Positron Emission Tomography Era Research Articles

Stereotactic Body Radiation Therapy Salvage for Lymph Node Recurrent Prostate Cancer in the Era of PSMA PET Imaging.

Our understanding of patterns of prostate cancer recurrence after primary treatment of localized disease has significantly evolved since the development of positron emission tomography (PET) agents targeting prostate cancer. Previously, most biochemical recurrences were not associated with imaging correlates when restaging with computed tomography (CT), magnetic resonance imaging (MRI), or bone scintigraphy and, hence, were typically assumed to represent occult metastases. A rising prostate specific antigen (PSA) after previous local therapy prompting a PET scan showing uptake limited to regional lymph nodes is an increasingly common clinical scenario as advanced prostate cancer imaging becomes more widely utilized. The optimal management strategy for patients who have lymph node recurrent prostate cancer is both unclear and evolving, particularly in terms of local and regionally directed therapies. Stereotactic body radiation therapy (SBRT) utilizes ablative radiation doses with steep gradients to achieve local tumor control while sparing nearby normal tissues. SBRT is an attractive therapeutic modality due to its efficacy, favorable toxicity profile, and flexibility to administer elective doses to areas of potential occult involvement. The purpose of this review is to briefly describe how SBRT is being implemented in the era of PSMA PET for the management of solely lymph node recurrent prostate cancer. SBRT has been shown to effectively control individual lymph node tumor deposits within the pelvis and retroperitoneum for prostate cancer and is well-tolerated with a favorable toxicity profile. However, a major limitation thus far has been the lack of prospective trials supporting the use of SBRT for oligometastatic nodal recurrent prostate cancer. As further trials are conducted, its exact role in the treatment paradigm of recurrent prostate cancer will be better established. Although PET-guided SBRT appears feasible and potentially beneficial, there is still considerable uncertainty about the use of elective nodal radiotherapy (ENRT) in patients with nodal recurrent oligometastatic prostate cancer. PSMA PET has undoubtedly advanced imaging of recurrent prostate cancer, revealing anatomic correlates for disease recurrence that previously went undetected. At the same time, SBRT continues to be explored in prostate cancer with feasibility, a favorable risk profile, and satisfactory oncologic outcomes. However, much of the existing literature comes from the pre-PSMA PET era and integration of this novel imaging approach has led to greater focus on new and ongoing clinical trials to rigorously evaluate this approach and compare to other established treatment modalities utilized for oligometastatic, nodal recurrence of prostate cancer.

Bleomycin-Induced Lung Toxicity in Hodgkin's Lymphoma: Risk Factors in the Positron Emission Tomography Era.

IntroductionBleomycin is a major antimitotic agent in the first-line treatment for Hodgkin's lymphoma. The main limitation of its use is its pulmonary toxicity. The objectives of this study are to find out the risk factors for the occurrence of bleomycin-induced lung toxicity in patients with Hodgkin's lymphoma and, on the other hand, to determine if positron emission tomography scan is a reliable means of early detection of this toxicity.MethodsThis is a retrospective study conducted in the clinical Hematology Department of Mohammed V Military Instruction Hospital, Rabat, Morocco. All patients with Hodgkin's lymphoma and treated with a bleomycin-based chemotherapy were included. The impact of different clinical and biological factors on the risk of bleomycin-induced lung toxicity occurrence was assessed using univariate and multivariate logistic regression. The benefit of positron emission tomography, usually performed as part of the re-assessment of Hodgkin’s lymphoma after two and four cycles, has been evaluated in the detection of bleomycin-induced lung toxicity.ResultsAmong 124 patients included in the study, 18 (14.5%) patients experienced bleomycin-induced lung toxicity. On multivariate analysis, smoking (p = 0.038) and the use of the ABVD regimen (doxorubicin, bleomycin, vinblastine, and dacarbazine) compared to the escalated BEACOPPe regimen (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone) (p = 0.018) were statistically significant risk factors.After two and four courses of therapy, the positron emission tomography was able to predict the occurrence of bleomycin-induced lung toxicity before the appearance of clinical symptoms only in 36.4 % and 12.5% of patients, respectively.ConclusionStudies to identify risk factors for the development of bleomycin-induced lung toxicity are crucial to reduce toxicity in the treatment of Hodgkin's lymphoma. However, two- and four-cycle positron emission tomography scans cannot be considered as a reliable means of early detection of this toxicity.

