Yttrium-90 Ibritumomab Tiuxetan is Cost-Effective Compared to Bendamustine + Rituximab in Low-grade Lymphomas.

BACKGROUND: Yttrium-90 ibritumomab tiuxetan [(90)Y-IT] is a CD20-targeted radio-immunotherapeutic agent. It has shown an excellent therapeutic activity with high tolerability against previously untreated follicular lymphoma (FL) and marginal zone B cell lymphoma (MZL). It is an attractive therapeutic option as the treatment schedule is short and convenient. The aim of our study is to determine the cost-effectiveness of (90)Y-IT in comparison to the standard-of-care bendamustine + rituximab (BR) in the first-line treatment of low-grade FL (LG-FL) and MZL in the real world. PATIENTS AND METHODS: We included all patients who were treated with standard-dose (90)Y-IT for previously untreated LG-FL and MZL at the Mayo Clinic Cancer Center (N = 51). A comparator arm with a historical cohort of previously untreated LG-FL and MZL patients who received BR was used (N = 92). RESULTS: Inverse propensity weighting was utilized to balance the 2 study arms. There were no differences in terms of overall response rate (100% vs. 98%, P = .18), complete response rate (94% vs. 95%, P = .91), or 5 years progression-free survival (76% vs. 75%, P = .63) between patients who received (90)Y-IT and BR, respectively. Within the first year, patients who received (90)Y-IT required an average of 4.5 fewer oncology clinic visits (P < .001), an average of 10 fewer days of therapeutic use (P < .001), and 40% less use of growth factors (P < .001) as compared to the BR group. The direct therapeutic cost of (90)Y-IT treatment was 54% less than that of 6 cycles of BR. CONCLUSION: The findings suggest that (90) Y-IT is more cost-effective than BR and is a viable alternative in up-front management of LG-FL and MZL.

Accuracy and prognostic impact of FDG PET/CT and biopsy in bone marrow assessment of follicular lymphoma at diagnosis: A Nation-Wide cohort study.

BACKGOUND: In the workup of follicular lymphoma (FL), bone marrow biopsy (BMB) assessment is a key component of FLIPI and FLIPI2, the most widely used outcome scores. During the previous decade, several studies explored the role of FDG-PET/CT for detecting nodal and extranodal disease, with only one large study comparing both techniques. METHODS: The aim of our study was to evaluate the diagnostic accuracy and the prognostic impact of both procedures in a retrospective cohort of 299 FL patients with both tests performed at diagnosis. In order to avoid a collinearity bias, FLIPI2 was deconstructed in its founding parameters, and the bone marrow involvement (BMI) parameter separately included as: a positive BMB, a positive PET/CT, the combined "PET/CT and BMB positive" or "PET/CT or BMB positive". These variables were also confronted independently with the POD24 in 233 patients treated with intensive regimens. RESULTS: In the total cohort, bone marrow was involved in 124 and 60 patients by BMB and PET/CT, respectively. In terms of overall survival, age > 60 y.o. and the combined "PET/CT or BMB positive" achieved statistical independence as a prognostic factor. In patients treated with an intensive regimen, only the combined "PET/CT or BMB positive" added prognostic value for a shorter overall survival, when confronted with the POD24. CONCLUSION: Our results show that in FL both BMB and PET/CT should be considered at diagnosis, as their combined assessment provides independent prognostic value in the context of the most widely use clinical scores.

Investigating the inequalities in route to diagnosis amongst patients with diffuse large B-cell or follicular lymphoma in England.

