrahepatic distant recurrence after curative ablation for HCC.