[Prognostic value and imaging features of (18)F-FDG PET-CT in follicular lymphoma with different histopathology grade].

Follicular lymphoma (FL) is highly heterogeneous with different histopathologic grades. Its biological characteristics and clinical management are different. This study retrospectively analyzed (18)F-FDG PET-CT metabolic parameters, clinical features, and their relationship with prognosis in 161 FL patients with different histopathological grades (grade 1-2, grade 3A, grade 3B) at the Shanxi Cancer Hospital. There were 93 cases in the grade 1-2 group, 40 cases in the grade 3A group, and 28 cases in the grade 3B group. The expression of LDH, CD10, EZH2, c-Myc, and CD37 proteins was correlated with histological grade (grade 1-2, grade 3A, and grade 3B) (all P values<0.05) . The SUVmax, TLG, TBR, and TLR for the three groups were different (all P values<0.05) . The optimal thresholds of SUVmax, MTV, TLG, TBR, and TLR for predicting FL disease progression were 8.32, 201.31, 2 342.55, 6.56, and 3.52, respectively, and the rate of disease progression increased in patients with higher thresholds (all P value<0.05) . ß(2)-MG (>2.3 µg/L) , Follicular lymphoma international prognostic index-1 (FLIPI-1) score (3-5 points) , negative CD37 expression, positive c-Myc expression, and TLG (>2 342.55 g) were all independent risk factors for PFS in the FL patients (HR=3.609, 2.509, 0.255, 3.506, 13.531, all P value<0.05) . (18)F-FDG PET-CT is a powerful complement to FL histopathological grading and the combination of the two may better predict the prognosis of FL patients.

Baseline 18F-FDG PET/CT may contribute to the determination of initial treatment strategy for newly diagnosed follicular lymphoma.

BACKGROUND: "Watch-and-wait" approach is an important management option in asymptomatic follicular lymphoma (FL) patients with low tumor burden. Since most FL lesions are FDG-avid, we wonder if 18F-FDG PET/CT at baseline can help to better choose the patients who can benefit from early chemotherapy. This study aimed to investigate the prognostic value of baseline 18F-FDG PET/CT in newly diagnosed FL patients treated with either watch-and-wait approach or chemotherapy. RESULTS: Patients received chemotherapy as initial treatment had higher Ann Arbor stage, higher incidence of extranodal involvement and bulky disease, more involved lymph nodes larger than 3 cm, and higher SUVmax, MTV, and TLG than those managed with watch-and-wait approach (p < 0.05). The median PFS and TTNT in patients received chemotherapy and under watch-and-wait did not show significant difference, however patients with MTV<111.66 mL or TLG<141.50 SUVbw*mL had significantly longer PFS and TTNT than those patients with MTV≥111.66 mL or TLG≥141.50 SUVbw*mL (p < 0.05). Further analysis revealed that for patients with TLG≥141.50 SUVbw*mL or MTV≥111.66 mL, those who received chemotherapy as initial treatment had a significantly longer PFS and TTNT than those managed with initial watch-and-wait approach (p < 0.05). However, for patients with MTV<111.66 mL or TLG<141.50 SUVbw*mL in baseline PET/CT, there was no significant difference in PFS or TTNT between patients who received chemotherapy and those under watch-and-wait. CONCLUSION: Baseline 18F-FDG PET/CT may provide prognostic value and help to improve the decision-making of initial treatment plans for newly diagnosed FL patients.

Lymphoma: The Added Value of Radiomics, Volumes and Global Disease Assessment.

Lymphoma represents a condition that holds promise for cure with existing treatment modalities; nonetheless, the primary clinical obstacle lies in advancing therapeutic outcomes by pinpointing high-risk individuals who are unlikely to respond favorably to standard therapy. In this article, the authors will delineate the significant strides achieved in the lymphoma field, with a particular emphasis on the 3 prevalent subtypes: Hodgkin lymphoma, diffuse large B-cell lymphomas, and follicular lymphoma.

End of induction [18F]FDG PET is prognostic for progression-free survival and overall survival in follicular lymphoma patients enrolled in the FOLL12 trial.