INTRODUCTION: Diagnostic delay is associated with lower chances of cancer survival. Underlying comorbidities are known to affect the timely diagnosis of cancer. Diffuse large B-cell (DLBCL) and follicular lymphomas (FL) are primarily diagnosed amongst older patients, who are more likely to have comorbidities. Characteristics of clinical commissioning groups (CCG) are also known to impact diagnostic delay. We assess the association between comorbidities and diagnostic delay amongst patients with DLBCL or FL in England during 2005-2013. METHODS: Multivariable generalised linear mixed-effect models were used to assess the main association. Empirical Bayes estimates of the random effects were used to explore between-cluster variation. The latent normal joint modelling multiple imputation approach was used to account for partially observed variables. RESULTS: We included 30,078 and 15,551 patients diagnosed with DLBCL or FL, respectively. Amongst patients from the same CCG, having multimorbidity was strongly associated with the emergency route to diagnosis (DLBCL: odds ratio 1.56, CI 1.40-1.73; FL: odds ratio 1.80, CI 1.45-2.23). Amongst DLBCL patients, the diagnostic delay was possibly correlated with CCGs that had higher population densities. CONCLUSIONS: Underlying comorbidity is associated with diagnostic delay amongst patients with DLBCL or FL. Results suggest a possible correlation between CCGs with higher population densities and diagnostic delay of aggressive lymphomas.

Cost-effectiveness of lenalidomide plus rituximab versus rituximab monotherapy in patients with previously treated follicular lymphoma: a societal view.

INTRODUCTION: Efficacy of lenalidomide plus rituximab (R-LEN) compared to rituximab monotherapy (R-mono) for patients with previously treated follicular lymphoma (FL) was investigated in AUGMENT (NCT01938001). Our aim was to evaluate the cost-effectiveness of R-LEN versus R-mono in this setting from a Dutch perspective. AREAS COVERED: Cost-effectiveness was assessed through a partitioned survival model from three perspectives (i.e. societal, healthcare, and societal, including future non-medical costs). Patient-level data from AUGMENT informed effectiveness parameters (i.e. long-term survival) and health state utilities. Resource use and prices were based on AUGMENT and the literature. Clinical experts validated efficacy input parameters and results. Uncertainty was explored through sensitivity and scenario analyses. EXPERT OPINION: R-LEN resulted in 1.7 incremental discounted quality-adjusted life years (QALYs). Total incremental discounted costs were 67,161 EUR from a societal perspective. In conclusion, R-LEN was cost-effective at a willingness-to-pay (WTP) threshold of 50,000 EUR/QALY in the base-case analyses(incremental cost-effectiveness ratio = 40,493 EUR/QALY). Scenario and sensitivity analyses indicated some level of uncertainty regarding this conclusion, depending on the chosen WTP-threshold and perspective.

Transformation Scoring System (TSS): A new assessment index for clinical transformation of follicular lymphoma.

Although histologic analysis is the gold standard for diagnosing follicular lymphoma (FL) transformation, many patients are diagnosed with transformation by clinical factors as biopsy specimens often cannot be obtained. Despite the frequency of clinical diagnosis, no clinical assessment tool has yet been established for FL transformation in the rituximab era. We derived and validated a transformation scoring system (TSS) based on retrospective analyses of 126 patients with biopsy-proven FL and histologic transformation (HT) at two hospitals of the National Cancer Center of Japan. In the derivation set (76 patients), the detailed analyses of the clinical characteristics at disease progression showed that lactate dehydrogenase (LDH) elevation, focal lymph nodal (LN) enlargement, hemoglobin <12 g/dl, and poor performance status (PS) (2-4) were associated with HT. The weights of these variables were decided based on the regression coefficients. Next, we constructed a TSS encompassing the above four factors: LDH, (> upper limit of normal [ULN], ≤ULN ×2) (1 point), (≥ULN ×2) (2 points); focal LN enlargement, (≥3 cm, <7 cm) (1 point), (≥7 cm) (2 points); hemoglobin <12 g/dl (1 point); poor PS (2 points). We identified a high positive predictive value (PPV) (96.4%) and negative predictive value (NPV) (85.4%) for diagnosing HT when a cutoff score of 2 was selected for our TSS. In an external validation set (50 patients), the probability of HT was high with scores ≥2 (PPV, 93.3%; NPV, 82.9%). We developed a TSS that offers a simple, yet, valuable tool, for diagnosing HT, especially in patients who cannot undergo biopsy.

