ABSTRACT
Objetivo Valorar la utilidad clínica de los criterios PERCIST y de los cambios en los parámetros cuantitativos de la PET/TC con [18F]FDG como factores pronósticos para la supervivencia libre de progresión y la supervivencia cáncer-específica en pacientes con cáncer de esófago tratados mediante quimiorradioterapia. Material y métodos Se valoraron retrospectivamente 50 pacientes (48 hombres) diagnosticados de cáncer de esófago durante un intervalo de 7,5 años. Se utilizaron los criterios PERCIST para valorar la respuesta a la neoadyuvancia. Asimismo, se determinaron las variaciones del SUV máximo, volumen metabólico tumoral y glucólisis tumoral total entre los estudios PET/TC pre- y postratamiento. Las curvas ROC, el método de Kaplan-Meier y el modelo de regresión de Cox se aplicaron para el análisis de factores pronósticos y curvas de supervivencia. Resultados El seguimiento medio fue de 26,8 meses, produciéndose 40 recurrencias-progresiones y 41 muertes. El análisis de supervivencia mostró curvas de supervivencia cáncer-específica con diferencias estadísticamente significativas en relación con los criterios PERCIST y la variación del volumen metabólico tumoral y la glucólisis tumoral total. Los criterios PERCIST fueron el único factor predictivo independiente en el análisis multivariante. Ni el SUV máximo ni el tamaño tumoral fueron predictores para ninguno de los criterios de evaluación. Conclusión La aplicación de los criterios PERCIST, así como el cambio de volumen metabólico tumoral y glucólisis tumoral total de los estudios PET/TC demostraron ser factores pronósticos para la supervivencia cáncer-específica en pacientes de nuestro entorno tratados por cáncer de esófago. Los resultados podrían ayudar a personalizar el tratamiento (AU)
Aim To assess the clinical utility of PERCIST criteria and changes in [18F]FDG PET/CT quantitative parameters as prognostic factors for progression-free survival and cancer-specific survival in patients with esophageal cancer treated by chemoradiotherapy. Material and methods Fifty patients (48 men) diagnosed with esophageal cancer were retrospectively evaluated over a 7.5-year interval. PERCIST criteria were used to assess response to neoadjuvant therapy. Variations in the metabolic parameters maximum SUV, metabolic tumor volume and total lesion glycolysis between pre- and post-treatment PET/CT studies were also determined. ROC curves, Kaplan-Meier method and Cox regression model were used for the analysis of prognostic factors and survival curves. Results The average follow-up was 26.8 months, with 40 recurrences-progressions and 41 deaths. Survival analysis showed statistically significant differences in cancer-specific survival curves for PERCIST criteria and variation of metabolic tumor volume and total lesion glycolysis. PERCIST criteria were the only independent predictor in the multivariate analysis. Neither maximum SUV nor tumor size were predictors for any of the assessment criteria Conclusion Application of PERCIST criteria as well as change in metabolic tumor volume and total lesion glycolysis from PET/CT studies proved to be prognostic factors for cancer-specific survival in patients in our setting treated for esophageal cancer. The results could help to personalize treatment (AU)
Subject(s)
Humans , Male , Female , Middle Aged , Aged , Esophageal Neoplasms/diagnostic imaging , Esophageal Neoplasms/therapy , Fluorodeoxyglucose F18/metabolism , Positron-Emission Tomography , Radiopharmaceuticals , Neoadjuvant Therapy , Chemoradiotherapy , PrognosisABSTRACT
AIM: To assess the clinical utility of PERCIST criteria and changes in [18F]FDG PET/CT quantitative parameters as prognostic factors for progression-free survival and cancer-specific survival (CSS) in patients with esophageal cancer treated by chemoradiotherapy. MATERIAL AND METHODS: Fifty patients (48 men) diagnosed with esophageal cancer were retrospectively evaluated over a 7.5-year interval. PERCIST criteria were used to assess response to neoadjuvant therapy. Variations in the metabolic parameters maximum SUV (SUVmax), metabolic tumor volume (MTV) and total lesion glycolysis (TLG) between pre- and post-treatment PET/CT studies were also determined. ROC curves, Kaplan-Meier method and Cox regression model were used for the analysis of prognostic factors and survival curves. RESULTS: The average follow-up was 26.8 months, with 40 recurrences-progressions and 41 deaths. Survival analysis showed statistically significant differences in CSS curves for PERCIST criteria and variation of MTV and TLG. PERCIST criteria were the only independent predictor in the multivariate analysis. Neither SUVmax nor tumor size were predictors for any of the assessment criteria. CONCLUSION: Application of PERCIST criteria as well as change in MTV and TLG from PET/CT studies proved to be prognostic factors for CSS in patients in our setting treated for esophageal cancer. The results could help to personalize treatment.
