RESUMEN
The purpose of this study was to study the impact of changes in clinical practice on outcome in patients treated with breast-conserving therapy (BCT) over a period of 28 years. Patients with early invasive breast cancer, who were treated with BCT at the Netherlands Cancer Institute between 1980 and 2008, were studied. Clinical characteristics, treatment and outcome were compared between groups (1980-1987; 1988-1998; 1999-2008). The main endpoint analyzed was ipsilateral breast tumor recurrence (IBTR). 8485 patients with a median follow-up of 9 years (IQR 6-14 years) were analyzed. The cumulative 5- and 10-year IBTR incidences were, respectively, 2 and 5 % for the whole cohort and 4 and 9 % in patients ≤40 years. Young age was a significant risk factor for IBTR in multivariable analysis. IBTR-free interval was better for patients who received a RT boost (HR 0.65) or systemic therapy (HR 0.52). In later years, patients less often received a boost and more often underwent adjuvant systemic treatment. 761 patients (9.0 %) underwent a re-excision; the tumor resection margins were tumor free for 85 %. In later years (1999-2008), 89 % of patients had a tumor-free margin. The margin status of invasive carcinoma did not influence IBTR, DM rate, or OS. Between 1980 and 2008, locoregional control after BCT remained stable with low IBTR rates, even in young patients. These good results were achieved under the policy of accepting close or focally positive margins, indicating this is a safe approach. The results of this study may help in lowering the re-excision rates, which are high in many centers.
Asunto(s)
Neoplasias de la Mama/cirugía , Mastectomía Segmentaria/métodos , Recurrencia Local de Neoplasia/epidemiología , Adulto , Factores de Edad , Anciano , Anciano de 80 o más Años , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/radioterapia , Quimioterapia Adyuvante , Terapia Combinada , Femenino , Humanos , Persona de Mediana Edad , Países Bajos/epidemiología , Análisis de Supervivencia , Resultado del Tratamiento , Adulto JovenRESUMEN
The 70-gene signature (MammaPrint) has been developed to predict the risk of distant metastases in breast cancer and select those patients who may benefit from adjuvant treatment. Given the strong association between locoregional and distant recurrence, we hypothesize that the 70-gene signature will also be able to predict the risk of locoregional recurrence (LRR). 1,053 breast cancer patients primarily treated with breast-conserving treatment or mastectomy at the Netherlands Cancer Institute between 1984 and 2006 were included. Adjuvant treatment consisted of radiotherapy, chemotherapy, and/or endocrine therapy as indicated by guidelines used at the time. All patients were included in various 70-gene signature validation studies. After a median follow-up of 8.96 years with 87 LRRs, patients with a high-risk 70-gene signature (n = 492) had an LRR risk of 12.6% (95% CI 9.7-15.8) at 10 years, compared to 6.1% (95% CI 4.1-8.5) for low-risk patients (n = 561; P < 0.001). Adjusting the 70-gene signature in a competing risk model for the clinicopathological factors such as age, tumour size, grade, hormone receptor status, LVI, axillary lymph node involvement, surgical treatment, endocrine treatment, and chemotherapy resulted in a multivariable HR of 1.73 (95% CI 1.02-2.93; P = 0.042). Adding the signature to the model based on clinicopathological factors improved the discrimination, albeit non-significantly [C-index through 10 years changed from 0.731 (95% CI 0.682-0.782) to 0.741 (95% CI 0.693-0.790)]. Calibration of the prognostic models was excellent. The 70-gene signature is an independent prognostic factor for LRR. A significantly lower local recurrence risk was seen in patients with a low-risk 70-gene signature compared to those with high-risk 70-gene signature.
Asunto(s)
Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/genética , Regulación Neoplásica de la Expresión Génica , Recurrencia Local de Neoplasia/tratamiento farmacológico , Recurrencia Local de Neoplasia/genética , Adulto , Anciano , Neoplasias de la Mama/patología , Neoplasias de la Mama/radioterapia , Neoplasias de la Mama/cirugía , Supervivencia sin Enfermedad , Femenino , Perfilación de la Expresión Génica , Humanos , Metástasis Linfática , Persona de Mediana Edad , Proteínas de Neoplasias/biosíntesis , Recurrencia Local de Neoplasia/patología , Recurrencia Local de Neoplasia/radioterapia , Recurrencia Local de Neoplasia/cirugía , Estadificación de Neoplasias , Países Bajos , Pronóstico , Radioterapia Adyuvante , Factores de RiesgoRESUMEN
BACKGROUND: In breast cancer treated with breast-conserving radiotherapy, the influence of the boost dose on cosmetic outcome after long-term follow-up is unknown. PATIENTS AND METHODS: We included 348 patients participating in the EORTC 'boost versus no boost' mega trial with a minimum follow-up of 6 years. Digitalised pictures were analysed using specific software, enabling quantification of seven relative asymmetry features associated with different aspects of fibrosis. RESULTS: After 3 years, we noted a statistically significantly poorer outcome for the boost patients for six features compared with those of the no boost patients. Up to 9 years of follow-up, results continued to worsen in the same magnitude for the both patient groups. We noted the following determinants for poorer outcome: (i) boost treatment, (ii) larger excision volumes, (iii) younger age, (iv) tumours located in the central lower quadrants of the breast and (v) a boost dose administered with photons. CONCLUSIONS: A boost dose worsens the change in breast appearance in the first 3 years. Moreover, the development of fibrosis associated with whole-breast irradiation, as estimated with the relative asymmetry features, is an ongoing process until (at least) 9 years after irradiation.
