RESUMEN
The PHERGain trial investigated the potential of metabolic imaging to identify candidates for chemotherapy deescalation in human epidermal growth factor receptor 2 (HER2)-positive, invasive, operable breast cancer with at least 1 breast lesion evaluable by [18F]FDG PET/CT. [18F]FDG PET/CT responders were defined as patients with an SUVmax reduction (ΔSUVmax) of at least 40% in all of their target lesions after 2 cycles of trastuzumab and pertuzumab (HP) (with or without endocrine therapy). In total, 227 of 285 patients (80%) included in the HP arm showed a predefined metabolic response and received a total of 8 cycles of HP (with or without endocrine therapy). Pathologic complete response (pCR), defined as ypT0/isN0, was achieved in 37.9% of the patients. Here, we describe the secondary preplanned analysis of the best cutoff of ΔSUVmax for pCR prediction. Methods: Receiver-operating-characteristic analysis was applied to look for the most appropriate ΔSUVmax cutoff in HER2-positive early breast cancer patients treated exclusively with neoadjuvant HP (with or without endocrine therapy). Results: The ΔSUVmax capability of predicting pCR in terms of the area under the receiver-operating-characteristic curve was 72.1% (95% CI, 65.1-79.2%). The optimal ΔSUVmax cutoff was found to be 77.0%, with a 51.2% sensitivity and a 78.7% specificity. With this cutoff, 74 of 285 patients (26%) would be classified as metabolic responders, increasing the pCR rate from 37.9% (cutoff ≥ 40%) to 59.5% (44/74 patients) (P < 0.01). With this optimized cutoff, 44 of 285 patients (15.4%) would avoid chemotherapy in either the neoadjuvant or the adjuvant setting compared with 86 of 285 patients (30.2%) using the original cutoff (P < 0.001). Conclusion: In the PHERGain trial, an increased SUVmax cutoff (≥77%) after 2 cycles of exclusive HP (with or without endocrine therapy) achieves a pCR in the range of the control arm with chemotherapy plus HP (59.5% vs. 57.7%, respectively), further identifying a subgroup of patients with HER2-addicted tumors. However, the original cutoff (≥40%) maximizes the number of patients who could avoid chemotherapy.
Asunto(s)
Neoplasias de la Mama , Tomografía Computarizada por Tomografía de Emisión de Positrones , Receptor ErbB-2 , Humanos , Neoplasias de la Mama/diagnóstico por imagen , Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/tratamiento farmacológico , Femenino , Receptor ErbB-2/metabolismo , Persona de Mediana Edad , Fluorodesoxiglucosa F18 , Anciano , Adulto , Resultado del Tratamiento , Trastuzumab/uso terapéutico , Anticuerpos Monoclonales Humanizados/uso terapéuticoRESUMEN
BACKGROUND: PHERGain was designed to assess the feasibility, safety, and efficacy of a chemotherapy-free treatment based on a dual human epidermal growth factor receptor 2 (HER2) blockade with trastuzumab and pertuzumab in patients with HER2-positive early breast cancer (EBC). It used an 18fluorine-fluorodeoxyglucose-PET-based, pathological complete response (pCR)-adapted strategy. METHODS: PHERGain was a randomised, open-label, phase 2 trial that took place in 45 hospitals in seven European countries. It randomly allocated patients in a 1:4 ratio with centrally confirmed, HER2-positive, stage I-IIIA invasive, operable breast cancer with at least one PET-evaluable lesion to either group A, where patients received docetaxel (75 mg/m2, intravenous), carboplatin (area under the curve 6 mg/mL per min, intravenous), trastuzumab (600 mg fixed dose, subcutaneous), and pertuzumab (840 mg loading dose followed by 420 mg maintenance doses, intravenous; TCHP), or group B, where patients received trastuzumab and pertuzumab with or without endocrine therapy, every 3 weeks. Random allocation was stratified by hormone receptor status. Centrally reviewed PET was conducted at baseline and after two treatment cycles. Patients in group B were treated according to on-treatment PET results. Patients in group B who were PET-responders continued with trastuzumab and pertuzumab with or without endocrine therapy for six cycles, while PET-non-responders were switched to receive six cycles of TCHP. After surgery, patients in group B who were PET-responders who did not achieve a pCR received six cycles of TCHP, and all patients completed up to 18 cycles of trastuzumab and pertuzumab. The primary endpoints were pCR in patients who were group B PET-responders after two treatment cycles (the results for which have been reported previously) and 3-year invasive disease-free survival (iDFS) in patients in group B. The study is registered with ClinicalTrials.gov (NCT03161353) and is ongoing. FINDINGS: Between June 26, 2017, and April 24, 2019, a total of 356 patients were randomly allocated (71 patients in group A and 285 patients in group B), and 63 (89%) and 267 (94%) patients proceeded to surgery in groups A and B, respectively. At this second analysis (data cutoff: Nov 4, 2022), the median duration of follow-up was 43·3 months (range 0·0-63·0). In group B, the 3-year iDFS rate was 94·8% (95% CI 91·4-97·1; p=0·001), meeting the primary endpoint. No new safety signals were identified. Treatment-related adverse events and serious adverse events (SAEs) were numerically higher in patients allocated to group A than to group B (grade ≥3 62% vs 33%; SAEs 28% vs 14%). Group B PET-responders with pCR presented the lowest incidence of treatment-related grade 3 or higher adverse events (1%) without any SAEs. INTERPRETATION: Among HER2-positive EBC patients, a PET-based, pCR-adapted strategy was associated with an excellent 3-year iDFS. This strategy identified about a third of patients who had HER2-positive EBC who could safely omit chemotherapy. FUNDING: F Hoffmann-La Roche.
