Tima Davidson

Does Choline PET/CT Change the Management of Prostate Cancer Patients With Biochemical Failure?

Purpose: The FDA approved C-11 choline PET/computed tomography (CT) for imaging patients with recurrent prostate cancer in 2012. Subsequently, the 2014 NCCN guidelines have introduced labeled choline PET/CT in the imaging algorithm of patients with suspected recurrent disease. However, there is only scarce data on the impact of labeled choline PET/CT findings on disease management. We hypothesized that labeled-choline PET/CT studies showing local or regional recurrence or distant metastases will have a direct role in selection of appropriate patient management and improve radiation planning in patients with disease that can be controlled using this mode of therapy. Methods: This retrospective study was approved by the Tel Aviv Sourasky and Sheba Medical Center’s Helsinki ethical review committees. Patient characteristics including age, PSA, stage, prior treatments, and pre-PET choline treatment recommendations based on NCCN guidelines were recorded. Patients with biochemical failure and without evidence of recurrence on physical examination or standard imaging were offered the option of additional imaging with labeled choline PET/CT. Treatment recommendations post-PET/CT were compared with pre-PET/CT ones. Pathologic confirmation was obtained before prostate retreatment. A nonparametric &khgr;2 test was used to compare the initial and final treatment recommendations following choline PET/CT. Results: Between June 2010 and January 2014, 34 labeled-choline PET/CT studies were performed on 33 patients with biochemical failure following radical prostatectomy (RP) (n=6), radiation therapy (RT) (n=6), brachytherapy (n=2), RP+salvage prostate fossa RT (n=14), and RP+salvage prostate fossa/lymph node RT (n=6). Median PSA level before imaging was 2 ng/mL (range, 0.16 to 79). Labeled choline PET/CT showed prostate, prostate fossa, or pelvic lymph node increased uptake in 17 studies, remote metastatic disease in 9 studies, and failed to identify the cause for biochemical failure in 7 scans. PET/CT altered treatment approach in 18 of 33 (55%) patients (P=0.05). Sixteen of 27 patients (59%) treated previously with radiation were retreated with RT and delayed or eliminated androgen deprivation therapy: 1 received salvage brachytherapy, 10 received salvage pelvic lymph node or prostate fossa irradiation, 2 brachytherapy failures received salvage prostate and lymph nodes IMRT, and 3 with solitary bone metastasis were treated with radiosurgery. Eleven of 16 patients retreated responded to salvage therapy with a significant PSA response (<0.2 ng/mL), 2 patients had partial biochemical responses, and 3 patients failed. The median duration of response was 500±447 days. Two of 6 patients with no prior RT were referred for salvage prostatic fossa RT: 1 received dose escalation for disease identified in the prostate fossa and another had inclusion of “hot” pelvic lymph nodes in the treatment volume. Conclusions: These early results suggest that labeled choline PET/CT imaging performed according to current NCCN guidelines may change management and improve care in prostate cancer patients with biochemical failure by identifying patients for referral for salvage radiation therapy, improving radiation planning, and delaying or avoiding use of androgen deprivation therapy.

Is there a role for therapy response assessment with 2-[fluorine-18] fluoro-2-deoxy-d-glucose-positron emission tomography/computed tomography in mantle cell lymphoma?

Abstract 2-[Fluorine-18] fluoro-2-deoxy-d-glucose–positron emission tomography/computed tomography (FDG-PET/CT) scanning is used for response assessment in mantle cell lymphoma (MCL). However, its ability to predict outcome is debatable. We retrospectively evaluated the prognostic impact of interim and post therapy FDG-PET/CT scan on outcome of 58 consecutive MCL patients. Scans performed at diagnosis, mid-therapy, post-chemotherapy and post-transplant were reviewed and outcome analyzed. Median age was 59; MCL International Prognostic Index (MIPI) was low in 45%, intermediate in 41% and high in 14%. Thirty-four patients (58%) received R-CHOP (rituximab, cyclophosphamide, hydroxydaunorubicin, oncovin, prednisone) or R-CHOP-like chemotherapy, 24 (42%) underwent upfront autologous stem-cell transplant (ASCT). Three-year overall (OS) and progression-free-survival (PFS) were 81% and 45%, respectively. No differences in OS or PFS between PET-positive and PET-negative groups both for interim and post-therapy scans were observed. We conclude that in patients treated with R-CHOP, using the International-Harmonization-Project criteria for FDG-PET/CT interpretation, there is no role for interim or post-therapy PET.

