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Abstract The purpose of this study was to assess the risks of hyperthyroidism and hypothyroidism related to gynecological cancers. Population-based retrospective cohort study. We conducted a cohort study using the Taiwan National Health Insurance Research Database to explore hyperthyroidism and hypothyroidism associated with site-specific gynecologic cancers in women from January 1, 2000 to December 31, 2018. The examined gynecologic cancers included endometrial (EC), uterine corpus cancer (UC), and ovarian cancer (OC). The incidence and hazard ratios were quantified using Cox proportional hazards models. The incidence of developing gynecological (Gyn) cancers in the hyperthyroid and hypothyroid women was 0.29 and 0.44 per 1000 person-years, which was 0.86 fold lower and 1.13 fold higher than that in the comparison cohort (p 65 years: aHR = 0.94; for hypothyroid, adjusted hazard ratio (aHR) = 1.26; > 65 years: aHR = 1.38). Compared with the non-hypothyroid women and non-hyperthyroid women beyond 6 years of follow-up, hypothyroid and hyperthyroid women showed decreased risk of Gyn cancers. Medication treatment for hyperthyroid and hypothyroid disease did not showed significant association in subgroup analyses (aHR = 0.99 and 0.80, respectively). Our results show that women with hyperthyroidism have a significantly reduced risk of gynecological cancers, whereas women with hypothyroidism have a slightly increased risk of gynecological cancers suggesting an association between thyroid function level and risk of gynecological cancers.

The routine use of granulocyte colony-stimulating factor (GCSF) is not recommended for the prevention or treatment of chemotherapy-induced neutropenia or febrile neutropenia because risks associated with certain types of cancers, distant organ metastases, and primary tumor growth cannot be excluded. We examined the association between GCSF use and the incidence of brain metastasis (BM), as well as BM-free survival (BMFS). This retrospective cohort study included 121 stage IV breast cancer patients without confirmed BM at the time of diagnosis and who received at least one course of systematic chemotherapy or target therapy at a tertiary teaching hospital between 1 January 2014 and 31 December 2022. The effect of GCSF use on BM was assessed with other confounding factors in Cox regression analyses. In this retrospective cohort, patients who received GCSF treatment had a significantly higher incidence of BM than those who did not (34.9% vs. 13.8%, p = 0.011). Univariate Cox regression analysis showed that GCSF use, menopause status, hormone treatment, HER2 treatment, cumulative dosage, dosage density, and neutropenia were independent risk factors for BMFS (p < 0.05). GCSF users had a higher risk of BM (adjusted HR: 2.538; 95% CI: 1.127–5.716, p = 0.025) than nonusers. BM risk was significantly associated with those with neutropenia (RR: 1.84, 95% CI: 1.21, 2.80) but not with those without neutropenia (RR: 0.59, 95% CI: 0.41–0.84, Interaction p-value < 0.05). The higher the dose density of GCSF, the higher the risk compared with those who do not use GCSF (p for trend < 0.01). These preliminary results suggest that GCSF is associated with BM in patients with stage IV breast cancer who did not have BM at initial diagnosis. Further comprehensively designed large-scale observational studies are needed to confirm our preliminary results.

BackgroundPortal vein tumor thrombus (PVTT) is a common complication and an obstacle to treatment, with a high recurrence rate and poor prognosis. There is still no global consensus or standard guidelines on the management of hepatocellular carcinoma (HCC) with PVTT. Increasing evidence suggests that more aggressive treatment modalities, including transarterial chemoembolization, radiotherapy, targeted therapy, and various combination therapies, may improve the prognosis and prolong the survival of advanced hepatocellular carcinoma (aHCC) patients with PVTT. We aim to comprehensively review and compare the efficacy and safety of these advanced options for aHCC with PVTT.MethodsA comprehensive literature search was conducted on PubMed and EMBASE for phase II or III randomized controlled trials (RCTs) investigating multimodality treatments for aHCC with PVTT. Kaplan–Meier curves for overall survival (OS) and progression-free survival were constructed to retrieve individual patient-level data to strengthen the comparison of the benefits of all multimodality treatments of interest. Each study was pooled in a fixed-effects network meta-analysis (NMA). We also conducted subgroup analyses using risk ratios extracted from each study, including viral etiology, Barcelona Clinic Liver Cancer (BCLC) staging, alpha-fetoprotein (AFP) levels, macrovascular invasion or portal vein tumor thrombosis, and extrahepatic spread. Multimodality treatments were ranked using SUCRA scores.ResultsWe identified 15 randomized controlled trials with 16 multimodality regimens that met the inclusion criteria. Among them, 5,236 patients with OS results and 5,160 patients with PFS results were included in the analysis. The hepatic arterial infusion chemotherapy of fluorouracil, leucovorin, and oxaliplatin (HAIC-FO) showed OS and PFS benefits over all the other therapies. In terms of OS, HAIC-FO, nivolumab, and TACE+Len were superior to sorafenib, lenvatinib, and donatinib monotherapies, as well as HAIC-FO+Sor. In terms of PFS, TACE+Len showed better benefits than lenvatinib, donatinib, and tremelimumab+durvalumab. A low heterogeneity (I2 < 50%) and consistency were observed. The SUCRA score for OS ranked HAIC-FO+sorafenib as the best treatment option among all multimodality treatments in hepatitis B, MVI, or PVTT with EHS and AFP 400 μg/L subgroups.ConclusionHAIC-FO and HAIC-FO+sorafenib are statistically better options for unresectable hepatocellular carcinoma with PVTT among the multimodality treatments, and their effective and safe implementation may provide the best outcomes for HCC-PVTT patients.

