RESUMEN
Prospective data are lacking on early somatostatin analog (SSA) therapy in bronchopulmonary neuroendocrine tumors (BP-NETs; typical carcinoids and atypical carcinoids (TCs and ACs)). SPINET (EudraCT: 2015-004992-62; NCT02683941) was a phase III, double-blind study of lanreotide autogel/depot (LAN; 120 mg every 28 days) plus best supportive care (BSC) vs placebo plus BSC, with an optional open-label treatment phase (LAN plus BSC). Patients had metastatic/unresectable, somatostatin receptor (SSTR)-positive TCs or ACs. Recruitment was stopped early owing to slow accrual; eligible patients from the double-blind phase transitioned to open-label LAN. The adapted primary endpoint was progression-free survival (PFS) during either phase for patients receiving LAN. Seventy-seven patients were randomized (LAN, n = 51 (TCs, n = 29; ACs, n = 22); placebo, n = 26 (TCs, n = 16; ACs, n = 10)). Median (95% CI) PFS during double-blind and open-label phases in patients receiving LAN was 16.6 (11.3; 21.9) months overall (primary endpoint), 21.9 (12.8, not calculable (NC)) months in TCs, and 13.8 (5.4; 16.6) months in ACs. During double-blind treatment, median (95% CI) PFS was 16.6 (11.3; 21.9) months for LAN vs 13.6 (8.3; NC) months for placebo (not significant); corresponding values were 21.9 (13.8; NC) and 13.9 (13.4; NC) months, respectively, in TCs and 13.8 (5.4; 16.6) and 11.0 (2.8; 16.9) months, respectively, in ACs. Patients' quality of life did not deteriorate and LAN was well tolerated. Although recruitment stopped early and the predefined sample size was not met, SPINET is the largest prospective study to date of SSA therapy in SSTR-positive TCs and ACs and suggests clinical benefit in TCs.
Asunto(s)
Tumores Neuroendocrinos , Péptidos Cíclicos , Somatostatina , Humanos , Somatostatina/análogos & derivados , Somatostatina/uso terapéutico , Somatostatina/administración & dosificación , Péptidos Cíclicos/administración & dosificación , Péptidos Cíclicos/uso terapéutico , Femenino , Masculino , Persona de Mediana Edad , Método Doble Ciego , Anciano , Tumores Neuroendocrinos/tratamiento farmacológico , Adulto , Antineoplásicos/uso terapéutico , Antineoplásicos/administración & dosificación , Neoplasias Pulmonares/tratamiento farmacológico , Anciano de 80 o más AñosRESUMEN
BACKGROUND: The European Society for Medical Oncology (ESMO)-Magnitude of Clinical Benefit Scale (MCBS) has been accepted as a robust tool to evaluate the magnitude of clinical benefit reported in trials for oncological therapies. However, the ESMO-MCBS hitherto has only been validated for solid tumours. With the rapid development of novel therapies for haematological malignancies, we aimed to develop an ESMO-MCBS version that is specifically designed and validated for haematological malignancies. METHODS: ESMO and the European Hematology Association (EHA) initiated a collaboration to develop a version for haematological malignancies (ESMO-MCBS:H). The process incorporated five landmarks: field testing of the ESMO-MCBS version 1.1 (v1.1) to identify shortcomings specific to haematological diseases, drafting of the ESMO-MCBS:H forms, peer review and revision of the draft based on re-scoring (resulting in a second draft), assessment of reasonableness of the scores generated, final review and approval by ESMO and EHA including executive boards. RESULTS: Based on the field testing results of 80 haematological trials and extensive review for feasibility and reasonableness, five amendments to ESMO-MCBS were incorporated in the ESMO-MCBS:H addressing the identified shortcomings. These concerned mainly clinical trial endpoints that differ in haematology versus solid oncology and the very indolent nature of nevertheless incurable diseases such as follicular lymphoma, which hampers presentation of mature data. In addition, general changes incorporated in the draft version of the ESMO-MCBS v2 were included, and specific forms for haematological malignancies generated. Here we present the final approved forms of the ESMO-MCBS:H, including instructions. CONCLUSION: The haematology-specific version ESMO-MCBS:H allows now full applicability of the scale for evaluating the magnitude of clinical benefit derived from clinical studies in haematological malignancies.
