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Rodney J Hicks

Publications and source records attributed to Rodney J Hicks.

At least 37 records · Page 2Linked to original sources
PubMed2005

An in vivo tumor model exploiting metabolic response as a biomarker for targeted drug development.

In vivo models that recapitulate oncogene-dependent tumorigenesis will greatly facilitate development of molecularly targeted anticancer therapies. We have developed a model based on activating mutations in c-KIT in gastrointestinal stromal tumors (GISTs). This model comprises murine tumors of FDC-P1 cell lines expressing c-KIT mutations that render the tumors either responsive (V560G) or resistant (D816V) to the small-molecule c-KIT inhibitor, imatinib. Clinically, GIST response to imatinib is associated with rapid reduction in fluorodeoxyglucose (FDG) uptake on positron emission tomography (PET), preceding changes in conventional response criteria by several weeks. Using the FDC-P1 model in small animal PET, FDG uptake into tumors expressing the c-KIT V560G mutation was significantly reduced as early as 4 hours after imatinib treatment. In contrast, no change in FDG uptake was observed in resistant c-KIT D816V-expressing tumors after 48 hours of imatinib treatment. Consistent with the PET results, expression of the glucose transporter, GLUT1, was significantly reduced in V560G tumors at 4 hours, preceding changes in markers of proliferation by several hours. In vitro, imatinib treatment of V560G cells resulted in a reduction of glucose transporter numbers at the cell surface and decreased glucose uptake well before changes in cell viability. Notably, decreased ambient glucose concentrations enhanced the cytotoxic effect of imatinib. Taken together, these data account for the rapidity and significance of the PET response to imatinib and suggest that metabolic effects may contribute to imatinib cytotoxicity. Further, the FDC-P1 model represents a very useful paradigm for molecularly targeted drug development.

Animals↗
PubMed2005

Utility of FMISO PET in advanced head and neck cancer treated with chemoradiation incorporating a hypoxia-targeting chemotherapy agent.

PURPOSE: The purpose of the study was to evaluate [(18)F]fluoromisonidazole (FMISO) PET in advanced head and neck cancer during hypoxia-targeting therapy. METHODS: Fifteen of 16 patients in a phase I trial of chemoradiation plus tirapazamine (specific cytotoxin for hypoxic cells) in advanced (T3/4 and/or N2/3) head and neck cancer underwent serial [(18)F]fluorodeoxyglucose (FDG) and FMISO PET. We have previously reported excellent early clinical outcome of these patients and now review FMISO PET results in the context of longer follow-up of this patient cohort. RESULTS: Based on blinded qualitative scoring by two readers, FMISO PET was positive in 13/15 patients at baseline: 12/15 of primary sites and 8/13 neck nodes were scored as positive. All sites of corresponding FDG and FMISO abnormality at baseline showed marked qualitative reduction of uptake within 4 weeks of commencing therapy, consistent with effective hypoxia-targeted therapy. With a median follow-up of 6.9 years, there have been only four locoregional failures, while three other patients have died of metachronous lung cancer. The 5-year overall survival was 50% (95% CI 27-73%), the 5-year failure-free survival was 44% (95% CI 22-68%) and the 5-year freedom from locoregional failure was 68% (95% CI 38-88%). CONCLUSION: The high prevalence of hypoxia demonstrated on FMISO PET imaging is consistent with the advanced disease stage of these patients and would be expected to predict an adverse prognosis. Evidence of the early resolution of FMISO abnormality during treatment, associated with excellent locoregional control in this patient cohort, supports further investigation of hypoxia-targeting agents in advanced head and neck cancer.

Adult↗
PubMed2005

The role of PET in monitoring therapy.

