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Biomedical subjects

R Arriagada

Publications and source records attributed to R Arriagada.

At least 109 records · Page 6Linked to original sources

The value of adjunctive radiotherapy when chemotherapy is the major curative method.

Chemotherapy is the main treatment in many human malignancies including non-Hodgkin lymphomas and some solid tumors such as those of embryonal origin and small cell lung carcinomas. The high responsiveness to chemotherapy of these tumors has led some groups to treatment policies limited to chemotherapy alone. A long follow-up has shown a high incidence of recurrence in the sites that were initially macroscopically involved. Some randomized trials evaluating the adjunction of radiotherapy to chemotherapy have shown that a failure in local control can be associated with a decreased overall survival. The survival benefit of combined chemotherapy and radiotherapy is generally moderate and is best evaluated by randomized trials entering a large number of patients. The adjunction of radiotherapy to chemotherapy can lead to an increased rate of acute and late toxicity that may overshadow a therapeutic benefit. Critical points of the combined approach are: types of drugs, radiotherapy parameters, radiotherapy-chemotherapy doses, and timing. In this review, two clinical models, one with a low potential of cure, limited small cell lung cancer, and one with a medium potential of cure, non-Hodgkin lymphoma, are reviewed emphasizing information obtained from randomized trials. The modalities of combining radiotherapy and chemotherapy, particularly the timing, are analyzed to define optimal schedules for a definite therapeutic gain.

Breast Neoplasms↗

[Combined radiotherapy-chemotherapy in inoperable bronchial carcinoma (small cell carcinoma excluded)].

When treated by irradiation alone, non small cell carcinomas of the lung usually experience a very poor outcome. Consequently, more interest is being focussed on radiotherapy and chemotherapy association. The analysis of a randomized trial comparing irradiation alone to a sequential or an alternated combination of radio and chemotherapy did not reveal any clear advantage of the association of both therapies on each technique used alone. It is only when using concurrent irradiation and chemotherapy that some encouraging results are reported. Several non randomized studies used radio and chemotherapy prior to surgery, aiming at increasing the resectability rate. However, the criteria for initial unresectability were not homogeneous and it is not yet clear if such an association really allowed the state of surgical resection to be improved. In the near future it could be worth considering the use of radiosensitizing drugs, synchroneously given with an irradiation delivered with a multiple daily fractionation. This technique would possibly lead to a therapeutic gain, by increasing the local control rate and reducing the metastasis rate, while keeping it to an acceptable level of toxicity.

Antineoplastic Combined Chemotherapy Protocols↗

Limited small cell lung cancer treated by combined radiotherapy and chemotherapy: evaluation of a grading system of lung fibrosis.

A grading system of radiological fibrosis was defined and applied by four observers for the reading of 218 posterior-anterior chest X-rays of 78 patients. These patients with limited small cell lung cancer were treated from May 1980 to July 1983 in two consecutive alternating radiotherapy-chemotherapy schedules. Chest X-rays performed at each 6-month interval were read by each observer. A second reading was performed the day after. The analysis of results showed that in spite of some systematic variations in intra- and inter-observations, the proposed grading system had a good reproducibility. The radiological lung fibrosis score progressed between 6 and 12 months but was stable after one year of follow-up. There was no difference in the score of lung fibrosis between the two protocols which delivered a total dose of 45 and 55 Gy to the mediastinum. There was no significant correlation between the radiological changes and clinical symptoms.

Antineoplastic Combined Chemotherapy Protocols↗

Ten-year results of a randomized trial comparing a conservative treatment to mastectomy in early breast cancer.

A randomized trial was conducted at the Institut Gustave-Roussy (IGR) between 1972 and 1980 comparing tumorectomy and breast irradiation with modified radical mastectomy. One hundred and seventy-nine patients with an infiltrating breast carcinoma up to 20 mm in diameter at macroscopic examination were included: 88 had conservative management, and 91 a mastectomy. All patients had a low-axillary dissection with immediate histological examination. For the patients with positive axillary nodes, a complete axillary dissection was undertaken. Overall survival, distant metastasis, contralateral breast cancer and locoregional recurrence rates were not significantly different between the two treatment groups.

Adenocarcinoma↗

Limited small cell lung cancer: possible prognostic impact of initial chemotherapy doses.

While the effect of chemotherapy dose on tumor response in small cell lung cancer has been fairly well established, the effect on survival has been retrospectively analyzed only in some series. This particular point was studied in a series of 52 consecutive patients with limited small cell lung cancer treated by an alternating radiotherapy-chemotherapy schedule. The induction treatment consisted of 6 chemotherapy cycles (the planned doses were: doxorubicin 40 mg/m2 day 1, VP16213 75 mg/m2 days 1-3, cyclophosphamide 300 mg/m2 days 3-6, and cisplatinum 100 mg/m2 day 2) alternated after the first 2 cycles with 3 courses of thoracic radiotherapy delivering a total dose of 55 Gy. Eighty-one percent of patients went into complete remission and the 3-year relapse-free survival was 24%. A multivariate analysis of prognostic factors took into account age, sex, T stage, performance status, delayed hematological toxicity to the first course of chemotherapy, actual dose/m2 of each drug during the first course and mean dose/course delivered during the induction treatment after the first cycle of chemotherapy. It was possible to identify 3 independent factors influencing overall survival and relapse-free survival: actual initial dose of cisplatinum, actual initial dose of cyclophosphamide and the T stage. The effect of the initial dose of cisplatinum and cyclophosphamide proved to be linear on relapse-free survival. The results of this analysis show a possible effect of initial doses of chemotherapy in the management of limited small cell lung cancer in terms of both distant metastasis and overall survival rates.

