RESUMO
In 165 women with breast cancer who were candidates for mastectomy because the largest diameter of the tumor was 3 cm or more, we administered primary chemotherapy in the attempt to substitute conservative for mutilating surgery. We then systematically quantitated tumor reduction by clinical, radiologic, and histopathologic evaluations. Five consecutive groups of 33 patients received cyclophosphamide, methotrexate, and fluorouracil (CMF); fluorouracil, doxorubicin (Adriamycin), and cyclophosphamide (FAC); or fluorouracil, epirubicin, and cyclophosphamide (FEC). The regimens for the five groups were as follows: group 1, three cycles of CMF; group 2, four cycles of CMF; group 3, three cycles of FAC; group 4, four cycles of FAC; and group 5, three cycles of FEC. In response to primary chemotherapy, 157 of the 161 assessable patients showed measurable tumor shrinkage; progressive disease was documented in four. Tumor shrinkage to less than 3 cm was documented in 127 (81%) of the 157 women subjected to surgery, thus allowing a breast-saving procedure, rather than modified radical mastectomy, in these 127 women. Histopathologic complete remission was documented in seven patients. Tumor response was unrelated to age, menopausal status, DNA content (ploidy), [3H]thymidine-labeling index, drug combination used, or number of treatment cycles in excess of three. The degree of response was inversely proportional to the initial tumor size, and the frequency of response was greater in receptor-negative tumors. Severe vomiting and hair loss were less frequent with CMF than with anthracycline-containing regimens, and the frequency of severe leukopenia and thrombocytopenia was minimal. Our results challenge the classical indication for primary mastectomy by showing that use of full-dose primary chemotherapy, sequentially combined with conservative surgery and radiation, can offer an effective and safe alternative to women concerned about the preservation of body integrity.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Mastectomia , Neoplasias da Mama/patologia , Neoplasias da Mama/cirurgia , Cisplatino/administração & dosagem , Ciclofosfamida/administração & dosagem , Doxorrubicina/administração & dosagem , Esquema de Medicação , Epirubicina/administração & dosagem , Feminino , Fluoruracila/administração & dosagem , Seguimentos , Humanos , Menopausa , Metotrexato/administração & dosagem , RecidivaRESUMO
BACKGROUND: In clinical breast cancer research, the utility of certain biomarkers as predictors of response to surgery, chemotherapy, or hormonal therapy has been studied intensively. Much less research has been done on the relevance of biologic predictors of response to radiotherapy, which represents an effective local-regional treatment for breast cancer. PURPOSE: The utility of biomarkers involved in DNA damage repair (p53 protein), control of programmed cell death (p53 and Bcl-2 proteins), and cellular detoxification (glutathione S-transferase-pi [GST-pi] enzyme) in predicting local breast cancer recurrence was analyzed retrospectively in two cohorts of breast cancer patients. These patients had had no detectable metastases in the axillary lymph nodes (i.e., node-negative) or in distant sites and had had similar distributions of clinicopathologic and biologic prognostic features. They had been treated by conservative surgery alone (139 case patients) or by conservative surgery followed by adjuvant radiotherapy (496 case patients) during the period from 1984 through 1990. METHODS: The expression of the p53, GST-pi, and Bcl-2 proteins in the specimens of primary breast tumor obtained from these patients was determined by use of immunohistochemistry; cell proliferation activity and levels of steroid receptors were determined by use of a [3H]thymidine-labeling index assay and the dextran-coated charcoal technique, respectively. The median time of follow-up of patients was 6 years. In the analyses of patient outcomes, only local failures that presented as first events were considered. RESULTS: After surgery alone, the risk of local recurrence at 6 years was higher for patients with tumors exhibiting elevated levels of p53 and GST-pi protein expression than for patients with low levels (hazard ratio [HR] = 3.1, 95% confidence interval [CI] = 1.3-7.7, two-sided P = .012; HR = 2.7, 95% CI = 1.1-6.4, two-sided P = .026, respectively). Weak or no observable expression of Bcl-2 protein was only suggestive of a higher frequency of local failures. Adjustment for patient age, tumor size, cell proliferation, and estrogen receptor status did not change these findings. Conversely, in the series of patients given conservative surgery followed by radiotherapy, there was no difference in local tumor recurrence between patients with tumors expressing or not expressing each of the three markers. CONCLUSIONS: Our study provides indirect evidence of a benefit from radiation therapy in preventing local breast cancer relapse, particularly among node-negative patients with tumors that express elevated levels of the p53 or GST-pi proteins or that express little or no Bcl-2 protein.
