Aurore Oudoux

FDG-PET/CT predicts outcome in patients with aggressive non-Hodgkin's lymphoma and Hodgkin's disease.

Early therapy response assessment with metabolic imaging is potentially useful to determine prognosis in aggressive lymphoma and, thus, can guide first-line therapy. Forty-eight patients with aggressive lymphoma [24 Hodgkin’s disease (HD); 24 non-Hodgkin’s lymphoma (NHL)] underwent fluoro-deoxyglucose positron emission tomography (FDG-PET) before chemotherapy (PET1) and at mid-treatment (PET2). Therapeutic response was evaluated using conventional methods at mid-treatment. PET2 results were related to event-free survival (EFS) and overall survival (OS) using Kaplan–Meier analyses. PET1 was positive in all patients. PET2 was negative in 38 patients (18 NHL-20 HD) and positive in 10 (6 NHL-4 HD). Of the PET-negative patients, 61 and 65% achieved complete remission, and only 50 and 25% of PET-positive patients, respectively, for NHL and HD, achieved complete remission. Significant associations were found between PET2 and EFS (p=0.0006) and OS (p=0.04) for NHL, and EFS (p<0.0001) for HD (but not for OS, because no HD patient died). FDG-PET at mid-treatment can predict the outcome of patients with aggressive lymphoma and should be a useful tool to modify an ineffective therapy.

Phase II Trial of Anticarcinoembryonic Antigen Pretargeted Radioimmunotherapy in Progressive Metastatic Medullary Thyroid Carcinoma: Biomarker Response and Survival Improvement

The prognosis of medullary thyroid carcinoma (MTC) varies from long- to short-term survival based on such prognostic factors as serum calcitonin and carcinoembryonic antigen (CEA) doubling times (DTs). This prospective phase II multicenter trial evaluated the efficacy and safety of anti-CEA pretargeted radioimmunotherapy (pRAIT) in rapidly progressing metastatic MTC patients and also how serum biomarker DTs correlate with clinical outcome. Methods: From June 2004 to January 2008, 42 patients were treated with anti-CEA × anti–diethylenetriaminepentaacetic acid (DTPA) bispecific antibody (hMN-14 × m734) (40 mg/m2), followed by 131I-di-DTPA-indium bivalent hapten (1.8 GBq/m2) 4–6 d later. Results: The disease control rate (durable stabilization plus objective response) was 76.2%. Grade 3–4 hematologic toxicity was observed in 54.7% of patients and myelodysplastic syndrome in 2, including 1 heavily treated previously. After pRAIT, 21 of 37 assessed patients (56.7%) showed a significant impact on DT (≥100% increase of pre-pRAIT calcitonin or CEA DT or prolonged decrease of the biomarker concentration after pRAIT). Pre-pRAIT DT and post-pRAIT DT were significant independent predictors for overall survival (OS) from pRAIT (pre-pRAIT: hazard ratio [HR], 0.46; 95% confidence interval [CI], 0.24–0.86; P = 0.016; and post-pRAIT: HR, 5.32; 95% CI, 1.63–17.36; P = 0.006) and OS from diagnosis (pre-pRAIT: HR, 0.21; 95% CI, 0.08–0.51; P = 0.001; and post-pRAIT: HR, 6.16; 95% CI, 1.81–20.98; P = 0.004). Conclusion: pRAIT showed antitumor activity, with manageable hematologic toxicity in progressive MTC. Increased biomarker DT after treatment correlated with increased OS.

Toxicity and efficacy of combined radioimmunotherapy and bevacizumab in a mouse model of medullary thyroid carcinoma

Significant antitumor effects were previously observed with radioimmunotherapy (RIT) using an anti‐carcinoembryonic antigen (CEA) monoclonal antibody (F6) labeled with iodine‐131 in medullary thyroid cancer (MTC)‐bearing nude mice. Nevertheless, no complete response was achieved. Because angiogenesis is critical for tumor growth, bevacizumab is used to treat solid tumor in clinical practice. The present pilot study evaluated toxicity and efficacy of RIT combined with bevacizumab in mice subcutaneously grafted with TT MTC cells.

Pretargeted radioimmunotherapy in rapidly progressing, metastatic, medullary thyroid cancer†

Medullary thyroid cancer (MTC) patients with localized residual disease and/or distant metastases may survive for several years or rapidly progress and die of their disease. Thus, highly reliable prognostic factors are needed for an early distinction between high‐risk patients who need to be treated and low‐risk patients who warrant a watch‐and‐wait approach. Calcitonin doubling time is an independent predictor of survival, with a high predictive value in a population of patients who have not normalized their calcitonin, even after repeated surgery. Several imaging methods should be proposed for patients with abnormal residual calcitonin levels persisting after complete surgery: ultrasonography and computed tomography (CT) for neck exploration, and CT for chest, abdomen, and pelvis. Magnetic resonance imaging (MRI) appears to have an advantage over CT for the detection of liver metastases from endocrine tumors. Moreover, MRI appears to be a sensitive imaging technique for detecting the spread of MTC to bone/bone marrow. 2‐Fluoro‐2‐deoxy‐D‐glucose positron emission tomography/CT could be used for staging patients with progressive MTC, with possible prognostication by standard uptake value quantification. For systemic treatment of patients with rapidly progressing metastatic MTC, chemotherapy is not considered a valid therapeutic option. It is too early to evaluate the potential effectiveness of multikinase inhibitors, although interesting results of phase 2 studies have shown a transient stabilization in 30% to 50% of patients. Pretargeted radioimmunotherapy has been the only innovative treatment modality convincingly showing some survival benefit when compared with a historical untreated control group. Cancer 2010;116(4 suppl):1118–25.

