-
1.
Thyroidectomy without Radioiodine in Patients with Low-Risk Thyroid Cancer.
Leboulleux, S, Bournaud, C, Chougnet, CN, Zerdoud, S, Al Ghuzlan, A, Catargi, B, Do Cao, C, Kelly, A, Barge, ML, Lacroix, L, et al
The New England journal of medicine. 2022;(10):923-932
Abstract
BACKGROUND In patients with low-risk differentiated thyroid cancer undergoing thyroidectomy, the postoperative administration of radioiodine (iodine-131) is controversial in the absence of demonstrated benefits. METHODS In this prospective, randomized, phase 3 trial, we assigned patients with low-risk differentiated thyroid cancer who were undergoing thyroidectomy to receive ablation with postoperative administration of radioiodine (1.1 GBq) after injections of recombinant human thyrotropin (radioiodine group) or to receive no postoperative radioiodine (no-radioiodine group). The primary objective was to assess whether no radioiodine therapy was noninferior to radioiodine therapy with respect to the absence of a composite end point that included functional, structural, and biologic abnormalities at 3 years. Noninferiority was defined as a between-group difference of less than 5 percentage points in the percentage of patients who did not have events that included the presence of abnormal foci of radioiodine uptake on whole-body scanning that required subsequent treatment (in the radioiodine group only), abnormal findings on neck ultrasonography, or elevated levels of thyroglobulin or thyroglobulin antibodies. Secondary end points included prognostic factors for events and molecular characterization. RESULTS Among 730 patients who could be evaluated 3 years after randomization, the percentage of patients without an event was 95.6% (95% confidence interval [CI], 93.0 to 97.5) in the no-radioiodine group and 95.9% (95% CI, 93.3 to 97.7) in the radioiodine group, a difference of -0.3 percentage points (two-sided 90% CI, -2.7 to 2.2), a result that met the noninferiority criteria. Events consisted of structural or functional abnormalities in 8 patients and biologic abnormalities in 23 patients with 25 events. Events were more frequent in patients with a postoperative serum thyroglobulin level of more than 1 ng per milliliter during thyroid hormone treatment. Molecular alterations were similar in patients with or without an event. No treatment-related adverse events were reported. CONCLUSIONS In patients with low-risk thyroid cancer undergoing thyroidectomy, a follow-up strategy that did not involve the use of radioiodine was noninferior to an ablation strategy with radioiodine regarding the occurrence of functional, structural, and biologic events at 3 years. (Funded by the French National Cancer Institute; ESTIMABL2 ClinicalTrials.gov number, NCT01837745.).
-
2.
Comparison of Image-Guided Iodine-125 Seed Interstitial Brachytherapy and Local Chemotherapy Perfusion in Treatment of Advanced Pancreatic Cancer.
Zhou, L, Yang, H, Xie, L, Sun, J, Qian, J, Zhu, L
Journal of investigative surgery : the official journal of the Academy of Surgical Research. 2022;(1):1-6
Abstract
OBJECTIVE To compare the efficacy and safety of iodine-125 seed interstitial brachytherapy and local chemotherapy perfusion in treatment of advanced pancreatic cancer. METHODS The present open prospective randomized control study included a total of 165 cases of advanced pancreatic cancer patients who were admitted in our hospital during December 2016 to April 2019. All patients were randomized into two groups with 84 cases in iodine-125 group and 81 cases in chemotherapy perfusion group. Basic clinical characteristics and demographic data were collected. The main outcome was the tumor efficiency. The pain condition was measured by visual analogue scale (VAS) and the Karnofsky score was also measured at different time points, before the treatment, 1 d, 7 d, 14 d, 1 mon, 2 mon and 3 mon after treatment. Serum levels of CEA, CA19-9 and CA50 were measured by immunochemiluminescence. The overall survival was analyzed by K-M curve. RESULTS The ratio of partial remission patients was significantly higher, and the ratio of stable disease (SD)+progressive disease patients was also remarkably lower in iodine-125 group than the chemotherapy perfusion group. The mean VAS scores decreased markedly after treatment and were significantly lower and the mean Karnofsky scores were remarkably higher in iodine-125 group than the chemotherapy perfusion group. The levels of CA19-9 and CA50 were remarkably lower in iodine-125 group, however no significant difference was found for CEA. The survival analysis by K-M curve showed the iodine-125 patients had longer overall survival time than the chemotherapy perfusion group. No infection, pancreatic fistula, biliary fistula, intestinal fistula, gastrointestinal obstruction or radiation enteritis was found in both groups. CONCLUSION Iodine-125 seed interstitial brachytherapy could achieve better efficacy with no increased side complications than chemotherapy perfusion in advanced pancreatic cancer.
