Localised disease in cancer of unknown primary (CUP): The value of positron emission tomography (PET) for individual therapeutic management

Background:Two to four percent of cancer patients presentwith CUP syndrome. Median survival for localised disease is 20 and fordisseminated disease, seven months. For localised disease, curativetreatment is more likely and individual therapeutic strategies becomemore important. After conservative diagnostic procedures including MRI,the primary is detected in less than 25%. The diagnostic value ofPET and its influence on therapeutic strategies was evaluated. Patients and methods:Forty-two patients with localised CUPwere investigated from 5 of 98 to 10 of 2000. The presenting site waslymph node metastasis in 34 and visceral metastasis in 8 patients. Aftera median of 7 (3–11) diagnostic procedures without detection ofthe primary, but evidence of localised disease, PET was performed withfluorine-18-fluorodeoxyglucose. Results:In 26 of 42patients (62%), a primary was suggested by PET and confirmed in18 (43%). In 5 of 18 patients beyond localised disease,additional dissemination, not detected by previous diagnostic measures,was diagnosed by PET. Overall, dissemination was only detected only byPET in 16 of 42 patients (38%). In 29 of 42 patients(69%), the PET result influenced selection of the definitivetreatment. Conclusion:In CUP patients, PET has acertain impact on detection of the primary as well as of thedisseminated disease, and may also have a certain impact on therapeuticmanagement.     

Influence of 18F‐fluorodeoxyglucose‐positron emission tomography on computed tomography‐based radiation treatment planning for oesophageal cancer

The addition of positron emission tomography (PET) information to CT‐based radiotherapy treatment planning has the potential to improve target volume definition through more accurate localization of the primary tumour and involved regional lymph nodes. This case report describes the first patient enrolled to a prospective study evaluating the effects of coregistered positron emission tomography/CT images on radiotherapy treatment planning for oesophageal cancer. The results show that if combined positron emission tomography/CT is used for radiotherapy treatment planning, there may be alterations to the delineation of tumour volumes when compared to CT alone. For this patient, a geographic miss of tumour would have occurred if CT data alone were used for radiotherapy planning.     

Coregistered whole body magnetic resonance imaging‐positron emission tomography (MRI‐PET) versus PET‐computed tomography plus brain MRI in staging resectable lung cancer

BACKGROUND:

The objective of this study was to assess whether coregistered whole brain (WB) magnetic resonance imaging‐positron emission tomography (MRI‐PET) would increase the number of correctly upstaged patients compared with WB PET‐computed tomography (PET‐CT) plus dedicated brain MRI in patients with nonsmall cell lung cancer (NSCLC).

METHODS:

From January 2010 through November 2011, patients with NSCLC who had resectable disease based on conventional staging were assigned randomly either to coregistered MRI‐PET or WB PET‐CT plus brain MRI (ClinicalTrials.gov trial NCT01065415). The primary endpoint was correct upstaging (the identification of lesions with higher tumor, lymph node, or metastasis classification, verified with biopsy or other diagnostic test) to have the advantage of avoiding unnecessary thoracotomy, to determine appropriate treatment, and to accurately predict patient prognosis. The secondary endpoints were over staging and under staging compared with pathologic staging.

RESULTS:

Lung cancer was correctly upstaged in 37 of 143 patients (25.9%) in the MRI‐PET group and in 26 of 120 patients (21.7%) in the PET‐CT plus brain MRI group (4.2% difference; 95% confidence interval, ?6.1% to 14.5%; P = .426). Lung cancer was over staged in 26 of 143 patients (18.2%) in the MRI‐PET group and in 7 of 120 patients (5.8%) in the PET‐CT plus brain MRI group (12.4% difference; 95% confidence interval, 4.8%‐20%; P = .003), whereas lung cancer was under staged in 18 of 143 patients (12.6%) and in 28 of 120 patients (23.3%), respectively (?10.7% difference; 95% confidence interval, ?20.1% to ?1.4%; P = .022).

CONCLUSIONS:

Although both staging tools allowed greater than 20% correct upstaging compared with conventional staging methods, coregistered MRI‐PET did not appear to help identify significantly more correctly upstaged patients than PET‐CT plus brain MRI in patients with NSCLC. Cancer 2013. © 2013 American Cancer Society.     

