Clinical impact of fluorine-18 fluorodeoxyglucose positron emission tomography in cancer patients. A comparative study between dedicated camera and dual-head coincidence gamma camera.

AIM: Positron emission tomography (PET) using fluorine-18 fluorodeoxyglucose (FDG) can be performed using a dedicated PET scanner (PET-I) or a dual-head coincidence gamma camera (CGC-I). The aim of this study was to comparatively assess the impact of PET-I and CGC-I on clinical management in cancer patients. METHODS: From November 2000 to November 2002, PET-I and CGC-I were performed at an interval of 2 days in 151 patients with colorectal cancer (n=40), breast cancer (n=28), thyroid cancer (n=23), lung tumors (n=22), germ cell tumors (n=14), unknown primary cancer (n=7) and other cancers (n=17). PET-I and CGC-I were interpreted independently with knowledge of conventional imaging (CI). In June 2003, theoretical management, e.g. treatment modality/ies and treatment intent (curative or palliative), after CI, PET-I and CGC-I were stated during multidisciplinary sessions and were a posteriori considered as appropriate or inappropriate using pathological and follow-up data. RESULTS: The theoretical management proposed after PET-I and after CGC-I was similar in 112/151 (74%; 95% CI: 66-81%) patients. In 125 assessable patients, theoretical management after PET-I was appropriate in 86% (95% CI: 79-92%), significantly higher (P=0.0033) than after CGC-I (70%; 95% CI: 62-78%). Both proportions were also higher than after CI (46%; 95% CI: 37-56%), (P<0.0001). A similar trend for higher proportions of appropriate management after PET-I than after CGC-I was observed for each tumor localization. CONCLUSIONS: The clinical impact of PET-I is superior to that of CGC-I in a large series of cancer patients. Although CGC-I could be considered as an acceptable alternative, PET-I remains the standard and should preferably equip nuclear medicine departments.

[Double-blinded controlled study comparing clodronate versus placebo in patients with breast cancer bone metastases]. / Essai comparatif randomisé en double aveugle clodronate oral 1 600 mg/j versus placebo chez des patientes avec métastases osseuses de cancer du sein.

One hundred forty-four patients with breast cancer and osteolytic bone metastases were randomized to receive either oral clodronate 1,600 mg/d (73 patients) or placebo (71 patients), in addition to either chemotherapy or hormonal therapy, for up to 12 months. Patients were withdrawn from the study when the 12 months of treatment had been achieve or a new bone event occurred, which was defined as: hypercalcemia (> 3 mmol/l), increase in, or onset of new bone pain due to metastases, requirement of radiotherapy for bone pain relief, pathological fractures (including vertebral collapse, spinal cord compression) or death due to bone metastases. Patients are well balanced according to age, performance status, bone condition, except for fractures, more frequent in the clodronate group (25% vs 12%). Of the 137 evaluable patients, 69 received oral clodronate and 68 placebo. Clodronate significantly delayed the median time to onset of new bone events compared to placebo, respectively 244 days and 180 days (p = 0.05). Hypercalcemia did not occur in the clodronate group but was observed in four placebo-treated patients. Clodronate-treated patients had a significant reduction in pain intensity compared to placebo (p = 0.01; measured using a visual pain scale) and significantly fewer patients receiving clodronate required analgesics (p = 0.02). The evaluation of global efficacy by physicians and patients indicated that clodronate was more efficacious than placebo (respectively p = 0.02 and p = 0.01). No significant difference in incidence of adverse effects was observed between the two groups. Clodronate therapy significantly delayed the occurrence of new bone events in these patients with bone metastases from breast cancer and adds to treatment of malignant osteolysis.

Delayed adjuvant tamoxifen: ten-year results of a collaborative randomized controlled trial in early breast cancer (TAM-02 trial)

AIM: Immediate adjuvant tamoxifen reduces disease recurrence and improves survival in patients with early breast cancer. However, is it too late to administer tamoxifen to patients who have already undergone treatment, but were unable to benefit from this adjuvant therapy? The French National Cancer Centers (FNCLCC) have investigated the efficacy of delayed tamoxifen administration in a randomized controlled trial. PATIENTS AND METHODS: From September 1986 to October 1989, women with primary breast cancer, who had undergone surgery, radiotherapy, and/or received adjuvant chemotherapy but not hormone therapy more than two years earlier, were randomized to receive either 30 mg/day tamoxifen or no treatment. The 10-year disease-free and overall survival rates of the two groups of patients and of various subgroups were determined according to the Kaplan-Meyer method and compared by the log-rank test. RESULTS: This intention-to-treat analysis comprised 250 Introduction women in the tamoxifen group and 244 in the control group. Patient characteristics (age, T stage, number of positive nodes, receptor status, and interval since tumor treatment) were comparable in both groups. Delayed adjuvant tamoxifen significantly improved overall survival only in node-positive patients and in patients with estrogen receptor-positive (ER+) or progesterone receptor-positive (PR+) tumors. Disease-free survival, however, was significantly improved in the global population and in several patient subgroups (node-positive, ER+, PR+). Patients in whom the interval between primary treatment and delayed adjuvant tamoxifen was greater than five years also had significantly improved disease-free survival. CONCLUSIONS: Overall and disease-free survival results indicate that delayed adjuvant tamoxifen administration (30 mg/day) is justified in women with early breast cancer, even if this treatment is initiated two or more years after primary treatment.