Subject(s)
Esophageal Neoplasms , Positron Emission Tomography Computed Tomography , Male , Humans , Positron Emission Tomography Computed Tomography/methods , Neoadjuvant Therapy , Prognosis , Radiopharmaceuticals , Retrospective Studies , Fluorodeoxyglucose F18/metabolism , Esophageal Neoplasms/diagnostic imaging , Esophageal Neoplasms/therapyABSTRACT
Objetivo El estreñimiento crónico es una patología frecuente en la práctica clínica. Ante la falta de respuesta al tratamiento se recomienda evaluar la función gastrointestinal. Para ello puede ser útil la gammagrafía, aunque su uso no es generalizado. El objetivo del estudio fue valorar la utilidad de la gammagrafía de tránsito gastrointestinal en pacientes con estreñimiento crónico. Material y métodos Se valoraron 20 pacientes (13 niños) remitidos para estudio gammagráfico por estreñimiento crónico refractario al tratamiento, siringomielia, rectocele o migraña abdominal. Todos fueron sometidos a valoración clínica, determinación analítica, estudio de imagen radiológica y/o biopsia rectal. Se realizó un protocolo de estudio completo, incluyendo gammagrafía de vaciamiento gástrico, tránsito de intestino delgado y colónico. Para ello, se administró una dosis de [111In]In-DTPA diluida en agua (37MBq) junto con comida estandarizada. Siguiendo las guías internacionales, se definieron áreas de interés en el estómago, en el íleon terminal y en diferentes regiones del intestino grueso para calcular el centro geométrico como medida de progresión. Resultados De los 13 pacientes en edad pediátrica, 10 presentaron patrones gammagráficos anormales, modificando el tratamiento en 8 de ellos. La mayoría de los niños no mostraron alteraciones en las exploraciones radiológicas. En pacientes adultos, el resultado de la prueba conllevó el cambio del manejo terapéutico en todos ellos, Conclusiones El estudio gammagráfico proporcionó información útil en el estudio del estreñimiento crónico, influyendo en el diagnóstico y en el manejo terapéutico del paciente. La información fisiológica y cuantitativa que proporciona permite la determinación global y regional del tránsito gastrointestinal (AU)
Aim Chronic constipation is a common pathology in clinical practice. In the absence of response to treatment, assessment of gastrointestinal function is recommended. This can be performed by scintigraphy, although its use is not widespread. The aim of this paper was to assess the utility of gastrointestinal transits scintigraphy in patients with chronic constipation. Material and methods Twenty patients (13 children) sent for scintigraphy for chronic constipation refractory to treatment, syringomyelia, rectocele or abdominal migraine were evaluated. All underwent clinical assessment, analytical determination, radiological imaging and/or rectal biopsy. A complete study protocol was performed, including gastric emptying, small bowel and colonic transits scintigraphy. For this, a dose of [111In]In-DTPA diluted in water (37MBq) was administered together with standardized food. Following international guidelines, regions of interest were defined in the stomach, terminal ileum and different regions of the large intestine to calculate the geometric center as a measure of progression. Results Of the 13 pediatric patients, 10 had abnormal gammagraphic patterns, with treatment being modified in 8 of them. Most of the children showed no alterations on radiological explorations. In adult patients, the results of the test changed the therapeutic management in all of them. Conclusions Scintigraphic study provided useful information in the study of chronic constipation, influencing the diagnosis and therapeutic management of the patient. The physiological and quantitative information it provides allows both global and regional of gastrointestinal transit time determination (AU)
Subject(s)
Humans , Male , Female , Child, Preschool , Child , Adolescent , Adult , Middle Aged , Aged , Constipation/diagnostic imaging , Gastrointestinal Transit , Retrospective Studies , Radionuclide Imaging , Chronic DiseaseABSTRACT
AIM: Chronic constipation is a common pathology in clinical practice. In the absence of response to treatment, assessment of gastrointestinal function is recommended. This can be performed by scintigraphy, although its use is not widespread. The aim of this paper was to assess the utility of gastrointestinal transits scintigraphy in patients with chronic constipation. MATERIAL AND METHODS: Twenty patients (13 children) sent for scintigraphy for chronic constipation refractory to treatment, syringomyelia, rectocele or abdominal migraine were evaluated. All underwent clinical assessment, analytical determination, radiological imaging and/or rectal biopsy. A complete study protocol was performed, including gastric emptying, small bowel and colonic transits scintigraphy. For this, a dose of [111In]In-DTPA diluted in water (37MBq) was administered together with standardized food. Following international guidelines, regions of interest were defined in the stomach, terminal ileum and different regions of the large intestine to calculate the geometric center as a measure of progression. RESULTS: Of the 13 pediatric patients, 10 had abnormal gammagraphic patterns, with treatment being modified in 8 of them. Most of the children showed no alterations on radiological explorations. In adult patients, the results of the test changed the therapeutic management in all of them. CONCLUSIONS: Scintigraphic study provided useful information in the study of chronic constipation, influencing the diagnosis and therapeutic management of the patient. The physiological and quantitative information it provides allows both global and regional of gastrointestinal transit time determination.