-
3.
A Randomized Study of Lenvatinib 18 mg vs 24 mg in Patients With Radioiodine-Refractory Differentiated Thyroid Cancer.
Brose, MS, Panaseykin, Y, Konda, B, de la Fouchardiere, C, Hughes, BGM, Gianoukakis, AG, Joo Park, Y, Romanov, I, Krzyzanowska, MK, Leboulleux, S, et al
The Journal of clinical endocrinology and metabolism. 2022;(3):776-787
-
-
Free full text
-
Abstract
BACKGROUND Lenvatinib is a multikinase inhibitor approved to treat radioiodine-refractory differentiated thyroid cancer (RR-DTC) at a starting dose of 24 mg/day. This study explored, in a double-blinded fashion, whether a starting dose of 18 mg/day would provide comparable efficacy with reduced toxicity. METHODS Patients with RR-DTC were randomized to lenvatinib 24 mg/day or 18 mg/day. The primary efficacy endpoint was objective response rate as of week 24 (ORRwk24); the odds ratio noninferiority margin was 0.4. The primary safety endpoint was frequency of grade ≥3 treatment-emergent adverse events (TEAEs) as of week 24. Tumors were assessed using RECIST v1.1. TEAEs were monitored and recorded. RESULTS The ORRwk24 was 57.3% (95% CI 46.1, 68.5) in the lenvatinib 24-mg arm and 40.3% (95% CI 29.3, 51.2) in the lenvatinib 18-mg arm, with an odds ratio (18/24 mg) of 0.50 (95% CI 0.26, 0.96). As of week 24, the rates of TEAEs grade ≥3 were 61.3% in the lenvatinib 24-mg arm and 57.1% in the lenvatinib 18-mg arm, a difference of -4.2% (95% CI -19.8, 11.4). CONCLUSION A starting dose of lenvatinib 18 mg/day did not demonstrate noninferiority compared to a starting dose of 24 mg/day as assessed by ORRwk24 in patients with RR-DTC. The results represent a clinically meaningful difference in ORRwk24. The safety profile was comparable, with no clinically relevant difference between arms. These results support the continued use of the approved starting dose of lenvatinib 24 mg/day in patients with RR-DTC and adjusting the dose as necessary.
-
4.
Therapeutic effects and prognostic factors of 125I brachytherapy for pelvic recurrence after early cervical cancer surgery.
