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Biomedical subjects

R Arriagada

Publications and source records attributed to R Arriagada.

At least 145 records · Page 8Linked to original sources

[High-doses chemotherapy followed by bone marrow autograft in the treatment of small cell bronchial cancer].

Nineteen patients were treated with high dose chemotherapy followed by an autologous bone marrow transplantation. The chemotherapy regimen was an association of BCNU, procarbazine, etoposide, melphalan. Six patients had a progressive disease; 4 short-term complete remissions were observed. In 13 responding patients, 6 maintained complete remissions were noted.

Antineoplastic Combined Chemotherapy Protocols↗

Conservative management of breast cancer.

Between 1970 and 1982, 592 patients with T1 and small T2 breast cancers were treated at the Institut Gustave-Roussy by a combination of conservative surgery and radiotherapy. Mean follow-up was 78 months. The actuarial survival rate at 5 and 10 years was 92 per cent and 80 per cent respectively. There were 36 locoregional relapses of which 26 were within the treated breast. The actuarial relapse rate within the breast was 5 per cent at 5 years. If operable, a relapse within the breast did not significantly affect overall survival. The efficacy of conservative management of small breast tumours is confirmed.

Adult↗

Human cancer natural history, radiation induced immunodepression and post-operative radiation therapy.

For several types of cancers, post-operative radiation therapy is able to reduce the incidence of local recurrences, but has only a relatively small beneficial effect on total survival. Conversely to what has been claimed, this discrepancy is not due to a detrimental effect of radiotherapy. The data do not substantiate the hypothesis that irradiation through an impact on the immune system enhances growth of neoplastic foci outside of the irradiated volume. Several sets of data show that uncontrolled primary tumors or lymph node metastases can be important foci for distant spread. However the analysis of the data shows that post-operative radiotherapy can prevent metastatic spread only in a small subset of patients, those without distant metastases at the initial treatment and in whom local recurrences can be a nidus for distant dissemination before being detected and treated. The results of the clinical trials carried out on patients with breast cancers show that this situation is frequently observed in patients with tumors located in the inner quadrants of the breast who are those in whom the involvement of the internal mammary chain is relatively frequent.

Breast Neoplasms↗

Primary chemotherapy in the treatment of inflammatory breast carcinoma: a study of 230 cases from the Institut Gustave-Roussy.

We report the largest series of induction chemotherapy for inflammatory breast carcinoma (IBC). Results of two chemotherapy protocols with radiation therapy (RT) (170 patients) are compared with results with radiation alone (60 patients) in the treatment of this disease. From 1973 to 1975, 60 patients (control, group C) received RT (45 Gy and 20 to 30 Gy boost) and hormonal manipulation. From 1976 to 1980, 91 patients (group A) were treated with induction chemotherapy: Adriamycin (Adria Laboratories, Columbus, Ohio), vincristine, and methotrexate (AVM) and RT on a cyclical schedule; and maintenance chemotherapy: vincristine, cyclophosphamide, and 5-fluorouracil (5-FU) (VCF). From 1980 to 1982, 79 patients (group B) received induction chemotherapy, Adriamycin, vincristine, cyclophosphamide, methotrexate, and 5-FU (AVCMF) and RT on a cyclical schedule and VCF maintenance. Hormonal manipulation was performed in all groups. Disease-free survival at 4 years was 15% for group C, 32% for group A, and 54% for group B (P less than .005 group C v group A, less than .00001 group C v group B, and less than .01 group A v group B). Total survival at 4 years was 42% for group C, 53% for group A, and 74% for group B (P = .17 group C v group A, less than .00001 group C v group B, and less than .001 group A v group B). Clinical assessment of tumor aggressiveness, nodal status, type of chemotherapy administered, and early response to chemotherapy (by third course) were all prognostic factors. There is an important, highly statistically significant benefit in terms of both disease-free survival and total survival observed in patients treated with the addition of chemotherapy compared with radiation alone in IBC.