Subject(s)
Constipation , Gastrointestinal Transit , Adult , Child , Colon , Constipation/diagnostic imaging , Gastric Emptying/physiology , Gastrointestinal Transit/physiology , Humans , Radionuclide ImagingABSTRACT
Objetivo: Determinar la utilidad de los parámetros cuantitativos de la PET/TC con 18F-FDG como factores pronósticos para la respuesta al tratamiento neoadyuvante, la supervivencia libre de progresión (SLP) y la supervivencia cáncer específica (SCE) en pacientes con carcinoma de células escamosas de esófago (CCE). Material y métodos: Se valoraron retrospectivamente 30 pacientes (29 hombres) diagnosticados de CCE durante un intervalo de 6años. Se determinaron los parámetros metabólicos SUV máximo (SUVmax), SUV medio (SUVmed), volumen metabólico tumoral (MTV) y glucólisis tumoral total (TLG) del estudio PET/TC al diagnóstico. Tras tratamiento con quimioterapia y/o radioterapia, se valoró la respuesta al tratamiento y la supervivencia de los pacientes. La comparación de parámetros entre grupos de respondedores y no respondedores se realizó mediante la prueba U de Mann-Whitney. Las curvas ROC y el método de Kaplan-Meier se utilizaron para el análisis de factores pronósticos y curvas de supervivencia. Resultados: El seguimiento medio fue de 22,4meses, produciéndose 22 recurrencias-progresiones y 25 fallecimientos. Se demostraron diferencias significativas entre respondedores y no respondedores con respecto al tamaño tumoral, el MTV y la TLG. El análisis de supervivencia halló diferencias significativas para SCE y SLP dependiendo de estos tres parámetros. Conclusión: Los parámetros metabólicos MTV y TLG, así como el tamaño tumoral, fueron factores pronósticos para la respuesta al tratamiento neoadyuvante, la SLP y la SCE en pacientes diagnosticados de CCE. Ni el SUVmax ni el SUVmed fueron predictores para ninguno de los criterios de evaluación. Los resultados permitirían personalizar el tratamiento de los pacientes (AU)
Aim: To determine the utility of 18F-FDG PET/CT quantitative parameters as prognostic factors for the response to neoadjuvant treatment, progression-free survival (PFS) and cancer-specific survival (CSS) in patients with esophageal squamous cell carcinoma (SCC). Material and methods: Thirty patients (29 men) diagnosed with SCC were retrospectively evaluated over a 6-year interval. Metabolic parameters were determined: maximum SUV (SUVmax), mean SUV (SUVmed), metabolic tumor volume (MTV) and total lesion glycolysis (TLG) from baseline PET/CT study. After treatment with chemotherapy and/or radiotherapy, response to treatment and patient survival were assessed. The comparison of parameters between groups of responders and non-responders was carried out using a Mann-Whitney U test. ROC curves and the Kaplan-Meier method were used for analysis of prognostic factors and survival curves. Results: The average follow-up was 22.4months, with 22 recurrence-progressions and 25 deads. Significant differences were demonstrated between responders and non-responders with respect to tumor size, MTV and TLG. Survival analysis found significant differences for SCE and CSS depending on these three parameters. Conclusion: Metabolic parameters MTV and TLG, and tumor size were prognostic factors for neoadjuvant treatment response, PFS, and CSS in patients diagnosed with SCC. Neither SUVmax nor SUVmed were predictive for any of the evaluation criteria. Results could help to personalize patient treatment (AU)
Subject(s)
Humans , Male , Female , Adult , Middle Aged , Aged , Aged, 80 and over , Esophageal Squamous Cell Carcinoma/diagnostic imaging , Esophageal Neoplasms/diagnostic imaging , Positron Emission Tomography Computed Tomography , Fluorodeoxyglucose F18 , Retrospective Studies , Follow-Up Studies , Disease-Free Survival , Radiopharmaceuticals , PrognosisABSTRACT
AIM: To determine the utility of [18F]FDG PET/CT quantitative parameters as prognostic factors for the response to neoadjuvant treatment, progression-free survival (PFS) and cancer-specific survival (CSS) in patients with esophageal squamous cell carcinoma (SCC). MATERIAL AND METHODS: Thirty patients (29 men) diagnosed with SCC were retrospectively evaluated over a 6-year interval. Metabolic parameters were determined: maximum SUV (SUVmax), mean SUV (SUVmed), metabolic tumor volume (MTV) and total lesion glycolysis (TLG) from baseline PET/CT study. After treatment with chemotherapy and/or radiotherapy, response to treatment and patient survival were assessed. The comparison of parameters between groups of responders and non-responders was carried out using a Mann-Whitney U test ROC curves and the Kaplan-Meier method were used for analysis of prognostic factors and survival curves. RESULTS: The average follow-up was 22.4 months, with 22 recurrence-progressions and 25 deaths. Significant differences were demonstrated between responders and non-responders with respect to tumor size, MTV and TLG. Survival analysis found significant differences for SCE and CSS depending on these three parameters. CONCLUSION: Metabolic parameters MTV and TLG, and tumor size were prognostic factors for neoadjuvant treatment response, PFS, and CSS in patients diagnosed with SCC. Neither SUVmax nor SUVmed were predictive for any of the evaluation criteria. Results could help to personalize patient treatment.
Subject(s)
Carcinoma, Squamous Cell , Esophageal Neoplasms , Esophageal Squamous Cell Carcinoma , Carcinoma, Squamous Cell/diagnostic imaging , Carcinoma, Squamous Cell/therapy , Epithelial Cells , Esophageal Neoplasms/diagnostic imaging , Esophageal Neoplasms/therapy , Esophageal Squamous Cell Carcinoma/diagnostic imaging , Fluorodeoxyglucose F18 , Humans , Male , Positron Emission Tomography Computed Tomography/methods , Prognosis , Radiopharmaceuticals , Retrospective StudiesABSTRACT
AIM: To determine the utility of 18F-FDG PET/CT quantitative parameters as prognostic factors for the response to neoadjuvant treatment, progression-free survival (PFS) and cancer-specific survival (CSS) in patients with esophageal squamous cell carcinoma (SCC). MATERIAL AND METHODS: Thirty patients (29 men) diagnosed with SCC were retrospectively evaluated over a 6-year interval. Metabolic parameters were determined: maximum SUV (SUVmax), mean SUV (SUVmed), metabolic tumor volume (MTV) and total lesion glycolysis (TLG) from baseline PET/CT study. After treatment with chemotherapy and/or radiotherapy, response to treatment and patient survival were assessed. The comparison of parameters between groups of responders and non-responders was carried out using a Mann-Whitney U test. ROC curves and the Kaplan-Meier method were used for analysis of prognostic factors and survival curves. RESULTS: The average follow-up was 22.4months, with 22 recurrence-progressions and 25 deads. Significant differences were demonstrated between responders and non-responders with respect to tumor size, MTV and TLG. Survival analysis found significant differences for SCE and CSS depending on these three parameters. CONCLUSION: Metabolic parameters MTV and TLG, and tumor size were prognostic factors for neoadjuvant treatment response, PFS, and CSS in patients diagnosed with SCC. Neither SUVmax nor SUVmed were predictive for any of the evaluation criteria. Results could help to personalize patient treatment.
