FDG‐PET/CT in the management of lymphomas: current status and future directions

FDG‐PET/CT is the current state‐of‐the‐art imaging in lymphoma and plays a central role in treatment decisions. At diagnosis, accurate staging is crucial for appropriate therapy selection: FDG‐PET/CT can identify areas of lymphoma missed by CT alone and avoid under‐treatment of patients with advanced disease stage who would have been misclassified as having limited stage disease by CT. Particularly in Hodgkin lymphoma, positive interim FDG‐PET/CT scans are adversely prognostic for clinical outcomes and can inform PET‐adapted treatment strategies, but such data are less consistent in diffuse large B‐cell lymphoma. The use of quantitative FDG‐PET/CT metrics using metabolic tumour volume, possibly in combination with other biomarkers, may better define prognostic subgroups and thus facilitate better treatment selection. After chemotherapy, FDG‐PET/CT response is predictive of outcome and may identify a subgroup who benefit from consolidative radiotherapy. Novel therapies, in particular immunotherapies, exhibit different response patterns than conventional chemotherapy, which has led to modified response criteria that take into account the risk of transient pseudo‐progression. In relapsed lymphoma, FDG‐PET/CT after second‐line therapy and prior to high‐dose therapy is also strongly associated with outcome and may be used to guide intensity of salvage therapy in relapsed Hodgkin lymphoma. Currently, FDG‐PET/CT has no role in the routine follow‐up after complete metabolic response to therapy, but it remains a powerful tool for excluding relapse if patients develop clinical features suggestive of disease relapse. In conclusion, FDG‐PET/CT plays major roles in the various phases of management of lymphoma and constitutes a step towards the pursuit of personalized treatment.     

Risk-adapted BEACOPP regimen can reduce the cumulative dose of chemotherapy for standard and high-risk Hodgkin lymphoma with no impairment of outcome

Therapy of Hodgkin disease (HD) is designed to prolong progression-free survival and minimize toxicity. The best regimen to achieve this has not yet been defined. A total of 108 patients with newly diagnosed HD and adverse prognostic factors were prospectively studied between 1999 and 2004. They were assigned to therapy according to defined risk stratification. Patients were defined depending on the International Prognostic Score (IPS). Those with IPS of 3 or higher received 2 cycles of escalated therapy, including bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone (BEACOPP [EB]). All others received 2 cycles of standard BEACOPP (SB). Subsequent therapy was prospectively assigned following 2 cycles according to results of early interim 67Ga or positron emission tomography/computed tomography (PET/CT). Following a positive interim scan, 4 cycles of EB were administered, whereas 4 cycles of SB were given to patients with a negative scan. The complete remission rate, the 5-year event-free survival (EFS), and overall survival (OS) rates were 97%, 85% and 90%, respectively. Relapse or progression occurred in 27% of patients with interim positive PET/CT versus 2.3% of negative scans (P<.02). Early interim fluorine-18 2-fluoro-2-deoxy-D-glucose (FDG)-PET/CT is a useful tool for adjustment of chemotherapy on an individual basis. Similar EFS and OS rates were observed for patients in both risk groups.     

Management of children with high‐risk Hodgkin lymphoma

Most children and adolescents with newly diagnosed high‐risk Hodgkin lymphoma (HL) will achieve remission and cure with conventional chemotherapy with or without radiation therapy. However, these therapies can lead to long‐term side effects. Therapy is titrated on the basis of risk group stratification using clinical prognostic factors and, in most cases, then refined through assessment of interim or end of chemotherapy response, primarily using functional imaging with fluorodeoxyglucose positron emission tomography. No study has clearly demonstrated the factors that are sufficient in identifying the patients at highest risk for relapse that may benefit from therapy intensification. This review summarizes recent clinical trials in paediatric high‐risk HL, along with key findings from studies in adults with high‐risk HL that are applicable to the paediatric population. New directions in prognostic classification and targeted therapies are reviewed. Considerations for clinical practice at the current time outside the clinical trial setting are provided.     

