Sze Ting Lee

Hypoxia-targeted radiotherapy dose painting for head and neck cancer using (18)F-FMISO PET: a biological modeling study.

Abstract Background. This study investigates the use of 18F-fluoromisonidazole (FMISO) PET-guided radiotherapy dose painting for potentially overcoming the radioresistant effects of hypoxia in head and neck squamous cell carcinoma (HNSCC). Material and methods. The study cohort consisted of eight patients with HNSCC who were planned for definitive radiotherapy. Hypoxic subvolumes were automatically generated on pre-radiotherapy FMISO PET scans. Three radiotherapy plans were generated for each patient: a standard (STD) radiotherapy plan to a dose of 70 Gy, a uniform dose escalation (UDE) plan to the standard target volumes to a dose of 84 Gy, and a hypoxia dose-painted (HDP) plan with dose escalation only to the hypoxic subvolume to 84 Gy. Plans were compared based on tumor control probability (TCP), normal tissue complication probability (NTCP), and uncomplicated tumor control probability (UTCP). Results. The mean TCP increased from 73% with STD plans to 95% with the use of UDE plans (p < 0.001) and to 93% with HDP plans (p < 0.001). The mean parotid NTCP increased from 26% to 44% with the use of UDE plans (p = 0.003), and the mean mandible NTCP increased from 2% to 27% with the use of UDE plans (p = 0.001). There were no statistically significant differences between any of the NTCPs between the STD plans and HDP plans. The mean UTCP increased from 48% with STD plans to 66% with HDP plans (p = 0.016) and dropped to 37% with UDE plans (p = 0.138). Conclusion. Hypoxia-targeted radiotherapy dose painting for head and neck cancer using FMISO PET is technically feasible, increases the TCP without increasing the NTCP, and increases the UTCP. This approach is superior to uniform dose escalation.

Intensity Modulated Radiation Therapy Dose Painting for Localized Prostate Cancer Using 11C-choline Positron Emission Tomography Scans

PURPOSE To demonstrate the technical feasibility of intensity modulated radiation therapy (IMRT) dose painting using (11)C-choline positron emission tomography PET scans in patients with localized prostate cancer. METHODS AND MATERIALS This was an RT planning study of 8 patients with prostate cancer who had (11)C-choline PET scans prior to radical prostatectomy. Two contours were semiautomatically generated on the basis of the PET scans for each patient: 60% and 70% of the maximum standardized uptake values (SUV(60%) and SUV(70%)). Three IMRT plans were generated for each patient: PLAN(78), which consisted of whole-prostate radiation therapy to 78 Gy; PLAN(78-90), which consisted of whole-prostate RT to 78 Gy, a boost to the SUV(60%) to 84 Gy, and a further boost to the SUV(70%) to 90 Gy; and PLAN(72-90), which consisted of whole-prostate RT to 72 Gy, a boost to the SUV(60%) to 84 Gy, and a further boost to the SUV(70%) to 90 Gy. The feasibility of these plans was judged by their ability to reach prescription doses while adhering to published dose constraints. Tumor control probabilities based on PET scan-defined volumes (TCP(PET)) and on prostatectomy-defined volumes (TCP(path)), and rectal normal tissue complication probabilities (NTCP) were compared between the plans. RESULTS All plans for all patients reached prescription doses while adhering to dose constraints. TCP(PET) values for PLAN(78), PLAN(78-90), and PLAN(72-90) were 65%, 97%, and 96%, respectively. TCP(path) values were 71%, 97%, and 89%, respectively. Both PLAN(78-90) and PLAN(72-90) had significantly higher TCP(PET) (P=.002 and .001) and TCP(path) (P<.001 and .014) values than PLAN(78). PLAN(78-90) and PLAN(72-90) were not significantly different in terms of TCP(PET) or TCP(path). There were no significant differences in rectal NTCPs between the 3 plans. CONCLUSIONS IMRT dose painting for localized prostate cancer using (11)C-choline PET scans is technically feasible. Dose painting results in higher TCPs without higher NTCPs.

Therapeutic efficacy of 177Lu-CHX-A''-DTPA-hu3S193 radioimmunotherapy in prostate cancer is enhanced by EGFR inhibition or docetaxel chemotherapy.

This study investigated the biodistribution and therapeutic efficacy of Lutetium‐177 (177Lu) radiolabeled anti‐Lewis Y monoclonal antibody hu3S193 radioimmunotherapy (RIT) in mice bearing prostate cancer xenografts. The ability of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor AG1478 and docetaxel chemotherapy to enhance the efficacy of RIT was also assessed in vivo.

