Comparison of FDG-PET/CT and contrast-enhanced CT for monitoring therapy response in patients with metastatic breast cancer.

PURPOSE: The aim of this study was to compare fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT) and contrast-enhanced computed tomography (CE-CT) for the prediction of progression-free survival (PFS) and disease-specific survival (DSS) in patients with stage IV breast cancer undergoing systemic therapy. METHODS: Sixty-five patients with metastatic breast cancer treated with first- or second-line systemic therapy in prospective clinical trials were included. Response to treatment was evaluated by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 for CE-CT and by PET Response Criteria in Solid Tumors (PERCIST), respectively. RESULTS: All responders by RECIST (n = 22) were also responders by PERCIST, but 40% (17/43) of non-responders by RECIST were responders by PERCIST. Responses according to RECIST and PERCIST both correlated with PFS, but PERCIST showed a significantly higher predictive accuracy (concordance index for PFS: 0.70 vs. 0.60). One-year PFS for responders vs. non-responders by RECIST was 59% vs. 27%, compared to 63% vs. 0% by PERCIST. Four-year DSS of responders and non-responders by RECIST was 50% and 38%, respectively (p = 0.2, concordance index: 0.55) as compared to 58% vs. 18% for PERCIST (p < 0.001, concordance index: 0.65). Response on PET/CT was also a significantly better predictor for DSS than disease control on CE-CT. CONCLUSIONS: In patients with metastatic breast cancer, tumor response on PET/CT appears to be a superior predictor of PFS and DSS than response on CE-CT. Monitoring tumor response by PET/CT may increase the power of clinical trials using tumor response as an endpoint, and may improve patient management in clinical routine.

A phase 2 trial of everolimus and pasireotide long-acting release in patients with metastatic uveal melanoma.

The aim of this study was to test the hypothesis that inhibiting mammalian target of rapamycin and insulin-like growth factor-1 receptor would be efficacious in metastatic uveal melanoma. This was a phase 2 trial of everolimus 10 mg daily plus pasireotide long-acting release 60 mg every 28 days enrolling patients with progressive, metastatic uveal melanoma to treatment until progression by Response Evaluation Criteria In Solid Tumors 1.1 (RECIST 1.1) or unacceptable toxicity. The primary endpoint was clinical benefit rate, defined as any objective response or RECIST 1.1 stable disease at 16 weeks. A subset of patients underwent baseline indium-111-octreotide scans. A total of 14 patients were enrolled, of which 13 were evaluable for the primary endpoint, before the study was terminated due to poor accrual. Three of 13 (26%) patients obtained clinical benefit. Seven of 13 (54%) had stable disease lasting for a median of 8 weeks (range: 8-16 weeks). Grade 3 adverse events deemed at least possibly related to study drugs were hyperglycemia (n=7), oral mucositis (n=2), diarrhea (n=1), hypophosphatemia (n=1), and anemia (n=1). Seven of 14 (50%) patients required at least one dose reduction due to toxicity. Seven of eight (88%) patients with baseline indium-111-octreotide scans had at least one avid lesion, with significant intrapatient heterogeneity. There was a trend toward an association between octreotide avidity and cytostatic response to therapy (P=0.078). The combination of everolimus and pasireotide has limited clinical benefit in this small metastatic uveal melanoma cohort. Dose reductions for side effects were common. Further investigation into the relationship between somatostatin receptor expression and cytostatic activity of somatostatin analogues is warranted.

Prognostic Value of Preradiotherapy (18)F-FDG PET/CT Volumetrics in Limited-Stage Small-Cell Lung Cancer.

BACKGROUND: Whether (18)F-fludeoxyglucose positron emission tomography (PET)/computed tomography (CT) metrics predict outcome in limited-stage (LS) small-cell lung cancer (SCLC) has not been well established; most previous reports have only analyzed maximal standardized uptake values (SUVmax). We investigated multiple pretreatment PET metrics, including SUVmax, mean SUV (SUVmean), total lesion glycolysis, and metabolic tumor volume (MTV) in LS-SCLC patients undergoing chemoradiotherapy (CRT) and correlated them with survival and disease control outcomes. PATIENTS AND METHODS: All patients received platinum-based chemotherapy and a median radiation dose of 45 Gy. Kaplan-Meier and competing-risks analyses were performed to assess the prognostic value of PET metrics with respect to overall survival (OS), distant failure (DF), disease-free survival (DFS), and locoregional failure (LRF). Univariate and multivariate analyses were performed to account for the effect of other clinical factors on outcomes. RESULTS: A total of 120 patients with LS-SCLC had analyzable pre-CRT PET/CTs. The median follow up was 34 months. Median OS was 26.9 months. OS was 53.2% at 2 years and 33.1% at 5 years. SUVmax, SUVmean, MTV, and total lesion glycolysis of the primary tumor were not significantly associated with OS, LRF, and DFS on univariate analysis. MTV was significantly associated with DF (P = .024) on univariate but not multivariate analysis. CONCLUSION: This is the largest reported series to date evaluating the prognostic value of baseline PET metrics in LS-SCLC. Neither SUVmax nor other analyzed PET metrics demonstrated significant correlation with OS or LRF. MTV was correlated with DF and DFS, but this association was no longer significant after adjustment for other clinical factors. This analysis suggests that pretreatment PET scans, even with the use of advanced metrics, do not have independent prognostic value for outcomes in LS-SCLC patients after CRT.

Prognostic significance of PET assessment of metabolic response to therapy in oesophageal squamous cell carcinoma.

OBJECTIVES: The role of maximum standard uptake value (SUVmax) at baseline and after induction chemotherapy (CT) on positron emission tomography (PET) as an imaging biomarker has not been well established in oesophageal squamous cell carcinoma (SCC). In this retrospective analysis, we investigated the prognostic significance of various PET metrics in oesophageal SCC patients treated with induction chemotherapy followed by concurrent chemoradiotherapy (CRT). METHODS: A total of 57 patients were treated with CRT; 52 patients received induction chemotherapy and 10 patients underwent surgery following CRT. Scans were independently analysed by a nuclear medicine physician blinded to patient outcome. Using region of interest analysis, SUVmax and metabolic tumour volume (MTV) were calculated for the index lesion and lymph node metastases in each patient. Kaplan-Meier analysis was used to evaluate overall survival (OS), disease-free survival (DFS), local recurrence-free survival (LRFS) and distant metastasis-free survival (DMFS). Cox proportional hazards regression was used to assess correlation between outcomes and PET metrics. RESULTS: Median follow-up for those who are alive was 4.4 years, with a median survival for all patients of 2.9 years. The 3-year OS, DFS, DMFS and LRFS rates were 47, 40, 44 and 36%, respectively. Using a pre-established cutoff of a 35% decrease in SUVmax from baseline to post-induction PET, 3-year OS for responders (⩾35% decrease from baseline) was 64%, whereas non-responders (<35% decrease from baseline) had a 3-year OS of 15% (P=0.004). CONCLUSIONS: The pre-specified 35% decrease in SUVmax after induction chemotherapy was prognostic for OS. Baseline and post-induction PET metrics provide prognostic information for oesophageal SCC.