Breast cancer survival varies widely across middle-income settings and may be influenced by clinical stage at diagnosis and access pathways within oncology care networks. In Brazil, evidence from statewide cohorts using linked registry and mortality data remains limited.
To investigate the association between clinical factors and breast cancer–specific survival among women treated in all hospitals comprising the Oncology Care Network of a state in Southeastern Brazil.
A retrospective cohort study was conducted using data from the Hospital Cancer Registry linked to the state Mortality Information System. Women aged ≥ 18 years diagnosed with primary breast cancer (ICD-10: C50.x) between 2000 and 2016 were included and followed until December 31, 2021. Five-year breast cancer–specific survival was estimated using the Kaplan–Meier method, and factors associated with mortality were assessed using cause-specific Cox proportional hazards models with complete-case analysis. A total of 12,096 women were included, of whom 7,191 had complete data for multivariable analysis. The mean age at diagnosis was 54.7 years. Five-year breast cancer–specific survival ranged from 97% (95% CI: 96−97%) in stage I to 32% (95% CI: 31−37%) in stage IV. Women referred from the private healthcare system had a significantly lower risk of breast cancer mortality than those referred from the public system (HR: 0.83; 95% CI: 0.75−0.93; p = 0.001). Advanced clinical stage remained the strongest predictor of mortality, and the presence of distant metastasis at diagnosis increased the risk of breast cancer death by 49% (HR: 1.49; 95% CI: 1.14−1.94; p = 0.003).
Breast cancer–specific survival in Espírito Santo is strongly determined by stage at diagnosis and by differential access pathways within the oncology care network. Strengthening early diagnostic strategies, improving referral coordination, and ensuring equitable access to timely treatment are essential to reduce survival disparities in this setting.
We present the case of 72–year-old male with metastatic de-differentiated chondrosarcoma (“DDCS”). DDCS is a rare soft tissue cancer that carries a dismal prognosis in the metastatic stage, and is resistant to both traditional chemotherapy and radiotherapy. There is a distinct lack of proven systemic therapies.
This case report is distinguished in that our patient had a significant clinical response to combination therapy with an immune checkpoint inhibitor (Pembrolizumab) and a multi-targeted tyrosine kinase inhibitor (Pazopanib). Our patient presented with bony pain after suffering a pathological fracture of the left humerus after grabbing a fence. He did not report prior constitutional symptoms or bony pain. On examination he was clinically in atrial fibrillation and reported reduced exercise tolerance with a New York Heart association grading of 2. There were no other pertinent clinical findings. FDG PET-CT scan revealed a 10cmx5cm destructive intra-osseous lesion of the proximal humerus, markedly FDG-avid, without evidence of metastatic disease. He underwent immediate surgical resection, followed by adjuvant radiotherapy to the left humerus. Tumour histology revealed a high-grade DDCS. Genetic sequencing revealed alterations in IDH2, PTCH1 and TERT promoter. Restaging FDG PET scan 3 months after diagnosis revealed lung metastases. The patient was commenced on Vismodegib with best disease response of progressive disease. Eight months after diagnosis he was commenced on combination therapy of Pazopanib and Pembrolizumab, with significant reduction in size of lung metastases. He sustained a progression free period of 6 months on this regime. Treatment course was complicated primarily by hepatotoxicity, which resolved with dose reduction of Pazopanib. Eleven months after diagnosis, FDG PET-CT revealed relapse and significant progression of metastatic disease and systemic therapy was ceased. The patient passed away 14 months after diagnosis.
This case report is a valuable example of promising emerging systemic therapies for advanced DDCS, where the present standard of care lacks a repertoire of effective therapies.
Enfortumab vedotin (EV) has demonstrated clinical benefits as a third-line monotherapy after chemotherapy and immune checkpoint inhibitors and is currently established, in combination with pembrolizumab, as a first-line standard therapy for metastatic urothelial carcinoma (mUC). However, dermatologic adverse events (DAEs) are common and may necessitate treatment interruption. While EV rechallenge is often considered, evidence regarding the recurrence and management of DAEs after rechallenge is limited.
To analyze the incidence, timing, and severity of DAEs following EV rechallenge and assess the impact of dose modifications and initial inpatient versus outpatient management on clinical outcomes.
This retrospective observational study included patients with mUC who received EV at a single institution between January 2022 and December 2024. Of the 48 patients treated with EV, 36 (75.0%) developed DAEs, with a median onset of 11 days. Twenty patients resumed EV after interruption due to DAEs; 13 (65%) experienced recurrence. Recurrent DAEs tended to be of lower grade than the initial events and to be similar to the initial episode in terms of the type of DAEs. Early-onset (≤ 7 days) DAEs were more likely to progress to grade ≥ 3. Although inpatient management enabled earlier detection and intervention, it did not reduce the incidence of severe toxicity compared to outpatient care.
