Corrigendum: Compassionate use of ripretinib for patients with metastatic gastrointestinal stromal tumors: Taiwan and Hong Kong experience.

[This corrects the article DOI: 10.3389/fonc.2022.883399.].

Compassionate Use of Ripretinib for Patients With Metastatic Gastrointestinal Stromal Tumors: Taiwan and Hong Kong Experience.

Background: Ripretinib was recently approved for the fourth-line targeted therapy for advanced gastrointestinal stromal tumor (GIST) refractory to imatinib, sunitinib, and regorafenib based on the pivotal INVICTUS phase III study. The INVICTUS study demonstrated significantly improved median progression-free survival (PFS) of 6.3 months and an overall survival (OS) insignificant benefit of ripretinib of 15.1 months as compared with placebo in 85 patients with advanced metastatic GIST. However, treatment outcome for the Chinese population, including in Taiwan and Hong Kong, was lacking. Material and Method: A compassionate study regarding ripretinib use for patients with advanced/metastatic GIST was conducted from March 2020 to March 2021 to assess the treatment efficacy and safety in Taiwan and Hong Kong patients. Result: Twenty evaluable patients (16 men and 4 women) with heavily pretreated metastatic GIST receiving ripretinib from March 2020 to March 2021 were enrolled to evaluate the treatment outcome. The response and clinical benefit rates to ripretinib were 25% (5/20) and 60% (12/20), respectively. The median PFS and OS in this compassionate cohort receiving ripretinib were 6.1 months and not reachable, respectively. Albumin less than 3.5 and disease progression after ripretinib use were the two independent unfavorable factors for PFS. There were 14 out of 20 (70%) experiencing any grade adverse event (AE). Loss of hair is the most common grade I to II AE with an incidence of 55%. Grade III AEs included diarrhea, skin rash, and anemia with one patient (5%) for each AE. Conclusions: Late-line ripretinib use in pretreated Taiwan and Hong Kong patients with advanced GIST showed efficacy consistent with the INVICTUS study. Albumin less than 3.5 and disease progression after ripretinib use were the two independent unfavorable factors for PFS. Ripretinib is generally tolerable, with loss of hair being the most common AE.

Atrial fibrillation and risk of hip fracture: A population-based analysis of 113,600 individuals.

BACKGROUND: A number of cardiovascular diseases have been linked with bone health and an increased risk of osteoporotic fracture. Whether atrial fibrillation (AF) is associated with subsequent fracture risk is not known. METHODS: Administrative, clinical and hospitalisation information were linked over a 14-year period. From this longitudinal, population-based dataset of 113,600 individuals, time-dependent exposures using multivariate Cox proportional hazards regression models were employed to determine incidence rates and hazard ratios (HR) for hip fracture according to a history of AF. RESULTS: The annualised incidence rate for hip fracture was 7.4 per 1000 person-years (95% CI 7.1-7.7) in those without AF and 17.5 per 1000 person-years (95% CI 16.8-18.1) in those with AF. Compared to individuals without AF, those with AF were more likely to develop incident hip fracture in both men (unadjusted HR 2.39 [95% CI 1.96-2.91]) and women (unadjusted HR 2.91 [95% CI 2.55-3.34]). After adjusting for potential confounders, these associations were attenuated but remained statistically significant (adjusted HR 1.97 [95% CI 1.61-2.42] in men; adjusted HR 2.08 [95% CI 1.80-2.39] in women). CONCLUSIONS: A history of AF was associated with an increased risk of hip fracture in this large, population-based analysis. This association appeared to remain significant even after adjusting for potential confounders such as age, comorbidities and medication use. Patients with a history of AF may represent a clinical population in whom screening for and treatment of osteoporosis may be warranted to reduce the risk of subsequent fracture.

Reirradiation with intensity-modulated radiotherapy for locally recurrent T3 to T4 nasopharyngeal carcinoma.

BACKGROUND: The purpose of this study was to assess the efficacy and toxicities of reirradiation using intensity-modulated radiotherapy (IMRT) in patients with locally advanced recurrent nasopharyngeal carcinoma (NPC). METHODS: Thirty-eight patients with consecutive rT3 to rT4 NPC treated between 2005 and 2013 were retrospectively analyzed. RESULTS: The 3-year overall survival (OS), progression-free survival (PFS), and local control rate were 47.2%, 17.5%, and 44.3%, respectively. Gross target volume (GTV) D95 , GTV D50 , and age were all important prognostic factors for OS and PFS, but only GTV D95 was an important determinant for local control. A total of 73.7% patients experienced ≥1 grade 3 late toxicities and 3 patients died of massive epistaxis. Temporal lobe necrosis (TLN) developed sooner with a higher total biological equivalent dose. CONCLUSION: Adequate tumor dose coverage was important for treating rT3 to rT4 NPC. Although late complications were common, treatment-related mortality was solely vascular in nature. Dose constraints of neurologic structures for reirradiation should be revised with the latest information on late toxicities. © 2016 Wiley Periodicals, Inc. Head Neck 39: 533-540, 2017.

