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PATIENTS AND METHODS: The primary endpoints were objective response rate (ORR) and disease control rate (DCR). Secondary endpoints were duration of response, blood pressure control, safety, overall and progression-free survival rates, MIBG uptake, and correlations with genetic background. RESULTS: The study included 25 patients. Twenty-four patients had distant metastases, 17 (68%) had hormonally active tumors, and 13 (52%) had previously received antineoplastic treatment. In 24 evaluable patients, the ORR was 38%, including 2 patients with complete response, and the DCR was 83%; median time to response was 12.5 months (95% confidence interval, 4.6-25.1). Twelve patients had sporadic disease, among whom the ORR was 25% and DCR was 83%. Twelve patients had hereditary disease ( SDHB , VHL , RET ); among these, the ORR was 50%, and DCR was 83%. Plasma metanephrines normalized in 30% of patients and improved by greater than 50% in 46%. Sixteen patients had hormonally active tumors and hypertension; in 9 (56%) of these, blood pressure normalized, leading to discontinuation of antihypertensive therapy.The most common adverse events were grades 1-2 nausea/vomiting and transient bone marrow suppression. One patient developed premature ovarian failure. Reversible grades 3-4 myelosuppression were seen in 7 patients (28%). One patient had fatal pneumonitis. CONCLUSIONS: HSA- 131 I-MIBG is associated with a high DCR in patients with MPPGL, regardless of underlying genetic mutation.
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3-Iodobenzilguanidina , Neoplasias das Glândulas Suprarrenais , Paraganglioma , Feocromocitoma , Humanos , Feocromocitoma/diagnóstico por imagem , Feocromocitoma/radioterapia , Feocromocitoma/tratamento farmacológico , Feminino , Masculino , Paraganglioma/radioterapia , Paraganglioma/diagnóstico por imagem , Paraganglioma/tratamento farmacológico , Adulto , Pessoa de Meia-Idade , Neoplasias das Glândulas Suprarrenais/diagnóstico por imagem , Neoplasias das Glândulas Suprarrenais/radioterapia , Idoso , Adulto Jovem , Resultado do Tratamento , Adolescente , Radioisótopos do IodoRESUMO
BACKGROUND: Diabetic cardiomyopathy (DCM) is a serious complication in patients with type 1 diabetes mellitus (T1DM), which still lacks adequate therapy. Irisin, a cleavage peptide off fibronectin type III domain-containing 5, has been shown to preserve cardiac function in cardiac ischemia-reperfusion injury. Whether or not irisin plays a cardioprotective role in DCM is not known. METHODS AND RESULTS: T1DM was induced by multiple low-dose intraperitoneal injections of streptozotocin (STZ). Our current study showed that irisin expression/level was lower in the heart and serum of mice with STZ-induced TIDM. Irisin supplementation by intraperitoneal injection improved the impaired cardiac function in mice with DCM, which was ascribed to the inhibition of ferroptosis, because the increased ferroptosis, associated with increased cardiac malondialdehyde (MDA), decreased reduced glutathione (GSH) and protein expressions of solute carrier family 7 member 11 (SLC7A11) and glutathione peroxidase 4 (GPX4), was ameliorated by irisin. In the presence of erastin, a ferroptosis inducer, the irisin-mediated protective effects were blocked. Mechanistically, irisin treatment increased Sirtuin 1 (SIRT1) and decreased p53 K382 acetylation, which decreased p53 protein expression by increasing its degradation, consequently upregulated SLC7A11 and GPX4 expressions. Thus, irisin-mediated reduction in p53 decreases ferroptosis and protects cardiomyocytes against injury due to high glucose. CONCLUSION: This study demonstrated that irisin could improve cardiac function by suppressing ferroptosis in T1DM via the SIRT1-p53-SLC7A11/GPX4 pathway. Irisin may be a therapeutic approach in the management of T1DM-induced cardiomyopathy.