Asunto(s)
Antineoplásicos , Neoplasias Hematológicas , Linfoma Folicular , Neoplasias , Humanos , Neoplasias/tratamiento farmacológico , Oncología Médica , Neoplasias Hematológicas/terapia , Sociedades Médicas , Linfoma Folicular/tratamiento farmacológico , Antineoplásicos/uso terapéuticoRESUMEN
AIMS: Synovial sarcomas are a rare subgroup of soft-tissue sarcoma arising in adolescents and young adults (AYA) and in adult patients. The objective of our analysis was to investigate the outcomes and potential differences of AYA versus adult patients with initially localised disease. MATERIALS AND METHODS: In total, 51 patients (25 AYA and 26 adult) were identified and evaluated in this retrospective single centre analysis. Baseline characteristics, treatment and outcome were assessed. RESULTS: The predominant subtype in both groups was monophasic synovial sarcoma (17 AYA and 21 adult) and the most common site was the extremities (14 and 19 patients) with deep tumour location in both groups (33 and 24 patients). More AYA patients had tumours >5 cm (13/25 patients) when compared with adults (10/26 patients, P = n.s.). Primary wide resection was carried out in 15 AYAs and in 18 adults. Postoperative radiation therapy was the only statistical difference between AYA (n = 19) and adult patients (n = 12; P = 0.029). Nineteen and 17 patients, respectively, received adjuvant chemotherapy with no evidence of disease after six cycles. Nine and 11 patients relapsed after initial therapy and the most common metastatic site was the lung (eight versus nine patients). Five-year overall survival rates were 85% and 75%. Female gender, tumour size ≤5 cm and absence of progressive disease showed a significant association with overall survival in AYA patients (P = 0.013, P = 0.04 and P < 0.001), whereas non-extremity tumours and progression after initial therapy were significant for worse overall survival in adult patients (P = 0.012 and P < 0.001). No difference in overall survival between AYA and adult patients was observed (P = 0.899). CONCLUSIONS: AYA and adult patients showed no significant difference in terms of overall survival. Male gender, tumour size >5 cm and progressive disease were prognostic markers for worse outcome, whereas tumour location (non-extremity) and progression after initial therapy were markers for worse outcome in adult patients.
Asunto(s)
Sarcoma Sinovial , Sarcoma , Neoplasias de los Tejidos Blandos , Humanos , Masculino , Adolescente , Femenino , Adulto Joven , Sarcoma Sinovial/terapia , Sarcoma Sinovial/patología , Estudios Retrospectivos , Sarcoma/patología , Neoplasias de los Tejidos Blandos/patología , Quimioterapia AdyuvanteRESUMEN
AIMS: Cancer patients often present with psychological symptoms that affect their quality of life, physical health outcomes and survival. Two of the most frequent psychiatric comorbidities are anxiety and depression. However, the prevalence of these disorders among cancer patients remains unclear, as studies frequently report varying rates. In the present study, we aimed to provide robust point estimates for the prevalence of anxiety and depression for both a mixed cancer sample and for 13 cancer types separately, considering confounding variables. METHODS: In a sample of 7509 cancer outpatients (51.4% female), we used the Hospital Anxiety and Depression Scale to assess rates of anxiety and depression. Applying ordinal logistic regression models, we compared the prevalence of anxiety and depression between different cancer types, controlling for age and gender. RESULTS: About one third of our sample showed symptoms of anxiety (35.2%) or depression (27.9%), and every sixth patient had a very likely psychiatric condition, with women being more frequently affected. Elderly patients more often showed signs of depression. The prevalence of anxiety and depression was significantly higher in lung and brain cancer patients, than in other cancer patients. Lowest depression rates were found in breast cancer patients. CONCLUSIONS: The prevalence of anxiety and depression is high in cancer patients. Type of cancer is an important predictor for anxiety and depressive symptoms, with lung and brain cancer patients being highly burdened. Considering a personalised medicine approach, physicians should take into account the high prevalence of psychiatric comorbidities and include psychiatric consultations in the treatment plan.