ABSTRACT
AIM: To assess the utility of 18F-FDG PET/CT quantitative parameters as prognostic factor in patients diagnosed with localized and inoperable lung cancer treated by stereotactic body radiotherapy (SBRT). MATERIAL AND METHODS: Fifty patients (42 men) diagnosed in the last 7years with early-stage lung cancer and treated with SBRT alone were assessed by a prospective study. After PET/CT study, metabolic parameters maximum SUV (SUVmax), metabolic tumor volume (MTV) and total lesion glycolysis (TLG) were determined at different thresholds. The prognostic factors for overall survival (OS), cause-specific survival (CS) and disease-free survival (DFS) were analysed by Cox proportional hazards model and the survival analysis by Kaplan-Meier method. RESULTS: The average follow-up was 39.6months, with 21 recurrences and 24 dead. Univariate analysis determined MTV30 and MTV40 as predictors for OS; MTV30, MTV40, TLG30 and TLG40 for CS, and MTV2, MTV30, MTV40, TLG2, TLG30 and TLG40 for DFS. Survival analysis found statistically significant differences for CS and DFS depending on tumor size and for DFS considering the cut-off values of MTV2 and TLG2 (threshold SUVmax=2). SUVmax, age and sex were not shown to be significant factors. CONCLUSION: Pre-treatment quantitative assessment using metabolic parameters MTV2 and TLG2 as well as tumor size proved to be prognostic factors in patients diagnosed with localized and inoperable lung cancer treated by SBRT. Results could help to personalize treatment.
Subject(s)
Carcinoma, Non-Small-Cell Lung/diagnostic imaging , Fluorine Radioisotopes , Fluorodeoxyglucose F18 , Lung Neoplasms/diagnostic imaging , Positron Emission Tomography Computed Tomography/methods , Radiopharmaceuticals , Aged , Aged, 80 and over , Area Under Curve , Carcinoma, Non-Small-Cell Lung/etiology , Carcinoma, Non-Small-Cell Lung/surgery , Combined Modality Therapy , Cone-Beam Computed Tomography , Female , Follow-Up Studies , Humans , Kaplan-Meier Estimate , Lung Neoplasms/etiology , Lung Neoplasms/surgery , Male , Middle Aged , Neoplasm Recurrence, Local , Prognosis , Proportional Hazards Models , Prospective Studies , ROC Curve , Radiosurgery , Radiotherapy, Intensity-ModulatedABSTRACT
BACKGROUND: Checkpoint kinase 1 (Chk1) inhibition following chemotherapy-elicited DNA damage overrides cell cycle arrest and induces mitotic catastrophe and cell death. GDC-0575 is a highly-selective oral small-molecule Chk1 inhibitor that results in tumor shrinkage and growth delay in xenograft models. We evaluated the safety, tolerability, and pharmacokinetic properties of GDC-0575 alone and in combination with gemcitabine. Antitumor activity and Chk1 pathway modulation were assessed. PATIENTS AND METHODS: In this phase I open-label study, in the dose escalation stage, patients were enrolled in a GDC-0575 monotherapy Arm (1) or GDC-0575 combination with gemcitabine Arm (2) to determine the maximum tolerated dose. Patients in arm 2 received either i.v. gemcitabine 1000 mg/m2 (arm 2a) or 500 mg/m2 (arm 2b), followed by GDC-0575 (45 or 80 mg, respectively, as RP2D). Stage II enrolled disease-specific cohorts. RESULTS: Of 102 patients treated, 70% were female, the median age was 59 years (range 27-85), and 47% were Eastern Cooperative Oncology Group PS 0. The most common tumor type was breast (37%). The most frequent adverse events (all grades) related to GDC-0575 and/or gemcitabine were neutropenia (68%), anemia (48%), nausea (43%), fatigue (42%), and thrombocytopenia (35%). Maximum concentrations of GDC-0575 were achieved within 2 hours of dosing, and half-life was â¼23 hours. No pharmacokinetic drug-drug interaction was observed between GDC-0575 and gemcitabine. Among patients treated with GDC-0575 and gemcitabine, there were four confirmed partial responses, three occurring in patients with tumors harboring TP53 mutation. Pharmacodynamic data were consistent with GDC-0575 inhibition of gemcitabine-induced expression of pCDK1/2. CONCLUSION: GDC-0575 can be safely administered as a monotherapy and in combination with gemcitabine; however, overall tolerability with gemcitabine was modest. Hematological toxicities were frequent but manageable. Preliminary antitumor activity was observed but limited to a small number of patients with a variety of refractory solid tumors treated with GDC-0575 and gemcitabine. CLINICAL TRIAL NUMBER: NCT01564251.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Deoxycytidine/analogs & derivatives , Neoplasms/drug therapy , Piperidines/administration & dosage , Protein Kinase Inhibitors/administration & dosage , Pyridines/administration & dosage , Pyrroles/administration & dosage , Adult , Aged , Aged, 80 and over , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Antineoplastic Combined Chemotherapy Protocols/pharmacokinetics , Checkpoint Kinase 1/antagonists & inhibitors , Deoxycytidine/administration & dosage , Deoxycytidine/adverse effects , Deoxycytidine/pharmacokinetics , Dose-Response Relationship, Drug , Drug Interactions , Fatigue , Female , Half-Life , Humans , Male , Maximum Tolerated Dose , Middle Aged , Nausea , Neutropenia/chemically induced , Neutropenia/epidemiology , Piperidines/adverse effects , Piperidines/pharmacokinetics , Protein Kinase Inhibitors/adverse effects , Protein Kinase Inhibitors/pharmacokinetics , Pyridines/adverse effects , Pyridines/pharmacokinetics , Pyrroles/adverse effects , Pyrroles/pharmacokinetics , Thrombocytopenia , Treatment Outcome , GemcitabineABSTRACT