Asunto(s)
Anticuerpos Monoclonales Humanizados , Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias de la Mama , Docetaxel , Fluorodesoxiglucosa F18 , Receptor ErbB-2 , Trastuzumab , Humanos , Femenino , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/patología , Persona de Mediana Edad , Trastuzumab/uso terapéutico , Trastuzumab/administración & dosificación , Receptor ErbB-2/metabolismo , Docetaxel/uso terapéutico , Docetaxel/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Anticuerpos Monoclonales Humanizados/uso terapéutico , Anticuerpos Monoclonales Humanizados/administración & dosificación , Anticuerpos Monoclonales Humanizados/efectos adversos , Adulto , Supervivencia sin Enfermedad , Anciano , Tomografía de Emisión de Positrones/métodos , Carboplatino/administración & dosificación , Carboplatino/uso terapéutico , RadiofármacosRESUMEN
ABSTRACT: A 77-year-old man with a personal history of familial Mediterranean fever presented with a slowly enlarging tumefaction of the left abdominal wall and persistent inflammatory syndrome despite good adherence to colchicine. 18 F-FDG PET/CT showed a hypermetabolic muscular mass of the abdominal wall along with other hypermetabolic lesions including a peritoneal mass and several subcutaneous soft tissue nodules. CT-guided needle biopsy led to the diagnosis of a muscular localization of a malignant peritoneal mesothelioma, which is an extremely rare complication of familial Mediterranean fever. Six courses of chemotherapy with carboplatin and pemetrexed allowed an almost complete response.
Asunto(s)
Fiebre Mediterránea Familiar , Mesotelioma Maligno , Mesotelioma , Neoplasias Peritoneales , Masculino , Humanos , Anciano , Fiebre Mediterránea Familiar/complicaciones , Fiebre Mediterránea Familiar/diagnóstico por imagen , Fiebre Mediterránea Familiar/tratamiento farmacológico , Tomografía Computarizada por Tomografía de Emisión de Positrones , Mesotelioma/complicaciones , Mesotelioma/diagnóstico por imagen , Fluorodesoxiglucosa F18 , Mesotelioma Maligno/complicaciones , Neoplasias Peritoneales/complicaciones , Neoplasias Peritoneales/diagnóstico por imagen , Neoplasias Peritoneales/patologíaRESUMEN
BACKGROUND: During the past decade, 18F-fluorocholine (FCH) PET/CT has been continuously performed at Tenon Hospital (Paris, France) for the detection of hyperfunctioning parathyroid glands (PT). METHODS: A cohort of 401 patients, deliberately referred for HPT since September 2012, has been analyzed. The aim of this real-life retrospective study was to determine the diagnostic utility of FCH in this setting, overall and in subgroups according to the type of hyperparathyroidism (HPT), the context of FCH in the imaging work-up and in the patient's history: initial imaging or persistence or recurrence after previous parathyroidectomy (PTX). The influence of the histologic type of resected PTs, hyperplasia or adenoma, on the preoperatory detection on FCH PET/CT has been studied as well. RESULTS: Four hundred one FCH PET/CTs were included in the cohort, performed in 323 patients with primary HPT (pHPT), including 18 with familial HPT (fHPT), and in 78 patients with secondary renal HPT (rHPT). The overall positivity rate in the 401 FCH PET/CTs was 73%. The PTX rate was twice greater in patients whose FCH PET/CT was positive than negative (73% vs. 35%). Abnormal PT(s) were pathology proven in 214 patients: only hyperplastic gland(s) in 75 cases and at least one adenoma in 136 cases; FCH PET/CT sensitivity was 89% and 92%, respectively. Similarly, there was no significant difference in patient-based sensitivity whether FCH PET/CT was performed as 1st line or later in the imaging work-up, or indicated for initial imaging or for suspicion of persistent or recurrent HPT. Gland-based sensitivity was significantly lower for hyperplasia than for adenoma (72% and 86%, respectively). The lowest gland-based sensitivity value was 65%, observed in case of hyperplasia and when FCH was performed late in the imaging work-up. FCH PET/CT correctly showed multiglandular HPT (MGD) in 