Conventional Staging Modalities Research Articles

Prospective study to assess the role of FDG PET/CT in detecting systemic metastatic spread in rectal cancers with lateral pelvic lymph nodes

IntroductionThe utility of positron emission tomography (PET) in detecting additional M1 patients over conventional staging modalities is not known in rectal cancer patients with enlarged lateral pelvic nodes. MethodsProspective, single center, single-arm interventional study of consecutive rectal cancer patients that had baseline lateral pelvic nodes on MRI (>10 mm) between February 2017 to December 2018. Such patients underwent PET after confirming non-metastatic status on CT of thorax and abdomen. Primary outcome measure was additional M1 sites detected on PET. A 10% distant metastasis rate was expected with 80% confidence interval (CI) set at 5% as the lower limit. Results44 patients were included and the concordance between MRI and PET in detection of lateral nodes was 97.7% (43 patients). Additional sites of metastasis were detected in 5 patients (11.36%; 80% CI - 5.63%–20.6%), and there was a change in treatment plan in 7 (15.9%). The number needed to treat (NNT) for PET scans to detect additional metastatic sites and change treatment were 9 and 6 respectively. There was a change in treatment intent (curative to palliative) in 2 patients (4.5%, NNT – 22). ConclusionIn rectal cancer patients with LPLN, the use of FDG-PET-CT over conventional staging studies led to the detection of additional extra-pelvic metastasis in 11.4% and changed the treatment plan in 15.9%. This met the pre-defined threshold to endorse the use of PET-CT in patients that match the study characteristics.

Tc-99m depreotide SPECT/CT for lymph node staging of non-small-cell lung cancer

To investigate the potential role of Tc-99m depreotide (Tc-DEPR) in the preoperative lymph node (N) staging of non-small-cell lung cancer (NSCLC). Sixty-one patients with NSCLC at the potentially operable stage were enrolled and underwent scintigraphy before surgery (n=56) or mediastinoscopy (n=5). Imaging was performed with a hybrid single photon emission computed tomography/computed tomography (SPECT/CT) system. Depreotide uptake in N stations was evaluated visually and semi-quantitatively and compared to histology. Quantification was carried out in attenuation-corrected SPECT slices. Different sites of normal uptake were used as a reference for comparison with lesional uptake. Receiver operating characteristic analysis was employed to identify the most preferable reference area and the cut-off best discriminating disease-free from disease-involved lymph nodes. With reference to 53 Ν1 hilar and 147 Ν2/Ν3 sampled stations, sensitivity of scintigraphy by visual interpretation was 100 and 94%, specificity 43 and 59% and accuracy 55 and 67%, respectively. No patient was down-staged, but 52% were incorrectly up-staged and 44% were misclassified as inoperable. Compared to scintigraphy, preoperative contrast-enhanced diagnostic CT demonstrated lower sensitivity (36% for hilar and 73% for N2/N3 stations), higher specificity (79 and 75%) and similar accuracy (70 and 75%). Regarding the ultimate N-stage and the prediction of surgical disease, diagnostic CT was wrong in 51 and 34% of cases. Dichotomy of quantitative scintigraphic data by the use of certain N-to-spine ratio cut-offs resulted in a significant increase of specificity (76% for hilar and 89% for N2/N3 stations), while sensitivity remained high (82% in both circumstances) and accuracy for Ν2/Ν3 stations was substantially improved (88%). By this quantitative approach, misclassifications as to the N-stage and patient operability (25 and 16%) were considerably less than that of visual Tc-DEPR and diagnostic CT interpretations. Tc-99m depreotide SPECT/CT seems to have a role in the N-staging of NSCLC, mainly because of its high sensitivity and negative predictive value. Quantification of uptake can improve specificity, at a low cost of sensitivity. If F-18 fluoro-deoxyglucose positron emission tomography is not available, this method may be used as a surrogate to conventional staging modalities.

Has integrated 18F FDG PET/CT improved staging, reduced early recurrence or increased survival in oesophageal cancer?