Outcome of primary mediastinal large B-cell lymphoma using R-CHOP: impact of a PET-adapted approach

AbstractCure rates for primary mediastinal large B-cell lymphoma (PMBCL) have improved with the integration of rituximab. However, the type of primary therapy and role of radiotherapy (RT) remains ill-defined. Herein, we evaluated the outcome of PMBCL primarily treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) and the impact of an end-of-treatment (EOT) 18F-fluorodeoxyglucose positron emission tomography (PET) scan to guide consolidative RT. Patients ≥18 years of age with PMBCL treated with curative intent rituximab-chemotherapy were identified. Prior to 2005, patients were recommended to receive R-CHOP + RT (RT era). Beginning in 2005, EOT PET was used to guide RT and only those with a PET-positive scan received RT (PET era). In total, 159 patients were identified, 94% were treated with R-CHOP and 44% received RT (78% in RT era, 28% in PET era). The 5-year time to progression (TTP) and overall survival (OS) for the entire cohort were 80% and 89%, respectively, similar across treatment eras. Overall, 10% had refractory disease. In total, 113 patients had an EOT PET scan: 63% negative and 37% positive with a 5-year TTP of 90% vs 71% and 5-year OS of 97% vs 88%, respectively. For those with Deauville (D)-scored PET scans (n = 103), the 5-year TTP for PET-negative cases by Deauville criteria (D1-D3, DX) was 91%, with inferior outcomes for D5 vs D4 (5-year TTP 33% vs 87%, P = .0002). Outcomes for PMBCL treated with RCHOP are favorable and use of a PET-adapted approach reduces RT in the majority of patients. A small proportion have refractory disease and may benefit from an alternate treatment.

Outcome of Limited Stage Nodular Lymphocyte Predominant Hodgkin Lymphoma (NLPHL) and Evaluation of a PET-Adapted Approach

Outcome of Limited Stage Nodular Lymphocyte Predominant Hodgkin Lymphoma (NLPHL) and Evaluation of a PET-Adapted Approach

Outcomes of stage I/II follicular lymphoma in the PET era: an international study from the Australian Lymphoma Alliance

AbstractManagement practices in early-stage (I/II) follicular lymphoma (FL) are variable and include radiation (RT), systemic therapy, or combined modality therapy (CMT). There is a paucity of data regarding maintenance rituximab in this cohort. We conducted an international retrospective study of patients with newly diagnosed early-stage FL staged with positron emission tomography (PET)–computed tomography and bone marrow biopsy. Three hundred sixty-five patients (stage I, n = 221), median age 63 years, treated from 2005-2017 were included, with a median follow-up of 45 months. Management included watchful waiting (WW; n = 85) and active treatment (n = 280). The latter consisted of RT alone (n = 171) or systemic therapy (immunochemotherapy [n = 63] or CMT [n = 46]). Forty-nine systemically treated patients received maintenance rituximab; 72.7% of stage I patients received RT alone, compared to 42.6% with stage II (P < .001). Active therapies yielded comparable overall response rates (P = .87). RT alone and systemic therapy without maintenance rituximab yielded similar progression-free survival (PFS) (hazard ratio [HR], 1.32; 95% confidence interval [CI], 0.77-2.34; P = .96). Maintenance rituximab improved PFS (HR, 0.24; 95% CI, 0.095-0.64; P = .017). The incidence of transformation was lower with systemic therapy compared to RT or WW (HR, 0.20; 95% CI, 0.070-0.61; P = .034). Overall survival was similar among all practices, including WW (P = .40). In the largest comparative assessment of management practices in the modern era, variable practices each resulted in similar excellent outcomes. Randomized studies are required to determine the optimal treatment in early-stage FL.

Outcomes and relapse patterns following chemotherapy in advanced Hodgkin lymphoma in the positron emission tomography era.

BackgroundThis study evaluated relapse patterns and survival in advanced Hodgkin lymphoma (HL) patients treated with doxorubicin, bleomycin, vinblastine and dacarbazine (ABVD) with positron emission tomography (PET) used for staging and response assessment.Patients and methodsPatients aged 18 years or above with newly diagnosed histologically proven Stage III or IV HL treated with ABVD at Calvary Mater Newcastle from January 2005 to December 2012 were included in this study. All patients underwent pre-chemotherapy staging with 18F-fluorodeoxyglucose PET or PET/computed tomography and post-chemotherapy PET or PET/computed tomography for the assessment of response.ResultsForty-three patients were included in the study. The 5-year disease-free survival, progression-free survival and overall survival were 88%, 74% and 86%, respectively. PET complete response was seen in 35 patients (81%), and the 5-year overall survival for this group was 94%. Relapse following a PET complete response was low (three patients) and occurred predominantly at the initial sites of disease. Four of five patients with bulky disease received consolidative radiotherapy and no in-field relapses were observed.ConclusionAdvanced stage HL with a PET complete response following ABVD is associated with an excellent prognosis.

