RESUMO
BACKGROUND: In the randomized phase II REGOMA trial, regorafenib showed promising activity in patients with recurrent glioblastoma. We conducted a large, multicenter, prospective, observational study to confirm the REGOMA data in a real-world setting. PATIENTS AND METHODS: The major inclusion criteria were histologically confirmed diagnosis of glioblastoma according to the World Health Organization (WHO) 2016 classification and relapse after radiotherapy with concurrent/adjuvant temozolomide treatment, good performance status [Eastern Cooperative Oncology Group performance status (ECOG PS 0-1)] and good liver function. Regorafenib was administered at the standard dose of 160 mg/day for 3 weeks on/1 week off. Brain magnetic resonance imaging was carried out within 14 days before starting regorafenib and every 8-12 weeks. The primary endpoint was overall survival (OS). The secondary endpoints were progression-free survival (PFS), objective response rate, disease control rate (DCR), safety and health-related quality of life. The Response Assessment in Neuro-Oncology (RANO) criteria were used for response evaluation and Common Terminology Criteria for Adverse Events (CTCAE) version 5 for assessment of adverse events (AEs). RESULTS: From September 2020 to October 2022, 190 patients with recurrent glioblastoma were enrolled from 30 cancer centers in Italy: their median age was 58.5 years [interquartile range (IQR) 53-67 years], 68% were male and 85 (44.7%) were in optimal clinical condition (ECOG PS 0). The number of patients taking steroids at baseline was 113 (60%); the second surgery was carried out in 39 (20.5%). O6-methylguanine-DNA methyltransferase (MGMT) was methylated in 80 patients (50.3%) and 147 (92.4%) of the patients analyzed had isocitrate dehydrogenase (IDH) wild type. The median follow-up period was 20 months (IQR 15.6-25.5 months). The median OS was 7.9 months ([95% confidence interval (CI) 6.5-9.2 months] and the median PFS was 2.6 months (95% CI 2.3-2.9 months). Radiological response was partial response and stable disease in 13 (7.3%) and 26 (14.6%) patients, respectively, with a DCR of 21.9%. The median number of regorafenib cycles per patient was 3 (IQR 2.0-4.0). Grade 3-4 drug-related adverse events were reported in 22.6% of patients. A dose reduction due to AEs was required in 36% of patients. No deaths were considered as treatment-related AEs. CONCLUSIONS: This large, real-world observational study showed similar OS with better tolerability of regorafenib in patients with relapsed glioblastoma compared with the REGOMA study.
Assuntos
Neoplasias Encefálicas , Glioblastoma , Recidiva Local de Neoplasia , Compostos de Fenilureia , Piridinas , Humanos , Glioblastoma/tratamento farmacológico , Masculino , Feminino , Pessoa de Meia-Idade , Estudos Prospectivos , Piridinas/uso terapêutico , Piridinas/farmacologia , Idoso , Compostos de Fenilureia/uso terapêutico , Compostos de Fenilureia/farmacologia , Neoplasias Encefálicas/tratamento farmacológico , Itália , Adulto , Antineoplásicos/uso terapêutico , Antineoplásicos/farmacologia , Qualidade de Vida , Resultado do TratamentoRESUMO
OBJECTIVE: SAMITAL®, a botanical drug containing three highly standardized extracts (Vaccinium myrtillus, Macleaya cordata and Echinacea angustifolia), has shown promising results in treating or preventing oral mucositis (OM) in adult patients, but it has not been fully investigated in children. In this study, we assessed the feasibility of SAMITAL administration in pediatric patients receiving anticancer treatment to prevent or treat OM, focusing on identifying an appropriate dose and evaluating safety and tolerability and palatability and treatment compliance. PATIENTS AND METHODS: We conducted an open-label, monocentric, prospective study on 18 children receiving anticancer therapy to prevent or treat OM. RESULTS: No SAMITAL®-related side effects were observed or reported during the study; moreover, no systemic absorption of SAMITAL® metabolites was detected in the bloodstream. However, compliance to SAMITAL® was unsatisfactory and variable (from 2 to 100%), and patients reported low palatability (median taste of 4.8; range 1.0-8.0). CONCLUSIONS: SAMITAL® administration appears to be safe in the pediatric population, as it is not absorbed in the bloodstream and does not cause any local or systemic side effects. However, the current formulation is only partially suitable for children, and future studies on SAMITAL® in children would need an adapted formulation to increase compliance.