Positron emission tomography (PET) is being increasingly used for the evaluation of patients with known or suspected cancer at all phases of the management process from diagnosis, through staging to follow-up after treatment. The role of PET in therapeutic monitoring is expanding rapidly due to its ability to provide earlier and more robust identification of non-responders than provided by conventional non-invasive imaging approaches. PET can thereby potentially provide important benefits to the individual patient by allowing an earlier change to alternative treatments that may be more efficacious or by avoiding the unnecessary toxicity related to ineffective therapy. As therapies become ever more expensive, this could also produce cost savings because of earlier termination of ineffective treatment. Conversely, PET may demonstrate important biological effects despite a lack of apparent morphological response and therefore prevent premature withdrawal of effective therapies. Globally, the vast majority of therapeutic monitoring studies use the glucose analogue, fluorine-18 fluorodeoxyglucose (FDG) but new tracers such as fluorine-18 fluorothymidine (FLT) also offer promise for this application. In this review, the potential benefits and limitations of FDG PET are discussed along with suggestions regarding the most practical methodologies for response evaluation using this modality.

Humans↗
PubMed2005

Functional imaging techniques for evaluation of sarcomas.

Sarcomas are often characterised by significant histopathologic heterogeneity, both between and within tumours. This heterogeneity reflects physiologic, biochemical and genetic processes that are amenable to characterisation by functional imaging. Although anatomically based imaging modalities such as plain radiography, X-ray computed tomography (CT) and magnetic resonance imaging (MRI) remain the primary diagnostic modalities for staging sarcomas, nuclear medicine approaches including gamma camera scintigraphy and positron emission tomography (PET) are being used increasingly to provide complementary information in specific clinical situations. These include biopsy guidance within anatomically complex masses, staging, therapeutic response assessment and evaluation of residual mass lesions after treatment. This review aims to address the range of nuclear medicine techniques available for evaluation of bone and soft tissue sarcomas. A subsequent review discusses the clinical application of these techniques with a particular focus on PET.

Diagnostic Imaging↗
PubMed2005

Clinical applications of molecular imaging in sarcoma evaluation.

A wide range of molecular imaging techniques are available that can provide complementary information to conventional, anatomical imaging for the evaluation of known or suspected bone and soft tissue sarcomas. In particular, positron emission tomography (PET), particularly in the form of hybrid PET/CT technology, offers many potential advantages over current imaging approaches by delineating not only the extent of disease but also the biological heterogeneity that can exist both between and within sarcomas. This review discusses the clinical situations where nuclear medicine techniques can aid in the management of patients with sarcoma. These include biopsy guidance, whole body staging, therapeutic response assessment and evaluation of residual mass lesions after treatment.

Biopsy, Needle↗
PubMed2005

Clinical experience with the first combined positron emission tomography/computed tomography scanner in Australia.

Metabolic imaging with fluorine-18-fluorodeoxyglucose positron emission tomography (FDG-PET) is increasing rapidly worldwide because of superior accuracy compared with conventional non-invasive techniques used for evaluating cancer. Limited anatomical information from FDG-PET images alone dictates that complementary use with structural imaging is required to optimise benefit. Recently, combined positron emission tomography/computed tomography (PET/CT) scanners have overtaken standalone PET scanners as the most commonly purchased PET devices. We describe our experience of over 5500 scans performed since the first PET/CT scanner in Australia was commissioned at the Peter MacCallum Cancer Centre (PMCC), Melbourne, in January 2002. Clinical indications for PET/CT scans performed at PMCC largely reflect current Medicare reimbursement policy. Advantages of PET/CT include greater patient comfort and higher throughput, greater diagnostic certainty and accuracy, improved biopsy methods, and better treatment planning. We believe PET/CT will underpin more effective and efficient imaging paradigms for many common tumours, and lead to a decrease in imaging costs.

Australia↗
PubMed2005

Metabolic (FDG-PET) response after radical radiotherapy/chemoradiotherapy for non-small cell lung cancer correlates with patterns of failure.

