The value of positron emission tomography (PET) imaging in disease staging and therapy assessment.
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Female↗
Biomedical subjects
G Fillet
Publications and source records attributed to G Fillet.
[Clinical study of the month. Adjuvant radio-chemotherapy and chemotherapy following curative resection of pancreatic cancer: results of the randomized trial ESPAC-1].
The prognosis of pancreatic adenocarcinoma remains poor, with a 5-year survival rate lower than 5%. Resection, the gold standard treatment, can be performed in less than 15% of patients. Following surgery, the median survival is 12 months for the most favourable cancer patients. Adjuvant treatment have attempted to improve results. However, chemotherapy, radiotherapy and multimodal treatments don't have demonstrated a clear advantage in controlled trials. We will discuss results of the current trials in this topic. The randomised trial of the European Study Group for Pancreatic Cancer (ESPAC) recently published in the Lancet revealed a potential benefit of adjuvant chemotherapy. A critical analysis of the publication showed, however, that definitive conclusions of this trial must be interpreted with caution.
Adenocarcinoma↗
[How I treat ... An advanced pancreatic cancer].
Median survival of advanced pancreatic cancer is about three months. Unfortunately, chemotherapy is not a curative approach. Chemotherapy improves the quality of life and overall survival compared to best supportive care. Nevertheless, as the overall survival remains disappointing, clinical research must ongoing to define better treatment regimen.
Antimetabolites, Antineoplastic↗
[How I treat...advanced cancer of the pancreas with a novel approach directed against new targets].
A better knowledge of fundamental mechanisms of carcinogenesis allows the development of novel therapeutic tools specifically targeting the cancer cell. Our understanding of cellular and molecular mechanisms controlling cellular cycle and cell survival is an important step for new anti-cancer treatments. This review will focus on new therapeutic's strategies in advanced pancreatic cancer.
Alkyl and Aryl Transferases↗
[How I manage patients developing thromboembolic complications as a result of breast cancer treatment with tamoxifen ].
Thromboembolic complications are well known side effects of treatment with tamoxifen in patients with breast cancer. The authors review the pathophysiology and the risk factors that increase the probability to develop these complications. The most appropriate treatment is discussed.
Aged↗
[Hepatic metastases of colorectal cancer: current therapies].
Important progress has been made in the treatment of liver metastases of advanced colorectal cancer. Surgery with curative intent, when possible, shows evidence of prolonged survival. Response rate and overall survival can be improved with modern polychemotherapy. Cytotoxic drug combinations and sequential treatments sometimes make surgery possible for initially non resectable lesions. Impact of loco-regional treatment such as hepatic arterial infusion chemotherapy must be defined in randomised trials. Radiofrequency ablation is also currently evaluated in clinical trials. In this review the benefit of each treatment is discussed.
Antineoplastic Combined Chemotherapy Protocols↗
[End of treatment evaluation in patients with aggressive non-Hodgkin's lymphoma].
Incomplete regression of a lymphomatous mass after chemotherapy and/or radiotherapy constitutes a major problem in the treatment of lymphoma. In patients with persisting tumor, it could be reasonable to use salvage therapy and possibly hematopoietic stem cell transplantation at the time of minimal disease rather than at the time of clinically overt relapse. The authors reviewed the most appropriate imaging techniques for the assessment of response to treatment. The limitations of CT and MRI for predicting the nature of residual masses are well known. 67Ga scintigraphy has become a standard procedure for the posttreatment evaluation of patients with lymphoma, but it appears that 18F-FDG PET may be a more effective method. Personal experience in the field of PET scan is reported. Although PET should be considered the noninvasive imaging modality of choice, a histological confirmation of residual disease is always necessary before starting salvage therapy. 18F-fluorodeoxyglucose is not a tumor specific radiotracer.
Fluorodeoxyglucose F18↗
Cessation of intensive treatment with recombinant human erythropoietin is followed by secondary anemia.