36/61 proven cases, 59%. Results of ultrasonography (US) and 99mTc-sestaMIBI (MIBI) imaging were available in 346 and 178 patients, respectively. For both modalities, the corresponding sensitivity values were significantly less than those of FCH PET/CT (e.g., overall gland-based sensitivity 78% for FCH, 45% for US, 30% for MIBI) and MGD was detected in 32% of cases by US and 15% by MIBI. CONCLUSIONS: Although FCH PET/CT has been performed since 2017 as 1st line imaging for HPT at Tenon Hospital (Paris, France), a large majority of patients underwent prior US and/or MIBI in their preoperative work-up. Therefore, a selection bias is very likely, as most patients referred to FCH PET/CT had non-conclusive or discordant results of US and MIBI, explaining the low performance of those modalities in the present cohort compared to published results. Nevertheless, the superiority of FCH PET/CT over US and MIBI in detecting abnormal PTs reported in various comparative studies is definitely confirmed in this larger real-life cohort. The detection with FCH PET/CT of hyperplastic PTs was somewhat lower than that of adenomas but was better than using US or MIBI. The present results lead to recommend FCH PET/CT as the first line imaging modality in HPT when it is widely available or, if less available, at least in HPT with predominance of hyperplasia and/or MGD.
Asunto(s)
Adenoma , Hiperparatiroidismo Primario , Humanos , Tomografía Computarizada por Tomografía de Emisión de Positrones/métodos , Glándulas Paratiroides/diagnóstico por imagen , Glándulas Paratiroides/cirugía , Estudios Retrospectivos , Hiperplasia/diagnóstico por imagen , Hiperparatiroidismo Primario/cirugía , Colina , Tecnecio Tc 99m Sestamibi , Adenoma/diagnóstico por imagenRESUMEN
WHAT IS THIS SUMMARY ABOUT?: This is a summary of a publication about the PHERGain study, which was published in The Lancet Oncology in May 2021. The study includes 376 women with a type of breast cancer called HER2-positive breast cancer that can be removed by surgery. In the study, researchers wanted to learn if participants could be treated with two medicines called trastuzumab and pertuzumab without the need for chemotherapy. To identify HER2-positive tumors with more sensitivity to anti-HER2 therapies, the researchers used a type of imaging called a FDG-PET scan to check how well the treatments were working. WHAT HAPPENED IN THE PHERGAIN STUDY?: Participants took a treatment before surgery, consisting of either chemotherapy (docetaxel and carboplatin) plus trastuzumab and pertuzumab (group A) or trastuzumab and pertuzumab alone (plus hormone therapy if the tumor was hormone receptor-positive; group B). After two cycles of treatment, participants underwent a FDG-PET scan. Participants assigned to group A completed 6 cycles of treatment regardless of 18F-FDG-PET results. Participants in group B continued the same treatment until surgery if their FDG-PET scan showed the treatment was working. While participants who did not show a response started treatment with chemotherapy in addition to trastuzumab and pertuzumab. All participants then had surgery. WHAT WERE THE RESULTS?: The results revealed that, of the participants in group B who showed a response using FDG-PET scan, 37.9% achieved a disappearance of all invasive cancer in the breast and axillary lymph nodes. This rate appears to be higher than those reported in previous studies evaluating the same treatment. These participants also had less side effects and improved overall quality of life compared with participants taking chemotherapy plus trastuzumab and pertuzumab. WHAT DO THE RESULTS OF THE STUDY MEAN?: Early monitoring of how well participants respond to treatment by FDG-PET scan seems to identify participants with operable HER2-positive breast cancer who were more likely to benefit from trastuzumab and pertuzumab without the need to have chemotherapy. The PHERGain study is still ongoing and results on long-term survival are expected to be released in 2023. Clinical Trial Registration: NCT03161353 (ClinicalTrials.gov).