Assuntos
Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Estomatite , Vaccinium myrtillus , Criança , Humanos , Estudos de Viabilidade , Estudos Prospectivos , Estomatite/induzido quimicamente , Estomatite/tratamento farmacológicoRESUMO
BACKGROUND: Colonic J pouch reconstruction has been found to be associated with a lower incidence of anastomotic leakage than straight anastomosis. However, studies on this topic are underpowered and retrospective. This randomized trial evaluated whether the incidence of anastomotic leakage was reduced after colonic J pouch reconstruction compared with straight colorectal anastomosis following anterior resection for rectal cancer. METHODS: This multicentre RCT included patients with rectal carcinoma who underwent low anterior resection followed by colorectal anastomosis. Patients were assigned randomly to receive a colonic J pouch or straight colorectal anastomosis. The main outcome measure was the occurrence of major anastomotic leakage. The incidence of global (major plus minor) anastomotic leakage and general complications were secondary outcomes. Risk factors for anastomotic leakage were identified by regression analysis. RESULTS: Of 457 patients enrolled, 379 were evaluable (colonic J pouch arm 190, straight colorectal arm 189). The incidence of major and global anastomotic leakage, and general complications was 14·2, 19·5 and 34·2 per cent respectively in the colonic J pouch group, and 12·2, 19·0 and 27·0 per cent in the straight colorectal anastomosis group. No statistically significant differences were observed between the two arms. In multivariable logistic regression analysis, male sex (odds ratio 1·79, 95 per cent c.i. 1·02 to 3·15; P = 0·042) and high ASA fitness grade (odds ratio 2·06, 1·15 to 3·71; P = 0·015) were independently associated with the occurrence of anastomotic leakage. CONCLUSION: Colonic J pouch reconstruction does not reduce the incidence of anastomotic leakage and postoperative complications compared with conventional straight colorectal anastomosis. Registration number NCT01110798 (http://www.clinicaltrials.gov).
Assuntos
Colo/cirurgia , Bolsas Cólicas , Procedimentos de Cirurgia Plástica , Neoplasias Retais/cirurgia , Reto/cirurgia , Grampeamento Cirúrgico , Idoso , Anastomose Cirúrgica/efeitos adversos , Anastomose Cirúrgica/métodos , Fístula Anastomótica/epidemiologia , Fístula Anastomótica/etiologia , Bolsas Cólicas/efeitos adversos , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Procedimentos de Cirurgia Plástica/efeitos adversos , Procedimentos de Cirurgia Plástica/métodos , Grampeamento Cirúrgico/métodosRESUMO
BACKGROUND: In human epidermal growth factor receptor 2 (HER2+) breast cancers, neoadjuvant trials of chemotherapy plus anti-HER2 treatment consistently showed lower pathologic complete response (pCR) rates in hormone receptor (HR) positive versus negative tumors. The PerELISA study was aimed to evaluate the efficacy of a de-escalated, chemotherapy-free neoadjuvant regimen in HR+/HER2+ breast cancer patients selected on the basis of Ki67 inhibition after 2-week letrozole. PATIENTS AND METHODS: PerELISA is a phase II, multicentric study for postmenopausal patients with HR+/HER2+ operable breast cancer. Patients received 2-week letrozole, and then underwent re-biopsy for Ki67 evaluation. Patients classified as molecular responders (Ki67 relative reduction >20% from baseline) continued letrozole and started trastuzumab-pertuzumab for five cycles. Patients classified as molecular non-responders started weekly paclitaxel for 13 weeks combined with trastuzumab-pertuzumab. Primary aim was breast and axillary pCR. According to a two-stage Simon's design, to reject the null hypothesis, at least 8/43 pCR had to be documented. RESULTS: Sixty-four patients were enrolled, 44 were classified as molecular responders. All these patients completed the assigned treatment with letrozole-trastuzumab-pertuzumab and underwent surgery. A pCR was observed in 9/44 cases (20.5%, 95% confidence interval 11.1% to 34.5%). Among molecular non-responders, 16/17 completed treatment and underwent surgery, with pCR observed in 81.3% of the cases. PAM50 intrinsic subtype was significantly associated with Ki67 response and pCR. Among molecular responders, the pCR rate was significantly higher in HER2-enriched than in other subtypes (45.5% versus 13.8%, P = 0.042). CONCLUSIONS: The primary end point of the study was met, by reaching the pre-specified pCRs. In patients selected using Ki67 reduction after short-term letrozole exposure, a meaningful pCR rate can be achieved without chemotherapy. PAM50 intrinsic subtyping further refines our ability to identify a subset of patients for whom chemotherapy might be spared. EUDRACT NUMBER: 2013-002662-40. CLINICALTRIALS.GOV IDENTIFIER: NCT02411344.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Antígeno Ki-67/metabolismo , Receptor ErbB-2/metabolismo , Receptores de Estrogênio/metabolismo , Receptores de Progesterona/metabolismo , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais Humanizados/administração & dosagem , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Neoplasias da Mama/cirurgia , Carcinoma Ductal de Mama/tratamento farmacológico , Carcinoma Ductal de Mama/metabolismo , Carcinoma Ductal de Mama/patologia , Carcinoma Ductal de Mama/cirurgia , Carcinoma Lobular/tratamento farmacológico , Carcinoma Lobular/metabolismo , Carcinoma Lobular/patologia , Carcinoma Lobular/cirurgia , Relação Dose-Resposta a Droga , Feminino , Seguimentos , Humanos , Letrozol/administração & dosagem , Pessoa de Meia-Idade , Terapia Neoadjuvante , Invasividade Neoplásica , Prognóstico , Indução de Remissão , Trastuzumab/administração & dosagemRESUMO
BACKGROUND: Cutaneous metastases represent a therapeutic challenge. An increasing body of experience suggests that electrochemotherapy (ECT) provides effective tumor control, although its evidence basis should be strengthened. METHODS: This prospective, multicenter, observational study enrolled patients with superficial metastases, who underwent ECT at 10 centers between 2008 and 2013. Outcomes included adherence to European Standard Operating Procedures of ECT (ESOPE), tumor response, local progression-free survival (LPFS), toxicity and patient-reported outcomes (PROs, EORTC QLQ-C30 plus an 8-item questionnaire). RESULTS: We enrolled 376 eligible patients. Tumor histotype distribution was as follows: melanoma, 56%; squamous cell carcinoma, 11%; Kaposi sarcoma, 11%; breast carcinoma, 8%; basal cell carcinoma, 6%; soft tissue sarcomas, 3%; others, 5%. We registered 1304 target tumors (median size 1 cm). Treatment adhered to ESOPE in 88% of patients as to the route of drug administration, and in 70% as to electrode application. The procedure was mainly performed under sedation (64.6%) and by using intravenous chemotherapy (93.4%). Tumor response rate at 60 days was 88% (complete, 50%). Small tumor size predicted complete response achievement (OR 2.24, p = 0.003), higher LPFS (HR 0.68, p = 0.004) and improved PROs (Global Health Status, p < 0.001; wound bleeding, p < 0.001; healing, p = 0.002; and aesthetics, p < 0.001). Skin toxicity (grade ≥3, 7.8%) was lower in patients with tumors <2 cm (p≤0.001). One-year LPFS was 73.7% (95%CI 68.4-78.3). CONCLUSIONS: ECT represents a valuable skin-directed therapy across a range of malignancies. The most frequently applied treatment modality is intravenous chemotherapy under sedation. Small tumor size predicts durable tumor control, fewer side-effects and better PROs.
