Carmen Alonso

Assessment of anthracycline-induced myocardial damage by quantitative indium 111 myosin-specific monoclonal antibody studies

To assess chemotherapeutically induced myocardial damage, myosin-specific antibody scans and ejection fraction measurements were performed in 32 patients with breast cancer and in 9 patients with other tumours. All patients had received chemotherapy including anthracyclines. The ejection fraction decreased by ≥ 10% in 14 of 41 (34%) patients after chemotherapy. Antimyosin uptake in the myocardium was observed in 38 of 41 (92%) patients after chemotherapy. Antimyosin uptake was quantified by means of a heart-to-lung ratio, revealing a correlation between the degree of antimyosin uptake in the myocardium and the cumulative dose of anthracycline. Patients with a decreased ejection fraction showed more intense antimyosin uptake, indicating more severe myocardial damage. A higher degree of antimyosin uptake was found in 17 breast cancer patients treated with doxorubicin compared with 15 patients treated with mitoxantrone. We conclude that antimyosin studies provide a sensitive, non-invasive method to monitor myocardial damage in patients treated with anthracyclines. Antimyosin uptake in the myocardium precedes ejection fraction deterioration. This technique may be helpful in the early identification of patients at risk of congestive heart failure during chemotherapy including anthracyclines.

Use of somatostatin analogue scintigraphy in the localization of recurrent medullary thyroid carcinoma

Abstract.Detection of recurrence of medullary thyroid carcinoma (MTC) remains a diagnostic problem. Increased serum tumour marker levels frequently indicate recurrence while conventional imaging techniques (CIT) are non-diagnostic. In this study, we performed indium-111 octreotide scintigraphy and CIT in a series of 20 patients with MTC presenting with elevated serum tumour markers after surgery. 111In-octreotide whole-body studies detected 15 pathological uptake foci in 11 of the 20 patients studied and CIT detected 17 lesions in 11 of the 20 patients. Ten patients underwent reoperation, five of them with positive 111In-octreotide scintigraphy and CIT and two with positive isotopic exploration and negative CIT. Surgical findings demonstrated that the results of isotopic study and CIT had been false-positive for MTC in one case (sarcoidosis). The six patients with true-positive 111In-octreotide studies had significantly higher basal calcitonin (CT) and carcinoembryonic antigen (CEA) levels than the patients with negative isotopic studies. The expression of somatostatin receptor (SSTR) subtypes by PC-PCR could be investigated in four cases with a positive isotopic study. Among the three cases with a true-positive study, SSTR2, the SSTR subtype that preferentially binds to the somatostatin analogue octreotide, was detected in two, SSTR5 was demonstrated in the three, and SSTR3 was detected in one. No subtype of SSTR was detected in the case with a final diagnosis of sarcoidosis. We conclude that 111In-octreotide has limited sensitivity in detecting recurrence in patients with MTC, although its sensitivity may improve with high serum CT levels. This radionuclide imaging technique should be employed when conventional imaging techniques are negative or inconclusive or when the presence of somatostatin receptors may provide the basis for treatment with somatostatin analogues.

Bone pain palliation with strontium-89 in breast cancer patients with bone metastases and refractory bone pain

Fifteen patients with breast cancer and skeletal metastases who had bone pain refractory to opioid analgesics and who were not eligible for or had not responded to local field radiotherapy, were treated with strontium-89. All patients had received previous treatment with chemotherapy and radiotherapy for bone metastases. Severity of bone pain, sleeping pattern, mobility and dependency on analgesics were evaluated before and 4, 8 and 12 weeks after89Sr administration. Patients received 2 MBq/kg (118–148 MBq) of89Sr by i.v. injection. Pain relief and a reduction in analgesic requirements were observed in 7 of the 15 (47%) patients, with a reduction in the severity score from 34% to 71%. Duration of the response varied from 3 to 7 months. A decrease in peripheral blood cell count was observed in 11 patients: a 15%–66% reduction in white cell count and a 14%–75% reduction in platelet count were detected at 12 weeks after treatment in these patients. We conclude that89Sr is effective (47% response rate) for bone pain palliation in patients with bone metastases from breast cancer. Dependency on opioid analgesics may be reduced in patients with refractory bone pain.