Assuntos
Biomarcadores Tumorais/análise , Neoplasias da Mama/química , Neoplasias da Mama/radioterapia , Regulação Neoplásica da Expressão Gênica , Glutationa Transferase/análise , Isoenzimas/análise , Proteínas Proto-Oncogênicas c-bcl-2/análise , Proteína Supressora de Tumor p53/análise , Neoplasias da Mama/genética , Neoplasias da Mama/fisiopatologia , Neoplasias da Mama/cirurgia , Feminino , Glutationa S-Transferase pi , Humanos , Imuno-Histoquímica , Mastectomia Segmentar , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Valor Preditivo dos Testes , Radioterapia Adjuvante , Estudos Retrospectivos , Resultado do TratamentoRESUMO
PURPOSE: The prognostic role of the site of the primary breast cancer has not been clarified. This study aimed to gather more information about this issue from a large series of patients with long-term follow-up data. PATIENTS AND METHODS: Data from 2,396 patients treated for early breast cancer with a conservative approach were reviewed (1973 to 1989). In 1,619 patients, the tumor had a lateral site, while in 777 cases, it was situated in the internal/central quadrants. The characteristics of the two groups were well balanced, apart from axillary nodal metastases, which were more frequent for lateral tumors (38.1% v 26.3%). RESULTS: Analysis of distant metastases indicated that the regression coefficient associated with tumor site was significant and the hazards ratio estimate was 1.291, which indicates the risk of distant metastases was increased by approximately 30% for internal/central tumors. The analysis of overall survival yielded a significant coefficient and a hazards ratio of 1.192, which indicates an approximately 20% increase of mortality for internal/central tumors. CONCLUSION: Early breast cancers situated in central/ internal quadrants have a worse prognosis compared with those in lateral quadrants, in terms of distant metastases and survival. Irradiation of the internal mammary chain for internal/medial tumors could be suggested, but, to date, the therapeutic strategy is still controversial.
Assuntos
Neoplasias da Mama/patologia , Metástase Neoplásica , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/radioterapia , Neoplasias da Mama/cirurgia , Terapia Combinada , Feminino , Seguimentos , Humanos , Pessoa de Meia-Idade , Prognóstico , Modelos de Riscos Proporcionais , Análise de SobrevidaRESUMO
PURPOSE: This prospective phase II study was designed to test the activity and toxicity of a regimen of fluorouracil (5-FU) and cisplatin (CDDP) in combination with radiation therapy in the treatment of epidermoid cancer of the anal canal. PATIENTS AND METHODS: Thirty-five consecutive patients with untreated epidermoid cancer of the anal canal were candidates for chemoradiation therapy (CRT). Staging of cancer was as follows: T1, 26%; T2, 60%; T3, 14%; and N1, 2,3, 26%. No patient had distant metastases. The treatment protocol consisted of two to three cycles of chemotherapy starting on days 1 and 21 and concurrent radiotherapy at a daily dose of 1.8 Gy up to a total dose of 36 to 38 Gy in 4 weeks, delivered to the anal region, perineum, middle and lower pelvis, and inguinal and external iliac nodes. Radiotherapy was then delivered to the anoperineal region and metastatic inguinal nodes to a total dose of 18 to 24 Gy in 10 fractions. Chemotherapy consisted of 24-hour intravenous (IV) infusion of 5-FU 750 mg/m2 on days 1 to 4 and CDDP 100 mg/m2 by 60-minute IV infusion on day 1. RESULTS: All patients received two cycles of chemotherapy; the second was delayed in three patients because of leukopenia that was evident in 11 (31%). In eight patients, a third cycle was added. They all experienced nausea or vomiting; one patient showed signs of cardiotoxicity and one developed proctitis, dermatitis, and diarrhea (grade 3). Complete regression (CR) was assessed in 33 patients (94%); nine patients with metastatic lymph nodes also had CR. Two patients had a partial response (PR); both underwent abdominoperineal resection, which was not curative in one. Two patients (6%) had a local recurrence; in one, this was associated with hepatic metastases. One of these patients underwent surgery and is alive after about 4 years, while the other is undergoing chemotherapy. After a median follow-up duration of 37 months, 94% of patients are alive without evidence of disease and 86% are colostomy-free. CONCLUSION: This regimen is well tolerated; its toxicity does not exceed that observed with the combination of 5-FU and mitomycin (MMC). Compared with our previous experience based on the classic CRT (5-FU, MMC, and radiation), the objective response rate observed with this new combination was similar. However, the local recurrence rate, observed in patients treated with the new regimen, was lower (6% v 24%). According to more recent data from the literature, primary CRT is the elective indication in epidermoid cancer of the anus and replacement of MMC with CDDP seems an effective and logical evolution.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias do Ânus/tratamento farmacológico , Neoplasias do Ânus/radioterapia , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/radioterapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Cisplatino/administração & dosagem , Terapia Combinada , Esquema de Medicação , Feminino , Fluoruracila/administração & dosagem , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Estudos ProspectivosRESUMO
