Tamoxifen in early breast cancer.
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Age Factors↗
Biomedical subjects
R Arriagada
Publications and source records attributed to R Arriagada.
Normal serum neuron specific enolase (NSE) value after the first cycle of chemotherapy: an early predictor of complete response and survival in patients with small cell lung carcinoma.
BACKGROUND: Serum neuron specific enolase (NSE) is the most sensitive tumor marker of small cell lung carcinoma (SCLC) at diagnosis. Its prognostic value is still debated. Thus, the authors decided to assess the predictive value, in terms of complete response and survival, of serum NSE measured before and after one cycle of chemotherapy in patients with SCLC. METHODS: Sera from 135 patients with histologically proven limited (n = 63) or metastatic (n = 72) SCLC were obtained. Clinical and biologic parameters with a known or suspected prognostic relevance were reviewed. Serum NSE was measured before chemotherapy (D1-NSE) and 28 days after its initiation (D28-NSE). The prognostic value of the parameters under study was evaluated in univariate and multivariate analyses using the Cox proportional hazards model and logistic regression analysis. RESULTS: The level of serum NSE was raised in 120 patients (88%) prior to therapy. The probability of a normal D28-NSE value was not affected by the baseline D1-NSE value. Disease extension (P = 0.0005), performance status (P = 0.0001), D28-NSE (P = 0.003), and carcinoembryonic antigen (CEA) levels (P = 0.008) were found to be predictive for survival, whereas age, gender, plasma sodium, serum protides, and D1-NSE were not. Median survival and 2-year overall survival were 15.3 months and 21% (95% confidence interval [CI], 13-31%) when D28-NSE was normal and 8.1 months and 15% (95% CI, 8-27%) when it was not (P < 0.03). Only performance status (P = 0.001), disease extension (P = 0.002), and D28-NSE (P = 0.02) were found to be independent prognostic parameters for survival in the multivariate analysis. A simple prognostic index was developed using these 3 variables. Limited disease, a normal D28-NSE value, and a normal CEA value prior to therapy were the only parameters predictive for complete response in the univariate analysis, and D28-NSE (P = 0.01) and disease extension (P = 0.0001) were found to be independent variables in multivariate analysis. A complete response to therapy occurred in 62% with a normal D28-NSE value and in only 34% in the opposite case. CONCLUSIONS: Normal serum D28-NSE is a strong, independent early predictor of both complete response to therapy and survival. This simple tool may be proposed for use in the clinic and in research, in association with an assessment of disease extension and performance status, to predict the outcome of patients with SCLC.
Adult↗
Alternating radiotherapy and chemotherapy in limited disease small cell lung cancer.
In a pilot study of 29 patients treated for localized small cell lung cancer, three new approaches were introduced, i.e. an increased initial drug dose, an early alternation of chemotherapy and thoracic radiotherapy and initial accelerated and hyperfractionated irradiation. The results were interesting. However, a high rate of fatal toxicity (21%) was observed.
Adult↗
[Duration of adjuvant treatment with tamoxifen in patients with resectable breast cancer].
Tamoxifen administered in patients after breast cancer surgery is one of the most effective adjuvant treatments in this pathology. A large number of randomized studies including thousands of patients allowed to quantify the treatment benefits in terms of recurrence, contralateral breast cancer and overall survival rates. The treatment is generally given for more than 2 years. However, the optimal treatment duration is unknown. Uncertainties appeared when adverse effects were described after some years of treatment (e.g. a higher incidence of endometrial adenocarcinoma). New ongoing multicentric trials will clearly define in the next years the optimal duration of this adjuvant treatment.
Antineoplastic Agents, Hormonal↗
[Radiotherapy in a multidisciplinary approach].
For a long time, thoracic radiotherapy has been the standard treatment of stage III non-small cell lung cancer. Because of the low rate of cure and the high rate of metastases in this group, strategies that combine radiotherapy with chemotherapy have undergone extensive investigation during the past decade with both positive and negative results. The combined treatment can be administered either sequentially, concurrently, or in an alternating mode. Some of the randomized trials have reported a positive impact of the addition of chemotherapy to radiotherapy with a positive impact of 2 to 4 months in terms of median survival. New therapeutic strategies are needed in order to improve control of both local disease and distant metastases. Improved local control could be achieved with higher radiation doses, conformal radiotherapy, altered fractionation schedules and possibly adjuvant surgery. Control of extrathoracic micrometastases may be improved with new combined modality strategies and new drugs. Increased toxic effects of these combined modality treatments should not diminish the expected therapeutic efficacy.
