RESUMO
BACKGROUND: For primary triple-negative breast cancer (TNBC) treated with neoadjuvant chemotherapy (NAC), higher pretreatment tumor-infiltrating lymphocytes (TILs) correlates with increased pathologic complete response (pCR) rates, and improved survival. We evaluated the added prognostic value of residual disease (RD) TILs to residual cancer burden (RCB) in predicting survival post-NAC. PATIENTS AND METHODS: We combined four TNBC NAC patient cohorts who did not achieve pCR. RD TILs were investigated for associations with recurrence-free survival (RFS), and overall survival (OS) using Cox models with stromal TILs as a continuous variable (per 10% increment). The likelihood ratio test was used to evaluate added prognostic value of RD TILs. RESULTS: A total of 375 RD TNBC samples were evaluable for TILs and RCB. The median age was 50 years, with 62% receiving anthracycline/taxane chemotherapy. The RCB class after NAC was 11%, 50%, and 39% for I, II, and III, respectively. The median RD TIL level was 20% (IQR 10-40). There was a positive correlation between RD TIL levels and CD8+ T-cell density (ρ = 0.41). TIL levels were significantly lower with increasing post-NAC tumor (P = 0.005), nodal stage (P = 0.032), but did not differ by RCB class (P = 0.84). Higher RD TILs were significantly associated with improved RFS (HR: 0.86; 95% CI 0.79-0.92; P < 0.001), and improved OS (HR: 0.87; 95% CI 0.80-0.94; P < 0.001), and remained significant predictors in multivariate analysis (RFS P = 0.032; OS P = 0.038 for OS). RD TILs added significant prognostic value to multivariate models including RCB class (P < 0.001 for RFS; P = 0.021 for OS). The positive prognostic effect of RD TILs significantly differed by RCB class for RFS (PInt=0.003) and OS (PInt=0.008) with a greater magnitude of positive effect observed for RCB class II than class III. CONCLUSIONS: TIL levels in TNBC RD are significantly associated with improved RFS and OS and add further prognostic information to RCB class, particularly in RCB class II.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Linfócitos do Interstício Tumoral/imunologia , Terapia Neoadjuvante/mortalidade , Neoplasia Residual/patologia , Neoplasias de Mama Triplo Negativas/patologia , Idoso , Linfócitos T CD8-Positivos/imunologia , Progressão da Doença , Feminino , Seguimentos , Humanos , Neoplasia Residual/tratamento farmacológico , Neoplasia Residual/imunologia , Prognóstico , Receptor ErbB-2/metabolismo , Taxa de Sobrevida , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Neoplasias de Mama Triplo Negativas/imunologiaRESUMO
The detection of CTCs prior to and during therapy is an independent and strong prognostic marker, and it is predictive of poor treatment outcome. A major challenge is that different technologies are available for isolation and characterization of CTCs in peripheral blood (PB). We compare the CellSearch system and AdnaTest BreastCancer Select/Detect, to evaluate the extent that these assays differ in their ability to detect CTCs in the PB of MBC patients. CTCs in 7.5 ml of PB were isolated and enumerated using the CellSearch, before new treatment. Two cutoff values of ≥2 and ≥5 CTCs/7.5 ml were used. AdnaTest requires 5 ml of PB to detect gene transcripts of tumor markers (GA733-2, MUC-1, and HER2) by RT-PCR. AdnaTest was scored positive if ≥1 of the transcript PCR products for the 3 markers were detected at a concentration ≥0.15 ng/µl. A total of 55 MBC patients were enrolled. 26 (47%) patients were positive for CTCs by the CellSearch (≥2 cutoff), while 20 (36%) were positive (≥5 cutoff). AdnaTest was positive in 29 (53%) with the individual markers being positive in 18% (GA733-2), 44% (MUC-1), and 35% (HER2). Overall positive agreement was 73% for CTC≥2 and 69% for CTC≥5. These preliminary data suggest that the AdnaTest has equivalent sensitivity to that of the CellSearch system in detecting 2 or more CTCs. While there is concordance between these 2 methods, the AdnaTest complements the CellSearch system by improving the overall CTC detection rate and permitting the assessment of genomic markers in CTCs.