Assuntos
Antineoplásicos/uso terapêutico , Carcinoma/terapia , Eletroquimioterapia/métodos , Melanoma/terapia , Sarcoma de Kaposi/terapia , Sarcoma/terapia , Neoplasias Cutâneas/terapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Bleomicina/uso terapêutico , Neoplasias da Mama/patologia , Carcinoma/secundário , Carcinoma Basocelular/secundário , Carcinoma Basocelular/terapia , Carcinoma de Células Escamosas/secundário , Carcinoma de Células Escamosas/terapia , Cisplatino/uso terapêutico , Feminino , Humanos , Injeções Intralesionais , Estimativa de Kaplan-Meier , Masculino , Melanoma/secundário , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Estudos Prospectivos , Sarcoma/secundário , Sarcoma de Kaposi/secundário , Neoplasias Cutâneas/patologia , Neoplasias Cutâneas/secundário , Resultado do Tratamento , Adulto JovemRESUMO
BACKGROUND: To report the results of the first European prospective nonrandomized trial dedicated to pediatric synovial sarcoma. PATIENTS AND METHODS: From August 2005 to August 2012, 138 patients <21 years old with nonmetastatic synovial sarcoma were registered in 9 different countries (and 60 centers). Patients were treated with a multimodal therapy including ifosfamide-doxorubicin chemotherapy and radiotherapy, according to a risk stratification based on surgical stage, tumor size and site, and nodal involvement. RESULTS: With a median follow-up of 52.1 months (range 13.8-104.4 months), event-free survival (EFS) was 81.9% and 80.7%, and overall survival (OS) was 97.2% and 90.7%, at 3 and 5 years, respectively. The only significant prognostic variable at univariate analysis was the risk group: 3-year EFS was 91.7% for low-risk, 91.2% for intermediate-risk, and 74.4% for high-risk cases. In 24 low-risk patients (completely resected tumor ≤5 cm in size) treated with surgery alone, there were two local relapses and no metastatic recurrences. Among 67 high-risk patients (unresected, or axial tumor or nodal involvement), 66 underwent surgery after neoadjuvant chemotherapy. Response to chemotherapy was 55.2%, including 22.4% cases with complete or major partial remissions, and 32.8% with minor partial remissions. CONCLUSION: This study demonstrates that collaborative prospective studies on rare pediatric sarcomas are feasible even on a European scale, with excellent treatment compliance. The overall results of treatment were satisfactory, with higher survival rates than those previously published by pediatric groups. Nonetheless, larger, international projects are needed, based on a cooperative effort of pediatric and adult oncologists. CLINICAL TRIALS NUMBER: European Union Drug Regulating Authorities Clinical Trials No. 2005-001139-31.
Assuntos
Sarcoma Sinovial/diagnóstico , Sarcoma Sinovial/epidemiologia , Neoplasias de Tecidos Moles/diagnóstico , Neoplasias de Tecidos Moles/epidemiologia , Adolescente , Criança , Europa (Continente)/epidemiologia , Feminino , Seguimentos , Humanos , Masculino , Estudos Prospectivos , Sarcoma Sinovial/terapia , Neoplasias de Tecidos Moles/terapiaRESUMO
BACKGROUND: AMP-activated protein kinase (AMPK) has a central role in cellular energy sensing and is activated in preclinical tumour models following anti-vascular endothelial growth factor (VEGF) therapy. The possible predictive or prognostic role of AMPK status in cancer patients treated with anti-VEGF drugs has not been investigated so far. METHODS: Expression of components of the AMPK pathway including phosphorylated AMPK (pAMPK), phosphorylated acetyl-Coa carboxylase (pACC) and liver kinase B1 (LKB1) was investigated by immunohistochemistry in 48 colorectal cancers treated with FOLFIRI plus bevacizumab. Correlation between pAMPK and pACC and associations between the AMPK pathway scores and clinico-pathological characteristics were assessed. Overall survival (OS) was estimated through Kaplan-Meier method, whereas hazard ratios were computed to identify prognostic factors. RESULTS: Fourteen patients (29.2%) were included in the pAMPK-negative group (score ≤5), whereas 34 patients (70.8%) were included in the pAMPK-positive group (score >5). The Spearman's coefficient for the correlation between pAMPK and pACC scores in primary tumour samples was 0.514 (P=0.0002). Low pAMPK levels were associated with worse OS (P-value 0.0002) but not with PFS, whereas low pACC levels were associated both with worse OS and PFS (P-value 0.0007 and 0.01, respectively). CONCLUSIONS: Our findings suggest that high tissue AMPK activation is a prognostic biomarker in this cohort of metastatic colorectal cancer patients.