Asunto(s)
Neoplasias de la Mama , Humanos , Femenino , Trastuzumab/efectos adversos , Trastuzumab/administración & dosificación , Neoplasias de la Mama/patología , Fluorodesoxiglucosa F18/uso terapéutico , Calidad de Vida , Receptor ErbB-2 , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Terapia NeoadyuvanteAsunto(s)
Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Humanos , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/genética , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/genética , Pirazoles/uso terapéutico , Piridinas , Inhibidores de Proteínas Quinasas/uso terapéutico , Inhibidores de Proteínas Quinasas/farmacología , Proteínas Proto-Oncogénicas c-ret/genéticaRESUMEN
BACKGROUND: Several de-escalation approaches are under investigation in patients with HER2-positive, early-stage breast cancer. We assessed early metabolic responses to neoadjuvant trastuzumab and pertuzumab using 18F-fluorodeoxyglucose (18F-FDG)-PET (18F-FDG-PET) and the possibility of chemotherapy de-escalation using a pathological response-adapted strategy. METHODS: We did a multicentre, randomised, open-label, non-comparative, phase 2 trial in 45 hospitals in Spain, France, Belgium, Germany, the UK, Italy, and Portugal. Eligible participants were women aged 18 years or older with centrally confirmed, HER2-positive, stage I-IIIA, invasive, operable breast cancer (≥1·5 cm tumour size) with at least one breast lesion evaluable by 18F-FDG-PET, an Eastern Cooperative Oncology Group performance status of 0 or 1, and a baseline left ventricular ejection fraction of at least 55%. We randomly assigned participants (1:4), via an interactive response system using central block randomisation with block sizes of five, stratified by hormone receptor status, to either docetaxel (75 mg/m2 intravenous), carboplatin (area under the concentration-time curve 6 mg/mL per min intravenous), trastuzumab (subcutaneous 600 mg fixed dose), and pertuzumab (intravenous 840 mg loading dose, 420 mg maintenance doses; group A); or trastuzumab and pertuzumab (group B). Hormone receptor-positive patients allocated to group B were additionally given letrozole if postmenopausal (2·5 mg/day orally) or tamoxifen if premenopausal (20 mg/day orally). Centrally reviewed 18F-FDG-PET scans were done before randomisation and after two treatment cycles. Patients assigned to group A completed six cycles of treatment (every 3 weeks) regardless of 18F-FDG-PET results. All patients assigned to group B initially received two cycles of trastuzumab and pertuzumab. 18F-FDG-PET responders in group B continued this treatment for six further cycles; 18F-FDG-PET non-responders in this group were switched to six cycles of docetaxel, carboplatin, trastuzumab, and pertuzumab. Surgery was done 2-6 weeks after the last dose of study treatment. Adjuvant treatment was selected according to the neoadjuvant treatment administered, pathological response, hormone receptor status, and clinical stage at diagnosis. The coprimary endpoints were the proportion of 18F-FDG-PET responders in group B with a pathological complete response in the breast and axilla (ypT0/is ypN0) as determined by a local pathologist after surgery after eight cycles of treatment, and 3-year invasive disease-free survival of patients in group B, both assessed by intention to treat. The definitive assessment of pathological complete response was done at this primary analysis; follow-up to assess invasive disease-free survival is continuing, hence these data are not included in this Article. Safety was assessed in all participants who received at least one dose of study drug. Health-related quality-of-life was assessed with EORTC QLQ-C30 and QLQ-BR23 questionnaires at baseline, after two cycles of treatment, and before surgery. This trial is registered with EudraCT (2016-002676-27) and ClinicalTrials.gov (NCT03161353), and is ongoing. FINDINGS: Between June 26, 2017, and April 24, 2019, we randomly assigned 71 patients to group A and 285 to group B. Median follow-up was 5·7 months (IQR 5·3-6·0). 