Effect of PET before liver resection on surgical management for colorectal adenocarcinoma metastases: a randomized clinical trial.

IMPORTANCE: Patients with colorectal cancer with liver metastases undergo hepatic resection with curative intent. Positron emission tomography combined with computed tomography (PET-CT) could help avoid noncurative surgery by identifying patients with occult metastases. OBJECTIVES: To determine the effect of preoperative PET-CT vs no PET-CT (control) on the surgical management of patients with resectable metastases and to investigate the effect of PET-CT on survival and the association between the standardized uptake value (ratio of tissue radioactivity to injected radioactivity adjusted by weight) and survival. DESIGN, SETTING, AND PARTICIPANTS: A randomized trial of patients older than 18 years with colorectal cancer treated by surgery, with resectable metastases based on CT scans of the chest, abdomen, and pelvis within the previous 30 days, and with a clear colonoscopy within the previous 18 months was conducted between 2005 and 2013, involving 21 surgeons at 9 hospitals in Ontario, Canada, with PET-CT scanners at 5 academic institutions. INTERVENTIONS: Patients were randomized using a 2 to 1 ratio to PET-CT or control. MAIN OUTCOMES AND MEASURES: The primary outcome was a change in surgical management defined as canceled hepatic surgery, more extensive hepatic surgery, or additional organ surgery based on the PET-CT. Survival was a secondary outcome. RESULTS: Of the 263 patients who underwent PET-CT, 21 had a change in surgical management (8.0%; 95% CI, 5.0%-11.9%). Specifically, 7 patients (2.7%) did not undergo laparotomy, 4 (1.5%) had more extensive hepatic surgery, 9 (3.4%) had additional organ surgery (8 of whom had hepatic resection), and the abdominal cavity was opened in 1 patient but hepatic surgery was not performed and the cavity was closed. Liver resection was performed in 91% of patients in the PET-CT group and 92% of the control group. After a median follow-up of 36 months, the estimated mortality rate was 11.13 (95% CI, 8.95-13.68) events/1000 person-months for the PET-CT group and 12.71 (95% CI, 9.40-16.80) events/1000 person-months for the control group. Survival did not differ between the 2 groups (hazard ratio, 0.86 [95% CI, 0.60-1.21]; P = .38). The standardized uptake value was associated with survival (hazard ratio, 1.11 [90% CI, 1.07-1.15] per unit increase; P < .001). The C statistic for the model including the standardized uptake value was 0.62 (95% CI, 0.56-0.68) and without it was 0.50 (95% CI, 0.44-0.56). The difference in C statistics is 0.12 (95% CI, 0.04-0.21). The low C statistic suggests that the standard uptake value is not a strong predictor of overall survival. CONCLUSIONS AND RELEVANCE: Among patients with potentially resectable hepatic metastases of colorectal adenocarcinoma, the use of PET-CT compared with CT alone did not result in frequent change in surgical management. These findings raise questions about the value of PET-CT scans in this setting. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00265356.

A multi-institutional feasibility lead-in trial of lymphatic mapping with SPECT-CT for evaluating contralateral disease in lateralized oropharynx cancer using 99m-technetium sulfur colloid.

BACKGROUND: Lymphatic mapping with SPECT-CT has been demonstrated to accurately define lymphatic drainage patterns in oropharyngeal cancer but there has yet to be a study demonstrating its feasibility across multiple institutions. METHODS: Twelve adult patients with lateralized oropharyngeal carcinoma (T1-T3) who were planned for definitive or adjuvant radiotherapy without contralateral nodal disease underwent injection of 99-m technetium sulfur colloid followed by static planar lymphoscintigraphy to verify tracer migration, and SPECT-CT acquired at 30 ± 15 min (optional) and 3 h (±1 h) (mandatory time-point). RESULTS: All 12 patients completed the study with 7/12 patients having the injections performed under local anesthetic and 5 patients requiring general anesthetic. There were no tracer migration failures and there were no serious adverse events or complications encountered. Four out of 12 patients (33%) showed contralateral drainage patterns. CONCLUSIONS: Lymphatic mapping with SPECT-CT of lateralized oropharyngeal squamous cell carcinoma can be performed safely across multiple institutions.

Evaluating contralateral neck failure in patients with lateralized OPSCC treated with transoral robotic surgery and neck management based on pre-operative SPECT-CT lymphatic mapping.