Unsuspected bone and soft tissue lesions identified at cancer screening using positron emission tomography

BACKGROUND: [F-18]-fluorodeoxy-D-glucose (18FDG) positron emission tomography (PET) is a sensitive modality for detecting malignant lesions. The purpose of the present study was to describe unknown bone and soft tissue lesions in adults identified at cancer screening using PET. METHODS: A total of 4283 individuals of more than or equal to 40 years of age were enrolled. All individuals underwent scans from the base of the skull to proximal thigh. The images were reviewed and a consensus was reached by two board-certified radiologists and a nuclear medicine specialist for the diagnoses. Diagnoses of the lesions were confirmed by histological examination, typical radiologic findings, obvious progression in number and/or size of the lesion on follow-up examinations, and medical examination of interview. RESULTS: Unsuspected focal abnormality in the bone and soft tissue were found in 62 individuals (1.4%). The mean size of the lesion was 26 mm (range, 6-155 mm). There were 29 bone lesions (47%) and 33 soft tissue lesions (53%). A malignant lesion was found in one case (1.6%) and histologic diagnosis was primary non-Hodgkin lymphoma of the vertebra. Other major diagnoses were healing bone (n = 11, 18%) and benign cystic lesions of bone and soft tissue (n = 9, 15%), and brown fat of soft tissue (n = 4, 6%). CONCLUSION: Unsuspected bone and soft tissue lesions of a wide variation of pathologic and clinical diagnoses were encountered at cancer screening using PET. Correlation with clinical history and other imaging findings is essential in the differential diagnosis.     

Characteristics of advantages of positron emission tomography over computed tomography for N-staging in lung cancer patients

OBJECTIVE: We analyzed the characteristics of advantages of positron emission tomography (PET) over computed tomography (CT) for N-staging in lung cancer patients. METHODS: Preoperative PET and CT scans were performed for 2057 lymph node stations in 205 patients with peripheral-type lung cancer. The advantages of PET over CT for N-staging were analyzed among lymph node locations and histological subtypes. RESULTS: The pathological N-stages were N0 in 143 patients, N1 in 31, N2 in 24 and N3 in 7. PET was able to diagnose N0, N2 and N3 diseases more accurately than CT (P=0.03, 0.01 and 0.02, respectively), but there was no significant difference between the two modalities for N1 disease. In the upper mediastinal lymph node stations, both false-negative and false-positive were significantly less frequent with PET than with CT (P=0.001). In the lower mediastinal and supra clavicle lymph nodes, PET showed a lower frequency of false-negative than CT (P=0.04 and 0.003, respectively), but there was no significant difference in the frequency of false-positive between the two modalities. Among histological types, PET could stage adenocarcinoma with less frequent false-negative and squamous cell carcinoma with less frequent false-positive than CT (P=0.02 and 0.005, respectively). CONCLUSION: For N-staging, PET was superior to CT for the following: (1) more accurate for N0, N2 and N3 diseases but not for N1; (2) lower frequency of false-positive in the upper mediastinal nodes; and (3) lower frequencies of false-negative in adenocarcinoma and false-positive in squamous cell carcinoma. Recognizing these advantages of PET could make the N-staging of lung cancer more accurate.     

Detection of occult bone metastases of lung cancer with Fluorine‐18 fluorodeoxyglucose positron emission tomography

Accurate staging of cancer has a critical role in optimal patient management. Fluorine‐18 fluorodeoxyglucose positron emission tomography (FDG PET) is superior to CT in the detection of local and distant metastases in patients with non‐small cell lung cancer. Although Tc‐99 m methylene diphosphonate (MDP) bone scanning is well established in the evaluation of bone metastases, there are conflicting reports on the use of FDG PET in the evaluation of skeletal metastases. We report on a patient with locally advanced lung carcinoma in whom FDG PET accurately identified previously unsuspected widespread asymptomatic bone metastases (bone scan and X‐rays negative, confirmed on MRI). Assessment of glucose metabolism with FDG PET might represent a more powerful tool to detect bone metastases in lung cancer compared with conventional bone scans.     