227 (80%) of 285 patients in group B were 18F-FDG-PET responders, of whom 86 (37·9%, 95% CI 31·6-44·5; p<0·0001 compared with the historical rate) of 227 had a pathological complete response. The most common haematological grade 3-4 adverse events were anaemia (six [9%] of 68 patients in group A vs four [1%] of 283 patients in group B), neutropenia (16 [24%] vs ten [4%]), and febrile neutropenia (14 [21%] vs 11 [4%]). Serious adverse events occurred in 20 (29%) of 68 patients in group A versus 13 (5%) of 283 patients in group B. No deaths were reported during neoadjuvant treatment. Global health status declined by at least 10% in 65·0% (95% CI 46·5-72·4) and 35·5% (29·7-41·7) of patients in groups A and B, respectively INTERPRETATION: 18F-FDG-PET identified patients with HER2-positive, early-stage breast cancer who were likely to benefit from chemotherapy-free dual HER2 blockade with trastuzumab and pertuzumab, and a reduced impact on global health status. Depending on the forthcoming results for the 3-year invasive disease-free survival endpoint, this strategy might be a valid approach to select patients not requiring chemotherapy. FUNDING: F Hoffmann-La Roche.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Neoplasias de la Mama/tratamiento farmacológico , Carboplatino/administración & dosificación , Docetaxel/administración & dosificación , Adulto , Anciano , Anticuerpos Monoclonales Humanizados/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Biomarcadores de Tumor/genética , Neoplasias de la Mama/diagnóstico por imagen , Neoplasias de la Mama/genética , Neoplasias de la Mama/patología , Supervivencia sin Enfermedad , Femenino , Fluorodesoxiglucosa F18/administración & dosificación , Humanos , Persona de Mediana Edad , Estadificación de Neoplasias , Posmenopausia , Premenopausia , Receptor ErbB-2/genética , Tamoxifeno/administración & dosificación , Trastuzumab/administración & dosificaciónRESUMEN
OBJECTIVES: Immunohistochemistry (IHC) is considered as a screening method for ALK rearrangement thanks to its excellent sensitivity. Strong marking on immunohistochemistry give the go-ahead to start ALK tyrosine kinase inhibitors (ALK TKI). Lack of therapeutic response may then lead to the suspicion of molecular alterations other than ALK rearrangements. METHODS: We present a patient with strong ALK and PD-L1 positive IHC expression lung sarcomatoid carcinoma with initial life-threatening disease progression after beginning ALK TKI. We also review the literature to summarize ALK amplification clinical features and therapeutic management in lung cancers. RESULTS: Fluorescence in situ Hybridization (FISH) revealed ALK amplification on the initial anatomopathological samples. Lack of ALK rearrangement and strong PD-L1 positive IHC expression led to the initiation of immune checkpoint inhibitor (ICI) as a second line of treatment, with an excellent response. CONCLUSION: We demonstrated that IHC positive test, in these cases, must be interpreted with caution. FISH analysis has to be recommended to confirm IHC results in case of unusual phenotype, such as smoker or lung cancer other than adenocarcinoma. Although lung carcinoma with ALK rearrangement seems to be not sensitive to ICI, further investigations should be conducted on other types of ALK molecular alterations. ALK amplifications, as observed in the present case, should not be an impediment to taking into account the PD-L1 marking for the initiation of treatment by immunotherapy.
Asunto(s)
Adenocarcinoma , Neoplasias Pulmonares , Adenocarcinoma/genética , Antígeno B7-H1/genética , Reordenamiento Génico , Humanos , Inmunohistoquímica , Hibridación Fluorescente in Situ , Pulmón , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/genética , Proteínas Tirosina Quinasas Receptoras/genéticaRESUMEN
Coronavirus disease 2019 (COVID-19) is an infectious disease caused by a new virus that has never been identified in humans before. COVID-19 caused at the time of writing of this article, 2.5 million cases of infections in 193 countries with 165,000 deaths, including two-third in Europe. In this context, Oncology Departments of the affected countries had to adapt quickly their health system care and establish new organizations and priorities. Thus, numerous recommendations and therapeutic options have been reported to optimize therapy delivery to patients with chronic disease and cancer. Obviously, while these cancer care recommendations are immediately applicable in Europe, they may not be applicable in certain emerging and low- and middle-income countries (LMICs). In this review, we aimed to summarize these international guidelines in accordance with cancer types, making a synthesis for daily practice to protect patients, staff and tailor anti-cancer therapy delivery taking into account patients/tumour criteria and tools availability. Thus, we will discuss their applicability in the LMICs with different organizations, limited means and different constraints.