PURPOSE: To evaluate the reliability of the Deauville score (DS) in therapy response assessment and to define the prognostic value of the metabolic response of end of induction (EOI) [18F]FDG PET (PET) in follicular lymphoma patients. METHODS: Adult patients with untreated grade 1-3a FL/ stage II-IV enrolled in the multicentre, prospective, phase III FOLL12 trial (NCT02063685) were randomized to receive standard immunochemotherapy followed by rituximab maintenance (standard arm) versus standard immunochemotherapy followed by response-adapted post-induction management (experimental arm). Baseline and EOI PET were mandatory for the study. All PET scans were centralized on the WIDEN® platform and classified according to DS in a blind independent central review. DS1-3 was considered negative (CMR), whereas DS4-5 was considered positive (not CMR). The primary endpoint was PFS. The main secondary endpoint was overall survival (OS). RESULTS: Overall, 807 follicular lymphoma patients-52% women, 89% stage III-IV disease, 40% with a high-risk FLIPI-2 score (3-5)-were enrolled in the study; 729 (90.4%) baseline and EOI PET were available for the analysis. EOI PET was positive (DS4-5) in 88/729 (12.1%) cases. Overall inter-reviewer agreement on PET pos/neg result was 0.92, while agreement on positive and negative cases was 0.77 and 0.94, respectively. The median follow-up was 69 months; 247 events were registered in the 5-yr follow-up, with a 5-yr PFS of 67% (95%CI: 63%-70%). The 5-yr PFS rate for PET neg (DS1-3) and PET pos (DS4-5) patients was 71% (95%CI: 67%-75%) and 36% (95%CI: 25%-46%), respectively, with HR 3.49 (95%CI: 2.57-4.72). Five-year PFS was worse as DS increased, with 74% (70%-78%), 58% (48%-67%; HR 1.71; p = 0.001)] and 36% (25%-46%; HR 3.88; p < 0.001) in DS1-2, DS3 and DS4-5, respectively. EOI PET maintained its prognostic value in both the standard and experimental arms. In the whole population, 5-yr OS was 94% (95%CI: 92%-96%), with 96% (95%CI: 94-97) and 82% (95%CI: 72%-89%) in EOI PET negative (DS1-3) and positive (DS4-5), respectively (HR 4.48; p < 0.001). When DS was associated with FLIPI-2, patients with DS3 or DS1-2 with high FLIPI-2 (3-5) experienced worse OS than patients with DS1-2 and low FLIPI-2 (1-2) (p = 0.003). CONCLUSION: This study shows that DS is a reliable prognostic tool to evaluate EOI PET in follicular lymphoma patients, with prognostic value maintained both in the standard and experimental arms, making metabolic imaging a robust tool to assess response in FL. Moreover, although preliminary, this study provides further information on DS3 patients, who are considered as CMR but show a less favourable PFS than DS1-2 patients.

Prognostic value of the combination of volume, massiveness and fragmentation parameters measured on baseline FDG pet in high-burden follicular lymphoma.

The prognostic value of radiomic quantitative features measured on pre-treatment 18F-FDG PET/CT was investigated in patients with follicular lymphoma (FL). We conducted a retrospective study of 126 FL patients (grade 1-3a) diagnosed between 2006 and 2020. A dozen of PET/CT-derived features were extracted via a software (Oncometer3D) from baseline 18F-FDG PET/CT images. The receiver operating characteristic (ROC) curve, Kaplan-Meier method and Cox analysis were used to assess the prognostic factors for progression of disease within 24 months (POD24) and progression-free survival at 24 months. Four different clusters were identified among the twelve PET parameters analyzed: activity, tumor burden, fragmentation-massiveness and dispersion. On ROC analyses, TMTV, the total metabolic tumor volume, had the highest AUC (0.734) followed by medPCD, the median distance between the centroid of the tumors and their periphery (AUC: 0.733). Patients with high TMTV (HR = 4.341; p < 0.001), high Tumor Volume Surface Ratio (TVSR) (HR = 3.204; p < 0.003) and high medPCD (HR = 4.507; p < 0.001) had significantly worse prognosis in both Kaplan-Meier and Cox univariate analyses. Furthermore, a synergistic effect was observed in Kaplan-Meier and Cox analyses combining these three PET/CT-derived parameters (HR = 12.562; p < 0.001). Having two or three high parameters among TMTV, TVSR and medPCD was able to predict POD24 status with a specificity of 68% and a sensitivity of 75%. TMTV, TVSR and baseline medPCD are strong prognostic factors in FL and their combination better predicts disease prognosis.