Assuntos
Biomarcadores Tumorais/análise , Biomarcadores Tumorais/sangue , Neoplasias da Mama/sangue , Neoplasias da Mama/diagnóstico , Técnicas de Laboratório Clínico/métodos , Células Neoplásicas Circulantes/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Pessoa de Meia-Idade , Células Neoplásicas Circulantes/química , Prognóstico , Estudos Prospectivos , Adulto JovemRESUMO
BACKGROUND: Circulating tumor cells (CTCs) are associated with inferior prognosis in metastatic breast cancer (MBC). We hypothesized that the relationship between CTCs and disease subtype would provide a better understanding of the clinical and biologic behavior of MBC. PATIENTS AND METHODS: We retrospectively analyzed 517 MBC patients treated at a single institution. Subtypes of primary tumors were analyzed by immunohistochemical (IHC) or fluorescent in situ hybridization analyses and CTCs were enumerated by CellSearch(®) at starting a new therapy. Overall survival (OS) and progression-free survival durations for each IHC subtype were determined. RESULTS: At a median follow-up of 24.6 months, 276 of 517 (53%) patients had died. The median OS for patients with <5 and ≥ 5 CTCs were 32.4 and 18.3 months, respectively (P < 0.001). Except in HER2+ patients, the prognostic value of CTCs was independent of disease subtype and disease site. CONCLUSIONS: In this large retrospective study, CTCs were strongly predictive of survival in all MBC subtypes except HER2+ patients who had been treated with targeted therapy. Our results clearly demonstrate the value of enumerating CTCs in MBC and strongly suggest an interesting biological implication in the HER2+ subset of patients that need to be further explored.
Assuntos
Neoplasias da Mama/diagnóstico , Neoplasias da Mama/terapia , Carcinoma/diagnóstico , Carcinoma/terapia , Terapia de Alvo Molecular , Células Neoplásicas Circulantes/patologia , Neoplasias da Mama/classificação , Neoplasias da Mama/mortalidade , Carcinoma/classificação , Carcinoma/mortalidade , Estudos de Coortes , Feminino , Humanos , Imuno-Histoquímica , Pessoa de Meia-Idade , Terapia de Alvo Molecular/métodos , Estadiamento de Neoplasias/métodos , Células Neoplásicas Circulantes/metabolismo , Valor Preditivo dos Testes , Prognóstico , Receptor ErbB-2/metabolismo , Estudos Retrospectivos , Análise de SobrevidaRESUMO
BACKGROUND: Recent retrospective studies have suggested that patients with T1a,bN0M0 human epidermal growth factor receptor 2 (HER2)-positive breast cancer are at a higher risk for recurrence and might benefit from adjuvant trastuzumab. The absolute benefits associated with treating this subgroup are uncertain. DESIGN: We reviewed recent studies examining the prognostic value of HER2 in patients with node-negative T1a,b HER2-positive breast cancer. We calculated the number needed to treat (NNT) using baseline risk estimates for untreated T1a,bN0M0 breast cancer and the number needed to harm (NNH) using the incidence of cardiac events in each of the adjuvant trastuzumab clinical trials. RESULTS: Several studies were identified, each with limitations inherent to retrospective database analyses: small cohort sizes, lack of systematic HER2 testing in older specimens, variations in the use of adjuvant therapy and definitions of study end points, and lack of information relating to comorbidities. The 5-year disease-free survival in the pre-trastuzumab era ranged from 77% to 95%. Comparisons between small HER2 -positive and small HER2 -negative cancers showed numerically worse outcome for the HER2-positive cohort in some but not all studies. In many instances, the NNH was larger (26-250) than the NNT (13-35); however, in a subset of patients, the NNH was lower (6) than the NNT (13-35). CONCLUSIONS: Better prediction tools to estimate more precisely the risk for death due to comorbid illness versus breast cancer are needed. In some patients, the risks of therapy could outweigh the benefits. Treatment selection for T1a,bN0 HER2-positive cancers remains in the transition area between evidence- and subjective judgment-based medicine.
Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Antineoplásicos/uso terapêutico , Biomarcadores Tumorais/biossíntese , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/enzimologia , Receptor ErbB-2/biossíntese , Neoplasias da Mama/patologia , Quimioterapia Adjuvante , Tomada de Decisões , Feminino , Humanos , Estadiamento de Neoplasias , Valor Preditivo dos Testes , Prognóstico , Estudos Retrospectivos , Trastuzumab , IncertezaRESUMO
BACKGROUND: The purpose of this study was to determine the incidence of and survival following brain metastases among women with inflammatory breast cancer (IBC). PATIENTS AND METHODS: Two hundred and three women with newly diagnosed stage III/IV IBC diagnosed from 2003 to 2008, with known Human epidermal growth factor receptor 2 (HER2) and hormone receptor status, were identified. Cumulative incidence of brain metastases was computed. Survival estimates were computed using the Kaplan-Meier product limit method. Multivariable Cox proportional hazards models were fitted to explore the relationship between breast tumor subtype and time to brain metastases. RESULTS: Median follow-up was 20 months. Thirty-two (15.8%) patients developed brain metastases with a cumulative incidence at 1 and 2 years of 2.7% and 18.7%, respectively. Eleven (5.3%) patients developed brain metastases as the first site of recurrence with cumulative incidence at 1 and 2 years of 1.6% and 5.7%, respectively. Compared with women with triple receptor-negative IBC, those with hormone receptor-positive/HER2-negative disease [hazard ratio (HR) = 0.55, 95% confidence interval (CI) 0.19-1.51, P = 0.24] had a decreased risk of developing brain metastases, and those with HER2-positive disease (HR = 1.02, 95% CI 0.43-2.40, P = 0.97) had an increased risk of developing brain metastases, although these associations were not statistically significant. Median survival following a diagnosis of brain metastases was 6 months. CONCLUSION: Women with newly diagnosed IBC have a high early incidence of brain metastases associated with poor survival and may be an ideal cohort to target for site-specific screening.