Asunto(s)
Betacoronavirus/patogenicidad , Infecciones por Coronavirus/prevención & control , Control de Infecciones/organización & administración , Oncología Médica/organización & administración , Neoplasias/terapia , Pandemias/prevención & control , Neumonía Viral/prevención & control , Guías de Práctica Clínica como Asunto , COVID-19 , Infecciones por Coronavirus/epidemiología , Infecciones por Coronavirus/transmisión , Infecciones por Coronavirus/virología , Países en Desarrollo/economía , Carga Global de Enfermedades , Humanos , Control de Infecciones/economía , Control de Infecciones/normas , Oncología Médica/economía , Oncología Médica/normas , Neoplasias/diagnóstico , Neumonía Viral/epidemiología , Neumonía Viral/transmisión , Neumonía Viral/virología , Pobreza , SARS-CoV-2RESUMEN
PURPOSE: Cancer is a leading cause of mortality worldwide. Its incidence is still increasing, particularly in developing countries. Recent progresses further strengthen the differences between low/middle and high-income countries. This situation calls for joint action to reduce inequities in cancer outcomes among the patients. The Association of Radiotherapy and Oncology of the Mediterranean Area (AROME) and the European School of Oncology (ESO), have initiated joint conferences devoted to access to innovations in oncology in the Mediterranean area. The heterogeneity of the economic, political and cultural situations of the different participating countries, offers the opportunity to develop consensus conference. METHODS: Cancer prevention and treatment strategies were discussed according to existing international guidelines. The Scientific committee prepared 111 questions with an objective to prioritize the access to treatments and innovations in low/middle-income Mediterranean countries. The results from the votes of 65 oncology experts, coming from 16 countries and 33 institutions have been analysed and access priorities classified accordingly. RESULTS: Ninety six percent of the proposed general recommendations concerning national health care strategies, oncology education, and treatment organization were considered to be high priorities. Regarding access to systemic treatments, 41% of the drugs without validated predictive markers and 53% of those with validated predictive markers were considered to be 1st level priority. Only 4 biological tests were considered to be 1st level priority to access to innovation. CONCLUSIONS: AROME-ESO consensus offers to cancer specialists from developing countries a basis for discussion with health authorities and payers on the prioritization of access to innovations in cancer care.
Asunto(s)
Atención a la Salud/tendencias , Oncología Médica/tendencias , Neoplasias/epidemiología , Humanos , Neoplasias/tratamiento farmacológico , Neoplasias/radioterapia , ParisAsunto(s)
Neoplasias Pulmonares/tratamiento farmacológico , Compuestos Organofosforados/uso terapéutico , Inhibidores de Proteínas Quinasas/uso terapéutico , Pirimidinas/uso terapéutico , Sulfonas/uso terapéutico , Anciano , Humanos , Masculino , Mutación , Compuestos Organofosforados/farmacología , Inhibidores de Proteínas Quinasas/farmacología , Pirimidinas/farmacología , Sulfonas/farmacologíaRESUMEN
Splenic metastasis from cancers is extremely rare. They usually occur and are detected simultaneously with metastasis to other organs. We present a case of splenic metastasis from carcinoma of the breast occurring 5 years after initial treatment. The metastatic recurrence was an oligometastic form made from the association of a unique bone metastasis to a rib and the metastasis to the spleen. Treatment of the metastatic recurrence was a second line hormonotherapy as the primitive tumor was estrogen receptors positive and gave a 2 year's long control of the disease. A clinical progression occurred then, the patient complained from pain in the left hypochondrium and was objective on [18F]-FDG PET which leaded to splenectomy. This case is being reported because of the rarity of the lesion and its originality is the first reported case with use of an in vivo demonstration of estrogen receptors expression in the spleen metastasis using PET/CT with 16α-[18F]-Fluoroestradiol.
RESUMEN
Common sites for metastatic spreading from breast cancer are bones, lungs and liver, the skeletal muscle being an unusual site. Although rare, when skeletal muscle metastases occur they are associated with a poor prognosis. These metastases are clinically difficult to diagnose since they can be found without pain symptoms. Radiologically, magnetic resonance imaging has been considered better than computed tomography for imaging of the muscles and has been the first procedure to use in case of muscle metastasis suspicion. In the last years, positron emission tomography (PET) with 18Fluorine-2-fluoro-2-deoxy-d-glucose (18F-FDG) has emerged as the main imaging tool. We here report a case of a hormone receptor-positive/human epidermal growth factor receptor 2-negative patient who presented with a recurrent infiltrating ductal carcinoma and diffuse skeletal muscle metastases detected by 18F-FDG-PET. The treatment of the patient with exemestane and everolimus led to a durable complete response.
RESUMEN
We describe the potentiality of a new liposomal formulation enabling positron emission tomography (PET) and magnetic resonance MR() imaging. The bimodality is achieved by coupling a 68Ga-based radiotracer on the bilayer of magnetic liposomes. In order to enhance the targeting properties obtained under a permanent magnetic field, a sugar moiety was added in the lipid formulation. Two new phospholipids were synthesized, one with a specific chelator of 68Ga (DSPE-PEG-NODAGA) and one with a glucose moiety (DSPE-PEG-glucose). The liposomes were produced according to a fast and safe process, with a high radiolabeling yield. MR and PET imaging were performed on mice bearing human glioblastoma tumors (U87MG) after iv injection. The accumulation of the liposomes in solid tumor is evidenced by MR imaging and the amount is evaluated in vivo and ex vivo according to PET imaging. An efficient magnetic targeting is achieved with these new magnetic liposomes.