PURPOSE: This phase I trial evaluated the safety, pharmacokinetic profile, and antitumor activity of investigational oral TORC1/2 inhibitor TAK-228 plus paclitaxel, with/without trastuzumab, in patients with advanced solid malignancies. METHODS: Sixty-seven patients received TAK-228 6-40 mg via three dosing schedules; once daily for 3 days (QDx3d QW) or 5 days per week (QDx5d QW), and once weekly (QW) plus paclitaxel 80 mg/m2 (dose-escalation phase, n = 47) and with/without trastuzumab 2 mg/kg (expansion phase, n = 20). Doses were escalated using a modified 3 + 3 design, based upon dose-limiting toxicities in cycle 1. RESULTS: TAK-228 pharmacokinetics exhibited dose-dependent increase in exposure when dosed with paclitaxel and no apparent differences when administered with or 24 h after paclitaxel. Dose-limiting toxicities were dehydration, diarrhea, stomatitis, fatigue, rash, thrombocytopenia, neutropenia, leukopenia, and nausea. The maximum tolerated dose of TAK-228 was determined as 10-mg QDx3d QW; the expansion phase proceeded with 8-mg QDx3d QW. Overall, the most common grade ≥3 drug-related toxicities were neutropenia (21%), diarrhea (12%), and hyperglycemia (12%). Of 54 response-evaluable patients, eight achieved partial response and six had stable disease lasting ≥6 months. CONCLUSION: TAK-228 demonstrated a safety profile consistent with other TORC inhibitors and promising preliminary antitumor activity in a range of tumor types; no meaningful difference was noted in the pharmacokinetics of TAK-228 when administered with or 24 h after paclitaxel. These findings support further investigation of TAK-228 in combination with other agents including paclitaxel, with/without trastuzumab, in patients with advanced solid tumors. CLINICALTRIALS. GOV IDENTIFIER: NCT01351350.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Benzoxazoles/administration & dosage , Neoplasms/drug therapy , Pyrimidines/administration & dosage , Adult , Aged , Aged, 80 and over , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Antineoplastic Combined Chemotherapy Protocols/pharmacokinetics , Benzoxazoles/adverse effects , Benzoxazoles/pharmacokinetics , Dose-Response Relationship, Drug , Female , Humans , Male , Maximum Tolerated Dose , Mechanistic Target of Rapamycin Complex 1 , Mechanistic Target of Rapamycin Complex 2 , Middle Aged , Multiprotein Complexes/antagonists & inhibitors , Neoplasms/pathology , Paclitaxel/administration & dosage , Pyrimidines/adverse effects , Pyrimidines/pharmacokinetics , TOR Serine-Threonine Kinases/antagonists & inhibitors , Trastuzumab/administration & dosage , Treatment Outcome , Young AdultABSTRACT
AIM: Chronic constipation is a common pathology in children. The aim of this paper was to show the usefulness of gastrointestinal transit scintigraphy in pediatric patients with chronic constipation, and the advantages with respect to other imaging techniques, despite our limited experience. MATERIAL AND METHODS: We evaluated 5 patients sent to our service with a diagnosis of chronic constipation refractory to treatment. We performed a complete study protocol, including liquid gastric emptying scintigraphy and small and large bowel transit times, using a single dose of 111In-DTPA. Following international guidelines regions of interest were defined in stomach, terminal ileum and in 6 regions of the large intestine. RESULTS: All patients showed altered scintigraphy study, showing 4 of them normal radiological tests. Radioisotopic study changed diagnosis in 2 patients and in other 2 patients contributed to clarify it, since discordance between normal radiological tests and abnormal rectal biopsy. One of the patients showed concordance between each imaging modality. The results of the test changed the therapeutic management in 2 cases. CONCLUSIONS: Our limited experience coincides with published data in which scintigraphy study turns out to be a reproducible and accurate method. It provides physiological, quantitative and useful information in the study of constipation, being the unique exploration that allows both global and regional gastrointestinal transit time determination.
Subject(s)
Constipation/diagnostic imaging , Constipation/physiopathology , Gastrointestinal Transit , Adolescent , Child , Child, Preschool , Chronic Disease , Female , Humans , Male , Radionuclide ImagingABSTRACT
BACKGROUND: MUC16 is a tumor-specific antigen overexpressed in ovarian (OC) and pancreatic (PC) cancers. The antibody-drug conjugate (ADC), DMUC5754A, contains the humanized anti-MUC16 monoclonal antibody conjugated to the microtubule-disrupting agent, monomethyl auristatin E (MMAE). PATIENTS AND METHODS: This phase I study evaluated safety, pharmacokinetics (PK), and pharmacodynamics of DMUC5754A given every 3 weeks (Q3W, 0.3-3.2 mg/kg) or weekly (Q1W, 0.8-1.6 mg/kg) to patients with advanced recurrent platinum-resistant OC or unresectable PC. Biomarker studies were also undertaken. RESULTS: Patients (66 OC, 11 PC) were treated with DMUC5754A (54 Q3W, 23 Q1W). Common related adverse events (AEs) in >20% of patients (all grades) over all dose levels were fatigue, peripheral neuropathy, nausea, decreased appetite, vomiting, diarrhea, alopecia, and pyrexia in Q3W patents, and nausea, vomiting, anemia, fatigue, neutropenia, alopecia, decreased appetite, diarrhea, and hypomagnesemia in Q1W patients. Grade ≥3-related AE in ≥5% of patients included neutropenia (9%) and fatigue (7%) in Q3W patients, and neutropenia (17%), diarrhea (9%), and hyponatremia (9%) in Q1W patients. Plasma antibody-conjugated MMAE (acMMAE) and serum total antibody exhibited non-linear PK across tested doses. Minimal accumulation of acMMAE, total antibody, or unconjugated MMAE was observed. Confirmed responses (1 CR, 6 PRs) occurred in OC patients whose tumors were MUC16-positive by IHC (2+ or 3+). Two OC patients had unconfirmed PRs; six OC patients had stable disease lasting >6 months. For CA125, a cut-off of ≥70% reduction was more suitable for monitoring treatment response due to the binding and clearance of serum CA125 by MUC16 ADC. We identified circulating HE4 as a potential novel surrogate biomarker for monitoring treatment response of MUC16 ADC and other anti-MUC16 therapies in OC. CONCLUSIONS: DMUC5754A has an acceptable safety profile and evidence of anti-tumor activity in patients with MUC16-expressing tumors. Objective responses were only observed in MUC16-high patients, although prospective validation is required. CLINICAL TRIAL NUMBER: NCT01335958.