Impact of positron emission tomography/computed tomography surveillance at 12 and 24 months for detecting head and neck cancer recurrence

BACKGROUND:

In head and neck cancer (HNC), 3‐month post‐treatment positron emission tomography (PET)/computed tomography (CT) reliably identifies persistent/recurrent disease. However, further PET/CT surveillance has unclear benefit. The impact of post‐treatment PET/CT surveillance on outcomes is assessed at 12 and 24 months.

METHODS:

A 10‐year retrospective analysis of HNC patients was carried out with long‐term serial imaging. Imaging at 3 months included either PET/CT or magnetic resonance imaging, with all subsequent imaging comprised of PET/CT. PET/CT scans at 12 and 24 months were evaluated only if preceding interval scans were negative. Of 1114 identified patients, 284 had 3‐month scans, 175 had 3‐ and 12‐month scans, and 77 had 3‐, 12‐, and 24‐month scans.

RESULTS:

PET/CT detection rates in clinically occult patients were 9% (15 of 175) at 12 months, and 4% (3 of 77) at 24 months. No difference in outcomes was identified between PET/CT‐detected and clinically detected recurrences, with similar 3‐year disease‐free survival (41% vs 46%, P = .91) and 3‐year overall survival (60% vs 54%, P = .70) rates. Compared with 3‐month PET/CT, 12‐month PET/CT demonstrated fewer equivocal reads (26% vs 10%, P < .001). Of scans deemed equivocal, 6% (5 of 89) were ultimately found to be positive.

CONCLUSIONS:

HNC patients with negative 3‐month imaging appear to derive limited benefit from subsequent PET/CT surveillance. No survival differences were observed between PET/CT‐detected and clinically detected recurrences, although larger prospective studies are needed for further investigation. Cancer 2013. © 2012 American Cancer Society.     

Fluorodeoxyglucose positron emission tomography in the evaluation of germ cell tumours at relapse

Differentiation of active disease from fibrosis/mature teratoma in patients with residual masses or identifying of sites of recurrence in patients with raised markers following treatment of their testicular cancer remains a problem.(18)F-fluorodeoxyglucose positron emission tomography (FDG-PET) has the potential to identify active disease and thereby influence further management in these patients. We performed a retrospective study of the use of FDG-PET in detecting residual/recurrent testicular carcinoma in 55 patients (seventy FDG-PET scans). Forty-seven scans were for the assessment of residual masses (18 had raised markers) and 23 scans were for the investigation of raised markers in the presence of normal CT scans. True positive results were based on positive histology or clinical follow-up. FDG-PET had a positive predictive value (PPV) of 96% and a negative predictive value (NPV) of 90% in patients with residual masses. This PPV was equivalent to that of markers (94%) but FDG-PET had the advantage of identifying the site of that recurrence. The NPV was higher than that of markers. In patients with raised markers alone the PPV of FDG-PET was 92% but the NPV was only 50%. However, subsequent FDG-PET imaging was frequently the first imaging modality to identify the site of disease. FDG-PET effected a management change in 57% of cases. FDG-PET scanning detected viable tumour in residual masses and identified sites of disease in suspected recurrence.     

Differential diagnosis of gallbladder cancer using positron emission tomography with fluorine-18-labeled fluoro-deoxyglucose (FDG-PET)

BACKGROUND AND OBJECTIVES: The purpose of this paper is to evaluate the utility of positron emission tomography (PET) with fluorine-18-labeled fluoro-deoxyglucose (FDG) in the preoperative differential diagnosis of gallbladder tumors. We performed PET studies of gallbladder tumors in order to predict the malignancy of these tumors preoperatively. METHODS: Sixteen patients who had protuberant lesions in the gallbladder and who were scheduled to undergo surgery were studied with PET using FDG. Focally increased FDG uptake in the gallbladder region was considered malignant. The FDG-PET findings were compared with the histological findings of surgical pathology. RESULTS: Sensitivity of FDG-PET was 75% (6/8 patients). One of two false-negative cases suffered from diabetes mellitus, and in the other case, the lesion was small. Specificity was 87.5% (7/8 patients). A case with xanthogranulomatous cholecystitis (XGC) was the only false-positive case. CONCLUSIONS: FDG-PET may be able to provide important information for evaluating the malignancy of gallbladder tumors.     