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Diabetes Mellitus Tipo 1 , Cardiomiopatias Diabéticas , Ferroptose , Humanos , Animais , Camundongos , Cardiomiopatias Diabéticas/tratamento farmacológico , Cardiomiopatias Diabéticas/etiologia , Cardiomiopatias Diabéticas/prevenção & controle , Sirtuína 1 , Fibronectinas , Diabetes Mellitus Tipo 1/complicações , Diabetes Mellitus Tipo 1/tratamento farmacológico , Proteína Supressora de Tumor p53 , Miócitos CardíacosRESUMO
A gelled Pickering emulsion system was fabricated by first stabilizing linseed oil droplets in water with dialdehyde cellulose nanocrystals (DACNCs) and then cross-linking with cystamine. Cross-linking of the DACNCs was shown to occur by a reaction between the amine groups on cystamine and the aldehyde groups on the CNCs, causing gelation of the nanocellulose suspension. Fourier transform infrared spectroscopy and X-ray photoelectron spectroscopy were used to characterize the cystamine-cross-linked CNCs (cysCNCs), demonstrating their presence. Transmission electron microscopy images evidenced that cross-linking between cysCNCs took place. This cross-linking was utilized in a linseed oil-in-water Pickering emulsion system, creating a novel gelled Pickering emulsion system. The rheological properties of both DACNC suspensions and nanocellulose-stabilized Pickering emulsions were monitored during the cross-linking reaction. Dynamic light scattering and confocal laser scanning microscopy (CLSM) of the Pickering emulsion before gelling imaged CNC-stabilized oil droplets along with isolated CNC rods and CNC clusters, which had not been adsorbed to the oil droplet surfaces. Atomic force microscopy imaging of the air-dried gelled Pickering emulsion also demonstrated the presence of free CNCs alongside the oil droplets and the cross-linked CNC network directly at the oil-water interface on the oil droplet surfaces. Finally, these gelled Pickering emulsions were mixed with poly(vinyl alcohol) solutions and fabricated into self-healing composite coating systems. These self-healing composite coatings were then scratched and viewed under both an optical microscope and a scanning electron microscope before and after self-healing. The linseed oil was demonstrated to leak into the scratches, healing the gap automatically and giving a practical approach for a variety of potential applications.
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Cistamina , Nanopartículas , Emulsões/química , Óleo de Semente do Linho , Celulose/química , Nanopartículas/química , Água/químicaRESUMO
Breast lymphoscintigraphy is commonly performed before initial surgical intervention and surgical staging in the setting of breast cancer. Breast lymphoscintigraphy injections can often be quite painful and are routinely performed without any anesthesia or analgesia, thus representing a significant unmet need for the breast cancer population. Although vapocoolants have been previously available, they have typically been used on intact skin and not been recommended for sterile procedures. Methods: Thirty consecutive patients were enrolled in our prospective study of which 29 received vapocoolant analgesia in the setting of breast lymphoscintigraphy. Patients were given a postinjection questionnaire that included a self-reported pain score and boolean question regarding whether they would recommend vapocoolant for future patients. Results: The lymposcintigraphy procedure was successful in 100% of cases with an ipsilateral axillary node identified on average within 2.4 h of injection (median, 1 h; range 1-4.5 h). The average self-reported pain score was 1.98 (median, 1; range, 1-10). Conclusion: Vapocoolant analgesia in the setting of breast lymphoscintigraphy is feasible, does not appear to compromise lymphoscintigraphy, and appears to be associated with generally low self-reported pain scores.
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ABSTRACT: We herein present a potential pitfall in the setting of restaging PSMA PyL PET/CT. In this case, there is large non-PSMA-avid cystic structure in the mid pelvis, probably representing a postprostatectomy lymphocele, which was mistaken for the urinary bladder, resulting in the displaced and somewhat crescentic urinary bladder to be deemed recurrence. Subsequently, biopsy and retrospective review of images confirms displaced urinary bladder containing physiologic excreted activity.