Treatment of newly diagnosed advanced stage Hodgkin lymphoma

ABVD continues to be the standard of care for patients with advanced stage Hodgkin Lymphoma (HL) although escalated BEACOPP has improved survival in one randomized controlled trial (RCT). More intensive regimens have higher rates of acute and late toxicities and this poses significant issues for patients. Consolidation strategies such as radiation or autologous stem cell transplantation (ASCT) have not demonstrated an improvement in overall survival in RCTs. Novel technology and therapeutics are leading us to investigate new questions. Interim FDG-PET scanning is now being tested in prospective studies. Small, typically retrospective trials suggest that interim PET scans are independent markers of outcome and current trials are piloting the use of PET-adapted therapy. Targeted therapeutics have been evaluated in the relapsed and refractory setting and now show promising single agent activity. Agents including brentuximab vedotin (a conjugated anti-CD30 monoclonal antibody) and the histone deacetylase inhibitor panabinostat have reported encouraging single agent activity and a large study of brentuximab vedotin maintenance post ASCT is underway. Combination and maintenance trials are planned or ongoing in the primary treatment setting that will hopefully improve on the treatment standards of the past decade. This review will discuss the current standard of care in advanced stage HL, summarize some of the current data regarding interim FDG-PET scans and will conclude with some issues related to the development of new agents that are likely to be involved in the future standard of therapy.     

Early‐stage Hodgkin lymphoma outcomes after combined modality therapy according to the post‐chemotherapy 5‐point score: can residual pet‐positive disease be cured with radiotherapy alone?

Early‐stage classical Hodgkin lymphoma (HL) patients are evaluated by an end‐of‐chemotherapy positron emission tomography‐computed tomography (eoc‐PET‐CT) after doxorubicin, bleomycin, vinblastine and dacarbazine (ABVD) and before radiation therapy (RT). We determined freedom from progression (FFP) in patients treated with ABVD and RT according to the eoc‐PET‐CT 5‐point score (5PS). Secondarily, we assessed whether patients with a positive eoc‐PET‐CT (5PS of 4–5) can be cured with RT alone. The cohort comprised 174 patients treated for stage I‐II HL with ABVD and RT alone. ABVD was given with a median of four cycles and RT with a median dose of 30·6 Gy. Five‐year FFP was 97%. Five‐year FFP was 100% (0 relapses/98 patients) for patients with a 5PS of 1–2, 97% (2/65) for a 5PS of 3, 83% (1/8) for a 5PS of 4, and 67% (1/3) for a 5PS of 5 (P < 0·001). Patients with positive eoc‐PET‐CT scans who were selected for salvage RT alone had experienced a very good partial response to ABVD. Risk factors for recurrence in this subgroup included a small reduction in tumour size and a ‘bounce’ in ≥1 PET‐CT parameter (reduction then rise from interim to final scan). Thus, a positive eoc‐PET‐CT is associated with inferior FFP; however, appropriately selected patients can be cured with RT alone.     

Modification of initial therapy in early and advanced Hodgkin lymphoma,based on interim PET/CT is beneficial: a prospective multicentre trial of 355 patients

This multicentre study evaluated 5‐year progression‐free (PFS) and overall survival (OS) in early and advanced Hodgkin lymphoma (HL), where therapy was individualized based on initial prognostic factors and positron emission tomography‐computed tomography performed after two cycles (PET‐2). Between September 2006 and August 2013, 359 patients aged 18–60 years, were recruited in nine Israeli centres. Early‐HL patients initially received ABVD (adriamycin, bleomycin, vinblastine, dacarbazine) ×2. Depending on initial unfavourable prognostic features, PET‐2‐positive patients received additional ABVD followed by involved‐site radiotherapy (ISRT). Patients with negative PET‐2 and favourable disease received ISRT or ABVD ×2; those with unfavourable disease received ABVD ×2 with ISRT or, alternatively, ABVD ×4. Advanced‐HL patients initially received ABVD ×2 or escalated BEACOPP (bleomycin, etoposide, adriamycin, cyclophosphamide, vincristine, procarbazine, prednisone; EB) ×2 based on their international prognostic score (≤2 or ≥3). PET‐2‐negative patients further received ABVD ×4; PET‐2‐positive patients received EB ×4 and ISRT to residual masses. With a median follow‐up of 55 (13–119) months, 5‐year PFS was 91% and 69% for PET‐2‐negative and positive early‐HL, respectively; 5‐year OS was 100% and 95%, respectively. For advanced‐HL, the PFS was 81% and 68%, respectively (P = 0·08); 5‐year OS was 98% and 91%, respectively. PET‐2 positivity is associated with inferior prognosis in early‐HL, even with additional ABVD and ISRT. Advanced‐HL patients benefit from therapy escalation following positive PET‐2. EB can be safely de‐escalated to ABVD in PET‐2‐negative patients.     