Asunto(s)
Neoplasias de la Mama/cirugía , Mastectomía Segmentaria , Femenino , HumanosRESUMEN
To study whether the effects of prognostic factors associated with the occurrence of distant metastases (DM) at primary diagnosis change after the incidence of loco-regional recurrences (LRR) among women treated for invasive stage I or II breast cancer. The study population consisted of 3,601 women, enrolled in EORTC trials 10801, 10854, or 10902 treated for early-stage breast cancer. Data were analysed in a multivariate, multistate model by using multivariate Cox regression models, including a state-dependent covariate. The presence of a LRR in itself is a significant prognostic risk factor (HR: 3.64; 95%-CI: 2.02-6.5) for the occurrence of DM. Main prognostic risk factors for a DM are young age at diagnosis (< or =40: HR: 1.79; 95%-CI: 1.28-2.51), larger tumour size (HR: 1.58; 95%-CI: 1.35-1.84) and node positivity (HR: 2.00; 95%-CI: 1.74-2.30). Adjuvant chemotherapy is protective for a DM (HR: 0.66; 95%-CI: 0.55-0.80). After the occurrence of a LRR the latter protective effect has disappeared (P = 0.009). The presence of LRR in itself is a significant risk factor for DM. For patients who are at risk of developing LRR, effective local control should be the main target of therapy.
Asunto(s)
Neoplasias de la Mama/patología , Metástasis de la Neoplasia/patología , Recurrencia Local de Neoplasia/patología , Adulto , Edad de Inicio , Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias de la Mama/terapia , Quimioterapia Adyuvante , Ensayos Clínicos como Asunto , Terapia Combinada , Progresión de la Enfermedad , Femenino , Humanos , Mastectomía Segmentaria , Persona de Mediana Edad , Recurrencia Local de Neoplasia/terapia , Estadificación de Neoplasias , Pronóstico , Radioterapia Adyuvante , Análisis de RegresiónRESUMEN
AIM: To assess whether preoperative contrast-enhanced magnetic resonance imaging (MRI) of the breast influences the rate of incomplete tumor excision. METHODS: In a cohort of 349 women with invasive breast cancer, patients eligible for breast-conserving therapy (BCT) on the basis of conventional imaging and palpation only (N = 176) were compared to those who had an additional preoperative MRI (N = 173). Multivariate analysis was applied to explore associations with incomplete tumor excision. RESULTS: MRI detected larger extent of breast cancer in 19 women (11.0%), leading to treatment change: mastectomy (8.7%) or wider excision (2.3%). Tumor excision was incomplete in 22/159 (13.8%) wide local excisions in the MRI group and in 35/180 (19.4%) in the non-MRI group (P = 0.17). Stratified to tumor type, incompletely excised infiltrating ductal carcinoma (IDC) was significantly associated with absence of MRI: 11/136 (8.1%) versus 2/126 (1.6%) (MRI present) (P = 0.02). No significant factors explained incomplete excision of other tumor types. CONCLUSION: Preoperative MRI did not significantly affect the overall rate of incomplete tumor excision, but it yielded significantly lower rate of incompletely excised IDC. The reduction of incomplete excisions after MRI was smaller than the rate of a prior treatment change incurred by MRI.