Little information is available on the evolution of erythropoiesis after interruption of recombinant human erythropoietin (rHuEpo) therapy. Iron-overloaded rats received 20 daily injections of rHuEpo. During treatment, reticulocytes, soluble transferrin receptor (sTfR), and hematocrit increased progressively. This was accompanied by a substantial expansion of spleen erythropoiesis but a decrease in the bone marrow. Five weeks after treatment, rats developed a significant degree of a regenerative anemia. Erythropoietic activity, as assessed by reticulocytes, sTfR, erythroid cellularity, iron incorporation into heme, and the number of erythroid colonies, was severely depressed 3 weeks after cessation of rHuEpo. This was followed by regeneration of erythroblasts and reticulocytes at weeks 6 to 7 post-Epo, but erythroid progenitors recovered only partially by that time. The anemia was definitely corrected 2 months after cessation of rHuEpo treatment. Serum Epo levels remained elevated for several weeks, but the sensitivity of marrow erythroid precursors to Epo was preserved. No rat antibodies to rHuEpo were detected, and serum from post-Epo animals did not exert any inhibitory activity on erythropoiesis. In conclusion, after cessation of intensive rHuEpo therapy, there was a strong inhibition of erythropoietic activity with secondary anemia followed by late recovery. This was not due to antibodies or other soluble inhibitory factors, a defect in endogenous Epo production, or a loss of sensitivity to Epo. This may rather represent intrinsic erythroid marrow exhaustion, mostly at the level of erythroid progenitors but also at later stages of erythropoiesis.
Anemia↗
Positron emission tomography (PET) with 18F-fluorodeoxyglucose (18F-FDG) for the staging of low-grade non-Hodgkin's lymphoma (NHL).
BACKGROUND: Although PET has been shown to be highly sensitive in the primary staging of lymphoma, previous studies with small numbers of patients indicated that low-grade NHL may not always be adequately detected by PET. We undertook this study to determine factors influencing the detection of lesions by PET in low-grade NHL and to evaluate the utility of PET in this indication. PATIENTS AND METHODS: Forty-two patients underwent conventional staging procedures (clinical examination, oto-rhino-laryngologic examination, computed tomography of the chest, abdomen and pelvis, gastroscopy and bone marrow biopsy as well as whole-body non-attenuation corrected 18F-FDG-PET RESULTS: PET detected 40% more abnormal lymph node areas than conventional staging in follicular lymphoma but was inappropriate for the staging of small lymphocytic lymphoma where it detected less than 58% of abnormal lymph node areas. PET showed more lesions than conventional staging for peripheral (34% more lymph node areas detected) and thoracic lymph node (39% more) areas but not for abdominal or pelvic lymph nodes (26% fewer areas detected). The sensitivity to detect bone marrow infiltration was unacceptably low for PET. In contrast, PET was as effective as standard procedures for the detection of other extranodal localizations, although a few localizations were detected only by PET and a few others only by conventional procedures. CONCLUSIONS: PET may contribute to the management of patients with low-grade follicular NHL. For the other low-grade lymphoma subtypes, the role of PET is less evident. Further studies using PET to evaluate the results of treatment or to diagnose disease recurrence are warranted in low-grade follicular NHL.
Adult↗
Outcome is not improved by the use of alternating chemotherapy in elderly patients with aggressive lymphoma.
INTRODUCTION: A prospective randomised study involving 810 elderly patients was conducted in an attempt to compare alternating chemotherapy with conventional first-line chemotherapy in aggressive non-Hodgkin's lymphoma in order to improve prognosis with an acceptable toxicity for elderly patients. PATIENTS AND METHODS: Patients included were 55-69 years old and had at least one adverse prognostic factor. Patients were treated either with ACVBP followed by consolidation (n = 396) or with an alternating regimen (n = 414). This regimen was an association of active drugs in NHL relapsing patients, alternating VIMMM with ACVBP for induction and alternation of VIM and ACVM in consolidation. Eight hundred and sixty-six patients were randomised. After histological review, 810 patients met the inclusion criteria: 396 in arm A, 414 in arm B. RESULTS: The complete response rate after induction was superior for conventional first-line therapy (58.5% vs 48%, P = 0.003) but at the end of treatment, the CR rate was not statistically different (52% vs 48%, P = 0.19). Conventional chemotherapy had a better five-year event-free survival than alternating regimen (33% (95% CI: 30-36%) vs 28% (95% CI: 26-30%), P = 0.0289) but overall survival was not statistically different (40% (CI 95% 38-42%) vs 36% (CI 95% 34-38%), P = 0.068). In this elderly high risk population, the toxicity was very high: 19% in arm A and 26% in arm B died during treatment. CONCLUSION: Alternating regimen did not improve outcome, was less efficient and more toxic.