In an attempt to reduce some of the delayed sequelae associated with combined modality therapy in Hodgkin's disease, we randomly tested stages IIB, IIIA, and IIIB MOPP (mechlorethamine, vincristine, procarbazine, and prednisone) v ABVD (Adriamycin, bleomycin, vinblastine, and dacarbazine). In 232 previously untreated patients, three cycles of either combination preceded and followed extensive irradiation. The complete remission rate was 80.7% following MOPP and 92.4% following ABVD (P less than .02). The 7-year results indicated that ABVD was superior to MOPP in terms of freedom from progression (80.8% v 62.8%; P less than .002), relapse-free survival (87.7% v 77.2%; P = .06), and overall survival (77.4% v 67.9%; P = .03). Moreover, the comparative iatrogenic morbidity showed that irreversible gonadal dysfunction as well as acute leukemia occurred only in patients subjected to MOPP, while cardiopulmonary studies failed to document significant laboratory differences between the two treatment groups. Present findings indicate that ABVD followed by extensive irradiation represents a valid therapeutic alternative to the widely used alkylating agent-containing regimens plus radiotherapy.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Doença de Hodgkin/tratamento farmacológico , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Bleomicina/administração & dosagem , Ensaios Clínicos como Assunto , Terapia Combinada , Dacarbazina/administração & dosagem , Doxorrubicina/administração & dosagem , Feminino , Seguimentos , Doenças dos Genitais Femininos/induzido quimicamente , Doenças dos Genitais Masculinos/induzido quimicamente , Cardiopatias/induzido quimicamente , Doença de Hodgkin/mortalidade , Doença de Hodgkin/radioterapia , Humanos , Pneumopatias/induzido quimicamente , Masculino , Mecloretamina/administração & dosagem , Estadiamento de Neoplasias , Prednisona/administração & dosagem , Procarbazina/administração & dosagem , Distribuição Aleatória , Estatística como Assunto , Vimblastina , Vincristina/administração & dosagemRESUMO
To evaluate the effect of adjuvant chemotherapy in patients with local-regional nasopharyngeal carcinoma (NPC) (squamous or undifferentiated) in complete remission at the end of curative radiotherapy (RT) 229 patients were randomized from 1979 to 1983 in a multicenter study to no further therapy (116 patients) or a combination of vincristine, cyclophosphamide, and Adriamycin (doxorubicin; Adria Laboratories, Columbus, OH) (VCA) for six monthly cycles (113 patients). The RT and RT + VCA groups were well balanced for median age (50 v 49 years), histology (undifferentiated carcinoma, 73% v 70%), tumor extent (tumor limited to nasopharynx, 57% v 57%), and nodal extent (negative nodes 26% v 24%, nodes in the lower cervical levels, 17% v 16%). RT was delivered to the nasopharynx, the base of the skull, and bilateral cervical nodes using a split course technique over 10 weeks up to the dose of 60 to 70 Gy in involved sites and 50 Gy to negative nodes. Response to RT was evaluated within 65 days post-RT treatment. Analysis at 48 months did not show significant difference between the two treatment groups in terms of relapse-free survival (RT, 55.8%, RT + VCA, 57.7%, P = .45) and overall survival (RT, 67.3%, RT + VCA, 58.5%, P = .13). The pattern of relapse was similar in the two treatment arms. Distant metastases were the cause of treatment failure in about 50% of relapsing patients. Although the results of the present study did not show any benefit from VCA administered after curative RT, combined systemic chemotherapy should be further explored due to the high incidence of local and distant failure after intensive RT.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma/tratamento farmacológico , Neoplasias Nasofaríngeas/tratamento farmacológico , Carcinoma/mortalidade , Carcinoma/radioterapia , Ensaios Clínicos como Assunto , Terapia Combinada , Ciclofosfamida/administração & dosagem , Doxorrubicina/administração & dosagem , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Nasofaríngeas/mortalidade , Neoplasias Nasofaríngeas/radioterapia , Dosagem Radioterapêutica , Distribuição Aleatória , Vincristina/administração & dosagemRESUMO