Indication for relumpectomy—a useful scoring system in cases of invasive breast cancer†

In two‐thirds of breast cancer patients undergoing reoperation no residual tumor will be found. A scoring system for selection of patients who might benefit from relumpectomy is proposed.

Combined Increased and Decreased Skeletal Uptake of F-18 Fdg

Increased uptake of F-18 FDG is the general mainstay of diagnosis, because it indicates hypermetabolic foci of pathology. This case, describing a patient with relapsing lymphoma, represents the diagnostic dilemmas of both locally decreased and diffusely increased uptake in the skeleton.

Metabolic assessment of Merkel cell carcinoma: the role of 18F-FDG PET/CT.

ObjectivesMerkel cell carcinoma (MCC) is a rare aggressive skin tumor associated with a high mortality rate. The present study evaluated the role of fluorine-18 fluorodeoxyglucose (18F-FDG) PET/computed tomography (CT) in subsequent management of patients with MCC. MethodsA total of 101 consecutive 18F-FDG PET/CT studies of 46 patients with MCC (28 men, 68±15.4 years) were retrospectively evaluated and the role in clinical care was documented. ResultsThere were 40 positive studies (40%) in 28 patients (61%); of these, 33 studies (33%) in 27 patients (59%) showed metastatic disease. Fifty-two PET/CT studies (51%) in 23/46 (50%) patients were negative. Fifty-three studies (52%) were performed for staging or restaging in 41 patients, 29 scans (29%) were performed for routine follow-up in 10 patients, nine studies were carried out for suspected recurrent disease in eight patients, and 10 studies were carried out for assessment of response to therapy in seven patients. On the basis of PET/CT results, there was a change in disease stage in 12 studies in 12 patients (26%) and further change in the management of seven patients (15%). Overall, 2/29 routine follow-up studies were positive with further impact on management in one patient. Conclusion18F-FDG PET-CT altered the stage of one of four patients and changed the management of one of seven MCC patients. In the majority of patients, a negative 18F-FDG PET-CT study excluded active MCC with a high degree of confidence. PET-CT contributed toward patient management when performed for staging and restaging, monitoring response to treatment, and suspected recurrent disease, but not in the routine follow-up of asymptomatic patients with MCC.

FDG PET-CT evaluation in neurolymphomatosis: imaging characteristics and clinical outcomes

Abstract Neurolymphomatosis (NL) often represents unidentified non-Hodgkin lymphoma relapses. Considering its severity, early detection and treatment are crucial. We outline one hospital’s 18F-FDG-PET-CT imaging findings of NL, along with the patients’ clinical characteristics. Clinical records and imaging findings of 19 NL patients, PET-CT diagnosed, were retrospectively reviewed. Patient data, FDG-PET-CT findings and the presence of coexisting diseases, especially CNS involvement, were documented. Available MRI and clinical data verified the findings. All cases had increased linear FDG uptake along anatomic nerve sites. CTs showed varying degrees of corresponding soft-tissue-thickening. Clinical correlations also contributed to the diagnosis. In 4/19 patients, lymphoma presented with NL, in 15/19 it appeared with disease recurrence/progression. In 9/19, clinical symptoms suggested neural involvement while 10/19 had nonspecific symptoms. Eleven died of lymphoma within 0.9 years of diagnosis despite directed-therapy. Eight, however, survived up to 7.82 years post-diagnosis. Whole-body FDG-PET-CT can assist in early NL diagnosis, possibly enhancing survival.

Use of 18F-FDG PET-CT imaging to determine internal mammary lymph node location for radiation therapy treatment planning in breast cancer patients