Asunto(s)
Neoplasias Encefálicas , Neoplasias de la Mama , Neoplasias Hematológicas , Anciano , Ansiedad/epidemiología , Ansiedad/psicología , Neoplasias de la Mama/epidemiología , Estudios Transversales , Depresión/epidemiología , Depresión/psicología , Femenino , Neoplasias Hematológicas/epidemiología , Humanos , Masculino , Prevalencia , Calidad de VidaRESUMEN
BACKGROUND: The use of somatostatin analogues (SSAs) has not been formally approved in pulmonary neuroendocrine tumours (NETs) in the absence of positive controlled trials, even though it is recommended as a potential therapeutic option in recent guidelines. PATIENTS AND METHODS: We have assessed the use of SSA in the general practice in Austria by retrospectively analysing patients with pulmonary NETs referred to our European Neuroendocrine Tumor Society centre in Vienna for second opinion or further therapy. In addition, we have analysed the somatostatin receptor (SSTR) expression of those patients by immunohistochemistry (IHC) and SSTR imaging, e.g. 68Ga-DOTANOC-positron emission tomography/computed tomography, and whether such analyses had been carried out before referral at our centre. RESULTS: Out of 34 patients (19 atypical and 15 typical carcinoids) with metastatic or advanced disease, 10/34 (29%) had been prescribed SSA before referral. No IHC for SSTR had been carried out, and only 9/34 (27%) had undergone SSTR imaging by nuclear medicine. Sufficient material for IHC was available in 29/34 (85%) patients and SSTR-IHC was rated negative in 13/29 (45%), weakly positive in 4/29 (14%), moderately positive in 5/29 (17%) and strongly positive in 7/29 (24%) patients. On SSTR imaging, 8/34 patients (24%) were positive, 13/34 (38%) negative and 13/34 patients (38%) showed a mix of positive and negative NET lesions. In 11/29 (38%) patients with both IHC and imaging available, discordance of SSTR expression on imaging and histological assessment was detected. CONCLUSIONS: These data show that uncritical use of SSA should be discouraged, and assessment of SSTR, preferably by imaging, is mandatory before prescription of SSA in pulmonary NETs.
Asunto(s)
Tumores Neuroendocrinos , Receptores de Somatostatina , Humanos , Tumores Neuroendocrinos/tratamiento farmacológico , Tumores Neuroendocrinos/patología , Tomografía Computarizada por Tomografía de Emisión de Positrones , Receptores de Somatostatina/metabolismo , Estudios Retrospectivos , Somatostatina/farmacología , Somatostatina/uso terapéuticoRESUMEN
Medullary thyroid cancer (MTC) represents a rare neuroendocrine neoplasm originating from neoplastic C-cells in the thyroid gland. While localized disease is potentially curable with an optimized surgical approach, the number of relapses is high, and a considerable number of patients present with primary metastatic disease. Multidisciplinary management including standardized surveillance following surgery, but also early involvement of medical oncologists, is therefore important. Several oncogenic pathways are involved in the pathogenesis of MTC including vascular endothelial growth factor receptor, epidermal growth factor receptor, MET, and most importantly RET, and the multi-tyrosine kinase inhibitors vandetanib and cabozantinib have been approved for advanced MTC based on data from phase III studies. As activating RET mutations represent the most important driver, specific RET inhibitors were introduced and suggest high response rates with limited off-target toxicities. The current review provides a practical overview on clinical presentation and management from early to advanced MTC.
Asunto(s)
Neoplasias de la Tiroides , Factor A de Crecimiento Endotelial Vascular , Carcinoma Neuroendocrino , Humanos , Recurrencia Local de Neoplasia , Proteínas Proto-Oncogénicas c-ret , Neoplasias de la Tiroides/diagnóstico , Neoplasias de la Tiroides/tratamiento farmacológico , Neoplasias de la Tiroides/genéticaRESUMEN
BACKGROUND: Lenvatinib has proven efficacy in progressive, radioiodine- (RAI-) refractory thyroid cancer (TC). Dose reductions are commonly performed due to decreased tolerability and adverse effects. This retrospective multicenter study analyzed overall survival (OS) and progression-free survival (PFS) and tolerability in the Austrian patient population treated with lenvatinib. METHODS: Clinical data of 43 patients (25 males and 18 females) with a median age of 70 years (range: 39-91 years) and RAI-refractory TC with metastases to the lymph nodes (74%), lungs (86%), bone (35%), liver (16%), and brain (12%) were analyzed. The mean duration of treatment with lenvatinib was 26.6 ± 15.4 months with dosage reductions required in 39 patients (91%). RESULTS: PFS after 24 months was 71% (95% CI: 56-87), and overall survival (OS) was 74% (95% CI: 60-88), respectively. OS was significantly shorter (p=0.048) in patients with a daily maintenance dosage ≤ 10 mg (63%) (95% CI: 39-86) as compared to patients on ≥ 14 mg lenvatinib (82%) (95% CI: 66-98) daily. Dose reduction was noted in 39 patients (91%). Grade ≥3 toxicities (hypertension, diarrhea, weight loss, and palmar-plantar erythrodysesthesia syndrome) were most common leading to discontinuation of lenvatinib in 7 patients (16%). CONCLUSION: Lenvatinib showed sustained clinical efficacy in patients with metastatic RAI-refractory TC even with reduced maintenance dosages over years. The effects were comparable to the registration trial, although patients had a higher median age and, more commonly, dose reductions.