Assuntos
Proteínas Quinases Ativadas por AMP/metabolismo , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/enzimologia , Adulto , Idoso , Inibidores da Angiogênese/administração & dosagem , Anticorpos Monoclonais Humanizados/administração & dosagem , Bevacizumab , Biomarcadores Tumorais/metabolismo , Camptotecina/administração & dosagem , Camptotecina/análogos & derivados , Ativação Enzimática , Feminino , Fluoruracila/administração & dosagem , Humanos , Imuno-Histoquímica , Irinotecano , Masculino , Pessoa de Meia-Idade , PrognósticoRESUMO
BACKGROUND: Parameningeal (PM) site is a well-known adverse prognostic factor in children with localized rhabdomyosarcoma (RMS). To identify risk factors associated with outcome at this site, we pooled data from 1105 patients treated in 10 studies conducted by European and North American cooperative groups between 1984 and 2004. PATIENTS AND METHODS: Clinical factors including age, histology, size, invasiveness, nodal involvement, Intergroup Rhabdomyosarcoma Study (IRS) clinical group, site, risk factors for meningeal involvement (MI), study group, and application of radiotherapy (RT) were studied for their impact on event-free and overall survival (EFS and OS). RESULTS: Ten-year EFS and OS were 62.6 and 66.1% for the whole group. Patients without initial RT showed worse survival (10-year OS 40.8% versus 68.5% for RT treated patients). Multivariate analysis focusing on 862 patients who received RT as part of their initial treatment revealed four unfavorable prognostic factors: age <3 or >10 years, signs of MI, unfavorable site, and tumor size. Utilizing these prognostic factors, patients could be classified into different risk groups with 10-year OS ranging between 51.1 and 80.9%. CONCLUSIONS: While, in general, PM localization is regarded as an adverse prognostic factor, the current analysis differentiates those with good prognosis (36% patients with 0-1 risk factor: 10-year OS 80.9%) from high-risk PM patients (28% with 3-4 factors: 10-year OS 51.1%). Furthermore, this analysis reinforces the necessity for RT in PM RMS.
Assuntos
Neoplasias do Sistema Nervoso Central/mortalidade , Rabdomiossarcoma/mortalidade , Neoplasias do Sistema Nervoso Central/radioterapia , Terapia Combinada , Humanos , Estimativa de Kaplan-Meier , Análise Multivariada , Prognóstico , Modelos de Riscos Proporcionais , Rabdomiossarcoma/radioterapiaRESUMO
The reported incidence of hereditary colorectal cancers (CRCs) is widely variable. The principal aim of the study was to prospectively evaluate the incidence of familial CRCs in a region of northern Italy using a standardized method. Consecutive CRC patients were prospectively enrolled from October 2002 to December 2003. Patients underwent a structured family history, the microsatellite instability (MSI) test and a screen for MUTYH mutations. Following family history patients were classified as belonging to high, moderate and mild risk families. Immunohistochemistry for MLH1, MSH2, MSH6 and PMS2 proteins and investigation for MLH1/MSH2 mutations, for MLH1 promoter methylation and for the V600E hotspot BRAF mutation were performed in high MSI (MSI-H) cases. Of the 430 patients enrolled, 17 (4%) were high risk [4 hereditary non-polyposis colorectal cancer (HNPCC), 12 suspected HNPCC and 1 MUTYH-associated adenomatous polyposis coli (MAP)], 53 moderate risk and 360 mild risk cases. The MSI test was performed on 393 tumours, and 46 (12%) of them showed MSI-H. In these patients, one MLH1 pathogenetic mutations and two MSH2 pathogenetic mutations were found. Thirty-two (70%) MSI-H cases demonstrated MLH1 methylation and/or BRAF mutation: None of them showed MLH1/MSH2 mutation. Two biallelic germline MUTYH mutations were found, one with clinical features of MAP. A strong family history of CRC was present in 4% of the enrolled cases; incidence of MLH1/MSH2 or MUTHY mutations was 1.3% and of MSI-H phenotype was 12%. MLH1 methylation and BRAF mutation can exclude 70% of MSI-H cases from gene sequencing.
