Timothy Akhurst

Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia

Are you Timothy Akhurst?

Claim your profile

Publications (72)366.06 Total impact

  • ANZ Journal of Surgery 11/2014; DOI:10.1111/ans.12854 · 1.12 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Purpose Increased glycolytic activity on FDG PET/CT defines a subgroup of patients with metastatic gastroenteropancreatic neuroendocrine tumour (NET) with a poor prognosis. A limited range of systemic treatment options exist for more aggressive NET. The role of peptide receptor chemoradionuclide therapy (PRCRT) in such patients is, however, unclear. This retrospective study assessed the outcomes of patients with FDG-avid NET treated with PRCRT. Methods Clinical, biochemical and imaging response was assessed after completion of induction treatment of PRCRT with 5-fluorouracil in 52 patients selected for treatment on the basis of somatostatin-receptor imaging without spatially discordant FDG-avid disease. Of the cohort, 67 % had received prior chemotherapy. Overall survival (OS) and progression-free survival (PFS) were also analysed. Results PRCRT was well tolerated with negligible grade 3/4 toxicities. After a median follow-up period of 36 months, the median OS was not achieved with a median PFS of 48 months. At 3 months after completion of PRCRT 2 % of patients showed a complete anatomical response, 28 % a partial response, 68 % stable disease, and only 2 % progression. On FDG PET/CT, 27 % achieved a complete metabolic response during the follow-up period. A biochemical response (>25 % fall in chromogranin-A levels) was seen in 45 %. Conclusion PRCRT is an effective treatment in patients with FDG-avid NET, even in patients who have failed conventional therapies. Given apparently higher response rates than with alternative therapeutic options and low toxicity, further research is needed to establish whether PRCRT should be used as a first-line treatment modality in this patient population.
    European journal of nuclear medicine and molecular imaging 09/2014; 42(2). DOI:10.1007/s00259-014-2906-4 · 5.22 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Objective. Increased glycolytic activity on FDG PET/CT is an adverse prognostic indicator in metastatic gastro-entero-pancreatic neuroendocrine tumor (GEP-NET). A range of systemic treatment options exist for more aggressive GEP-NET, including chemotherapy and targeted agents such as everolimus and sunitinib, particularly for pancreatic primaries. Peptide receptor radionuclide therapy (PRRT) has mainly been applied in patients with low grade GEP-NET but can also be used in patients with higher grade NET if there is sufficient somatostatin expression (SSTR) to enable targeted therapy. This retrospective study assesses the outcomes of patients with FDG-avid GEP-NET treated with peptide receptor chemo-radionuclide therapy (PRCRT). Materials and Methods: Clinical, biochemical and imaging response was assessed after completion of induction treatment of PRCRT with Lu-177 octreotate and infusional 5-fluorouracil chemotherapy in 52 patients. To be eligible, we required tumour uptake intensity of greater than liver on SSTR SPECT/CT or PET/CT, and no sites of spatially discordant FDG-avid disease. Ki,67 was available in 36 patients, with the 78% having ENETS Grade II or III disease. Prior chemotherapy had been received in 67% of the cohort . Overall survival (OS) and progression free survival (PFS) were analysed. Results: The median induction administered activity was 33 GBq over a median of 4 cycles. PRCRT was well tolerated with negligible Grade 3-4 hematologic toxicity. After a median follow-up period of 36 months, the median OS was not achieved with median PFS of 48 months. At 3 months post completion of PRCRT there was a complete anatomic response in 2%, a partial response in 28%, stable disease in 68%, and progression in only 2%. On FDG PET/CT, 27% achieved a complete metabolic response in the follow-up period. Biochemical response (>25% fall in Chromogranin-A levels) occurred in 45%. Conclusions: PRCRT is a highly effective treatment in patients with FDG-avid GEP-NET, even in patients who have failed conventional therapies. Given apparently higher response rates than alternative therapeutic options and low toxicity, further research is needed to establish whether PRCRT should be used as a first-line treatment modality.