Assuntos
Neoplasias Encefálicas/epidemiologia , Neoplasias Encefálicas/mortalidade , Neoplasias Encefálicas/secundário , Carcinoma/patologia , Neoplasias Inflamatórias Mamárias/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma/epidemiologia , Carcinoma/mortalidade , Feminino , Seguimentos , Humanos , Incidência , Neoplasias Inflamatórias Mamárias/epidemiologia , Neoplasias Inflamatórias Mamárias/mortalidade , Pessoa de Meia-Idade , Metástase Neoplásica , Análise de Sobrevida , Adulto JovemRESUMO
BACKGROUND: Cancer is a risk factor for venous thromboembolism (VTE). Circulating tumour cells (CTCs) are an independent predictor of survival in metastatic breast cancer (MBC) patients. The aim of this study was to test the hypothesis that CTCs are associated with the risk of VTE in MBC patients. METHODS: This retrospective study included 290 MBC patients treated in the MD Anderson Cancer Center from January 2004 to December 2007. Circulating tumour cells were detected and enumerated using the CellSearch system before starting new lines of therapy. RESULTS: At a median follow-up of 12.5 months, 25 patients experienced VTE and 53 patients died without experiencing thrombosis. Cumulative incidence of thrombosis at 12 months was 8.5% (95% confidence interval (CI)=5.5%, 12.4%). Patients with CTCs > or = 1 and > or = 5 had a higher incidence of VTE compared with patients with 0 and <5 CTCs (12-month estimate, 11.7 and 11.6% vs 3 and 6.6%; P=0.006 and P=0.076, respectively). In the multivariate model, patients with CTCs > or = 1 had a hazard ratio of VTE of 5.29 (95% CI=1.58, 17.7, P=0.007) compared with patients with no CTCs. CONCLUSION: These results suggest that CTCs in MBC patients are associated with increased risk of VTE. These patients should be followed up more closely for the risk of VTE.
Assuntos
Neoplasias da Mama/patologia , Células Neoplásicas Circulantes/patologia , Tromboembolia Venosa/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/sangue , Feminino , Humanos , Estimativa de Kaplan-Meier , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Taxa de Sobrevida , Tromboembolia Venosa/sangue , Adulto JovemRESUMO
BACKGROUND: Inflammatory breast cancer (IBC) is the most aggressive form of breast cancer. Circulating tumor cells (CTCs) are an independent prognostic factor in metastatic breast cancer. The aim of this study was to assess the prognostic value of baseline CTCs in metastatic IBC patients. PATIENTS AND METHODS: This retrospective study included 42 metastatic IBC and 107 metastatic non-IBC patients treated with first- or second-line chemotherapy from January 2004 to December 2007 at MD Anderson Cancer Center. CTCs were detected and enumerated before patients started chemotherapy using the CellSearch system. RESULTS: Ten (23.8%) IBC patients versus 48 (44.9%) non-IBC patients had baseline CTCs > or =5 per 7.5 ml of peripheral blood. IBC patients had a lower mean +/- SEM CTCs than non-IBC patients (7.6 +/- 2.9 versus 34.2 +/- 9.1; P = 0.02). The estimated median overall survival was 26.5 versus 18.3 months (P = 0.68) in IBC patients and 37.4 versus 18.3 months (P = 0.016) in non-IBC patients with CTCs <5 and CTCs > or =5, respectively. CONCLUSIONS: Metastatic IBC patients had a lower prevalence and fewer CTCs in comparison to metastatic non-IBC patients. Survival of metastatic IBC patients with <5 CTCs was not significantly better than that of patients with > or =5 CTCs. Further research is warranted with prospective assessment of CTCs in IBC patients and their biological characterization.