Pretransplant FDG‐PET in aggressive non‐Hodgkin lymphoma: systematic review and meta‐analysis

This study aimed to systematically review and meta‐analyze the value of pretransplant FDG‐PET in predicting outcome after autologous stem cell transplantation in aggressive non‐Hodgkin lymphoma. MEDLINE was systematically searched; included studies were methodologically assessed and meta‐analyzed, when possible. Overall methodological quality of included studies (n = 11) was poor, with moderate risk of bias in the domains of study participation (n = 7) and prognostic factor measurement (n = 7), and high risk of bias in the domains of outcome measurement (n = 10), and study confounding (n = 11). In all aggressive non‐Hodgkin lymphomas, pooled sensitivity and specificity were 54.0% and 73.1% in predicting treatment failure, and 54.5% and 68.7% in predicting death. Because of interstudy heterogeneity, additional subgroup analyses were performed. In newly diagnosed aggressive non‐Hodgkin lymphoma, pooled sensitivity and specificity were 20.0% and 70.0% in predicting treatment failure, and 8.3% % and 30.5% in predicting death. In refractory/relapsed aggressive non‐Hodgkin lymphoma, pooled sensitivity and specificity were 68.1% and 72.1% in predicting treatment failure, and 77.3% and 69.6% in predicting death. At present, pretransplant FDG‐PET cannot be recommended in aggressive non‐Hodgkin lymphoma, because available studies suffer from major methodological flaws, and reported prognostic estimates are low (i.e., poor in newly diagnosed and moderate in refractory/relapsed aggressive non‐Hodgkin lymphoma).     

Minimal residual disease in non‐Hodgkin lymphoma – current applications and future directions

Non‐Hodgkin Lymphomas (NHLs) are a heterogeneous group of tumours with distinct treatment paradigms, but in all cases the goal of treatment is to maximize quality and duration of remission while minimizing therapy‐related toxicity. Identification of persistent disease or relapse is most often the trigger to intensify or re‐initiate anti‐neoplastic therapy, respectively. In the current era of NHL treatment, this determination is mostly based on imaging and clinical evaluations, tools with imperfect sensitivity and specificity. The availability of minimal residual disease (MRD) monitoring could transform treatment paradigms by allowing intensification of treatment in at‐risk patients or early intervention for impending relapse. Novel methods based on polymerase chain reaction and next‐generation sequencing are now being studied in NHL with promising results. This review outlines the current status of the field in the use of MRD techniques for diffuse large B‐cell lymphoma, mantle cell lymphoma and follicular lymphoma. Specifically, we address their demonstrated and potential clinical utility in risk stratification, monitoring of remission status, and guiding interim and post‐treatment escalation. Future applications of these techniques could identify novel markers of MRD, improve initial treatment selection, guide treatment escalation or de‐escalation, and allow for real‐time monitoring of patterns of clonal evolution, which together could redefine NHL treatment paradigms.     