Impact of 18F-fluorodeoxyglucose positron emission tomography in the staging and treatment response assessment of extra-pulmonary small-cell cancer

The aim of this study was to retrospectively evaluate the value of ¹⁸F-fluorodeoxyglucose (FDG) positron emission tomography (PET) in extrapulmonary small-cell cancer (EPSCC). Patients with EPSCC who underwent PET for staging or response assessment between 1996 and 2007 were identified from a database. Patient records were reviewed. PET-based, and conventional staging and restaging results were compared. The binary staging classification of limited disease (LD) versus extensive disease (ED) was used. Patients with LD had tumours that could be encompassed within a tolerable radiation therapy (RT) volume. Of 33 eligible patients, 12 had staging PET scans, 11 had restaging scans and 10 had both. All known gross disease sites were FDG-avid. PET and conventional stage groupings were concordant in 21 of 22 cases. One patient was appropriately upstaged from LD to ED by PET. PET detected additional disease sites, without causing upstaging in three further patients. Restaging PET scans identified previously unrecognised persistent or progressive disease in 4 of 21 cases. In four further cases, persistent FDG uptake after treatment was either false positive (n = 2) or of uncertain (n = 2) aetiology. PPV was 100% for staging and 82% for restaging. In 8 of 43 imaging episodes (19%), PET appropriately influenced management in five cases by changing treatment intent from radical to palliative, and in three cases by altering the RT volume. PET has incremental value compared to conventional imaging for staging EPSCC, and may also be useful for restaging after therapy. PET influenced patient management in 19% of 43 imaging episodes.     

The role of positron emission tomography in management of small cell lung cancer

Accurate radiological staging of small-cell lung cancer (SCLC) is of paramount importance in selection of individual patients with limited stage disease for potentially curative treatment while avoiding toxic treatment in those with distant metastatic disease. [¹⁸F] flurodeoxy-d-glucose (FDG) positron emission tomography (PET) is an attractive tool for this purpose but there is limited evidence to support its use in the routine staging of SCLC. Whether therapeutic decisions based on FDG-PET imaging should be made remains uncertain. There is only preliminary evidence for use of FDG-PET as a prognostic biomarker, in the assessment of response to treatment and delineation of disease in conformal radiation planning.     

Evaluating the role of fluorodeoxyglucose positron emission tomography-computed tomography in multi-disciplinary team recommendations for oesophago-gastric cancer

Background:

National guidelines recommend that fluorodeoxyglucose positron emission tomography-computed tomography (PET-CT) is performed in all patients being considered for radical treatment of oesophageal or oesophago-gastric cancer without computerised tomography scan (CTS) evidence of metastasis. Guidance also mandates that all patients with cancer have treatment decisions made within the context of a multi-disciplinary team (MDT) meeting. Little is known, however, about the influence of PET-CT on decision making within MDTs. The aim of this study was to assess the role of PET-CT in oesophago-gastric cancer on MDT decision making.

Methods:

A retrospective analysis of a prospectively held database of all patients with biopsy-proven oesophageal or oesophago-gastric cancer discussed by a specialist MDT was interrogated. Patients selected for radical treatment without CTS evidence of M1 disease were identified. The influence of PET-CT on MDT decision making was examined by establishing whether the PET-CT confirmed CTS findings of M0 disease (and did not change the patient staging pathway) or whether the PET-CT changed the pathway by showing unsuspected M1 disease, refuting CTS suspicious metastases, or identifying another lesion (needing further investigation).

Results:

In 102 MDT meetings, 418 patients were discussed, of whom 240 were initially considered for radical treatment and 238 undergoing PET-CT. The PET-CT confirmed CTS findings for 147 (61.8%) and changed MDT recommendations in 91 patients (38.2%) by (i) identifying M1 disease (n=43), (ii) refuting CTS suspicions of M1 disease (n=25), and (iii) identifying new lesions required for investigations (n=23).

Conclusion:

The addition of PET-CT to standard staging for oesophageal cancer led to changes in MDT recommendations in 93 (38.2%) patients, improving patient selection for radical treatment. The validity of the proposed methods for evaluating PET-CT on MDT decision making requires more work in other centres and teams.     

