Trond Velde Bogsrud

Nordic MCL3 study: 90Y-ibritumomab-tiuxetan added to BEAM/C in non-CR patients before transplant in mantle cell lymphoma

The main objective of the MCL3 study was to improve outcome for patients not in complete remission (CR) before transplant by adding (90)Y-ibritumomab-tiuxetan (Zevalin) to the high-dose regimen. One hundred sixty untreated, stage II-IV mantle cell lymphoma patients <66 years received rituximab (R)-maxi-CHOP (cyclophosphamide, hydroxydaunorubicin, vincristine, and prednisone) alternating with R-high-dose cytarabine (6 cycles total), followed by high-dose BEAM/C (bis-chloroethylnitrosourea, etoposide, cytarabine, and melphalan or cyclophosphamide) and autologous stem cell transplantation from 2005 to 2009. Zevalin (0.4 mCi/kg) was given to responders not in CR before transplant. Overall response rate pretransplant was 97%. The outcome did not differ from that of the historic control: the MCL2 trial with similar treatment except for Zevalin. Overall survival (OS), event-free survival (EFS), and progression-free survival (PFS) at 4 years were 78%, 62%, and 71%, respectively. For responding non-CR patients who received Zevalin, duration of response was shorter than for the CR group. Inferior PFS, EFS, and OS were predicted by positron emission tomography (PET) positivity pretransplant and detectable minimal residual disease (MRD) after transplant. In conclusion, positive PET and MRD were strong predictors of outcome. Intensification with Zevalin may be too late to improve the outcome of patients not in CR before transplant. This trial was registered at www.clinicaltrials.gov as #NCT00514475.

18F-FDG PET in the management of patients with anaplastic thyroid carcinoma.

BACKGROUND Anaplastic thyroid carcinoma (ATC) is one of the most aggressive solid tumors in humans. The use of positron emission tomography (PET) with 18F-fluorodeoxyglucose (18F-FDG) in ATC has not been studied, and only a few case reports have been published. The objective of this study was to investigate the potential contribution of 18F-FDG PET to the clinical management of patients with ATC. METHODS All patients with ATC studied with 18F-FDG PET from August 2001 through March 2007 were included. The PET results were correlated with computed tomography, ultrasound, magnetic resonance imaging, bone scan, histology, and clinical follow-up. The FDG uptake was semiquantified as maximum standard uptake value. Any change in the treatment plan as a direct result of the PET findings as documented in the clinical notes was recorded. RESULTS Sixteen patients were included. True-positive PET findings were seen for all primary tumors, in all nine patients with lymph node metastases, in five out of eight patients with lung metastases, and in two patients with distant metastases other than lung metastases. In 8 of the 16 patients, the medical records reported a direct impact of the PET findings on the clinical management. CONCLUSIONS ATC demonstrates intense uptake on 18F-FDG PET images. In 8 of the 16 patients (50%), the medical records reported a direct impact of the PET findings on the management of the patient. PET may improve disease detection and have an impact on the management of patients with ATC relative to other imaging modalities.

Anti-1-Amino-3-18F-Fluorocyclobutane-1-Carboxylic Acid: Physiologic Uptake Patterns, Incidental Findings, and Variants That May Simulate Disease

Anti-1-amino-3-18F-fluorocyclobutane-1-carboxylic acid (18F-FACBC) is a synthetic amino acid analog PET radiotracer undergoing clinical trials for the evaluation of prostate and other cancers. We aimed to describe common physiologic uptake patterns, incidental findings, and variants in patients who had undergone 18F-FACBC PET. Methods: Sixteen clinical trials involving 611 18F-FACBC studies from 6 centers, which included dosimetry studies on 12 healthy volunteers, were reviewed. Qualitative observations of common physiologic patterns, incidental uptake, and variants that could simulate disease were recorded and compared with similar observations in studies of the healthy volunteers. Quantitative analysis of select data and review of prior published reports and observations were also made. Results: The liver and pancreas demonstrated the most intense uptake. Moderate salivary and pituitary uptake and variable mild to moderate bowel activity were commonly visualized. Moderate bone marrow and mild muscle activity were present on early images, with marrow activity decreasing and muscle activity increasing with time. Brain and lungs demonstrated activity less than blood pool. Though 18F-FACBC exhibited little renal excretion or bladder uptake during the clinically useful early imaging time window, mild to moderate activity might accumulate in the bladder and interfere with evaluation of adjacent prostate bed and seminal vesicles in 5%–10% of patients. Uptake might also occur from benign processes such as infection, inflammation, prostatic hyperplasia, and metabolically active benign bone lesions such as osteoid osteoma. Conclusion: Common physiologic uptake patterns were similar to those noted in healthy volunteers. The activity in organs followed the presence of amino acid transport and metabolism described with other amino acid–based PET radiotracers. As with other PET radiotracers such as 18F-FDG, focal nonphysiologic uptake may represent incidental malignancy. Uptake due to benign etiologies distinct from physiologic background also occurred and could lead to misinterpretations if the reader is unaware of them.