Aged↗

[Alternating chemotherapy and radiotherapy in the induction treatment of small cell bronchial carcinoma (forms limited to the thorax)].

Sixty three patients with limited small cell lung carcinoma were entered into a pilot study alternating monthly cycles of combination chemotherapy (doxorubicin, VP16213, cyclophosphamide and methotrexate (group A) or cis platinum (group B) with 3 courses of mediastinal radiotherapy. The total mediastinal dose was 45 Gy for the first 28 patients (group A) and 55 Gy for the remaining 35 (group B). The complete response rate was 86% in group A (median survival 14 months) and 91% in group B (median survival 20 months). Local control at two years was 61% in group A and 82% in group B, while relapse-free 2 year survival rates were 32% and 37% respectively. The acceptable toxicity and high response rate of this combined modality therapy lead us to further research in maintenance therapy.

Antineoplastic Agents↗

Sequencing of drugs and radiation. The integrated alternating regimen.

The association of radiotherapy (RT) and chemotherapy (CT) constitutes one of the main avenues for research in therapeutic oncology. This association has two aims: (1) increase in control rate of primary tumor (this requires either the potentiation of one of the two modalities by the other or the additivity of their effect on tumor cells without a parallel increase in the toxic effects on critical normal tissues); (2) spatial cooperation (RT being used for the control of the primary tumor or of the sanctuaries, and CT for the control of the disseminated disease). In these two strategies, RT and CT should be given up to full doses in order to be effective. The main risk is an increase in the number and severity of the early and late side effects. To circumvent this problem, two possibilities are being explored: (1) use of drugs without serious toxic effects on those critical tissues which are included in the irradiated volume; and (2) avoidance of concomitant administration and introduction of a sufficiently long-time gap between the completion of one modality and initiation of the other. However, in such sequential treatment, a delay of CT until after the completion of RT, or an interruption of CT cycle during the course of RT, allows the occult metastases to increase in size; a similar delay in initiation of RT is also detrimental, as drugs are often not effective on bulky tumors. Moreover, under CT, the cells which are resistant to the cytotoxic drugs may disseminate and initiate chemoresistant metastases. Taking these disadvantages into account, a treatment protocol was proposed in 1980 in which CT and RT are given alternately, without undue delay. Chemotherapy is started with the usual scheduling of one cycle every month. Radiotherapy courses are interdigitated between CT cycles. Each course is initiated 1 week after interrupting CT and continued until 1 week before beginning the subsequent cycle of chemotherapy, and so on until completion of RT. Such split-course RT should have an effect on a tumor comparable to that of a conventional fractionation. This protocol has been used on 24 patients with non-Hodgkin's lymphoma (NHL) of diffuse histology, and 63 patients with small cell carcinoma of the lung. The 2-year relapse-free survivals are promising (in clinical stage II NHL of diffuse histology, 75%; and in small cell lung carcinomas, 33%).(ABSTRACT TRUNCATED AT 400 WORDS)

Antineoplastic Agents↗

Radiotherapy alone in breast cancer. I. Analysis of tumor parameters, tumor dose and local control: the experience of the Gustave-Roussy Institute and the Princess Margaret Hospital.

This retrospective study involved 463 breast cancer patients treated by radiotherapy alone at the Princess Margaret Hospital and at the Institut Gustave-Roussy. These patients either had operable tumors, but were unfit for general anesthesia, or had inoperable tumors due to local contraindications to surgery. Results were analyzed according to tumor response, local recurrence rate, tumor size, tumor fixation, nodal fixation and tumor dose. Conventional statistical analysis of local control showed two significant factors: tumor dose and tumor size. Multivariate analysis permitted to define an "individual risk" (IR) of local recurrence according to three independent factors: tumor size, tumor fixation, and nodal fixation. It was shown that the IR was a good prognostic factor for local control. Increase in tumor dose gave a similar effect in the local recurrence relative risk for all the IR groups. According to the slope of the dose-effect curve, it was deduced that a dose increase of 15 Gy can decrease the relative risk of local recurrence 2-fold. In fact, it was shown that tumor dose was the most significant independent factor on local control, able to produce up to a 10-fold increase compared to 2-fold decrease for tumor size. If the IR of local recurrence is known, a theoretical predictive value on local control, taking into account the tumor dose, can be determined according to the present data.

