Follicular lymphoma treated with first-line immunochemotherapy: a review of PET-CT in patients who did not achieve CMR in the GALLIUM study

Abstract Introduction First-line immunochemotherapy followed by two years of rituximab (R) maintenance is now the standard of care for high-tumor burden follicular lymphoma (FL). In spite of an old controversy regarding the heterogeneous metabolic activity of FL lesions, either interim or final PET-CT after R-CHOP first-line therapy is now recognize to be strongly predictive of outcome. At the time of relapse, R-chemotherapy and autologous stem cell transplantation (ASCT) is a recommended option. Though, some patients will relapse quickly while others achieve long-term remissions. We investigated the prognostic value of PET-CT in patients with high-tumor burden relapsed FL treated with salvage R-chemotherapy followed by ASCT. Patients and Methods Seventy-five patients with relapsed FL referred to three French institutions were retrospectively analyzed. Patients with grade 3b follicular lymphoma or transformed into diffuse large B-cell lymphoma were excluded. Patients received second-line immunochemotherapy according to the local physician’s choice. We classified these salvage treatments into three groups: fludarabine-based regimen (n=29, group 1), cytarabine-based regimen (n=31, group 2), or ifosfamide-based regimen (n=15, group 3). PET-CT scans performed after salvage therapy (before ASCT) were included in the analyses. The local investigator’s interpretation of the imaging physician’s scan report defined a positive or negative PET. Results Median age was 56 years and 60% were men. Sixty eight patients received ASCT. Among this whole high-risk study population, 87% relapsed before 36 months after R-CHOP and 42% relapsed within 6 months and were therefore considered as R-CHOP refractory, with a median progression free survival (PFS) after R-CHOP first-line therapy of 15 months. Only 21% of the patients received R maintenance after R-CHOP. PET-CT scans after salvage therapy (before ASCT) were considered negative in 57%/76%/47% among the 3 groups respectively (p=0.06). Median stem cell harvest was higher in group 3-ifosfamide-based (8.3.106) than in both fludarabine and cytarabine-based regimens (4.47 and 4.8.106 respectively, Mann-Whitney p=0.15). Conditioning regimen was BEAM (37%) or Zevalin-BEAM (56%). Thirteen patients received R maintenance after ASCT. At a median follow-up of 28 months, 26/75 patients relapsed and 62 are alive. At 2 years, median PFS was 63.8%/66%/53.5% and median overall survival (OS) 68%/94%/92% among the 3 groups, respectively. PFS was only correlated to PET-CT results (p=0.0006). OS was correlated to group of therapy (2-3 versus 1), FLIPI score at relapse and PET-CT negativity. The latter was the strongest OS predictor on a multivariate analysis (p<0.01). On the other hand, age, gender, conditioning regimen, and PFS after R-CHOP (<36 months or even <12 months) were not linked to shorter PFS/OS. We observed 12% of second non-hematologic cancer. Conclusion PET-CT scan negativity after salvage treatment is the most important favourable factor for relapsed/refractory FL patients who receive ASCT. Disclosures: No relevant conflicts of interest to declare.

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Clinical Significance of Uptake Value on F18-FDG PET/CT and Histological Grade in 164 Patients with Follicular Lymphoma Including Transformation - a Single Center Retrospective Study

Blood ◽

10.1182/blood-2019-130837 ◽

2019 ◽

Vol 134 (Supplement_1) ◽

pp. 1529-1529

Author(s):

Mitsuhiro Yuasa ◽

Daisuke Kaji ◽

Kosei Kageyama ◽

Yuki Taya ◽

Shinsuke Takagi ◽

...