Assuntos
Neoplasias da Mama/sangue , Neoplasias da Mama/mortalidade , Neoplasias da Mama/patologia , Células Neoplásicas Circulantes/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Estimativa de Kaplan-Meier , Pessoa de Meia-Idade , PrognósticoRESUMO
INTRODUCTION: The PI3K/AKT/mTOR pathway is an oncogenic driver in breast cancer (BC). In this multi-center, pre-surgical study, we evaluated the tissue effects of the AKT inhibitor MK-2206 in women with stage I-III BC. MATERIALS AND METHODS: Two doses of weekly oral MK2206 were administered at days - 9 and - 2 before surgery. The primary endpoint was reduction of pAktSer473 in breast tumor tissue from diagnostic biopsy to surgery. Secondary endpoints included changes in PI3K/AKT pathway tumor markers, tumor proliferation (ki-67), insulin growth factor pathway blood markers, pharmacokinetics (PK), genomics, and MK-2206 tolerability. Paired t tests were used to compare biomarker changes in pre- and post-MK-2206, and two-sample t tests to compare with prospectively accrued untreated controls. RESULTS: Despite dose reductions, the trial was discontinued after 12 patients due to grade III rash, mucositis, and pruritus. While there was a trend to reduction in pAKT after MK-2206 (p = 0.06), there was no significant change compared to controls (n = 5, p = 0.65). After MK-2206, no significant changes in ki-67, pS6, PTEN, or stathmin were observed. There was no significant association between dose level and PK (p = 0.11). Compared to controls, MK-2206 significantly increased serum glucose (p = 0.02), insulin (p < 0.01), C-peptide (p < 0.01), and a trend in IGFBP-3 (p = 0.06). CONCLUSION: While a trend to pAKT reduction after MK-2206 was observed, there was no significant change compared to controls. However, the accrued population was limited, due to toxicity being greater than expected. Pre-surgical trials can identify in vivo activity in the early drug development, but side effects must be considered in this healthy population.
Assuntos
Neoplasias da Mama/tratamento farmacológico , Carcinoma Ductal de Mama/tratamento farmacológico , Compostos Heterocíclicos com 3 Anéis/uso terapêutico , Proteínas Proto-Oncogênicas c-akt/antagonistas & inibidores , Adulto , Idoso , Biomarcadores/sangue , Biomarcadores/metabolismo , Neoplasias da Mama/patologia , Neoplasias da Mama/cirurgia , Carcinoma Ductal de Mama/patologia , Carcinoma Ductal de Mama/cirurgia , Avaliação de Medicamentos , Feminino , Compostos Heterocíclicos com 3 Anéis/efeitos adversos , Compostos Heterocíclicos com 3 Anéis/farmacologia , Humanos , Pessoa de Meia-Idade , Estadiamento de Neoplasias , New York , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais/efeitos dos fármacosRESUMO
The authors report and discuss a case of a mucinous carcinoma of the appendix, a rare entity with a distinct natural history that poses diagnostic and therapeutic challenges. Mucinous peritoneal carcinomatosis is most commonly associated with primary tumors of the appendix and colon. Typically, spread remains confined to the abdominal cavity. Imaging assessment of these mucinous lesions is difficult, while tumor markers (CEA and CA19.9) may be surrogates for extent of disease. Treatment consists of surgical debulking, sometimes coupled with intraperitoneal drug delivery, but recurrence is universal. New treatment approaches are needed. Mucin genes are regulated in part by epidermal growth factor receptor signaling. Therefore, we initiated a phase II study of cetuximab for mucinous peritoneal carcinomatosis, that was part of this patient's treatment.
Assuntos
Adenocarcinoma Mucinoso/diagnóstico , Adenocarcinoma Mucinoso/cirurgia , Neoplasias do Apêndice/diagnóstico , Neoplasias do Apêndice/cirurgia , Apêndice , Adenocarcinoma Mucinoso/patologia , Idoso , Neoplasias do Apêndice/patologia , Apêndice/patologia , Antígeno CA-19-9/análise , Antígeno Carcinoembrionário/análise , Evolução Fatal , Feminino , HumanosRESUMO
BACKGROUND: The usefulness of tumor volumetry in ovarian epithelial cancer has never been intensively investigated. The aim of the present study was to determine the value of quantitative analysis of tumor volume as a predictive method for response to treatment and as a prognostic method for disease outcome. MATERIALS AND METHODS: Seventy-five women with advanced ovarian cancer who presented with measurable disease on CT scan prior to chemotherapy were retrospectively studied. The patients were treated with platinum-based chemotherapy. The median follow-up was 113.36 weeks. An independent radiologist identified and delineated tumor contours in each slice of sequential CT scans before and after therapy. Volumetry was measured with a three-dimensional approach by utilizing a digitizer and a specific algorithm on a software computed program. RESULTS: Data were analyzed according to initial and to residual tumor volumes. Patients with low initial volume of <52 cm3 exhibited higher responses (p<0.01), while patients with medium (52-165 cm3) or high (>165 CM3) initial tumor volume had a shorter time to progression (p<0.01). Patients without or with low residual volume of <35 cm3 were found to have a longer time to progression (p<0.05) and longer survival (p<0.01 and p<0.05). In addition, serum CA 125 levels followed precisely tumor volumetry for both initial and residual disease. CONCLUSION: Tumor volumetry in advanced ovarian cancer was found to have predictive value for response to platinum-based chemotherapy. Initial tumor volume has prognostic significance only for the time to progression, whereas residual tumor volume has for both time to progression and survival.