RESUMEN
INTRODUCTION: Still little is known about factors, influencing the organ uptake of somatostatin receptor (SSTR)-targeting radiopharmaceuticals. The aim of this study was to assess the influence of gender on [68Ga]Ga-DOTANOC uptake. Further on, we assessed other factors such as diabetes, proton pump inhibitors (PPIs) and oral antidiabetics (OADs). METHODS: In 118 studies of patients with a [68Ga]Ga-DOTANOC PET/CT (mâ¯=â¯60, fâ¯=â¯58; mean age: 61⯱â¯15â¯yrs) SUVmax and SUVmean of the stomach, liver, spleen, kidneys, adrenal glands, and pancreas were assessed. Patients with history of splenectomy and significant tumor burden were excluded. Additionally, clinical information (gender, diabetes, age, pre-medications such as PPIs, OADs and somatostatin analogues (SSAs), were collected. RESULTS: [68Ga]Ga-DOTANOC uptake proved to be significantly lower in female patients compared to males for the SUVmax of the stomach (7.1, 9.1; Pâ¯=â¯0.04), liver (8.3, 9.4; Pâ¯=â¯0.0007), adrenal glands (15.9, 19.9; Pâ¯=â¯0.05) kidneys (20.3, 18.9; Pâ¯=â¯0.05) and the SUVmean of the pancreatic tail (2.9, 3.2; Pâ¯=â¯0.03) and the kidneys (11.8, 10.6, Pâ¯=â¯0.004). Additionally, patients with diabetes and below the age of 50â¯yrs. showed significantly higher SUVmax and SUVmean values of the stomach (diabetes: 9.1, 7.8; Pâ¯=â¯0.01 and 6.0, 5.3; Pâ¯=â¯0.004; age: 6.3, 8.3; Pâ¯=â¯0.01 and 4.4, 5.5; Pâ¯=â¯0.03). In contrast, intake of PPIs only affected the SUVmean of the liver (11.0, 9.0; Pâ¯=â¯0.005), whereas OADs caused higher SUVmax values in the stomach (10.0, 7.8; Pâ¯=â¯0.02), spleen (42.5, 32.6; Pâ¯=â¯0.0005) adrenal glands (25.0, 16.9; Pâ¯=â¯0.0003) and also higher SUVmean in the spleen (26.1, 21.4; Pâ¯=â¯0.002) and adrenal glands (14.8, 12.4; Pâ¯=â¯0.02). CONCLUSION: Factors such as gender, diabetes and age influence [68Ga]Ga-DOTANOC uptake, whereas ongoing medications such as PPIs and OADs exerted less influence.