Aged↗
Factors affecting hematopoietic recovery after autologous peripheral blood progenitor-cell transplantation in aggressive non-Hodgkin's lymphoma: a prospective study of 123 patients.
PURPOSE: To analyse prognostic factors influencing hematopoietic recovery in patients with aggressive non-Hodgkin's lymphomas prospectively treated with intensive chemotherapy followed by peripheral blood progenitor-cells transplantation. PATIENTS AND METHODS: Untreated patients with at least two unfavorable factors according to the age-adjusted international prognostic index were included in the LNH 93-3 trial. Patients received three cycles of chemotherapy and PBPC were mobilized using filgrastim. On day 60, a BEAM regimen was initiated followed by PBPC rescue. Among the 123 patients analysed, 60 received G-CSF (5 microg/kg/d) after PBPC transplantation at day 1 and 63 did not. RESULTS: Patients received a mean number of 12.4 x 10(6)/kg (1.86-111.5) CD34+ cells. After transplantation, neutrophil counts exceeded 0.5 x 10(9)/l at a median of 12.4 days (7-41 days) and platelet counts exceeded 50 x 10(9)/l at a median of 15.6 days (9-141 days). Platelets recovery > 50 x 10(9)/l was negatively influenced by BM involvement (20 s 14 days; P = 0.04). The number of CD34+ cells infused (> vs < or = 5 x 10(6)/kg) was correlated with faster platelet recovery (18.7 days vs 13.7 days) (P = 0.007). In 26 patients for whom administration of G-CSF was randomized, time to neutrophil recovery was significantly shorter for patients treated with G-CSF: 10 vs 13 days (P = 0.0005). The incidence of grade 3/4 infection, was similar in both groups. CONCLUSION: In the patient population treated with the same first-line regimen, BM involvement and infusion of fewer CD34+ cells delayed platelet recovery. Administration of G-CSF after PBPC significantly reduced neutropenia.
Adolescent↗
Positron emission tomography (PET) for staging low-grade non-Hodgkin's lymphomas (NHL).
Although positron emission tomography (PET) imaging is now recognized as a useful tool for staging intermediate and high-grade non-Hodgkin's lymphoma (NHL), few data are available regarding its accuracy in low grade NHL. We therefore studied 36 patients with histologically proven low-grade NHL. Whole-body 2-(fluorine-18) fluoro-2-deoxy-D-glucose (FDG) PET was performed at the time of initial diagnosis (n = 21) or for disease recurrence (n = 15) prior to any treatment. PET results were compared to those of physical examination and computed tomography (CT). PET studies were read without knowledge of any clinical data. Any focus of increased activity was described and given a probability of malignancy using a 5 point-scale (0: normal to 4: definitively malignant). An individual biopsy was available for a total of 31 lesions. The sensitivity and specificity were 87% and 100% for FDG-PET, 100% and 100% for physical examination and 90% and 100% for CT respectively. In addition, 42 of 97 peripheral lymph node lesions observed by FDG-PET were clinically undetected, whereas the physical examination detected 23 additional nodal lesions. PET and CT both indicated 12 extranodal lymphomatous localizations. FDG-PET showed 7 additional extranodal lesions while 5 additional unconfirmed lesions were observed on CT. Regarding bone marrow infiltration, PET and biopsy were concordant in 24 patients with 11 true positive (TP) and 13 true negative (TN). However PET was FN in 11 patients and no biopsy was performed in one patient. The combination PET/CT/physical examination seems to be more sensitive than the conventional approach for staging low grade NHL. Its sensitivity however is unacceptably low for diagnosing bone marrow infiltration.