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Carcinoma , Neoplasias da Próstata , Masculino , Humanos , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Bexiga Urinária , Recidiva Local de Neoplasia/patologia , Neoplasias da Próstata/patologia , Pelve , Radioisótopos de Gálio , Ácido EdéticoRESUMO
PURPOSE: The aim of this study was to investigate the role of 18 F-DCFPyL PET/CT in the evaluation of prostate cancer (PC) patients after definitive treatment and with low-level prostate-specific antigen (PSA) level of ≤0.2 ng/mL. PATIENTS AND METHODS: This retrospective study was conducted in PC patients who received definitive treatments with PSA level of ≤0.2 ng/mL and underwent 18 F-DCFPyL PET/CT within a 1-week interval of PSA examination, and without interval treatment change or history of other cancer. Patient and tumor characteristics at initial diagnosis, treatment regimens, and findings on 18 F-DCFPyL PET/CT were collected. Patients with minimal 6-month (median, 11 months; range, 6-21 months) follow-up or definitive biopsy results of the suspected PET/CT findings were included. Imagine findings were reached with consensus among experienced board-certified nuclear medicine physicians. Comprehensive follow-up and/or biopsy results were used as definitive determination of presence or absence of disease. Comparisons between groups of positive and negative 18 F-DCFPyL PET/CT were done by using descriptive statistics. RESULTS: A total of 96 18 F-DCFPyL PET/CTs from 93 patients met the inclusion criteria. The median Gleason score (GS) of positive group is 8 (range, 6-10), whereas negative group is 7 (range, 6-10). The median age of positive group is 71 (range, 50-90), whereas negative group is 69 (range, 45-88). There were 49 positive (51%) and 47 negative 18 F-DCFPyL PET/CTs (49%). Detection rates at PSA level of ≤0.1 and 0.2 ng/mL were 58.7% (27/46) and 44% (22/50), respectively. The scan-based sensitivity, specificity, positive predictive value, and negative predictive value are 100%, 95%, 96%, and 100% in group with PSA level of ≤0.1 ng/mL, and 100%, 97%, 95%, and 100% in group with PSA level of 0.2 ng/mL, respectively. Sites of involvement on positive 18 F-DCFPyL PET/CTs were prostate bed, pelvic lymph nodes, bone, chest and supraclavicular lymph nodes, lung, and adrenal glands. The SUV max value on positive lesions ranged from 1.9 to 141.4; the smallest positive lymph node was 0.4 cm. High GS of 8-10, known metastatic status (M1), presence of extraprostatic extension, presence of seminal vesicle invasion, and very high-risk PC are significantly associated with positive 18 F-DCFPyL PET/CT results ( P < 0.05). Of all analyzed treatment regimes, upfront surgery (radical prostatectomy with or without pelvic lymph node dissection) had strong correlation with negative PET/CT results ( P < 0.001). If patients received ADT only, or ADT plus chemotherapy, the PET/CT results were most likely positive ( P = 0.026). For other treatment regimes, there were no statistical differences between the groups ( P > 0.05). CONCLUSIONS: In the presence of low PSA level in PC patients after definitive treatment, 18 F-DCFPyL PET/CT is most beneficial in detection of disease in patients with GS of 8 or higher at the time of diagnosis, and the ones who have history of ADT only, or ADT plus chemotherapy. There is excellent negative prediction value of 18 F-DCFPyL PET/CT. However, there is no cutoff PSA level for 18 F-DCFPyL PET/CT indication and no correlation between PSA level and SUV max of positive lesions on 18 F-DCFPyL PET/CT.
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Antígeno Prostático Específico , Neoplasias da Próstata , Masculino , Humanos , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Estudos Retrospectivos , Neoplasias da Próstata/patologia , Próstata/patologiaRESUMO
Obesity defined by high body mass index (BMI) has traditionally been associated with gastrointestinal inflammatory processes but has recently been correlated with better survival in patients receiving immune checkpoint inhibitors (ICI). We sought to investigate the association between BMI and immune-mediated diarrhea and colitis (IMDC) outcomes and whether BMI reflects body fat content on abdominal imaging. This retrospective, single-center study included cancer patients with ICI exposure who developed IMDC and had BMI and abdominal computed tomography (CT) obtained within 30 days before initiating ICI from April 2011 to December 2019. BMI was categorized as <25, ≥25 but <30, and ≥30. Visceral fat area (VFA), subcutaneous fat area (SFA), total fat area (TFA: VFA+SFA), and visceral to subcutaneous fat (V/S) ratio were obtained from CT at the umbilical level. Our sample comprised 202 patients; 127 patients (62.9%) received CTLA-4 monotherapy or a combination, and 75 (37.1%) received PD-1/PD-L1 monotherapy. Higher BMIs ≥ 30 were associated with a higher incidence of IMDC than BMIs ≤ 25 (11.4% vs. 7.9%, respectively; p = 0.029). Higher grades of colitis (grade 3-4) correlated with lower BMI (p = 0.03). BMI level was not associated with other IMDC characteristics or did not influence overall survival (p = 0.83). BMI is strongly correlated with VFA, SFA, and TFA (p < 0.0001). Higher BMI at ICI initiation was linked to a higher incidence of IMDC but did not appear to affect outcomes. BMI strongly correlated with body fat parameters measured by abdominal imaging, suggesting its reliability as an obesity index.