    11th Congress of the World Federation in Nuclear Medicine and Biology World Federation in Nuclear Medicine and Biology (WFNMB), Cancún, Mexico; 08/2014
  • [Show abstract] [Hide abstract]
    ABSTRACT: Advances in the management of rectal cancer have resulted in an increased application of multimodal therapy with the aim of tailoring therapy to individual patients. Complete pathological response (pCR) is associated with improved survival and may be potentially managed without radical surgical resection. Over the last decade, there has been increasing interest in the ability of functional imaging to predict complete response to treatment. The aim of this review was to assess the role of (18)F-flurordeoxyglucose positron emission tomography (FDG-PET) in prediction of pCR and prognosis in resectable locally advanced rectal cancer. A search of the MEDLINE and Embase databases was conducted, and a systematic review of the literature investigating positron emission tomography (PET) in the prediction of pCR and survival in rectal cancer was performed. Seventeen series assessing PET prediction of pCR were included in the review. Seven series assessed postchemoradiation SUVmax, which was significantly different between response groups in all six studies that assessed this. Nine series assessed the response index (RI) for SUVmax, which was significantly different between response groups in seven series. Thirteen studies investigated PET response for prediction of survival. Metabolic complete response assessed by SUV2max or visual response and RISUVmax showed strong associations with disease-free survival (DFS) and overall survival (OS). SUV2max and RISUVmax appear to be useful FDG-PET markers for prediction of pCR and these parameters also show strong associations with DFS and OS. FDG-PET may have a role in outcome prediction in patients with advanced rectal cancer.
    Annals of Surgical Oncology 05/2014; 21(11). DOI:10.1245/s10434-014-3753-z · 3.94 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Ga-1,4,7,10-Tetraazacyclododecane-N,N',N'',N'''-tetraacetic acid (DOTA)-F(ab')2-trastuzumab [Ga-DOTA-F(ab')2-trastuzumab] has been developed at our institution as a positron imaging reagent for assessing human epidermal growth factor receptor 2 (HER2) expression status by in-vivo imaging. Initial studies on animals demonstrated promising results in the monitoring of treatment response to heat shock protein 90-targeted drugs that inhibit the client protein HER2. We report here our initial clinical experience in the assessment of the toxicity, pharmacokinetics, biodistribution, and dosimetry profile of Ga-DOTA-F(ab')2-trastuzumab with PET/computed tomography using a mean of 236 MBq/5 mg administered intravenously. A group of 16 women with breast cancer were enrolled in this study. The one patient who did not receive Ga-DOTA-F(ab')2-trastuzumab was excluded from analysis. Both HER2-negative (n=7) and HER2-positive (n=8) cases were studied. Among the latter, seven had undergone trastuzumab treatment previously and one had not. It was determined that Ga-DOTA-F(ab')2-trastuzumab was well tolerated, with a T ½ of ∼3.6±0.9 h; the critical organ was the kidney, with a mean dose of 0.383 cGy/37 MBq; and tumor targeting was seen in 4/8 patients with HER2-positive disease. The reagent is safe, and assessments through additional studies in a better-defined group of patients, using larger administered masses of antibodies, with a better immunoreactive fraction are needed.
    Nuclear Medicine Communications 10/2013; 34(12). DOI:10.1097/MNM.0b013e328365d99b · 1.37 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: OBJECTIVE:: To prospectively compare the ability of flourodeoxyglucose-positron emission tomography (FDG-PET) and computed tomography (CT) to identify a pathological complete response (pCR) in patients with rectal cancer treated by chemoradiation. BACKGROUND:: A major obstacle in pursuing nonoperative management in patients with rectal cancer after chemoradiation is the inability to identify a pCR preoperatively. METHODS:: A total of 121 patients with rectal cancer were prospectively enrolled. FDG-PET scans and helical CT scans were obtained before and after neoadjuvant chemoradiation. Consensus readings of PET and CT scans were used to classify certainty of disease (5-point confidence rating scale). The ability of PET and CT scans to accurately distinguish a pCR (ypT0) from an incomplete response (ypT1-4) was estimated using the area under the receiver operating characteristic curve (AUC). RESULTS:: Of the 121 patients, 26 (21%) had a pCR. PET and CT scans were equally inadequate at distinguishing a pCR from an incomplete response (AUC = 0.64 for both, P = 0.97). Among the 26 patients with a pCR, 14 (54%) and 5 (19%) were classified as complete responders on PET and CT scans, respectively. Among the 95 patients with an incomplete pathological response, 63 (66%) and 90 (95%) were classified as incomplete responders on PET and CT scans, respectively. None of the individual PET parameters, including visual response score, mean standard uptake value (SUVmean), maximum SUV (SUVmax), and total lesion glycolysis, accurately distinguished a pCR (AUCs = 0.57-0.73). CONCLUSIONS:: Neither PET nor CT scans have adequate predictive value to be clinically useful in distinguishing a pCR from an incomplete response and, therefore, should not be obtained for the purpose of attempting to predict a pCR after neoadjuvant chemoradiation for rectal cancer.
