Whole-body MRI radiomics model to predict relapsed/refractory Hodgkin Lymphoma: A preliminary study.

PURPOSE: A strong prognostic score that enables a stratification of newly diagnosed Hodgkin Lymphoma (HL) to identify patients at high risk of refractory/relapsed disease is still needed. Our aim was to investigate the potential value of a radiomics analysis pipeline from whole-body MRI (WB-MRI) exams for clinical outcome prediction in patients with HL. MATERIALS AND METHODS: Index lesions from baseline WB-MRIs of 40 patients (22 females; mean age 31.7 ± 11.4 years) with newly diagnosed HL treated by ABVD chemotherapy regimen were manually segmented on T1-weighted, STIR, and DWI images for texture analysis feature extraction. A machine learning approach based on the Extra Trees classifier and incorporating clinical variables, 18F-FDG-PET/CT-derived metabolic tumor volume, and WB-MRI radiomics features was tested using cross-validation to predict refractory/relapsed disease. RESULTS: Relapsed disease was observed in 10/40 patients (25%), two of whom died due to progression of disease and graft versus host disease, while eight reached the complete remission. In total, 1403 clinical and radiomics features were extracted, of which 11 clinical variables and 171 radiomics parameters from both original and filtered images were selected. The 3 best performing Extra Trees classifier models obtained an equivalent highest mean accuracy of 0.78 and standard deviation of 0.09, with a mean AUC of 0.82 and standard deviation of 0.08. CONCLUSIONS: Our preliminary results demonstrate that a combined machine learning and texture analysis model to predict refractory/relapsed HL on WB-MRI exams is feasible and may help in the clinical outcome prediction in HL patients.

Consolidation Radiotherapy Could Be Safely Omitted in Advanced Hodgkin Lymphoma With Large Nodal Mass in Complete Metabolic Response After ABVD: Final Analysis of the Randomized GITIL/FIL HD0607 Trial.

PURPOSE: To investigate the role of consolidation radiotherapy (cRT) in advanced-stage Hodgkin lymphoma (HL) presenting at baseline with a large nodal mass (LNM) in complete metabolic response after doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) chemotherapy. PATIENTS AND METHODS: Advanced-stage (IIB-IVB) HL patients, enrolled in the HD 0607 trial (Clinicaltrial.gov identifier NCT00795613), with both a negative PET after two (PET-2) and six (PET-6) ABVD cycles, who presented at baseline with an LNM, defined as a nodal mass with the largest diameter ≥ 5 cm, were prospectively randomly assigned to receive cRT over the LNM or no further treatment (NFT). RESULTS: Among 296 randomly assigned patients, the largest diameter of LNM at baseline was 5-7 cm in 101 (34%; subgroup A) and 8-10 cm in 96 (32%; subgroup B), whereas classic bulky (diameter > 10 cm) was detected in 99 (33%; subgroup C). Two hundred eighty patients (88%) showed a postchemotherapy RM. The median dose of cRT was 30.6 Gy (range, 24-36 Gy). After a median follow-up of 5.9 years (range, 0.5-10 years), the 6-year progression-free survival rate of patients who underwent cRT or NFT was, respectively, 91% (95% CI, 84% to 99%) and 95% (95% CI, 89% to 100%; P = .62) in subgroup A; 98% (95% CI, 93% to 100%) and 90% (95% CI, 80% to 100%; P = .24) in subgroup B; 89% (95% CI, 81% to 98%) and 86% (95% CI, 77% to 96%; P = .53) in subgroup C (classic bulky). CONCLUSION: cRT could be safely omitted in patients with HL presenting with an LNM and a negative PET-2 and PET-6 scan, irrespective from the LNM size detected at baseline.

Early Chemotherapy Intensification With Escalated BEACOPP in Patients With Advanced-Stage Hodgkin Lymphoma With a Positive Interim Positron Emission Tomography/Computed Tomography Scan After Two ABVD Cycles: Long-Term Results of the GITIL/FIL HD 0607 Trial.