Keyword(s):

Follicular Lymphoma ◽

Ct Scan ◽

Risk Group ◽

Histological Grade ◽

Tumor Burden ◽

First Line ◽

Pet Ct ◽

Fdg Pet Ct ◽

Pet Ct Scan

Introduction: Follicular lymphoma is the most common indolent non-Hodgkin lymphoma, but has heterogeneous clinical behavior. PET-CT scan has the central role of determining of clinical staging and its five-point Deauville scale to grade response has been widely accepted in the management of follicular lymphoma. PET-CT scan also plays a significant role of predicting transformation of follicular lymphoma by considering high uptake of standardized uptake value (SUV). Recently, the total metabolic tumor volume (TMTV) measured by PET-CT scan and histological grades are prognostic factors of FL. But TMTV is not easily measured as everyday medical care, more simplified marker such as SUV value is desired. Methods: We retrospectively analyzed 275 patients who were diagnosed as follicular lymphoma including transformed form in our hospital between January 2008 and November 2018. One patient had also been diagnosed as rectal cancer as well as follicular lymphoma, aso we excluded this patient from our study. Results: We first investigated the relationship between histological grade and SUV value on FDG PET/CT. One hundred and ninety-eight biopsies were conducted at the same time of PET-CT. The median SUVmax value was 6.6 (range, 0-34.1) in FL grade 1 patients (n=89), 7.4 (0-23.9) in FL grade 2 patients (n=59), 12.1 (4.6-26.5) in FL grade 3a patients (n=33), and 14.8 (6.5-34.4) in FL grade 3b (n=17) (p<0.01). We then analyzed clinical impact of SUVmax value on follicular lymphoma grade 1-3a. Patients with follicular lymphoma grade 3b, or lack of information were excluded, so we finally analyzed 164 patients. Median follow-up of survivors was 47.5 (0.4-10989) months. The median age at diagnosis was 62 (31-90) years. Ninety patients were male. Thirty-two patients were diagnosed as duodenum follicular lymphoma. Ninety-four patients were advanced clinical stage (III/IV). Using FLIPI2 score, 32 patients (20%) were in the low risk group, 105 (64%) in the intermediate group, and 27 (16%) in the high risk group. Thirty-six patients had high tumor burdens defined by GELF criteria. The median SUVmax value was 7.5 (range, 0-34.1). As first line treatment strategy, 83 patients (51%) received watch and wait strategy, 38 (23%) received R-CHOP, 3 patients (2%) received R-CVP, 14 (9%) received R-Benda, 20 (12%) received RIT, and 6 (4%) received others. High uptake value (SUV max ≧ 10 vs. SUV max < 10) correlated with high tumor burden and sIL2-R (p<0.01), but did not affect OS and time to next treatment (TNT) (97.3% vs. 98.9% in 5-year OS (p=0.82), 54.6% vs. 72.3% in 5-year TNT (p=0.09)), regarless of first line treatment. Conclusion: Uptake value of SUVmax correlated with histological grade of FL and high tumor burden, but did not affect OS and TNT. Disclosures No relevant conflicts of interest to declare.

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PROGNOSTIC VALUE OF PET-CT AFTER FIRST-LINE IMMUNOCHEMOTHERAPY FOR FOLLICULAR LYMPHOMA IN THE PHASE III GALLIUM STUDY

Hematological Oncology ◽

10.1002/hon.2437_20 ◽

2017 ◽

Vol 35 ◽

pp. 38-40 ◽

Cited By ~ 3

Author(s):

J. Trotman ◽

S. Barrington ◽

D. Belada ◽

M. Meignan ◽

R. MacEwan ◽

...

Keyword(s):

Follicular Lymphoma ◽

Prognostic Value ◽

Phase Iii ◽

First Line ◽

Pet Ct

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Faculty Opinions recommendation of Prognostic value of PET-CT after first-line therapy in patients with follicular lymphoma: a pooled analysis of central scan review in three multicentre studies.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.735260621.793557439 ◽

2019 ◽

Author(s):

Pierre Feugier

Keyword(s):

Follicular Lymphoma ◽

Prognostic Value ◽

Pooled Analysis ◽

First Line ◽

First Line Therapy ◽

Line Therapy ◽

Multicentre Studies ◽

Pet Ct

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First-line immunochemotherapy for follicular lymphoma in the GALLIUM study: Prognostic value of PET-CT status after long-term follow-up.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.15_suppl.8025 ◽

2020 ◽

Vol 38 (15_suppl) ◽

pp. 8025-8025

Author(s):

Tina Nielsen ◽

Sally Barrington ◽

Michel Meignan ◽

Deniz Sahin ◽

Andrea Knapp ◽

...