    Annals of surgery 11/2012; 258(2). DOI:10.1097/SLA.0b013e318277b625 · 7.19 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: BackgroundHSP90 inhibition leads to proteosomal degradation of activated KIT and has in vitro activity against gastrointestinal stromal tumors (GIST). BIIB021 is an oral non-ansamycin HSP90 inhibitor. We carried out a phase II study of BIIB021 in patients with GIST refractory to imatinib and sunitinib.Patients and methodsThe primary end-point was metabolic partial response (mPR) as assessed by fluorodeoxyglucose positron emission tomography (FDG-PET). The secondary end-points were pharmacokinetic assessments of BIIB021 and pharmacodynamic assessments of HSP70. Twenty-three patients were treated on two schedules: 12 pts received 600 mg twice a week (BIW) and 11 patients received 400 mg three times a week (TIW). All had prior imatinib and sunitinib but stopped >14 days before starting BIIB021.ResultsThe median age was 59 years (33-88 years), 61% male, 44% Eastern Cooperative Oncology Group 1 (ECOG1). The best response was PR by FDG-PET for five patients (3/12 at 600 mg BIW and 2/9 at 400 TIW) for an overall response rate of 22%. The response duration was 25-138 days. Adverse events (AEs) were mild to moderate. The mean C(max) was 1.5 µmol and the mean AUC was 2.9 µmol h. C(max) >1.5 µmol was associated with a decrease in standardized uptake value (SUV(max)). HSP70 increased substantially following treatment.Conclusions This study met its primary end-point. BIIB021 leads to objective responses in refractory GIST patients. Pharmacodynamic studies confirmed HSP90 inhibition. Further evaluation of BIIB021 in GIST is warranted.
    Annals of Oncology 08/2012; 24(1). DOI:10.1093/annonc/mds275 · 6.58 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: At present there is no defined role for routine FDG-PET in the preoperative evaluation of nonmetastatic rectal cancer. The primary objective of this study was to evaluate the ability of FDG-PET to predict long-term prognosis based on the response to neoadjuvant chemoradiotherapy in patients with locally advanced rectal cancer. This was a prospective study. This study was performed at an academic, tertiary care, comprehensive cancer center. One hundred twenty-seven patients with locally advanced rectal cancer were enrolled between September 1999 and December 2005. All patients underwent FDG-PET scans before and after neoadjuvant chemoradiotherapy. FDG-PET parameters were evaluated by at least 2 study board-certified nuclear medicine physicians, and included mean standard uptake value, maximum standard uptake value, total lesion glycolysis, and visual response score. The main outcome measures were time to recurrence and disease-specific survival. Of 127 patients, 82 (65%) were men, the median age was 60 years (range, 27-82), 110 patients had stage II/III disease, and 17 patients had stage IV disease. Median follow-up among survivors was 77 months (range, 1-115 months). Nine patients had unresectable metastatic disease and were excluded from the time-to-recurrence analysis. At 5 years, 74% (95% CI = 66%-81%) of patients had not had recurrences (locally and/or distantly). The 5-year disease-specific survival was 89% (95% CI = 81%-93%). On univariate analysis, visual response score and time to recurrence came closest to having an association (HR = 0.83, 95% CI = 0.68-1.01, p = 0.06). On multivariate analysis, the visual response score was not significant (p = 0.85). No FDG-PET parameter was associated with disease-specific survival. Assessment of rectal cancer response to neoadjuvant chemoradiotherapy by FDG-PET provides no prognostic information. Therefore, serial FDG-PET before and after neoadjuvant chemoradiotherapy should not be performed for this purpose.