Asunto(s)
Neoplasias de la Mama/patología , Neoplasias de la Mama/cirugía , Imagen por Resonancia Magnética , Mastectomía Segmentaria , Cuidados Preoperatorios/métodos , Adulto , Anciano , Anciano de 80 o más Años , Estudios de Cohortes , Femenino , Humanos , Persona de Mediana Edad , Resultado del TratamientoRESUMEN
PURPOSE: In this study, the formation of cisplatin-DNA adducts after concurrent cisplatin-radiation and the relationship between adduct-formation in primary tumor tissue and normal tissue were investigated. METHODS: Three intravenous cisplatin-regimens, given concurrently with radiation, were studied: daily low-dose (6 mg/m(2)) cisplatin, weekly 40 mg/m(2), three-weekly 100 mg/m(2). A (32)P-postlabeling technique was used to quantify adducts in normal tissue [white blood cells (WBC) and buccal cells] and tumor. RESULTS: Normal tissue samples for adduct determination were obtained from 63 patients and tumor biopsies from 23 of these patients. Linear relationships and high correlations were observed between the levels of two guanosine- and adenosine-guanosine-adducts in normal and tumor tissue. Adduct levels in tumors were two to five times higher than those in WBC (P<0.001). No significant correlations were found between adduct levels in normal tissues and primary tumor biopsies, nor between WBC and buccal cells. CONCLUSIONS: In concurrent chemoradiotherapy schedules, cisplatin adduct levels in tumors were significantly higher than in normal tissues (WBC). No evidence of a correlation was found between adduct levels in normal tissues and primary tumor biopsies. This lack of correlation may, to some extent, explain the inconsistencies in the literature regarding whether or not cisplatin-DNA adducts can be used as a predictive test in anticancer platinum therapy.
Asunto(s)
Antineoplásicos/efectos adversos , Cisplatino/efectos adversos , Aductos de ADN/efectos de los fármacos , Neoplasias/metabolismo , Antineoplásicos/uso terapéutico , Carcinoma de Células Escamosas/tratamiento farmacológico , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/radioterapia , Cisplatino/uso terapéutico , Terapia Combinada , Neoplasias de Cabeza y Cuello/tratamiento farmacológico , Neoplasias de Cabeza y Cuello/metabolismo , Neoplasias de Cabeza y Cuello/radioterapia , Humanos , Recuento de Leucocitos , Mucosa Bucal/citología , Neoplasias/tratamiento farmacológico , Neoplasias/radioterapia , Valor Predictivo de las PruebasRESUMEN
PURPOSE: To investigate the impact of the boost dose to the primary tumour bed in the framework of breast conserving therapy on local control, cosmetic results, fibrosis and overall survival for patients with early stage breast cancer. PATIENTS AND METHODS: Five thousand five hundred and sixty-nine patients after lumpectomy followed by whole breast irradiation of 50 Gy were randomised. After a microscopically complete lumpectomy (5318 patients), the boost doses were either 0 or 16 Gy, while after a microscopically incomplete (251 patients) lumpectomy randomisation was between 10 and 26 Gy. The results at a median follow-up of 10 years are presented. RESULTS: At 10 years, the cumulative incidence of local recurrence was 10.2% versus 6.2% for the 0 Gy and the 16 Gy boost groups (p < 0.0001) and 17.5% versus 10.8% for the 10 and 26 Gy boost groups, respectively (p > 0.1). There was no statistically significant interaction per age group but recurrences tended to occur earlier in younger patients. As younger patients had a higher cumulative risk of local relapse by year 10, the magnitude of the absolute 10-year risk reduction achieved with the boost decreased with increasing age. Development of fibrosis was significantly dependent on the boost dose with a 10-year rate for severe fibrosis of 1.6% after 0 Gy, 3.3% after 10 Gy, 4.4% after 16 Gy and 14.4% after 26 Gy, respectively. CONCLUSION: An increase of the dose with 16 Gy improved local control for patients after a complete lumpectomy only. The development of fibrosis was clearly dose dependent. With 10 years median follow-up, no impact of survival was observed.
Asunto(s)
Neoplasias de la Mama/radioterapia , Neoplasias de la Mama/cirugía , Mastectomía Segmentaria/métodos , Adulto , Anciano , Envejecimiento , Neoplasias de la Mama/patología , Terapia Combinada , Femenino , Fibrosis , Estudios de Seguimiento , Humanos , Metástasis Linfática/patología , Persona de Mediana Edad , Recurrencia Local de Neoplasia/epidemiología , Dosificación Radioterapéutica , Conducta de Reducción del RiesgoRESUMEN
The rapid increase in the use of both radiotherapy and systemic therapy for patients with early breast cancer requires reconsideration of the strategies that have been used in the past for combining both treatments. In these considerations the impact of both radiotherapy as well as systemic therapy on local control and survival of breast cancer have to be considered. An important point for discussion has often been the sequencing of radiotherapy and systemic treatment. Nowadays the possibilities of trastuzumab for her-2 neu positive breast cancer leads to the question whether or not this can be combined with radiotherapy. Finally new possibilities of sophisticated radiotherapy approaches allow further minimizing the late toxicity of radiotherapy.