Imaging tumour hypoxia with positron emission tomography

Hypoxia, a hallmark of most solid tumours, is a negative prognostic factor due to its association with an aggressive tumour phenotype and therapeutic resistance. Given its prominent role in oncology, accurate detection of hypoxia is important, as it impacts on prognosis and could influence treatment planning. A variety of approaches have been explored over the years for detecting and monitoring changes in hypoxia in tumours, including biological markers and noninvasive imaging techniques. Positron emission tomography (PET) is the preferred method for imaging tumour hypoxia due to its high specificity and sensitivity to probe physiological processes in vivo, as well as the ability to provide information about intracellular oxygenation levels. This review provides an overview of imaging hypoxia with PET, with an emphasis on the advantages and limitations of the currently available hypoxia radiotracers.     

Pancreatic cancer: Preliminary experience with sodium iodide fluorodeoxyglucose positron emission tomography in Australia

Previous studies of fluorodeoxyglucose positron emission tomography (FDG‐PET) in pancreatic cancer have used Bismuth Germinate detector systems. This preliminary Australian study aims to confirm the accuracy of FDG‐PET in pancreatic cancer using a dedicated sodium iodide (NaI) PET system. Fifteen consecutive patients underwent FDG‐PET using a GE QUEST dedicated NaI PET scanner. The indications were the characterization of a pancreatic mass seen on CT or ultrasonographic imaging (nine cases), diagnosis or exclusion of recurrent disease following surgery and adjuvant therapy (four cases) and presurgical staging of primary pancreatic cancer (two cases). The final diagnosis was determined from histology or, when no histology was available, by radiological and clinical follow up. The FDG‐PET accurately characterized eight out of nine pancreatic masses (seven were true negative, one was true positive and one was false positive). Of the four cases performed to determine recurrent disease, three were accurately diagnosed (two true negatives and one true positive). In the fourth case, PET accurately detected a liver metastasis but did not detect the local recurrence. Results in the two cases where PET was performed for preoperative staging comprised one true positive and one false negative. Sodium iodide FDG‐PET is useful in the diagnosis of pancreatic cancer, particularly in the presence of a previously detected mass.     

The expanding role of PET technology in the management of patients with colorectal cancer.

The therapeutic options and subsequent survival of colorectal cancer (CRC) patients has increased substantially over recent years. While surgical excision of the primary cancer results in cure of approximately 50% of patients, recurrence and metastatic disease still remains a significant cause of death. Although resection of liver or lung metastases can result in cure, relapse rates remain high, indicating that patient selection needs improvement. Positron emission tomography (PET) technology has a great deal to offer with respect to CRC management, particularly in the setting of patient selection for metastasectomy and in the evaluation of possible recurrent disease, however it has not yet become a routine part of the management of all CRC patients. This review article aims to discuss the current and future implications of PET technology in the optimal management of CRC patients throughout their care pathway.     

Laparoscopic extraperitoneal para-aortic lymphadenectomy in locally advanced cervical cancer: a prospective correlation of surgical findings with positron emission tomography/computed tomography findings

BACKGROUND:

Failure to detect metastasis to para‐aortic nodes in patients with locally advanced cervical cancer leads to suboptimal treatment. No previous studies have prospectively compared positron emission tomography (PET)/computed tomography (CT) with laparoscopic extraperitoneal staging in the evaluation of para‐aortic lymph nodes.

METHODS:

Sixty‐five patients were enrolled; 60 were available for analysis. Patients with stage IB2‐IVA cervical cancer without evidence of para‐aortic lymphadenopathy on preoperative CT or magnetic resonance imaging (MRI) were prospectively enrolled. All patients underwent preoperative PET/CT. Laparoscopic extraperitoneal lymphadenectomy was performed from the common iliac vessels to the left renal vein.

RESULTS:

The median age at diagnosis was 48 years (range, 23‐84). The median operative time was 140 minutes (range, 89‐252). The median blood loss was 22.5 mL (range, 5‐150). The median length of hospital stay was 1 day (range, 0‐4). The median number of lymph nodes retrieved was 11 (range, 1‐39). Fourteen (23%) patients had histopathologically positive para‐aortic nodes. Of the 26 patients with negative pelvic and para‐aortic nodes on PET/CT, 3 (12%) had histopathologically positive para‐aortic nodes. Of the 27 patients with positive pelvic but negative para‐aortic nodes on PET/CT, 6 (22%) had histopathologically positive para‐aortic nodes. The sensitivity and specificity of PET/CT in detecting positive para‐aortic nodes when nodes were negative on CT or MRI were 36% and 96%, respectively. Eleven (18.3%) patients had a treatment modification based on surgical findings.