PURPOSE: To assess the efficacy, toxicity, and applicability of high-dose therapy administered as adjuvant initial treatment to women with breast cancer with extensive nodal involvement. PATIENTS AND METHODS: Sixty-seven patients with stage II to III breast cancer involving > or = 10 axillary nodes received a novel high-dose sequential (HDS) regimen, including the high-dose administration of three non-cross-resistant drugs (cyclophosphamide, methotrexate, and melphalan) given within the shortest interval of time as possible with hematologic and nonhematologic toxicity. RESULTS: Sixty-three patients completed the program as planned, one patient died of acute toxicity, and three patients were switched to standard-dose adjuvant therapy. After a median follow-up duration of 48.5 months and a lead follow-up of 78 months, actuarial relapse-free survival for all 67 registered patients is 57% and overall survival is 70%, respectively. Comparison with a historical control group of 58 consecutive patients showed a significantly superior rate of freedom from relapse for the HDS-treated group (57% v 41%, respectively), in particular when two subgroups of patients, more homogeneous for their number of involved nodes, were compared (65% v 42%). Overall, treatment was of short duration (median, 70 days), required a median of 32 days of hospital stay, and was associated with only a few severe side effects (the most distressing being oral mucositis after melphalan therapy). CONCLUSION: HDS therapy emerges as an effective and applicable regimen, whose major toxicity was occasional. Final assessment of its value in a randomized, multicenter trial is presently underway.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Linfonodos/patologia , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Axila/patologia , Neoplasias da Mama/cirurgia , Quimioterapia Adjuvante , Ciclofosfamida/administração & dosagem , Ciclofosfamida/efeitos adversos , Intervalo Livre de Doença , Relação Dose-Resposta a Droga , Doxorrubicina/administração & dosagem , Doxorrubicina/efeitos adversos , Feminino , Fator Estimulador de Colônias de Granulócitos e Macrófagos/uso terapêutico , Humanos , Linfonodos/efeitos dos fármacos , Mastectomia , Melfalan/administração & dosagem , Melfalan/efeitos adversos , Metotrexato/administração & dosagem , Metotrexato/efeitos adversos , Pessoa de Meia-IdadeRESUMO
Two hundred and seventy-seven consecutive patients with T3b-T4 breast cancer referred to the Milan Cancer Institute between 1973 and 1980 were treated with a combined modality approach. Chemotherapy (CT) consisted of AV, i.e. adriamycin (60-75 mg/m2 day 1) and vincristine (1.2 mg/m2 days 1 and 8) and was given for three to four cycles prior to local regional modality. Local-regional treatment consisted of either radiotherapy (RT) in 198 patients or surgery (S) in 79 women. Additional chemotherapy was then administered to a total of 205 patients. In the absence of distant metastases, frequency of good local control was significantly inferior in patients given CT + RT (63.9 per cent) compared to those treated with CT + RT + CT (75.4 per cent) and CT + S + CT (82.3 per cent, P = 0.033). Also freedom from progression (FFP) and overall survival (SURV) were significantly superior in the groups receiving more prolonged chemotherapy treatment compared to patients treated with CT + RT (FFP: P less than 0.0001; SURV: P = 0.002). None of the variables examined was able to affect the response rate, while axillary nodal status and tumor size played a major role in the duration of FFP and SURV. Our findings indicate that a more aggressive treatment is needed to improve current results in this stage of disease. To overcome the problem of local-regional recurrence, treatment should probably begin with cytoreductive surgery followed by postoperative radiotherapy in all patients with the exception of those having inflammatory carcinoma. Systemic treatment should then be delivered to control distant micrometastases.
Assuntos
Neoplasias da Mama/terapia , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Neoplasias da Mama/radioterapia , Ensaios Clínicos como Assunto , Terapia Combinada , Doxorrubicina/administração & dosagem , Feminino , Humanos , Pessoa de Meia-Idade , Estudos Prospectivos , Distribuição Aleatória , Vincristina/administração & dosagemRESUMO
The lymph nodes of the internal mammary chain represent a primary station draining the lymph from the breast and their removal or their irradiation has been considered an important step in breast cancer treatment. From January 1964 to January 1968, 737 patients with breast cancer were randomised at the National Cancer Institute in Milan to undergo either Halsted mastectomy or extended mastectomy with internal mammary node dissection. Patients with non-disseminated carcinoma classified as T1, T2, T3, N0, N1 were eligible for the study. No patients received postoperative radiotherapy or systemic therapy. After 30 years of follow-up, the overall survival curves and the specific survival curves do not show any difference between the patients of the two groups. Among the 558 patients who died in the 30 year interval period, 395 (71%) died from breast carcinoma (201 in the Halsted group and 194 in the extended mastectomy group) and 163 from other causes. This study shows that the removal of internal mammary nodes does not improve the survival of patients treated for breast carcinoma. This finding supports the theory that treatment of regional nodes does not influence the survival of cancer patients. The prognostic value of internal mammary node status is, however, high and a biopsy on a selected lymph node should be considered for staging purposes.