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While Tc-99m MDP bone scan (BS) remains the conventional standard for detection of bone metastasis in prostate cancer, newly FDA-approved imaging with PSMA-based 18F-DCFPyL PET/CT has shown promise for early detection of metastatic disease. However, a paucity of data remains in the diagnostic accuracy of PSMA PET/CT in detecting bone metastasis compared to BS. This retrospective study included 91 patients who received both BS and PSMA PET/CT within a 3-month interval from August 2021 to February 2022. Separate concurrent primary cancer, interval PSA levels greater than a 2-fold difference (or absolute difference >1 ng/ml) between the two studies were excluded. All abnormal bone lesions on either scan were compared. The findings were verified by pathological findings and/or 6-month clinical follow-up. High concordance (78%) was found between modalities with discordant findings (20/91, 22%) demonstrating more false positives (4/20, 20%) and false negatives (3/20, 15%) on BS compared to PET/CT. Additionally, more bone metastases were detected on PSMA PET/CT (13/20, 65%) with all true positive BS lesions also detected PET/CT. The sensitivity, specificity, PPV and NPV for BS were 89%, 91%, 80%, and 95% respectively; and 100%, 97%, 93%, and 100% for 18F-DCFPyL PET/CT respectively. Our results demonstrate that 18F-DCFPyL PET/CT identified more bone metastases while also identifying all bone metastases identified on BS. With the added diagnostic value of detecting primary tumor and soft tissue metastasis, 18F-DCFPyL PET/CT may render BS unnecessary to investigate bone metastases in patients with prostate cancer.
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ABSTRACT: High-specific-activity 131 I-MIBG (Azedra) is the only Food and Drug Administration-approved therapy for metastatic pheochromocytomas and paragangliomas, which are rare neuroendocrine tumors with limited treatment options. Based on our experience, we proposed here functional imaging-based tumor response criteria for these patient cohorts. Each response category was illustrated with typical sample cases, and clinical correlation was provided.
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Neoplasias das Glândulas Suprarrenais , Neoplasias Encefálicas , Segunda Neoplasia Primária , Tumores Neuroendócrinos , Paraganglioma , Neoplasias do Sistema Nervoso Periférico , Feocromocitoma , Humanos , Feocromocitoma/patologia , 3-Iodobenzilguanidina/uso terapêutico , Paraganglioma/patologia , Neoplasias das Glândulas Suprarrenais/patologia , Neoplasias Encefálicas/tratamento farmacológicoRESUMO
PURPOSE: Immune checkpoint inhibitors (ICIs) are efficacious for treating various malignancies. In addition to immune-related adverse events (irAEs), growing evidence suggests that ICIs might also be associated with diverticulitis. We aim to assess the clinical presentations and management of colonic diverticulitis among cancer patients after ICI treatment. METHODS: A retrospective study was conducted on ICI-treated adult cancer patients between 01/2010 and 06/2020. Patients were grouped based on when diverticulitis developed relative to ICI treatment, either before (controls) or after (cases). Patient clinical characters, treatment, and outcomes were compared between both groups. RESULTS: 77 eligible patients were included: 63 patients developed diverticulitis after ICI exposure (46 had initial episode after ICI exposure, 17 had a history of diverticulitis prior then recurred after ICI exposure), and 14 had diverticulitis before ICI exposure. Diverticulitis occurred after a median of 129 days after ICI initiation. Clinical characteristics overlapped with traditional diverticulitis. 93% of patients had symptom resolution after treatment, while 23.8% experienced complications. These patients exhibited higher rates of hospitalization (87% vs 48%, P = 0.015) and surgery/interventional radiology procedures (27% vs 0, P = 0.002), and worse overall survival (P = 0.022). History of diverticulitis was not associated with a more severe disease course. Immunosuppressants (e.g., corticosteroids) were rarely required unless for concurrent ICI-mediated colitis. CONCLUSION: Colonic diverticulitis can occur after ICI therapy at very low incidence (0.5%). Its clinical presentation, evaluation, and management are similar to traditional diverticulitis, but associated with higher complication rates requiring surgical intervention and has lower overall survival.
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Colite , Doença Diverticular do Colo , Neoplasias , Adulto , Humanos , Doença Diverticular do Colo/tratamento farmacológico , Inibidores de Checkpoint Imunológico/efeitos adversos , Estudos Retrospectivos , Colite/induzido quimicamenteRESUMO
Salvage chemotherapy followed by high-dose chemotherapy and autologous stem cell transplantation (ASCT) is a potentially curative treatment for patients with relapsed or refractory large B-cell lymphoma (rrLBCL) with chemosensitive disease. A18 F-fluorodeoxyglucose positron emission tomography (PET) scan after salvage chemotherapy is used to assess response and eligibility for ASCT, but metrics for chemosensitivity in patients with residual disease are not well defined. We performed a single-centre retrospective analysis of 92 patients with a partial response or stable disease after salvage chemotherapy for rrLBCL who received ASCT to investigate PET-derived parameters and their prognostic utility. The Deauville 5-point Scale (D-5PS) score, maximum standardised uptake value (SUVmax ), total metabolic tumour volume (TMTV), and total lesion glycolysis (TLG) were calculated from the post-salvage/pre-ASCT PET scan. The 5-year progression-free survival (PFS) and overall survival (OS) rates were 40% and 54% respectively. A D-5PS score of 5 (p = 0.0082, hazard ratio [HR] 2.09), high SUVmax (p = 0.0015, HR 2.48), TMTV (p = 0.035, HR 1.83) and TLG (p = 0.0036, HR 2.27) were associated with inferior PFS. A D-5PS score of 5 (p = 0.030, HR 1.98) and high SUVmax (p = 0.0025, HR 2.55) were associated with inferior OS. PET-derived parameters may help prognosticate outcomes after ASCT in patients with rrLBCL with residual disease after salvage chemotherapy.