Assuntos
Neoplasias Ovarianas/patologia , Adulto , Idoso , Antígeno Ca-125/sangue , Progressão da Doença , Feminino , Humanos , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neoplasia Residual , Neoplasias Ovarianas/sangue , Neoplasias Ovarianas/tratamento farmacológico , Valor Preditivo dos Testes , Prognóstico , Estudos RetrospectivosRESUMO
AIMS: Uterine sarcomas are rare tumours with histopathological diversity characterised by rapid clinical progression and poor prognosis. Optimal management consists of complete surgical removal, but is not clear whether adjuvant radiotherapy improves the prognosis. The aim of this retrospective study was to investigate the clinical and histopathological characteristics together with treatment and outcome of patients with uterine sarcomas. MATERIALS AND METHODS: Records of 100 patients treated at the Royal Marsden Hospital between 1974-1998 were reviewed: 47 leiomyosarcoma (LMS), 30 mixed mullerian tumours (MMT), 19 endometrial stromal sarcoma (ESS), one haemangiopericytoma, one rhabdomyosarcoma and two unspecified sarcoma. There were 50, 11, 21 and 18 patients with stage I, II, III and IV carcinoma, respectively. Thirty-four patients had high-grade disease. Fifty-three patients received adjuvant radiotherapy. The median age was 55 years (range: 18-83 years). The median follow-up was 54 months (range: 3 months to 27 years). RESULTS: The overall 3, 5 and 10-year survival rates were 39%, 30% and 20%, respectively. Survival was significantly related to stage (P = 0.002), grade (P = 0.003) and histological type (P = 0.04), but not to use of postoperative irradiation. At 3 years, the survival rate was 42% for LMS, 22% for MMT and 63% for ESS. Local recurrence rate, however, was significantly improved after adjuvant radiotherapy with dose higher than 50 Gy (P = 0.001). CONCLUSIONS: Prognosis is dependent on histopathological sub-type, grade and tumour stage. Adjuvant radiotherapy decreases local recurrence rate, but without significant impact on survival.
Assuntos
Recidiva Local de Neoplasia/epidemiologia , Recidiva Local de Neoplasia/terapia , Sarcoma/epidemiologia , Sarcoma/terapia , Neoplasias Uterinas/epidemiologia , Neoplasias Uterinas/terapia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Terapia Combinada , Intervalo Livre de Doença , Inglaterra/epidemiologia , Feminino , Humanos , Prontuários Médicos , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/etiologia , Recidiva Local de Neoplasia/mortalidade , Recidiva Local de Neoplasia/patologia , Estadiamento de Neoplasias , Estudos Retrospectivos , Sarcoma/etiologia , Sarcoma/mortalidade , Sarcoma/patologia , Análise de Sobrevida , Neoplasias Uterinas/etiologia , Neoplasias Uterinas/mortalidade , Neoplasias Uterinas/patologiaRESUMO
Introduction: The PI3K/AKT/mTOR pathway is an oncogenic driver in breast cancer (BC). In this multi-center, pre-surgical study, we evaluated the tissue effects of the AKT inhibitor MK-2206 in women with stage I-III BC. Materials and methods: Two doses of weekly oral MK2206 were administered at days − 9 and − 2 before surgery. The primary endpoint was reduction of pAktSer473 in breast tumor tissue from diagnostic biopsy to surgery. Secondary endpoints included changes in PI3K/AKT pathway tumor markers, tumor proliferation (ki-67), insulin growth factor pathway blood markers, pharmacokinetics (PK), genomics, and MK-2206 tolerability. Paired t tests were used to compare biomarker changes in pre- and post-MK-2206, and two-sample t tests to compare with prospectively accrued untreated controls. Results: Despite dose reductions, the trial was discontinued after 12 patients due to grade III rash, mucositis, and pruritus. While there was a trend to reduction in pAKT after MK-2206 (p = 0.06), there was no significant change compared to controls (n = 5, p = 0.65). After MK-2206, no significant changes in ki-67, pS6, PTEN, or stathmin were observed. There was no significant association between dose level and PK (p = 0.11). Compared to controls, MK-2206 significantly increased serum glucose (p = 0.02), insulin (p < 0.01), C-peptide (p < 0.01), and a trend in IGFBP-3 (p = 0.06). Conclusion: While a trend to pAKT reduction after MK-2206 was observed, there was no significant change compared to controls. However, the accrued population was limited, due to toxicity being greater than expected. Pre-surgical trials can identify in vivo activity in the early drug development, but side effects must be considered in this healthy population