BackgroundSurvival in oesophageal cancer remains poor with high post-operative recurrence rates. PET/CT was introduced to the Three-Counties Cancer Network (3CCN) in 2006 to detect ‘occult’ metastatic disease not seen with conventional staging modalities. This study aims to determine whether the introduction of Integrated fluorodeoxyglucose (18F) Positron Emission Tomography (PET/CT) has changed the management, improved survival or reduced the rate of early post-operative recurrence in patients with operable oesophageal cancer. MethodsA retrospective review was undertaken of all patients diagnosed with oesophageal cancer in the 3CCN from 2005 to 2009. Early recurrence was defined as proven recurrence locally or at a distant site within one year of resection. Results725 patients were identified. 200 (27.6%) patients underwent staging PET/CT. PET/CT altered treatment intent in 19 (9.5%) patients. 128 (17.7%) patients underwent oesophageal resection, 90 (70.3%) of which had a staging PET/CT. No significant difference was noted in post-operative mortality (4.4% Vs 5.3%, p = 0.8) or early recurrence where PET/CT was performed when adjusted for age, sex, stage or neo-adjuvant chemotherapy (p = 0.761, OR 1.136[95% CI 0.499–2.585]). PET/CT had no significant effect on survival (log-rank test; Chi-square 0.710, p = 0.4). ConclusionPET/CT has improved the accuracy of oesophageal cancer staging avoiding potentially unnecessary surgery. Ultimately however, its use has had no effect on early recurrence or survival rates. Inaccurate identification of occult metastatic disease prior to the introduction of staging PET/CT does not appear to be the primary cause of early recurrence in patients with oesophageal cancer.

The accuracy of 18F-fluorodeoxyglucose-positron emission tomography/computed tomography (FDG-PET/CT) in the staging of newly diagnosed nasopharyngeal carcinoma: A systematic review and meta-analysis.

5553 Background: The specific role of FDG-PET/CT in pretreatment staging of nasopharyngeal carcinoma (NPC) remains to be validated. We performed a systematic review and meta-analysis to assess the diagnostic accuracy of staging FDG-PET/CT for newly diagnosed NPC with reference to conventional staging modalities and/or clinical follow up. Methods: We searched MEDLINE, Cochrane central register of controlled trials, proceedings of ASTRO and ASCO as well as Chinese databases (Chinese National Knowledge Infrastructure and CBMdisc) from the date of inception to September 2011 for relevant studies. Study quality was assessed using the Quality Assessment of Diagnostic Accuracy Studies (QUADAS) checklist. We determined the sensitivities and specificities across studies, pooled diagnostic odds ratios (DOR) and constructed summary receiver operating characteristic curves using hierarchical regression model. Results: We found 15 relevant studies (of which seven were in English) including 851 patients. Of the 15 studies: five addressed primary tumor (T), nine addressed regional lymph nodes (N) and seven addressed distant metastasis (M). The combined sensitivity estimate for FDG-PET/CT in T classification was 0.77(95% confidence interval (CI) 0.59-0.95). The combined sensitivity estimate for N classification was 0.88 (95% CI 0.86-0.90), specificity 0.85(95% CI 0.83-0.88), DOR 82.4 (23.2 to 292.6) and Q-index was 0.90. For M classification, the combined sensitivity estimate was 0.82(95% CI 0.65-0.93), specificity 0.98 (95% CI 0.96 – 0.99), DOR 120.9 (43.0 to 340.0) and Q-index was 0.89. Conclusions: FDG-PET/CT showed good accuracy in N and M but not T classification for newly diagnosed pre-treated NPC. FDG-PET/CT, together with Magnetic resonance imaging (MRI) of the nasopharynx, should be part of the routine staging investigations for NPC. Future research should evaluate the accuracy of FDG-PET/MRI fusion as a single staging modality for NPC.

Positron-emission tomography/computed tomography (PET/CT) in the initial staging of primary rectal cancer