    Diseases of the Colon & Rectum 04/2012; 55(4):378-86. DOI:10.1097/DCR.0b013e318244a666 · 3.20 Impact Factor
  • J. Ruby · T. Leibold · E. Riedel · J. Shia · S. Larson · T. Akhurst · W. Wong · J. Guillem
    Annual Meeting of the American-Society-of-Colon-and-Rectal-Surgeons; 05/2011
  • [Show abstract] [Hide abstract]
    ABSTRACT: Early identification of inadequate response to preoperative chemoradiotherapy (CRT) may spare rectal cancer patients the toxicity of ineffective treatment. We prospectively evaluated tumor response with (18)F-fluorodeoxyglucose (FDG) positron emission tomography (PET) early in the course of preoperative CRT. A total of 27 prospectively accrued patients with locally advanced rectal cancer (T(3-4)/N(1)) received preoperative CRT (5040 cGy + 5FU-based chemotherapy). Patients underwent PET scanning before and 8-14 days after commencement of CRT. Scans were interpreted using 3 standard parameters: SUV(max), SUV(avg), and total lesion glycolysis (TLG) as well as an investigational parameter: visual response score (VRS). Percent pathologic response was quantified as a continuous variable. All PET parameters were correlated with pathology. Pathologic complete/near-complete response was defined as ≥95% tumor destruction, suboptimal response as <95%. Statistical analysis was performed using the Wilcoxon rank sum test and receiver operating characteristic (ROC) curve analysis. Of the 27 patients, 11 (41%) had pathologic complete/near-complete response; 16 (59%) had suboptimal response. SUV(max), SUV(avg), and TLG did not discriminate between responders and nonresponders. Visual response score (VRS) was statistically significantly higher for complete/near-complete responders than for suboptimal responders (65 vs. 33%, P = 0.02). Suboptimal responders were identified with 94% sensitivity and 78% accuracy using a VRS cut-off of 50%. In this pilot study, FDG-PET at 8-14 days after the beginning of preoperative CRT was unsuccessful at predicting pathological response with enough accuracy to justify an early change in therapy.
    Annals of Surgical Oncology 04/2011; 18(10):2783-9. DOI:10.1245/s10434-011-1634-2 · 3.94 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The purpose of this study is to establish and validate a methodology for estimating the standard deviation of voxels with large activity concentrations within a PET image using replicate imaging that is immediately available for use in the clinic. To do this, ensembles of voxels in the averaged replicate images were compared to the corresponding ensembles in images derived from summed sinograms. In addition, the replicate imaging noise estimate was compared to a noise estimate based on an ensemble of voxels within a region. To make this comparison two phantoms were used. The first phantom was a seven-chamber phantom constructed of 1 liter plastic bottles. Each chamber of this phantom was filled with a different activity concentration relative to the lowest activity concentration with ratios of 1:1, 1:1, 2:1, 2:1, 4:1, 8:1 and 16:1. The second phantom was a GE Well-Counter phantom. These phantoms were imaged and reconstructed on a GE DSTE PET/CT scanner with 2D and 3D reprojection filtered backprojection (FBP), and with 2D- and 3D-ordered subset expectation maximization (OSEM). A series of tests were applied to the resulting images that showed that the region and replicate imaging methods for estimating standard deviation were equivalent for backprojection reconstructions. Furthermore, the noise properties of the FBP algorithms allowed scaling the replicate estimates of the standard deviation by a factor of 1/square root N, where N is the number of replicate images, to obtain the standard deviation of the full data image. This was not the case for OSEM image reconstruction. Due to nonlinearity of the OSEM algorithm, the noise is shown to be both position and activity concentration dependent in such a way that no simple scaling factor can be used to extrapolate noise as a function of counts. The use of the Well-Counter phantom contributed to the development of a heuristic extrapolation of the noise as a function of radius in FBP. In addition, the signal-to-noise ratio for high uptake objects was confirmed to be higher with backprojection image reconstruction methods. These techniques were applied to several patient data sets acquired in either 2D or 3D mode, with (18)F (FLT and FDG). Images of the standard deviation and signal-to-noise ratios were constructed and the standard deviations of the tumors' uptake were determined. Finally, a radial noise extrapolation relationship deduced in this paper was applied to patient data.