Purpose To investigate the progression-free survival (PFS) of patients with advanced Hodgkin lymphoma (HL) after a risk-adapted treatment strategy that was based on a positive positron emission tomography scan performed after two doxorubicin, vinblastine, vincristine, and dacarbazine (ABVD) cycles (PET2). Patients and Methods Patients with advanced-stage (IIB to IVB) HL were consecutively enrolled. After two ABVD cycles, PET2 was performed and centrally reviewed according to the Deauville five-point scale. Patients with a positive PET2 were randomly assigned to four cycles of escalated bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone (BEACOPP) followed by four cycles of standard BEACOPP with or without rituximab. Patients with a negative PET2 continued ABVD, and those with a large nodal mass at diagnosis (≥ 5 cm) in complete remission with a negative PET at the end of chemotherapy were randomly assigned to radiotherapy or no further treatment. The primary end point was 3-year PFS. Results Of 782 enrolled patients, 150 (19%) had a positive and 630 (81%) a negative PET2. The 3-year PFS of all patients was 82%. The 3-year PFS of those with a positive and negative PET2 was 60% and 87%, respectively ( P < .001). The 3-year PFS of patients with a positive PET2 assigned to BEACOPP with or without rituximab was 63% versus 57% ( P = .53). In 296 patients with both interim and post-ABVD-negative PET who had a large nodal mass at diagnosis, radiotherapy was randomly added after chemotherapy without a significant PFS improvement (97% v 93%, respectively; P = .29). The 3-year overall survival of all 782 patients was 97% (99% and 89% for PET2 negative and positive, respectively). Conclusion The PET-driven switch from ABVD to escalated BEACOPP is feasible and effective in high-risk patients with advanced-stage HL.

Abdomen/pelvis computed tomography in staging of pediatric Hodgkin Lymphoma: is it always necessary?

The purpose of the study was to determine if abdomen/pelvis computed tomography (CT) can be safety omitted in the initial staging of a subgroup of children affected by Hodgkin Lymphoma (HL). Every participating center of A.I.E.O.P (Associazione Italiana di Ematologia ed Oncologia Pediatrica) sent local staging reports of 18F-fluorodeoxyglucose positron emission tomography (PET) and abdominal ultrasound (US) along with digital images of staging abdomen/pelvis CT to the investigation center where the CT scans were evaluated by an experienced pediatric radiologist. The local radiologist who performed the US was unaware of local CT and PET reports (both carried out after US), and the reviewer radiologist examining the CT images was unaware of local US, PET and CT reports. A new abdominal staging of 123 patients performed on the basis of local US report, local PET report, and centralized CT report was then compared to a simpler staging based on local US and PET. No additional lesion was discovered by CT in patients with abdomen/pelvis negativity in both US and PET or isolated spleen positivity in US (or US and PET), and so it seems that in the initial staging, abdomen/pelvis CT can be safety omitted in about 1/2 to 2/3 of children diagnosed with HL.

Comparison between whole-body MRI with diffusion-weighted imaging and PET/CT in staging newly diagnosed FDG-avid lymphomas.

OBJECTIVES: To compare whole body-MRI (WB-MRI) with diffusion-weighted imaging and FDG-PET/CT in staging newly diagnosed FDG-avid lymphomas. METHODS: 68 patients (37 males, 31 females; median age 42 years; range 15-86 years) with histologically confirmed lymphoma (37 Classical Hodgkin, 16 Diffuse large B-cell, 10 Follicular, 5 Mantle cell) underwent both MRI and FDG-PET/CT before treatment. Ann Arbor stages obtained with WB-MRI and FDG-PET/CT were compared using Cohen's k statistics. Moreover WB-MRI and FDG-PET/CT stages were compared with the pathological stages obtained after the diagnostic iter using also bone marrow and available biopsies if clinically indicated. RESULTS: The agreement between WB-MRI and FDG-PET/CT was excellent. WB-MRI stage was equal to those of FDG-PET/CT in 62/68 patients (91.2%). There was an excellent agreement between WB-MRI stage and pathological stage (63/68 patients; 92.6%), and between FDG-PET/CT and pathological stage (64/68 patients; 94.1%). The differences between the stages were more frequent in the patients with Mantle cell lymphoma. CONCLUSIONS: WB-MRI can be considered as a promising technique for FDG-avid lymphoma staging.