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Transplante de Células-Tronco Hematopoéticas , Linfoma Difuso de Grandes Células B , Humanos , Transplante de Células-Tronco Hematopoéticas/métodos , Estudos Retrospectivos , Transplante Autólogo , Tomografia por Emissão de Pósitrons/métodos , Transplante de Células-Tronco , Prognóstico , Linfoma Difuso de Grandes Células B/diagnóstico por imagem , Linfoma Difuso de Grandes Células B/terapia , Linfoma Difuso de Grandes Células B/patologia , Fluordesoxiglucose F18 , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêuticoRESUMO
OBJECTIVES: Imaging appearances of immune checkpoint inhibitor-related nephritis have not yet been described. The primary objective of this study is to describe the appearances of immunotherapy-related nephritis on computerized tomography (CT) and positron emission tomography (PET). The secondary objectives are to investigate the association of radiologic features with clinical outcomes. METHODS: CT and PET-CT scans before the initiation of immunotherapy (baseline), at nephritis, and after resolution of pathology-proven nephritis cases were reviewed. Total kidney volume, renal parenchymal SUVmax, renal pelvis SUVmax, and blood pool SUVmean were obtained. RESULTS: Thirty-four patients were included. The total kidney volume was significantly higher at nephritis compared to baseline (464.7 ± 96.8 mL vs. 371.7 ± 187.7 mL; p < 0.001). Fifteen patients (44.1%) had > 30% increase in total kidney volume, which was associated with significantly higher renal toxicity grade (p = 0.007), higher peak creatinine level (p = 0.004), and more aggressive medical treatment (p = 0.011). New/increasing perinephric fat stranding was noted in 10 patients (29.4%) at nephritis. Among 8 patients with contrast-enhanced CT at nephritis, one (12.5%) developed bilateral wedge-shaped hypoenhancing cortical. On PET-CT, the renal parenchymal SUVmax-to-blood pool ratio was significantly higher at nephritis compared to baseline (2.13 vs. 1.68; p = 0.035). The renal pelvis SUVmax-to-blood pool SUVmean ratio was significantly lower at nephritis compared to baseline (3.47 vs. 8.22; p = 0.011). CONCLUSIONS: Bilateral increase in kidney size, new/increasing perinephric stranding, and bilateral wedge-shaped hypoenhancing cortical foci can occur in immunotherapy-related nephritis. On PET-CT, a diffuse increase in radiotracer uptake throughout the renal cortex and a decrease in radiotracer activity in the renal pelvis can be seen. KEY POINTS: ⢠CT features of immune checkpoint inhibitor-related nephritis include an increase in kidney volume, new/increasing perinephric stranding, and bilateral ill-defined wedge-shaped hypoenhancing cortical foci. ⢠FDG-PET features of immune checkpoint inhibitor-related nephritis include an increase in FDG uptake throughout the renal cortex and a decrease in FDG activity/excretion in the collecting system. ⢠> 30% increase in total kidney volume is associated with worse toxicity grade and more aggressive medical management.