Histopathological correlation of 11C-choline PET scans for target volume definition in radical prostate radiotherapy

BACKGROUND AND PURPOSE To evaluate the accuracy of (11)C-choline PET scans in defining dominant intraprostatic lesions (DILs) for radiotherapy target volume definition. MATERIAL AND METHODS Eight men with prostate cancer who had (11)C-choline PET scans prior to radical prostatectomy were studied. Several methods were used to contour the DIL on the PET scans: visual, PET Edge, Region Grow, absolute standardised uptake value (SUV) thresholds and percentage of maximum SUV thresholds. Prostatectomy specimens were sliced in the transverse plane and DILs were delineated on these by a pathologist. These were then compared with the PET scans. The accuracy of correlation was assessed by the Dice similarity coefficient (DSC) and the Youden index. RESULTS The contouring method resulting in both the highest DSC and the highest Youden index was 60% of the maximum SUV (SUV(60%)), with values of 0.64 and 0.51, respectively. However SUV(60%) was not statistically significantly better than all of the other methods by either measure. CONCLUSIONS Although not statistically significant, SUV(60%) resulted in the best correlation between (11)C-choline PET and pathology amongst all the methods studied. The degree of correlation shown here is consistent with previous studies that have justified using imaging for DIL radiotherapy target volume definition.

PET in Prostate and Bladder Tumors

(18)F-fluorodeoxyglucose (FDG) is the most common positron emission tomography (PET) radiotracer used in prostate and bladder cancer evaluation, but its role is hampered by a generally low glucose metabolic rate in primary prostate carcinoma, and physiological excretion of FDG through the urinary system masking FDG uptake in primary bladder and prostate carcinoma. FDG-PET may have a role in selected patients for staging and restaging advanced prostate cancer, particularly in patients with an increasing prostatic-specific antigen (PSA) level. The use of diuresis strategies facilitates the identification of primary bladder cancer, and may be useful in staging extravesical spread of disease. FDG-PET may also be useful in patients with ureteric and urethral cancers. New PET tracers are showing promise in the staging and biological characterization of prostate cancer, which can assist with therapeutic decision making in patients undergoing radiotherapy of primary disease, and in the assessment of metastatic disease.

18F-fluorodeoxyglucose–Positron Emission Tomography/Computed Tomography Aids Staging and Predicts Mortality in Patients With Muscle-invasive Bladder Cancer

OBJECTIVE To investigate the association between extravesical (18)F-fluorodeoxyglucose (FDG) avid lesions on FDG-positron emission tomography/computed tomography (PET/CT) and mortality in patients with muscle-invasive bladder cancer. METHODS An international, bi-institutional cohort study of 211 patients with muscle-invasive bladder cancer who underwent staging CT and FDG-PET/CT imaging. On the basis of the presence of extravesical FDG-avid lesions suspicious for malignancy on PET/CT images, patients were divided into a PET/CT-positive and PET/CT-negative group. Data on staging and mortality were retrospectively analyzed from prospective databases. Kaplan-Meier analyses were performed to compare overall (OS) and disease-specific survival (DSS) between the groups. Multivariable Cox regression models were used to investigate the association between extravesical PET/CT lesions and mortality. Extravesical lesions suspicious for malignancy on conventional CT were included in the models. RESULTS Of the 211 patients, 98 (46.4%) had 1 or more extravesical lesions on PET/CT, 113 (53.5%) had a negative PET/CT. Conventional CT revealed extravesical lesions in 51 patients (24.4%). Median follow-up was 18 months. Patients with a positive PET/CT had a significantly shorter OS and DSS (median OS: 14 vs 50 months, P = .001; DSS: 16 vs 50 months, P <.001). In multivariable analysis, the presence of extravesical lesions on PET/CT was an independent prognostic indicator of mortality (OS: hazard ratio = 3.0, confidence interval 95% 1.7-5.1). This association was not statistically significant for conventional CT (hazard ratio = 1.6 (95% confidence interval 0.9-2.7). CONCLUSION On the basis of our results, the presence of extravesical FDG-avid lesions on PET/CT might be considered an independent indicator of mortality.