Antineoplastic Combined Chemotherapy Protocols↗
Prophylactic cranial irradiation for small-cell lung cancer.
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Brain Neoplasms↗
Post-operative adjuvant therapy for non-small-cell lung cancer.
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Carcinoma, Non-Small-Cell Lung↗
Optimizing chemotherapy and radiotherapy in locally advanced non-small cell lung cancer.
In recent years, three treatment methods have been shown to improve overall survival of patients with locally advanced non-small cell lung cancer. These are: sequential combined radiotherapy and cisplatin-based chemotherapy, concurrent administration of cisplatin and thoracic radiotherapy, and accelerated hyper fractionated radiotherapy. Optimization of results can be attained by integrating these three treatment approaches.
Antineoplastic Agents↗
Breast cancer in patients treated for Hodgkin's disease: clinical and pathological analysis of 76 cases in 63 patients.
In a retrospective multicentric analysis, 63 women treated between 1941 to 1988 for Hodgkin's disease (HD) subsequently developed 76 breast cancers (BC). The median age at diagnosis of HD was 26 years (range 7-67), and 22 women (35%) were 20 years old or less. Exclusive radiotherapy (RT) was used in 36 women (57%) and combined modalities with chemotherapy (CT) in 25 (39%). Breast cancer occurred after a median interval of 16 years (range 2-40) and the median age at diagnosis of the first BC was 42 years (range 25-73). TNM classification (UICC, 1978) showed 10 T0 (non-palpable lesions) (13%), 20 T1 (26%), 22 T2 (29%), 8 T3 (11%), 7 T4 (9%) and 9 Tx (12%), giving altogether a total of 76 tumours, including, respectively, 5 and 8 bilateral synchronous and metachronous lesions. Among the 68 tumours initially discovered, 53 ductal infiltrating, one lobular infiltrating and two medullary carcinomas were found. Moreover, two fibrosarcomas and 10 ductal carcinoma in situ (DCIS) were also found. Among 50 axillary dissections for invasive carcinomas, histological involvement was found in 31 cases (62%). 45 tumours were treated by mastectomy, without (n = 35) or with (n = 10) RT. 27 tumours had lumpectomy, without (n = 7) or with RT (n = 20). 2 others received RT only, and one only CT. 7 patients (11%) developed isolated local recurrence. 20 patients (32%) developed metastases and all died; 38 are in complete remission, whereas 5 died of intercurrent disease. The 5-year disease-specific survival rate by the Kaplan-Meier method was 61%. The 5-year disease-specific survival rate for pN0, pN1-3 and pN > or = 3 groups were 91%, 66% and 0%, respectively (P < 0.0001) and 100%, 88%, 64% and 23% for the T0, T1, T2 and T3T4 groups, respectively. These secondary BCs seem to be of two types: a large number of aggressive tumours with a very unfavourable prognosis (especially in the case of pN > 3 and/or T3T4); and many tumours with a 'slow development' such as DCIS and microinvasive lesions, especially in patients treated exclusively by RT. Moreover, a very unusual rate of bilateral tumours (21%) was observed. These secondary BC could be 'in field', in 'border of field' or 'out of field'. However, a complete analysis of doses delivered by supradiaphragmatic irradiation was often very difficult, due to large variations in several parameters. We conclude that young women and girls treated for HD should be carefully monitored by clinical examination, mammography and ultrasonography.
Adult↗
Small cell lung cancer and prophylactic cranial irradiation (PCI): perhaps the question is not who needs PCI but who wants PCI?
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Brain Neoplasms↗
[Bilateral breast cancer after Hodgkin disease. Clinical and pathological characteristics and therapeutic possibilities: an analysis of 13 cases].