DAEs frequently recur after EV rechallenge but are typically less severe than the initial episode. Early-onset DAEs may predict severe toxicity, underscoring the need for close monitoring and proactive management. Prospective studies are warranted to optimize rechallenge strategies and improve the safety of EV therapy.
Lenvatinib-related hypothyroidism occurs in 16%–22% of patients with hepatocellular carcinoma and may affect treatment management. Previous studies have reported elevated serum thyroid stimulating hormone (TSH) levels despite levothyroxine therapy, indicating the need for research on the optimal levothyroxine dose during lenvatinib therapy.
We aimed to explore the effect of lenvatinib on thyroid function, focusing on lenvatinib pharmacokinetics and factors influencing hypothyroidism development.
A retrospective cohort study involving 56 patients with hepatocellular carcinoma treated with lenvatinib was conducted at the Mie University Hospital. The primary outcome was grade ≥ 2 hypothyroidism. Demographic data, treatment details, and clinical outcomes were analyzed to identify factors associated with lenvatinib-related hypothyroidism. In addition, we assessed the levothyroxine dose administered during treatment and the dose required to achieve TSH levels < 10 mIU/L. Twelve patients (21%) developed hypothyroidism during lenvatinib therapy. The median levothyroxine dose and time to onset of hypothyroidism were 25.0 [25.0–50.0] μg/day and 81.0 [15.0–208.0] days, respectively. Levothyroxine therapy was initiated at either a low or recommended dose, with 10 patients achieving TSH levels < 10 mIU/L. Significant predictors of hypothyroidism included age ≤ 63 years and a higher daily lenvatinib dose (≥ 0.152 mg/kg/day).
Initiation of levothyroxine therapy, even at lower doses, may be effective in managing lenvatinib-related hypothyroidism. Underweight patients (e.g., body weight < 50 kg) require particular attention due to their increased susceptibility to hypothyroidism. Even though this study has limitations such as a small sample size and the lack of multivariate analysis, it provides valuable information for managing lenvatinib-related hypothyroidism.
Nonsmall cell lung cancer (NSCLC) with mesenchymal-epithelial transition exon 14 skipping mutation (METex14) represents a distinct molecular subtype with limited therapeutic options. Selective MET tyrosine kinase inhibitors (MET-TKIs) such as tepotinib, capmatinib, and gumarontinib have improved outcomes, but toxicities frequently limit their use. Previous case reports have described sequential rechallenge with two MET-TKIs and, in rare cases, with three agents including an investigational drug. To our knowledge, this is the first reported case worldwide of sequential treatment with all three MET-TKIs currently approved in Japan—tepotinib, capmatinib, and gumarontinib.
We report a 72-year-old man with METex14-positive NSCLC who underwent surgery and adjuvant chemotherapy, later developing pleural dissemination. Tepotinib was discontinued after 2 months due to Grade 3 interstitial lung disease (ILD). Following chemotherapy and immune checkpoint inhibitors, capmatinib was introduced but stopped within 10 days for fever, mucositis, and possible ILD. Gumarontinib was subsequently initiated, but treatment was interrupted on Day 36 due to Grade 2 hepatotoxicity before resumption at a reduced dose.
Although all three MET-TKIs share similar mechanisms of action, they exhibit differing toxicity profiles. In this case, treatment discontinuation was not due to ILD recurrence but rather to distinct non-ILD adverse events. Furthermore, the toxicities experienced by the patient varied between agents, suggesting that rechallenge may remain a viable strategy depending on individual tolerance. Careful toxicity monitoring and personalized risk assessment are essential when considering sequential MET-TKI therapy.
Chemotherapy resistance in colorectal cancer (CRC) is often mediated by enhanced DNA damage repair (DDR). Transmembrane protein TMEM59L is implicated in cancer progression, but its role in CRC chemoresistance is unclear. We investigated whether TMEM59L regulates 5-fluorouracil (5-FU) sensitivity through PTPRN-mediated DDR.
This study aimed to investigate the role of TMEM59L in regulating PTPRN-mediated DNA damage repair and its impact on 5-FU sensitivity in colorectal cancer, with the goal of identifying potential therapeutic targets to overcome chemoresistance.