BACKGROUND: We previously reported that F-18 fluorodeoxyglucose (FDG) positron emission tomography (PET) response correlated strongly with survival after radical radiotherapy (RT)/chemoradiotherapy for non-small cell lung cancer (NSCLC). PET-response, survival and patterns of failure data are presented with long-term follow-up. METHODS: Pre- and post-treatment FDG-PET scans were performed for 88 patients after concurrent platinum-based radical chemo/RT (n = 73) or radical RT alone (n = 15). PET responses were prospectively assessed as either complete metabolic response (CMR), partial metabolic response (PMR), stable metabolic disease (SMD), or progressive metabolic disease (PMD). RESULTS: RT was 60 Gy in 30 fractions in 6 weeks. Follow-up PET was performed at a median of 70 days after treatment. PET responses were: CMR, n = 40 (45%); PMR, n = 32 (36%); SMD, n = 5 (6%) and PMD 11 (13%). Estimated median survival after follow-up PET was 23 months; median follow-up duration 35 months. One and 2 year survival after follow-up PET was 68% and 45%, respectively. Median survival for CMR and non-CMR patients was 31 and 11 months, respectively (p = 0.0001). One-year survival for CMR and non-CMR patients was 93% and 47%, respectively and 2 years survival was 62% and 30%, respectively. Excluding PMD patients, non-CMR patients had higher rates of local failure (HR 2.15, p = 0.009) and distant metastasis (HR 2.05, p = 0.041) than CMR patients. By last follow-up, 20 of 40 CR patients (50%) had PMD, with local failure (n = 8), distant metastasis (n = 2) or both (n = 10). CONCLUSIONS: Attainment of CMR after radical RT/chemoRT for NSCLC bestows superior freedom from local and distant relapse; late local relapse is common.

Carcinoma, Non-Small-Cell Lung↗
PubMed2005

Utility of positron emission tomography for the detection of disease in residual neck nodes after (chemo)radiotherapy in head and neck cancer.

BACKGROUND: This study evaluates the utility of fluorine-18 fluorodeoxyglucose positron emission tomography (FDG PET) in patients with a node-positive mucosal head and neck squamous cell carcinoma who achieved a complete response at the primary site but had a residual mass in the neck 8 weeks or more after definitive (chemo)radiotherapy. METHODS: Between October 1996 and July 2002, 39 eligible patients were identified. The reference PET scan was performed at a median of 12 weeks (range, 8-32 weeks) after treatment. RESULTS: PET showed no metabolic activity in the residual mass in 32 patients. Five of these patients had a neck dissection and were all pathologically negative. The remaining 27 patients were observed for a median of 34 months (range, 16-86 months), with only one locoregional failure. The negative predictive value of PET for viable disease in a residual anatomic abnormality was 97%. CONCLUSION: Patients who have achieved a complete response at the primary site but have a residual abnormality in the neck that is PET negative approximately 12 weeks after treatment do not require neck dissection and can be safely observed. Head Neck

Adult↗
PubMed2005

PET imaging for suspected residual tumour or thoracic recurrence of non-small cell lung cancer after pneumonectomy.

F-18 fluorodeoxyglucose-positron emission tomography (PET) was investigated in patients with suspected residual disease or intrathoracic recurrence after pneumonectomy. Patients were identified from a prospective database. Impact of PET on staging and patient management was assessed. Clinical outcome was used to assess appropriateness of management. PET was performed in 17 cases, either post-operatively (n = 8), or later for suspected recurrence (n = 9) in patients with good performance status and without extensive disease on conventional imaging. PET changed treatment in 10 cases (59%). In five patients (29%), PET changed treatment intent (curative versus non-curative) from radical radiotherapy (RT) to palliative RT (n = 1), or observation or supportive care (n = 3), or from palliative to radical RT (n = 1). In a further patient with unexplained pain, PET appropriately showed no evidence of disease. In additional five cases (29%), PET influenced choice of RT dose and the use of concurrent chemotherapy (n = 3) or target volume (n = 2). Patients without tumour or with limited disease on PET had favourable outcomes whereas those with extensive disease suffered early tumour progression. PET was discordant with conventional assessment in >50% of cases. PET may be valuable after pneumonectomy if the patient is being considered for adjuvant or salvage radiotherapy although specificity may be reduced due to post-operative inflammatory changes.