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Nefrite , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Humanos , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Fluordesoxiglucose F18 , Inibidores de Checkpoint Imunológico , Compostos Radiofarmacêuticos , Estudos Retrospectivos , Nefrite/induzido quimicamente , Nefrite/diagnóstico por imagemRESUMO
PURPOSE: The aim of this study was to develop a pretherapy PET/CT-based prediction model for treatment response to ibrutinib in lymphoma patients. PATIENTS AND METHODS: One hundred sixty-nine lymphoma patients with 2441 lesions were studied retrospectively. All eligible lymphomas on pretherapy 18F-FDG PET images were contoured and segmented for radiomic analysis. Lesion- and patient-based responsiveness to ibrutinib was determined retrospectively using the Lugano classification. PET radiomic features were extracted. A radiomic model was built to predict ibrutinib response. The prognostic significance of the radiomic model was evaluated independently in a test cohort and compared with conventional PET metrics: SUVmax, metabolic tumor volume, and total lesion glycolysis. RESULTS: The radiomic model had an area under the receiver operating characteristic curve (ROC AUC) of 0.860 (sensitivity, 92.9%, specificity, 81.4%; P < 0.001) for predicting response to ibrutinib, outperforming the SUVmax (ROC AUC, 0.519; P = 0.823), metabolic tumor volume (ROC AUC, 0.579; P = 0.412), total lesion glycolysis (ROC AUC, 0.576; P = 0.199), and a composite model built using all 3 (ROC AUC, 0.562; P = 0.046). The radiomic model increased the probability of accurately predicting ibrutinib-responsive lesions from 84.8% (pretest) to 96.5% (posttest). At the patient level, the model's performance (ROC AUC = 0.811; P = 0.007) was superior to that of conventional PET metrics. Furthermore, the radiomic model showed robustness when validated in treatment subgroups: first (ROC AUC, 0.916; P < 0.001) versus second or greater (ROC AUC, 0.842; P < 0.001) line of defense and single treatment (ROC AUC, 0.931; P < 0.001) versus multiple treatments (ROC AUC, 0.824; P < 0.001). CONCLUSIONS: We developed and validated a pretherapy PET-based radiomic model to predict response to treatment with ibrutinib in a diverse cohort of lymphoma patients.
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Fluordesoxiglucose F18 , Linfoma , Adenina/análogos & derivados , Humanos , Linfoma/diagnóstico por imagem , Linfoma/tratamento farmacológico , Piperidinas , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Estudos RetrospectivosRESUMO
ABSTRACT: A 63-year-old man with prostate cancer was treated with prostatectomy who had postoperative PSA of 0.6 ng/mL. A pelvic MRI, whole body bone scan, CT chest and abdomen exams did not show any residual or metastatic prostate disease. His PSA increased to 0.9 ng/mL in two months. A fluciclovine PET did not show any tracer avid metastatic or recurrent disease. A 0.7 cm non-fluciclovine-avid nodule at the left prostatectomy bed was considered benign. A 68Ga-PSMA-11 PET one month later showed avid radiotracer uptake within this nodule. The patient received androgen deprivation treatment after PSMA PET/CT and responded well.
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Antígeno Prostático Específico , Neoplasias da Próstata , Antagonistas de Androgênios , Isótopos de Gálio , Radioisótopos de Gálio , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/patologia , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Prostatectomia , Neoplasias da Próstata/diagnóstico por imagem , Neoplasias da Próstata/patologia , Neoplasias da Próstata/cirurgiaRESUMO
PURPOSE OF REVIEW: Multiple therapies with novel mechanisms have been explored in clinical trials for the treatment of metastatic pheochromocytomas and paragangliomas. We review current and future therapies for this disease and provide guidance on how and when to prescribe them based on tumor progression, clinical manifestations, molecular features, and social factors. RECENT FINDINGS: Approximately 60-70% of metastatic pheochromocytomas and paragangliomas express the noradrenaline transporter in their cell membranes. High specific activity iodine-131 metaiodobenzylguanidine has been recently approved by the US Food and Drug Administration for the treatment of metastatic pheochromocytomas and paragangliomas that express the noradrenaline transporter, in patients aged ≥ 12 years. More than 90% of patients treated with this medication exhibit clinical benefits. However, other therapies with novel mechanisms of action are needed to help all patients with this disease. Treatment of metastatic pheochromocytomas and paragangliomas is recommended based on the severity of symptoms, the progression of the disease, and the patient's performance status. Currently available therapies include surgery; systemic chemotherapy with cyclophosphamide, vincristine, and dacarbazine, or with temozolomide; high specific activity iodine-131 metaiodobenzylguanidine; peptide receptor radionuclide therapy; immunotherapy; tyrosine kinase inhibitors; and hypoxia-inducible factor 2 alpha inhibitors. Financial and social factors such as health insurance coverage and disparities also impact current clinical practice in the USA.