Assuntos
Neoplasias da Mama/cirurgia , Excisão de Linfonodo/métodos , Adulto , Distribuição por Idade , Idoso , Feminino , Humanos , Metástase Linfática , Mastectomia Radical Extensa/métodos , Pessoa de Meia-Idade , Análise de Sobrevida , Resultado do TratamentoRESUMO
We report the 10-year results of a randomised clinical trial in which two different breast conservation treatment strategies were compared in women with small, non-metastatic primary breast cancer: quadrantectomy, axillary dissection and radiotherapy (QUART) versus tumorectomy and axillary dissection followed by external radiotherapy and a boost with 192Ir implantation (TART). No second surgery was given to women with affected surgical margins. Axillary node positive women received adjuvant medical therapy. From 1985-1987, this trial accrued 705 patients, 360 in the QUART and 345 in the TART arm. Crude cumulative incidence curves for intrabreast tumour recurrence (IBTR) and metastases as first events and mortality curves in each of the two treatment arms were computed. A crude cumulative incidence curve of IBTR as a second event (in women who had already had a local recurrence) was also computed. The two groups were compared in terms of hazard for IBTR, metastases or death occurrence by using Cox regression models, both with and without adjustment for patient age, tumour size, number of metastatic axillary nodes and histology. Possible interactions between the aforementioned prognostic factors and the type of surgery were also investigated. The two groups were well matched for baseline patient and tumour characteristics, the only exception being resection margins, which were more often positive in the TART group. At the Cox model, a significant difference between groups was detected for IBTR (P < 0.0001), but not for distant metastases and overall survival. In particular, 5- and 10-year estimates of crude cumulative incidence of IBTR were 4.7 and 7.4% in the QUART group and 11.6 and 18.6% in the TART group. The difference was not substantially affected by patient or disease characteristics. Likewise, the status of resection margins in women who underwent TART treatment did not significantly influence the risk of occurrence of IBTRs. Finally, the rate of second IBTR occurrence was relatively high, when compared with the rate of IBTR occurrence as first event. In summary, the results of this trial show that a better local control of the disease can be obtained with the more extensive surgical resection, i.e. QUART.
Assuntos
Neoplasias da Mama/radioterapia , Neoplasias da Mama/cirurgia , Mastectomia/métodos , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/epidemiologia , Neoplasias da Mama/patologia , Terapia Combinada , Feminino , Humanos , Incidência , Excisão de Linfonodo , Metástase Linfática , Pessoa de Meia-Idade , Metástase Neoplásica , Recidiva Local de Neoplasia/epidemiologia , Análise de Sobrevida , Taxa de Sobrevida , Resultado do TratamentoRESUMO
From 1973 to 1980, 701 women with small breast cancer (less than 2 cm in diameter) were randomized into two different treatments. 349 patients received classic Halsted mastectomy and 352 patients received quadrantectomy, axillary dissection and radiotherapy on the ipsilateral breast. 24.6% of the patients in the mastectomy group and 27.0% of the patients in the conservation group had axillary metastases. Overall 10 year survival was 76% in the Halsted patients and 79% in the quadrantectomy patients; 13 year survival was 69% and 71%, respectively. No differences were observed after analysis by site and size of the primary tumour and age of the patients. Patients with positive axillary nodes had consistently better survival curves in the quadrantectomy group compared with the Halsted group (not significant). Among the quadrantectomy patients there were 11 local recurrences (with 4 deaths) while among the Halsted patients, 7 had local recurrences (5 deaths). There were 19 cases of contralateral breast carcinomas in the quadrantectomy group and 20 in the Halsted group. At 16 years from the beginning of the trial no evidence of oncogenic radiation risk was observed. In patients with small size carcinomas total mastectomy should have no role.