Carcinoma, Non-Small-Cell Lung↗
PubMed2005

Initial staging of lymphoma with positron emission tomography and computed tomography.

Lymphomas represent a diverse range of diseases with manifold presentations, outlook, and therapeutic approaches. Key to the modern management of lymphoma is accurate delineation of the extent of disease. The inability of computed tomography (CT) to identify the involvement of nonenlarged nodes and its relatively poor sensitivity in the detection of extra-nodal sites of involvement limit the performance of noninvasive staging techniques. Functional imaging techniques such as Ga-67 scintigraphy have been used for many years to improve the evaluation of patients with lymphoma. While providing complementary information to CT in many clinical settings, functional imaging has never had sufficient accuracy or localizing ability to seriously challenge conventional primary staging paradigms. (18)F-Fluorodeoxyglucose positron emission tomography (FDG PET), however, has been demonstrated to have both higher sensitivity and specificity than CT in many comparative series. Now that this technology also can be performed at the same time as structural imaging in the form of hybrid PET/CT devices, clinicians are rethinking the methods used to select, plan, and monitor therapy of lymphoma patients. In our institution, FDG PET/CT has become the preferred initial staging tool for patients with lymphoma.

Humans↗
PubMed2005

Modulation of intratumoral hypoxia by the epidermal growth factor receptor inhibitor gefitinib detected using small animal PET imaging.

Blockade of signaling through the epidermal growth factor receptor (EGFR) tyrosine kinase by inhibitors such as gefitinib (Iressa) can inhibit tumor angiogenesis and enhance responses to ionizing radiation. In this study, the ability of gefitinib to modulate intratumoral oxygenation was evaluated in human EGFR-expressing A431 squamous cell carcinoma xenografts using in vivo small animal positron emission tomography (PET) imaging with the hypoxia marker [(18)F]fluoroazomycin arabinoside (FAZA) and by the immunohistochemical detection of hypoxia-induced adducts of the 2-nitroimidazole, pimonidazole. Serial noninvasive PET imaging of A431 xenografts showed a significant reduction in FAZA uptake following treatment with 75 mg/kg/d of gefitinib [tumor to background ratio, 6.1 +/- 1.0 (pretreatment) versus 2.3 +/- 0.6 (posttreatment); P = 0.0004]. Similarly, ex vivo quantitation of FAZA uptake showed significantly reduced FAZA uptake in established A431 xenografts treated with gefitinib compared with vehicle control (tumor to blood ratio for controls versus gefitinib, 8.0 +/- 3.0 versus 2.7 +/- 0.8; P = 0.007; or tumor to muscle ratio controls versus gefitinib, 8.6 +/- 2.8 versus 2.6 +/- 1.0; P = 0.002). The effect of gefitinib treatment seemed to be independent of tumor size. In addition, gefitinib treatment reduced pimonidazole-binding in A431 xenografts measured after 5 and 8 days of gefitinib treatment compared with baseline and with tumors treated with vehicle alone. A strong correlation was observed between pimonidazole binding and FAZA uptake. Together, these findings show that gefitinib reduces intratumoral hypoxia.

Animals↗
PubMed2004

Early FDG-PET imaging after radical radiotherapy for non-small-cell lung cancer: inflammatory changes in normal tissues correlate with tumor response and do not confound therapeutic response evaluation.

PURPOSE: To investigate the relationship between positron emission tomography (PET) detected inflammatory changes in irradiated normal tissues and metabolic response at tumor sites in patients receiving radical radiotherapy for non-small-cell lung cancer. The prognostic significance of these changes was also studied. METHODS: In 73 consecutive patients, (18)F-fluorodeoxyglucose (FDG) PET was performed at a median of 70 days after completion of radical radiotherapy. Radiation-induced inflammatory change was scored for normal tissues within the radiation treatment volume using a 0-3 grading scale. Metabolic tumor response was assessed using a pattern-recognition algorithm comparing pre- and posttreatment scans. Prognostic significance of inflammatory changes was tested using the Cox proportional hazards regression model. RESULTS: Increased FDG uptake in normal tissues (radiotoxicity) was associated with a greater likelihood of complete or partial tumor response on both PET (p = 0.0044) and computed tomography (p = 0.029). Prognostic stratification provided by PET response was both significant and of a similar magnitude in patients with low- and high-grade radiotoxicity. CONCLUSION: Postradiotherapy inflammatory changes detected by FDG-PET are positively correlated with tumor response, suggesting that tumor radioresponsiveness and normal tissue radiosensitivity may be linked. Prognostic stratification provided by PET is not compromised by inflammatory changes if a meticulous visual response assessment technique is used.