BACKGROUND: Risk of contralateral nodal metastases in oropharyngeal squamous cell carcinoma (OPSCC) is relatively low, however, many OPSCC patients receive bilateral neck treatment. This study evaluates the oncological outcomes with management of the contralateral cN0 neck based on lymphatic mapping with single photon emission computed tomography (SPECT-CT). METHODS: Retrospective evaluation of patients with lateralized cT1-2 and contralateral cN0 OPSCC treated with primary surgery between December 2017 and October 2019. All patients underwent pre-operative lymphatic mapping using SPECT-CT. Clinical parameters including demographics, tumor characteristics and oncological outcomes were recorded. RESULTS: Thirteen patients underwent primary site resection with transoral robotic surgery (TORS) and ipsilateral neck dissection with or without adjuvant therapy. Twelve patients (92.3%) had ipsilateral drainage on SPECT-CT, whereas 1 (7.7%) patient had bilateral neck lymphatic drainage. Four patients (30.8%) underwent post-operative radiation therapy (PORT). Three patients with unilateral drainage on SPECT-CT underwent PORT with unilateral neck irradiation, and 1 patient with bilateral drainage underwent PORT with bilateral neck irradiation. Seven (53.8%) patients were staged as pT1, 6 (46.2%) patients as pT2, 6 (46.2%) patients were pN0, 3 (23.1%) patients were pN1, 1 (7.7%) patient was pN2a for and 3 (23.1%) patients were N2b. The median distance of the tumor from midline was 1.05 cm (0.0-1.58). Primary sites included tonsil (n = 10, 76.9%) and tongue base (n = 3, 23.1%). The median follow-up time was 15.4 months. All patients were disease free at the latest follow-up with no contralateral neck failures. CONCLUSIONS: Pre-operative mapping of lymphatic drainage in early stage OPSCC with SPECT-CT is a promising tool which can reduce treatment to the contralateral neck potentially without compromising oncological outcomes.

Assessment of tumor recurrence in patients with colorectal cancer and elevated carcinoembryonic antigen level: FDG PET/CT versus contrast-enhanced 64-MDCT of the chest and abdomen.

OBJECTIVE: The purpose of this study was to compare FDG PET/CT and contrast-enhanced 64-MDCT of the chest, abdomen, and pelvis in the detection of tumor recurrence in patients with colorectal cancer and an elevated level of carcinoembryonic antigen (CEA). MATERIALS AND METHODS: A retrospective analysis included 50 patients (31 men, 19 women; mean age, 61 years; range, 28-89 years) with 55 clinical events of elevated or increasing CEA level who underwent FDG PET/CT and MDCT for suspected tumor recurrence. RESULTS: Recurrent or metastatic disease was found in 36 of 55 events (65.5%) of elevated CEA. Fifty-four of 61 tumor sites suspected as tumor recurrence with any imaging technique were found to be local recurrence or metastatic colorectal cancer at final analysis. The other seven sites were one separate malignant tumor (small lymphocytic lymphoma) and six benign lesions. Diagnosis was based on histopathologic findings (n = 27) or clinical and imaging findings (n = 35) during a median follow-up period of 12 months (range, 6-31 months). One site of tumor recurrence was missed prospectively at both MDCT and PET/CT. On an event-based analysis, the sensitivity of PET/CT and MDCT was 97.3% and 70.3% (p = 0.002); the specificity of both techniques was 94.4% (p = 1.0). In a tumor site-based analysis, the sensitivities of PET/CT and MDCT were 98.1% and 66.7% (p < 0.0001), and the specificities were 75% and 62.5% (p = 0.56). Tumors correctly identified with PET/CT and missed with MDCT were local recurrence in the presacral space (n = 5), metastatic subcentimeter lymph nodes (n = 4), peritoneal deposits (n = 3), and recurrences at the periphery of radiofrequency ablated metastatic lesions of the liver (n = 2) and in the abdominal wall (n = 1), liver (n = 1), and uterine cervix (n = 1). CONCLUSION: FDG PET/CT has higher sensitivity than MDCT in the identification of sites of recurrent and metastatic disease in patients with colorectal cancer and an elevated CEA level. The two techniques appear to have similar specificity.

Lymphatic mapping with SPECT-CT for evaluation of contralateral drainage in lateralized oropharyngeal cancers using an awake injection technique.