Assuntos
Neoplasias da Mama/cirurgia , Mastectomia/métodos , Neoplasias da Mama/mortalidade , Neoplasias da Mama/radioterapia , Terapia Combinada , Feminino , Humanos , Metástase Linfática , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/cirurgia , Período Pós-Operatório , Ensaios Clínicos Controlados Aleatórios como Assunto , Fatores de TempoRESUMO
Between 1985 and 1987 quadrantectomy plus external radiotherapy and lumpectomy plus external and interstitial radiotherapy were compared in a randomized trial of patients with small carcinomas of the breast. Quadrantectomy involves excision of 2-3 cm of normal tissue around the tumour plus the removal of a sufficiently large portion of overlying skin and underlying fascia whilst lumpectomy removes only the tumour mass with a narrow margin of normal tissue. Patients in both groups also received total axillary dissection. 705 cases were evaluable, 360 quadrantectomies and 345 lumpectomies. No differences in distant metastases and survival were observed in the two groups. However, lumpectomy patients had a much higher frequency of local recurrences (7.0 vs. 2.2%). Since a local recurrence needs a second operation and creates severe psychological distress to the patient, conservative surgical procedures should include generous excision of normal tissue around the primary carcinoma plus intensive postoperative radiotherapy.
Assuntos
Neoplasias da Mama/cirurgia , Mastectomia/métodos , Neoplasias da Mama/radioterapia , Terapia Combinada , Feminino , Humanos , Mastectomia Segmentar , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/cirurgia , Complicações Pós-Operatórias/cirurgia , Ensaios Clínicos Controlados Aleatórios como Assunto , ReoperaçãoRESUMO
From September 1976 to June 1982, 201 consecutive patients with stage I (A and B)-IIA Hodgkin's disease were stratified in two groups according to prognostic factors. The F group included 116 patients with favourable presentation: they were staged with laparotomy and treated with subtotal or total nodal radiotherapy alone. The U group included 85 cases with unfavourable presentation who were staged by laparoscopy and treated with 3MOPP (mechlorethamine, vincristine, procarbazine, prednisone)-radiotherapy-3MOPP. At 10 years the F group showed a freedom from progression (FFP) of 71% with significant difference between stage I and II (85% vs. 59%; P = 0.003) and an overall survival of 84%. The results of the U group were: FFP 83%, overall survival 74%, and the findings were not influenced by stage. FFP in patients with bulky vs. not bulky lymphoma was 70% vs. 87% (P = 0.04). No secondary acute non-lymphocytic leukaemia developed among patients treated with radiotherapy and in continuous complete remission, while acute leukaemia occurred in the F group patients who received salvage chemotherapy (4 of 31 cases) and in the U group (3 of 85 cases). Present results confirm the usefulness of radiotherapy alone in favourable pathological stage IA. All other disease stages will require a different strategy that should consist of radiotherapy combined with short-term effective regimens, such as ABVD (doxorubicin, bleomycin, vinblastine and decarbazine) or VBM (vinblastine, bleomycin and methotrexate) to reduce the incidence of MOPP-associated gonadal dysfunction and leukaemogenesis.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Doença de Hodgkin/tratamento farmacológico , Doença de Hodgkin/radioterapia , Adolescente , Adulto , Idoso , Terapia Combinada , Feminino , Doença de Hodgkin/patologia , Humanos , Leucemia/etiologia , Masculino , Mecloretamina/administração & dosagem , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prednisona/administração & dosagem , Procarbazina/administração & dosagem , Prognóstico , Terapia de Salvação , Fatores de Tempo , Vincristina/administração & dosagemRESUMO
Cis-Dichlorodiammine platinum (II) (cis-DDP) was demonstrated to be a potentiator of radiation therapy (RT) in experimental tumor models and in cultured cells. To assess the effectiveness of a combined modality treatment including RT and a weekly low-dose administration of cis-DDP, from January 1986 to June 1987, 95 patients with unresectable locally advanced non-small cell carcinoma of the lung (stage IIIa, b) were randomized for study. Fifty patients received RT alone at doses of 50 Gy; 45 patients received the same RT plus cis-DDP 15 mg/m2 IV weekly. An overall response rate of 50% and 64% was observed in the RT and RT + cis-DDP group, respectively. No statistically significant differences were detected with regard to median survival time (11 months for RT v 16 months for RT + cis-DDP) and progression-free interval (7 months in the RT arm v 9 months in the RT + cis-DDP arm), but the patterns of the first failure appeared to be affected by treatment. In fact, a lower number of intrathoracic relapses was observed in the RT + cis-DDP arm (12 in the RT + cis-DDP v 23 in the RT arm). Toxicity was mild and the feasibility of this schedule must be remarked. A better local control of disease can be obtained using cis-DDP as a radiation potentiator, but the true influence of this combined modality treatment on the length of survival, and the optimal cis-DDP timing and dosage are still to be evaluated in further clinical trials.