Recent treatment advances in Hodgkin lymphoma: a concise review

The majority of patients with Hodgkin lymphoma enjoy durable remissions following front‐line treatment. This typically involves combination chemotherapy with or without radiotherapy. A significant minority of patients experience relapsed/refractory disease, of whom only approximately half can be ‘salvaged’ with conventional second‐line treatments. Until recently, for those patients either failing or who are not fit for salvage, there have been few curative alternatives. Furthermore, there is a significant risk of delayed treatment complications to conventional therapies, including secondary malignancies and cardiac disease. However, novel targeted therapies are producing excellent results in clinical trials. They provide additional treatment options for those with relapsing/refractory disease; they may have potential in front‐line therapy. The anti‐CD30 antibody brentuximab vedotin (BV) has been tested as monotherapy and in combination in a variety of clinical settings, including in relapsed/refractory patients and as consolidative therapy following standard second‐line therapy. Nivolumab and pembrolizumab, currently used in other malignancies that are known to utilise the programmed death pathway for survival, have shown outstanding results when used as single agents in heavily pre‐treated (including BV refractory) patients. Individualising and adapting a patient's treatment course, whether augmenting or rationalising therapy, based on an interim positron emission tomography/computed tomography response is an important strategy currently under exploration to minimise toxicity while maximising response. Further work is needed to explore clinical and biological factors associated with improved outcomes. Knowledge of these factors combined with the movement of novel therapies into the front‐line setting will enable individualised therapy to enhance clinical responses and minimise toxicities.     

The role of FDG‐PET/CT in the evaluation of residual disease in paediatric non‐Hodgkin lymphoma

¹⁸F‐labelled–fluorodeoxyglucose positron emission tomography (FDG‐PET) findings are challenging to interpret for residual disease versus complete response in paediatric patients with non‐Hodgkin lymphoma (NHL). A biopsy is often warranted to confirm the presence or absence of viable tumour if there is clinical or radiographic evidence of residual disease. In this study, we compared conventional imaging and FDG‐PET/computerized tomography (CT) findings with biopsy results in 18 children with NHL. Our goal was to provide additional data to establish more reliable criteria for response evaluation. Residual disease was suspected after conventional imaging alone in eight patients, after FDG‐PET/CT alone in three and after both modalities in seven patients. Biopsy confirmed the presence of viable tumour in two patients. Two additional patients experienced progressive disease or relapse. The sensitivity and negative predictive value of FDG‐PET/CT using the London criteria to indicate residual tumour detectable by biopsy were 100%, but specificity was low (60%), as was the positive predictive value (25%). Thus, in this study, a negative FDG‐PET/CT finding was a good indicator of complete remission. However, because false‐positive FDG‐PET/CT findings are common, biopsy and close monitoring are required for accurate determination of residual disease in individual patients.     

Improved survival for relapsed diffuse large B cell lymphoma is predicted by a negative pre‐transplant FDG‐PET scan following salvage chemotherapy

The utility of ^[18F]fluoro‐2‐deoxy‐ d ‐glucose positron‐emission tomography (FDG‐PET) for predicting outcome after autologous stem cell transplantation (ASCT) for diffuse large B cell lymphoma (DLBCL) is uncertain – existing studies include a range of histological subtypes or have a limited duration of follow‐up. Thirty‐nine patients with primary‐refractory or relapsed DLBCL with pre‐ASCT PET scans were analysed. The median follow‐up was 3 years. The 3‐year progression‐free survival (PFS) for patients with positive PET scans pre‐ASCT was 35% vs. 81% for those who had negative PET scans (P = 0·003). The overall survival (OS) in these groups was 39% and 81% (P = 0·01), respectively. In a multivariate analysis, PET result, number of salvage cycles and the presence of relapsed or refractory disease were shown to predict a longer PFS; PET negativity (P = 0·04) was predictive of a longer OS. PET is useful for defining those with an excellent prognosis post‐ASCT. Although those with positive scans can still be salvaged with current treatments, PET may useful for selecting patients eligible for novel consolidation strategies after salvage therapies.     