Antineoplastic Combined Chemotherapy Protocols↗

[Role of radiotherapy in the treatment of small cell lung carcinoma].

For several years, chemotherapy has been the only treatment of small-cell carcinoma of the lung, but radiotherapy is increasingly used for its local effect in various ways. Irradiation of the chest alternating or concomitant with chemotherapy has become a basic principle in localized forms of the disease and may perhaps be useful in its diffuse forms. The so-called "prophylactic" brain irradiation is routinely performed, even though its beneficial effect on survival has not yet been demonstrated. As for extensive irradiation, it is still under study. Radiotherapy therefore plays an important role which, added to that of chemotherapy, should result in an improvement of long-term survival in patients with small-cell carcinoma of the lung.

Brain↗

[Therapeutic advances in small cell bronchial cancers].

Small cell lung cancer is one of the most chemo and radiosensitive adult solid malignancies. The effects of treatment should be evaluated according to standardized rules to ensure reproducibility. Recent randomized clinical trials have shown that combined chemo and radiotherapy can improve survival. A 5-year survival rate of 20 per cent can be obtained for an initially limited disease. However, further improvement of results requires optimized drug combinations and multimodality approaches as well as a better integration of new biological concepts in therapeutic trials.

Carcinoma, Small Cell↗

Long-term effect of internal mammary chain treatment. Results of a multivariate analysis of 1195 patients with operable breast cancer and positive axillary nodes.

A multivariate analysis on 1195 patients with operable breast cancer and histologically positive axillary nodes treated by mastectomy and complete axillary dissection at the Institut Gustave-Roussy between 1958 and 1978 suggests a beneficial effect of treatment of the internal mammary chain (IMC) on the risks of death and distant metastasis for the patients with medial tumors. For these patients, surgical IMC dissection and post-operative irradiation have similar effects on both the risk of death and of distant metastasis. For the patients with lateral tumors, no beneficial effect of the treatment of the IMC on these two risks was observed. Postoperative irradiation to the IMC, axilla, chest wall and supraclavicular nodes significantly decreases the risk of locoregional recurrences independent of the tumor site and surgical management of the lymph nodes.

Adult↗

Cosmetic results following lumpectomy, axillary dissection and radiotherapy for small breast cancers.

Between 1970 and April 1982, 592 women with T(1), small T2, N0, N1, M0 breast cancer were managed by lumpectomy, axillary dissection and radiotherapy at the Institut Gustave-Roussy (IGR). The overall cosmetic result and the degree of asymmetry, fibrosis and telangiectasia of the treated breast were assessed by the radiation oncologist at each follow-up visit. The changes in these cosmetic parameters with time are shown. At 5 years the overall cosmetic result was excellent in 59%, good in 38% and fair or poor in 8%. A multivariate analysis was performed of the factors associated with a cosmetic defect. The most significant factors were tumour size, the presence of defect after surgery and the daily applied dose per fraction to the breast. Surgical and radiotherapy technique (especially alternate day fractionation) can significantly affect the cosmetic result obtained.

Axilla↗

Radical radiotherapy alone in non-operable breast cancer: the major impact of tumor size and histological grade on prognosis.

This retrospective study involved 319 non-operable breast cancer patients treated by radiotherapy alone with doses of 65 Gy at the Institut Gustave-Roussy (IGR). These patients either had operable tumors but were unfit for general anesthesia or had inoperable tumors due to local contraindications. Most of them had advanced tumors: 21% less than 7 cm; 30% N2 or N3; 30% with inflammatory carcinomas. The 5- and 10-year survival was 40 and 19%, respectively. The local and distant relapse-free rate was 56 and 33% at 5 years and 44 and 28% at 10 years respectively. Results were analyzed according to tumor size, clinical node involvement, histologic grade, age, skin invasion and tumor dose. A multivariate analysis demonstrated that tumor size (p = 10(-3)) and histological grade (HG) (p = 10(-2)) were both significant factors predicting local relapse. Histological grade (p = 10(-3)), tumor size (p = 10(-2)) and clinical node involvement (p = 10(-2)) were the most significant factors predicting distant relapses. An individual risk (IR) of local recurrence and of distant recurrence was defined according to the above factors and was demonstrated to be good prognostic index. Tumor doses above 80 Gy did not increase local control. We recommend the general use of histological grading as it seems important for prediction of local and distant control in patients treated by radiotherapy alone.

Actuarial Analysis↗