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BACKGROUND: MABp1, an antibody that targets interleukin 1α, has been associated with antitumour activity and relief of debilitating symptoms in patients with advanced colorectal cancer. We sought to establish the effect of MABp1 with a new primary endpoint in patients with advanced colorectal cancer. METHODS: Eligible patients for the double-blind phase of this ongoing, placebo-controlled, randomised, phase 3 trial, had metastatic or unresectable disease, Eastern Cooperative Oncology Group performance status score 1 or 2, systemic inflammation, weight loss, and other disease-related morbidities associated with poor prognosis, and were refractory to oxaliplatin and irinotecan. Patients were randomly assigned 2:1 to receive either MABp1 or placebo. Randomisation codes were obtained from a centrally held list via an interactive web response system. Patients received an intravenous infusion of 7·5 mg/kg MABp1 or placebo given every 2 weeks for 8 weeks. The primary endpoint was assessed in patients who received at least one dose of MABp1 or placebo (modified intention-to-treat population), and was a composite of stable or increased lean body mass and stability or improvement in two of three symptoms (pain, fatigue, or anorexia) at week 8 compared with baseline measurements. This study is registered with ClinicalTrials.gov, number NCT02138422. FINDINGS: Patients were enrolled between May 20, 2014, and Sept 2, 2015. The double-blind phase of the study was completed on Nov 3, 2015. Of 333 patients randomly assigned treatment, 207 received at least one dose of MABp1 and 102 at least one dose of placebo. 68 (33%) and 19 (19%) patients, respectively, achieved the primary endpoint (relative risk 1·76, 95% CI 1·12-2·77, p=0·0045). The most common grade 3-4 adverse events in the MABp1 group compared with in the placebo group were anaemia (eight [4%] of 207 vs five [5%] of 102 patients), increased concentration of alkaline phosphatase (nine [4%] vs two [2%]), fatigue (six [3%] vs seven [7%]), and increased concentration of aspartate aminotransferase (six [3%] vs two [2%]). After 8 weeks, 17 (8%) patients in the MABp1 group and 11 (11%) in the placebo group had died, but no death was judged to be related to treatment. The incidence of serious adverse events was not significantly different in the MABp1 group and placebo groups (47 [23%] vs 33 [32%], p=0·07). INTERPRETATION: The primary endpoint was a useful means of measuring clinical performance in patients. MABp1 might represent a new standard in the management of advanced colorectal cancer. FUNDING: XBiotech.
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Adenocarcinoma/tratamento farmacológico , Anticorpos Monoclonais/uso terapêutico , Neoplasias Colorretais/tratamento farmacológico , Adenocarcinoma/imunologia , Adenocarcinoma/secundário , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias Colorretais/imunologia , Neoplasias Colorretais/patologia , Método Duplo-Cego , Feminino , Seguimentos , Humanos , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Taxa de SobrevidaRESUMO
AIM: This study assessed whether absolute chromogranin A (CgA) values at various stages of treatment have prognostic value in patients with pancreatic and midgut neuroendocrine tumors, subjected to peptide receptor radionuclide therapy with 90Y-[DOTA0, D-Phe1, Tyr3]-octreotate. PATIENTS & METHODS: CgA was determined before peptide receptor radionuclide therapy, 6 weeks, 6, 12, 18 and 24 months after the last dose of 90Y-[DOTA0, D-Phe1, Tyr3]-octreotate. The primary end point was overall survival. RESULTS: Elevated baseline CgA concentrations and their relative increase within the first year of observation were unfavorable predictors of overall survival, but not progression. CONCLUSION: Even a single baseline measurement of CgA can be useful in establishing prognosis in this group, if this parameter exceeds its upper normal limit more than tenfold.