PURPOSE: Though Hodgkin's disease (HD) is one of the malignancies in which considerable progress has been made, long-term side effects have been observed, second primary cancer being the most significant. Several recent reports have indicated an increased risk of breast cancer (BC) in girls and young women among HD patients. MATERIALS AND METHODS: In a retrospective multicenter analysis, 63 women treated for HD subsequently developed BC. Results that were obtained in 13 women (21%) who developed either synchronous (five cases) or metachronous (eight cases) BC were analyzed. The median age at diagnosis of HD was 19 years. Seven patients underwent exclusive radiotherapy (RT) (including "mantle" supradiaphragmatic irradiation) and six received concomittant radiation therapy and chemotherapy. RESULTS: The first breast tumor occurred after a median delay of 16 years. According to the TNM classification, we showed nine stage T0 (non palpable lesions), four stage T1, five stage T2, one stage T3, two stage T4 and five stage Tx BC. Seventeen infiltrating carcinomas, two fibrosarcomas and seven ductal carcinomas in situ were observed. Among 15 axillary dissections performed for invasive carcinomas, histological involvement was found in 10 cases. Seventeen tumors were treated by mastectomy and nine patients underwent conservative surgical treatment. With a 70-month median follow-up (range: 15-125), three patients developed locoregional recurrence and four other metastases. At present, eight are alive with no evidence of disease and one died of intercurrent disease. CONCLUSION: According to previous works, BC represents 6.3 to 9% of all second cancers occurring after HD treatment. The risk is higher in young women treated before 20 years of age, especially before 15 years of age. Factors that favour the development of secondary BC are: supradiaphragmatic irradiation, very young age at treatment, chemotherapy with alkylating agents, and probably genetic factors. We conclude that young women and girls treated for HD should be carefully monitored at least 10 years after the end of the treatment for HD, using clinical examination, mammography and ultrasonography. The optimal rythm of this follow-up is not yet clearly defined. Moreover, after multidisciplinary concertation, we suggest that secondary BC be sometimes treated by conservative radiosurgical approach.
Adolescent↗
[Optimization of combined radiotherapy and chemotherapy in treatment of non-small cell lung carcinoma].
PURPOSE: To report the results of CEBI 140 and 142 trials. These trials were aimed at improving the local control in stage III non-small cell carcinoma with concomitant chemotherapy and radiotherapy in the CEBI 140 trial, and with concomitant chemotherapy and radiotherapy followed by local excision in the CEBI 142 trial. MATERIAL AND METHODS: Thirty-four patients presenting with stage III non-small cell lung carcinoma were included into the CEBI 140 trial from December 1989 to December 1992. Patients were treated with a combination of daily cisplatin (6 mg/m2 per day, 144 mg/m2 in total), vindesine once a week (2.5 mg/m2, 15 mg/m2 in total) and bifractionated radiotherapy (60 Gy/48 fractions/6 weeks) followed by two cycles of cisplatin 120 mg/m2 (at d18 and d45 after completion of radiochemotherapy) and three cycles of vindesine (6 mg/m2 at d24, d31, and d38 after completion of radiochemotherapy). Twenty-eight patients presenting with stage IIIB non-small cell carcinoma-were included into the CEBI 142 trial since January 1993. Patients received a combination of cisplatin (100 mg/m2 at d1 and d24, 200 mg/m2 in total), vinblastine (4 mg/m2 at d1 and d24, 8 mg/m2 in total), 5-fluorouracil in continuous infusion (1,000 mg/m2 from d1 to d3, and from d24 to 26, 6,000 mg/m2 in total) and bifractionated radiotherapy (two series of 21 Gy/14 fractions/9 days, 11 days apart) followed by a new evaluation and surgical excision. RESULTS: In the CEBI 140 trial, all patients received a complete course of radiotherapy, but the dose of cisplatin was decreased in 27% of the cases, and the dose of vindesine in 88%. There were two toxicity-related deaths. Three months after completion of the protocol, there were 50% of complete responders. The overall survival rates at 1, 2 and 3 years were 53, 33, and 11%, respectively, and disease-free survival rates 21 11, and 11%, respectively. In the CEBI 142 trial the immediate tolerance was good. Twenty-one patients (75%) underwent surgical resection. Four tumors could not be resected. Resection was histologically incomplete in one case, and complete in the 16 remaining cases. With a median follow-up of 14 months, ten patients were alive and disease-free. CONCLUSION: Preliminary results of the CEBI 142 trial are encouraging. More patients and longer follow-up are needed for definitive conclusion. It would be of interest to implement a randomized trial comparing the CEBI 142 scheme and classical radiation therapy.
Adult↗
Current strategies for radiation therapy in non-small cell lung cancer.
