Interim Fluorodeoxyglucose Positron Emission Tomography Research Articles

Positron Emission Tomography-Adapted Therapy in Bulky Stage I/II Classic Hodgkin Lymphoma: CALGB 50801 (Alliance).

Patients with bulky stage I/II classic Hodgkin lymphoma (cHL) are typically treated with chemotherapy followed by radiation. Late effects associated with radiotherapy include increased risk of second cancer and cardiovascular disease. We tested a positron emission tomography (PET)-adapted approach in patients with bulky, early-stage cHL, omitting radiotherapy in patients with interim PET-negative (PET-) disease and intensifying treatment in patients with PET-positive (PET+) disease. Eligible patients with bulky disease (mass > 10 cm or 1/3 the maximum intrathoracic diameter on chest x-ray) received two cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) followed by interim fluorodeoxyglucose PET (PET2). Patients with PET2-, defined as 1-3 on the 5-point scale, received four additional cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine. Patients with PET2+ received four cycles of escalated bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone followed by 30.6 Gy involved-field radiation. Of 94 evaluable patients, 53% were female with median age 30 years (range, 18-58 years). Eight-five (90%) had stage II disease, including 48 (51%) with stage IIB/IIBE. Seventy-eight (78%) were PET2- and 21 (22%) were PET2+. The predominant toxicity was neutropenia, with 9% of patients developing febrile neutropenia and one developing sepsis. The primary end point of 3-year progression-free survival (PFS) was 93.1% in PET2- and 89.7% in PET2+ patients. Three-year overall survival was 98.6% and 94.4%, respectively. The estimated hazard ratio comparing PFS of patients with PET2+ and patients with PET2- was 1.03 (85% upper bound 2.38) and was significantly less than the null hypothesis of 4.1 (one-sided P = .04). Our study of PET-adapted therapy in bulky stage I/II cHL met its primary goal and was associated with an excellent 3-year PFS rate of 92.3% in all patients, with the majority being spared radiotherapy and exposure to intensified chemotherapy.

The GETUG SEMITEP Trial: De-escalating Chemotherapy in Good-prognosis Seminoma Based on Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography

BackgroundIn metastatic seminoma, a strategy is needed for selecting patients for less intensive chemotherapy, to limit toxicities. ObjectiveTo assess whether men with good-prognosis metastatic seminoma could be treated with two cycles of etoposide-cisplatin (EP) followed by only one cycle of carboplatin (CARBO) based on negative interim fluorodeoxyglucose positron emission tomography (FDG-PET)/computed tomography (CT). Design, setting, and participantsA nonrandomised, multicentre, phase 2 trial was conducted (NCT01887340). InterventionAll patients with baseline-positive FDG-PET/CT received EP for two cycles. After completing the first two cycles, the patients underwent a second FDG-PET/CT to assess the response. Patients with positive FDG-PET/CT proceeded directly to two additional EP cycles; those who achieved FDG-PET/CT negativity received one cycle of CARBO. Outcome measurements and statistical analysisThe proportion of patients with negative interim FDG-PET/CT who received carboplatin was determined. Results and limitationsBetween 2013 and 2017, 102 patients were enrolled. After the first two EP cycles, FDG-PET/CT was available in 98 patients. Overall, 67 patients (68.4%; 95% confidence interval [CI]: 58.2–77.4) had negative FDG-PET/CT and proceeded to a single CARBO cycle. Twenty-seven patients (27.6%; 95% CI: 19.0–37.5) had positive FDG-PET/CT after two EP cycles. The 3-yr progression-free survival rate was 90.0% (95% CI: 74.4–96.5) in the EP group and 90.8% (95% CI: 81.4–95.7) in the CARBO group. The cumulative incidences of peripheral neuropathy and ototoxicity were significantly higher in the EP group. ConclusionsOmission of two cycles of EP based on negative FDG-PET/CT after two cycles of chemotherapy appears to be feasible. However, the absence of consensus criteria for FDG-PET/CT interpretation and the short follow-up need additional studies. This strategy does not warrant routine integration yet. Patient summaryMen with good-prognosis metastatic seminoma were treated with fewer cycles of chemotherapy based on interim fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT). Omission of two cycles of chemotherapy based on negative FDG-PET/CT after two initial cycles appears to be feasible, thereby limiting the burden of treatment and toxicity.

Prognostic Role of Early Interim Fluorodeoxyglucose Positron Emission Tomography in Patients With Advanced Seminoma Undergoing Standard Treatment.