Subject(s)
Antibodies, Anti-Idiotypic/administration & dosage , Immunoconjugates/administration & dosage , Ovarian Neoplasms/drug therapy , Pancreatic Neoplasms/drug therapy , Adult , Aged , Antibodies, Anti-Idiotypic/adverse effects , CA-125 Antigen/genetics , CA-125 Antigen/immunology , Drug Administration Schedule , Drug-Related Side Effects and Adverse Reactions/pathology , Female , Humans , Immunoconjugates/adverse effects , Immunoconjugates/pharmacokinetics , Membrane Proteins/genetics , Membrane Proteins/immunology , Middle Aged , Ovarian Neoplasms/pathology , Pancreatic Neoplasms/pathologyABSTRACT
Introduction This Phase Ib trial investigated the safety, tolerability, and recommended phase 2 dose for the pan-PI3K/mTOR inhibitor, GSK2126458 (GSK458), and trametinib combination when administered to patients with advanced solid tumors. Patients and Methods Patients with advanced solid tumors received escalating doses of GSK458 (once or twice daily, and continuous or intermittent) and trametinib following a zone-based 3 + 3 design to determine the maximum tolerated dose (MTD). Assessments included monitoring for adverse events and response, and evaluating pharmacokinetic (PK) measures. Archival tissue and circulating free DNA samples were collected to assess biomarkers of response in the PI3K and RAS pathways. Results 57 patients were enrolled onto the continuous dosing cohort and 12 patients onto an intermittent BID dosing cohort. Two MTDs were established for the continuous daily dosing: 2 mg of GSK458 with 1.0 mg of trametinib or 1.0 mg of GSK458 with 1.5 mg of trametinib; no MTD was determined in the intermittent dosing cohort. The most frequent adverse events were rash (74 %) and diarrhea (61 %). Dose interruptions due to adverse events occurred in 42 % of patients. No significant PK interaction was observed. One patient achieved partial response and 12 patients had stable disease >16 weeks. Mutations in RAS/RAF/PI3K were detected in 70 % of patients, but no pattern emerged between response and mutational status. Conclusion GSK458 plus trametinib is poorly tolerated, due to skin and GI-related toxicities. Responses were minimal, despite enrichment for PI3K/RAS pathway driven tumors, which may be due to overlapping toxicities precluding sufficient dose exposure.
Subject(s)
Biomarkers, Tumor/metabolism , MAP Kinase Kinase 1/antagonists & inhibitors , Neoplasms/drug therapy , Phosphoinositide-3 Kinase Inhibitors , Pyridones/therapeutic use , Pyrimidinones/therapeutic use , Quinolines/therapeutic use , Sulfonamides/therapeutic use , TOR Serine-Threonine Kinases/antagonists & inhibitors , Adult , Aged , Drug Therapy, Combination , Female , Follow-Up Studies , Humans , Male , Maximum Tolerated Dose , Middle Aged , Neoplasm Staging , Neoplasms/metabolism , Neoplasms/pathology , Prognosis , Protein Kinase Inhibitors/therapeutic use , Pyridazines , Pyridones/pharmacokinetics , Pyrimidinones/pharmacokinetics , Quinolines/pharmacokinetics , Sulfonamides/pharmacokinetics , Survival Rate , Tissue Distribution , Young AdultABSTRACT
BACKGROUND: A phase I/II study and subsequent phase III study (MPACT) reported significant correlations between CA19-9 decreases and prolonged overall survival (OS) with nab-paclitaxel plus gemcitabine (nab-P + Gem) treatment for metastatic pancreatic cancer (MPC). CA19-9 changes at week 8 and potential associations with efficacy were investigated as part of an exploratory analysis in the MPACT trial. PATIENTS AND METHODS: Untreated patients with MPC (N = 861) received nab-P + Gem or Gem alone. CA19-9 was evaluated at baseline and every 8 weeks. RESULTS: Patients with baseline and week-8 CA19-9 measurements were analyzed (nab-P + Gem: 252; Gem: 202). In an analysis pooling the treatments, patients with any CA19-9 decline (80%) versus those without (20%) had improved OS (median 11.1 versus 8.0 months; P = 0.005). In the nab-P + Gem arm, patients with (n = 206) versus without (n = 46) any CA19-9 decrease at week 8 had a confirmed overall response rate (ORR) of 40% versus 13%, and a median OS of 13.2 versus 8.3 months (P = 0.001), respectively. In the Gem-alone arm, patients with (n = 159) versus without (n = 43) CA19-9 decrease at week 8 had a confirmed ORR of 15% versus 5%, and a median OS of 9.4 versus 7.1 months (P = 0.404), respectively. In the nab-P + Gem and Gem-alone arms, by week 8, 16% (40/252) and 6% (13/202) of patients, respectively, had an unconfirmed radiologic response (median OS 13.7 and 14.7 months, respectively), and 79% and 84% of patients, respectively, had stable disease (SD) (median OS 11.1 and 9 months, respectively). Patients with SD and any CA19-9 decrease (158/199 and 133/170) had a median OS of 13.2 and 9.4 months, respectively. CONCLUSION: This analysis demonstrated that, in patients with MPC, any CA19-9 decrease at week 8 can be an early marker for chemotherapy efficacy, including in those patients with SD. CA19-9 decrease identified more patients with survival benefit than radiologic response by week 8.