Positron emission tomography and stage migration for head and neck cancer.

6018 Background: Positron emission tomography (PET) is often used for the staging of head and neck cancer (HNC). The purpose of this study is to explore the association between the increased utilization of PET and stage/survival in the managed care environment. Methods: Adult patients diagnosed with HNC (n=958) between 2000-2008, at 4 integrated health systems (Group Health Cooperative, Seattle; Health Alliance Plan/Henry Ford Health System, Detroit; Kaiser Permanente Colorado and Northwest, Portland) were identified via tumor registries linked to claims data. We compared AJCC stage distribution, patient/treatment characteristics, and survival between pre-PET era (2000-2004) vs. PET era (2005-2008), and those with PET vs. those without, during the PET era. AJCC stage was grouped into stage I/II (localized), stage III/IVa/IVb (locally advanced), and stage IVc (metastatic). Ordered logistic regression estimated the effects of PET utilization on upstaging. Kaplan-Meier estimates described overall survival (OS) differences between PET users and nonusers in the PET era. Cox proportional hazards regression evaluated the effect of PET use on survival. Results: There was a non-significant increase in stage III/IVa/IVb (40% to 44%) with a decrease in stage I/II (58% to 52%) between pre-PET era and PET era (p=0.11). During the PET era, patients with PET were more likely stage III/IVa/IVb and less likely stage I/II compared to patients without PET (III/IVa/IVb: 62% vs. 29%, I/II: 35% vs. 68%). On multivariate analysis those who were staged with PET were twice as likely to have locally advanced disease (OR 2.091; p=0.006). There was no difference in stage IVc. Patients with PET scans were more likely to receive chemotherapy with radiation and less likely to receive no treatment. 3-year actuarial OS for patients (all stages) with and without PET was 81% vs. 77% (p=0.261). 3-year actuarial OS for patients staged III/IVa/IVb with and without PET was 58% vs. 41% (p= 0.001). Conclusions: HNC patients were more likely to be upstaged with the use of PET. There was an improvement in survival in stage III/IVa/IVb patients, but no difference in survival across all stages. This likely reflects selection bias and stage migration rather than improved outcomes among individual patients.

Prognostic factors for patients with diffuse large B cell lymphoma and transformed indolent lymphoma undergoing autologous stem cell transplantation in the positron emission tomography era

In the positron emission tomography (PET) era, traditional prognostic factors may not apply for patients with relapsed/refractory (R/R) diffuse large B cell lymphoma (DLBCL) undergoing autologous stem cell transplantation (ASCT). Moreover, little is known about prognostic factors in patients transplanted for transformed indolent lymphoma (TIL). We conducted a retrospective study of 143 patients with R/R DLBCL and TIL who were transplanted in the last decade and had a post-salvage PET scan. We examined prognostic factors in both groups, and constructed a prognostic score for DLBCL patients. For patients with DLBCL, post-salvage PET response was an important prognostic factor. Advanced age and symptomatic relapse were also significantly associated with outcome. A simple score could stratify patients into three risk groups with 4-year post-ASCT overall survival of 84%, 59%, and 10%, and 4-year progression-free survival of 67%, 41% and 0% (P<0.0001 for both). However, none of those factors (including PET response to salvage) appeared relevant for patients with TIL, despite their comparable overall outcome. Our prognostic score for DLBCL patients undergoing ASCT may be useful for prognostication, for stratification in clinical trials, and to motivate the design of new strategies for patients in the high-risk group, who may not derive benefit from standard ASCT.

Routine bone marrow biopsy is not necessary in the staging of patients with classical Hodgkin lymphoma in the 18F-fluoro-2-deoxyglucose positron emission tomography era

Accurate staging of classical Hodgkin lymphoma (CHL) directs treatment intensity. Functional imaging can detect marrow/bone involvement making the role of bone marrow biopsy (BMB) unclear. We assessed current UK practice in CHL staging by questionnaire and retrospectively analyzed patients staged at a single center with BMB and 18F-fluoro-2-deoxyglucose positron emission tomography/computed tomography (FDG-PET/CT). From 34 questionnaire responses 50% used FDG-PET/CT routinely. BMB was employed in 97% with advanced-stage and 30% of patients with limited-stage disease (70% of those not using routine FDG-PET/CT). Ten out of 50 patients were BM+, all of which were identified by FDG-PET/CT (PET+). Conventional BMB changed management in 2% of cases. There were no clinically significant FDG-PET/CT false positives. Conventional routine BMB staging in CHL is extremely insensitive. FDG-PET/CT can rule out marrow/bone involvement in CHL. In the FDG-PET/CT staging era BMB should be targeted to a minority of patients with FDG-PET/CT + bone/marrow uptake and only when management would be altered by the result.