Thoracic radiotherapy is widely used in patients with non-small cell lung cancer. Its role as adjuvant treatment before or after surgery has not been established clearly. In patients with locally advanced disease, the main cause of failure is the absence of local control. Recently, three treatment approaches have shown a beneficial effect on overall survival in randomized trials conducted in this group of patients: sequential combination of thoracic radiotherapy and cisplatin-based chemotherapy, concomitant use of radiation and daily low-dose cisplatin therapy, and hyperfractionated accelerated radiotherapy. Another area that merits further investigation is the role of adjuvant surgery.
Antineoplastic Agents↗
[New therapeutic strategies and current research in inoperable locally advanced non small-cell lung cancers (stage IIIB)].
Treatment of patients with inoperable locally advanced non small-cell lung cancer (NSCLC) remains disappointing with less of 5% of patients alive at 5 years. Both initial local control and circumvention of concomitant undetectable metastatic chemoresistant cells are the critical targets for the oncologists in charge of this disease. Results of a recent meta-analysis including 22 randomized studies comparing standard treatment (i.e. radiotherapy) to sequential chemoradiotherapy have undoubtabely well defined the role of cisplatine-containing chemotherapy in stage IIIB NSCLC, even if the 5 year survival benefit remains modest. However, high complete response rates and prolonged overall survival were observed with combinations of new promising chemotherapy regimens and new fractionated radiation schedules in several phase II studies. These results have to be corroborated by prospective randomized trials. Integration of more aggressive and more toxic strategies such as radical surgery in these initial inoperable locally advanced NSCLC are evaluating. Around these conventional therapies, the stage IIIB NSCLC represent a favoured target to elaborate innovative therapeutic approaches based on emergence of biotherapies as recombinant cytokines, antitumoral vaccine and gene therapy programs. The contribution of these new therapeutic options opens new directions in the therapeutic strategy and leads to hope a new promising era in the management and outcome of patients with these tumors.
Antineoplastic Combined Chemotherapy Protocols↗
Concurrent cisplatin-vindesine and hyperfractionated thoracic radiotherapy in locally advanced nonsmall cell lung cancer.
PURPOSE: Local failure is a major problem in locally advanced nonsmall cell lung cancer. The main objective of this Phase II trial was to test the feasibility of a combined concurrent radiotherapy and chemotherapy approach in an attempt to improve local control. METHODS AND MATERIALS: From December 1989 to December 1992, 34 patients were included. The treatment schedule consisted of hyperfractionated radiotherapy (60 Gy in 48 fractions and 6 weeks with two daily sessions of 1.25 Gy), cisplatin (6 mg/m2 every day of radiotherapy), and vindesine (2.5 mg/m2 once weekly). After a 3-week rest period, two full cycles of cisplatin (120 mg/m2 on weeks 10 and 14) and vindesine (2.5 mg/m2 on weeks 11, 12, and 13) were given. Treatment evaluation with thoracic computed scan, bronchoscopy, and bronchial biopsies was performed 3 months after completion of radiation therapy. Failure rates were estimated using a competing risk approach. RESULTS: The complete response rate was 50%. Local failure rates at 1 and 3 years were 53 and 56%, respectively. Distant metastases rates at 1 and 3 years were 26.5 and 29%. Overall survival rates at 1, 2, and 3 years were respectively 53, 33, and 12%. Severe esophagitis was observed in three patients (9%). Lethal toxicity was observed in two patients. CONCLUSION: This Phase II trial confirms the feasibility of this type of approach with specific dose reduction and suggests that it may improve local control compared to conventional approaches.
Adult↗
Conservative treatment versus mastectomy in early breast cancer: patterns of failure with 15 years of follow-up data. Institut Gustave-Roussy Breast Cancer Group.
PURPOSES: A randomized trial was conducted to compare tumorectomy and breast irradiation with modified radical mastectomy. We have analyzed the patterns of failure in each arm of the trial and the prognostic factors that have an independent effect on treatment failures and overall survival. PATIENTS AND METHODS: The trial included 179 patients with breast cancer of up to 20 mm in diameter at macroscopic examination. Eighty-eight patients had conservative management and 91 a mastectomy. All patients had axillary dissection with frozen-section examination. For patients with positive axillary nodes (N+), a second randomization was performed: lymph node irradiation versus no further regional treatment. Patterns of failure were determined by a competing-risk approach and multivariate analysis. A prognostic-score was determined by multivariate analysis. RESULTS: Overall survival, distant metastasis, contralateral breast cancer, new primary malignancy, and locoregional recurrence rates were not significantly different between the two surgical groups, or between lymph node irradiation groups. Most recurrences appeared during the first 10 years. Three distinct prognostic groups were determined taking into account age, tumor size, histologic grading, and number of positive axillary nodes. CONCLUSION: Long-term results support conservative treatment with limited surgery and systematic breast irradiation as a safe procedure for the management of small breast cancers. Four easily obtainable clinical and histologic factors may be combined in a prognostic score that is highly predictive of overall and event-free survival.