Subject(s)
Adenocarcinoma/drug therapy , Albumins/administration & dosage , CA-19-9 Antigen/blood , Deoxycytidine/analogs & derivatives , Paclitaxel/administration & dosage , Pancreatic Neoplasms/drug therapy , Adenocarcinoma/blood , Adenocarcinoma/pathology , Adult , Aged , Biomarkers, Pharmacological/blood , Deoxycytidine/administration & dosage , Disease-Free Survival , Female , Humans , Male , Middle Aged , Pancreatic Neoplasms/blood , Pancreatic Neoplasms/pathology , Treatment Outcome , GemcitabineABSTRACT
AIM: The evaluation of the salivary scintigraphy is part of the classification criteria of Sjögren's syndrome (SS). The aim of the study was to determine a method of quantitative evaluation of this technique with easy application and high diagnostic accuracy. MATERIAL AND METHODS: A review was carried out on a total of 111 patients with clinical suspicion of SS, referred to our department over the last 4 years (94 women, range 14-82 years). Thirty-minute dynamic studies were performed after injection of (99m)Tc-pertechnetate, with secretory stimulus at 15 minutes. After drawing regions of interest in both parotids, submandibular glands, and in the background, quantitative parameters were determined. These included the ejection fraction, uptake ratio at 15 min, and the percentage uptake (PC). Based on the definitive diagnosis, the subjects were classified into patients with SS, with sicca syndrome, and healthy subjects. RESULTS: Significant differences were found between the SS group and healthy subjects in the 3 quantitative parameters for the 4 glands. Significant differences in the PC parameter were observed between the group with sicca syndrome and healthy subjects. ROC analysis showed that the best differentiation parameter for the 3 groups was the PC in both parotid and submandibular glands. CONCLUSIONS: The quantitative analysis of salivary scintigraphy has proved to be a useful method and easy to apply in daily practice to differentiate patients with SS from healthy subjects, with the PC, both in parotid and submandibular glands, being the parameter with highest diagnostic accuracy.
Subject(s)
Parotid Gland/diagnostic imaging , Sjogren's Syndrome/diagnostic imaging , Adolescent , Adult , Aged , Aged, 80 and over , Diagnosis, Differential , Female , Humans , Male , Middle Aged , ROC Curve , Radionuclide Imaging/methods , Radiopharmaceuticals , Sodium Pertechnetate Tc 99m , Submandibular Gland/diagnostic imagingSubject(s)
Bone Neoplasms/diagnostic imaging , Exostoses, Multiple Hereditary/diagnostic imaging , Adolescent , Bone Neoplasms/genetics , Disease Progression , Female , Femoral Neoplasms/diagnostic imaging , Femoral Neoplasms/genetics , Humans , Humerus/diagnostic imaging , Male , Radiopharmaceuticals/analysis , Technetium Tc 99m Medronate/analysis , Whole Body Imaging , Young AdultABSTRACT
Distant soft-tissue metastases (subcutaneous tissues and skeletal muscle) are extremely rare, particularly in oesophageal carcinoma. The case is described of a patient who was treated for oesophageal adenocarcinoma 2.5 years previously. A PET/CT was performed showing metastatic spread due to a solitary focus of increased tracer uptake corresponding to one subcutaneous node in the upper abdomen. An excisional biopsy showed a metastasis from the carcinoma. Restaging PET/CT (18)F-FDG study was performed 2 year later, demonstrating foci of increased uptake within several muscles as isolated distant haematogenous spread of metastases, histopathologically confirmed. As most of soft-tissue metastases are asymptomatic, the physicians should recommend a histopathological study of focal FDG uptake at subcutaneous tissues and/or skeletal muscles, because they may be the first sign of disease spread, so therapeutic management of these patients could be changed.
