RESUMO
Peptide receptor radionucleotide therapy (PRRT) with 177Lu-dotatate is widely used for the treatment of patients with neuroendocrine tumors (NETs). We analyzed data from 104 patients with NETs treated with 177Lu -dotatate at a US academic center between December 2017 and October 2020 to better understand patterns of long-term efficacy, safety, and toxicity in the real-world setting. 177Lu-dotatate (200 mCi) was administered every eight weeks for four doses. The most common sites of primary disease were small intestine NETs (n = 49, 47%), pancreatic NETs (n = 32, 31%), and lung NETs (n = 7, 7%). Twenty-seven percent had Ki-67 <3%, 49% had Ki-67 between 3-20%, and 13.5% had Ki-67 >20%. The cohort had been pretreated with a median of two prior lines of treatment. Forty percent had received prior liver-directed treatment. Seventy-four percent of patients completed all four doses of treatment. The objective response rate was 18%. The median time-to-treatment failure/death was significantly longer for small-bowel NETs when compared to pancreatic NETs (37.3 months vs. 13.2 months, p = 0.001). In a multivariate model, Ki-67, primary site, and liver tumor burden ≥50% were found to independently predict time-to-treatment failure/death. Around 40% of patients experienced adverse events of ≥grade 3 severity. Treatment-related adverse events leading to discontinuation of therapy happened in 10% of patients. Preexisting mesenteric/peritoneal disease was present in 33 patients; seven of these patients developed bowel-related toxicities including two grade 5 events. We also report two cases of delayed-onset minimal change nephrotic syndrome, which occurred 14 and 27 months after the last dose of PRRT. Lastly, we describe six patients who developed rapid tumor progression in the liver leading to terminal liver failure within 7.3 months from the start of PRRT, and identify potential risk factors associated with this occurrence, which will need further study.
Assuntos
Tumores Neuroendócrinos , Octreotida , Receptores de Peptídeos , Humanos , Tumores Neuroendócrinos/radioterapia , Tumores Neuroendócrinos/patologia , Tumores Neuroendócrinos/metabolismo , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Octreotida/análogos & derivados , Octreotida/uso terapêutico , Octreotida/efeitos adversos , Octreotida/administração & dosagem , Receptores de Peptídeos/metabolismo , Adulto , Resultado do Tratamento , Compostos Organometálicos/uso terapêutico , Compostos Organometálicos/efeitos adversos , Compostos Organometálicos/administração & dosagem , Idoso de 80 Anos ou mais , Compostos Radiofarmacêuticos/uso terapêutico , Compostos Radiofarmacêuticos/efeitos adversos , Compostos Radiofarmacêuticos/administração & dosagem , Neoplasias Pancreáticas/radioterapia , Neoplasias Pancreáticas/patologia , Estudos RetrospectivosRESUMO
Basal cell carcinoma (BCC) is highly curable by surgical excision or radiation. In rare cases, BCC can be locally destructive or difficult to surgically remove. Hedgehog inhibition (HHI) with vismodegib or sonidegib induces a 50-60% response rate. Long-term toxicity includes muscle spasms and weight loss leading to dose decreases. This retrospective chart review also investigates the impact of CoQ10 and calcium supplementation in patients treated with HHI drugs at a single academic medical center from 2012 to 2022. We reviewed the charts of adult patients diagnosed with locally advanced or metastatic BCC treated with vismodegib or sonidegib primarily for progression-free survival (PFS). Secondary objectives included overall survival, BCC-specific survival, time to and reasons for discontinuation, overall response rate, safety and tolerability, use of CoQ10 and calcium supplements, and insurance coverage. Of 55 patients assessable for outcome, 34 (61.8%) had an overall clinical benefit, with 25 (45.4%) having a complete response and 9 (16.3%) a partial response. Stable disease was seen in 14 (25.4%) and 7 (12.7%) progressed. Of the 34 patients who responded to treatment, 9 recurred. Patients who were rechallenged with HHI could respond again. The median overall BCC-specific survival rate at 5 years is 89%. Dose reductions or discontinuations for vismodegib and sonidegib occurred in 59% versus 24% of cases, or 30% versus 9% of cases, respectively. With CoQ10 and calcium supplementation, only 17% required a dose reduction versus 42% without. HHI is highly effective for treating advanced BCC but may require dosing decreases. Sonidegib was better tolerated than vismodegib. CoQ10 and calcium supplementation can effectively prevent muscle spasms.