Adult↗
Local relapse and contralateral tumor rates in patients with breast cancer treated with conservative surgery and radiotherapy (Institut Gustave Roussy 1970-1982). IGR Breast Cancer Group.
BACKGROUND: Breast conservation is now established treatment for patients with small breast cancers. The authors reviewed a large series of patients with long term follow-up who underwent conservative treatment. Clinical and pathologic factors were analyzed to identify patients at an increased risk of relapse in the breast (local relapse) or development of a contralateral tumor. METHODS: Seven hundred fifty-seven patients with unilateral invasive breast cancer (T0-2, N0-1, M0) were treated conservatively (wide local excision and radiotherapy) at the Institut Gustave-Roussy between 1970 and 1982. The median follow-up was 9 years. The risk of local relapse or development of a contralateral tumor (as first event) was studied by univariate analysis for the main clinical, pathologic, and treatment factors. Those found to be significant were entered into a Cox proportional regression analysis. RESULTS: Fifty-one patients relapsed in the treated breast (actuarial local relapse rates at 5 and 10 years were 5% and 8%, respectively) and 34 in the contralateral breast (actuarial contralateral tumor rates at 5 and 10 years were 3% and 6%, respectively). Multivariate analysis of the risk factors for local relapse showed that only age younger than 40 years (P < 0.02) or inadequate surgical excisioin (P < 0.02) were significant. No particular risk factors for contralateral tumor development were identified. CONCLUSIONS: Overall, for most patients, the risk of local relapse or of developing a contralateral tumor was low. A small number of young patients with inadequately excised tumors are at higher risk of local relapse, need more meticulous surgery, and may merit higher dose radiotherapy.
Actuarial Analysis↗
Pattern of failure in patients with inflammatory breast cancer treated by alternating radiotherapy and chemotherapy.
BACKGROUND: Patients with inflammatory breast cancer have a high risk of developing a local recurrence and/or distant metastases. Treatment with combined chemotherapy and locoregional radiotherapy contributes to a decrease in both risks. This study presents treatment results and evaluates the pattern of failure when an alternating chemoradiotherapy schedule is used. METHODS: One hundred twenty-five patients with nonmetastatic inflammatory breast cancer were treated with an alternating schedule of radiotherapy and chemotherapy. All women recruited were younger than 70 years of age and had a T4d, histologically proven infiltrating carcinoma with N0 to N2 axillary disease. The protocol consisted of three cycles of induction chemotherapy with doxorubicin, vincristine, cyclophosphamide, methotrexate, and 5-fluorouracil followed by three series of locoregional radiotherapy, delivering a total dose of 65-75 Gy to the breast tumor. Five additional cycles of chemotherapy with 5-fluorouracil/doxorubicin/cyclophosphamide were to be administered in between the first two and after the third radiotherapy course. A 1-week gap was respected between each course of chemotherapy and each series of radiotherapy. RESULTS: Toxicity was moderate and this strategy proved feasible although most of the patients only received six instead of the eight planned cycles of chemotherapy. Eighty-two percent of the patients achieved a complete response at the end of the treatment. The cumulative 5-year local failure and distant metastasis rates were 27% and 53%, respectively. Assuming competing events, local failures, contralateral recurrences, and distant metastases were the first site of failure in 18%, 5%, and 38% of patients, respectively. The 5-year overall and disease free survival rates were 50% and 38%, respectively. The main prognostic factor was tumor size. CONCLUSIONS: Alternating high doses of radiotherapy and chemotherapy is a feasible treatment schedule and permits breast conservation. Disease free survival is comparable to that of recently published series. As the main causes of failure are distant metastases, higher dose chemotherapy should be evaluated, in an attempt to further improve overall survival.
Adenocarcinoma↗