The aim of this study was to assess the role of (18)flourodeoxyglucose positron-emission tomography/computed tomography (PET/CT) in the initial staging of primary rectal adenocarcinoma. A total of 20 patients with adenocarcinoma of the rectum were assessed with both PET/CT and conventional staging (CT chest/abdomen/pelvis, MRI rectum). Discordance with conventional imaging and incidental findings on PET were recorded and the patients presented to a colorectal cancer multidisciplinary team to assess management changes. Patients were followed up so that discordant or incidental findings could be verified by intra-operative examination, imaging or histology where possible. Positron-emission tomography/computed tomography correctly identified the primary tumour in all 20 patients. Comparing PET/CT with conventional staging modalities, there were 11 discordant or incidental findings in nine patients (45%). This resulted in a potential change in stage in 30% (four patients downstaged and two upstaged). PET/CT suggested additional neoplastic pathology in three patients and excluded the same in two patients. The incidental neoplastic findings were of minor clinical significance and one was eventually deemed false positive. While PET/CT resulted in potential management changes in five patients (25%), no changes in surgical management occurred. When tumours were grouped according to conventional stage, PET/CT resulted in fewer changes in stage in stage I (0%), compared with stages II to IV (43%) (P = 0.08). Positron-emission tomography/computed tomography provides additional information to conventional staging in primary rectal cancer. This information produced minor management changes in this study and did not effect surgical management. PET/CT may be most appropriately used selectively in more advanced stages and where indeterminate findings exist with conventional staging.

Detection of lymph node metastases with ultrasmall superparamagnetic iron oxide (USPIO)-enhanced magnetic resonance imaging in oesophageal cancer: a feasibility study

Aim: In this feasibility study we investigated whether magnetic resonance imaging (MRI) with ultrasmall superparamagnetic iron oxide (USPIO) can be used to identify regional and distant lymph nodes, including mediastinal and celiac lymph node metastases in patients with oesophageal cancer.Patients and methods: Ten patients with a potentially curative resectable cancer of the oesophagus were eligible for this study. All patients included in the study had positive lymph nodes on conventional staging (including endoscopic ultrasound, computed tomography and fluorodeoxyglucose-positron emission tomography). Nine patients underwent MRI + USPIO before surgery. Results were restricted to those patients who had both MRI + USPIO and histological examination. Results were compared with conventional staging and histopathologic findings.Results: One patient was excluded due to expired study time. Five out of 9 patients underwent an exploration; in 1 patient prior to surgery MRI + USPIO diagnosed liver metastases and in 3 patients an oesophageal resection was performed. USPIO uptake in mediastinal lymph nodes was seen in 6 out of 9 patients; in 3 patients non-malignant nodes were not visible. In total, 9 lymph node stations (of 6 patients) were separately analysed; 7 lymph node stations were assessed as positive (N1) on MRI+USPIO compared with 9 by conventional staging. According to histology findings, there was one false-positive and one false-negative result in MRI + USPIO. Also, conventional staging modalities had one false-positive and one false-negative result. MRI + USPIO had surplus value in one patient. Not all lymph node stations could be compared due to unforeseen explorations. No adverse effects occurred after USPIO infusion.Conclusion: MRI+USPIO identified the majority of mediastinal and celiac (suspect) lymph nodes in 9 patients with oesophageal cancer. MRI+USPIO could have an additional value in loco-regional staging; however, more supplementary research is needed.

Evidence for Management of Small Cell Lung Cancer: ACCP Evidence-Based Clinical Practice Guidelines (2nd Edition)

This systematic review addressed the following key questions on managing small cell lung cancer (SCLC): the sequence, timing, and dosing characteristics of primary thoracic radiotherapy (TRTx) for limited-stage disease; primary TRTx for extensive-stage disease; effect of prophylactic cranial irradiation (PCI); positron emission tomography (PET) for staging; treatment of mixed histology tumors; surgery; and second-line and subsequent-line treatment for relapsed/progressive disease.The review methods were defined prospectively in a written protocol. We primarily sought randomized controlled trials that compared the interventions of interest.Robust evidence was lacking for all questions except PCI, for which a patient-level metaanalysis showed that PCI improves survival of SCLC patients who achieved complete response after primary therapy from 15.3 to 20.7% (p = 0.01). The case for concurrent over sequential radiation delivery rests largely on a single multicenter trial. Support for early concurrent therapy comes from one multicenter trial, but two other multicenter trials found no advantage. Metaanalysis did not find significant reductions in 2-year and 3-year mortality rates for early TRTx. Favorable results from a single-center trial on TRTx for extensive stage disease need replication in a multicenter setting. Relevant comparative studies were nonexistent for management of mixed histology disease and surgery for early limited SCLC. PET may be more sensitive in detecting extracranial disease than conventional staging modalities, but studies were of poor quality.PCI improves survival among those with a complete remission to primary therapy. A research agenda is needed to optimize the effectiveness of TRTx and its components.