Patients with advanced seminoma have an exceedingly favorable prognosis. Studies aiming to reduce the total treatment burden and side effects in patients with well-defined disease and very good prognosis are warranted. In a prospective observational study, patients with advanced stage seminoma were treated with bleomycin, etoposide, and cisplatin (BEP) or EP according to guidelines. Fluorodeoxyglucose with positron emission tomography and computed tomography (FDG-PET/CT) examinations were performed at baseline, after 2 cycles (PET/CT2) in all patients, and after chemotherapy at the physician's discretion. Disease response to treatment assessed by PET/CT was qualitatively evaluated by 2 independent nuclear medicine physicians. Contrast-enhanced CT scans were also performed according to guidelines (at baseline, after treatment, during follow-up). The study's primary endpoint was to evaluate the association between PET/CT2 findings and relapse-free survival. From January 2009 to January 2017, a total of 75 consecutive patients were enrolled, of whom 70 were included for analysis. The clinical disease stage was IIA-B and IIC-III in 40% and 60%, respectively. By local assessment, 46 PET/CT2 scans (65.7%) were reported as negative, and 46% of these patients had stage IIC-III disease. Five-year relapse-free survival of PET/CT2-positive patients was 75% (95% confidence interval, 60-95) compared to 97.8% (95% confidence interval, 93.7-100) of PET/CT2-negative patients (P= .002). In univariate analyses, PET/CT2 was significantly associated with relapse-free survival (P= .02). No residual FDG uptake after 2 cycles of conventional chemotherapy is prognostic in advanced seminoma, but it may be useful to optimize the standard prognostic risk groups and may be tested within larger prospective clinical trials of chemotherapy deescalation.

Prognostic value of interim FDG-PET in diffuse large cell lymphoma: results from the CALGB 50303 Clinical Trial

AbstractAs part of a randomized, prospective clinical trial in large cell lymphoma, we conducted serial fluorodeoxyglucose positron emission tomography (FDG-PET) at baseline, after 2 cycles of chemotherapy (interim PET [i-PET]), and at end of treatment (EoT) to identify biomarkers of response that are predictive of remission and survival. Scans were interpreted in a core laboratory by 2 imaging experts, using the visual Deauville 5-point scale (5-PS), and by calculating percent change in FDG uptake (change in standardized uptake value [ΔSUV]). Visual scores of 1 through 3 and ΔSUV ≥66% were prospectively defined as negative. Of 524 patients enrolled in the parent trial, 169 agreed to enroll in the PET substudy and 158 were eligible for final analysis. In this selected population, all had FDG-avid disease at baseline; by 5-PS, 55 (35%) remained positive on i-PET and 28 (18%) on EoT PET. Median ΔSUV on i-PET was 86.2%. With a median follow-up of 5 years, ΔSUV, as continuous variable, was associated with progression-free survival (PFS) (hazard ratio [HR] = 0.99; 95% confidence interval [CI], 0.97-1.00; P = .02) and overall survival (OS) (HR, 0.98; 95% CI, 0.97-0.99; P = .03). ΔSUV ≥66% was predictive of OS (HR, 0.31; 95% CI, 0.11-0.85; P = .02) but not PFS (HR, 0.47; 95% CI, 0.19-1.13; P = .09). Visual 5-PS on i-PET did not predict outcome. ΔSUV, but not visual analysis, on i-PET predicted OS in DLBCL, although the low number of events limited the statistical analysis. These data may help guide future clinical trials using PET response-adapted therapy. This trial was registered at www.clinicaltrials.gov as #NCT00118209.

Serum levels of TARC, MDC, IL-10, and soluble CD163 in Hodgkin lymphoma: a SWOG S0816 correlative study