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Neoplasias das Glândulas Suprarrenais , Neoplasias Encefálicas , Paraganglioma , Feocromocitoma , Neoplasias das Glândulas Suprarrenais/tratamento farmacológico , Neoplasias Encefálicas/tratamento farmacológico , Humanos , Radioisótopos do Iodo , Proteínas da Membrana Plasmática de Transporte de Norepinefrina , Paraganglioma/tratamento farmacológico , Feocromocitoma/tratamento farmacológicoRESUMO
BACKGROUND: Induction with ibrutinib and rituximab provides an opportunity to minimise chemotherapy exposure, because upfront use of these targeted therapies could result in remission without chemotherapy and allow for consolidation with only four cycles of chemotherapy instead of the conventional eight. We aimed to determine the activity and safety of ibrutinib-rituximab induction followed by shortened chemoimmunotherapy (four cycles) with rituximab plus hyper-fractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone (R-HCVAD) alternating with methotrexate-cytarabine in previously untreated patients with mantle cell lymphoma. METHODS: We did a single-centre, single-arm, phase 2 trial in previously untreated patients with mantle cell lymphoma. Eligible patients were aged 65 years or younger and had serum bilirubin of less than 1·5 mg/dL, creatinine clearance of 30 mL/min or more, Eastern Cooperative Oncology Group performance status of 2 or less, and cardiac ejection fraction 50% or more by echocardiogram. Patients received 12 cycles of ibrutinib-rituximab induction (part A; oral ibrutinib 560 mg daily and intravenous rituximab 375 mg/m2 weekly for the first 4 weeks and then on day 1 of cycles 3-12). As soon as patients had a complete response, four cycles of R-HCVAD alternating with methotrexate-cytarabine (part B) were administered. If they did not have a complete response or had a partial response, patients received two cycles of R-HCVAD alternating with methotrexate-cytarabine followed by reassessment, up to a total of eight cycles. Patients were taken off study if they had stable disease or progression during R-HCVAD. The primary outcome was the overall response rate after part A. The analyses were conducted on an intention-to-treat basis. This trial is registered with ClinicalTrials.gov, number NCT02427620. FINDINGS: 131 patients were enrolled between June 12, 2015, and Dec 6, 2018. The median age was 56 years (IQR 49-60). 58 (50%) of 117 patients had high Ki-67 (≥30%). 129 (98%, 95% CI 95-100) of 131 patients had an overall response in part A. The most common grade 3-4 adverse events were lymphocytopenia (19 [14%] of 131), skin rash (16 [12%]), thrombocytopenia (12 [9%]), infections (11 [8%]), and fatigue (ten [8%]) in part A and lymphocytopenia (96 [73%]), leukocytopenia (42 [32%]), thrombocytopenia (40 [30%]), and neutropenia (26 [20%]) in part B. There was one on-study death, which was not deemed to be treatment-related. INTERPRETATION: Induction with ibrutinib-rituximab in the frontline treatment of young patients with mantle cell lymphoma is active and safe. This approach allowed minimisation of the number of chemotherapy cycles, thereby reducing the adverse events associated with chemotherapy. Newer trials bringing the next-generation Bruton's tyrosine kinase inhibitors into the frontline setting might obviate the need for chemotherapy altogether in patients with mantle cell lymphoma. FUNDING: Pharmacyclics, Janssen.
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Linfoma de Célula do Manto , Linfopenia , Trombocitopenia , Adenina/análogos & derivados , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Ciclofosfamida , Citarabina , Doxorrubicina , Humanos , Linfoma de Célula do Manto/tratamento farmacológico , Linfoma de Célula do Manto/patologia , Linfopenia/induzido quimicamente , Metotrexato , Pessoa de Meia-Idade , Piperidinas , Rituximab , Trombocitopenia/induzido quimicamente , Resultado do Tratamento , VincristinaRESUMO
PURPOSE: Most patients with mantle cell lymphoma (MCL) are older. In this study, we investigated the efficacy and safety of a chemotherapy-free combination with ibrutinib and rituximab (IR) in previously untreated older patients with MCL (age ≥ 65 years). METHODS: We enrolled 50 patients with MCL in this single-institution, single-arm, phase II clinical trial (NCT01880567). Patients with Ki-67% ≥ 50% and blastoid morphology were excluded. Ibrutinib was administered with rituximab up to 2 years with continuation of ibrutinib alone. The primary objective was to assess the overall response rate and safety of IR. In evaluable samples, whole-exome sequencing and bulk RNA sequencing from baseline tissue samples were performed. RESULTS: The median age was 71 years (interquartile range 69-76 years). Sixteen percent of patients had high-risk simplified MCL international prognostic index. The Ki-67% was low (< 30%) in 38 (76%) and moderately high (≥ 30%-50%) in 12 (24%) patients. The best overall response rate was 96% (71% complete response). After a median follow-up of 45 months (interquartile range 24-56 months), 28 (56%) patients came off study for various reasons (including four progression, 21 toxicities, and three miscellaneous reasons). The median progression-free survival and overall survival were not reached, and 3-year survival was 87% and 94%, respectively. None of the patients died on study therapy. Notably, 11 (22%) patients had grade 3 atrial fibrillation. Grade 3-4 myelosuppression was seen in < 5% of patients. Differential overexpression of CCND1, BIRC3, BANK1, SETBP1, AXIN2, and IL2RA was noted in partial responders compared with patients with complete response. CONCLUSION: IR combination is effective in older patients with MCL. Baseline evaluation for cardiovascular risks is highly recommended. Randomized trial is needed for definitive conclusions.