Wang, R, Zhu, J, Yang, S, Chen, X, Gu, C, Liang, T, Li, L, Liu, D, Cao, Y
Scientific reports. 2021;(1):11356
Abstract
To investigate the efficacy of 125I seed implantation in the treatment regimen of pelvic recurrence after early cervical cancer surgery and to analyse prognostic factors. To evaluate efficacy and analyse prognostic factors of 125I seed implantation for pelvic recurrence after early cervical cancer surgery. A prospective study was conducted on 62 patients who experienced pelvic recurrence after early cervical cancer surgery between August 2005 and September 2015. The 62 patients were treated and assessed in 2 groups (n = 30). All 62 patients were randomized into two groups that received two different treatment regimens: the treatment group (n = 30), which received 125I particle implantation therapy, and the control group (n = 32), which received whole-pelvic irradiation using the anteroposterior/posteroanterior field and cisplatin-based concurrent chemoradiation therapy. The efficacy/efficiency of 125I seed implantation and prognostic factors were analysed by logistic regression. Overall survival was determined by Kaplan-Meier analysis. Multivariate analysis results were obtained by the Cox proportional hazards regression model. The effective control rates at 1, 3, 6 and 12 months were 76.7%, 80.0%, 83.3%, and 86.7% in the 125I particle implantation group. The total effective control rates at 1, 3, 6 and 12 months were 65.6%, 65.5%, 62.5%, and 71.9% in the chemoradiotherapy group. Significant differences were observed between the two groups. The overall survival rates at 1, 2, 3, 4, and 5 years and the median overall were 96.7%, 93.3%, 86.7%, 71.9%, 65.6% and 4.34 years, respectively, in the 125I seed implantation group and 81.3%, 71.9%, 62.5%, 56.3%, 53.1% and 3.59 years, respectively, in the control group. There were statistically significant differences in survival rates depending on the diameter of the largest recurrent pelvic tumour (χ2 = 6.611, P = 0.010). The multivariate analysis showed that the survival rates were related to the diameter of the largest recurrent pelvic tumour (χ2 = 4.538, P = 0.033). 125I implantation is an effective, safe, and promising method for the treatment of pelvic recurrence after early cervical cancer surgery. The diameter of the recurrent pelvic tumour was identified as a significant independent prognostic factor in patients who received 125I implantation.
-
5.
Cost-effectiveness of radioguided occult lesion localization using 125I seeds versus hookwire localization before breast-conserving surgery for non-palpable breast cancer.
Wright, CM, Moorin, RE, Saunders, C, Marinovich, ML, Taylor, DB, ,
The British journal of surgery. 2021;(7):843-850
Abstract
BACKGROUND The aim was to determine the cost-effectiveness of radioguided occult lesion localization using 125I-labelled seeds (125I seeds) versus hookwire localization in terms of incremental cost per reoperation avoided for women with non-palpable breast cancer undergoing breast-conserving surgery. METHODS This study was based on a multicentre RCT with eight study sites comprising seven public hospitals and one private hospital. An Australian public health system perspective was taken. The primary effectiveness outcome for this study was reoperations avoided. Cost-effectiveness was expressed as an incremental cost-effectiveness ratio (ICER). One-way and probabilistic sensitivity analyses were used to explore uncertainty. The willingness to pay (additional cost of localization using 125I seeds justified by reoperation cost avoided) was set at the weighted, top-down cost of reoperation. Costs were in 2019 Australian dollars ($1 was equivalent to €0.62). RESULTS The reoperation rate was 13.9 (95 per cent confidence interval 10.7 to 18.0) per cent for the 125I seed group and 18.9 (14.8 to 23.8) per cent for the hookwire localization group. The ICER for 125I seed versus hookwire localization was $4474 per reoperation averted. The results were most sensitive to uncertainty around the probability of reoperation. Accounting for transition probability and cost uncertainty for 125I seed localization, there was a 77 per cent probability that using 125I seeds would be cost-effective, with a willingness to pay of $7693 per reoperation averted. CONCLUSION Radioguided occult lesion localization using 125I seeds is likely to be cost-effective, because the marginal (additional) cost compared with hookwire localization is less than the cost of reoperations avoided.
-
6.
Donafenib in Progressive Locally Advanced or Metastatic Radioactive Iodine-Refractory Differentiated Thyroid Cancer: Results of a Randomized, Multicenter Phase II Trial.