BACKGROUND: Risk of contralateral nodal metastases in oropharyngeal squamous cell carcinoma (OPSCC) is currently based on clinical risk factors. We propose lymphatic mapping with single photon emission computed tomography (SPECT-CT) for tumor-specific delineation of lymphatic drainage to guide treatment. METHODS: Retrospective review of lymphatic drainage patterns in cT1-2 OPSCC and contralateral cN0 neck with a nonoperative, awake injection of 99 m-Tc sulfur colloid and SPECT-CT. RESULTS: Ten patients were reviewed. Primary sites included tonsil (n = 8, 80%) and tongue base (n = 2, 20%). All patients tolerated awake injections with no complications. Nine patients (90%) demonstrated satisfactory migration of radiotracer to neck node(s) with seven (78%) to the ipsilateral lateral neck, one (11%) to the ipsilateral lateral neck and retropharynx, and one (11%) to bilateral lateral neck nodes. CONCLUSIONS: Characterization of lymphatic drainage in OPSCC is feasible using a nonoperative injection technique and SPECT-CT. Drainage to the contralateral neck is rare, warranting further study to tailor treatment appropriately.

Intraobserver and interobserver variability in GTV delineation on FDG-PET-CT images of head and neck cancers.

PURPOSE: To determine if the addition of fluorodeoxyglucose positron emission tomography (FDG-PET) data changes primary site gross tumor volumes (GTVs) in head and neck cancers. METHODS AND MATERIALS: Computed tomography (CT), contrast-enhanced CT, and FDG-PET-CT scans were obtained in 10 patients with head and neck cancers. Eight experienced observers (6 head and neck oncologists and 2 neuro-radiologists) with access to clinical and radiologic reports outlined primary site GTVs on each modality. Three cases were recontoured twice to assess intraobserver variability. The magnitudes of the GTVs were compared. Intra- and interobserver variability was assessed by a two-way repeated measures analysis of variance. Inter- and intraobserver reliability were calculated. RESULTS: There were no significant differences in the GTVs across the image modalities when compared as ensemble averages; the Wilcoxon matched-pairs signed-rank test showed that CT volumes were larger than PET-CT. Observers demonstrated the greatest consistency and were most interchangeable on contrast-enhanced CT; they performed less reliably on PET-CT. CONCLUSIONS: The addition of PET-CT to primary site GTV delineation of head and neck cancers does not change the volume of the GTV defined by this group of expert observers in this patient sample. An FDG-PET may demonstrate differences in neck node delineation and in other disease sites.

Positron Emission Tomography-Computed Tomography (PET-CT) Versus No PET-CT in the Management of Potentially Resectable Colorectal Cancer Liver Metastases: Cost Implications of a Randomized Controlled Trial.

PURPOSE: To evaluate whether positron emission tomography (PET) combined with computed tomography (PET-CT) is cost saving, or cost neutral, compared with conventional imaging in management of patients with resectable colorectal cancer liver metastases. METHODS: Cost evaluation of a randomized trial that compared the effect of PET-CT on surgical management of patients with resectable colorectal cancer liver metastases. Health care use data ≤ 1 year after random assignment was obtained from administrative databases. Cost analysis was undertaken from the perspective of a third-party payer (ie, Ministry of Health). Mean costs with 95% credible intervals (CrI) were estimated by using a Bayesian approach. RESULTS: The estimated mean cost per patient in the 263 patients who underwent PET-CT was $45,454 CAD (range, $1,340 to $181,420) and in the 134 control patients, $40,859 CAD (range, $279 to $293,558), with a net difference of $4,327 CAD (95% CrI, -$2,207 to $10,614). The primary cost driver was hospitalization for liver surgery (difference of $2,997 CAD for PET-CT; 95% CrI, -$2,144 to $8,010), which was mainly a result of a longer length of hospital stay for the PET-CT arm (median, 7 v 6 days; P = .03) and a higher postoperative complication rate (20% v 10%; P = .01). Baseline characteristics were similar between groups, including the number of liver segments involved with cancer, number of segments resected, and type of liver resection performed. No difference in survival was detected between arms. CONCLUSION: PET-CT was associated with limited clinical benefit and a nonsignificant increased cost. Universal funding of PET-CT in the management of patients with resectable colorectal cancer liver metastases does not seem justified.

Prevalence of "silent" pulmonary emboli in adults after the Fontan operation.