A randomized multicentric study comparing alternating combination chemotherapy (VCMP/VBAP) and melphalan-prednisone in multiple myeloma

SummaryBetween January 1985 and December 1988, 386 patients with multiple myeloma were randomized to receive either MP or combination chemotherapy based on alternating cycles of VCMP and VBAP. The major prognostic parameters did not differ significantly between both treatment groups. A significantly higher proportion of objective responses was observed with combination chemotherapy as compared to MP (47.8 vs 32.2,P = 0.01). The median survival for all patients was 33.5 months. So far no significant differences were found when comparing the survival curves from both groups of patients. However, the median survival of MP-treated patients is 26.8 months, whereas the median survival of patients receiving VCMP/VBAP has not yet been reached. The definitive analysis must await the evaluation of all patients entered into the study and a longer follow-up time.

Malignant ovarian germ cell tumors: The experience at the Hospital de la Santa Creu i Sant Pau

Abstract From 1979 to 1990, 33 patients with pathologically confirmed malignant ovarian germ cell tumors (MOGCT) were referred after initial surgical procedure at the Department of Oncology, Hospital de la Santa Creu i Sant Pau. The median age was 22 years (range, 10 to 39). Stage distribution was as follows: stage I, 12 patients; stage II, 6 patients; stage III, 11 patients; stage IV, 3 patients; and unstaged, 1 patient. The histologic diagnoses were 10 dysgerminomas, 4 endodermal sinus tumors, 11 immature teratomas, and 8 mixed germ cell tumors. Twenty-eight out of the thirty-three patients received postoperative chemotherapy with POMB-ACE-PAV or other platinum-containing regimens. One patient with stage IV disease failed to respond to chemotherapy and she died. Sixteen out of the twenty-eight treated patients had second-look laparotomy, which showed mature teratoma in six and persistent malignant teratoma in one patient. This last patient had complete remission with second regimen. No patient has developed recurrence. With a median follow-up of 66 months (range, 10 to 133), 32 patients (97%) are alive without evidence of disease. These data confirm that platinum-containing regimens have dramatically improved the prognosis for patients with MOGCT. This paper discusses primary chemotherapy and the role of the second-look in these patients.

External and interstitial radiation therapy of locally advanced carcinoma of the breast

The present report concerns 164 cases of locally advanced breast cancer (stage III), treated between December 1977 and January 1987. The local therapy consisted exclusively of radiation therapy including external beam irradiation (60Co) up to 45-50 Gy supplemented with a boost, delivered either by interstitial 192Ir (30-40 Gy) or by external irradiation from limited fields (15-22 Gy). Eighty-one patients also received adjuvant systemic chemotherapy. A total of 51 local failures (31%) occurred. The actuarial rate of survival with local tumor control was 53% at 5 years and 49% at 6.5 years. A total of 69 patients developed distant metastases (42%). The actuarial survival without distant failure was 43% at 5 years and 37% at 6 years. The actuarial survival rate at 5 years was 53% and 38% at 7 years. The cosmetic results were excellent in 58 patients and poor in 13 patients (9.7%). The result suggests that stage III breast cancer can be satisfactorily treated with radiation therapy alone as local treatment.