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Biomarcadores Tumorais , Cromogranina A/sangue , Neoplasias Intestinais/sangue , Neoplasias Intestinais/mortalidade , Tumores Neuroendócrinos/sangue , Tumores Neuroendócrinos/mortalidade , Neoplasias Pancreáticas/sangue , Neoplasias Pancreáticas/mortalidade , Neoplasias Gástricas/sangue , Neoplasias Gástricas/mortalidade , Terapia Combinada , Progressão da Doença , Feminino , Humanos , Neoplasias Intestinais/diagnóstico , Neoplasias Intestinais/terapia , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Metástase Neoplásica , Estadiamento de Neoplasias , Tumores Neuroendócrinos/diagnóstico , Tumores Neuroendócrinos/terapia , Neoplasias Pancreáticas/diagnóstico , Neoplasias Pancreáticas/terapia , Prognóstico , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/terapia , Resultado do TratamentoRESUMO
BACKGROUND: Ganglioneuroma (GN) is a rare benign tumor arising from the neural crest cells. The reported incidence of GN is one per million population. As a primary retroperitoneal tumor, it constitutes only a small percentage of 0.72 to 1.6%. GN can arise de novo or as a result of maturation of a neuroblastoma either spontaneously or after chemotherapy. The most common location is the posterior paraspinal mediastinum, retroperitoneum, neck and adrenal gland. However, GN can potentially occur anywhere along the peripheral autonomic ganglion sites. Most ganglioneuromas are asymptomatic and found incidentally. CASE REPORT: We present a case of retroperitoneal ganglioneuroma that mimicked renal mass on imaging. The tumor was incidentally discovered during an abdominal ultrasound examination 43-year-old male patient without clinical symptoms. Complete surgical resection was subsequently performed and histopathological examination of the retroperitoneal mass revealed GN. CONCLUSIONS: Retroperitoneal ganglioneuroma is a rare bening tumor, generally asymptomatic, which grows slowly, and appears large when it is identified. Preoperative diagnosis can be challenging, particularly in asymptomatic case. Histopathological examination is currently the mainstay of diagnosis. In the case presented herein GN stricktly adjoined to the left kidney mimicking renal mass.
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Bexarotene, a synthetic retinoid licensed for the treatment of refractory cutaneous T-cell lymphoma (CTCL), has been used clinically in Poland since 2007 in 21 patients. The objective of our retrospective, multicenter study was to evaluate our experience with bexarotene therapy, including efficacy, safety, and survival outcomes. We retrospectively identified 21 adult patients who were treated with bexarotene between the years 2007 and 2012. Starting dose of bexarotene was 300 mg/m per day. The analysis included 3 patients with early-stage mycosis fungoides (MF), 16 patients with advanced-stage MF, and 2 patients with Sézary syndrome (SS). The mean duration of therapy with bexarotene was 14.5 months. Use of bexarotene resulted in an overall response rate of 81.0%, although the overall mortality rate was 52.8%. In our study, early-stage CTCL responded better than advanced-stage CTCL (100.0% vs. 77.8%, respectively). The mean time to observable response was 1.8 months, and the mean duration of the response was 16.4 months. Most significant side effects were hyperlipidemia, hypothyroidism, and a bleeding gastric ulcer. Based on the results of our analysis, bexarotene is a valuable tool in the treatment of refractory early-stage CTCL. Although a majority of patients initially responded to therapy, the high mortality rate in the advanced-stage group suggests that bexarotene does not completely resolve the therapeutic problems in all stages of CTCL. Patient stratification for bexarotene treatment may need a thorough reassessment, in that bexarotene may not be an effective drug in the very advanced stages of CTCL.
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Anticarcinógenos/uso terapêutico , Micose Fungoide/tratamento farmacológico , Retinoides/uso terapêutico , Síndrome de Sézary/tratamento farmacológico , Neoplasias Cutâneas/tratamento farmacológico , Tetra-Hidronaftalenos/uso terapêutico , Administração Cutânea , Administração Oral , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticarcinógenos/administração & dosagem , Anticarcinógenos/efeitos adversos , Bexaroteno , Feminino , Humanos , Hiperlipidemias/induzido quimicamente , Hipotireoidismo/induzido quimicamente , Masculino , Pessoa de Meia-Idade , Micose Fungoide/mortalidade , Úlcera Péptica Hemorrágica/induzido quimicamente , Polônia/epidemiologia , Retinoides/administração & dosagem , Retinoides/efeitos adversos , Estudos Retrospectivos , Síndrome de Sézary/mortalidade , Neoplasias Cutâneas/mortalidade , Úlcera Gástrica/induzido quimicamente , Tetra-Hidronaftalenos/administração & dosagem , Tetra-Hidronaftalenos/efeitos adversos , Resultado do Tratamento , Adulto JovemRESUMO
AIM: To determine the efficacy of (90)Y [DOTA(0), D-Phe(1), Tyr(3)]-octreotate (DOTATATE) in 67 patients with pancreatic and small bowel neuroendocrine tumors (NETs). PATIENTS & METHODS: The primary efficacy end point was overall survival (OS) and secondary end points were progression-free survival (PFS) and tumor response. RESULTS: Median PFS in pancreatic and small bowel NETs was 25 and 28 months, respectively, and median OS was 42 and 38.5 months, respectively. No intergroup differences in median OS (p = 0.945) or PFS (p = 0.174) were found, also after adjustment for tumor origin, secretory status and grade, and patient's gender. CONCLUSION: (90)Y-DOTATATE may have similar efficacy in pancreatic and small bowel NETs. Better WHO performance status at baseline seems to be associated with more favorable outcomes.
