[Positron emission tomography (PET): characteristics and potential applications in clinical oncology].
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Humans↗
Biomedical subjects
F Crippa
Publications and source records attributed to F Crippa.
Single-dose intraperitoneal radioimmunotherapy with the murine monoclonal antibody I-131 MOv18: clinical results in patients with minimal residual disease of ovarian cancer.
Sixteen of 19 enrolled patients with minimal residual disease of ovarian cancer (macroscopic disease < 5 mm or positive blind biopsies and/or positive peritoneal washing), demonstrated by surgical second-look, underwent intraperitoneal radioimmunotherapy (RIT) with the radiolabelled monoclonal antibody I-131 MOv18 (mean dose 14 mg of MOv18 with 3700 GBq of I-131) 30-40 days after the second-look procedure. Clinical follow-up and/or third-look evaluation performed 90 days after RIT showed complete response (CR) in 5 patients, no change (NC) in 6 patients and progressive disease (PD) in 5 patients. Follow-up study showed long-term maintained CR in 1 patient (34 months) and relapses in the other 4 patients after a mean disease-free period of 10.5 months. 5 NC patients showed clinical or instrumental progression after a mean disease-free period of 13 months. The toxicity of RIT was negligible. Only 1 patient showed mild and transient bone marrow suppression (platelet count nadir 52,000 mm3 after 30 days). HAMA production was demonstrated in 94% (15/16) of patients. In conclusion, RIT appears to be a very promising therapeutic approach to treat minimal residual disease of ovarian cancer.
Adult↗
Somatostatin receptor imaging of small cell lung cancer (SCLC) by means of 111In-DTPA octreotide scintigraphy.
Somatostatin receptors have been described on the membrane of neoplastic cells derived from the APUD system and their expression has also been demonstrated on small cell lung cancer (SCLC) in vitro and in vivo. 21 patients with SCLC were studied using 111In-octreotide (111In-OCT) scintigraphy. Scintigraphic examinations were performed following intravenous (i.v.) injection of 111 MBq 111In-OCT with whole-body scintigraphy and planar scintigraphy of the thorax as well as the SPET technique. No short-term side effects were described following 111In-OCT administration. We studied the 111In-OCT biodistribution in 3 patients with serial scintigraphies at 1, 5 and 24 h. We used the 5 h as standard scanning time for the following 18 patients. The scintigraphic results were compared with those of other conventional diagnostic procedures. 111In-OCT detected 86% (48/56) of the lesions already known at the time of scintigraphy. It was positive in all 20 SCLC patients and negative in one lung adenocarcinoma. 111In-OCT showed high sensitivity for mediastinal metastases (94%) and good sensitivity for bone metastases (75%) and abdominal lymph node metastases (71%). 111In-OCT did not detect two liver metastases. 111In-OCT detected five unknown lesions which were confirmed by other diagnostic examinations. 111In-OCT was also effective in cancer patients with low levels of NSE. Our study shows that 111In-OCT scintigraphy is a reliable, non-invasive technique to detect primary SLCL and its locoregional or distant metastases. The clinical utility of receptor status characterisation obtained with 111In-OCT scintigraphy should be evaluated by means of an appropriate prospective study.
Aged↗
111In-DTPA-D-Phe-1-octreotide scintigraphy of small cell lung cancer.
Twenty-one patients with small cell lung cancer (SCLC) were investigated with 111in-octreotide (111-In-OCT) scintigraphs, 5 hours after the i.v. injection of 111 MBq of the radiotracer. Whole-body and planar scintigraphy as well as SPECT of the thorax were required. The scintigraphic results were compared to those of other conventional diagnostic procedures used for the staging and follow-up of SCLC patients. 111In-OCT detected 86% (48/56) of the lesions already known at the time of scintigraphy, being positive for all 20 SCLC lesions and negative for one lung adenocarcinoma. 111In-OCT showed a high sensitivity for mediastinal metastases (94%) and good sensitivity for bone (75%) and abdominal lymph node metastases (71%). It did not detect 2 liver metastases but revealed 5 unknown lesions which were then confirmed by other diagnostic examinations. 111In-OCT was also effective in patients with low levels of NSE. Three patients received cold octreotide for seven days to investigate whether this treatment might affect SCLC imaging. Scans were performed before and after treatment. The 111In-OCT uptake increased in the cancer lesions while the fixation in normal tissues decreased, demonstrating enhancement of SCLC imaging following cold octreotide administration.