Visible and near-infrared hyperspectral imaging techniques allow the reliable quantification of prognostic markers in lymphomas: A pilot study using the Ki67 proliferation index as an example.

In this study, we examined the suitability of visible and infrared (Vis-NIR) hyperspectral imaging (HSI) for the quantification of prognostic markers in non-Hodgkin lymphoma on the example of the Ki67 proliferation index. Ki67 quantification was done on six follicular lymphomas (FLs) and 12 diffuse large B-cell lymphomas (DLBCLs) by applying classic immunohistochemistry. The Ki67 index was comparatively assessed visually, using HSI-based quantification and a digital imaging analysis (DIA) platform. There was no significant difference between visual assessment (VA), DIA, and HSI in FLs. For DLBCLs, VA resulted in significantly higher Ki67 values than HSI (p = 0.023) and DIA (p = 0.006). No such difference was seen comparing analysis by HSI and DIA (p = 0.724). Cohen's κ revealed a "substantial correlation" of Ki67 values for HSI and DIA in FLs and DLBCLs (κ = 0.667 and 0.657). Here we provide the first evidence that, comparably to traditional DIA, HSI can be used reliably to quantify protein expression, as exemplified by the Ki67 proliferation index. By covering the near-infrared spectrum, HSI might offer additional information on the biochemical composition of pathological specimens, although our study could not show that HSI is clearly superior to conventional DIA. However, the analysis of multiplex immunohistochemistry might benefit from such an approach, especially if overlapping immunohistochemical reactions were possible. Further studies are needed to explore the impact of this method on the analysis and quantification of multiple marker expression in pathological specimens.

Obinutuzumab plus chemotherapy followed by obinutuzumab monotherapy is cost-effective vs. rituximab plus chemotherapy followed by rituximab monotherapy for previously untreated follicular lymphoma patients in the United States.

The GALLIUM trial compared obinutuzumab (GA101, G)-based chemotherapy followed by G monotherapy (G + chemo) for up to two years to rituximab (R)-based chemotherapy followed by R monotherapy (R + chemo) for up to two years in previously untreated follicular lymphoma (FL) patients. We estimated the cost-effectiveness of G + chemo versus R + chemo utilizing GALLIUM trial data and published literature. G + chemo had increased drug costs (undiscounted: $135,200 versus $127,700 for R + chemo), representing a relative increase of 5.9%. However, this was offset by a $6,400 lower cost for disease progression. G + chemo led to increased quality-adjusted life years (QALYs) relative to R + chemo of 0.81 (95% credible range, [CR]: 0.22-1.37), and the overall discounted incremental cost was $1,900 (95% CR: -$7,400 to $8,900). The incremental cost-effectiveness ratio was ∼$2,300 per QALY gained, and the results were highly robust to sensitivity analyses. Treatment with G + chemo compared to R + chemo is cost-effective in previously untreated FL patients in the US.

Obinutuzumab in Combination with Chemotherapy for the First-Line Treatment of Patients with Advanced Follicular Lymphoma : An Evidence Review Group Evaluation of the NICE Single Technology Appraisal.