124I-MIBG: a new promising positron-emitting radiopharmaceutical for the evaluation of neuroblastoma.

Neuroblastoma is the most common extra-cranial solid tumor in pediatric patients. Despite the established role of 123I-MIBG and 131I-MIBG scintigraphy in this tumor, only limited data are available regarding the use of 124I-metaiodobenzylguanidine (MIBG) positron emission tomography (PET)/computed tomography (CT). We present our preliminary experience with 124I-MIBG PET/CT: two pediatric patients affected by neuroblastoma, who underwent 124I-MIBG PET/CT for pre-therapy distribution evaluation and restaging purposes. We aimed to evaluate whether 124I-MIBG PET/CT can detect as many or more neuroblastoma lesions than 123I/131I-MIBG imaging. Our cases show promising results, although further validation and standardization of 124I-MIBG PET/CT are required.

WIDEN: A tool for medical image management in multicenter clinical trials.

Background It has been proposed that in clinical trials in which the therapeutic strategy is driven by functional imaging, central review of the images should be done in real time. Purpose We report our experience with a new tool for image exchange and review, called Web-Based Imaging Diagnosis by Expert Network (WIDEN), which we implemented for the HD0607 prospective multicenter Italian clinical trial in which Hodgkin lymphoma treatment was adapted based on results of an interim positron emission tomography (PET) scan performed after the first two cycles of chemotherapy. Methods We used WIDEN for general management of the clinical trial, site imaging qualification, image exchange, workflow control, blinded independent central review, inter-observer variability assessment, consensus creation, audit, and statistical analysis. Results As of February 2013, the interim PET was available for 512 patients; upon central review, 103 of the scans were judged to be positive and 409 to be negative. The median scan uploading and downloading times were 1 min, 25 s and 1 min, 55 s, respectively; the average and median times for diagnosis exchange were 47 h, 53 min and 37 h, 43 min, respectively. The binary concordance between pairs of reviewers (Cohen's kappa) ranged from 0.72 to 0.85. The 5-point scale concordance among all reviewers (Krippendorf's alpha) was 0.77. Conclusions WIDEN proved to be an effective tool for medical imaging exchange and online review. Data security, simplicity, feasibility, and prompt scan review were demonstrated. Central reviews were completed promptly.

Is %ΔSUVmax a useful indicator of survival in patients with advanced nonsmall-cell lung cancer?

PURPOSE: To investigate the impact of the maximum standardized uptake value (SUVmax), size of primary lung lesion, and %ΔSUVmax on outcome (overall survival (OS) and 2-year disease-free survival (2-year DFS)) of patients with advanced nonsmall-cell lung cancer (NSCLC). MATERIALS AND METHODS: 86 stage III-IV NSCLC patients underwent 18 F-FDGPET/CT, before and after chemotherapy, and were classified into subgroups according to the response criteria of the European Organization for Research and Treatment of Cancer. SUVmax values and tumor size with the best prognostic significance were searched. Correlation between the SUVmax value and the initial response to therapy (best response) and the relationship between %ΔSUVmax and OS were assessed. RESULTS: In patients in PD (20/86), the average pretreatment SUVmax was 11.8 ± 5.23, and the mean size of the primary lesion was 43.35 mm ± 16.63. In SD, PR, and CR patients (66/86), the average pretreatment SUVmax was 12.7 ± 8.05, and the mean size of the primary lesion was 41.6 mm ± 21.15. Correlation was identified only for %ΔSUVmax; patients with PD (ΔSUVmax > +25%) showed a worse OS than patients with ΔSUVmax < +25% (CR, PR, and SD) (P = 0.0235). CONCLUSIONS: In stage III-IV NSCLC, among the assessed factors, only %ΔSUVmax may be considered as a useful prognostic factor.

Prediction of 2 years-survival in patients with stage I and II non-small cell lung cancer utilizing (18)F-FDG PET/CT SUV quantification.