PURPOSE Adjuvant internal mammary lymph node (IMN) radiation is often delivered with 2-dimensional techniques that use anatomic landmarks and predetermined depths for field placement and dose specification. In contrast, 3-dimensional planning uses the internal mammary vessels (IMVs) to localize the IMNs for planning. Our purpose was to determine if localization of the involved IMN (i-IMN) by 18F-labeled fluorodeoxyglucose positron emission tomography-computed tomography (18F-FDG PET-CT) offers opportunities to improve treatment. METHODS AND MATERIALS Breast cancer patients (n = 80) who had i-IMNs (n = 112) on PET-CT for initial staging (n = 40) or recurrence (n = 40) were studied. Size, intercostal space (IC), and distance from skin, sternum, and IMVs were recorded. Effects on 2- and 3-dimensional planning were evaluated. RESULTS Most i-IMNs (94.6%) were in the first to third ICs. Few were in the fourth (4.5%) or fifth (0.9%) IC. Mean i-IMN depth was 3.4 cm (range, 1.1-7.3 cm). Prescriptive depths of 4, 5, and 6 cm would result in undertreatment of 25%, 10.7%, and 5.3% of IMNs, respectively. Most IMNs (86.6%) were lateral or adjacent to the sternal edge. Only 13.4% of IMNs were posterior to the sternum. Use of the ipsilateral or contralateral sternal edge for field placement increases the risk of geographic miss or excess normal tissue exposure. Most i-IMNs were adjacent to (83%) or ≤0.5 cm (14%) from the IMV edge. Three (3%) were >0.5 cm beyond the IMV edge. The clinical target volume (CTV) defined by the first to third ICs encompassed 78% of i-IMNs. IMN-CTV coverage of i-IMNs increased with inclusion of the fourth IC (82%), 0.5 cm medial and lateral margin expansion (93%), or both (96.5%). CONCLUSION Two-dimensional treatment techniques risk geographic miss of IMNs and exposure of excess normal tissue to radiation. An IMN-CTV defined by the IMVs from the first to third ICs with 0.5-cm medial and lateral margin expansion encompasses almost all i-IMNs identified on PET-CT imaging. Inclusion of the fourth IC offers modest coverage improvement, and its inclusion should be weighed against potential increase in cardiac exposure. SUMMARY The use of 2-dimensional treatment techniques for adjuvant internal mammary lymph node (IMN) radiation may cause geographic miss of tumor and expose normal tissue to radiation injury. Conformal 3-dimensional planning improves coverage and reduces risk of normal tissue damage by using the internal mammary vessel to define an IMN clinical target volume (CTV). Contouring the IMN-CTV from the first to third intercostal spaces with a 0.5-cm expansion medially and laterally encompasses most IMN. Positron emission tomography-computed tomography may have a role in radiation planning by identifying involved-IMN for dose escalation.

CAR T cells induce a complete response in refractory Burkitt Lymphoma

We describe a 32-year-old male who presented with lymphadenopathy in December 2016. Morphology and immunohistochemistry from a lymph node biopsy were compatible with Burkitt Lymphoma (BL). Next-generation sequencing identified a TP53 mutation. Fluorescence in situ hybridization confirmed the presence of MYC translocation. The disease was refractory to rituximab, cyclophosphamide, vincristine, doxorubicin, high-dose methotrexate, ifosfamide, cytarabine, etoposide, and intrathecal methotrexate (R-CODOX-M/R-IVAC), etoposide, methylprednisolone, cytarabine, and cisplatin (ESHAP), as well as CY/TBI (cyclophosphamide 120 mg/kg and total body irradiation 12 Gy) conditioning followed by an allogeneic haemopoietic stem cell transplantation (HSCT) from an HumanLeukocyte-Antigen (HLA)-matched sibling donor. Within 3 weeks of transplantation, the disease progressed to a leukemic phase, refractory to high dose cytarabine and mitoxantrone, and donor lymphocyte infusion. On October 2017, the patient was enrolled in our phase 1b/2 study of anti-CD19 chimeric antigen receptor (CAR) T-cell therapy (NCT02772198). The CAR construct is composed of an anti-CD19 single-chain Fv, FMC63, CD28 co-stimulatory, and CD3-zeta intracellular domains. Positron-emission tomography and computed tomography (PET–CT) before treatment demonstrated innumerable Ffluorodeoxyglucose (FDG) avid lesions throughout the skeleton, involvement of the small intestine, and pelvic and inguinal lymph nodes (Fig. 1a, b). Multifocal non-avid lesions, related to blood culture proven candidiasis, were observed in the spleen and liver. Following lymphodepletion with fludarabine (30 mg/m/ day on days 1–3) and cyclophosphamide (900 mg/m on day 3), 1 × 10 autologous CAR T cells/kg (i.e., donorengrafted T cells) were infused. The patient developed grade II cytokine release syndrome and grade II CAR T cell-related encephalopathy syndrome (Fig. 1e) [1]. He was treated with broad-spectrum antibiotics and low-dose norepinephrine. Anti-interleukin 6 and steroids were not administered. On day +13 the patient was afebrile and neurological symptoms had resolved. One month after cell infusion, the PET–CT showed significant improvement with resolution of previous FDG-avid lesions consistent with a complete metabolic response (Fig. 1c, d). Three weeks later the patient was treated with a haploidentical HSCT followed by post-transplantation cyclophosphamide. The conditioning regimen included thiotepa (5 mg/kg), fludarabine (120 mg/m), IV busulfan (6.4 mg/kg), and thymoglobulin (2.5 mg/kg). The transplantation was complicated by sinusoidal obstruction syndrome (SOS), treated with defibrotide, and sepsis resulting in the patient’s death 9 days following the graft infusion. Patients with BL refractory to primary treatment have a dismal prognosis. Salvage regimens, including autologous or allogeneic HSCT, have limited efficacy [2–5]. Phase II trials have led to the approval of anti-CD19 CAR T-cell therapy for relapsed/refractory large B-cell lymphoma and precursor B-acute lymphoblastic leukemia (ALL) [6–9]. Data regarding the efficacy of CAR T-cell therapy in BL are lacking. We present a unique case of a patient with refractory BL, who achieved a complete metabolic response with CAR T cells after failing multiple lines of treatment including allogeneic HSCT. Despite a high disease burden, the toxicity profile was acceptable [9]. Overall response rates among large B-cell lymphoma patients, included in the pivotal trials, ranged from 50 to 80%, with ~40% achieving sustained remissions [6, 7]. These authors contributed equally: Abraham Avigdor, Roni Shouval.