Asunto(s)
Anticuerpos Monoclonales/uso terapéutico , Antineoplásicos/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/radioterapia , Mastectomía Segmentaria , Anticuerpos Monoclonales Humanizados , Neoplasias de la Mama/cirugía , Quimioterapia Adyuvante , Supervivencia sin Enfermedad , Femenino , Humanos , Radioterapia Adyuvante , Trastuzumab , Resultado del TratamientoRESUMEN
Breast carcinoma frequently metastasises to bone, most often to the thoracic and lumbosacral spine. 3 women, aged 66, 47 and 54 years, who had been previously treated for breast cancer presented with sternal pain. Bone scintigraphy revealed a solitary sternal hot spot in all 3 patients. In the final diagnosis, 1 patient had nonmalignant reactive changes, which required no further therapy; 1 patient had a bone metastasis, which was treated with radiation therapy and tamoxifen; and 1 patient had radionecrotic tissue, which was treated with hyperbaric oxygen therapy. Symptoms resolved in all 3 patients. Skeletal scintigraphy is the most sensitive method for detecting bone metastases, but it is not specific. Bone metastases are usually multifocal, but sometimes a solitary bone lesion is found. A solitary sternal metastasis must be differentiated from other sternal disorders. Various treatment options exist for patients who are ultimately diagnosed with a solitary sternal metastasis.
Asunto(s)
Neoplasias Óseas/diagnóstico por imagen , Neoplasias Óseas/secundario , Neoplasias de la Mama/patología , Carcinoma/patología , Esternón/diagnóstico por imagen , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias de la Mama/radioterapia , Carcinoma/radioterapia , Diagnóstico Diferencial , Femenino , Humanos , Persona de Mediana Edad , Necrosis/inducido químicamente , Necrosis/diagnóstico por imagen , Cintigrafía , Radioterapia/efectos adversos , Esternón/patologíaRESUMEN
The aim of this study was to evaluate prognostic factors for isolated loco-regional recurrence in patients treated for invasive stage I or II breast cancer. The study population comprised 3602 women who had undergone primary surgery for early stage breast cancer, who were enrolled in European Organisation for Research and Treatment of Cancer (EORTC) trials 10801, 10854, or 10902, by breast conservation (55%) and mastectomy (45%). The median follow-up time varied from 5.3 (range: 0.6-9.5) to 11.9 years (range: 0.6-17.4). Main outcome was the occurrence of isolated loco-regional recurrence. The results of multivariate analysis showed that younger age and breast conservation were risk factors for isolated loco-regional recurrence (breast cancer under 35 years of age versus over 50 years of age: hazard ratio 2.80 (95% CI 1.41-5.60)); breast cancer age 35-50 years versus over 50 years: hazard ratio 1.72 (95% CI 1.17-2.54); breast conservation (hazard ratio: 1.82 (95% CI 1.17-2.86)). After perioperative chemotherapy, less isolated loco-regional recurrences were observed (hazard ratio 0.63 (95% CI 0.44-0.91)). No significant interaction effects were observed. It is concluded that young age and breast conserving therapy are both independent predictors for isolated loco-regional recurrence. As an isolated loco-regional recurrence is a potentially curable condition, women treated with breast conservation or diagnosed with breast cancer at a young age should be monitored closely to detect local recurrence at an early stage.
Asunto(s)
Neoplasias de la Mama/etiología , Recurrencia Local de Neoplasia/etiología , Adulto , Factores de Edad , Edad de Inicio , Neoplasias de la Mama/mortalidad , Neoplasias de la Mama/cirugía , Europa (Continente)/epidemiología , Femenino , Estudios de Seguimiento , Humanos , Mastectomía Segmentaria/efectos adversos , Persona de Mediana Edad , Recurrencia Local de Neoplasia/mortalidad , Recurrencia Local de Neoplasia/prevención & control , Pronóstico , Ensayos Clínicos Controlados Aleatorios como Asunto , Factores de Riesgo , Análisis de SupervivenciaRESUMEN
BACKGROUND: Breast-conserving therapy (BCT) has been shown to be as effective as mastectomy in the treatment of tumors 2 cm or smaller. However, evidence of its efficacy, over the long term, in patients with tumors larger than 2 cm is limited. From May 1980 to May 1986, the European Organization for Research and Treatment of Cancer carried out a randomized, multicenter trial comparing BCT with modified radical mastectomy for patients with tumors up to 5 cm. In this analysis, we investigated whether the treatments resulted in different overall survival, time to distant metastasis, or time to locoregional recurrence. METHODS: Of 868 eligible breast cancer patients randomly assigned to the BCT arm or to the modified radical mastectomy arm, 80% had a tumor of 2.1-5 cm. BCT comprised lumpectomy with an attempted margin of 1 cm of healthy tissue and complete axillary clearance, followed by radiotherapy to the breast and a supplementary dose to the tumor bed. The median follow-up was 13.4 years. All P values are two-sided. RESULTS: At 10 years, there was no difference between the two groups in overall survival (66% for the mastectomy patients and 65% for the BCT patients; P =.11) or in their distant metastasis-free rates (66% for the mastectomy patients and 61% for the BCT patients; P =.24). The rate of locoregional recurrence (occurring before or at the same time as distant metastasis) at 10 years did show a statistically significant difference (12% of the mastectomy and 20% of the BCT patients; P =. 01). CONCLUSIONS: BCT and mastectomy demonstrate similar survival rates in a trial in which the great majority of the patients had stage II breast cancer.