AbstractSerum soluble chemokines/cytokines produced by Hodgkin cells and the tumor microenvironment might be of value as biomarkers in classic Hodgkin lymphoma (cHL). We assessed serum thymus and activation-related chemokine (TARC), macrophage-derived chemokine (MDC), interleukin-10 (IL-10), and soluble CD163 (sCD163) levels at baseline, time of interim fluorodeoxyglucose positron emission tomography (PET), and after therapy in cHL patients treated on S0816, an intergroup phase 2 response-adapted study evaluating escalated therapy for interim PET (PET2)–positive patients (www.clinicaltrials.gov #NCT00822120). Epstein-Barr virus (EBV) status was assessed, and 559 serum samples were evaluated for TARC, MDC, IL-10, and sCD163 by immunoassay. EBV positivity correlated with higher sCD163 and IL-10 levels but lower TARC levels. While baseline biomarker levels were not associated with outcome, sCD163 levels at the time of PET2 were associated with favorable progression-free survival (PFS), adjusting for PET2 status. After therapy TARC, MDC, and IL-10 correlated with PFS and overall survival (OS) on univariable analysis, which remained significant adjusting for international prognostic score. When also adjusting for end-of-therapy PET results, TARC and IL-10 remained significantly associated with shorter PFS and OS. Exploratory analysis in PET2-negative patients showed that elevated posttherapy TARC and IL-10 levels were associated with PFS. Serum cytokine levels correlate with outcome in cHL and should be investigated further in risk-adapted cHL trials.

Interim Fluorodeoxyglucose Positron Emission Tomography–Adapted Therapy Is Not an Efficient Approach to Improving Outcome in Early-Stage Hodgkin Lymphoma

Interim Fluorodeoxyglucose Positron Emission Tomography–Adapted Therapy Is Not an Efficient Approach to Improving Outcome in Early-Stage Hodgkin Lymphoma

The role of FDG-PET imaging as a prognostic marker of outcome in primary mediastinal B-cell lymphoma.

Primary mediastinal B-cell lymphoma (PMBL) is a subtype of diffuse large B-cell lymphoma (DLBCL) that arises in the mediastinum from B-cells of thymic origin. Optimal management of patients with PMBL remains controversial. The present study evaluates outcomes of 27 PMBL patients treated with R-CHOP with or without radiation therapy (RT). It investigates the role of both interim and posttreatment fluorodeoxyglucose-positron emission tomography (FDG-PET) as prognostic markers of outcome. Additionally, it assesses postprogression therapies in the six patients who had progressive disease. At a median follow-up of 41.5 months (range: 6.1–147.2 months), OS was 95.5% (95% CI = 71.9–99.4) and progression-free survival (PFS) was 70.4% (95% CI = 49.4–83.9) for the entire cohort. The negative predictive values of interim and posttreatment FDG-PET scans were both 100%. Patients who failed initial therapy and were treated with salvage regimens and autologous stem cell transplantation (ASCT) all achieved and maintained CR. PMBL patients can achieve excellent outcomes with minimal toxicities when treated with R-CHOP with or without RT. Negative interim and negative posttreatment FDG-PET results identified PMBL patients who achieve long-term remission. However, the significance of both positive interim and positive posttreatment FDG-PET results needs to be better defined. Those who failed initial therapy were successfully treated with salvage regimens and ASCT.

Hodgkin's lymphoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up

D. A. Eichenauer1, A. Engert1, M. Andre2, M. Federico3, T. Illidge4, M. Hutchings5, & M. Ladetto6 on behalf of the ESMO Guidelines Working Group* First Department of Internal Medicine, University Hospital Cologne and German Hodgkin Study Group (GHSG), Cologne, Germany; CHU Dinant-Godinne, UCL Namur, Yvoir, Belgium; Department of Oncology, Hematology and Respiratory Diseases, University of Modena and Reggio Emilia, Modena, Italy; Institute of Cancer Sciences, University of Manchester, Manchester, UK; Department of Hematology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark; Divisione di Ematologia, Azienda Ospedaliera Santi Antonio e Biagio e Cesare Arrigo, Alessandria, Italy

Negative Interim FDG-PET Scan Is Predictive of Superior Outcome in T Cell Lymphoma.