No disponible
Assuntos
Humanos , Feminino , Neoplasias da Mama/terapia , Proteína Oncogênica v-akt/antagonistas & inibidores , Cuidados Pré-Operatórios/métodos , Estudos de Casos e Controles , Fatores de Risco , Neoplasias da Mama/patologia , Resultado do TratamentoRESUMO
BACKGROUND: We hypothesized that a response to pegylated liposomal doxorubicin (PLD, Caelyx/Doxil) followed by maintenance is beneficial and safe in recurrent ovarian cancer. PATIENTS AND METHODS: Sixteen patients have received PLD for more than 1 year for recurrent ovarian (14) or fallopian tube (2) cancer. All had stable disease or better responses to PLD + carboplatin (5) or topotecan (9) doublets or to PLD alone (2). PLD maintenance therapy 30-40 mg/m(2) was given every 4-8 weeks. This analysis focuses on cardiac status, overall tolerance, and time to recurrence. RESULTS: Termination of PLD was due to progression in all patients. Noteworthy was the lack of cumulative myelosuppression and, with one exception, clinical cardiac toxicity. This patient was hospitalized with cardiogenic shock and fever complicating grade 4 pancytopenia from topotecan ten months after discontinuation of PLD. Seven patients continue to receive PLD after a median of 1680 mg/m(2) (1180-2460 mg/m(2)). Four of these had documented relapses after 3-6 years on maintenance occurring in the setting of lengthening of the treatment interval. Maintenance PLD was reinstituted after 'reinduction' with a platinum. CONCLUSIONS: PLD appears to be safe as long-term maintenance in ovarian cancer and may be important for a continued response.
Assuntos
Antibióticos Antineoplásicos/uso terapêutico , Doxorrubicina/uso terapêutico , Recidiva Local de Neoplasia/tratamento farmacológico , Neoplasias Epiteliais e Glandulares/tratamento farmacológico , Neoplasias Ovarianas/tratamento farmacológico , Idoso , Doxorrubicina/efeitos adversos , Feminino , Humanos , Lipossomos , Pessoa de Meia-Idade , PolietilenoglicóisRESUMO
With breast cancer incidence rates showing no signs of abating, advances in risk stratification and increasing awareness of cancer control, there is interest in expanding the breast imaging arsenal. Mammography is still the standard of care, and a recent meta-analysis of seven large studies supports its value as a screening tool. There is, however, clear need for improved sensitivity and specificity. Imaging of function, metabolism and molecular activity in breast tissue is of potential benefit in addressing these issues. In this article we provide an overview of the current methods of imaging in breast cancer, including mammography, ultrasound, digital mammography, magnetic resonance, positron emission tomography and magnetic resonance spectroscopy. Screening and surveillance should, ideally, be tailored to an individual's cancer risk and breast tissue. Current evidence questions the recent move toward magnetic resonance imaging as a single or multimodality strategy for breast cancer screening. In a high-risk group, the cost effectiveness of technical innovations may be justified.
Assuntos
Neoplasias da Mama/diagnóstico , Diagnóstico por Imagem/métodos , Diagnóstico por Imagem/economia , Feminino , Humanos , Imageamento por Ressonância Magnética/economia , Espectroscopia de Ressonância Magnética , Mamografia , Programas de Rastreamento/economia , Programas de Rastreamento/métodos , Estadiamento de Neoplasias , Tomografia por Emissão de Pósitrons , Ultrassonografia MamáriaRESUMO
Lymphadenopathy (LAP) is a frequent sign of systemic lupus erythematosus (SLE). The lymph nodes are usually soft, nontender, varying in size from 0.5 cm to several centimeters. However, generalized LAP in SLE is extremely rare, while to our knowledge, the presentation of extensive LAP with blocks of retrosternal, mesenteric, and retroperitoneal nodes has not been previously reported as the first clinical manifestation of the disease. In this report we describe a patient with extensive LAP and active SLE and we point out that generalized LAP should be included among the clinical findings indicating disease activity in SLE patients.