End-of-treatment 18[F]-FDG PET can predict early progression in patients receiving bendamustine-rituximab for follicular lymphoma in first relapse: a prospective West Japan hematology Study Group (W-JHS) NHL01 trial.

Response determined by 18[F]-fluoro-2-deoxy-D-glucose (18F-FDG) positron emission tomography (PET)-CT after induction therapy can predict progression-free survival (PFS) in follicular lymphoma (FL). However, little prospective research has examined the significance of PET after second-line therapy. We conducted a prospective multicenter phase II trial (W-JHS NHL01) of bendamustine plus rituximab (BR) without rituximab maintenance for FL in first relapse. This study aimed to evaluate the usefulness of end-of-treatment (EOT)-PET for predicting PFS in FL patients in first relapse. EOT-PET examinations were performed between 6 and 8 weeks from the start of the last BR cycle. The primary endpoint was 1-year PFS. Key secondary endpoints were overall response rate (ORR), complete response rate (CRR), and 1-year overall survival (OS). Seventy-five patients were enrolled, and 8 were excluded from analysis. ORR was 86.6% and CRR was 59.7%. One-year PFS was 88.9% (95% confidence interval [CI] 80.7-94.3%) and 1-year OS in 75 patients was 97.3% (95% CI 89.6-99.3%). One-year PFS was significantly inferior in EOT-PET-positive patients (n = 9) compared with PET-negative patients (n = 58) (77.8% vs. 93.1%; p = 0.02). We confirmed that EOT-PET after second-line BR therapy could predict early progression in FL patients in first relapse.

PET/CT in a 65-Year-Old Woman With Epstein-Barr Virus-Associated Smooth Muscle Tumor After Chemotherapy for Follicular Lymphoma.

ABSTRACT: The Epstein-Barr virus-associated smooth muscle tumor (SMT) is an uncommon neoplasm. It arises mainly in 3 immunosuppression settings: HIV-associated SMT; drug-related immunosuppression in transplant recipients; and congenital immunodeficiency disorder-associated SMT. We present 18 F-FDG PET/CT findings of an adrenal Epstein-Barr virus-associated SMT in a 65-year-old woman with a history of follicular lymphoma after chemotherapy.

Metabolic tumor volume predicts outcome in patients with advanced stage follicular lymphoma from the RELEVANCE trial.

BACKGROUND: We investigated the prognostic value of baseline positron emission tomography (PET) parameters for patients with treatment-naïve follicular lymphoma (FL) in the phase III RELEVANCE trial, comparing the immunomodulatory combination of lenalidomide and rituximab (R2) versus R-chemotherapy (R-chemo), with both regimens followed by R maintenance therapy. PATIENTS AND METHODS: Baseline characteristics of the entire PET-evaluable population (n = 406/1032) were well balanced between treatment arms. The maximal standard uptake value (SUVmax) and the standardized maximal distance between tow lesions (SDmax) were extracted, the standardized distance between two lesions the furthest apart, were extracted. The total metabolic tumor volume (TMTV) was computed using the 41% SUVmax method. RESULTS: With a median follow-up of 6.5 years, the 6-year progression-free survival (PFS) was 57.8%, the median TMTV was 284 cm3, SUVmax was 11.3 and SDmax was 0.32 m-1, with no significant difference between arms. High TMTV (>510 cm3) and FLIPI were associated with an inferior PFS (P = 0.013 and P = 0.006, respectively), whereas SUVmax and SDmax were not (P = 0.08 and P = 0.12, respectively). In multivariable analysis, follicular lymphoma international prognostic index (FLIPI) and TMTV remained significantly associated with PFS (P = 0.0119 and P = 0.0379, respectively). These two adverse factors combined stratified the overall population into three risk groups: patients with no risk factors (40%), with one factor (44%), or with both (16%), with a 6-year PFS of 67.7%, 54.5%, and 41.0%, respectively. No significant interaction between treatment arms and TMTV or FLIPI (P = 0.31 or P = 0.59, respectively) was observed. The high-risk group (high TMTV and FLIPI 3-5) had a similar PFS in both arms (P = 0.45) with a median PFS of 68.4% in the R-chemo arm versus 71.4% in the R2 arm. CONCLUSIONS: Baseline TMTV is predictive of PFS, independently of FLIPI, in patients with advanced FL even in the context of antibody maintenance.