Front‐line management of indolent non‐Hodgkin lymphoma in Australia. Part 2: mantle cell lymphoma and marginal zone lymphoma

Mantle cell lymphoma (MCL) and the marginal zone lymphoma (MZL) subtypes (nodal MZL, extra‐nodal MZL of mucosa‐associated lymphoid tissue (MALT lymphoma) and splenic MZL) are uncommon lymphoma subtypes, accounting for less than 5–10% of all non‐Hodgkin lymphoma. The evidence base for therapy is therefore limited and enrolment into clinical trials is preferred. Outcomes for patients with MCL have been steadily improving mainly due to the adoption of more intense strategies in younger patients, the use of rituximab maintenance and the recent introduction of bendamustine in older patients. MZL is a more heterogeneous group of cancer with both nodal, extra‐nodal and splenic subtypes. Extranodal MZL may be associated with autoimmune or infectious aetiologies, and can respond to eradication of the causative pathogen. Proton pump inhibitor plus dual antibiotics in Helicobacter pylori positive gastric MALT lymphoma is curative in many patients. Watchful waiting is appropriate in most patients with asymptomatic advanced stage disease, which tends to behave in a particularly indolent manner. Other options for symptomatic disease include splenectomy, chemoimmunotherapy with rituximab and, more recently, targeted therapies.     

F‐18 FDG‐PET predicts outcomes for patients receiving total lymphoid irradiation and autologous blood stem‐cell transplantation for relapsed and refractory Hodgkin lymphoma

Total lymphoid irradiation (TLI) followed by high‐dose chemotherapy and autologous haematopoietic stem cell transplant (aHSCT) is an effective strategy for patients with relapsed/refractory classical Hodgkin lymphoma (HL). We report outcomes for patients with relapsed/refractory HL who received TLI followed by high‐dose chemotherapy and aHSCT. Pre‐transplant fludeoxyglucose positron emission tomography (FDG‐PET) studies were scored on the 5‐point Deauville scale. Of 51 patients treated with TLI and aHSCT, 59% had primary refractory disease and 63% had active disease at aHSCT. The 10‐year progression‐free survival (PFS) and overall survival (OS) for all patients was 56% and 54%, respectively. Patients with complete response (CR) by PET prior to aHSCT had a 5‐year PFS and OS of 85% and 100% compared to 52% and 48% for those without CR (P = 0·09 and P = 0·007, respectively). TLI and aHSCT yields excellent disease control and long‐term survival rates for patients with relapsed/refractory HL, including those with high‐risk disease features. Achievement of CR with salvage therapy is a powerful predictor of outcome.     

Utility of interim and end‐of‐treatment PET/CT in peripheral T‐cell lymphomas: A review of 124 patients

According to the updated guidelines for imaging in lymphoma, 18F‐FDG positron emission tomography/computed tomography (PET/CT) is recommended for staging and evaluation of treatment response in FDG‐avid lymphomas. The purpose of the study was to evaluate the utility of PET/CT in nodal peripheral T‐cell lymphomas (PTCL). Patients with newly diagnosed nodal PTCL (peripheral T‐cell lymphoma NOS, anaplastic large‐cell lymphoma, or angioimmunoblastic T‐cell lymphoma) seen at five Danish hematology centers during the period 2006 to 2012 were included, if they had been pretherapeutically staged with PET/CT. Medical records were reviewed for baseline clinical and follow‐up information. Staging, interim (I‐PET), and end‐of‐treatment PET/CT (E‐PET) studies were centrally reviewed, and reported using the Deauville 5‐point score (DS). A total of 124 patients fulfilled the inclusion criteria. The median age was 58 years, and 88% received CHOP/CHOP‐like therapy. Five years PFS and OS of the study population was 36.8% (95% CI 27.3–46.4) and 49.7% (95% CI 38.9–59.6), respectively. The presence of PET/CT‐ascertained lung and/or liver involvement was associated with a worse outcome. The sensitivity of PET/CT for detecting biopsy‐defined bone marrow involvement was only 18% (95% CI 4–43). An interim DS >3 was not prognostic for worse OS and PFS among CHOP/CHOP‐like treated patients in uni‐ or multivariate analyses. A DS >3 after treatment predicted a worse prognosis. In conclusion, I‐PET was not predictive of outcome in CHOP/CHOP‐like treated PTCL patients when using the DS. Prospective studies are needed to determine the optimal use of PET/CT in PTCL including the role of quantitative PET/CT analysis. Am. J. Hematol. 90:975–980, 2015. © 2015 Wiley Periodicals, Inc.     