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Antineoplásicos/uso terapêutico , Neoplasias Intestinais/tratamento farmacológico , Tumores Neuroendócrinos/tratamento farmacológico , Octreotida/análogos & derivados , Compostos Organometálicos/uso terapêutico , Neoplasias Pancreáticas/tratamento farmacológico , Intervalo Livre de Doença , Feminino , Humanos , Neoplasias Intestinais/mortalidade , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Tumores Neuroendócrinos/mortalidade , Octreotida/uso terapêutico , Neoplasias Pancreáticas/mortalidade , Modelos de Riscos Proporcionais , Compostos Radiofarmacêuticos/uso terapêuticoRESUMO
We still do not know whether the presently used protocol of the first-line palliative treatment of disseminated colorectal cancer (FOLFOX/FOLFIRI protocol) allows maximization of therapeutic response and minimization of side effects. No-one has verified whether continuation of the first-line chemotherapy despite the lack of progression is reflected by improved prognosis or significant risk of toxicity. This issue is of vital importance in the case of developing countries where targeted therapies are not available due to financial shortages. We have identified three potential strategies of the palliative therapy of disseminated colorectal cancer: 1) discontinuation of chemotherapy after a fixed number of cycles with its restart on progression (stop-and-go strategy), 2) intermittent protocol of chemotherapy, and 3) continuation of chemotherapy with discontinuation of the most toxic agent. None of the studies proved the superiority of the most commonly used standard, i.e. 12 cycles of the FOLFOX or FOLFIRI regimen. Although longer duration of this treatment may be associated with higher response rates and longer progression-free survival, these improvements frequently prove insignificant on statistical analysis.
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AIM OF THE STUDY: The Patient Assistance Program, a type of expanded access program, was initiated for compassionate purposes to provide ipilimumab to patients with unresectable stage III or IV melanoma with failed previous treatment. The aim of this analysis is to evaluate efficacy, safety, and tolerability of ipilimumab therapy in daily clinical practice. MATERIAL AND METHODS: We analyzed 50 patients (29 males, 21 females) aged 21 to 76 years (median: 49 years). An ipilimumab dose of 3 mg/kg was administered intravenously every 3 weeks for a total of 4 doses. Patients were assessed for response rate, progression-free survival and overall survival, and monitored for adverse events. RESULTS: The objective response (complete or partial response) rate was 12%. Median overall survival was 8 months and median progression-free survival was 3 months. In patients with ECOG-PS 0, the median overall survival was 16 months. Immune-related adverse events (irAEs) occurred in 48% of the patients, grade 3 or 4 irAEs were reported in 8% of the patients, and there were no toxic deaths. CONCLUSIONS: Ipilimumab demonstrated clinical benefit in previously treated advanced melanoma patients. Although clinical benefit is limited to a minority of the patients, there is a benefit in terms of overall survival in this group of patients.
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INTRODUCTION: We investigated the status of estrogen receptor alpha (ERα), progesterone receptor (PR), and epidermal growth factor receptor 2 (HER2) in primary tumor and in the corresponding brain metastases in a consecutive series of breast cancer patients. Additionally, we studied factors potentially influencing conversion and evaluated its association with survival. METHODS: The study group included 120 breast cancer patients. ERα, PR, and HER2 status in primary tumors and in matched brain metastases was determined centrally by immunohistochemistry and/or fluorescence in situ hybridization. RESULTS: Using the Allred score of ≥ 3 as a threshold, conversion of ERα and PR in brain metastases occurred in 29% of cases for both receptors, mostly from positive to negative. Conversion of HER2 occurred in 14% of patients and was more balanced either way. Time to brain relapse and the use of chemotherapy or trastuzumab did not influence conversion, whereas endocrine therapy induced conversion of ERα (P = 0.021) and PR (P = 0.001), mainly towards their loss. Receptor conversion had no significant impact on survival. CONCLUSIONS: Receptor conversion, particularly loss of hormone receptors, is a common event in brain metastases from breast cancer, and endocrine therapy may increase its incidence. Receptor conversion does not significantly affect survival.