Physiologic uptake of 18F-FDG in transposed ovaries may mimic metastasis on 18F-FDG PET/CT imaging

Background Ovarian transposition is aimed at preserving ovarian function before irradiation in pelvic malignancies. The extrapelvic location of the ovaries and their physiologic fluorine-18-fluorodeoxyglucose (18F-FDG)-uptake is a potential source of misdiagnosis as metastasis on 18F-FDG PET/CT. We describe the 18F-FDG PET/CT characteristics of transposed ovaries and their changes over time. Patients and methods We reviewed 18F-FDG PET/CT studies of all consecutive women with pelvic malignancies who underwent ovarian transposition between 2007 and 2013. Studies were grouped according to the time period over which they were carried out. Findings were categorized by location, size, appearance (solid/mixed/cystic), presence of surgical clips, ovarian 18F-FDG uptake (maximum standardized uptake value), and attenuation values on CT (Hounsfield units). Group time-period differences were assessed. Results Seventy-nine 18F-FDG PET/CT studies were reviewed, 30 before and 49 after transposition. Time-period groups after transposition were up to 4 months (18 studies), 4.1–12 months (n=14), and more than 12 months (n=17). After transposition, ovaries were located mainly in the paracolic gutter (n=32) and subhepatic regions (n=18). Surgical clips were present in 67%. Both ovaries appeared more solid 1 year after surgery than preoperatively (13.7% before vs. 61.3% after surgery; P<0.001). Transient 18F-FDG-avidity was observed in 11 ovaries. Hounsfield unit values were higher within 4 months after surgery than preoperatively, reverting thereafter to preoperative values. Conclusion After ovarian transposition, nonanatomic location, loss of cysts formation in favor of solid appearance over time, and intermittent 18F-FDG uptake of functioning transposed ovaries might mimic metastatic lesions. Careful interpretation of 18F-FDG PET/CT findings is mandatory in women with pelvic malignancies who have undergone ovarian transposition.

Incidental detection of elastofibroma dorsi on PET-CT: initial findings and changes in tumor size and standardized uptake value on serial scans.

ObjectiveWe describe changes in elastofibroma dorsi (EFD) as observed in serial fluorine-18 fluorodeoxyglucose (18F-FDG) PET-computed tomography (CT) imaging studies. Materials and methods18F-FDG PET-CT studies carried out between January 2006 and January 2015 at a single institution were reviewed by an experienced radiologist and nuclear medicine specialist. When available, previous or subsequent imaging studies were reviewed to evaluate changes in EFD. ResultsOf 28 500 PET-CT studies carried out, EFD was identified in 68 from 20 patients (mean age 67.1±10.2 years; 14 women). Five patients had unilateral lesions and 15 patients had bilateral lesions. Eighteen patients had oncologic diseases. The mean size of EFD at first presentation was 13.95±5.90 mm and the mean homogeneous low-grade 18F-FDG uptake was maximum standardized uptake value (SUVmax) 2.24±0.95. One or more additional CT scans were performed in 17 patients; the mean interval between the first and last scans was 57.4±39.2 months. EFD was unchanged in size in 7/17 (41%) and showed slow growth in 10/17, reaching a mean size of 19 mm. The mean monthly growth rate was 0.1±0.10 mm. PET imaging in 11 patients showed a mean first SUVmax of 2.08±1.17 and a mean last SUVmax of 2.74±1.05 after a mean of 47.5±31.5 months (P=0.63). ConclusionSerial PET-CT studies may show a stable or slowly enlarging mass on a CT scan without changes in 18F-FDG uptake on PET imaging. Familiarity with CT appearances and 18F-FDG uptake of EFD are important for correct interpretation of 18F-FDG PET-CT studies.