Asunto(s)
Octreótido/análogos & derivados , Compuestos Organometálicos/farmacocinética , Caracteres Sexuales , Envejecimiento/metabolismo , Transporte Biológico/efectos de los fármacos , Diabetes Mellitus/metabolismo , Femenino , Humanos , Masculino , Persona de Mediana Edad , Octreótido/metabolismo , Octreótido/farmacocinética , Compuestos Organometálicos/metabolismo , Distribución TisularRESUMEN
Bleeding because of impaired platelet function is a major side effect of the Bruton's tyrosine kinase (BTK) inhibitor ibrutinib. We quantitatively assessed ristocetin-induced platelet aggregation (RIPA) in 64 patients with chronic lymphocytic leukemia (CLL) under ibrutinib at 287 time points. Eighty-seven bleeding episodes in 39 patients were registered (85 Common Toxicity Criteria (CTC) grade 1 or 2, 2 CTC grade 3) during a median observation period of 10.9 months. At times of bleeding, RIPA values were significantly lower (14 vs 28 U; P<0.0001). RIPA was impaired in patients receiving concomitant antiplatelet therapy or anticoagulation (14 vs 25 U, P=0.005). A gradual decline of median RIPA values was observed with increasing bleeding severity. Importantly, no CTC grade 2 or 3 bleeding were observed with RIPA values of >36 U. Sequential monitoring indicated a decrease of RIPA values from a median of 17 to 9 U within 2 weeks after initiation of treatment as well as an increase above the critical threshold of 36 U within 7 days when ibrutinib was paused. Low RIPA values were similar during treatment with another BTK inhibitor, CC292. Quantitative assessment of platelet function is a practical tool to monitor bleeding tendency under BTK-inhibitor therapy.
Asunto(s)
Hemorragia/inducido químicamente , Leucemia Linfocítica Crónica de Células B/tratamiento farmacológico , Agregación Plaquetaria/efectos de los fármacos , Pirazoles/efectos adversos , Pirimidinas/efectos adversos , Ristocetina/farmacología , Adenina/análogos & derivados , Adulto , Anciano , Anciano de 80 o más Años , Monitoreo de Drogas/métodos , Femenino , Hemorragia/tratamiento farmacológico , Humanos , Leucemia Linfocítica Crónica de Células B/complicaciones , Masculino , Persona de Mediana Edad , Piperidinas , Inhibidores de Proteínas Quinasas/efectos adversos , Pirazoles/administración & dosificación , Pirimidinas/administración & dosificaciónRESUMEN
BACKGROUND: Clarithromycin displays immunomodulatory and antineoplastic properties. As single agent, this macrolide is associated with tumor responses in anecdotal cases of relapsed/refractory extranodal marginal zone lymphoma (rrEMZL), with a putative dose-dependent effect. Tolerability and activity of high-dose clarithromycin (HD-K) in patients with rrEMZL were addressed in a phase II trial (clinicaltrials.gov NCT01516606). METHODS: HIV-negative adults with rrEMZL and at least one measurable/parametrable lesion were enrolled and treated with four courses of oral clarithromycin 2 g/day, days 1-14, every 21 days. Activity (overall response rate, ORR) was the primary end point. RESULTS: Twenty-three patients were registered (median age 70 years, range 47-88 years; M:F ratio: 0.27). HD-K was given at greater than or equal to second relapse in 11 patients. Ocular adnexae were the most commonly involved organs. Five patients had hepatitis B virus/hepatitis C virus (HBV/HCV) infections; Helicobacter pylori and Chlamydophila psittaci infections were excluded at the time of patient registration.Tolerability was excellent, even among HBV/HCV-positive patients; only two patients had grade >2 toxicity (nausea). Six patients achieved a complete remission and six a partial response (ORR = 52%; 95% confidence interval 32% to 72%). Age, previous treatment and stage did not influence activity. At a median follow-up of 24 (16-33) months, only two patients with responsive disease experienced relapse, with a 2-year progression-free survival of 56 ± 10%; all patients are alive. CONCLUSIONS: HD-K is a safe and active salvage treatment in EMZL patients. This macrolide deserves to be further investigated in EMZL and other lymphoma categories.
Asunto(s)
Antibacterianos/administración & dosificación , Claritromicina/administración & dosificación , Neoplasias del Ojo/tratamiento farmacológico , Linfoma de Células B de la Zona Marginal/tratamiento farmacológico , Neoplasias Primarias Múltiples/tratamiento farmacológico , Neoplasias Gástricas/tratamiento farmacológico , Anciano , Anciano de 80 o más Años , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias Colorrectales/tratamiento farmacológico , Supervivencia sin Enfermedad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Neoplasias de la Boca/tratamiento farmacológico , Terapia Recuperativa , Neoplasias Cutáneas/tratamiento farmacológicoRESUMEN
There is no clear standard therapy for patients with radioactive iodine (131I)-refractory locally advanced or metastatic differentiated thyroid cancer. The therapeutic options for this indication have expanded with the recently approved multiple kinase inhibitor sorafenib. Recommendations for the definition and the management of iodine refractory patients were worked up by an interdisciplinary expert panel, consisting of endocrine surgeons, medical oncologists and nuclear medicine specialists.