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Neoplasias Encefálicas/genética , Neoplasias Encefálicas/secundário , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Receptor ErbB-2/genética , Receptores de Estrogênio/genética , Receptores de Progesterona/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/mortalidade , Neoplasias da Mama/terapia , Terapia Combinada , Feminino , Seguimentos , Humanos , Imuno-Histoquímica , Hibridização in Situ Fluorescente , Pessoa de Meia-Idade , Gradação de Tumores , Receptor ErbB-2/metabolismo , Receptores de Estrogênio/metabolismo , Receptores de Progesterona/metabolismoRESUMO
BACKGROUND: This study evaluated the tolerability and antitumor activity of AMG 386, a peptibody (a peptide Fc fusion) that neutralizes the interaction of angiopoietin-1 and angiopoietin-2 with Tie2 (tyrosine kinase with immunoglobulin-like and EGF-like domains 2), plus sorafenib in patients with clear cell metastatic renal cell carcinoma (mRCC) in a randomized controlled study. METHODS: Previously untreated patients with mRCC were randomized 1:1:1 to receive sorafenib 400 mg orally twice daily plus intravenous AMG 386 at 10 mg/kg (arm A) or 3 mg/kg (arm B) or placebo (arm C) once weekly (qw). Patients in arm C could receive open-label AMG 386 at 10 mg/kg qw plus sorafenib following disease progression. The primary endpoint was progression-free survival (PFS). RESULTS: A total of 152 patients were randomized. Median PFS was 9.0, 8.5, and 9.0 months in arms A, B, and C, respectively (hazard ratio for arms A and B vs arm C, 0.88; 95% confidence interval [CI], 0.60-1.30; P = .523). The objective response rate (95% CI) for arms A, B, and C, respectively, was 38% (25%-53%), 37% (24%-52%), and 25% (14%-40%). Among 30 patients in arm C who had disease progression and subsequently received open-label AMG 386 at 10 mg/kg qw, the objective response rate was 3% (95% CI, 0%-17%). Frequently occurring adverse events (AEs) included diarrhea (arms A/B/C, 70%/67%/56%), palmar-plantar erythrodysesthesia syndrome (52%/47%/54%), alopecia (50%/45%/50%), and hypertension (42%/49%/46%). Fifteen patients had grade 4 AEs (arms A/B/C, n = 3/7/5); 4 had fatal AEs (n = 2/1/1), with 1 (abdominal pain, arm B) considered possibly related to AMG 386. CONCLUSIONS: In patients with mRCC, AMG 386 plus sorafenib was tolerable but did not significantly improve PFS compared with placebo plus sorafenib.
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Antineoplásicos/uso terapêutico , Benzenossulfonatos/uso terapêutico , Carcinoma de Células Renais/tratamento farmacológico , Neoplasias Renais/tratamento farmacológico , Piridinas/uso terapêutico , Proteínas Recombinantes de Fusão/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica , Biomarcadores Tumorais/metabolismo , Carcinoma de Células Renais/mortalidade , Carcinoma de Células Renais/secundário , Método Duplo-Cego , Ensaio de Imunoadsorção Enzimática , Feminino , Seguimentos , Humanos , Neoplasias Renais/mortalidade , Neoplasias Renais/patologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Niacinamida/análogos & derivados , Compostos de Fenilureia , Prognóstico , Sorafenibe , Taxa de SobrevidaRESUMO
BACKGROUND: Cancer stroma contains the neural compartment with specific components and action. Neural microenvironment processing includes among others axonogenesis, perineural invasion (PNI), neurosignaling, and tumor cell neural/neuroendocrine differentiation. Growing data suggest that tumor-neural crosstalk plays an important function in prostate cancer (PCa) biology. However, the mechanisms involved in PNI and axonogenesis, as well as their patho-clinical correlations in this tumor are unclear. METHODS: The present study was carried out on FFPE samples of 73 PCa and 15 benign prostate (BP) cases. Immunohistochemistry with neural markers PGP9.5, TH, and NFP was performed on constructed TMAs and selected tissue sections. The analyzed parameters of tumor innervation included small nerve density (ND) measured on pan-neural marker (PGP9.5) and TH s4tained slides, as well assessment of PNI presence and morphology. The qualitative and topographic aspects were studied. In addition, the expression of neuroendocrine marker chromogranin and NPY was assessed with dedicated indexes. The correlations of the above parameters with basic patho-clinical data such as patients' age, tumor stage, grade, angioinvasion, and ERG status were examined. RESULTS: The study showed that innervation parameters differed between cancer and BP. The neural network in PCa revealed heterogeneity, and ND PGP9.5 in tumor was significantly lower than in its periphery. The density of sympathetic TH-positive fibers and its proportion to all fibers was lower in cancer than in the periphery and BP samples. Perineural invasion was confirmed in 76% of cases, usually multifocally, occurring more commonly in tumors with a higher grade. NPY expression in PCa cells was common with its intensity often rising towards PNI. ERG+ tumors showed higher ND, more frequent PNI, and a higher stage. Moreover, chromogranin-positive cells were more pronounced in PCa with higher NPY expression. CONCLUSIONS: The analysis showed an irregular axonal network in prostate cancer with higher neural density (panneural and adrenergic) in the surroundings and the invasive front. ND and PNI interrelated with NPY expression, neuroendocrine differentiation, and ERG status. The above findings support new evidence for the presence of autocrine and paracrine interactions in prostate cancer neural microenvironment.