Background: The rising cost of cancer drug therapy threatens the long-term sustainability of Taiwan National Health Insurance. Cost savings can be achieved through various strategies, e.g., using smaller vial sizes, sharing vials, weight-based dosing, or switching to biosimilars. Here we aimed to examine the cost-effectiveness of a trastuzumab biosimilar combined with docetaxel (TDbiol) for treatment-naïve HER2+ metastatic breast cancer (MBC), and the financial impact of drug wastage. Methods: A Markov model with three health states was developed to assess the cost-effectiveness of trastuzumab biosimilars plus docetaxel over a 40-month time horizon in patients with HER2+ MBC. Based on the literature and our expert opinion, we assumed similar efficacy between the trastuzumab biosimilar and its reference product. The primary clinical input for the biosimilar was the same as for the reference product in the Catastrophic Patient Database (HV). Health state utilities were derived from the literature, and direct medical costs were obtained from the National Health Insurance Administration (NHIA). Results: In the base-case scenario, the incremental cost-effectiveness ratio (ICER) was NTD 811,050 per QALY gained. One-way sensitivity analyses showed that the model was sensitive to utilities and transition probabilities, but not particularly sensitive to the wastage assumption. In scenario analyses, the ICER was higher when applying the price for trastuzumab reference biologic (branded), than for trastuzumab biosimilar. Conclusion: The trastuzumab biosimilar combination regimen is cost-effective and offers significant drug cost savings in Taiwan.

Objective: To evaluate the association between radiation exposure from repeated nuclear medicine (NM) examinations and the subsequent risk of neoplasm in pediatric patients.Methods: From 2000 to 2017, participants under 18 years of age who underwent NM scanning were identified using the Health and Welfare Data Science Center (HWDC) dataset, which was extracted from the Taiwan National Health Insurance Research Database (NHIRD). Both the exposed cohort and unexposed subjects were followed up with until the presence of any malignancy arose, including malignant brain, lymphoid and hematopoietic tumors and benign brain or other central nervous tumors.Results: There were 35,292 patients in the exposed cohort and 141,152 matched subjects in the non-exposed group. The exposed cohort had an overall higher IR (IR: incidence rate, per 100,000 person-years) of any malignancy and benign central nervous tumor than the non-exposed group [IR, 16.9 vs. 1.54; adjusted hazard ratio (HR), 10.9; 95% CI, 6.53–18.2]. Further stratifying the number of NM examinations into 1-2, 3-4, and 5 or more times revealed that the IR of pediatric neoplasms increased gradually with the increased frequency of NM examinations (IR, 11.5; adjusted HR, 7.5; 95% CI, 4.29–13.1; IR, 25.8; adjusted HR, 15.9; 95% CI, 7.00–36.1; IR, 93.8; adjusted HR, 56.4; 95% CI, 28.8–110.3).Conclusion: NM examination is significantly associated with a higher risk of pediatric neoplasms, according to our population-based data. Thorough radiation protection and dose reduction in pediatric NM procedures should be an issue of concern.

Background and Objectives: To evaluate the effectiveness of hepatic arterial infusion chemotherapy (HAIC) followed by lipiodol infusion in advanced hepatocellular carcinoma (HCC) with portal vein tumor thrombus (PVTT). Materials and Methods: Thirty-two patients with advanced HCC and PVTT who received HAIC with regimens of cisplatin, mitomycin-C, and 5-fluorouracil followed by lipiodol infusion were enrolled. The primary efficacy endpoint was tumor response rate. The modified Response Evaluation Criteria in Solid Tumors (mRECIST) was used for assessment of treatment response. The secondary endpoints were overall survival (OS) and progression free survival (PFS). Prognostic factors for survival also were evaluated. Results: The median OS and PFS were 11.9 and 9.5 months, respectively. Seventeen patients (53.1%) achieved objective response, and 23 patients (71.9%) achieved disease control. The length of survival in the responder and disease control groups was longer than in the non-responder and progressive disease groups after two cycles of HAIC (responder vs. non-responder: 16.5 vs. 7.9 months, p = 0.001; disease control vs. progressive disease: 12.3 vs. 5.6 months, p < 0.001) and after completing HAIC (responder vs. non-responder: 15.7 vs. 6.9 months, p = 0.001; disease control vs. progressive disease: 13.6 vs. 6.9 months, p < 0.001). Better survival was associated with Child-Pugh A liver function (p = 0.013), with early response to two HAIC cycles (p = 0.009), and with response (p = 0.02) and disease control (p = 0.001) after completing HAIC treatment. Conclusion: HAIC followed by lipiodol infusion is a safe and feasible treatment for advanced HCC with PVTT. Patients with early response could continue HAIC treatment with expected prolonged survival.