OBJECTIVES: The study was done to determine the prevalence of pulmonary emboli (PE) in asymptomatic adult Fontan patients and to identify the risk factors associated with PE. BACKGROUND: Right atrial thrombi and systemic thromboembolic complications have been reported after the Fontan procedure. However, the frequency of silent PE in this patient population is not known. METHODS: All consecutive adult Fontan patients attending the adult congenital clinic over a six-month period underwent ventilation-perfusion (VQ) scanning and blood testing for thrombophilia tendency. If the VQ scan showed an intermediate or high probability for PE, a computerized tomography (CT) pulmonary angiogram was performed to confirm the presence of PE. RESULTS: Thirty patients (mean age 26 +/- 7 years, 57% men) were included in this study. Five (17%) adult Fontan patients had an intermediate or high probability for PE on VQ scan, all of which were confirmed on CT pulmonary angiography. No patient had a thrombophilia tendency. Pulmonary emboli were not present in any patients (30%) taking warfarin. Late age at time of Fontan operation (19 +/- 6 years vs. 11 +/- 6 years, p = 0.012) and type of Fontan anatomy (p = 0.001) were associated with increased risk of silent PE. CONCLUSIONS: Seventeen percent of adult patients with Fontan procedure have clinically silent PE. The long-term hemodynamic implications of this with respect to Fontan attrition over time are unknown. Large randomized prospective studies looking at anticoagulation therapy in all Fontan patients are urgently needed.

Comparative antiproliferative effects of (111)In-DTPA-hEGF, chemotherapeutic agents and gamma-radiation on EGFR-positive breast cancer cells.

The antiproliferative effects of (111)In-DTPA-hEGF on breast cancer cells expressing high levels of EGFR were compared with those of chemotherapeutic agents or gamma-radiation. MDA-MB-468 cells were cultured with (111)In-DTPA-hEGF (30 MBq/microg, 1.8 x 10(5) MBq/micromol), DTPA-hEGF, methotrexate, doxorubicin, paclitaxel or 5-fluorouracil. Cell growth was measured colorimetrically. The IC(50) for 111In-DTPA-hEGF was < 70 pM (11 kBq/mL) versus 500 pM for DTPA-hEGF. The IC(50) for paclitaxel, methotrexate, doxorubicin and 5-fluorouracil was 6 nM, 15 nM, 20 nM and 4 microM respectively. (111)In-DTPA-hEGF (70 pM, 11 kBq/mL) delivered approx. 6 Gy to breast cancer cells producing growth inhibition equivalent to 4 Gy of gamma-radiation. We conclude that (111)In-DTPA-hEGF exhibited potent antiproliferative effects towards breast cancer cells at concentrations much lower than chemotherapeutic agents and equivalent to those produced by several Gy of high dose rate gamma-radiation.

Potential role of 18fluorodeoxyglucose-positron emission tomography/computed tomography in differentiating benign neurofibroma from malignant peripheral nerve sheath tumor associated with neurofibromatosis 1.

OBJECTIVE: Benign plexiform neurofibromas (PNfib), especially those occurring in patients with neurofibromatosis type 1, are at a significant risk of progressing to a malignant peripheral nerve sheath tumor (MPNST). Early diagnosis, followed by radical surgery and adjuvant radiation to maintain local tumor control, is of critical importance to prevent metastasis and subsequent mortality from MPNSTs. However, early diagnosis is hampered by the sensitivity of current imaging modalities such as computed tomography (CT) or magnetic resonance imaging to reliably detect this malignant transformation, which can occur heterogeneously in a PNfib to a MPNST. 18Fluorodeoxyglucose (18FDG)-positron emission tomography (PET) is linked to metabolism and proliferation of tissues and has been widely used in oncology including PNSTs. 18FDG-PET/CT has the added advantage of fusing metabolic and anatomic imaging data sets. METHODS: In this prospective study, 9 neurofibromatosis type 1-associated PNfibs suspected to have undergone transformation to an MPNST were preoperatively evaluated by 18FDG-PET/CT and magnetic resonance imaging. A detailed histological evaluation correlated the average and regional standard uptake value (SUV) from the 18FDG-PET/CT to grade of malignancy of the suspected MPNST. RESULTS: Imaging from 18FDG-PET/CT and associated SUV of the suspected MPNSTs demonstrated either a homogeneous or a heterogeneous pattern. Stratification of the maximal SUV to low (<4.0), intermediate (4.0-7.0), or high (>7.0) correlated to the proliferative index (Ki-67) and grade of MPNST. A maximal SUV of more than 7.0 was closely correlated to a focus of malignant transformation. CONCLUSION: This study, on a limited number of cases, demonstrates the potential use of 18FDG-PET/CT to augment management of PNfibs, especially in the context of neurofibromatosis type 1, which is characterized by multiple tumors. The addition of CT anatomic imaging to 18FGD-PET can facilitate targeting biopsies to metabolic hot spots, to further augment diagnostic sensitivity. Much larger numbers of MPNSTs, which can only be accrued in a collaborative manner among institutions, are required to further assess the specificity and sensitivity of 18FDG-PET/CT in the diagnosis of MPNSTs.