Assuntos
Lúpus Eritematoso Sistêmico/diagnóstico , Doenças Linfáticas/etiologia , Adulto , Feminino , Humanos , Lúpus Eritematoso Sistêmico/diagnóstico por imagem , Lúpus Eritematoso Sistêmico/patologia , Linfonodos/diagnóstico por imagem , Linfonodos/patologia , Doenças Linfáticas/diagnóstico por imagem , Doenças Linfáticas/patologia , Tomografia Computadorizada por Raios XRESUMO
BACKGROUND: Based on the high activity of single-agent paclitaxel and the superior one-year survival rates of patients with non-small-cell lung cancer (NSCLC) treated with carboplatin, a phase II trial was initiated using both agents in patients with inoperable stages III and IV disease to investigate the efficacy and toxicity of the combination. PATIENTS AND METHODS: Since July 1995, 60 patients fulfilling all eligibility criteria entered this study. All patients received paclitaxel 175 mg/m2 as a three-hour infusion, and carboplatin dosed to an area under the concentration-time curve of seven, every three weeks. No granulocyte colony-stimulating factor was given. Of the 56 male and four female patients, the median age was 57 years (range 29 to 75 years) and the median Eastern Co-Operative Oncology Group performance status was one. Most of the patients had stage IV (34) adenocarcinoma (31) with low differentiation (28). The median number of chemotherapy cycles was three, with a range of one to eight. RESULTS: Of 55 evaluable patients, 15 (27.3%) achieved partial responses, 15 (27.3%) had stable disease, and 25 (45.4%) had progressive disease. The median survival was 8.95 months and 21.6% of the patients survived more than one year. Grade 2/3 nonhematologic toxicity included alopecia (59%), neurotoxicity (3%), and myalgia/arthralgia (10%). Grade 2/3 neutropenia occurred in 14% of patients, whereas grade 3/4 thrombocytopenia was seen in only 4%. One patient died of complications of a severe allergic reaction. CONCLUSION: Combination treatment using paclitaxel and carboplatin is active and well tolerated in patients with inoperable non-small-cell lung cancer. The dose-response relationship to paclitaxel and results of comparison with other platinum-based regimens remain to be determined.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Adulto , Idoso , Carboplatina/administração & dosagem , Carboplatina/efeitos adversos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Paclitaxel/administração & dosagem , Paclitaxel/efeitos adversosRESUMO
BACKGROUND: Cancer antigen 15-3 (CA 15-3), a circulating marker that determines secreted products of the polymorphic MUC1 gene, has been established as a convenient tool for monitoring breast carcinoma patients. METHODS: The authors investigated alterations of soluble CA 15-3 in 57 postoperative breast carcinoma patients while they were receiving intensified adjuvant chemotherapy with granulocyte colony stimulating factor (G-CSF) support; 26 patients had American Joint Committee on Cancer (AJCC) Stage II, and 31 patients had AJCC Stage III breast carcinoma. Serial CA 15-3 values recorded thoughout the treatment were compared with baseline values, analyzed for correlation with hematologic and biochemical parameters, and compared with clinicopathologic characteristics and patient outcome. At a median follow-up time of 32 months, 47 of these patients remained relapse-free. RESULTS: A twofold increase of CA 15-3 was detected at the end of the second week of treatment, remained significantly elevated in most patients at above the cutoff level of 30 U/mL throughout the treatment period (P < 0.0001), and subsided to pretreatment values 1-2 months after treatment cessation. CA 15-3 values were found to be associated strongly with absolute neutrophil count, serum lactate dehydrogenase, and alkaline phosphatase. The median values and the kinetics of tumor markers did not differ over time in regard to hormonal receptor status and disease recurrence. CONCLUSIONS: These data provide strong evidence that G-CSF administration can induce elevation of CA 15-3 and indicate that false-positive results should be considered when evaluating CA 15-3 in patients who are receiving G-CSF. It is speculated that this phenomenon occurs through the induction of MUC1 antigen of unknown origin by G-CSF. Experimental investigation of this clinical observation is warranted.
Assuntos
Biomarcadores Tumorais/análise , Neoplasias da Mama/imunologia , Carcinoma/imunologia , Fator Estimulador de Colônias de Granulócitos/farmacologia , Mucina-1/análise , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/classificação , Neoplasias da Mama/patologia , Carcinoma/classificação , Carcinoma/patologia , Reações Falso-Positivas , Feminino , Humanos , Pessoa de Meia-IdadeRESUMO