Validation of Postinduction Curie Scores in High-Risk Neuroblastoma: A Children’s Oncology Group and SIOPEN Group Report on SIOPEN/HR-NBL1

A semiquantitative 123I-metaiodobenzylguanidine (123I-MIBG) scoring method (the Curie score, or CS) was previously examined in the Children’s Oncology Group (COG) high-risk neuroblastoma trial, COG A3973, with a postinduction CS of more than 2 being associated with poor event-free survival (EFS). The validation of the CS in an independent dataset, International Society of Paediatric Oncology European Neuroblastoma/High-Risk Neuroblastoma 1 (SIOPEN/HR-NBL1), is now reported. Methods: A retrospective analysis of 123I-MIBG scans obtained from patients who had been prospectively enrolled in SIOPEN/HR-NBL1 was performed. All patients exhibited 123I-MIBG–avid, International Neuroblastoma Staging System stage 4 neuroblastoma. 123I-MIBG scans were evaluated at 2 time points, diagnosis (n = 345) and postinduction (n = 330), before consolidation myeloablative therapy. Scans of 10 anatomic regions were evaluated, with each region being scored 0–3 on the basis of disease extent and a cumulative CS generated. Cut points for outcome analysis were identified by Youden methodology. CSs from patients enrolled in COG A3973 were used for comparison. Results: The optimal cut point for CS at diagnosis was 12 in SIOPEN/HR-NBL1, with a significant outcome difference by CS noted (5-y EFS, 43.0% ± 5.7% [CS ≤ 12] vs. 21.4% ± 3.6% [CS > 12], P < 0.0001). The optimal CS cut point after induction was 2 in SIOPEN/HR-NBL1, with a postinduction CS of more than 2 being associated with an inferior outcome (5-y EFS, 39.2% ± 4.7% [CS ≤ 2] vs. 16.4% ± 4.2% [CS > 2], P < 0.0001). The postinduction CS maintained independent statistical significance in Cox models when adjusted for the covariates of age and MYCN gene copy number. Conclusion: The prognostic significance of postinduction CSs has now been validated in an independent cohort of patients (SIOPEN/HR-NBL1), with a postinduction CS of more than 2 being associated with an inferior outcome in 2 independent large, cooperative group trials.

Efficacy and safety of 153 Sm-EDTMP as treatment of painful bone metastasis: a large single-center study

PurposeThe purpose of this study is to assess the efficacy of 153Sm-EDTMP (Quadramet®) in a clinical setting.MethodsWe have conducted a retrospective study of all consecutive patients (pts) treated with 153Sm-EDTMP for painful bone metastases. At each visit (before and after treatment), four parameters were collected: (i) pain assessment according to the 10-step visual analogue scale (VAS), (ii) sleep disturbance related to pain, (iii) dose of analgesic medication, and (iv) answer to the following closed question “Do you think you obtained a benefit from treatment?” Success of treatment was defined by the combination of these four parameters.ResultsThree hundred seventy consecutive 153Sm-EDTMP treatments for painful bone metastases were given. Patients had the following primary tumors: breast carcinoma (153), prostate carcinoma (155), lung carcinoma (27), or other cancers (35). Fifty-eight percent of the patients had received previous external osseous radiotherapy. Ninety-seven percent of the patients were treated with concomitant analgesics and 61% were treated with diphosphonates. A clinical benefit was described in 55.0% of cases at D30. Treatment was more effective in cases of breast and prostate cancers compared with other types of primary cancers. Patients described a benefit at D30 in 62, 58, 6, and 38% of cases of breast, prostate, lung, and other cancers. The subjective efficacy was accompanied by a decrease in analgesic intake in 35.0% of cases.Conclusion153Sm-EDTMP therapy is an effective supportive treatment in patients who suffer from bone metastases, especially in patients with breast or prostate cancer.

Tumeur carcinoïde au stade métastatique : intérêt toujours d'actualité de la thérapie à la miBG-I131

Resume A propos d’une malade porteuse d’une tumeur carcinoide digestive avec metastases hepatiques, nous rapportons les differentes alternatives therapeutiques (actuelles et en cours d’evaluation), en soulignant l’interet de la radiotherapie metabolique par mIBG-I131 au sein de cet arsenal. En effet, pour cette pathologie au pronostic reserve, comme il est souligne dans la litterature, l’efficacite interessante de ce radiopharmaceutique a la fois sur les symptomes, la masse tumorale et la biochimie en fait une alternative trop souvent sous-utilisee. Les options therapeutiques etant multiples et non codifiees, nous proposons une strategie de prise en charge des tumeurs digestives carcinoides grâce a la mIBG-I131.