BACKGROUND: The purpose of the study was to evaluate the correlation between the maximum standardized uptake value (SUVmax), size of primary lung lesion, disease-free survival (DFS) and overall survival (OS) in patients with stage I and II non-small cell lung cancer (NSCLC) in 2 years follow-up. PATIENTS AND METHODS: Forty-nine patients with stage I-II NSCLC were included in this study. Pre-surgical 2-deoxy-2-[18F]fluoro-D-glucose positron-emission tomography ((18)F-FDG PET/CT) study was performed for all patients. The relationship between SUVmax, tumour size and clinical outcome was measured. The cut-off value for SUVmax and tumour size with the best prognostic significance, probability of DFS and the correlation between SUVmax and the response to therapy were calculated. RESULTS: There was a statistically significant correlation between SUVmax and DFS (p = 0.029). The optimal cut-offs were 9.00 for SUVmax (p = 0.0013) and 30mm for tumour size (p = 0.0028). Patients with SUVmax > 9 and primary lesion size > 30 mm had an expected 2years-DFS of 37.5%, while this rose to 90% if the tumour was <30 mm and/or SUVmax was <9. CONCLUSIONS: In stage I-II, SUVmax and tumour size might be helpful to identify the subgroup of patients with high chance for recurrence.

A comparison between ¹8F-FDG PET/CT imaging and biological and radiological findings in restaging of hepatoblastoma patients.

BACKGROUND: In this study we retrospectively evaluated if ¹8F-FDG-PET/CT provided incremental diagnostic information over CI in a group of hepatoblastoma patients performing restaging. PROCEDURE: Nine patients (mean age: 5.9 years; range: 3.1-12 years) surgically treated for hepatoblastoma were followed up by clinical examination, serum α-FP monitoring, and US. CI (CT or MRI) and PET/CT were performed in case of suspicion of relapse. Fine-needle aspiration biopsies (FNAB) were carried out for final confirmation if the results of CI, PET/CT, and/or α-FP levels were suggestive of relapse. PET/CT and CI findings were analyzed for comparison purposes, using FNAB as reference standard. RESULTS: α-FP level was suggestive of disease recurrence in 8/9 patients. Biopsy was performed in 8/9 cases. CI and PET/CT resulted to be concordant in 5/9 patients (CI identified recurrence of disease, but ¹8F-FDG-PET/CT provided a better definition of disease extent); in 4/9 cases, CI diagnostic information resulted in negative findings, whereas PET/CT correctly detected recurrence of disease. ¹8F-FDG-PET/CT showed an agreement of 100% (8/8) with FNAB results. CONCLUSIONS: ¹8F-FDG-PET/CT scan seems to better assess HB patients with respect to CI and may provide incremental diagnostic value in the restaging of this group of patients.

Assessment of a new 18F-FDG PET/CT protocol in the staging of oral cavity carcinomas.

UNLABELLED: Because image fusion using (18)F-FDG PET/CT allows a better localization of the pathologic uptake, this modality has a greater sensitivity than PET alone in examining the head-neck region. However, examination of this area is particularly critical because the head and neck are close to other anatomic structures and because of the high physiologic uptake of the radiocompound. The purpose of this study was to evaluate the utility of a new imaging protocol in the staging of oral carcinoma. METHODS: Thirty-four consecutive patients (21 women and 13 men; age range, 20-84 y) with untreated biopsy-proven oral squamous cell carcinomas were examined using whole-body (18)F-FDG PET/CT fusion imaging. All patients observed strict regulations before undergoing the PET/CT examination. At the end of the whole-body acquisition, another open-mouth scan was obtained. To compare the open- and closed-mouth methods, we analyzed features such as the feasibility of an accurate topographic localization of the tumor, evaluation of tumor extent, detection of tumor involvement with adjacent structures, and involvement of lymph nodes to which we assigned a score from 1 to 5. RESULTS: No cases of (18)F-FDG physiologic uptake in the tongue or muscles were observed. The open-mouth scan obtained a better score than did the closed-mouth scan when considering the tumor localization, tumor extent, and evaluation of adjacent anatomic structures near the clinically evident tumor. For lymph node involvement, the 2 methods showed similar results. CONCLUSION: The open-mouth scan improved the anatomic tumor localization and extent and detection of tumor involvement in adjacent anatomic structures achieved by the standard PET/CT procedure. In addition, time of the examination (mid morning), relaxation of muscles before the compound was administered, and an upright position while the patient waited caused a reduction of the frequent equivocal physiologic uptake in the head and neck region. The open-mouth method does not influence the nodal staging.

