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Correlation of Early Metastatic Response by123I-Metaiodobenzylguanidine Scintigraphy With Overall Response and Event-Free Survival in Stage IV Neuroblastoma

PURPOSE Metaiodobenzylguanidine (MIBG), specifically taken up in cells of sympathetic origin, provides a highly sensitive and specific indicator for the detection of metastases in neuroblastoma. The aim of this study was to correlate early response to therapy by MIBG scan, using a semiquantitative scoring method, with the end induction response and event-free survival (EFS) rate in stage IV neuroblastoma. PATIENTS AND METHODS Seventy-five children older than 1 year and with stage IV neuroblastoma had 123I-MIBG scans at diagnosis, after two and four cycles of induction therapy, and before autologous stem-cell transplantation. The scans were read by two independent observers (concordance > 95%) using a semiquantitative method. Absolute and relative (score divided by initial score) MIBG scores were then correlated with overall pretransplantation response, bone marrow response, and EFS. RESULTS The pretransplantation response rate was 81%, and the 3-year EFS rate was 32%, similar to a concomitant group of 375 stage IV patients. The median relative MIBG scores after two, four, and six cycles were 0.5, 0.24, and 0.12, respectively. The probability of having a complete response or very good partial response before transplantation was significantly higher if the relative score after two cycles was < or = 0.5, or, if after four cycles, the relative score was < or = 0.24. Patients with a relative score of < or = 0.5 after two cycles or a score of < or = 0.24 after four cycles had an improved EFS rate (P =.053 and.045, respectively). CONCLUSION Semiquantitative MIBG score early in therapy provides valuable prognostic information for overall response and EFS, which may be useful in tailoring treatment.

The conundrum of hodgkin lymphoma nodes: To be or not to be included in the involved node radiation fields. The EORTC-GELA lymphoma group guidelines

PURPOSE To develop easily applicable guidelines for the determination of initially involved lymph nodes to be included in the radiation fields. PATIENTS AND METHODS Patients with supra-diaphragmatic Hodgkin lymphoma. All the imaging procedures were carried out with patients in the treatment position. The prechemotherapy PET/CT was coregistered with the postchemotherapy CT simulation for planning purposes. Initially involved lymph nodes were determined on fused prechemotherapy CT and FDG-PET imaging data. The initial assessment was verified with the postchemotherapy CT scan. RESULTS The classic guidelines for determining the involvement of lymph nodes were not easily applicable and did not seem to reflect the exact extent of Hodgkin lymphoma. Three simple steps were used to pinpoint involved lymph nodes. First, FDG-PET scans were meticulously analysed to detect lymph nodes that were overlooked on CT imaging. Second, any morphological and/or functional asymmetry was sought on CT and FDG-PET scans. Third, a decrease in size or the disappearance of initially visible lymph nodes on the prechemotherapy CT scan as compared to the postchemotherapy CT scan was considered as surrogate proof of initial involvement. CONCLUSIONS All the radiological procedures should be performed on patients in the treatment position for proper coregistration. It is highly advisable that all CT and/or CT/PET scans be performed with IV contrast. Using the above-mentioned three simple guidelines, initially involved lymph nodes can be detected with very satisfactory accuracy. It is also emphasized that the classic guidelines (2, 3, 4) can always be used when deemed necessary.

Early Positron Emission Tomography Response-Adapted Treatment in Stage I and II Hodgkin Lymphoma: Final Results of the Randomized EORTC/LYSA/FIL H10 Trial.

Purpose Patients who receive combined modality treatment for stage I and II Hodgkin lymphoma (HL) have an excellent outcome. Early response evaluation with positron emission tomography (PET) scan may improve selection of patients who need reduced or more intensive treatments. Methods We performed a randomized trial to evaluate treatment adaptation on the basis of early PET (ePET) after two cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) in previously untreated-according to European Organisation for Research and Treatment of Cancer criteria favorable (F) and unfavorable (U)-stage I and II HL. The standard arm consisted of ABVD followed by involved-node radiotherapy (INRT), regardless of ePET result. In the experimental arm, ePET-negative patients received ABVD only (noninferiority design), whereas ePET-positive patients switched to two cycles of bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone (BEACOPPesc) and INRT (superiority design). Primary end point was progression-free survival (PFS). Results Of 1,950 randomly assigned patients, 1,925 received an ePET-361 patients (18.8%) were positive. In ePET-positive patients, 5-year PFS improved from 77.4% for standard ABVD + INRT to 90.6% for intensification to BEACOPPesc + INRT (hazard ratio [HR], 0.42; 95% CI, 0.23 to 0.74; P = .002). In ePET-negative patients, 5-year PFS rates in the F group were 99.0% versus 87.1% (HR, 15.8; 95% CI, 3.8 to 66.1) in favor of ABVD + INRT; the U group, 92.1% versus 89.6% (HR, 1.45; 95% CI, 0.8 to 2.5) in favor of ABVD + INRT. For both F and U groups, noninferiority of ABVD only compared with combined modality treatment could not be demonstrated. Conclusion In stage I and II HL, PET response after two cycles of ABVD allows for early treatment adaptation. When ePET is positive after two cycles of ABVD, switching to BEACOPPesc + INRT significantly improved 5-year PFS. In ePET-negative patients, noninferiority of ABVD only could not be demonstrated: risk of relapse is increased when INRT is omitted, especially in patients in the F group.