Asunto(s)
Glucosa/química , Liposomas/química , Acetatos/química , Animales , Línea Celular Tumoral , Química Farmacéutica/métodos , Femenino , Glioblastoma/diagnóstico , Compuestos Heterocíclicos con 1 Anillo/química , Humanos , Lípidos/química , Campos Magnéticos , Imagen por Resonancia Magnética/métodos , Ratones , Ratones Desnudos , Fosfatidiletanolaminas/química , Fosfolípidos/química , Polietilenglicoles/química , Tomografía de Emisión de Positrones/métodosRESUMEN
PURPOSE: Hybrid positron emission tomography/computed tomography (PET/CT) has now become available, as well as whole-body, low-dose multidetector row computed tomography (MDCT) or magnetic resonance imaging (MRI). The radioactive glucose analogue 18F-fluorodeoxyglucose (FDG) is the most widely used tracer but has a relatively low sensitivity in detecting multiple myeloma (MM). We compared FDG with a more recent metabolic tracer, 18F-fluorocholine (FCH), for the detection of MM lesions at time of disease relapse or progression. METHODS: We analyzed the results of FDG and FCH imaging in 21 MM patients undergoing PET/CT for suspected relapsing or progressive MM. For each patient and each tracer, an on-site reader and a masked reader independently determined the number of intraosseous and extraosseous foci of tracer and the intensity of uptake as measured by their SUVmax and the corresponding target/non-target ratio (T/NT). RESULTS: In the skeleton of 21 patients, no foci were found for two cases, uncountable foci were observed in four patients, including some mismatched FCH/FDG foci. In the 15 patients with countable bone foci, the on-site reader detected 72 FDG foci vs. 127 FCH foci (+76 %), whereas the masked reader detected 69 FDG foci vs. 121 FCH foci (+75 %), both differences being significant. Interobserver agreement on the total number of bone foci was very high, with a kappa coefficient of 0.81 for FDG and 0.89 for FCH. Measurement of uptake in the matched foci that took up both tracers revealed a significantly higher median SUVmax and T/NT for FCH vs. FDG. Almost all unmatched foci were FCH-positive FDG-negative (57/59 = 97 % on-site and 56/60 = 93 % on masked reading); they were more frequently observed than matched foci in the head and neck region. CONCLUSIONS: These findings suggest that PET/CT performed for suspected relapsing or progressive MM would reveal more lesions when using FCH rather than FDG.
Asunto(s)
Colina/análogos & derivados , Fluorodesoxiglucosa F18 , Mieloma Múltiple/diagnóstico por imagen , Tomografía Computarizada por Tomografía de Emisión de Positrones/métodos , Anciano , Anciano de 80 o más Años , Progresión de la Enfermedad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Proyectos Piloto , Radiofármacos , Recurrencia , Reproducibilidad de los Resultados , Sensibilidad y EspecificidadRESUMEN
A 59-year-old transexual (male to female) patient presented with a squamous cell carcinoma of the larynx. She underwent an F-FDG PET/CT for initial staging. The examination showed high F-FDG uptake of the primary lesion and a homolateral lymphadenopathy. Incidental heterogeneous uptake of round hyperdense lesions in the gluteal muscles and subcutaneous fat was visualized. The medical history revealed secondly that the patient had had free liquid silicone injections 30 years before the examination. Although the injection of free silicone is not practised since the 1980s, this incidental finding should prompt to check the patient's medical history over several decades.