Assuntos
Carcinoma Pulmonar de Células não Pequenas/terapia , Cisplatino/administração & dosagem , Neoplasias Pulmonares/terapia , Terapia Combinada , Humanos , Dosagem Radioterapêutica , Distribuição AleatóriaRESUMO
From 1973 to 1980, 701 patients with breast cancer measuring less than 2 cm in pathological diameter and with no palpable axillary lymph nodes were randomized to Halsted mastectomy (349) or to "quadrantectomy" with axillary dissection and radiotherapy to the ipsilateral breast tissue (QUART) (352). The two groups were comparable in age distribution, size and site of primary tumor; menopausal status; and frequency of axillary metastases. At 8 years, the disease-free survival was 77% for the Halsted patients and 80% for the "quadrantectomy" patients, while overall survival was 83% and 85%, respectively. Disease-free and overall survival curves show no difference between the two groups. Breast cancer of small size (less than 2 cm) may be safely treated with conservative treatment. Mutilating operations are not justified.
Assuntos
Neoplasias da Mama/cirurgia , Mastectomia , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/radioterapia , Ensaios Clínicos como Assunto , Terapia Combinada , Ciclofosfamida/administração & dosagem , Feminino , Fluoruracila/administração & dosagem , Humanos , Itália , Excisão de Linfonodo , Metástase Linfática , Metotrexato/administração & dosagem , Recidiva Local de Neoplasia , Distribuição Aleatória , Fatores de TempoRESUMO
Forty-five patients were treated from 1984 to 1988. Thirty-eight, with a minimum follow-up of 6 months, are considered evaluable: median age, 62 years (25-88); males 6, females 32; T1 = 7, T2 = 21, T3 = 10; inguinal positive nodes, 5 patients. Chemotherapy (CT) (Mitomycin C, 15 mg/sqm, bolus day 1; 5-FU, 750 mg/sqm, 24 hr infusion, days 1 to 5) and radiotherapy (RT) started the same day. A dose of 36 Gy was given to the tumor and to the pelvis including inguinal nodes, in 20 fractions. After 2 weeks a boost of RT (18 Gy) to the ano-perineal area and a second cycle of CT completed the treatment. CR (biopsy) was achieved in 32/38 patients (84.2%). Among the six patients on PR, four received a Miles operation (2 NED), and two a wide local resection (both NED). Five out of 32 CRs relapsed: 2/5 were rescued with a Miles resection, 3 died from progression. In conclusion, 32/38 patients (84.2%) are NED after a median follow-up of 22 months and 28 of them retained their anal sphincter. A longer follow-up is needed to define optimal treatment modality, but it is clear that surgery must play a minor role in the treatment of anal cancer.
Assuntos
Neoplasias do Ânus/tratamento farmacológico , Neoplasias do Ânus/radioterapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias do Ânus/epidemiologia , Terapia Combinada , Feminino , Humanos , Itália/epidemiologia , Masculino , Pessoa de Meia-Idade , Indução de Remissão , Estudos RetrospectivosRESUMO
PURPOSE: The influence of radiotherapy in the cosmetic outcome after conservative surgery for breast cancer was evaluated using an objective method of calculating the asymmetry between the two breasts. METHODS AND MATERIALS: One hundred and one patients treated with the same conservative surgery were evaluated for cosmetic outcome. Sixty-one of them received external radiotherapy (50 + 10 Gy) to the residual breast; the remaining 40 underwent surgery only. The aspect of the patients' breasts was objectively assessed for symmetry by means of a computerized technique. A subjective assessment of the cosmetic outcome was performed both by physician and patient. These objective and subjective assessments were compared in the two groups treated with or without radiotherapy. RESULTS: The results obtained did not show significant differences in terms of cosmetic outcome in the two groups. Skin telangectasia was noted in two radiotherapy patients, while hypertrophic breast scars were only noted in six nonirradiated patients. CONCLUSIONS: We found that standard radiotherapy does not seem to influence the symmetry and the cosmetic results in breast conservative treatment when compared to a similar group of patients with the same quadrantectomy procedure and no radiotherapy.