    Physics in Medicine and Biology 10/2010; 55(20):6299-326. DOI:10.1088/0031-9155/55/20/016 · 2.92 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: An asymptomatic 11-week-old male received no treatment after he was classified as having a suspected atypical form of MYCN-nonamplified hyperdiploid stage 4S neuroblastoma (NB), with masses in an adrenal gland, subcutaneous tissues, and the falx cerebri. Within 2 months, however, disease progressed in dura and bone marrow. Two cycles of low-dose chemotherapy achieved a partial response; treatment was discontinued. Complete remission was documented 24 weeks post-cycle 2, and has continued >6 years. The falx cerebri probably does not represent an atypical site for stage 4S NB, but stage 4 NB with favorable biology is sometimes curable with minimal therapy.
    Pediatric Blood & Cancer 12/2009; 53(7):1340-2. DOI:10.1002/pbc.22243 · 2.56 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: To facilitate future direct correlations between fluorine 18 fluorodeoxyglucose (FDG)-avid colonic lesions and immunohistochemical assay findings, the authors tested the feasibility of ex vivo FDG positron emission tomography (PET) of the colon resected from humans. In this institutional review board-approved, HIPAA-compliant study, the authors, after obtaining informed patient consent, injected FDG intraoperatively in five patients with neoplasms and imaged their resected colons approximately 3 hours later. The colon could be imaged during this fairly limited time interval, and polyps and cancers could be identified. No biologic tissue degradation occurred. The authors concluded that ex vivo FDG PET of the colon is feasible and, when combined with careful histologic and immunohistochemical analyses, may serve as a research tool to determine the mechanisms of the normal colonic uptake of FDG and the localization of FDG in polyps and cancers.
    Radiology 08/2009; 252(1):232-9. DOI:10.1148/radiol.2522081864 · 6.21 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: We have previously shown that in early clinical stage esophageal adenocarcinoma, a positron emission tomography standardized uptake values (PET SUVmax) of <4.5 is associated with earlier pathologic stage and predicts better survival. In this study, we analyze the impact of the pretreatment PET SUVmax in patients with locally advanced esophageal adenocarcinoma who undergo preoperative chemoradiotherapy. We performed a retrospective analysis, selecting patients with adenocarcinoma of the esophagus who had a pretreatment PET scan and who received chemoradiotherapy before esophagectomy. Data recorded included demographics, PET SUVmax, treatment details, pathologic details, and survival data. Comparison of categorical variables was done by chi analysis, continuous variables by t test, survival analysis by the Kaplan-Meier method, and comparisons of survival using the log-rank test. Between January 1996 and September 2007, 189 patients were appropriate for this analysis. The initial PET SUVmax was <4.5 in 28 patients and >or=4.5 in 161 patients. The two groups were similar with regards to demographics and treatment details. Patients in the low SUV group were less likely to show evidence of treatment response after chemoradiotherapy, including a higher likelihood of residual nodal disease and a lower likelihood of a pathologic complete response and estimated treatment response. However, both groups had similar survival. Although the initial PET SUVmax does not predict survival in patients with locally advanced esophageal adenocarcinoma who receive preoperative chemoradiotherapy, patients with a high initial SUVmax respond better to preoperative therapy. These results can be used to better select esophageal cancer patients for combined modality treatment.
    Journal of thoracic oncology: official publication of the International Association for the Study of Lung Cancer 07/2009; 4(7):875-9. DOI:10.1097/JTO.0b013e3181a8cebf · 5.80 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: PURPOSE To evaluate the potential benefit of continuous daily dosing sunitinib in patients with advanced nongastrointestinal stromal tumor (GIST) sarcomas. PATIENTS AND METHODS A total of 53 patients with advanced non-GIST soft tissue sarcomas received sunitinib 37.5 mg daily. Primary end point was Response Evaluation Criteria in Solid Tumors defined response. Secondary end points were stable disease at 16 and 24 weeks. [(18)F]-fluorodeoxyglucose positron emission tomography was performed on a subset of 24 patients at baseline and after 10 to 14 days of therapy. Results Forty-eight patients were eligible for response. One patient (desmoplastic round cell tumor [DSRCT]) achieved a confirmed partial response (PR) and remained on study for 56 weeks. Ten patients (20%) achieved stable disease for at least 16 weeks. Metabolic PR was seen in 10 (47%) of 21 of patients. Metabolic stable disease was seen in 11 (52%) of 21. There were no unexpected toxicities observed. CONCLUSION Sunitinib demonstrated notable evidence of metabolic response in several patients with non-GIST sarcoma. The relevance of disease control observed in subtypes with an indolent natural history is unknown, however, the durable disease control observed in DSRCT, solitary fibrous tumor, and giant cell tumor of bone suggests that future evaluation of sunitinib in these subtypes may be warranted.