Abstract 1956Poster Board I-979 Background:Fluoro-deoxy-glucose positron emission tomography (FDG-PET) is a required staging study for diffuse large B-cell lymphoma and Hodgkin lymphoma. Numerous studies have demonstrated that FDG-PET performed after one to four cycles of multiagent chemotherapy (interim restaging) is predictive of outcome, with relapse rates much higher in patients with positive FDG-PET scans at interim restaging. The prognostic role of FDG-PET in T-cell lymphoma however is unclear and has yet to be well defined. Small retrospective studies have demonstrated FDG-PET avidity of T-cell lymphoma. Our experience confirms that the great majority of patients with mature T or NK lymphomas have FDG-PET avid disease. We hypothesized that the interim FDG-PET (int FDG-PET) may have prognostic importance in patients with T-cell lymphomas as they do in diffuse large B-cell lymphoma and Hodgkin lymphoma. Methods:We reviewed our T-cell lymphoma database to identify patients with mature T or NK lymphomas who had FDG-PET scans as part of complete staging at initial diagnosis as well as repeat PET imaging as part of restaging. Inclusion criteria required FDG-PET avid disease at baseline and treatment administered with curative intent. Results:We reviewed fifty four patients who met the above criteria. Histologies were as follows: peripheral T-cell lymphoma NOS (N=18), angioimmunoblastic T-cell lymphoma (N=5), anaplastic large cell lymphoma ALK-1- (N=15), anaplastic large cell lymphoma ALK-1+ (N=3), and other subtypes (N=13). Patients received a variety of initial chemotherapy regimens including CHOP (N=18), EPOCH (N=6), CHOP/ICE (N=20) or other treatments provided with curative intent. Twenty two patients were consolidated with high dose therapy and either autologous (N=18), or allogeneic (N=4) SCT. Fifty nine percent were PET negative at interim restaging (32/54), 7.4% were positive (4/54), 22 % were not available (12/54), and 11% had equivocal scans (6/54). Median follow up was 17 months. Median PFS for the entire group was 15 months. Median OS for the entire group was 40 months. The median OS of patients with negative int FDG-PET has not been reached, compared to the OS of patients with positive int FDG-PET of 10.2 months (p<.001). Patients with equivocal int FDG-PET had a median OS of 62 months, which was statistically superior to patients with positive int FDG-PET (p=.02). There was no significant difference in median OS in patients with negative versus equivocal int FDG-PET. Similar to what was observed in OS, the median PFS of patients with negative int FDG-PET has not yet been reached, compared to the PFS of patients with a positive int FDG-PET of 4.8 months (p=<.001). Patients with equivocal int FDG-PET had a statistically improved PFS of 16 months when compared to those with a positive int FDG-PET (p<.01). Patients with equivocal int FDG-PET had similar outcomes to patients with a negative int FDG-PET, and superior to those with a positive int FDG-PET, whose results were very poor. Conclusions:In this dataset, interim PET scans are strongly predictive of outcome. Patients with negative int FDG-PET enjoyed significantly longer remissions and better overall survival. Patients with negative int FDG-PET were more likely to receive consolidative therapy, which may contribute to their superior outcomes. This may be a potentially confounding factor. Nonetheless, achievement of a negative int FDG-PET appears to be a reliable predictor of outcome in patients with T-cell lymphomas and may have similar prognostic importance in these patients as they do in diffuse large B-cell lymphoma and Hodgkin lymphoma. It is reasonable to consider int FDG-PET in the restaging of patients with T-cell lymphomas. Disclosures:Zelenetz:Millenium Advisory board: Membership on an entity's Board of Directors or advisory committees. Horwitz:Allos Therapeutics, Inc: Consultancy, Research Funding.

Nail dystrophy due to dose-intensive chemotherapy

A 27-year-old male was diagnosed with stage IIB Hodgkin’s lymphoma with bilateral involvement of cervical, supraclavicular and axillary lymph nodes. Additionally, he had a large mediastinal mass ([1/3 of the maximal thoracic diameter) and an elevated erythrocyte sedimentation rate ([30 mm/h) which classified as an advanced stage disease according to the treatment algorithm of the German Hodgkin’s Lymphoma Study Group (GHSG). Accordingly the patient was treated within the HD18 trial with two cycles of ‘‘escalated’’ BEACOPP [1] (bleomycin, etoposide, adriamycine, cyclophosphamide, vincristine, prednisone, and procarbazine) at a 3-week interval. An interim fluorodeoxyglucose positron emission tomography performed after completion of the second cycle did not reveal residual lymphoma activity. The patient therefore was randomised to receive only two more cycles of escalated BEACOPP. On physical examination a month after completion of therapy, the patient showed four white rings on all finger nails, one for every cycle of chemotherapy comparable to year rings in tree trunks. Another patient, a 31-year-old female was also diagnosed with stage IIB Hodgkin’s lymphoma and bilateral, perihilar involvement and a mediastinal mass of 9.5 cm. Despite a negative PET result after two cycles of BEACOPP, the patient was randomized to receive another six cycles within the standard treatment arm. Figure 1b shows her fingernails after four cycles of dose-intensive chemotherapy. Post-chemotherapy dystrophy of the nails is regularly encountered in daily oncologic practice, e.g., up to 60% of