CONCLUSIONS:

Laparoscopic extraperitoneal para‐aortic lymphadenectomy is safe and feasible. Surgical staging of patients with locally advanced cervical cancer should be considered before planned radiation and chemotherapy. Cancer 2011. © 2010 American Cancer Society.     

Distant metastasis of prostate cancer: early detection of recurrent tumor with dual-phase carbon-11 choline positron emission tomography/computed tomography in two cases

Several types of recurrence may be detected by radiologic assessment after treatment in patients with prostate cancer. However, early detection of distant metastasis using positron emission tomography has so far never been published. We report two patients who underwent hormone therapy or surgical resection for prostate cancer. They developed distant metastases which were detected on whole body [C-11] choline positron emission tomography/computed tomography with significant elevation of serum PSA level. In one patient, recurrent tumor of the supraclavicular node (6 mm) diminished in size after subsequent hormone therapy. Surgical resection of recurrent tumor of the lung (12 mm) was performed in the other patient, the pathology of which confirmed the metastatic adenocarcinoma derived from the prostate. The recurrent tumor can be correctly detected by dual-phase whole body [C-11] choline positron emission tomography/computed tomography.     

Brain tumor protein synthesis and histological grades: A study by positron emission tomography (PET) with C11-L-Methionine

Summary Brain protein synthesis may be evaluated in vivo by a PET three compartment methionine model. 14 human brain tumor patients were studied. Protein synthesis rate (PSR) was increased in any glial tumor even in low grades, but this increase was statistically more important in anaplastic tumor.Radiotherapy action was evaluated in two patients. Local tumoral PSR was reduced to normal brain PSR after treatment. No difference was seen in normal cortex contralateral to the lesion between pre and post radiotherapy examination.11 C-L-Methionine incorporation measured by PET looks as a very sensitive method for studying tumor metabolism and treatment effects.     

Impact of post-therapy positron emission tomography on prognostic stratification and surveillance after chemoradiotherapy for cervical cancer

BACKGROUND:

A study was undertaken to investigate the detection of relapse and survival outcomes in patients with cervical cancer treated with curative intent chemoradiotherapy, and evaluated with a post‐therapy ¹⁸F‐fluorodeoxyglucose positron emission tomography (FDG‐PET) scan.

METHODS:

Between January 2002 and June 2007, 105 consecutive patients were prospectively enrolled into a registry study designed to assess outcomes of chemoradiotherapy. A FDG‐PET scan was performed between 3 and 12 months (median, 4.9 months) post‐treatment at clinician discretion. Tumor response was graded as complete metabolic response, partial metabolic response, or progressive metabolic disease.

RESULTS:

Median follow‐up was 36 months. At post‐therapy FDG‐PET, 73 (70%) patients had complete metabolic response, 10 (9%) had partial metabolic response, and 22 (21%) had progressive metabolic disease. Overall survival at 3 years was 77% in all patients, and 95% for those with complete metabolic response. On multivariate analysis, complete metabolic response (P < .0001) and pretreatment tumor volume (P = .041) were strong predictors for overall survival. The number of involved lymph nodes (P < .005) and International Federation of Gynecology and Obstetrics stage (P = .04) were predictive of relapse‐free survival. In total, 18 patients relapsed at a single site, and 13 underwent salvage, with a 3‐year survival of 67%. Patients with complete metabolic response had a distant failure rate 36‐fold less than those with partial metabolic response (P < .0001). After complete metabolic response, only 1 patient (1.6%) relapsed without symptoms and was detected through physical examination.

CONCLUSIONS:

The presence of a complete metabolic response at post‐therapy FDG‐PET is a powerful predictor for survival after chemoradiation. The very low rate of recurrence in patients with a complete metabolic response justifies a conservative follow‐up approach for these patients, because relapse is usually symptomatic and not detected by routine clinical review. Cancer 2011. © 2011 American Cancer Society.