Bioinformatics analyses assessed TMEM59L/PTPRN expression and prognosis in CRC cohorts. Gain- and loss-of-function experiments were conducted in CRC cell lines (HCT116, SW480) and their 5-FU-resistant derivatives. Cell proliferation, migration, invasion, apoptosis, DNA damage, and reactive oxygen species (ROS) were measured. Protein interactions were examined by Western blot and immunofluorescence. A xenograft model in nude mice validated the TMEM59L/PTPRN axis on tumor growth, stemness, and EMT markers. TMEM59L expression was elevated in metastatic lesions and associated with poor CRC patient survival. Functionally, TMEM59L promoted malignant behaviors and epithelial–mesenchymal transition. It was upregulated in 5-FU-resistant cells and non-responsive patients. TMEM59L knockdown sensitized cells to 5-FU, increasing ROS, DNA damage, and apoptosis, while its overexpression induced resistance. Mechanistically, TMEM59L regulated 5-FU-induced DNA damage and ROS through PTPRN. PTPRN overexpression reversed the sensitization caused by TMEM59L silencing. In vivo, TMEM59L knockdown enhanced 5-FU's antitumor effect, which was counteracted by PTPRN overexpression.
The TMEM59L/PTPRN axis is a key regulator of DDR and 5-FU resistance in CRC. TMEM59L promotes chemoresistance via PTPRN by enhancing DNA repair and reducing ROS-mediated apoptosis. Targeting this pathway may offer a novel strategy to overcome 5-FU resistance.
In sub-Saharan Africa, traditional healers often serve as primary healthcare providers and are the first point of contact for patients. Given this, they are uniquely positioned to aid in early breast cancer detection. To evaluate this, we implemented a breast cancer training program to equip traditional healers in Tanzania with foundational knowledge and CBE skills, aiming to improve early detection and timely treatment.
To implement a breast cancer training program to equip traditional healers in Tanzania with foundational knowledge and CBE skills, aiming to improve early detection and timely treatment.
We conducted a breast cancer training program in Tanzania among rural registered traditional healers. Knowledge acquisition was assessed through pretest and posttest surveys.
Three male and three female rural traditional healers (average age: 53) participated in the training, with 67% having no prior formal breast cancer training, though 83% reported some breast cancer awareness. Pre- and post-training assessments showed an increase in breast cancer knowledge, with median scores rising from 41% to 74% (p = 0.01). All participants found the training valuable and felt empowered to serve as community health advocates, with widespread consensus that they would prioritize referring patients with suspicious breast findings to the hospital rather than attempting to treat.
Traditional healers, as trusted community figures and primary healthcare providers, offer a promising solution to bridging gaps in early breast cancer detection in Tanzania. Enhancing their breast cancer knowledge and equipping them with the skills to identify suspicious breast findings provides a scalable strategy for improving early detection in resource-limited settings.
Soft tissue sarcomas (STS) of the upper extremity (UE) are uncommon and may require complex surgical management. Socioeconomic disadvantage, race/ethnicity, sex, and marital status may influence presentation, surgical complexity, local recurrence (LR), and overall survival (OS).
The aim of this work is to examine the influence of socioeconomic and demographic factors on the presentation and outcomes of upper extremity soft tissue sarcomas.
We identified patients treated surgically for primary UE STS (2012-2022). Demographics, tumor characteristics, and outcomes were recorded. Associations between demographics and time to presentation, skin grafting, amputation, and LR were assessed using chi-square and t-tests. Competing risks regression analyzed 3- and 5-year LR, and Kaplan-Meier analysis assessed 5-year OS. Among 181 patients, the mean time to presentation was 17.1 months (SD 34.3), mean tumor size was 7.8 cm (SD 5.7) while 56% required re-excision, 15% underwent amputation, 15% required skin grafting, and 24% experienced LR. Hispanic/Latino patients presented with larger tumor sizes (9.17 ± 5.71 cm vs. 7.43 ± 5.61 cm, p = 0.037). Non-married patients had higher odds of amputation (OR 3.15, p = 0.012), and female sex predicted greater LR risk (OR 2.17, p = 0.037). Twenty-one patients (11.1%) died within five years. In multivariable analysis, increasing tumor size (OR = 1.08; p = 0.010) and high tumor grade (OR = 8.28; p = 0.038) significantly impacted 5-year OS.
While disparities across patient demographics may exist for surgical outcomes for UE STS, racial disparities in overall survival may be mitigated with treatment at an urban, tertiary care sarcoma center.
京公网安备 11010802042870号
京ICP备2023020795号-1
扫码关注我们
求助内容：
应助结果提醒方式：