Breast Neoplasms↗

Alternating radiotherapy and chemotherapy schedules in small cell lung cancer, limited disease.

Sixty-three evaluable patients with limited small cell lung carcinoma were entered into two pilot studies alternating 6 cycles of combination chemotherapy (Doxorubicin 40 mg/m2 d 1; VP16213 75 mg/m2 d 1, 2, 3; Cyclophosphamide 300 mg/m2 d 3, 4, 5, 6; and Methotrexate 400 mg/m2 d 2--plus folinic acid rescue--or Cis-Platinum 100 mg/m2 d 2) with 3 courses of mediastinal radiotherapy as induction treatment. The first course of radiotherapy started 10 days after the second cycle of chemotherapy; there was a 7 day rest between chemotherapy and radiotherapy courses. This 6 month induction treatment was followed by a maintenance chemotherapy. The total mediastinal radiation dose was increased from 4500 rad in the first study to 5500 rad in the second. Both protocols obtained a complete response (CR) rate of greater than 85% (with fiberoptic bronchoscopy and histological verification). Local control at 2 years was 61% in the first study and 82% in the second. Relapse-free survival at 2 years was 32 and 37%, respectively. Toxicity was acceptable. We conclude that our results justify further clinical research in alternating radiotherapy and chemotherapy schedules.

Antineoplastic Combined Chemotherapy Protocols↗

Analysis of local-regional relapses in patients with early breast cancers treated by excision and radiotherapy: experience of the Institut Gustave-Roussy.

Between 1970 and 1981, 436 patients with T1 and small T2 breast carcinoma were treated by tumor excision followed by radiotherapy at the Institut Gustave-Roussy. The mean follow-up was 5 years, with 50% of patients followed 5 years. Twenty-four patients have experienced a local-regional (LR) relapse for an actuarial LR control rate of 93% at 5 years and 90% at 10 years. Potential prognostic factors for all 24 local-regional recurrences and for the subgroup with relapses in the breast were analyzed. A high Bloom grade and low Nominal Standard Dose (NSD) were significant prognostic factors for predicting LR relapse in both groups. Disease-free survival (from initial presentation) was not adversely affected by a solitary breast recurrence, when patients with successful salvage treatment were considered disease free. However, the group of patients with nodal or dermal recurrences had a much worse prognosis. This paper describes the natural history of breast cancer following a local-regional relapse in irradiated patients without mastectomy. Most importantly, we observed that breast relapses following radiotherapy become clinically apparent more slowly than chest wall failures after mastectomy, and if detected early, that these patients may be successfully retreated.

Adolescent↗

[Inoperable lung epidermoid cancer non metastasizing. A phase II trial using radiotherapy and combined chemotherapy].

Thirty three evaluable patients with locally advanced squamous cell carcinoma of the lung were entered in a Phase II study combining chemotherapy (Vindesine 1.5 mg/m2 dl; CCNU 50 mg/m2 d2, 25 mg/m2 d3; Cis-Platinum 100 mg/m2 d3; Cyclophosphamide 200 mg/m2 d3, 4, 5) (VCPC) and radical radiotherapy to the primary tumor, mediastinum and supraclavicular nodes. Responders to chemotherapy resumed four additional cycles following radiation therapy. Fourteen patients (42%) presented an objective response to the first two cycles of VCPC. On final evaluation, 18 patients (54.5%) obtained a complete remission and 6 patients (18%) a partial remission. Median survival of all patients was 15.9 months and toxicity was acceptable. We conclude that our results justify a phase III study comparing combined treatment versus radiotherapy alone.

Adult↗

Combined chemotherapy (vindesine, lomustine, cisplatin, and cyclophosphamide) and radical radiotherapy in inoperable nonmetastatic squamous cell carcinoma of the lung.