Asunto(s)
Neoplasias de la Mama/patología , Neoplasias de la Mama/cirugía , Mastectomía Radical Modificada , Mastectomía Segmentaria , Neoplasias de la Mama/radioterapia , Europa (Continente) , Femenino , Estudios de Seguimiento , Humanos , Metástasis Linfática , Persona de Mediana Edad , Estadificación de Neoplasias , Modelos de Riesgos Proporcionales , Radioterapia Adyuvante , Riesgo , Análisis de Supervivencia , Factores de Tiempo , Resultado del TratamientoRESUMEN
Alkyl-lysophospholipids (ALPs) represent a new class of antitumor drugs that induce apoptotic cell death in a variety of tumor cell lines. Although their precise mechanism of action is unknown, ALPs primarily act on the cell membrane, where they inhibit signaling through the mitogen-activated protein kinase (MAPK) pathway. Because stimulation of the stress-activated protein kinase/c-Jun NH2-terminal kinase (SAPK/JNK) pathway is essential for radiation-induced apoptosis in certain cell types, we tested the effect of ALPs in combination with ionizing radiation on MAPK/SAPK signaling and apoptosis induction. Here, we present data showing that three ALPs, 1-O-octadecyl-2-O-methyl-rac-glycero-3-phosphocholine, hexadecylphosphocholine, and the novel compound octadecyl-(1,1-dimethyl-piperidinio-4-yl)-phosphate (D-21266) induce time- and dose-dependent apoptosis in the human leukemia cell lines U937 and Jurkat T but not in normal vascular endothelial cells. Moreover, in combination with radiation, ALPs strongly enhance the induction of apoptosis in both leukemic cell lines. All tested ALPs not only prevented MAPK activation, but, like radiation, stimulated the SAPK/JNK cascade within minutes. A dominant-negative mutant of c-Jun inhibited radiation- and ALP-induced apoptosis, indicating a requirement for the SAPK/JNK pathway. Our data support the view that ALPs and ionizing radiation cause an enhanced apoptotic effect by modulating the balance between the mitogenic, antiapoptotic MAPK, and the apoptotic SAPK/JNK pathways. This type of modulation of specific signal transduction pathways in tumor cells may lead to the development of new therapeutic strategies.
Asunto(s)
Apoptosis/efectos de los fármacos , Proteínas Quinasas Dependientes de Calcio-Calmodulina/metabolismo , Proteínas Quinasas Activadas por Mitógenos , Éteres Fosfolípidos/farmacología , Fosforilcolina/análogos & derivados , Proteínas Quinasas/metabolismo , Transducción de Señal/efectos de los fármacos , Apoptosis/efectos de la radiación , Línea Celular , Endotelio Vascular/citología , Endotelio Vascular/efectos de los fármacos , Endotelio Vascular/efectos de la radiación , Rayos gamma , Humanos , Proteínas Quinasas JNK Activadas por Mitógenos , Células Jurkat/efectos de los fármacos , Células Jurkat/efectos de la radiación , Proteína Quinasa 1 Activada por Mitógenos , Proteína Quinasa 12 Activada por Mitógenos , Proteína Quinasa 3 Activada por Mitógenos , Fosforilcolina/farmacología , Transducción de Señal/efectos de la radiación , Células U937/efectos de los fármacos , Células U937/efectos de la radiaciónRESUMEN
PURPOSE: To assess the long-term contribution of adjuvant chemotherapy (CT) and hormonal therapy (HT) in patients with locally advanced breast cancer, and to evaluate the impact of time of analysis on the results during accrual and up to 8 years after closure of a randomized phase III trial. MATERIALS AND METHODS: In a trial using a factorial design, 410 patients were randomized between radiotherapy (RT) alone, RT plus CT, RT plus HT, and RT plus HT plus CT. RESULTS: CT and HT each produced a significant prolongation of the time to locoregional tumor recurrence and to distant progression of disease, with the combined treatments providing the greatest therapeutic effect. At the time of trial closure, a significant improvement of survival was observed in patients who received CT (P = .004); however, with a longer follow-up duration, this effect disappeared (P > .05). HT did not initially appear to improve survival (P = .16); however, in the latest analysis with a long-term follow-up duration, a significant improvement of survival was seen (P = .02). A consistent 25% reduction in the death hazards ratio has been seen at all evaluations since trial closure in patients who received HT. The best survival results were observed in patients who received RT, HT, and CT (P = .02), with a reduction of 35% in the death hazards ratio. CONCLUSION: An improvement in survival attributable to HT has been shown in patients with locally advanced breast cancer. The greatest therapeutic effect was seen in the treatment group that received both CT and HT. The improvement obtained with HT became apparent only after long-term follow-up evaluation.