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Numerous different molecules of prostate-specific membrane antigen (PSMA) ligands are used to detect prostate cancer (PCa); most approaches utilize gallium PET and a few reports describe the role of SPECT/CT. [99mTc]Tc-PSMA-T4 is a new radiopharmaceutical designed for the diagnosis of patients with PCa. We conducted a single site, prospective, preliminary case series study that included 31 patients with PCa; all had undergone clinical, biochemical or imaging examination and exhibited clear or suspicious active disease or clinical/biochemical recurrence of PCa. Whole-body (WB) SPECT/CT after i.v. administration of [99mTc]Tc-PSMA-T4 was utilized; acquisition images were obtained at three time points. The clinical value of the images was assessed in regard to the evaluation of tumor extent in patients with confirmed PC that qualified for initial therapy and the evaluation of tumor recurrence; both provided encouraging results. The late acquisition of WB-SPECT resulted in better lesions delineation. The results of the analysis of the sensitivity/specificity were: 92%/100% in cases of primary cancer, 83%/100% in terms of pelvic lymph nodes disease, 100%/95% in other lymph nodes and soft tissue involvement, respectively, and bone mets were both 100%. An oncotropic SPECT [99mTc]Tc-PSMA-T4 can help in selecting a rational therapeutic strategy for a patient with an initial diagnosis of PCa by assessing the extent of cancer and also after complex radical or palliative therapy in case of biochemical recurrence for re-staging.
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Neoplasias da Medula Óssea/secundário , Neoplasias da Medula Óssea/terapia , Neoplasias Cerebelares/patologia , Neoplasias Cerebelares/terapia , Meduloblastoma/secundário , Meduloblastoma/terapia , Progressão da Doença , Evolução Fatal , Feminino , Humanos , Fatores de Tempo , Resultado do Tratamento , Adulto JovemRESUMO
BACKGROUND: Mycosis fungoides (MF) skin lesions are characterized by low-grade inflammation, which may be sustained by proinflammatory cytokines as probably interleukin-33 (IL-33). We compared serum concentrations of IL-33 and its receptor ST2 and the frequency of selected IL-33 single nucleotide polymorphisms (SNPs) between patients with MF and healthy controls. METHODS: In 88 patients with MF and 66 healthy controls, we analyzed SNPs in the 9894 and 11877 loci of the IL-33 gene. Moreover, we measured serum concentrations of IL-33 and its receptor ST2. RESULTS: There were no statistically significant differences in the frequencies of both IL-33 SNPs between patients and controls. Compared with controls, patients with MF had similar IL-33 serum concentrations (P = 0.71) but significantly increased ST2 concentrations (P < 0.001). Patients in MF-IA stage had significantly lower ST2 serum concentrations than those with the remaining MF stages (P = 0.002). The studied variables were not related to pruritus severity. Patients with the C(+) IL-33 11877 SNP had lower ST2 serum concentrations than patients with the C(-) 11877 SNP (P = 0.043). CONCLUSIONS: It was published before that the knockout of the ST2 gene after injection of IL-33 is associated with a reduced inflammatory reaction in the skin, as well as that IL-33 plays a role in allergic and neoplastic disorders. Concerning the difference in ST2 concentration between control and MF group, and C IL-33 11877 SNP possibly influencing the ST2 concentration, the role of IL-33/ST2 signaling, needs further studies.