Impact of FDG-PET Imaging Versus Conventional Staging Modalities on Staging and Treatment Decisions in Large B-Cell, Follicular, and Hodgkin's Lymphomas.

Clinical staging of lymphomas has a critical role in determining appropriate therapy and in therapeutic response assessment. While anatomic imaging by CT or MRI, together with physical examination and bone marrow biopsy (conventional staging modalities or CSM), have historically provided the basis for staging and response assessment, positron emission tomography using 18-fluoro-2-deoxyglucose (FDG-PET) has increasingly been employed in the management of patients (pts) with lymphomas. Studies comparing FDG-PET with anatomic imaging have generally found that FDG-PET identifies more sites of disease; however, the impact of FDG-PET imaging on assignment of clinical stage and treatment decisions is unclear. We retrospectively examined the impact of FDG-PET imaging on assignment of disease stage and treatment decisions compared with CSM alone in 91 pts with large B-cell lymphoma (LBCL; n=30), follicular lymphoma (FL; n=29) and Hodgkin's lymphoma (HL; n=32). 25/30 LBCL (83%), 26/32 HD (81%) and 17/29 FL pts (59%) were evaluated at initial diagnosis by FDG-PET imaging and CSM, while others were evaluated during subsequent relapse. FDG-PET and CSM defined the same stage in 69/91 pts (76%). Stage assignment was most concordant in LBCL with only 5/30 (17%) of cases having different stages, while stage assignments were discrepant in 7/32 (22%) of cases of HL and in 10/29 (34%) of cases of FL. Of the 22 pts with discrepant results, FDG-PET resulted in upstaging of disease in 11 pts and downstaging in 11 pts. Independent confirmatory tests resolving the discrepancy were obtained in 3 of 11 pts upstaged (27%) and 7 of 11 pts downstaged by FDG-PET (64%). Abnormal FDG uptake in lymph nodes accounted for all cases upstaged by FDG-PET in which no confirmatory test was available (8/8 pts). Among 10 cases resolved by biopsy, discrepant sites included bone marrow (n = 4), bone (n = 1), pelvic or abdominal structures (n = 3), and lymph nodes (n = 2). FDG-PET results were true positive in 2/10, true negative in 1/10, false positive in 1/10, and false negative in 6/10 cases (including 4 cases with BM involvement). Incorporation of FDG-PET led to treatment changes in a minority of patients (2%). We conclude that FDG-PET is an efficient single imaging modality in pts with LBCL, FL and HL, providing information complementary to CSM. However, changes in treatment based on FDG-PET results are rare. Discrepancies between FDG-PET and CSM should be resolved by biopsy when feasible, particularly in cases in which treatment would be altered.

Carcinoembryonic antigen as a predictive factor for postoperative tumor relapse in early-stage lung adenocarcinoma.

To clarify the usefulness of measuring serum carcinoembryonic antigen (CEA) preoperatively to detect patients who will have a poor outcome after surgery, and who cannot be selected by conventional staging modalities. One hundred patients with adenocarcinoma of the lung underwent standard surgical procedures between 1994 and April 2001 at our institution. Preoperative staging was assessed according to the TNM classification of the International Union Against Cancer. The associations between preoperative serum CEA level and the postoperative recurrence or lymph node metastasis were examined. The serum CEA level was classified into two groups according to concentration of CEA level: low (normal) CEA (<or=5.0 ng/ml) and high CEA (>5.0 ng/ml). The high CEA level was associated with tumor relapse (P=0.01). According to the preoperative staging, the increased CEA was associated with tumor relapse only in stage C-IA (P=0.001). Stage C-IB and more advanced stages did not show an association between increased CEA and tumor relapse. In C-IA, risk for lymph node involvement was significantly higher in the high CEA group (4/9; 44.4%) than in the low CEA group (6/47; 12.8%, P=0.03). Furthermore, the rate of tumor relapse in C-IA-pN0 was significantly higher in the high CEA group (4 of the 5, 80%) than in the low CEA group (9 of the 41, 22.0%, P=0.018). The 5-year disease-free survival rate for patients with a high serum CEA level (N=9) was 22.2%, and 75.0% for patients with a normal CEA (N=47) level (P=0.0004). Increased serum CEA is an important predictive factor for poor outcome after surgery in early-stage (C-IA) lung adenocarcinoma.