Assuntos
Polipose Adenomatosa do Colo/genética , Neoplasias Colorretais Hereditárias sem Polipose/genética , DNA Glicosilases/genética , Proteínas Adaptadoras de Transdução de Sinal/genética , Polipose Adenomatosa do Colo/epidemiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias Colorretais Hereditárias sem Polipose/epidemiologia , Metilação de DNA , Análise Mutacional de DNA , Proteínas de Ligação a DNA/genética , Feminino , Genes APC , Mutação em Linhagem Germinativa , Humanos , Incidência , Itália/epidemiologia , Masculino , Instabilidade de Microssatélites , Pessoa de Meia-Idade , Proteína 1 Homóloga a MutL , Proteína 2 Homóloga a MutS/genética , Proteínas Nucleares/genética , Regiões Promotoras Genéticas , Estudos Prospectivos , Proteínas Proto-Oncogênicas B-raf/genética , Estudos Retrospectivos , População Branca/genéticaRESUMO
BACKGROUND: This study compared the central nervous system (CNS) metastasis incidence between a temozolomide- and a dacarbazine-based regimen in untreated stage IV melanoma patients. METHODS: A total of 150 patients were randomly assigned to receive either oral temozolomide (200 mg m(-2) per day; days 1-5) or intravenous dacarbazine (800 mg m(-2); day 1), in combination with intravenous cisplatin (75 mg m(-2); day 1) and subcutaneous interleukin-2 (3 MU twice daily; days 9-18), every 28 days (CTI and CDI). RESULTS: A total of 149 patients were eligible for an intention-to-treat analysis (CTI: n=74, CDI: n=75). The 1-year cumulative CNS incidence failure was 20.6% for CTI and 31.1% for CDI (P=0.22). In all 24 patients in CTI (32%) and 34 (45%) in CDI developed CNS metastases; 31 patients died of early systemic progression, before CNS evaluation. Median survival time was 8.4 months in the CTI and 8.7 in the CDI arm; in patients with CNS metastases the median survival time was 13.5 months in the CTI and 11.5 in the CDI arm. No difference in toxicity was observed between the two arms. CONCLUSION: The incidence of CNS failures in metastatic melanoma was not significantly reduced and the clinical course was not modified substituting a dacarbazine-based regimen with a temozolomide-based regimen. Patients who developed CNS metastases did not have a worse prognosis than patients progressing in other sites and should not be excluded from new investigational studies.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Encefálicas/secundário , Dacarbazina/análogos & derivados , Dacarbazina/uso terapêutico , Melanoma/tratamento farmacológico , Neoplasias Cutâneas/tratamento farmacológico , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Barreira Hematoencefálica , Dacarbazina/administração & dosagem , Feminino , Humanos , Masculino , Melanoma/patologia , Pessoa de Meia-Idade , Neoplasias Cutâneas/patologia , TemozolomidaRESUMO
AIMS: To compare physical morbidity and health-related quality of life (HRQOL) in breast cancer patients who received standard axillary dissection (ALND) or sentinel lymph node biopsy (SLNB), followed by axillary dissection only in the case of sentinel-node positivity, within a randomised clinical trial. PATIENTS AND METHODS: Patients with early breast cancer < or =3cm and clinically negative axilla were randomly allocated to ALND or SLNB. All patients underwent physical examination every 6 months in order to assess any arm-related symptoms. A subset of patients completed the SF-36 quality of life questionnaire and the Psychological General Well Being Index (PGWBI) before randomisation, at 6 and 12 months after surgery and yearly thereafter. Results of the first 24 months are reported. RESULTS: Six-hundred and seventy-seven patients were available for analysis: 341 patients randomised to the ALND group and 336 to the SLNB group. Six months after surgery, the SLNB group had significantly less lymph-oedema, movement restrictions, pain and numbness with respect to the ALND group. Lymph-oedema was also significantly reduced at 12 months and numbness remained significantly less frequent in the SLNB arm at all time points. Three-hundred and ten patients participated in the HRQOL assessment. The mean scores of the PGWB questionnaire general index and anxiety domain were significantly better in the SLNB group than in the ALND group but the difference ceased to be significant at 24 months. CONCLUSIONS: The SLNB is associated with reduced arm morbidity without evidence of a negative impact on psychological well being. While waiting for long-term results of ongoing randomised clinical trials, the SLNB may be proposed for early stage breast cancer patients after adequate information on the expected advantages and the possible risks.