Asunto(s)
Nalgas/diagnóstico por imagen , Carcinoma de Células Escamosas/diagnóstico por imagen , Granuloma/diagnóstico por imagen , Neoplasias de Cabeza y Cuello/diagnóstico por imagen , Neoplasias Laríngeas/diagnóstico por imagen , Femenino , Fluorodesoxiglucosa F18 , Granuloma/inducido químicamente , Humanos , Hallazgos Incidentales , Inyecciones Intramusculares , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Tomografía Computarizada por Tomografía de Emisión de Positrones , Radiofármacos , Siliconas/efectos adversos , Carcinoma de Células Escamosas de Cabeza y Cuello , Personas TransgéneroRESUMEN
UNLABELLED: The standardized uptake lean body mass (SUL), calculated using lean body mass (LBM), is essential for the semiquantification of (18)F-FDG uptake using PET coupled with CT to avoid a bias linked to the adipose mass. It allows the evaluation of a response to therapy according PERCIST 1.0. The aim of this study was to evaluate the reliability of a method for the estimation of the LBM using the data of the low-dose CT from PET/CT acquired over standard acquisition fields (from skull base to ischia, from vertex to ischia, from skull base to mid thigh, from vertex to mid thigh). METHODS: We wrote an automated program that determined the LBM from a CT with limited fields of acquisition and applied this method in a large (184 patients) and heterogeneous population. Its results were compared with the measurement of LBM from whole-body CT (reference standard) and the results of 5 predictive equations described in the literature. RESULTS: The results of LBM measurement evaluated with this technique were much closer to the reference standard than those obtained by the mathematic formulas. The intraclass correlations (ICC) of this technique compared with the reference standard were excellent (the best ICC being obtained for the largest acquisition field, from vertex to mid thigh: ICC, 0.994; 95% confidence interval [95% CI], 0.992-0.995; P < 0.0001), much better than the ICC obtained with the mathematic formulas (the best ICC for a mathematic formula was 0.841; 95% CI, 0.714-0.903; P < 0.0001). Moreover, the analysis with the Bland-Altman plot showed that the differences in mean lean masses between the studied technique and the reference standard was the smallest for the proposed technique (for the largest acquisition field, mean difference 0.2 kg with the narrowest 95% CI [-1.8 to 2.2 kg]). CONCLUSION: This technique could be easily implemented on computers used in practice to allow a more reliable assessment of the SUL in clinical practice notably for the therapeutic evaluations after PERCIST 1.0.
Asunto(s)
Índice de Masa Corporal , Fluorodesoxiglucosa F18/metabolismo , Procesamiento de Imagen Asistido por Computador/métodos , Tomografía Computarizada por Tomografía de Emisión de Positrones , Dosis de Radiación , Adulto , Anciano , Anciano de 80 o más Años , Transporte Biológico , Femenino , Humanos , Masculino , Persona de Mediana Edad , Adulto JovenRESUMEN
We compared (18)F-fluorocholine hybrid positron emission tomography/X-ray computed tomography (FCH-PET/CT) with ultrasonography (US) and scintigraphy in patients with hyperparathyroidism and discordant, or equivocal results of US and (123)I/(99m)Tc-sesta-methoxyisobutylisonitrile (sestaMIBI) dual-phase parathyroid scintigraphy. FCH-PET/CT was performed in 17 patients with primary (nâ=â11) lithium induced (nâ=â1) or secondary hyperparathyroidism (1 dialyzed, 4 renal-transplanted).The reference standard was based on results of surgical exploration and histopathological examination. The results of imaging modalities were evaluated, on site and by masked reading, on per-patient and per-lesion bases.In a first approach, equivocal images/foci were considered as negative. On a per-patient level, the sensitivity was for US 38%, for scintigraphy 69% by open and 94% by masked reading, and for FCH-PET/CT 88% by open and 94% by masked reading. On a per-lesion level, sensitivity was for US 42%, for scintigraphy 58% by open and 83% by masked reading, and for FCH-PET/CT 88% by open and 96% by masked reading. One ectopic adenoma was missed by the 3 imaging modalities. Considering equivocal images/foci as positive increased the accuracy of the open reading of scintigraphy or of FCH-PET/CT, but not of US. FCH-PET/CT was significantly superior to US in all approaches, whereas it was more sensitive than scintigraphy only for open reading considering equivocal images/foci as negative (Pâ=â0.04). FCH uptake was more intense in adenomas than in hyperplastic parathyroid glands. Thyroid lesions were suspected in 9 patients. They may induce false-positive results as in one case of oncocytic thyroid adenoma, or false-negative results as in one case of intrathyroidal parathyroid adenoma. Thyroid cancer (4 cases) can be visualized with FCH as with (99m)Tc-sestaMIBI, but the intensity of uptake was moderate, similar to that of parathyroid hyperplasia.This pilot study confirmed that FCH-PET/CT is an adequate imaging tool in patients with primary or secondary hyperparathyroidism, since both adenomas and hyperplastic parathyroid glands can be detected. The sensitivity of FCH-PET/CT was better than that of US and was not inferior to that of dual-phase dual-isotope (123)I/(99m)Tc-scintigraphy. Further studies should evaluate whether FCH could replace (99m)Tc-sestaMIBI as the functional agent for parathyroid imaging, but US would still be useful to identify thyroid lesions.