Hodgkin lymphoma: 2016 update on diagnosis,risk‐stratification,and management

Disease overview : Hodgkin lymphoma (HL) is an uncommon B‐cell lymphoid malignancy affecting 9,050 new patients annually and representing approximately 11.2% of all lymphomas in the United States. Diagnosis: HL is composed of two distinct disease entities; the more commonly diagnosed classical HL and the rare nodular lymphocyte predominant HL. Nodular sclerosis, mixed cellularity, lymphocyte depletion, and lymphocyte‐rich HL are subgroups under the designation of classical HL. Risk stratification: An accurate assessment of the stage of disease in patients with HL is critical for the selection of the appropriate therapy. Prognostic models that identify patients at low or high risk for recurrence, as well as the response to therapy as determined by positron emission tomography (PET) scan, are used to optimize therapy. Risk‐Adapted Therapy: Initial therapy for HL patients is based on the histology of the disease, the anatomical stage and the presence of poor prognostic features. Patients with early stage disease are typically treated with combined modality strategies utilizing abbreviated courses of combination chemotherapy followed by involved‐field radiation therapy, while those with advanced stage disease receive a longer course of chemotherapy often without radiation therapy. Management of relapsed/refractory disease: High‐dose chemotherapy (HDCT) followed by an autologous stem cell transplant (ASCT) is the standard of care for most patients who relapse following initial therapy. For patients who fail HDCT with ASCT, brentuximab vedotin, PD‐1 blockade, nonmyeloablative allogeneic transplant or participation in a clinical trial should be considered. Am. J. Hematol. 91:435–442, 2016. © 2016 Wiley Periodicals, Inc.     

Hodgkin lymphoma: a negative interim‐PET cannot circumvent the need for end‐of‐treatment‐PET evaluation

We examined the outcome of a cohort of patients with Hodgkin lymphoma (HL) in order to assess if fluorodeoxyglucose (FDG) positron emission tomography–computed tomography (PET/CT) at the end of treatment (end‐PET) can be omitted when the interim PET (int‐PET) is negative. Seventy‐six ABVD(adriamycin, bleomycin, vinblastine, dacarbazine)‐treated patients were retrospectively included. No change in treatment was made on the basis of int‐PET results. Suspicious foci on end‐PET received biopsy confirmation whenever possible. Median follow‐up was 58·9 months. Uptake on int‐PET higher than liver (scores 4–5) was rated positive according to the Lugano classification, while a positive end‐PET corresponded to scores 3, 4 and 5. Fifteen patients had treatment failure. Sensitivity, specificity, positive predictive value (PPV), negative predictive value and accuracy of int‐PET were 46·7%, 85·2%, 43·8%, 86·7% and 77·6%, respectively. For end‐PET the figures were: 80%, 93·4%, 75%, 95% and 90·8%. Eight patients with negative int‐PET had treatment failure; six of them were identified as non‐responders with end‐PET. The 5‐year progression‐free survival (PFS) was 87% for patients with negative int‐PET versus 56% with positive int‐PET. The 5‐year PFS was 96% with negative end‐PET versus 23% with positive end‐PET. The prognostic information from int‐PET as regards PFS (log‐rank test P = 0·0048) was lower than that provided by end‐PET (P < 0·0001). Int‐PET predicted only half of the failures. When used in clinical routine, a negative int‐PET study cannot obviate the need for end‐PET examination.     