Assuntos
Imagem Corporal , Neoplasias da Mama/radioterapia , Neoplasias da Mama/cirurgia , Mama/patologia , Adulto , Feminino , Humanos , Pessoa de Meia-Idade , Resultado do TratamentoRESUMO
PURPOSE: The study was undertaken to evaluate the long-term results in a favorable subset of patients with pathological Stage IA-IIA treated with irradiation alone. METHODS AND MATERIALS: One hundred and forty-seven adults with laparotomy- Staged IA-IIA "favorable" Hodgkin's disease were treated with primary subtotal nodal irradiation. Patients with infradiaphragmatic presentation were irradiated through paraortic and inguino-iliac node chains (inverted Y field) followed by prophylactic mediastinal and supraclavicular fields. RESULTS: Actuarial overall survival (OS) at 7 years (median follow-up 77 months) was: 93% for the whole series, 94% for Stage I, and 92% for Stage II. The freedom from first progression (FFP) (80% for the whole series) showed a statistically significant difference (p = 0.008) between Stage I (88%) and Stage II (71%). By univariate analysis, stage alone had an independent prognostic significance for OS and FFP. Of the 29 relapsed patients, 8 were previously classified as Stage I and 21 as Stage II; 16 of 29 (55%) of the relapses occurred in the pelvis and 9 in extranodal sites. After salvage treatment with chemotherapy all patients achieved a second complete remission. Seven second malignancies (two acute nonlymphocytic leukemias, one preleukemic syndrome, and four solid tumors) have been detected so far. Hypothyroidism was observed in 16% of patients and a reversible pulmonary restrictive syndrome in 14% of cases, respectively. CONCLUSIONS: Within 7 years from radiation therapy, about one-quarter of the patients with Stage II disease will experience a relapse and need intensive salvage chemotherapy. This is not invariably successful and safe, for it may be complicated by either acute or potentially fatal long-term adverse effects, such as second malignancies and cardiac or pulmonary sequelae, in about 5% of patients. The high frequency of relapse in Stage IIA patients suggests a combined modality approach with relatively short-term chemotherapy not including alkylating agents.
Assuntos
Doença de Hodgkin/patologia , Doença de Hodgkin/radioterapia , Adolescente , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Bleomicina/administração & dosagem , Terapia Combinada , Ciclofosfamida/administração & dosagem , Dacarbazina/administração & dosagem , Doxorrubicina/administração & dosagem , Epirubicina/administração & dosagem , Etoposídeo/administração & dosagem , Feminino , Seguimentos , Doença de Hodgkin/complicações , Humanos , Masculino , Mecloretamina/administração & dosagem , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Segunda Neoplasia Primária/patologia , Prednisona/administração & dosagem , Procarbazina/administração & dosagem , Prognóstico , Fatores de Risco , Terapia de Salvação , Vimblastina , Vincristina/administração & dosagemRESUMO
From January 1975 through December 1983, 74 consecutive patients were given adjuvant radiotherapy on the whole pelvis after radical surgery for locally advanced rectal (44 cases) and rectosigmoidal (30 cases) cancer. Most patients received 45 Gy to the whole pelvis in 5-7 weeks through AP, PA opposed fields. Fourteen patients were also given adjuvant chemotherapy. Minimum follow-up time of the series is 24 months and median follow-up is 36 months. First relapse was evaluated. Pelvic failures occurred in 17.5% of patients, while distant metastases rate was 32%; median time to relapse was 18 and 10 months respectively. Thirty patients (40.5%) never relapsed and are alive and well, while five additional patients are alive with disease. Four patients died of treatment toxicity. Thirty-one patients died of cancer (41.9%); 8 of them from pelvic failure only. Actuarial relapse-free survival at 3 and 5 years was 51.7% and 46.8%, while actuarial overall survival was 63% and 49%.
Assuntos
Neoplasias Retais/radioterapia , Neoplasias do Colo Sigmoide/radioterapia , Adulto , Idoso , Terapia Combinada , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Radioterapia/efeitos adversos , Neoplasias Retais/cirurgia , Neoplasias do Colo Sigmoide/cirurgiaRESUMO
At Istituto Tumori of Milano in a series of 3295 patients treated with conservative surgery and radiotherapy for breast cancer from 1973 to 1989 three cases of soft tissue sarcoma were observed in irradiated breasts. One patient developed a fibrosarcoma of the breast stroma, 16 months after irradiation. A grade II bulky angiosarcoma was diagnosed in the breast of a patient treated 59 months previously. The third was a grade II angiosarcoma detected 41 months after therapy. At present, the risk of a second primary in the irradiated breast seems too low to justify modification of our present policy of conservative therapy of breast cancer, but a careful and longer follow-up is needed.