Assuntos
Axila/cirurgia , Neoplasias da Mama/epidemiologia , Neoplasias da Mama/mortalidade , Excisão de Linfonodo/estatística & dados numéricos , Biópsia de Linfonodo Sentinela/estatística & dados numéricos , Idoso , Neoplasias da Mama/patologia , Feminino , Humanos , Itália , Pessoa de Meia-Idade , Morbidade , Estadiamento de Neoplasias , Qualidade de Vida , Inquéritos e QuestionáriosRESUMO
AIMS: To evaluate the incidence of false-negative (FN) sentinel lymph node (SLN) cases, their correlation with a series of clinico-pathologic parameters and their impact on adjuvant treatment indications and on clinical axillary relapse in the setting of a multicentric clinical trial comparing SLN biopsy with axillary lymph node dissection (ALND). METHODS: A series of 697 patients with primary breast cancer < or = 3 cm were randomized to SLN biopsy associated with ALND (ALND arm) or to SLN biopsy followed by ALND only if the SLN was metastatic (SLN arm). The FN SLN rate was assessed in the ALND arm. A series of 11 clinico-pathological parameters were tested for a possible association with FN results. The indications for adjuvant treatments were evaluated by considering both the FN nodal stages, as indicated by the SLN, and the true positive axillary status, as indicated by completion ALND. The occurrence of clinically evident axillary recurrences was evaluated in the two arms. RESULTS: The FN rate was 16.7%. Of the clinico-pathologic parameters tested, only a tumour size < or = 2 cm and the presence of a single metastatic axillary node was significantly associated with a risk of FN (p = 0.033 and p = 0.018, respectively). The FN SLN would have led to different adjuvant therapy indications in 12/18 cases. At 56 months, no clinically evident axillary nodal recurrences were present in the ALND arm patients, whereas one case of axillary recurrence was detected in the SLN arm patients. CONCLUSIONS: FN SLN biopsy is not uncommon, especially in the presence of a small primary tumour with a single nodal metastasis. An FN finding can lead to less than optimal adjuvant treatment. However, the clinical impact of FN in terms of axillary recurrence at 56 months was minimal.
Assuntos
Neoplasias da Mama/patologia , Quimioterapia Adjuvante , Tomada de Decisões , Biópsia de Linfonodo Sentinela , Axila , Intervalo Livre de Doença , Reações Falso-Negativas , Feminino , Humanos , Incidência , Excisão de Linfonodo/métodos , Metástase Linfática , Pessoa de Meia-Idade , Recidiva Local de NeoplasiaRESUMO
BACKGROUND: Since vinorelbine and gemcitabine are both active in breast cancer with moderate toxicity, in 2002 we started a phase II trial with a combination regimen in elderly patients. PATIENTS AND METHODS: To evaluate complete plus partial response rates and toxicity of first-line vinorelbine 25 mg/m2 plus gemcitabine 1000 mg/m2 on days 1 and 8, every 3 weeks, in women>or=70 years with advanced breast cancer and measurable lesions. All patients underwent multidimensional geriatric assessment before enrollment. A two-step design was applied, and the trial would be completed if an overall response rate>or=30% was obtained with a grade 3-grade 4 (G3-G4) toxicity rate
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/patologia , Comorbidade , Desoxicitidina/administração & dosagem , Desoxicitidina/análogos & derivados , Feminino , Humanos , Qualidade de Vida , Taxa de Sobrevida , Vimblastina/administração & dosagem , Vimblastina/análogos & derivados , Vinorelbina , GencitabinaRESUMO
The clinical role of sentinel node biopsy (SNB) in thyroid cancer remains an open matter in literature. The main reason of this fact is that nodal disease is considered a non-relevant prognostic factor by some authors in differentiated thyroid cancer (DTC). Aim of this study was to investigate the efficacy of radiocolloid lymphoscintigraphy and of hand held gamma probe procedure for SNB in patients with DTC and its potential clinical role. Forty-one consecutive pts with a small thyroid nodule highly suspected for malignancy at fine-needle aspiration cytology (FNAC) and without clinical and ultrasonographic (US) evidence of lymph node involvement entered the study. All patients underwent lymphoscintigraphy 3 hours before intervention using a 99mTc-nanocolloid solution. One single intratumoral injection of 4-9 MBq in 0.1-02 ml normal saline was obtained under US-guidance followed by a dynamic lymphoscintigraphy. After total thyroidectomy central and lateral compartments of the neck were scanned with a hand held gamma probe. The hottest node and any lymph node with a count rate of more than 10% of the hottest node were removed. SLNs were sent to frozen section analysis and a surgical enlargement of corresponding compartment was performed when at least one SLN was positive at histology. Preoperative lymphoscintigraphy was able to identify one node in six cases, two nodes in five cases, three nodes in 14 cases, four or more nodes in 16 cases. A papillary thyroid carcinoma (PTC) was diagnosed in 39 cases, a mixed papillary-medullary carcinoma in one case and a micro-follicular adenoma in one case. In 21/40 patients (pts) positive lymph nodes were found: in 16/21 patient one node showed micrometastasis only, in 5/21 patients more nodes were metastatic. In particular in 11 cases the first hottest node was involved (true SLN), in 10 cases a second or third hot lymph node was involved. In our preliminary experience lymphoscintigraphy with 99mTc-nanocolloid resulted highly sensitive: in fact at least one lymph node was visualized in all cases and the surgeon was able to detect by means of hand held probe during intervention al least one hot SLN in all cases. In 21/40 pts (more than 50% of cases) metastatic lymph nodes were found despite preoperative clinical and US examination negative for lymph node involvement. In prospective SLN technique might be proposed as a relevant tool in lymphoadenectomy decision in DTC patients with a small tumor.