The National Institute for Health and Care Excellence (NICE), as part of the institute's single technology appraisal (STA) process, invited the company that makes obinutuzumab (Roche Products Limited) to submit evidence of the clinical and cost effectiveness of the drug in combination with chemotherapy, with or without obinutuzumab as maintenance therapy for adult patients with untreated, advanced follicular lymphoma (FL) in the UK. Kleijnen Systematic Reviews Ltd (KSR), in collaboration with Erasmus University Rotterdam, was commissioned to act as the Evidence Review Group (ERG). This paper describes the company's submission, the ERG review, and NICE's subsequent decisions. The clinical evidence was derived from two phase III, company-sponsored, randomised, open-label studies. Most evidence on obinutuzumab was based on the GALLIUM trial that compared obinutuzumab in combination with chemotherapy as induction followed by obinutuzumab maintenance monotherapy with rituximab in combination with chemotherapy as induction followed by rituximab maintenance monotherapy in previously untreated patients with FL (grades 1-3a). Long-term clinical evidence was based on the PRIMA trial, studying the benefit of two years of rituximab maintenance after first-line treatment in patients with FL. The cost-effectiveness evidence submitted by the company relied on a partitioned survival cost-utility model, implemented in Microsoft® Excel. The base-case incremental cost-effectiveness ratio (ICER) presented in the company submission was <£20,000 per quality-adjusted life-year (QALY) gained. Although the ERG concluded that the economic model met the NICE reference case to a reasonable extent, some errors were identified and several assumptions made by the company were challenged. A new base-case scenario produced by the ERG suggested an ICER that was higher than the company base case, but still below £30,000 per QALY gained. However, some ERG scenario analyses were close to or even above the threshold. This was the case in particular for assuming a treatment effect that did not extend beyond trial follow-up. These results led to an initial negative recommendation by the appraisal committee. Subsequently, the company submitted a revised base case focusing on patients at intermediate or high risk of premature mortality. Simultaneously, a further price discount for obinutuzumab was granted. In addition to the company's revised base case, the ERG suggested a restriction of the treatment effect to 5 years and implemented biosimilar uptake and cheaper prices for rituximab. All of these adjustments did not exceed £30,000 per QALY gained and therefore the use of obinutuzumab for patients with advanced FL and a Follicular Lymphoma International Predictive Index (FLIPI) score of two or more could be recommended.

Canine Splenic Nodular Lymphoid Lesions: Immunophenotyping, Proliferative Activity, and Clonality Assessment.

Canine splenic lymphoid nodules are currently classified as indolent lymphomas (marginal zone lymphoma [MZL], mantle cell lymphoma [MCL]) or nodular hyperplasia (lymphoid [LNH] or complex [CNH] type). Their differentiation can be difficult on morphology, because of similar histologic appearance and poorly defined diagnostic criteria. Thirty-five surgical samples of splenic lymphoid nodules were reviewed in order to assess the diagnostic contribution of immunophenotyping, proliferative activity and clonality (PARR) in differentiating between hyperplastic and neoplastic lesions. Proliferative activity was evaluated by double immunolabeling for Ki-67 and CD79a, in order to separately assess the proliferative activity of B cells and non-B cells. Definitive diagnoses were MZL ( n = 11), MCL ( n = 4), LNH ( n = 10), and CNH ( n = 10). The overall concordance between histology and PARR was above 90%. Lymphomas had a significantly higher percentage of CD79a-positive areas (mean, 36.30%; P = .0004) and a higher B-cell proliferative activity (median Ki-67 index, 5.49%; P = .0012). The threshold value most accurately predicting a diagnosis of lymphoma was ≥28% of B-cell areas, with a Ki-67 index above 3%. Dogs were monitored for a median follow-up time of 870 days (IQR, 569-1225), and no relapses were documented. Overall median survival time was 1282 days. The combination of histology, immunohistochemistry and PARR can improve the diagnostic accuracy for canine splenic lymphoid nodules, although the long-term behavior of these lesions appears similar.

Management of untreated advanced stage follicular lymphoma: Role of patient discernment.

Follicular lymphoma is the most common indolent non-Hodgkin lymphoma. Advanced stage disease is common at diagnosis. The timing of treatment for follicular lymphoma is best approached by considering the combination of presence or absence of symptoms along with estimation of tumor burden. Upfront treatment strategies should take into initial presentation variables, pace of disease progression and goals of care after discussion with the patient. Treatment approaches remain diverse and patient discernment is paramount.