Integrin scintimammography using a dedicated breast imaging, solid‐state γ‐camera and 99mTc‐labelled NC100692

Objective:  Integrin scintimammography with NC100692 and a dedicated γ‐camera, LumaGEM, based on semi‐conductor technology, was performed to investigate the detection ability of this combination in breast cancer.

Sequential intranodal immunotherapy induces antitumor immunity and correlated regression of disseminated follicular lymphoma

Advanced stage follicular lymphoma (FL) is incurable by conventional therapies. In the present pilot clinical trial, we explored the efficacy and immunogenicity of a novel in situ immunotherapeutic strategy. Fourteen patients with untreated or relapsed stage III/IV FL were included and received local radiotherapy to solitary lymphoma nodes and intranodal injections of low-dose rituximab (5 mg), immature autologous dendritic cells, and granulocyte-macrophage colony-stimulating factor at the same site. The treatment was repeated 3 times targeting different lymphoma nodes. Primary end points were clinical responses and induction of systemic immunity. Five out of 14 patients (36%) displayed objective clinical responses, including 1 patient with cutaneous FL who showed regression of skin lesions. Two of the patients had durable complete remissions. Notably, the magnitude of vaccination-induced systemic CD8 T-cell-mediated responses correlated closely with reduction in total tumor area (r = 0.71, P = .006), and immune responders showed prolonged time to next treatment. Clinical responders did not have a lower tumor burden than nonresponders pretreatment, suggesting that the T cells could eliminate large tumor masses once immune responses were induced. In conclusion, the combined use of 3 treatment modalities, and in situ administration in single lymphoma nodes, mediated systemic T-cell immunity accompanied by regression of disseminated FL. The trial was registered at www.clinicaltrials.gov as #NCT01926639.

The Prognostic Value of 2-Deoxy-2-[18F]Fluoro-d-Glucose Positron Emission Tomography in Patients With Suspected Residual or Recurrent Medullary Thyroid Carcinoma

PurposeTo explore the prognostic value of 2-deoxy-2-[18F]fluoro-d-glucose (FDG) positron emission tomography (PET) in patients with suspected residual or recurrent medullary thyroid carcinoma (MTC).ProceduresThis retrospective study included all patients with MTC examined with FDG-PET at Mayo Clinic, Rochester, Minnesota, from October 1999 to March 2008. The PET results were compared with other imaging studies and clinical findings, including carcinoembryonic antigen and calcitonin levels.ResultsTwenty-nine patients with MTC were included. PET was positive in 14 patients, with follow-up information for 11; six died from metastatic disease, four had disease progression, and one remained in stable condition. PET was negative in 15 patients, with follow-up for 12; one had recurrent disease, and 11 had no evidence of clinical disease. Calcitonin doubling time was shorter for PET-positive than for PET-negative patients.ConclusionFDG-PET has high prognostic value in patients with suspected residual or recurrent MTC.

Diffusion-weighted MRI compared to FDG PET/CT for assessment of early treatment response in lymphoma.

Background 18F fluoro-deoxyglucose (FDG) positron emission tomography / computed tomography (PET/CT) is a well-recognized diagnostic tool used for staging and monitoring of therapy response for lymphomas. During the past decade diffusion-weighted (DW) magnetic resonance imaging (MRI) is increasingly being included in the assessment of tumor response for various cancers. Purpose To compare the change in maximum standardized uptake value (ΔSUVmax) from FDG PET/CT with the change in apparent diffusion coefficient (ΔADC) from DW MRI after initiation of the first cycle of chemotherapy in patients with Hodgkins lymphoma (HL) and in patients with diffuse large B-cell lymphoma (DLBCL). Material and Methods Twenty-seven consecutive patients with histologically proven lymphoma and lymphomatous lymph nodes (LLN) of the neck (19 with HL, 8 with DLBCL) underwent FDG PET/CT and MRI of the neck before and after initiation of the first cycle of chemotherapy. The mean time interval from initiation of chemotherapy to imaging was 19 days and 2 days for FDG PET/CT and MRI, respectively. For each patient ΔSUVmax, ΔADC, and change in volume of the same LLN were compared. Results There was a significant mean decrease of SUVmax by 70%, but no significant change in ADC. There was no significant reduction in LLN volume. Conclusion There was no significant correlation between ΔSUVmax and ΔADC. Thus, our data do not support that FDG PET/CT can be replaced by early DW MRI for response evaluation in lymphoma patients.