Biliary obstruction secondary to duodenal follicular lymphoma with papillary involvement.

Duodenal-type follicular lymphoma is a clinical variant of follicular lymphoma located in the intestine, presenting as multiple small polyps. The estimated frequency is 1/7000 people and extraduodenal involvement is rare. It predominantly affects middle-aged women, although some cases of young patients have been published in the literature. They are usually located in the second periampullary portion of the duodenum. It is diagnosed incidentally or after performing an imaging test due to non-specific digestive symptoms (abdominalgia, diarrhea or hyporexia). The prognosis is usually favorable without specific treatment5.

Disease surveillance evaluation of primary small-bowel follicular lymphoma using capsule endoscopy images based on a deep convolutional neural network (with video).

BACKGROUND AND AIMS: Capsule endoscopy (CE) is useful in evaluating disease surveillance for primary small-bowel follicular lymphoma (FL), but some cases are difficult to evaluate objectively. This study evaluated the usefulness of a deep convolutional neural network (CNN) system using CE images for disease surveillance of primary small-bowel FL. METHODS: We enrolled 26 consecutive patients with primary small-bowel FL diagnosed between January 2011 and January 2021 who underwent CE before and after a watch-and-wait strategy or chemotherapy. Disease surveillance by the CNN system was evaluated by the percentage of FL-detected images among all CE images of the small-bowel mucosa. RESULTS: Eighteen cases (69%) were managed with a watch-and-wait approach, and 8 cases (31%) were treated with chemotherapy. Among the 18 cases managed with the watch-and-wait approach, the outcome of lesion evaluation by the CNN system was almost the same in 13 cases (72%), aggravation in 4 (22%), and improvement in 1 (6%). Among the 8 cases treated with chemotherapy, the outcome of lesion evaluation by the CNN system was improvement in 5 cases (63%), almost the same in 2 (25%), and aggravation in 1 (12%). The physician and CNN system reported similar results regarding disease surveillance evaluation in 23 of 26 cases (88%), whereas a discrepancy between the 2 was found in the remaining 3 cases (12%), attributed to poor small-bowel cleansing level. CONCLUSIONS: Disease surveillance evaluation of primary small-bowel FL using CE images by the developed CNN system was useful under the condition of excellent small-bowel cleansing level.

A Case of Adenomyosis Showing Size Reduction in a Follicular Lymphoma Patient Receiving Chemotherapy With R-Bendamustine.

ABSTRACT: We describe a case of adenomyosis that reduced in size in a patient with lymphoma on receiving chemotherapy. A 48-year-old woman with worsening left flank pain was diagnosed with follicular lymphoma. [ 18 F]FDG PET/CT revealed multiple hypermetabolic lymph nodes in the bilateral cervical, axillary, mediastinal, mesenteric, retroperitoneal, iliac, and inguinal regions. In addition, adenomyosis with mild hypermetabolism was demonstrated on [ 18 F]FDG PET/CT. The size and metabolism of adenomyosis decreased after chemotherapy with R-bendamustine; in addition, along with decrease in estradiol levels, the patient experienced amenorrhea and hot flushes. The patient was diagnosed with chemotherapy-induced early menopause.

[A case of gastric follicular lymphoma with rapid deterioration and transformation].

A 79-year-old male patient underwent esophagogastroduodenoscopy, which revealed a reddish lesion, 10mm in diameter, presenting as a surface recess in the angular incisure. He was diagnosed with gastric follicular lymphoma. Positron emission tomography-computed tomography revealed metastasis to the mediastinal lymph node, although the tumor size was small. Hence, we did not administer any treatment and continued following up. After 8 months, multiple enlarged lymphoma lesions in the stomach and a mass with ulceration on the oral side of the duodenal papilla were observed. The tumor had transformed into diffuse large B-cell lymphoma; therefore, chemotherapy was initiated. The patient has remained recurrence-free for 55 months after treatment.

Positron emission tomography to detect bone marrow involvement for patients with follicular lymphoma: a systematic review and meta-analysis.