Imaging of malignant tumours of the long bones in children: monitoring response to neoadjuvant chemotherapy and preoperative assessment

This review focuses on imaging of osteosarcoma and Ewing’s sarcoma of the long bones in children during preoperative neoadjuvant chemotherapy. Morphological criteria on plain films and conventional static MRI are insufficiently correlated with histological response. We review the contribution of dynamic MRI, diffusion-weighted MR and nuclear medicine (18FDG-PET) to monitor tumoural necrosis. MRI is currently the best method to evaluate local extension prior to tumour resection, especially to assess the feasibility of conservative surgery. Quantitative models in dynamic MRI and 18FDG-PET are currently being developed in order to find new early prognostic criteria, but for the time being, treatment protocols are still based on the gold standard of histological response.

Breast cancer recurrence diagnosis suspected on tumor marker rising: value of whole-body 18FDG-PET/CT imaging and impact on patient management.

Breast cancer recurrence is often suspected on tumor marker rising in asymptomatic patients. The value of fluorine‐18 fluorodeoxyglucose (18FDG)–positron emission tomography/computed tomography (PET/CT) imaging to detect recurrence and its subsequent impact on patient management were retrospectively assessed.

Development and Application of a Real-Time On-Line Blinded Independent Central Review of Interim Pet Scans to Determine Treatment Allocation in Lymphoma Trials

We appreciate the interest shown in our report by Gemici and the opportunity to respond to his comments. He published an excellent review article on tumor lysis syndrome (TLS) in 2006. He suggested that our patient may not be the third reported instance of TLS caused by radiotherapy because three patients had already been cited in his report. However, as we mentioned, only adult patients were included in our report. If pediatric patients were to be included, there would be more than three instances before his review. He also pointed out the inappropriateness of urine alkalinization during treatment of our patient. It is true that routine use of urine alkalinization is not recommended in most instances because of the potential risk of worsening renal problems or neurologic manifestations of hypocalcemia, although it seems not to have affected the clinical course of our patient. Therefore, as he described, physicians should be aware of this controversial issue during management of TLS. He also added that increasing the urinary flow rate is a better alternative than urine alkalinization. However, vigorous hydration with diuretics is not a matter of alternative choice because it is the single most important measure to treat TLS. The only decision to be made would be whether to use additional urine alkalinization for management of TLS. Finally, he mentioned that the daily fractionated dose in addition to total dose should also be considered. We agree on his opinion in the aspect that all reported patients with TLS had received 3 Gy of daily dose. He also suggested that TLS might develop later and at higher total dose if lower daily dose ( 2 Gy) were to be used. However, it is uncertain whether lower daily dose can result in TLS because there has been no such report on the matter. The threshold of radiation dose leading to rapid cell destruction might exist even in radiosensitive tumor cells. For better understanding, more experiences regarding radiotherapy-induced TLS need to be accumulated.

Single photon emission tomography/computed tomography (SPET/CT) and positron emission tomography/computed tomography (PET/CT) to image cancer

Hybrid systems associating the sharpness of anatomic images coming from computed tomography (CT) and radionuclide functional imaging (SPET or PET) are opening a new era in oncology. This multimodal imaging method is now routinely used for the diagnosis, extent, follow up, treatment response and detection of occult disease in different types of malignancies with a significant impact on the treatment strategy leading for a change for more than 68% of all investigated patients. J. Surg. Oncol. 2011;103:602–606.

Classical Hodgkin’s lymphoma: the Lymphoma Study Association guidelines for relapsed and refractory adult patients eligible for transplant

The Hodgkin’s Lymphoma Committee of the Lymphoma Study Association (LYSA) gathered in 2012 to prepare guidelines on the management of transplant-eligible patients with relapsing or refractory Hodgkin’s lymphoma. The working group is made up of a multidisciplinary panel of experts with a significant background in Hodgkin’s lymphoma. Each member of the panel of experts provided an interpretation of the evidence and a systematic approach to obtain consensus was used. Grades of recommendation were not required since levels of evidence are mainly based on phase II trials or standard practice. Data arising from randomized trials are emphasized. The final version was endorsed by the scientific council of the LYSA. The expert panel recommends a risk-adapted strategy (conventional treatment, or single/double transplantation and/or radiotherapy) based on three risk factors at progression (primary refractory disease, remission duration < 1 year, stage III/IV), and an early evaluation of salvage chemosensitivity, including 18fluorodeoxy glucose-positron emission tomography interpreted according to the Deauville scoring system. Most relapsed or refractory Hodgkin’s lymphoma patients chemosensitive to salvage should receive high-dose therapy and autologous stem-cell transplantation as standard. Efforts should be made to increase the proportion of chemosensitive patients by alternating non-cross-resistant chemotherapy lines or exploring the role of novel drugs.