Changes in prostate-specific antigen, markers of bone metabolism and bone scans after treatment with radium-223.

Abstract Objective.The aim of this study was to assess treatment-related changes in prostate-specific antigen (PSA), total and bone alkaline phosphatase (total ALP, bone ALP), and changes on conventional bone scans in patients with metastatic castration-resistant prostate cancer (mCRPC) with bone metastases who received six cycles of radium-223 (Ra-223). Materials and methods. Changes in PSA, total ALP and bone ALP (≥30% increase or decrease), and changes on bone scans were assessed before and after six monthly cycles of Ra-223 therapy (50 kBq/kg body weight) in 14 patients with mCRPC with bone metastases and four patients on placebo. Results.Post-treatment PSA increased by at least 30% in 11 out of 14 patients and remained stable in three. Total ALP and bone ALP decreased in six and nine patients, respectively. In 10 out of 12 evaluable patients the uptake on post-treatment bone scan was reduced in lesions with high pretreatment uptake, in 11 patients accompanied by the development of new or expanded bone lesions. FACBC position emission tomography/computed tomography scans confirmed the growth of new or expanded bone metastases in two patients. Conclusions.These observations support the notion that Ra-223 kills tumour cells in metastases surrounded by highly proliferating osteoblasts, consistent with the reported survival benefit. The radiation effect in small tumour deposits not surrounded by increased osteoblast activity seems, however, insufficient, thus allowing continuous tumour growth. Long-lasting PSA reductions are the exception rather than the rule during Ra-223 treatment, whereas alkaline phosphatases decrease more frequently. To improve the overall anticancer effect, Ra-223 might be a valuable component of combination treatment.

Sentinel node procedure in low-stage/low-grade penile carcinomas

To optimize the indication for sentinel lymph node (SLN) biopsy according to tumour size in penile carcinoma. This was a retrospective analysis of 23 consecutive patients (median age 65 years; range 49–85 years) with primary penile carcinoma classified according to the TNM classification as stage T1–T3 who were identified as having SLNs in the groins. SLNs were detected by means of preoperative injection of a 99mTc nanocolloid around the tumour and peroperative use of a gamma detector probe. The average tumour size was 2.9±1.3 cm. In 7/25 patients with penile carcinoma examined with the SLN method, metastases to inguinal lymph nodes could be demonstrated. Two out of three patients with primary penile carcinomas classified as T1 according to the TNM classification and tumours > 3 cm in diameter had inguinal lymph node metastases. One of the patients had a micrometastasis, which was detected by means of immunohistochemical analysis. Seven out of eight patients with penile carcinomas > 3 cm in diameter had lymph node metastases. We did not observe any major surgical complications associated with the SLN procedure. These data indicate that penile carcinomas with a diameter of >3 cm should be investigated with SLN biopsy regardless of stage. However, multicentre studies are needed in order to obtain the appropriate number of patients.

Synchronous and metachronous skeletal osteosarcomas: The Norwegian Radium Hospital experience

Background. The purpose of this work was to study clinical and histopathological tumor characteristics of patients treated for synchronous or metachronous skeletal osteosarcoma at The Norwegian Radium Hospital from January 1, 1980 to January 1, 2008. Patients and methods. The hospital sarcoma database and patient records were reviewed to identify cases with synchronous or metachronous skeletal osteosarcoma. Patients with more than one skeletal lesion in the absence of pulmonary or other soft tissue tumor manifestations were included in the study, and histopathological slides from these tumors were reviewed. Results. Among a total of 297 registered osteosarcoma patients, six with synchronous (2.0%) and 10 with metachronous (3.4%) skeletal osteosarcomas were identified. All tumors were of high-grade malignancy. Treatment at the time of the first osteosarcoma diagnosis was in most cases wide resections and multi-agent chemotherapy according to international protocols, whereas the treatment for metachronous tumors was individualized and in general much less intensive. One patient was diagnosed with Li-Fraumeni syndrome, two other individuals may be suspected to have the same syndrome, and yet another patient had previously been treated for a bilateral retinoblastoma. Thirteen patients are dead, 11 from metastatic osteosarcoma, one from myelodysplastic syndrome, and one from wound infection and methotrexate-related nephrotoxicity; whereas three patients are still alive with no evidence of osteosarcoma. Conclusions. The prognosis for patients with synchronous and metachronous skeletal osteosarcoma is poor. However, because long-term survival is seen, aggressive treatment to selected cases, e.g., patients with an osteosarcoma predisposing syndrome and/or late occurring metachronous tumours, is justified. Revealing a possible clonal relationship between these tumors, e.g., by karyotyping, may be of interest for estimating prognosis and guide therapy intensiveness.