Adenocarcinoma↗
PubMed2004

Enteropathy-associated T-cell lymphoma without a prior diagnosis of coeliac disease: diagnostic dilemmas and management options.

Enteropathy-associated T-cell lymphoma (EATL) ultimately develops in 7-10% of patients with long-standing coeliac disease. In patients without a prior diagnosis of coeliac disease this is a very rare disorder, and the diagnosis in such cases is often difficult and delayed due to the non-specific nature of the symptoms and a very low index of clinical suspicion. Standard anti-lymphoma therapies have minimal utility in patients with EATL, and their prognosis is poor. An added difficulty is the high risk of intestinal perforation especially with the commencement of treatment due to the multifocal nature of bowel disease and poor underlying nutrition and tissue integrity. To illustrate these problems and provide an example of how these issues may be addressed, we report the case of a patient with EATL who was completely asymptomatic from unsuspected underlying coeliac disease and presented initially with back pain followed by bowel obstruction. He was treated with gut rest with total parenteral nutrition before commencing an intensive chemotherapy regimen [hyper-CVAD (cyclophosphamide, vincristine, doxorubicin, and dexamethasone)] and is currently well in ongoing complete remission 34 months later.

Adult↗
PubMed2004

Does positron emission tomography change management in primary rectal cancer? A prospective assessment.

PURPOSE: The influence of positron emission tomography in the management of recurrent rectal cancer is well established but its role in primary rectal cancer remains uncertain. This study therefore prospectively assesses the impact of position emission tomography scanning on the management of primary rectal cancer. METHODS: Forty-six patients with advanced primary rectal cancer referred for consideration of adjuvant preoperative therapy underwent position emission tomography scanning. The referring physicians prospectively recorded each patient's stage following conventional imaging and the proposed treatment plan prior to position emission tomography scanning. This was then compared with subsequent stage and actual management implemented, and the appropriateness of position emission tomography-induced changes was noted by subsequent clinical follow-up. RESULTS: The surgical management of 36 of 46 patients (78 percent) was unchanged as a result of position emission tomography, even though position emission tomography upstaged disease in 3 of 36 cases (8 percent) and downstaged disease in 5 of 36 cases (14 percent). In 8 of 46 cases (17 percent), management was altered because of the position emission tomography scan findings, including 6 cases (13 percent) in which surgery was cancelled and 2 other cases (4 percent) in which the radiotherapy field was changed. Where available, follow-up confirmed the appropriateness of position emission tomography-induced management change in each case. Two patients had a change in therapy independent of the position emission tomography scan due to clinical circumstances. Overall tumor stage was changed following position emission tomography in 18 of 46 patients (39 percent). CONCLUSION: Position emission tomography scanning appears to accurately change the stage or appropriately alter the therapy of almost a third of patients with advanced primary rectal cancer. In view of this, we suggest that position emission tomography scanning be considered part of standard workup for such patients, particularly if neoadjuvant chemoradiation is being considered as part of primary management.

Adult↗
PubMed2004

Usefulness of fluorine-18 fluorodeoxyglucose positron emission tomography in patients with a residual structural abnormality after definitive treatment for squamous cell carcinoma of the head and neck.

