Elizabeth A. Kidd

Exploring feature-based approaches in PET images for predicting cancer treatment outcomes

Accumulating evidence suggests that characteristics of pre-treatment FDG-PET could be used as prognostic factors to predict outcomes in different cancer sites. Current risk analyses are limited to visual assessment or direct uptake value measurements. We are investigating intensity-volume histogram metrics and shape and texture features extracted from PET images to predict patients response to treatment. These approaches were demonstrated using datasets from cervix and head and neck cancers, where AUC of 0.76 and 1.0 were achieved, respectively. The preliminary results suggest that the proposed approaches could potentially provide better tools and discriminant power for utilizing functional imaging in clinical prognosis.

The standardized uptake value for F-18 fluorodeoxyglucose is a sensitive predictive biomarker for cervical cancer treatment response and survival†

The objective of this study was to evaluate cervical tumor uptake of F‐18 fluorodeoxyglucose (FDG) measured as the maximal standardized uptake value (SUVmax) by positron emission tomography (PET) and its association with treatment response and prognosis in patients with cervical cancer.

Lymph Node Staging by Positron Emission Tomography in Cervical Cancer: Relationship to Prognosis

PURPOSE A previous retrospective study demonstrated that positron emission tomography with [(18)F]fluorodeoxyglucose (FDG-PET) was more sensitive than computed tomography for lymph node staging in patients with cervical cancer; the findings on FDG-PET were strongly associated with progression-free survival. Therefore, a prospective cohort study was initiated to evaluate FDG-PET lymph node staging in a larger patient population. PATIENTS AND METHODS The study was conducted between July 2000 and March 2009. All 560 patients with cervical cancer underwent pretreatment FDG-PET lymph node staging. Treatment included surgery alone, surgery and postoperative radiation therapy, and definitive radiation or combination radiation and chemotherapy. PET findings were correlated with the risk of disease progression and with survival. Results Overall, 47% of patients had lymph node involvement by FDG-PET at diagnosis. The frequency of lymph node metastasis increased with clinical stage and was similar to that in historical surgical series. Within a stage, patients with PET-positive lymph nodes had significantly worse disease-specific survival than those with PET-negative lymph nodes (P < .001). Disease-specific survival was stratified into distinct groups based on the most distant level of PET-detected nodal disease (none, pelvic, para-aortic, or supraclavicular; P < .001). The hazard ratios for disease recurrence increased incrementally based on the most distant level of nodal disease: pelvic 2.40 (95% CI, 1.63 to 3.52), para-aortic 5.88 (95% CI, 3.80 to 9.09), and supraclavicular 30.27 (95% CI 16.56 to 55.34). CONCLUSION Nodal involvement detected by FDG-PET in cervical cancer relates to clinical stage, is comparable to historical data, and stratifies patient recurrence and survival outcomes.

Clinical Outcomes of Definitive Intensity-Modulated Radiation Therapy With Fluorodeoxyglucose-Positron Emission Tomography Simulation in Patients With Locally Advanced Cervical Cancer

PURPOSE This study aimed to evaluate the toxicity and clinical outcomes for cervical cancer patients treated definitively with intensity-modulated radiation therapy (IMRT) compared with non-IMRT treatment. METHODS AND MATERIALS This prospective cohort study included 452 patients with newly diagnosed cervical cancer treated with curative intent (135 IMRT and 317 non-IMRT). Treatment involved external irradiation and brachytherapy, and 85% of patients received concurrent chemotherapy. All IMRT patients underwent an F-18 fluorodeoxyglucose positron emission tomography (FDG-PET/CT) simulation. A 3-month post-therapy PET was obtained to evaluate treatment response. Toxicity was scored by the Common Terminology Criteria for Adverse Events Version 3.0. RESULTS The IMRT and non-IMRT groups had similar stage distribution and histology. For all patients, the post-therapy FDG-PET response correlated with overall recurrence risk (p < 0.0001) and cause-specific survival (p < 0.0001). Post-treatment FDG-PET findings were not significantly different between the IMRT and non-IMRT patients (p = 0.9774). The mean follow-up for all patients alive at the time of last follow-up was 52 months (72 months non-IMRT, 22 months IMRT). At last follow-up, 178 patients (39 IMRT, 139 non-IMRT) had developed a recurrence. The difference in recurrence-free survival between the two groups did not reach statistical significance (p = 0.0738), although the IMRT group showed better overall and cause-specific survivals (p < 0.0001). Of the patients, 62 patients (8 IMRT and 54 non-IMRT) developed Grade 3 or greater bowel or bladder complications, and by cumulative hazard function analysis the risk was significantly less for patients treated with IMRT (p = 0.0351). CONCLUSION Cervical cancer patients treated with FDG-PET/CT-guided IMRT have improved survival and less treatment-related toxicity compared with patients treated with non-IMRT radiotherapy.