Prospective study of 18F-FDG PET in pediatric mediastinal lymphoma: A single center experience

Hodgkin lymphoma (HL) and non-Hodgkin lymphoma (NHL) represent 15 – 20% of all malignancies in children [1]. One of the major problems for clinicians is the presence of radiological or clinical residual masses during or at the end of therapy. These residual lesions may correspond to active lymphoma or inactive fibrotic tissue. CT provides anatomical images but cannot differentiate between scar and persistent tumor [2]. This situation is particularly frequent in HD with initial bulky mediastinal masses: in roughly 50% of patients, the mediastinum may not return to normal. The aims of this study were to assess the feasibility of 18F-FDG PET imaging in children with mediastinal lymphoma and to evaluate the utility of 18F-FDG PET for the detection of residual mediastinal disease in this population. Twenty-six pediatric patients with newly diagnosed mediastinal HL (16 patients) or NHL (10 patients) were prospectively included in this study between September 1999 and August 2003. The characteristics of these children and adolescents are listed in Table I. Thirteen patients had 18F-FDG PET at diagnosis (13 could not be explored at diagnosis because of lack of PET availability before treatment), but all children completed the 18F-FDG PET imaging at the time of residual disease evaluation. In NHL, the median interval between the last course of chemotherapy and PET was 17.5 days (range, 8 – 44 days). For HD, the median interval between supradiaphragmatic irradiation and PET was 72 days (range, 52 – 320 days). The median follow-up was 26 months (range, 21 – 62 months). Patients with HL were treated according to the Société Française des Cancers de l’Enfant recommendations, with 4 – 6 courses of chemotherapy followed by irradiation of the involved fields (20 Gy). In the case of incomplete regression before radiotherapy, neoadjuvant chemotherapy was reinforced and radiotherapy delivered doses of 20 – 36 Gy. Patients with NHL were treated by chemotherapy alone, depending on the immunohistologic classification (Table I). The treatment regimens were completed regardless of the results of 18F-FDG PET evaluation. All 18F-FDG PET images were reviewed by three nuclear medicine specialists without knowledge of the patient’s data. The findings were classified into two categories: negative when no area of abnormal 18F-FDG uptake was seen (0), highly suspicious for active lymphoma (1). When focal 18F-FDG uptake, with intensity higher than that of surrounding tissues, was seen in an area unrelated to physiologic or benign processes, it was defined as lymphoma. Thymic ‘‘rebound’’ hyperplasia was defined as a global increase of the thymus gland with preservation of its triangular shape, not associated with any clinical, laboratory, or radiological sign of disease progression (3). All planned examinations were performed. No catheter-related artifact was observed when

18F-FDG PET and CT-scan Detect New Imaging Patterns of Response and Progression in Patients with Hodgkin Lymphoma Treated by Anti-PD1 Immune Checkpoint Inhibitor

The response evaluation criteria in patients with Hodgkin lymphoma (HL) were designed for the assessment of chemotherapy and targeted molecular agents. We investigated the accuracy of 3-mo 18F-FDG PET/CT for the identification of HL patients responding to immune-checkpoint blockade by anti–programmed death 1 antibodies (anti-PD1). We also reported the frequency of new immune patterns of response and progression. Methods: Retrospectively, we recruited consecutive HL patients treated by anti-PD1 (pembrolizumab or nivolumab) at Gustave Roussy from 2013 to 2015. 18F-FDG PET/CT and contrast-enhanced CT scans were acquired every 3 mo. We recorded the best overall response according to the International Harmonization Project Cheson 2014 criteria and LYmphoma Response to Immunomodulatory therapy Criteria (LYRIC) (2016 revised criteria). Patients achieving an objective response at any time during the anti-PD1 treatment were classified as responders. Results: Sixteen relapsed or refractory classic HL patients were included. The median age was 39 y (age range, 19–69 y). The median previous lines of therapy was 6 (range, 3–13). The mean follow-up was 22.6 mo. Nine of 16 patients (56%) achieved an objective response. Two deaths occurred due to progressive disease at 7 mo. 18F-FDG PET/CT detected all responders at 3 mo and reclassified best overall response in 5 patients compared with CT alone. A decrease in tumor metabolism and volume (SUVmean, metabolic tumor volume) and increase in healthy splenic metabolism at 3 mo were observed in responders (area under the curve > 0.85, P < 0.04). Five of 16 patients (31%) displayed new imaging patterns related to anti-PD1; we observed 2 transient progressions consistent with indeterminate response according to the LYRIC (2016) (IR2b at 14 mo and IR3 at 18 mo) and 3 patients with new lesions associated with immune-related adverse events. Conclusion: Three-month 18F-FDG PET/CT scans detected HL patients responding to anti-PD1. New patterns were encountered in 31% of patients, emphasizing the need for further evaluation in larger series and close collaboration between imaging and oncology specialists on a per-patient basis.