Asunto(s)
Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/radioterapia , Hormonas/uso terapéutico , Neoplasias de la Mama/mortalidad , Neoplasias de la Mama/patología , Quimioterapia Adyuvante , Femenino , Humanos , Metástasis de la Neoplasia , Recurrencia Local de Neoplasia , Análisis de SupervivenciaRESUMEN
PURPOSE: To identify clinical and pathologic factors associated with an increased risk of local recurrence following breast-conservation therapy (BCT) to assess the safety of this procedure for all subgroups of patients. PATIENTS AND METHODS: The study population consisted of 1,026 patients with clinical stage I and II breast cancer treated between 1979 and 1988 at the Netherlands Cancer Institute. The BCT regimen consisted of local excision and axillary lymph node dissection (ALND) followed by whole-breast irradiation to a total dose of 50 Gy in 2-Gy fractions and boost irradiation (mostly by iridium implant) of 15 to 25 Gy. RESULTS: With a median follow-up duration of 66 months, the actuarial breast recurrence rate was 4% at 5 years, counting all breast recurrences. Univariate analysis showed seven factors to be associated with an increased risk of local recurrence; age, residual tumor at reexcision, histologic tumor type, presence of any carcinoma-in-situ component, vascular invasion, microscopic margin involvement, and whole-breast radiation dose. Three factors remained independently significant after proportional hazard regression analysis: age, margin involvement, and the presence of vascular invasion. When the analysis was repeated, but counting only those breast recurrences that occurred before regional or distant failures, only young age and vascular invasion were independent predictive factors. In the third analysis, factors predicting the necessity of local salvage treatment were analyzed. In this analysis, the possible bias in the former analysis caused by censoring actuarial methods was avoided. The results were the same as in the second analysis, showing young age and vascular invasion as the only independent predictive factors. Breast recurrence rates were 6% for patients less than 40 years of age and 8% for patients with tumors showing vascular invasion. In the absence of risk factors, the breast recurrence rate is only 1% at 5 years. CONCLUSION: Slightly higher recurrence rates were found in patients less than 40 years of age and in patients with tumors showing vascular invasion. The role of margin involvement is uncertain.
Asunto(s)
Neoplasias de la Mama/patología , Neoplasias de la Mama/terapia , Recurrencia Local de Neoplasia/patología , Análisis Actuarial , Adulto , Factores de Edad , Anciano , Anciano de 80 o más Años , Vasos Sanguíneos/patología , Terapia Combinada , Femenino , Humanos , Persona de Mediana Edad , Invasividad Neoplásica , Valor Predictivo de las Pruebas , Pronóstico , Modelos de Riesgos Proporcionales , Dosificación Radioterapéutica , Factores de Riesgo , Resultado del TratamientoRESUMEN
PURPOSE: To investigate the potential gain of the concomitant use of radiotherapy and chemotherapy in improving local control and reducing the need for colostomy, a randomized phase III trial was performed in patients with locally advanced anal cancer. MATERIALS AND METHODS: From 1987 to 1994, 110 patients were randomized between radiotherapy alone and a combination of radiotherapy and chemotherapy. The patients had T3-4NO-3 or T1-2N1-3 anal cancer. Radiotherapy consisted of 45 Gy given in 5 weeks, with a daily dose of 1.8 Gy. After a rest period of 6 weeks, a boost of 20 or 15 Gy was given in case of partial or complete response, respectively. Surgical resection as part of the primary treatment was performed if possible in patients who had not responded 6 weeks after 45 Gy or with residual palpable disease after the completion of treatment. Chemotherapy was given during radiotherapy: 750 mg/m2 daily fluorouracil as a continuous infusion on days 1 to 5 and 29 to 33, and a single dose of mitomycin 15 mg/m2 administered on day 1. RESULTS: The addition of chemotherapy to radiotherapy resulted in a significant increase in the complete remission rate from 54% for radiotherapy alone to 80% for radiotherapy and chemotherapy, and from 85% to 96%, respectively, if results are considered after surgical resections. This led to a significant improvement of locoregional control and colostomy-free interval (P = .02 and P = .002, respectively), both in favor of the combined modality treatment. The locoregional control rate improved by 18% at 5 years, while the colostomy-free rate at that time increased by 32% by the addition of chemotherapy to radiotherapy. No significant difference was found when severe side effects were considered, although anal ulcers were more frequently observed in the combined-treatment arm. The survival rate remained similar in both treatment arms. Skin ulceration, nodal involvement, and sex were the most important prognostic factors for both local control and survival. These remained significant after multivariate analysis. The improvement seen in local control by adding chemotherapy to radiotherapy also remained significant after adjusting for prognostic factors in the multivariate analysis. Event-free survival, defined as free of locoregional progression, no colostomy, and no severe side effects or death, showed significant improvement (P = .03) in favor of the combined-treatment modality. The 5-year survival rate was 56% for the whole patient group. CONCLUSION: The concomitant use of radiotherapy and chemotherapy resulted in a significantly improved locoregional control rate and a reduction of the need for colostomy in patients with locally advanced anal cancer without a significant increase in late side effects.