    Journal of Clinical Oncology 06/2009; 27(19):3154-60. DOI:10.1200/JCO.2008.20.9890 · 18.43 Impact Factor
  • Ilya Laufer · Eric Lis · Leszek Pisinski · Timothy Akhurst · Mark H Bilsky
    [Show abstract] [Hide abstract]
    ABSTRACT: To determine the accuracy of [(18)F]fluorodeoxyglucose (FDG) positron emission tomography (PET) in the diagnosis of vertebral metastases in patients with cancer using needle-biopsy results and patient follow-up data. A retrospective chart review of all patients who underwent a needle biopsy of a spinal lesion and underwent FDG-PET within 6 weeks of the biopsy was performed. Biopsy results and magnetic resonance imaging and computed tomographic appearance of the biopsied lesion, as well as long-term clinical follow-up data, were recorded for each patient. A total of 82 patients with solid tumors and hematological spine metastases were included in this study. The mean standardized uptake values of lesions with active cancer were 7.1 and 2.1 in benign lesions (P < 0.02). In patients with metastatic solid tumors, the mean standardized uptake value was 7.3. Stratification of solid tumor lesions according to whether they had a sclerotic appearance on computed tomographic scans showed that FDG-PET was a significantly better predictor of cancer status in lytic or mixed lesions. In patients with a history of solid tumors, there was 100% concordance between the FDG-PET and needle-biopsy diagnoses in nonsclerotic lesions, when the standardized uptake value cutoff of 2 was used. FDG-PET is an accurate screening test for vertebral metastases in cancer patients. It is especially accurate in patients with nonsclerotic vertebral lesions and a history of solid malignancy.
    Neurosurgery 01/2009; 64(1):107-13; discussion 113-4. DOI:10.1227/01.NEU.0000335176.98788.A1 · 3.03 Impact Factor
  • Medical Physics 01/2009; 36(6). DOI:10.1118/1.3181087 · 3.01 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: After preoperative chemoradiotherapy of rectal cancer, the number of retrievable and metastatic lymph nodes is decreased. The current TNM classification is based on number and not location of lymph node metastases and may understage disease after chemoradiotherapy. The aim of this study was to examine the prognostic significance of location of involved lymph nodes in rectal cancer patients after preoperative chemoradiotherapy. We prospectively examined whole-mount specimens from 121 patients with uT3-4 and/or N+ rectal cancer who received preoperative chemoradiotherapy followed by resection. Location of involved lymph nodes was compared with median number of lymph nodes involved as well as presence of distant metastasis at presentation. Lymph node metastases were detected in 37 patients (31%). Thirteen patients with lymph node involvement along major supplying vessels (proximal lymph node metastases) had a significantly higher rate of distant metastatic disease at time of surgery than patients without proximal lymph node involvement (P < .001); median number of lymph nodes involved was two for patients with proximal lymph node metastases and 1.5 for patients with mesorectal lymph node involvement alone. Our data suggest that, after preoperative chemoradiotherapy, proximal lymph node involvement is associated with a high incidence of metastatic disease at time of surgery. Because the median number of involved lymph nodes is low after preoperative chemoradiotherapy, the TNM staging system may not provide an accurate assessment of metastatic disease. Therefore, the ypTNM staging system should incorporate distribution as well as number of lymph node metastases after preoperative chemoradiotherapy for rectal cancer.