Subject(s)
Abdominal Neoplasms/secondary , Adenocarcinoma/diagnostic imaging , Adenocarcinoma/secondary , Esophageal Neoplasms/pathology , Muscle Neoplasms/diagnostic imaging , Muscle Neoplasms/secondary , Positron Emission Tomography Computed Tomography , Soft Tissue Neoplasms/diagnostic imaging , Soft Tissue Neoplasms/secondary , Abdominal Neoplasms/diagnostic imaging , Abdominal Neoplasms/metabolism , Adenocarcinoma/metabolism , Adenocarcinoma/therapy , Combined Modality Therapy , Esophageal Neoplasms/therapy , Fluorine Radioisotopes/analysis , Fluorine Radioisotopes/pharmacokinetics , Fluorodeoxyglucose F18/analysis , Fluorodeoxyglucose F18/pharmacokinetics , Humans , Lymphatic Metastasis/diagnostic imaging , Male , Middle Aged , Muscle Neoplasms/metabolism , Radiopharmaceuticals/analysis , Radiopharmaceuticals/pharmacokinetics , Soft Tissue Neoplasms/metabolism , Subcutaneous Tissue/diagnostic imaging , Subcutaneous Tissue/pathologyABSTRACT
OBJECTIVE: Osteoid osteoma is the third most common benign bone tumor and complete surgical resection is definitive treatment. There are a limited number of publications on the use of radioguided surgery in this type of lesion. To assess the utility of radioguided surgery in our environment as a method of surgical treatment of this tumor. MATERIAL AND METHODS: We retrospectively evaluated 12 patients (2 women and 10 men, age range 9-44 years) with clinical and radiological suspicion of osteoid osteoma. Bone scintigraphy showed foci of pathology uptake compatible with suspected lesion in the femur (4 cases), tibia (3), vertebral column (3), humerus (1) and talus (1). Subsequently patients underwent surgical treatment by radioguided surgery after injection of a dose of (99m)Tc-hydroxy diphosphonate. The nidus was removed using gamma probe and mini gamma camera, considering the technique to be completed when its counts decreased to the levels of the surrounding bone counts. RESULTS: Lesions were located in all patients (12 of 12), and were confirmed histologically in 8 of them, including an osteoblastoma. The cure rate was 100%, based on the disappearance of pain after a minimum follow-up of 6 months. CONCLUSION: Use of radioguided surgery in the surgical treatment of osteoid osteoma showed satisfactory results, with 100% efficiency in both lesion location and outcome of treatment and without major postoperative complications.
Subject(s)
Bone Neoplasms/surgery , Osteoma, Osteoid/surgery , Surgery, Computer-Assisted , Adolescent , Adult , Bone Neoplasms/diagnostic imaging , Child , Diphosphonates , Female , Humans , Magnetic Resonance Imaging , Male , Middle Aged , Organotechnetium Compounds , Osteoblastoma/diagnostic imaging , Osteoblastoma/surgery , Osteoma, Osteoid/diagnostic imaging , Radiopharmaceuticals , Retrospective Studies , Single Photon Emission Computed Tomography Computed Tomography , Tomography, Emission-Computed, Single-Photon , Treatment Outcome , Young AdultABSTRACT
OBJECTIVE: The aim of this study was to evaluate the usefulness of ROLL technique (Radioguided Occult Lesion Localization) as a verification method of suspicious lesions not related to breast disease found in PET-CT studies. MATERIAL AND METHODS: We retrospectively evaluated 9 patients diagnosed of cancer or with suspected tumor disease who showed hypermetabolic lymph nodes in (18)F-FDG PET-CT. Subjects underwent diagnostic testing for evaluation of treatment response in lymphoma (3), suspected recurrence in other tumors (3) or biopsy guide (3). The study group consisted of 4 women and 5 men, age range 25-72 years. ROLL technique was performed in surgically accessible lesions (supraclavicular region, lateral cervical, axillary and inguinal) with an intralesional injection of (99m)Tc-albumin macroaggregates guided by ultrasound the day before surgery. A scintigraphic study confirmed the focal tracer deposit and absence of skin contamination. During surgery, a gamma probe and portable gammacamera were used to locate lymph nodes. RESULTS: Surgical localization of radiolabeled lymph nodes was achieved in all cases with minimally invasive surgery and few postoperative complications. Histological study resulted in five tumor involvement (3 lymphoma, 1 germ cell tumor and 1 neuroendocrine carcinoma) and confirmed the existence of four false-positives in PET-CT study (1 sarcoidosis and 3 reactive follicular hyperplasia). CONCLUSION: The ROLL technique proved to be a useful and relatively simple method for the study of no breast lesions suspicious of malignancy in PET-CT study.
Subject(s)
Image-Guided Biopsy/methods , Lymph Nodes/diagnostic imaging , Lymphatic Metastasis/diagnostic imaging , Positron Emission Tomography Computed Tomography , Adult , Aged , Carcinoma, Neuroendocrine/diagnostic imaging , Carcinoma, Neuroendocrine/secondary , Female , Humans , Lymph Node Excision , Lymphoma/diagnostic imaging , Male , Middle Aged , Neoplasms, Germ Cell and Embryonal/diagnostic imaging , Neoplasms, Germ Cell and Embryonal/secondary , Preoperative Care , Pseudolymphoma/diagnostic imaging , Recurrence , Retrospective Studies , Sarcoidosis/diagnostic imagingABSTRACT
BACKGROUND: This phase Ib trial investigated the safety, tolerability, and recommended phase II dose and schedule of the MEK inhibitor trametinib in combination with the mammalian target of rapamycin (mTOR) inhibitor everolimus. Secondary objectives included pharmacokinetic (PK) characterization and evaluation of clinical activity. PATIENTS AND METHODS: A total of 67 patients with advanced solid tumors were enrolled in this open-label, single-arm, dose-escalation study. Dose escalation followed a 3 + 3 design. Patients were assigned to one of 10 different cohorts, involving either daily dosing with both agents or daily dosing with trametinib and intermittent everolimus dosing. This included an expansion cohort comprising patients with pancreatic tumors. PKs samples were collected predose, as well as 1, 2, 4, and 6 h post-dose on day 15 of the first treatment cycle. RESULTS: Concurrent treatment with trametinib and everolimus resulted in frequent treatment-related adverse events, including mucosal inflammation (40%), stomatitis (25%), fatigue (54%), and diarrhea (42%). PK assessment did not suggest drug-drug interactions between these two agents. Of the 67 enrolled patients, 5 (7%) achieved partial response (PR) to treatment and 21 (31%) displayed stable disease (SD). Among the 21 patients with pancreatic cancer, PR was observed in 1 patient (5%) and SD in 6 patients (29%). CONCLUSIONS: This study was unable to identify a recommended phase II dose and schedule of trametinib in combination with everolimus that provided an acceptable tolerability and adequate drug exposure.