Lin, YS, Yang, H, Ding, Y, Cheng, YZ, Shi, F, Tan, J, Deng, ZY, Chen, ZD, Wang, RF, Ji, QH, et al
Thyroid : official journal of the American Thyroid Association. 2021;(4):607-615
Abstract
Background: An unmet need for more effective and affordable kinase inhibitors remains in patients with progressive radioactive iodine-refractory differentiated thyroid cancer (RAIR-DTC) in China, where only sorafenib is approved for this indication. This study evaluated the 24-week objective response rate (ORR) to donafenib-a new, domestic multikinase inhibitor-in the treatment of locally advanced or metastatic RAIR-DTC in patients with measurable lesions. Two dose regimens (300 mg twice daily vs. 200 mg twice daily) were used to determine its optimal dosage and safety for further phase III studies. Methods: This study was a randomized, open-label, multicenter phase II trial. Thirty-five adult RAIR-DTC patients with at least one measurable targeted lesion according to RECIST 1.1 were enrolled from 12 centers in China and randomized to receive either 200 mg (17 patients) or 300 mg (18 patients) of donafenib orally twice daily for 24 weeks. The primary endpoint was ORR, and the secondary endpoints included progression-free survival (PFS) among others. Additionally, biochemical (serum thyroglobulin) and structural (total tumor diameter [TTD]) responses were assessed, change (ΔTTD) rates were calculated, and safety was evaluated. Results: The ORRs for the 200- and 300-mg arms were 12.5% and 13.33% (p = 1.000), respectively. The 300-mg arm had a nonsignificant, longer median PFS than the 200-mg arm (14.98 months vs. 9.44 months) (p = 0.351). There was a trend toward more tumor shrinkage in the 300-mg arm compared with the 200-mg arm (average ΔTTD rate -0.52 ± 0.71 vs. -0.04 ± 1.55 mm/month, p = 0.103). Most treatment-related adverse events (AEs) in both arms were grades 1-2. The most common grade 3 treatment-related AEs in both arms were palmar-plantar erythrodysesthesia and hypertension; the sum occurrence rates of these two AEs in the 200-mg and 300-mg arms were 11.43% and 22.86%, respectively. Conclusions: Donafenib was generally well tolerated. Both donafenib regimens demonstrated similar efficacy in terms of the ORR in locally advanced or metastatic RAIR-DTC. The results warrant further studies on donafenib as a new, feasible treatment option for RAIR-DTC patients. Clinical Trials.gov IDs: NCT02870569; CTR20160220.
-
7.
Clinical analysis of 125I seed implantation combined with epidermal growth factor receptor-tyrosine kinase inhibitors in advanced non-small cell lung cancer.
Wang, X, Wang, D
Journal of B.U.ON. : official journal of the Balkan Union of Oncology. 2021;(5):1879-1886
Abstract
PURPOSE To explore the efficacy and safety of 125I radioactive seed implantation combined with epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) in the treatment of advanced non-small cell lung cancer (NSCLC). METHODS 108 patients with EGFR mutation-positive unresectable advanced NSCLC (stage IIIB-IV) were randomly divided into 125I group (treated with 125I radioactive seed implantation combined with EGFR-TKIs, n=54) and EGFR-TKIs group (treated with EGFR-TKIs alone, n=54). The short-term efficacy and adverse reactions were analyzed and evaluated, the changes in the levels of peripheral blood T lymphocyte subsets, natural killer (NK) cells and related immune-inflammatory factors were analyzed, and the long-term survival and progression of disease were recorded. RESULTS The objective response rate was 61.1% (33/54) and 51.9% (28/54), and the disease control rate was 88.9% (48/54) and 68.5% (37/54), respectively, in 125I group and EGFR-TKIs group. At 6 months after treatment, the levels of peripheral blood cluster of differentiation 3+ (CD3+), CD4+, CD4+/CD8+ and NK cells significantly rose in both groups compared with those before treatment (p<0.05), while the levels of CD8+, serum tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ), interleukin-6 (IL-6) and IL-10 significantly declined compared with those before treatment. The 2-year overall survival (OS) rate was 53.7% (29/54) and 40.7% (22/54), and the median progression-free survival (PFS) was 14.5 months and 9.8 months, respectively, in 125I group and EGFR-TKIs group. CONCLUSIONS 125I radioactive seed implantation combined with EGFR-TKIs is safe and effective in the treatment of advanced NSCLC, and its short-term efficacy and long-term survival rate of patients are significantly superior to those of EGFR-TKIs alone. At the same time, it can regulate the expressions of T lymphocyte subsets, NK cells and immune-inflammatory factors in patients, and improve their immune function.