BACKGROUND: Residual structural abnormalities after definitive treatment of head and neck squamous cell carcinoma (HNSCC) are common and pose difficult management problems. The usefulness of fluorine-18 fluorodeoxyglucose positron emission tomography (FDG PET) to supplement conventional evaluation with clinical and standard radiologic examination (CE) in such patients was assessed. METHODS: Fifty-three eligible patients were identified with residual structural abnormalities on CE. True disease extent could be validated in 46 patients. Patients had a median potential follow-up of 55 months (range, 41-75 months) from the date of PET scan to the analysis closeout date. RESULTS: PET had better diagnostic accuracy than CE (p = .0002) and induced management change in 21 patients (40%; 95% confidence interval [CI], 26%-54%), including avoidance of unnecessary planned surgery in 14 patients with negative PET. Appropriate management change was confirmed in 19 (95%) of 20 evaluable cases. Disease presence and extent assessment by PET were significant predictors of survival (p < .0001), whereas the extent of disease determined by CE was not. CONCLUSION: PET added significantly to the value of CE in restaging disease in patients with structural abnormalities after definitive treatment of HNSCC. Management decisions based on PET were appropriate in most patients.

Aged↗
PubMed2004

Impact of positron emission tomography on the management of patients with small-cell lung cancer: preliminary experience.

Accurate staging is important in small-cell lung cancer (SCLC). Patients with limited stage may benefit from chemoradiation, whereas those with extensive stage conventionally receive chemotherapy. Prophylactic cranial irradiation may benefit those attaining complete remission (CR). 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) enhances accuracy of staging in non-SCLC. Its role in SCLC remains unclear. We reviewed 36 consecutive SCLC patients who underwent 47 PET studies between December 1996 and January 2001, for either staging (n = 11), restaging after therapy (n = 21), or both (n = 4). Conventional imaging was also performed. Of 15 patients who had PET for staging, 5 (33%) were upstaged from limited to extensive disease and treated without thoracic radiotherapy. Twenty-five patients underwent 32 restaging PET scans, of which 20 (63%) were discordant with conventional imaging. In 8 cases PET showed more extensive disease than conventional imaging, and in 12 cases PET-apparent disease appeared less extensive. In 13 patients, 14 untreated discordant lesions were evaluable; PET was confirmed accurate in 11 (79%) sites by last follow-up. Restaging PET influenced management in 13 cases (52%). PET-CR conferred longer median time to progression (13.7 months) than no CR (9.7 months). FDG-PET for SCLC was often discordant with conventional assessment and frequently influenced management.

Aged↗
PubMed2003

Positron emission tomography is superior to computed tomography scanning for response-assessment after radical radiotherapy or chemoradiotherapy in patients with non-small-cell lung cancer.

PURPOSE: To prospectively study the capacity of positron emission tomography (PET) and computed tomography (CT) to determine response soon after radical radiotherapy or chemoradiotherapy and, thereby, predict survival. PET is known to provide a more accurate estimate of true extent of disease than CT when used to stage non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Seventy-three patients with NSCLC underwent [(18)F]fluorodeoxyglucose PET and CT scans before and after radical radiotherapy (n = 10) or chemoradiotherapy (n = 63). Follow-up PET scans were performed at a median of 70 days after radiotherapy. The median PET-CT interval was 1 day. Each patient had determinations of response to therapy made with PET and CT, categorized as complete response, partial response, no response, progressive disease, or nonassessable. Responses were correlated with subsequent survival. RESULTS: Median survival after follow-up PET was 24 months. There was poor agreement between PET and CT responses (weighted kappa = 0.35), which were identical in only 40% of patients. There were significantly more complete responders on PET (n = 34) than CT (n = 10), whereas fewer patients were judged to be nonresponders (12 patients on PET v 20 on CT) or nonassessable (zero patients on PET v six on CT) by PET. Both CT and PET responses were individually significantly associated with survival duration; but on multifactor analysis that included the known prognostic factors of CT response, performance status, weight loss, and stage, only PET response was significantly associated with survival duration (P <.0001). CONCLUSION: In NSCLC, a single, early, posttreatment PET scan is a better predictor of survival than CT response, stage, or pretreatment performance status.

Aged↗