Assuntos
Anilidas , Carcinoma Basocelular , Proteínas Hedgehog , Piridinas , Ubiquinona/análogos & derivados , Humanos , Carcinoma Basocelular/tratamento farmacológico , Carcinoma Basocelular/patologia , Estudos Retrospectivos , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Piridinas/uso terapêutico , Piridinas/administração & dosagem , Anilidas/uso terapêutico , Anilidas/administração & dosagem , Proteínas Hedgehog/antagonistas & inibidores , Proteínas Hedgehog/metabolismo , Neoplasias Cutâneas/tratamento farmacológico , Neoplasias Cutâneas/patologia , Compostos de Bifenilo/uso terapêutico , Adulto , Ubiquinona/uso terapêutico , Ubiquinona/administração & dosagem , Idoso de 80 Anos ou mais , Metástase NeoplásicaRESUMO
Background: Anaplastic thyroid carcinoma (ATC) is an aggressive thyroid malignancy that is associated with poor prognosis. Current treatment options include surgery, radiation, cytotoxic chemotherapy, and multikinase inhibitor therapy. The role of immunotherapy in ATC is an area of active interest and recent evidence suggests that it may be a potentially effective treatment option. Methods: We report a case series of 13 patients with locally advanced or metastatic unresectable ATC who received immune checkpoint inhibitor therapy (pembrolizumab or nivolumab) at a single institution. Results: The patients' median age was 70 years, 54% (7/13) were male, and 85% (11/13) had stage IVC disease with lungs and lymph nodes being the most common sites of metastases. Ten patients had tumor tissue available for programmed death-ligand 1 (PD-L1) expression testing, all of which were positive for PD-L1, and seven of these patients also had a BRAFV600E mutation. The median progression-free survival was 1.9 months and median overall survival (OS) was 4.4 months. The objective response rate was 16% (2/13). Two patients had partial response (PR), and three patients had durable stable disease. Among patients with a clinical benefit, after a median follow-up of 13.5 months, median OS had not been reached (range 4+ to 29+ months). Responses were ongoing in four subjects. The one-year survival rate was 38% (5/13). Six patients (46%) experienced an immune-related adverse event, and 15% (2/13) experienced a grade 3 or higher adverse event, including one patient with grade 5 immune checkpoint-related thyroiditis. Conclusions: Immune checkpoint blockade was well tolerated with a toxicity profile consistent with published literature on PD-1/PD-L1-targeting therapies. For ATC patients, immune checkpoint inhibition may represent an effective treatment option with robust sustained responses seen in a subset of patients.
Assuntos
Carcinoma Anaplásico da Tireoide , Neoplasias da Glândula Tireoide , Idoso , Antígeno B7-H1 , Feminino , Humanos , Inibidores de Checkpoint Imunológico/efeitos adversos , Masculino , Carcinoma Anaplásico da Tireoide/patologia , Neoplasias da Glândula Tireoide/patologia , Resultado do TratamentoRESUMO
BACKGROUND: The novel oral anticoagulants (NOACs) are used for stroke prevention in atrial fibrillation (AF), but their safety and efficacy in the periablation period are not well established. Additionally, no standard procedure for managing periprocedural and intraprocedural anticoagulation has been established. OBJECTIVE: To evaluate the frequency of hemorrhagic and thrombotic events as well as periprocedural management strategies of NOACs compared with warfarin as anticoagulation therapy for AF ablation. METHODS: This was a retrospective cohort study from a prospective AF ablation registry maintained at a large, academic medical center. RESULTS: A total of 374 cases (173 warfarin, 123 dabigatran, 61 rivaroxaban, and 17 apixaban) were included in the analysis. The overall hemorrhagic/thrombotic event rate was 14.2 % (major hemorrhage 2.7%, minor hemorrhage 11.2%, thrombotic stroke 0.5%). The frequency of minor hemorrhage was significantly higher with warfarin compared with dabigatran (15% vs 5.7%, P = 0.012). The average heparin dose required to reach the goal activated clotting time (ACT) was 5600 units for warfarin, 12 900 units for dabigatran (P < 0.001), 15 100 units for rivaroxaban (P < 0.001), and 14 700 units for apixaban (P < 0.001). The average time in minutes to reach the goal ACT was significantly longer, compared with warfarin, for dabigatran (57 vs 28, P < 0.001), rivaroxaban (63 vs 28, P < 0.001), and apixaban (72 vs 28, P < 0.001). CONCLUSIONS: Compared with warfarin, periprocedural anticoagulation with dabigatran resulted in fewer minor hemorrhages and total adverse events after AF ablation. Patients anticoagulated with NOACs required larger doses of heparin and took longer to reach the goal ACT compared with patients anticoagulated with warfarin.