Adenocarcinoma↗
111In-octreotide uptake in granulomatous and tumor lesions in a patient with small-cell lung cancer.
A case of a patient with small cell lung cancer and right submandibular node enlargement due to granulomatous lymphadenitis is presented. Diagnostic procedures included: biopsy of the cervical node, transmission computed tomography of the chest, bronchoscopic examination and biopsy of the pulmonary lesion. The patient underwent 111In-octreotide scintigraphy (whole body and single photon emission tomography) which revealed both lesions. We conclude that granulomatous lesions are to be considered as a possible cause of false positive results, when octreotide scintigraphy is used to evaluate distant metastases in patients with known cancer.
Carcinoma, Small Cell↗
Bone scintigraphy in breast cancer: a ten-year follow-up study.
Two-hundred and sixty patients with T2-T3a, pN1, M0 (TNM classification) breast cancer underwent clinical and instrumental follow-up (mean 122 months) including periodic bone scintigraphy. A total of 1971 scintigraphic examinations were performed (range 3 to 15 scintigraphies/patient, mean 8). The results of scintigraphy were compared to standard radiographs and to the clinical history of the patients. Bone metastases occurred in 71% of 122 patients who suffered from tumor recurrence during the study. Bone lesions (alone or associated with other tumor lesions) represented the most common site (42%) of first tumor relapse and occurred as first site of distant metastases in 11% of 29 patients with locoregional relapse. Bone metastases were symptomatic in 41% of cases. The sensitivity and specificity of bone scintigraphy were 98% and 95%, respectively; the positive and negative predictive values were 73% and 100%; the accuracy was 96%. Scintigraphic false positive results occurred particularly in the skull and in the ribs and generally when the examination detected less than three focal abnormalities. This study demonstrates that the number of positive scintigraphies during follow-up increases over the years, reaching a plateau only at approximately 8-10 years. It is therefore not advisable to stop performing bone scintigraphies after the first years of follow-up as this may lead to the loss of important information.
Adult↗
Radioimmunoscintigraphy of ovarian cancer with the MOv18 monoclonal antibody.
The monoclonal antibody (Mab) 131I-MOv18 was administered to 30 patients with ovarian carcinoma intravenously (n = 20) and intraperitoneally (n = 10). After intraperitoneal administration, higher tumour uptake (mean values 1.3% vs. 0.8%) and a better tumour/background ratio (mean values 2.8 vs. 1.9) than after intravenous injection were obtained. Moreover, after intraperitoneal administration the uptake in non-affected organs, such as liver and spleen, was lower. However, occasionally the favourable results of the intraperitoneal route were cancelled by persistent pelvic non-specific accumulations of 131I-MOv18. The possibility to change the biodistribution pattern in the latter cases with peritoneal washing was evaluated. 3 patients were submitted to this procedure and an improvement in the radiotracer biodistribution was obtained in 1 case. With regard to tumour detection, the average sensitivity (73%) showed a significant difference from the sensitivities for abdominal (61%) and pelvic lesions (90%). No false positive results were noted.
Adult↗
[Angiocardioscintigraphy in the cardiological surveillance of chemotherapy with anthracyclines].
Equilibrium angiocardioscintigraphy is a noninvasive nuclear medical method which allows cardiac function to be assessed. It is widely used in oncology since some clinically important drugs used in antitumor chemotherapy have a marked cardiotoxic effect. Angiocardioscintigraphy enables several parameters characteristic of cardiac function to be assessed, namely the left ventricular ejection fraction whose alterations during chemotherapy allow possible cardiotoxic side effects to be revealed before the development of irreversible heart failure.
Antibiotics, Antineoplastic↗
Mitoxantrone as first-salvage chemotherapy in relapsed breast cancer.