Detection of bone marrow involvement (BMI) for patients with follicular lymphoma (FL) is of great significance for staging and treatment. The clinical value of positron emission tomography/computed tomography (PET/CT) in assessing BMI is still under debate and investigation. PubMed, Embase, Web of Science, and Cochrane Library databases were systematically searched to identify studies evaluating PET/CT in detecting BMI in FL patients. Data extraction and quality evaluation were independently conducted by two reviewers, and nine eligible studies were selected as final quantitative analysis. Nine studies comprising 1119 FL patients were included. The pooled sensitivity was 0.67 (95% CI, 0.38-0.87), and the pooled specificity was 0.82 (95% CI, 0.75-0.87). The pooled positive likelihood ratio, negative likelihood ratio, and diagnostic odds ratio were 3.7 (95% CI, 2.1-6.3), 0.4 (95% CI, 0.18-0.91), and 9 (95% CI, 2-33), respectively. The area under the curve of PET/CT to detect BMI in FL patients was 0.83 (95% CI, 0.8-0.86). Current evidence suggests that PET/CT cannot replace bone marrow biopsy to detect BMI, but it is still of partial clinical significance for the prognosis of patients with follicular lymphoma.

Primary esophageal follicular lymphoma: a rare entity.

A 63-year-old woman presented with dyspepsia de novo. An esophagogastroduodenoscopy revealed a 30 mm flat yellowish esophageal lesion, 28 cm from the incisors (Fig. 1a), with the stomach and duodenum without any lesion. Helicobacter pylori infection was excluded. Histological examination was suggestive of a lymphoproliferative process (Fig. 1b). Immunohistochemistry showed diffuse positivity for CD20 (Fig. 1c) and BCL-2 (Fig. 1d), dim CD10 and BCL-6 staining, a Ki-67 of 20-25%, no CD21 or cyclin D1 expression, all these features compatible with low-grade follicular lymphoma. Physical examination was unremarkable. Computed tomography of the neck, chest, and abdomen revealed no lymph node enlargement, hepatosplenomegaly or metastasis. Blood routine tests and tumor markers were at normal levels. Bone marrow biopsy showed no involvement by lymphoma. Therefore, a diagnosis of primary follicular lymphoma of the esophagus was made. The patient opted for a watch-and-wait strategy and there is no evidence of disease progression after four years of follow-up.

Prognostic value of interim 18F-FDG PET/CT in adult follicular lymphoma treated with R-CHOP.

PURPOSE: The prognostic value of interim 18F-FDG PET/CT (I-PET) for follicular lymphoma (FL) is controversial, and may be related to the lack of strict standards in terms of age, chemotherapy regimen, and evaluation criteria in previous studies. This study aimed to investigate the prognostic value of I-PET in adult FL patients treated with R-CHOP. METHODS: I-PET was performed in 30 adult FL patients after treatment with 3-5 cycles of R-CHOP. PET/CT images were assessed using the Deauville 5-point scale (D-5PS) criteria. Baseline PET/CT (B-PET) was performed in 24 of the patients with FL before treatment. The PET/CT image parameters, such as the SUVmax, TLG, and tMTV, were recorded. The prognostic values of sex, age, grade, Ann Arbor stage, LDH level, and I-PET were evaluated. RESULTS: Kaplan-Meier analysis and Cox regression showed that sex, age, grade, Ann Arbor stage, LDH, and I-PET using the D-5PS criteria could not predict the PFS of adult patients with FL treated with R-CHOP (P>0.05). ROC curve analysis evaluated the predictive values of SUVmax, TLG, and tMTV in B-PET and I-PET and showed that none of them was predictive of PFS in adult FL patients (P>0.05). However, the variation in SUVmax (∆SUVmax) was predictive of PFS in adult FL patients (AUC=0.83, P=0.040), and the cutoff threshold was 4.85. CONCLUSIONS: I-PET using the D-5PS criteria cannot predict the PFS of adult FL patients treated with R-CHOP. However, the ∆SUVmax between B-PET and I-PET is applicable for the prognosis of adult patients with FL.

Impact of positron emission tomography - computed tomography status on progression-free survival for relapsed follicular lymphoma patients undergoing autologous stem cell transplantation.