Prognostic Ability of 18F-FDG PET/CT in the Assessment of Colorectal Liver Metastases

Modern multidisciplinary therapy for colorectal liver metastases (CRLM) is associated with significant morbidity and must be adapted to the patient’s relative risk. The tools currently available to risk-stratify patients are limited. This study assessed the prognostic utility of metabolic measurements derived from18F-FDG PET compared with previously proposed prognostic scoring systems. Methods: Preoperative 18F-FDG PET/CT studies from a series of 30 patients who underwent liver resection for CRLM after neoadjuvant chemotherapy were evaluated. Quantitative 18F-FDG PET analysis calculated the maximum and mean standardized uptake value, metabolic tumor volume (MTV), and tumor glycolytic volume (TGV) as measures of the metabolic activity of tumors. The predictive value of these parameters was compared with that of 4 prognostic scores developed by Fong, Iwatsuki, Nordlinger, and Rees. Results: High MTV and TGV in patients before metastasectomy were significantly associated with poorer overall survival (MTV: P = 0.001; TGV: P = 0.004) and recurrence-free survival (MTV: P = 0.001, TGV; P = 0.002). Maximum and mean standardized uptake value did not show any significant predictive ability. Of the prognostic scores, prediction of outcome was most accurate using the Basingstoke index (area under the curve, 0.898). Conclusion: Assessment of metabolic tumor burden with volumetric 18F-FDG PET parameters appears to be a valuable adjunct in determining the biology of CRLM before surgical resection and may enable better risk stratification of patients.

Establishing locoregional control of malignant pleural mesothelioma using high-dose radiotherapy and (18) F-FDG PET/CT scan correlation.

Introduction: The management of malignant pleural mesothelioma represents one of the most challenging issues in oncology, as there is no proven long‐term benefit from surgery, radiotherapy or chemotherapy alone or in combination. Locoregional progression remains the major cause of death, but radical surgical resection may produce major postoperative morbidity. While radical or postoperative radiotherapy using conventional techniques has resulted in severe toxicity with no impact on survival, recent advances in radiotherapy delivery may be more effective.

FDG PET/CT in the liver: lesions mimicking malignancies

Purpose18F-fluorodeoxyglucose (FDG) PET/CT is invaluable in managing liver lesions, in particular in the evaluation of suspected liver metastases. It is both sensitive and specific in detecting liver metastases from a wide range of primary cancers, and may change clinical management, most commonly by detecting additional lesions and decreasing the number of futile surgeries. However, some benign lesions may also show increased metabolic activity which can lead to false positive PET findings. We describe some of these lesions and their imaging characteristics that may help in differentiating them from malignant metastases.MethodsWe reviewed all whole body FDG PET/CT studies performed over a 5-year period in our institution, and identified those with focal liver lesions showing increased FDG uptake for which histological results were available.ResultsA majority of lesions showing increased metabolic activity were due to malignant disease, such as metastases or primary liver tumours. However, we also found increased FDG uptake in non-neoplastic lesions such as Cryptococcosis, abscesses, and secondary inflammation from cholecystitis. Increased metabolic activity was also seen in some benign neoplasms such as hepatic adenomas and hemangioendotheliomas.ConclusionFDG PET/CT is currently the most sensitive non-invasive imaging modality for the detection of hepatic metastases, particularly from the gastrointestinal tract. False positive results are rare, and have been described mainly in abscesses. However, other lesions can also show increased metabolic activity, and failure to differentiate these from metastases may result in inappropriate treatment.

Role of Low-dose, Noncontrast Computed Tomography from Integrated Positron Emission Tomography/Computed Tomography in Evaluating Incidental 2-Deoxy-2-[F-18]fluoro-d-glucose-avid Colon Lesions

PurposeTo assess the contribution of concurrent low-dose, noncontrast CT in the assessment of the malignant potential of incidental focal 2-deoxy-2-[F-18]fluoro-d-glucose (FDG)-avid colonic lesions on positron emission tomography/computed tomography (PET/CT).ProceduresRoutine FDG-PET/CT scans were reviewed for identification of focal FDG-avid colon lesions, and the CT component was independently reviewed for an anatomical lesion and malignant potential based on CT criteria. Clinical, endoscopic, and histopathology follow-up was obtained.ResultsA total of 85/2,916 (3%) oncology FDG-PET/CT scans had incidental focal colon lesions. Clinical and/or endoscopic follow-up was available in 83/85 (98%) patients. Focal, corresponding CT lesions were found in 44/83 (53%) patients, but features of malignancy were not assessable. Of the 44 patients with a final diagnosis, 32/44 (73%) were FDG-PET/CT true positives; 5/44 (11%) were false positives; and 7/44 (16%) had inconclusive FDG-PET/CT findings.ConclusionsConcurrent low-dose, noncontrast CT improves localization, but does not provide independent information on the malignant potential of incidental focal colonic activity on FDG-PET/CT.