Mitoxantrone was administered at the dose of 14 mg/m2 i.v. every 3 weeks to 25 consecutive women with measurable progressive disease who relapsed after adjuvant CMF and endocrine therapy. The treatment plan consisted in the delivery of 6 cycles, unless disease progression or severe toxicity occurred. All patients were evaluable for drug response and toxicity. One patient achieved complete remission and 6 partial remission, for a total response rate of 28%. Objective tumor response was observed in all major sites of disease. The median time to achieve remission was 3 months. The median duration of response was 7 months (range, 5-39+), and the median survival for the entire group was 10 months (range, 3-39+). Results were influenced only by the duration of disease-free status from the end of adjuvant CMF chemotherapy. In fact, all tumor responses were documented in woman with free intervals exceeding 1 year (7 of 17 or 41%). Treatment was generally well tolerated, with 10 patients developing leukopenia at some time during treatment. Only 2 patients received less than 75% of the projected dose because of granulocytopenia. Complete alopecia occurred in only 2 cases. Three patients developed a fall greater than 15% in left ventricular ejection fraction, but no episode of congestive heart failure was observed. We conclude that mitoxantrone is an effective and safe drug which can be utilized in women relapsing after adjuvant CMF.
Adult↗
Evaluation of cardiac toxicity of idarubicin (4-demethoxydaunorubicin).
Cardiac toxicity of idarubicin (4-demethoxydaunorubicin), a new daunorubicin derivative, was tested in 49 phase II patients with advanced malignancies. In 26 patients the drug was given intravenously at a dose of 13 mg/m2 and in 23 orally at a dose of 45 mg/m2. Cardiac toxicity was evaluated by means of electrocardiography, left ventricular systolic time intervals, echocardiography and radionuclide cineangiography. The type and incidence of ECG abnormalities were comparable to those observed with other anthracycline analogs. Other functional parameters, serially measured to evaluate delayed cardiotoxicity in patients who received more than 65 mg/m2 intravenously or 225 mg/m2 orally, were not significantly different from pretreatment values. No patient developed clinical congestive heart failure. Only one patient exhibited a drop in the left ventricular ejection fraction of more than 15% from pretreatment values. These data indicate that idarubicin given orally or intravenously at the tested doses has no significant cardiotoxic activity in the range of the cumulative doses attained.
Administration, Oral↗
Evaluation of ventricular function by echocardiography and radionuclide angiography in patients treated with mitoxantrone.
Mitoxantrone, an anthracenedione derivative structurally similar to anthracycline, was tested in 25 Phase II patients with advanced breast cancer, previously treated with different cycles of 5-fluorouracil. Cardiac toxicity was evaluated by means of electrocardiography, echocardiography and radionuclide left-ventricular ejection fraction. Ten patients received a cumulative dose less than 70 mg/m2 (median 33.6, range 28-63) and 15 a dose equal to or more than 70 mg/m2 (median 81, range 70-84). ECG abnormalities in the form of dysrhythmias and ST-T changes were observed in 41% of the patients. Echocardiographic myocardial function parameters recorded in 10 of the 15 patients who received more than 70 mg/m2 demonstrated a trend to deterioration, whereas the nuclear angiographic ejection fraction recorded in all 15 patients who had more than 70 mg/m2 had significantly decreased. No patients developed congestive heart failure but almost one-quarter of them had a fall in myocardial function parameters of more than 15% compared to pretreatment values. These data indicate that mitoxantrone has a significant toxic effect on myocardial cells also at cumulative doses of less than 85 mg/m2 which is generally considered beyond the limit of safety for patients without risk factors.
Adult↗
[Usefulness of gallium 67 in research into the need for radical cervical lymph node dissection in patients with head and neck carcinomas].