Pelvic Lymph Node F-18 Fluorodeoxyglucose Uptake as a Prognostic Biomarker in Newly Diagnosed Patients With Locally Advanced Cervical Cancer

The objective of the current study was to evaluate the prognostic significance of the maximum standardized uptake value (SUVmax) of F‐18 fluorodeoxyglucose (FDG) as measured by positron emission tomography (PET) in pelvic lymph nodes in patients with cervical cancer.

Changes in Cervical Cancer FDG Uptake During Chemoradiation and Association With Response

PURPOSE Previous research showed that pretreatment uptake of F-18 fluorodeoxyglucose (FDG), as assessed by the maximal standardized uptake value (SUVmax) and the variability of uptake (FDGhetero), predicted for posttreatment response in cervical cancer. In this pilot study, we evaluated the changes in SUVmax and FDGhetero during concurrent chemoradiation for cervical cancer and their association with post-treatment response. METHODS AND MATERIALS Twenty-five patients with stage Ib1-IVa cervical cancer were enrolled. SUVmax, FDGhetero, and metabolic tumor volume (MTV) were recorded from FDG-positron emission tomography (PET)/computed tomography (CT) scans performed pretreatment and during weeks 2 and 4 of treatment and were evaluated for changes and association with response assessed on 3-month post-treatment FDG-PET/CT. RESULTS For all patients, the average pretreatment SUVmax was 17.8, MTV was 55.4 cm3, and FDGhetero was -1.33. A similar decline in SUVmax was seen at week 2 compared with baseline and week 4 compared with week 2 (34%). The areas of highest FDG uptake in the tumor remained relatively consistent on serial scans. Mean FDGhetero decreased during treatment. For all patients, MTV decreased more from week 2 to week 4 than from pretreatment to week 2. By week 4, the average SUVmax had decreased by 57% and the MTV had decreased by 30%. Five patients showed persistent or new disease on 3-month post-treatment PET. These poor responders showed a higher average SUVmax, larger MTV, and greater heterogeneity at all 3 times. Week 4 SUVmax (P=.037), week 4 FDGhetero (P=.005), pretreatment MTV (P=.008), and pretreatment FDGhetero (P=.008) were all significantly associated with post-treatment PET response. CONCLUSIONS SUVmax shows a consistent rate of decline during treatment and declines at a faster rate than MTV regresses. Based on this pilot study, pretreatment and week 4 of treatment represent the best time points for prediction of response.

FDG-PET-based prognostic nomograms for locally advanced cervical cancer

PURPOSE We previously found several individual FDG/PET-based prognostic factors for cervical cancer, specifically cervical tumor SUVmax, tumor volume, and highest level of lymph node (LN) involvement. For this study, we evaluate the combined use of these three prognostic factors assessed on pretreatment FDG-PET for predicting recurrence-free survival (RFS), disease-specific survival (DSS), and overall survival (OS). PATIENTS AND METHODS The study included 234 cervical cancer patients, FIGO stage Ib1-IVa, treated with definitive radiation or chemoradiation therapy. All patients underwent FDG-PET or FDG-PET/CT at diagnosis, from which cervical tumor volume, SUVmax, and LN status were recorded. Using these PET-based factors, prognostic nomograms were created for RFS, DSS, and OS, and their prediction accuracies were measured using the concordance index (c-statistic). RESULTS Fifty-three percent of patients had FDG-avid LN on PET; the highest level of nodal involvement was pelvic in 84, para-aortic in 41, and supraclavicular in 10. The average cervix tumor SUVmax was 12.4 (range, 2.1-50.4) and PET tumor volume average was 66.4 cm3 (range, 3.0-535.7 cm3). The median follow-up was 40.7 months for patients alive at last follow-up. PET LN status had the greatest influence on outcome. The c-statistics for the 3 nomograms were 0.741 for RFS, 0.739 for DSS, and 0.658 for OS. The PET-based nomograms performed better than FIGO stage with c-statistics of 0.605, 0.600 and 0.559 for RFS, DSS and OS, respectively. CONCLUSIONS Pretreatment FDG-PET LN status, cervical tumor SUVmax, and tumor volume combined in a nomogram create good models for predicting cervical cancer RFS, DSS, and OS.