Adult↗
Itraconazole versus amphotericin B plus nystatin in the prophylaxis of fungal infections in neutropenic cancer patients.
The efficacy and safety of itraconazole oral solution and a combination of amphotericin B capsules plus nystatin oral suspension were compared in the prophylaxis of fungal infections in neutropenic patients. In an open, randomized, multicentre trial, 144 patients received itraconazole oral solution 100 mg bd, and 133 patients received amphotericin B 500 mg tds plus nystatin 2 MU qds. Overall, 65% of itraconazole-treated patients were considered to have had successful prophylaxis, compared with 53% in the polyene group. Proven deep fungal infections occurred in 5% of patients in each group. Fewer patients receiving itraconazole than amphotericin plus nystatin had superficial infections (3 versus 8%; P = 0.066). This trend in favour of itraconazole was seen in patients with profound neutropenia (neutrophil count <0.1 x 10(9) cells/L at least once) or prolonged neutropenia (neutrophil count <1.0 x 10(9) cells/L for >14 days). The median time to prophylactic failure was longer in the itraconazole group (37 days) than in the polyene group (34 days). The number of patients with fungal colonization (nose, sputum, stool) changed more favourably from baseline to endpoint in the itraconazole group than in the polyene group. Both treatments were safe and well tolerated; however, patients receiving amphotericin plus nystatin had a higher incidence of nausea and rash. In conclusion, itraconazole oral solution at doses of 100 mg bd and oral amphotericin B plus nystatin have similar prophylactic efficacy against fungal infections in neutropenic patients. On the basis of reduced incidence of superficial fungal infections, fungal colonization and specific adverse events, itraconazole may be the preferred treatment.
Adult↗
Whole-body positron emission tomography using 18F-fluorodeoxyglucose compared to standard procedures for staging patients with Hodgkin's disease.
BACKGROUND AND OBJECTIVES: Accurate staging is essential in order to determine appropriate treatment in Hodgkin's disease (HD). (18)F-fluorodeoxyglucose positron emission tomography ((18)F-FDG PET) offers the advantage of metabolic imaging that is largely independent of morphologic criteria. In the present study we evaluated the role of (18)F-FDG PET compared to routine procedures for the staging of patients with HD. DESIGN AND METHODS: Thirty-three patients with HD underwent standard staging procedures (clinical examination, laboratory screening, chest X-ray, computed tomography (CT) of the chest and abdomen and bilateral bone marrow biopsies) and a whole-body (18)F-FDG PET study. In clinical examination, an isolated lymph node > 1 cm or multiple lymph nodes > or = 1 cm in size were considered abnormal. Positive findings at both clinical examination or CT and (18)F-FDG PET were regarded as actual locations of disease. Negative findings with both methods were regarded as true negative (no involvement by HD). In cases of discrepancy, response to treatment and follow-up data were used to assess the overall accuracy of the patient's original evaluation. RESULTS: Completely concordant results in lymph node staging were observed in 20 patients. The two staging procedures indicated complementary information in 1 patient. Conventional staging indicated more pathologic lymph node areas in 6 patients (at least 1 false positive). (18)F-FDG PET showed more sites in 6 patients. The sensitivity of (18)F-FDG PET in detecting all known pathologic lymph nodes was 83% for peripheral lymph nodes, 91% for thoracic lymph nodes and 75% for abdominal and pelvic lymph nodes. Conventional staging procedures and (18)F-FDG PET indicated the same tumor stage in 26 patients. Based on (18)F-FDG PET, downstaging was suggested in 4 patients, including a biopsy-proven case. However in 1 of these cases this was incorrect. (18)F-FDG PET suggested upstaging in 3 patients. Based on conventional staging or (18)F-FDG PET the same treatment strategy was defined in 32 patients. In one patient (18)F-FDG PET downstaged disease extension (stage IIIA-->IIA) that would have suggested radiotherapy as a possible treatment option. INTERPRETATION AND CONCLUSIONS: (18)F-FDG PET provides an easy and efficient whole-body method for the evaluation of patients with HD. (18)F-FDG PET never missed tumor masses >1 cm. (18)F-FDG PET detected additional sites of disease not seen by conventional procedures and identified absence of disease in some sites suspected to be involved. However, in our patients this did not translate into changes in treatment strategy.