    Journal of Clinical Oncology 06/2008; 26(13):2106-11. DOI:10.1200/JCO.2007.12.7704 · 18.43 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Patients with locally advanced rectal cancer may present with synchronous distant metastases. Choice of optimal treatment--neoadjuvant chemoradiation versus systemic chemotherapy alone--depends on accurate assessment of distant disease. We prospectively evaluated the ability of [18F]fluorodeoxyglucose ([18F]FDG) positron emission tomography (PET) to detect distant disease in patients with locally advanced rectal cancer who were otherwise eligible for combined modality therapy (CMT). Ninety-three patients with locally advanced rectal cancer underwent whole-body [18F]FDG PET scanning 2-3 weeks before starting CMT. Sites other than the rectum, mesorectum, or the area along the inferior mesenteric artery were considered distant and were divided into nine groups: neck, lung, mediastinal lymph node (LN), abdomen, liver, colon, pelvis, peripheral LN, and soft tissue. Two nuclear medicine physicians blinded to clinical information used PET images and a five-point scale (0-4) to determine certainty of disease. A score greater than 3 was considered malignant. Confirmation was based on tissue diagnosis, surgical exploration, and subsequent imaging. At a median follow-up of 34 months, the overall accuracy, sensitivity, and specificity of PET in detecting distant disease were 93.7%, 77.8%, and 98.7% respectively. Greatest accuracy was demonstrated in detection of liver (accuracy = 99.9%, sensitivity = 100%, specificity = 98.8%) and lung (accuracy = 99.9%, sensitivity = 80%, specificity = 100%) disease; PET detected 11/12 confirmed malignant sites in liver and lung. A total of 10 patients were confirmed to have M1 stage disease. All 10 were correctly staged by pre-CMT PET; abdominopelvic computed tomography (CT) scans accurately detected nine of them. Baseline PET in patients with locally advanced rectal cancer reliably detects metastatic disease in liver and lung. PET may play a significant role in defining extent of distant disease in selected cases, thus impacting the choice of neoadjuvant therapy.
    Annals of Surgical Oncology 04/2008; 15(3):704-11. DOI:10.1245/s10434-007-9626-y · 3.94 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Although (18)F-fluorodeoxyglucose positron emission tomography (PET) has widespread clinical use, its role in cancers of the biliary tract is ill-defined. The aim of this study was to determine if preoperative PET provided additional staging information in patients with biliary tract cancer, beyond that obtained through conventional anatomic imaging. The role of PET in detecting disease recurrence after resection was also examined. Between March 2001 and October 2003, 126 patients with biopsy-proved or presumed biliary tract cancer (intrahepatic or extrahepatic cholangiocarcinoma and gallbladder carcinoma) underwent PET in addition to standard imaging evaluation. Histologic confirmation of the diagnosis was used as the reference standard with which PET results were compared. Patient followup information and serial imaging were reviewed for progression of lesions detected by PET. Of the 126 study patients, 93 (74%) underwent preoperative staging PET scans, the results of which changed the stage and treatment in 22 patients (24%): 15 of 62 (24%) with cholangiocarcinoma and 7 of 31 (23%) with gallbladder carcinoma. When used to assess for cancer recurrence (n=33), PET identified disease in 86% of patients but altered treatment in only 9%. So, of the entire study group, the findings of PET influenced management in 20% of patients (24% preoperative staging and 9% cancer recurrence). The sensitivity of PET for identifying the primary tumor was 80% overall: 78% for cholangiocarcinoma, 86% for gallbladder carcinoma. Most biliary tract cancers are (18)F-fluorodeoxyglucose avid tumors. In patients with potentially resectable tumors based on conventional imaging, PET identified occult metastatic disease and changed management in nearly one-fourth of all patients. PET also helped confirm recurrent cancer after resection.
    Journal of the American College of Surgeons 02/2008; 206(1):57-65. DOI:10.1016/j.jamcollsurg.2007.07.002 · 4.45 Impact Factor

Publication Stats

4k Citations
366.06 Total Impact Points


  • 2014
    • Peter MacCallum Cancer Centre
      Melbourne, Victoria, Australia
    • University of Melbourne
      Melbourne, Victoria, Australia
  • 1998–2012
    • Memorial Sloan-Kettering Cancer Center
      • • Department of Nuclear Medicine
      • • Department of Radiology
      • • Department of Surgery
      New York, New York, United States
  • 2004–2005
    • Cornell University
      Итак, New York, United States
  • 2000
    • Gracie Square Hospital, New York, NY
      New York City, New York, United States