2-Deoxy-2-[F-18]Fluoro-D-Glucose Imaging with Positron Emission Tomography for Initial Staging of Hodgkin's Disease and Lymphoma

Purpose: To assess the accuracy of 2-Deoxy-2-[F-18] Fluoro-D-Glucose positron emission imaging (FDG-PET) for staging Hodgkin's disease (HD) and non-Hodgkin's lymphoma (NHL) compared to conventional staging (CS) and to evaluate the impact on patient management. Methods: Forty-five consecutive patients with lymphoma underwent whole-body FDG-PET imaging for initial staging. Discordant lesions were verified with biopsy or clinical follow-up. The impact on staging and management was reviewed retrospectively. Results: A total of 129 sites of disease were identified, and 88 of those were concordant. FDG-PET and conventional staging demonstrated 24 and 17 additional sites, respectively. FDG-PET correctly upstaged five patients and down-staged two patients (16% total), leading to a change in therapy in 6/45 (13%) patients. However, FDG-PET understaged three patients (7%), correctly staged by conventional staging modalities. Assuming that the addition of FDG-PET to conventional staging modalities is 100% accurate for staging lymphoma, the accuracy of FDG-PET alone was 91%, compared to 84% for conventional staging modalities. Conclusions: FDG-PET is a noninvasive and efficient imaging modality for staging patients with lymphoma and should be used in conjunction with conventional staging modalities, as they appear complementary. (Mol Imag Biol 2002;4:105–114)

Value of positron emission tomography for lung cancer staging

Objective: The therapeutic strategy in non-small-cell lung cancer (NSCLC) requires exact staging of tumour invasion (T) as well as differentiation between ipsi- and contralateral lymph node invasion (N1/2 vs N3). [18F]FDG-positron emission tomography (FDG-PET) has been shown to detect invaded N with high accuracy while correct determination of T appears to be unclear. The purpose of this prospective study was to evaluate benefit and necessity of18FDG-PET as an additive to conventional staging modalities. Methods: Forty patients with suspected non-small-cell lung cancer (NSCLC) were staged by means of computed tomography (CT), bronchoscopy, mediastinoscopy and bone scintigraphy. Additionally, attenuation corrected FDG-PET of the thorax was performed pre-operatively for analysis of T and N topography. After surgical resection with radical lymphadenectomy T and N staging results of CT and PET were compared with the pathological diagnoses. Specificity, sensitivity, positive predictive value and accuracy of CT and PET were calculated. Results: Twenty three squamous cell carcinomas, 14 adenocarcinomas, and three non-malignant tumours were found. Accuracy of CT-T was 0.75 and of PET-T 0.78; accuracy of CT-N was 0.78 and of PET-N 0.80. By combination of CT-T and PET-T accuracy was 0.88. Combination of CT-N and PET-N yielded an accuracy of 0.90. In two out of three cases, PET correctly determined T0. In two cases non-malignant inflammatory lymph nodes were falsely staged as malignant by PET. Conclusions: Adequate pre-operative T- and N-staging is possible with both CT and FDG-PET. Accuracy can be improved by combination of CT and FDG-PET. FDG-PET is superior to CT in order to differentiate between malignant and benign tumours. However, acute inflammation can mimic malignant lymph node invasion. FDG-PET is justified as a supporting staging measure in cases presenting unclear differentiation between N2 and N3 after conventional staging and is helpful in cases with unclear cell type of the primary tumour.

Whole body FDG-PET for the evaluation and staging of small cell lung cancer: a preliminary study

[F18]-2-deoxy-2fluoro- d-glucose positron emission tomography (FDG-PET) is increasingly used in the diagnosis and staging of lung cancer. Despite its positive performance characteristics in non-small cell lung cancer (NSCLC), the role of FDG-PET in the staging of small cell lung cancer (SCLC) remains to be determined. We designed a prospective study to address this question. Eighteen patients with SCLC were enrolled prospectively to undergo total body FDG-PET in addition to conventional staging procedures (chest computed tomography (CT), abdominal CT, cranial CT or magnetic resonance imaging (MRI), and bone scan/bone marrow biopsy). The agreement between FDG-PET and conventional staging modalities in identifying the presence or absence of metastatic disease was compared using the Veterans Administration (VA) cooperative staging system for staging. Overall staging by FDG-PET agreed with conventional staging exams in 15/18 (83%) patients ( κ=0.67), which included eight extensive and seven limited cases. FDG-PET showed more extensive disease in two of the three patients for which FDG-PET and conventional staging disagreed. These data suggest that total body FDG-PET may be useful in the staging, treatment planning, and prognostication of SCLC. Whether FDG-PET will replace other more established staging modalities remains to be determined by larger prospective randomized controlled studies.