Adolescent↗
Treatment of leukemia relapse after allogeneic hematopoietic stem cell transplantation by donor lymphocyte infusion and STI-571.
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Adult↗
Administration of erythopoietin and granulocyte colony-stimulating factor in donor/recipient pairs to collect peripheral blood progenitor cells (PBPC) and red blood cell units for use in the recipient after allogeneic PBPC transplantation.
BACKGROUND AND OBJECTIVES: It may be useful to reduce the exposure of transplant recipients to homologous blood. This may be achieved by procuring donor-derived red blood cell (RBC) units, collecting more peripheral blood progenitor cells (PBPC) with a combination of granulocyte colony-stimulating factor (G-CSF) + recombinant human erythropoietin (rHuEpo) and by administering rHuEpo post-transplantation. DESIGN AND METHODS: Eight ABO-compatible donors were treated with rHuEpo and intravenous iron to collect 12 RBC units for use in their recipients. PBPC were collected after mobilization with rHuEpo and G-CSF in the same donors. The recipients received G-CSF and rHuEpo post-transplantation. A control group of 10 donor/recipient pairs received G-CSF alone for PBPC mobilization and after the transplantation. RESULTS: Eighty-six out of 91 planned RBC units were collected in the donors without significant decrease in hematocrit because of a 4-fold increase in RBC production despite functional iron deficiency. After 2 leukaphereses, the cumulative yields of NC and CFU-GM were lower in the study group while those of BFU-E, CFU-Mix and CD34+ cells were similar. However, erythroid recovery was significantly accelerated in the study group. INTERPRETATION AND CONCLUSIONS: Collection of 12 RBC units within 6 weeks is feasible with rHuEpo and intravenous iron; this strategy allows a dramatic reduction in recipient exposure to homologous blood; rHuEpo has no synergistic effect with G-CSF for mobilization of PBPC in normal donors and may even be deleterious; and rHuEpo in the recipient may enhance erythroid engraftment.
Adolescent↗
Hyperammonemia after high-dose chemotherapy and stem cell transplantation.
We report a patient with multiple myeloma who suffered from hyperammonemia after a second stem cell autograft. This syndrome is not well known but is associated with a high mortality rate. Considering the possibility of this diagnosis in patients developing confusion and neurological degradation with respiratory alkalosis after intensive chemotherapy, could allow earlier treatment and perhaps improved survival. Possible mechanisms and potential therapies are discussed. With rapid recognition and treatment of the syndrome, the patient fully recovered. One and a half years later, she is still alive and well, on interferon for persisting myeloma.
Antineoplastic Combined Chemotherapy Protocols↗
Cytosine deaminase suicide gene therapy for peritoneal carcinomatosis.
Gene therapy is a novel therapeutic approach that might soon improve the prognosis of some cancers. We investigated the feasibility of cytosine deaminase (CD) suicide gene therapy in a model of peritoneal carcinomatosis. DHD/K12 colorectal adenocarcinoma cells transfected in vitro with the CD gene were highly sensitive to 5-fluorocytosine (5-FC), and a bystander effect could also be observed. Treating CD+ cells with 5-FC resulted in apoptosis as detected by terminal deoxynucleotidyltransferase-mediated deoxyuridine triphosphate nick-end labeling. In vitro, several human cell lines derived from ovarian or colorectal carcinomas, as well as the rat glioblastoma 9 L cell line, responded to CD/5-FC and showed a very strong bystander effect. 5-FC treatment of peritoneal carcinomatosis generated in syngeneic BDIX rats by CD-expressing DHD/K12 cells led to a complete and prolonged response and to prolonged survival. Our study thus demonstrated the efficacy of CD suicide gene therapy for the treatment of peritoneal carcinomatosis.
Animals↗