Assuntos
Adenina/análogos & derivados , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Linfoma de Célula do Manto/tratamento farmacológico , Piperidinas/uso terapêutico , Rituximab/uso terapêutico , Adenina/efeitos adversos , Adenina/uso terapêutico , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Biomarcadores Tumorais/genética , Progressão da Doença , Feminino , Humanos , Linfoma de Célula do Manto/genética , Linfoma de Célula do Manto/mortalidade , Masculino , Piperidinas/efeitos adversos , Intervalo Livre de Progressão , Rituximab/efeitos adversos , Análise de Sequência de RNA , Fatores de Tempo , Sequenciamento do ExomaRESUMO
PURPOSE: To directly compare the performance of pelvic mpMRI versus recently approved and increasingly used PSMA-based 18F-DCFPyL PET/CT in intermediate-high risk and biochemical recurrent prostate cancer patient cohort while exploring their potential differing applications in specific clinical scenarios. METHODS: A retrospective analysis was performed on patients who had 18F-DCFPyL PET/CT and pelvic mpMRI done from September 2021 to January 2022 at a single institution. The inclusion criteria were paired exams within a 3-month interval. Exclusion criteria were intervening treatment between exams, a change in PSA by more than 50% and absolute difference more than 1 ng/mL, or concurrent history of other malignancy. Abnormal lesions on these 2 imaging exams were reviewed with the identification of concordant and discordant imaging findings. The findings were verified by pathology or other imaging techniques within minimal 5-month clinical follow-up. RESULTS: A total of 57 patients with 57 paired exams were included. The rate of concordant exams was 43/57 or 75.4%. Lesion-based analyses of sensitivity, specificity, PPV and NPV for mpMRI and 18F-DCFPyL PET/CT in the prostate bed were 96%, 94%, 98%, 89% and 96%, 100%, 100%, 90% respectively. For pelvic lymph node metastases, the sensitivity, specificity, PPV and NPV for mpMRI and 18F-DCFPyL PET/CT were 52%, 100%, 100%, 55% and 100%, 100%, 100%, 100% respectively. For bone metastases, the sensitivity, specificity, PPV and NPV for mpMRI and 18F-DCFPyL PET/CT were 86%, 73%, 50%, 94% and 100%, 98%, 95%, 100% respectively. Exact McNemar's test for paired data suggested that in diagnostic performance between 18F-DCFPyL PET/CT and mpMRI was not statistically significant in prostate bed (p-value = 1.00), but significantly in pelvic lymph nodes (p-value < 0.0001) and bone lesions (p-value = 0.0026). CONCLUSION: Our study demonstrated that PSMA-based 18F-DCFPyL PET/CT and pelvic mpMRI have a good concordance rate in the detection of primary or recurrence prostate disease and can have complementary roles in the clinical assessment of the prostate bed lesions. However, there are key differences in their performance, with the notably superior performance of PSMA-based 18F-DCFPyL PET/CT in the detection of small metastatic nodal disease and bone metastases.
RESUMO
ABSTRACT: A 65-year-old man with fluciclovine-avid metastatic prostate small cell carcinoma with prostate-specific antigen (PSA) 19.4 ng/mL at diagnosis underwent system therapy and subsequent surgery and achieved hormonal response with PSA <0.1 ng/mL. An 18F-fluciclovine PET/CT scan 3 months after surgery was negative for disease. Although PSA remained <0.1 ng/mL, the rising carcinoembryonic antigen prompted an 18F-FDG PET/CT 6 weeks later. It showed multiple hypermetabolic lesions in the prostatectomy bed, liver, and right iliac bone, suggestive of malignant disease. The FDG-avid prostatectomy lesions were further confirmed on MRI. This case demonstrates that FDG PET/CT has a role in suspected metastatic prostate small cell carcinoma with negative fluciclovine PET examination.