Is Computed Tomography Simulation Associated With Improved Survival, or Is This Finding a Result of Confounding Variables?

TO THEEDITOR: In a recent article, Chen et al 1 analyzed the use of computed tomography (CT) simulation in the treatment of stage III non–small-cell lung cancer (NSCLC). They found that CT simulation was associated with a lower risk of death with an adjusted hazard ratio of 0.77. For this large improvement, on par with the reduction seen with the addition of concurrent chemotherapy, to be associated with CT simulation alone is simply not plausible. The authors imply that the use of CT simulation in lung cancer is associated with higher thoracic radiotherapy doses and better targeting and that these may have led to the improved survival. These conclusions are mitigated by the fact that radiation oncologists have been using diagnostic CT scans to shape their fields since the early 1980s, as stated in the editorial 2 that accompanied the article by Chen at al. 1 What then can explain these results? It is likely that there is a confounding variable such as the increasing use of positron emission tomography (PET) scans during this same time period. The authors do not mention whether they accounted for PET scans as an instrumental variable when they assessed for confounding by unobserved factors. PET began to be increasingly used after the year 1998 in the staging of NSCLC after the approval of PET for reimbursement by Medicare. 3 The editorial 2 that accompanied the article by Chen et al 1 states that the receipt of CT simulation may have been a marker for overall quality of care. However, CT simulation could also well be a marker for patients who underwent advanced imaging studies. Centers with access to a CT simulator would have been more likely to offer their patients access to PET scans as well. PET scanning has been shown in prospective studies to detect metastatic disease 15% to 20% of the time when other staging studies are negative. 4 The use of PET scans in patients with NSCLC during the time period of the study by Chen et al 1 would have caused a stage migration. Patients with stage III NSCLC who received a PET scan would have had an improved survival compared with those who did not because of the exclusion of patients with PET-detected metastatic disease. This would have been independent of the CT simulation procedure. However, by not accounting for stage migration and the increasing use of PET scanning during the time period studied, the authors may have erroneously associated CT simulation with an improved survival. In fact, a large population-based study of patients with stage III cancer in a pre-PET era (1994-1998) and a PET era (1998-2004) found that PET use was significantly associated with a reduced hazard ratio of 0.77 (95% CI, 0.69 to 0.85). 5 This reduction in hazard ratio is similar to the reduction in hazard ratio of 0.77 that Chen et al 1 are associating with CT simulation. No one in the oncologic community questions the real benefits of CT simulation with respect to target delineation, dose calculations, and precise radiation therapy planning. However, before associating the improved hazard ratio with CT simulation, we should take into account the well-documented Will Rogers effect and stage migration as a result of PET scanning that occurred in stage III lung cancer during the time period studied. 6

Impact of preoperative positron emission tomography scans on survival after liver resection for metastatic colorectal cancer

Aim: Positron emission tomography (PET) has been used to detect extrahepatic disease in patients in order to determine their suitability for liver resection from colorectal metastases. Our hypothesis is that PET scanning would result in a better 5‐year survival after liver resection due to better patient selection through downstaging of disease.Methods: Between 1997 and 2005 there were 467 patients undergoing potentially curative liver resections in three cohorts. PET scanning was available to our patients without restriction from 2002. There were 215 patients in the pre‐PET era (Group 1), 188 in the PET era where a PET scan was not performed (Group 2) and 64 patients with preoperative PET scanning (Group 3). Our three cohorts were followed up at 1, 3, 6 and 12 months postoperatively with a median follow up of 24, 21 and 20 months, respectively.Results: The 5‐year survival rate for patients with preoperative PET scanning was 68%. The 5‐year survival rate for patients without preoperative PET scanning was 40% in the PET era and 30% in the pre‐PET era (P = 0.0113). The disease‐free interval was 35% in the PET group and 20% without PET scans at 3 years (P &lt; 0.05).Conclusion: The usage of preoperative PET scanning has led to an improved overall survival because of better patient selection from detection of occult extrahepatic disease missed by traditional staging techniques.