Asunto(s)
Antineoplásicos/administración & dosificación , Radioisótopos de Yodo/uso terapéutico , Niacinamida/análogos & derivados , Compuestos de Fenilurea/administración & dosificación , Guías de Práctica Clínica como Asunto , Neoplasias de la Tiroides/diagnóstico , Neoplasias de la Tiroides/terapia , Antineoplásicos/efectos adversos , Quimioradioterapia/normas , Medicina Basada en la Evidencia , Alemania , Humanos , Oncología Médica/normas , Niacinamida/administración & dosificación , Niacinamida/efectos adversos , Compuestos de Fenilurea/efectos adversos , Inhibidores de Proteínas Quinasas/administración & dosificación , Inhibidores de Proteínas Quinasas/efectos adversos , Radiofármacos/uso terapéutico , Sorafenib , Insuficiencia del Tratamiento , Resultado del TratamientoAsunto(s)
Infecciones por Helicobacter/complicaciones , Linfoma de Células B de la Zona Marginal/diagnóstico , Linfoma de Células B de la Zona Marginal/terapia , Linfoma no Hodgkin/diagnóstico , Linfoma no Hodgkin/terapia , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/terapia , Antibacterianos/uso terapéutico , Antineoplásicos/uso terapéutico , Europa (Continente)/epidemiología , Estudios de Seguimiento , Infecciones por Helicobacter/tratamiento farmacológico , Helicobacter pylori/efectos de los fármacos , Helicobacter pylori/patogenicidad , Humanos , Tejido Linfoide/patología , Linfoma de Células B de la Zona Marginal/epidemiología , Linfoma no Hodgkin/epidemiología , Estadificación de Neoplasias , Medición de Riesgo , Neoplasias Gástricas/epidemiologíaRESUMEN
Peptide receptor radionuclide therapy (PRRT) has recently been established as an important treatment modality for somatostatin receptor (SSTR)-positive tumors. The purpose of this study was to evaluate the clinical response, side-effects as well as the quality of life following (90)Y-DOTA-lanreotide (DOTALAN) and/or (90)Y-DOTA-Tyr (3)-DPhe(1)-octreotide (DOTATOC) therapy in patients with progressive metastatic disease during a 6-year follow-up period. Following dosimetric evaluation with (111)In-DOTALAN and (111)In-DOTATOC, 13 patients with estimated absorbed tumor doses of >5 Gy/GBq (carcinoid, n = 5; radioiodine-negative thyroid cancer, n = 4; gastrinoma, n = 1; insulinoma, n = 1; glucagonoma, n = 1; glomus jugularis tumor, n = 1) were assigned for PRRT. A dose of 925 MBq of (90)Y-DOTALAN (four patients) or 1.85-3.7 GBq of (90)Y-DOTATOC (10 patients) was administered intravenously and repeated every 4-8 weeks. Tumor dosimetry was performed prior to and under therapy, re-staging every 2-3 months. Pain intensity, Karnofsky score and general symptoms were evaluated in order to determine quality of life. Patients were followed until death. Altogether, 53 infusions of PRRT (1.85-14.1 GBq) were administered. After the first follow-up of 3 months of (90)Y-DOTALAN therapy, stable disease (SD) was observed in one patient and progressive disease (PD) in three patients. With (90)Y-DOTATOC therapy, SD was found in all 10 patients. During the re-evaluation period (4-27 months), one patient had to be shifted from (90)Y-DOTALAN to (90)Y-DOTATOC therapy due to reduced (111)In-DOTALAN uptake after 5.5 GBq. In the first 6 months after PRRT with DOTATOC, SD was found in nine of 10 patients and PD in one patient. Thereafter, SD was observed in two patients and PD in eight patients. Nine of 13 patients after PRRT with either DOTALAN or DOTATOC died. None of the patients had experienced severe acute hematological side-effects. Transient thrombocytopenia or lymphocytopenia was seen in 10 patients after 3.7 GBq, and a skin reaction in one patient. Total accumulated kidney dose ranged between 4 and 64 Gy, with reduced creatinine clearance in two patients. Pain relief was achieved in three of three patients after ~3.7 GBq ERT within 4-6 months. Appetite, weight, Karnofsky score and general well-being had improved in patients with SD during and after therapy. Based on the results of this study conducted on a small group of patients, we conclude that PRRT may offer an alternative treatment option for SSTR-positive tumors, with only mild transient side-effects and a marked improvement in the quality of life.