The optimum management approach for patients with relapsed or refractory follicular lymphoma remains uncertain. Autologous stem cell transplantation (autoSCT) is considered a standard option in suitable, younger patients with relapsed follicular lymphoma. AutoSCT is associated with very durable remissions in a minority of subjects, but also with significant, well-established toxicities. Although positron emission tomography (PET) status prior to autoSCT is an established prognostic factor in diffuse large B-cell lymphoma and Hodgkin lymphoma, no data exist in follicular lymphoma. We describe survival outcomes according to pre-transplant PET status, classified by the Lugano criteria into complete metabolic remission (CMR) versus non-CMR, in 172 patients with relapsed or refractory follicular lymphoma within a national, multicenter, retrospective British Society of Blood and Marrow Transplantation and Cellular Therapy registry study. The median number of lines of therapy prior to SCT was three (range, 1-6). The median follow-up after SCT was 27 months (range, 3-70). The median progression-free survival for all patients after autoSCT was 28 months (interquartile range, 23- 36). There was no interaction between age at transplantation, sex, number of months since last relapse, Karnofsky performance status or comorbidity index and achieving CMR prior to autoSCT. Superior progression-free survival was observed in 115 (67%) patients obtaining CMR versus 57 (33%) non-CMR patients (3-year progression-free survival 50% vs. 22%, P=0.011) and by pre-SCT Deauville score (continuous variable 1-5, hazard ratio [HR]=1.32, P=0.049). PET status was independently associated with progression-free status (non-CMR HR=2.02, P=0.003), overall survival (non-CMR HR=3.08, P=0.010) and risk of relapse (non-CMR HR=1.64, P=0.046) after autoSCT by multivariable analysis. Our data suggest that pre- SCT PET status is of clear prognostic value and may help to improve the selection of patients for autoSCT.

Primary small bowel follicular lymphoma: the role of balloon-assisted enteroscopy in diagnosis and follow-up.

An asymptomatic 38-year-old male with no significant previous medical history performed routine laboratory studies that revealed iron-deficiency anemia. Esophagogastroduodenoscopy and colonoscopy were unremarkable and he undergone videocapsule endoscopy that revealed multiple small polyps along jejunum and ileum. Double-balloon enteroscopy confirmed the presence of scattered small whitish nodules and small polyps carpeting segments of jejunal mucosal and sometimes forming conglomerates with a nodular appearance. Histopathological examination showed lamina propria expansion by neoplastic follicles, predominantly composed by small lymphoid cells that, by immunohistochemistry, showed expression of CD20, CD10 and bcl-2. Computed tomography scan of abdomen and pelvis did not reveal systemic involvement, consistent with primary small bowel follicular lymphoma. Chemotherapy was started and, at reevaluation enteroscopy, although nodular jejunal segments persisted, biopsies did not show involvement by lymphoproliferative disease, which was interpreted as complete remission. Periodic clinical and biochemical evaluation and annual enteroscopic surveillance was maintained and, after three years, local recurrence of low-grade follicular lymphoma was detected. As previously, there was no evidence of systemic involvement and the decision was to maintain close surveillance. After one year, the patient remains asymptomatic and without evidence of disease progression. This case illustrates the essential role of balloon-assisted enteroscopy for diagnosis and surveillance of primary small bowel follicular lymphoma.

FDG-PET/CT-guided rebiopsy may find clinically unsuspicious transformation of follicular lymphoma.

AIM: The purpose of the study was to evaluate the clinical impact of fluorodeoxyglucose-positron emission tomography/computed tomography (FDG-PET/CT) followed by a new biopsy from the site with maximum standardized uptake value (SUVmax) in case of high maximal SUV values, in detecting clinically unsuspected histologic transformations (HT) of follicular lymphoma (FL). METHODS: This retrospective study included all the patients who had undergone FDG-PET/CT during primary diagnosis or relapse of FL between 2010 and 2020 at Oulu University Hospital. RESULTS: The diagnosis changed from an indolent disease to a transformed lymphoma in >10% (7/63) of the patients who underwent diagnostic FDG-PET/CT. The HT risk associated with high SUVmax (>10) was 24% (7 of 29 performed biopsies). Four out of these seven patients with verified HT had no previous clinical suspicion of transformation. CONCLUSION: Our results suggest that a rebiopsy based on a high SUVmax in diagnostic FDG-PET/CT is valuable in detecting clinically unsuspected HT of FL.