A 10-year experience with treatment of high and standard risk Hodgkin disease: six cycles of tailored BEACOPP, with interim scintigraphy, are effective and female fertility is preserved

Therapy of Hodgkin lymphoma (HL) is designed to prolong survival and minimize toxicity. A total of 124 patients with newly diagnosed HL and adverse prognostic factors were prospectively studied between July, 1999 and August, 2005. Patients with early unfavorable and advanced disease were eligible for the study. Patients were assigned to therapy based on international prognostic score (IPS). Those with IPS ≥ 3 received three cycles of escalated BEACOPP (EB). All others received two cycles of standard BEACOPP (SB). Subsequent therapy was prospectively assigned according to early interim GA(67) or positron emission tomography (PET)/computerized tomography (CT). Four cycles of EB or SB were administered following a positive or negative scan, respectively. Complete remission rate, 10-year progression free (PFS), and overall survival (OS) were 97, 87, and 88%, respectively, at a median follow-up of 89 months (5-144). PFS and OS were similar in both groups. Fertility status was assessed in 38 females aged <40 years; 94% of females younger than 40 years preserved their cyclic ovarian function. Nineteen conceived during follow-up for 30 pregnancies, delivering 24 babies. Deliveries were reported up to 7 years from diagnosis. Predictive value of negative interim Ga(67) or PET/CT was 87 and 93%, respectively. Six cycles of tailored BEACOPP, for patients with adverse prognostic factors, provide encouraging long-term PFS and OS, and fertility is preserved in most females.     

Response‐adapted therapy for aggressive non‐Hodgkin's lymphomas based on early [18F] FDG‐PET scanning: ECOG‐ACRIN Cancer Research Group study (E3404)

A persistently positive positron emission tomography (PET) scan during therapy for diffuse large B‐cell lymphoma (DLBCL) is predictive of treatment failure. A response‐adapted strategy consisting of an early treatment change to four cycles of R‐ICE (rituximab, ifosfamide, carboplatin, etoposide) was studied in the Eastern Cooperative Oncology Group E3404 trial. Previously untreated patients with DLBCL stage III, IV, or bulky II, were eligible. PET scan was performed after three cycles of R‐CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) and scored as positive or negative by central review during the fourth cycle. PET‐positive patients received four cycles of R‐ICE, PET‐negative patients received two more cycles of R‐CHOP. A ≥45% 2‐year progression‐free survival (PFS) for mid‐treatment PET‐positive patients was viewed as promising. Of 74 patients, 16% were PET positive, 79% negative. The PET positivity rate was much lower than the 33% expected. Two‐year PFS was 70%; 42% [90% confidence interval (CI), 19–63%] for PET‐positives and 76% (90% CI 65–84%) for PET‐negatives. Three‐year overall survival (OS) was 69% (90% CI 43–85%) and 93% (90% CI 86–97%) for PET‐positive and ‐negative cases, respectively. The 2‐year PFS for mid‐treatment PET‐positive patients intensified to R‐ICE was 42%, with a wide confidence interval due to the low proportion of positive mid‐treatment PET scans. Treatment modification based on early PET scanning should remain confined to clinical trials.     

18F‐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.     

Positron emission tomography using F-18 fluorodeoxyglucose pre- and post-autologous stem cell transplant in non-Hodgkin's lymphoma

Positron emission tomography (PET) utilizing fluorodeoxyglucose (FDG) has an ever-increasing role in the management of numerous malignancies. FDG PET in lymphoma is being incorporated into the response assessment in lymphoma as published by the Imaging Subcommittee of International Harmonization Project in Lymphoma. The exact role of FDG PET in non-Hodgkin's lymphoma (NHL) associated with autologous stem cell transplant (ASCT) is unclear. Numerous studies have identified pretransplant PET scans as being highly prognostic with regard to overall and PFS after ASCT. Many included a wide range of histologies, including Hodgkin's lymphoma and NHL. In studies with mixed histologies, PFS at 2 years has been improved by as much as 82% in patients with negative pre-ASCT PET scans. In studies incorporating only patients with NHL, improvements in failure-free survival have been reported as high as 43% for patients with negative pre-ASCT PET imaging. Limitations have included inclusion of many histologies, different reported time points, small retrospective studies and variation in the interpretation of a positive PET. Validation is ongoing in larger prospective trials. Future directions include the potential incorporation of post-ASCT therapy, such as radiation therapy or maintenance antibody therapy, for patients with positive pre-ASCT PET scans.