Bone marrow biopsies do not impact response assessment for follicular lymphoma patients treated on clinical trials.

Clinical trials enrolling follicular lymphoma (FL) patients typically require bone marrow biopsies (BMBs) at baseline and at a subsequent point if complete response is achieved. These procedures are painful, take time and add cost. We hypothesized that BMBs do not provide information significant for response assessment in most follicular lymphoma patients on clinical trials. We identified 99 patients treated on clinical trials for follicular lymphoma between 2000 and 2016. BMBs resulted in a possible response assessment change in 1·0% of patients (95% confidence interval: 0·0-5·5%). We conclude that mandatory BMBs at baseline and for response assessment are unnecessary in clinical trials for follicular lymphoma.

(18) F-FDG PET-CT and trephine biopsy assessment of bone marrow involvement in lymphoma.

The ability of positron emission tomography-computerized tomography (PET-CT) to accurately detect bone marrow involvement (BMI) has been suggested in Hodgkin lymphoma (HL) and diffuse large B-cell lymphoma (DLBCL), but its abilities in other histologies is less established. The aim of this retrospective study was to confirm the role of PET-CT in detecting BMI in DLBCL and HL, and to explore its usefulness in other subtypes. Of the 149 newly diagnosed patients, common subtypes included DLBCL, follicular lymphoma (FL) and HL. In DLBCL, the sensitivity and specificity of PET-CT at diagnosis were 75% and 92%. In FL, the sensitivity and specificity of PET-CT were 67% and 85% at diagnosis, and 73% and 89% at relapse. In HL, the sensitivity and specificity were 100% and 74%. PET-CT was able to detect BMI in patients with negative biopsies. Most of the patients in which PET-CT failed to identify BMI were already advanced stage by imaging. In this analysis, PET-CT was highly accurate for detecting BMI at diagnosis in DLBCL and HL and highly specific in FL at diagnosis and relapse. Results also suggested the diagnostic advantage of PET-CT over bone marrow biopsy in detecting BMI. Prospective evaluation is necessary and may eliminate biopsies in future patients.

PET/CT Assessment of Follicular Lymphoma and High Grade B Cell Lymphoma - Good Correlation with Clinical and Histological Features at Diagnosis.

BACKGROUND: Follicular lymphoma is a common type of non-Hodgkin's lymphoma observed in Western countries. The diagnosis of this disease is based primarily on morphological and immunohistochemical assessment. The proliferative index Ki67 correlates with histological grading and clinical aggressiveness. Currently, positron emission tomography/computed tomography scanning are not applied for standard staging at diagnosis of follicular lymphoma and its use is limited to those patients for whom the identification of residual disease is crucial for therapeutic decisions and only when transformation to a high-grade lymphoma is suspected. OBJECTIVES: Our aim was to assess whether a correlation exists between the maximal standardized uptake value (SUVmax) at the biopsy site as detected via positron emission tomography/computed tomography and pathological (Ki67 and FL histological grade) and clinico-biological features (e.g. LDH, beta-2-microglobulin, Ann Arbor stage and FL International Prognostic Index--FLIPI) at diagnosis. MATERIAL AND METHODS: We retrospectively identified 16 patients during the previous 3.5 years in whom node biopsies were guided, taking into account the SUVmax as detected upon PET/CT scan at diagnosis. The results of these biopsies were diagnostic of follicular lymphoma. We also included 6 patients with high grade B cell lymphoma: 5 diffuse large B cell lymphoma (DLBCL) and 1 FL 3b histological grade. A 2-tailed non-parametric Spearman's correlation analysis of the SUVmax with Ki67, histological grade, LDH and b-2-microglobuline was performed. RESULTS: The Ki67 (r=0.73) and follicular lymphoma histological grade (r=0.75) at the biopsy displayed a significant correlation with the SUVmax at diagnosis (p<0.01). CONCLUSIONS: Our results suggest that SUV detected by positron emission tomography/computed tomography correlates with histological grade in follicular lymphoma/high grade B cell lymphoma, Ki67 and LDH. Positron emission tomography/computed tomography should be considered for guiding lymph node biopsy when transformation to a high-grade B cell lymphoma is suspected.