Keyword(s):

Follicular Lymphoma ◽

Prognostic Value ◽

Metabolic Response ◽

International Prognostic Index ◽

Phase Iii ◽

Response Analysis ◽

First Line ◽

Complete Metabolic Response ◽

Pet Ct

8025 Background: The prognostic value of 18F-fluorodeoxyglucose (FDG) positron emission tomography-computed tomography (PET-CT) response assessment following first-line immunochemotherapy for advanced-stage symptomatic follicular lymphoma (FL) was previously demonstrated for patients (pts) enrolled in the Phase III GALLIUM study (NCT01332968; Trotman et al. ICML 2017). Here, we evaluated the association between PET complete metabolic response (CMR) and survival after longer follow-up in this patient population. Methods: In the GALLIUM study, 1202 pts with previously untreated FL were randomized 1:1 to induction therapy of 1000mg obinutuzumab (G; Days 1, 8, 15 of Cycle 1 then Day 1 of subsequent cycles) or 375mg/m2 rituximab (R; Day 1 of each cycle), in combination with chemotherapy (CHOP, CVP, or bendamustine) (Marcus et al. New Engl J Med 2017). PET-CT scans were mandatory, where available, at baseline and end-of-induction (EOI) for the first 170 pts enrolled, and optional thereafter. For this response analysis, the Lugano 2014 criteria were applied by an independent review committee (IRC) (Cheson et al. J Clin Oncol 2014). Associations between EOI PET complete metabolic response (PET-CMR) status and progression-free survival (PFS) and overall survival (OS) were evaluated, with hazard ratios (HR) stratified according to chemotherapy regimen and FL International Prognostic Index. Results: Of the 609 pts with a baseline PET scan, 595 (98%) had detectable lesions. Of these, 519 pts had an EOI PET evaluable by Lugano 2014 criteria. At EOI, per IRC assessment, 450/595 (76%) pts had achieved CMR. Pts with non-available scans were considered as non-responders and were excluded from the landmark (LM) analyses. Pts who died or progressed (CT-based progression assessment) before or at EOI were excluded from the PFS LM analysis; pts who died before EOI were excluded from the OS LM analysis. After a median follow-up of 76.5 months, EOI PET status was highly prognostic for both longer investigator-assessed PFS (non-CMR vs CMR: HR 3.40; 95% CI: 2.33–4.97; p < 0.0001) and longer OS (HR 3.34; 95% CI: 1.81–6.17; p < 0.0001). Six-year investigator-assessed PFS from EOI was 62.6% (95% CI: 57.0–67.6) for CMR pts compared with 23.4% (95% CI: 12.2–36.7) for non-CMR pts; the corresponding OS was 91.3% (95% CI: 88.1–93.6) vs 79.6% (95% CI: 68.0–87.4). Conclusions: With more than 6 years of follow-up, this analysis confirms that after first-line chemoimmunotherapy for FL, achieving CMR on PET-CT is an early and strong predictor of increased PFS and OS. Clinical trial information: NCT01332968 .

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18Fluoro-choline PET/CT is a useful tool for patients with primary hyperparathyroidism negative at first-line imaging localization tecniques

Endocrine Abstracts ◽

10.1530/endoabs.70.aep207 ◽

2020 ◽

Author(s):

Matteo Apicella ◽

Stefano Bola ◽

Duccio Volterrani ◽

Laura Mazoni ◽

Gianluca Frustaci ◽

...

Keyword(s):

Primary Hyperparathyroidism ◽

First Line ◽

Choline Pet ◽

Pet Ct ◽

Line Imaging

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Influence of Baseline Positron Emission Tomography in Metastatic Gastroesophageal Cancer on Survival and Response to Therapy

Oncology ◽

10.1159/000517842 ◽

2021 ◽

pp. 1-6

Author(s):

Ahmed Abdelhakeem ◽

Madhavi Patnana ◽

Xuemei Wang ◽

Jane E. Rogers ◽

Mariela Blum Murphy ◽

...