-
8.
A novel irradiation stent versus conventional irradiation stent for malignant dysphagia: A prospective randomized controlled trial.
Zhu, GY, Lu, J, Wang, C, Guo, JH
Journal of cancer research and therapeutics. 2021;(5):1261-1268
-
-
Free full text
-
Abstract
AIM: To evaluate whether a novel irradiation stent (NIS) could decrease the rate of recurrent dysphagia, compared to the conventional irradiation stent (CIS) in patients with malignant dysphagia. MATERIALS AND METHODS We performed an open-label randomized controlled trial of participants with malignant dysphagia. A total of 94 participants were parallelly allocated into the NIS group or the NIS group between April 2019 and April 2020. The primary endpoint was the rate of recurrent dysphagia. The secondary endpoints included technical success, clinical success, overall survival, and adverse events. RESULTS The technical success rate and the clinical success rate was 100.0% (47/47) in both groups. The median follow-up period was 189 days (range 14-422 days). Recurrent dysphagia was observed in 12.8% (6/47) of patients in the NIS group and 31.9% (15/47) in the CIS group (P = 0.026). Tissue/tumor growth occurred in 4 patients (8.5%) after NIS placement and 12 (25.5%) after CIS placement (P = 0.028). Stent migration occurred in 2 patients (4.3%) after NIS placement and 3 (6.4%) after CIS placement (P = 0.646). No food obstruction was found in both groups. The median overall survival was 177 days (95% confidence interval [CI] 139-214) in the NIS group and 168 days (95% CI 153-183) in the CIS group (P = 0.932). The incidence of severe adverse events was comparable between the two groups (21.3% vs. 17.0%, P = 0.600). CONCLUSIONS In patients with malignant dysphagia, compared with CIS, NIS could decrease the rate of tissue/tumor growth without increase the rate of stent migration and therefore decrease the rate of recurrent dysphagia.
-
9.
Intermittent versus continuous administration of pazopanib in progressive radioiodine refractory thyroid carcinoma: Final results of the randomised, multicenter, open-label phase II trial PAZOTHYR.
de la Fouchardière, C, Godbert, Y, Dalban, C, Illouz, F, Wassermann, J, Do Cao, C, Bardet, S, Zerdoud, S, Chougnet, CN, Zalzali, M, et al
European journal of cancer (Oxford, England : 1990). 2021;:153-164
Abstract
INTRODUCTION Multikinase inhibitor (MKI) treatments have shown efficacy in progressive radioiodine refractory thyroid cancers (RAIR-TC), but most patients experienced substantial adverse effects. This randomised multicentric study investigated intermittent versus continuous pazopanib administration. PATIENTS AND METHODS The PAZOTHYR study included RAIR-TC patients with progressive disease in the last 12 months, who may have received one prior MKI. RAIR-TC patients received pazopanib for 6 months, and patients with stable disease or tumour response were randomly assigned (1:1) to receive continuous (CP) or intermittent (IP) pazopanib until progression. The primary end-point was time to treatment failure (TTF) defined as the time from randomisation to permanent discontinuation of pazopanib, due to any cause. One hundred randomised patients were needed to demonstrate an increase from 50% (CP) to 70% (IP) (hazard ratio (HR) 0.515, 80% power) in the rate of patients still under treatment 6 months (6m-SuT) post-randomisation. Secondary end-points included the overall response rate (ORR), progression-free survival (PFS) under pazopanib and safety. RESULTS RAIR-TC patients (168) enrolled from June 18, 2013 to January 16, 2018, received 6-month pazopanib treatment and showed 35.6% (95% CI 28.2-43.6) best response rate and 89.4% (83.5-93.7) disease control rate. One hundred patients were randomised (IP:50; CP:50). With a median follow-up of 31.3 months, median TTF was not statistically different between arms (IP:14.7, 95% confidence interval (CI) 9.3-17.4; CP:11.9, 95% CI 7.5-15.6) months (HR 0.79, 0.49-1.27). 