Cervical cancer histology and tumor differentiation affect 18F‐fluorodeoxyglucose uptake

This study aimed to evaluate the variation in cervical cancer glucose metabolism for different tumor histologies and levels of differentiation, as measured by the uptake of 18F‐fluorodeoxyglucose (FDG) by positron emission tomography (PET).

Anal cancer maximum F-18 fluorodeoxyglucose uptake on positron emission tomography is correlated with prognosis

PURPOSE To evaluate anal cancer uptake of F-18 fluorodeoxyglucose (FDG) measured as the maximum standardized uptake value (SUV(max)) by positron emission tomography (PET) and its correlation with prognostic factors. PATIENTS AND METHODS The study population consisted of 77 patients with stages 0-IIIB anal cancer who underwent pre-treatment FDG-PET. Tumor histology included 65 squamous cell, 11 basaloid, and 1 small cell cancers. SUV(max) and sites of lymph node metastasis were recorded. We analyzed the association between SUV(max) and prognostic factors. RESULTS The mean SUV(max) was 10.0 (range 1.0-43.1). The stage distribution included: 2 stage 0, 7 stage I, 49 stage II, 10 stage IIIA, 9 stage IIIB. SUV(max) and clinical tumor size were not associated (R(2)=0.338). Histology did not significantly influence SUV(max) (mean SUV(max) 10.0 for squamous versus 9.90 for basaloid). Higher SUV(max) was associated with an increased risk of nodal metastasis at diagnosis (p<0.0001). Higher SUV(max) was associated with worse disease-free survival (p=0.05). Patients with high anal tumor SUV(max) at diagnosis were at an increased risk of persistent or recurrent disease on post-therapy FDG-PET performed less than 4months after completing therapy (p=0.0402). CONCLUSIONS SUV(max) is a valuable biomarker of anal cancer prognosis, predicting increased risk of lymph node metastasis and worse disease-free survival.

Impact of Chemotherapy on Normal Tissue Complication Probability Models of Acute Hematologic Toxicity in Patients Receiving Pelvic Intensity Modulated Radiation Therapy

PURPOSE To determine how chemotherapy agents affect radiation dose parameters that correlate with acute hematologic toxicity (HT) in patients treated with pelvic intensity modulated radiation therapy (P-IMRT) and concurrent chemotherapy. METHODS AND MATERIALS We assessed HT in 141 patients who received P-IMRT for anal, gynecologic, rectal, or prostate cancers, 95 of whom received concurrent chemotherapy. Patients were separated into 4 groups: mitomycin (MMC) + 5-fluorouracil (5FU, 37 of 141), platinum ± 5FU (Cis, 32 of 141), 5FU (26 of 141), and P-IMRT alone (46 of 141). The pelvic bone was contoured as a surrogate for pelvic bone marrow (PBM) and divided into subsites: ilium, lower pelvis, and lumbosacral spine (LSS). The volumes of each region receiving 5-40 Gy were calculated. The endpoint for HT was grade ≥3 (HT3+) leukopenia, neutropenia or thrombocytopenia. Normal tissue complication probability was calculated using the Lyman-Kutcher-Burman model. Logistic regression was used to analyze association between HT3+ and dosimetric parameters. RESULTS Twenty-six patients experienced HT3+: 10 of 37 (27%) MMC, 14 of 32 (44%) Cis, 2 of 26 (8%) 5FU, and 0 of 46 P-IMRT. PBM dosimetric parameters were correlated with HT3+ in the MMC group but not in the Cis group. LSS dosimetric parameters were well correlated with HT3+ in both the MMC and Cis groups. Constrained optimization (0<n≤ 1) of the Lyman-Kutcher-Burman model resulted in n=1, m = 0.11, TD50 = 31 Gy for LSS in the MMC group and n=1, m = 0.27, TD50 = 35 Gy for LSS in the Cis group. CONCLUSIONS The incidence of HT3+ depends on type of chemotherapy received. Patients receiving P-IMRT ± 5FU have better bone marrow tolerance than those receiving irradiation concurrent with either Cis or MMC. Treatment with MMC has a lower TD50 and more steeply rising normal tissue complication probability curve compared with treatment with Cis. Dose tolerance of PBM and the LSS subsite may be lower for patients treated with MMC compared with Cis.