Frontline rituximab monotherapy induction versus a watch and wait approach for asymptomatic advanced-stage follicular lymphoma: A cost-effectiveness analysis.

BACKGROUND: A watch and wait (WW) strategy is the standard of care for patients with asymptomatic advanced-stage follicular lymphoma. Recent data have demonstrated an improvement in the time to progression with rituximab induction (RI) with or without rituximab maintenance (RM) in comparison with a WW strategy wait in such patients. It remains unclear whether this is a cost-effective strategy. METHODS: A Markov decision analysis model was developed to compare the clinical outcomes, costs, and cost-effectiveness of RI (4 weekly doses) plus RM (12 doses every 2 months), RI (4 weekly doses), and a WW strategy for patients newly diagnosed with low-burden, asymptomatic advanced-stage follicular lymphoma over a lifetime horizon. Baseline probabilities and utilities were derived from a systematic review of published studies, and they were evaluated on a 6-month cycle. A Canadian public health payer's perspective was adopted, and costs were presented in 2012 Canadian dollars. RESULTS: RI was the cheapest strategy. It was less costly at $59,953 versus $67,489 for the RM arm and $75,895 for the WW arm. It was also associated with a slightly lower quality-adjusted life expectancy at 6.16 quality-adjusted life years (QALYs) versus 6.28 QALYs for the RM strategy but was superior to WW (5.71 QALYs). In sensitivity analyses of key variables, this effectiveness was sensitive to the probability of first and second progression in the RI arm, and this indicated relatively neutral effectiveness between the 2 rituximab arms. CONCLUSIONS: RI without maintenance for asymptomatic advanced-stage follicular lymphoma is the preferred strategy: it minimizes costs per patient over a lifetime horizon.

Cost-effectiveness of rituximab as maintenance treatment for relapsed follicular lymphoma: results of a population-based study.

OBJECTIVES: On the basis of two population-based registries, our study aims to calculate the real-world cost-effectiveness of rituximab maintenance compared with observation in relapsed or refractory follicular lymphoma patients who responded to second-line chemotherapy. METHODS: Data were obtained from the EORTC20981 trial, the Netherlands Cancer Registry and two population-based registries. A Markov model was developed to calculate cost per life year gained (LYG) and quality-adjusted life years (QALYs) for three scenarios. RESULTS: Our real-world patients were (62 years) 6 to 7 years older and had higher complete response rates to second-line chemotherapy than the trial population. Differences between the real-world rituximab and observation group were observed for second-line chemotherapy and disease progression. Groups were more balanced after using propensity matching. Relying entirely on updated trial results (scenario1) in combination with local cost data resulted in ratios of €11,259 per LYG and €12,655 per QALY. For scenario2, consisting of trial efficacy and matched real-world costs, ratios of €21,202 per LYG and €23,821 per QALY were calculated. Using real-world matched evidence (scenario3) for both effectiveness and costs showed ratios of €10,591 per LYG and €11,245 per QALY. CONCLUSION: Although differences in real-world and trial population were found, using real-world data as well as results from long-term trial follow-up showed favourable ICERs for rituximab maintenance. Nevertheless, results showed that caution is required with data synthesis, interpretation and generalisability of results. As different scenarios provide answers to different questions, we recommend healthcare decision-makers to recognise the importance of calculating several cost-effectiveness scenarios.

Association of quantitative assessment of the intrafollicular proliferation index with outcome in follicular lymphoma.