Keyword(s):

Positron Emission Tomography ◽

Response To Therapy ◽

Emission Tomography ◽

Gastroesophageal Cancer ◽

First Line ◽

First Line Therapy ◽

Line Therapy ◽

Positron Emission ◽

Pet Ct ◽

Metastatic Burden

Background: The value of baseline fluorodeoxyglucose-positron emission tomography-computed tomography (PET-CT) remains uncertain once gastroesophageal cancer is metastatic. We hypothesized that assessment of detailed PET-CT parameters (maximum standardized uptake value [SUVmax] and/or total lesion glycolysis [TLG]), and the extent of metastatic burden could aid prediction of probability of response or prognosticate. Methods: We retrospectively analyzed treatment-naive patients with stage 4 gastroesophageal cancer (December 2002–August 2017) who had initial PET-CT for cancer staging at MD Anderson Cancer Center. SUVmax and TLG were compared with treatment outcomes for the full cohort and subgroups based on metastatic burden (≤2 or >2 metastatic sites). Results: We identified 129 patients with metastatic gastroesophageal cancer who underwent PET-CT before first-line therapy. The median follow-up time was 61 months. The median overall survival (OS) was 18.5 months; the first progression-free survival (PFS) was 5.5 months. SUVmax or TLG of the primary tumor or of all metastases combined had no influence on OS or PFS, whether the number of metastases was ≤2 or >2. Overall response rates (ORRs) to first-line therapy were 48% and 45% for patients with ≤2 and >2 metastases, respectively (nonsignificant). ORR did not differ based on low or high values of SUVmax or TLG. Conclusions: This is the first assessment of a unique set of PET-CT data and its association with outcomes in metastatic gastroesophageal cancer. In our large cohort of patients, detailed analyses of PET-CT (by SUVmax and/or TLG) did not discriminate any parameters examined. Thus, baseline PET-CT in untreated metastatic gastroesophageal cancer patients has limited or no utility.

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High Basal Maximal Standardized Uptake Value (SUVmax) in Follicular Lymphoma Identifies Patients with a Low Risk of Long-Term Relapse

Cancers ◽

10.3390/cancers13122876 ◽

2021 ◽

Vol 13 (12) ◽

pp. 2876

Author(s):

Giovanni Manfredi Assanto ◽

Giulia Ciotti ◽

Mattia Brescini ◽

Maria Lucia De Luca ◽

Giorgia Annechini ◽

...

Keyword(s):

Risk Factors ◽

Follicular Lymphoma ◽

Standardized Uptake Value ◽

Metabolic Tumor Volume ◽

Late Relapse ◽

Prognostic Role ◽

Pet Ct ◽

Group A ◽

Group B

Background: Despite that the unfavorable prognostic role of a high Total Metabolic Tumor Volume (TMTV) in Follicular Lymphoma has been demonstrated, the role of SUVmax alone at baseline PET/CT could have a different prognostic role. Patients and Methods: We performed a retrospective observational monocentric cohort study. All patients affected by FL who underwent a basal PET/CT were included. Two subgroups were identified and compared in terms of PFS and OS: (A) Basal SUVmax ≤ 6; and (B) Basal SUVmax > 6. Results: Ninety-four patients were included, 34 in group A (36.2%) and 60 in group B (63.8%). The PFS at two years was comparable in the two groups (97%). The five-year PFS was 73.5% for group A and 95% for group B (p 0.005). The five-year PFS in the whole cohort was 87.5%. A clear advantage was confirmed in group A in the absence of other risk factors. Patients with SUVmax ≤ 6 and no risk factors showed a 5-year PFS of 73% against 83% for patients with SUVmax > 6 and at least two risk factors. Conclusion: A high FDG uptake favorably correlated with PFS. A low basal SUVmax reflected a higher rate of late relapse requiring a prolonged follow-up. The basal SUVmax is an approachable parameter with prognostic implications.

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25 Line of therapy adjustment in a patient with advanced triple-negative breast cancer (TNBC) by using personalized ctDNA test for treatment response monitoring

Journal for ImmunoTherapy of Cancer ◽

10.1136/jitc-2020-sitc2020.0025 ◽

2020 ◽

Vol 8 (Suppl 3) ◽

pp. A24-A24

Author(s):

Georges Azzi ◽

Shifra Krinshpun ◽

Antony Tin ◽

Allyson Malashevich ◽

Meenakshi Malhotra ◽

...