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Interleucina-33/sangue , Interleucina-33/genética , Micose Fungoide/sangue , Micose Fungoide/genética , Neoplasias Cutâneas/sangue , Neoplasias Cutâneas/genética , Feminino , Humanos , Proteína 1 Semelhante a Receptor de Interleucina-1/sangue , Proteína 1 Semelhante a Receptor de Interleucina-1/genética , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo ÚnicoRESUMO
INTRODUCTION: Since the first reported case of coronavirus disease 2019 (COVID19) in Poland, the worldwide pandemic has spread throughout the country, leading to many hospital admissions. There has been an urgent need to determine clinical characteristics of Polish patients with laboratoryconfirmed severe acute respiratory syndrome coronavirus 2 (SARSCoV 2) infection in the clinical setting. OBJECTIVES: The aim of this retrospective study was to outline characteristics and short term outcomes of SARSCoV2-positive patients. PATIENTS AND METHODS: We retrospectively assessed 169 consecutive patients with laboratory confirmed COVID 19 with regard to their clinical manifestations, radiological findings, treatment, complications, and outcomes. RESULTS: Of the 169 patients, more than half was aged 65 years or older (88; 52.1%), 51.5% were male, and 78.3% had comorbidities. The majority of patients (106; 62.7%) were transferred from outbreak locations in medical facilities. The most common symptoms on admission were fever (42%), shortness of breath (35%), and fatigue (33%). Twenty seven (15.4%) patients required intensive care unit admission. Overall mortality was 26.3% (n = 46) and was significantly higher in patients transferred from other facilities (38 out of 106; 35.8%), than in patients admitted directly to the hospital (8 out of 63; 12.69%; P <0.001). Seventeen out of 29 patients admitted to the intensive care unit died (mortality, 58.6%), including 30 out of 41 patients with acute respiratory distress syndrome (73.2% mortality rate). CONCLUSIONS: Polish patients with COVID19 have similar characteristics and risk factors for adverse outcomes to those observed in countries in which outbreaks occurred earlier. Significantly higher mortality in patients transferred from other centers warrants special attention and transfer policy should be verified.
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Betacoronavirus/isolamento & purificação , Infecções por Coronavirus/diagnóstico , Unidades de Terapia Intensiva , Pneumonia Viral/diagnóstico , Adulto , Idoso , Biomarcadores/sangue , COVID-19 , Infecções por Coronavirus/sangue , Infecções por Coronavirus/terapia , Cuidados Críticos , Feminino , Hospitalização , Humanos , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/sangue , Pneumonia Viral/terapia , Polônia , Estudos Retrospectivos , Coronavírus Relacionado à Síndrome Respiratória Aguda Grave/isolamento & purificação , SARS-CoV-2RESUMO
INTRODUCTION: Many retrospective studies have confirmed that capecitabine combined with temozolomide is effective in neuroendocrine neoplasms. Most of the studies focused on grade 1 and grade 2 neuroendocrine tumours, mainly of pancreatic origin. There are limited data regarding the efficacy capecitabine with temozolomide in grade 3 neuroendocrine tumours. The new World Health Organisation 2017 classification distinguished well-differentiated grade 3 neuroendocrine tumours from poorly differentiated grade 3 neuroendocrine carcinomas. Treatment options for grade 3 neuroendocrine neoplasms are limited, and the overall prognosis is better in the subgroup of patients with grade 3 neuroendocrine tumours. MATERIAL AND METHODS: It was a retrospective study in the population of patients with diagnosed grade 3 neuroendocrine neoplasms of different origin treated with capecitabine and temozolomide. Data on clinical and demographic characteristics of the population were collected from four Polish clinical centres. This study aimed to evaluate response and survival parameters and compare outcomes of treatment of neuroendocrine tumours and carcinomas. RESULTS: The study included 32 patients with grade 3 neuroendocrine tumours treated with capecitabine and temozolomide. The disease control rate was twice as high in the group of patient with neuroendocrine tumours in comparison to carcinomas (70 vs. 30%). The progression-free survival for patients with neuroendocrine tumours was 15.3 months (95% CI: 3.9-30.4), and for patients with neuroendocrine carcinomas it was 3.3 months (95% CI: 2.5-7.1). Median overall survival was 22 months (95% CI: 11.8-22.0) and 4.6 months (95% CI: 2.2-5.9) for patients with tumours and carcinomas, respectively. The treatment regimen was generally well tolerated. CONCLUSIONS: The combination of capecitabine and temozolomide is an effective treatment for patients with grade 3 neuroendocrine tumours with Ki-67 index ranging between 20 and 54%. The treatment did not overcome the aggressive character of neuroendocrine carcinomas and resulted in low response and survival outcomes in comparison to those achieved in tumour therapy.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Capecitabina/uso terapêutico , Carcinoma Neuroendócrino/tratamento farmacológico , Temozolomida/uso terapêutico , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do TratamentoRESUMO