Germline ATM mutational analysis in BRCA1/BRCA2 negative hereditary breast cancer families by MALDI-TOF mass spectrometry

Biallelic inactivation of ATM gene causes the rare autosomal recessive disorder Ataxia-telangiectasia (A-T). Female relatives of A-T patients have a two-fold higher risk of developing breast cancer (BC) compared with the general population. ATM mutation carrier identification is laborious and expensive, therefore, a more rapid and directed strategy for ATM mutation profiling is needed. We designed a case–control study to determine the prevalence of 32 known ATM mutations causing A-T in Spanish population in 323 BRCA1/BRCA2 negative hereditary breast cancer (HBC) cases and 625 matched Spanish controls. For the detection of the 32 ATM mutations we used the matrix-assisted laser desorption/ionization time-of-flight mass spectrometry technique. We identified one patient carrier of the c.8264_8268delATAAG ATM mutation. This mutation was not found in the 625 controls. These results suggest a low frequency of these 32 A-T causing mutations in the HBC cases in our population. Further case–control studies analyzing the entire coding and flanking sequences of the ATM gene are warranted in Spanish BC patients to know its implication in BC predisposition.

Ultrasonic patterns observed in hepatic metastases from breast carcinoma: Diagnosis and evolution

A retrospective analysis was made of 78 patients presenting breast neoplasm with hepatic metastases confirmed by ultrasound. Clinical hepatomegaly was present in 61 %. The serum glutamic-oxaloacetic transaminase (SGOT) was elevated in 72%, the serum glutamic-pyruvic transaminase (SGPT) in 56%, the serum alkaline phosphatase (Aph) in 86%, and the gamma-glutamil transpeptidase (GGT) in 76%. A hypoechogenic multiple nodular pattern (HMN) was observed in 69%, a diffuse hypoechogenic pattern (DH) in 15%, and a mixed multiple nodular pattern (MMN) in 11%. No single nodular pattern was presented in any patient. The univariate analysis showed a better survival rate in patients with a mixed pattern (mean 11 months, range 1–29 months) (p=0.027). No significant differences were observed regarding the remaining patterns, age, presence or not of hepatomegaly, or altered enzymatic values.

CHEMOTHERAPY AND RADIOTHERAPY IN LOCALLY ADVANCED CERVICAL CANCER

Radiotherapy has been standard therapy for locally advanced squamous cell cervical cancer. Neoadjuvant chemotherapy is being studied to improve responses and survival. We report a phase II study in locally advanced squamous cell cervical cancer (FIGO stages III and IVA) using chemotherapy with bleomycin, methotrexate and cisplatin (BMP) followed by radical radiotherapy. Of the 35 patients, 31 in stage III and 4 in stage IVA, 3 complete responses (CR) and 22 partial responses (PR) were achieved after chemotherapy treatment. Thirty-one patients completed radiotherapy; 19 achieved CR and 4 PR. Five-year actuarial survival for the entire group was 45% (95% confidence interval, 37-53%) with a median survival of 56 months. Patients with CR had a significantly better survival: the 5-year actuarial survival was 74% (95% CI, 59-89%). Recurrence developed in 4 of 19 patients. The most frequent side-effects were nausea and vomiting. Myelosuppression and impaired renal function also occurred. There was no evidence of radiotherapy toxicity enhancement. The stage and Karnofsky index were significant prognostic factors. It is concluded that BMP chemotherapy in advanced cervical cancer is effective and, followed by radiotherapy, allows a good control of this tumor. The group of patients with complete response have a low rate of recurrences and a long survival chance.

Inflammatory component: a worsening factor in locally advanced breast cancer treated by radiotherapy and systemic therapy.

Locally advanced and inflammatory carcinomas of the breast are two distinct entities with clear differential clinical criteria. We described a particular type of locally advanced breast cancer which, during its evolution, developed inflammatory characteristics limited to a small area of the skin. It, therefore, did not meet the common diagnostic criteria of inflammatory carcinoma. In our series, studied from December 1977 to January 1987, we treated 59 cases of locally advanced breast cancer and 105 cases of locally advanced breast cancer with an inflammatory component. The actuarial overall survival was 53.3 % at 5 years and 38.4 % at 7 years. Differences were observed when the two tumor types were compared. Specifically, locally advanced breast cancer with an inflammatory component had a worse prognosis, poorer survival and poorer disease-free rates than locally advanced breast cancer.