Keyword(s):

Breast Cancer ◽

Ct Scan ◽

Treatment Response ◽

Triple Negative Breast Cancer ◽

Triple Negative ◽

Bilateral Mastectomy ◽

First Line ◽

Pet Ct ◽

Line Of Therapy ◽

Pet Ct Scan

BackgroundTriple negative breast cancer (TNBC) is an aggressive form of breast cancer that is most difficult to treat due to the absence of hormone/growth factor receptors.1 2 Metastatic TNBC (mTNBC) is particularly challenging, given the limited efficacy and duration of response to chemotherapy.3 The repertoire of therapeutic options for mTNBC patients continues to increase with chemotherapeutic and immuno oncology based treatments and now includes sacituzumab govitecan, a novel antibody-chemotherapy conjugate.4MethodsHere we present a case study of a 40-year-old female who on biopsy of her left breast mass was diagnosed with TNBC. The patient underwent neoadjuvant chemotherapy with weekly administration of paclitaxel and carboplatin followed by dose-dense doxorubicin with cyclophosphamide. Following one-month, the patient underwent bilateral mastectomy, showing pathological staging ypT2 pN0. The patient underwent periodic radiological imaging along with the assessment of circulating tumor DNA in blood using a personalized and tumor-informed multiplex PCR, next-generation sequencing assay (Signatera bespoke, mPCR NGS assay) to identify the minimal residual disease (MRD) and treatment response.ResultsAfter surgery, MRD assessment revealed ctDNA positive status (0.41 MTM/mL) prompting PET/CT scan that revealed liver metastasis. Continued ctDNA monitoring showed continuous increase in ctDNA concentration (287.09 MTM/mL). Separate analyses indicated MSI-high and PD-L1 positive tumor status, leading to the initiation of the first line of therapy (nab-paclitaxel and Atezolizumab), which resulted in ctDNA decline (39.62 MTM/ml). Weekly ctDNA monitoring noted a rapid increase a month later (178 MTM/ml to 833.69 MTM/ml) within a 2-week interval, which corresponded to disease progression on imaging. Given non-responsiveness with the first-line therapy, the patient was initiated with sacituzumab govitecan. Following this, a rapid decline in the ctDNA level was observed within a week (364.07 MTM/mL) with a downward trend to 73.03 MTM/ml by two weeks. An interval PET/CT scan showed a mixed response. Continued monitoring of ctDNA demonstrated ctDNA levels <5MTM/mL for a period of two months before serially rising again (to 89.27 MTM/ml). PET-CT ordered in response to increasing ctDNA levels confirmed progression involving hepatic and lung lesions. A new line of therapy with nivolumab and ipilimumab was subsequently initiated.ConclusionsSerial monitoring of ctDNA enables early detection of therapy resistance and provides a rationale for treatment change/optimization/discontinuation as compared to periodic imaging that is currently the standard of care. The ease and convenience of using ctDNA-based testing as frequently as every week clearly identified earlier non-responsiveness to IO and also identified earlier acquired resistance to antibody-drug conjugate, enabling a prompt switch to alternative therapy.Ethics ApprovalN/AConsentN/AReferencesAnders C, Carey LA. Understanding and treating triple-negative breast cancer. Oncology (Williston Park). 2008;22(11):1233–1243.Mehanna J, Haddad FG, Eid R, Lambertini M, Kourie HR. Triple-negative breast cancer: current perspective on the evolving therapeutic landscape. Int J Womens Health2019;11:431–437. Published 2019 Jul 31. doi:10.2147/IJWH.S178349Treatment of Triple-negative Breast Cancer. American Cancer Society Website. Updated 2020. Accessed August 10, 2020. https://www.cancer.org/cancer/breast-cancer/treatment/treatment-of-triple-negative.htmlBardia A, Mayer IA, Vahdat LT, et al. Sacituzumab govitecan-hziy in refractory metastatic triple-negative breast cancer. N Engl J Med 2019;380(8):741–751. doi:10.1056/NEJMoa1814213

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