Background: Knowledge of factors able to predict the clinical outcome of homogenous series of entero-pancreatic endocrine tumours treated with somatostatin analogues is poor. This study was aimed at ...identifying predictors for efficacy of somatostatin analogues at inhibiting tumour growth and modifying patients' survival during long-term follow-up. Patients and methods: 31 patients with entero-pancreatic well-differentiated endocrine carcinoma received long-acting somatostatin analogues. All had progressive, metastatic disease (87% liver metastases, 38.7% distant extra-hepatic metastases). Results: Response rate after 6 months of treatment was 45.2% (all disease stabilisation: 27.8% of pancreatic vs. 81.8% of intestinal tumours, P = 0.007). The predictors for non-response were: pancreatic tumour (OR 5.8), no previous surgery (OR 6.7), and the presence of distant extra-hepatic metastases, the latter being also confirmed by multivariate analysis (OR 10.0). Responders maintained stabilisation for 26.5 months, and none died during follow-up. Different survival curves were observed for patients, responding at 6 months compared to non-responders (P = 0.004), 3-year survival rate being 100% and 52.3%, respectively. Conclusions: Distant extra-hepatic metastases are the major predictor of poor efficacy of somatostatin analogues in progressive, metastatic, well-differentiated entero-pancreatic endocrine carcinomas. Patients achieving response after 6 months of treatment, maintain it throughout a long-term follow-up. Non-responders after 6 months of treatment, have a worse survival, and should be considered for alternative treatments.
Absence seizures represent a complex group of epilepsy, characterized by lapse of consciousness with staring. Bilateral, synchronous, and symmetric bursts of 3-Hz spike-and-wave discharges are ...observed on the electroencephalogram, whereas interictal background activity is normal. This kind of epilepsy has to be differentiated from other generalized epilepsies such as juvenile absence epilepsy and juvenile myoclonic epilepsy. Moreover, absence seizures, together with generalized spike-and-wave discharges, may coexist with other types of epilepsy such as frontal lobe epilepsy, temporal lobe epilepsy, benign epilepsy with centrotemporal spikes, and childhood epilepsy with occipital paroxysms. We have carried out ictal single photon emission computed tomography (SPECT) in 10 patients with clinical evidence of absence seizures with the aim to better understand and to distinguish this kind of seizure as primarily or secondarily generalized to a specific area and to obtain more information on the neuronal mechanisms involved in the different types of seizures, usually not identifiable at the first appearance. During the long follow-up period (9 months to 14 years), 7 of the 10 examined patients underwent interictal SPECT when they became seizure free. Our data permitted, in two patients, the diagnosis of childhood absence seizures; in three patients, they suggested the possibility of later appearance of other seizure types, on the basis of focal hyperperfusion indicating a possible focal firing. In three of the examined patients, the diagnosis of idiopathic localization-related epilepsies mimicking childhood absence seizures could be performed. In the last two patients, the hypothesis of a coexistence of absences with partial and generalized seizures was considered. From our results, it can be presumed that ictal SPECT findings may contribute to the physiopathologic classification of the different types of epilepsies. Moreover, anticonvulsant treatment more appropriate to the different forms of seizures can be used. (J Child Neurol 2001;16:339-344).
Strontium-89 (89Sr) is currently used for the treatment of painful bone metastases. This study reports the use of low-dose carboplatin as a radiosensitizer in 89Sr radioisotope therapy. The study ...design comprised two groups: 15 patients treated with 89Sr (148 MBq) followed by carboplatin (100 mg m-2 at 7 and 21 days) and 15 patients treated with 89Sr alone. Their pain response was assessed 8 weeks post-injection. Follow-up was continued for up to 1 year in the survivors. Twenty-seven patients were evaluable. A pain response was observed in 20 of 27 (74%) patients. The pain response in the patients treated with 89Sr and carboplatin was clearly superior to that seen in the patients treated with 89Sr alone (P = 0.025), whereas survival was only marginally better in the combined treatment group (8.1 vs 5.7 months, P = 0.19). No clinically significant adverse effects or myelosuppression by carboplatin were observed. Low-dose carboplatin enhances the effects of 89Sr radioisotope therapy on pain from bone metastases.
The study evaluates the therapeutic efficacy of Strontium-89-chloride (89Sr) and 186Re-1,1-hydroxyethylidene diphosphonate (186Re-HEDP) in the palliation of painful bone metastases from breast ...cancer.