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias del Ano/tratamiento farmacológico , Neoplasias del Ano/radioterapia , Neoplasias del Ano/patología , Neoplasias del Ano/cirugía , Colostomía , Terapia Combinada , Supervivencia sin Enfermedad , Esquema de Medicación , Femenino , Fluorouracilo/administración & dosificación , Humanos , Masculino , Persona de Mediana Edad , Mitomicinas/administración & dosificación , Dosificación Radioterapéutica , Inducción de Remisión , Tasa de SupervivenciaRESUMEN
PURPOSE: Risk factors for local and distant recurrence after breast-conserving therapy and mastectomy were compared to define guidelines for the decision making between both treatments. PATIENTS AND METHODS: The data of two randomized clinical trials for stage I and II breast cancer patients were pooled. The total number of patients in the study was 1,772, of whom 879 underwent breast conservation, and 893, modified radical mastectomy. Representative slides of the primary tumor were available for histopathologic review in 1,610 cases (91%). RESULTS: There were 79 patients with local recurrence after breast-conservation and 80 after mastectomy, the 10-year rates being 10% (95% confidence interval [CI], 8% to 13%) and 9% (95% CI, 7% to 12%), respectively. Age no more than 35 years (compared with age >60: hazard ratio [HR], 9.24; 95% CI, 3.74 to 22.81) and an extensive intraductal component (HR, 2.52; 95% CI, 1.26 to 5.00) were significantly associated with an increased risk of local recurrence after breast-conserving therapy. Vascular invasion was predictive of the risk of local recurrence, irrespective of the type of primary treatment (P <.01). Tumor size, nodal status, high histologic grade, and vascular invasion were all highly significant predictors of distant disease after breast-conserving therapy and mastectomy (P <.01). Age no more than 35 years and microscopic involvement of the excision margin were additional independent predictors of distant disease after breast-conserving therapy (P <.01). CONCLUSION: Age no more than 35 years and the presence of an extensive intraductal component are associated with an increased risk of local recurrence after breast-conserving therapy. Vascular invasion causes a higher risk of local recurrence after mastectomy as well as after breast-conserving therapy and should therefore not be used for deciding between the two treatments.
Asunto(s)
Neoplasias de la Mama/cirugía , Mastectomía Segmentaria , Mastectomía , Recurrencia Local de Neoplasia , Adulto , Factores de Edad , Anciano , Neoplasias de la Mama/patología , Toma de Decisiones , Femenino , Humanos , Persona de Mediana Edad , Invasividad Neoplásica , Guías de Práctica Clínica como Asunto , Estudios Retrospectivos , Factores de RiesgoRESUMEN
PURPOSE: To study the response rates and duration of response after low-dose (4 Gy) involved field radiotherapy (LD-IF-RT) in patients with recurrent indolent lymphoma. PATIENTS AND METHODS: A total of 109 assessable patients (304 symptomatic sites) were irradiated (53 males and 56 females; median age, 62 years; range, 35 to 93), including 98 patients with follicular lymphoma (43 grade 1 and 55 grade 2), nine extranodal marginal zone lymphomas of mucosa-associated lymphoid tissue-type and two patients with lymphoplasmacytoid lymphoma. Bulky disease (> or =5 cm) was present in 52% of all patients. A median of two prior regimens (range, 0 to 11) preceded LD-IF-RT. The median time since diagnosis was 41 months (range, 2 to 358 months). Time to (local) progression was calculated according to the Kaplan-Meier method. Differences in response rates between treatments within the same patient were compared using the McNemar test. RESULTS: The overall response rate was 92%; complete response was reached in 67 patients (61%), partial response in 34 patients (31%), stable disease in six patients (6%), and progressive disease in two patients (2%). The median time to progression was 14 months. The median time to local progression was 25 months. The 67 patients with complete response showed a median time to progression of 25 months and a median time to local progression of 42 months. None of the factors studied (age, sex, follicular lymphoma grade, radiotherapy regimen, number of previous regimens and previous history, number of positive sites or largest lymphoma diameter) were found to be related to response rate. CONCLUSION: LD-IF-RT is a valuable asset in the management of patients with follicular lymphoma and should be considered in patients with recurrent disease.