Clinical relevance of gallium-67 scintigraphy in lymphoma before and after therapy.

The clinical impact of gallium-67 scintigraphy before and after therapy for lymphoma remains controversial. The aims of this study were: (1) to compare the staging of lymphoma by 67Ga scintigraphy only with staging by clinical examination and conventional imaging (CI), and (2) to analyse the clinical relevance of both 67Ga imaging and CI after treatment. From March 1995 to November 1998, 86 67Ga scintigraphy studies were performed in 62 patients with Hodgkin's disease (n=52) or non-Hodgkin's lymphoma (n=10). 67Ga scintigraphy was performed at diagnosis (n=44) or after therapy (n=42) using 185-220 MBq 67Ga citrate and planar and single-photon emission tomography (SPET) studies. Treatment comprised radiotherapy, chemotherapy or combined modalities. CI included plain chest radiography, computed tomography (CT) of the chest and abdomen/pelvis, ultrasound of the abdomen, lymphography, bone marrow biopsy and, when necessary, magnetic resonance imaging (MRI) and bone scintigraphy. For individual suspected sites of disease before treatment, complete agreement between clinical examination and CI on the one hand and 67Ga scintigraphy on the other hand was observed in 25/44 patients (57%; 95% confidence interval 41%-72%). Clinical examination and CI showed more sites than did 67Ga scintigraphy in 12/44 patients (27%) and 67Ga imaging demonstrated more sites than CI in 6/44 patients (11%). The clinical stage of the disease as assessed using 67Ga scintigraphy only was in agreement with that using all diagnostic procedures in 34/44 patients (77%; 95% confidence interval 62%-89%). Compared with CI staging, 67Ga scintigraphy downstaged seven patients (16%) and upstaged three (7%). 67Ga scintigraphy downstaged mainly because of the limited value of the technique below the diaphragm and upstaged owing to the good sensitivity in the lung. After therapy, both CI and 67Ga scintigraphy were normal in 11 patients. All but one of these patients were in complete remission after a median follow-up of 31 months. In contrast, radiological residual mass was observed in 31/42 patients. 67Ga imaging was normal in 22/31 (71%); 17 of these 22 patients, including nine with a large residual mass (> or =2 cm), were in complete remission after a median follow-up of 32 months, while four suffered relapses 8-45 months later. The cause of death remained unknown in one patient. 67Ga scintigraphy showed abnormal uptake in 9 of the 31 patients with a large residual mass. Active disease was demonstrated in eight patients and one patient was in complete remission 30 months thereafter. Our data show that 67Ga imaging cannot replace CI in initial staging but can demonstrate additional individual sites of disease in more than 10% of patients and can lead to clinical upstaging with potential prognostic and therapeutic consequences. After therapy, 67Ga scintigraphy has a clinical impact when radiological abnormalities persist because it can either avoid unnecessary complementary treatment or confirm the need to change treatment modalities.

[Tamoxifen adjuvant delays early breast cancer. Results of a cooperative randomized trial]. / Tamoxifène adjuvant retardé dans le cancer du sein curable. Résultats d'un essai coopératif randomisé.

Adjuvant tamoxifen (TAM) has been proved to reduce recurrence and mortality in early breast cancer, nevertheless many patients did not receive TAM as adjuvant therapy after local treatment. In order to study the efficacy of delayed TAM therapy in patients who were not given immediate adjuvant hormonal treatment, a multicenter randomized trial has been conducted by the French National Cancer Centers (FNCLCC). According to eligibility criterias all women with breast cancer who received curative local treatment at least 2 years before (surgery +/- radiotherapy) with or without adjuvant chemotherapy but no hormonal treatment could have been included. Between September 1986 and October 1989, 494 women were randomized to receive either TAM 30 mg/day for 5 years or no treatment. Patients' characteristics such as age, tumoral stage, number of positive nodes, receptors status and time from local treatment were equally distributed in the 2 groups. An improvement in the disease free survival in the TAM treated patients can be observed with a significative difference (p = 0.05), nevertheless the overall survival is not improved in the TAM group. In the same way, in nodes positive patients although no significative improvement in the overall survival can be observed, a significative improvement in the disease free survival (p = 0.05) can be noted. In estradiol receptors positive patients tamoxifen gives a significative reduction in the odds of death (p = 0.04) and recurrence (p = 0.03). The disease free improvement seems to be limited to 50 and more years old patients. The first results of this trial lead to prescribe tamoxifen to all postmenopausal women previously treated for an early breast cancer without adjuvant tamoxifen treatment.