The role of the proliferation index (PI) as an outcome predictor in follicular lymphoma (FL) isn't clear. We have previously demonstrated that quantitative image analysis (QIA) is a robust tool for PI determination and the present study aimed to determine the significance of the PI for outcome in low-grade FL. One hundred and twenty-nine patients with grade 1-2 FL were retrospectively analysed. Slides were scanned digitally and follicle/tumour-involved areas were annotated. The intrafollicular PI was estimated by analysing a median of 10 follicles per case. Patients were divided into two groups: PI < 30%, PI ≥ 30% and clinical outcome was analysed. Among the 129 patients analysed, intrafollicular PI ranged from 0·6 to 63·2% with a median of 23·3%. Overall survival was not influenced by PI group. Among those patients initially observed, intrafollicular PI < 30% was associated with longer time to first therapy compared to patients with a PI ≥ 30%. In the group of patients that were treated at diagnosis, PI was not predictive of time to treatment failure (TTTF). Intrafollicular PI is an important predicator of TTFT for patients who are candidates for observation. Further confirmation in an independent cohort of patients is necessary to determine the clinical validity of the results.

End-therapy positron emission tomography for treatment response assessment in follicular lymphoma: a systematic review and meta-analysis.

PURPOSE: Use of 2[(18)F]fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET) in postchemotherapy response assessment in follicular lymphoma is still a controversial issue. Here, we conducted the first systematic review and meta-analysis to determine the predictive value of FDG-PET in predicting outcome after chemotherapy of follicular lymphoma. EXPERIMENTAL DESIGN: Comprehensive literature search in Ovid-MEDLINE and EMBASE databases was performed to identify studies which evaluate predictive value of end-therapy PET and/or computed tomography (CT) in patients with follicular lymphoma. To quantitatively compare the predictive value of PET and CT, pooled hazard ratios (HRs) comparing progression-free survival (PFS) between patients with positive and negative results were adopted as the primary indicators for meta-analysis. To explore the efficiency in determining complete remission (CR), pooled CR rates of PET- and CT-based response criteria were calculated. Pooling of these parameters was based on the random-effects model. RESULTS: Review of 285 candidate articles identified eight eligible articles with a total of 577 patients for qualitative review and meta-analysis. The pooled HRs of end-therapy PET and CT were 5.1 [95% confidence interval (CI), 3.7-7.2] and 2.6 (95% CI, 1.2-5.8), respectively, which implies that PET is more predictive of PFS after chemotherapy than CT. The pooled CR rates of PET- and CT-based response criteria were 75% (95% CI, 70-79%) and 63% (95% CI, 53-73%), respectively, which implies that PET is more efficient in distinguishing CR (without residual disease) from other states with residual disease. In addition, qualitative systematic review indicates the same findings. CONCLUSIONS: Consistent evidence favoring PET-based treatment assessment should be considered in the management of patients with follicular lymphoma.

Oral follicular lymphomas. A short report of 8 cases with assessment of the IGH/BCL2 gene fusion with fluorescence in situ hybridization.

OBJECTIVE: To present the clinicopathologic features and confirm the presence of the IGH/BCL2 gene fusion in an oral follicular lymphoma (OFL) series. STUDY DESIGN: Cases of OFLs were retrieved from a data base of non-Hodgkin lymphomas (NHL). Fluorescence in situ hybridization (FISH) was performed to confirm the IGH/BCL2 fusion. RESULTS: Eight (8.7%) of 92 NHL were OFLs. Six (75%) patients were male and two female (mean age: 73.4 ± 14.8). The most frequent site was the palate. Five of the 8 patients are alive and without disease. Five (three grade 1 and two grade 2) of six successfully hybridized cases revealed the IGH/BCL2 gene fusion. The sixth case, a grade 3 follicular lymphoma (FL), demonstrated multiple BCL2 signals without IGH/BCL2 fusion. CONCLUSIONS: OFLs exhibit an indolent clinical behavior. In the present study, 5/6 cases in which FISH was successful had an IGH/BCL2 fusion as would result from the t(14; 18)(q32; q21) translocation commonly seen in FL of extraoral sites.