6m-SuT rates were similar (IP:80% 66.0-88.7%; CP:78% 63.8-87.2%). Median PFS under pazopanib were not statistically different (IP:5.7 4.8-7.8; CP: 9.2 7.3-11.1) months (HR 1.36, 0.88-2.12). Pazopanib-related adverse events grade 3-4 occurred in 36 (IP: 19, 38%; CP: 17, 34%) randomised patients. Seven pazopanib-related deaths occurred. CONCLUSIONS Intermittent administration of pazopanib did not demonstrate significant superiority in efficacy or tolerance compared with continuous treatment. An intermittent administration scheme cannot be recommended outside clinical trials. This study was registered with ClinicalTrial.gov, number NCT01813136.
-
10.
Correlation of Performance Status and Neutrophil-Lymphocyte Ratio with Efficacy in Radioiodine-Refractory Differentiated Thyroid Cancer Treated with Lenvatinib.
Taylor, MH, Takahashi, S, Capdevila, J, Tahara, M, Leboulleux, S, Kiyota, N, Dutcus, CE, Xie, R, Robinson, B, Sherman, S, et al
Thyroid : official journal of the American Thyroid Association. 2021;(8):1226-1234
-
-
Free full text
-
Abstract
Background: Radioiodine-refractory differentiated thyroid cancer (RR-DTC) has a low 10-year patient-survival rate and is challenging to treat. Lenvatinib is a multikinase inhibitor approved for the treatment of RR-DTC. This study aims to assess Eastern Cooperative Oncology Group performance status (ECOG PS) and neutrophil-to-lymphocyte ratio (NLR) as prognostic markers for patients with RR-DTC treated with lenvatinib. Methods: In this retrospective analysis of the Study of (E7080) LEnvatinib in Differentiated Cancer of the Thyroid (SELECT), patients randomly assigned to receive lenvatinib were classified according to baseline ECOG PS (0 or 1) or baseline NLR (≤3 or >3). The effects of baseline ECOG PS and NLR on progression-free survival (PFS), overall survival (OS), and objective response rate (ORR) were evaluated. In addition, the effects of baseline ECOG PS on the change in diameter of target lesions and correlations between baseline NLR and the sums of the diameters of target lesions were calculated. Results: Among patients who received lenvatinib, patients with a baseline ECOG PS of 0 had statistically improved PFS (hazard ratio [HR] 0.52; 95% confidence interval [CI 0.35-0.77]; p = 0.001), OS (HR 0.42 [CI 0.26-0.69]; p = 0.0004), and ORR (odds ratio [OR] 3.51 [CI 2.02-6.10]; p < 0.0001) compared with patients with a baseline ECOG PS of 1. Patients who received lenvatinib with a baseline NLR ≤3 also had improved PFS (HR 0.43 [CI 0.29-0.65]; p < 0.0001) and OS (HR 0.48 [CI 0.29-0.78]; p = 0.0029) versus patients with a baseline NLR >3. Moreover, patients with a baseline NLR ≤3 had a trend toward increased ORR (OR 1.57 [CI 0.94-2.64]; p = 0.08) compared with patients with a baseline NLR >3. Treatment-emergent adverse events were generally similar among patients who received lenvatinib, irrespective of patients' ECOG PS at baseline. Conclusion: Lower ECOG PS and NLR may provide prognostic value for improved efficacy in patients with RR-DTC. ClinicalTrials.gov no. NCT01321554.