Fifty patients with painful multifocal bone metastases from breast cancer entered the study and were randomized into two groups according to the radiopharmaceutical used: 148 MBq 89Sr i.v. (Group A: 25 patients) and 1406 MBq 186Re-HEDP i.v. (Group B: 25 patients). Pain palliation was evaluated on the basis of the Wisconsin pain test improvement at two months and response was graded as complete, partial, minimal or absent. Hematological toxicity and side effects were reported according to WHO guidelines.
The global response rate was 84% (21/25) for 89Sr and 92% (23/25) for 186Re-HEDP, respectively. The onset of pain palliation appeared significantly earlier in Group B (p < 0.0001). The duration of pain relief ranged from two months to 14 months (mean of 125 days with a median value of 120 days) in Group A and from one month to 12 months (mean of 107 days with a median value of 60 days) in Group B (p = 0.39). A moderate hematological toxicity was apparent in both groups. Platelet and white blood cell counts returned to baseline levels within 12 weeks after 89Sr administration and 6 weeks after 186Re-HEDP administration (p < 0.01).
Both 89Sr and 186Re-HEDP are effective and safe in bone pain palliation in breast cancer with the latter showing a significantly faster onset of pain relief.
We conducted a randomized trial to evaluate primarily the cardioprotective effect of dexrazoxane (DEX) in patients with advanced breast cancer and soft tissue sarcomas (STS) treated with high-dose ...epirubicin (EPI). We wished also to determine the value of radioimmunoscintigraphy (RIS) in the assessment of anthracycline cardiotoxicity.
Patients with breast cancer (n = 95) or STS (n = 34) received EPI 160 mg/m2 by intravenous (I.V.) bolus every 3 weeks with or without DEX 1,000 mg/m2 I.V. Cardiac monitoring included multigated radionuclide (MUGA) scans with determination of resting left ventricular ejection fraction (LVEF), and RIS with indium 111 antimyosin monoclonal antibodies.
In either disease, antitumor response rates, time to progression, and survival did not significantly differ between the two arms. There was little difference in noncardiac toxicity for the two treatment groups. All methods of cardiac evaluation clearly documented the cardioprotective effect of DEX. Four patients developed congestive heart failure (CHF), all in the EPI arm. The decrease in LVEF from baseline was significantly greater in the control group. An abnormal antimyosin uptake was observed early in both arms and progressively increased during treatment. However, this increase was significantly higher in the EPI group (P = .004).
DEX significantly protects against the development of cardiotoxicity when high single doses of EPI are used. Apparently, there was no evidence of an adverse impact of DEX on antitumor activity. Although RIS is a sensitive technique in detecting anthracycline cardiac damage, its specificity is low and it cannot be considered a primary test for guiding anthracycline treatment.
Abstract
Background: The accuracy of the OSNA assay for metastases detection in sentinel lymph nodes (SLNs) has recently been validated in our Institute and adopted as an intra-operative test for ...breast cancer (BC) patient management. The aims of this study in a series of early BC patients, were: 1) to correlate the copy numbers of cytokeratin 19 (CK19) mRNA with the size of nodal metastases and with the risk of additional disease in non-sentinel lymph nodes (NSLNs); 2) to investigate the relationship between SLN status with OSNA method, and conventional bio-pathological factors taking into account the molecular BC classification: luminal A, luminal B, HER2 subtype, and triple-negative; 3) to identify a subgroup of patients with positive SLN with higher risk of NSLNs metastatic involvement. Material and Methods: 750 SLNs from 580 patients were clinically processed using both OSNA assay and post-operative histology. The results of these two methods were then compared. The correlation between the size of metastases and the copy numbers of CK19 mRNA was calculated using the Spearman correlation coefficient. Complementary axillary lymph node dissection (ALND) was performed concurrently in case of OSNA assay positivity and the probability of having a positive lymph node axillary dissection was calculated by the unconditional logistic regression model. This series of BC patients were divided into four main subtypes taking in account the BC classification based on the immunohistochemistry phenotypic patterns.
Results: OSNA positivity was reported in 24.6% of the patients for a sensitivity of 94.2%. Considering the 145 patients with SLN positivity the size of metastatic foci was significantly correlated to the copy numbers of CK19 mRNA. The complex relationships among the bio-pathological variables analyzed by multiple correspondence analysis (MCA) showed that the metastatic involvement of NSLNs is associated with SLNs with a high copy numbers of CK19 mRNA and HER2 subtype tumors. OSNA specificity (95%) and negative predictive value (98.4%) clearly demonstrated its reliability to guide ALND decision. Conclusions: Our results showed that OSNA is an excellent method for the detection of metastases in SLN and its adoption in our clinical practice has determined a significant improvement in the diagnosis of metastatic BC.
Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P1-01-09.
Background: Intra-arterial injection of super(90)Y resin microspheres radiotherapy (SIRT) enables delivery of tumorcidal doses of radiation to malignant tumor, with minimal damage to adjacent tissue. ...This multicentre phase II study is the first prospective evaluation of SIRT as salvage therapy for patients with colorectal liver metastases who had failed prior oxaliplatin- and irinotecan-based regimens. Methods: Eligible patients had a life expectancy of >6 months, adequate hepatic and renal function and an absence of major vascular anomalies and pulmonary shunt >10%. The gastroduodenal and right gastric arteries were embolized before injection of microspheres (median dose 1.7 GBq; range 0.9-2.2) into the hepatic artery by arteriography. Results: Patients were enrolled and followed up for a median of 11 months (mos) (range 2-27). Of 50 eligible patients, 38 (76%) had received at least 4 lines of chemotherapy. Most patients had synchronous disease (72%), >4 hepatic metastases (58%) (median size 50 mm; range 8-120), involving 25-50% of the liver tissue (60%) and bilateral spread (70%). Early and late (after 48 h) WHO G1-2 toxic events (mostly fever and pain) were observed in 16% and 22% of patients, respectively. One responding patient died after 60 days due to liver failure. Of 46 patients who were evaluable for response using RECIST criteria, 1 patient (2%) had a complete response (CR), 11 (22%) a partial response (PR), 12 (24%) stable disease (SD) and 22 (44%) progressive disease (PD). In responders (CR + PR + SD), the maximum diameter of nodules diminished to 35 mm. The Kaplan-Meyer overall median survival was 13 (CI 7-18) mos, with a significant difference (p=0.0006) between responders 16 (CI 13-19) mos and PD 8 (CI 4-12) mos. At 2 years, survival was 40.3% and 0% in responders and PD, respectively. The median time to progression (mostly extrahepatic) was 4 (CI 3-5) mos. Conclusion: In heavily pretreated patients, super(90)Y resin microspheres produced an encouraging median survival, with acceptable toxicity, that compares favorably with previous phase II/III studies of chemotherapy regimens used as third- or subsequent lines of therapy.
Presurgical neoadjuvant chemotherapy (PSNC) is the treatment of choice for patients with locally advanced breast carcinoma (LABC). Accurate assessment of tumor response is important in planning ...subsequent treatments. Conventional response assessment by mammography and clinical evaluation is not fully reliable. This study evaluates the diagnostic yield of serial 99mTc-MIBI scintigraphy in the assessment of LABC response to PSNC.
Twenty-nine patients affected by LABC underwent clinical, mammographic and 99mTc-MIBI scintigraphy before and after 3 cycles of FEC (500 mg/m2 5-fluorouracil, 50 mg/m2 epirubicin and 400 mg/m2 cyclophosphamide) on Days 1 and 8. Surgery was planned for 15 days after the third cycle of chemotherapy. Pathological status was obtained after surgery in all patients.
Sensitivities (i.e., true-positive ratios) for a correct prediction of tumor presence after PSNC were 65% for scintigraphy, 35% for clinical evaluation and 69% for mammography. Specificities (i.e., true-negative ratios) for a correct prediction of tumor absence after PSNC were 100% for scintigraphy, 67% for clinical evaluation and 33% for mammography. Technetium-99m-MIBI uptake in this series did not correlate with P-170 expression, proliferating cell nuclear antigen, Her-2/neu oncogene protein, antihuman endothelial cell CD31 antigen and estrogenic and progestinic receptor status.
Technetium-99m-MIBI scintigraphy is effective in monitoring the response to PSNC in LABC patients. Its diagnostic yield is clearly superior to clinical evaluation alone. Scintigraphy performs as does mammography in patients with negative response, but it is clearly superior in patients with positive response.
Radionuclide therapy with bone seeking radiopharmaceuticals is one of the oldest interventions in nuclear medicine and has been now in use for many years as an effective method of palliating painful ...bone metastases. Clinical indications have slowly but progressively increased starting from end-stage prostate cancer with diffuse painful bone metastases to earlier stages of several cancers with only microinvolvement of the skeleton. Several newer bone seeking agents for therapeutic applications have been developed during the last 10 years. A large body of specific literature is now available, but only a few well designed clinical trials can be selected to obtain evidence-based guidelines. This study summarizes the therapeutic effects of the three commercially available radiopharmaceuticals, the current indication for their use as supported by the most rigorous literature studies and the original contributions of the "Regina Elena" ten-year experience. Innovative strategies and future research questions are also breafly addressed.
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