RESUMEN
Mucosa-associated lymphoid tissue (MALT) lymphoma is thought to be a multifocal disease with sometimes synchronous involvement of various mucosal structures. In this study we aimed to evaluate the potential involvement of the small bowel in patients suffering from gastric MALT lymphoma by analyzing the results of enteroscopy, a technique that allows easy and safe access to the small bowel with the potential for histological assessment of biopsy samples. We have retrospectively evaluated 347 enteroscopies and found nine patients with gastric MALT lymphoma who had undergone push enteroscopy with serial biopsies during staging. All patients tolerated enteroscopy without side effects, and no local complications occurred. In eight cases no evidence of duodenal or jejunal involvement was found macroscopically or by histological assessment of biopsies, while in one patient enteroscopy revealed jejunal MALT lymphoma infiltration with macroscopic accentuation of mucosal parts and consecutive histopathological verification more distal than 50 cm. This single-center retrospective analysis shows that enteroscopy can provide additional diagnostic information in patients with gastric MALT lymphoma, although the number of patients was small and only one out of nine patients showed hitherto undetected MALT lymphoma deposits. Further studies may quantify the additional diagnostic yield provided by this easy and safe endoscopic method.
Asunto(s)
Endoscopía Gastrointestinal , Neoplasias del Yeyuno/secundario , Linfoma de Células B de la Zona Marginal/patología , Neoplasias Gástricas/patología , Adulto , Anciano , Anciano de 80 o más Años , Biopsia , Femenino , Humanos , Neoplasias del Yeyuno/patología , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Estudios RetrospectivosRESUMEN
This consensus report of the EGILS (European Gastro-Intestinal Lymphoma Study) group includes recommendations on the management of gastric extranodal marginal zone B-cell lymphoma of MALT. They are based on data from the literature and on intensive discussions and votings of the experts during their annual meetings.
Asunto(s)
Linfoma de Células B de la Zona Marginal/diagnóstico , Neoplasias Gástricas/diagnóstico , Infecciones por Helicobacter/complicaciones , Helicobacter pylori , Humanos , Cuidados a Largo Plazo/métodos , Linfoma de Células B de la Zona Marginal/microbiología , Linfoma de Células B de la Zona Marginal/terapia , Estadificación de Neoplasias , Neoplasias Gástricas/microbiología , Neoplasias Gástricas/terapia , Resultado del TratamientoRESUMEN
Mucosa-associated lymphoid tissue (MALT) lymphoma is characterized by t(11;18)(q21;q21)/API2-MALT1, t(1;14)(p22;q32)/BCL10-IGH and t(14;18)(q32;q21)/IGH-MALT1, which commonly activate the nuclear factor (NF)-kappaB pathway. Gastric MALT lymphomas harboring such translocations usually do not respond to Helicobacter pylori eradication, while most of those without translocation can be cured by antibiotics. To understand the molecular mechanism of these different MALT lymphoma subgroups, we performed gene expression profiling analysis of 21 MALT lymphomas (13 translocation-positive, 8 translocation-negative). Gene set enrichment analysis (GSEA) of the NF-kappaB target genes and 4394 additional gene sets covering various cellular pathways, biological processes and molecular functions have shown that translocation-positive MALT lymphomas are characterized by an enhanced expression of NF-kappaB target genes, particularly toll like receptor (TLR)6, chemokine, CC motif, receptor (CCR)2, cluster of differentiation (CD)69 and B-cell CLL/lymphoma (BCL)2, while translocation-negative cases were featured by active inflammatory and immune responses, such as interleukin-8, CD86, CD28 and inducible T-cell costimulator (ICOS). Separate analyses of the genes differentially expressed between translocation-positive and -negative cases and measurement of gene ontology term in these differentially expressed genes by hypergeometric test reinforced the above findings by GSEA. Finally, expression of TLR6, in the presence of TLR2, enhanced both API2-MALT1 and BCL10-mediated NF-kappaB activation in vitro. Our findings provide novel insights into the molecular mechanism of MALT lymphomas with and without translocation, potentially explaining their different clinical behaviors.