Thirty-three evaluable patients with locally advanced squamous cell carcinoma of the lung were entered in a phase II study combining chemotherapy (vindesine, lomustine, cisplatin, and cyclophosphamide) and radical radiotherapy. Fourteen patients had an objective response rate of 42% (two complete responses and 12 partial responses) with the first two cycles of chemotherapy. All patients received radiation therapy to the primary tumor, mediastinum, and supraclavicular nodes, and responders to chemotherapy received four additional cycles. On final evaluation, 18 patients (54.5%) achieved complete response and six patients (18%) achieved partial response. The objective response rate was 73% with the combined therapy. The median survival was 15.9 months. Toxicity was acceptable. We conclude that our results justify a phase III study comparing combined treatment versus radiotherapy alone.

Adult↗

Invasive carcinoma of the thymus. A multicenter retrospective review of 56 cases.

This multicenter retrospective study included 56 cases of histologically reviewed invasive epithelial thymic tumors. All these patients underwent surgical treatment or exploration and were referred for complementary radiotherapy. The majority received a dose higher than 4000 rad. Twenty-three out of 50 patients (46%) with incomplete resection received some chemotherapy. The local recurrence rate at 2 yr was 34%. The overall 5-yr actuarial survival was 46%. There was no evidence of any relationship between radiation dose and local control. No difference in survival was observed with or without chemotherapy, nor according to histological type or lymphocytic infiltration, except cases with very undifferentiated carcinomas which presented a worse prognosis. Nor was any difference in survival observed between patients benefiting from incomplete resection and those only having undergone exploratory thoracotomy and biopsy. Radiotherapy seems to decrease the rate of local recurrence in invasive carcinoma of the thymus. The role of chemotherapy is still debatable, but it could have a role in decreasing tumor volume before radiotherapy. This study has shown the necessity of histological review by a panel of histopathologists in an attempt to better define terminology and diagnosis. A prospective study is necessary in order to solve the problems of concepts and management in epithelial thymic tumors.

Adolescent↗

[Superior vena cava compression syndrome. Apropos of 69 cases].

Sixty-nine patients with a superior vena cava syndrome were treated by radiotherapy. Forty were also given chemotherapy before or after irradiation. Twenty-nine had bronchial carcinoma, thirteen had other solid tumors, fourteen had lymphosarcoma and thirteen had no histological diagnosis. Subjective improvement was recorded in 86% of cases and the objective response rate was 41%. The response was obtained in a mean period of 4 weeks and its duration was 39 weeks for lymphosarcomas and only 6 weeks for solid tumors. Overall 1 year survival was 18%. Poor results obtained in superior vena cava syndrome incites recommendation of more intensive radiochemotherapeutic management.

Adolescent↗

The value of combining radiotherapy with surgery in the treatment of hypopharyngeal and laryngeal cancers.

Two-hundred and six cases of hypopharyngeal and laryngeal squamous cell carcinoma treated at the Institut Gustave-Roussy were retrospectively analyzed. All of them were treated by surgery and they were divided into three therapeutic groups following the adjuvant radiotherapy: (A) Postoperative radiotherapy at doses equal to or greater than 4500 rad; (B) Postoperative radiotherapy at doses less than 4500 rad; and (C) Preoperative irradiation at doses less than 4500 rad. Group A included a greater proportion of patients with hypopharyngeal cancer and patients with advanced tumors (T3, T4; N1b, N2, N3). However, the local and regional control rate in this group is significantly higher than those of the other groups in spite of the poor prognostic factors. The survival rate is comparable in all the three groups, with distant metastases more frequently found in group A. The results showing a significant improvement in lymph node control with postoperative radiotherapy, this adjuvant therapy is used systematically in this center in patients being operated on for hypopharyngeal and laryngeal cancer with incomplete histologically defined resection and/or with lymph nodes histologically involved.

Carcinoma, Squamous Cell↗