Transient or constant impaired immunity is often associated with neoplastic disease or oncological treatment. Among the most common pathogens found in patients with HIV or patients undergoing chemotherapy are protozoans of the Cryptosporidium genus, which cause diarrhea in humans and animals. The present study determined the frequency of Cryptosporidium spp. infections in patients with colorectal cancer (N = 108; 42 women; 66 men; median age, 65 years), before beginning oncological treatment, compared to a control group (N = 125; 56 women, 69 men; median age, 63 years) without colorectal cancer or a history of oncological disease. We also assessed whether Cryptosporidium spp. infections were associated with age, gender, cancer stage (based on Astler-Coller or TNM classification), histological grade, or cancer location. Patients were treated at the Pomeranian Medical University, in 2009-2014. The presence of Cryptosporidium spp. antigen was determined in stool samples, analyzed with a commercial immunoenzymatic test. Cryptosporidium spp. infections occurred significantly more often (p = 0.015) in patients (13%) compared to controls (4%). The patient group showed no significant relationship between Cryptosporidium spp. infection and sex, age, tumor location, cancer grade, or stage. A multivariate logistic regression analysis adjusted for age and sex that included all subjects (patient + control groups, n = 233) showed that the odds of a Cryptosporidium spp. infection were more than three-fold higher in patients than in controls, and more than six-fold higher among men than among women. CONCLUSIONS: 1) Cryptosporidium spp. infections occurred significantly more frequently in patients with colorectal cancer (before oncological treatment) compared to controls, independent of age and sex. 2) Cryptosporidium spp. infections were not associated with the colorectal cancer stage, grade, or location or with patient age. 3) Male gender was significantly related to the frequency of Cryptosporidium spp. infections, independent of age and the presence of colorectal cancer.
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Neoplasias Colorretais/complicações , Neoplasias Colorretais/epidemiologia , Criptosporidiose/epidemiologia , Criptosporidiose/etiologia , Cryptosporidium , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/terapia , Criptosporidiose/diagnóstico , Cryptosporidium/classificação , Cryptosporidium/imunologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Fatores SexuaisRESUMO
This study presents a unique series of malignant supratentorial gliomas in children previously cured from non-CNS primary cancer. On neuroimaging these tumors were not specific, so the patients were suspected of cerebral recurrence of their primary neoplasm: leukemia in four children and sarcoma in one child. Histologically, the group contained four glioblastomas and one anaplastic astrocytoma. Three patients underwent neurosurgical resection, while the other two underwent stereotactic diagnostic biopsy only. Despite combined oncological treatment, four children died during 20 months, and only one glioblastoma patient continued to live for another twelve years. Microscopically, the neoplasms consisted of small cells with some morphologic features of astrocytic lineage, having scanty or prominent processes. Microvascular proliferation and focal or diffuse necrosis were encountered in four cases. The GFAP reactivity in neoplastic cells was low or nil, together with the expression of Olig2, vimentin, and nestin. In two cases a subpopulation of synaptophysin-positive cells was present. Molecular immunohistochemical profiling revealed the expression of phosphorylated forms of PI3Kp110 and AKT, in parallel to a strong PTEN and p53 positivity. The tumors were of IDH1R132H-wild type and immunoreactive for ATRX, HER3, and EGFR. Secondary malignant gliomas in pediatric cancer survivors pose a diagnostic challenge. The present study shows that these tumors are of IDH wild type, PI3K/AKT-activated, having no PTEN and EGFR mutations. Therefore, the biopsy of brain tumors in such patients is crucial both for accurate diagnosis and material preservation for molecular typing.