BACKGROUND: With the rising incidence of malignant mesothelioma (MM), it is important to optimise treatment to control symptoms, maintain quality of life and, if possible, prolong life. We have analysed prospectively collected data to evaluate a frequently used palliative chemotherapy regimen. PATIENTS AND METHODS: Between October 1986 and May 2002 all patients with inoperable pleural mesothelioma were considered for treatment with MVP (mitomycin C 8 mg/m2 every 6 weeks, vinblastine 6 mg/m2 every 3 weeks and cisplatin 50 mg/m2 every 3 weeks) chemotherapy. Symptoms were assessed by physician assessment at baseline and after each cycle of chemotherapy. RESULTS: One hundred and fifty patients were treated with MVP for mesothelioma. Forty-three per cent had a performance status (PS) 2 or worse. The response rate was 15.3%, with 68.6% having stable disease. Sixty-nine per cent reported an improvement in symptoms; in particular there were good responses for pain (71%), cough (62%) and dyspnoea (50%). The most common grade 3/4 toxicity was neutropenia (22%). Median overall survival was 7 months, with 1-year survival 31% and 2-year survival 11%. Median survival for patients with PS 0/1 was 10 months, and was 6 months for patients with PS 2/3. Poor prognostic factors in univariate analysis included poor PS, weight loss, mixed or sarcomatoid histology, low haemoglobin and high white blood cell count. Excluding pathological subtype, the prognostic significance of poor PS and weight loss were retained in multivariate analysis. CONCLUSIONS: Palliation of symptoms in MM is achievable with current cisplatin-based treatments.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Mesotelioma/tratamento farmacológico , Neoplasias Pleurais/tratamento farmacológico , Adulto , Idoso , Antibióticos Antineoplásicos/efeitos adversos , Antibióticos Antineoplásicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Cisplatino/administração & dosagem , Cisplatino/efeitos adversos , Feminino , Humanos , Masculino , Mesotelioma/mortalidade , Pessoa de Meia-Idade , Mitomicina/administração & dosagem , Mitomicina/efeitos adversos , Análise Multivariada , Neoplasias Pleurais/mortalidade , Estudos Prospectivos , Análise de Sobrevida , Taxa de Sobrevida , Resultado do Tratamento , Vimblastina/administração & dosagem , Vimblastina/efeitos adversos , Redução de Peso/efeitos dos fármacosRESUMO
PURPOSE: To evaluate the outcome and the prognosis of patients with ovarian germ cell malignancies who were treated with platinum-based chemotherapy immediately after initial surgery. METHODS: We conducted a retrospective review of patients with ovarian germ cell tumors who were referred for consideration of treatment to the Departments of Medical Oncology participating in the Hellenic Cooperative Oncology Group. RESULTS: Over a 14-year period 53 patients were included in our study. There were 13 patients with dysgerminoma and 40 patients with nondysgerminomatous tumors. Forty percent of patients underwent complete resection of their tumors. Platinum-based chemotherapy consisted primarily of cisplatin, vinblastine, and bleomycin (PVB) in 9 patients; bleomycin, etoposide, and cisplatin (BEP) in 15 patients; and bleomycin, etoposide, and carboplatin (BEC) in 25 patients. With a median follow-up of 39 months, 5 patients developed progressive disease and died of their tumor and 1 patient died of bleomycin-induced lung toxicity with no evidence of active tumor. The 5-year overall survival was 100% for patients with dysgerminoma and 85% for patients with nondysgerminomatous tumors. Eighty percent of patients with advanced nondysgerminomatous tumors and residual disease after surgery remain disease free. CONCLUSION: With this study we confirm that patients with ovarian germ cell malignancies have a favorable outcome when treated with platinum-based chemotherapy.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Germinoma/tratamento farmacológico , Neoplasias Ovarianas/tratamento farmacológico , Adolescente , Adulto , Idoso , Bleomicina/administração & dosagem , Carboplatina/administração & dosagem , Criança , Cisplatino/administração & dosagem , Etoposídeo/administração & dosagem , Feminino , Germinoma/mortalidade , Humanos , Pessoa de Meia-Idade , Neoplasias Ovarianas/mortalidade , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida , Resultado do Tratamento , Vimblastina/administração & dosagemRESUMO
PURPOSE: To evaluate the impact on the response rate in patients with advanced breast cancer (ABC) of the doubling of the dose intensity (DI) of epirubicin monotherapy. PATIENTS AND METHODS: From January 1991 until April 1996, 167 patients with ABC were randomized to receive epirubicin (110 mg/m2) either every four (81 patients, group A) or every two weeks (86 patients, group B). Filgrastim (5 micrograms/kg/daily) was administered prophylactically on days 2-12 of each cycle. RESULTS: The two groups were equally balanced in terms of major patient and tumor characteristics. Even though the median cumulative dose of epirubicin was identical in the two groups (651 mg/m2), the median DI of epirubicin was doubled in group B (27.2 vs. 52.9 mg/m2/wk, respectively). The complete response (CR) rate was significantly increased in group B (5%, 95% CI: 0.16%-9.84% vs. 17%, 95% CI: 8.9%-25.08%, P = 0.011), although overall response rates were similar (49% vs. 53%, P = 0.5957). Also, there was no significant difference in the incidence of grade 3-4 toxicity between the two groups. After a median follow-up of 25 months (range, 0.43-43.3+) no significant difference was observed in the duration of response (median, 10 months vs. 8.5 months, P = 0.5130), time to progression (median, 7.2 months vs. 7.4 months, P = 0.2970) or survival (median, 14.6 months vs. 14.9 months, P = 0.4483). Logistic regression analysis showed that performance status was a significant variable for response (P = 0.0068) and multivariate analysis using the Cox proportional hazards model revealed that performance status was significant for survival (P = 0.0049), while the presence of multiple metastases (P = 0.0020) was significant for time to progression. CONCLUSION: Doubling the planned DI of epirubicin monotherapy significantly increases the CR rate but has no influence on time to progression or survival in patients with ABC.