Nonossifying fibroma: A possible pitfall in F18-FD-PET/CT imaging of Hodgkin's disease.

A 14-year-old girl was examined for a right lateral neck swelling and radiographic mediastinal widening. Biopsy of a right supraclavicular lymph node demonstrated the nodular sclerosing form of Hodgkin's lymphoma. An 18F-fluorodeoxyglucose-positron emission tomography/computed tomography (F18-FDG-PET/CT) study showed several pathological areas of lymph-node uptake in the upper mediastum and right distal tibia. Radiography of the tibia revealed a nonossifying fibroma in the site corresponding to the distal tibial uptake. The PET appearance of benign fibro-osseous lesions may be similar to those of skeletal metastases. Information obtained by the CT component of the PET/CT study and by conventional radiography can be useful in preventing erroneous interpretations of F18-FDG-PET uptake.

Early chemotherapy intensification with BEACOPP in advanced-stage Hodgkin lymphoma patients with a interim-PET positive after two ABVD courses.

UNLABELLED: Interim 2-[18F]Fluoro-2-deoxy-D-glucose Positron Emission Tomography performed after two chemotherapy cycles (PET-2) is the most reliable predictor of treatment outcome in ABVD-treated Hodgkin Lymphoma (HL) patients. We retrospectively analysed the treatment outcome of a therapeutic strategy based on PET-2 results: positive patients switched to BEACOPP, while negative patients continued with ABVD. Between January 2006 and December 2007, 219 newly diagnosed HL patients admitted to nine centres were enrolled; 54 patients, unfit to receive this treatment were excluded from the analysis. PET-2 scans were reviewed by a central panel of nuclear medicine experts, according to the Deauville score (Meignan, 2009). After a median follow up of 34 months (12-52) the 2-year failure free survival (FFS) and overall survival for the entire cohort of 165 patients were 88% and 98%; the FFS was 65% for PET-2 positive and 92% for PET-2 negative patients. For 154 patients in which treatment was correctly given according to PET-2 review, the 2-year FFS was 91%: 62% for PET-2 positive and 95% for PET-2 negative patients. CONCLUSIONS: this strategy, with BEACOPP intensification only in PET-2 positive patients, showed better results than ABVD-treated historic controls, sparing BEACOPP toxicity to the majority of patients.

The role of sentinel lymph-node biopsy (SLNB) in the treatment of breast cancer.

Sentinel lymph-node biopsy is an innovative method for axillary staging in breast cancer patients, based on the concept that information about the status of the entire lymphatic drainage from a tumour site could be obtained by identification and sampling of a "sentinel node". The aim of the study was to evaluate the impact of sentinel lymph-node biopsy in the management of patients with early invasive breast carcinoma. Three hundred and forty-one patients with primary invasive breast carcinoma measuring less than 2 cm (less than 3 cm from January 2001) and clinically negative axillary nodes were recruited into the study. Sentinel lymph-nodes were positive for metastases in 108/341 cases (31.7%). Micrometastases were found in 22 patients and isolated tumour cells in 1 case. The mean number of sentinel lymph-nodes removed was 1.8 per patient. The sentinel lymph-node was the only positive node in 57 of 108 patients (52.8%). The percentage of axillary recurrence in sentinel lymph-node-negative patients was 0%. The accuracy of sentinel lymph-node biopsy for axillary staging has been confirmed in many studies. Axillary recurrences after sentinel lymph-node biopsy range from 0 to 1.6% in many series, while axillary recurrence after axillary lymph-node dissection is about 0-3%. In our experience we observed no axillary recurrences in 233 patients with sentinel lymph-node biopsy alone, with a median follow-up of 33 months, confirming the accuracy of the procedure, and sentinel lymph-node-negative patients with sentinel lymph-node biopsy alone are no more at risk for axillary recurrences than those undergoing axillary lymph-node dissection.