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Neoplasias Encefálicas/patologia , Glioma/patologia , Segunda Neoplasia Primária/patologia , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Neoplasias Encefálicas/diagnóstico por imagem , Sobreviventes de Câncer , Criança , Pré-Escolar , Estudos de Coortes , Glioma/diagnóstico por imagem , Humanos , Imuno-Histoquímica , Segunda Neoplasia Primária/diagnóstico por imagemRESUMO
The predictive value of thymidylate synthase (TS) expression alone for 5FU-based treatment of colorectal cancer (CRC) has not been clinically confirmed. Little is known on the association of expression of E2F1, which controls the transcription of genes encoding proteins engaged in DNA synthesis including TS, and survival of patients with CRC. The purpose of this study is to assess the correlation between expression of both E2F1 and TS in CRCs and survival of patients administered adjuvant 5FU-based chemotherapy, in order to find a better predictor of treatment outcome than expression of TS or E2F1 alone. Nuclear TS and E2F1 were detected by immunohistochemistry in tissue microarrays from 190 CRCs (Astler-Coller stage B2 or C). Multivariate analysis identified significant association of the combined E2F1+TS+ immunophenotype with worse OS (HR = 3,78, P = 0,009) and DFS (HR = 2,30, P = 0,03) of patients with colon cancer. There were significant differences between E2F1+TS+ and E2F1-TS- Kaplan-Meier survival curves in relation to DFS (P = 0.008) and OS (P = 0.01). About 37 and 31 % difference in 3-year DFS and OS respectively were seen between patients with E2F1+TS+ vs. E2F1-TS- colon cancer immunophenotype. The E2F1+TS+ immunophenotype may be a marker of poor prognosis (the worst DFS and OS) of patients with colon cancer treated with 5FU-based adjuvant therapy. A subgroup of patients with this immunophenotype may require different and perhaps more aggressive treatment than 5FU-based chemotherapy. Thus, the combined E2F1/TS immunophenotype could be a potential indicator of colon cancer sensitivity to 5FU.
Assuntos
Antineoplásicos/uso terapêutico , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/patologia , Fator de Transcrição E2F1/metabolismo , Fluoruracila/uso terapêutico , Timidilato Sintase/metabolismo , Quimioterapia Adjuvante/métodos , Neoplasias Colorretais/metabolismo , Feminino , Humanos , Imuno-Histoquímica/métodos , Imunofenotipagem/métodos , Masculino , Pessoa de Meia-Idade , Prognóstico , Resultado do TratamentoRESUMO
OBJECTIVE: To analyze whether the presence of congenital anomalies of the genitourinary system that are accompanied by specific types of cancer and predispose patients to many complications, including infection, obstruction, stasis, calculus formation, and impaired renal function, could help in the diagnosis of the primary site of a metastatic tumor. CASE PRESENTATION: We report a case of a 58-year-old man with metastatic adenocarcinoma, in whom congenital anomalies of the genitourinary system proved helpful for the diagnosis of the primary site of cancer originating in the seminal vesicles. CONCLUSION: We report an extremely rare case of primary adenocarcinoma arising probably from the left seminal vesicle associated with ipsilateral renal agenesis. The lesion was detected on ultrasound and contrast-enhanced computed tomography and confirmed histologically with ultrasound-guided biopsy. Serum markers, ie, CA19-9 and CA125, were elevated, while prostate-specific antigen and carcinoembryonic antigen were within normal limits. Such a constellation of markers strengthened the diagnosis. Our patient unfortunately presented very late in the course of the disease. Hence, we decided to initiate antiandrogen therapy and best supportive care in a hospice setting. Only early detection seems to be the key factor that may result in improved cure rates for cancer of the seminal vesicles. We also performed a literature search for current concepts related to the diagnosis and clinical management of primary adenocarcinoma of seminal vesicles.
RESUMO
BACKGROUND: Bone complications, also known as skeletal-related events (SREs), are common in patients with bone metastases secondary to advanced cancers. OBJECTIVE: To provide a detailed estimate of the health resource utilization (HRU) burden associated with SREs across eight European countries. METHODS: Eligible patients from centers in Austria, the Czech Republic, Finland, Greece, Poland, Portugal, Sweden, and Switzerland with bone metastases or lesions secondary to breast cancer, prostate, or lung cancer or multiple myeloma who had experienced at least one SRE (defined as radiation to bone, long-bone pathologic fracture, other bone pathologic fracture, surgery to bone or spinal cord compression) were entered into this study. HRU data were extracted retrospectively from the patients' charts from 3.5 months before the index SRE until 3 months after the index SRE (defined as an SRE preceded by an SRE-free period of at least 6.5 months). RESULTS: Overall, the mean number of inpatient stays per SRE increased from baseline by approximately 0.5-1.5 stays, with increases in the total duration of inpatient stays of approximately 6-37 days per event. All SREs were associated with substantial increases from baseline in the frequency of procedures and the number of outpatient and day-care visits. CONCLUSIONS: SREs are associated with substantial HRU owing to considerable increases in the number and duration of inpatient stays, and in the number of procedures, outpatient visits, and day-care visits. These data collectively provide a valuable summary of the real-world SRE burden on European healthcare systems.