Asunto(s)
Linfoma de Células B/radioterapia , Linfoma Folicular/radioterapia , Adulto , Anciano , Anciano de 80 o más Años , Progresión de la Enfermedad , Relación Dosis-Respuesta en la Radiación , Femenino , Humanos , Linfoma de Células B/patología , Linfoma Folicular/patología , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Sobrevida , Resultado del TratamientoRESUMEN
In this work, we have studied the response rates and duration of response after low-dose (4 Gy) involved field radiotherapy (LD-IF-RT) in relapsed or chemotherapy refractory indolent and aggressive lymphoma patients. 71 patients (177 symptomatic sites) received LD-IF-RT consisting of 39 males and 32 females with a median age of 69 years (range 43-93). Patients included were those with small lymphocytic lymphoma/chronic lymphocytic leukaemia (n=23), marginal zone lymphoma, nodal type (n=18), mantle cell lymphoma (n=17), and diffuse large B-cell lymphoma (n=13). Bulky disease (5 cm) was present in 73% of all patients. A median of two prior chemotherapy regimens (range 0-10) preceded LD-IF-RT. Median time since diagnosis was 31 months (range 1-216 months). Time to (local) progression was calculated according to the Kaplan-Meier method. Differences in response rates were compared using the chi2-test. The results showed that overall response rate was 87%; complete remission (CR) was reached in 34 patients (48%) and a partial remission (PR) in 28 patients (39%). Stable disease (SD) was maintained in nine patients (13%). The median time to progression (TP) was 12 months and the median time to local progression (TLP) was 22 months. The 34 CR patients showed a median TP of 16 months and a median TLP of 23 months. None of the factors studied (age, sex, lymphoma subtype, radiotherapy regimen, number of prior regimens or time since diagnosis, number of positive sites or largest lymphoma diameter) were found to relate to response. At time of death 70% of patients were without in-field progression after LD-IF-RT. It appears that LD-IF-RT is a valuable asset in the management of relapsed disease in both indolent and aggressive lymphoma and should be considered to palliate symptoms in patients with recurrent and/or chemotherapy refractory disease.
Asunto(s)
Linfoma/radioterapia , Cuidados Paliativos/métodos , Adulto , Anciano , Anciano de 80 o más Años , Progresión de la Enfermedad , Supervivencia sin Enfermedad , Resistencia a Antineoplásicos , Humanos , Linfoma/tratamiento farmacológico , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Radioterapia/efectos adversos , Recurrencia , Resultado del TratamientoRESUMEN
A man (78 years) and a woman (55 years) experienced one-sided weakness and a woman (61 years) had language-expression problems between 4 and 37 years after having received radiotherapy for carcinoma of the larynx. All three patients had a significant degree of stenosis of the carotid artery. In two patients angioplasty and stenting was carried out. It was decided not to operate or stent the younger woman as her right internal carotid artery was occluded. No new symptoms developed in any of the patients. Radiation-induced stroke is not an uncommon disorder after radiotherapy for a laryngeal carcinoma in the past. The interval between radiation treatment and occurrence of stroke varies, but after a follow-up period of more than 5 years the risk of stroke is significantly increased. In the first instance the work-up should be similar to that in stroke patients with classical age-related atherosclerosis. However treatment of symptomatic radiation-induced carotid stenosis is often a challenge due to fibrotic changes and alterations of the anatomical layers within the radiation field. Screening and modification of additional cerebrovascular risk factors is recommended before radiation treatment is started, in order to prevent worsening of atherosclerotic changes.
Asunto(s)
Traumatismos por Radiación/complicaciones , Radioterapia/efectos adversos , Accidente Cerebrovascular/etiología , Anciano , Carcinoma/radioterapia , Estenosis Carotídea/epidemiología , Estenosis Carotídea/etiología , Estenosis Carotídea/cirugía , Femenino , Humanos , Neoplasias Laríngeas/radioterapia , Masculino , Persona de Mediana Edad , Traumatismos por Radiación/etiología , Factores de Riesgo , Accidente Cerebrovascular/epidemiologíaRESUMEN
Some of the major changes in radiotherapy over the last years are reviewed in this paper. Radiotherapy has played a role in the changes in oncological practice including an increase in organ-sparing treatment and achieving good local control and improving survival. About half of all breast cancer patients are now treated with breast conserving therapy. Organ preservation, usually with multimodality therapy, has also been further developed in the treatment of cancers in the head and neck, anus, bladder and soft tissue sarcomas. Developments in radiobiology have led to the development of new fractionation schedules. Hyperfractionation allows an increase in the tumour dose whilst sparing normal tissues and accelerated fractionation combats accelerated tumour proliferation during treatment. Advances in accelerator technology and computerized treatment planning have enabled the development of three-dimensional conformal radiotherapy. This gives the oportunity to spare normal tissues and escalate the dose to the tumour. Quality control and standardization of dosimetry and treatment delivery at departmental and international level has also improved treatment results.