Fifty-nine patients with head and neck carcinoma were examined with 67Ga scintigraphy. All patients had undergone lymph node dissection of the neck. They were followed for a minimum of 2 years after the examination. The primary tumor, treated prior/contemporaneously to the lymph node dissection, did not evolve in this interval. Metastatic involvement of the lymph node capsule was observed in all 44 cases with metastatic lymph nodes; macroscopic radicality was surgically obtained since involvement of the capsule was only microscopic. Nevertheless, complementary radiotherapy was given. The whole of 17 recurrences in the soft tissues of the neck were found, within 2 years, in the group of 26 patients who had undergone dissection of lymph nodes with metastatic capsular involvement and whose postoperative 67Ga scintigraphy was positive. On the contrary, no recurrences in the soft tissues of the neck were observed in the group of 18 patients who had undergone dissection of lymph nodes with metastatic capsular involvement and whose scintigraphy was negative. This result proves (P less than 0.001) 67Ga capable of evidencing eventual microscopic diffusion. Such a possibility has not yet been realized in vivo with any other investigation technique. Scintigraphy was negative in a control group of 15 patients who had undergone lymph node dissection, and with nonmetastatic lymph nodes. This finding leads us to exclude that the use of 67Ga might result in misinterpreted findings in the exploration of relatively superficial tissues. In fact, the eventual accumulation of radioisotope in nonneoplastic pathologies is quite easily recognizable in the neck. We can therefore conclude that in those 9 cases with positive scintigraphy and in whom no recurrence was found, microscopic diffusion was probably present, but local recurrence of the disease was prevented by complementary radiotherapy.
Carcinoma↗
Clinical evaluation of the cardiac toxicity of 4'-deoxy-doxorubicin.
4'-deoxy-doxorubicin, a new doxorubicin analog, was tested in 65 phase II patients with advanced malignancies. Cardiac toxicity evaluation was performed by means of electrocardiography (ECG), left ventricular systolic time intervals, echocardiography and radionuclide left ventricular ejection fraction. ECG abnormalities were observed in a lower percentage of patients (23%) compared to that described for doxorubicin and other anthracycline analogs such as 4'-epi-doxorubicin and 4-demethoxy-daunorubicin. Other functional parameters serially measured to evaluate chronic cardiotoxicity in 23 patients, who received more than 200 mg/m2 were not significantly different from mean pretreatment values. No patient developed congestive heart failure but some of them exhibited a fall of left ventricular function parameters more than 15% from pretreatment values. These data suggest that this new analogue is probably less cardiotoxic than the parent compound doxorubicin but not completely devoid of cardiotoxicity.
Adolescent↗
Long-term results of combined chemotherapy-radiotherapy approach in Hodgkin's disease: superiority of ABVD plus radiotherapy versus MOPP plus radiotherapy.
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.
Adult↗
New anthracycline analogs in advanced breast cancer.
To test the activity and toxicity of new anthracycline analogs, a series of Phase II disease-oriented studies were performed in women with advanced breast cancer previously untreated with doxorubicin. All drugs were administered every 3 weeks, and the doses in mg/m2 were as follows: doxorubicin and epirubicin 75 i.v., esorubicin 35 i.v., idarubicin 13 i.v. and 45 p.o. When epirubicin was tested vs doxorubicin, both response rate (13 of 21 or 62% vs 11 of 21 or 52%) and median response duration (11 months vs 13 months) were comparable. In 24 patients, esorubicin yielded complete plus partial response in 21% with a median duration of 15 months. In 27 patients given idarubicin intravenously the response rate was 11% for 4 months and the corresponding findings when the drug was administered orally to 25 women were 24% for 8 months. Acute toxic manifestations were lower following treatment with all three analogs compared to doxorubicin. Cardiac toxicity, as documented by echocardiography, systolic time interval and left ventricular ejection fraction was virtually absent following therapy with epirubicin and idarubicin. After a median cumulative dose of 600 mg/m2 for doxorubicin-treated women there was a significant fall in LVEF compared to basal values. Similar findings were observed after a median cumulative dose of 210 mg/m2 for esorubicin. We conclude that epirubicin is as effective as doxorubicin but comparatively less toxic when administered at the same dose schedule. At the doses and schedules utilized in this study, esorubicin and idarubicin resulted less active in breast cancer.
Adult↗
Phase II study of doxorubicin versus epirubicin in advanced breast cancer.