A comparison of 111In-octreotide and 67Ga scintigraphy in malignant lymphoma

We compared 111In-octreotide and 67Ga scintigraphy for staging malignant lymphoma. In 11 patients, planar imaging was performed 4 and 24 h after the injection of 111In-octreotide and 48 and 72 h after the administration of 67Ga. Radiological and clinical data were used as the 'gold standard', resulting in the identification of 26 lesions. Twenty-three (88%) of these lesions were detected by 67Ga and 18 (69%) by 111In scintigraphy. All 14 supra-diaphragmatic lesions were detected by 67Ga and 13 by 111In. In the intra-abdominal areas, only two of eight known localizations were identified by 111In scintigraphy, whereas 67Ga uptake was seen in six of them. In the inguinal regions, both tracers detected three of four lesions. Of the eight lesions of low-grade malignancy, seven were visualized by 67Ga and five by 111In-octreotide imaging. For the intermediate and high-grade lymphomas, 67Ga showed a similar detection rate (16/18 lesions), whereas 111In was only able to detect 13 lesions. We conclude that 111In-octreotide provides less information than 67Ga scintigraphy and conventional staging modalities. The best results for both tracers were observed above the diaphragm. The 67Ga results were more reliable for the detection of infra-diaphragmatic lesions.

THE ROLE OF THE REVERSE-TRANSCRIPTASE POLYMERASE CHAIN REACTION ASSAY FOR PROSTATE-SPECIFIC ANTIGEN IN THE SELECTION OF PATIENTS FOR RADICAL PROSTATECTOMY

Prostate cells present in the peripheral circulation can be detected using an enhanced reverse-transcriptase polymerase chain reaction (RT-PCR) for prostate-specific antigen (PSA) assay. In one study, preoperative enhanced RT-PCR for PSA status was a significant predictor of surgical pathology and postoperative biomechanical recurrence. The use of RT-PCR may enhance the urologist's ability to stage potential candidates for radical prostatectomy, as the assay is a more sensitive and specific predictor of microscopic extracapsular extension than conventional staging modalities. This highly adaptable assay also may have roles in screening for recurrence and in staging other solid tumors.

Reverse transcriptase- polymerase chain reaction (RT-PCR) to detect prostate cancer micrometastasis in the blood.

Since the high mortality rate of prostate cancer is directly associated with the incidence of cancer metastasis, early detection of metastasizing prostate cancer cells in the blood has very important clinical implications. Conventional screening and staging modalities often fail to identify patients who may have prostate cancer that is already metastatic [1], and it has been estimated that 60% of new patients may have asymptomatic micrometastasis. It is therefore of great importance to be able to define which patients are at risk for the development of further metastatic disease [2,3]. It has been suggested that the detection of circulating prostate cancer cells in the peripheral blood may allow assessment of disease state [4], although the exact clinical significance of circulating cancer cells remains unclear. Animal experiments using solid tumors have shown that only two cells per milliliter of blood may be enough for tumor metastasis from hematogenous dissemination [5–7]. Based on these studies, a technique to detect circulating cells must be highly sensitive, detecting ten tumor cells in a five milliliter blood sample. Although immunohistochemical and other immunological techniques that use antibodies against tumor-associated antigens or tissue-specific antigens are helpful in detecting the primary site of metastatic disease and the presence of small foci of metastatic disease, these techniques are not sensitive enough to detect such a small number of cancer cells in a large quantity of nonneoplastic cells. It is through the development of Reverse Transcriptase-Polymerase Chain Reaction (RT-PCR) and new tumor markers that the desired sensitivity for this approach becomes possible. The high sensitivity and specificity obtained from this technique as well as the small quantity of test material required makes RT-PCR a definite front runner in the race for early detection of micrometastasis in prostate cancer.