Prognostic nomogram for refining the prognostication of the proposed 8th edition of the AJCC/UICC staging system for nasopharyngeal cancer in the era of intensity-modulated radiotherapy.

BACKGROUND: The objective of this study was to develop a nomogram for refining prognostication for patients with nondisseminated nasopharyngeal cancer (NPC) staged with the proposed 8th edition of the American Joint Committee on Cancer (AJCC)/Union for International Cancer Control (UICC) staging system. METHODS: Consecutive patients who had been investigated with magnetic resonance imaging, staged with the proposed 8th edition of the AJCC/UICC staging system, and irradiated with intensity-modulated radiotherapy from June 2005 to December 2010 were analyzed. A cohort of 1197 patients treated at Fujian Provincial Cancer Hospital was used as the training set, and the results were validated with 412 patients from Pamela Youde Nethersole Eastern Hospital. Cox regression analyses were performed to identify significant prognostic factors for developing a nomogram to predict overall survival (OS). The discriminative ability was assessed with the concordance index (c-index). A recursive partitioning algorithm was applied to the survival scores of the combined set to categorize the patients into 3 risk groups. RESULTS: A multivariate analysis showed that age, gross primary tumor volume, and lactate dehydrogenase were independent prognostic factors for OS in addition to the stage group. The OS nomogram based on all these factors had a statistically higher bias-corrected c-index than prognostication based on the stage group alone (0.712 vs 0.622, P <.01). These results were consistent for both the training cohort and the validation cohort. Patients with <135 points were categorized as low-risk, patients with 135 to <160 points were categorized as intermediate-risk, and patients with ≥160 points were categorized as high-risk. Their 5-year OS rates were 92%, 84%, and 58%, respectively. CONCLUSIONS: The proposed nomogram could improve prognostication in comparison with the TNM stage group. This could aid in risk stratification for individual NPC patients. Cancer 2016;122:3307-3315. © 2016 American Cancer Society.

Chemotherapy for Nasopharyngeal Cancer: Neoadjuvant, Concomitant, and/or Adjuvant.

Nasopharyngeal cancers are unique among other head and neck cancers, not only in epidemiology and histological characteristics, but also on treatment strategies as well. Radiotherapy is the primary treatment due to its radiosensitivity. In locally advanced stages, concurrent chemoradiation has been established to be effective to eradicate the disease and improve survival, in favor of radiotherapy alone. While increasing studies have explored the potential benefit of adding more chemotherapy to the concurrent regimen, whether adjuvant or neoadjuvant, it is generally agreed that proper patient selection is needed to stratify high-risk groups to intensify treatment and to optimize the disease outcome. Future studies are ongoing, possibly with the addition of biomarkers such as EBV DNA for risk group stratification. Refinement of patient groups that should be selected for combined modality treatment in stage II disease is also warranted.

Underuse and overuse of anticoagulation for atrial fibrillation: A study in Indigenous and non-Indigenous Australians.

BACKGROUND: Atrial fibrillation (AF) is a leading cause of preventable stroke in Australia. Given that anticoagulation therapy can significantly reduce this stroke risk, we sought to characterise anticoagulation use in Indigenous and non-Indigenous Australians with AF. METHODS: Administrative, clinical and prescription data from patients with AF were linked. Anticoagulation use was characterised according to guideline-recommended risk scores and Indigenous status. RESULTS: 19,613 individuals with AF were studied. Despite a greater prevalence of other risk factors, Indigenous Australians were significantly younger than their non-Indigenous counterparts (p<0.001) and thus had lower CHADS2- (1.19±0.32 vs 1.99±0.47, p<0.001) and CHA2DS2VASc-scores (1.47 ± 0.03 vs 2.82 ± 0.08, p<0.001). Correspondingly, the percentage of Indigenous Australians with CHADS2 ≥ 2 (39.6% vs 44.1%, p<0.001) and CHA2DS2VASc-scores ≥ 2 (62.9% vs 78.8%, p<0.001) was also lower. Indigenous Australians, however, had greater rates of under- and over-anticoagulation. Overall, 72.1% and 68.9% of Indigenous and non-Indigenous Australians with CHADS2 scores ≥2, and 76.3% and 71.3% with CHA2DS2VASc scores ≥2, were under-anticoagulated. Similarly, 27.4% and 24.1% of Indigenous and non-Indigenous Australians with CHADS2 scores=0, and 24.0% and 16.7% with CHA2DS2VASc-scores=0, were over-anticoagulated. In multivariate analyses, Indigenous Australians were more likely to receive under- or over-anticoagulation according to CHADS2- or CHA2DS2VASc-score (p=0.045 and p<0.001 respectively). CONCLUSION: Anticoagulation for AF is frequently not prescribed in accordance with guideline recommendations. Under-anticoagulation in those at high stroke risk, and over-anticoagulation in those at low risk, is common and more likely in Indigenous patients with AF. Improving adherence to guideline recommendations for anticoagulation in AF may reduce both ischaemic and haemorrhagic strokes in Indigenous and non-Indigenous Australians.