Doxorubicin and its epimerized analog epirubicin were tested at a dose of 75 mg/m2 given iv every 3 weeks to 42 patients with advanced breast cancer, 23 of whom were in relapse from prior cyclophosphamide, methotrexate, and 5-FU (CMF) chemotherapy. The median cumulative dose was 540 mg/m2 (range, 225-650) for doxorubicin and 565 mg/m2 (range, 150-600) for epirubicin. Complete plus partial response was documented in 11 of 21 patients (52%) following doxorubicin and in 13 of 21 patients (62%) following epirubicin. The median observation period was 22 months (range, 14-30); the median duration of response and the median survival were superimposable. Doxorubicin and epirubicin exhibited a superior response rate in previously untreated patients [six of eight (75%) vs eight of 11 (73%)] compared to those previously given CMF with or without endocrine therapy [five of 13 (38%) vs five of ten (50%)]. Vomiting, mucositis, and leukopenia were documented less frequently following administration of epirubicin as compared to doxorubicin. Regarding cardiac evaluation, no significant differences were evident between the two drugs. However, a significant fall in the left ventricular ejection fraction was documented in women who received doxorubicin following a cumulative dose greater than 550 mg/m2. Following completion of doxorubicin therapy at cumulative doses of 580 and 562 mg/m2, two women developed left ventricular failure at 6 and 14 months, respectively. Epirubicin appears to be an effective drug for the treatment of breast cancer and, given at equal doses, is less toxic than doxorubicin.
Adult↗
Adriamycin and epirubicin treatment monitored by radionuclide ejection fraction during therapy and follow-up.
Twenty-four patients with advanced breast cancer were studied with serial determinations of the radionuclide ejection fraction at rest (RST-LVEF) during anthracycline chemotherapy (CT) and with a mean follow-up (FU) of 8 months. We had 2 cases of anthracycline congestive heart failure (CHF) during FU, 3 and 12 months respectively after the end of CT. The RST-LVEF changes observed during CT were not able to predict which patients were to develop a symptomatic cardiomyopathy. The type of RST-LVEF change that is generally considered a worsening of cardiac performance is a decline greater than or equal to 15%. We had this type of RST-LVEF change, in addition to the 2 CHF, in 5 other patients without symptomatic cardiomyopathy. Nevertheless none of these 5 patients attained pathological values of RST-LVEF, while the 2 CHF showed symptomatic cardiomyopathy only when RST-LVEF became clearly pathologic (less than or equal to 46%). Therefore, although in our study the RST-LVEF changes during CT did not have predictive value for CHF, the method may give a notable clinical contribution all the same. In fact, by submitting the patients with a RST-LVEF fall greater than or equal to 15% to frequent sequential RST-LVEF determinations and stopping the CT if the RST-LVEF becomes pathologic it is possible to avoid severe and irreversible CHF.
Adult↗
Preliminary evaluation of myocardial toxicity of 4'-deoxydoxorubicin: experimental and clinical results.
4'-deoxydoxorubicin (4'-deoxy-DXR), a new doxorubicin (DXR) analogue with interesting antineoplastic activity, was tested for its cardiotoxicity in guinea pigs and humans. In experiments on isolated guinea pig heart, which is considered a highly predictive model of acute anthracycline cardiotoxicity in humans, 4'-deoxy-DXR was found to be significantly less cardiotoxic than DXR. This effect was correlated with a lower degree of inhibition of the fast-exchanging calcium compartment and of the low affinity sarcolemmal calcium-binding sites. The preliminary study on 4'-deoxy-DXR in humans was conducted on 117 patients affected by advanced malignancies resistant to conventional chemotherapy. The drug was administered by bolus i.v. injection in doses ranging from 10 to 40 mg/m2 in the phase I study and in doses of 35 mg/m2 in the phase II study, which is still ongoing. Cardiologic evaluation consisted of recording of EKG, left ventricular systolic time intervals (STI), echocardiography and radionuclide ejection fraction. Preliminary data indicated a lower percentage of EKG abnormalities in comparison not only with DXR but also with other anthracycline analogues. Analysis of STI recorded 1 h after different doses of 4'-deoxy-DXR failed to show the dose-dependent effect on left ventricular function which has been described for DXR, thus confirming the lower acute cardiotoxic effect. Functional parameters serially measured to evaluate chronic cardiotoxicity in 15 patients who received more than 200 mg/m2 were not significantly different from basal values.
Adult↗