Assuntos
Neoplasias da Glândula Tireoide/diagnóstico por imagem , Neoplasias da Glândula Tireoide/cirurgia , Adulto , Idoso , Biópsia por Agulha Fina , Diagnóstico Diferencial , Feminino , Humanos , Excisão de Linfonodo , Linfonodos/diagnóstico por imagem , Linfonodos/patologia , Linfonodos/cirurgia , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Cintilografia , Biópsia de Linfonodo Sentinela , Glândula Tireoide/diagnóstico por imagem , Glândula Tireoide/patologia , Glândula Tireoide/cirurgia , Neoplasias da Glândula Tireoide/patologia , Nódulo da Glândula Tireoide/diagnóstico por imagem , Nódulo da Glândula Tireoide/patologia , Nódulo da Glândula Tireoide/cirurgiaRESUMO
AIMS: To investigate early and late complications in 44 patients with locally advanced mid-low rectal cancer enrolled in a phase I-II study, who had received an aggressive chemoradiation treatment (50.4Gy/28F; 5-FU continuous infusion and weekly Oxaliplatin) followed by total mesorectal excision and 5-FU based postoperative chemotherapy. The aim of the present study is also to evaluate functional outcome and quality of life (QoL) in a sub-group of 22 patients. METHODS: Standardized forms for early and late surgical complications were completed for all patients. Anorectal function and QoL were also investigated in 22 patients who underwent surgery in the same surgical unit, using the fecal incontinence scoring system (FIS) and EORTC-QLQ-CR38 questionnaires, compiled before and after radiotherapy and at least 8 months after surgery. The differences over time in scores were analyzed using repeated measure ANOVA. RESULTS: The median age of patients (25 males and 19 females) was 58 (range: 34-73) years. A low anterior resection was performed in 39 cases, radical resection in 41, and 12 patients had a pathological complete response. There were no operative deaths; 4 and 9 patients required re-operation for early and late complications, respectively. FIS score did not present a significant worsening over time. According to data in the EORTC-QLQ-CR38 questionnaire, a significant improvement over time was found only for "future perspective". CONCLUSION: Our findings seem to indicate that this aggressive 5-FU-Oxalipaltin-based treatment implies no impairment of QoL and anorectal function, even if a high rate of late major complications was observed. Studies on larger series are required to confirm these results.
Assuntos
Adenocarcinoma/cirurgia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Terapia Neoadjuvante , Complicações Pós-Operatórias , Qualidade de Vida , Neoplasias Retais/cirurgia , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/radioterapia , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Terapia Combinada , Incontinência Fecal/etiologia , Feminino , Fluoruracila/administração & dosagem , Fluoruracila/efeitos adversos , Humanos , Masculino , Pessoa de Meia-Idade , Compostos Organoplatínicos/administração & dosagem , Compostos Organoplatínicos/efeitos adversos , Oxaliplatina , Neoplasias Retais/tratamento farmacológico , Neoplasias Retais/radioterapia , Reto/cirurgia , Inquéritos e QuestionáriosRESUMO
AIMS: To determine the axillary recurrence rate in breast cancer patients with negative sentinel lymph nodes (SLN) who did not undergo further axillary lymph node dissection (ALND), and to establish whether this conservative axillary approach leads to an increased recourse to diagnostic axillary biopsy during the follow-up period because of the clinical suspicion of nodal recurrence. METHODS: In 479 patients, operated on for early breast cancer between 1998 and 2002 in five institutions, SLN biopsy was negative and no further axillary surgery was performed. SLN was localized using subdermal injection with 30-50 MBq of 99m-Tc-colloidal albumin. Follow-up controls were performed at 6-monthly intervals. RESULTS: The mean number of SLNs removed was 1.4 per patient. Most patients (90.6%) were given adjuvant systemic therapy, based on the primary tumour characteristics. At a median follow-up of 35.8 months, no clinical axillary recurrence was found. No patient underwent surgical axillary biopsy for suspicious clinical or ultrasonographic findings. CONCLUSIONS: Our results confirm that SLN biopsy without ALND in SLN-negative patients with early breast cancer is not followed by clinically evident axillary recurrence in the short-term.
Assuntos
Neoplasias da Mama/patologia , Recidiva Local de Neoplasia , Biópsia de Linfonodo Sentinela , Adulto , Idoso , Idoso de 80 Anos ou mais , Axila , Estudos de Casos e Controles , Feminino , Seguimentos , Humanos , Excisão de Linfonodo , Pessoa de Meia-Idade , PrognósticoRESUMO
BACKGROUND: In 8 to 29% of patients with colorectal carcinoma, obstruction is the main symptom at diagnosis, and 85% of patients undergoing emergency colorectal surgery have obstruction from colorectal carcinoma. The prognosis of patients who undergo emergency surgery for obstruction is often poor. So far, two types of surgical approach have been used for this condition: primary resection (primary anastomosis or Hartmann's procedure) with simultaneous treatment of carcinoma and obstruction, or staged resection (treatment of the obstruction prior to resection).However, neither strategy has been found to have any advantages over the other. OBJECTIVES: To ascertain whether primary resection in patients with obstruction from left colorectal carcinoma has advantages over staged resection in terms of morbidity and mortality. SEARCH STRATEGY: Electronic database searches of Cochrane Controlled Trials Register, Medline, Cancerlit, Embase. Hand searching of the most important journals in the fields of oncology and surgery from 2003 and onward until the time of writing. SELECTION CRITERIA: Randomised Clinical Trials (RCT) and Controlled Clinical Trials (CCT), in which a group of patients who undergo primary resection for intestinal obstruction from left primary colorectal carcinoma is compared with a group of patients who undergo staged resection for the same condition. Since only one study of this type was available, we considered all other studies, except for case-controls, on the basis of the best possible available evidence. Studies were considered without language restrictions. DATA COLLECTION AND ANALYSIS: Two reviewers (GLDS, CG) examined all the citations and abstracts derived from the electronic search strategy. Reports of potentially relevant trials were retrieved in full. Both reviewers independently applied the selection criteria to trials reports. Reviewers were not blind to the names of institutions, journals or authors of trials. A third opinion (SP, ML) was obtained to resolve disagreements. MAIN RESULTS: We identified 2043 citations: Medline 1205, Embase 635, Cancerlit 203. One study for potential inclusion was identified, but was then excluded (Kronborg 1995). REVIEWERS' CONCLUSIONS: The limited number of identified trials together with their methodological weaknesses do not allow a reliable assessment of the role of either therapeutic strategy in the treatment of patients with bowel obstruction from colorectal carcinoma. It would appear advisable to conduct high quality large scale RCT to establish which treatment is more effective. However, it is doubtful whether they could be carried out in a timely and satisfactory way in this particular surgical context.
Assuntos
Neoplasias Colorretais/cirurgia , Obstrução Intestinal/cirurgia , Neoplasias Colorretais/complicações , Procedimentos Cirúrgicos do Sistema Digestório/métodos , Humanos , Obstrução Intestinal/etiologiaRESUMO
We report here the results of 27 patients who underwent hyperthermic isolated limb perfusion with low-dose TNFalpha (1 mg) and doxorubicin (8.5 mg/l of limb volume) for locally advanced soft tissue sarcomas. A tumor response was observed in 85% of cases. After a median follow-up of 30 months, limb salvage and local disease control were achieved in 82 and 85% of patients, respectively. Locoregional toxicity was low or mild in 14 patients, while 2 patients had severe limb toxicity. Systemic side effects were negligible. The perfusate/plasma area under the curve (AUC) ratio for TNFalpha was 56. HILP with low-dose TNFalpha and DXR proved to be an active neoadjuvant drug regimen against limb-threatening STS.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Quimioterapia do Câncer por Perfusão Regional/métodos , Doxorrubicina/administração & dosagem , Hipertermia Induzida , Sarcoma/tratamento farmacológico , Fator de Necrose Tumoral alfa/administração & dosagem , Adulto , Idoso , Extremidades , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Sarcoma/mortalidade , Fator de Necrose Tumoral alfa/farmacocinéticaRESUMO
This study analyses the health related quality of life (HRQOL) of advanced melanoma patients, in a randomised trial comparing bio-chemotherapy (bio-CT) versus chemotherapy (CT). The trial enrolled 178 patients and the median survival was not statistically different between the two arms. HRQOL was assessed at baseline and before each cycle of therapy, using the Rotterdam Symptom Checklist (RSCL) questionnaire completed with 140 patients. At baseline, overall quality of life and psychological distress scores were the most impaired, compared with the normal population. During treatment, the difference between the two arms in the changes from baseline was statistically significant (P=0.03) only in the overall quality of life score, with a decrease of 6.28 points in the bio-CT arm. The mean values decreased significantly in all domains in bio-CT arm, but only in activity level and physical symptom distress scores in the CT arm. Testing HRQOL variables and prognostic clinical factors in a Cox model, only the serum level of lactic dehydrogenase, baseline overall quality of life and the physical symptom distress scores remained significant independent prognostic factors for survival. A score of less than 75 points in the overall quality of life and in the physical symptom distress domains was associated with a Hazard Ratio (HR) of 2.31 (95% Confidence Interval (CI): 1.09-4.90) and 1.92 (95% CI: 1.10-3.36), respectively.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Melanoma/tratamento farmacológico , Qualidade de Vida , Neoplasias Cutâneas/tratamento farmacológico , Adulto , Idoso , Carmustina/administração & dosagem , Cisplatino/administração & dosagem , Dacarbazina/administração & dosagem , Feminino , Humanos , Interferon alfa-2 , Interferon-alfa/administração & dosagem , Interleucina-2/administração & dosagem , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Prognóstico , Proteínas RecombinantesRESUMO
Isolation limb perfusion (ILP) is the treatment of choice for locally advanced limb melanoma. With melphalan, the referral drug, complete response (CR) is achieved in about 50% of patients, but significant local toxicity occurs in up to 30%. The aim of the present phase I-II study was to challenge fotemustine (F) in ILP after systemic chemosensitization with dacarbazine (DTIC), given its lower toxicity and greater efficacy, as reported in a previous pilot study. Eleven patients with locally advanced limb melanoma were subdivided into triplets, and given F ILP at escalating doses (starting from 25 mg/l) after intravenous administration of 500 mg/m2 DTIC. Acute and chronic locoregional and systemic toxicity, tumour response and clinical outcome were evaluated. Two patients in the first triplet had G3-G4 local toxicity, so that the scheduled F dosage was halved. At drug levels of 12.5, 15.6 and 18.2 mg/l, local toxicity decreased, but only one of eight patients showed CR. The trial was then interrupted due to the low tolerability and poor efficacy of this perfusion regimen. At present, F ILP after DTIC chemosensitization should not be recommended for the treatment of locally advanced limb melanoma.